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Sample records for long-term immune responses

  1. 17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients

    NARCIS (Netherlands)

    Wieten, R. W.; Goorhuis, A.; Jonker, E. F. F.; de Bree, G. J.; de Visser, A. W.; van Genderen, P. J. J.; Remmerswaal, E. B. M.; ten Berge, I. J. M.; Visser, L. G.; Grobusch, M. P.; van Leeuwen, E. M. M.

    2016-01-01

    The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. Fifteen

  2. Intranasal immunization with protective antigen of Bacillus anthracis induces a long-term immunological memory response.

    Science.gov (United States)

    Woo, Sun-Je; Kang, Seok-Seong; Park, Sung-Moo; Yang, Jae Seung; Song, Man Ki; Yun, Cheol-Heui; Han, Seung Hyun

    2015-10-01

    Although intranasal vaccination has been shown to be effective for the protection against inhalational anthrax, establishment of long-term immunity has yet to be achieved. Here, we investigated whether intranasal immunization with recombinant protective antigen (rPA) of Bacillus anthracis induces immunological memory responses in the mucosal and systemic compartments. Intranasal immunization with rPA plus cholera toxin (CT) sustained PA-specific antibody responses for 6 months in lung, nasal washes, and vaginal washes as well as serum. A significant induction of PA-specific memory B cells was observed in spleen, cervical lymph nodes (CLNs) and lung after booster immunization. Furthermore, intranasal immunization with rPA plus CT remarkably generated effector memory CD4(+) T cells in the lung. PA-specific CD4(+) T cells preferentially increased the expression of Th1- and Th17-type cytokines in lung, but not in spleen or CLNs. Collectively, the intranasal immunization with rPA plus CT promoted immunologic memory responses in the mucosal and systemic compartments, providing long-term immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1976-01-01

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

  4. Long-Term Protective Immune Response Elicited by Vaccination with an Expression Genomic Library of Toxoplasma gondii

    OpenAIRE

    Fachado, Alberto; Rodriguez, Alexandro; Molina, Judith; Silvério, Jaline C.; Marino, Ana P. M. P.; Pinto, Luzia M. O.; Angel, Sergio O.; Infante, Juan F.; Traub-Cseko, Yara; Amendoeira, Regina R.; Lannes-Vieira, Joseli

    2003-01-01

    Immunization of BALB/c mice with an expression genomic library of Toxoplasma gondii induces a Th1-type immune response, with recognition of several T. gondii proteins (21 to 117 kDa) and long-term protective immunity against a lethal challenge. These results support further investigations to achieve a multicomponent anti-T. gondii DNA vaccine.

  5. 17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients.

    Science.gov (United States)

    Wieten, R W; Goorhuis, A; Jonker, E F F; de Bree, G J; de Visser, A W; van Genderen, P J J; Remmerswaal, E B M; Ten Berge, I J M; Visser, L G; Grobusch, M P; van Leeuwen, E M M

    2016-06-01

    The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. Fifteen patients using different immunosuppressive drugs and 30 healthy individuals vaccinated 0-22 years ago were included. The serological response was measured using the plaque reduction neutralization test (PRNT). CD8(+) and CD4(+) T-cell responses were measured following proliferation and re-stimulation with YFV peptide pools. Phenotypic characteristics and cytokine responses of CD8(+) T-cells were determined using class I tetramers. The geometric mean titre of neutralizing antibodies was not different between the groups (p = 0.77). The presence of YFV-specific CD4(+) and CD8(+) T-cell did not differ between patients and healthy individuals (15/15, 100.0% vs. 29/30, 96.7%, p = 0.475). Time since vaccination correlated negatively with the number of YFV-specific CD8(+) T-cells (r = -0.66, p = 0.0045). Percentages of early-differentiated memory cells increased (r = 0.67, p = 0.017) over time. These results imply that YF vaccination is effective despite certain immunosuppressive drug regimens. An early-differentiated memory-like phenotype persisted, which is associated with effective expansion upon re-encounter with antigen, suggesting a potent memory T-cell pool remains. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  6. Clay Nanoparticles Elicit Long-Term Immune Responses by Forming Biodegradable Depots for Sustained Antigen Stimulation.

    Science.gov (United States)

    Chen, Weiyu; Zuo, Huali; Li, Bei; Duan, Chengcheng; Rolfe, Barbara; Zhang, Bing; Mahony, Timothy J; Xu, Zhi Ping

    2018-05-01

    Nanomaterials have been widely tested as new generation vaccine adjuvants, but few evoke efficient immunoreactions. Clay nanoparticles, for example, layered double hydroxide (LDH) and hectorite (HEC) nanoparticles, have shown their potent adjuvanticity in generating effective and durable immune responses. However, the mechanism by which clay nanoadjuvants stimulate the immune system is not well understood. Here, it is demonstrated that LDH and HEC-antigen complexes form loose agglomerates in culture medium/serum. They also form nodules with loose structures in tissue after subcutaneous injection, where they act as a depot for up to 35 d. More importantly, clay nanoparticles actively and continuously recruit immune cells into the depot for up to one month, and stimulate stronger immune responses than FDA-approved adjuvants, Alum and QuilA. Sustained antigen release is also observed in clay nanoparticle depots, with 50-60% antigen released after 35 d. In contrast, Alum-antigen complexes show minimal antigen release from the depot. Importantly, LDH and HEC are more effective than QuilA and Alum in promoting memory T-cell proliferation. These findings suggest that both clay nanoadjuvants can serve as active vaccine platforms for sustained and potent immune responses. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Debabrata [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Datta, Soma [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Bhattacharya, Shelley [Environmental Toxicology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India); Mazumder, Shibnath [Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731235 (India)]. E-mail: shibnath1@yahoo.co.in

    2007-02-15

    The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 {mu}M) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of 'IL-4 like factors' from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge.

  8. Long-term exposure to arsenic affects head kidney and impairs humoral immune responses of Clarias batrachus

    International Nuclear Information System (INIS)

    Ghosh, Debabrata; Datta, Soma; Bhattacharya, Shelley; Mazumder, Shibnath

    2007-01-01

    The present study was aimed at determining the effects of long-term arsenic exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias batrachus L. Long-term exposure (150 days) to non-lethal concentrations of arsenic (42.42 μM) resulted in significant time-dependent alterations in HK cell number eventually affecting the HK somatic index. Prolonged exposure to arsenic also suppressed HK-B cell proliferation and led to significant reduction in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin titers. A decline in the number of antigen-specific plaque-forming cells with duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent assays further revealed that arsenic exposure inhibited the release of 'IL-4 like factors' from HK-T cells. Histological studies documented time-dependent changes in the structure and cellular composition of HK characterized by extensive lymphocytopenia, decrease in melano-macrophage population and hemosiderin accumulation. From exposure-challenge studies with Aeromonas hydrophila it was evident that pathogens could efficiently disseminate and colonize distant host tissues in the exposed fish. Moreover, the ability to decrease the pathogen load was also significantly reduced in the arsenic-exposed fish. Thus long-term exposure to non-lethal concentrations of arsenic affects HK and interferes with the humoral immune system of C. batrachus rendering them immunocompromised and susceptible to pathogenic challenge

  9. Long term immune responses to pandemic influenza A/H1N1 infection in solid organ transplant recipients.

    Directory of Open Access Journals (Sweden)

    Aliyah Baluch

    Full Text Available In solid organ transplant (SOT recipients it is unknown if natural infection with influenza confers protection from re-infection with the same strain during the next influenza season. The purpose of this study was to determine if infection with pandemic influenza A/H1N1 (pH1N1 resulted in a long-term immunologic response. Transplant recipients with microbiologically proven pH1N1 infection in 2009/2010 underwent humoral and cell-mediated immunity (CMI testing for pH1N1 just prior to the next influenza season. Concurrent testing for A/Brisbane/59/2007 was done to rule-out cross-reacting antibody. We enrolled 22 adult transplant patients after pH1N1 infection. Follow up testing was done at a median of 7.4 months (range 5.8-15.4 after infection. After excluding those with cross-reactive antibody, 7/19 (36.8% patients were seroprotected. Detectable pH1N1-specific CD4+ and CD8+ interferon-γ producing T-cells were found in 11/22 (50% and 8/22 (36.4% patients respectively. Humoral immunity had a significant correlation with a CD4 response. This is the first study in transplant patients to evaluate long-term humoral and cellular response after natural influenza infection. We show that a substantial proportion of SOT recipients with previous pH1N1 infection lack long-term humoral and cellular immune responses to pH1N1. These patients most likely are at risk for re-infection.

  10. Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

    Science.gov (United States)

    Fazio, V M; Ria, F; Franco, E; Rosati, P; Cannelli, G; Signori, E; Parrella, P; Zaratti, L; Iannace, E; Monego, G; Blogna, S; Fioretti, D; Iurescia, S; Filippetti, R; Rinaldi, M

    2004-03-01

    Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

  11. Long term evolution of the immune response in the rat irradiated at mean and high doses

    International Nuclear Information System (INIS)

    Malarbet, J.L.; Veyrat, M.; Le Go, R.; Prudhomme, J.; Genest, L.; Castelnau, L.

    1977-01-01

    In irradiated animals, the lymphocytes, immunity vectors, are quickly and quantitatively depressed. Their ability to respond to an antigenic stimulus was tested in rats during post-irradiation lymphopenia and after restoration of normal lymphocytosis. The antigenic stimulus, sheep erythrocytes, was applied first 2 and 3 weeks, then 1, 2 and 3 months after exposures to 60 Co gamma rays (doses 300 and 600 rads). This study covered the 3rd through the 10th day after immunisation. Blood lymphocytes were separated by the Ficoll-Contrix gradient method and spleen lymphocytes were obtained by crushing. A lymphocyte sub-population separation was obtained from centrifugation on 4 discontinuous Ficoll-Contrix gradients. Size distribution spectra show that the lighter sub-population is made up of large-sized cells and that the heavier the cells, the smaller they are. The determination of surface immunoglobulins with fluorescent antigens shows that cells bearing immunoglobulins are predominant in the low-density sub-population. The measurement of electrophoretic mobility shows a low-mobility, low-density population and a higher density, faster mobility population which could reflect a higher proportion of B-cells in the low density population and of T-cells in the higher density population. The immune response was tested on the sub-populations. The rosette-forming ability was depressed during 1 month after irradiation then became progressively normal. The cellular plaque-forming ability was markedly suppressed 15 days after irradiation, but was soon active again. These results show the qualitative aspect of the post-irradiation immune defect [fr

  12. T-Cell-Mediated Immune Responses in Patients with Cutaneous or Mucosal Leishmaniasis: Long-Term Evaluation after Therapy

    Science.gov (United States)

    Da-Cruz, Alda Maria; Bittar, Rita; Mattos, Marise; Oliveira-Neto, Manuel P.; Nogueira, Ricardo; Pinho-Ribeiro, Vanessa; Azeredo-Coutinho, Rilza Beatriz; Coutinho, Sergio G.

    2002-01-01

    T-cell immune responses in patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) were studied during the active disease, at the end of therapy, and 1 to 17 years posttherapy (long-term follow-up). Lymphocyte proliferative responses, phenotypic characterization of CD4+ and CD8+ Leishmania-reactive T cells, and cytokine production were assayed. Patients with active ML and CL showed higher proportions of CD4+ than CD8+ T cells. In CL, the healing process was associated with a decrease of CD4+ and an increase of CD8+, leading to similar CD4+ and CD8+ proportions. This pattern was only seen in ML after long-term therapy. Long-term follow-up of patients with CL showed a positive CD4+/CD8+ ratio as observed during the active disease, although the percentages of these T cell subsets were significantly lower. Patients with CL did not show significant differences between gamma interferon (IFN-γ) and interleukin-5 (IL-5) production during the period of study. Patients with active ML presented higher IFN-γ and IL-5 levels compared to patients with active CL. IL-4 was only detected during active disease. Patients long term after cure from ML showed increasing production of IFN-γ, significant decrease of IL-5, and no IL-4 production. Two apparently beneficial immunological parameters were detected in tegumentary leishmaniasis: (i) decreasing proportions of CD4+ Leishmania-reactive T cells in the absence of IL-4 production associated with cure of CL and ML and (ii) decreasing levels of IL-5 long after cure, better detected in patients with ML. The observed T-cell responses maintained for a long period in healed patients could be relevant for immunoprotection against reinfection and used as a parameter for determining the prognosis of patients and selecting future vaccine preparations. PMID:11874860

  13. Selective CD28 Antagonist Blunts Memory Immune Responses and Promotes Long-Term Control of Skin Inflammation in Nonhuman Primates.

    Science.gov (United States)

    Poirier, Nicolas; Chevalier, Melanie; Mary, Caroline; Hervouet, Jeremy; Minault, David; Baker, Paul; Ville, Simon; Le Bas-Bernardet, Stephanie; Dilek, Nahzli; Belarif, Lyssia; Cassagnau, Elisabeth; Scobie, Linda; Blancho, Gilles; Vanhove, Bernard

    2016-01-01

    Novel therapies that specifically target activation and expansion of pathogenic immune cell subsets responsible for autoimmune attacks are needed to confer long-term remission. Pathogenic cells in autoimmunity include memory T lymphocytes that are long-lived and present rapid recall effector functions with reduced activation requirements. Whereas the CD28 costimulation pathway predominantly controls priming of naive T cells and hence generation of adaptive memory cells, the roles of CD28 costimulation on established memory T lymphocytes and the recall of memory responses remain controversial. In contrast to CD80/86 antagonists (CTLA4-Ig), selective CD28 antagonists blunt T cell costimulation while sparing CTLA-4 and PD-L1-dependent coinhibitory signals. Using a new selective CD28 antagonist, we showed that Ag-specific reactivation of human memory T lymphocytes was prevented. Selective CD28 blockade controlled both cellular and humoral memory recall in nonhuman primates and induced long-term Ag-specific unresponsiveness in a memory T cell-mediated inflammatory skin model. No modification of memory T lymphocytes subsets or numbers was observed in the periphery, and importantly no significant reactivation of quiescent viruses was noticed. These findings indicate that pathogenic memory T cell responses are controlled by both CD28 and CTLA-4/PD-L1 cosignals in vivo and that selectively targeting CD28 would help to promote remission of autoimmune diseases and control chronic inflammation. Copyright © 2015 by The American Association of Immunologists, Inc.

  14. Silica Vesicle Nanovaccine Formulations Stimulate Long-Term Immune Responses to the Bovine Viral Diarrhoea Virus E2 Protein.

    Directory of Open Access Journals (Sweden)

    Karishma T Mody

    Full Text Available Bovine Viral Diarrhoea Virus (BVDV is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2 antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0.934 cm3 g(-1 have proven to be ideal candidates to load oE2 antigen and generate immune response. The current study for the first time demonstrates the ability of freeze-dried (FD as well as non-FD oE2/SV140 nanovaccine formulation to induce long-term balanced antibody and cell mediated memory responses for at least 6 months with a shortened dosing regimen of two doses in small animal model. The in vivo ability of oE2 (100 μg/SV-140 (500 μg and FD oE2 (100 μg/SV-140 (500 μg to induce long-term immunity was compared to immunisation with oE2 (100 μg together with the conventional adjuvant Quil-A from the Quillaja saponira (10 μg in mice. The oE2/SV-140 as well as the FD oE2/SV-140 nanovaccine generated oE2-specific antibody and cell mediated responses for up to six months post the final second immunisation. Significantly, the cell-mediated responses were consistently high in mice immunised with oE2/SV-140 (1,500 SFU/million cells at the six-month time point. Histopathology studies showed no morphological changes at the site of injection or in the different organs harvested from the mice immunised with 500 μg SV-140 nanovaccine compared to the unimmunised control. The platform has the potential for developing single dose vaccines without the requirement of cold chain storage for veterinary and human applications.

  15. Characterization of the long-term immune response to vaccination against Mycobacterium avium subsp. paratuberculosis in Danish dairy cows

    DEFF Research Database (Denmark)

    Thomsen, Vibeke Thulstrup; Nielsen, Søren Saxmose; Thakur, Aneesh

    2012-01-01

    including 895 vaccinated and 2526 non-vaccinated dairy cows in 9 Danish dairy herds aiming at characterizing the long-term antibody-response to vaccination; and (2) a cross-sectional study of responses in the IFN-γ assay carried out in 140 vaccinated animals in two herds to evaluate the effect....... The prevalence of antibody responses of the vaccinated animals was relatively constant from 2 to 6years of age, but decreased in older animals. Among the 140 vaccinated animals 88% tested positive with the IFN-γ test to johnin PPD and 50% responded to PPDb with IFN-γ production above a similar cut-off. Although...

  16. Short-term and long-term antibody response by mice after immunization against Neisseria meningitidis B or diphtheria toxoid

    Directory of Open Access Journals (Sweden)

    G.P. Silva

    2013-02-01

    Full Text Available Serogroup B Neisseria meningitidis (MenB is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization. Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine, its use should be restricted to outbreaks of meningococcal disease.

  17. Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

    International Nuclear Information System (INIS)

    Fujita, Tetsuo; Teh, Bin S.; Timme, Terry L.; Mai, W.-Y.; Satoh, Takefumi; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

    2006-01-01

    Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR + CD8 + T cells were increased at all timepoints up to 8 months. The mean percentages of DR + CD4 + T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer

  18. Two doses of bovine viral diarrhea virus DNA vaccine delivered by electroporation induce long-term protective immune responses.

    Science.gov (United States)

    van Drunen Littel-van den Hurk, Sylvia; Lawman, Zoe; Snider, Marlene; Wilson, Don; van den Hurk, Jan V; Ellefsen, Barry; Hannaman, Drew

    2013-02-01

    Bovine viral diarrhea virus (BVDV) is a pathogen of major importance in cattle, so there is a need for new effective vaccines. DNA vaccines induce balanced immune responses and are relatively inexpensive and thus promising for both human and veterinary applications. In this study, newborn calves with maternal antibodies were vaccinated intramuscularly (i.m.) with a BVDV E2 DNA vaccine with the TriGrid Delivery System for i.m. delivery (TDS-IM). Two doses of this vaccine spaced 6 or 12 weeks apart were sufficient to induce significant virus-neutralizing antibody titers, numbers of activated T cells, and reduction in viral shedding and clinical presentations after BVDV-2 challenge. In contrast to the placebo-treated animals, the vaccinated calves did not lose any weight, which is an excellent indicator of the well-being of an animal and has a significant economic impact. Furthermore, the interval between the two vaccinations did not influence the magnitude of the immune responses or degree of clinical protection, and a third immunization was not necessary or beneficial. Since electroporation may enhance not only the magnitude but also the duration of immunity after DNA immunization, the interval between vaccination and challenge was extended in a second trial, which showed that two doses of this E2 DNA vaccine again significantly reduced clinical disease against BVDV for several months. These results are promising and support this technology for use against infectious diseases in cattle and large species, including humans, in general.

  19. Long term protection after immunization with P. berghei sporozoites correlates with sustained IFNγ responses of hepatic CD8+ memory T cells.

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    Krystelle Nganou-Makamdop

    Full Text Available Protection against P. berghei malaria can successfully be induced in mice by immunization with both radiation attenuated sporozoites (RAS arresting early during liver stage development, or sporozoites combined with chloroquine chemoprophylaxis (CPS, resulting in complete intra-hepatic parasite development before killing of blood-stages by chloroquine takes place. We assessed the longevity of protective cellular immune responses by RAS and CPS P. berghei immunization of C57BL/6j mice. Strong effector and memory (T(EM CD8+ T cell responses were induced predominantly in the liver of both RAS and CPS immunized mice while CD4+ T cells with memory phenotype remained at base line levels. Compared to unprotected naïve mice, we found high sporozoite-specific IFNγ ex vivo responses that associated with induced levels of in vivo CD8+ T(EM cells in the liver but not spleen. Long term evaluation over a period of 9 months showed a decline of malaria-specific IFNγ responses in RAS and CPS mice that significantly correlated with loss of protection (r(2 = 0.60, p<0.0001. The reducing IFNγ response by hepatic memory CD8+ T cells could be boosted by re-exposure to wild-type sporozoites. Our data show that sustainable protection against malaria associates with distinct intra-hepatic immune responses characterized by strong IFNγ producing CD8+ memory T cells.

  20. Long term protection after immunization with P. berghei sporozoites correlates with sustained IFNγ responses of hepatic CD8+ memory T cells.

    Science.gov (United States)

    Nganou-Makamdop, Krystelle; van Gemert, Geert-Jan; Arens, Theo; Hermsen, Cornelus C; Sauerwein, Robert W

    2012-01-01

    Protection against P. berghei malaria can successfully be induced in mice by immunization with both radiation attenuated sporozoites (RAS) arresting early during liver stage development, or sporozoites combined with chloroquine chemoprophylaxis (CPS), resulting in complete intra-hepatic parasite development before killing of blood-stages by chloroquine takes place. We assessed the longevity of protective cellular immune responses by RAS and CPS P. berghei immunization of C57BL/6j mice. Strong effector and memory (T(EM)) CD8+ T cell responses were induced predominantly in the liver of both RAS and CPS immunized mice while CD4+ T cells with memory phenotype remained at base line levels. Compared to unprotected naïve mice, we found high sporozoite-specific IFNγ ex vivo responses that associated with induced levels of in vivo CD8+ T(EM) cells in the liver but not spleen. Long term evaluation over a period of 9 months showed a decline of malaria-specific IFNγ responses in RAS and CPS mice that significantly correlated with loss of protection (r(2) = 0.60, pmemory CD8+ T cells could be boosted by re-exposure to wild-type sporozoites. Our data show that sustainable protection against malaria associates with distinct intra-hepatic immune responses characterized by strong IFNγ producing CD8+ memory T cells.

  1. Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04-adjuvanted vaccine in preteen/adolescent girls and young women

    DEFF Research Database (Denmark)

    Petäjä, T; Pedersen, Court; Poder, A

    2011-01-01

    Vaccination against oncogenic human papillomavirus (HPV) types is one key intervention for cervical cancer prevention. This follow-up study assessed the persistence of the systemic and mucosal immune responses together with the safety profile of the HPV-16/18 AS04-adjuvanted vaccine administered...... of transudation or exudation of serum IgG antibodies through the cervical epithelium. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile. In conclusion, this follow-up study shows that the HPV-16/18 AS04-adjuvanted vaccine administered to preteen/adolescents girls and young women...... induces long-term systemic and mucosal immune response and has a clinically acceptable safety profile up to four years after the first vaccine dose....

  2. Long-term persistence of systemic and mucosal immune response to HPV-16/18 AS04-adjuvanted vaccine in preteen/adolescent girls and young women

    DEFF Research Database (Denmark)

    Petäjä, T; Pedersen, C; Andersen, Anne Poder

    2010-01-01

    Vaccination against oncogenic human papillomavirus (HPV) types is one key intervention for cervical cancer prevention. This follow-up study assessed the persistence of the systemic and mucosal immune responses together with the safety profile of the HPV-16/18 AS04-adjuvanted vaccine administered...... of transudation or exudation of serum IgG antibodies through the cervical epithelium. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile. In conclusion, this follow-up study shows that the HPV-16/18 AS04-adjuvanted vaccine administered to preteen/adolescents girls and young women...... induces long-term systemic and mucosal immune response and has a clinically acceptable safety profile up to four years after the first vaccine dose....

  3. Induction of long-term protective immune responses by influenza H5N1 virus-like particles.

    Directory of Open Access Journals (Sweden)

    Sang-Moo Kang

    Full Text Available Recurrent outbreaks of highly pathogenic H5N1 avian influenza virus pose a threat of eventually causing a pandemic. Early vaccination of the population would be the single most effective measure for the control of an emerging influenza pandemic.Influenza virus-like particles (VLPs produced in insect cell-culture substrates do not depend on the availability of fertile eggs for vaccine manufacturing. We produced VLPs containing influenza A/Viet Nam1203/04 (H5N1 hemagglutinin, neuraminidase, and matrix proteins, and investigated their preclinical immunogenicity and protective efficacy. Mice immunized intranasally with H5N1 VLPs developed high levels of H5N1 specific antibodies and were 100% protected against a high dose of homologous H5N1 virus infection at 30 weeks after immunization. Protection is likely to be correlated with humoral and cellular immunologic memory at systemic and mucosal sites as evidenced by rapid anamnestic responses to re-stimulation with viral antigen in vivo and in vitro.These results provide support for clinical evaluation of H5N1 VLP vaccination as a public health intervention to mitigate a possible pandemic of H5N1 influenza.

  4. Activation of immunity, immune response, antioxidant ability, and resistance against Vibrio alginolyticus in white shrimp Litopenaeus vannamei decrease under long-term culture at low pH.

    Science.gov (United States)

    Chen, Yu-Yuan; Chen, Jiann-Chu; Tseng, Kuei-Chi; Lin, Yong-Chin; Huang, Chien-Lun

    2015-10-01

    The growth, activation of immunity, immune parameters, and transcript levels of cytMnSOD, mtMnSOD, ecCuZnSOD, glutathione peroxidase (GPx), catalase, lysozyme, and penaeidin 3a were examined in white shrimp Litopenaeus vannamei reared at pH 6.8 and 8.1 after 24 weeks. No significant difference in growth was observed between the two groups. An in vitro study indicated that phenoloxidase activity and respiratory bursts (RB, release of the superoxide anion) were significantly higher in the haemocytes of pH 8.1 shrimp (shrimp reared at pH 8.1) than in pH 6.8 shrimp (shrimp reared at pH 6.8). An in vivo study indicated that the levels of immune parameters of pH 8.1 shrimp were significantly higher than in pH 6.8 shrimp, and the transcript levels of cytMnSOD, ecCuZnSOD, glutathione peroxidase, lysozyme, and penaeidin 3a were down-regulated in pH 6.8 shrimp. In another experiment, shrimp reared at pH 6.8 and 8.1 for 24 weeks were challenged with Vibrio alginolyticus. The mortality rate of pH 6.8 shrimp was significantly higher than in pH 8.1 shrimp over 12-168 h. Phagocytic activity, phagocytic index, and clearance efficiency to V. alginolyticus were significantly lower in pH 6.8 shrimp. We concluded that shrimp under long-term culture at pH 6.8 exhibited decreased resistance against V. alginolyticus as evidenced by reductions in the activation of immunity and immune parameters together with decreased transcript levels of cytMnSOD, ecCuZnSOD, GPx, lysozyme, and penaeidin 3a. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Multiple myeloma patients in long-term complete response after autologous stem cell transplantation express a particular immune signature with potential prognostic implication.

    Science.gov (United States)

    Arteche-López, A; Kreutzman, A; Alegre, A; Sanz Martín, P; Aguado, B; González-Pardo, M; Espiño, M; Villar, L M; García Belmonte, D; de la Cámara, R; Muñoz-Calleja, C

    2017-06-01

    The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naïve, effector, central memory and regulatory), B-cells (naïve, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC). Heavy/light chains (HLC) were quantified by nephelometry. The percentage of CD4 + T-cells was lower in patients, whereas an increment in the percentage of CD4 + and CD8 + effector memory T-cells was associated with the LTCR. Regulatory T-cells and NK-cells were similar in both groups but a particular redistribution of inhibitory and activating receptors in NK-cells were found in patients. Regarding B-cells, an increase in naïve cells and a corresponding reduction in marginal zone-like and class-switched memory B-cells was observed. The HLC values were normal. Our results suggest that LTCR-MM patients express a particular immune signature, which probably reflects a 'high quality' immune reconstitution that could exert a competent anti-tumor immunological surveillance along with a recovery of the humoral immunity.

  6. Long-term persistence of immunity and B-cell memory following Haemophilus influenzae type B conjugate vaccination in early childhood and response to booster.

    Science.gov (United States)

    Perrett, K P; John, T M; Jin, C; Kibwana, E; Yu, L-M; Curtis, N; Pollard, A J

    2014-04-01

    Protection against Haemophilus influenzae type b (Hib), a rapidly invading encapsulated bacteria, is dependent on maintenance of an adequate level of serum antibody through early childhood. In many countries, Hib vaccine booster doses have been implemented after infant immunization to sustain immunity. We investigated the long-term persistence of antibody and immunological memory in primary-school children following infant (with or without booster) Hib vaccination. Anti-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) concentration and the frequency of circulating Hib-specific memory B cells were measured before a booster of a Hib-serogroup C meningococcal (MenC) conjugate vaccine and again 1 week, 1 month, and 1 year after the booster in 250 healthy children aged 6-12 years in an open-label phase 4 clinical study. Six to 12 years following infant priming with 3 doses of Hib conjugate vaccine, anti-PRP IgG geometric mean concentrations were 3.11 µg/mL and 0.71 µg/mL and proportions with anti-PRP IgG ≥1.0 µg/mL were 79% and 43% in children who had or had not, respectively, received a fourth Hib conjugate vaccine dose (mean age, 3.9 years). Higher baseline and post-Hib-MenC booster responses (anti-PRP IgG and memory B cells) were found in younger children and in those who had received a fourth Hib dose. Sustained Hib conjugate vaccine-induced immunity in children is dependent on time since infant priming and receipt of a booster. Understanding the relationship between humoral and cellular immunity following immunization with conjugate vaccines may direct vaccine design and boosting strategies to sustain individual and population immunity against encapsulated bacteria in early childhood. Clinical Trials Registration ISRCTN728588998.

  7. Long-term complications of splenectomy in adult immune thrombocytopenia.

    Science.gov (United States)

    Thai, Lan-Huong; Mahévas, Matthieu; Roudot-Thoraval, Françoise; Limal, Nicolas; Languille, Laetitia; Dumas, Guillaume; Khellaf, Mehdi; Bierling, Philippe; Michel, Marc; Godeau, Bertrand

    2016-11-01

    The recent large decrease in splenectomy use for chronic immune thrombocytopenia (ITP) is partly due to still-unsolved questions about long-term safety. We performed the first single-center exposed/unexposed cohort study evaluating the long-term incidence of splenectomy complications in patients with primary ITP. Overall, 83 patients who underwent splenectomy more than 10 years ago (exposed) were matched with 83 nonsplenectomized patients (unexposed) on the date of ITP diagnosis ±5 years, age and gender. After a median follow-up of 192 months (range 0.5-528), 43 patients (52%) achieved overall response after splenectomy. Splenectomized patients experienced more venous thromboembolism (VTE) than controls (n = 13 vs n = 2, P = 0.005). On multivariate analysis, splenectomy was an independent risk factor of VTE (hazard ratio = 4.006, P = 0.032 [95% confidence interval: 1.13-14.21]). Splenectomized patients presented more severe infections on long-term follow-up: all required hospitalization, and 5/26 (19%) infections led to severe sepsis or septic shock and to death for 3 cases (none in controls). However, the incidence of malignancy was similar in both groups, as was cardiovascular risk, which appeared to be related more to ITP than splenectomy. Finally, splenectomy did not significantly decrease overall survival. Despite the risk of thrombosis and severe sepsis, splenectomy remains an effective and curative treatment for ITP.

  8. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy

    NARCIS (Netherlands)

    Pakker, NG; Otto, SA; Hall, D; Wit, FWNM; Hamann, D; van der Ende, Marchina E.; Claessen, FAP; Kauffmann, RH; Koopmans, PP; Sprenger, HG; Weigel, HM; Montaner, JSG; Lange, JMA; Reiss, P; Schellekens, PTA; Miedema, F; Ten Napel, Chris H. H.

    1999-01-01

    Background: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. Objectives: In this study, long-term immune reconstitution was investigated during highly active antiretroviral

  9. Prior DNA immunization enhances immune response to dominant and subdominant viral epitopes induced by a fowlpox-based SIVmac vaccine in long-term slow-progressor macaques infected with SIVmac251

    International Nuclear Information System (INIS)

    Radaelli, Antonia; Nacsa, Janos; Tsai, W.-P.; Edghill-Smith, Yvette; Zanotto, Carlo; Elli, Veronica; Venzon, David; Tryniszewska, Elzbieta; Markham, Phil; Mazzara, Gail P.; Panicali, Dennis; Morghen, Carlo De Giuli; Franchini, Genoveffa

    2003-01-01

    A therapeutic vaccine for individuals infected with HIV-1 and treated with antiretroviral therapy (ART) should be able to replenish virus-specific CD4+ T-cells and broaden the virus-specific CD8+ T-cell response in order to maintain CD8+ T-cell function and minimize viral immune escape after ART cessation. Because a combination of DNA and recombinant poxvirus vaccine modalities induces high levels of virus-specific CD4+ T-cell response and broadens the cytolytic activity in naive macaques, we investigated whether the same results could be obtained in SIVmac251-infected macaques. The macaques studied here were long-term nonprogressors that naturally contained viremia but were nevertheless treated with a combination of antiviral drugs to assess more carefully the effect of vaccination in the context of ART. The combination of a DNA expressing the gag and pol genes (DNA-SIV-gp) of SIVmac239 followed by a recombinant fowlpox expressing the same SIVmac genes (FP-SIV-gp) was significantly more immunogenic than two immunizations of FP-SIV-gp in SIVmac251-infected macaques treated with ART. The DNA/FP combination significantly expanded and broadened Gag-specific T-cell responses measured by tetramer staining, ELISPOT, and intracellular cytokine staining and measurement of ex vivo cytolytic function. Importantly, the combination of these vaccine modalities also induced a sizeable expansion in most macaques of Gag-specific CD8-(CD4+) T-cells able to produce TNF-α. Hopefully, this modality of vaccine combination may be useful in the clinical management of HIV-1-infected individuals

  10. Prime-booster vaccination of cattle with an influenza viral vector Brucella abortus vaccine induces a long-term protective immune response against Brucella abortus infection.

    Science.gov (United States)

    Tabynov, Kaissar; Yespembetov, Bolat; Ryskeldinova, Sholpan; Zinina, Nadezhda; Kydyrbayev, Zhailaubay; Kozhamkulov, Yerken; Inkarbekov, Dulat; Sansyzbay, Abylai

    2016-01-20

    This study analyzed the duration of the antigen-specific humoral and T-cell immune responses and protectiveness of a recently-developed influenza viral vector Brucella abortus (Flu-BA) vaccine expressing Brucella proteins Omp16 and L7/L12 and containing the adjuvant Montadine Gel01 in cattle. At 1 month post-booster vaccination (BV), both humoral (up to 3 months post-BV; GMT IgG ELISA titer 214±55 to 857±136, with a prevalence of IgG2a over IgG1 isotype antibodies) and T-cell immune responses were observed in vaccinated heifers (n=35) compared to control animals (n=35, injected with adjuvant/PBS only). A pronounced T-cell immune response was induced and maintained for 12 months post-BV, as indicated by the lymphocyte stimulation index (2.7±0.4 to 10.1±0.9 cpm) and production of IFN-γ (13.7±1.7 to 40.0±3.0 ng/ml) at 3, 6, 9, and 12 months post-BV. Prime-boost vaccination provided significant protection against B. abortus infection at 3, 6, 9 and 12 months (study duration) post-BV (7 heifers per time point; alpha=0.03-0.01 vs. control group). Between 57.1 and 71.4% of vaccinated animals showed no signs of B. abortus infection (or Brucella isolation) at 3, 6, 9 and 12 months post-BV; the severity of infection, as indicated by the index of infection (P=0.0003 to Brucella colonization (P=0.03 to abortus infection was also observed among pregnant vaccinated heifers (alpha=0.03), as well as their fetuses and calves (alpha=0.01), for 12 months post-BV. Additionally, 71.4% of vaccinated heifers calved successfully whereas all pregnant control animals aborted (alpha=0.01). Prime-boost vaccination of cattle with Flu-BA induces an antigen-specific humoral and pronounced T cell immune response and most importantly provides good protectiveness, even in pregnant heifers, for at least 12 months post-BV. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Long-term persistence in protection and response to a hepatitis B vaccine booster among adolescents immunized in infancy in the western region of China.

    Science.gov (United States)

    Wang, Zhen-Zi; Gao, Yu-Hua; Lu, Wei; Jin, Cun-Duo; Zeng, Ying; Yan, Ling; Ding, Feng; Li, Tong; Liu, Xue-En; Zhuang, Hui

    2017-04-03

    To evaluate the persistence of protection from hepatitis B (HB) vaccination among adolescents immunized with a primary series of HB vaccine as infants, and the immune response to booster doses. Healthy adolescents aged 15-17 y vaccinated with HB vaccine only at birth were enrolled. Baseline serum hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected by Enzyme-Linked Immunosorbent Assay (ELISA) and anti-HBs level was measured using Chemiluminescent Microparticle Immunoassay (CMIA). The rate of HBV infection was calculated. The seroprotection rate of anti-HBs (≥ 10 mIU/ml) and GMC level were used to evaluate the persistence of immunity from HB vaccination. Those with anti-HBs infants, 3 (1.7%) had HBV infection and 74 (41.1%) had anti-HBs ≥ 10 mIU/ml with a GMC of 145.11 mIU/ml. The remaining 103 (57.2%) with anti-HBs < 10 mIU/ml received a booster dose of 20 μg HB vaccine and achieved the seroprotection rate of 84% (84/100) and a GMC of 875.19 mIU/ml at one month post-booster. An additional dose of 60 μg HB vaccine was administered to the 16 adolescents with anti-HBs < 10 mIU/ml after the first booster. All of them obtained anti-HBs seroprotection with a GMC of 271.02 mIU/ml at 1.5 months after an additional dose. Vaccine-induced immunity persisted for up to 15-17 y in 89.3% (158/177) of participants after a primary HB vaccination in infancy. Administering a booster dose of 20μg HB vaccine elicited an anamnestic immune responses in the majority of individuals with baseline anti-HBs <10 mIU/ml.

  12. Investigating the acute and long-term effects of traumatic brain injury on the immune and fibrinolytic system

    OpenAIRE

    MARIA DAGLAS

    2018-01-01

    Traumatic brain injury is a serious condition that results in long-term disability in most patients. This thesis investigated the early and long-term effects of the immune and fibrinolytic response (blood clot breakdown), and the link between these two systems after brain injury in mice. A unique discovery was that the chronic immune response, over a period of 8 months, directly contributes to a worse outcome after brain injury. We also found gender-specific differences occurring at the early...

  13. Long term protection after immunization with P. berghei sporozoites correlates with sustained IFNgamma responses of hepatic CD8+ memory T cells.

    NARCIS (Netherlands)

    Nganou Makamdop, C.K.; Gemert, G.J.A. van; Arens, T.; Hermsen, C.C.; Sauerwein, R.W.

    2012-01-01

    Protection against P. berghei malaria can successfully be induced in mice by immunization with both radiation attenuated sporozoites (RAS) arresting early during liver stage development, or sporozoites combined with chloroquine chemoprophylaxis (CPS), resulting in complete intra-hepatic parasite

  14. Managerial Long-Term Responsibility in Family-Controlled Firms

    Directory of Open Access Journals (Sweden)

    Dietmar Sternad

    2013-01-01

    Full Text Available Evidence suggests that long-term orientation (LTO as a dominantstrategic logic contributes to the sustainable performance offamily-controlled firms (FCFS. Combining a review of the literatureon lto with stewardship theory and upper echelons theoryreasoning, this article presents a typology of managerial responsibilityand introduces the concept of long-term responsibility as amanagerial characteristic constituting a major driving force behindcreating lto. The antecedents of long-term responsibilityunder family firm-specific conditions (stemming from the familysystem, the governance system, and family-firm managers’ personalcharacteristics are also identified and presented in an integratedmodel. The paper contributes to a more comprehensiveunderstanding of intertemporal choice in fcfs and explains whythey tend to be more long-term oriented than other types of firms.

  15. Hantavirus Gc induces long-term immune protection via LAMP-targeting DNA vaccine strategy.

    Science.gov (United States)

    Jiang, Dong-Bo; Zhang, Jin-Peng; Cheng, Lin-Feng; Zhang, Guan-Wen; Li, Yun; Li, Zi-Chao; Lu, Zhen-Hua; Zhang, Zi-Xin; Lu, Yu-Chen; Zheng, Lian-He; Zhang, Fang-Lin; Yang, Kun

    2018-02-01

    Hemorrhagic fever with renal syndrome (HFRS) occurs widely throughout Eurasia. Unfortunately, there is no effective treatment, and prophylaxis remains the best option against the major pathogenic agent, hantaan virus (HTNV), which is an Old World hantavirus. However, the absence of cellular immune responses and immunological memory hampers acceptance of the current inactivated HFRS vaccine. Previous studies revealed that a lysosome-associated membrane protein 1 (LAMP1)-targeting strategy involving a DNA vaccine based on the HTNV glycoprotein Gn successfully conferred long-term immunity, and indicated that further research on Gc, another HTNV antigen, was warranted. Plasmids encoding Gc and lysosome-targeted Gc, designated pVAX-Gc and pVAX-LAMP/Gc, respectively, were constructed. Proteins of interest were identified by fluorescence microscopy following cell line transfection. Five groups of 20 female BALB/c mice were subjected to the following inoculations: inactivated HTNV vaccine, pVAX-LAMP/Gc, pVAX-Gc, and, as the negative controls, pVAX-LAMP or the blank vector pVAX1. Humoral and cellular immunity were assessed by enzyme-linked immunosorbent assays (ELISAs) and 15-mer peptide enzyme-linked immunospot (ELISpot) epitope mapping assays. Repeated immunization with pVAX-LAMP/Gc enhanced adaptive immune responses, as demonstrated by the specific and neutralizing antibody titers and increased IFN-γ production. The inactivated vaccine induced a comparable humoral reaction, but the negative controls only elicited insignificant responses. Using a mouse model of HTNV challenge, the in vivo protection conferred by the inactivated vaccine and Gc-based constructs (with/without LAMP recombination) was confirmed. Evidence of pan-epitope reactions highlighted the long-term cellular response to the LAMP-targeting strategy, and histological observations indicated the safety of the LAMP-targeting vaccines. The long-term protective immune responses induced by pVAX-LAMP/Gc may be

  16. Mapping long-term wetland response to climate

    Science.gov (United States)

    Zhou, Q.; Gallant, A.; Rover, J.

    2016-12-01

    Wetlands provide unique feeding and breeding habitat for numerous waterfowl species. The distribution of wetlands has been considerably changed due to agricultural land conversion and hydrologic modification. Climate change may further impact wetlands through altered moisture regimes. This study characterized long-term variation in wetland conditions by using dense time series from all available Landsat data from 1985 to 2014. We extracted harmonic frequencies from 30 years to two years to delineate the long-term variation in all seven Landsat bands. A cluster analysis and unsupervised classification then enabled us to map different classes of wetland response. We demonstrated the method in the Prairie Pothole Region in North Dakota.

  17. Long-term salt stress responsive growth, carbohydrate metabolism ...

    African Journals Online (AJOL)

    We investigated the long-term responses of tobacco tissues to salt stress, with a particular interest for growth parameters, proline (Pro) accumulation, and carbohydrate metabolism. Exposure of 17-day-old tobacco plants to 0.2 M NaCl was followed by a higher decrease in dry matter in roots than shoots with a decrease of ...

  18. Age and long-term protective immunity in dogs and cats.

    Science.gov (United States)

    Schultz, R D; Thiel, B; Mukhtar, E; Sharp, P; Larson, L J

    2010-01-01

    Vaccination can provide an immune response that is similar in duration to that following a natural infection. In general, adaptive immunity to viruses develops earliest and is highly effective. Such anti-viral immune responses often result in the development of sterile immunity and the duration of immunity (DOI) is often lifelong. In contrast, adaptive immunity to bacteria, fungi or parasites develops more slowly and the DOI is generally short compared with most systemic viral infections. Sterile immunity to these infectious agents is less commonly engendered. Old dogs and cats rarely die from vaccine-preventable infectious disease, especially when they have been vaccinated and immunized as young adults (i.e. between 16 weeks and 1 year of age). However, young animals do die, often because vaccines were either not given or not given at an appropriate age (e.g. too early in life in the presence of maternally derived antibody [MDA]). More animals need to be vaccinated to increase herd (population) immunity. The present study examines the DOI for core viral vaccines in dogs that had not been revaccinated for as long as 9 years. These animals had serum antibody to canine distemper virus (CDV), canine parvovirus type 2 (CPV-2) and canine adenovirus type-1 (CAV-1) at levels considered protective and when challenged with these viruses, the dogs resisted infection and/or disease. Thus, even a single dose of modified live virus (MLV) canine core vaccines (against CDV, cav-2 and cpv-2) or MLV feline core vaccines (against feline parvovirus [FPV], feline calicivirus [FCV] and feline herpesvirus [FHV]), when administered at 16 weeks or older, could provide long-term immunity in a very high percentage of animals, while also increasing herd immunity. Copyright 2009 Elsevier Ltd. All rights reserved.

  19. Recovery of humoral immunity parameters in mice under a long-term action of tritium oxide

    International Nuclear Information System (INIS)

    Kirillova, E.N.; Man'ko, V.M.; Muksinova, K.N.

    1986-01-01

    Using the mice-males of the CBA line at the age of 10-12 weeks and body mass of 20-23 g the recovery value of quantitative and qualitative factors of humoral immunity under a long-term action of tritium oxide which has been injected during 6 months in the quantity of 370 kBq per 1g of body mass (cumulative dose 8.73 Gy). The long-term internal mice irradiation with tritium oxide resulted in marked devastation of central and peripheral organs of immune system. An earlier and complete recovery of cells quantity in the bone marrow and spleen, recover up to 50% in lymphnodes and minimum repopulation (from 10 to 20%) in thymus as compared with tested animals of the same age is pointed out. In experimental mice CFU 5 pool decrease in bone marrow and spleen is found. CFUs content in the spleen recovered up to the norm, whereas in the bone marrow it constituted not more than 55% of the control. Deep function injury of V-lymphocyte and T - helper precursors the activity of which has not recovered during the whole observation period. The long-term tritium oxide intake lead to antibodies production suppression (by 30-50%), the tendency to the decrease of antibody formation of these animals has been conserved up to the end of life. The functional activity of T - suppressors in humoral response to thymus-dependent antigen during the remote periods upon long-term irradiation decreased more than twice

  20. Long-term ecophysiological responses to climate change

    DEFF Research Database (Denmark)

    Boesgaard, Kristine Stove; Ro-Poulsen, Helge

    Plant physiology is affected by climate change. Acclimations of photosynthetic processes are induced by short-term changes in climatic conditions. Further acclimation can be caused by longterm adjustments to climate change due to ecosystem-feedbacks. The aim of this PhD was to investigate plant...... term responses of plant physiology to the climate change factors were investigated. In the CLIMAITE-experiment it has been shown that 2 years of treatment altered physiological responses in Deschampsiaand Calluna. In the work of this PhD similar responses were observed after 6 years of treatment...... physiological responses to climate change in a seasonal and long-term perspective. The effects of elevated CO2, passive night time warming and periodic summer drought as single factor and in combination, on plant physiology were investigated in the long-term multifactorial field experiment CLIMAITE in a Danish...

  1. Young Long-term Unemployed and the Individualization of Responsibility

    Directory of Open Access Journals (Sweden)

    Jennifer Hobbins

    2016-06-01

    Full Text Available In Sweden, as in most Western societies, a common belief is that unemployment is somehow linked to the individual, her lack of work ethic, or other personal shortcomings rather than to structural causes. This is not only manifested in public arenas such as the media or political debates but also in our social surroundings. In recent years, these views have gained importance, indicating a shift in the location of responsibilities from the welfare state to the individual. This shift entails high demands and expectations on unemployed people and is something they have to deal with and relate to. One of the most exposed groups is young long-term unemployed. The aim of this article is to highlight how the discourse of individualized responsibility is reflected in unemployed peoples’ stories, and to shed light on the ways in which young long-term unemployed adults relate to and position themselves toward this discourse. Based on 18 qualitative interviews with young Swedish long-term unemployed people, the findings show three approaches to the discourse: conformity, distancing, and resistance.

  2. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group

    NARCIS (Netherlands)

    Pakker, N. G.; Kroon, E. D.; Roos, M. T.; Otto, S. A.; Hall, D.; Wit, F. W.; Hamann, D.; van der Ende, M. E.; Claessen, F. A.; Kauffmann, R. H.; Koopmans, P. P.; Kroon, F. P.; ten Napel, C. H.; Sprenger, H. G.; Weigel, H. M.; Montaner, J. S.; Lange, J. M.; Reiss, P.; Schellekens, P. T.; Miedema, F.

    1999-01-01

    BACKGROUND: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. OBJECTIVES: In this study, long-term immune reconstitution was investigated during highly active antiretroviral

  3. Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

    Science.gov (United States)

    Pessoa de Magalhães, Roberto J.; Vidriales, María-Belén; Paiva, Bruno; Fernandez-Gimenez, Carlos; García-Sanz, Ramón; Mateos, Maria-Victoria; Gutierrez, Norma C.; Lecrevisse, Quentin; Blanco, Juan F; Hernández, Jose; de las Heras, Natalia; Martinez-Lopez, Joaquin; Roig, Monica; Costa, Elaine Sobral; Ocio, Enrique M.; Perez-Andres, Martin; Maiolino, Angelo; Nucci, Marcio; De La Rubia, Javier; Lahuerta, Juan-Jose; San-Miguel, Jesús F.; Orfao, Alberto

    2013-01-01

    Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8+ T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes

  4. Long-term outcomes of laparoscopic versus open splenectomy for immune thrombocytopenia.

    Science.gov (United States)

    Tada, Kazuhiro; Ohta, Masayuki; Saga, Kunihiro; Takayama, Hiroomi; Hirashita, Teijiro; Endo, Yuichi; Uchida, Hiroki; Iwashita, Yukio; Inomata, Masafumi

    2018-02-01

    Splenectomy is the standard therapy for medically refractory immune thrombocytopenia (ITP). Laparoscopic splenectomy (LS) has gained wide acceptance; however, the long-term outcomes of LS versus open splenectomy (OS) for patients with ITP remain unclear. We analyzed, retrospectively, 32 patients who underwent splenectomy, as LS in 22 and OS in 10, for refractory ITP at our institute. Data were evaluated based on the American Society of Hematology 2011 evidence-based practice guidelines for ITP. Although the operation time was significantly longer in the LS group (p < 0.01), LS was associated with less blood loss (p < 0.01), infrequent blood transfusion during surgery (p < 0.01), quicker resumption of oral intake (p < 0.01), and shorter hospital stay (p < 0.01) than OS. Positive responses, including complete and partial remission, were achieved in 90% of the OS group patients and 77% of the LS group patients. The mean follow-up periods were 183 and 92 months, respectively. Relapse-free survival rates, 15 years after the operation were 63% in the OS group and 94% in the LS group. LS can provide better short-term results and comparable long-term results to those of OS for ITP.

  5. Long-term results of splenectomy in adult chronic immune thrombocytopenia.

    Science.gov (United States)

    Guan, Yue; Wang, Shixuan; Xue, Feng; Liu, Xiaofan; Zhang, Lei; Li, Huiyuan; Yang, Renchi

    2017-03-01

    We performed this study in adult patients with chronic primary immune thrombocytopenia to explore the long-term efficacy and safety of splenectomy. Data of 174 patients who underwent splenectomy in our hospital from 1994 to 2014 were analyzed. After splenectomy, 126 (72.4%) patients achieved a complete response (CR) and 28 (16.1%) achieved a response (R). Thirty-two (20.8%) responders relapsed with a median time of 24 months. Compared with non-responders and recurrent patients, the stable responders were younger and had higher preoperation and postoperation peak platelet count, later peak platelet count emergence time, and more megakaryocytes. Corticosteroid-dependent patients were more likely to response to splenectomy than those refractory to corticosteroid. We performed a relapse-free survival analysis among the 154 responders. In univariate analyses, corticosteroid dependent and time from diagnosis to splenectomy ≤24 months showed predictive value to persistent response. But only corticosteroid dependent was a significant predictor in multivariate analysis. The 30-d complication rate after the surgery was 25.9%. There were five (2.9%) patients experienced thrombosis and three (1.7%) refractory patients died during follow-up. Splenectomy was a safe treatment with a cure rate of 58.0%. Corticosteroid dependent showed predictive value to persistent response. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Cell response to long term mechanical interaction with nanopipettes

    Science.gov (United States)

    Orynbayeva, Zulfiya; Singhal, Riju; Vitol, Elina; Bouchard, Michael; Azizkhan-Clifford, Jane; Layton, Bradley; Friedman, Gary; Gogotsi, Yury

    2009-03-01

    Traditional microinjection into cells is performed over a relatively short term. Pipettes are typically withdrawn following any kind of injection. On the other hand, there is growing interest in using nanopipettes for cellular and subcellular probing. This interest is partly due to new developments in nanopipette technology which employ carbon nanotubes and provide robustness, flexibility, and biocompatibility. However, as far as we know, no systematic study of physiological, biochemical, and biophysical processes associated with cell response to lengthy mechanical stimulations by nanopipette probing have been performed so far. We present a detailed investigation of a wide range of effects of long term pipette insertion into a cell. Both traditional glass micropipettes and the novel carbon nanotube-tipped probes were involved in this study. The mechanism of Ca2+ response to the mechanical stimuli introduced by the nanopipette, and the role of different organelles in this mechanism were studied. We hypothesize that the calcium response is a function of cytoskeleton integrity and the mode of coupling between the cytoskeleton and the plasma membrane domains.

  7. ESBWR long term containment response to loss of coolant accidents

    International Nuclear Information System (INIS)

    Alamgir, M. D.; Marquino, W.; Diaz-Quiroz, J.; Tucker, L.

    2010-01-01

    ESBWR is a 4500 MWt generation III+ natural circulation reactor with an array of robust passive safety systems to keep the reactor safe during postulated transients and accidents. With the submittal of the latest revision of the Design Control Document (DCD) to US Nuclear Regulatory Commission, ESBWR is nearing the completion of the US certification process. This paper focuses on the bounding licensing analysis of the long-term (30-day) response of the ESBWR containment to limiting Loss of Coolant Accident (LOCA) performed with the TRACG code. It is shown that using only passive systems available during the first 72 hours after the limiting Main Steam Line Break LOCA, the predicted peak containment pressure in the ESBWR containment remain well below the design limits with good margin. After 72 hours of LOCA initiation, PCCS Vent Fans (non-safety system) become available that remove non-condensable gases from, and further enhance the effectiveness of, PCCS heat exchangers to reduce the containment pressure and temperature to values substantially below the design limits. During the post- 72 hour period, the beneficial effects of the Vent Fan operation, combined with the available operator action to refill of PCCS pools, continue to maintain the containment pressure to about 30% below the design limit at 30 days after a limiting ESBWR LOCA. (authors)

  8. Long-term nonprogression and broad HIV-1-specific proliferative T-cell responses

    Directory of Open Access Journals (Sweden)

    Nesrina eImami

    2013-03-01

    Full Text Available Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term nonprogressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilising cure, involving clearance of virus from the host, remains a primary aim, a functional cure may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilised in future strategies designed to improve upon existing therapy. The aim will be to induce long-term nonprogressor or elite controller status in every infected host, through immune-mediated control of viraemia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.

  9. Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity.

    Science.gov (United States)

    Chua, Brendon Y; Wong, Chinn Yi; Mifsud, Edin J; Edenborough, Kathryn M; Sekiya, Toshiki; Tan, Amabel C L; Mercuri, Francesca; Rockman, Steve; Chen, Weisan; Turner, Stephen J; Doherty, Peter C; Kelso, Anne; Brown, Lorena E; Jackson, David C

    2015-10-27

    exposure to infectious agents, while adaptive immunity takes several days to become effective. Here we show, by using a simple lipopeptide-based TLR2 agonist, that an influenza detergent-split vaccine can be made to simultaneously stimulate and amplify both systems to provide immediate antiviral protection while giving the adaptive immune system time to implement long-term immunity. Both types of immunity induced by this approach protect against vaccine-matched as well as unrelated virus strains and potentially even against strains yet to be encountered. Conferring dual functionality to influenza vaccines is beneficial for improving community protection, particularly during periods between the onset of an outbreak and the time when a vaccine becomes available or in scenarios in which mass vaccination with a strain to which the population is immunologically naive is imperative. Copyright © 2015 Chua et al.

  10. Long-term protective immunity from an influenza virus-like particle vaccine administered with a microneedle patch.

    Science.gov (United States)

    Quan, Fu-Shi; Kim, Yeu-Chun; Song, Jae-Min; Hwang, Hye Suk; Compans, Richard W; Prausnitz, Mark R; Kang, Sang-Moo

    2013-09-01

    Skin vaccination with influenza virus-like particles (VLPs) using microneedles has been shown to induce protection similar to or better than that induced by intramuscular immunization. In this study, we examined the long-term protective efficacy of influenza (H1N1 A/PR/8/34) VLPs after skin vaccination using microneedle patches coated with the vaccine. Microneedle vaccination of mice in the skin induced 100% protection against lethal challenge infection with influenza A/PR/8/34 virus 14 months after a single vaccine dose. Influenza virus-specific total IgG response and hemagglutination inhibition (HAI) titers were maintained at high levels for over 1 year after microneedle vaccination. Microneedle vaccination also induced substantial levels of lung IgG and IgA antibody responses, and antibody-secreting plasma cells from spleen and bone marrow, as well as conferring effective control of lung viral loads, resulting in complete protection 14 months after vaccination. These strong and long-lasting immune responses were enabled in part by stabilization of the vaccine by formulation with trehalose during microneedle patch fabrication. Administration of the stabilized vaccine using microneedles was especially effective at enabling strong recall responses measured 4 days after lethal virus challenge, including increased HAI and antibody-secreting cells in the spleen and reduced viral titer and inflammatory response in the lung. The results in this study indicate that skin vaccination with VLP vaccine using a microneedle patch provides long-term protection against influenza in mice.

  11. Study Design to Test the Hypothesis That Long-Term Space Travel Harms the Human and Animal Immune Systems

    Science.gov (United States)

    Shearer, William T.; Lugg, Desmond J.; Ochs, H. D.; Pierson, Duane L.; Reuben, James M.; Rosenblatt, Howard M.; Sams, Clarence; Smith, C. Wayne; Smith, E. Obrian; Smolen, James E.

    1999-01-01

    The potential threat of immunosuppression and abnormal inflammatory responses in long-term space travel, leading to unusual predilection for opportunistic infections, malignancy, and death, is of ma or concern to the National Aeronautics and Space Administration (NASA) Program. This application has been devised to seek answers to questions of altered immunity in space travel raised by previous investigations spanning 30-plus years. We propose to do this with the help of knowledge gained by the discovery of the molecular basis of many primary and secondary immunodeficiency diseases and by application of molecular and genetic technology not previously available. Two areas of immunity that previously received little attention in space travel research will be emphasized: specific antibody responses and non-specific inflammation and adhesion. Both of these areas of research will not only add to the growing body of information on the potential effects of space travel on the immune system, but be able to delineate any functional alterations in systems important for antigen presentation, specific immune memory, and cell:cell and cell:endothelium interactions. By more precisely defining molecular dysfunction of components of the immune system, it is hoped that targeted methods of prevention of immune damage in space could be devised.

  12. Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines

    DEFF Research Database (Denmark)

    Blok, Bastiaan A; Arts, Rob J W; van Crevel, Reinout

    2015-01-01

    An increasing body of evidence shows that the innate immune system has adaptive characteristics that involve a heterologous memory of past insults. Both experimental models and proof-of-principle clinical trials show that innate immune cells, such as monocytes, macrophages, and NK cells, can...... provide protection against certain infections in vaccination models independently of lymphocytes. This process is regulated through epigenetic reprogramming of innate immune cells and has been termed "trained immunity." It has been hypothesized that induction of trained immunity is responsible...... for the protective, nonspecific effects induced by vaccines, such as BCG, measles vaccination, and other whole-microorganism vaccines. In this review, we will present the mechanisms of trained immunity responsible for the long-lasting effects of vaccines on the innate immune system....

  13. The effect on immunity of long-term intensive training in elite swimmers.

    Science.gov (United States)

    Gleeson, M; McDonald, W A; Cripps, A W; Pyne, D B; Clancy, R L; Fricker, P A

    1995-10-01

    The impact of long-term training on systemic and mucosal immunity was assessed prospectively in a cohort of elite swimmers over a 7-month training season in preparation for national championships. The results indicated significant suppression (P training at an intensive level. There was also a trend towards lower IgG2 subclass levels in serum in athletes compared with controls (P = 0.07). There were no significant changes in numbers or percentages of B or T cell subsets, but there was a significant fall in natural killer (NK) cell numbers and percentages in athletes over the training season (P training sessions there was a significant decrease in salivary IgA levels for athletes compared with controls (P = 0.002). In athletes there was a downward trend in salivary IgA levels over the 7-month training period in both the pre-exercise (P = 0.06) and post-exercise samples (P = 0.04). There were no significant trends in salivary IgG levels over the study period in either athletes or controls. The only significant change in salivary IgM levels was an increase in detection rate in the pre-competition phase in athletes (P = 0.03). The study suggests that training of elite athletes at an intensive level over both short- and long-time frames suppresses both systemic and mucosal immunity. Protracted immune suppression linked with prolonged training may determine susceptibility to infection, particularly at times of major competitions.

  14. Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity

    DEFF Research Database (Denmark)

    Arts, Rob J W; Blok, Bastiaan A; Aaby, Peter

    2015-01-01

    were less strong than those induced by live BCG. γBCG vaccination in volunteers had only minimal effects on innate immunity, whereas a significant increase in heterologous Th1/Th17 immunity was observed. Our results indicate that γBCG induces long-term training of innate immunity in vitro. In vivo, γ......BCG vaccination is associated with a reduced mortality from nonmycobacterial infections. This is likely to be mediated by a combination of innate-immune memory ("trained immunity") and heterologous effects on adaptive immunity. As such, BCG could be used to boost host immunity...

  15. How Do Observer's Responses Affect Visual Long-Term Memory?

    Science.gov (United States)

    Makovski, Tal; Jiang, Yuhong V.; Swallow, Khena M.

    2013-01-01

    How does responding to an object affect explicit memory for visual information? The close theoretical relationship between action and perception suggests that items that require a response should be better remembered than items that require no response. However, conclusive evidence for this claim is lacking, as semantic coherence, category size,…

  16. Long-term response of Caribbean palm forests to hurricanes

    Science.gov (United States)

    Ariel Lugo; J.L. Frangi

    2016-01-01

    We studied the response of Prestoea montana (Sierra Palm, hereafter Palm) brakes and a Palm floodplain forest to hurricanes in the Luquillo Experimental Forest in Puerto Rico. Over a span of 78 years, 3 hurricanes passed over the study sites for which we have 64 years of measurements for Palm brakes and 20 years for the Palm floodplain forest. For each stand, species...

  17. Effect of long-term fluticasone treatment on immune function in horses with heaves.

    Science.gov (United States)

    Dauvillier, J; Felippe, M J B; Lunn, D P; Lavoie-Lamoureux, A; Leclère, M; Beauchamp, G; Lavoie, J-P

    2011-01-01

    Corticosteroids currently are the most effective pharmacological treatment available to control heaves in horses. Systemically administered corticosteroids have been shown to alter immune response in horses, humans, and other species. Aerosolized administration theoretically minimizes systemic adverse effects, but the effect of inhaled corticosteroids on immune function has not been evaluated in horses. To evaluate the effects of prolonged administration of inhaled fluticasone on the immune system of heaves-affected horses. Heaves-affected horses were treated with inhaled fluticasone (n = 5) for 11 months or received environmental modifications only (n = 5). Prospective analysis. Clinical parameters and CBC, lymphocyte subpopulations and function, and circulating neutrophil gene expression were sequentially measured. Primary and anamnestic immune responses also were evaluated by measuring antigen-specific antibodies in response to vaccination with bovine viral antigen and tetanus toxoid, respectively. No clinical adverse effects were observed and no differences in immune function were detected between treated and untreated horses. The treatment of heaves-affected horses with inhaled fluticasone at therapeutic dosages for 11 months has no significant detectable effect on innate and adaptive (both humoral and cell-mediated) immune parameters studied. These results suggest that prolonged administration of fluticasone would not compromise the systemic immune response to pathogens nor vaccination in adult horses. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  18. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid beta-42 and alpha-synuclein in children and young adults.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Solt, Anna C; Henríquez-Roldán, Carlos; Torres-Jardón, Ricardo; Nuse, Bryan; Herritt, Lou; Villarreal-Calderón, Rafael; Osnaya, Norma; Stone, Ida; García, Raquel; Brooks, Diane M; González-Maciel, Angelica; Reynoso-Robles, Rafael; Delgado-Chávez, Ricardo; Reed, William

    2008-02-01

    Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Abeta42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment.

  19. HIV-1 Gag-specific exosome-targeted T cell-based vaccine stimulates effector CTL responses leading to therapeutic and long-term immunity against Gag/HLA-A2-expressing B16 melanoma in transgenic HLA-A2 mice

    Directory of Open Access Journals (Sweden)

    Rong Wang

    2014-01-01

    Full Text Available Human immunodeficiency virus type-1 (HIV-1-specific dendritic cell (DC vaccines have been applied to clinical trials that show only induction of some degree of immune responses, warranting the search of other more efficient vaccine strategies. Since HIV-1-specific CD8+ cytotoxic T lymphocytes (CTLs have been found to recognize some HIV-1 structural protein Gag conserved and cross-strain epitopes, Gag has become one of the most attractive target candidates for HIV-1 vaccine development. In this study, we generated HIV-1 Gag-specific Gag-Texo vaccine by using ConA-stimulated polyclonal CD8+ T-cells with uptake of Gag-expressing adenoviral vector AdVGag-transfected DC (DCGag-released exosomes (EXOs, and assessed its stimulation of Gag-specific CD8+ CTL responses and antitumor immunity. We demonstrate that Gag-Texo and DCGag vaccines comparably stimulate Gag-specific effector CD8+ CTL responses. Gag-Texo-stimulated CTL responses result in protective immunity against Gag-expressing BL6-10Gag melanoma in 8/8 wild-type C57BL/6 mice. In addition, we show that Gag-Texo vaccine also induces CTL responses leading to protective and long-term immunity against Gag/HLA-A2-expressing BL6-10Gag/A2 melanoma in 8/8 and 2/8 transgenic HLA-A2 mice, respectively. The average number of lung tumor colonies in mice with 30-days post-immunization is only 23, which is significantly less than that (>300 in control ConA-T-immunized HLA-A2 mice. Furthermore, Gag-Texo vaccine also induces some degree of therapeutic immunity. The average number (50 and size (0.23 mm in diameter of lung tumor colonies in Gag-Texo-immunized HLA-A2 mice bearing 6-day-established lung BL6-10Gag/A2 melanoma metastasis are significantly less than the average number (>300 and size (1.02 mm in diameter in control ConA-T-immunized HLA-A2 mice. Taken together, HIV-1 Gag-Texo vaccine capable of stimulating Gag-specific CTL responses and therapeutic immunity may be useful as a new immunotherapeutic

  20. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

    Science.gov (United States)

    Pakker, N G; Kroon, E D; Roos, M T; Otto, S A; Hall, D; Wit, F W; Hamann, D; van der Ende, M E; Claessen, F A; Kauffmann, R H; Koopmans, P P; Kroon, F P; ten Napel, C H; Sprenger, H G; Weigel, H M; Montaner, J S; Lange, J M; Reiss, P; Schellekens, P T; Miedema, F

    1999-02-04

    Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported

  1. Infection and immunity in Down syndrome: a trial of long-term low oral doses of zinc.

    Science.gov (United States)

    Lockitch, G; Puterman, M; Godolphin, W; Sheps, S; Tingle, A J; Quigley, G

    1989-05-01

    To determine whether orally administered zinc supplements could correct the abnormal humoral and cell-mediated immunity of Down syndrome, we randomly assigned 64 children with Down syndrome, aged 1 to 19 years and living at home, to receive either zinc gluconate or placebo daily for 6-month periods with crossover from one regimen to another. Control subjects were siblings and age-matched, unrelated children. Serum zinc, copper, and measures of immune system competence were tested at 3- or 6-month intervals. Parents kept daily logs of clinical symptoms such as cough and diarrhea and of physician visits. Mean serum zinc concentrations increased to about 150% of baseline during zinc supplementation, but we found no effect on serum levels of copper, immunoglobulins, or complement; on lymphocyte number or subset distribution; or on in vitro response to mitogens. Children with Down syndrome who were receiving zinc had a trend toward fewer days or episodes of cough and fever but no change in other clinical variables. Long-term, low-dose oral zinc supplementation to improve depressed immune response or to decrease infections in children with Down syndrome cannot be recommended.

  2. Tumor vaccine composed of C-class CpG oligodeoxynucleotides and irradiated tumor cells induces long-term antitumor immunity

    Directory of Open Access Journals (Sweden)

    Cerkovnik Petra

    2010-09-01

    Full Text Available Abstract Background An ideal tumor vaccine should activate both effector and memory immune response against tumor-specific antigens. Beside the CD8+ T cells that play a central role in the generation of a protective immune response and of long-term memory, dendritic cells (DCs are important for the induction, coordination and regulation of the adaptive immune response. The DCs can conduct all of the elements of the immune orchestra and are therefore a fundamental target and tool for vaccination. The present study was aimed at assessing the ability of tumor vaccine composed of C-class CpG ODNs and irradiated melanoma tumor cells B16F1 followed by two additional injections of CpG ODNs to induce the generation of a functional long-term memory response in experimental tumor model in mice (i.p. B16F1. Results It has been shown that the functional memory response in vaccinated mice persists for at least 60 days after the last vaccination. Repeated vaccination also improves the survival of experimental animals compared to single vaccination, whereas the proportion of animals totally protected from the development of aggressive i.p. B16F1 tumors after vaccination repeated three times varies between 88.9%-100.0%. Additionally, the long-term immune memory and tumor protection is maintained over a prolonged period of time of at least 8 months. Finally, it has been demonstrated that following the vaccination the tumor-specific memory cells predominantly reside in bone marrow and peritoneal tissue and are in a more active state than their splenic counterparts. Conclusions In this study we demonstrated that tumor vaccine composed of C-class CpG ODNs and irradiated tumor cells followed by two additional injections of CpG ODNs induces a long-term immunity against aggressive B16F1 tumors.

  3. Coordinated approaches to quantify long-term ecosystem dynamics in response to global change

    DEFF Research Database (Denmark)

    Liu, Y.; Melillo, J.; Niu, S.

    2011-01-01

    a coordinated approach that combines long-term, large-scale global change experiments with process studies and modeling. Long-term global change manipulative experiments, especially in high-priority ecosystems such as tropical forests and high-latitude regions, are essential to maximize information gain......Many serious ecosystem consequences of climate change will take decades or even centuries to emerge. Long-term ecological responses to global change are strongly regulated by slow processes, such as changes in species composition, carbon dynamics in soil and by long-lived plants, and accumulation...... to be the most effective strategy to gain the best information on long-term ecosystem dynamics in response to global change....

  4. DNA vaccination with all-trans retinoic acid treatment induces long-term survival and elicits specific immune responses requiring CD4+ and CD8+ T-cell activation in an acute promyelocytic leukemia mouse model

    Czech Academy of Sciences Publication Activity Database

    Furugaki, K.; Pokorná, Kateřina; le Pogam, C.; Aoki, M.; Reboul, M.; Bajzik, V.; Krief, P.; Janin, A.; Noguera, M.-E.; West, R.; Charron, D.; Chomienne, C.; Pla, M.; Moins-Teisserenc, H.; Padua, R.A.

    2010-01-01

    Roč. 115, č. 3 (2010), s. 653-656 ISSN 0006-4971 Grant - others:GA UK(CZ) 94308 Institutional research plan: CEZ:AV0Z50520514 Keywords : all-trans retinoic acid * DNA vaccination * protective immunity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.558, year: 2010

  5. Long-term tryptophan supplementation decreased the welfare and innate immune status of pikeperch juveniles

    DEFF Research Database (Denmark)

    Mandiki, Syaghalirwa N. M.; Redivo, Baptiste; Baekelandt, Sebastien

    2016-01-01

    was slowed by the long- term dietary TRP in association to an increase in FCR values. The available results indicate that long-term TRP supplementation has negative impact on the overall welfare status of pikeperch. Other analyses are ongoing and more results concerning key- brain neurotransmitters...

  6. Long-term effects of di-octyl phthalate on the expression of immune-related genes in Tegillarca granosa

    Science.gov (United States)

    Wang, Ji; Li, Ye; Dai, Juan; Su, Xiurong; Li, Chenghua; Shen, Lingling

    2016-05-01

    Di-octyl phthalate (DOP) is widely used as a plasticizer in the plastics industry. As a result, DOP is often found in marine water ecosystems where many species are exposed to it. Our objective was to evaluate the effect of long-term (14 d) DOP exposure (2.6, 7.8, or 31.2 mg/L) on the expression of immunerelated genes in Tegillarca granosa. The expression of small heat shock protein (sHSPs) and tissue inhibitor of metalloproteinase (TIMP) were highest in clams exposed to 31.2 mg/L DOP on days 7 and 14. The relative expression of Tg-ferritin, superoxide dismutase (SOD), and metallothionein (MT) increased initially then decreased as the concentration of DOP increased. The hemoglobin of T. granosa (Tg-HbI) exhibited two distinct expression patterns at two time points. Our results suggest that the immune response of T. granosa against DOP pollution varies depending on the dose. Additionally, we identified some immune-related genes that are promising candidates for biomarkers of DOP.

  7. Maize Stem Response to Long-Term Attack by Sesamia nonagrioides

    Directory of Open Access Journals (Sweden)

    Victor M. Rodriguez

    2018-04-01

    Full Text Available Plants defend themselves against herbivores by activating a plethora of genetic and biochemical mechanisms aimed at reducing plant damage and insect survival. The short-term plant response to insect attack is well understood, but less is known about the maintenance of this response over time. We performed transcriptomic and metabolomics analyses in order to identify genes and metabolites involved in the long-term response of maize to attack by the corn borer Sesamina nonagrioides. To determine the role of elicitors present in caterpillar secretions, we also evaluated the response of maize stem challenged with insect regurgitates. The integrative analysis of the omics results revealed that the long-term response in maize is characterized by repression of the primary metabolism and a strong redox response, mainly mediated by germin-like proteins to produce anti-nutritive and toxic compounds that reduce insect viability, and with the glutathione–ascorbate cycle being crucial to minimize the adverse effects of reactive oxygen species (ROS on the plant. Our results suggest that different defense mechanisms are involved in the long-term response compared to those reported during the early response. We also observed a marginal effect of the caterpillar regurgitates on the long-term defensive response.

  8. Long-term effect of postoperative irradiation on the immune functions in patients with mammary carcinoma

    International Nuclear Information System (INIS)

    Toivanen, A.; Nordman, E.

    1981-01-01

    The effect of postoperative irradiation on the immune functions of 13 patients with breast carcinoma is reported, using as parameters the peipheral blood lymphocyte count, percentages of E and EAC rosette forming cells, and lymphocyte proliferative responses to PHA, Con A and PPD. After irradiation the number of peripheral blood lymphocytes was reduced during 8 months. The percentages of E and EAC rosette forming cells were not altered during the observation time of 7 to 36 months. In the proliferative responses of lymphocytes to PHA, Con A and PPD, the postoperative irradiation caused a decrease which, regarding PHA and Con A, lasted up to 8 months and then recovered. The decrease in the proliferative responses to PPD was stronger and lasted during the whole observation time. In the mitogenic responses of patients with recurrent or disseminating disease no difference could be demonstrated as compared with the patients living recurrence-free. (Auth.)

  9. Long-term outcome following splenectomy for chronic and persistent immune thrombocytopenia (ITP) in adults and children : Splenectomy in ITP.

    Science.gov (United States)

    Ahmed, Rayaz; Devasia, Anup J; Viswabandya, Auro; Lakshmi, Kavitha M; Abraham, Aby; Karl, Sampath; Mathai, John; Jacob, Paul M; Abraham, Deepak; Srivastava, Alok; Mathews, Vikram; George, Biju

    2016-09-01

    The purpose of this research is to study the outcomes of splenectomy for chronic and persistent immune thrombocytopenia (ITP). This study is a retrospective analysis of 254 patients with chronic or persistent ITP who underwent splenectomy at CMC, Vellore, India between 1995 and 2009. Responses were assessed based on standard criteria. One hundred and sixty seven adults and 87 children with a median age of 29 years (range 2-64) with persistent (n = 103) or chronic ITP (n = 151) was studied. Response was seen in 229 (90.2 %) including CR in 74.4 % at a median time of 1 day (range 1-54). Infections following splenectomy were reported in 16 %. Deaths related to post splenectomy sepsis occurred in 1.57 % and major bleeding in 0.78 %. At median follow-up of 54.3 months (range 1-290), 178 (70.1 %) remain in remission. The 5-year and 10-year overall survival (OS) is 97.4 ± 1.2 % and 94.9 ± 2.1 %, respectively, while the 5-year and 10-year event-free survival (EFS) is 76.5 + 2.9 % and 71.0 + 3.9 %, respectively. Splenectomy is associated with long-term remission rates of >70 % in chronic or persistent ITP.

  10. Coordinated approaches to quantify long-term ecosystem dynamics in response to global change

    Science.gov (United States)

    Yiqi Luo; Jerry Melillo; Shuli Niu; Claus Beier; James S. Clark; Aime E.T. Classen; Eric Dividson; Jeffrey S. Dukes; R. Dave Evans; Christopher B. Field; Claudia I. Czimczik; Michael Keller; Bruce A. Kimball; Lara M. Kueppers; Richard J. Norby; Shannon L. Pelini; Elise Pendall; Edward Rastetter; Johan Six; Melinda Smith; Mark G. Tjoelker; Margaret S. Torn

    2011-01-01

    Many serious ecosystem consequences of climate change will take decades or even centuries to emerge. Long-term ecological responses to global change are strongly regulated by slow processes, such as changes in species composition, carbon dynamics in soil and by long-lived plants, and accumulation of nutrient capitals. Understanding and predicting these processes...

  11. Long-term response of the mamane forest to feral herbivore management on Mauna Kea, Hawaii

    Science.gov (United States)

    E. Reddy; D. H. Van Vuren; P. G. Scowcroft; J. B. Kauffman; L. Perry

    2012-01-01

    Seven exclosure sites located on Mauna Kea, Hawaii and established in the 1960s and 70s were sampled to characterize long-term response of the mamane (Sophora chrysophylla) forest to protection from feral sheep grazing, and to assess impacts of non-native plant species and recurrent sheep presence on forest recovery. The forest provides essential...

  12. Preface: long-term response of a forest watershed ecosystem, clearcutting in the Southern Appalachians

    Science.gov (United States)

    Wayne Swank; Jackson Webster

    2014-01-01

    Our North American forests are no longer the wild areas of past centuries; they are an economic and ecological resource undergoing changes from both natural and management disturbances. A watershed-scale and long-term perspective of forest ecosystem responses is requisite to understanding and predicting cause and effect relationships. This book synthesizes...

  13. Long-term Effects of Hepatitis B Immunization of Infants in Preventing Liver Cancer.

    Science.gov (United States)

    Chang, Mei-Hwei; You, San-Lin; Chen, Chien-Jen; Liu, Chun-Jen; Lai, Ming-Wei; Wu, Tzee-Chung; Wu, Shu-Fen; Lee, Chuan-Mo; Yang, Sheng-Shun; Chu, Heng-Cheng; Wang, Tsang-Eng; Chen, Bor-Wen; Chuang, Wan-Long; Soon, Maw-Soan; Lin, Ching-Yih; Chiou, Shu-Ti; Kuo, Hsu-Sung; Chen, Ding-Shinn

    2016-09-01

    The incidence of hepatocellular carcinoma (HCC) increases with age, but protective antibody responses decrease with time after infants are immunized against hepatitis B virus (HBV). We investigated whether immunization of infants against HBV prevents their developing HCC as adults. We also searched for strategies to maximize the cancer-preventive effects. We collected data from 2 Taiwan HCC registry systems on 1509 patients (6-26 years old) diagnosed with HCC from 1983 through 2011. Data on history of HBV immunization and prenatal maternal levels of HBV antigens of all HCC patients born after July 1984 were retrieved from the HBV immunization data bank of the Taiwan Center for Disease Control. We collected data on birth cohort-specific populations (6-26 years old) of Taiwan using the National Household Registry System. Rates of HCC incidence per 10(5) person-years were derived by dividing the number of patients with HCC by the person-years of the general population. Relative risks (RR) for HCC were estimated by Poisson regression analysis in vaccinated vs unvaccinated birth cohorts. We stratified patients by age group to evaluate the association of birth cohorts and HCC risks. Of the 1509 patients with HCC, 1343 were born before, and 166 were born after, the HBV vaccination program began. HCC incidence per 10(5) person-years was 0.92 in the unvaccinated cohort and 0.23 in the vaccinated birth cohorts. The RRs for HCC in patients 6-9 years old, 10-14 years old, 15-19 years old, and 20-26 years old who were vaccinated vs unvaccinated were 0.26 (95% confidence interval [CI], 0.17-0.40), 0.34 (95% CI, 0.25-0.48), 0.37 (95% CI, 0.25-0.51), and 0.42 (95% CI, 0.32-0.56), respectively. The RR for HCC in 6- to 26-year-olds was lower in the later vs the earlier cohorts (born in 1992-2005 vs 1986-1992; P Taiwan, immunization of infants against HBV reduces their risk of developing HCC as children and young adults. Improving HBV vaccination strategies and overcoming risk

  14. Responses and damages during long-term continuous irradiation in plants

    International Nuclear Information System (INIS)

    Watanabe, Yoshito

    2011-01-01

    Effects of long-term continuous irradiation are relevant to studies in radiation ecotoxicology. To investigate plants biological responses to continuous irradiation, we performed metabolome and transcriptome analysis in a model plant, arabidopsis. Comprehensive analysis of primary metabolites using capillary electrophoresis mass spectrometry revealed extensive metabolic changes at early onset of growth inhibition in plants exposed to gamma rays at the dose rate of 20 Gy/day. The changes included elevated levels of B vitamins and second metabolites, commonly responsive to many abiotic and biotic stresses. Responses at early onset of growth inhibition were also observed in the transcriptome analysis using microarray, which showed up-regulation of 55 genes in plants exposed to gamma rays at 20 Gy/day. Although about a half of the up-regulated genes were also responsive just after acute irradiation, the other half was responsive only during long-term continuous irradiation. Database analyses showed that the specifically up-regulated genes to long-term continuous irradiation included genes relating to general stress responses and protein metabolism. The results of these analyses appear to reflect plants responses to progressive radiation damages, from radiation-specific responses, which repair primary DNA damage, to more general stress responses, which maintain homoeostasis against secondary damages. (author)

  15. Characterization of the rapid transcriptional response to long-term sensitization training in Aplysia californica.

    Science.gov (United States)

    Herdegen, Samantha; Holmes, Geraldine; Cyriac, Ashly; Calin-Jageman, Irina E; Calin-Jageman, Robert J

    2014-12-01

    We used a custom-designed microarray and quantitative PCR to characterize the rapid transcriptional response to long-term sensitization training in the marine mollusk Aplysia californica. Aplysia were exposed to repeated noxious shocks to one side of the body, a procedure known to induce a long-lasting, transcription-dependent increase in reflex responsiveness that is restricted to the side of training. One hour after training, pleural ganglia from the trained and untrained sides of the body were harvested; these ganglia contain the sensory nociceptors which help mediate the expression of long-term sensitization memory. Microarray analysis from 8 biological replicates suggests that long-term sensitization training rapidly regulates at least 81 transcripts. We used qPCR to test a subset of these transcripts and found that 83% were confirmed in the same samples, and 86% of these were again confirmed in an independent sample. Thus, our new microarray design shows strong convergent and predictive validity for analyzing the transcriptional correlates of memory in Aplysia. Fully validated transcripts include some previously identified as regulated in this paradigm (ApC/EBP and ApEgr) but also include novel findings. Specifically, we show that long-term sensitization training rapidly up-regulates the expression of transcripts which may encode Aplysia homologs of a C/EBPγ transcription factor, a glycine transporter (GlyT2), and a vacuolar-protein-sorting-associated protein (VPS36). Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Immune Cells Depletion During Wound Healing as a Long-Term Effect of Undernutrition

    OpenAIRE

    Zuanassi Macari, Marcelo; Misael Cavenaghi, Fabiano; Chinali Komesu, Marilena; Orive Lunardi, Laurelúcia; Sala, Miguel Angel; Novaes Júnior, Arthur Belém; Grisi, Márcio Fernando de Moraes; Taba Júnior, Mário; Scombatti de Souza, Sérgio Luiz

    2005-01-01

    Undernutrition in early life is associated with a number of acute and chronic sequelae, and recovering is a controversial issue. Even if undernutrition in Brazil is declining, studies have shown that about 31% of brazilian children still present severe or moderate malnutrition. The present study goal was to induce early malnutrition in rats and observe short- (undernourished) and long-term (after recovered) effects on defense cells involved in wound healing. Undernutrition was produced by sep...

  17. Assessing long-term effects of demand response policies in wholesale electricity markets

    International Nuclear Information System (INIS)

    Cepeda, Mauricio; Saguan, Marcelo

    2014-05-01

    This paper deals with the practical problems related to long-term issues in electricity markets in the presence of demand response development. Different policies have been implemented around the world aiming to develop demand response potential. Externalities, in particular the CO_2 externality, have been one of the key elements in the debate on the effectiveness of different policies regarding demand response development. Policy makers have several options to deal with this externality. The most direct one is to correct the externality by setting a CO_2 price at a level that corresponds to the cost to society of the corresponding CO_2 emissions. One alternative solution could be to subsidize carbon-free technologies as demand response. In this paper we examine potential long-term impacts of these two policies. We rely on a long-term market simulation model that characterizes expansion decisions in a competitive regime. We test for each policy two different scenarios regarding the possibility of internalization of the CO_2 externality. The results show that differences in development policies affect both investments and social costs in the wholesale electricity market and confirm previous findings that a market-driven development of demand response with the internalization of the CO_2 externality is the most efficient approach. (authors)

  18. Long-Term IgG Response to Porcine Neu5Gc Antigens without Transmission of PERV in Burn Patients Treated with Porcine Skin Xenografts

    Czech Academy of Sciences Publication Activity Database

    Scobie, L.; Padler-Karavani, V.; Les Bas-Bernardet, S.; Crossan, C.; Bláha, J.; Matoušková, Magda; Hector, R.D.; Cozzi, E.; Vanhove, B.; Charreau, B.; Blancho, G.; Bourdais, L.; Tallacchini, M.; Ribes, J.; Yu, H.; Chen, X.; Kracíková, J.; Brož, L.; Hejnar, Jiří; Veselý, Pavel; Takeuchi, Y.; Varki, A.; Soulillou, J.P.

    2013-01-01

    Roč. 191, č. 6 (2013), s. 2907-2915 ISSN 0022-1767 Grant - others:EK(XE) LSHB-CT-2006-037377 Source of funding: R - rámcový projekt EK Keywords : PERV transmission * xenotransplantation * long-term immune response Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.362, year: 2013

  19. Determinants of Private Long-Term Care Insurance Purchase in Response to the Partnership Program.

    Science.gov (United States)

    Lin, Haizhen; Prince, Jeffrey T

    2016-04-01

    To assess three possible determinants of individuals' response in their private insurance purchases to the availability of the Partnership for Long-Term Care (PLTC) insurance program: bequest motives, financial literacy, and program awareness. The health and retirement study (HRS) merged with data on states' implementation of the PLTC program. Individual-level decision on private long-term care insurance is regressed on whether the PLTC program is being implemented for a given state-year, asset dummies, policy determinant variable, two-way and three-way interactions of these variables, and other controls, using fixed effects panel regression. Analysis used a sample between 50 and 69 years of age from 2002 to 2010, resulting in 12,695 unique individuals with a total of 39,151 observations. We find mild evidence that intent to bequest influences individual purchase of insurance. We also find that program awareness is necessary for response, while financial literacy notably increases responsiveness. Increasing response to the PLTC program among the middle class (the stated target group) requires increased efforts to create awareness of the program's existence and increased education about the program's benefits, and more generally, about long-term care risks and needs. © Health Research and Educational Trust.

  20. Environmental and genetic preconditioning for long-term anoxia responses requires AMPK in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Bobby L LaRue

    2011-02-01

    Full Text Available Preconditioning environments or therapeutics, to suppress the cellular damage associated with severe oxygen deprivation, is of interest to our understanding of diseases associated with oxygen deprivation. Wildtype C. elegans exposed to anoxia enter into a state of suspended animation in which energy-requiring processes reversibly arrest. C. elegans at all developmental stages survive 24-hours of anoxia exposure however, the ability of adult hermaphrodites to survive three days of anoxia significantly decreases. Mutations in the insulin-like signaling receptor (daf-2 and LIN-12/Notch (glp-1 lead to an enhanced long-term anoxia survival phenotype.In this study we show that the combined growth environment of 25°C and a diet of HT115 E. coli will precondition adult hermaphrodites to survive long-term anoxia; many of these survivors have normal movement after anoxia treatment. Animals fed the drug metformin, which induces a dietary-restriction like state in animals and activates AMPK in mammalian cell culture, have a higher survival rate when exposed to long-term anoxia. Mutations in genes encoding components of AMPK (aak-2, aakb-1, aakb-2, aakg-2 suppress the environmentally and genetically induced long-term anoxia survival phenotype. We further determine that there is a correlation between the animals that survive long-term anoxia and increased levels of carminic acid staining, which is a fluorescent dye that incorporates in with carbohydrates such as glycogen.We conclude that small changes in growth conditions such as increased temperature and food source can influence the physiology of the animal thus affecting the responses to stress such as anoxia. Furthermore, this supports the idea that metformin should be further investigated as a therapeutic tool for treatment of oxygen-deprived tissues. Finally, the capacity for an animal to survive long bouts of severe oxygen deprivation is likely dependent on specific subunits of the heterotrimeric

  1. Changes in the long-term delayed response of platinum self-powered detector with irradiation

    International Nuclear Information System (INIS)

    Parent, G.; Serdula, K.J.; Eng, P.

    1989-01-01

    Two long-term delayed response characteristics have been observed for platinum, Pt, detectors in the Gentilly-2 600 MW(e) CANDU PHWR reactor. The first effect is a dip in the signal two to three hours after a shutdown, due to the (n,beta) interactions of Mn-55 and Ni-64 which exist as impurities in the detector assembly. The second effect is an increase of the delayed fraction of the signal. The low neutron absorption cross-section of Pt-196 combined with the conversion of the Pt-194 and Pt-195 results in build-up of the Pt-196. The long half-lives associated with the beta-emission in the transmutation of Pt-196 to Hg-198 or Hg-199 give rise to the observed long-term delayed response

  2. Long-term accessibility of e-books: challenges, obstacles, responsibilities

    Directory of Open Access Journals (Sweden)

    Maja Krtalić

    2015-07-01

    Full Text Available The traditional life cycle of books has gone through many changes in the digital environment - enough to start questioning the effects of such changes on the process of creating, publishing, distributing, reading and preserving books. This paper focuses on issues concerning the preservation and archiving of published authors’ works in the digital environment for the purpose of their long-term accessibility. The aim of this paper is to give an overview of relevant legal, technical, societal and organisational issues from which challenges, obstacles and responsibilities in ensuring long-term accessibility of e-books arise. Issues related to authorship, editions, changes in content, copyright and digital rights management, selection criteria for preservation, and preservation responsibility will be discussed, specifically focusing on libraries’ and publishers’ roles in this process. The paper is based on a literature review and content analysis aiming to answer two basic research questions: What specific characteristics of e-books influence their preservation possibilities? Who is responsible for long-term accessibility of e-books?

  3. The effects of long-term endurance training on the immune and endocrine systems of elderly men: the role of cytokines and anabolic hormones

    Directory of Open Access Journals (Sweden)

    Natale Valéria

    2006-08-01

    Full Text Available Abstract Background a decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed. Results elderly runners showed a significantly higher T cell proliferative response and IL-2 production than sedentary elderly controls. IL-2 production was similar to that in young adults. Their serum IL-6 levels were significantly lower than their sedentary peers. They also showed significantly lower IL-3 production in comparison to sedentary elderly subjects but similar to the youngs. Anabolic hormone levels did not differ between elderly groups and no clear correlation was found between hormones and cytokine levels. Conclusion highly conditioned elderly men seem to have relatively better preserved immune system than the sedentary elderly men. Long-term endurance training has the potential to decelerate the age-related decline in immune function but not the deterioration in endocrine function.

  4. Long-term dataset on aquatic responses to concurrent climate change and recovery from acidification

    Science.gov (United States)

    Leach, Taylor H.; Winslow, Luke A.; Acker, Frank W.; Bloomfield, Jay A.; Boylen, Charles W.; Bukaveckas, Paul A.; Charles, Donald F.; Daniels, Robert A.; Driscoll, Charles T.; Eichler, Lawrence W.; Farrell, Jeremy L.; Funk, Clara S.; Goodrich, Christine A.; Michelena, Toby M.; Nierzwicki-Bauer, Sandra A.; Roy, Karen M.; Shaw, William H.; Sutherland, James W.; Swinton, Mark W.; Winkler, David A.; Rose, Kevin C.

    2018-04-01

    Concurrent regional and global environmental changes are affecting freshwater ecosystems. Decadal-scale data on lake ecosystems that can describe processes affected by these changes are important as multiple stressors often interact to alter the trajectory of key ecological phenomena in complex ways. Due to the practical challenges associated with long-term data collections, the majority of existing long-term data sets focus on only a small number of lakes or few response variables. Here we present physical, chemical, and biological data from 28 lakes in the Adirondack Mountains of northern New York State. These data span the period from 1994-2012 and harmonize multiple open and as-yet unpublished data sources. The dataset creation is reproducible and transparent; R code and all original files used to create the dataset are provided in an appendix. This dataset will be useful for examining ecological change in lakes undergoing multiple stressors.

  5. Long-term trihexyphenidyl exposure alters neuroimmune response and inflammation in aging rat: relevance to age and Alzheimer's disease.

    Science.gov (United States)

    Huang, Yuqi; Zhao, Zhe; Wei, Xiaoli; Zheng, Yong; Yu, Jianqiang; Zheng, Jianquan; Wang, Liyun

    2016-07-01

    Clinical studies have shown an association between long-term anticholinergic (AC) drug exposure and Alzheimer's disease (AD) pathogenesis, which has been primarily investigated in Parkinson's disease (PD). However, long-term AC exposure as a risk factor for developing neurodegenerative disorders and the exact mechanisms and potential for disease progression remain unclear. Here, we have addressed the issue using trihexyphenidyl (THP), a commonly used AC drug in PD patients, to determine if THP can accelerate AD-like neurodegenerative progression and study potential mechanisms involved. Male Sprague-Dawley rats (SD) were intraperitoneally injected with THP (0.3 and 1.0 mg/kg) or normal saline (NS) for 7 months. Alterations in cognitive and behavioral performance were assessed using the Morris water maze (MWM) and open field tests. After behavior tests, whole genome oligo microarrays, quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry, and immunofluorescence-confocal were used to investigate the global mechanisms underlying THP-induced neuropathology with aging. Compared with NS controls, the MWM test results showed that THP-treated rats exhibited significantly extended mean latencies during the initial 3 months of testing; however, this behavioral deficit was restored between the fourth and sixth month of MWM testing. The same tendencies were confirmed by MWM probe and open field tests. Gene microarray analysis identified 68 (47 %) upregulated and 176 (53 %) downregulated genes in the "THP-aging" vs. "NS-aging" group. The most significant populations of genes downregulated by THP were the immune response-, antigen processing and presentation-, and major histocompatibility complex (MHC)-related genes, as validated by qRT-PCR. The decreased expression of MHC class I in THP-treated aging brains was confirmed by confocal analysis. Notably, long-term THP treatment primed hippocampal and cortical microglia to

  6. Childhood optic chiasm gliomas: radiographic response following radiotherapy and long-term clinical outcome

    International Nuclear Information System (INIS)

    Tao, May L.; Barnes, Patrick D.; Billett, Amy L.; Leong, Traci; Shrieve, Dennis C.; Scott, R. Michael; Tarbell, Nancy J.

    1997-01-01

    Purpose: In children with chiasmal gliomas, radiation therapy can arrest progressive visual and neurologic impairment. We examined the radiographic response and clinical outcomes after irradiation. Methods and Materials: Forty-two children (median age at diagnosis, 6.6 years) with chiasmal gliomas were managed as follows: 11 asymptomatic patients with neurofibromatosis-1 (NF-1) were observed only; 2 patients, less than 3 years old, underwent surgery and chemotherapy to delay irradiation; and 29 patients with progressive disease received radiation with or without prior surgery or chemotherapy. Time to radiographic response, long-term tumor control and late sequelae were reviewed for the 29 irradiated patients. Results: The probability of at least 50% radiographic response at 24 months after irradiation was 18.1% and increased to 38.2% by 48 months and 45.9% by 60 months. By actuarial analysis, the median time for such radiographic response was 62 months. For the 29 irradiated patients, the 10-year freedom from progression and overall survival rates were 100% and 89%, respectively (median follow-up for surviving patients, 108 months). Stabilization or improvement in vision occurred in 81% of 26 evaluable irradiated patients. Conclusions: Notable radiographic response may be observed years after irradiation. Radiation therapy provides excellent long-term tumor control and vision preservation or improvement in the majority of patients with progressive chiasmal gliomas

  7. Dynamic response of land use and river nutrient concentration to long-term climatic changes.

    Science.gov (United States)

    Bussi, Gianbattista; Janes, Victoria; Whitehead, Paul G; Dadson, Simon J; Holman, Ian P

    2017-07-15

    The combined indirect and direct impacts of land use change and climate change on river water quality were assessed. A land use allocation model was used to evaluate the response of the catchment land use to long-term climatic changes. Its results were used to drive a water quality model and assess the impact of climatic alterations on freshwater nitrate and phosphorus concentrations. Climatic projections were employed to estimate the likelihood of such response. The River Thames catchment (UK) was used as a case-study. If land use is considered as static parameter, according to the model results, climate change alone should reduce the average nitrate concentration, although just by a small amount, by the 2050s in the Lower Thames, due to reduced runoff (and lower export of nitrate from agricultural soils) and increased instream denitrification, and should increase the average phosphorus concentration by 12% by the 2050s in the Lower Thames, due to a reduction of the effluent dilution capacity of the river flow. However, the results of this study also show that these long-term climatic alterations are likely to lead to a reduction in the arable land in the Thames, replaced by improved grassland, due to a decrease in agriculture profitability in the UK. Taking into account the dynamic co-evolution of land use with climate, the average nitrate concentration is expected to be decreased by around 6% by the 2050s in both the upper and the lower Thames, following the model results, and the average phosphorus concentration increased by 13% in the upper Thames and 5% in the lower Thames. On the long term (2080s), nitrate is expected to decrease by 9% and 8% (upper and lower Thames respectively) and phosphorus not to change in the upper thames and increase by 5% in the lower Thames. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Extra-auditory responses to long-term intermittent noise stimulation in humans.

    Science.gov (United States)

    Fruhstorfer, B; Hensel, H

    1980-12-01

    Respiration, heart rate, cutaneous blood flow, and electroencephalogram (EEG) reactions to long-term intermittent noise exposure were recorded from 13 volunteers (20-29 yr) with normal hearing and vegetative reactivity. They received daily within 1 h 12 noise stimuli (16 s 100 dB (A) white noise) for 10 or 21 days, respectively. Most subjects reported partial subjective adaptation to the noise. Heart rate adapted within a session but did not change considerably during successive days. Vascular responses did not change during one session but diminished mainly during the first 10 days. Noise responses in the EEG remained constant, but a decrease in vigilance occurred during the whole experimental series. Respiration responses were unpredictable and showed no trend within the sessions. It was concluded that certain physiological responses adapt to loud noise but that the time course of adaptation is different. Therefore a general statement about physiological noise adaptation is not possible.

  9. Immunization of mice with the nef gene from Human Immunodeficiency Virus type 1: Study of immunological memory and long-term toxicology

    Directory of Open Access Journals (Sweden)

    Engström Gunnel

    2007-07-01

    Full Text Available Abstract Background The human immunodeficiency virus type 1 (HIV-1 regulatory protein, Nef, is an attractive vaccine target because it is involved in viral pathogenesis, is expressed early in the viral life cycle and harbors many T and B cell epitopes. Several clinical trials include gene-based vaccines encoding this protein. However, Nef has been shown to transform certain cell types in vitro. Based on these findings we performed a long-term toxicity and immunogenicity study of Nef, encoded either by Modified Vaccinia virus Ankara or by plasmid DNA. BALB/c mice were primed twice with either DNA or MVA encoding Nef and received a homologous or heterologous boost ten months later. In the meantime, the Nef-specific immune responses were monitored and at the time of sacrifice an extensive toxicological evaluation was performed, where presence of tumors and other pathological changes were assessed. Results The toxicological evaluation showed that immunization with MVAnef is safe and does not cause cellular transformation or other toxicity in somatic organs. Both DNAnef and MVAnef immunized animals developed potent Nef-specific cellular responses that declined to undetectable levels over time, and could readily be boosted after almost one year. This is of particular interest since it shows that plasmid DNA vaccine can also be used as a potent late booster of primed immune responses. We observed qualitative differences between the T cell responses induced by the two different vectors: DNA-encoded nef induced long-lasting CD8+ T cell memory responses, whereas MVA-encoded nef induced CD4+ T cell memory responses. In terms of the humoral immune responses, we show that two injections of MVAnef induce significant anti-Nef titers, while repeated injections of DNAnef do not. A single boost with MVAnef could enhance the antibody response following DNAnef prime to the same level as that observed in animals immunized repeatedly with MVAnef. We also demonstrate

  10. Dissimilar response of plant and soil biota communities to long-term nutrient adition in grasslands

    NARCIS (Netherlands)

    Wal, van der A.; Geerts, R.H.E.M.; Korevaar, H.; Schouten, A.J.; Jagers op Akkerhuis, G.A.J.M.; Rutgers, M.; Mulder, C.

    2009-01-01

    The long-term effect of fertilizers on plant diversity and productivity is well known, but long-term effects on soil biota communities have received relatively little attention. Here, we used an exceptional long-lasting (>40 years) grassland fertilization experiment to investigate the long-term

  11. Evaluation of long-term effects of 50-Hz magnetic fields on immune functions in humans

    Energy Technology Data Exchange (ETDEWEB)

    Touitou, Y.; Auzeby, A.; Camus, F. [Faculty of Medicine Pierre et Marie Curie, 75 - Paris (France); Lambrozo, J.; Souques, M.; Verrier, A. [Gaz de France (EDF/GDF), SEM, 75 - Paris (France)

    2006-07-01

    The relationship between exposure to 50-Hz magnetic fields (E.L.F.) and human health is of increasing interest since this exposure has been implicated in many different diseases including cancers in epidemiological studies, though the results are controversial. The identification of possible mechanisms of interaction between E.L.F. and biological systems that could provide a biological plausibility to the observed effects has failed so far. In this study we investigate the possible chronic effects of exposure to E.L.F. in humans. We examine the circadian rhythm of CD{sub 3}, CD{sub 4}, CD{sub 8}, Nk cells and B cells in 15 men (38.0{+-}8.9 yrs) exposed chronically and daily for a period of 1-20 years, in the workplace and at home, to a 50-Hz magnetic field in search of any cumulative effect from those chronic conditions of exposure. The weekly geometric mean of individual exposures ranged from 0.1 to 2.6 {mu}T. The results are compared to those for 15 unexposed men similar in a (39.4 {+-}1.2 yrs), with the same synchronization and physical activity who served as controls (individual exposures ranged from 0.004 to 0.092 {mu}T). Blood samples were taken hourly from 2000 to 0800. This work shows that subjects exposed over a long period (up to 20 years) and on a daily basis to magnetic fields experienced no changes in their plasma immune variables. Our data suggest therefore that magnetic fields have no cumulative effects on immune functions, at least for the variables under study. (authors)

  12. Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus.

    Science.gov (United States)

    Wahie, S; Meggitt, S J

    2013-09-01

    The recommended first-line oral therapy for discoid lupus erythematosus (DLE) is the antimalarial hydroxychloroquine. To the best of our knowledge, there is no published information regarding the long-term (i.e. > 6 months) response of DLE to hydroxychloroquine in clinical practice. To describe the long-term clinical response of DLE to hydroxychloroquine after 6 months of use. A multicentre retrospective cohort study was conducted in patients with DLE who had received treatment with hydroxychloroquine. All patients were recruited and interviewed by a single investigator and response to hydroxychloroquine assessed by the same individual through a retrospective review of case notes using a specified protocol. A total of 200 patients with DLE were recruited (F:M = 4 : 1) with a median age at diagnosis of 40 years (range 16-81) and median follow-up of 8 years (range 0·5-37). An adequate clinical response to hydroxychloroquine was recorded in 91 patients (45·5%) but nonresponse occurred in 85 patients (42·5%). The remainder of patients either had partial response or withdrew from therapy due to toxicity or were unclassifiable. Importantly, of those individuals that did respond to hydroxychloroquine within the first 6 months of use, almost one in five eventually lost their response, despite continued administration, after a median interval of 2 years. These patients often regained disease control if treated with a combination of hydroxychloroquine and mepacrine. Of those that did not respond to hydroxychloroquine within the first 6 months of use, almost one in 10 became eventual responders either after continued administration for up to 2 years or when rechallenged on hydroxychloroquine. The remaining nonresponders relied frequently on oral corticosteroid. In this cohort of patients with DLE, long-term clinical response to hydroxychloroquine occurred in less than 50% of patients. Nonresponders to hydroxychloroquine frequently required oral steroid to achieve disease

  13. The role of stress in absenteeism: cortisol responsiveness among patients on long-term sick leave.

    Directory of Open Access Journals (Sweden)

    Henrik B Jacobsen

    Full Text Available OBJECTIVE: This study aimed to (1 See whether increased or decreased variation relate to subjective reports of common somatic and psychological symptoms for a population on long-term sick leave; and (2 See if this pattern in variation is correlated with autonomic activation and psychological appraisal. METHODS: Our participants (n = 87 were referred to a 3.5-week return-to-work rehabilitation program, and had been on paid sick leave >8 weeks due to musculoskeletal pain, fatigue and/or common mental disorders. An extensive survey was completed, addressing socio-demographics, somatic and psychological complaints. In addition, a physician and a psychologist examined the participants, determining baseline heart rate, medication use and SCID-I diagnoses. During the 3.5-week program, the participants completed the Trier Social Stress Test for Groups. Participants wore heart rate monitors and filled out Visual Analogue Scales during the TSST-G. RESULTS: Our participants presented a low cortisol variation, with mixed model analyses showing a maximal increase in free saliva cortisol of 26% (95% CI, 0.21-0.32. Simultaneously, the increase in heart rate and Visual Analogue Scales was substantial, indicating autonomic and psychological activation consistent with intense stress from the Trier Social Stress Test for Groups. CONCLUSIONS: The current findings are the first description of a blunted cortisol response in a heterogeneous group of patients on long-term sick leave. The results suggest lack of cortisol reactivity as a possible biological link involved in the pathway between stress, sustained activation and long-term sick leave.

  14. The stability of vacuum phototriodes to varying light pulse loads and long term changes in response.

    CERN Document Server

    Hobson, Peter

    2012-01-01

    Mesh anode Vacuum Phototriodes (VPTs) are radiation resistant, single gain-stage photomultipliers which are designed to operate in a strong quasi-axial magnetic field. These VPTs are used in the endcap electromagnetic calorimeter of the CMS experiment at the CERN LHC to detect scintillation light from lead tungstate crystals. Short term dynamic response changes occur because of pulse rate variations during normal LHC operation cycles. Over the longer term the effect of increasing integrated charge taken from the photocathode causes an overall degradation of response. We have investigated these effects over time periods exceeding two years of simulated operation and discuss the implications for the long term performance of the VPTs in CMS.

  15. HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses.

    Science.gov (United States)

    Pigna, Eva; Renzini, Alessandra; Greco, Emanuela; Simonazzi, Elena; Fulle, Stefania; Mancinelli, Rosa; Moresi, Viviana; Adamo, Sergio

    2018-02-24

    Denervation triggers numerous molecular responses in skeletal muscle, including the activation of catabolic pathways and oxidative stress, leading to progressive muscle atrophy. Histone deacetylase 4 (HDAC4) mediates skeletal muscle response to denervation, suggesting the use of HDAC inhibitors as a therapeutic approach to neurogenic muscle atrophy. However, the effects of HDAC4 inhibition in skeletal muscle in response to long-term denervation have not been described yet. To further study HDAC4 functions in response to denervation, we analyzed mutant mice in which HDAC4 is specifically deleted in skeletal muscle. After an initial phase of resistance to neurogenic muscle atrophy, skeletal muscle with a deletion of HDAC4 lost structural integrity after 4 weeks of denervation. Deletion of HDAC4 impaired the activation of the ubiquitin-proteasome system, delayed the autophagic response, and dampened the OS response in skeletal muscle. Inhibition of the ubiquitin-proteasome system or the autophagic response, if on the one hand, conferred resistance to neurogenic muscle atrophy; on the other hand, induced loss of muscle integrity and inflammation in mice lacking HDAC4 in skeletal muscle. Moreover, treatment with the antioxidant drug Trolox prevented loss of muscle integrity and inflammation in in mice lacking HDAC4 in skeletal muscle, despite the resistance to neurogenic muscle atrophy. These results reveal new functions of HDAC4 in mediating skeletal muscle response to denervation and lead us to propose the combined use of HDAC inhibitors and antioxidant drugs to treat neurogenic muscle atrophy.

  16. Physiological and Biochemical Responses of Saltmarsh Plant Spartina alterniflora to Long-term Wave Exposure

    Science.gov (United States)

    Zhou, W.

    2017-12-01

    In recent years, ecosystem-based flood defence, i.e., eco-shoreline or living shoreline, that is more sustainable and cost-effective than conventional coastal engineering structures has been brought into large-scale practice. Numerous laboratory experiments have been performed to explore the wave-attenuation effects of saltmarsh plants that are widely used in eco-shoreline, and yet no study has ever been conducted on the physiological and biochemical responses of saltmarsh plants to long-term wave exposure, presumably due to the constraint that traditional wave generator fails to provide long-term stable wave conditions necessary for physiological experiments. In this study, a long-term shallow water wave environment simulator using crank-yoke mechanism was built in the laboratory to address this gap. Experiments using the wave simulator were conducted for 8 weeks in a greenhouse and the temperature was maintained at 24-30°C. 5‰ artificial sea water was filled in the test tank, and the water was changed every week. After being acclimatized, nine S. alterniflora individual plants (initial height 30 cm) were planted in each of the three streamlined cuboid containers (12cm×12cm×20cm), which were partially submerged in a test tank, and undertook horizontal sinusoidal motion imposed by the crank-yoke mechanism to mimic plants exposed to shallow water waves. The substrate filled in the containers were soils collected from the Yellow River Delta, so were the S. alterniflora plants. A realistic stem density of 400 stems/m2 was tested, which corresponded to a grid spacing of 5.0 cm. Shallow water waves with six wave heights (H: 0.041, 0.055, 0.069, 0.033, 0.044 and 0.056m), one plants submerged depth (0.1m) and two wave periods (2s and 3s) were simulated in the experiments. A no wave condition was also tested as control. Key physiological and biochemical parameters, such as stem length, peroxidase activity, catalase, superoxide dismutase, ascorbate peroxidase, etc

  17. Long Term Recovery in Disaster Response and the Role of Non-Profits

    Directory of Open Access Journals (Sweden)

    Victor B Flatt

    2013-04-01

    Full Text Available The Legal Framework of Disaster Response does not deal as well with long term recovery. In particular, the role of non-profits is unexamined. This paper examines the role of non-profits in disaster recovery and argues for a legal framework acknowledging its important role. El marco legal de las respuestas ante desastres no tiene en cuenta la recuperación a largo plazo. En particular, no se analiza el papel de las organizaciones sin ánimo de lucro. Este artículo estudia el papel de las organizaciones sin ánimo de lucro en la recuperación de desastres, y se muestra a favor de establecer un marco legal que reconozca la importancia de su papel.

  18. Long term ionization response of several BiCMOS VLSIC technologies

    International Nuclear Information System (INIS)

    Pease, R.L.; Combs, W.; Clark, S.

    1992-01-01

    BiCMOS is emerging as a strong competitor to CMOS for gate arrays and memories because of its performance advantages for the same feature size. In this paper, the authors examine the long term ionization response of five BiCMOS technologies by characterizing test structures which emphasize the various failure modes of CMOS and bipolar. The primary failure modes are found to be associated with the recessed field oxide isolation; edge leakage in the n channel MOSFETs and buried layer to buried layer leakage in the bipolar. The ionization failure thresholds for worst case bias were in the range of 5-20 Krad(Si) for both failure modes in all five technologies

  19. Principles of exercise physiology: responses to acute exercise and long-term adaptations to training.

    Science.gov (United States)

    Rivera-Brown, Anita M; Frontera, Walter R

    2012-11-01

    Physical activity and fitness are associated with a lower prevalence of chronic diseases, such as heart disease, cancer, high blood pressure, and diabetes. This review discusses the body's response to an acute bout of exercise and long-term physiological adaptations to exercise training with an emphasis on endurance exercise. An overview is provided of skeletal muscle actions, muscle fiber types, and the major metabolic pathways involved in energy production. The importance of adequate fluid intake during exercise sessions to prevent impairments induced by dehydration on endurance exercise, muscular power, and strength is discussed. Physiological adaptations that result from regular exercise training such as increases in cardiorespiratory capacity and strength are mentioned. The review emphasizes the cardiovascular and metabolic adaptations that lead to improvements in maximal oxygen capacity. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  20. Differentiating Visual from Response Sequencing during Long-term Skill Learning.

    Science.gov (United States)

    Lynch, Brighid; Beukema, Patrick; Verstynen, Timothy

    2017-01-01

    The dual-system model of sequence learning posits that during early learning there is an advantage for encoding sequences in sensory frames; however, it remains unclear whether this advantage extends to long-term consolidation. Using the serial RT task, we set out to distinguish the dynamics of learning sequential orders of visual cues from learning sequential responses. On each day, most participants learned a new mapping between a set of symbolic cues and responses made with one of four fingers, after which they were exposed to trial blocks of either randomly ordered cues or deterministic ordered cues (12-item sequence). Participants were randomly assigned to one of four groups (n = 15 per group): Visual sequences (same sequence of visual cues across training days), Response sequences (same order of key presses across training days), Combined (same serial order of cues and responses on all training days), and a Control group (a novel sequence each training day). Across 5 days of training, sequence-specific measures of response speed and accuracy improved faster in the Visual group than any of the other three groups, despite no group differences in explicit awareness of the sequence. The two groups that were exposed to the same visual sequence across days showed a marginal improvement in response binding that was not found in the other groups. These results indicate that there is an advantage, in terms of rate of consolidation across multiple days of training, for learning sequences of actions in a sensory representational space, rather than as motoric representations.

  1. Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain.

    Science.gov (United States)

    Kosek, Eva; Rosen, Annelie; Carville, Serena; Choy, Ernest; Gracely, Richard H; Marcus, Hanke; Petzke, Frank; Ingvar, Martin; Jensen, Karin B

    2017-07-01

    Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and because placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. In our study we examined the placebo group (n = 37, mean age 45 years) from a 12-week, randomized, double-blind, placebo-controlled trial investigating the effects of milnacipran or placebo. Twenty-two patients were classified as placebo nonresponders and 15 as responders, according to the Patient Global Impression of Change scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (visual analog scale), FM effect (Fibromyalgia Impact Questionnaire), and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity (r = .689, P = .004), but not among nonresponders (r = -.348, P = .112). In our study we showed that FM duration influences endogenous pain regulation, because pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, because endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results. This study presents a novel perspective on placebo analgesia, because placebo responses among patients with chronic pain were analyzed. Long-term exposure to fibromyalgia pain was associated with lower placebo analgesia, and the results show the importance of taking pain duration into account when interpreting the results from placebo-controlled trials. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Impact of the raising immunizations safely and effectively (RISE) program on healthcare worker influenza immunization rates in long term care settings.

    Science.gov (United States)

    Nace, David A; Handler, Steven M; Hoffman, Erika L; Perera, Subashan

    2012-11-01

    National influenza immunization rates for healthcare workers (HCW) in long-term care (LTC) remain unacceptably low. This poses a serious public health threat to residents. Prior work has suggested high staff turnover rates as a contributing factor to low immunization rates. There is a critical need to identify and deploy successful models of HCW influenza immunization programs to LTC facilities. This report describes one potential model that has been successfully initiated in a network of LTC facilities. All facilities served by a single regional LTC pharmacy were invited to participate in a HCW influenza immunization program. This voluntary immunization program began in 2005 and continues to the present. As part of the program, the pharmacy promoted organizational change by assuming oversight and control of HCW immunization policies and processes for all facilities. Primary and secondary outcomes are the number of facilities reaching HCW influenza immunization rates of 60% and 80%. Fourteen of the 16 LTC facilities participated. Facilities were diverse and included both nursing and assisted living facilities; unionized and nonunionized facilities; and urban, suburban, and rural facilities. The pharmacy provided educational and communication materials, centralized data collection using a standardized definition for HCW immunization rates, and facility feedback. All 14 LTC facilities achieved the primary goal of 60% and nearly two thirds reached the secondary goal of 80%. Twenty percent reached the new Healthy People 2020 goal of 90%. It is possible for LTC facilities to improve HCW immunization rates using a pharmacy based, voluntary HCW influenza immunization approach. Such an approach may help attenuate the negative influence of staff turnover on HCW immunizations. Attainment of the new Health People 2020 goals still remains a challenge and may require mandatory programs. Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc

  3. The Responsive Leadership Intervention: Improving leadership and individualized care in long-term care.

    Science.gov (United States)

    Caspar, Sienna; Le, Anne; McGilton, Katherine S

    The Responsive Leadership Intervention (RLI) is a multi-faceted intervention. We evaluated the influence of the RLI on i) responsive leadership practices by team leaders; ii) health care aides' (HCAs) self-determination; iii) HCAs' perceived ability to provide individualized care. A quasi-experimental repeated measures non-equivalent control group design was used to assess participant outcomes in four long-term care facilities (two control, two intervention) across four time periods. Change from baseline to 1-month post-intervention was greater in the intervention group than control group for Individualized Care (IC) (p = 0.001), but not for Self Determination (p = 0.26). Perceived levels of responsive leadership was greater following the intervention among participants with baseline measures that were less than the median (p = 0.007), but not if greater. At 3-months post-intervention, the intervention group retained 32% of the difference from control in IC, and 49% of the difference from control in responsive leadership; at 6-months post-intervention, 35% and 28%, respectively. The RLI is a feasible method for improving responsive leadership practices and individualized care. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Modeling Long Term Corn Yield Response to Nitrogen Rate and Crop Rotation

    Directory of Open Access Journals (Sweden)

    Laila Alejandra Puntel

    2016-11-01

    Full Text Available Improved prediction of optimal N fertilizer rates for corn (Zea mays L. can reduce N losses and increase profits. We tested the ability of the Agricultural Production Systems sIMulator (APSIM to simulate corn and soybean (Glycine max L. yields, the economic optimum N rate (EONR using a 16-year field-experiment dataset from central Iowa, USA that included two crop sequences (continuous corn and soybean-corn and five N fertilizer rates (0, 67, 134, 201, and 268 kg N ha-1 applied to corn. Our objectives were to: a quantify model prediction accuracy before and after calibration, and report calibration steps; b compare crop model-based techniques in estimating optimal N rate for corn; and c utilize the calibrated model to explain factors causing year to year variability in yield and optimal N. Results indicated that the model simultaneously simulated well long-term crop yields response to N (relative root mean square error, RRMSE of 19.6% before and 12.3% after calibration, which provided strong evidence that important soil and crop processes were accounted for in the model. The prediction of EONR was more complex and had greater uncertainty than the prediction of crop yield (RRMSE of 44.5% before and 36.6% after calibration. For long-term site mean EONR predictions, both calibrated and uncalibrated versions can be used as the 16-yr mean differences in EONR’s were within the historical N rate error range (40 to 50 kg N ha-1. However, for accurate year-by-year simulation of EONR the calibrated version should be used. Model analysis revealed that higher EONR values in years with above normal spring precipitation were caused by an exponential increase in N loss (denitrification and leaching with precipitation. We concluded that long term experimental data were valuable in testing and refining APSIM predictions. The model can be used as a tool to assist N management guidelines in the US Midwest and we identified five avenues on how the model can add

  5. Dryland ecosystem responses to precipitation extremes and wildfire at a long-term rainfall manipulation experiment

    Science.gov (United States)

    Brown, R. F.; Collins, S. L.

    2017-12-01

    Climate is becoming increasingly more variable due to global environmental change, which is evidenced by fewer, but more extreme precipitation events, changes in precipitation seasonality, and longer, higher severity droughts. These changes, combined with a rising incidence of wildfire, have the potential to strongly impact net primary production (NPP) and key biogeochemical cycles, particularly in dryland ecosystems where NPP is sequentially limited by water and nutrient availability. Here we utilize a ten-year dataset from an ongoing long-term field experiment established in 2007 in which we experimentally altered monsoon rainfall variability to examine how our manipulations, along with naturally occurring events, affect NPP and associated biogeochemical cycles in a semi-arid grassland in central New Mexico, USA. Using long-term regional averages, we identified extremely wet monsoon years (242.8 mm, 2013), and extremely dry monsoon years (86.0 mm, 2011; 80.0 mm, 2015) and water years (117.0 mm, 2011). We examined how changes in precipitation variability and extreme events affected ecosystem processes and function particularly in the context of ecosystem recovery following a 2009 wildfire. Response variables included above- and below-ground plant biomass (ANPP & BNPP) and abundance, soil nitrogen availability, and soil CO2 efflux. Mean ANPP ranged from 3.6 g m-2 in 2011 to 254.5 g m-2 in 2013, while BNPP ranged from 23.5 g m-2 in 2015 to 194.2 g m-2 in 2013, demonstrating NPP in our semi-arid grassland is directly linked to extremes in both seasonal and annual precipitation. We also show increased nitrogen deposition positively affects NPP in unburned grassland, but has no significant impact on NPP post-fire except during extremely wet monsoon years. While soil respiration rates reflect lower ANPP post-fire, patterns in CO2 efflux have not been shown to change significantly in that efflux is greatest following large precipitation events preceded by longer drying

  6. Modeling Long-Term Corn Yield Response to Nitrogen Rate and Crop Rotation.

    Science.gov (United States)

    Puntel, Laila A; Sawyer, John E; Barker, Daniel W; Dietzel, Ranae; Poffenbarger, Hanna; Castellano, Michael J; Moore, Kenneth J; Thorburn, Peter; Archontoulis, Sotirios V

    2016-01-01

    Improved prediction of optimal N fertilizer rates for corn ( Zea mays L. ) can reduce N losses and increase profits. We tested the ability of the Agricultural Production Systems sIMulator (APSIM) to simulate corn and soybean ( Glycine max L. ) yields, the economic optimum N rate (EONR) using a 16-year field-experiment dataset from central Iowa, USA that included two crop sequences (continuous corn and soybean-corn) and five N fertilizer rates (0, 67, 134, 201, and 268 kg N ha -1 ) applied to corn. Our objectives were to: (a) quantify model prediction accuracy before and after calibration, and report calibration steps; (b) compare crop model-based techniques in estimating optimal N rate for corn; and (c) utilize the calibrated model to explain factors causing year to year variability in yield and optimal N. Results indicated that the model simulated well long-term crop yields response to N (relative root mean square error, RRMSE of 19.6% before and 12.3% after calibration), which provided strong evidence that important soil and crop processes were accounted for in the model. The prediction of EONR was more complex and had greater uncertainty than the prediction of crop yield (RRMSE of 44.5% before and 36.6% after calibration). For long-term site mean EONR predictions, both calibrated and uncalibrated versions can be used as the 16-year mean differences in EONR's were within the historical N rate error range (40-50 kg N ha -1 ). However, for accurate year-by-year simulation of EONR the calibrated version should be used. Model analysis revealed that higher EONR values in years with above normal spring precipitation were caused by an exponential increase in N loss (denitrification and leaching) with precipitation. We concluded that long-term experimental data were valuable in testing and refining APSIM predictions. The model can be used as a tool to assist N management guidelines in the US Midwest and we identified five avenues on how the model can add value toward

  7. Pathologic complete response predicts long-term survival following preoperative radiation therapy for rectal cancer

    International Nuclear Information System (INIS)

    Ahmad, Neelofur R.; Nagle, Deborah A.; Topham, Allan

    1997-01-01

    Purpose: The finding of a pathologic complete response (pCR) after preoperative radiation therapy (RT) for rectal cancer is frequently used as a surrogate endpoint for treatment outcome. In most reported series, the pCR rate ranges from 10 to 25%. An underlying assumption is that pCR relates to favorable long-term patient outcome; however, such results are rarely reported. The purpose of this study was to determine the long-term outcome of patients having pCR's following preoperative RT and surgery for rectal cancer. Materials and Methods: Between 1978 and 1993, 49 of 315 patients (16%) were found to have pCR's following 40 to 65 Gy of preoperative RT for rectal cancer (median RT dose 55.8 Gy). Six complete responders also received concurrent 5-FU chemotherapy with RT. Follow-up time ranged from 7 to 224 months (median 52 months). Actuarial overall survival (OS), disease-free survival (DFS), and local control (LC) rates were calculated. Patient outcome was analyzed with respect to pretreatment clinical stage (mobile vs. tethered/fixed on digital exam), tumor level in the rectum as measured from the anorectal ring (0-3 cm vs. >3 cm), type of surgery (local excision, APR, or other), and use of concurrent chemotherapy vs. RT alone. Results: Prior to treatment, clinical stage tumor stage was 43% mobile ((21(49))) and 35% tethered/fixed ((17(49))). Twenty-two percent ((11(49))) did not have palpable tumor at presentation to our institution due to prior local excision of an invasive cancer. Tumor level in the rectum was 74% 0-3 cm, 16% >3 to 6 cm, and 10% > 6 cm. Surgical procedures were 12% APR, 24% LAR, 6% combined abdominal transsacral resection (CATS), 27% coloanal anastamosis, and 31% full thickness local excision. Overall, 2 of 49 patients (4%) developed a local tumor recurrence, and 4 of 49 (8%) developed distant metastases. The overall 5- and 10-year actuarial survival rates were 91% and 86%, respectively. The 5- and 10-year actuarial DFS rate was 85%, and the

  8. Comment and response document for the long-term surveillance plan for the Falls City disposal site, Falls City, Texas

    International Nuclear Information System (INIS)

    1996-11-01

    This is the Comment and Response Document dated November 1996 for the Long-Term Surveillance Plan for the Falls City Disposal Site in Falls City, Texas. The site is part of the U.S. DOE's Uranium Mill Tailings Remedial Action Project (UMTRA). Several comments regarding the hydrology and surface erosion described in the Long-Term Surveillance Plan are addressed in this document

  9. Solar Cycle Response and Long-Term Trends in the Mesospheric Metal Layers

    Science.gov (United States)

    Dawkins, E. C. M.; Plane, J. M. C.; Chipperfield, M.; Feng, W.; Marsh, D. R.; Hoffner, J.; Janches, D.

    2016-01-01

    The meteoric metal layers (Na, Fe, and K) which form as a result of the ablation of incoming meteors act as unique tracers for chemical and dynamical processes that occur within the upper mesosphere lower thermosphere region. In this work, we examine whether these metal layers are sensitive Fe indicators of decadal long-term changes within the upper atmosphere. Output from a whole-atmosphere climate model is used to assess the response of the Na, K, and Fe layers across a 50 year period (1955-2005). At short timescales, the K layer has previously been shown to exhibit a very different seasonal behavior compared to the other metals. Here we show that this unusual behavior is also exhibited at longer time scales (both the 11 year solar cycle and 50 year periods), where K displays a much more pronounced response to atmospheric temperature changes than either Na or Fe. The contrasting solar cycle behavior of the K and Na layers predicted by the model is confirmed using satellite and lidar observations for the period 2004-2013.

  10. Arctic plants are capable of sustained responses to long-term warming

    Directory of Open Access Journals (Sweden)

    Robert T. Barrett

    2016-05-01

    Full Text Available Previous studies have shown that Arctic plants typically respond to warming with increased growth and reproductive effort and accelerated phenology, and that the magnitude of these responses is likely to change over time. We investigated the effects of long-term experimental warming on plant growth (leaf length and reproduction (inflorescence height, reproductive phenology and reproductive effort using 17–19 years of measurements collected as part of the International Tundra Experiment (ITEX at sites near Barrow and Atqasuk, Alaska. During the study period, linear regressions indicated non-significant tendencies towards warming air temperatures at our study sites. Results of our meta-analyses on the effect size of experimental warming (calculated as Hedges’ d indicated species generally responded to warming by increasing inflorescence height, increasing leaf length and flowering earlier, while reproductive effort did not respond consistently. Using weighted least-squares regressions on effect sizes, we found a significant trend towards dampened response to experimental warming over time for reproductive phenology. This tendency was consistent, though non-significant, across all traits. A separate analysis revealed significant trends towards reduced responses to experimental warming during warmer summers for all traits. We therefore propose that tendencies towards dampened plant responses to experimental warming over time are the result of regional warming. These results show that Arctic plants are capable of sustained responses to warming over long periods of time but also suggest that, as the region continues to warm, factors such as nutrient availability, competition and herbivory will become more limiting to plant growth and reproduction than temperature.

  11. Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

    Full Text Available In response to hypoxia and other stress, the sympathetic (adrenergic nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1 - adrenergic receptor (AR subtypes (α1A-, α1B-, and α1D-AR. Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH, contractility of middle cerebral arteries (MCA is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m and those exposed to LTH (110 days at 3801 m. Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05 in the maximum tension achieved by 10-5 M phenylephrine (PHE. LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05 inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05 α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

  12. Long-term responses of the endemic reef-builder Cladocora caespitosa to Mediterranean warming.

    Directory of Open Access Journals (Sweden)

    Diego K Kersting

    Full Text Available Recurrent climate-induced mass-mortalities have been recorded in the Mediterranean Sea over the past 15 years. Cladocora caespitosa, the sole zooxanthellate scleractinian reef-builder in the Mediterranean, is among the organisms affected by these episodes. Extensive bioconstructions of this endemic coral are very rare at the present time and are threatened by several stressors. In this study, we assessed the long-term response of this temperate coral to warming sea-water in the Columbretes Islands (NW Mediterranean and described, for the first time, the relationship between recurrent mortality events and local sea surface temperature (SST regimes in the Mediterranean Sea. A water temperature series spanning more than 20 years showed a summer warming trend of 0.06°C per year and an increased frequency of positive thermal anomalies. Mortality resulted from tissue necrosis without massive zooxanthellae loss and during the 11-year study, necrosis was recorded during nine summers separated into two mortality periods (2003-2006 and 2008-2012. The highest necrosis rates were registered during the first mortality period, after the exceptionally hot summer of 2003. Although necrosis and temperature were significantly associated, the variability in necrosis rates during summers with similar thermal anomalies pointed to other acting factors. In this sense, our results showed that these differences were more closely related to the interannual temperature context and delayed thermal stress after extreme summers, rather than to acclimatisation and adaption processes.

  13. Long-term periodontal response to orthodontic treatment of palatally impacted maxillary canines.

    Science.gov (United States)

    Caprioglio, Alberto; Vanni, Arianna; Bolamperti, Laura

    2013-06-01

    One of the most important aspects to take into consideration when evaluating the outcome of treatment of impacted maxillary canines is the final periodontal status. The aim of the present study was to evaluate the long-term periodontal response of palatally impacted maxillary canines aligned using a codified procedure and the 'Easy Cuspid' compared with contralateral spontaneously erupted teeth. The periodontal conditions of the adjacent teeth were also considered. From an initial sample of 124 patients, 33 patients (24 females and 9 males) were selected. All patients who had undergone surgical orthodontic treatment conducted in accordance with a standardized protocol were recalled for follow-up at an average of 4.6 years after the end of treatment. The average treatment time was 29 months and the mean eruption time of the previously impacted tooth was 3.1 months. The average probing depth values showed no significant clinical differences. Probing depths recorded at the vestibular surface of the lateral incisor (P alignment of palatally impacted canines without damage to the periodontium.

  14. An experimental protocol for the establishment of dogs with long-term cellular immune reactions to Leishmania antigens

    Directory of Open Access Journals (Sweden)

    Márcia Cristina Aquino Teixeira

    2011-03-01

    Full Text Available Domestic dogs are considered to be the main reservoirs of zoonotic visceral leishmaniasis. In this work, we evaluated a protocol to induce Leishmania infantum/Leishmania chagasi-specific cellular and humoral immune responses in dogs, which consisted of two injections of Leishmania promastigote lysate followed by a subcutaneous inoculation of viable promastigotes. The primary objective was to establish a canine experimental model to provide positive controls for testing immune responses to Leishmania in laboratory conditions. After inoculation of viable promastigotes, specific proliferative responses of peripheral blood mononuclear cells (PBMCs to either Leishmania lysate or recombinant proteins, the in vitro production of interferon-γ by antigen-stimulated PBMCs and a significant increase in circulating levels of anti-Leishmania antibodies were observed. The immunized dogs also displayed positive delayed-type hypersensitivity reactions to Leishmania crude antigens and to purified recombinant proteins. An important finding that supports the suitability of the dogs as positive controls is that they remained healthy for the entire observation period, i.e., more than seven years after infection. Following the Leishmania antigen lysate injections, the infection of dogs by the subcutaneous route appears to induce a sustained cellular immune response, leading to an asymptomatic infection. This provides a useful model for both the selection of immunogenic Leishmania antigens and for immunobiological studies on their possible immunoprotective activities.

  15. Long-term evaluation of mucosal and systemic immunity and protection conferred by different polio booster vaccines.

    Science.gov (United States)

    Xiao, Yuhong; Daniell, Henry

    2017-09-25

    Oral polio vaccine (OPV) and Inactivated Polio Vaccine (IPV) have distinct advantages and limitations. IPV does not provide mucosal immunity and introduction of IPV to mitigate consequences of circulating vaccine-derived polio virus from OPV has very limited effect on transmission and OPV campaigns are essential for interrupting wild polio virus transmission, even in developed countries with a high coverage of IPV and protected sewer systems. The problem is magnified in many countries with limited resources. Requirement of refrigeration for storage and transportation for both IPV and OPV is also a major challenge in developing countries. Therefore, we present here long-term studies on comparison of a plant-based booster vaccine, which is free of virus and cold chain with IPV boosters and provide data on mucosal and systemic immunity and protection conferred by neutralizing antibodies. Mice were primed subcutaneously with IPV and boosted orally with lyophilized plant cells containing 1μg or 25μg polio viral protein 1 (VP1), once a month for three months or a single booster one year after the first prime. Our results show that VP1-IgG1 titers in single or double dose IPV dropped to background levels after one year of immunization. This decrease correlated with >50% reduction in seropositivity in double dose and <10% seropositivity in single dose IPV against serotype 1. Single dose IPV offered no or minimal protection against serotype 1 and 2 but conferred protection against serotype 3. VP1-IgA titers were negligible in IPV single or double dose vaccinated mice. VP1 antigen with two plant-derived adjuvants induced significantly high level and long lasting VP1-IgG1, IgA and neutralizing antibody titers (average 4.3-6.8 log2 titers). Plant boosters with VP1 and plant derived adjuvants maintained the same level titers from 29 to 400days and conferred the same level of protection against all three serotypes throughout the duration of this study. Even during period, when

  16. No long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine.

    Science.gov (United States)

    Licciardi, Paul V; Toh, Zheng Quan; Clutterbuck, Elizabeth A; Balloch, Anne; Marimla, Rachel A; Tikkanen, Leena; Lamb, Karen E; Bright, Kathryn J; Rabuatoka, Uraia; Tikoduadua, Lisi; Boelsen, Laura K; Dunne, Eileen M; Satzke, Catherine; Cheung, Yin Bun; Pollard, Andrew J; Russell, Fiona M; Mulholland, Edward K

    2016-06-01

    A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage. Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Collagen Type III and VI Turnover in Response to Long-Term Immobilization.

    Directory of Open Access Journals (Sweden)

    Shu Sun

    Full Text Available Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated with immobilization and/or remobilization.In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week's strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage.Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected at all. We found that Pro-C3 and C6M levels are related to LBM at baseline and that high levels of Pro-C6 are associated with smaller changes in muscle mass during both immobilization and remobilization.The Pro-C3 and-C6 biomarkers change likely reflect remodeling changes in response to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading.

  18. Thermo-hydro-mechanical coupling in long-term sedimentary rock response

    Science.gov (United States)

    Makhnenko, R. Y.; Podladchikov, Y.

    2017-12-01

    Storage of nuclear waste or CO2 affects the state of stress and pore pressure in the subsurface and may induce large thermal gradients in the rock formations. In general, the associated coupled thermo-hydro-mechanical effect on long-term rock deformation and fluid flow have to be studied. Principles behind mathematical models for poroviscoelastic response are reviewed, and poroviscous model parameter, the bulk viscosity, is included in the constitutive equations. Time-dependent response (creep) of fluid-filled sedimentary rocks is experimentally quantified at isotropic stress states. Three poroelastic parameters are measured by drained, undrained, and unjacketed geomechanical tests for quartz-rich Berea sandstone, calcite-rich Apulian limestone, and clay-rich Jurassic shale. The bulk viscosity is calculated from the measurements of pore pressure growth under undrained conditions, which requires time scales 104 s. The bulk viscosity is reported to be on the order of 1015 Pa•s for the sandstone, limestone, and shale. It is found to be decreasing with the increase of pore pressure despite corresponding decrease in the effective stress. Additionally, increase of temperature (from 24 ºC to 40 ºC) enhances creep, where the most pronounced effect is reported for the shale with bulk viscosity decrease by a factor of 3. Viscous compaction of fluid-filled porous media allows a generation of a special type of fluid flow instability that leads to formation of high-porosity, high-permeability domains that are able to self-propagate upwards due to interplay between buoyancy and viscous resistance of the deforming porous matrix. This instability is known as "porosity wave" and its formation is possible under conditions applicable to deep CO2 storage in reservoirs and explains creation of high-porosity channels and chimneys. The reported experiments show that the formation of high-permeability pathways is most likely to occur in low-permeable clay-rich materials (caprock

  19. Determining a functional responsibility allocation between public and private parties in a long-term maintenance contract for waterworks

    NARCIS (Netherlands)

    Brommet, O.D.; Schoenmaker, R.; Hertogh, M.J.C.M.; Kleijn van Willigen, G.R.; Chen, Y.; Bakker, Jaap; Frangopol, Dan M.; van Breugel, Klaas

    2017-01-01

    A proper allocation of risks and responsibilities is vital for the success of long-term maintenance contracts. This paper focuses on a method to identify an adequate allocation of responsibilities for the maintenance of waterworks. The Dutch agency recently started outsourcing the maintenance of

  20. Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab.

    Science.gov (United States)

    McDermott, David F; Drake, Charles G; Sznol, Mario; Choueiri, Toni K; Powderly, John D; Smith, David C; Brahmer, Julie R; Carvajal, Richard D; Hammers, Hans J; Puzanov, Igor; Hodi, F Stephen; Kluger, Harriet M; Topalian, Suzanne L; Pardoll, Drew M; Wigginton, Jon M; Kollia, Georgia D; Gupta, Ashok; McDonald, Dan; Sankar, Vindira; Sosman, Jeffrey A; Atkins, Michael B

    2015-06-20

    Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC. © 2015 by American Society of Clinical Oncology.

  1. Emergency Response and Long Term Planning: Two sides of the Coin for Managing Water Resources

    Science.gov (United States)

    Metchis, K.; Beller-Simms, N.

    2014-12-01

    As projected by the US National Climate Assessment and the IPCC, extreme climate and weather events are occurring more frequently and with more intensity across the nation. Communities - and the water resource managers that serve them - are facing difficult choices to increase emergency preparedness, recover from costly impacts, and increase long term resilience. The presentation is based on a recent set of case studies about what happened in six communities that experienced one or more extreme events, focusing on water resource management. Two of the case studies will be presented, revealing that building climate resilience is not just about long term planning - it is also about taking the steps to be prepared for - and to be able to recover from - emergency events. The results of this study have implications for educating local officials on ways to think about resilience to balance both long-term and short-term preparedness.

  2. Seagrass ecosystem response to long-term high CO2 in a Mediterranean volcanic vent.

    Science.gov (United States)

    Apostolaki, Eugenia T; Vizzini, Salvatrice; Hendriks, Iris E; Olsen, Ylva S

    2014-08-01

    We examined the long-term effect of naturally acidified water on a Cymodocea nodosa meadow growing at a shallow volcanic CO2 vent in Vulcano Island (Italy). Seagrass and adjacent unvegetated habitats growing at a low pH station (pH = 7.65 ± 0.02) were compared with corresponding habitats at a control station (pH = 8.01 ± 0.01). Density and biomass showed a clear decreasing trend at the low pH station and the below- to above-ground biomass ratio was more than 10 times lower compared to the control. C content and δ(13)C of leaves and epiphytes were significantly lower at the low pH station. Photosynthetic activity of C. nodosa was stimulated by low pH as seen by the significant increase in Chla content of leaves, maximum electron transport rate and compensation irradiance. Seagrass community metabolism was intense at the low pH station, with significantly higher net community production, respiration and gross primary production than the control community, whereas metabolism of the unvegetated community did not differ between stations. Productivity was promoted by the low pH, but this was not translated into biomass, probably due to nutrient limitation, grazing or poor environmental conditions. The results indicate that seagrass response in naturally acidified conditions is dependable upon species and geochemical characteristics of the site and highlight the need for a better understanding of complex interactions in these environments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Threshold responses of songbirds to long-term timber management on an active industrial forest

    Science.gov (United States)

    Becker, Douglas A.; Wood, Petra Bohall; Keyser, Patrick D.; Wigley, T. Bently; Dellinger, Rachel; Weakland, Cathy A.

    2011-01-01

    Forest managers often seek to balance economic benefits from timber harvesting with maintenance of habitat for wildlife, ecosystem function, and human uses. Most research on the relationship between avian abundance and active timber management has been short-term, lasting one to two years, creating the need to investigate long-term avian responses and to identify harvest thresholds when a small change in habitat results in a disproportionate response in relative abundance and nest success. Our objectives were to identify trends in relative abundance and nest success and to identify landscape-scale disturbance thresholds for avian species and habitat guilds in response to a variety of harvest treatments (clear-cuts, heavy and light partial harvests) over 14 years. We conducted point counts and monitored nests at an industrial forest in the central Appalachians of West Virginia during 1996–1998, 2001–2003, and 2007–2009. Early successional species increased in relative abundance across all three time periods, whereas interior-edge and forest-interior guilds peaked in relative abundance mid-study after which the forest-interior guild declined. Of 41 species with >10 detections, four (10%) declined significantly, 13 (32%) increased significantly (only three species among all periods), and 9 (22%) peaked in abundance mid-study (over the entire study period, four species had no significant change in abundance, four declined, and one increased). Based on piecewise linear models, forest-interior and interior-edge guilds’ relative abundance harvest thresholds were 28% total harvests (all harvests combined), 10% clear-cut harvests, and 18% light partial harvests, after which abundances declined. Harvest thresholds for the early successional guild were 42% total harvests, 11% clear-cut harvest, and 10% light partial harvests, and relative abundances increased after surpassing thresholds albeit at a reduced rate of increase after the clear-cut threshold. Threshold

  4. Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant

    DEFF Research Database (Denmark)

    Aberer, Werner; Maurer, Marcus; Bouillet, Laurence

    2017-01-01

    BACKGROUND: Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long-term prop...

  5. Response to Intervention as a Predictor of Long-Term Reading Outcomes in Children with Dyslexia.

    Science.gov (United States)

    van der Kleij, Sanne W; Segers, Eliane; Groen, Margriet A; Verhoeven, Ludo

    2017-08-01

    The goal of this study was to investigate how growth during a phonics-based intervention, as well as reading levels at baseline testing, predicted long-term reading outcomes of children with dyslexia. Eighty Dutch children with dyslexia who had completed a 50-week phonics-based intervention in grade 4 were tested in grade 5 on both word and pseudoword (following regular Dutch orthographic patterns) reading efficiency and compared to 93 typical readers. In grade 5 the children with dyslexia were still significantly slower in word and pseudoword reading than their typically developing peers. Results showed that long-term pseudoword reading in the group with dyslexia was predicted by pseudoword reading at pretest and growth in pseudoword reading during the intervention, which was itself predicted by pseudoword reading at pretest. This was not the case for word reading. We found that long-term word reading was directly predicted from pretest word reading, and indirectly via pretest pseudoword reading, via growth in pseudoword and word reading. It can be concluded that pseudoword reading is not only a good indicator of severity of reading difficulties in children with dyslexia, it is also an indicator of who will profit from intervention in the long-term. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Response to intervention as a predictor of long-term reading outcomes in children with dyslexia

    NARCIS (Netherlands)

    Kleij, S.W. van der; Segers, P.C.J.; Groen, M.A.; Verhoeven, L.T.W.

    2017-01-01

    The goal of this study was to investigate how growth during a phonics-based intervention, as well as reading levels at baseline testing, predicted long-term reading outcomes of children with dyslexia. Eighty Dutch children with dyslexia who had completed a 50-week phonics-based intervention in grade

  7. Responses of the African catfish Clarias gariepinus to long-term ...

    African Journals Online (AJOL)

    ... environment by pesticides results in a decrease in fish productivity and may elevate concentrations of undesirable chemicals in edible fish tissues. The effects of long-term exposure of Clarias gariepinus juveniles to sublethal concentrations of glyphosate and paraquat, two commonly used herbicides, for eight weeks were ...

  8. Long-term leaf production response to elevated atmospheric carbon dioxide and tropospheric ozone

    Science.gov (United States)

    Alan F. Talhelm; Kurt S. Pregitzer; Christian P. Giardina

    2011-01-01

    Elevated concentrations of atmospheric CO2 and tropospheric O3 will profoundly influence future forest productivity, but our understanding of these influences over the long-term is poor. Leaves are key indicators of productivity and we measured the mass, area, and nitrogen concentration of leaves collected in litter traps...

  9. Emergency planning and long-term care: least paid, least powerful, most responsible.

    Science.gov (United States)

    Covan, Eleanor Krassen; Fugate-Whitlock, Elizabeth

    2010-11-01

    As disasters can occur anywhere, planning to avoid emergencies is an international concern. Our research specifically addresses planning for the needs and safety of a vulnerable population, long-term care residents. Our initial purposes in this evaluation research were to assess the utility of a template to gather emergency management information for individual long-term care communities, to report on how prepared they are to cope with emergencies that have occurred elsewhere in areas like ours, and to assess the effectiveness of employing gerontology students in the planning process. As we began analyzing our data, we realized that it is imperative to consider whether it is possible for long-term care communities to respond effectively to disasters. In our findings we focus on the impact of gender in the planning process, the importance of size with regard to template utility, the positive and negative consequences of student aid, and the fact that gathering plans for individual long-term care communities may have detracted from collaborative community planning.

  10. Adaptation to social isolation - Acute and long-term stress responses of growing gilts with different coping characteristics

    NARCIS (Netherlands)

    Ruis, MAW; te Brake, JHA; Engel, B; Buist, WG; Blokhuis, HJ; Koolhaas, JM

    The present experiment studied the acute and long-term stress responses of reactive and proactive prepubertal gilts to social isolation. Gilts with either reactive or proactive features were identified according to behavioral resistance in a backtest at a young age (2-4 days), respectively being low

  11. Quality of life and stress response symptoms in long-term and recent spouses of testicular cancer survivors

    NARCIS (Netherlands)

    Tuinman, MA; Fleer, J; Hoekstra, HJ; Sleijfer, DT; Hoekstra-Weebers, JEHM

    The aim of this study was to gain insight into the quality of life (QoL) and stress response of female spouses of men cured of testicular cancer in the long-term. Time since treatment completion varied from 0.5 to 23.8 years. Two hundred and fifty nine testicular cancer survivors and their spouses

  12. Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome

    Directory of Open Access Journals (Sweden)

    Valderrama Elsa

    2007-08-01

    had Chronic Kidney Disease Stage 3, all of whom were also hypertensive. Conclusion IMN is a rare but serious glomerulopathy in pediatrics. We estimate that it accounts for approximately 3% of renal biopsies. Long-term prognosis is guarded because approximately 50% of patients may have evidence of progressive kidney disease.

  13. Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors.

    Science.gov (United States)

    González, Nuria; McKee, Krisha; Lynch, Rebecca M; Georgiev, Ivelin S; Jimenez, Laura; Grau, Eulalia; Yuste, Eloísa; Kwong, Peter D; Mascola, John R; Alcamí, José

    2018-01-01

    Only a small fraction of HIV-1-infected patients develop broadly neutralizing antibodies (bNAbs), a process generally associated to chronic antigen stimulation. It has been described that rare aviremic HIV-1-infected patients can generate bNAbs but this issue remains controversial. To address this matter we have assessed bNAb responses in a large cohort of long-term non-progressors (LTNPs) with low or undetectable viremia. Samples from the LTNP cohort of the Spanish AIDS Research Network (87 elite and 42 viremic controllers) and a control population of 176 viremic typical-progressors (TPs) were screened for bNAbs using Env-recombinant viruses. bNAb specificities were studied by ELISA using mutated gp120, neutralization assays with mutated viruses, and peptide competition. Epitope specificities were also elucidated from the serum pattern of neutralization against a panel of diverse HIV-1 isolates. Broadly neutralizing sera were found among 9.3% LTNPs, both elite (7%) and viremic controllers (14%). Within the broadly neutralizing sera, CD4 binding site antibodies were detected by ELISA in 4/12 LTNPs (33%), and 16/33 of TPs (48%). Anti-MPER antibodies were detected in 6/12 LTNPs (50%) and 14/33 TPs (42%) whereas glycan-dependent HIV-1 bNAbs were more frequent in LTNPs (11/12, 92%) as compared to TPs (12/33, 36%). A good concordance between standard serum mapping and neutralization-based mapping was observed. LTNPs, both viremic and elite controllers, showed broad humoral immune responses against HIV-1, including activity against many major epitopes involved in bNAbs-mediated protection.

  14. Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence

    Directory of Open Access Journals (Sweden)

    Lauren eChaby

    2013-07-01

    Full Text Available Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid stress hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g. isolation, crowding, cage tilt were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias (F1,12 = 5.000, P < 0.05, altered coping response (T1,14 = 2.216, P = 0.04, and accelerated decision making (T1,14 = 3.245, P = 0.01. Exposure to chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object (T1,14 = 2.240, P = 0.04; T1,14 = 2.419, P = 0.03, respectively. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions. Stress during adolescence also induced short-term changes in the way animals moved around a novel environment.

  15. Short- and long-term behavioural, physiological and stoichiometric responses to predation risk indicate chronic stress and compensatory mechanisms.

    Science.gov (United States)

    Van Dievel, Marie; Janssens, Lizanne; Stoks, Robby

    2016-06-01

    Prey organisms are expected to use different short- and long-term responses to predation risk to avoid excessive costs. Contrasting both types of responses is important to identify chronic stress responses and possible compensatory mechanisms in order to better understand the full impact of predators on prey life history and population dynamics. Using larvae of the damselfly Enallagma cyathigerum, we contrasted the effects of short- and long-term predation risk, with special focus on consequences for body stoichiometry. Under short-term predation risk, larvae reduced growth rate, which was associated with a reduced food intake, increased metabolic rate and reduced glucose content. Under long-term predation risk, larvae showed chronic predator stress as indicated by persistent increases in metabolic rate and reduced food intake. Despite this, larvae were able to compensate for the short-term growth reduction under long-term predation risk by relying on physiological compensatory mechanisms, including reduced energy storage. Only under long-term predation risk did we observe an increase in body C:N ratio, as predicted under the general stress paradigm (GSP). Although this was caused by a predator-induced decrease in N content, there was no associated increase in C content. These stoichiometric changes could not be explained by GSP responses because, under chronic predation risk, there was no decrease in N-rich proteins or increase in C-rich fat and sugars; instead glycogen decreased. Our results highlight the importance of compensatory mechanisms and the value of explicitly integrating physiological mechanisms to obtain insights into the temporal dynamics of non-consumptive effects, including effects on body stoichiometry.

  16. Anticancer immune reactivity and long-term survival after treatment of metastatic ovarian cancer with dendritic cells

    Science.gov (United States)

    BERNAL, SAMUEL D.; ONA, ENRIQUE T.; RIEGO-JAVIER, AILEEN; DE VILLA, ROMULO; CRISTAL-LUNA, GLORIA R.; LAGUATAN, JOSEPHINE B.; BATAC, EUNICE R.; CANLAS, OSCAR Q.

    2012-01-01

    Hematopoietic stem cells collected by leukapheresis of a patient with metastatic ovarian carcinoma (OVCA) were induced into dendritic cell (DC) differentiation and fused with liposomal constructs of autologous and allogeneic ovarian carcinoma antigens (DC-OVCA). The proliferation of autologous T cells induced by DCs was determined by [3H]-thymidine uptake. Maximal T-cell proliferation was observed in co-cultures of DCs fused with liposomal OVCA constructs compared with intact autologous OVCA cells. The combination of autologous and allogeneic liposomal OVCA constructs induced greater T-cell proliferation than either alone. The cytotoxicity of DC-activated T cells against various target cells were analyzed by a 51Cr-release assay. The combination of autologous and allogeneic liposomal OVCA constructs showed the highest stimulation of T cell-mediated cytotoxicity against OVCA cells, but had minimal cytotoxicity against normal fibroblasts or leukemia cells. The liposomal preparations of DC-OVCA were injected monthly into a patient with metastatic ovarian carcinoma whose tumors progressed following multiple courses of chemotherapy. DCs analyzed from the patient post-immunization showed 2- to 3-fold greater OVCA cytotoxicity compared to pre-immunization DCs. Immunoblots using the patient's serum showed reactivity with a number of proteins from ovarian cancer extracts, but not in normal fibroblasts and breast cancer. Following the DC-OVCA treatment, the metastatic lesions progressively decreased in size to the point of being undetectable by serial CAT scans. Seven years following the initial diagnosis, the patient continues to be free of cancer. This report described the anticancer immune reactivity and anti-tumor response induced by DCs sensitized with liposomal constructs of OVCA antigens. Immune cell therapy may therefore be a useful adjunct to surgery and chemotherapy for the treatment of ovarian cancer. PMID:22740858

  17. Brief, pre-retrieval stress differentially influences long-term memory depending on sex and corticosteroid response.

    Science.gov (United States)

    Zoladz, Phillip R; Kalchik, Andrea E; Hoffman, Mackenzie M; Aufdenkampe, Rachael L; Burke, Hanna M; Woelke, Sarah A; Pisansky, Julia M; Talbot, Jeffery N

    2014-03-01

    Previous work has indicated that stress generally impairs memory retrieval. However, little research has addressed discrepancies that exist in this line of work and the factors that could explain why stress can exert differential effects on retrieval processes. Therefore, we examined the influence of brief, pre-retrieval stress that was administered immediately before testing on long-term memory in males and females. Participants learned a list of 42 words varying in emotional valence and arousal. Following the learning phase, participants were given an immediate free recall test. Twenty-four hours later, participants submerged their non-dominant hand in a bath of ice cold (Stress) or warm (No Stress) water for 3 min. Immediately following this manipulation, participants' memory for the word list was assessed via free recall and recognition tests. We observed no group differences on short-term memory. However, male participants who showed a robust cortisol response to the stress exhibited enhanced long-term recognition memory, while male participants who demonstrated a blunted cortisol response to the stress exhibited impaired long-term recall and recognition memory. These findings suggest that the effects of brief, pre-retrieval stress on long-term memory are sex-specific and mediated by corticosteroid mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Craving Responses to Methamphetamine and Sexual Visual Cues in Individuals With Methamphetamine Use Disorder After Long-Term Drug Rehabilitation

    Directory of Open Access Journals (Sweden)

    Shucai Huang

    2018-04-01

    Full Text Available Studies utilizing functional magnetic resonance imaging (fMRI cue-reactivity paradigms have demonstrated that short-term abstinent or current methamphetamine (MA users have increased brain activity in the ventral striatum, caudate nucleus and medial frontal cortex, when exposed to MA-related visual cues. However, patterns of brain activity following cue-reactivity in subjects with long-term MA abstinence, especially long-term compulsory drug rehabilitation, have not been well studied. To enrich knowledge in this field, functional brain imaging was conducted during a cue-reactivity paradigm task in 28 individuals with MA use disorder following long-term compulsory drug rehabilitation, and 27 healthy control subjects. The results showed that, when compared with controls, individuals with MA use disorder displayed elevated activity in the bilateral medial prefrontal cortex (mPFC and right lateral posterior cingulate cortex in response to MA-related images. Additionally, the anterior cingulate region of mPFC activation during the MA-related cue-reactivity paradigm was positively correlated with craving alterations and previous frequency of drug use. No significant differences in brain activity in response to pornographic images were found between the two groups. Compared to MA cues, individuals with MA use disorder had increased activation in the occipital lobe when exposed to pornographic cues. In conclusion, the present study indicates that, even after long-term drug rehabilitation, individuals with MA use disorder have unique brain activity when exposed to MA-related cues. Additionally, our results illustrate that the libido brain response might be restored, and that sexual demand might be more robust than drug demand, in individuals with MA use disorder following long-term drug rehabilitation.

  19. Craving Responses to Methamphetamine and Sexual Visual Cues in Individuals With Methamphetamine Use Disorder After Long-Term Drug Rehabilitation.

    Science.gov (United States)

    Huang, Shucai; Zhang, Zhixue; Dai, Yuanyuan; Zhang, Changcun; Yang, Cheng; Fan, Lidan; Liu, Jun; Hao, Wei; Chen, Hongxian

    2018-01-01

    Studies utilizing functional magnetic resonance imaging (fMRI) cue-reactivity paradigms have demonstrated that short-term abstinent or current methamphetamine (MA) users have increased brain activity in the ventral striatum, caudate nucleus and medial frontal cortex, when exposed to MA-related visual cues. However, patterns of brain activity following cue-reactivity in subjects with long-term MA abstinence, especially long-term compulsory drug rehabilitation, have not been well studied. To enrich knowledge in this field, functional brain imaging was conducted during a cue-reactivity paradigm task in 28 individuals with MA use disorder following long-term compulsory drug rehabilitation, and 27 healthy control subjects. The results showed that, when compared with controls, individuals with MA use disorder displayed elevated activity in the bilateral medial prefrontal cortex (mPFC) and right lateral posterior cingulate cortex in response to MA-related images. Additionally, the anterior cingulate region of mPFC activation during the MA-related cue-reactivity paradigm was positively correlated with craving alterations and previous frequency of drug use. No significant differences in brain activity in response to pornographic images were found between the two groups. Compared to MA cues, individuals with MA use disorder had increased activation in the occipital lobe when exposed to pornographic cues. In conclusion, the present study indicates that, even after long-term drug rehabilitation, individuals with MA use disorder have unique brain activity when exposed to MA-related cues. Additionally, our results illustrate that the libido brain response might be restored, and that sexual demand might be more robust than drug demand, in individuals with MA use disorder following long-term drug rehabilitation.

  20. Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence.

    Science.gov (United States)

    Chaby, Lauren E; Cavigelli, Sonia A; White, Amanda; Wang, Kayllie; Braithwaite, Victoria A

    2013-01-01

    Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid "stress" hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision-making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g., isolation, crowding, cage tilt) were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias [F (1, 12) = 5.000, P chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object [T (1, 14) = 2.240, P = 0.04; T (1, 14) = 2.419, P = 0.03, respectively]. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions.

  1. Cardiovascular responses to orthostasis: methods, assessments, and their association with falls in older adults in long-term care

    OpenAIRE

    Shaw, Brett Harrison

    2013-01-01

    Background: Orthostatic hypotension (OH) refers to a significant decline in blood pressure that occurs upon assuming an upright posture and represents an intrinsic risk factor for falls in older adults. Methods: Beat-to-beat blood pressure and cerebral blood flow velocity responses were assessed during a passive seated orthostatic stress test (PSOST). In healthy controls, PSOST responses were compared to head up tilt (the ‘gold-standard’). In a cohort of long-term care residents, data from PS...

  2. Effect of long-term oral administration of an immunostimulant diet on innate immunity in sea bass (Dicentrarchus labrax).

    Science.gov (United States)

    Bagni, M; Archetti, L; Amadori, M; Marino, G

    2000-12-01

    Immunostimulants represent a modern and promising tool in aquaculture, enhancing the resistance of cultured fish to disease and stress. This study investigated the effect of a combination of dietary glucans, alpha-tocopherol and ascorbic acid on the innate immune response of cultured sea bass (Dicentrarchus labrax). After 5 weeks of adaptation on a commercial diet containing 100 p.p.m. ascorbic acid and 200 p.p.m. alpha-tocopherol, sea bass were switched to a diet supplemented with 2% beta-1.3/beta-1.6 glucans and ascorbic acid and alpha-tocopherol at 500 p.p.m. The supplemented diet was given at 2% of body weight per day over a 2-week period, every 3 months. Plasma lysozyme concentration, content and distribution of major plasma proteins and complement activity were measured prior to feeding the supplemented diet and after 40 weeks. Alternative pathways of complement activation and lysozyme activity were both significantly enhanced in fish fed on glucans and elevated doses of vitamins. No significant differences were observed in protein content or in albumin/globulin ratio. Compared to lysozyme activity, which showed marked individual variation, complement-mediated haemolytic activity has been shown to be a more reliable indicator of sea bass immunocompetence. Further studies are in progress to clarify the effect of each dietary component on the innate immune response and disease resistance.

  3. A single exposure to severe stressors causes long-term desensitisation of the physiological response to the homotypic stressor.

    Science.gov (United States)

    Armario, Antonio; Vallès, Astrid; Dal-Zotto, Silvina; Márquez, Cristina; Belda, Xavier

    2004-09-01

    Although some laboratories have reported that a single session of stress is able to induce a long-lasting sensitisation of the hypothalamic-pituitary-adrenal (HPA) response to further exposures to stress, we have found that a single exposure to severe emotional (immobilisation, restraint or shock) or systemic (endotoxin) stressors reduces the responsiveness of the HPA to the same, but not to a novel (heterotypic), stressor, in which case a slight sensitisation was observed. Long-term desensitisation has been found to reduce not only secretion of peripheral HPA hormones (ACTH and corticosterone), but also to reduce responses of central components of the HPA axis (c-fos and CRF gene expression at the level of the paraventricular nucleus of the hypothalamus, PVN). In addition, desensitisation also applies to the impact of the stressor on food intake and, probably, to stress-induced hyperglycaemia. The development of long-term desensitisation of the HPA axis does not appear to be a universal consequence of exposure to severe stressors as it was not observed in response to insulin-induced hypoglycaemia. Whether or not the development of long-term effects of stress depend on the specific pathways activated by particular stressors remains to be tested. The observed desensitisation of the HPA axis in response to the homotypic stressor shows two special features which makes it difficult to be interpreted in terms of an habituation-like process: (a) the effect increased with time (days to weeks) elapsed between the first and second exposure to the stressor, suggesting a progressive maturational process; and (b) the stronger the stressor the greater the long-term desensitisation. Therefore, it is possible that desensitisation of the HPA axis is the sum of two different phenomena: long-term effects and habituation-like processes. The contribution of the former may be more relevant with severe stressors and longer inter-stress intervals, and that of the latter with mild

  4. Transplantation of mouse HSCs genetically modified to express a CD4-restricted TCR results in long-term immunity that destroys tumors and initiates spontaneous autoimmunity.

    Science.gov (United States)

    Ha, Sung P; Klemen, Nicholas D; Kinnebrew, Garrett H; Brandmaier, Andrew G; Marsh, Jon; Hangoc, Giao; Palmer, Douglas C; Restifo, Nicholas P; Cornetta, Kenneth; Broxmeyer, Hal E; Touloukian, Christopher E

    2010-12-01

    The development of effective cancer immunotherapies has been consistently hampered by several factors, including an inability to instigate long-term effective functional antitumor immunity. This is particularly true for immunotherapies that focus on the adoptive transfer of activated or genetically modified mature CD8+ T cells. In this study, we sought to alter and enhance long-term host immunity by genetically modifying, then transplanting, mouse HSCs. We first cloned a previously identified tumor-reactive HLA-DR4-restricted CD4+ TCR specific for the melanocyte differentiation antigen tyrosinase-related protein 1 (Tyrp1), then constructed both a high-expression lentivirus vector and a TCR-transgenic mouse expressing the genes encoding this TCR. Using these tools, we demonstrated that both mouse and human HSCs established durable, high-efficiency TCR gene transfer following long-term transplantation into lethally irradiated mice transgenic for HLA-DR4. Recipients of genetically modified mouse HSCs developed spontaneous autoimmune vitiligo that was associated with the presence of a Th1-polarized memory effector CD4+ T cell population that expressed the Tyrp1-specific TCR. Most importantly, large numbers of CD4+ T cells expressing the Tyrp1-specific TCR were detected in secondary HLA-DR4-transgenic transplant recipients, and these mice were able to destroy subcutaneously administered melanoma cells without the aid of vaccination, immune modulation, or cytokine administration. These results demonstrate the creation of what we believe to be a novel translational model of durable lentiviral gene transfer that results in long-term effective immunity.

  5. Behavioural and physiological responses of shelter dogs to long-term confinement

    Directory of Open Access Journals (Sweden)

    Paolo Dalla Villa

    2013-06-01

    Full Text Available In Italy, National Law (281/1991 prohibits euthanasia of shelter dogs if they are not dangerous or suffering seriously. Adoption rates in rescue shelters are often lower than entrance rates, leading inevitably to overcrowded facilities where animals are likely to spend the rest of their lives in kennels. In this situation, housing conditions (i.e. space provided, environmental, and social stimulation may have an impact on canine welfare. In this research project, the effects of two different forms of housing (group- and pair housing on long-term shelter dogs were compared using behavioural and physiological parameters. Observational data and saliva samples were collected from dogs exposed to both experimental settings; behaviour and cortisol concentration levels were used as welfare indicators. Pair housing offered fewer social and environmental stimuli and behavioural analysis showed a significant decrease in locomotor, exploratory, and social behaviour. Cortisol levels show that this parameter varied independently of housing conditions. Although this study found no evidence suggesting that one form of confinement reduced animal welfare more than the other (e.g. in terms of abnormal behaviour, or higher cortisol concentrations, the type of confinement did affect the expression of a variety of behaviours and these variations should not be ignored with respect to housing decisions for long-term shelter dogs.

  6. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies.

    Science.gov (United States)

    Finsterwald, Charles; Alberini, Cristina M

    2014-07-01

    A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitary-adrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the formation of

  7. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies

    Science.gov (United States)

    Finsterwald, Charles; Alberini, Cristina M.

    2013-01-01

    A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitaryadrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the effects of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the

  8. A Long-term Forest Fertilization Experiment to Understand Ecosystem Responses to Atmospheric Nitrogen Deposition

    Science.gov (United States)

    Baron, J.; Advani, S. M.; Allen, J.; Boot, C.; Denef, K.; Denning, S.; Hall, E.; Moore, J. C.; Reuth, H.; Ryan, M. G.; Shaw, E.

    2016-12-01

    Long-term field experiments can reveal changes in ecosystem processes that may not be evident in short-term studies. Short-term measurements or experiments may have narrower objectives or unrealistic treatments in order to see a change, whereas long-term studies can reveal complex interactions that take longer to manifest. We report results from a long-term experiment (1996 to present) in subalpine forests to simulate the consequences of sustained atmospheric nitrogen (N) deposition. Loch Vale watershed in Rocky Mountain National Park, the location of the experiment, has received an order of magnitude greater atmospheric N deposition than estimated background since mid-20th Century. Augmenting that, in 1996 we began adding 25 kg NH4NO3 ha-1 yr-1 to three 30m x 30m old-growth Engelmann spruce and subalpine fir plots. Treated stands were matched by nearby controls. N addition caused rapid leaching of nitrate and cations from soils, and increased N mineralization and nitrification rates. These observations in the fertilized plots have been sustained over time. Soluble aluminum concentrations do not differ significantly between fertilized and control plots, but treated soils are now markedly more acidic (pH of 4.7) than original soil and controls (pH of 5.1); further acidification might increase aluminum leaching. Effects on soil carbon were complex, mediated by reductions in total microbial biomass, decreases in arbuscular mychorrizal and saprotropic fungi, and increased potential rates of N enzyme degrading activities. Initial soil C:N of 24 was lower than similar soils in low N deposition stands (C:N of 36). The C:N declined to 22 with treatment. Fertilized plots lost 11% soil C, but the mechanism is unclear. We did not measure changes in C inputs from litter, microbial biomass, or plant uptake, but there was no change in summer CO2 flux, measured in 2003, 2004, and 2014. Leaching of DOC from fertilized plots was elevated throughout the experiment, providing one

  9. Response of stiff piles in sand to long-term cyclic lateral loading

    DEFF Research Database (Denmark)

    Bakmar, Christian LeBlanc; Houlsby, Guy T.; Byrne, Byron W.

    2010-01-01

    . To address this, a series of laboratory tests were conducted where a stiff pile in drained sand was subjected to between 8000 and 60000 cycles of combined moment and horizontal loading. A typical design for an offshore wind turbine monopile was used as a basis for the study, to ensure that pile dimensions...... and loading ranges were realistic. A complete non-dimensional framework for stiff piles in sand is presented and applied to interpret the test results. The accumulated rotation was found to be dependent on relative density and was strongly affected by the characteristics of the applied cyclic load. The pile...... stiffness increased with number of cycles, which contrasts with the current methodology where static p - y curves are degraded to account for cyclic loading. Methods are presented to predict the change in stiffness and the accumulated rotation of a stiff pile due to long-term cyclic loading. The use...

  10. Response of Soil Mesofauna to Long-Term Application of Feedlot Manure on Irrigated Cropland.

    Science.gov (United States)

    Miller, Jim J; Battigelli, Jeff P; Beasley, Bruce W; Drury, Craig F

    2017-01-01

    Long-term application of feedlot manure to cropland may influence soil mesofauna. These organisms affect the health, structure, and fertility of soils, organic matter decomposition, and crop growth. The objective was to study the long-term (16-17 yr) influence of feedlot manure type and bedding on soil mesofauna over 2 yr (2014-2015). Stockpiled or composted feedlot manure with straw (ST) or wood-chip (WD) bedding (plus unamended control) was annually applied (13 Mg ha dry wt.) to an irrigated clay loam soil with continuous barley (). Intact cores were taken from surface (0-5 cm) soil in the fall, and the densities of Acari (mites) suborders and Collembola (springtails) families were determined. Manure type had no significant ( > 0.05) effect on soil mesofauna density. In contrast, there was a significant two- to sixfold increase in density with WD- compared with ST-amended soils of total Acari in 2014 and 2015, as well as total Collembola, total Acari and Collembola, oribatid mites, and entomobryid springtails in 2014. The bedding effect was attributed to significantly greater soil water content and lower bulk density for WD than ST. Density of soil mesofauna was not significantly greater in amended soils than in unamended soils. A shift by feedlot producers from stockpiled to composted feedlot manure application should have no effect on soil mesofauna density, whereas a shift from ST to WD bedding may increase the density of certain soil mesofauna, which may have a beneficial effect on soil. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  11. Ecosystem responses to long-term nutrient management in an urban estuary: Tampa Bay, Florida, USA

    Science.gov (United States)

    Greening, H.; Janicki, A.; Sherwood, E. T.; Pribble, R.; Johansson, J. O. R.

    2014-12-01

    In subtropical Tampa Bay, Florida, USA, we evaluated restoration trajectories before and after nutrient management strategies were implemented using long-term trends in nutrient loading, water quality, primary production, and seagrass extent. Following citizen demands for action, reduction in wastewater nutrient loading of approximately 90% in the late 1970s lowered external total nitrogen (TN) loading by more than 50% within three years. Continuing nutrient management actions from public and private sectors were associated with a steadily declining TN load rate and with concomitant reduction in chlorophyll-a concentrations and ambient nutrient concentrations since the mid-1980s, despite an increase of more than 1 M people living within the Tampa Bay metropolitan area. Water quality (chlorophyll-a concentration, water clarity as indicated by Secchi disk depth, total nitrogen concentration and dissolved oxygen) and seagrass coverage are approaching conditions observed in the 1950s, before the large increases in human population in the watershed. Following recovery from an extreme weather event in 1997-1998, water clarity increased significantly and seagrass is expanding at a rate significantly different than before the event, suggesting a feedback mechanism as observed in other systems. Key elements supporting the nutrient management strategy and concomitant ecosystem recovery in Tampa Bay include: 1) active community involvement, including agreement about quantifiable restoration goals; 2) regulatory and voluntary reduction in nutrient loadings from point, atmospheric, and nonpoint sources; 3) long-term water quality and seagrass extent monitoring; and 4) a commitment from public and private sectors to work together to attain restoration goals. A shift from a turbid, phytoplankton-based system to a clear water, seagrass-based system that began in the 1980s following comprehensive nutrient loading reductions has resulted in a present-day Tampa Bay which looks and

  12. p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis.

    Science.gov (United States)

    Paradiso, A; Rabinovich, M; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriquez, R; Leone, B; Sapia, M G; Simone, G; De Lena, M

    1996-12-20

    In a series of 71 patients with advanced colorectal cancer treated with biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we investigated the relationship between the proliferating-cell nuclear antigen (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with respect to clinical response and long-term prognosis. Nuclear p53 expression was demonstrated in 44% of samples (any number of positive tumor cells) while all tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was correlated with histopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical response to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated with short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment and survival from diagnosis, according to univariate and multivariate analysis, particularly in the sub-set of colon-cancer patients. We conclude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA and p53 primary-tumor expression, but high PCNA expression appears to be independently related to long-term prognosis.

  13. Long-term heat stress induces the inflammatory response in dairy cows revealed by plasma proteome analysis.

    Science.gov (United States)

    Min, Li; Zheng, Nan; Zhao, Shengguo; Cheng, Jianbo; Yang, Yongxin; Zhang, Yangdong; Yang, Hongjian; Wang, Jiaqi

    2016-03-04

    In this work we employed a comparative proteomic approach to evaluate seasonal heat stress and investigate proteomic alterations in plasma of dairy cows. Twelve lactating Holstein dairy cows were used and the treatments were: heat stress (n = 6) in hot summer (at the beginning of the moderate heat stress) and no heat stress (n = 6) in spring natural ambient environment, respectively. Subsequently, heat stress treatment lasted 23 days (at the end of the moderate heat stress) to investigate the alterations of plasma proteins, which might be employed as long-term moderate heat stress response in dairy cows. Changes in plasma proteins were analyzed by two-dimensional electrophoresis (2-DE) combined with mass spectrometry. Analysis of the properties of the identified proteins revealed that the alterations of plasma proteins were related to inflammation in long-term moderate heat stress. Furthermore, the increase in plasma tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) directly demonstrated that long-term moderate heat stress caused an inflammatory response in dairy cows. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Assessing Forest Carbon Response to Climate Change and Disturbances Using Long-term Hydro-climatic Observations and Simulations

    Science.gov (United States)

    Trettin, C.; Dai, Z.; Amatya, D. M.

    2014-12-01

    Long-term climatic and hydrologic observations on the Santee Experimental Forest in the lower coastal plain of South Carolina were used to estimate long-term changes in hydrology and forest carbon dynamics for a pair of first-order watersheds. Over 70 years of climate data indicated that warming in this forest area in the last decades was faster than the global mean; 35+ years of hydrologic records showed that forest ecosystem succession three years following Hurricane Hugo caused a substantial change in the ratio of runoff to precipitation. The change in this relationship between the paired watersheds was attributed to altered evapotranspiration processes caused by greater abundance of pine in the treatment watershed and regeneration of the mixed hardwood-pine forest on the reference watershed. The long-term records and anomalous observations are highly valuable for reliable calibration and validation of hydrological and biogeochemical models capturing the effects of climate variability. We applied the hydrological model MIKESHE that showed that runoff and water table level are sensitive to global warming, and that the sustained warming trends can be expected to decrease stream discharge and lower the mean water table depth. The spatially-explicit biogeochemical model Forest-DNDC, validated using biomass measurements from the watersheds, was used to assess carbon dynamics in response to high resolution hydrologic observation data and simulation results. The simulations showed that the long-term spatiotemporal carbon dynamics, including biomass and fluxes of soil carbon dioxide and methane were highly regulated by disturbance regimes, climatic conditions and water table depth. The utility of linked-modeling framework demonstrated here to assess biogeochemical responses at the watershed scale suggests applications for assessing the consequences of climate change within an urbanizing forested landscape. The approach may also be applicable for validating large

  15. Long-term effect of oral immunization against influenza with a gamma-inactivated vaccine in mice

    International Nuclear Information System (INIS)

    Noack, K.; Tischner, H.; Pohl, W.D.; Braeuniger, S.; Nordheim, W.

    1986-01-01

    NMRI mice were immunized orally twice within 10 days with an influenza vaccine inactivated by gamma radiation. The immunization with a relatively low dosis led to the occurence of low specific antibody titer in the lung lavage fluid up to 6th month. Despite of the low titer, immunized mice were protected against aerogenic infection for about 6 months. Protection was demonstrated in comparison to non-immunized mice by a limited increase of cells in bronchoalveolar lavage, low virus titer in the lung and survival of most animals after a lethal aerosol challenge with the live virus. (author)

  16. Lessons learned from Three Mile Island (TMI), USNRC long-term trends, industry response

    International Nuclear Information System (INIS)

    Szalay, R.A.

    1981-01-01

    Studies resulting from Three Mile Island (TMI) showed that corrections were needed in information processing, operator training and procedures, and certain aspects of the safety review process. These have been undertaken by industry and NRC and the results are positive. New safety instructions have been set up. The Nuclear Safety Analysis Center (NSAC) is providing a focus for analysis of issues which have generic elements affecting a number of plants of similar or related design. The Institute of Nuclear Power Operations (INPO) is setting industry standards for training and certification of operators and supervisory personnel, and for training of the managerial chain which oversees safety practices. Changes in procedures and in some design features called for in the recommendations of the NRC Lessons Learned Task Force (NUREG-0578) have been simplemented by utilities. Other requirements included in the NRC Action Plan (NUREG-0660) and its companion document clarification of TMI Action Plan Requirements (NUREG-0737), are also being addressed. Improved operator training and emergency procedures provide a continuing opportunity to make safety gains. Problems remain to be faced in the regulatory and political arenas. The long-term licensing trend will be affected by the manner in which degraded core issues and the development of a safety goal proceed. The Industry Degraded Core Rulemaking (IDCOR) program has been undertaken to develop the nuclear industry's position in anticipation of an impending rulemaking. Both industry and NRC are working on the development of a safety goal and standard risk assessment methodology. (AF)

  17. Responses of Soil Organic Carbon to Long-Term Understory Removal in Subtropical Cinnamomum camphora Stands

    Directory of Open Access Journals (Sweden)

    Yacong Wu

    2014-01-01

    Full Text Available We conducted a study on a 48-year-old Cinnamomum camphora plantation in the subtropics of China, by removing understory gradually and then comparing this treatment with a control (undisturbed. This study analyzed the content and storage soil organic carbon (SOC in a soil depth of 0–60 cm. The results showed that SOC content was lower in understory removal (UR treatment, with a decrease range from 5% to 34%, and a decline of 10.16 g·kg−1 and 8.58 g·kg−1 was noticed in 0–10 cm and 10–20 cm layers, respectively, with significant differences (P<0.05. Carbon storage was reduced in UR, ranging from 2% to 43%, with a particular drastic decline of 15.39 t·hm−2 and 11.58 t·hm−2 in 0–10 cm (P<0.01 and 10–20 cm (P<0.01 layers, respectively. Content of SOC had an extremely significant (P<0.01 correlation with soil nutrients in the two stands, and the correlation coefficients of CK were higher than those of UR. Our data showed that the presence of understory favored the accumulation of soil organic carbon to a large extent. Therefore, long-term practice of understory removal weakens the function of forest ecosystem as a carbon sink.

  18. Long-term anisotropic mechanical response of surgical meshes used to repair abdominal wall defects.

    Science.gov (United States)

    Hernández-Gascón, B; Peña, E; Pascual, G; Rodríguez, M; Bellón, J M; Calvo, B

    2012-01-01

    Routine hernia repair surgery involves the implant of synthetic mesh. However, this type of procedure may give rise to pain and bowel incarceration and strangulation, causing considerable patient disability. The purpose of this study was to compare the long-term behaviour of three commercial meshes used to repair the partially herniated abdomen in New Zealand White rabbits: the heavyweight (HW) mesh, Surgipro(®) and lightweight (LW) mesh, Optilene(®), both made of polypropylene (PP), and a mediumweight (MW) mesh, Infinit(®), made of polytetrafluoroethylene (PTFE). The implanted meshes were mechanical and histological assessed at 14, 90 and 180 days post-implant. This behaviour was compared to the anisotropic mechanical behaviour of the unrepaired abdominal wall in control non-operated rabbits. Both uniaxial mechanical tests conducted in craneo-caudal and perpendicular directions and histological findings revealed substantial collagen growth over the repaired hernial defects causing stiffness in the repair zone, and thus a change in the original properties of the meshes. The mechanical behaviour of the healthy tissue in the craneo-caudal direction was not reproduced by any of the implanted meshes after 14 days or 90 days of implant, whereas in the perpendicular direction, SUR and OPT achieved similar behaviour. From a mechanical standpoint, the anisotropic PP-lightweight meshes may be considered a good choice in the long run, which correlates with the structure of the regenerated tissue. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Short- and long-term response to corticosteroid therapy in chronic beryllium disease.

    Science.gov (United States)

    Marchand-Adam, S; El Khatib, A; Guillon, F; Brauner, M W; Lamberto, C; Lepage, V; Naccache, J-M; Valeyre, D

    2008-09-01

    Chronic beryllium disease (CBD) is a granulomatous disorder that affects the lung after exposure to beryllium. The present study reports short- and long-term evolution of granulomatous and fibrotic components in eight patients with severe CBD receiving corticosteroid therapy. Eight patients with confirmed CBD were studied at baseline, after initial corticosteroid treatment (4-12 months), at relapse and at the final visit. Beryllium exposure, Glu(69) (HLA-DPB1 genes coding for glutamate at position beta69) polymorphism, symptoms, pulmonary function tests (PFT), serum angiotensin-converting enzyme (SACE) and high-resolution computed tomography (HRCT) quantification of pulmonary lesions were analysed. The CBD patients were observed for a median (range) of 69 (20-180) months. After stopping beryllium exposure, corticosteroids improved symptoms and PFT (vital capacity +26%, diffusing capacity of the lung for carbon monoxide +15%), and decreased SACE level and active lesion HRCT score. In total, 18 clinical relapses occurred after the treatment was tapered and these were associated with SACE and active lesion HRCT score impairment. At the final visit, corticosteroids had completely stabilised all parameters including both HRCT scores of active lesions and fibrotic lesions in six out of eight patients. Corticosteroids were beneficial in chronic beryllium disease. They were effective in suppressing granulomatosis lesions in all cases and in stopping the evolution to pulmonary fibrosis in six out of eight patients.

  20. Neonatal overfeeding disrupts pituitary ghrelin signalling in female rats long-term; Implications for the stress response.

    Science.gov (United States)

    Sominsky, Luba; Ziko, Ilvana; Spencer, Sarah J

    2017-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis responses to psychological stress are exacerbated in adult female but not male rats made obese due to overfeeding in early life. Ghrelin, traditionally known for its role in energy homeostasis, has been recently recognised for its role in coordinating the HPA responses to stress, particularly by acting directly at the anterior pituitary where the growth hormone secretagogue receptor (GHSR), the receptor for acyl ghrelin, is abundantly expressed. We therefore hypothesised that neonatal overfeeding in female rats would compromise pituitary responsiveness to ghrelin, contributing to a hyperactive central stress responsiveness. Unlike in males where hypothalamic ghrelin signalling is compromised by neonatal overfeeding, there was no effect of early life diet on circulating ghrelin or hypothalamic ghrelin signalling in females, indicating hypothalamic feeding and metabolic ghrelin circuitry remains intact. However, neonatal overfeeding did lead to long-term alterations in the pituitary ghrelin system. The neonatally overfed females had increased neonatal and reduced adult expression of GHSR and ghrelin-O-acyl transferase (GOAT) in the pituitary as well as reduced pituitary responsiveness to exogenous acyl ghrelin-induced adrenocorticotropic hormone (ACTH) release in vitro. These data suggest that neonatal overfeeding dysregulates pituitary ghrelin signalling long-term in females, potentially accounting for the hyper-responsive HPA axis in these animals. These findings have implications for how females may respond to stress throughout life, suggesting the way ghrelin modifies the stress response at the level of the pituitary may be less efficient in the neonatally overfed.

  1. Grain yield and crop N offtake in response to residual fertilizer N in long-term field experiments

    DEFF Research Database (Denmark)

    Petersen, Jens; Thomsen, Ingrid Kaag; Mattsson, L.

    2010-01-01

    in four long-term (>35 yr) field experiments, we measured the response of barley (grain yield and N offtake at crop maturity) to six rates (0, 30, 60, 90, 120 and 150 kg N/ha) of mineral fertilizer N (Nnew) applied in subplots replacing the customary long-term plot treatments of fertilizer inputs (Nprev......). Rates of Nprev above 50-100 kg N/ha had no consistent effect on the soil N content, but this was up to 20% greater than that in unfertilized treatments. Long-term unfertilized plots should not be used as control to test the residual value of N in modern agriculture with large production potentials....... Although the effect of mineral Nprev on grain yield and N offtake could be substituted by Nnew within a range of previous inputs, the value of Nprev was not eliminated irrespective of Nnew rate. Provided a sufficient supply of plant nutrients other than N, the use-efficiency of Nnew did not change...

  2. Change of exposure response over time and long-term risk of silicosis among a cohort of Chinese pottery workers.

    Science.gov (United States)

    Sun, Yi; Bochmann, Frank; Morfeld, Peter; Ulm, Kurt; Liu, Yuewei; Wang, Heijiao; Yang, Lei; Chen, Weihong

    2011-07-01

    An analysis was conducted on a cohort of Chinese pottery workers to estimate the exposure-response relationship between respirable crystalline silica dust exposure and the incidence of radiographically diagnosed silicosis, and to estimate the long-term risk of developing silicosis until the age of 65. The cohort comprised 3,250 employees with a median follow-up duration of around 37 years. Incident cases of silicosis were identified via silicosis registries (Chinese X-ray stage I, similar to International Labor Organisation classification scheme profusion category 1/1). Individual exposure to respirable crystalline silica dust was estimated based on over 100,000 historical dust measurements. The association between dust exposure, incidence and long-time risk of silicosis was quantified by Poisson regression analysis adjusted for age and smoking. The risk of silicosis depended not only on the cumulative respirable crystalline silica dust exposures, but also on the time-dependent respirable crystalline silica dust exposure pattern (long-term average concentration, highest annual concentration ever experienced and time since first exposure). A long-term "excess" risk of silicosis of approximately 1.5/1,000 was estimated among workers with all annual respirable crystalline silica dust concentration estimates less than 0.1 mg/m(3), using the German measurement strategy. This study indicates the importance of proper consideration of exposure information in risk quantification in epidemiological studies.

  3. Change of Exposure Response over Time and Long-Term Risk of Silicosis among a Cohort of Chinese Pottery Workers

    Directory of Open Access Journals (Sweden)

    Yuewei Liu

    2011-07-01

    Full Text Available An analysis was conducted on a cohort of Chinese pottery workers to estimate the exposure-response relationship between respirable crystalline silica dust exposure and the incidence of radiographically diagnosed silicosis, and to estimate the long-term risk of developing silicosis until the age of 65. The cohort comprised 3,250 employees with a median follow-up duration of around 37 years. Incident cases of silicosis were identified via silicosis registries (Chinese X-ray stage I, similar to International Labor Organisation classification scheme profusion category 1/1. Individual exposure to respirable crystalline silica dust was estimated based on over 100,000 historical dust measurements. The association between dust exposure, incidence and long-time risk of silicosis was quantified by Poisson regression analysis adjusted for age and smoking. The risk of silicosis depended not only on the cumulative respirable crystalline silica dust exposures, but also on the time-dependent respirable crystalline silica dust exposure pattern (long-term average concentration, highest annual concentration ever experienced and time since first exposure. A long-term “excess” risk of silicosis of approximately 1.5/1,000 was estimated among workers with all annual respirable crystalline silica dust concentration estimates less than 0.1 mg/m3, using the German measurement strategy. This study indicates the importance of proper consideration of exposure information in risk quantification in epidemiological studies.

  4. Efficacy of DHMEQ, a NF-κB inhibitor, in islet transplantation: II. Induction DHMEQ treatment ameliorates subsequent alloimmune responses and permits long-term islet allograft acceptance.

    Science.gov (United States)

    Watanabe, Masaaki; Yamashita, Kenichiro; Kamachi, Hirofumi; Kuraya, Daisuke; Koshizuka, Yasuyuki; Shibasaki, Susumu; Asahi, Yoh; Ono, Hitoshi; Emoto, Shin; Ogura, Masaomi; Yoshida, Tadashi; Ozaki, Michitaka; Umezawa, Kazuo; Matsushita, Michiaki; Todo, Satoru

    2013-09-15

    Long-term graft deterioration remains a major obstacle in the success of pancreatic islet transplantation (PITx). Antigen-independent inflammatory and innate immune responses strengthen subsequent antigen-dependent immunity; further, activation of nuclear factor (NF)-κB plays a key role during these responses. In this study, we tested our hypothesis that, by the inhibition of NF-κB activation, the suppression of these early responses after PITx could facilitate graft acceptance. Full major histocompatibility complex (MHC)-mismatched BALB/c (H-2) mice islets were transplanted into streptozotocin-induced diabetic C57BL/6 (B6: H-2) mice. The NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) was administered for either 3 or 14 days after PITx. To some PITx recipients, tacrolimus was also administered. Islet allograft survival, alloimmune responses, and in vitro effects of DHMEQ on dendritic cells (DCs) were assessed. With a vehicle treatment, 600 islet allografts were promptly rejected after PITx. In contrast, 3-day treatment with DHMEQ, followed by 2-week treatment with tacrolimus, allowed permanent acceptance of islet allografts. The endogenous danger-signaling molecule high mobility group complex 1 (HMGB1) was elevated in sera shortly after PITx, whereas DHMEQ administration abolished this elevation. DHMEQ suppressed HMGB1-driven cellular activation and proinflammatory cytokine secretion in mouse bone marrow-derived DCs and significantly reduced the capacity of DCs to prime allogeneic T-cell proliferation in vitro. Finally, the DHMEQ plus tacrolimus regimen reverted the diabetic state with only 300 islet allografts. Inhibition of NF-κB activation by DHMEQ shortly after PITx suppresses HMGB1, which activates DCs and strengthens the magnitude of alloimmune responses; this permits long-term islet allograft acceptance, even in case of fewer islet allografts.

  5. Immune-related Colitis Induced by the Long-term Use of Nivolumab in a Patient with Non-small Cell Lung Cancer.

    Science.gov (United States)

    Yasuda, Yuichiro; Urata, Yoshiko; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Hattori, Yoshihiro; Tsuda, Masahiro; Sakuma, Toshiko; Negoro, Shunichi; Satouchi, Miyako

    2018-05-01

    We herein report a case of immune-related colitis induced by the long-term use of nivolumab. A 62-year-old Japanese man was treated with nivolumab at 3 mg/kg every 2 weeks for advanced lung adenocarcinoma. The patient was admitted to our hospital due to non-bloody watery diarrhea after the 70th dose of nivolumab. A biopsy specimen of the colon mucosa revealed evidence of colitis with cryptitis and crypt microabscesses. He was diagnosed with immune-related colitis and started on predonisolone 60 mg/day. Subsequently, his symptoms remarkably resolved. Consideration of immune-related adverse events up to several years after the initiation of nivolumab is important.

  6. Clinical characteristics and long-term response to mood stabilizers in patients with bipolar disorder and different age at onset

    Science.gov (United States)

    Dell’Osso, Bernardo; Buoli, Massimiliano; Riundi, Riccardo; D’Urso, Nazario; Pozzoli, Sara; Bassetti, Roberta; Mundo, Emanuela; Altamura, A Carlo

    2009-01-01

    Introduction Bipolar disorder (BD) is a prevalent, comorbid, and impairing condition. Potential predictors of response to pharmacological treatment are object of continuous investigation in patients with BD. The present naturalistic study was aimed to assess clinical features and long-term response to mood stabilizers in a sample of bipolar subjects with different ages at onset. Methods The study sample included 108 euthymic patients, diagnosed as affected by BD, either type I or II, according to the DSM-IV-TR, who were started on mood stabilizer treatment. Patients were followed-up for 24 months and the occurrence of any mood episode collected. At the end of the follow-up, patients were divided in 3 subgroups according to the age at onset (early-onset ≤30 years, middle-onset >30–≤45 years, and late-onset >45 years, respectively) and the long-term response to mood stabilizers was compared between them along with other clinical features. Results The three subgroups showed significant differences in terms of clinical and demographic features and, with respect to long-term response to mood stabilizers, the early-onset subgroup showed a better outcome in terms of reduction of major depressive episodes during the 24-month follow-up compared to the other subgroups (one way ANOVA, F = 3.57, p = 0.032). Conclusions Even though further controlled studies are needed to clarify the relationship between age at onset and outcome in BD, the present follow-up study suggests clinical peculiarities and different patterns of response to mood stabilizers across distinct subgroups of patients with BD and different ages at onset. PMID:19649214

  7. Opportunistic visitors: long-term behavioural response of bull sharks to food provisioning in Fiji.

    Directory of Open Access Journals (Sweden)

    Juerg M Brunnschweiler

    Full Text Available Shark-based tourism that uses bait to reliably attract certain species to specific sites so that divers can view them is a growing industry globally, but remains a controversial issue. We evaluate multi-year (2004-2011 underwater visual (n = 48 individuals and acoustic tracking data (n = 82 transmitters; array of up to 16 receivers of bull sharks Carcharhinus leucas from a long-term shark feeding site at the Shark Reef Marine Reserve and reefs along the Beqa Channel on the southern coast of Viti Levu, Fiji. Individual C. leucas showed varying degrees of site fidelity. Determined from acoustic tagging, the majority of C. leucas had site fidelity indexes >0.5 for the marine reserve (including the feeding site and neighbouring reefs. However, during the time of the day (09:00-12:00 when feeding takes place, sharks mainly had site fidelity indexes <0.5 for the feeding site, regardless of feeding or non-feeding days. Site fidelity indexes determined by direct diver observation of sharks at the feeding site were lower compared to such values determined by acoustic tagging. The overall pattern for C. leucas is that, if present in the area, they are attracted to the feeding site regardless of whether feeding or non-feeding days, but they remain for longer periods of time (consecutive hours on feeding days. The overall diel patterns in movement are for C. leucas to use the area around the feeding site in the morning before spreading out over Shark Reef throughout the day and dispersing over the entire array at night. Both focal observation and acoustic monitoring show that C. leucas intermittently leave the area for a few consecutive days throughout the year, and for longer time periods (weeks to months at the end of the calendar year before returning to the feeding site.

  8. Opportunistic visitors: long-term behavioural response of bull sharks to food provisioning in Fiji.

    Science.gov (United States)

    Brunnschweiler, Juerg M; Barnett, Adam

    2013-01-01

    Shark-based tourism that uses bait to reliably attract certain species to specific sites so that divers can view them is a growing industry globally, but remains a controversial issue. We evaluate multi-year (2004-2011) underwater visual (n = 48 individuals) and acoustic tracking data (n = 82 transmitters; array of up to 16 receivers) of bull sharks Carcharhinus leucas from a long-term shark feeding site at the Shark Reef Marine Reserve and reefs along the Beqa Channel on the southern coast of Viti Levu, Fiji. Individual C. leucas showed varying degrees of site fidelity. Determined from acoustic tagging, the majority of C. leucas had site fidelity indexes >0.5 for the marine reserve (including the feeding site) and neighbouring reefs. However, during the time of the day (09:00-12:00) when feeding takes place, sharks mainly had site fidelity indexes <0.5 for the feeding site, regardless of feeding or non-feeding days. Site fidelity indexes determined by direct diver observation of sharks at the feeding site were lower compared to such values determined by acoustic tagging. The overall pattern for C. leucas is that, if present in the area, they are attracted to the feeding site regardless of whether feeding or non-feeding days, but they remain for longer periods of time (consecutive hours) on feeding days. The overall diel patterns in movement are for C. leucas to use the area around the feeding site in the morning before spreading out over Shark Reef throughout the day and dispersing over the entire array at night. Both focal observation and acoustic monitoring show that C. leucas intermittently leave the area for a few consecutive days throughout the year, and for longer time periods (weeks to months) at the end of the calendar year before returning to the feeding site.

  9. Long-term response to recombinant human growth hormone treatment: a new predictive mathematical method.

    Science.gov (United States)

    Migliaretti, G; Ditaranto, S; Guiot, C; Vannelli, S; Matarazzo, P; Cappello, N; Stura, I; Cavallo, F

    2018-07-01

    Recombinant GH has been offered to GH-deficient (GHD) subjects for more than 30 years, in order to improve height and growth velocity in children and to enhance metabolic effects in adults. The aim of our work is to describe the long-term effect of rhGH treatment in GHD pediatric patients, suggesting a growth prediction model. A homogeneous database is defined for diagnosis and treatment modalities, based on GHD patients afferent to Hospital Regina Margherita in Turin (Italy). In this study, 232 GHD patients are selected (204 idiopathic GHD and 28 organic GHD). Each measure is shown in terms of mean with relative standard deviations (SD) and 95% confidence interval (95% CI). To estimate the final height of each patient on the basis of few measures, a mathematical growth prediction model [based on Gompertzian function and a mixed method based on the radial basis functions (RBFs) and the particle swarm optimization (PSO) models] was performed. The results seem to highlight the benefits of an early start of treatment, further confirming what is suggested by the literature. Generally, the RBF-PSO method shows a good reliability in the prediction of the final height. Indeed, RMSE is always lower than 4, i.e., in average the forecast will differ at most of 4 cm to the real value. In conclusion, the large and accurate database of Italian GHD patients allowed us to assess the rhGH treatment efficacy and compare the results with those obtained in other Countries. Moreover, we proposed and validated a new mathematical model forecasting the expected final height after therapy which was validated on our cohort.

  10. Long-term dose-response studies of inhaled or injected radionuclides

    International Nuclear Information System (INIS)

    Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L.

    1994-01-01

    This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of their life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques

  11. Long-term response to genomic selection: effects of estimation method and reference population structure for different genetic architectures.

    Science.gov (United States)

    Bastiaansen, John W M; Coster, Albart; Calus, Mario P L; van Arendonk, Johan A M; Bovenhuis, Henk

    2012-01-24

    Genomic selection has become an important tool in the genetic improvement of animals and plants. The objective of this study was to investigate the impacts of breeding value estimation method, reference population structure, and trait genetic architecture, on long-term response to genomic selection without updating marker effects. Three methods were used to estimate genomic breeding values: a BLUP method with relationships estimated from genome-wide markers (GBLUP), a Bayesian method, and a partial least squares regression method (PLSR). A shallow (individuals from one generation) or deep reference population (individuals from five generations) was used with each method. The effects of the different selection approaches were compared under four different genetic architectures for the trait under selection. Selection was based on one of the three genomic breeding values, on pedigree BLUP breeding values, or performed at random. Selection continued for ten generations. Differences in long-term selection response were small. For a genetic architecture with a very small number of three to four quantitative trait loci (QTL), the Bayesian method achieved a response that was 0.05 to 0.1 genetic standard deviation higher than other methods in generation 10. For genetic architectures with approximately 30 to 300 QTL, PLSR (shallow reference) or GBLUP (deep reference) had an average advantage of 0.2 genetic standard deviation over the Bayesian method in generation 10. GBLUP resulted in 0.6% and 0.9% less inbreeding than PLSR and BM and on average a one third smaller reduction of genetic variance. Responses in early generations were greater with the shallow reference population while long-term response was not affected by reference population structure. The ranking of estimation methods was different with than without selection. Under selection, applying GBLUP led to lower inbreeding and a smaller reduction of genetic variance while a similar response to selection was

  12. Impaired immunity in harbour seals (Phoca vitulina) exposed to bioaccumulated environmental contaminants: review of a long-term feeding study.

    NARCIS (Netherlands)

    R.L. de Swart (Rik); P.S. Ross (Peter); J.G. Vos (Joseph); A.D.M.E. Osterhaus (Albert)

    1996-01-01

    textabstractMass mortalities among seals and dolphins inhabiting contaminated marine regions have led to speculation about a possible involvement of immunosuppression associated with environmental pollution. To evaluate whether contaminants at ambient environmental levels can affect immune function

  13. Prime-Boost Vaccination Using Chemokine-Fused gp120 DNA and HIV Envelope Peptides Activates Both Immediate and Long-Term Memory Cellular Responses in Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Hong Qin

    2010-01-01

    Full Text Available HIV vaccine candidates with improved immunogenicity and induction of mucosal T-cell immunity are needed. A prime-boost strategy using a novel HIV glycoprotein 120 DNA vaccine was employed to immunize rhesus macaques. The DNA vaccine encoded a chimeric gp120 protein in fusion with monocyte chemoattractant protein-3, which was hypothesized to improve the ability of antigen-presenting cells to capture viral antigen through chemokine receptor-mediated endocytosis. DNA vaccination induced virus-reactive T cells in peripheral blood, detectable by T cell proliferation, INFγ ELISPOT and sustained IL-6 production, without humoral responses. With a peptide-cocktail vaccine containing a set of conserved polypeptides of HIV-1 envelope protein, given by nasogastric administration, primed T-cell immunity was significantly boosted. Surprisingly, long-term and peptide-specific mucosal memory T-cell immunity was detected in both vaccinated macaques after one year. Therefore, data from this investigation offer proof-of-principle for potential effectiveness of the prime-boost strategy with a chemokine-fused gp120 DNA and warrant further testing in the nonhuman primate models for developing as a potential HIV vaccine candidate in humans.

  14. Long-term lesser prairie-chicken nest ecology in response to grassland management

    Science.gov (United States)

    Fritts, Sarah R.; Grisham, Blake A.; Haukos, David A.; Boal, Clint W.; Patten, Michael; Wolfe, Don H.; Dixon, Charles; Cox, Robert D.; Heck, Willard R.

    2016-01-01

    Long-term population and range declines from habitat loss and fragmentation caused the lesser prairie-chicken (Tympanuchus pallidicinctus) to be a species of concern throughout its range. Current lesser prairie-chicken range in New Mexico and Texas is partially restricted to sand shinnery oak (Quercus havardii; hereafter shinnery oak) prairies, on which cattle grazing is the main socioeconomic driver for private landowners. Cattle producers within shinnery oak prairies often focus land management on shrub eradication using the herbicide tebuthiuron to promote grass production for forage; however, herbicide application alone, and in combination with grazing, may affect nest site selection and nest survival of lesser prairie-chickens through the reduction of shinnery oak and native grasses. We used a controlled, paired, completely randomized design study to assess the influence of grazing and tebuthiuron application and their combined use on nest site selection and nest survival from 2001 to 2010 in Roosevelt County, New Mexico, USA at 2 spatial scales (i.e., treatment and microhabitat) in 4 treatments: tebuthiuron with grazing, tebuthiuron without grazing, no tebuthiuron with grazing, and a control of no tebuthiuron and no grazing. Grazing treatment was a short-duration system in which plots were grazed once during the dormant season and once during the growing season. Stocking rate was calculated each season based on measured forage production and applied to remove ≤25% of available herbaceous material per season. At the treatment scale, we compared nest site selection among treatments using 1-way χ2 tests and nest survival among treatments using a priori candidate nest survival models in Program MARK. At the microhabitat scale, we identified important habitat predictors of nest site selection and nest survival using logistic regression and a priori candidate nest survival models in Program MARK, respectively. Females typically used treatments as expected and

  15. Immune responses to metastases

    International Nuclear Information System (INIS)

    Herberman, R.B.; Wiltrout, R.H.; Gorelik, E.

    1987-01-01

    The authors present the changes in the immune system in tumor-bearing hosts that may influence the development of progression of metastases. Included are mononuclear cell infiltration of metastases; alterations in natural resistance mediated by natural killer cells and macrophages; development of specific immunity mediated by T-lymphocytes or antibodies; modulation of tumor-associated antigen expression; and the down-regulation of the immune response to the tumor by several suppressor mechanisms; the augmentation of the immune response and its potential for therapeutic application; includes the prophylaxis of metastases formation by NK cells; the therapy of metastases by augmentation NK-, macrophage-, or T-lymphocyte-mediated responses by biological response modifiers; and the transfer of anticancer activity by cytoxic T-lymphocytes or immunoconjugates of monoclonal antibodies with specificity for tumors

  16. Human dendritic cells sequentially matured with CD4+ T cells as a secondary signal favor CTL and long-term T memory cell responses

    Directory of Open Access Journals (Sweden)

    Thomas Simon

    2012-01-01

    Full Text Available Dendritic cells (DCs are professional antigen-presenting cells involved in the control and initiation of immune responses. In vivo, DCs exposed at the periphery to maturation stimuli migrate to lymph nodes, where they receive secondary signals from CD4+ T helper cells. These DCs become able to initiate CD8+ cytotoxic T lymphocyte (CTL responses. However, in vitro investigations concerning human monocyte-derived DCs have never focused on their functional properties after such sequential maturation. Here, we studied human DC phenotypes and functions according to this sequential exposure to maturation stimuli. As first signals, we used TNF-α/polyI:C mimicking inflammatory and pathogen stimuli and, as second signals, we compared activated CD4+ T helper cells to a combination of CD40-L/ IFN-γ. Our results show that a sequential activation with activated CD4+ T cells dramatically increased the maturation of DCs in terms of their phenotype and cytokine secretion compared to DCs activated with maturation stimuli delivered simultaneously. Furthermore, this sequential maturation led to the induction of CTL with a long-term effector and central memory phenotypes. Thus, sequential delivery of maturation stimuli, which includes CD4+ T cells, should be considered in the future to improve the induction of long-term CTL memory in DC-based immunotherapy.

  17. Human dendritic cells sequentially matured with CD4(+) T cells as a secondary signal favor CTL and long-term T memory cell responses.

    Science.gov (United States)

    Simon, Thomas; Tanguy-Royer, Séverine; Royer, Pierre-Joseph; Boisgerault, Nicolas; Frikeche, Jihane; Fonteneau, Jean-François; Grégoire, Marc

    2012-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells involved in the control and initiation of immune responses. In vivo, DCs exposed at the periphery to maturation stimuli migrate to lymph nodes, where they receive secondary signals from CD4+ T helper cells. These DCs become able to initiate CD8+ cytotoxic T lymphocyte (CTL) responses. However, in vitro investigations concerning human monocyte-derived DCs have never focused on their functional properties after such sequential maturation. Here, we studied human DC phenotypes and functions according to this sequential exposure to maturation stimuli. As first signals, we used TNF-α/polyI:C mimicking inflammatory and pathogen stimuli and, as second signals, we compared activated CD4+ T helper cells to a combination of CD40-L/ IFN-γ. Our results show that a sequential activation with activated CD4+ T cells dramatically increased the maturation of DCs in terms of their phenotype and cytokine secretion compared to DCs activated with maturation stimuli delivered simultaneously. Furthermore, this sequential maturation led to the induction of CTL with a long-term effector and central memory phenotypes. Thus, sequential delivery of maturation stimuli, which includes CD4+ T cells, should be considered in the future to improve the induction of long-term CTL memory in DC-based immunotherapy.

  18. Reduction on OFF-responses of Electroretinogram in Monkeys with Long-term High Intraocular Pressure

    Directory of Open Access Journals (Sweden)

    Ke-Gao Liu

    2017-01-01

    Conclusions: Reduced OFF-responses are recorded in monkeys with high IOP when dysfunction of photoreceptor is involved. The reduced OFF-responses to long-flash stimulus show evidence of anomalous retinal circuitry in glaucomatous retinopathy.

  19. Structural and functional responses of extremity veins to long-term gravitational loading or unloading—lessons from animal systems

    Science.gov (United States)

    Monos, Emil; Raffai, Gábor; Dörnyei, Gabriella; Nádasy, György L.; Fehér, Erzsébet

    2007-02-01

    Long, transparent tubular tilt-cages were developed to maintain experimental rats either in 45∘ head-up (orthostasis model), or in 45∘ head-down body position (antiorthostasis model) for several weeks. In order to study the functional and structural changes in extremity blood vessels, also novel pressure angiograph systems, as well as special quantitative electron microscopic methods were applied. It was found that several adaptive mechanisms are activated in the lower limb superficial veins and microvessels of muscles when an organism is exposed to long-term (1-2 weeks) orthostatic-type gravitational load including a reversible amplification of the pressure-dependent myogenic response, tuning of the myogenic tone by Ca++- and voltage-sensitive K+ channels in humans, augmentation of the intramural sympathetic innervation involving an increased nerve terminal density and synaptic vesicle count with functional remodeling, reorganization of vascular network properties (microvascular rarefaction in muscles, decreased branching angles in superficial veins), and responses of an endothelin and platelet-derived growth factor (PDGF) containing vesicle system in the endothelium. On the other hand, when applying long-term head-down tilting, the effects are dichotomous, e.g. it suppresses significantly the pressure-induced myogenic response, however does not diminish the adventitial sympathetic innervation density.

  20. Long-term In Vivo Calcium Imaging of Astrocytes Reveals Distinct Cellular Compartment Responses to Sensory Stimulation.

    Science.gov (United States)

    Stobart, Jillian L; Ferrari, Kim David; Barrett, Matthew J P; Stobart, Michael J; Looser, Zoe J; Saab, Aiman S; Weber, Bruno

    2018-01-01

    Localized, heterogeneous calcium transients occur throughout astrocytes, but the characteristics and long-term stability of these signals, particularly in response to sensory stimulation, remain unknown. Here, we used a genetically encoded calcium indicator and an activity-based image analysis scheme to monitor astrocyte calcium activity in vivo. We found that different subcellular compartments (processes, somata, and endfeet) displayed distinct signaling characteristics. Closer examination of individual signals showed that sensory stimulation elevated the number of specific types of calcium peaks within astrocyte processes and somata, in a cortical layer-dependent manner, and that the signals became more synchronous upon sensory stimulation. Although mice genetically lacking astrocytic IP3R-dependent calcium signaling (Ip3r2-/-) had fewer signal peaks, the response to sensory stimulation was sustained, suggesting other calcium pathways are also involved. Long-term imaging of astrocyte populations revealed that all compartments reliably responded to stimulation over several months, but that the location of the response within processes may vary. These previously unknown characteristics of subcellular astrocyte calcium signals provide new insights into how astrocytes may encode local neuronal circuit activity. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Interactions between lithology and biology drive the long-term response of stream chemistry to major hurricanes in a tropical landscape

    Science.gov (United States)

    W.H. McDowell; R.L. Brereton; F.N. Scatena; J.B. Shanley; N.V. Brokaw; A.E. Lugo

    2013-01-01

    Humid tropical forests play a dominant role in many global biogeochemical cycles, yet long-term records of tropical stream chemistry and its response to disturbance events such as severe storms and droughts are rare. Here we document the long-term variability in chemistry of two streams in the Luquillo Mountains, Puerto Rico over a period of 27 years. Our two focal...

  2. Long-term trends of changes in pine and oak foliar nitrogen metabolism in response to chronic nitrogen amendments at Harvard Forest, MA

    Science.gov (United States)

    Rakesh Minocha; Swathi A. Turlapati; Stephanie Long; William H. McDowell; Subhash C. Minocha

    2015-01-01

    We evaluated the long-term (1995-2008) trends in foliar and sapwood metabolism, soil solution chemistry and tree mortality rates in response to chronic nitrogen (N) additions to pine and hardwood stands at the Harvard Forest Long Term Ecological Research (LTER) site. Common stress-related metabolites like polyamines (PAs), free amino acids (AAs) and inorganic elements...

  3. Enhancement of Immune Memory Responses to Respiratory Infection

    Science.gov (United States)

    2017-08-01

    Unlimited Distribution 13. SUPPLEMENTARY NOTES 14. ABSTRACT Maintenance of long - term immunological memory against pathogens is crucial for the rapid...highly expressed in memory B cells in mice, and Atg7 is required for maintenance of long - term memory B cells needed to protect against influenza...AWARD NUMBER: W81XWH-16-1-0361 TITLE: Enhancement of Immune Memory Responses to Respiratory Infection PRINCIPAL INVESTIGATORs: Dr Farrah

  4. Long-term culture change related to rapid response system implementation.

    Science.gov (United States)

    Stevens, Jennifer; Johansson, Anna; Lennes, Inga; Hsu, Douglas; Tess, Anjala; Howell, Michael

    2014-12-01

    Increasing attention to patient safety in training hospitals may come at the expense of trainee autonomy and professional growth. This study sought to examine changes in medical trainees' self-reported behaviour after the institution-wide implementation of a rapid response system. We conducted a two-point cross-sectional survey of medical trainees in 2006, during the implementation of a rapid response system, and in 2010, in a single academic medical centre. A novel instrument was used to measure trainee likelihood of calling for supervisory assistance, perception of autonomy, and comfort in managing decompensating patients. Non-parametric tests to assess for change were used and year of training was evaluated as an effect modifier. Response rates were 38% in 2006 and 70% in 2010. After 5 years of the full implementation of the rapid response system, residents were significantly more likely to report calling their attending physicians for assistance (rising from 40% to 65% of relevant situations; p autonomy at 5 years after the implementation of the rapid response system. These changes were mirrored in the actual use of the rapid response system, which increased by 41% during the 5-year period after adjustment for patient volume (p < 0.0001). A primary team-focused implementation of a rapid response system was associated with durable changes in resident physicians' reported behaviour, including increased comfort with involving more experienced physicians and managing unstable patients. © 2014 John Wiley & Sons Ltd.

  5. Evidence from Individual Inference for High-Dimensional Coexistence: Long-Term Experiments on Recruitment Response

    Science.gov (United States)

    Clark, James S.; Soltoff, Benjamin D.; Powell, Amanda S.; Read, Quentin D.

    2012-01-01

    Background For competing species to coexist, individuals must compete more with others of the same species than with those of other species. Ecologists search for tradeoffs in how species might partition the environment. The negative correlations among competing species that would be indicative of tradeoffs are rarely observed. A recent analysis showed that evidence for partitioning the environment is available when responses are disaggregated to the individual scale, in terms of the covariance structure of responses to environmental variation. That study did not relate that variation to the variables to which individuals were responding. To understand how this pattern of variation is related to niche variables, we analyzed responses to canopy gaps, long viewed as a key variable responsible for species coexistence. Methodology/Principal Findings A longitudinal intervention analysis of individual responses to experimental canopy gaps with 12 yr of pre-treatment and 8 yr post-treatment responses showed that species-level responses are positively correlated – species that grow fast on average in the understory also grow fast on average in response to gap formation. In other words, there is no tradeoff. However, the joint distribution of individual responses to understory and gap showed a negative correlation – species having individuals that respond most to gaps when previously growing slowly also have individuals that respond least to gaps when previously growing rapidly (e.g., Morus rubra), and vice versa (e.g., Quercus prinus). Conclusions/Significance Because competition occurs at the individual scale, not the species scale, aggregated species-level parameters and correlations hide the species-level differences needed for coexistence. By disaggregating models to the scale at which the interaction occurs we show that individual variation provides insight for species differences. PMID:22393349

  6. Evidence from individual inference for high-dimensional coexistence: long-term experiments on recruitment response.

    Directory of Open Access Journals (Sweden)

    James S Clark

    Full Text Available BACKGROUND: For competing species to coexist, individuals must compete more with others of the same species than with those of other species. Ecologists search for tradeoffs in how species might partition the environment. The negative correlations among competing species that would be indicative of tradeoffs are rarely observed. A recent analysis showed that evidence for partitioning the environment is available when responses are disaggregated to the individual scale, in terms of the covariance structure of responses to environmental variation. That study did not relate that variation to the variables to which individuals were responding. To understand how this pattern of variation is related to niche variables, we analyzed responses to canopy gaps, long viewed as a key variable responsible for species coexistence. METHODOLOGY/PRINCIPAL FINDINGS: A longitudinal intervention analysis of individual responses to experimental canopy gaps with 12 yr of pre-treatment and 8 yr post-treatment responses showed that species-level responses are positively correlated--species that grow fast on average in the understory also grow fast on average in response to gap formation. In other words, there is no tradeoff. However, the joint distribution of individual responses to understory and gap showed a negative correlation--species having individuals that respond most to gaps when previously growing slowly also have individuals that respond least to gaps when previously growing rapidly (e.g., Morus rubra, and vice versa (e.g., Quercus prinus. CONCLUSIONS/SIGNIFICANCE: Because competition occurs at the individual scale, not the species scale, aggregated species-level parameters and correlations hide the species-level differences needed for coexistence. By disaggregating models to the scale at which the interaction occurs we show that individual variation provides insight for species differences.

  7. Hepatitis A vaccine. A new convenient single-dose schedule with booster when long-term immunization is warranted

    DEFF Research Database (Denmark)

    Victor, J; Knudsen, J D; Nielsen, L P

    1994-01-01

    A total of 162 anti-HAV-negative healthy adults were immunized with a single high dose (1440 ELISA units = 1 ml) of inactivated hepatitis A vaccine and a booster was given at month 6. Antibodies were measured after modification of a commercial ELISA kit, enabling quantification of titres down to 6...

  8. Long-term anti-HBs antibody persistence following infant vaccination against hepatitis B and evaluation of anamnestic response: a 20-year follow-up study in Thailand.

    Science.gov (United States)

    Poovorawan, Yong; Chongsrisawat, Voranush; Theamboonlers, Apiradee; Crasta, Priya Diana; Messier, Marc; Hardt, Karin

    2013-08-01

    Hepatitis B vaccine has been available worldwide since the mid-1980s. This vaccine was evaluated in a clinical trial in Thailand, conducted on subjects born to hepatitis B surface antigen positive and hepatitis B e-antigen positive mothers and vaccinated according to a 4-dose schedule at 0, 1, 2 and 12 mo of age and a single dose of hepatitis B immunoglobulin concomitantly at birth. All enrolled subjects seroconverted and were followed for 20 y to assess the persistence of antibody to the hepatitis B surface antigen (anti-HBs) (NCT00240539). At year 20, 64% of subjects had anti-HBs antibody concentrations≥10 milli-international units per milli liter (mIU/ml) and 92% of subjects had detectable levels (≥3.3 mIU/ml) of anti-HBs antibodies. At year 20, subjects with anti-HBs antibody titermemory (NCT00657657). Anamnestic response to the challenge dose was observed in 96.6% of subjects with an 82-fold (13.2 to 1082.4 mIU/ml) increase in anti-HBs antibody geometric mean concentrations. This study confirms the long-term immunogenicity of the 4-dose regimen of the HBV vaccine eliciting long-term persistence of antibodies and immune memory against hepatitis B for up to at least 20 y after vaccination.

  9. Employer, insurance, and health system response to long-term sick leave in the public sector: policy implications.

    Science.gov (United States)

    Heijbel, Bodil; Josephson, Malin; Jensen, Irene; Vingård, Eva

    2005-06-01

    This study has been conducted to describe the situation of long-term sick-listed persons employed in the public sector regarding the medical reasons of their sick leave, the duration of their problems, the duration of the actual sick leave, rehabilitation support, rehabilitation measures, and the persons expectations of the future. Response rate of a postal questionnaire, where 484 women and 51 men on long-term sick leave answered, was 69%. The study-group consisted of 90% women with a median age of 50 years. The most common reasons for sick listing were long-lasting musculoskeletal problems, especially neck/shoulder pain, low back pain and osteoarthritis or other joint problems and mental problems, especially depression and burn-out syndromes. Forty-seven procent of the men and 57% of the women had been on the sick list for more than a year. Only half of them had been subjected to the legally required rehabilitation investigation of the employer This half got access to rehabilitation programs and/or vocational rehabilitation to a greater extent than those who not had been subjected to rehabilitation investigation. Less than half had been in contact with the workplace-connected rehabilitation actors, the Occupational Health Service or the Trade Union. In spite of this the sick-listed persons had a positive view of their future return to work. For long-term sick-listed persons in the public sector, there is a great potential for improvements of the rehabilitation at the workplace arena, in the involvement and cooperation between the already existing rehabilitation actors, in order to promote return to work.

  10. Assessment of the long-term response to rehabilitation of two ...

    African Journals Online (AJOL)

    Assessing the ecological outcomes of wetland rehabilitation activities is an important need recognised by the 'Working for Wetlands' programme in South Africa. An assessment of ecological response was conducted in the Killarney and Kruisfontein wetlands, KwaZulu-Natal, in 2005 prior to rehabilitation in 2006, and again ...

  11. Long-term Root Growth Response to Thinning, Fertilization, and Water Deficit in Plantation Loblolly Pine

    Science.gov (United States)

    M.A. Sword-Sayer; Z. Tang

    2004-01-01

    High water deficits limit the new root growth of loblolly pine (Pinus taeda L.), potentially reducing soil resource availability and stand growth. We evaluated new root growth and stand production in response to thinning and fertilization in loblolly pine over a 6-year period that consisted of 3 years of low water deficit followed by 3 years of high...

  12. Therapeutic Responses of Psychopathic Sexual Offenders: Treatment Attrition, Therapeutic Change, and Long-Term Recidivism

    Science.gov (United States)

    Olver, Mark E.; Wong, Stephen C. P.

    2009-01-01

    The authors examined the therapeutic responses of psychopathic sex offenders (greater than or equal to 25 Psychopathy Checklist-Revised; PCL-R) in terms of treatment dropout and therapeutic change, as well as sexual and violent recidivism over a 10-year follow-up among 156 federally incarcerated sex offenders treated in a high-intensity inpatient…

  13. Metastatic phaeochromocytoma with a long-term response after iodine-131 metaiodobenzylguanidine therapy

    International Nuclear Information System (INIS)

    Pujol, P.; Bringer, J.; Faurous, P.; Jaffiol, C.

    1995-01-01

    Iodine-131 metaiodobenzylguanidine ([ 131 I] MIBG), a radiopharmaceutical agent, is used for treating malignant phaeochromocytoma. [ 131 I]MIBG therapy results in a hormone response rate of approximately 50%, but generally it yields only a partial or no tumour response. We present a case of a 46-year-old woman with a familial history of von Hippel-Lindau disease, who was treated with [ 131 I]MIBG for a metastatic phaeochromocytoma involving the lungs, liver and bones. The patient received a cumulative dose of 33.3 GBq (900 mCi) and a complete hormone response was observed, as evaluated on the basis of catecholamine and metanephrine levels. Conventional radiography, computerized tomography and [ 131 I]MIBG scintigraphy indicated that a near-complete tumour regression was achieved, with no evidence of relapse during a 4-year follow-up period. This case thus demonstrates that treatment with [ 131 I]MIBG may lead to a dramatic tumour response in malignant phaeochromocytoma presenting both soft tissue and bone metastases. (orig.)

  14. Immunization with DAT fragments is associated with long-term striatal impairment, hyperactivity and reduced cognitive flexibility in mice

    Directory of Open Access Journals (Sweden)

    Adriani Walter

    2012-11-01

    Full Text Available Abstract Background Possible interactions between nervous and immune systems in neuro-psychiatric disorders remain elusive. Levels of brain dopamine transporter (DAT have been implicated in several impulse-control disorders, like attention deficit / hyperactivity disorder (ADHD and obsessive-compulsive disorder (OCD. Here, we assessed the interplay between DAT auto-immunity and behavioural / neurochemical phenotype. Methods Male CD-1 mice were immunized with DAT peptide fragments (DAT-i, or vehicle alone (VEH, to generate elevated circulating levels of DAT auto-antibodies (aAbs. Using an operant delay-of-reward task (20 min daily sessions; timeout 25 sec, mice had a choice between either an immediate small amount of food (SS, or a larger amount of food after a delay (LL, which increased progressively across sessions (from 0 to 150 sec. Results DAT-i mice exhibited spontaneous hyperactivity (2 h-longer wake-up peak; a wake-up attempt during rest. Two sub-populations differing in behavioural flexibility were identified in the VEH control group: they showed either a clear-cut decision to select LL or clear-cut shifting towards SS, as expected. Compared to VEH controls, choice-behaviour profile of DAT-i mice was markedly disturbed, together with long-lasting alterations of the striatal monoamines. Enhanced levels of DA metabolite HVA in DAT-i mice came along with slower acquisition of basal preferences and with impaired shifting; elevation also in DOPAC levels was associated with incapacity to change a rigid selection strategy. This scarce flexibility of performance is indicative of a poor adaptation to task contingencies. Conclusions Hyperactivity and reduced cognitive flexibility are patterns of behaviour consistent with enduring functional impairment of striatal regions. It is yet unclear how anti-DAT antibodies could enter or otherwise affect these brain areas, and which alterations in DAT activity exactly occurred after immunization

  15. RELATIONSHIP OF LIPID PROFILE AND IMMUNE STATUS IN THE DYNAMICS OF LONG-TERM EXPOSURE TO COAL-ROCK DUST ON THE BODY (EXPERIMENTAL STUDIES

    Directory of Open Access Journals (Sweden)

    Анастасия Сергеевна Казицкая

    2017-10-01

    Full Text Available Subject. The relationship between lipid metabolism and immune reactivity in the dynamics of long-term exposure to coal-rock dust (CRD on the body. Objective. In the experiment to examine the impact of the changes in the lipid profile on immune status under the conditions of long-term exposure to CRD on the body. Methods. The experiments were carried out on 110 white male rats weighing 200-250 g. The inhalation method was used for modeling that best fits the conditions of coal-mine production. Animals were divided into 2 groups: the control (n = 30; the experiment (n = 80, that are the rats who inhaled CRD with a particle size of up to 5 microns in an average concentration of 50 mg/m3 for 4 hours daily for 12 weeks. Main results. Early terms of the CRD impact are characterized by the activation of the immune system against the background of metabolic shifts as well as by morphological changes of the immune nature in the bronchopulmonary system and liver of the rats that can be regarded as compensatory-adaptive. Prolonged exposure to the dust factor leads to an increase in dyslipidemia, which contributes to the development of immune imbalance as well as morphological changes that are indicative of the chronic inflammation and disturbance of compensatory mechanisms. Field of application. The results of the conducted experimental studies broaden the fundamental ideas about the mechanisms of immune body defense. The detection of pathogenetic mechanisms underlying the formation and course of occupational diseases allows assessing the functional state of the organism at the stage of pre-existing disease, revealing the initial signs of developing pathology and determining the ways of their correction. Conclusions. CRD intake is characterized by the development of metabolic changes, which are closely related to immune reactivity. An integrated approach to the study of occupational and industrially-caused pathology makes it possible to assess the

  16. Long-term strain response of polymer optical fiber FBG sensors

    DEFF Research Database (Denmark)

    Bundalo, Ivan-Lazar; Nielsen, Kristian; Woyessa, Getinet

    2017-01-01

    We report on the viscoelastic response of PMMA microstructured polymer optical fibers (mPOFs) when exposed to long periods of strain and relaxation, with the strain period ranging from 0.5 min to 50 min. The behavior of the fibers was monitored by inscribing a fiber Bragg grating (FBG) in them...... and tracking the reflection peak. We demonstrate that the fiber, when relaxing from strains of up to 0.9%, has a two-phase recovery: initially linear (elastic driven) and subsequently nonlinear (viscoelastic driven) contraction. The linear (elastic) relaxation wavelength range depends both on the strain level...

  17. Collagen Type III and VI Turnover in Response to Long-Term Immobilization

    DEFF Research Database (Denmark)

    Sun, Shu; Henriksen, Kim; Karsdal, Morten A

    2015-01-01

    with immobilization and/or remobilization. METHODS: In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week's strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured...... to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading....

  18. Biosynthetic hydrogels--studies on chemical and physical characteristics on long-term cellular response for tissue engineering.

    Science.gov (United States)

    Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

    2014-07-01

    Biosynthetic hydrogels can meet the drawbacks caused by natural and synthetic ones for biomedical applications. In the current article we present a novel biosynthetic alginate-poly(propylene fumarate) copolymer based chemically crosslinked hydrogel scaffolds for cardiac tissue engineering applications. Partially crosslinked PA hydrogel and fully cross linked PA-A hydrogel scaffolds were prepared. The influence of chemical and physical (morphology and architecture of hydrogel) characteristics on the long term cellular response was studied. Both these hydrogels were cytocompatible and showed no genotoxicity upon contact with fibroblast cells. Both PA and PA-A were able to resist deleterious effects of reactive oxygen species and sustain the viability of L929 cells. The hydrogel incubated oxidative stress induced cells were capable of maintaining the intra cellular reduced glutathione (GSH) expression to the normal level confirmed their protective effect. Relatively the PA hydrogel was found to be unstable in the cell culture medium. The PA-A hydrogel was able to withstand appreciable cyclic stretching. The cyclic stretching introduced complex macro and microarchitectural features with interconnected pores and more structured bound water which would provide long-term viability of around 250% after the 24th day of culture. All these qualities make PA-A hydrogel form a potent candidate for cardiac tissue engineering. © 2013 Wiley Periodicals, Inc.

  19. Improving simulated long-term responses of vegetation to temperature and precipitation extremes using the ACME land model

    Science.gov (United States)

    Ricciuto, D. M.; Warren, J.; Guha, A.

    2017-12-01

    While carbon and energy fluxes in current Earth system models generally have reasonable instantaneous responses to extreme temperature and precipitation events, they often do not adequately represent the long-term impacts of these events. For example, simulated net primary productivity (NPP) may decrease during an extreme heat wave or drought, but may recover rapidly to pre-event levels following the conclusion of the extreme event. However, field measurements indicate that long-lasting damage to leaves and other plant components often occur, potentially affecting the carbon and energy balance for months after the extreme event. The duration and frequency of such extreme conditions is likely to shift in the future, and therefore it is critical for Earth system models to better represent these processes for more accurate predictions of future vegetation productivity and land-atmosphere feedbacks. Here we modify the structure of the Accelerated Climate Model for Energy (ACME) land surface model to represent long-term impacts and test the improved model against observations from experiments that applied extreme conditions in growth chambers. Additionally, we test the model against eddy covariance measurements that followed extreme conditions at selected locations in North America, and against satellite-measured vegetation indices following regional extreme events.

  20. Long-term evolution of brainstem electrical evoked responses to sound after restricted ablation of the auditory cortex.

    Directory of Open Access Journals (Sweden)

    Verónica Lamas

    Full Text Available INTRODUCTION: This study aimed to assess the top-down control of sound processing in the auditory brainstem of rats. Short latency evoked responses were analyzed after unilateral or bilateral ablation of auditory cortex. This experimental paradigm was also used towards analyzing the long-term evolution of post-lesion plasticity in the auditory system and its ability to self-repair. METHOD: Auditory cortex lesions were performed in rats by stereotactically guided fine-needle aspiration of the cerebrocortical surface. Auditory Brainstem Responses (ABR were recorded at post-surgery day (PSD 1, 7, 15 and 30. Recordings were performed under closed-field conditions, using click trains at different sound intensity levels, followed by statistical analysis of threshold values and ABR amplitude and latency variables. Subsequently, brains were sectioned and immunostained for GAD and parvalbumin to assess the location and extent of lesions accurately. RESULTS: Alterations in ABR variables depended on the type of lesion and post-surgery time of ABR recordings. Accordingly, bilateral ablations caused a statistically significant increase in thresholds at PSD1 and 7 and a decrease in waves amplitudes at PSD1 that recover at PSD7. No effects on latency were noted at PSD1 and 7, whilst recordings at PSD15 and 30 showed statistically significant decreases in latency. Conversely, unilateral ablations had no effect on auditory thresholds or latencies, while wave amplitudes only decreased at PSD1 strictly in the ipsilateral ear. CONCLUSION: Post-lesion plasticity in the auditory system acts in two time periods: short-term period of decreased sound sensitivity (until PSD7, most likely resulting from axonal degeneration; and a long-term period (up to PSD7, with changes in latency responses and recovery of thresholds and amplitudes values. The cerebral cortex may have a net positive gain on the auditory pathway response to sound.

  1. Altered Polarization, Morphology, and Impaired Innate Immunity Germane to Resident Peritoneal Macrophages in Mice with Long-Term Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Hui-Fang Liu

    2012-01-01

    Full Text Available Type 2 diabetes (T2D is associated with perturbed innate immunity. Macrophages, bridging innate immunity and metabolic disturbances, play important roles in controlling immune homeostasis. However, the effect of long-term diabetic milieu (DM on the functions and phenotypes of macrophages is still not clear. In this study, we used resident peritoneal macrophages (RPMs from 5-month-old db/db mice to investigate the changes of macrophages. It was found that RPMs in db/db mice significantly reduced phagocytosis and adhesion capacity. After standardization with body weight, the number of F4/80+ RPMs markedly reduced in db/db mice, and, furthermore, the macrophages skewed to M2-polarizated macrophages. The results of morphology found that the RPMs shape of db/db mice was nearly round, but the RPMs shape of control mice was spindle-shaped and irregular. In this study, we found the cell numbers, morphology, and innate immunity functions of RPMs in 5-month-old type 2 diabetic mice (db/db mice obtained by abdominal cavity lavage were significantly altered. Importantly, we also found the remarkably increased M2-RPMs in diabetic mice for the first time.

  2. Water Relations, Gas Exchange, and Nutrient Response to a Long Term Constant Water Deficit

    Science.gov (United States)

    Berry, Wade L.; Goldstein, Guillermo; Dreschel, Thomas W.; Wheeler, Raymond M.; Sager, John C.; Knott, William M.

    1992-01-01

    Wheat plants (Triticum aestivum) were grown for 43 days in a micro-porous tube nutrient delivery system. Roots were unable to penetrate the microporous tube, but grew on the surface and maintained capillary contact with the nutrient solution on the inside of the tube through the 5-micron pores of the porous tube. Water potential in the system was controlled at -0.4, -0.8, and -3.0 kPa by adjusting the applied pressure (hydrostatic head) to the nutrient solution flowing through the microporous tubes. A relatively small decrease in applied water potential from -0.4 to -3.0 kPa resulted in a 34% reduction of shoot growth but only a moderate reduction in the midday leaf water potential from -1.3 to -1.7 MPa. Carbon dioxide assimilation decreased and water use efficiency increased with the more negative applied water potentials, while intercellular CO2 concentration remained constant. This was associated with a decrease in stomatal conductance to water vapor from 1.90 to 0.98 mol/(sq m sec) and a decrease in total apparent hydraulic conductance from 47 to 12 (micro)mol/(sec MPa). Although the applied water potentials were in the -0.4 to -3.0 kPa range, the actual water potential perceived by the plant roots appeared to be in the range of -0.26 to -0.38 MPa as estimated by the leaf water potential of bagged plants. The amount of K, Ca, Mg, Zn, Cu, and B accumulated with each unit of transpired water increased as the applied water potential became less negative. The increase in accumulation ranged from 1.4-fold for K to 2.2-fold for B. The physiological responses observed in this study in response to small constant differences in applied water potentials were much greater than expected from either the applied water potential or the observed plant water potential. Even though the micro-porous tube may not represent natural conditions and could possibly introduce morphological and physiological artifacts, it enables a high degree of control of water potential that

  3. Long-term effect of whole-body X-irradiation on cell-mediated immune reaction in mice

    International Nuclear Information System (INIS)

    Norimura, Toshiyuki; Tsuchiya, Takehiko

    1989-01-01

    Age-related change in immunological activity was examined at 10 to 91 weeks following whole-body irradiation by determining the specific anti-tumor cell-mediated immunity in host mice induced and/or enhanced by local irradiation to transplanted tumor. Median survival time of the non-irradiated C3H/He female mice was 98.6 weeks while the median life-span of the mice exposed to two and four Gy of 250 kVp X-rays at the age of 10-12 weeks was shortened by 14.9 and 23.4 weeks, respectively. The rate of tumor reduction within two weeks after local irradiation to tumor and the growth inhibitory activitiy of spleen cells from tumor irradiated mice were reduced in a dose-dependent manner when assessed 10 weeks after whole-body irradiation, but recovered to the near-complete level of the non-irradiated controls within a few months, then gradually decreased with normal aging. These results suggest that the age-dependent decline of this immunological activity apears earlier in the irradiated mice as a result of whole-body X-irradiation at a young age, suggesting accelerated aging of the immune system. (author)

  4. Environmental response to long-term mariculture activities in the Weihai coastal area, China.

    Science.gov (United States)

    Li, Hongmei; Li, Xiaomin; Li, Qiang; Liu, Ying; Song, Jide; Zhang, Yongyu

    2017-12-01

    The environmental impacts of rapid expansion of mariculture have garnered worldwide attention. China is currently one of the largest countries to engage in this practice. In this study, a representative mariculture zone, the Weihai coastal area in China, was explored to determine the temporal variations in regional nutrients, N/P ratio, dissolved oxygen (DO), pH, chlorophyll a (Chl-a), and cellular abundance of diatoms and dinoflagellates in response to the rapid growth in mariculture activities between 2006 and 2014. The temporal variations in inorganic and organic nitrogen concentrations in the surface water presented significantly increasing trends during August, between 2009 and 2014. A marked increase in the ratios of dinoflagellate to diatom abundance, concurrently with ascending N/P ratios, was also observed during August between 2011 and 2014. In addition, dissolved inorganic nitrogen and phosphate variations revealed the highest concentrations during October and lower levels during May and August, which was attributed in part to the seasonal growth characteristics of kelp cultivated in the study area. Moreover, the nutrient concentrations in Sanggou, Rongcheng, Wulei, and Rushan bays were affected significantly by the various cultured organisms in these bays. The intensive mariculture activity in the Weihai coastal area is likely one of the causes of the negative effects on water quality, such as eutrophication and future ocean acidification. The exploration of effective strategies is quite necessary in the future for keeping good quality of coastal environment and sustainable mariculture development. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Physiological responses of Tillandsia albida (Bromeliaceae) to long-term foliar metal application.

    Science.gov (United States)

    Kováčik, Jozef; Klejdus, Bořivoj; Stork, František; Hedbavny, Josef

    2012-11-15

    The impact of 2-month foliar application of cadmium, nickel and their combination (10 μM) on Tillandsia albida was studied. Cadmium caused damage of tissue but assimilation pigments were depressed in Cd+Ni variant only. Stress-related parameters (ROS and peroxidase activities) were elevated by Cd and Cd+Ni while MDA content remained unaffected. Free amino acids accumulated the most in Ni alone but soluble proteins were not influenced. Among phenolic acids, mainly vanillin contributed to increase of their sum in all variants while soluble phenols even decreased in Cd+Ni and flavonols slightly increased in Cd variants. Phenolic enzymes showed negligible responses to almost all treatments. Mineral nutrients (K, Ca, Na, Mg, Fe, and Zn) were not affected by metal application but N content increased. Total Cd or Ni amounts reached over 400 μg g(-1) DW and were not affected if metal alone and combined treatment is compared while absorbed content differed (ca. 50% of total Cd was absorbed while almost all Ni was absorbed). These data indicate tolerance of T. albida to foliar metal application and together with strong xerophytic morphology, use for environmental studies is recommended. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Historical land-use influences the long-term stream turbidity response to a wildfire.

    Science.gov (United States)

    Harrison, Evan T; Dyer, Fiona; Wright, Daniel W; Levings, Chris

    2014-02-01

    Wildfires commonly result in an increase in stream turbidity. However, the influence of pre-fire land-use practices on post-fire stream turbidity is not well understood. The Lower Cotter Catchment (LCC) in south-eastern Australia is part of the main water supply catchment for Canberra with land in the catchment historically managed for a mix of conservation (native eucalypt forest) and pine (Pinus radiata) plantation. In January 2003, wildfires burned almost all of the native and pine forests in the LCC. A study was established in 2005 to determine stream post-fire turbidity recovery within the native and pine forest areas of the catchment. Turbidity data loggers were deployed in two creeks within burned native forest and burned pine forest areas to determine turbidity response to fire in these areas. As a part of the study, we also determined changes in bare soil in the native and pine forest areas since the fire. The results suggest that the time, it takes turbidity levels to decrease following wildfire, is dependent upon the preceding land-use. In the LCC, turbidity levels decreased more rapidly in areas previously with native vegetation compared to areas which were previously used for pine forestry. This is likely because of a higher percentage of bare soil areas for a longer period of time in the ex-pine forest estate and instream stores of fine sediment from catchment erosion during post-fire storm events. The results of our study show that the previous land-use may exert considerable control over on-going turbidity levels following a wildfire.

  7. Physiological responses of Tillandsia albida (Bromeliaceae) to long-term foliar metal application

    Energy Technology Data Exchange (ETDEWEB)

    Kovacik, Jozef, E-mail: jozkovacik@yahoo.com [Institute of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, 613 00 Brno (Czech Republic); CEITEC - Central European Institute of Technology, Mendel University in Brno, Zemedelska 1, 613 00 Brno (Czech Republic); Klejdus, Borivoj [Institute of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, 613 00 Brno (Czech Republic); CEITEC - Central European Institute of Technology, Mendel University in Brno, Zemedelska 1, 613 00 Brno (Czech Republic); Stork, Frantisek [Department of Botany, Institute of Biology and Ecology, Faculty of Science, P. J. Safarik University, Manesova 23, 041 67 Kosice (Slovakia); Hedbavny, Josef [Institute of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, 613 00 Brno (Czech Republic)

    2012-11-15

    Highlights: Black-Right-Pointing-Pointer Impact of foliar Cd, Ni and Cd + Ni application on Tillandsia albida was studied. Black-Right-Pointing-Pointer Cd caused visible damage and enhanced stress parameters in combined treatment. Black-Right-Pointing-Pointer Nitrogenous compounds were slightly affected but phenols were up- and down-regulated. Black-Right-Pointing-Pointer Mineral nutrients (K, Ca, Na, Mg, Fe, and Zn) were not affected by any of treatments. Black-Right-Pointing-Pointer Total Cd or Ni reached ca. 0.04% and Ni was more absorbed than Cd. - Abstract: The impact of 2-month foliar application of cadmium, nickel and their combination (10 {mu}M) on Tillandsia albida was studied. Cadmium caused damage of tissue but assimilation pigments were depressed in Cd + Ni variant only. Stress-related parameters (ROS and peroxidase activities) were elevated by Cd and Cd + Ni while MDA content remained unaffected. Free amino acids accumulated the most in Ni alone but soluble proteins were not influenced. Among phenolic acids, mainly vanillin contributed to increase of their sum in all variants while soluble phenols even decreased in Cd + Ni and flavonols slightly increased in Cd variants. Phenolic enzymes showed negligible responses to almost all treatments. Mineral nutrients (K, Ca, Na, Mg, Fe, and Zn) were not affected by metal application but N content increased. Total Cd or Ni amounts reached over 400 {mu}g g{sup -1} DW and were not affected if metal alone and combined treatment is compared while absorbed content differed (ca. 50% of total Cd was absorbed while almost all Ni was absorbed). These data indicate tolerance of T. albida to foliar metal application and together with strong xerophytic morphology, use for environmental studies is recommended.

  8. Response of soil microbial communities and microbial interactions to long-term heavy metal contamination.

    Science.gov (United States)

    Li, Xiaoqi; Meng, Delong; Li, Juan; Yin, Huaqun; Liu, Hongwei; Liu, Xueduan; Cheng, Cheng; Xiao, Yunhua; Liu, Zhenghua; Yan, Mingli

    2017-12-01

    Due to the persistence of metals in the ecosystem and their threat to all living organisms, effects of heavy metal on soil microbial communities were widely studied. However, little was known about the interactions among microorganisms in heavy metal-contaminated soils. In the present study, microbial communities in Non (CON), moderately (CL) and severely (CH) contaminated soils were investigated through high-throughput Illumina sequencing of 16s rRNA gene amplicons, and networks were constructed to show the interactions among microbes. Results showed that the microbial community composition was significantly, while the microbial diversity was not significantly affected by heavy metal contamination. Bacteria showed various response to heavy metals. Bacteria that positively correlated with Cd, e.g. Acidobacteria_Gp and Proteobacteria_thiobacillus, had more links between nodes and more positive interactions among microbes in CL- and CH-networks, while bacteria that negatively correlated with Cd, e.g. Longilinea, Gp2 and Gp4 had fewer network links and more negative interactions in CL and CH-networks. Unlike bacteria, members of the archaeal domain, i.e. phyla Crenarchaeota and Euryarchaeota, class Thermoprotei and order Thermoplasmatales showed only positive correlation with Cd and had more network interactions in CH-networks. The present study indicated that (i) the microbial community composition, as well as network interactions was shift to strengthen adaptability of microorganisms to heavy metal contamination, (ii) archaea were resistant to heavy metal contamination and may contribute to the adaption to heavy metals. It was proposed that the contribution might be achieved either by improving environment conditions or by cooperative interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Physiological responses of Tillandsia albida (Bromeliaceae) to long-term foliar metal application

    International Nuclear Information System (INIS)

    Kováčik, Jozef; Klejdus, Bořivoj; Štork, František; Hedbavny, Josef

    2012-01-01

    Highlights: ► Impact of foliar Cd, Ni and Cd + Ni application on Tillandsia albida was studied. ► Cd caused visible damage and enhanced stress parameters in combined treatment. ► Nitrogenous compounds were slightly affected but phenols were up- and down-regulated. ► Mineral nutrients (K, Ca, Na, Mg, Fe, and Zn) were not affected by any of treatments. ► Total Cd or Ni reached ca. 0.04% and Ni was more absorbed than Cd. - Abstract: The impact of 2-month foliar application of cadmium, nickel and their combination (10 μM) on Tillandsia albida was studied. Cadmium caused damage of tissue but assimilation pigments were depressed in Cd + Ni variant only. Stress-related parameters (ROS and peroxidase activities) were elevated by Cd and Cd + Ni while MDA content remained unaffected. Free amino acids accumulated the most in Ni alone but soluble proteins were not influenced. Among phenolic acids, mainly vanillin contributed to increase of their sum in all variants while soluble phenols even decreased in Cd + Ni and flavonols slightly increased in Cd variants. Phenolic enzymes showed negligible responses to almost all treatments. Mineral nutrients (K, Ca, Na, Mg, Fe, and Zn) were not affected by metal application but N content increased. Total Cd or Ni amounts reached over 400 μg g −1 DW and were not affected if metal alone and combined treatment is compared while absorbed content differed (ca. 50% of total Cd was absorbed while almost all Ni was absorbed). These data indicate tolerance of T. albida to foliar metal application and together with strong xerophytic morphology, use for environmental studies is recommended.

  10. Dynamic sensorimotor planning during long-term sequence learning: the role of variability, response chunking and planning errors.

    Science.gov (United States)

    Verstynen, Timothy; Phillips, Jeff; Braun, Emily; Workman, Brett; Schunn, Christian; Schneider, Walter

    2012-01-01

    Many everyday skills are learned by binding otherwise independent actions into a unified sequence of responses across days or weeks of practice. Here we looked at how the dynamics of action planning and response binding change across such long timescales. Subjects (N = 23) were trained on a bimanual version of the serial reaction time task (32-item sequence) for two weeks (10 days total). Response times and accuracy both showed improvement with time, but appeared to be learned at different rates. Changes in response speed across training were associated with dynamic changes in response time variability, with faster learners expanding their variability during the early training days and then contracting response variability late in training. Using a novel measure of response chunking, we found that individual responses became temporally correlated across trials and asymptoted to set sizes of approximately 7 bound responses at the end of the first week of training. Finally, we used a state-space model of the response planning process to look at how predictive (i.e., response anticipation) and error-corrective (i.e., post-error slowing) processes correlated with learning rates for speed, accuracy and chunking. This analysis yielded non-monotonic association patterns between the state-space model parameters and learning rates, suggesting that different parts of the response planning process are relevant at different stages of long-term learning. These findings highlight the dynamic modulation of response speed, variability, accuracy and chunking as multiple movements become bound together into a larger set of responses during sequence learning.

  11. Early FDG PET response assessment of preoperative radiochemotherapy in locally advanced rectal cancer: correlation with long-term outcome

    International Nuclear Information System (INIS)

    Avallone, Antonio; Casaretti, Rossana; Montano, Massimo; Silvestro, Lucrezia; Aloj, Luigi; Caraco, Corradina; Di Gennaro, Francesca; Lastoria, Secondo; Delrio, Paolo; Pecori, Biagio; Tatangelo, Fabiana; Scott, Nigel; Budillon, Alfredo

    2012-01-01

    The aim of the present study is to prospectively evaluate the prognostic value of previously defined [ 18 F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) criteria of early metabolic response in patients with locally advanced rectal cancer (LARC) after long-term follow-up. Forty-two patients with poor prognosis LARC underwent three biweekly courses of chemotherapy with oxaliplatin, raltitrexed and 5-fluorouracil modulated by levofolinic acid during pelvic radiotherapy. FDG PET studies were performed before and 12 days after the beginning of the chemoradiotherapy (CRT) treatment. Total mesorectal excision (TME) was carried out 8 weeks after completion of CRT. A previously identified cutoff value of ≥52 % reduction of the baseline mean FDG standardized uptake value (SUV mean ) was applied to differentiate metabolic responders from non-responders and correlated to tumour regression grade (TRG) and survival. Twenty-two metabolic responders showed complete (TRG1) or subtotal tumour regression (TRG2) and demonstrated a statistically significantly higher 5-year relapse-free survival (RFS) compared with the 20 non-responders (86 vs 55 %, p =.014) who showed TRG3 and TRG4 pathologic responses. A multivariate analysis demonstrated that early ∇SUV mean was the only pre-surgical parameter correlated to the likelihood of recurrence (p =.05). This study is the first prospective long-term evaluation demonstrating that FDG PET is not only an early predictor of pathologic response but is also a valuable prognostic tool. Our results indicate the potential of FDG PET for optimizing multidisciplinary management of patients with LARC. (orig.)

  12. Adrenocortical and Adipose Responses to High-Altitude-Induced, Long-Term Hypoxia in the Ovine Fetus

    Directory of Open Access Journals (Sweden)

    Dean A. Myers

    2012-01-01

    Full Text Available By late gestation, the maturing hypothalamo-pituitary-adrenal (HPA axis aids the fetus in responding to stress. Hypoxia represents a significant threat to the fetus accompanying situations such as preeclampsia, smoking, high altitude, and preterm labor. We developed a model of high-altitude (3,820 m, long-term hypoxia (LTH in pregnant sheep. We describe the impact of LTH on the fetal HPA axis at the level of the hypothalamic paraventricular nucleus (PVN, anterior pituitary corticotrope, and adrenal cortex. At the PVN and anterior pituitary, the responses to LTH are consistent with hypoxia being a potent activator of the HPA axis and potentially maladaptive, while the adrenocortical response to LTH appears to be primarily adaptive. We discuss mechanisms involved in the delicate balance between these seemingly opposing responses that preserve the normal ontogenic rise in fetal plasma cortisol essential for organ maturation and in this species, birth. Further, we examine the response to, and ramifications of, an acute secondary stressor in the LTH fetus. We provide an integrative model on the potential role of adipose in modulating these responses to LTH. Integration of these adaptive responses to LTH plays a key role in promoting normal fetal growth and development under conditions of a chronic stress.

  13. Integrated response and transit time distributions of watersheds by combining hydrograph separation and long-term transit time modeling

    Directory of Open Access Journals (Sweden)

    M. C. Roa-García

    2010-08-01

    Full Text Available We present a new modeling approach analyzing and predicting the Transit Time Distribution (TTD and the Response Time Distribution (RTD from hourly to annual time scales as two distinct hydrological processes. The model integrates Isotope Hydrograph Separation (IHS and the Instantaneous Unit Hydrograph (IUH approach as a tool to provide a more realistic description of transit and response time of water in catchments. Individual event simulations and parameterizations were combined with long-term baseflow simulation and parameterizations; this provides a comprehensive picture of the catchment response for a long time span for the hydraulic and isotopic processes. The proposed method was tested in three Andean headwater catchments to compare the effects of land use on hydrological response and solute transport. Results show that the characteristics of events and antecedent conditions have a significant influence on TTD and RTD, but in general the RTD of the grassland dominated catchment is concentrated in the shorter time spans and has a higher cumulative TTD, while the forest dominated catchment has a relatively higher response distribution and lower cumulative TTD. The catchment where wetlands concentrate shows a flashier response, but wetlands also appear to prolong transit time.

  14. Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques

    International Nuclear Information System (INIS)

    Yankee, Thomas M.; Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

    2009-01-01

    Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of ΔvpuSHIV PPC , a live virus vaccine derived from SHIV PPC . Macaques were administered two inoculations of ΔvpuSHIV PPC , three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years

  15. An integrated stochastic multi-regional long-term energy planning model incorporating autonomous power systems and demand response

    International Nuclear Information System (INIS)

    Koltsaklis, Nikolaos E.; Liu, Pei; Georgiadis, Michael C.

    2015-01-01

    The power sector faces a rapid transformation worldwide from a dominant fossil-fueled towards a low carbon electricity generation mix. Renewable energy technologies (RES) are steadily becoming a greater part of the global energy mix, in particular in regions that have put in place policies and measures to promote their utilization. This paper presents an optimization-based approach to address the generation expansion planning (GEP) problem of a large-scale, central power system in a highly uncertain and volatile electricity industry environment. A multi-regional, multi-period linear mixed-integer linear programming (MILP) model is presented, combining optimization techniques with a Monte Carlo (MCA) method and demand response concepts. The optimization goal concerns the minimization of the total discounted cost by determining optimal power capacity additions per time interval and region, and the power generation mix per technology and time period. The model is evaluated on the Greek power system (GPS), taking also into consideration the scheduled interconnection of the mainland power system with those of selected autonomous islands (Cyclades and Crete), and aims at providing full insight into the composition of the long-term energy roadmap at a national level. - Highlights: • A spatial, multi-period, long-term generation expansion planning model is presented. • A Monte-Carlo method along with a demand response mechanism are incorporated. • Autonomous power systems interconnection is considered. • Electricity and CO 2 emission trade are taken into account. • Lignite, natural gas and wind power comprise the dominant power technologies

  16. Abnormal Savda syndrome: long-term consequences of emotional and physical stress on endocrine and immune activities in an animal model.

    Science.gov (United States)

    Ablimit, Adiljan; Kühnel, Harald; Strasser, Alois; Upur, Halmurat

    2013-08-01

    To investigate the relationship between emotional status, cold-dry environment and long-term immune responses to the stressors, and the potential pathological mechanisms between causative factors of abnormal Savda syndrome (ASS) and the susceptibility to disease; thus to clarify the ASS, and secondly to identify the optimal ASS animal model for further studies on traditional Uighur therapeutical formulations. Sixty mice were randomly and equally divided into 4 groups: control and 3 stress groups. The cold-dry environment was applied by keeping the mice in a climatic chamber. The emotional stress was induced by the application of the repeated electric foot-shocks in the electric foot-shock apparatus. The mice of the combined stress group underwent the repeated electric foot-shock treatment before being housed in the climatic chamber. The experimental routine was repeated for 21 days. In order to look into endocrine and immune stress responses, ELISA was used to determine the serum levels of the hormones corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), Beta-endorphin (β-END) and corticosterone (CORT), of the cytokines interleukin 2 (IL-2), interleukin 6 (IL-6), interferon-gamma (INF-γ) and tumor necrosis factor-alpha (TNF-α), and of the immunoglobulins immunoglobulin A (IgA), immunoglobulin M (IgM) and immunoglobulin G (IgG). Lymphocyte subsets were analyzed in duplicate in order to determine differences in the T cell ratio. In the cold-dry environment group, the serum levels of CRH, ACTH and CORT were significantly higher than those of the control group, whereas serum β-END was not found significantly different. In both the repeated electric foot-shock group as well as in the combined stress group the serum levels of CRH, ACTH, β-END and CORT were significantly higher. Compared to the control animals, the serum concentration of INF-γ was significantly lower in all three different stress groups. The serum level of IL-2 was decreased in

  17. Successive oral immunizations against Piscirickettsia salmonis and infectious salmon anemia virus are required to maintain a long-term protection in farmed salmonids

    Directory of Open Access Journals (Sweden)

    Ivan eTobar

    2015-05-01

    Full Text Available Currently, there is a growing demand to determine the protective status of vaccinated fish in order to prevent diseases outbreaks. A set of different parameters that include the infectious and immunological status of vaccinated salmonids from 622 Chilean farms were analyzed during 2011-2014. The aim of this study was to optimize the vaccination program of these centers through the determination of the protective state of vaccinated fish using oral immunizations. This state was measured by the association of the concentration of the immunoglobulin M (IgM in the serum and the mortality rate of vaccinated fish. Salmonids were vaccinated with different commercial mono- or polyvalent vaccines against SRS and ISAv, first by the intraperitoneal injection of oil-adjuvanted antigens and then by the stimulation of mucosal immunity using oral vaccines as booster. The results showed that high levels of specific IgM antibodies were observed after injectable vaccination, reaching a maximum concentration at 600-800 degree-days. Similar levels of antibodies were observed when oral immunizations were administrated. The high concentration of antibodies (above 2750 ng/mL for ISAv and 3500 ng/mL for SRS was maintained for a period of 800 degree-days after each vaccination procedure. In this regard, oral immunizations maintained a long-term high concentration of anti-SRS and anti-ISAv specific IgM antibodies. When the concentration of antibodies decreased below 2000 pg/mL, a window of susceptibility to SRS infection was observed in the farm, suggesting the close association between antibody levels and fish protective status. These results demonstrated that, in the field, several oral immunizations are essential to uphold a high level of specific anti-pathogens antibodies and, therefore, a protective status during the whole productive cycle.

  18. Low anti-staphylococcal IgG responses in granulomatosis with polyangiitis patients despite long-term Staphylococcus aureus exposure

    NARCIS (Netherlands)

    Glasner, Corinna; van Timmeren, Mirjan M; Stobernack, Tim; Omansen, Till F; Raangs, Gerwin; Rossen, John W; de Goffau, Marcus C; Arends, Jan P; Kampinga, Greetje A; Koedijk, Danny; Neef, Jolanda; Buist, Girbe; Tavakol, Mehri; van Wamel, Willem J B; Rutgers, Abraham; Stegeman, Coen A; Kallenberg, Cornelis; Heeringa, Peter; van Dijl, Jan Maarten

    2015-01-01

    Chronic nasal carriage of the bacterium Staphylococcus aureus in patients with the autoimmune disease granulomatosis with polyangiitis (GPA) is a risk factor for disease relapse. To date, it was neither known whether GPA patients show similar humoral immune responses to S. aureus as healthy

  19. Low anti-staphylococcal IgG responses in granulomatosis with polyangiitis patients despite long-term Staphylococcus aureus exposure

    NARCIS (Netherlands)

    C. Glasner (Corinna); M.M. Van Timmeren (Mirjan M.); T. Stobernack (Tim); T.F. Omansen (Till F.); E.C. Raangs (Erwin C.); J.W. Rossen (John); M.C. De Goffau (Marcus C.); J.P.A. Arends (Jan); G.A. Kampinga (Greetje); D.G.A.M. Koedijk (Denny); J. Neef (Jolanda); G. Buist (Girbe); M. Tavakol (Mehri); W.J.B. van Wamel (Willem); A. Rutgers (Abraham); C.A. Stegeman; C.G.M. Kallenberg (Cees G. M.); P. Heeringa (Peter); J.M. Dijl (Jan Maarten)

    2015-01-01

    textabstractChronic nasal carriage of the bacterium Staphylococcus aureus in patients with the autoimmune disease granulomatosis with polyangiitis (GPA) is a risk factor for disease relapse. To date, it was neither known whether GPA patients show similar humoral immune responses to S. aureus as

  20. A model integrating longshore and cross-shore processes for predicting long-term shoreline response to climate change

    Science.gov (United States)

    Vitousek, Sean; Barnard, Patrick; Limber, Patrick W.; Erikson, Li; Cole, Blake

    2017-01-01

    We present a shoreline change model for coastal hazard assessment and management planning. The model, CoSMoS-COAST (Coastal One-line Assimilated Simulation Tool), is a transect-based, one-line model that predicts short-term and long-term shoreline response to climate change in the 21st century. The proposed model represents a novel, modular synthesis of process-based models of coastline evolution due to longshore and cross-shore transport by waves and sea-level rise. Additionally, the model uses an extended Kalman filter for data assimilation of historical shoreline positions to improve estimates of model parameters and thereby improve confidence in long-term predictions. We apply CoSMoS-COAST to simulate sandy shoreline evolution along 500 km of coastline in Southern California, which hosts complex mixtures of beach settings variably backed by dunes, bluffs, cliffs, estuaries, river mouths, and urban infrastructure, providing applicability of the model to virtually any coastal setting. Aided by data assimilation, the model is able to reproduce the observed signal of seasonal shoreline change for the hindcast period of 1995-2010, showing excellent agreement between modeled and observed beach states. The skill of the model during the hindcast period improves confidence in the model's predictive capability when applied to the forecast period (2010-2100) driven by GCM-projected wave and sea-level conditions. Predictions of shoreline change with limited human intervention indicate that 31% to 67% of Southern California beaches may become completely eroded by 2100 under sea-level rise scenarios of 0.93 to 2.0 m.

  1. Response of soil physicochemical properties and enzyme activities to long-term reclamation of coastal saline soil, Eastern China.

    Science.gov (United States)

    Xie, Xuefeng; Pu, Lijie; Wang, Qiqi; Zhu, Ming; Xu, Yan; Zhang, Meng

    2017-12-31

    Soil enzyme activity during different years of reclamation and land use patterns could indicate changes in soil quality. The objective of this research is to explore the dynamics of 5 soil enzyme activities (dehydrogenase, amylase, urease, acid phosphatase and alkaline phosphatase) involved in C, N, and P cycling and their responses to changes in soil physicochemical properties resulting from long-term reclamation of coastal saline soil. Soil samples from a total of 55 sites were collected from a coastal reclamation area with different years of reclamation (0, 7, 32, 40, 63a) in this study. The results showed that both long-term reclamation and land use patterns have significant effects on soil physicochemical properties and enzyme activities. Compared with the bare flat, soil water content, soil bulk density, pH and electrical conductivity showed a decreasing trend after reclamation, whereas soil organic carbon, total nitrogen and total phosphorus tended to increase. Dehydrogenase, amylase and acid phosphatase activities initially increased and then decreased with increasing years of reclamation, whereas urease and alkaline phosphatase activities were characterized by an increase-decrease-increase trend. Moreover, urease, acid phosphatase and alkaline phosphatase activities exhibited significant differences between coastal saline soil with 63years of reclamation and bare flat, whereas dehydrogenase and amylase activities remained unchanged. Aquaculture ponds showed higher soil water content, pH and EC but lower soil organic carbon, total nitrogen and total phosphorus than rapeseed, broad bean and wheat fields. Rapeseed, broad bean and wheat fields displayed higher urease and alkaline phosphatase activities and lower dehydrogenase, amylase and acid phosphatase activities compared with aquaculture ponds. Redundancy analysis revealed that the soil physicochemical properties explained 74.5% of the variation in soil enzyme activities and that an obvious relationship

  2. Redox proteomics and physiological responses in Cistus albidus shrubs subjected to long-term summer drought followed by recovery.

    Science.gov (United States)

    Brossa, Ricard; Pintó-Marijuan, Marta; Francisco, Rita; López-Carbonell, Marta; Chaves, Maria Manuela; Alegre, Leonor

    2015-04-01

    The interaction between enzymatic and non-enzymatic antioxidants, endogenous levels of ABA and ABA-GE, the rapid recuperation of photosynthetic proteins under re-watering as well the high level of antioxidant proteins in previously drought-stressed plants under re-watering conditions, will contribute to drought resistance in plants subjected to a long-term drought stress under Mediterranean field conditions. This work provides an overview of the mechanisms of Cistus albidus acclimation to long-term summer drought followed by re-watering in Mediterranean field conditions. To better understand the molecular mechanisms of drought resistance in these plants, a proteomic study using 2-DE and MALDI-TOF/TOF MS/MS was performed on leaves from these shrubs. The analysis identified 57 differentially expressed proteins in water-stressed plants when contrasted to well watered. Water-stressed plants showed an increase, both qualitatively and quantitatively, in HSPs, and downregulation of photosynthesis and carbon metabolism enzymes. Under drought conditions, there was considerable upregulation of enzymes related to redox homeostasis, DHA reductase, Glyoxalase, SOD and isoflavone reductase. However, upregulation of catalase was not observed until after re-watering was carried out. Drought treatment caused an enhancement in antioxidant defense responses that can be modulated by ABA, and its catabolites, ABA-GE, as well as JA. Furthermore, quantification of protein carbonylation was shown to be a useful marker of the relationship between water and oxidative stress, and showed that there was only moderate oxidative stress in C. albidus plants subjected to water stress. After re-watering plants recovered although the levels of ABA-GE and antioxidant enzymes still remain higher than in well-watered plants. We expect that our results will provide new data on summer acclimation to drought stress in Mediterranean shrubs.

  3. Long-term Increases in Flower Production by Growth Forms in Response to Anthropogenic Change in a Tropical Forest

    Science.gov (United States)

    Pau, S.; Wright, S. J.

    2016-12-01

    There is mounting evidence that anthropogenic global change is altering the ecology of tropical forests. A limited number of studies have focused on long-term trends in tropical reproductive activity, yet differences in reproductive activity should have consequences for demography and ultimately forest carbon, water, and energy balance. Here we analyze a 28-year record of tropical flower production in response to anthropogenic climate change. We show that a multi-decadal increase in flower production is most strongly driven by rising atmospheric CO2, which had approximately 8x the effect of the Multivariate ENSO Index and approximately 13x the effect of rainfall or solar radiation. Interannual peaks in flower production were associated with greater solar radiation and low rainfall during El Niño years. Observed changes in solar radiation explained flower production better than rainfall (models including solar radiation accounted for 94% of cumulative AICc weight compared to 87% for rainfall). All growth forms (lianas, canopy trees, midstory trees, and shrubs) produced more flowers with increasing CO2 except for understory treelets. The increase in flower production was matched by a lengthening of flowering duration for canopy trees and midstory trees; duration was also longer for understory treelets. Given that anthropogenic CO2 emissions will continue to climb over the next century, the long-term increase in flower production may persist unless offset by increasing cloudiness in the tropics, or until rising CO2 and/or warming temperatures associated with the greenhouse effect pass critical thresholds for plant reproduction.

  4. Long-term plasticity determines the postsynaptic response to correlated afferents with multivesicular short-term synaptic depression

    Directory of Open Access Journals (Sweden)

    Alexander David Bird

    2014-01-01

    Full Text Available Synchrony in a presynaptic population leads to correlations in vesicle occupancy at the active sites for neurotransmitter release. The number of independent release sites per presynaptic neuron, a synaptic parameter recently shown to be modifed during long-term plasticity, will modulate these correlations and therefore have a significant effect on the firing rate of the postsynaptic neuron. To understand how correlations from synaptic dynamics and from presynaptic synchrony shape the postsynaptic response, we study a model of multiple release site short-term plasticity and derive exact results for the crosscorrelation function of vesicle occupancy and neurotransmitter release, as well as the postsynaptic voltage variance. Using approximate forms for the postsynaptic firing rate in the limits of low and high correlations, we demonstrate that short-term depression leads to a maximum response for an intermediate number of presynaptic release sites, and that this leads to a tuning-curve response peaked at an optimal presynaptic synchrony setby the number of neurotransmitter release sites per presynaptic neuron. These effects arise because, above a certain level of correlation, activity in the presynaptic population is overly strong resulting in wastage of the pool of releasable neurotransmitter. As the nervous system operates under constraints of efficient metabolism it is likely that this phenomenon provides an activity-dependent constraint on network architecture.

  5. Quantitative analysis of the acute and long-term CD4(+) T-cell response to a persistent gammaherpesvirus

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Doherty, P C

    1999-01-01

    The murine gammaherpesvirus 68 (MHV-68) replicates in respiratory epithelial cells, where it establishes a persistent, latent infection limited predominantly to B lymphocytes. The virus-specific CD4(+) T-cell response in C57BL/6 mice challenged intranasally with MHV-68 is detected first...... in the mediastinal lymph nodes and then in the cervical lymph nodes and the spleen. The numbers of MHV-68-specific CD4(+) T cells generated in congenic mice homozygous for disruption of the beta2-microglobulin gene tended to be higher, indicating that the absence of the CD8(+) set in this group resulted...... in a compensatory response. The peak frequency within the splenic CD4(+) T-cell population may reach 1:50 in the acute response; it then drops to 1:400 to 1:500 within 4 months and stays at that level in the very long term. Sorting for L-selectin (CD62L) expression established that all virus-specific CD4(+) T cells...

  6. Association of Clinical Response and Long-term Outcome Among Patients With Biopsied Orbital Pseudotumor Receiving Modern Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Prabhu, Roshan S., E-mail: rprabhu@emory.edu [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Kandula, Shravan; Liebman, Lang [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Wojno, Ted H.; Hayek, Brent [Division of Oculoplastics, Orbital and Cosmetic Surgery, Emory University, Atlanta, Georgia (United States); Hall, William A.; Shu, Hui-Kuo; Crocker, Ian [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2013-03-01

    Purpose: To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). Methods and Materials: Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without an increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). Results: Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. Conclusions: RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors.

  7. Association of Clinical Response and Long-term Outcome Among Patients With Biopsied Orbital Pseudotumor Receiving Modern Radiation Therapy

    International Nuclear Information System (INIS)

    Prabhu, Roshan S.; Kandula, Shravan; Liebman, Lang; Wojno, Ted H.; Hayek, Brent; Hall, William A.; Shu, Hui-Kuo; Crocker, Ian

    2013-01-01

    Purpose: To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). Methods and Materials: Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without an increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). Results: Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. Conclusions: RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors

  8. Enhanced Stress Response in 5-HT1AR Overexpressing Mice: Altered HPA Function and Hippocampal Long-Term Potentiation.

    Science.gov (United States)

    Pilar-Cuéllar, Fuencisla; Vidal, Rebeca; Díaz, Álvaro; Garro-Martínez, Emilio; Linge, Raquel; Castro, Elena; Haberzettl, Robert; Fink, Heidrun; Bert, Bettina; Brosda, Jan; Romero, Beatriz; Crespo-Facorro, Benedicto; Pazos, Ángel

    2017-11-15

    Postsynaptic 5-HT 1A receptors (5-HT 1A R) play an important role in anxiety and stress, although their contribution is still controversial. Previous studies report that mice overexpressing postsynaptic 5-HT 1A Rs show no changes in basal anxiety, though the influence of stress conditions has not been addressed yet. In this study, we used this animal model to evaluate the role of 5-HT 1A Rs in anxiety response after pre-exposure to an acute stressor. Under basal conditions, 5-HT 1A R overexpressing animals presented high corticosterone levels and a lower mineralocorticoid/glucocorticoid receptor ratio. After pre-exposure to a single stressor, they showed a high anxiety-like response, associated with a blunted increase in corticosterone levels and higher c-Fos activation in the prefrontal cortex. Moreover, these mice also presented a lack of downregulation of hippocampal long-term potentiation after stress exposure. Therefore, higher postsynaptic 5-HT 1A R activation might predispose to a high anxious phenotype and an impaired stress coping behavior.

  9. A Methodology to Infer Crop Yield Response to Climate Variability and Change Using Long-Term Observations

    Directory of Open Access Journals (Sweden)

    Manfred A. Lange

    2013-11-01

    Full Text Available A new methodology to extract crop yield response to climate variability and change from long-term crop yield observations is presented in this study. In contrast to the existing first-difference approach (FDA, the proposed methodology considers that the difference in value between crop yields of two consecutive years reflects necessarily the contributions of climate and management conditions, especially at large spatial scales where both conditions may vary significantly from one year to the next. Our approach was applied to remove the effect of non-climatic factors on crop yield and, hence, to isolate the effect of the observed climate change between 1961 and 2006 on three widely crops grown in three Mediterranean countries—namely wheat, corn and potato—using national-level crop yield observations’ time-series. Obtained results show that the proposed methodology provides us with a ground basis to improve substantially our understanding of crop yield response to climate change at a scale that is relevant to large-scale estimations of agricultural production and to food security analyses; and therefore to reduce uncertainties in estimations of potential climate change effects on agricultural production. Furthermore, a comparison of outputs of our methodology and FDA outputs yielded a difference in terms of maize production in Egypt, for example, that exceeds the production of some neighbouring countries.

  10. Predicting long-term temperature increase for time-dependent SAR levels with a single short-term temperature response.

    Science.gov (United States)

    Carluccio, Giuseppe; Bruno, Mary; Collins, Christopher M

    2016-05-01

    Present a novel method for rapid prediction of temperature in vivo for a series of pulse sequences with differing levels and distributions of specific energy absorption rate (SAR). After the temperature response to a brief period of heating is characterized, a rapid estimate of temperature during a series of periods at different heating levels is made using a linear heat equation and impulse-response (IR) concepts. Here the initial characterization and long-term prediction for a complete spine exam are made with the Pennes' bioheat equation where, at first, core body temperature is allowed to increase and local perfusion is not. Then corrections through time allowing variation in local perfusion are introduced. The fast IR-based method predicted maximum temperature increase within 1% of that with a full finite difference simulation, but required less than 3.5% of the computation time. Even higher accelerations are possible depending on the time step size chosen, with loss in temporal resolution. Correction for temperature-dependent perfusion requires negligible additional time and can be adjusted to be more or less conservative than the corresponding finite difference simulation. With appropriate methods, it is possible to rapidly predict temperature increase throughout the body for actual MR examinations. © 2015 Wiley Periodicals, Inc.

  11. Long-term responses of rainforest erosional systems at different spatial scales to selective logging and climatic change

    Science.gov (United States)

    Walsh, R. P. D.; Bidin, K.; Blake, W. H.; Chappell, N. A.; Clarke, M. A.; Douglas, I.; Ghazali, R.; Sayer, A. M.; Suhaimi, J.; Tych, W.; Annammala, K. V.

    2011-01-01

    Long-term (21–30 years) erosional responses of rainforest terrain in the Upper Segama catchment, Sabah, to selective logging are assessed at slope, small and large catchment scales. In the 0.44 km2 Baru catchment, slope erosion measurements over 1990–2010 and sediment fingerprinting indicate that sediment sources 21 years after logging in 1989 are mainly road-linked, including fresh landslips and gullying of scars and toe deposits of 1994–1996 landslides. Analysis and modelling of 5–15 min stream-suspended sediment and discharge data demonstrate a reduction in storm-sediment response between 1996 and 2009, but not yet to pre-logging levels. An unmixing model using bed-sediment geochemical data indicates that 49 per cent of the 216 t km−2 a−1 2009 sediment yield comes from 10 per cent of its area affected by road-linked landslides. Fallout 210Pb and 137Cs values from a lateral bench core indicate that sedimentation rates in the 721 km2 Upper Segama catchment less than doubled with initially highly selective, low-slope logging in the 1980s, but rose 7–13 times when steep terrain was logged in 1992–1993 and 1999–2000. The need to keep steeplands under forest is emphasized if landsliding associated with current and predicted rises in extreme rainstorm magnitude-frequency is to be reduced in scale. PMID:22006973

  12. Cytokines related to three major types of cell-mediated immunity in short- and long-term exposures to lead compounds.

    Science.gov (United States)

    Dobrakowski, Michał; Boroń, Marta; Czuba, Zenon P; Kasperczyk, Aleksandra; Machoń-Grecka, Anna; Kasperczyk, Sławomir

    2016-11-01

    Many investigators have posited on the significant influence of lead on the immune system function. However, available data on this topic are not conclusive. Therefore, a study was undertaken to examine associations between lead exposure and levels of cytokines related to the T-helper (T H )-1, T H 2, and T H 17 types of immune response in humans. For these analyses, three population groups were examined: the first consisted of male workers exposed to lead for a short period of time (36-44 days); the second included male workers chronically exposed to lead (13 ± 10 years); and a control group that was composed of male administrative workers with blood lead levels (BLL) immune responses, while chronic exposure modifies their levels. Taken together, these modifications do not evidence an ability of lead to promote specifically one type of immune response in an exposed host.

  13. [Bone marrow stromal damage mediated by immune response activity].

    Science.gov (United States)

    Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

    1994-01-01

    The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

  14. Cerebrospinal fluid analysis for HIV replication and biomarkers of immune activation and neurodegeneration in long-term atazanavir/ritonavir monotherapy treated patients.

    Science.gov (United States)

    Ferretti, Francesca; Bigoloni, Alba; Passeri, Laura; Galli, Laura; Longo, Valeria; Gerevini, Simonetta; Spagnuolo, Vincenzo; Gisslen, Magnus; Zetterberg, Henrik; Fuchs, Dietmar; Cattaneo, Dario; Caramatti, Giada; Lazzarin, Adriano; Cinque, Paola; Castagna, Antonella

    2016-07-01

    Cerebrospinal fluid (CSF) viral escape is a concern in ritonavir-boosted protease inhibitors monotherapy. The aim was to assess HIV-RNA, biomarkers of immune activation and neurodegeneration, and atazanavir concentrations in CSF of patients on successful long-term atazanavir/ritonavir (ATV/r) monotherapy. This is a substudy of the multicentric, randomized, open-label, noninferiority trial monotherapy once a day with atazanavir/ritonavir (NCT01511809), comparing the ongoing ATV/r along with 2 nucleoside retrotranscriptase inhibitors (NRTIs) regimen to a simplified ATV/r monotherapy. Patients with plasma HIV-RNA < 50 copies/mL after at least 96 study weeks were eligible.We assessed HIV-RNA, soluble (s)CD14, sCD163, CCL2, CXCL10, interleukin-6, and YKL40 by enzyme-linked immunosorbent assay; neopterin, tryptophan, kynurenine, and neurofilament by immunoassays; and ATV concentrations by liquid chromatography-mass spectrometry in paired plasma and CSF samples. Variables were compared with Wilcoxon rank-sum or Fisher exact test, as appropriate. HIV-RNA was detected in the CSF of 1/11 patients on ATV/r monotherapy (114 copies/mL), without neurological symptoms, who was successfully reintensified with his previous 2NRTIs, and in none of the 12 patients on ATV/r + 2NRTIs. CSF biomarkers and ATV concentrations did not differ between the 2 arms. CSF escape was uncommon in patients on long-term ATV/r monotherapy and was controlled with reintensification.

  15. Corticosterone stress response shows long-term repeatability and links to personality in free-living Nazca boobies.

    Science.gov (United States)

    Grace, Jacquelyn K; Anderson, David J

    2014-11-01

    The concept of "coping styles", or consistently different responses to stressors, is of broad interest in behavioral ecology and biomedicine. Two critical predictions of this concept are individual consistency of neurophysiological and behavioral responses (relative to population variability) and a negative relationship between aggression/proactivity and hypothalamic-pituitary-adrenal axis reactivity. Recent studies failed to provide strong support for these predictions, especially outside of strictly controlled conditions, and long-term measures to test the first prediction are rare. Here, we demonstrate individual repeatability across 2-3years of maximum circulating corticosterone concentration [CORT] and area under the [CORT] response curve (AUCI) during a standard capture-restraint test in wild, free-living adult Nazca boobies (Sula granti). We also show that the stress response predicts the personality traits aggression and anxiety in these birds (measured in the wild); however, the strength of these results was weak. Maximum [CORT] and AUCI showed higher repeatability between years than baseline [CORT]. After controlling breeding status, sex, mass, date sampled, and their interactions, baseline [CORT] was most closely related to personality traits, followed by AUCI, and then maximum [CORT]. The direction of these relationships depended on whether the testing context was social or non-social. [CORT] parameters had little to no relationship with cross-context plasticity in personality traits. Our results generally affirm two critical predictions of coping styles, but match the emerging trend that these relationships are weak in the wild, and may depend on testing context. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Long-term persistence of robust antibody and cytotoxic T cell responses in recovered patients infected with SARS coronavirus.

    Directory of Open Access Journals (Sweden)

    Taisheng Li

    2006-12-01

    Full Text Available Most of the individuals infected with SARS coronavirus (SARS-CoV spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.

  17. Prior exposure to interpersonal violence and long-term treatment response for boys with a disruptive behavior disorder.

    Science.gov (United States)

    Shenk, Chad E; Dorn, Lorah D; Kolko, David J; Rausch, Joseph R; Insana, Salvatore P

    2014-10-01

    Interpersonal violence (IPV) is common in children with a disruptive behavior disorder (DBD) and increases the risk for greater DBD symptom severity, callous-unemotional (CU) traits, and neuroendocrine disruption. Thus, IPV may make it difficult to change symptom trajectories for families receiving DBD interventions given these relationships. The current study examined whether IPV prior to receiving treatment for a DBD predicted trajectories of a variety of associated outcomes, specifically DBD symptoms, CU traits, and cortisol concentrations. Boys with a DBD diagnosis (N = 66; age range = 6-11 years; 54.5% of whom experienced IPV prior to treatment) of either oppositional defiant disorder or conduct disorder participated in a randomized clinical trial and were assessed 3 years following treatment. Multilevel modeling demonstrated that prior IPV predicted smaller rates of change in DBD symptoms, CU traits, and cortisol trajectories, indicating less benefit from intervention. The effect size magnitudes of IPV were large for each outcome (d = 0.88-1.07). These results suggest that IPV is a predictor of the long-term treatment response for boys with a DBD. Including trauma-focused components into existing DBD interventions may be worth testing to improve treatment effectiveness for boys with a prior history of IPV. Copyright © 2014 International Society for Traumatic Stress Studies.

  18. Long-term memory for instrumental responses does not undergo protein synthesis-dependent reconsolidation upon retrieval.

    Science.gov (United States)

    Hernandez, Pepe J; Kelley, Ann E

    2004-01-01

    Recent evidence indicates that certain forms of memory, upon recall, may return to a labile state requiring the synthesis of new proteins in order to preserve or reconsolidate the original memory trace. While the initial consolidation of "instrumental memories" has been shown to require de novo protein synthesis in the nucleus accumbens, it is not known whether memories of this type undergo protein synthesis-dependent reconsolidation. Here we show that low doses of the protein synthesis inhibitor anisomycin (ANI; 5 or 20 mg/kg) administered systemically in rats immediately after recall of a lever-pressing task potently impaired performance on the following daily test sessions. We determined that the nature of this impairment was attributable to conditioned taste aversion (CTA) to the sugar reinforcer used in the task rather than to mnemonic or motoric impairments. However, by substituting a novel flavored reinforcer (chocolate pellets) prior to the administration of doses of ANI (150 or 210 mg/kg) previously shown to cause amnesia, a strong CTA to chocolate was induced sparing any aversion to sugar. Importantly, when sugar was reintroduced on the following session, we found that memory for the task was not significantly affected by ANI. Thus, these data suggest that memory for a well-learned instrumental response does not require protein synthesis-dependent reconsolidation as a means of long-term maintenance.

  19. Cross-sectional Survey of Long-Term Care Facilities in the Rockaway Peninsula: Preparedness and Response During Hurricane Sandy.

    Science.gov (United States)

    Jiang, Lynn; Tedeschi, Christopher; Subaiya, Saleena

    2018-04-01

    Few studies have described the challenges experienced by long-term care facilities (LTCFs) following Hurricane Sandy. This study examined LTCF preparedness and experiences during and after the storm. A cross-sectional survey was conducted 2 years after Hurricane Sandy to assess LTCF demographics, preparation, and post-storm resources. Surveys were conducted at LTCFs located on the Rockaway Peninsula of New York City. All LTCFs located in a heavily affected area were approached. Of 29 facilities, 1 had closed, 5 did not respond, 9 declined to participate, and 14 participated, yielding a response rate of 50% for open facilities. Twenty-one percent of the facilities had preparations specifically for hurricanes. More than 70% of the facilities had lost electricity, heat, and telephone service, and one-half had evacuated. Twenty-one percent of the facilities reported not receiving any assistance and over one-half reported that relief resources did not meet their needs. Many LTCFs lacked plans specific to such a large-scale event. Since nearly all of the LTCFs in the region were affected, preexisting transportation and housing plans may have been inadequate. Future preparation could include hazard-specific planning and reliance on resources from a wider geographic area. Access to electricity emerged as a top priority. (Disaster Med Public Health Preparedness. 2018;12:194-200).

  20. Long-term change of site response after the M W 9.0 Tohoku earthquake in Japan

    Science.gov (United States)

    Wu, Chunquan; Peng, Zhigang

    2012-12-01

    The recent M W 9.0 off the Pacific coast of Tohoku earthquake is the largest recorded earthquake in Japan's history. The Tohoku main shock and its aftershocks generated widespread strong shakings as large as ~3000 Gal along the east coast of Japan. Wu and Peng (2011) found clear drop of resonant frequency of up to 70% during the Tohoku main shock at 6 sites and correlation of resonance (peak) frequency and peak ground acceleration (PGA) during the main shock. Here we follow that study and systematically analyze long-term changes of material properties in the shallow crust from one year before to 5 months after the Tohoku main shock, using seismic data recorded by the Japanese Strong Motion Network KiK-Net. We use sliding window spectral ratios computed from a pair of surface and borehole stations to track the temporal changes in the site response of 6 sites. Our results show two stages of logarithmic recovery after a sharp drop of resonance frequency during the Tohoku main shock. The first stage is a rapid recovery within several hundred seconds to several hours, and the second stage is a slow recovery of more than five months. We also investigate whether the damage caused by the Tohoku main shock could make the near surface layers more susceptible to further damages, but we do not observe clear changes in susceptibility to further damage before and after the Tohoku main shock.

  1. Long-term dynamics of tropical walking sticks in response to multiple large-scale and intense disturbances.

    Science.gov (United States)

    Willig, Michael R; Presley, Steven J; Bloch, Christopher P

    2011-02-01

    Understanding the effects of disturbance and secondary succession on spatio-temporal patterns in the abundance of species is stymied by a lack of long-term demographic data, especially in response to infrequent and high intensity disturbances, such as hurricanes. Moreover, resistance and resilience to hurricane-induced disturbance may be mediated by legacies of previous land use, although such interactive effects are poorly understood, especially in tropical environments. We address these central issues in disturbance ecology by analyzing an extensive dataset, spanning the impacts of Hurricanes Hugo and Georges, on the abundance of a Neotropical walking stick, Lamponius portoricensis, in tabonuco rainforest of Puerto Rico during the wet and dry seasons from 1991 to 2007. By synthesizing data from two proximate sites in tabonuco forest, we show that resistance to Hurricane Hugo (97% reduction in abundance) was much less than resistance to Hurricane Georges (21% reduction in abundance). Based on a powerful statistical approach (generalized linear mixed-effects models with Poisson error terms), we documented that the temporal trajectories of abundance during secondary succession (i.e., patterns of resilience) differed between hurricanes and among historical land use categories, but that the effects of hurricanes and land use histories were independent of each other. These complex results likely arise because of differences in the intensities of the two hurricanes with respect to microclimatic effects (temperature and moisture) in the forest understory, as well as to time-lags in the response of L. portoricensis to changes in the abundance and distribution of preferred food plants (Piper) in post-hurricane environments.

  2. Antenatal maternal long-term hypoxia: acclimatization responses with altered gene expression in ovine fetal carotid arteries.

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

    Full Text Available In humans and other species, long-term hypoxia (LTH during pregnancy can lead to intrauterine growth restriction with reduced body/brain weight, dysregulation of cerebral blood flow (CBF, and other problems. To identify the signal transduction pathways and critical molecules, which may be involved in acclimatization to high altitude LTH, we conducted microarray with advanced bioinformatic analysis on carotid arteries (CA from the normoxic near-term ovine fetus at sea-level and those acclimatized to high altitude for 110+ days during gestation. In response to LTH acclimatization, in fetal CA we identified mRNA from 38 genes upregulated >2 fold (P2-fold (P<0.05. The major genes with upregulated mRNA were SLC1A3, Insulin-like growth factor (IGF binding protein 3, IGF type 2 receptor, transforming growth factor (TGF Beta-3, and genes involved in the AKT and BCL2 signal transduction networks. Most genes with upregulated mRNA have a common motif for Pbx/Knotted homeobox in the promoter region, and Sox family binding sites in the 3' un translated region (UTR. Genes with downregulated mRNA included those involved in the P53 pathway and 5-lipoxygenase activating proteins. The promoter region of all genes with downregulated mRNA, had a common 49 bp region with a binding site for DOT6 and TOD6, components of the RPD3 histone deacetylase complex RPD3C(L. We also identified miRNA complementary to a number of the altered genes. Thus, the present study identified molecules in the ovine fetus, which may play a role in the acclimatization response to high-altitude associated LTH.

  3. Comment and response document for the long-term surveillance plan for the Bodo Canyon Disposal Site, Durango, Colorado, Revision 0

    International Nuclear Information System (INIS)

    1995-11-01

    This report contains the comment and response document for the Draft Long-Term Surveillance Plan of the Bodo Canyon Site in Durango, California. This is a part of the Uranium Mill Tailings Remedial Action (UMTRA) Project. Questions and comments regarding specific sections or statements in the report are described and then a response to each review comment or question is provided

  4. Behavioural and physiological responses of heifer calves to acute stressors : Long-term consistency and relationship with adult reactivity to milking

    NARCIS (Netherlands)

    Van Reenen, Cornelis G.; Van der Werf, Jozef T. N.; O'Connell, Niamh E.; Heutinck, Leonie F. M.; Spoolder, Hans A. M.; Jones, R. Bryan; Koolhaas, Jaap M.; Blokhuis, Harry J.; O’Connell, Niamh E.

    The present study investigated the long-term consistency of individual differences in dairy cattles' responses in tests of behavioural and hypothalamo-pituitary-adrenocortical (HPA) axis reactivity, as well as the relationship between responsiveness in behavioural tests and the reaction to first

  5. Behavioural and physiological responses of heifer calves to acute stressors: Long-term consistency and relationship with adult reactivity to milking

    NARCIS (Netherlands)

    Reenen, van C.G.; Werf, van der J.T.N.; O'Connell, N.E.; Heutinck, L.F.M.; Spoolder, H.A.M.; Jones, R.B.; Koolhaas, J.M.; Blokhuis, H.J.

    2013-01-01

    The present study investigated the long-term consistency of individual differences in dairy cattles’ responses in tests of behavioural and hypothalamo–pituitary–adrenocortical (HPA) axis reactivity, as well as the relationship between responsiveness in behavioural tests and the reaction to first

  6. Transient nature of long-term nonprogression and broad virus-specific proliferative T-cell responses with sustained thymic output in HIV-1 controllers.

    Directory of Open Access Journals (Sweden)

    Samantha J Westrop

    Full Text Available HIV-1(+ individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+ T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+ individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+ patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory.

  7. A prospective study of long-term results and the red blood cell immune adherence function following 131I treatment of Graves' disease

    International Nuclear Information System (INIS)

    Sun Zengjun; Ma Yuqin; Liu Junqing; Zhang Xia

    2003-01-01

    Objective: To observe the long-term curative effect and red blood cell immune function in patients with Graves' Disease (GD) after radioactive iodine ( 131 I) treatment. Methods: To observe the hyperthyroid symptoms, physical signs and to measure the concentration of FT3, FT4, FSH by radioimmunoassay, the percent of RBC-C 3b R-YR(%), RBC-IC-YR(%). Results: Patients with GD treated by 131 I after three month, these hyperthyroid symptoms, Physical signs are alleviated and even vanished in patients who were treated by 131 I after 1.5 years, RBC-C 3b R-YR(%) are normal in all patients, but RBC-IC-YR(%) are higher than before treatment with 131 I, then become lower after three months, treatment by 131 I but they were higher than those in normal group, when treated with 131 I after 1.5 years, RBC-IC-YR(%) are normal, the relationship between RBC-C 3b R-YR(%) and RBC-IC-YR(%) are positively interacted. Conclusion: The 131 I treatment produces a good rapid curative effect for GD patients, the disorder state of the red cell immune adherence system is rapidly corrected and this effect is unidirectional. So RBC-C 3b R-YR(%), RBC-IC-YR(%) are the useful predictors of GD remission and their relationship, RBC-IC-YR(%) are helpful in explaining the mechanism of radioactive iodine therapy and are the predictors of GD remission after 131 I treatment

  8. Differential response of carbon cycling to long-term nutrient input and altered hydrological conditions in a continental Canadian peatland

    Science.gov (United States)

    Berger, Sina; Praetzel, Leandra S. E.; Goebel, Marie; Blodau, Christian; Knorr, Klaus-Holger

    2018-02-01

    Peatlands play an important role in global carbon cycling, but their responses to long-term anthropogenically changed hydrologic conditions and nutrient infiltration are not well known. While experimental manipulation studies, e.g., fertilization or water table manipulations, exist on the plot scale, only few studies have addressed such factors under in situ conditions. Therefore, an ecological gradient from the center to the periphery of a continental Canadian peatland bordering a eutrophic water reservoir, as reflected by increasing nutrient input, enhanced water level fluctuations, and increasing coverage of vascular plants, was used for a case study of carbon cycling along a sequence of four differently altered sites. We monitored carbon dioxide (CO2) and methane (CH4) surface fluxes and dissolved inorganic carbon (DIC) and CH4 concentrations in peat profiles from April 2014 through September 2015. Moreover, we studied bulk peat and pore-water quality and we applied δ13C-CH4 and δ13C-CO2 stable isotope abundance analyses to examine dominant CH4 production and emission pathways during the growing season of 2015. We observed differential responses of carbon cycling at the four sites, presumably driven by abundances of plant functional types and vicinity to the reservoir. A shrub-dominated site in close vicinity to the reservoir was a comparably weak sink for CO2 (in 1.5 years: -1093 ± 794, in 1 year: +135 ± 281 g CO2 m-2; a net release) as compared to two graminoid-moss-dominated sites and a moss-dominated site (in 1.5 years: -1552 to -2260 g CO2 m-2, in 1 year: -896 to -1282 g CO2 m-2). Also, the shrub-dominated site featured notably low DIC pore-water concentrations and comparably 13C-enriched CH4 (δ13C- CH4: -57.81 ± 7.03 ‰) and depleted CO2 (δ13C-CO2: -15.85 ± 3.61 ‰) in a more decomposed peat, suggesting a higher share of CH4 oxidation and differences in predominant methanogenic pathways. In comparison to all other sites, the graminoid

  9. Long-term sub second-response monitoring of gaseous ammonia in ambient air by positive inhaling ion mobility spectrometry.

    Science.gov (United States)

    Huang, Wei; Wang, Weiguo; Chen, Chuang; Li, Mei; Peng, Liying; Li, Hang; Liu, Jiwei; Hou, Keyong; Li, Haiyang

    2017-12-01

    A real-time dynamic measurements of ammonia (NH 3 ) is crucial for understanding the atmospheric nucleation process. A novel method was developed for on line monitoring at the sub-second time scale for the gaseous ammonia in ambient air for months, based on a positive inhaling ion mobility spectrometry (IMS) with a 63 Ni ion source. The selective detection of NH 3 was achieved using a high resolution IMS with an optimization of the drift tube temperature above 150°C. This method improved the peak-to-peak resolution significantly, thus avoided the interferences of the adjacent peaks to the quantitative analysis of NH 3 . The time resolution of the IMS was less than 0.1s at a data averaging of 10 times. The limit of detection (LOD) achieved at sub-ppb level while a linear response of peak intensity versus concentration of NH 3 in the range of 10-60ppb and 60-400ppb were obtained. The relative standard deviations (RSD), the confidence level and the errors were 1.06%, 95% and ± 0.21ppb by measuring 100ppb NH 3 for 100 times. The effect of ambient humidity could be greatly reduced by using the drift temperature of over 150°C. At last, the application of measuring the NH 3 concentration evolutions of Dalian city was performed from June 19 to December 3 in 2015. The results illustrated a potential method of using IMS for a real-time measuring atmospheric NH 3 at an unprecedented accuracy and sensitivity with long-term stability. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Changes in antioxidants are critical in determining cell responses to short- and long-term heat stress.

    Science.gov (United States)

    Sgobba, Alessandra; Paradiso, Annalisa; Dipierro, Silvio; De Gara, Laura; de Pinto, Maria Concetta

    2015-01-01

    Heat stress can have deleterious effects on plant growth by impairing several physiological processes. Plants have several defense mechanisms that enable them to cope with high temperatures. The synthesis and accumulation of heat shock proteins (HSPs), as well as the maintenance of an opportune redox balance play key roles in conferring thermotolerance to plants. In this study changes in redox parameters, the activity and/or expression of reactive oxygen species (ROS) scavenging enzymes and the expression of two HSPs were studied in tobacco Bright Yellow-2 (TBY-2) cells subjected to moderate short-term heat stress (SHS) and long-term heat stress (LHS). The results indicate that TBY-2 cells subjected to SHS suddenly and transiently enhance antioxidant systems, thus maintaining redox homeostasis and avoiding oxidative damage. The simultaneous increase in HSPs overcomes the SHS and maintains the metabolic functionality of cells. In contrast the exposure of cells to LHS significantly reduces cell growth and increases cell death. In the first phase of LHS, cells enhance antioxidant systems to prevent the formation of an oxidizing environment. Under prolonged heat stress, the antioxidant systems, and particularly the enzymatic ones, are inactivated. As a consequence, an increase in H2 O2 , lipid peroxidation and protein oxidation occurs. This establishment of oxidative stress could be responsible for the increased cell death. The rescue of cell growth and cell viability, observed when TBY-2 cells were pretreated with galactone-γ-lactone, the last precursor of ascorbate, and glutathione before exposure to LHS, highlights the crucial role of antioxidants in the acquisition of basal thermotolerance. © 2014 Scandinavian Plant Physiology Society.

  11. Long-term potentiation of synaptic response and intrinsic excitability in neurons of the rat medial vestibular nuclei.

    Science.gov (United States)

    Pettorossi, V E; Dieni, C V; Scarduzio, M; Grassi, S

    2011-07-28

    Using intracellular recordings, we investigated the effects of high frequency stimulation (HFS) of the primary vestibular afferents on the evoked excitatory postsynaptic potential (EPSP) and intrinsic excitability (IE) of type-A and type-B neurons of the medial vestibular nucleus (MVN), in male rat brainstem slices. HFS induces long-term potentiation (LTP) of both EPSP and IE, which may occur in combination or separately. Synaptic LTP is characterized by an increase in the amplitude, slope and decay time constant of EPSP and IE-LTP through enhancements of spontaneous and evoked neuron firing and of input resistance (Rin). Moreover, IE-LTP is associated with a decrease in action potential afterhyperpolarization (AHP) amplitude and an increase in interspike slope steepness (ISS). The more frequent effects of HFS are EPSP-LTP in type-B neurons and IE-LTP in type-A neurons. In addition, the development of EPSP-LTP is fast in type-B neurons but slow in type-A, whereas IE-LTP develops slowly in both types. We have demonstrated that activation of N-methyl-d aspartate receptors (NMDARs) is only required for EPSP-LTP induction, whereas metabotropic glutamate receptors type-1 (mGluR1) are necessary for IE-LTP induction as well as the full development and maintenance of EPSP-LTP. Taken together, these findings demonstrate that brief and intense activation of vestibular afferent input to the MVN neurons may provoke synaptic LTP and/or IE-LTP that, induced in combination or separately, may assure the different selectivity of the MVN neuron response enhancement to the afferent signals. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Changing forest water yields in response to climate warming: results from long-term experimental watershed sites across North America

    Science.gov (United States)

    Creed, Irena F; Spargo, Adam T; Jones, Julia A; Buttle, Jim M; Adams, Mary B; Beall, Fred D; Booth, Eric G; Campbell, John L; Clow, Dave; Elder, Kelly; Green, Mark B; Grimm, Nancy B; Miniat, Chelcy; Ramlal, Patricia; Saha, Amartya; Sebestyen, Stephen; Spittlehouse, Dave; Sterling, Shannon; Williams, Mark W; Winkler, Rita; Yao, Huaxia

    2014-01-01

    Climate warming is projected to affect forest water yields but the effects are expected to vary. We investigated how forest type and age affect water yield resilience to climate warming. To answer this question, we examined the variability in historical water yields at long-term experimental catchments across Canada and the United States over 5-year cool and warm periods. Using the theoretical framework of the Budyko curve, we calculated the effects of climate warming on the annual partitioning of precipitation (P) into evapotranspiration (ET) and water yield. Deviation (d) was defined as a catchment's change in actual ET divided by P [AET/P; evaporative index (EI)] coincident with a shift from a cool to a warm period – a positive d indicates an upward shift in EI and smaller than expected water yields, and a negative d indicates a downward shift in EI and larger than expected water yields. Elasticity was defined as the ratio of interannual variation in potential ET divided by P (PET/P; dryness index) to interannual variation in the EI – high elasticity indicates low d despite large range in drying index (i.e., resilient water yields), low elasticity indicates high d despite small range in drying index (i.e., nonresilient water yields). Although the data needed to fully evaluate ecosystems based on these metrics are limited, we were able to identify some characteristics of response among forest types. Alpine sites showed the greatest sensitivity to climate warming with any warming leading to increased water yields. Conifer forests included catchments with lowest elasticity and stable to larger water yields. Deciduous forests included catchments with intermediate elasticity and stable to smaller water yields. Mixed coniferous/deciduous forests included catchments with highest elasticity and stable water yields. Forest type appeared to influence the resilience of catchment water yields to climate warming, with conifer and deciduous catchments more susceptible to

  13. Long-term power generation expansion planning with short-term demand response: Model, algorithms, implementation, and electricity policies

    Science.gov (United States)

    Lohmann, Timo

    Electric sector models are powerful tools that guide policy makers and stakeholders. Long-term power generation expansion planning models are a prominent example and determine a capacity expansion for an existing power system over a long planning horizon. With the changes in the power industry away from monopolies and regulation, the focus of these models has shifted to competing electric companies maximizing their profit in a deregulated electricity market. In recent years, consumers have started to participate in demand response programs, actively influencing electricity load and price in the power system. We introduce a model that features investment and retirement decisions over a long planning horizon of more than 20 years, as well as an hourly representation of day-ahead electricity markets in which sellers of electricity face buyers. This combination makes our model both unique and challenging to solve. Decomposition algorithms, and especially Benders decomposition, can exploit the model structure. We present a novel method that can be seen as an alternative to generalized Benders decomposition and relies on dynamic linear overestimation. We prove its finite convergence and present computational results, demonstrating its superiority over traditional approaches. In certain special cases of our model, all necessary solution values in the decomposition algorithms can be directly calculated and solving mathematical programming problems becomes entirely obsolete. This leads to highly efficient algorithms that drastically outperform their programming problem-based counterparts. Furthermore, we discuss the implementation of all tailored algorithms and the challenges from a modeling software developer's standpoint, providing an insider's look into the modeling language GAMS. Finally, we apply our model to the Texas power system and design two electricity policies motivated by the U.S. Environment Protection Agency's recently proposed CO2 emissions targets for the

  14. Photosynthetic responses of yellow poplar and white oak to long term atmospheric CO2 enrichment in the field

    International Nuclear Information System (INIS)

    Gunderson, C.A.; Norby, R.J.

    1991-01-01

    A critical consideration in evaluating forest response to rising atmospheric CO 2 is whether the enhancement of net photosynthesis (P N ) by elevated CO 2 can be sustained over the long term. There are reports of declining enhancement of P N with duration of exposure to elevated CO 2 , associated with decreases in photosynthetic capacity and carboxylation efficiency. We investigated whether this photosynthetic acclimation occurs in two tree species under field conditions. Seedlings of yellow-poplar (Liriodendron tulipifera L.) and white oak (Quercus alba L.) were planted in the ground within six open-top field chambers in May 1989 and have been exposed continuously to CO 2 enrichment during the last two growing seasons. The three CO 2 treatment levels were: ambient, ambient +150, and ambient +300 μL/L. Throughout the second season, gas exchange of upper, light-saturated leaves was surveyed periodically, and leaves of different ages and canopy positions were measured occasionally. Net photosynthesis remained higher at higher CO 2 levels (28-32% higher in +150 and 49-67% higher in +300 seedlings) in both species throughout the season, regardless of increasing leaf age and duration of exposure to CO 2 enrichment. Stomatal conductance remained unchanged or decreased slightly with increasing CO 2 , but instantaneous water use efficiency (P N /transpiration) increased significantly with CO 2 . Analysis of P N versus internal CO 2 concentration indicated no significant treatment differences in carboxylation efficiency, CO 2 -saturated P N , or CO 2 compensation point. There was no evidence of a downward acclimation of photosynthesis to CO 2 enrichment in this system

  15. Long-term effects of a single exposure to stress in adult rats on behavior and hypothalamic-pituitary-adrenal responsiveness: comparison of two outbred rat strains.

    Science.gov (United States)

    Belda, Xavier; Márquez, Cristina; Armario, Antonio

    2004-10-05

    We have previously observed that a single exposure to immobilization (IMO), a severe stressor, caused long-term (days to weeks) desensitization of the response of the hypothalamic-pituitary-adrenal (HPA) axis to the homotypic stressor, with no changes in behavioral reactivity to novel environments. In contrast, other laboratories have reported that a single exposure to footshock induced a long-term sensitization of both HPA and behavioral responses to novel environments. To test whether these apparent discrepancies can be explained by the use of different stressors or different strains of rats, we studied in the present work the long-term effects of a single exposure to two different stressors (footshock or IMO) in two different strains of rats (Sprague-Dawley from Iffa-Credo and Wistar rats from Harlan). We found that both strains showed desensitization of the HPA response to the same (homotypic) stressor after a previous exposure to either shock or IMO. The long-term effects were higher after IMO than shock. No major changes in behavior in two novel environments (circular corridor, CC and elevated plus-maze, EPM) were observed after a single exposure to shock or IMO in neither strain, despite the fact that shocked rats showed a conditioned freezing response to the shock boxes. The present results demonstrate that long-term stress-induced desensitization of the HPA axis is a reliable phenomenon that can be observed with different stressors and strains. However, only behavioral changes related to shock-induced conditioned fear were found, which suggests that so far poorly characterized factors are determining the long-term behavioral consequences of a single exposure to stress.

  16. From basalts to badlands : modelling long-term landscape response to lava damming of an upland catchment in western Turkey

    NARCIS (Netherlands)

    Gorp, van W.

    2014-01-01

    Combining field reconstruction and landscape evolution modelling can be useful to investigate the relative role of different drivers (tectonics, climate, local base level) on long term catchment evolution. In this thesis, field reconstruction and landscape evolution modelling are combined to

  17. Changing forest water yields in response to climate warming: results from long-term experimental watershed sites across North America

    Science.gov (United States)

    Irena F. Creed; Adam T. Spargo; Julia A. Jones; Jim M. Buttle; Mary B. Adams; Fred D. Beall; Eric G. Booth; John L. Campbell; Dave Clow; Kelly Elder; Mark B. Green; Nancy B. Grimm; Chelcy Miniat; Patricia Ramlal; Amartya Saha; Stephen Sebestyen; Dave Spittlehouse; Shannon Sterling; Mark W. Williams; Rita Winkler; Huaxia. Yao

    2014-01-01

    Climate warming is projected to affect forest water yields but the effects are expected to vary.We investigated how forest type and age affect water yield resilience to climate warming. To answer this question, we examined the variability in historical water yields at long-term experimental catchments across Canada and the United States over 5-year cool and warm...

  18. Ecosystem processes and human influences regulate streamflow response to climate change at long-term ecological research sites

    Science.gov (United States)

    Julia A. Jones; Irena F. Creed; Kendra L. Hatcher; Robert J. Warren; Mary Beth Adams; Melinda H. Benson; Emery Boose; Warren A. Brown; John L. Campbell; Alan Covich; David W. Clow; Clifford N. Dahm; Kelly Elder; Chelcy R. Ford; Nancy B. Grimm; Donald L Henshaw; Kelli L. Larson; Evan S. Miles; Kathleen M. Miles; Stephen D. Sebestyen; Adam T. Spargo; Asa B. Stone; James M. Vose; Mark W. Williams

    2012-01-01

    Analyses of long-term records at 35 headwater basins in the United States and Canada indicate that climate change effects on streamflow are not as clear as might be expected, perhaps because of ecosystem processes and human influences. Evapotranspiration was higher than was predicted by temperature in water-surplus ecosystems and lower than was predicted in water-...

  19. Changes in gene expression caused by insect venom immunotherapy responsible for the long-term protection of insect venom-allergic patients

    NARCIS (Netherlands)

    Niedoszytko, Marek; Bruinenberg, Marcel; de Monchy, Jan; Weersma, Rinse K.; Wijmenga, Cisca; Jassem, Ewa; Oude Elberink, Joanne N. G.

    Background: Insect venom immunotherapy (VIT) is the only causative treatment of insect venom allergy (IVA). The immunological mechanism(s) responsible for long-term protection achieved by VIT are largely unknown. A better understanding is relevant for improving the diagnosis, prediction of

  20. Compensating for non-response in a study estimating the incidence of mental disorders in long-term sickness absence by a two-phased design

    DEFF Research Database (Denmark)

    Søgaard, Hans Jørgen; Bech, Per

    2010-01-01

    AIMS: The study compensates for the non-response that was observed in a previous study that estimated the frequencies of mental disorders in long-term sickness absence (LSA) (more than eight weeks of continuous sickness absence). In this study, the frequency of any mental disorder was estimated a...

  1. Potential of the solid-Earth response for limiting long-term West Antarctic Ice Sheet retreat

    Science.gov (United States)

    Konrad, Hannes; Sasgen, Ingo; Pollard, David; Klemann, Volker

    2016-04-01

    for asthenosphere viscosities of 3x10^20 Pa s or higher. References Gomez, N., Pollard, D., Mitrovica, J. X., Huybers, P., & Clark, P. U. (2012). Evolution of a coupled marine ice sheet-sea level model. J. Geophys. Res. 117(F1). Konrad, H., Sasgen, I., Pollard, D. & Klemann, V. (2015). Potential of the solid-Earth response for limiting long-term West Antarctic Ice Sheet retreat in a warming climate. Earth Planet. Sci. Lett. 432, 2015.

  2. Cardiovascular Autonomic Responses in the VCD Rat Model of Menopause: Effects of Short- and Long-Term Ovarian Failure.

    Science.gov (United States)

    Huber, Domitila A; Bazilio, Darlan; Lorenzon, Flaviano; Sehnem, Sibele; Pacheco, Lucas; Anselmo-Franci, Janete A; Lima, Fernanda B

    2017-01-01

    After menopause, hypertension elevates the risk of cardiac diseases, one of the major causes of women's morbidity. The gradual depletion of ovarian follicles in rats, induced by 4-vinylcyclohexene diepoxide (VCD), is a model for studying the physiology of menopause. 4-Vinylcyclohexene diepoxide treatment leads to early ovarian failure (OF) and a hormonal profile comparable to menopause in humans. We have hypothesized that OF can compromise the balance between sympathetic and parasympathetic tones of the cardiovascular system, shifting toward dominance of the former. We aimed to study the autonomic modulation of heart and blood vessels and the cardiovascular reflexes in rats presenting short-term (80 days) or long-term (180 days) OF induced by VCD. Twenty-eight-day-old Wistar rats were submitted to VCD treatment (160 mg/kg, intraperitoneally) or vehicle (control) for 15 consecutive days and experiments were conducted at 80 or 180 days after the onset of treatment. Long-term OF led to an increase in the sympathetic activity to blood vessels and an impairment in the baroreflex control of the heart, evoked by physiological changes in arterial pressure. Despite that, long-term OF did not cause hypertension during the 180 days of exposure. Short-term OF did not cause any deleterious effect on the cardiovascular parameters analyzed. These data indicate that long-term OF does not disrupt the maintenance of arterial pressure homeostasis in rats but worsens the autonomic cardiovascular control. In turn, this can lead to cardiovascular complications, especially when associated with the aging process seen during human menopause.

  3. Long-term collections

    CERN Multimedia

    Collectes à long terme

    2007-01-01

    The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

  4. Brucella abortusΔcydCΔcydD and ΔcydCΔpurD double-mutants are highly attenuated and confer long-term protective immunity against virulent Brucella abortus.

    Science.gov (United States)

    Truong, Quang Lam; Cho, Youngjae; Park, Soyeon; Kim, Kiju; Hahn, Tae-Wook

    2016-01-04

    We constructed double deletion (ΔcydCΔcydD and ΔcydCΔpurD) mutants from virulent Brucella abortus biovar 1 field isolate (BA15) by deleting the genes encoding an ATP-binding cassette-type transporter (cydC and cydD genes) and a phosphoribosylamine-glycine ligase (purD). Both BA15ΔcydCΔcydD and BA15ΔcydCΔpurD double-mutants exhibited significant attenuation of virulence when assayed in murine macrophages or in BALB/c mice. Both double-mutants were readily cleared from spleens by 4 weeks post-inoculation even when inoculated at the dose of 10(8) CFU per mouse. Moreover, the inoculated mice showed no splenomegaly, which indicates that the mutants are highly attenuated. Importantly, the attenuation of in vitro and in vivo growth did not impair the ability of these mutants to confer long-term protective immunity in mice against challenge with B. abortus strain 2308. Vaccination of mice with either mutant induced humoral and cell-mediated immune responses, and provided significantly better protection than commercial B. abortus strain RB51 vaccine. These results suggest that highly attenuated BA15ΔcydCΔcydD and BA15ΔcydCΔpurD mutants can be used effectively as potential live vaccine candidates against bovine brucellosis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2

    Directory of Open Access Journals (Sweden)

    Anders Carey

    2007-09-01

    Full Text Available Abstract Background The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additionally, the beneficial effect of trastuzumab is expected to decrease once the drug is discontinued. We proposed to address these concerns by using cancer vaccines to stimulate HER2 intracellular domain (ICD-specific T cell and antibody responses. Methods Subjects with stage II (≥ 6 +LN, III, or stage IV breast cancerwith > 50% HER2 overexpressing tumor cells who were disease-free after surgery and adjuvant therapy were eligible. Vaccines consisted of immature, cultured DC (n = 3, mature cultured DC (n = 3, or mature Flt3-ligand mobilized peripheral blood DC (n = 1 loaded with ICD, or tetanus toxoid, keyhole limpet hemocyanin or CMV peptide as controls, and were administered intradermally/subcutaneously four times at 3 week intervals. ICD-specific T cell and antibody responses were measured. Cardiac function was determined by MUGA or ECHO; long term disease status was obtained from patient contact. Results All seven patients successfully underwent DC generation and five received all 4 immunizations. There were no toxicities greater than grade 1 or ejection fraction decrements below normal. Delayed-type hypersensitivity (DTH reactions at the injection site occurred in 6/7 patients and HER2 specificity was detected by cytokine flow cytometry or ELISPOT in 5 patients. At more than 5 years of follow-up, 6/7 had detectable anti-ICD antibodies. One patient experienced a pulmonary recurrence at 4 years from their study immunizations. This recurrence was resected and they are without evidence of disease. All patients are alive and disease-free at 4.6–6.7 years of follow-up. Conclusion Although this was a small pilot study, the well-tolerated nature of the vaccines, the lack of cardiac

  6. Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV

    International Nuclear Information System (INIS)

    Buckner, Clarisa; Gines, Leoned G.; Saunders, Cheryl J.; Vojtech, Lucia; Srivastava, Indresh; Gettie, Agegnehu; Bohm, Rudolph; Blanchard, James; Barnett, Susan W.; Safrit, Jeffrey T.; Stamatatos, Leonidas

    2004-01-01

    The potential of vaccine-elicited anti-HIV envelope antibodies to control HIV-infection was evaluated by immunizing macaques with the HIV envelope protein and transiently depleting them of their CD8+ cells before intravenous challenge with the pathogenic CCR5-tropic SIV/HIV chimeric virus, SHIV SF162P4 . Although sterilizing immunity was not achieved, all vaccinated animals effectively controlled infection and remained free of disease for the duration of observation (over 3 years). In contrast, during the same period, the control animals progressed to disease. Both the vaccinees and the controls developed robust cell-mediated antiviral and neutralizing antibody responses following infection. A comparative analysis of these responses suggests that the more effective long-term control of infection by the vaccinated animals is due to the more rapid development of anti-HIV envelope antibodies. These studies suggest that priming by vaccination of B cell anti-HIV envelope responses maybe crucial for the long-term control of HIV infection

  7. T-cell responses targeting HIV Nef uniquely correlate with infected cell frequencies after long-term antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Allison S Thomas

    2017-09-01

    Full Text Available HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART, these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of latency, we observed that a Nef-specific CD8+ T-cell clone exhibited low-level recognition of infected cells prior to reactivation and robust recognition shortly thereafter. A Gag-specific CD8+ T-cell clone failed to recognized infected cells under these conditions, corresponding with a lack of detectable Gag expression. We measured HIV-specific T-cell responses in 96 individuals who had been suppressed on ART for a median of 7 years, and observed a significant, direct correlation between cell-associated HIV DNA levels and magnitudes of IFN-γ-producing Nef/Tat/Rev-specific T-cell responses. This correlation was confirmed in an independent cohort (n = 18. Correlations were not detected between measures of HIV persistence and T-cell responses to other HIV antigens. The correlation with Nef/Tat/Rev-specific T-cells was attributable to Nef-specific responses, the breadth of which also correlated with HIV DNA levels. These results suggest that ongoing Nef expression in ART-treated individuals drives preferential maintenance and/or expansion of T-cells reactive to this protein, implying sensing of infected cells by the immune system. The direct correlation, however, suggests that recognition does not result in efficient elimination of infected cells. These results raise the possibility that

  8. Response of aerobic granular sludge to the long-term presence to nanosilver in sequencing batch reactors: Reactor performance, sludge property, microbial activity and community

    Energy Technology Data Exchange (ETDEWEB)

    Quan, Xiangchun, E-mail: xchquan@bnu.edu.cn; Cen, Yan; Lu, Fang; Gu, Lingyun; Ma, Jingyun

    2015-02-15

    The increasing use of silver nanoparticles (Ag NPs) raises concerns about their potential toxic effects on the environment. Granular shape sludge is a special type of microbial aggregate. The response of aerobic granular sludge (AGS) to the long-term presence of Ag NPs has not been well studied. In this study, AGS was exposed to 5 and 50 mg/L Ag NPs in sequence batch reactors (SBRs) for 69 days, and its response was evaluated based on the sludge properties, microbial activity and community, and reactor performance. The results showed that Ag NPs caused inhibition to microbial activities of AGS from Day 35. At the end of 69 days of Ag NPs exposure, the microbial activity of AGS was significantly inhibited in terms of inhibitions of the ammonia oxidizing rate (33.0%), respiration rate (17.7% and 45.6%) and denitrification rate (6.8%), as well as decreases in the ammonia mono-oxygenase and nitrate reductase activities. During the long-term exposure, the AGS maintained its granular shape and large granule size (approximately 900 μm); the microbial community of AGS slightly changed, but the dominant microbial population remained. Overall, the AGS tolerated the toxicity of Ag NPs well, but a long-term exposure may produce chronic toxicity to the AGS, which is concerning. - Highlights: • AGS demonstrated a good tolerance to the long-term presence of Ag NPs. • Ag NPs did not produce acute toxicity but cause chronic toxicity to AGS. • AGS maintained granular shape, granule size and good settling ability. • The microbial community of AGS slightly changed after long-term Ag NPs exposure.

  9. Response of aerobic granular sludge to the long-term presence to nanosilver in sequencing batch reactors: Reactor performance, sludge property, microbial activity and community

    International Nuclear Information System (INIS)

    Quan, Xiangchun; Cen, Yan; Lu, Fang; Gu, Lingyun; Ma, Jingyun

    2015-01-01

    The increasing use of silver nanoparticles (Ag NPs) raises concerns about their potential toxic effects on the environment. Granular shape sludge is a special type of microbial aggregate. The response of aerobic granular sludge (AGS) to the long-term presence of Ag NPs has not been well studied. In this study, AGS was exposed to 5 and 50 mg/L Ag NPs in sequence batch reactors (SBRs) for 69 days, and its response was evaluated based on the sludge properties, microbial activity and community, and reactor performance. The results showed that Ag NPs caused inhibition to microbial activities of AGS from Day 35. At the end of 69 days of Ag NPs exposure, the microbial activity of AGS was significantly inhibited in terms of inhibitions of the ammonia oxidizing rate (33.0%), respiration rate (17.7% and 45.6%) and denitrification rate (6.8%), as well as decreases in the ammonia mono-oxygenase and nitrate reductase activities. During the long-term exposure, the AGS maintained its granular shape and large granule size (approximately 900 μm); the microbial community of AGS slightly changed, but the dominant microbial population remained. Overall, the AGS tolerated the toxicity of Ag NPs well, but a long-term exposure may produce chronic toxicity to the AGS, which is concerning. - Highlights: • AGS demonstrated a good tolerance to the long-term presence of Ag NPs. • Ag NPs did not produce acute toxicity but cause chronic toxicity to AGS. • AGS maintained granular shape, granule size and good settling ability. • The microbial community of AGS slightly changed after long-term Ag NPs exposure

  10. The effect of banana (Musa acuminata) peels hot-water extract on the immunity and resistance of giant freshwater prawn, Macrobrachium rosenbergii via dietary administration for a long term: Activity and gene transcription.

    Science.gov (United States)

    Rattanavichai, Wutti; Chen, Ying-Nan; Chang, Chin-Chyuan; Cheng, Winton

    2015-10-01

    The non-specific immune parameters, disease resistance and immune genes expressions in Macrobrachium rosenbergii were evaluated at 120 days of post feeding the diets containing the extracts of banana, Musa acuminate, fruit's peel (banana peels extract, BPE) at 0, 1.0, 3.0 and 6.0 g kg(-1). Results showed that prawns fed with a diet containing BPE at the level of 1.0, 3.0 and 6.0 g kg(-1) for 120 days had a significantly higher survival rate (30.0%, 40.0% and 56.7%, respectively) than those fed with the control diet after challenge with Lactococcus garvieae for 144 h, and the respective relative survival percentages were 22.2%, 33.3%, and 51.9%, respectively. Dietary BPE supplementation at 3.0 and/or 6.0 g kg(-1) for 120 days showed a significant increase total haemocyte count (THC), granular cell (GC), superoxide dismutase (SOD) activity, phenoloxidase (PO) activity, transglutaminase (TG) activity, and phagocytic activity and clearance efficiency to L. garvieae infection, and meanwhile, the significant decrease in haemolymph clotting times and respiratory bursts (RBs) per haemocyte of prawns were revealed. Furthermore, the mRNA expressions of prophenoloxidase (proPO), lipopolysaccharide and β-1,3-glucan binding protein (LGBP), peroxinectin (PE), transglutaminase (TG), and crustin (CT) were significantly increased. We therefore recommend that BPE can be used as an immunomodulator for prawns through dietary administration at 6.0 g kg(-1) for a long term (over 120 days) to modify immune responses and genes expression following the enhanced resistance against pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The six year report: Acidification of surface water in Europe and North America. Dose/response relationships and long-term trends

    Energy Technology Data Exchange (ETDEWEB)

    Skjelkvaale, B L; Newell, A D; Raddum, G; Johannessen, M; Hovind, H; Tjomsland, T; Wathne, B M

    1994-12-31

    This report discusses The International Cooperative Programme on Assessment and Monitoring of Acidification of Rivers and Lakes, which is designed to (1) establish degree and extent of acidification of surface waters, (2) evaluate dose/response relationships and (3) define long-term trends and variations in aquatic chemistry and biota attributable to atmospheric pollution. Data from 200 sites in 14 countries of Europe and North America are available. Dose/response relationships show that the fauna is adapted to different water qualities in different regions, and that critical limits for the fauna must be calculated according to data for the specific region. Long-term trends of water chemistry show decreases in SO{sub 4}{sup 2-} and Ca{sup 2+} at many sites. Nitrate shows no consistent trends. 66 refs., 26 figs., 16 tabs.

  12. Sustainability strategies for real-estates. Thinking long-term and shoulder entrepreneurial responsibility; Nachhaltigkeitsstrategien fuer Immobilien. Langfristig denken und unternehmerische Verantwortung wahrnehmen

    Energy Technology Data Exchange (ETDEWEB)

    Kaeding, Uta; Sigg, Rene [Intep - Integrale Planung GmbH, Hamburg (Germany); Intep - Integrale Planung GmbH, Muenchen (Germany)

    2011-07-01

    On the basis of their corporate strategy and sustainability strategy responsible companies set suitable objectives for their real-estate portfolio. The companies recognized that sustainable real-estates offer long-term economic advantages and reduced risks. For the development and conversion of a sustainability strategy for real-estates innovative tools and aids are available today which make the life cycle costs or the surplus value of sustainable real-estates transparent.

  13. Density and permeability of a loess soil: long-term organic matter effect and the response to compressive stress

    DEFF Research Database (Denmark)

    Arthur, Emmanuel; Schjønning, Per; Møldrup, Per

    2013-01-01

    to compressive stress, undisturbed soil cores were collected from a long-term fertilisation experiment in Bad Lauchstädt in Germany, including combinations of animal manure and mineral fertilisers. The cores were drained to -100 hPa matric potential and exposed to uniaxial confined compression (200k......Pa). Investigated indicators for compression resistance included compression index, precompression stress, and resistance and resilience indices based on measured soil physical properties (bulk density, air-filled porosity, air permeability, and void ratio). Soil resilience was assessed following exposure...... but the correlation was not significant. However, initial bulk density (ρbi) and initial gravimetric water content (wi) were significantly positively correlated to the indices of soil compression resistance, with the effect of ρbi being significantly stronger. Significant recovery of airfilled porosity and air...

  14. Blood leukocyte responses to extracorporeal circulation. 3. Long term extracorporeal circulation without and with irradiation in normal and splenectomized dogs

    Energy Technology Data Exchange (ETDEWEB)

    Szemere, P.; Fliedner, T.M. (Ulm Univ. (Germany, F.R.). Abt. Klinische Physiologie)

    1983-01-01

    Long term (12-48 h) extracorporeal circulation without and with irradiation of the blood was performed in normal and splenectomized dogs in order to observe the effect of these procedures on blood leukocyte counts including CFU-C. A transient granulocytopenia and a decrease of lymphocyte count were observed. The blood CFU-C level diminished to a very low level and remained low for the whole time of the experiments. There was no significant difference between the results of procedures with or without irradiation. The similar effect of a shortened tubing system on the blood leukocyte count is also reported. Heparin infusion alone did not decrease the peripheral CFU-C concentration. The possible explanations for the observed phenomena are discussed.

  15. Long-term performance of anaerobic digestion for crop residues containing heavy metals and response of microbial communities.

    Science.gov (United States)

    Lee, Jongkeun; Kim, Joonrae Roger; Jeong, Seulki; Cho, Jinwoo; Kim, Jae Young

    2017-01-01

    In order to investigate the long-term stability on the performance of the anaerobic digestion process, a laboratory-scale continuous stirred-tank reactor (CSTR) was operated for 1100 days with sunflower harvested in a heavy metal contaminated site. Changes of microbial communities during digestion were identified using pyrosequencing. According to the results, soluble heavy metal concentrations were lower than the reported inhibitory level and the reactor performance remained stable up to OLR of 2.0g-VS/L/day at HRT of 20days. Microbial communities commonly found in anaerobic digestion for cellulosic biomass were observed and stably established with respect to the substrate. Thus, the balance of microbial metabolism was maintained appropriately and anaerobic digestion seems to be feasible for disposal of heavy metal-containing crop residues from phytoremediation sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Beyond "Home-Like" Design: Visitor Responses to an Immersive Creative Space in a Canadian Long-Term Care Facility.

    Science.gov (United States)

    Graham, Megan E; Fabricius, Andréa

    2017-11-01

    This study examined the benefits of expanding upon the "home-like" design by introducing an immersive creative space for residents, staff, and visitors to explore in a long-term care facility in Eastern Ontario, Canada. Data were collected through guestbook comments ( N = 93) and coded for themes according to guidelines for thematic analysis. Selected themes included visitors' enjoyment of the winter aesthetic, expressions of gratitude to the artists, time spent socializing with family and visitors in a creative milieu, and the experience of remembering in an evocative space. The results indicate that residents and visitors benefited from the experience of a creative space that was neither institutional, nor "home-like." Implications for future research are discussed.

  17. Satellite tagging and biopsy sampling of killer whales at subantarctic Marion Island: effectiveness, immediate reactions and long-term responses.

    Directory of Open Access Journals (Sweden)

    Ryan R Reisinger

    Full Text Available Remote tissue biopsy sampling and satellite tagging are becoming widely used in large marine vertebrate studies because they allow the collection of a diverse suite of otherwise difficult-to-obtain data which are critical in understanding the ecology of these species and to their conservation and management. Researchers must carefully consider their methods not only from an animal welfare perspective, but also to ensure the scientific rigour and validity of their results. We report methods for shore-based, remote biopsy sampling and satellite tagging of killer whales Orcinus orca at Subantarctic Marion Island. The performance of these methods is critically assessed using 1 the attachment duration of low-impact minimally percutaneous satellite tags; 2 the immediate behavioural reactions of animals to biopsy sampling and satellite tagging; 3 the effect of researcher experience on biopsy sampling and satellite tagging; and 4 the mid- (1 month and long- (24 month term behavioural consequences. To study mid- and long-term behavioural changes we used multievent capture-recapture models that accommodate imperfect detection and individual heterogeneity. We made 72 biopsy sampling attempts (resulting in 32 tissue samples and 37 satellite tagging attempts (deploying 19 tags. Biopsy sampling success rates were low (43%, but tagging rates were high with improved tag designs (86%. The improved tags remained attached for 26±14 days (mean ± SD. Individuals most often showed no reaction when attempts missed (66% and a slight reaction-defined as a slight flinch, slight shake, short acceleration, or immediate dive-when hit (54%. Severe immediate reactions were never observed. Hit or miss and age-sex class were important predictors of the reaction, but the method (tag or biopsy was unimportant. Multievent trap-dependence modelling revealed considerable variation in individual sighting patterns; however, there were no significant mid- or long-term changes

  18. Characterization of host immune responses in Ebola virus infections.

    Science.gov (United States)

    Wong, Gary; Kobinger, Gary P; Qiu, Xiangguo

    2014-06-01

    Ebola causes highly lethal hemorrhagic fever in humans with no licensed countermeasures. Its virulence can be attributed to several immunoevasion mechanisms: an early inhibition of innate immunity started by the downregulation of type I interferon, epitope masking and subversion of the adaptive humoural immunity by secreting a truncated form of the viral glycoprotein. Deficiencies in specific and non-specific antiviral responses result in unrestricted viral replication and dissemination in the host, causing death typically within 10 days after the appearance of symptoms. This review summarizes the host immune response to Ebola infection, and highlights the short- and long-term immune responses crucial for protection, which holds implications for the design of future vaccines and therapeutics.

  19. Long-Term Collections

    CERN Multimedia

    Comité des collectes à long terme

    2011-01-01

    It is the time of the year when our fireman colleagues go around the laboratory for their traditional calendars sale. A part of the money of the sales will be donated in favour of the long-term collections. We hope that you will welcome them warmly.

  20. Responses of bacterial and archaeal ammonia oxidizers to soil organic and fertilizer amendments under long-term management

    Energy Technology Data Exchange (ETDEWEB)

    Wessen, E.; Nyberg, K.; Jansson, J.K.; Hallin, S.

    2010-05-01

    Ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) co-exist in soil, but their relative distribution may vary depending on the environmental conditions. Effects of changes in soil organic matter and nutrient content on the AOB and AOA are poorly understood. Our aim was to compare effects of long-term soil organic matter depletion and amendments with labile (straw) and more recalcitrant (peat) organic matter, with and without easily plant-available nitrogen, on the activities, abundances and community structures of AOB and AOA. Soil was sampled from a long-term field site in Sweden that was established in 1956. The potential ammonia oxidation rates, the AOB and AOA amoA gene abundances and the community structures of both groups based on T-RFLP of amoA genes were determined. Straw amendment during 50 years had not altered any of the measured soil parameters, while the addition of peat resulted in a significant increase of soil organic carbon as well as a decrease in pH. Nitrogen fertilization alone resulted in a small decrease in soil pH, organic carbon and total nitrogen, but an increase in primary production. Type and amount of organic matter had an impact on the AOB and AOA community structures and the AOA abundance. Our findings confirmed that AOA are abundant in soil, but showed that under certain conditions the AOB dominate, suggesting niche differentiation between the two groups at the field site. The large differences in potential rates between treatments correlated to the AOA community size, indicating that they were functionally more important in the nitrification process than the AOB. The AOA abundance was positively related to addition of labile organic carbon, which supports the idea that AOA could have alternative growth strategies using organic carbon. The AOB community size varied little in contrast to that of the AOA. This indicates that the bacterial ammonia oxidizers as a group have a greater ecophysiological diversity and

  1. ADAPTIVE CHANGES OF MYOSIN ISOFORMS IN RESPONSE TO LONG-TERM STRENGTH AND POWER TRAINING IN MIDDLE-AGED MEN

    Directory of Open Access Journals (Sweden)

    Raivo Puhke

    2006-06-01

    Full Text Available The purpose of the study was to examine the adaptive changes in myosin heavy chain (MHC and light chain (MLC isoforms in human vastus lateralis muscle caused by long-term strength and power training (54 weeks, approximately 3 times a week in untrained middle- aged men (16 in the training and 6 in the control group. Muscular MHC and MLC isoforms were determined by means of SDS-PAGE gel electrophoresis. During the training period, maximal anaerobic cycling power increased by 64 W (p < 0.001 and the maximal jumping height by 1.5 cm (p < 0. 05 in the training group, but no significant changes were found in the control group. However, the group by time effect was not significant. In the training group, the increase of the maximal jumping height correlated with the number of strength and power training sessions (r = 0.56; p < 0.05. The change of the proportion of MHC IIa isoform from 52.6 ± 12.2% to 59.4 ± 11.6% did not reach statistical significance (p = 0.070 for group by time; within training group p = 0.061 and neither did the change of the proportion of MHC IIx isoform from 18.1 ± 11.4% to 11.1 ± 9.1% (p = 0.104 for group by time; within training group p=0.032. The degree of change of MHC IIx isoform correlated with the amount of earlier recreational sports activity (r = 0.61; p < 0.05. In the training group, the changes of MLC1s isoform correlated negatively with the changes of MLC1f isoform (r = -0. 79; p < 0.05 as well as with the changes in maximal anaerobic cycling power (r = -0.81; p < 0.05, and positively with those of MHC I isoform (r = 0.81; p < 0.05. In conclusion, the long- term strength and power training ~3 times a week seemed to have only slight effects on fast MHC isoforms in the vastus lateralis muscle of untrained middle-aged men; the proportion of MHC IIa tended to increase and that of MHC IIx tended to decrease. No changes in MLC isoform profile could be shown

  2. Response of NDVI, biomass, and ecosystem gas exchange to long-term warming and fertilization in wet sedge tundra.

    Science.gov (United States)

    Boelman, Natalie T; Stieglitz, Marc; Rueth, Heather M; Sommerkorn, Martin; Griffin, Kevin L; Shaver, Gaius R; Gamon, John A

    2003-05-01

    This study explores the relationship between the normalized difference vegetation index (NDVI), aboveground plant biomass, and ecosystem C fluxes including gross ecosystem production (GEP), ecosystem respiration (ER) and net ecosystem production. We measured NDVI across long-term experimental treatments in wet sedge tundra at the Toolik Lake LTER site, in northern Alaska. Over 13 years, N and P were applied in factorial experiments (N, P and N + P), air temperature was increased using greenhouses with and without N + P fertilizer, and light intensity (photosynthetically active photon flux density) was reduced by 50% using shade cloth. Within each treatment plot, NDVI, aboveground biomass and whole-system CO(2) flux measurements were made at the same sampling points during the peak-growing season of 2001. We found that across all treatments, NDVI is correlated with aboveground biomass ( r(2)=0.84), GEP ( r(2)=0.75) and ER ( r(2)=0.71), providing a basis for linking remotely sensed NDVI to aboveground biomass and ecosystem carbon flux.

  3. Short communication. Response of bacterial community composition to long-term applications of different composts in agricultural soils

    Energy Technology Data Exchange (ETDEWEB)

    Ros, M; Knapp, B A; Peintner, U; Insam, H

    2011-07-01

    Differences in the bacterial community composition of agricultural soils caused by a long-term (12 year) application of different composts were identified by cultivation-dependent and -independent methods (PCR-DGGE and 16S rRNA clone libraries). The number of colony forming units indicated that the successive incorporation of organic amendments increased the bacterial abundance (6.41-5.66 log10 cfu g-1dry soil) compared to control and mineral soils (5.54-3.74 log10 cfu g-1 dry soil). Isolated bacteria were dominated by Actinobacteria, whereby compost-amended soils and green compost-amended soils showed, respectively, higher number of members of Actinobacteria (100% and 64%) than control and mineral soils (50% and 40%). The 16S rRNA clone libraries were dominated by Proteobacteria (43%), Acidobacteria (21%) and Actinobacteria (13%). Proteobacteria and Actinobacteria were most abundant in compost amended soils while Acidobacteria were more frequently found in mineral fertilizer and control soils. Partial 16S rRNA gene clone libraries revealed a higher bacterial diversity than cultivation. In conclusion, we found differences of bacterial community composition with a cultivation approach and clone libraries between compost amended soils and control and mineral soil. (Author) 31 refs.

  4. Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia.

    Science.gov (United States)

    Spaeth, Michael; Alegre, Cayetano; Perrot, Serge; Wang, Youyu; Guinta, Diane R; Alvarez-Horine, Sarah; Russell, Irwin

    2013-11-11

    The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. ClinicalTrials.gov NCT00423605.

  5. Long-term tolerability and maintenance of therapeutic response to sodium oxybate in an open-label extension study in patients with fibromyalgia

    Science.gov (United States)

    2013-01-01

    Introduction The long-term safety and therapeutic response of sodium oxybate (SXB) in fibromyalgia syndrome (FM) patients were assessed for a combined period of up to 1 year in a prospective, multicenter, open-label, extension study in patients completing 1 of 2 phase 3 randomized, double-blind, controlled, 14-week trials that examined the efficacy and safety of SXB 4.5 g, SXB 6 g, and placebo for treatment of FM. Methods This extension study comprised an additional 38 weeks of treatment and was carried out at 130 clinical sites in 7 countries. Initial entry criteria for the previous 2 double-blind clinical trials required that patients aged ≥ 18 years met the American College of Rheumatology 1990 criteria for FM, had a body mass index (BMI) Fibromyalgia Impact Questionnaire (FIQ) total scores, and other measures. Responder analyses showed that 68.8% of patients achieved ≥ 30% reduction in pain VAS and 69.7% achieved ≥ 30% reduction in FIQ total score at study endpoint. Conclusions The long-term safety profile of SXB in FM patients was similar to that in the previously reported controlled clinical trials. Improvement in pain and other FM clinical domains was maintained during long-term use. Trial registration ClinicalTrials.gov NCT00423605. PMID:24286114

  6. Biochemical responses and mitochondrial mediated activation of apoptosis on long-term effect of aspartame in rat brain

    Directory of Open Access Journals (Sweden)

    Iyaswamy Ashok

    2014-01-01

    Full Text Available Aspartame, an artificial sweetener, is very widely used in many foods and beverages. But there are controversies about its metabolite which is marked for its toxicity. Hence it is believed to be unsafe for human use. Previous studies have reported on methanol exposure with involvements of free radicals on excitotoxicity of neuronal apoptosis. Hence, this present study is proposed to investigate whether or not chronic aspartame (FDA approved Daily Acceptable Intake (ADI,40 mg/kg bwt administration could release methanol, and whether or not it can induce changes in brain oxidative stress status and gene and protein expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax and caspase-3 in the rat brain region. To mimic the human methanol metabolism, Methotrexate (MTX-treated Wistar strain male albino rats were used and after the oral administration of aspartame, the effects were studied along with controls and MTX-treated controls. Aspartame exposure resulted with a significant increase in the enzymatic activity in protein carbonyl, lipid peroxidation levels, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and catalase activity in (aspartame MTX-treated animals and with a significant decrease in reduced glutathione, glutathione reductase and protein thiol, pointing out the generation of free radicals. The gene and protein expression of pro apoptotic marker Bax showed a marked increase whereas the anti-apoptotic marker Bcl-2 decreased markedly indicating the aspartame is harmful at cellular level. It is clear that long term aspartame exposure could alter the brain antioxidant status, and can induce apoptotic changes in brain.

  7. Dynamic imaging response following radiation therapy predicts long-term outcomes for diffuse low-grade gliomas.

    Science.gov (United States)

    Pallud, Johan; Llitjos, Jean-François; Dhermain, Frédéric; Varlet, Pascale; Dezamis, Edouard; Devaux, Bertrand; Souillard-Scémama, Raphaëlle; Sanai, Nader; Koziak, Maria; Page, Philippe; Schlienger, Michel; Daumas-Duport, Catherine; Meder, Jean-François; Oppenheim, Catherine; Roux, François-Xavier

    2012-04-01

    Quantitative imaging assessment of radiation therapy (RT) for diffuse low-grade gliomas (DLGG) by measuring the velocity of diametric expansion (VDE) over time has never been studied. We assessed the VDE changes following RT and determined whether this parameter can serve as a prognostic factor. We reviewed a consecutive series of 33 adults with supratentorial DLGG treated with first-line RT with available imaging follow-up (median follow-up, 103 months). Before RT, all patients presented with a spontaneous tumor volume increase (positive VDE, mean 5.9 mm/year). After RT, all patients demonstrated a tumor volume decrease (negative VDE, mean, -16.7 mm/year) during a mean 49-month duration. In univariate analysis, initial tumor volume (>100 cm(3)), lack of IDH1 expression, p53 expression, high proliferation index, and fast post-RT tumor volume decrease (VDE at -10 mm/year or faster, fast responders) were associated with a significantly shorter overall survival (OS). The median OS was significantly longer (120.8 months) for slow responders (post-RT VDE slower than -10.0 mm/year) than for fast responders (47.9 months). In multivariate analysis, fast responders, larger initial tumor volume, lack of IDH1 expression, and p53 expression were independent poor prognostic factors for OS. A high proliferation index was significantly more frequent in the fast responder subgroup than in the slow responder subgroup. We conclude that the pattern of post-RT VDE changes is an independent prognostic factor for DLGG and offers a quantitative parameter to predict long-term outcomes. We propose to monitor individually the post-RT VDE changes using MRI follow-up, with particular attention to fast responders.

  8. Biochemical responses and mitochondrial mediated activation of apoptosis on long-term effect of aspartame in rat brain.

    Science.gov (United States)

    Ashok, Iyaswamy; Sheeladevi, Rathinasamy

    2014-01-01

    Aspartame, an artificial sweetener, is very widely used in many foods and beverages. But there are controversies about its metabolite which is marked for its toxicity. Hence it is believed to be unsafe for human use. Previous studies have reported on methanol exposure with involvements of free radicals on excitotoxicity of neuronal apoptosis. Hence, this present study is proposed to investigate whether or not chronic aspartame (FDA approved Daily Acceptable Intake (ADI),40 mg/kg bwt) administration could release methanol, and whether or not it can induce changes in brain oxidative stress status and gene and protein expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax and caspase-3 in the rat brain region. To mimic the human methanol metabolism, Methotrexate (MTX)-treated Wistar strain male albino rats were used and after the oral administration of aspartame, the effects were studied along with controls and MTX-treated controls. Aspartame exposure resulted with a significant increase in the enzymatic activity in protein carbonyl, lipid peroxidation levels, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and catalase activity in (aspartame MTX)-treated animals and with a significant decrease in reduced glutathione, glutathione reductase and protein thiol, pointing out the generation of free radicals. The gene and protein expression of pro apoptotic marker Bax showed a marked increase whereas the anti-apoptotic marker Bcl-2 decreased markedly indicating the aspartame is harmful at cellular level. It is clear that long term aspartame exposure could alter the brain antioxidant status, and can induce apoptotic changes in brain.

  9. Immune response to H pylori

    Science.gov (United States)

    Suarez, Giovanni; Reyes, Victor E; Beswick, Ellen J

    2006-01-01

    The gastric mucosa separates the underlying tissue from the vast array of antigens that traffic through the stomach lumen. While the extreme pH of this environment is essential in aiding the activation of enzymes and food digestion, it also renders the gastric epithelium free from bacterial colonization, with the exception of one important human pathogen, H pylori. This bacterium has developed mechanisms to survive the harsh environment of the stomach, actively move through the mucosal layer, attach to the epithelium, evade immune responses, and achieve persistent colonization. While a hallmark of this infection is a marked inflammatory response with the infiltration of various immune cells into the infected gastric mucosa, the host immune response is unable to clear the infection and may actually contribute to the associated pathogenesis. Here, we review the host responses involved during infection with H pylori and how they are influenced by this bacterium. PMID:17007009

  10. Long-term Treatment Response and Patient Outcomes for Vestibular Schwannoma Patients Treated with Hypofractionated Stereotactic Radiotherapy

    Directory of Open Access Journals (Sweden)

    Mira A. Patel

    2017-09-01

    Full Text Available PurposeThe aim of this study is to evaluate long-term treatment outcome and toxicities among vestibular schwannoma (VS patients treated with hypofractionated stereotactic radiotherapy (HSRT.Methods383 patients with unilateral VS treated with HSRT (25 Gy, five fractions between 1995 and 2007 were retrospectively reviewed. Treatment failure was defined as requiring salvage microsurgery. Posttreatment new/progressive clinical symptoms or increases in baseline tumor volume (BTV due to treatment effect or progression were noted. Symptom outcomes were reported as baseline and posttreatment ± improvement, respectively. Symptoms were grouped by cranial nerve (CN VII or CNVIII. Audiometry was assessed baseline and posttreatment hearing. Patients were grouped as having greater than serviceable hearing [Gardner Robertson (GR score 1–2] or less than non-serviceable hearing (GR score 3–5 by audiometry.ResultsMedian follow-up was 72.0 months. Nine (2.3% experienced treatment failure. At last follow-up, 74 (19.3% had new/progressive symptoms and were categorized as radiologic non-responders, whereas 300 (78.3% had no tumor progression and were grouped as radiologic responders. Average pretreatment BTV for treatment failures, radiologic non-responders, and radiologic responders was 2.11, 0.44, and 1.87 cm3, respectively. Pretreatment CNVII and CNVIII symptoms were present in 9.4 and 93.4% of patients, respectively. Eight (24% with pre-HSRT CNVII and 37 (10% with pre-HSRT CNVIII symptoms recovered CN function post-HSRT. Thirty-five (9% and 36 (9.4% experienced new CNVII and CNVIII deficit, respectively, after HSRT. Of these, 20 (57% and 18 (50% recovered CNVII and CNVIII function, respectively, after HSRT. Evaluable audiograms were available in 199 patients. At baseline and at last follow-up, 65.8 and 36.2% had serviceable hearing, respectively. Fifty-one percent had preservation of serviceable hearing at last follow-up.ConclusionTreatment of VS

  11. Final programmatic environmental impact statement for alternative strategies for the long-term management and use of depleted uranium hexafluoride. Volume 3: Responses to public comments

    International Nuclear Information System (INIS)

    1999-04-01

    This PEIS assesses the potential impacts of alternative management strategies for depleted uranium hexafluoride (UF 6 ) currently stored at three DOE sites: Paducah site near Paducah, Kentucky, Portsmouth site near Portsmouth, Ohio; and K-25 site on the Oak Ridge Reservation, Oak Ridge, Tennessee. The alternatives analyzed in the PEIS include no action, long-term storage as UF 6 , long-term storage as uranium oxide, use as uranium oxide, use as uranium metal, and disposal. DOE's preferred alternative is to begin conversion of the depleted UF 6 inventory as soon as possible, either to uranium oxide, uranium metal, or a combination of both, while allowing for use of as much of this inventory as possible. This volume of the Final PEIS contains the comments and DOE's responses to comments received during the comment period. Chapter 2 contains photocopies of written submissions received by DOE on the Draft PEIS; DOE's responses to those comments are listed in Chapter 3. Chapter 4 provides the oral comments received at the public hearings and DOE's responses. Chapter 5 provides indices to comments and responses arranged by commentor name and by comment number

  12. The Long-term Impact of Early Life Pain On Adult Responses to Anxiety and Stress: Historical Perspectives and Empirical Evidence

    Science.gov (United States)

    Victoria, Nicole C.; Murphy, Anne Z.

    2016-01-01

    Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10–18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU. PMID:26210872

  13. Resilience of Mediterranean terrestrial ecosystems and fire severity in semiarid areas: Responses of Aleppo pine forests in the short, mid and long term.

    Science.gov (United States)

    González-De Vega, S; De Las Heras, J; Moya, D

    2016-12-15

    In recent decades, the fire regime of the Mediterranean Basin has been disturbed by various factors: climate change; forest management policies; land cover; changed landscape. Size and severity have notably increased, which in turn have increased large fires events with >500ha burned (high severity). In spite of Mediterranean ecosystems' high resilience to fire, these changes have implied more vulnerability and reduced natural recovery with irreparable long-term negative effects. Knowledge of the response of ecosystems to increasing severity, mainly in semiarid areas, is still lacking, which is needed to rehabilitate and restore burned areas. Our approach assessed the resilience concept by focusing on the recovery of ecosystem functions and services, measured as changes in the composition and diversity of plant community vegetation and structure. This will be validated in the long term as a model of ecosystem response. Also, depending on the pre-fire characteristics of vegetation, fire severity and the post-fire management, this approach will lead to tools that can be applied to implement post-fire restoration efforts in order to help decision making in planning activities. Regarding Mediterranean ecosystems' ability to recover after wildfires, this study concludes that pre-fire communities are resilient in these fire-prone areas, but the window for natural recovery in semiarid areas of Aleppo pine forest in SE Iberian Peninsula varied from 3 to 15 post-fire years. Fire severity was also key for effects on the ecosystem: the vegetation types of areas burned with low and medium severity recovered naturally, while those areas with a high-severity burn induced shrublands. We concluded that very strong regeneration activity exists in the short term, and that the negative effects of medium- and high-severity fire are evidenced in the mid and long term, which affect natural recovery. Adaptive forest management to rehabilitate and restore burned Mediterranean ecosystems

  14. Long-Term Collections

    CERN Multimedia

    Staff Association

    2016-01-01

    45 years helping in developing countries! CERN personnel have been helping the least fortunate people on the planet since 1971. How? With the Long-Term Collections! Dear Colleagues, The Staff Association’s Long-Term Collections (LTC) Committee is delighted to share this important milestone in the life of our Laboratory with you. Indeed, whilst the name of CERN is known worldwide for scientific discoveries, it also shines in the many humanitarian projects which have been supported by the LTC since 1971. Several schools and clinics, far and wide, carry its logo... Over the past 45 years, 74 projects have been supported (9 of which are still ongoing). This all came from a group of colleagues who wanted to share a little of what life offered them here at CERN, in this haven of mutual understanding, peace and security, with those who were less fortunate elsewhere. Thus, the LTC were born... Since then, we have worked as a team to maintain the dream of these visionaries, with the help of regular donat...

  15. Long-Term Collection

    CERN Multimedia

    Staff Association

    2016-01-01

    Dear Colleagues, As previously announced in Echo (No. 254), your delegates took action to draw attention to the projects of the Long-Term Collections (LTC), the humanitarian body of the CERN Staff Association. On Tuesday, 11 October, at noon, small Z-Cards were widely distributed at the entrances of CERN restaurants and we thank you all for your interest. We hope to have achieved an important part of our goal, which was to inform you, convince you and find new supporters among you. We will find out in the next few days! An exhibition of the LTC was also set up in the Main Building for the entire week. The Staff Association wants to celebrate the occasion of the Long-Term Collection’s 45th anniversary at CERN because, ever since 1971, CERN personnel have showed great support in helping the least fortunate people on the planet in a variety of ways according to their needs. On a regular basis, joint fundraising appeals are made with the Directorate to help the victims of natural disasters around th...

  16. Collectes à long terme

    CERN Multimedia

    Collectes à long terme

    2014-01-01

    En cette fin d’année 2014 qui approche à grands pas, le Comité des Collectes à Long Terme remercie chaleureusement ses fidèles donatrices et donateurs réguliers pour leurs contributions à nos actions en faveur des plus démunis de notre planète. C’est très important, pour notre Comité, de pouvoir compter sur l’appui assidu que vous nous apportez. Depuis plus de 40 ans maintenant, le modèle des CLT est basé principalement sur des actions à long terme (soit une aide pendant 4-5 ans par projet, mais plus parfois selon les circonstances), et sa planification demande une grande régularité de ses soutiens financiers. Grand MERCI à vous ! D’autres dons nous parviennent au cours de l’année, et ils sont aussi les bienvenus. En particulier, nous tenons à remercier...

  17. Long term radioactive waste management

    International Nuclear Information System (INIS)

    Lavie, J.M.

    1984-01-01

    In France, waste management, a sensitive issue in term of public opinion, is developing quickly, and due to twenty years of experience, is now reaching maturity. With the launching of the French nuclear programme, the use of radioactive sources in radiotherapy and industry, waste management has become an industrial activity. Waste management is an integrated system dealing with the wastes from their production to the long term disposal, including their identification, sortage, treatment, packaging, collection and transport. This system aims at guaranteing the protection of present and future populations with an available technology. In regard to their long term management, and the design of disposals, radioactive wastes are divided in three categories. This classification takes into account the different radioisotopes contained, their half life and their total activity. Presently short-lived wastes are stored in the shallowland disposal of the ''Centre de la Manche''. Set up within the French Atomic Energy Commission (CEA), the National Agency for waste management (ANDRA) is responsible within the framework of legislative and regulatory provisions for long term waste management in France [fr

  18. The effects of short-term and long-term learning on the responses of lateral intraparietal neurons to visually presented objects.

    Science.gov (United States)

    Sigurdardottir, Heida M; Sheinberg, David L

    2015-07-01

    The lateral intraparietal area (LIP) is thought to play an important role in the guidance of where to look and pay attention. LIP can also respond selectively to differently shaped objects. We sought to understand to what extent short-term and long-term experience with visual orienting determines the responses of LIP to objects of different shapes. We taught monkeys to arbitrarily associate centrally presented objects of various shapes with orienting either toward or away from a preferred spatial location of a neuron. The training could last for less than a single day or for several months. We found that neural responses to objects are affected by such experience, but that the length of the learning period determines how this neural plasticity manifests. Short-term learning affects neural responses to objects, but these effects are only seen relatively late after visual onset; at this time, the responses to newly learned objects resemble those of familiar objects that share their meaning or arbitrary association. Long-term learning affects the earliest bottom-up responses to visual objects. These responses tend to be greater for objects that have been associated with looking toward, rather than away from, LIP neurons' preferred spatial locations. Responses to objects can nonetheless be distinct, although they have been similarly acted on in the past and will lead to the same orienting behavior in the future. Our results therefore indicate that a complete experience-driven override of LIP object responses may be difficult or impossible. We relate these results to behavioral work on visual attention.

  19. Unconventional cytokine profiles and development of T cell memory in long-term survivors after cancer vaccination

    DEFF Research Database (Denmark)

    Kyte, Jon Amund; Trachsel, Sissel; Risberg, Bente

    2009-01-01

    Cancer vaccine trials frequently report on immunological responses, without any clinical benefit. This paradox may reflect the challenge of discriminating between effective and pointless immune responses and sparse knowledge on their long-term development. Here, we have analyzed T cell responses...... in long-term survivors after peptide vaccination. There were three main study aims: (1) to characterize the immune response in patients with a possible clinical benefit. (2) To analyze the long-term development of responses and effects of booster vaccination. (3) To investigate whether the Th1/Th2...... display unconventional cytotoxicity and specifically kill tumor cells expressing mutated TGFbeta receptor II. Cytokine profiling on the long-term survivors demonstrates high IFN gamma/IL10-ratios, favoring immunity over tolerance, and secretion of multiple chemokines likely to mobilize the innate...

  20. Predicting the long-term effects of human-robot interaction: a reflection on responsibility in medical robotics.

    Science.gov (United States)

    Datteri, Edoardo

    2013-03-01

    This article addresses prospective and retrospective responsibility issues connected with medical robotics. It will be suggested that extant conceptual and legal frameworks are sufficient to address and properly settle most retrospective responsibility problems arising in connection with injuries caused by robot behaviours (which will be exemplified here by reference to harms occurred in surgical interventions supported by the Da Vinci robot, reported in the scientific literature and in the press). In addition, it will be pointed out that many prospective responsibility issues connected with medical robotics are nothing but well-known robotics engineering problems in disguise, which are routinely addressed by roboticists as part of their research and development activities: for this reason they do not raise particularly novel ethical issues. In contrast with this, it will be pointed out that novel and challenging prospective responsibility issues may emerge in connection with harmful events caused by normal robot behaviours. This point will be illustrated here in connection with the rehabilitation robot Lokomat.

  1. Inter and intra-specific variation in photosynthetic acclimation response to long term exposure of elevated carbon dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Wilkinson, M. [Univ. of Essex, Colchester (United Kingdom)]|[Writtle Coll. (United Kingdom)

    1996-08-01

    The response of intra and interspecific variation in photosynthetic acclimation to growth at elevated atmospheric CO{sub 2} concentration (600{micro}mol mol-l) in six important grassland species was investigated. Plants were grown in a background sward of Lolium perenne and measurements were made after four years of growth at elevated C{sub a}. Elevated CO{sub 2} was maintained using a FACE (Free-Air Carbon Enrichment) system. Significant intra and interspecific variation in acclimation response was demonstrated. The response of adaxial and abaxial stomatal conductance to elevated CO{sub 2} was also investigated. The stomatal conductance of both the adaxial and abaxial leaf surfaces was found to be reduced by elevated C{sub a}. Significant asymmetric responses in stomatal conductance was demonstrated in D. glomerata and T. pratense. Analysis of stomatal indices and densities indicated that the observed reductions in stomatal conductance were probably the result of changes in stomatal aperture.

  2. Contrasts in short- and long-term responses of Mediterranean reptile species to fire and habitat structure.

    Science.gov (United States)

    Santos, Xavier; Badiane, Arnaud; Matos, Cátia

    2016-01-01

    Changes in habitat structure constitute a major factor explaining responses of reptiles to fire. However, few studies have examined habitat factors that covary with fire-history variables to explain reptile responses. We hypothesise that more complex habitats should support richer reptile communities, and that species-specific relative abundance should be related to particular habitat features. From spring 2012-2014, twenty-five transects were surveyed in the Albera Region (north-east Iberia). The vegetation structure was measured and the extent of habitat types in a 1000-m buffer around each transect calculated. Reptile-community metrics (species richness and reptile abundance) were related to fire history, vegetation structure, and habitat types, using generalized additive models. These metrics correlated with habitat-structure variables but not with fire history. The number of species increased with more complex habitats but decreased with pine-plantation abundance in the 1000-m buffer. We found contrasting responses among reptiles in terms of time since fire and those responses differed according to vegetation variables and habitat types. An unplanned fire in August 2012 provided the opportunity to compare reptile abundance values between pre-fire and the short term (1-2 years) after the fire. Most species exhibited a negative short-term response to the 2012 fire except Tarentola mauritanica, a gecko that inhabits large rocks, as opposed to other ground-dwelling species. In the reptiles studied, contrasting responses to time since fire are consistent with the habitat-accommodation model of succession. These differences are linked to specific microhabitat preferences and suggest that functional traits can be used to predict species-specific responses to fire.

  3. Quantifying long-term responses of crop yield and nitrate leaching in an intensive farmland using agro-eco-environmental model.

    Science.gov (United States)

    Sun, Mei; Huo, Zailin; Zheng, Yanxia; Dai, Xiaoqin; Feng, Shaoyuan; Mao, Xiaomin

    2018-02-01

    Quantitatively ascertaining and analyzing long-term responses of crop yield and nitrate leaching on varying irrigation and fertilization treatments are focal points for guaranteeing crop yield and reducing nitrogen loss. The calibrated agricultural-hydrological RZWQM2 model was used to explore the long-term (2003-2013) transport processes of water and nitrogen and the nitrate leaching amount into groundwater in summer maize and winter wheat rotation field in typical intensive plant area in the North China Plain, Daxing district of Beijing. Simulation results showed that application rates of irrigation and nitrogen fertilizer have couple effects on crop yields and nitrogen leaching of root zone. When both the irrigation and fertilizer for summer maize and winter wheat were 400mm and 400kgNha -1 , respectively, nitrate leaching into groundwater accounted for 47.9% of application amount of nitrogen fertilizer. When application amount of irrigation is 200mm and fertilization is 200kgNha -1 , NUPE (nitrogen uptake efficiency), NUE (nitrogen use efficiency), NPFP (nitrogen partial factor productivity), and W pi (irrigation water productive efficiency) were in general higher than that under other irrigation and fertilization condition (irrigation from 104-400mm, fertilizer 104-400kgNha -1 ). Irrigation bigger than 200mm could shorten the response time of nitrate leaching in deeper soil layer in different irrigation treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. SKI and SSI's recommendations to the government concerning long-term responsibility after closure of a repository for spent nuclear fuel

    International Nuclear Information System (INIS)

    Paeivioe Jonsson, Josefin

    2008-01-01

    Many activities will cease at the closure of a repository, but not responsibilities. The candidate municipalities in Sweden expressed concern about who will take over after the implementer is released from responsibility for the facility. The government thus commissioned SKI (Swedish Nuclear Power Inspectorate) and SSI (Swedish Radiation Protection Authority) to review the legal obligations of institutional players as laid out today in legislation in Sweden. After closure of the repository in about 100 years there will be post-closure monitoring, possibly for a few hundred years. This will be a part of the conditions on SKB (Swedish Nuclear Fuel and Waste Management Company) which will be set out at the time. Some activities will end at the closure of the facility but monitoring and safeguards obligations may continue. The exact nature of this monitoring and safeguard work needs to be discussed and agreed upon. With the proposed approach most of the liabilities rest with the state in the long term, the waste producers only have liabilities in the short term but their decisions could have big impacts on long term liabilities

  5. Integrated long-term responses of an arctic-alpine willow and associated ectomycorrhizal fungi to an altered environment

    DEFF Research Database (Denmark)

    Clemmensen, Karina Engelbrecht; Michelsen, Anders

    2006-01-01

    We evaluated ectomycorrhizal (ECM) colonization and morphotype community composition together with growth response and biomass distribution in the arctic-alpine, prostrate willow Salix herbacea L. x Salix polaris Wahlenb. after 11 seasons of shading, warming, and fertilization at a fellfield...

  6. Evaluation of Seismic Response Trends from Long-Term Monitoring of Two Instrumented RC Buildings Including Soil-Structure Interaction

    Directory of Open Access Journals (Sweden)

    Faheem Butt

    2012-01-01

    Full Text Available This paper presents analyses of the seismic responses of two reinforced concrete buildings monitored for a period of more than two years. One of the structures was a three-storey reinforced concrete (RC frame building with a shear core, while the other was a three-storey RC frame building without a core. Both buildings are part of the same large complex but are seismically separated from the rest of it. Statistical analysis of the relationships between maximum free field accelerations and responses at different points on the buildings was conducted and demonstrated strong correlation between those. System identification studies using recorded accelerations were undertaken and revealed that natural frequencies and damping ratios of the building structures vary during different earthquake excitations. This variation was statistically examined and relationships between identified natural frequencies and damping ratios, and the peak response acceleration at the roof level were developed. A general trend of decreasing modal frequencies and increasing damping ratios was observed with increased level of shaking and response. Moreover, the influence of soil structure interaction (SSI on the modal characteristics was evaluated. SSI effects decreased the modal frequencies and increased some of the damping ratios.

  7. Response of the benthic food web to short- and long-term nutrient enrichment in saltmarsh mudflats

    NARCIS (Netherlands)

    Pascal, P.-Y.; Fleeger, J.W.; Boschker, H.T.S.; Mitwally, H.M.; Johnson, D.S.

    2013-01-01

    We examined the responses of biota at or near the base of the benthic food web to nutrient enrichment in salt marsh mudflats in Plum Island estuary (Massachusetts, USA). To simulate eutrophication, nitrate and phosphate loading rates were increased 10- to 15-fold in creeks fertilized for 2 mo (i.e.

  8. Initial cognitive response to cholinesterase inhibitors and subsequent long-term course in patients with mild Alzheimer's disease

    NARCIS (Netherlands)

    Droogsma, Erika; van Asselt, Dieneke; Diekhuis, Marjolein; Veeger, Nic; van der Hooft, Cornelis; De Deyn, Peter Paul

    Background: Some guidelines recommend to discontinue treatment with cholinesterase inhibitors (ChEIs) in patients with Alzheimer's disease (AD) without an initial response to ChEI treatment. Evidence supporting this recommendation, however, is limited. This study aimed to investigate the relation

  9. CARDIAC AND BEHAVIORAL-RESPONSES OF LONG-TERM OBESE AND LEAN ZUCKER RATS TO EMOTIONAL-STRESS

    NARCIS (Netherlands)

    NYAKAS, C; BALKAN, B; STEFFENS, AB; BOHUS, B

    1995-01-01

    Obesity is known as a risk factor in stress-related cardiovascular pathology in man. The length of obesity can be an important interacting variable. Therefore, cardiac and behavioral responses to emotional stress were studied in 1-year-old, genetically obese (fa/fa) and lean (Fa/-) male Zucker rats,

  10. Infant Long-Term Memory for a Conditioned Response and Intelligence Test Performance at 2 Years of Age.

    Science.gov (United States)

    Fagen, Jeffrey W.; And Others

    To find predictive relations between measures taken in infancy and later scores on intelligence tests, a study was made that measured in the infant those cognitive processes examined later in life. Operant conditioning tasks were employed which required 3-, 7-, and 11-month-old infants to execute some response to produce an environmental…

  11. Modeling context-sensitive, dynamic activity travel behavior by linking short-and long-term responses to accumulated stress

    NARCIS (Netherlands)

    Psarra, I.; Liao, F.; Arentze, T.A.; Timmermans, H.J.P.

    2014-01-01

    As existing activity-based models of travel demand simulate activity travel patterns for a typical day, dynamic models simulate behavioral response to endogenous or exogenous change along various time horizons. Prior research predominantly addressed a specific kind of change, which usually affected

  12. Aqueous exposure to Aroclor 1254 modulates the mitogenic response of Atlantic salmon anterior kidney T-cells: indications of short- and long-term immunomodulation.

    Science.gov (United States)

    Iwanowicz, Luke R; Lerner, Darren T; Blazer, Vicki S; McCormick, Stephen D

    2005-05-15

    Polychlorinated biphenyls (PCBs) exist as persistent organic pollutants in numerous river systems in the United States. Unfortunately, some of these rivers are sites of active Atlantic salmon restoration programs, and polychlorinated biphenyls have been implicated as ancillary factors contributing to failed salmon restoration. Here, we investigate the immediate and chronic effects of intermediate duration aqueous PCB exposure (1 or 10 microgL-1 Aroclor 1254) on the mitogen-stimulated lymphoproliferative response of Atlantic salmon anterior kidney leukocytes (AKLs). A short-term study was designed to examine immunomodulation in Atlantic salmon smolts immediately following 21 days of aqueous exposure, while a long-term study evaluated chronic impacts in the mitogen response in parr 15 months post-exposure as larvae. The proliferative response of AKLs to the mitogens concanavalin A (CON A), phytohemaglutinnin-P (PHA-P), pokeweed mitogen (PWM), and lipopolysaccharide were used as an indice of immunomodulation. The proliferative response to the T-cell mitogens CON A and PHA-P was significantly increased in the 10 microgL-1 group (n=10; P=0.043 and 0.002, respectively) immediately following exposure of smolts. Additionally, The PHA-P response was significantly increased in the 1 microgL-1 exposure group (n=10, P=0.036). In fish treated as larvae and tested 15 months later, the PHA-P sensitive populations exhibited elevated proliferation in the 1 and 10 microgL-1 groups (n=12, P<0.04) relative to the vehicle control while the PWM response was significantly increased (n=12, P=0.036) only in the 10 microgL-1 treated groups. These results demonstrate an immunomodulatory effect of PCBs on T-cell mitogen sensitive populations of lymphocytes in Atlantic salmon as well as long-term immunomodulation in PHA-P and PWM sensitive populations.

  13. Asymmetric Responses of Primary Productivity to Altered Precipitation Simulated by Land Surface Models across Three Long-term Grassland Sites

    Science.gov (United States)

    Wu, D.; Ciais, P.; Viovy, N.; Knapp, A.; Wilcox, K.; Bahn, M.; Smith, M. D.; Ito, A.; Arneth, A.; Harper, A. B.; Ukkola, A.; Paschalis, A.; Poulter, B.; Peng, C.; Reick, C. H.; Hayes, D. J.; Ricciuto, D. M.; Reinthaler, D.; Chen, G.; Tian, H.; Helene, G.; Zscheischler, J.; Mao, J.; Ingrisch, J.; Nabel, J.; Pongratz, J.; Boysen, L.; Kautz, M.; Schmitt, M.; Krohn, M.; Zeng, N.; Meir, P.; Zhang, Q.; Zhu, Q.; Hasibeder, R.; Vicca, S.; Sippel, S.; Dangal, S. R. S.; Fatichi, S.; Sitch, S.; Shi, X.; Wang, Y.; Luo, Y.; Liu, Y.; Piao, S.

    2017-12-01

    Changes in precipitation variability including the occurrence of extreme events strongly influence plant growth in grasslands. Field measurements of aboveground net primary production (ANPP) in temperate grasslands suggest a positive asymmetric response with wet years resulting in ANPP gains larger than ANPP declines in dry years. Whether land surface models used for historical simulations and future projections of the coupled carbon-water system in grasslands are capable to simulate such non-symmetrical ANPP responses remains an important open research question. In this study, we evaluate the simulated responses of grassland primary productivity to altered precipitation with fourteen land surface models at the three sites of Colorado Shortgrass Steppe (SGS), Konza prairie (KNZ) and Stubai Valley meadow (STU) along a rainfall gradient from dry to wet. Our results suggest that: (i) Gross primary production (GPP), NPP, ANPP and belowground NPP (BNPP) show nonlinear response curves (concave-down) in all the models, but with different curvatures and mean values. In contrast across the sites, primary production increases and then saturates along increasing precipitation with a flattening at the wetter site. (ii) Slopes of spatial relationships between modeled primary production and precipitation are steeper than the temporal slopes (obtained from inter-annual variations). (iii) Asymmetric responses under nominal precipitation range with modeled inter-annual primary production show large uncertainties, and model-ensemble median generally suggests negative asymmetry (greater declines in dry years than increases in wet years) across the three sites. (iv) Primary production at the drier site is predicted to more sensitive to precipitation compared to wetter site, and median sensitivity consistently indicates greater negative impacts of reduced precipitation than positive effects of increased precipitation under extreme conditions. This study implies that most models

  14. Early Life Arsenic Exposure and Acute and Long-term Responses to Influenza A Infection in Mice

    OpenAIRE

    Ramsey, Kathryn A.; Foong, Rachel E.; Sly, Peter D.; Larcombe, Alexander N.; Zosky, Graeme R.

    2013-01-01

    Background: Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood. Objective: We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice. Methods: C57BL/6 mice were exposed to arsenic in utero and throughout postnatal lif...

  15. Exposure–response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development

    Science.gov (United States)

    Han, Seunghoon; Jeon, Sangil; Hong, Taegon; Lee, Jongtae; Bae, Soo Hyeon; Park, Wan-su; Park, Gab-jin; Youn, Sunil; Jang, Doo Yeon; Kim, Kyung-Soo; Yim, Dong-Seok

    2015-01-01

    No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure–response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120). Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure–response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects’ sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg) and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure–response model, which included the placebo effect, is the first example of a quantitative model that can be used to predict the efficacy of weight-control drugs. Similar approaches can help decision-making during clinical development of novel weight-loss drugs. PMID:26392753

  16. Exposure-response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development.

    Science.gov (United States)

    Han, Seunghoon; Jeon, Sangil; Hong, Taegon; Lee, Jongtae; Bae, Soo Hyeon; Park, Wan-su; Park, Gab-jin; Youn, Sunil; Jang, Doo Yeon; Kim, Kyung-Soo; Yim, Dong-Seok

    2015-01-01

    No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure-response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120). Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure-response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects' sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg) and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure-response model, which included the placebo effect, is the first example of a quantitative model that can be used to predict the efficacy of weight-control drugs. Similar approaches can help decision-making during clinical development of novel weight-loss drugs.

  17. World Experience of Introduction of Socio-Economic Responsibility of Entrepreneurship as a Long-Term Strategy of its Development

    Directory of Open Access Journals (Sweden)

    Datskevych Nataliya O.

    2013-11-01

    Full Text Available The main goal of the article is analysis of existing models of social responsibility of entrepreneurship (American, European, British and Asian with consideration of regional specific features of its application. The article uses methods of abstraction and synthesis along with historical and practical approaches. In the conclusions the article generalises prospects for further search for the most optimal variants of development of this concept under conditions of development of the modern society. It also provides principal differences and main forms of realisation of social responsibility in such countries as USA, France, Germany, China and Japan. Social consequence of the article is re-consideration of the role of entrepreneurship as an important component of effective development of the society and observance of the concept of sustainable development as strategically important in the scale of the world. Value of the article is a proof of urgency of consideration of the issue of the socio-economic responsibility of entrepreneurship under conditions of modern global challenges and a necessity of their effective solution both from the side of the state and business.

  18. Aqueous exposure to Aroclor 1254 modulates the mitogenic response of Atlantic salmon anterior kidney T-cells: Indications of short- and long-term immunomodulation

    International Nuclear Information System (INIS)

    Iwanowicz, Luke R.; Lerner, Darren T.; Blazer, Vicki S.; McCormick, Stephen D.

    2005-01-01

    Polychlorinated biphenyls (PCBs) exist as persistent organic pollutants in numerous river systems in the United States. Unfortunately, some of these rivers are sites of active Atlantic salmon restoration programs, and polychlorinated biphenyls have been implicated as ancillary factors contributing to failed salmon restoration. Here, we investigate the immediate and chronic effects of intermediate duration aqueous PCB exposure (1 or 10 μg L -1 Aroclor 1254) on the mitogen-stimulated lymphoproliferative response of Atlantic salmon anterior kidney leukocytes (AKLs). A short-term study was designed to examine immunomodulation in Atlantic salmon smolts immediately following 21 days of aqueous exposure, while a long-term study evaluated chronic impacts in the mitogen response in parr 15 months post-exposure as larvae. The proliferative response of AKLs to the mitogens concanavalin A (CON A), phytohemaglutinnin-P (PHA-P), pokeweed mitogen (PWM), and lipopolysaccharide were used as an indice of immunomodulation. The proliferative response to the T-cell mitogens CON A and PHA-P was significantly increased in the 10 μg L -1 group (n = 10; P = 0.043 and 0.002, respectively) immediately following exposure of smolts. Additionally, The PHA-P response was significantly increased in the 1 μg L -1 exposure group (n = 10, P = 0.036). In fish treated as larvae and tested 15 months later, the PHA-P sensitive populations exhibited elevated proliferation in the 1 and 10 μg L -1 groups (n = 12, P -1 treated groups. These results demonstrate an immunomodulatory effect of PCBs on T-cell mitogen sensitive populations of lymphocytes in Atlantic salmon as well as long-term immunomodulation in PHA-P and PWM sensitive populations

  19. Exposure–response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development

    Directory of Open Access Journals (Sweden)

    Han S

    2015-09-01

    Full Text Available Seunghoon Han,1,2 Sangil Jeon,1,2 Taegon Hong,1,2 Jongtae Lee,1,2 Soo Hyeon Bae,1,2 Wan-su Park,1,2 Gab-jin Park,1,2 Sunil Youn,1,2 Doo Yeon Jang,1,2 Kyung-Soo Kim,3 Dong-Seok Yim1,2 1Department of Pharmacology, College of Medicine, The Catholic University of Korea, 2Pharmacometrics Institute for Practical Education and Training, 3Department of Family Medicine, Seoul St Mary’s Hospital, Seochogu, Seoul, Republic of KoreaAbstract: No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure–response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120. Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost <2 kg after 4 weeks’ treatment were escalated to 12.55 mg. The duration of treatment was 24 weeks. Drug concentration and body weight were measured predose and at 4 weeks, 8 weeks, and 24 weeks after treatment initiation. Exposure and response to sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure–response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects’ sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure–response model, which

  20. Long-term fate of crankcase oil in rainbow trout: A time- and dose-response study

    International Nuclear Information System (INIS)

    Hellou, J.; Warren, W.; Andrews, C.; Mercer, G.; Payne, J.F.; Howse, D.

    1997-01-01

    Rainbow trout (Oncorhynchus mykiss) were exposed to waste crankcase oil, a recognized source of polycyclic aromatic hydrocarbon (PAH) contamination in urban runoff. Dietary exposure was to a mean concentration of 0, 3.5, 8.9, and 13 microg oil/g fish, and sampling took place after 3, 7, 11, and 15 weeks. The accumulation of compounds in muscle tissue, the elimination of bile metabolites, the activity of 7-ethoxyresorufin O-deethylase (EROD) in liver, and morphometric variables were compared at the different concentrations and times of sampling. The concentration of fluorescing compounds in muscle displayed the best dose- and time-response pattern, whereas other biological, chemical, and biochemical responses were not as well defined. No correlation could be drawn between the concentration of PAH in the oil and the measured variables. The environmentally relevant concentrations used in the experiment show the importance of choosing broad and specific indicators of exposure in a multidisciplinary investigation and the need for further research in chemical and toxicologic areas

  1. Association between frequent cardiac resynchronization therapy optimization and long-term clinical response: a post hoc analysis of the Clinical Evaluation on Advanced Resynchronization (CLEAR) pilot study

    Science.gov (United States)

    Delnoy, Peter Paul; Ritter, Philippe; Naegele, Herbert; Orazi, Serafino; Szwed, Hanna; Zupan, Igor; Goscinska-Bis, Kinga; Anselme, Frederic; Martino, Maria; Padeletti, Luigi

    2013-01-01

    Aims The long-term clinical value of the optimization of atrioventricular (AVD) and interventricular (VVD) delays in cardiac resynchronization therapy (CRT) remains controversial. We studied retrospectively the association between the frequency of AVD and VVD optimization and 1-year clinical outcomes in the 199 CRT patients who completed the Clinical Evaluation on Advanced Resynchronization study. Methods and results From the 199 patients assigned to CRT-pacemaker (CRT-P) (New York Heart Association, NYHA, class III/IV, left ventricular ejection fraction failure-related hospitalization, NYHA functional class, and Quality of Life score, at 1 year. Systematic CRT optimization was associated with a higher percentage of improved patients based on the composite endpoint (85% in Group 1 vs. 61% in Group 2, P < 0.001), with fewer deaths (3% in Group 1 vs. 14% in Group 2, P = 0.014) and fewer hospitalizations (8% in Group 1 vs. 23% in Group 2, P = 0.007), at 1 year. Conclusion These results further suggest that AVD and VVD frequent optimization (at implant, at 3 and 6 months) is associated with improved long-term clinical response in CRT-P patients. PMID:23493410

  2. Changes in gene expression caused by insect venom immunotherapy responsible for the long-term protection of insect venom-allergic patients.

    Science.gov (United States)

    Niedoszytko, Marek; Bruinenberg, Marcel; de Monchy, Jan; Weersma, Rinse K; Wijmenga, Cisca; Jassem, Ewa; Elberink, Joanne N G Oude

    2011-06-01

    Insect venom immunotherapy (VIT) is the only causative treatment of insect venom allergy (IVA). The immunological mechanism(s) responsible for long-term protection achieved by VIT are largely unknown. A better understanding is relevant for improving the diagnosis, prediction of anaphylaxis, and monitoring and simplifying treatment of IVA. To find genes that are differentially expressed during the maintenance phase of VIT and after stopping, to get clues about the pathways involved in the long-term protective effect of immunotherapy. Whole genome gene expression analysis was performed on RNA samples from 50 patients treated with VIT and 43 healthy controls. Patients were divided into three groups: (1) before the start of VIT; (2) on maintenance phase of VIT for at least 3 years still receiving injections; and (3) after VIT. Of all 48,804 probes present in the array, 48,773 transcripts had sufficient data for further analysis. The list of genes that were differentially expressed (at least log2 FC > 2; P Immunology. Published by Elsevier Inc. All rights reserved.

  3. Systems-Wide Analysis of Acclimation Responses to Long-Term Heat Stress and Recovery in the Photosynthetic Model Organism Chlamydomonas reinhardtii[W][OPEN

    Science.gov (United States)

    Hemme, Dorothea; Veyel, Daniel; Mühlhaus, Timo; Sommer, Frederik; Jüppner, Jessica; Unger, Ann-Katrin; Sandmann, Michael; Fehrle, Ines; Schönfelder, Stephanie; Steup, Martin; Geimer, Stefan; Kopka, Joachim; Giavalisco, Patrick; Schroda, Michael

    2014-01-01

    We applied a top-down systems biology approach to understand how Chlamydomonas reinhardtii acclimates to long-term heat stress (HS) and recovers from it. For this, we shifted cells from 25 to 42°C for 24 h and back to 25°C for ≥8 h and monitored abundances of 1856 proteins/protein groups, 99 polar and 185 lipophilic metabolites, and cytological and photosynthesis parameters. Our data indicate that acclimation of Chlamydomonas to long-term HS consists of a temporally ordered, orchestrated implementation of response elements at various system levels. These comprise (1) cell cycle arrest; (2) catabolism of larger molecules to generate compounds with roles in stress protection; (3) accumulation of molecular chaperones to restore protein homeostasis together with compatible solutes; (4) redirection of photosynthetic energy and reducing power from the Calvin cycle to the de novo synthesis of saturated fatty acids to replace polyunsaturated ones in membrane lipids, which are deposited in lipid bodies; and (5) when sinks for photosynthetic energy and reducing power are depleted, resumption of Calvin cycle activity associated with increased photorespiration, accumulation of reactive oxygen species scavengers, and throttling of linear electron flow by antenna uncoupling. During recovery from HS, cells appear to focus on processes allowing rapid resumption of growth rather than restoring pre-HS conditions. PMID:25415976

  4. The long-term resistance mechanisms, critical irrigation threshold and relief capacity shown by Eugenia myrtifolia plants in response to saline reclaimed water

    DEFF Research Database (Denmark)

    Acosta-Motos, José Ramón; Hernández, José Antonio; Álvarez, Sara

    2017-01-01

    water potential, the relative water content of leaves, leaf stomatal conductance, the leaf photosynthetic rate, water-use efficiency and accumulated evapotranspiration in order to limit water loss; and 4) changes in the antioxidant defence mechanisms. These different responses induced oxidative stress...... to different electric conductivities of the treatments. Based on these premises, we studied the long-term effect of three reclaimed water treatments with different saline concentrations on Eugenia myrtifolia plants. We also looked at the ability of these plants to recover when no drainage was applied. The RW...... with the highest electric conductivity (RW3, EC = 6.96 dS m(-1)) provoked a number of responses to salinity in these plants, including: 1) accumulation and extrusion of phytotoxic ions in roots; 2) a decrease in the shoot/root ratio, leaf area, number of leaves; 3) a decrease in root hydraulic conductivity, leaf...

  5. Bird-community responses to habitat creation in a long-term, large-scale natural experiment.

    Science.gov (United States)

    Whytock, Robin C; Fuentes-Montemayor, Elisa; Watts, Kevin; Barbosa De Andrade, Patanjaly; Whytock, Rory T; French, Paul; Macgregor, Nicholas A; Park, Kirsty J

    2018-04-01

    Ecosystem function and resilience are compromised when habitats become fragmented due to land-use change. This has led to national and international conservation strategies aimed at restoring habitat extent and improving functional connectivity (i.e., maintaining dispersal processes). However, biodiversity responses to landscape-scale habitat creation and the relative importance of spatial and temporal scales are poorly understood, and there is disagreement over which conservation strategies should be prioritized. We used 160 years of historic post-agricultural woodland creation as a natural experiment to evaluate biodiversity responses to habitat creation in a landscape context. Birds were surveyed in 101 secondary, broadleaf woodlands aged 10-160 years with ≥80% canopy cover and in landscapes with 0-17% broadleaf woodland cover within 3000 m. We used piecewise structural equation modeling to examine the direct and indirect relationships between bird abundance and diversity, ecological continuity, patch characteristics, and landscape structure and quantified the relative conservation value of local and landscape scales for bird communities. Ecological continuity indirectly affected overall bird abundance and species richness through its effects on stand structure, but had a weaker influence (effect size near 0) on the abundance and diversity of species most closely associated with woodland habitats. This was probably because woodlands were rapidly colonized by woodland generalists in ≤10 years (minimum patch age) but were on average too young (median 50 years) to be colonized by woodland specialists. Local patch characteristics were relatively more important than landscape characteristics for bird communities. Based on our results, biodiversity responses to habitat creation depended on local- and landscape-scale factors that interacted across time and space. We suggest that there is a need for further studies that focus on habitat creation in a landscape

  6. Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival.

    Science.gov (United States)

    Viganò, Luca; Capussotti, Lorenzo; De Rosa, Giovanni; De Saussure, Wassila Oulhaci; Mentha, Gilles; Rubbia-Brandt, Laura

    2013-11-01

    We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy. CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear. Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases. A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival

  7. Local Seismicity Recorded by ChilePEPPER: Implications for Dynamic Accretionary Prism Response and Long-term Prism Evolution

    Science.gov (United States)

    de Moor, A.; Trehu, A. M.; Tryon, M. D.

    2015-12-01

    To investigate the dynamic response of the outer accretionary wedge updip from the patch of greatest slip during the Mw8.8 2010 Maule earthquake, 10 Ocean Bottom Seismometers (OBS) were deployed from May 2012 to March 2013 in a small array with an inter-instrument spacing of ~12 km . Nine instruments were recovered, with 4 recording data on 3 intermediate-band 3-component seismometers and a differential pressure gauge and 5 recording data from absolute pressure gauges. [note: All instruments were also equipped with a fluid flow meter sensitive to flow rates as low as 0.0001 cm/yr in or out of the sediments. However, no flow signal was detected.] Here we present hypocenters for 569 local events that have S-P times less than 17 seconds (i.e. within ~125 km of the array) using hand-picked arrival times and a 1D velocity model derived from a 2D seismic refraction profile through the region (Moscoso et al 2011, EPSL). We analyze the distribution of seismicity in the context of published slip models, ChilePEPPER high-resolution seismic reflection data, critical taper analysis done by Cubas et al 2013 (EPSL), and offshore gravity data. The data show distinct segmentation within the outer prism. The northern section of the study area is characterized by a lack of seismicity, accretion of nearly all incoming sediment and a prism at critical taper. In contrast, abundant seismicity, significant sediment underthrusting at the deformation front and a prism below critical taper angle characterize the southern part of the study area. Both coseismic slip and post-rupture local seismicity can be related to density anomalies within the upper plate as revealed by free air gravity data corrected for the effects of bathymetry and the subducting plate. [ChilePEPPER - Project Evaluating Prism Post-Earthquake Response

  8. Innate Immune Responses in Leprosy

    Science.gov (United States)

    Pinheiro, Roberta Olmo; Schmitz, Veronica; Silva, Bruno Jorge de Andrade; Dias, André Alves; de Souza, Beatriz Junqueira; de Mattos Barbosa, Mayara Garcia; de Almeida Esquenazi, Danuza; Pessolani, Maria Cristina Vidal; Sarno, Euzenir Nunes

    2018-01-01

    Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Several studies have clarified the role of various T cell populations in leprosy; however, recent evidences suggest that local innate immune mechanisms are key determinants in driving the disease to its different clinical manifestations. Leprosy is an ideal model to study the immunoregulatory role of innate immune molecules and its interaction with nervous system, which can affect homeostasis and contribute to the development of inflammatory episodes during the course of the disease. Macrophages, dendritic cells, neutrophils, and keratinocytes are the major cell populations studied and the comprehension of the complex networking created by cytokine release, lipid and iron metabolism, as well as antimicrobial effector pathways might provide data that will help in the development of new strategies for leprosy management. PMID:29643852

  9. Clinical outcome of HIV-infected patients with sustained virologic response to antiretroviral therapy: long-term follow-up of a multicenter cohort.

    Directory of Open Access Journals (Sweden)

    Félix Gutierrez

    Full Text Available BACKGROUND: Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. METHODS: Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. RESULTS: Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9% patients died (mortality rate 0.86 per 100 person-years, and 40 (5.3% died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68-10.83]; P = .002, and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02-1.09; P = .001. Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. CONCLUSIONS: Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected.

  10. Introduction: Long term prediction

    International Nuclear Information System (INIS)

    Beranger, G.

    2003-01-01

    Making a decision upon the right choice of a material appropriate to a given application should be based on taking into account several parameters as follows: cost, standards, regulations, safety, recycling, chemical properties, supplying, transformation, forming, assembly, mechanical and physical properties as well as the behaviour in practical conditions. Data taken from a private communication (J.H.Davidson) are reproduced presenting the life time range of materials from a couple of minutes to half a million hours corresponding to applications from missile technology up to high-temperature nuclear reactors or steam turbines. In the case of deep storage of nuclear waste the time required is completely different from these values since we have to ensure the integrity of the storage system for several thousand years. The vitrified nuclear wastes should be stored in metallic canisters made of iron and carbon steels, stainless steels, copper and copper alloys, nickel alloys or titanium alloys. Some of these materials are passivating metals, i.e. they develop a thin protective film, 2 or 3 nm thick - the so-called passive films. These films prevent general corrosion of the metal in a large range of chemical condition of the environment. In some specific condition, localized corrosion such as the phenomenon of pitting, occurs. Consequently, it is absolutely necessary to determine these chemical condition and their stability in time to understand the behavior of a given material. In other words the corrosion system is constituted by the complex material/surface/medium. For high level nuclear wastes the main features for resolving problem are concerned with: geological disposal; deep storage in clay; waste metallic canister; backfill mixture (clay-gypsum) or concrete; long term behavior; data needed for modelling and for predicting; choice of appropriate solution among several metallic candidates. The analysis of the complex material/surface/medium is of great importance

  11. Long-Term Symbolic Learning

    National Research Council Canada - National Science Library

    Kennedy, William G; Trafton, J. G

    2007-01-01

    What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

  12. Population-expression models of immune response

    International Nuclear Information System (INIS)

    Stromberg, Sean P; Antia, Rustom; Nemenman, Ilya

    2013-01-01

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable. (paper)

  13. Responses of soil Collembola to long-term atmospheric CO2 enrichment in a mature temperate forest

    International Nuclear Information System (INIS)

    Xu Guoliang; Fu Shenglei; Schleppi, Patrick; Li Maihe

    2013-01-01

    Responses of Collembola to 7 years of CO 2 enrichment (550 ppm) in a Swiss free-air CO 2 enrichment (FACE) experiment in a forest with 80- to 120-year-old trees were investigated in this study. Contrary to our expectations, increased CO 2 caused a significant decrease in Collembola numbers, including a significant decrease in euedaphic Collembola. Increased CO 2 , however, did not affect community group richness. Collembola biomass was not significantly changed by CO 2 enrichment, regardless of whether it was considered in terms of the total community, life-strategy groups, or individual species (with an exception of Mesaphorura krausbaueri). The reason for this is that CO 2 enrichment caused a general increase in individual body size, which compensated for reduced abundances. The results are consistent with the idea that the rhizosphere is important for soil fauna, and the combination of reduced fine root growth and increased soil moisture might trigger a reduction in Collembola abundance. - Highlights: ► Increased CO 2 caused a significant decrease in Collembola abundance. ► Increased CO 2 caused a significant decrease in euedaphic Collembola. ► Collembola body size tended to be larger. ► A decrease in fine roots biomass might trigger the reduction in Collembola. - Seven years of CO 2 enrichment caused a significant decrease in Collembola abundance, especially in euedaphic species.

  14. Clinical response to long term enzyme replacement treatment in children, adolescent and adult patients with Hunter syndrome.

    Science.gov (United States)

    Dalmau Serra, Jaime; Vitoria Miñana, Isidro; Calderón Fernández, Rafael; Cortell Aznar, Isidoro

    2015-11-06

    Since enzyme replacement treatment (ERT) with idursulfase is available for Hunter syndrome (HS; mucopolysaccharidosis type II), for the first time, disease progression can be limited and organ damage reduced or prevented. We described retrospectively the clinical evolution of eight HS males, treated with ERT and followed in routine clinical practice in Hospital Infantil La Fe (Valencia, Spain). We studied three children, three adolescents and two adults. Time from diagnosis to ERT ranged from 13.7 to 0.2 years, and duration of ERT ranged from 24 to 77.1 months. From the start of ERT, weight and height increased in children and adolescents and remained stable in adults. Glycosaminoglycans (GAG) decreased in all patients; in patient 5 (aged 23 years), we observed the highest reduction (86%) with recovery of carpal tunnel syndrome, splenomegaly and a decrease in nocturnal oxygen dependence. Our results show that ERT improve respiratory impairment and organomegalies and decrease GAGs levels in all patients including children, adolescent and adults. While cardiac manifestations and facial features stabilized, responses in other parameters were heterogeneous. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  15. Differential cellular responses by oncogenic levels of c-Myc expression in long-term confluent retinal pigment epithelial cells.

    Science.gov (United States)

    Wang, Yiping; Cheng, Xiangdong; Samma, Muhammad Kaleem; Kung, Sam K P; Lee, Clement M; Chiu, Sung Kay

    2018-06-01

    c-Myc is a highly pleiotropic transcription factor known to control cell cycle progression, apoptosis, and cellular transformation. Normally, ectopic expression of c-Myc is associated with promoting cell proliferation or triggering cell death via activating p53. However, it is not clear how the levels of c-Myc lead to different cellular responses. Here, we generated a series of stable RPE cell clones expressing c-Myc at different levels, and found that consistent low level of c-Myc induced cellular senescence by activating AP4 in post-confluent RPE cells, while the cells underwent cell death at high level of c-Myc. In addition, high level of c-Myc could override the effect of AP4 on cellular senescence. Further knockdown of AP4 abrogated senescence-like phenotype in cells expressing low level of c-Myc, and accelerated cell death in cells with medium level of c-Myc, indicating that AP4 was required for cellular senescence induced by low level of c-Myc.

  16. Factors affecting the long-term response of surface waters to acidic deposition: state-of-the-science

    Energy Technology Data Exchange (ETDEWEB)

    Turner, R.S.; Johnson, D.W.; Elwood, J.N.; Van Winkle, W.; Clapp, R.B.; Jones, M.L.; Marmarek, D.R.; Thornton, K.W.; Gherinig, S.A.; Schnoor, J.L.

    1986-01-01

    Recent intensive study of the causes of surface water acidification has led to numerous hypothesized controlling mechanisms. Among these are the salt-effect reduction of alkalinity, the base cation buffering and sulfate adsorption capacities of soils, availability of weatherable minerals (weathering rates), depth of till, micropore flow, and type of forest cover. Correlative and predictive models have been developed to show the relationships (if any) between hypothesized controlling mechanisms and surface water acidity, and to suggest under what conditions additional surface water might become acid. This document (Part A) is a review of our current knowledge of factors and processes controlling soil and surface water acidification, as well as an assessment of the adequacy of that knowledge for making predictions of future acidification. Section 2 is a data extensive, conceptual overview of how watersheds function. Section 3 is a closer look at the theory and evidence for the key hypotheses. Section 4 is a review of existing methods of assessing system response to acidic deposition.

  17. Microbial response to oil enrichment in Gulf of Mexico sediment measured using a novel long-term benthic lander system

    Directory of Open Access Journals (Sweden)

    Beth N. Orcutt

    2017-04-01

    Full Text Available Weathered crude oil sank to the seafloor following the 'Deepwater Horizon' disaster in 2010, removing this oil from further physical and photo-chemical degradation processes and leaving benthic processes as the mechanisms for altering and remediating this hydrocarbon source. To quantify potential microbial oil degradation rates at the seafloor, and associated changes in sediment microbial community structure and pore fluid composition, we used a benthic lander system to deploy novel sediment flow-through chambers at a natural hydrocarbon seep in the Gulf of Mexico (at a depth of 1226 m in lease block GC600 roughly 265 km southwest of the 'Deepwater Horizon' wellhead (at 1500 m depth. Sediment amended with 20% unweathered crude oil had elevated rates of sulfate reduction over the course of the 5-month-long experiment as compared to an unamended control, yielding potential rates of sulfate reduction (600–800 mmol m–2 d–1 among the highest measured in hydrocarbon-influenced seafloor sediment. Oil amendment also stimulated methane production towards the end of the experiment, and led to slightly higher cell densities without significant changes in microbial community structure, based on 16S rRNA gene sequence libraries and fatty acid profiles. Assuming a link between sulfate reduction and hydrocarbon degradation, these results suggest that electron acceptor availability may become limiting in heavily oiled deep-sea environments, resulting in minimal degradation of deposited oil. This study provides unique data on seafloor sediment responses to oil deposition, and reveals the value of using observatories to fill the gap in understanding deep-sea microbial processes, especially for ephemeral and stochastic events such as oil spills.

  18. Assessing the long-term implementation costs versus benefits associated with laser fluorosensor spill response technology. Volume 1

    International Nuclear Information System (INIS)

    Tebeau, P.A.; Hansen, K.A.; Fant, J.W.; Terrien, M.M.

    2007-01-01

    The laser fluorosensor (LF) is a developmental oil spill sensor capable of conclusively identifying oil in the marine environment, detecting the presence of oil on the surface of the water, even during darkness or reduced visibility conditions. LF can also detect oil below the surface of the water in typical marine environments. A study was conducted to determine the potential benefits and cost savings associated with the availability of an LF in supporting oil spill response operations, particularly heavy oil spills which are likely to sink below the surface of the water as it weathers with time. Since LF is expensive, the enhanced operational capabilities and associated cost-savings must be quantified and carefully weighed against the system acquisition and operation costs. The methodology used in this study to identify and quantify the benefits and cost savings was to conduct a scenario-based cost-benefit analysis in which significant spills that have occurred in the past were analyzed in detail to determine the costs incurred in responding to the spill with and without the availability of the LF technology. Four different implementation approaches were examined: installation on a United States Coast Guard (USCG) fixed-wing aircraft; installation on a USCG helicopter; installation on an aircraft-of-opportunity; and, contracting for the capability of another agency. The implementation costs considered in this study were system acquisition costs, system installation and integration costs, airborne platform costs, maintenance costs, personnel costs and training costs. It was determined that the annual implementation costs were approximately equal to the project annual cost savings. 12 refs., 4 tabs., 2 figs

  19. Prolonged asymmetric vestibular stimulation induces opposite, long-term effects on self-motion perception and ocular responses.

    Science.gov (United States)

    Pettorossi, V E; Panichi, R; Botti, F M; Kyriakareli, A; Ferraresi, A; Faralli, M; Schieppati, M; Bronstein, A M

    2013-04-01

    Self-motion perception and the vestibulo-ocular reflex (VOR) were investigated in healthy subjects during asymmetric whole body yaw plane oscillations while standing on a platform in the dark. Platform oscillation consisted of two half-sinusoidal cycles of the same amplitude (40°) but different duration, featuring a fast (FHC) and a slow half-cycle (SHC). Rotation consisted of four or 20 consecutive cycles to probe adaptation further with the longer duration protocol. Self-motion perception was estimated by subjects tracking with a pointer the remembered position of an earth-fixed visual target. VOR was measured by electro-oculography. The asymmetric stimulation pattern consistently induced a progressive increase of asymmetry in motion perception, whereby the gain of the tracking response gradually increased during FHCs and decreased during SHCs. The effect was observed already during the first few cycles and further increased during 20 cycles, leading to a totally distorted location of the initial straight-ahead. In contrast, after some initial interindividual variability, the gain of the slow phase VOR became symmetric, decreasing for FHCs and increasing for SHCs. These oppositely directed adaptive effects in motion perception and VOR persisted for nearly an hour. Control conditions using prolonged but symmetrical stimuli produced no adaptive effects on either motion perception or VOR. These findings show that prolonged asymmetric activation of the vestibular system leads to opposite patterns of adaptation of self-motion perception and VOR. The results provide strong evidence that semicircular canal inputs are processed centrally by independent mechanisms for perception of body motion and eye movement control. These divergent adaptation mechanisms enhance awareness of movement toward the faster body rotation, while improving the eye stabilizing properties of the VOR.

  20. Persisting Inflammation and Chronic Immune Activation but Intact Cognitive Function in HIV-Infected Patients After Long-Term Treatment With Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C

    2013-01-01

    Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function...

  1. cDNA-AFLP analysis reveals the adaptive responses of citrus to long-term boron-toxicity.

    Science.gov (United States)

    Guo, Peng; Qi, Yi-Ping; Yang, Lin-Tong; Ye, Xin; Jiang, Huan-Xin; Huang, Jing-Hao; Chen, Li-Song

    2014-10-28

    Boron (B)-toxicity is an important disorder in agricultural regions across the world. Seedlings of 'Sour pummelo' (Citrus grandis) and 'Xuegan' (Citrus sinensis) were fertigated every other day until drip with 10 μM (control) or 400 μM (B-toxic) H3BO3 in a complete nutrient solution for 15 weeks. The aims of this study were to elucidate the adaptive mechanisms of citrus plants to B-toxicity and to identify B-tolerant genes. B-toxicity-induced changes in seedlings growth, leaf CO2 assimilation, pigments, total soluble protein, malondialdehyde (MDA) and phosphorus were less pronounced in C. sinensis than in C. grandis. B concentration was higher in B-toxic C. sinensis leaves than in B-toxic C. grandis ones. Here we successfully used cDNA-AFLP to isolate 67 up-regulated and 65 down-regulated transcript-derived fragments (TDFs) from B-toxic C. grandis leaves, whilst only 31 up-regulated and 37 down-regulated TDFs from B-toxic C. sinensis ones, demonstrating that gene expression is less affected in B-toxic C. sinensis leaves than in B-toxic C. grandis ones. These differentially expressed TDFs were related to signal transduction, carbohydrate and energy metabolism, nucleic acid metabolism, protein and amino acid metabolism, lipid metabolism, cell wall and cytoskeleton modification, stress responses and cell transport. The higher B-tolerance of C. sinensis might be related to the findings that B-toxic C. sinensis leaves had higher expression levels of genes involved in photosynthesis, which might contribute to the higher photosyntheis and light utilization and less excess light energy, and in reactive oxygen species (ROS) scavenging compared to B-toxic C. grandis leaves, thus preventing them from photo-oxidative damage. In addition, B-toxicity-induced alteration in the expression levels of genes encoding inorganic pyrophosphatase 1, AT4G01850 and methionine synthase differed between the two species, which might play a role in the B-tolerance of C. sinensis. C. sinensis

  2. LONG TERM COLLECTIONS

    CERN Multimedia

    STAFF ASSOCIATION

    2010-01-01

    ACKNOWLEDGMENTS The Long-Term Collections (CLT) committee would like to warmly thank its faithful donors who, year after year, support our actions all over the world. Without you, all this would not be possible. We would like to thank, in particular, the CERN Firemen’s Association who donated 5000 CHF in the spring thanks to the sale of their traditional calendar, and the generosity of the CERN community. A huge thank you to the firemen for their devotion to our cause. And thank you to all those who have opened their door, their heart, and their purses! Similarly, we warmly thank the CERN Yoga Club once again for its wonderful donation of 2000 CHF we recently received. We would also like to tell you that all our projects are running well. Just to remind you, we are currently supporting the activities of the «Réflexe-Partage» Association in Mali; the training centre of «Education et Développement» in Abomey, Benin; and the orphanage and ...

  3. The long-term impact of early life pain on adult responses to anxiety and stress: Historical perspectives and empirical evidence.

    Science.gov (United States)

    Victoria, Nicole C; Murphy, Anne Z

    2016-01-01

    Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10-18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 25% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of insult, remains unclear. Work in our lab using a rodent model of early life pain suggests that inflammatory pain experienced on the day of birth blunts adult responses to stress- and pain-provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis in part through a permanent upregulation in central endogenous opioid tone. This review focuses on the long-term impact of neonatal inflammatory pain on adult anxiety- and stress-related responses, and underlying neuroanatomical changes in the context of endogenous pain control and the HPA axis. These two systems are in a state of exaggerated developmental plasticity early in postnatal life, and work in concert to respond to noxious or aversive stimuli. We present empirical evidence from animal and clinical studies, and discuss historical perspectives underlying the lack of analgesia/anesthetic use for early life pain in the modern NICU. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Long-term human immune system reconstitution in non-obese diabetic (NOD)-Rag (-)-γ chain (-) (NRG) mice is similar but not identical to the original stem cell donor.

    Science.gov (United States)

    Harris, D T; Badowski, M; Balamurugan, A; Yang, O O

    2013-12-01

    The murine immune system is not necessarily identical to it human counterpart, which has led to the construction of humanized mice. The current study analysed whether or not a human immune system contained within the non-obese diabetic (NOD)-Rag1(null) -γ chain(null) (NRG) mouse model was an accurate representation of the original stem cell donor and if multiple mice constructed from the same donor were similar to one another. To that end, lightly irradiated NRG mice were injected intrahepatically on day 1 of life with purified cord blood-derived CD34(+) stem and progenitor cells. Multiple mice were constructed from each cord blood donor. Mice were analysed quarterly for changes in the immune system, and followed for periods up to 12 months post-transplant. Mice from the same donor were compared directly with each other as well as with the original donor. Analyses were performed for immune reconstitution, including flow cytometry, T cell receptor (TCR) and B cell receptor (BCR) spectratyping. It was observed that NRG mice could be 'humanized' long-term using cord blood stem cells, and that animals constructed from the same cord blood donor were nearly identical to one another, but quite different from the original stem cell donor immune system. © 2013 British Society for Immunology.

  5. Activation of the Akt/mTOR signaling pathway: A potential response to long-term neuronal loss in the hippocampus after sepsis

    Directory of Open Access Journals (Sweden)

    Jia-nan Guo

    2017-01-01

    Full Text Available Survivors of sepsis may suffer chronic cognitive impairment as a long-term sequela. However, the precise mechanisms of cognitive dysfunction after sepsis are not well understood. We employed the cecal ligation-and-puncture-induced septic mouse model. We observed elevated phosphorylation of Akt, mammalian target of rapamycin (mTOR and p70S6K on days 14 and 60, progressive neuronal loss in the cornu ammonis 1 region, and abnormal neuronal morphology in the hippocampus in the sepsis mouse model. These findings indicate that changes in neuronal morphology and number in the hippocampus after sepsis were associated with strong activation of the Akt/mTOR signaling pathway, and may reflect a “self-rescuing” feedback response to neuronal loss after sepsis.

  6. Evaluating long term forecasts

    Energy Technology Data Exchange (ETDEWEB)

    Lady, George M. [Department of Economics, College of Liberal Arts, Temple University, Philadelphia, PA 19122 (United States)

    2010-03-15

    The U.S. Department of Energy's Energy Information Administration (EIA), and its predecessor organizations, has published projections of U.S. energy production, consumption, distribution and prices annually for over 30 years. A natural issue to raise in evaluating the projections is an assessment of their accuracy compared to eventual outcomes. A related issue is the determination of the sources of 'error' in the projections that are due to differences between the actual versus realized values of the associated assumptions. One way to do this would be to run the computer-based model from which the projections are derived at the time the projected values are realized, using actual rather than assumed values for model assumptions; and, compare these results to the original projections. For long term forecasts, this approach would require that the model's software and hardware configuration be archived and available for many years, possibly decades, into the future. Such archival creates many practical problems; and, in general, it is not being done. This paper reports on an alternative approach for evaluating the projections. In the alternative approach, the model is run many times for cases in which important assumptions are changed individually and in combinations. A database is assembled from the solutions and a regression analysis is conducted for each important projected variable with the associated assumptions chosen as exogenous variables. When actual data are eventually available, the regression results are then used to estimate the sources of the differences in the projections of the endogenous variables compared to their eventual outcomes. The results presented here are for residential and commercial sector natural gas and electricity consumption. (author)

  7. Long-term biodosimetry Redux

    International Nuclear Information System (INIS)

    Simon, Steven L.; Bouville, Andre

    2016-01-01

    This paper revisits and reiterates the needs, purposes and requirements of bio-dosimetric assays for long-term dose and health risk assessments. While the most crucial need for bio-dosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure

  8. Long-term programing of psychopathology-like behaviors in male rats by peripubertal stress depends on individual's glucocorticoid responsiveness to stress.

    Science.gov (United States)

    Walker, Sophie E; Sandi, Carmen

    2018-02-07

    Experience of adversity early in life and dysregulation of hypothalamus-pituitary-adrenocortical (HPA) axis activity are risk factors often independently associated with the development of psychopathological disorders, including depression, PTSD and pathological aggression. Additional evidence suggests that in combination these factors may interact to shape the development and expression of psychopathology differentially, though little is known about underlying mechanisms. Here, we studied the long-term consequences of early life stress exposure on individuals with differential constitutive glucocorticoid responsiveness to repeated stressor exposure, assessing both socio-affective behaviors and brain activity in regions sensitive to pathological alterations following stress. Two rat lines, genetically selected for either low or high glucocorticoid responsiveness to repeated stress were exposed to a series of unpredictable, fear-inducing stressors on intermittent days during the peripuberty period. Results obtained at adulthood indicated that having high glucocorticoid responses to repeated stress and having experience of peripuberty stress independently enhanced levels of psychopathology-like behaviors, as well as increasing basal activity in several prefrontal and limbic brain regions in a manner associated with enhanced behavioral inhibition. Interestingly, peripuberty stress had a differential impact on aggression in the two rat lines, enhancing aggression in the low-responsive line but not in the already high-aggressive, high-responsive rats. Taken together, these findings indicate that aberrant HPA axis activity around puberty, a key period in the development of social repertoire in both rats and humans, may alter behavior such that it becomes anti-social in nature.

  9. SNP analyses of postprandial responses in (an)orexigenic hormones and feelings of hunger reveal long-term physiological adaptations to facilitate homeostasis.

    Science.gov (United States)

    den Hoed, M; Smeets, A J P G; Veldhorst, M A B; Nieuwenhuizen, A G; Bouwman, F G; Heidema, A G; Mariman, E C M; Westerterp-Plantenga, M S; Westerterp, K R

    2008-12-01

    The postprandial responses in (an)orexigenic hormones and feelings of hunger are characterized by large inter-individual differences. Food intake regulation was shown earlier to be partly under genetic control. This study aimed to determine whether the postprandial responses in (an)orexigenic hormones and parameters of food intake regulation are associated with single nucleotide polymorphisms (SNPs) in genes encoding for satiety hormones and their receptors. Peptide YY (PYY), glucagon-like peptide 1 and ghrelin levels, as well as feelings of hunger and satiety, were determined pre- and postprandially in 62 women and 41 men (age 31+/-14 years; body mass index 25.0+/-3.1 kg/m(2)). Dietary restraint, disinhibition and perceived hunger were determined using the three-factor eating questionnaire. SNPs were determined in the GHRL, GHSR, LEP, LEPR, PYY, NPY, NPY2R and CART genes. The postprandial response in plasma ghrelin levels was associated with SNPs in PYY (215G>C, PG and 688A>G, PGHRL (-501A>C, PA, PG and 585T>C, PA, PA and 204T>C, P<0.05). Part of the inter-individual variability in postprandial responses in (an)orexigenic hormones can be explained by genetic variation. These postprandial responses represent either long-term physiological adaptations to facilitate homeostasis or reinforce direct genetic effects.

  10. Sea level anomaly in the North Atlantic and seas around Europe: Long-term variability and response to North Atlantic teleconnection patterns.

    Science.gov (United States)

    Iglesias, Isabel; Lorenzo, M Nieves; Lázaro, Clara; Fernandes, M Joana; Bastos, Luísa

    2017-12-31

    Sea level anomaly (SLA), provided globally by satellite altimetry, is considered a valuable proxy for detecting long-term changes of the global ocean, as well as short-term and annual variations. In this manuscript, monthly sea level anomaly grids for the period 1993-2013 are used to characterise the North Atlantic Ocean variability at inter-annual timescales and its response to the North Atlantic main patterns of atmospheric circulation variability (North Atlantic Oscillation, Eastern Atlantic, Eastern Atlantic/Western Russia, Scandinavian and Polar/Eurasia) and main driven factors as sea level pressure, sea surface temperature and wind fields. SLA variability and long-term trends are analysed for the North Atlantic Ocean and several sub-regions (North, Baltic and Mediterranean and Black seas, Bay of Biscay extended to the west coast of the Iberian Peninsula, and the northern North Atlantic Ocean), depicting the SLA fluctuations at basin and sub-basin scales, aiming at representing the regions of maximum sea level variability. A significant correlation between SLA and the different phases of the teleconnection patterns due to the generated winds, sea level pressure and sea surface temperature anomalies, with a strong variability on temporal and spatial scales, has been identified. Long-term analysis reveals the existence of non-stationary inter-annual SLA fluctuations in terms of the temporal scale. Spectral density analysis has shown the existence of long-period signals in the SLA inter-annual component, with periods of ~10, 5, 4 and 2years, depending on the analysed sub-region. Also, a non-uniform increase in sea level since 1993 is identified for all sub-regions, with trend values between 2.05mm/year, for the Bay of Biscay region, and 3.98mm/year for the Baltic Sea (no GIA correction considered). The obtained results demonstrated a strong link between the atmospheric patterns and SLA, as well as strong long-period fluctuations of this variable in spatial and

  11. Long-term trends of changes in pine and oak foliar nitrogen metabolism in response to chronic nitrogen amendments at Harvard Forest, MA.

    Science.gov (United States)

    Minocha, Rakesh; Turlapati, Swathi A; Long, Stephanie; McDowell, William H; Minocha, Subhash C

    2015-08-01

    We evaluated the long-term (1995-2008) trends in foliar and sapwood metabolism, soil solution chemistry and tree mortality rates in response to chronic nitrogen (N) additions to pine and hardwood stands at the Harvard Forest Long Term Ecological Research (LTER) site. Common stress-related metabolites like polyamines (PAs), free amino acids (AAs) and inorganic elements were analyzed for control, low N (LN, 50 kg NH4NO3 ha(-1) year(-1)) and high N (HN, 150 kg NH4NO3 ha(-1) year(-1)) treatments. In the pine stands, partitioning of excess N into foliar PAs and AAs increased with both N treatments until 2002. By 2005, several of these effects on N metabolites disappeared for HN, and by 2008 they were mostly observed for LN plot. A significant decline in foliar Ca and P was observed mostly with HN for a few years until 2005. However, sapwood data actually showed an increase in Ca, Mg and Mn and no change in PAs in the HN plot for 2008, while AAs data revealed trends that were generally similar to foliage for 2008. Concomitant with these changes, mortality data revealed a large number of dead trees in HN pine plots by 2002; the mortality rate started to decline by 2005. Oak trees in the hardwood plot did not exhibit any major changes in PAs, AAs, nutrients and mortality rate with LN treatment, indicating that oak trees were able to tolerate the yearly doses of 50 kg NH4NO3 ha(-1) year(-1). However, HN trees suffered from physiological and nutritional stress along with increased mortality in 2008. In this case also, foliar data were supported by the sapwood data. Overall, both low and high N applications resulted in greater physiological stress to the pine trees than the oaks. In general, the time course of changes in metabolic data are in agreement with the published reports on changes in soil chemistry and microbial community structure, rates of soil carbon sequestration and production of woody biomass for this chronic N study. This correspondence of selected metabolites

  12. Modulation of innate immunity and gene expressions in white shrimp Litopenaeus vannamei following long-term starvation and re-feeding

    Science.gov (United States)

    Lin, Yong-Chin; Chen, Jiann-Chu; C. Man, Siti Nursafura; W. Morni, Wan Zabidii; N.A. Suhaili, Awangku Shahrir; Cheng, Sha-Yen; Hsu, Chih-Hung

    2012-01-01

    The survival rate, weight loss, immune parameters, resistance against Vibrio alginolyticus and white-spot syndrome virus (WSSV), and expressions of lipopolysaccharide- and ß-glucan-binding protein (LGBP), peroxinectin (PX), prophenoloxidase-activating enzyme (ppA), prophenoloxidase (proPO) I, proPO II, α2-macroglobulin (α2-M), integrin ß, heat shock protein 70 (HSP70), cytosolic manganese superoxide dismutase (cytMnSOD), mitochondrial manganese superoxide dismutase (mtMnSOD), and extracellular copper and zinc superoxide dismutase (ecCuZnSOD) were examined in the white shrimp Litopenaeus vannamei (8.18 ± 0.86 g body weight) which had been denied food (starved) for up to 14–28 days. Among shrimp which had been starved for 7, 14, 21, and 28 days, 100%, 90%, 71%, and 59% survived, and they lost 3.2%, 7.3%, 9.2%, and 10.4% of their body weight, respectively. Hyaline cells (HCs), granular cells (GCs, including semi-granular cells), the total haemocyte count (THC), phenoloxidase (PO) activity, respiratory bursts (RBs), and SOD activity significantly decreased in shrimp which had been starved for 1, 1, 1, 5, 14, and 3 days, respectively. The expression of integrin ß significantly decreased after 0.5–5 days of starvation, whereas the expressions of LGBP, PX, proPO I, proPO II, ppA, and α2-M increased after 0.5–1 days. Transcripts of all genes except ecCuZnSOD decreased to the lowest level after 5 days, and tended to background values after 7 and 14 days. Cumulative mortality rates of 7-day-starved shrimp challenged with V. alginolyticus and WSSV were significantly higher than those of challenged control-shrimp for 1–7 and 1–4 days, respectively. In another experiment, immune parameters of shrimp which had been starved for 7 and 14 days and then received normal feeding (at 5% of their body weight daily) were examined after 3, 6, and 12 h, and 1, 3, and 5 days. All immune parameters of 7-day-starved shrimp were able to return to their baseline values

  13. Global gene expression analysis of the response of physic nut (Jatropha curcas L.) to medium- and long-term nitrogen deficiency.

    Science.gov (United States)

    Kuang, Qi; Zhang, Sheng; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

    2017-01-01

    Jatropha curcas L. is an important biofuel plant with excellent tolerance of barren environments. However, studies on the regulatory mechanisms that operate in this plant in response to nitrogen (N) shortage are scarce. In this study, genome-wide transcriptional profiles of the roots and leaves of 8-week old physic nut seedlings were analyzed after 2 and 16 days of N starvation. Enrichment results showed that genes associated with N metabolism, processing and regulation of RNA, and transport predominated among those showing alterations in expression. Genes encoding transporter families underwent major changes in expression in both roots and leaves; in particular, those with roles in ammonia, amino acid and peptide transport were generally up-regulated after long-term starvation, while AQUAPORIN genes, whose products function in osmoregulation, were down-regulated. We also found that ASPARA-GINASE B1 and SARCOSINE OXIDASE genes were up-regulated in roots and leaves after 2 and 16 d N starvation. Genes associated with ubiquitination-mediated protein degradation were significantly up-regulated. In addition, genes in the JA biosynthesis pathway were strongly activated while expression of those in GA signaling was inhibited in leaves. We showed that four major classes of genes, those with roles in N uptake, N reutilization, C/N ratio balance, and cell structure and synthesis, were particularly influenced by long-term N limitation. Our discoveries may offer clues to the molecular mechanisms that regulate N reallocation and reutilization so as to maintain or increase plant performance even under adverse environmental conditions.

  14. Responses of Plant Community Composition to Long-term Changes in Snow Depth at the Great Basin Desert - Sierra Nevada ecotone.

    Science.gov (United States)

    Loik, M. E.

    2015-12-01

    Snowfall is the dominant hydrologic input for many high-elevation ecosystems of the western United States. Many climate models envision changes in California's Sierra Nevada snow pack characteristics, which would severely impact the storage and release of water for one of the world's largest economies. Given the importance of snowfall for future carbon cycling in high elevation ecosystems, how will these changes affect seedling recruitment, plant mortality, and community composition? To address this question, experiments utilize snow fences to manipulate snow depth and melt timing at a desert-montane ecotone in eastern California, USA. Long-term April 1 snow pack depth averages 1344 mm (1928-2015) but is highly variable from year to year. Snow fences increased equilibrium drift snow depth by 100%. Long-term changes in snow depth and melt timing are associated with s shift from shurbs to graminoids where snow depth was increased for >50 years. Changes in snow have impacted growth for only three plant species. Moreover, annual growth ring increments of the conifers Pinus jeffreyi and Pi. contorta were not equally sensitive to snow depth. There were over 8000 seedlings of the shrubs Artemisia tridentata and Purshia tridentata found in 6300 m2 in summer 2009, following about 1400 mm of winter snow and spring rain. The frequency of seedlings of A. tridentata and P. tridentata were much lower on increased-depth plots compared to ambient-depth, and reduced-depth plots. Survival of the first year was lowest for A. tridentata. Survival of seedlings from the 2008 cohort was much higher for P. tridentata than A. tridentata during the 2011-2015 drought. Results indicate complex interactions between snow depth and plant community characteristics, and that responses of plants at this ecotone may not respond similarly to increases vs. decreases in snow depth. These changes portend altered carbon uptake in this region under future snowfall scenarios.

  15. Inter-annual variability of NDVI in response to long-term warming and fertilization in wet sedge and tussock tundra.

    Science.gov (United States)

    Boelman, Natalie T; Stieglitz, Marc; Griffin, Kevin L; Shaver, Gaius R

    2005-05-01

    This study explores the relationship between the normalized difference vegetation index (NDVI) and aboveground plant biomass for tussock tundra vegetation and compares it to a previously established NDVI-biomass relationship for wet sedge tundra vegetation. In addition, we explore inter-annual variation in NDVI in both these contrasting vegetation communities. All measurements were taken across long-term experimental treatments in wet sedge and tussock tundra communities at the Toolik Lake Long Term Ecological Research (LTER) site, in northern Alaska. Over 15 years (for wet sedge tundra) and 14 years (for tussock tundra), N and P were applied in factorial experiments (N, P and N+P), air temperature was increased using greenhouses with and without N+P fertilizer, and light intensity was reduced by 50% using shade cloth. during the peak growing seasons of 2001, 2002, and 2003, NDVI measurements were made in both the wet sedge and tussock tundra experimental treatment plots, creating a 3-year time series of inter-annual variation in NDVI. We found that: (1) across all tussock experimental tundra treatments, NDVI is correlated with aboveground plant biomass (r2 = 0.59); (2) NDVI-biomass relationships for tussock and wet sedge tundra communities are community specific, and; (3) NDVI values for tussock tundra communities are typically, but not always, greater than for wet sedge tundra communities across all experimental treatments. We suggest that differences between the response of wet sedge and tussock tundra communities in the same experimental treatments result from the contrasting degree of heterogeneity in species and functional types that characterize each of these Arctic tundra vegetation communities.

  16. Long-term changes in migration timing of Song Thrush Turdus philomelos at the southern Baltic coast in response to temperatures on route and at breeding grounds.

    Science.gov (United States)

    Redlisiak, Michał; Remisiewicz, Magdalena; Nowakowski, Jarosław K

    2018-05-26

    Climate warming causes the advancement of spring arrival of many migrant birds breeding in Europe, but the effects on their autumn migration are less known. We aimed to determine any changes in the timing of Song Thrush captured during spring and autumn migrations at the Polish Baltic coast from 1975 to 2014, and if these were related to long-term changes of temperature at their breeding grounds and migration routes. The timing of spring migration at Hel ringing station in 1975-2014 did not show long-term advance, but they had responded to environmental conditions on the year-to-year basis. The warmer the temperatures were in April on their migration route, the earlier were the dates of the median and the end of spring migration at Hel. The beginning of autumn migration at the Mierzeja Wiślana ringing station advanced by 5 days between 1975 and 2014. The warmer the April on route, and the July at the Song Thrushes' breeding grounds, the earlier young birds began autumn migration across the Baltic coast. We suggest this was a combined effect of adults' migration and breeding early during warm springs and young birds getting ready faster for autumn migration during warm summers. The average time span of 90% of the autumn migration was extended by 5 days, probably because of early migration of young birds from first broods and late of those from second broods enabled by warm springs and summers. The response of Song Thrushes' migration timing to temperatures on route and at the breeding grounds indicated high plasticity in the species and suggested it might adapt well to climate changes.

  17. A single low dose of Fe ions can cause long-term biological responses in NL20 human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Qianlin; Wang, Jingdong; Cao, Jianping; Yang, Hongying [Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, School of Radiation Medicine and Protection, Suzhou, Jiangsu (China); Liu, Wei [Soochow University, Department of Radiotherapy and Oncology, Second Affiliated Hospital, Suzhou, Jiangsu (China)

    2018-03-15

    Space radiation cancer risk may be a potential obstacle for long-duration spaceflight. Among all types of cancer space radiation may induce, lung cancer has been estimated to be the largest potential risk. Although previous animal study has shown that Fe ions, the most important contributor to the total dose equivalent of space radiation, induced a higher incidence of lung tumorigenesis per dose than X-rays, the underlying mechanisms at cellular level remained unclear. Therefore, in the present study, we investigated long-term biological changes in NL20 human bronchial epithelial cells after exposure to Fe ion or X-ray irradiation. We found that compared with sham control, the progeny of NL20 cells irradiated with 0.1 Gy of Fe ions showed slightly increased micronucleus formation, significantly decreased cell proliferation, disturbed cell cycle distribution, and obviously elevated intracellular ROS levels accompanied by reduced SOD1 and SOD2 expression, but the progeny of NL20 cells irradiated with 0.9 Gy of X-rays did not show any significant changes. More importantly, Fe ion exposure caused much greater soft-agar colony formation than X-rays did in the progeny of irradiated NL20 cells, clearly suggesting higher cell transformation potential of Fe ions compared with X-rays. These data may shed the light on the potential lung tumorigenesis risk from Fe ion exposure. In addition, ATM inhibition by Ku55933 reversed some of the changes in the progeny of Fe ion-irradiated cells but not others such as soft-agar colony formation, suggesting complex processes from DNA damage to carcinogenesis. These data indicate that even a single low dose of Fe ions can induce long-term biological responses such as cell transformation, etc., suggesting unignorable health risk from space radiation to astronauts. (orig.)

  18. Long-Term Monitoring of Physical Behavior Reveals Different Cardiac Responses to Physical Activity among Subjects with and without Chronic Neck Pain

    Directory of Open Access Journals (Sweden)

    David M. Hallman

    2015-01-01

    Full Text Available Background. We determined the extent to which heart rate variability (HRV responses to daily physical activity differ between subjects with and without chronic neck pain. Method. Twenty-nine subjects (13 women with chronic neck pain and 27 age- and gender-matched healthy controls participated. Physical activity (accelerometry, HRV (heart rate monitor, and spatial location (Global Positioning System (GPS were recorded for 74 hours. GPS data were combined with a diary to identify periods of work and of leisure at home and elsewhere. Time- and frequency-domain HRV indices were calculated and stratified by period and activity type (lying/sitting, standing, or walking. ANCOVAs with multiple adjustments were used to disclose possible group differences in HRV. Results. The pain group showed a reduced HRV response to physical activity compared with controls (p=.001, according to the sympathetic-baroreceptor HRV index (LF/HF, ratio between low- and high-frequency power, even after adjustment for leisure time physical activity, work stress, sleep quality, mental health, and aerobic capacity (p=.02. The parasympathetic response to physical activity did not differ between groups. Conclusions. Relying on long-term monitoring of physical behavior and heart rate variability, we found an aberrant sympathetic-baroreceptor response to daily physical activity among subjects with chronic neck pain.

  19. Long-Term Monitoring of Physical Behavior Reveals Different Cardiac Responses to Physical Activity among Subjects with and without Chronic Neck Pain

    Science.gov (United States)

    Hallman, David M.; Mathiassen, Svend Erik; Lyskov, Eugene

    2015-01-01

    Background. We determined the extent to which heart rate variability (HRV) responses to daily physical activity differ between subjects with and without chronic neck pain. Method. Twenty-nine subjects (13 women) with chronic neck pain and 27 age- and gender-matched healthy controls participated. Physical activity (accelerometry), HRV (heart rate monitor), and spatial location (Global Positioning System (GPS)) were recorded for 74 hours. GPS data were combined with a diary to identify periods of work and of leisure at home and elsewhere. Time- and frequency-domain HRV indices were calculated and stratified by period and activity type (lying/sitting, standing, or walking). ANCOVAs with multiple adjustments were used to disclose possible group differences in HRV. Results. The pain group showed a reduced HRV response to physical activity compared with controls (p = .001), according to the sympathetic-baroreceptor HRV index (LF/HF, ratio between low- and high-frequency power), even after adjustment for leisure time physical activity, work stress, sleep quality, mental health, and aerobic capacity (p = .02). The parasympathetic response to physical activity did not differ between groups. Conclusions. Relying on long-term monitoring of physical behavior and heart rate variability, we found an aberrant sympathetic-baroreceptor response to daily physical activity among subjects with chronic neck pain. PMID:26557711

  20. Long-term responses of Burrunan dolphins (Tursiops australis to swim-with dolphin tourism in Port Phillip Bay, Victoria, Australia: A population at risk

    Directory of Open Access Journals (Sweden)

    Nicole E. Filby

    2014-12-01

    Full Text Available This study investigated Burrunan dolphin responses to dolphin-swim tour vessels across two time periods: 1998–2000 and 2011–2013. A total of 211 dolphin sightings were documented across 306 surveys. Sighting success rate and mean encounter time with dolphins decreased significantly by 12.8% and 8.2 min, respectively, between periods. Approaches that did not contravene regulations elicited highest approach responses by dolphins towards tour vessels, whereas dolphins’ responded to illegal approaches most frequently with avoidance. Small groups responded to tour vessels with avoidance significantly more than large groups. Initial dolphin behaviour had a strong effect on dolphin’s responses to tour vessels, with resting groups the most likely to exhibit avoidance. Calves were significantly more likely to be present during swims in 2011–2013. Dolphin’s responses to tour vessels changed across time, with effect responses (avoidance and approach increasing significantly as dolphins gained cumulative experience. These dolphins are forced to expend a greater level of time and energy avoiding or approaching boats, shifting from a non-effect response to an effect response. Consequences of this include possible decrease in biological fitness by detracting from core biological activities such as foraging and resting. Combined with a decrease in sighting success between periods, the results imply that this population of dolphins, which is endemic to Australia and listed as threatened under the Victorian Flora and Fauna Guarantee Act 1988, may not be well suited to the dolphin-swim industry. The management implications of these results warrant a shift from passive to active management in Port Phillip Bay. The importance of long-term research is highlighted, given behavioural responses detected herein would be undetected in short-term studies. Keywords: Burrunan dolphin (Tursiops australis, Avoidance, Behaviour, Compliance, Management

  1. Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials.

    Science.gov (United States)

    Franz, Sandra; Rammelt, Stefan; Scharnweber, Dieter; Simon, Jan C

    2011-10-01

    A key for long-term survival and function of biomaterials is that they do not elicit a detrimental immune response. As biomaterials can have profound impacts on the host immune response the concept emerged to design biomaterials that are able to trigger desired immunological outcomes and thus support the healing process. However, engineering such biomaterials requires an in-depth understanding of the host inflammatory and wound healing response to implanted materials. One focus of this review is to outline the up-to-date knowledge on immune responses to biomaterials. Understanding the complex interactions of host response and material implants reveals the need for and also the potential of "immunomodulating" biomaterials. Based on this knowledge, we discuss strategies of triggering appropriate immune responses by functional biomaterials and highlight recent approaches of biomaterials that mimic the physiological extracellular matrix and modify cellular immune responses. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Long-Term Coffee Consumption Is Associated with Decreased Incidence of New-Onset Hypertension: A Dose-Response Meta-Analysis.

    Science.gov (United States)

    Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Bes-Rastrollo, Maira; Galvano, Fabio; Martinez-Gonzalez, Miguel A

    2017-08-17

    To perform a dose-response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose-response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose-response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.

  3. Living on the edge: adaptive and plastic responses of the tree Nothofagus pumilio to a long-term transplant experiment predict rear-edge upward expansion.

    Science.gov (United States)

    Mathiasen, Paula; Premoli, Andrea C

    2016-06-01

    Current climate change affects the competitive ability and reproductive success of many species, leading to local extinctions, adjustment to novel local conditions by phenotypic plasticity or rapid adaptation, or tracking their optima through range shifts. However, many species have limited ability to expand to suitable areas. Altitudinal gradients, with abrupt changes in abiotic conditions over short distances, represent "natural experiments" for the evaluation of ecological and evolutionary responses under scenarios of climate change. Nothofagus pumilio is the tree species which dominates as pure stands the montane forests of Patagonia. We evaluated the adaptive value of variation in quantitative traits of N. pumilio under contrasting conditions of the altitudinal gradient with a long-term reciprocal transplant experimental design. While high-elevation plants show little response in plant, leaf, and phenological traits to the experimental trials, low-elevation ones show greater plasticity in their responses to changing environments, particularly at high elevation. Our results suggest a relatively reduced potential for evolutionary adaptation of high-elevation genotypes, and a greater evolutionary potential of low-elevation ones. Under global warming scenarios of forest upslope migration, high-elevation variants may be outperformed by low-elevation ones during this process, leading to the local extinction and/or replacement of these genotypes. These results challenge previous models and predictions expected under global warming for altitudinal gradients, on which the leading edge is considered to be the upper treeline forests.

  4. Long-Term Coffee Consumption Is Associated with Decreased Incidence of New-Onset Hypertension: A Dose–Response Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Giuseppe Grosso

    2017-08-01

    Full Text Available Objective: To perform a dose–response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. Methods: An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose–response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Results: Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose–response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Conclusions: Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.

  5. Long Term Financing of Infrastructure

    OpenAIRE

    Sinha, Sidharth

    2014-01-01

    Infrastructure projects, given their long life, require long term financing. The main sources of long term financings are insurance and pension funds who seek long term investments with low credit risk. However, in India household financial savings are mainly invested in bank deposits. Insurance and pension funds account for only a small percentage of household financial savings. In addition most infrastructure projects do not qualify for investment by insurance and pension funds because of t...

  6. Modulation of Long-term Potentiation of Cortico-amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid

    Directory of Open Access Journals (Sweden)

    Daisuke Yamada

    2016-08-01

    Full Text Available Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA in the brain is involved in mental illnesses such as anxiety disorders. However, the underlying mechanism is unknown. We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory. In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala. However, it is not known whether long-term synaptic plasticity in the amygdala is influenced by the dietary ratio of ω3 to ω6 PUFA. In the present study, we examined long-term potentiation (LTP of optogenetically–evoked excitatory synaptic responses in synapses between the terminal of the projection from the auditory cortex and the pyramidal cells in the lateral nucleus of the amygdala. We found that LTP in this pathway was attenuated in mice fed a diet with a high ω3 to ω6 PUFA ratio (0.97, compared with mice fed a diet with a low ω3 to ω6 PUFA ratio (0.14. Furthermore, mice in the former condition showed reduced fear responses in an auditory fear conditioning test, compared with mice in the latter condition. In both electrophysiological and behavioral experiments, the effect of a diet with a high ω3 to ω6 PUFA ratio was completely blocked by treatment with a CB1 receptor antagonist. Furthermore, a significant reduction was observed in cholesterol content, but not in the level of an endogenous CB1 receptor agonist, 2-arachidonoylglycerol, in brain samples containing the amygdala. These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor–dependent manner.

  7. Eosinophils in mucosal immune responses

    Science.gov (United States)

    Travers, J; Rothenberg, M E

    2015-01-01

    Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

  8. Focal radiation therapy combined with 4-1BB activation and CTLA-4 blockade yields long-term survival and a protective antigen-specific memory response in a murine glioma model.

    Directory of Open Access Journals (Sweden)

    Zineb Belcaid

    Full Text Available Glioblastoma (GBM is the most common malignant brain tumor in adults and is associated with a poor prognosis. Cytotoxic T lymphocyte antigen -4 (CTLA-4 blocking antibodies have demonstrated an ability to generate robust antitumor immune responses against a variety of solid tumors. 4-1BB (CD137 is expressed by activated T lymphocytes and served as a co-stimulatory signal, which promotes cytotoxic function. Here, we evaluate a combination immunotherapy regimen involving 4-1BB activation, CTLA-4 blockade, and focal radiation therapy in an immune-competent intracranial GBM model.GL261-luciferace cells were stereotactically implanted in the striatum of C57BL/6 mice. Mice were treated with a triple therapy regimen consisted of 4-1BB agonist antibodies, CTLA-4 blocking antibodies, and focal radiation therapy using a small animal radiation research platform and mice were followed for survival. Numbers of brain-infiltrating lymphocytes were analyzed by FACS analysis. CD4 or CD8 depleting antibodies were administered to determine the relative contribution of T helper and cytotoxic T cells in this regimen. To evaluate the ability of this immunotherapy to generate an antigen-specific memory response, long-term survivors were re-challenged with GL261 glioma en B16 melanoma flank tumors.Mice treated with triple therapy had increased survival compared to mice treated with focal radiation therapy and immunotherapy with 4-1BB activation and CTLA-4 blockade. Animals treated with triple therapy exhibited at least 50% long-term tumor free survival. Treatment with triple therapy resulted in a higher density of CD4+ and CD8+ tumor infiltrating lymphocytes. Mechanistically, depletion of CD4+ T cells abrogated the antitumor efficacy of triple therapy, while depletion of CD8+ T cells had no effect on the treatment response.Combination therapy with 4-1BB activation and CTLA-4 blockade in the setting of focal radiation therapy improves survival in an orthotopic mouse

  9. Chemokine-mediated immune responses in the female genital tract mucosa.

    Science.gov (United States)

    Deruaz, Maud; Luster, Andrew D

    2015-04-01

    The genital tract mucosa is the site where sexually transmitted infections gain entry to the host. The immune response at this site is thus critical to provide innate protection against pathogens that are seen for the very first time as well as provide long-term pathogen-specific immunity, which would be required for an effective vaccine against sexually transmitted infection. A finely regulated immune response is therefore required to provide an effective barrier against pathogens without compromising the capacity of the genital tract to allow for successful conception and fetal development. We review recent developments in our understanding of the immune response in the female genital tract to infectious pathogens, using herpes simplex virus-2, human immunodeficiency virus-1 and Chlamydia trachomatis as examples, with a particular focus on the role of chemokines in orchestrating immune cell migration necessary to achieve effective innate and adaptive immune responses in the female genital tract.

  10. Assessing groundwater availability and the response of the groundwater system to intensive exploitation in the North China Plain by analysis of long-term isotopic tracer data

    Science.gov (United States)

    Su, Chen; Cheng, Zhongshuang; Wei, Wen; Chen, Zongyu

    2018-03-01

    The use of isotope tracers as a tool for assessing aquifer responses to intensive exploitation is demonstrated and used to attain a better understanding of the sustainability of intensively exploited aquifers in the North China Plain. Eleven well sites were selected that have long-term (years 1985-2014) analysis data of isotopic tracers. The stable isotopes δ18O and δ2H and hydrochemistry were used to understand the hydrodynamic responses of the aquifer system, including unconfined and confined aquifers, to groundwater abstraction. The time series data of 14C activity were also used to assess groundwater age, thereby contributing to an understanding of groundwater sustainability and aquifer depletion. Enrichment of the heavy oxygen isotope (18O) and elevated concentrations of chloride, sulfate, and nitrate were found in groundwater abstracted from the unconfined aquifer, which suggests that intensive exploitation might induce the potential for aquifer contamination. The time series data of 14C activity showed an increase of groundwater age with exploitation of the confined parts of the aquifer system, which indicates that a larger fraction of old water has been exploited over time, and that the groundwater from the deep aquifer has been mined. The current water demand exceeds the sustainable production capabilities of the aquifer system in the North China Plain. Some measures must be taken to ensure major cuts in groundwater withdrawals from the aquifers after a long period of depletion.

  11. Combining short-term manipulative experiments with long-term palaeoecological investigations at high resolution to assess the response of Sphagnum peatlands to drought, fire and warming

    Directory of Open Access Journals (Sweden)

    M. Lamentowicz

    2016-09-01

    Full Text Available Northern hemisphere peatlands are substantial carbon stores. However, recent climate change and human impacts (e.g., drainage and atmospheric nutrient deposition may trigger the emission of their stored carbon to the atmosphere. Biodiversity losses are also an important consequence of those changes. Therefore, there is a need to recognise these processes in space and time. Global change experiments are often conducted to improve our understanding of the potential responses of various ecosystems to global warming and drought. Most of the experiments carried out in peatlands are focused on carbon balance and nitrogen deposition. Nevertheless, it is still unclear how fast peatlands respond to temperature changes and water-table lowering in the continental climate setting. This is important because continental regions account for a significant proportion of all northern hemisphere peatlands. A combination of short-term and long-term approaches in a single research project is especially helpful because it facilitates the correct interpretation of experimental data. Here we describe the CLIMPEAT project - a manipulative field experiment in a Sphagnum-dominated peatland supported by a high-resolution multi-proxy palaeoecological study. The design of the field experiment (e.g., treatments, methodology and biogeographical setting are presented. We suggest it is beneficial to support field experiments with an investigation of past environmental changes in the studied ecosystem, as human impacts during the past 300 years have already caused substantial changes in ecosystem functioning which may condition the response in experimental studies.

  12. Cellular immune responses to respiratory viruses

    NARCIS (Netherlands)

    van Helden, M.J.G.

    2011-01-01

    When a respiratory virus successfully infects the lungs, cascades of immune responses are initiated aimed to remove the pathogen. Immediate non-specific protection is provided by the innate immune system and this reduces the viral load during the first days of infection. The adaptive immune response

  13. Long-Term Survival According to Histology and Radiologic Response to Preoperative Chemotherapy in 126 Patients Undergoing Resection of Non-GIST Sarcoma Liver Metastases.

    Science.gov (United States)

    Goumard, Claire; Marcal, Leonardo P; Wang, Wei-Lien; Somaiah, Neeta; Okuno, Masayuki; Roland, Christina L; Tzeng, Ching-Wei D; Chun, Yun Shin; Feig, Barry W; Vauthey, Jean-Nicolas; Conrad, Claudius

    2018-01-01

    Non-gastrointestinal stromal tumor sarcomas (NGSs) have heterogeneous histology, and this heterogeneity may lead to uncertainty regarding the prognosis of patients with liver metastases from NGS (NGSLM) and decision regarding their surgical management. Furthermore, the role of preoperative chemotherapy in treatment of NGSLM remains poorly defined. We investigated long-term survival and its correlation to response to preoperative chemotherapy in patients with NGSLM. Patients who underwent liver resection for NGSLM during 1998-2015 were identified. Clinical, histopathologic, and survival data were analyzed. Multivariate analysis was performed using a Cox proportional hazards model. 126 patients [62 (49%) with leiomyosarcoma] were included. Five-year overall survival (OS) and recurrence-free survival (RFS) rates were 49.3 and 14.9%, respectively. Survival did not differ by histologic subtype, primary tumor location, or use of preoperative or postoperative chemotherapy. NGSLM ≥ 10 cm and extrahepatic metastases at NGSLM diagnosis were the only independent risk factors for OS. In the 83 (66%) patients with metachronous NSGLM, disease-free interval > 6 months was associated with improved OS and RFS. Among the 65 patients (52%) who received preoperative chemotherapy, radiologic response according to Choi criteria specifically was associated with improved OS (p = 0.04), but radiologic response according to RECIST 1.1 criteria was not. Resection of NGSLM led to a 5-year OS rate of 49%, independent of histologic subtype and primary tumor location. Choi criteria (which take into account tumor density) are superior to RECIST 1.1 in assessing radiologic response and should be used to assess response to preoperative chemotherapy.

  14. [(90)Yttrium-DOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial.

    Science.gov (United States)

    Iten, Fabienne; Muller, Beat; Schindler, Christian; Rasch, Helmut; Rochlitz, Christoph; Oertli, Daniel; Maecke, Helmut R; Muller-Brand, Jan; Walter, Martin A

    2009-05-15

    The authors aimed to explore the efficacy of (90)Yttrium-1,4,7,10-tetra-azacyclododecane N,N',N'',N'''-tetraacetic acid [(90)Y-DOTA]-Tyr(3)-octreotide (TOC) in advanced iodine-refractory thyroid cancer. In a phase 2 trial, the authors investigated biochemical response (assessed by serum thyroglobulin levels), survival, and the long-term safety profile of systemic [(90)Y-DOTA]-TOC treatment in metastasized iodine-refractory thyroid cancer. Adverse events were assessed according to the National Cancer Institute criteria. Survival analyses were performed by using multiple regression models. A total of 24 patients were enrolled. A median cumulative activity of 13.0 GBq (range, 1.7-30.3 GBq) was administered. Response was found in 7 (29.2%) patients. Eight (33.3%) patients developed hematologic toxicity grade 1-3, and 4 (16.7%) patients developed renal toxicity grade 1-4. The median survival was 33.4 months (range, 3.6-126.8 months) from time of diagnosis and 16.8 months (range, 1.8-99.1 months) from time of first [(90)Y-DOTA]-TOC treatment. Response to treatment was associated with longer survival from time of diagnosis (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.03-0.92; P = .04) and from time of first [(90)Y-DOTA]-TOC therapy (HR, 0.20; 95% CI, 0.04-0.94; P = .04). The visual grade of scintigraphic tumor uptake was not associated with treatment response (odds ratio [OR], 0.98; 95% CI, 0.26-3.14; P = 1.00). Response to [(90)Y-DOTA]-TOC in metastasized iodine-refractory thyroid cancer was associated with longer survival. Upcoming trials should aim to increase the number of treatment cycles.

  15. Soil mineral composition matters: response of microbial communities to phenanthrene and plant litter addition in long-term matured artificial soils.

    Science.gov (United States)

    Babin, Doreen; Vogel, Cordula; Zühlke, Sebastian; Schloter, Michael; Pronk, Geertje Johanna; Heister, Katja; Spiteller, Michael; Kögel-Knabner, Ingrid; Smalla, Kornelia

    2014-01-01

    The fate of polycyclic aromatic hydrocarbons (PAHs) in soil is determined by a suite of biotic and abiotic factors, and disentangling their role in the complex soil interaction network remains challenging. Here, we investigate the influence of soil composition on the microbial community structure and its response to the spiked model PAH compound phenanthrene and plant litter. We used long-term matured artificial soils differing in type of clay mineral (illite, montmorillonite) and presence of charcoal or ferrihydrite. The soils received an identical soil microbial fraction and were incubated for more than two years with two sterile manure additions. The matured artificial soils and a natural soil were subjected to the following spiking treatments: (I) phenanthrene, (II) litter, (III) litter + phenanthrene, (IV) unspiked control. Total community DNA was extracted from soil sampled on the day of spiking, 7, 21, and 63 days after spiking. Bacterial 16S rRNA gene and fungal internal transcribed spacer amplicons were quantified by qPCR and subjected to denaturing gradient gel electrophoresis (DGGE). DGGE analysis revealed that the bacterial community composition, which was strongly shaped by clay minerals after more than two years of incubation, changed in response to spiked phenanthrene and added litter. DGGE and qPCR showed that soil composition significantly influenced the microbial response to spiking. While fungal communities responded only in presence of litter to phenanthrene spiking, the response of the bacterial communities to phenanthrene was less pronounced when litter was present. Interestingly, microbial communities in all artificial soils were more strongly affected by spiking than in the natural soil, which might indicate the importance of higher microbial diversity to compensate perturbations. This study showed the influence of soil composition on the microbiota and their response to phenanthrene and litter, which may increase our understanding of

  16. Effects of radiochemotherapy and splenectomy on cellular immunity in long-term survivors of Hodgkin's disease and non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Steele, R.; Han, T.

    1978-01-01

    Thirty-six patients treated for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) who had been in complete remission and off all therapy for greater than two years were examined for evidence of immunosuppression. All patients were found to have marked depression of their lymphocyte blastogenic response to phytohemagglutinin (PHA) and of their skin test responses. No abnormalities of serum protein or immunoglobulins were found. T cells were significantly lower than normal in patients who had had Hodgkin's disease, but not in those who had had NHL. B cells, on the other hand, were significantly elevated in both groups. Splenectomy elevated the total lymphocyte count, while those who had not had a splenectomy had lower than normal lymphocyte counts. B cells were elevated while T cells tended to be lower in both splenectomy and nonsplenectomy groups, though only in the nonsplenectomized patients did this reach statistical significance. The PHA response tended to be higher in patients with less advanced disease and less extensive treatment than in those with more advanced disease and more extensive treatment, although there was no statistically significant difference. Skin test response though, was shown to correlate well with both stage of disease at diagnosis and extent of treatment

  17. Long-term urethral catheterisation.

    Science.gov (United States)

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  18. Long-term response to nivolumab and acute renal failure in a patient with metastatic papillary renal-cell carcinoma and a PD-L1 tumor expression increased with sunitinib therapy: A case report.

    Directory of Open Access Journals (Sweden)

    Juan Ruiz-Bañobre

    2016-11-01

    Full Text Available Introduction: Papillary renal-cell carcinoma, which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programmed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus, but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal-cell carcinoma. Case report: We describe a case of a young man diagnosed with papillary renal-cell carcinoma that achieved a durable response to nivolumab despite a temporary suspension of the treatment due to a renal function side effect. To our knowledge, it is the first renal failure secondary to nivolumab in a metastatic renal-cell carcinoma patient.Concluding Remarks: Nivolumab is a promising drug in patients with metastatic papillary renal-cell carcinoma and long-term responses can be achieved. In case of acute renal failure secondary to this treatment, temporary therapy suspension and a low dose of systemic corticosteroids can recover renal function without a negative impact on treatment efficacy.

  19. Long-term hepatitis B virus (HBV response to lamivudine-containing highly active antiretroviral therapy in HIV-HBV co-infected patients in Thailand.

    Directory of Open Access Journals (Sweden)

    Woottichai Khamduang

    Full Text Available Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV. In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known.HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030 and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg. At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log(10 IU/mL and 4.47 log(10 copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24% lost HBsAg and 7 of 8 (88% HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months. HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L.All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for the management of co-infected patients

  20. Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

    Directory of Open Access Journals (Sweden)

    Swee Lin G Chen Yi Mei

    Full Text Available Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR in people with chronic hepatitis C (CHC infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart.CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM using transient elastography [FibroScan] were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa or advanced (METAVIR F3-4/ LSM >9.5 kPa. The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2 to advanced fibrosis at follow-up liver fibrosis assessment.131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62 years with median estimated duration of infection 33-years (IQR 29-38. At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17. 109 (83% participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002. The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343. However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F

  1. Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

    Science.gov (United States)

    Chen Yi Mei, Swee Lin G; Thompson, Alexander J; Christensen, Britt; Cunningham, Georgina; McDonald, Lucy; Bell, Sally; Iser, David; Nguyen, Tin; Desmond, Paul V

    2017-01-01

    Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart. CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa) or advanced (METAVIR F3-4/ LSM >9.5 kPa). The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to advanced fibrosis at follow-up liver fibrosis assessment. 131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62) years with median estimated duration of infection 33-years (IQR 29-38). At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17). 109 (83%) participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343). However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F/U (p

  2. The role of radiotherapy for the induction of antitumor immune responses

    International Nuclear Information System (INIS)

    Multhoff, G.; Helmholtz-Zentrum Muenchen; Gaipl, U.S.; Niedermann, G.

    2012-01-01

    Effective radiotherapy is aimed to control the growth of the primary carcinoma and to induce a long-term specific antitumor immune response against the primary tumor, recurrence and metastases. The contribution covers the following issues: T cells and tumor specific immune responses, dendritic cells (DCs) start adaptive immune responses, NK (natural killer) cells for HLA independent tumor control, abscopal effects of radiotherapy, combination of radiotherapy and immune therapy, radiotherapy contribution to the induction of immunogenic cell death, combinability of radiotherapy and DC activation, combinability of radiotherapy and NK cell therapy. It turns out that the combination of radio-chemotherapy and immune therapy can change the microenvironment initiating antitumor immune reactions that inhibit the recurrence risk and the development of metastases.

  3. The Immune Response of Maternally Immune Chicks to Vaccination ...

    African Journals Online (AJOL)

    The Immune Response of Maternally Immune Chicks to Vaccination with Newcastle Disease Virus. ... G A El-Tayeb, M Y El-Ttegani, I E Hajer, M A Mohammed ... This study was conducted to determine the persistence of maternally derived antibodies (MDA) to Newcastle disease virus (NDV) in newly hatched chicks and the ...

  4. Long-term boron-deficiency-responsive genes revealed by cDNA-AFLP differ between Citrus sinensis roots and leaves

    Science.gov (United States)

    Lu, Yi-Bin; Qi, Yi-Ping; Yang, Lin-Tong; Lee, Jinwook; Guo, Peng; Ye, Xin; Jia, Meng-Yang; Li, Mei-Li; Chen, Li-Song

    2015-01-01

    Seedlings of Citrus sinensis (L.) Osbeck were supplied with boron (B)-deficient (without H3BO3) or -sufficient (10 μM H3BO3) nutrient solution for 15 weeks. We identified 54 (38) and 38 (45) up (down)-regulated cDNA-AFLP bands (transcript-derived fragments, TDFs) from B-deficient leaves and roots, respectively. These TDFs were mainly involved in protein and amino acid metabolism, carbohydrate and energy metabolism, nucleic acid metabolism, cell transport, signal transduction, and stress response and defense. The majority of the differentially expressed TDFs were isolated only from B-deficient roots or leaves, only seven TDFs with the same GenBank ID were isolated from the both. In addition, ATP biosynthesis-related TDFs were induced in B-deficient roots, but unaffected in B-deficient leaves. Most of the differentially expressed TDFs associated with signal transduction and stress defense were down-regulated in roots, but up-regulated in leaves. TDFs related to protein ubiquitination and proteolysis were induced in B-deficient leaves except for one TDF, while only two down-regulated TDFs associated with ubiquitination were detected in B-deficient roots. Thus, many differences existed in long-term B-deficiency-responsive genes between roots and leaves. In conclusion, our findings provided a global picture of the differential responses occurring in B-deficient roots and leaves and revealed new insight into the different adaptive mechanisms of C. sinensis roots and leaves to B-deficiency at the transcriptional level. PMID:26284101

  5. High environmental ammonia exposure has developmental-stage specific and long-term consequences on the cortisol stress response in zebrafish.

    Science.gov (United States)

    Williams, Tegan A; Bonham, Luke A; Bernier, Nicholas J

    2017-12-01

    The capacity for early life environmental stressors to induce programming effects on the endocrine stress response in fish is largely unknown. In this study we determined the effects of high environmental ammonia (HEA) exposure on the stress response in larval zebrafish, assessed the tolerance of embryonic and larval stages to HEA, and evaluated whether early life HEA exposure has long-term consequences on the cortisol response to a novel stressor. Exposure to 500-2000μM NH 4 Cl for 16h did not affect the gene expression of corticotropin-releasing factor (CRF) system components in 1day post-fertilization (dpf) embryos, but differentially increased crfa, crfb and CRF binding protein (crfbp) expression and stimulated both dose- and time-dependent increases in the whole body cortisol of 5dpf larvae. Pre-acclimation to HEA at 1dpf did not affect the cortisol response to a subsequent NH 4 Cl exposure at 5dpf. In contrast, pre-acclimation to HEA at 5dpf caused a small but significant reduction in the cortisol response to a second NH 4 Cl exposure at 10dpf. While continuous exposure to 500-2000μM NH 4 Cl between 0 and 5dpf had a modest effect on mean survival time, exposure to 400-1000μM NH 4 Cl between 10 and 14dpf decreased mean survival time in a dose-dependent manner. Moreover, pre-acclimation to HEA at 5dpf significantly decreased the risk of mortality to continuous NH 4 Cl exposure between 10 and 14dpf. Finally, while HEA at 1dpf did not affect the cortisol stress response to a novel vortex stressor at 5dpf, the same HEA treatment at 5dpf abolished vortex stressor-induced increases in whole body cortisol at 10 and 60dpf. Together these results show that the impact of HEA on the cortisol stress response during development is life-stage specific and closely linked to ammonia tolerance. Further, we demonstrate that HEA exposure at the larval stage can have persistent effects on the capacity to respond to stressors in later life. Copyright © 2017 Elsevier Inc. All

  6. Characterizing the Long-Term PM2.5 Concentration-Response Function: Comparing the Strengths and Weaknesses of Research Synthesis Approaches.

    Science.gov (United States)

    Fann, Neal; Gilmore, Elisabeth A; Walker, Katherine

    2016-09-01

    The magnitude, shape, and degree of certainty in the association between long-term population exposure to ambient fine particulate matter (PM2.5 ) and the risk of premature death is one of the most intensely studied issues in environmental health. For regulatory risk analysis, this relationship is described quantitatively by a concentration-response (C-R) function that relates exposure to ambient concentrations with the risk of premature mortality. Four data synthesis techniques develop the basis for, and derive, this function: systematic review, expert judgment elicitation, quantitative meta-analysis, and integrated exposure-response (IER) assessment. As part of an academic workshop aiming to guide the use of research synthesis approaches, we developed criteria with which to evaluate and select among the approaches for their ability to inform policy choices. These criteria include the quality and extent of scientific support for the method, its transparency and verifiability, its suitability to the policy problem, and the time and resources required for its application. We find that these research methods are both complementary and interdependent. A systematic review of the multidisciplinary evidence is a starting point for all methods, providing the broad conceptual basis for the nature, plausibility, and strength of the associations between PM exposure and adverse health effects. Further, for a data-rich application like PM2.5 and premature mortality, all three quantitative approaches can produce estimates that are suitable for regulatory and benefit analysis. However, when fewer data are available, more resource-intensive approaches such as expert elicitation may be more important for understanding what scientists know, where they agree or disagree, and what they believe to be the most important areas of uncertainty. Whether implicitly or explicitly, all require considerable judgment by scientists. Finding ways for all these methods to acknowledge

  7. Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial

    NARCIS (Netherlands)

    Y. van Pareren; M. Houdijk; M. Jansen (Maarten); M. Reeser; P.G.H. Mulder (Paul); A.C.S. Hokken-Koelega (Anita)

    2003-01-01

    textabstractThe GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly

  8. Immune oncology, immune responsiveness and the theory of everything.

    Science.gov (United States)

    Turan, Tolga; Kannan, Deepti; Patel, Maulik; Matthew Barnes, J; Tanlimco, Sonia G; Lu, Rongze; Halliwill, Kyle; Kongpachith, Sarah; Kline, Douglas E; Hendrickx, Wouter; Cesano, Alessandra; Butterfield, Lisa H; Kaufman, Howard L; Hudson, Thomas J; Bedognetti, Davide; Marincola, Francesco; Samayoa, Josue

    2018-06-05

    Anti-cancer immunotherapy is encountering its own checkpoint. Responses are dramatic and long lasting but occur in a subset of tumors and are largely dependent upon the pre-existing immune contexture of individual cancers. Available data suggest that three landscapes best define the cancer microenvironment: immune-active, immune-deserted and immune-excluded. This trichotomy is observable across most solid tumors (although the frequency of each landscape varies depending on tumor tissue of origin) and is associated with cancer prognosis and response to checkpoint inhibitor therapy (CIT). Various gene signatures (e.g. Immunological Constant of Rejection - ICR and Tumor Inflammation Signature - TIS) that delineate these landscapes have been described by different groups. In an effort to explain the mechanisms of cancer immune responsiveness or resistance to CIT, several models have been proposed that are loosely associated with the three landscapes. Here, we propose a strategy to integrate compelling data from various paradigms into a "Theory of Everything". Founded upon this unified theory, we also propose the creation of a task force led by the Society for Immunotherapy of Cancer (SITC) aimed at systematically addressing salient questions relevant to cancer immune responsiveness and immune evasion. This multidisciplinary effort will encompass aspects of genetics, tumor cell biology, and immunology that are pertinent to the understanding of this multifaceted problem.

  9. Perinatal respiratory infections and long term consequences

    Directory of Open Access Journals (Sweden)

    Luciana Indinnimeo

    2015-10-01

    Full Text Available Respiratory syncytial virus (RSV is the most important pathogen in the etiology of respiratory infections in early life. 50% of children are affected by RSV within the first year of age, and almost all children become infected within two years. Numerous retrospective and prospective studies linking RSV and chronic respiratory morbidity show that RSV bronchiolitis in infancy is followed by recurrent wheezing after the acute episod. According to some authors a greater risk of wheezing in children with a history of RSV bronchiolitis would be limited to childhood, while according to others this risk would be extended into adolescence and adulthood. To explain the relationship between RSV infection and the development of bronchial asthma or the clinical pathogenetic patterns related to a state of bronchial hyperreactivity, it has been suggested that RSV may cause alterations in the response of the immune system (immunogenic hypothesis, activating directly mast cells and basophils and changing the pattern of differentiation of immune cells present in the bronchial tree as receptors and inflammatory cytokines. It was also suggested that RSV infection can cause bronchial hyperreactivity altering nervous airway modulation, acting on nerve fibers present in the airways (neurogenic hypothesis.The benefits of passive immunoprophylaxis with palivizumab, which seems to represent an effective approach in reducing the sequelae of RSV infection in the short- and long-term period, strengthen the implementation of prevention programs with this drug, as recommended by the national guidelines of the Italian Society of Neonatology. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the

  10. Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae.

    Science.gov (United States)

    Nguyen, Ut V; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Van Poucke, Mario; Peelman, Luc; Goddeeris, Bruno M; Cox, Eric

    2015-06-23

    F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA(+) B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA(+) B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity.

  11. Gastrointestinal immune responses in HIV infected subjects

    Directory of Open Access Journals (Sweden)

    LRR Castello-Branco

    1996-06-01

    Full Text Available The gut associated lymphoid tissue is responsible for specific responses to intestinal antigens. During HIV infection, mucosal immune deficiency may account for the gastrointestinal infections. In this review we describe the humoral and cellular mucosal immune responses in normal and HIV-infected subjects.

  12. Impact of age and vaccination history on long-term serological responses after symptomatic B. pertussis infection, a high dimensional data analysis

    Science.gov (United States)

    van Twillert, Inonge; Bonačić Marinović, Axel A.; Kuipers, Betsy; van Gaans-van den Brink, Jacqueline A. M.; Sanders, Elisabeth A. M.; van Els, Cécile A. C. M.

    2017-01-01

    Capturing the complexity and waning patterns of co-occurring immunoglobulin (Ig) responses after clinical B. pertussis infection may help understand how the human host gradually loses protection against whooping cough. We applied bi-exponential modelling to characterise and compare B. pertussis specific serological dynamics in a comprehensive database of IgG, IgG subclass and IgA responses to Ptx, FHA, Prn, Fim2/3 and OMV antigens of (ex-) symptomatic pertussis cases across all age groups. The decay model revealed that antigen type and age group were major factors determining differences in levels and kinetics of Ig (sub) classes. IgG-Ptx waned fastest in all age groups, while IgA to Ptx, FHA, Prn and Fim2/3 decreased fast in the younger but remained high in older (ex-) cases, indicating an age-effect. While IgG1 was the main IgG subclass in response to most antigens, IgG2 and IgG3 dominated the anti-OMV response. Moreover, vaccination history plays an important role in post-infection Ig responses, demonstrated by low responsiveness to Fim2/3 in unvaccinated elderly and by elevated IgG4 responses to multiple antigens only in children primed with acellular pertussis vaccine (aP). This work highlights the complexity of the immune response to this re-emerging pathogen and factors determining its Ig quantity and quality. PMID:28091579

  13. Phenology of species interactions in response to climate change: two case studies of plant-pollinator interactions using long-term data

    Science.gov (United States)

    McKinney, A. M.; Inouye, D. W.

    2012-12-01

    Climate change may alter the temporal overlap among interacting taxa with potential demographic consequences. Evidence of mistimed interactions in response to climate change, especially between plants and pollinators, is mixed, and few long-term datasets exist to test for changes in synchrony. Furthermore, advancements in flowering driven by climate change are especially pronounced at higher latitudes, so that migratory pollinators from lower latitudes may increasingly arrive at breeding grounds after the appearance of floral resources. We explored long-term shifts in phenological synchrony in two plant-pollinator systems:1) syrphid fly and flowering phenology in the Colorado Rocky Mountains, USA (1992-2011) and 2) hummingbird arrival relative to onset of early-season nectar resources in the Colorado Rocky Mountains (1975-2011) and the Santa Catalina Mountains, Arizona, USA (1984-2010). We investigated the abiotic cues associated with the phenology of the activity period of syrphid flies and their floral resources, including degree days above freezing, precipitation, and timing of snowmelt as potential explanatory variables. Timing of snowmelt was the best predictor of the onset of flowering and syrphid emergence. Snowmelt was also the best predictor of the end of flowering, while temperature and precipitation best predicted the end of the syrphid period. Both the onset and end of flowering advanced more rapidly than syrphids in response to earlier snowmelt. These different rates of phenological advancement resulted in increased temporal overlap between the flower and syrphid community in years of early snowmelt, because of longer flowering and fly activity periods during these years. If snowmelt continues to advance, temporal overlap between syrphids and their floral resources is therefore likely to increase. This case study shows that the phenology of interacting taxa may respond differently to climate cues, but that this does not necessarily lead to phenological

  14. Long term complications of diabetes

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000327.htm Long-term complications of diabetes To use the sharing features on this page, ... other tests. All these may help you keep complications of diabetes away. You will need to check your blood ...

  15. Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in Malian Children Coinfected with Schistosoma haematobium

    Directory of Open Access Journals (Sweden)

    Kirsten E. Lyke

    2018-02-01

    Full Text Available Polyparasitism is common in the developing world. We have previously demonstrated that schistosomiasis-positive (SP Malian children, aged 4–8 years, are protected from malaria compared to matched schistosomiasis-negative (SN children. The effect of concomitant schistosomiasis upon acquisition of T cell memory is unknown. We examined antigen-specific T cell frequencies in 48 Malian children aged 4–14 to a pool of malaria blood stage antigens, and a pool of schistosomal antigens, at a time point during a malaria episode and at a convalescent time point ~6 months later, following cessation of malaria transmission. CD4+ T cell-derived memory responses, defined as one or more significant cytokine (IFN-γ, TNF-α, IL-2, and/or IL-17A responses, was measured to schistoma antigens in 18/23 SP children at one or both time points, compared to 4/23 SN children (P < 0.0001. At the time of malaria infection, 12/24 SN children and 15/23 SP children (P = 0.29 stimulated with malaria antigens demonstrated memory recall as defined by CD4-derived cytokine production. This compares to 7/23 SN children and 16/23 SP children (P = 0.009 at the convalescent timepoint. 46.2% of cytokine-producing CD4+ T cells expressed a single cytokine after stimulation with malaria antigen during the malaria episode. This fell to 40.9% at follow-up with a compensatory rise of multifunctional cytokine secretion over time, a phenomenon consistent with memory maturation. The majority (53.2–59.5% of responses derived from CD45RA−CD62L− effector memory T cells with little variation in the phenotype depending upon the time point or the study cohort. We conclude that detectable T cell memory responses can be measured against both malaria and schistosoma antigens and that the presence of Schistosoma haematobium may be associated with long-term maintenance of T memory to malaria.

  16. Long-Term Coffee Consumption and Risk of Cardiovascular Disease: A Systematic Review and a Dose-Response Meta-Analysis of Prospective Cohort Studies

    Science.gov (United States)

    Ding, Ming; Bhupathiraju, Shilpa N; Satija, Ambika; van Dam, Rob M; Hu, Frank B

    2013-01-01

    Background Considerable controversy exists regarding the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk. Methods and Results Pubmed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1,279,804 participants and 36,352 CVD cases. A non-linear relationship of coffee consumption with CVD risk was identified (P for heterogeneity = 0.09, P for trend coffee consumption (median: 0 cups/d), the relative risk of CVD was 0.95 (95% CI, 0.87 to 1.03) for the highest (median: 5 cups/d) category, 0.85 (0.80 to 0.90) for the second highest (median: 3.5 cups/d), and 0.89 (0.84 to 0.94) for the third highest category (median: 1.5 cups/d). Looking at separate outcomes, coffee consumption was non-linearly associated with both CHD (P for heterogeneity = 0.001, P for trend 0.05). Conclusions A non-linear association between coffee consumption with CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups/d, and heavy coffee consumption was not associated with elevated CVD risk. PMID:24201300

  17. Changes in glucose-elicited blood metabolite responses following weight loss and long term weight maintenance in obese individuals with impaired glucose tolerance.

    Science.gov (United States)

    Geidenstam, Nina; Danielsson, Anders P H; Spégel, Peter; Ridderstråle, Martin

    2016-03-01

    Weight loss improves insulin sensitivity and glucose tolerance in obese subjects with impaired glucose tolerance (IGT), but the long term dynamic effects on blood metabolites other than glucose during an oral glucose tolerance test (OGTT), are largely unknown. Here, we studied changes in OGTT-elicited metabolite patterns in obese subjects during a diet-induced weight loss study. Blood samples from 14 obese individuals with IGT were collected at 0, 30 and 120 min during a standard 75 g OGTT at baseline (BMI 44 ± 2 kg/m(2)), after weight loss (BMI 36 ± 2 kg/m(2)) and after weight maintenance (BMI 35 ± 2 kg/m(2)). Serum metabolite levels were analyzed by gas chromatography/mass spectrometry and compared to a lean glucose tolerant group. Changes in the OGTT-elicited metabolite patterns occurred differentially during weight loss and weight maintenance. Enhanced suppression of aromatic amino acids were associated with decreased insulinogenic index observed after weight loss (tyrosine: r=0.72, p=0.013; phenylalanine: r=0.63, p=0.039). The OGTT-elicited suppression and/or lack of increase in levels of glutamate, glutamine, isoleucine, leucine, and the fatty acids laurate, oleate and palmitate, improved towards the lean profile after weight maintenance, paralleling an improvement in glucose tolerance. The greater heterogeneity in the response before and after weight loss in the obese, compared to lean subjects, was markedly reduced after weight maintenance. Diet-induced weight loss followed by weight maintenance results in changes in metabolite profiles associated with either hepatic insulin sensitivity or peripheral glucose tolerance. Our results highlight the importance of evaluating the effects of weight loss and weight maintenance separately. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Long-term coffee consumption and risk of cardiovascular disease: a systematic review and a dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Ding, Ming; Bhupathiraju, Shilpa N; Satija, Ambika; van Dam, Rob M; Hu, Frank B

    2014-02-11

    Considerable controversy exists on the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk. PubMed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1 279 804 participants and 36 352 CVD cases. A nonlinear relationship of coffee consumption with CVD risk was identified (P for heterogeneity=0.09, P for trend coffee consumption (median, 0 cups per day), the relative risk of CVD was 0.95 (95% confidence interval, 0.87-1.03) for the highest category (median, 5 cups per day) category, 0.85 (95% confidence interval, 0.80-0.90) for the second highest category (median, 3.5 cups per day), and 0.89 (95% confidence interval, 0.84-0.94) for the third highest category (median, 1.5 cups per day). Looking at separate outcomes, coffee consumption was nonlinearly associated with both coronary heart disease (P for heterogeneity=0.001, P for trend 0.05) risks. A nonlinear association between coffee consumption and CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups per day, and heavy coffee consumption was not associated with elevated CVD risk.

  19. Local and systemic response to intramammary lipopolysaccharide challenge during long-term manipulated plasma glucose and insulin concentrations in dairy cows.

    Science.gov (United States)

    Vernay, M C M B; Wellnitz, O; Kreipe, L; van Dorland, H A; Bruckmaier, R M

    2012-05-01

    The metabolic load during periods of high milk production in dairy cows causes a variety of changes of metabolite blood concentrations including dramatically decreased glucose levels. These changes supposedly impair the immune system. The goal of this study was, therefore, to evaluate adaptations of the cow's immune system in response to an intramammary lipopolysaccharide (LPS) stimulation during a 3-d modification of plasma glucose and insulin induced by different clamp infusions. Seventeen midlactating dairy cows received a hypoglycemic hyperinsulinemic clamp induced by insulin infusion (HypoG; n=5), a euglycemic hyperinsulinemic clamp induced by insulin and glucose infusion (EuG; n=6), or infusion of saline solution (NaCl; n=6) for 56 h. At 48 h of infusion, 2 udder quarters were challenged with 200 μg of Escherichia coli LPS. At 48 h of infusion (immediately before LPS challenge), tumor necrosis factor α, lactoferrin, and serum amyloid A (SAA) mRNA abundance was increased in HypoG and Il-1β mRNA abundance was decreased in EuG. After LPS challenge, plasma glucose concentration did not decrease, although plasma insulin increased simultaneously in all groups either due to enhanced endogenous release (NaCl) or due to increased insulin infusion rate (HypoG; EuG). Plasma cortisol, rectal temperatures, and milk somatic cell count of challenged quarters increased, whereas plasma nonesterified fatty acid concentrations were similarly decreased across treatments. In mammary biopsies, increased mRNA expression of tumor necrosis factor α, IL-1β, IL-8, and IL-10, and SAA were observed in LPS-treated quarters of all groups, with a more pronounced increase in IL-1β, IL-10, and SAA expression in EuG. Nuclear factor-κB mRNA expression was upregulated in NaCl and EuG but not in HypoG in response to LPS. Lactoferrin, toll-like receptor 4, and cyclooxygenase-2 mRNA expression was increased in LPS-treated quarters of EuG only, and 5-lipoxygenase mRNA expression was decreased

  20. Protective effects of long-term administration of Ziziphus jujuba fruit extract on cardiovascular responses in L-NAME hypertensive rats.

    Science.gov (United States)

    Mohebbati, Reza; Bavarsad, Kosar; Rahimi, Maryam; Rakhshandeh, Hasan; Khajavi Rad, Abolfazl; Shafei, Mohammad Naser

    2018-01-01

    Ziziphus jujuba stimulates the release of nitric oxide (NO). Because NO is involved in cardiovascular regulations, in this study the effects of hydroalcoholic extract of Z. jujuba on cardiovascular responses in acute NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats were evaluated. Rats were divided into 6 group (n=6): 1) saline, 2) L-NAME received (10mg/kg) intravenously, 3) sodium nitroprusside (SNP) (50µg/kg)+L-NAME group received SNP before L-NAME and 4-6) three groups of Z. jujuba (100, 200 and 400mg/kg) that treated for four weeks and on the 28 th day, L-NAME was injected. Femoral artery and vein were cannulated for recording cardiovascular responses and drug injection, respectively. Systolic blood pressure (SBP), Mean arterial pressure (MAP) and heart rate (HR) were recorded continuously. Maximal changes (∆) of SBP, MAP and HR were calculated and compared to control and L-NAME groups. In L-NAME group, maximal ΔSBP (L-NAME: 44.15±4.0 mmHg vs control: 0.71±2.1 mmHg) and ΔMAP (L-NAME: 40.8±4.0 mmHg vs control: 0.57±1.6 mmHg) significantly increased (p0.05). All doses of Z. jujuba attenuated maximal ∆SBP and ∆MAP induced by L-NAME but only the lowest dose (100 mg/kg) had significant effects (ΔSBP: 20.36±5.6 mmHg vs L-NAME: 44.1±4.0 mmHg and ΔMAP: 20.8±4.5 mmHg vs L-NAME: 40.8±3.8 mmHg (pL-NAME group (p>0.05). Because long-term consumption of Z. jujuba extract, especially its lowest dose, attenuated cardiovascular responses induced by L-NAME, we suggest that Z. jujuba has potential beneficial effects in prevention of hypertension induced by NO deficiency.

  1. Could the long term cover change of three Mediterranean shrubs be explained by their photosynthetic responses to drought in a rainfall exclusion experiment ?

    Science.gov (United States)

    Liberati, Dario; De Dato, Giovanbattista; Guidolotti, Gabriele; De Angelis, Paolo

    2013-04-01

    In the Mediterranean climates water stress is considered to be the main environmental factor limiting plant growth. In front of water limitations plants have developed a wide diversity of adaptation mechanism, and co-occurring species often display different physiological, functional, and life history strategies. In the contest of a rainfall exclusion experiment (project INCREASE), the present work is aimed to assess if the seasonal response of photosynthesis to the water stress (based on gas exchange data collected during 2010) can explain the long term change in the cover degree (assessed by seven pin point survey carried out from 2001 to 2012) of the three main species present in the Italian experimental site, Cistus monspeliensis L. (Cistaceae), Dorycnium pentaphyllum Scop. (Fabaceae) and Helichrysum italicum subsp. microphyllum (Willd.) Nyman (Asteraceae) From 2001 to 2012, in the untreated plots, the cover degree increased in C. monspeliensis (+ 0.34% per year), did not show any significant trend in D. pentaphyllum and decreased in H. italicum (- 1.54% per year). In the same period the rainfall exclusion system has worked during Spring and Autumn, mainly reducing the soil water content of the drought plots in Autumn: this treatment did not affect the cover trend of D. pentaphyllum and H. italicum, whereas C. monspeliensis displayed in the drought plots an opposite dynamic (- 1.23% per year) compared to the natural conditions. During 2010 all monitored species reached the maximum photosynthesis rates in spring, with a depression during summer drought and a recovery after the first Autumn rainfalls. The recovery of the spring rates was almost complete in C. monspeliensis and D. pentaphyllum, while in H. italicum did not exceed the 30% of the spring value. The rainfall exclusion reduced the photosynthesis rates in C. monspeliensis and H. italicum in Autumn. In the control plots the opposite cover trend observed in C. monspeliensis and H.italicum could be

  2. Changes in soil physical and chemical properties following organic matter removal and compaction: 20-year response of the aspen Lake-States Long Term Soil Productivity installations

    Science.gov (United States)

    Robert A. Slesak; Brian J. Palik; Anthony W. D' Amato; Valerie J. Kurth

    2017-01-01

    Soil functions that control plant resource availability can be altered by management activities such as increased organic matter (OM) removal and soil compaction during forest harvesting. The Long Term Soil Productivity study was established to evaluate how these practices influence soil and site productivity using experimental treatments that span a range of forest...

  3. Eastern hemlock response to even- and uneven-age management in the Acadian forest: results from the Penobscot Experimental Forest long-term silviculture study

    Science.gov (United States)

    John C. Brissette; Laura S. Kenefic

    2000-01-01

    Eastern hemlock (Tsuga canadensis (L.) Carr.) is an important tree species in the mixed-species conifer forests of northern New England and adjacent Canada. Hemlock is very tolerant of understory conditions; consequently, it responds differently to various silvicultural treatments. In a long-term study at the Penobscot Experimental Forest in east-...

  4. Body proportions during long-term growth hormone treatment in girls with Turner syndrome participating in a randomized dose-response trial

    NARCIS (Netherlands)

    T.C.J. Sas (Theo); W.J. Gerver; R. de Bruin (Rob); Th. Stijnen (Theo); S.M.P.F. de Muinck Keizer-Schrama (Sabine); T.J. Cole (Trevor); A. van Teunenbroek (Arne); S.L.S. Drop (Stenvert)

    1999-01-01

    textabstractTo assess body proportions in girls with Turner syndrome (TS) during long term GH treatment, height, sitting height (SH), hand (Hand) and foot (Foot) lengths, and biacromial (Biac) and biiliacal (Biil) diameters were measured in 68 girls with TS

  5. Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder

    NARCIS (Netherlands)

    Schrantee, Anouk; Bouziane, C.; Bron, E. E.; Klein, S.; Bottelier, M. A.; Kooij, J. J. S.; Rombouts, S. A. R. B.; Reneman, L.

    2017-01-01

    Stimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the DA system. We

  6. Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder

    NARCIS (Netherlands)

    Schrantee, A. (Anouk); C. Bouziane (Cheima); E.E. Bron (Esther); S. Klein (Stefan); Bottelier, M.A.; Kooij, J.J.S.; S.A.R.B. Rombouts (Serge); L. Reneman (Liesbeth)

    2017-01-01

    textabstractStimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the

  7. Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate and behavior in attention-deficit hyperactivity disorder.

    NARCIS (Netherlands)

    Schrantee, A.; Bouziane, C.; Bron, E.E.; Klein, S.; Bottelier, M.A.; Kooij, J.J.S.; Rombouts, S.A.R.B.; Reneman, L.

    2017-01-01

    Stimulant prescription rates for attention deficit hyperactivity disorder (ADHD) are increasing, even though potential long-term effects on the developing brain have not been well-studied. A previous randomized clinical trial showed short-term age-dependent effects of stimulants on the DA system. We

  8. Soilaluminum, iron, and phosphorus dynamics in response to long-term experimental nitrogen and sulfur additions at the Bear Brook Watershed in Maine, USA

    Science.gov (United States)

    Jessica Sherman; Ivan J. Fernandez; Stephen A. Norton; Tsutomu Ohno; Lindsey E. Rustad

    2006-01-01

    Atmospheric deposition of nitrogen (N) and sulfur (S) containing compounds affects soil chemistry in forested ecosystems through (1) acidification and the depletion of base cations, (2) metal mobilization, particularly aluminum (Al), and iron (Fe), (3) phosphorus (P) mobilization, and (4) N accumulation. The Bear BrookWatershed in Maine (BBWM) is a long-term paired...

  9. Using long-term ecosystem service and biodiversity data to study the impacts and adaptation options in response to climate change: insights from the global ILTER sites network

    Czech Academy of Sciences Publication Activity Database

    Vihervaara, P.; D'Amato, D.; Forsius, M.; Angelstam, P.; Baessler, C.; Balvanera, P.; Boldgiv, B.; Bourgeron, P.; Dick, J.; Kanka, R.; Klotz, S.; Maass, M.; Melecis, V.; Petřík, Petr; Shibata, H.; Tang, J.; Thompson, J.; Zacharias, S.

    2013-01-01

    Roč. 5, č. 1 (2013), s. 53-66 ISSN 1877-3435 R&D Projects: GA MŠk 7AMB12SK156 Institutional support: RVO:67985939 Keywords : climate change * long-term ecological monitoring * prmanen research plot Subject RIV: EF - Botanics Impact factor: 2.758, year: 2013

  10. [Long-term psychiatric hospitalizations].

    Science.gov (United States)

    Plancke, L; Amariei, A

    2017-02-01

    Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

  11. Short and long-term physiological responses of male and female rats to two dietary levels of pre-gelatinized maca (lepidium peruvianum chacon).

    Science.gov (United States)

    Meissner, H O; Kedzia, B; Mrozikiewicz, P M; Mscisz, A

    2006-02-01

    The aim of this study is to identify physiological responses of male and female rats to either a short- or long-term administration of two doses of Maca (Lepidium peruvianum) and observe relationships which may exist between groups of hormones and effects mediated by them. The effect of pre-gelatinized (extruded) organic Maca powder (Maca-GO) was studied on Sprague-Dowley male and female rats (1:1 ratio) receiving two dietary levels of Maca-GO (0.75 g/kg and 7.5 g/kg body weight) and assessed against control during 28 and 90 day laboratory trials on 30 and 60 rats respectively. Blood morphology, biochemistry (hormones, lipids and minerals) and histology of internal organs were determined. Homogenates of skeletal muscles and bones of rats were also analyzed. Maca-GO has low toxicity (LD=7.5 g/kg) and appears to be safe for short-term and extended use as dietary supplement or as a component of functional dietary and therapeutic preparations. There were different responses of male and female rats to different levels of Maca-GO administered during a short- and a longer-term periodl. When administered at higher dose for extended period of time (90 days), Maca-GO acted as a toner of hormonal processes in adult female rats at increased progesterone and a steady estradiol level, without affecting levels of blood FSH, LH and TSH. Obtained results justify further clinical research on use of Maca-GO in sportsmen, physically-active people of both sexes and peri-menopausal women to clarify mechanisms underlaying physiological mode of action of Maca-GO validaet in clinical study on humans. Substantial decrease in blood cortisol levels in a short- and longer-term trial and simultaneous tendency to lower blood ACTH, may indicate antidepressive effect of Maca-GO, which together with reduction in body weight, lowering triglycerides in blood plasma and increasing calcium and phosphorus deposition in bone and muscle tissues is worthy consideration in potential application to women at

  12. Uncertainty functions of modelled soil organic carbon changes in response to crop management derived from a French long term experiments dataset

    Science.gov (United States)

    Dimassi, Bassem; Guenet, Bertrand; Mary, Bruno; Trochard, Robert; Bouthier, Alain; Duparque, Annie; Sagot, Stéphanie; Houot, Sabine; Morel, Christian; Martin, Manuel

    2016-04-01

    The land use, land-use change and forestry (LULUCF) activities and crop management (CM) in Europe could be an important carbon sink through soil organic carbon (SOC) sequestration. Recently, the (EU decision 529/2013) requires European Union's member states to assess modalities to include greenhouse gas (GHG) emissions and removals resulting from activities relating to LULUCF and CM into the Union's (GHG) emissions reduction commitment and their national inventories reports (NIR). Tier 1, the commonly used method to estimate emissions for NIR, provides a framework for measuring SOC stocks changes. However, estimations have high uncertainty, especially in response to crop management at regional and specific national contexts. Understanding and quantifying this uncertainty with accurate confidence interval is crucial for reliably reporting and support decision-making and policies that aims to mitigate greenhouse gases through soil C storage. Here, we used the Tier 3 method, consisting of process-based modelling, to address the issue of uncertainty quantification at national scale in France. Specifically, we used 20 Long-term croplands experiments (LTE) in France with more than 100 treatments taking into account different agricultural practices such as tillage, organic amendment, inorganic fertilization, cover crops, etc. These LTE were carefully selected because they are well characterized with periodic SOC stocks monitoring overtime and covered a wide range of pedo-climatic conditions. We applied linear mixed effect model to statistically model, as a function of soil, climate and cropping system characteristics, the uncertainty resulting from applying this Tier 3 approach. The model was fitted on the dataset yielded by comparing the simulated (with the Century model V 4.5) to the observed SOC changes on the LTE at hand. This mixed effect model will then be used to derive uncertainty related to the simulation of SOC stocks changes of the French Soil Monitoring

  13. Investigation regarding the long-term security developments in the Swedish nuclear power and the response to the accident at Fukushima

    International Nuclear Information System (INIS)

    Skaanberg, Lars

    2012-01-01

    Swedish nuclear plants need to continue to work on analysis and actions in the plants, partly to meet the demands of legislation and agreed action plans, and partly due to additional security requirements on account of experiences from the Fukushima Dai-ichi accident, stress tests, security investigations and investigations relating to physical protection. It is also essential to continue with safety improvements to gradually increase margins against unforeseen events in aging plants during long-term operation

  14. [Human milk, immune responses and health effects].

    Science.gov (United States)

    Løland, Beate Fossum; Baerug, Anne B; Nylander, Gro

    2007-09-20

    Besides providing optimal nutrition to infants, human milk contains a multitude of immunological components. These components are important for protection against infections and also support the development and maturation of the infant's own immune system. This review focuses on the function of some classical immunocomponents of human milk. Relevant studies are presented that describe health benefits of human milk for the child and of lactation for the mother. Relevant articles were found mainly by searching PubMed. Humoral and cellular components of human milk confer protection against infections in the respiratory--, gastrointestinal--and urinary tract. Human milk also protects premature children from neonatal sepsis and necrotizing enterocolitis. There is evidence that human milk may confer long-term benefits such as lower risk of certain autoimmune diseases, inflammatory bowel disease and probably some malignancies. Human milk possibly affects components of the metabolic syndrome. Recent studies demonstrate long-term health benefits of lactation also for the mother. A reduced incidence of breast cancer is best documented. An increasing number of studies indicate protection against ovarian cancer, rheumatoid arthritis and type II diabetes.

  15. Immunomodulatory effect of ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice.

    Science.gov (United States)

    Shi, Yali; Cai, Dehua; Wang, Xiaojie; Liu, Xinshen

    2012-12-01

    Long-term heavy-load exercise can lead to a decrease in the organism's immune response. In this study, we used 100 Kunming (KM) mice to investigate the immune-regulatory effects of Ganoderma lucidum polysaccharides (GLP) on long-term heavy-load exercising mice. Peripheral white blood cells (WBC), the absolute value of neutrophils (NEUT), the phagocytic function of macrophages, serum agglutination valence, and the number of plaque-forming cells (PFC) were evaluated 4 weeks after gavaging long-term heavy-load exercising mice with GLP. After exercise, the WBC count in peripheral blood, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells were significantly reduced in the mice not fed GLP. Both medium and high doses of GLP drastically increased peripheral WBC, absolute neutrophil count, macrophage phagocytic index, serum agglutination valence, and the number of plaque-forming cells in long-term heavy-load exercising mice. High doses of GLP increased peritoneal macrophage phagocytic rate considerably. With this study, we demonstrate that 4 weeks of heavy-load exercise can lead to exercise-induced immunosuppression in mice. A supplement of GLP fed to these mice improves both non-specific and specific immune responses among these mice. The effect for the high-dose GLP treatment is especially significant.

  16. The impact of a diet with fructan-rich chicory roots on Oesophagostomum dentatum worm population dynamics and host immune responses in pigs

    DEFF Research Database (Denmark)

    Thamsborg, Stig Millan; Mejer, Helena; Skovgaard, Kerstin

    Oesophagostomum infections in pigs persist for months. We hypothesized that feeding fructans (dried chicory roots) may improve immunity and facilitate worm expulsion. We therefore examined the effects of long-term chicory on O. dentatum population dynamics and host immune responses. Methods: Seve...

  17. Antimicrobial peptides in innate immune responses

    DEFF Research Database (Denmark)

    Sorensen, O.E.; Borregaard, N.; Cole, A.M.

    2008-01-01

    Antimicrobial peptides (AMPs) are ancient effector molecules in the innate immune response of eukaryotes. These peptides are important for the antimicrobial efficacy of phagocytes and for the innate immune response mounted by epithelia of humans and other mammals. AMPs are generated either by de...... novo synthesis or by proteolytic cleavage from antimicrobially inactive proproteins. Studies of human diseases and animal studies have given important clues to the in vivo role of AMPs. It is now evident that dysregulation of the generation of AMPs in innate immune responses plays a role in certain...

  18. Cholinergic Modulation of Type 2 Immune Responses

    Directory of Open Access Journals (Sweden)

    Goele Bosmans

    2017-12-01

    Full Text Available In recent years, the bidirectional relationship between the nervous and immune system has become increasingly clear, and its role in both homeostasis and inflammation has been well documented over the years. Since the introduction of the cholinergic anti-inflammatory pathway, there has been an increased interest in parasympathetic regulation of both innate and adaptive immune responses, including T helper 2 responses. Increasing evidence has been emerging suggesting a role for the parasympathetic nervous system in the pathophysiology of allergic diseases, including allergic rhinitis, asthma, food allergy, and atopic dermatitis. In this review, we will highlight the role of cholinergic modulation by both nicotinic and muscarinic receptors in several key aspects of the allergic inflammatory response, including barrier function, innate and adaptive immune responses, and effector cells responses. A better understanding of these cholinergic processes mediating key aspects of type 2 immune disorders might lead to novel therapeutic approaches to treat allergic diseases.

  19. A trade-off between natural and acquired antibody production in a reptile: implications for long-term resistance to disease

    Directory of Open Access Journals (Sweden)

    Franziska C. Sandmeier

    2012-08-01

    Vertebrate immune systems are understood to be complex and dynamic, with trade-offs among different physiological components (e.g., innate and adaptive immunity within individuals and among taxonomic lineages. Desert tortoises (Gopherus agassizii immunised with ovalbumin (OVA showed a clear trade-off between levels of natural antibodies (NAbs; innate immune function and the production of acquired antibodies (adaptive immune function. Once initiated, acquired antibody responses included a long-term elevation in antibodies persisting for more than one year. The occurrence of either (a high levels of NAbs or (b long-term elevations of acquired antibodies in individual tortoises suggests that long-term humoral resistance to pathogens may be especially important in this species, as well as in other vertebrates with slow metabolic rates, concomitantly slow primary adaptive immune responses, and long life-spans.

  20. Surface coal mine land reclamation using a dry flue gas desulfurization product: Short-term and long-term water responses.

    Science.gov (United States)

    Chen, Liming; Stehouwer, Richard; Tong, Xiaogang; Kost, Dave; Bigham, Jerry M; Dick, Warren A

    2015-09-01

    Abandoned coal-mined lands are a worldwide concern due to their potential negative environmental impacts, including erosion and development of acid mine drainage. A field study investigated the use of a dry flue gas desulfurization product for reclamation of abandoned coal mined land in USA. Treatments included flue gas desulfurization product at a rate of 280 Mg ha(-1) (FGD), FGD at the same rate plus 112 Mg ha(-1) yard waste compost (FGD/C), and conventional reclamation that included 20 cm of re-soil material plus 157 Mg ha(-1) of agricultural limestone (SOIL). A grass-legume sward was planted after treatment applications. Chemical properties of surface runoff and tile water (collected from a depth of 1.2m below the ground surface) were measured over both short-term (1-4 yr) and long-term (14-20 yr) periods following reclamation. The pH of surface runoff water was increased from approximately 3, and then sustained at 7 or higher by all treatments for up to 20 yr, and the pH of tile flow water was also increased and sustained above 5 for 20 yr. Compared with SOIL, concentrations of Ca, S and B in surface runoff and tile flow water were generally increased by the treatments with FGD product in both short- and long-term measurements and concentrations of the trace elements were generally not statistically increased in surface runoff and tile flow water over the 20-yr period. However, concentrations of As, Ba, Cr and Hg were occasionally elevated. These results suggest the use of FGD product for remediating acidic surface coal mined sites can provide effective, long-term reclamation. Copyright © 2015. Published by Elsevier Ltd.

  1. Response of aboveground carbon balance to long-term, experimental shifts in precipitation seasonality is contingent on plant community type in cold-desert rangelands

    Science.gov (United States)

    Reinhardt, K.; McAbee, K.; Germino, M. J.; Bosworth, A.

    2016-12-01

    Semi-arid rangelands have been identified as potential carbon (C) sinks. However, the degree of net C storage or release in water-limited systems is a function of precipitation amount and timing, as well as plant community composition. In northern latitudes of western North America, climate models predict increases in wintertime precipitation and decreases in summertime precipitation. In theory, this should boost C storage in cold-desert ecosystems that have deep-rooted woody plants due to greater wintertime soil water storage that enhances summertime productivity. However, there are few long-term, manipulative field-based studies investigating how shrub- and grass-dominated rangelands will respond to changing precipitation patterns. We measured aboveground C pools and fluxes at leaf, soil, and ecosystem scales over the 2014 growing season on plots that had supplemental precipitation added in either winter or summer for 21 years, in shrub- and exotic-bunchgrass-dominated plots. We hypothesized that increased winter precipitation would stimulate aboveground C uptake and storage relative to ambient conditions, in our cold-desert-adapted plant species. We further hypothesized that long-term gains in aboveground C storage due to precipitation manipulations would be greater in plots containing shrubs. Our hypotheses were generally supported: ecosystem C uptake and long-term biomass accumulation were greater in winter- and summer-irrigated plots compared to control plots in both vegetation communities. However, substantial increases in aboveground biomass occurred only in winter-irrigated plots that contained shrubs. Our findings suggest that increases in winter precipitation will enhance C storage of this widespread ecosystem, provided that the ecosystems have resisted conversion to exotic grassland.

  2. Unintentional Long-Term Esophageal Stenting due to a Complete Response in a Patient with Stage UICC IV Adenocarcinoma of the Gastroesophageal Junction

    Directory of Open Access Journals (Sweden)

    Anna Paeschke

    2016-05-01

    Full Text Available Endoscopic stent implantation is a common short-treatment option in palliative settings in patients with esophageal cancer. Advanced disease is associated with low survival rates; therefore, data on the long-term outcome are limited. So far, cases of long-term remission or even cure of metastasized adenocarcinoma of the gastroesophageal junction or stomach (AGS have only been reported from Asia. A 51-year-old male patient primarily diagnosed with metastasized adenocarcinoma of the gastroesophageal junction (GEJ [type I, cT3cN+cM1 (hep, CEA positive, UICC stage IV] received palliative esophageal stenting with a self-expandable metal stent. As disease progressed after four cycles with epirubicin, oxaliplatin, and capecitabin, treatment was changed to 5-FU and Irinotecan. The patient did not return after 5 cycles of FOLFIRI, but presented 4 years later with mild dysphagia. Endoscopy surprisingly revealed no relevant stenosis or stent migration. Repeated histological analyses of a residual mass at the GEJ did not detect malignancy. Since the initially diagnosed hepatic metastases were no longer detectable by computed tomography, cure from esophageal cancer was assumed. Dysphagia was ascribed to esophageal motility disorder by a narrowed esophageal lumen after long-term stenting. Thus, endoscopic stent implantation is an important method in palliative treatment of dysphagia related to AGS. New systemic treatment strategies like trastuzumab in Her2neu positive cases or new VEGF-inhibitors like ramucirumab will lead to more long-time survivors with AGS. In conclusion, future endoscopic treatment strategies in AGS represent a challenge for the development of new stent techniques in either extraction or programmed complete dissolution.

  3. Nuclear Energy, Long Term Requirements

    International Nuclear Information System (INIS)

    Knapp, V.

    2006-01-01

    There are serious warnings about depletion of oil and gas and even more serious warnings about dangers of climate change caused by emission of carbon dioxide. Should developed countries be called to replace CO2 emitting energy sources as soon as possible, and the time available may not be longer then few decades, can nuclear energy answer the call and what are the requirements? Assuming optimistic contribution of renewable energy sources, can nuclear energy expand to several times present level in order to replace large part of fossil fuels use? Paper considers intermediate and long-term requirements. Future of nuclear power depends on satisfactory answers on several questions. First group of questions are those important for near and intermediate future. They deal with economics and safety of nuclear power stations in the first place. On the same time scale a generally accepted concept for radioactive waste disposal is also required. All these issues are in the focus of present research and development. Safer and more economical reactors are targets of international efforts in Generation IV and INPRO projects, but aiming further ahead these innovative projects are also addressing issues such as waste reduction and proliferation resistance. However, even assuming successful technical development of these projects, and there is no reason to doubt it, long term and large-scale nuclear power use is thereby not yet secured. If nuclear power is to play an essential role in the long-term future energy production and in reduction of CO2 emission, than several additional questions must be replied. These questions will deal with long-term nuclear fuel sufficiency, with necessary contribution of nuclear power in sectors of transport and industrial processes and with nuclear proliferation safety. This last issue is more political then technical, thus sometimes neglected by nuclear engineers, yet it will have essential role for the long-term prospects of nuclear power. The

  4. Response of microbial community of organic-matter-impoverished arable soil to long-term application of soil conditioner derived from dynamic rapid fermentation of food waste.

    Science.gov (United States)

    Hou, Jiaqi; Li, Mingxiao; Mao, Xuhui; Hao, Yan; Ding, Jie; Liu, Dongming; Xi, Beidou; Liu, Hongliang

    2017-01-01

    Rapid fermentation of food waste can be used to prepare soil conditioner. This process consumes less time and is more cost-effective than traditional preparation technology. However, the succession of the soil microbial community structure after long-term application of rapid fermentation-derived soil conditioners remains unclear. Herein, dynamic rapid fermentation (DRF) of food waste was performed to develop a soil conditioner and the successions and diversity of bacterial communities in an organic-matter-impoverished arable soil after six years of application of DRF-derived soil conditioner were investigated. Results showed that the treatment increased soil organic matter (SOM) accumulation and strawberry yield by 5.3 g/kg and 555.91 kg/ha, respectively. Proteobacteria, Actinobacteria, Acidobacteria, and Firmicutes became the dominant phyla, occupying 65.95%-77.52% of the bacterial sequences. Principal component analysis (PCA) results showed that the soil bacterial communities were largely influenced by the treatment. Redundancy analysis (RDA) results showed that the relative abundances of Gemmatimonadetes, Chloroflexi, Verrucomicrobia, Nitrospirae, and Firmicutes were significantly correlated with soil TC, TN, TP, NH4+-N, NO3--N, OM, and moisture. These communities were all distributed in the soil samples collected in the sixth year of application. Long-term treatment did not enhance the diversity of bacterial species but significantly altered the distribution of major functional bacterial communities in the soils. Application of DRF-derived soil conditioner could improve the soil quality and optimize the microbial community, ultimately enhancing fruit yields.

  5. Final Activity Report: The Effects of Iron Complexing Ligands on the Long Term Ecosystem Response to Iron Enrichment of HNLC waters

    Energy Technology Data Exchange (ETDEWEB)

    Trick, Charles Gordon [Western University

    2013-07-30

    Substantial increases in the concentrations of the stronger of two Fe(III) complexing organic ligand classes measured during the mesoscale Fe enrichment studies IronEx II and SOIREE appeared to sharply curtailed Fe availability to diatoms and thus limited the efficiency of carbon sequestration to the deep. Detailed observations during IronEx II (equatorial Pacific Ocean) and SOIREE (Southern Ocean –Pacific sector) indicate that the diatoms began re-experiencing Fe stress even though dissolved Fe concentrations remained elevated in the patch. This surprising outcome likely is related to the observed increased concentrations of strong Fe(III)-complexing ligands in seawater. Preliminary findings from other studies indicate that diatoms may not readily obtain Fe from these chemical species whereas Fe bound by strong ligands appears to support growth of cyanobacteria and nanoflagellates. The difficulty in assessing the likelihood of these changes with in-situ mesoscale experiments is the extended monitoring period needed to capture the long-term trajectory of the carbon cycle. A more detailed understanding of Fe complexing ligand effects on long-term ecosystem structure and carbon cycling is essential to ascertain not only the effect of Fe enrichment on short-term carbon sequestration in the oceans, but also the potential effect of Fe enrichment in modifying ecosystem structure and trajectory.

  6. Stress responses of adolescent male and female rats exposed repeatedly to cat odor stimuli, and long-term enhancement of adult defensive behaviors.

    Science.gov (United States)

    Wright, Lisa D; Muir, Katherine E; Perrot, Tara S

    2013-07-01

    In order to characterize the short- and long-term effects of repeated stressor exposure during adolescence, and to compare the effects of using two sources of cat odor as stressor stimuli, male and female adolescent rats (postnatal day (PND) ∼ 38-46) were exposed on five occasions to either a control stimulus, a cloth stimulus containing cat hair/dander, or a section of cat collar previously worn by a cat. Relative to control stimulus exposure, activity was suppressed and defensive behavior enhanced during exposure to either cat odor stimulus (most pervasively in rats exposed to the collar). Only cloth-exposed rats showed elevated levels of corticosterone (CORT), and only after repeated stressor exposure, but interestingly, rats exposed to the collar stimulus during adolescence continued to show increased behavioral indices of anxiety in adulthood. In this group, the time an individual spent in physical contact with a cagemate during the final adolescent exposure was negatively related to stress-induced CORT output in adulthood, which suggests that greater use of social support during adolescent stress may facilitate adult behavioral coping, without necessitating increased CORT release. These findings demonstrate that adolescent male and female rats respond defensively to cat odor stimuli across repeated exposures and that exposure to such stressors during adolescence can augment adult anxiety-like behavior in similar stressful conditions. These findings also suggest a potential role for social behavior during adolescent stressor exposure in mediating long-term outcomes. Copyright © 2012 Wiley Periodicals, Inc.

  7. Analysing long term discursive processes

    DEFF Research Database (Denmark)

    Horsbøl, Anders

    which extend beyond the single interaction, for instance negotiations or planning processes, seems to have played a less important role, with studies such as Iedema 2001 and Wodak 2000 as exceptions. These long term processes, however, are central to the constitution and workings of organizations......What do timescales - the notion that processes take place or can be viewed within a shorter or longer temporal range (Lemke 2005) - mean for the analysis of discourse? What are the methodological consequences of analyzing discourse at different timescales? It may be argued that discourse analysis...... in general has favored either the analysis of short term processes such as interviews, discussions, and lessons, or the analysis of non-processual entities such as (multimodal) texts, arguments, discursive repertoires, and discourses (in a Foucaultian sense). In contrast, analysis of long term processes...

  8. Types of adult attention-deficit hyperactivity disorder (ADHD): baseline characteristics, initial response, and long-term response to treatment with methylphenidate.

    Science.gov (United States)

    Reimherr, Fred W; Marchant, Barrie K; Gift, Thomas E; Steans, Tammy A; Wender, Paul H

    2015-06-01

    Much recent research describes the importance of emotional symptoms in ADHD. While there is no accepted system for including emotionality in diagnosing ADHD, the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) provides a tool to facilitate this. It assesses a range of adult ADHD symptoms which load on two factors: inattentive and emotional dysregulation. The consistently high inattentive factor was used to define significant elevation on the more variable emotional dysregulation factor (which contains four WRAADDS domains: hyperactivity/restlessness, temper, affective lability, and emotional over-reactivity) allowing the definition of two ADHD diagnostic types. We compared these two types on a broad range of adult subject characteristics, including response to methylphenidate (MPH) treatment assessed during two clinical trials. Marked impairment in three of the four emotional domains reflected a symptom severity level equivalent to that of the inattentive factor. 59 % met this threshold, defining them as ADHD emotion dysregulation presentation, as opposed to 41 % with ADHD inattentive presentation. Cluster analysis validated these groups by generating similar clusters with 85 % agreement regarding membership. ADHD emotional dysregulation presentation subjects showed more childhood ADHD symptoms, adult symptoms of oppositional defiant disorder, and evidence of personality disorder. Both types showed similar improvement during the double-blind MPH arm of the trials and during a 6-month open-label phase. Based on the presence of symptoms of emotional dysregulation, ADHD in adults can be conceptualized as two types. Impairment and comorbidity in adults with ADHD are largely concentrated in ADHD emotional dysregulation presentation patients.

  9. Comparing long term energy scenarios

    International Nuclear Information System (INIS)

    Cumo, M.; Simbolotti, G.

    2001-01-01

    Major projection studies by international organizations and senior analysts have been compared with reference to individual key parameters (population, energy demand/supply, resources, technology, emissions and global warming) to understand trends and implications of the different scenarios. Then, looking at the long term (i.e., 2050 and beyond), parameters and trends have been compared together to understand and quantify whether and when possible crisis or market turbulence might occur due to shortage of resources or environmental problems [it

  10. Interplay between immune responses to HLA and non-HLA self-antigens in allograft rejection.

    Science.gov (United States)

    Angaswamy, Nataraju; Tiriveedhi, Venkataswarup; Sarma, Nayan J; Subramanian, Vijay; Klein, Christina; Wellen, Jason; Shenoy, Surendra; Chapman, William C; Mohanakumar, T

    2013-11-01

    Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection. Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo- and autoimmunity leading to allograft dysfunction. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  11. Non-alcoholic fatty liver disease and impaired proinsulin conversion as newly identified predictors of the long-term non-response to a lifestyle intervention for diabetes prevention: results from the TULIP study.

    Science.gov (United States)

    Schmid, Vera; Wagner, Robert; Sailer, Corinna; Fritsche, Louise; Kantartzis, Konstantinos; Peter, Andreas; Heni, Martin; Häring, Hans-Ulrich; Stefan, Norbert; Fritsche, Andreas

    2017-12-01

    Lifestyle intervention is effective to prevent type 2 diabetes. However, a considerable long-term non-response occurs to a standard lifestyle intervention. We investigated which risk phenotypes at baseline and their changes during the lifestyle intervention predict long-term glycaemic non-response to the intervention. Of 300 participants at high risk for type 2 diabetes who participated in a 24 month lifestyle intervention with diet modification and increased physical activity, 190 participants could be re-examined after 8.7 ± 1.6 years. All individuals underwent a five-point 75 g OGTT and measurements of body fat compartments and liver fat content with MRI and spectroscopy at baseline, 9 and 24 months during the lifestyle intervention, and at long-term follow-up. Fasting proinsulin to insulin conversion (PI/I ratio) and insulin sensitivity and secretion were calculated from the OGTT. Non-response to lifestyle intervention was defined as no decrease in glycaemia, i.e. no decrease in AUC for glucose at 0-120 min during OGTT (AUCglucose 0-120 min ). Before the lifestyle intervention, 56% of participants had normal glucose regulation and 44% individuals had impaired fasting glucose and/or impaired glucose tolerance. At long-term follow-up, 11% had developed diabetes. Multivariable regression analysis with adjustment for age, sex, BMI and change in BMI during the lifestyle intervention revealed that baseline insulin secretion and insulin sensitivity, as well as change in insulin sensitivity during the lifestyle intervention, predicted long-term glycaemic control after 9 years. In addition, increased hepatic lipid content as well as impaired fasting proinsulin conversion at baseline were newly detected phenotypes that independently predicted long-term glycaemic control. Increased hepatic lipid content and impaired proinsulin conversion are new predictors, independent of change in body weight, for non-response to lifestyle intervention in addition to the

  12. Histological chorioamnionitis shapes the neonatal transcriptomic immune response.

    Science.gov (United States)

    Weitkamp, Jörn-Hendrik; Guthrie, Scott O; Wong, Hector R; Moldawer, Lyle L; Baker, Henry V; Wynn, James L

    2016-07-01

    Histologic chorioamnionitis (HCA) is commonly associated with preterm birth and deleterious post-natal outcomes including sepsis and necrotizing enterocolitis. Transcriptomic analysis has been used to uncover gene signatures that permit diagnosis and prognostication, show new therapeutic targets, and reveal mechanisms that underlie differential outcomes with other complex disease states in neonates such as sepsis. To define the transcriptomic and inflammatory protein response in peripheral blood among infants with exposure to histologic chorioamnionitis. Prospective, observational study. Uninfected preterm neonates retrospectively categorized based on placental pathology with no HCA exposure (n=18) or HCA exposure (n=15). We measured the transcriptomic and inflammatory mediator response in prospectively collected whole blood. We found 488 significant (p<0.001), differentially expressed genes in whole blood samples among uninfected neonates with HCA exposure that collectively represented activated innate and adaptive immune cellular pathways and revealed a potential regulatory role for the pleotropic microRNA molecule miR-155. Differentially secreted plasma cytokines in patients with HCA exposure compared to patients without HCA included MCP-1, MPO, and MMP-9 (p<0.05). Exposure to HCA distinctively activates the neonatal immune system in utero with potentially long-term health consequences. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Forest Growth Responses to Drought at Short- and Long-Term Scales in Spain: Squeezing the Stress Memory from Tree Rings

    Directory of Open Access Journals (Sweden)

    J. Julio Camarero

    2018-02-01

    Full Text Available Drought-triggered declines in forest productivity and associated die-off events have increased considerably due to climate warming in the last decades. There is an increasing interest in quantifying the resilience capacity of forests against climate warming and drought to uncover how different stands and tree species will resist and recover after more frequent and intense droughts. Trees form annual growth rings that represent an accurate record of how forest growth responded to past droughts. Here we use dendrochronology to quantify the radial growth of different forests subjected to contrasting climatic conditions in Spain during the last half century. Particularly, we considered four climatically contrasting areas where dominant forests showed clear signs of drought-induced dieback. Studied forests included wet sites dominated by silver fir (Abies alba in the Pyrenees and beech (Fagus sylvatica stands in northern Spain, and drought-prone sites dominated by Scots pine (Pinus sylvestris in eastern Spain and black pine (Pinus nigra in the semi-arid south-eastern Spain. We quantified the growth reduction caused by different droughts and assessed the short-and long-term resilience capacity of declining vs. non-declining trees in each forest. In all cases, drought induced a marked growth reduction regardless tree vigor. However, the capacity to recover after drought (resilience at short- and long-term scales varied greatly between declining and non-declining individuals. In the case of beech and silver fir, non-declining individuals presented greater growth rates and capacity to recover after drought than declining individuals. For Scots pine, the resilience to drought was found to be lower in recent years regardless the tree vigor, but the growth reduction caused by successive droughts was more pronounced in declining than in non-declining individuals. In the black pine forest an extreme drought induced a marked growth reduction in declining

  14. Private long-term care insurance and state tax incentives.

    Science.gov (United States)

    Stevenson, David G; Frank, Richard G; Tau, Jocelyn

    2009-01-01

    To increase the role of private insurance in financing long-term care, tax incentives for long-term care insurance have been implemented at both the federal and state levels. To date, there has been surprisingly little study of these initiatives. Using a panel of national data, we find that market take-up for long-term care insurance increased over the last decade, but state tax incentives were responsible for only a small portion of this growth. Ultimately, the modest ability of state tax incentives to lower premiums implies that they should be viewed as a small piece of the long-term care financing puzzle.

  15. Patterns of long-term and short-term responses in adult patients with attention-deficit/hyperactivity disorder in a completer cohort of 12 weeks or more with atomoxetine.

    Science.gov (United States)

    Sobanski, E; Leppämäki, S; Bushe, C; Berggren, L; Casillas, M; Deberdt, W

    2015-11-01

    Atomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns. From 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD who completed atomoxetine treatment at long-term (24 weeks; n=1443) and/or short-term (12 weeks; n=2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling. Based on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24 weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term (12 weeks) treatment. Four of the 5 long-term clusters (comprising 95% of completer patients) showed positive trajectories: 2 faster responding clusters (L1 and L2), and 2 more gradually responding clusters (L3 and L4). Responses (i.e.≥30% reduction in CAARS-Inv:SV total score, and CGI-S score≤3) were observed at 8 and 24 weeks in 80% and 95% of completers in Cluster L1, versus 5% and 48% in Cluster L4. While many adults with ADHD responded relatively rapidly to atomoxetine, others responded more gradually without a clear plateau at 24 weeks. Longer-term treatment may be associated with greater numbers of responders. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Acute and long-term changes in T-lymphocyte subsets in response to clinical and subclinical measles. A community study from rural Senegal

    DEFF Research Database (Denmark)

    Lisse, I; Samb, B; Whittle, H

    1998-01-01

    To investigate the possibility of long-term suppression of T-lymphocyte subsets, we examined children exposed to measles at home during an epidemic in rural Senegal, at time of exposure and 1 and 6 months later. The measles case fatality ratio was 1%. Subclinical measles was common among vaccinated...... children exposed to measles (45%). Both clinical and subclinical cases of measles showed a significant rise in absolute CD4 count in the incubation period. In the prodromal phase and the first week after the rash, the lymphocyte percentage, the white blood cell count and the absolute CD4 cell numbers were...... significantly reduced. There was no persistent decrease of absolute CD4 or CD8 numbers at 1 or 6 months after exposure. Measles infection was followed by significant changes in the subset composition, both CD4 and CD8 percentages being significantly higher in the second month after measles than among non...

  17. Oxidative and antioxidative responses in submandibular and parotid glands of rats exposed to long-term extremely low frequency magnetic field

    Directory of Open Access Journals (Sweden)

    Mehmet Akdağ

    2014-06-01

    Full Text Available Background: Some epidemiologic and laboratory studies have suggested a possible associations between exposure to extremely low frequency magnetic field (ELF-MF and cancer. However, it is not known underlying mechanisms of this interaction. The aim of the study was to investigate the possible oxidative damage induced by long-term ELF-MF exposure on submandibular and parotis glands of rats. Methods: Rats in the experimental group were exposed to 100 and 500 µT ELF-MF (2 h/day, 7 days/week, for 10 months corresponding to exposure levels that are considered safe for humans. The same experimental procedures were applied to the sham group, but the ELF generator was turned off. The levels of catalase (CAT, malondialdehyde (MDA, myeloperoxidase (MPO, total antioxidative capacity (TAC, total oxidant status (TOS, and oxidative stress index (OSI were measured in rat submandibular and parotis gland. Results: Although some oxidative and antioxidative parameters of submandibular gland were altered by ELF-100 and ELF-500 exposure groups, these changes were not statistically significant ( p >0.05. However, a decrease observed in CAT levels of parotid gland in both the ELF-100 and ELF-500 exposure groups (p0.05. Conclusions: Our results showed that long-term ELF-MF exposure did not alter oxidative, antioxidative processes and lipid peroxidation in submandibular gland of rats. However, 100 µT and 500 µT ELF-MF exposure decreased CAT activity in parotid gland. J Clin Exp Invest 2014; 5 (2: 219-225

  18. Long term stability of power systems

    Energy Technology Data Exchange (ETDEWEB)

    Kundur, P; Gao, B [Powertech Labs. Inc., Surrey, BC (Canada)

    1994-12-31

    Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

  19. Holocene sediment distribution on the inner continental shelf of northeastern South Carolina: implications for the regional sediment budget and long-term shoreline response

    Science.gov (United States)

    Denny, Jane F.; Schwab, William C.; Baldwin, Wayne E.; Barnhardt, Walter A.; Gayes, Paul T.; Morton, R.A.; Warner, John C.; Driscoll, Neal W.; Voulgaris, George

    2013-01-01

    High-resolution geophysical and sediment sampling surveys were conducted offshore of the Grand Strand, South Carolina to define the shallow geologic framework of the inner shelf. Results are used to identify and map Holocene sediment deposits, infer sediment transport pathways, and discuss implications for the regional coastal sediment budget. The thickest deposits of Holocene sediment observed on the inner shelf form shoal complexes composed of moderately sorted fine sand, which are primarily located offshore of modern tidal inlets. These shoal deposits contain ~67 M m3 of sediment, approximately 96% of Holocene sediment stored on the inner shelf. Due to the lack of any significant modern fluvial input of sand to the region, the Holocene deposits are likely derived from reworking of relict Pleistocene and older inner-shelf deposits during the Holocene marine transgression. The Holocene sediments are concentrated in the southern part of the study area, due to a combination of ancestral drainage patterns, a regional shift in sediment supply from the northeast to the southwest in the late Pleistocene, and proximity to modern inlet systems. Where sediment is limited, only small, low relief ridges have formed and Pleistocene and older deposits are exposed on the seafloor. The low-relief ridges are likely the result of a thin, mobile veneer of sediment being transported across an irregular, erosional surface formed during the last transgression. Sediment textural trends and seafloor morphology indicate a long-term net transport of sediment to the southwest. This is supported by oceanographic studies that suggest the long-term sediment transport direction is controlled by the frequency and intensity of storms that pass through the region, where low pressure systems yield net along-shore flow to the southwest and a weak onshore component. Current sediment budget estimates for the Grand Strand yield a deficit for the region. Volume calculations of Holocene deposits on the

  20. Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention.

    Science.gov (United States)

    Szulc-Lerch, Kamila U; Timmons, Brian W; Bouffet, Eric; Laughlin, Suzanne; de Medeiros, Cynthia B; Skocic, Jovanka; Lerch, Jason P; Mabbott, Donald J

    2018-01-01

    There is growing evidence that exercise induced experience dependent plasticity may foster structural and functional recovery following brain injury. We examined the efficacy of exercise training for neural and cognitive recovery in long-term pediatric brain tumor survivors treated with radiation. We conducted a controlled clinical trial with crossover of exercise training (vs. no training) in a volunteer sample of 28 children treated with cranial radiation for brain tumors (mean age = 11.5 yrs.; mean time since diagnosis = 5.7 yrs). The endpoints were anatomical T1 MRI data and multiple behavioral outcomes presenting a broader analysis of structural MRI data across the entire brain. This included an analysis of changes in cortical thickness and brain volume using automated, user unbiased approaches. A series of general linear mixed effects models evaluating the effects of exercise training on cortical thickness were performed in a voxel and vertex-wise manner, as well as for specific regions of interest. In exploratory analyses, we evaluated the relationship between changes in cortical thickness after exercise with multiple behavioral outcomes, as well as the relation of these measures at baseline. Exercise was associated with increases in cortical thickness within the right pre and postcentral gyri. Other notable areas of increased thickness related to training were present in the left pre and postcentral gyri, left temporal pole, left superior temporal gyrus, and left parahippocampal gyrus. Further, we observed that compared to a separate cohort of healthy children, participants displayed multiple areas with a significantly thinner cortex prior to training and fewer differences following training, indicating amelioration of anatomical deficits. Partial least squares analysis (PLS) revealed specific patterns of relations between cortical thickness and various behavioral outcomes both after training and at baseline. Overall, our results indicate that

  1. Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention

    Directory of Open Access Journals (Sweden)

    Kamila U. Szulc-Lerch

    Full Text Available There is growing evidence that exercise induced experience dependent plasticity may foster structural and functional recovery following brain injury. We examined the efficacy of exercise training for neural and cognitive recovery in long-term pediatric brain tumor survivors treated with radiation.We conducted a controlled clinical trial with crossover of exercise training (vs. no training in a volunteer sample of 28 children treated with cranial radiation for brain tumors (mean age = 11.5 yrs.; mean time since diagnosis = 5.7 yrs. The endpoints were anatomical T1 MRI data and multiple behavioral outcomes presenting a broader analysis of structural MRI data across the entire brain. This included an analysis of changes in cortical thickness and brain volume using automated, user unbiased approaches. A series of general linear mixed effects models evaluating the effects of exercise training on cortical thickness were performed in a voxel and vertex-wise manner, as well as for specific regions of interest. In exploratory analyses, we evaluated the relationship between changes in cortical thickness after exercise with multiple behavioral outcomes, as well as the relation of these measures at baseline.Exercise was associated with increases in cortical thickness within the right pre and postcentral gyri. Other notable areas of increased thickness related to training were present in the left pre and postcentral gyri, left temporal pole, left superior temporal gyrus, and left parahippocampal gyrus. Further, we observed that compared to a separate cohort of healthy children, participants displayed multiple areas with a significantly thinner cortex prior to training and fewer differences following training, indicating amelioration of anatomical deficits. Partial least squares analysis (PLS revealed specific patterns of relations between cortical thickness and various behavioral outcomes both after training and at baseline.Overall, our results

  2. Persistent hepatitis virus infection and immune homeostasis

    OpenAIRE

    ZHOU Yun

    2014-01-01

    Homeostasis between the host and viruses is naturally maintained. On the one hand, the immune system activates the immune response to kill or eliminate viruses; on the other hand, the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance. Long-term coexistence of the host and viruses is the pr...

  3. Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood

    International Nuclear Information System (INIS)

    Ordonhez Rigato, Paula; Maciel, Milton; Goldoni, Adriana Leticia; Piubelli, Orlando; Alves de Brito, Cyro; Fusaro, Ana Elisa; Eurico de Alencar, Liciana Xavier; August, Thomas; Torres Azevedo Marques, Ernesto; Silva Duarte, Alberto Jose da; Sato, Maria Notomi

    2010-01-01

    Successful T cell priming in early postnatal life that can generate effective long-lasting responses until adulthood is critical in HIV vaccination strategies because it prevents early sexual initiation and breastfeeding transmission of HIV. A chimeric DNA vaccine encoding p55 HIV gag associated with lysosome-associated membrane protein 1 (LAMP-1; which drives the antigen to the MIIC compartment), has been used to enhance cellular and humoral antigen-specific responses in adult mice and macaques. Herein, we investigated LAMP-1/gag vaccine immunogenicity in the neonatal period in mice and its ability to generate long-lasting effects. Neonatal vaccination with chimeric LAMP/gag generated stronger Gag-specific immune responses, as measured by the breadth of the Gag peptide-specific IFN-γ, proliferative responsiveness, cytokine production and antibody production, all of which revealed activation of CD4+ T cells as well as the generation of a more robust CTL response compared to gag vaccine alone. To induce long-lived T and B cell memory responses, it was necessary to immunize neonates with the chimeric LAMP/gag DNA vaccine. The LAMP/gag DNA vaccine strategy could be particularly useful for generating an anti-HIV immune response in the early postnatal period capable of inducing long-term immunological memory.

  4. Pathogen recognition in the innate immune response.

    Science.gov (United States)

    Kumar, Himanshu; Kawai, Taro; Akira, Shizuo

    2009-04-28

    Immunity against microbial pathogens primarily depends on the recognition of pathogen components by innate receptors expressed on immune and non-immune cells. Innate receptors are evolutionarily conserved germ-line-encoded proteins and include TLRs (Toll-like receptors), RLRs [RIG-I (retinoic acid-inducible gene-I)-like receptors] and NLRs (Nod-like receptors). These receptors recognize pathogens or pathogen-derived products in different cellular compartments, such as the plasma membrane, the endosomes or the cytoplasm, and induce the expression of cytokines, chemokines and co-stimulatory molecules to eliminate pathogens and instruct pathogen-specific adaptive immune responses. In the present review, we will discuss the recent progress in the study of pathogen recognition by TLRs, RLRs and NLRs and their signalling pathways.

  5. Financing long term liabilities (Germany)

    International Nuclear Information System (INIS)

    2003-01-01

    charges and fees levied from the waste producers. Altogether, financial resources for decommissioning are needed for the following steps: the post-operational phase in which the facility is prepared for dismantling after its final shut-down, dismantling of the radioactive part of the facility, management, storage and disposal of the radioactive waste, restoration of the site, licensing and regulatory supervision of all these steps. Additional means are necessary for the management, storage and disposal of the spent fuel. The way in which the availability of financial resources is secured differs between public owned installations and installations of the private power utilities. In Germany, past practices has resulted in singular contaminated sites of limited extent, mainly during the first half of the 20. century. Those contaminated sites have been or are being cleaned up and redeveloped. In large areas of Saxony and Thuringia, the geological formations permitted the surface and underground mining of Uranium ore. Facilities of the former Soviet-German WISMUT Ltd. where ore was mined and processed from 1946 until the early 1990's can be found at numerous sites. In the course of the re-unification of Germany, the soviet shares of the WISMUT were taken over by the Federal Republic of Germany and the closure of the WISMUT facilities was initiated. In that phase the extent of the damages to the environment and of the necessary remediation work became clear. All mining and milling sites are now closed and are under decommissioning. A comprehensive remediation concept covers all WISMUT sites. Heaps and mill-tailing ponds are transferred into a long-term stable condition. The area of the facilities to be remediated amounts to more than 30 km 2 . Heaps cover a total area of ca. 15,5 km 2 , tailing ponds in which the tailings resulting from the Uranium production are stored as sludges cover 6,3 km 2 ). In total, the remediation issues are very complex and without precedent. The

  6. Navigating Long-Term Care

    Directory of Open Access Journals (Sweden)

    James D. Holt MD

    2017-03-01

    Full Text Available Americans over age 65 constitute a larger percentage of the population each year: from 14% in 2010 (40 million elderly to possibly 20% in 2030 (70 million elderly. In 2015, an estimated 66 million people provided care to the ill, disabled, and elderly in the United States. In 2000, according to the Centers for Disease Control and Prevention (CDC, 15 million Americans used some form of long-term care: adult day care, home health, nursing home, or hospice. In all, 13% of people over 85 years old, compared with 1% of those ages 65 to 74, live in nursing homes in the United States. Transitions of care, among these various levels of care, are common: Nursing home to hospital transfer, one of the best-studied transitions, occurs in more than 25% of nursing home residents per year. This article follows one patient through several levels of care.

  7. Dissolved oxygen stratification and response to thermal structure and long-term climate change in a large and deep subtropical reservoir (Lake Qiandaohu, China).

    Science.gov (United States)

    Zhang, Yunlin; Wu, Zhixu; Liu, Mingliang; He, Jianbo; Shi, Kun; Zhou, Yongqiang; Wang, Mingzhu; Liu, Xiaohan

    2015-05-15

    From January 2010 to March 2014, detailed depth profiles of water temperature, dissolved oxygen (DO), and chromophoric dissolved organic matter (CDOM) were collected at three sites in Lake Qiandaohu, a large, deep subtropical reservoir in China. Additionally, we assessed the changes in DO stratification over the past 61 years (1953-2013) based on our empirical models and long-term air temperature and transparency data. The DO concentration never fell below 2 mg/L, the critical value for anoxia, and the DO depth profiles were closely linked to the water temperature depth profiles. In the stable stratification period in summer and autumn, the significant increase in CDOM in the metalimnion explained the decrease in DO due to the oxygen consumed by CDOM. Well-developed oxygen stratification was detected at the three sites in spring, summer and autumn and was associated with thermal stratification. Oxycline depth was significantly negatively correlated with daily air temperature and thermocline thickness but significantly positively correlated with thermocline depth during the stratification weakness period (July-February). However, there were no significant correlations among these parameters during the stratification formation period (March-June). The increase of 1.67 °C in yearly average daily air temperature between 1980 and 2013 and the decrease of 0.78 m in Secchi disk depth caused a decrease of 1.65 m and 2.78 m in oxycline depth, respectively, facilitating oxygen stratification and decreasing water quality. Therefore, climate warming has had a substantial effect on water quality through changing the DO regime in Lake Qiandaohu. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. NDVI indicated long-term interannual changes in vegetation activities and their responses to climatic and anthropogenic factors in the Three Gorges Reservoir Region, China.

    Science.gov (United States)

    Wen, Zhaofei; Wu, Shengjun; Chen, Jilong; Lü, Mingquan

    2017-01-01

    Natural and social environmental changes in the China's Three Gorges Reservoir Region (TGRR) have received worldwide attention. Identifying interannual changes in vegetation activities in the TGRR is an important task for assessing the impact these changes have on the local ecosystem. We used long-term (1982-2011) satellite-derived Normalized Difference Vegetation Index (NDVI) datasets and climatic and anthropogenic factors to analyze the spatiotemporal patterns of vegetation activities in the TGRR, as well as their links to changes in temperature (TEM), precipitation (PRE), downward radiation (RAD), and anthropogenic activities. At the whole TGRR regional scale, a statistically significant overall uptrend in NDVI variations was observed in 1982-2011. More specifically, there were two distinct periods with different trends split by a breakpoint in 1991: NDVI first sharply increased prior to 1991, and then showed a relatively weak rate of increase after 1991. At the pixel scale, most parts of the TGRR experienced increasing NDVI before the 1990s but different trend change types after the 1990s: trends were positive in forests in the northeastern parts, but negative in farmland in southwest parts of the TGRR. The TEM warming trend was the main climate-related driver of uptrending NDVI variations pre-1990s, and decreasing PRE was the main climate factor (42%) influencing the mid-western farmland areas' NDVI variations post-1990s. We also found that anthropogenic factors such as population density, man-made ecological restoration, and urbanization have notable impacts on the TGRR's NDVI variations. For example, large overall trend slopes in NDVI were more likely to appear in TGRR regions with large fractions of ecological restoration within the last two decades. The findings of this study may help to build a better understanding of the mechanics of NDVI variations in the periods before and during TGDP construction for ongoing ecosystem monitoring and assessment in the

  9. Long-term geomorphic response to flow regulation in a 10-km reach downstream of the Mississippi–Atchafalaya River diversion

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2016-12-01

    Full Text Available A recent study reported considerable sediment trapping by three large channel bars downstream 18–28 km of the Mississippi–Atchafalaya River diversion (commonly known as the Old River Control Structure, ORCS during the 2011 Mississippi River flood. In this study, we analyzed 3-decadal morphological changes of the 10-km river channel and the three bars to elucidate the long-term effects of river engineering including diversion, revetment and dike constructions. Satellite images captured between 1985 and 2015 in approximate 5-year intervals were selected to estimate the change of channel morphology and bar surface area. The images were chosen based on river stage heights at the time when they were captured to exclude the temporal water height effect on channel and bar morphology. Using a set of the satellite images captured during the period of 1984–1986 and of 2013–2014, we developed rating curves of emerged bar surface area with the corresponding river stage height for determining the change in bar volume from 1985 to 2013. Two of the three bars have grown substantially in the past 30 years, while one bar has become braided and its surface area has shrunken. As a whole, there were a net gain of 4,107,000 m2 in surface area and a net gain of 30,271,000 m3 in volume, an equivalent of approximately 36 million metric tons of sediment assuming a bulk density of 1.2 t/m3. Sediment trapping on the bars was prevalent during the spring floods, especially during the period of 1990–1995 and of 2007–2011 when large floods occurred. The results suggest that although revetments and dikes have largely changed the morphology of the channel and the bars, they seem to have a limited impact on the overwhelming trend of sediment deposition caused by the river diversion.

  10. Long-term dose-response studies of inhaled or injected radionuclides. Biennial report, 1 October 1991--30 September 1993

    Energy Technology Data Exchange (ETDEWEB)

    Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L. [eds.

    1994-01-01

    This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of their life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques.

  11. Stress proteins and the immune response.

    Science.gov (United States)

    Moseley, P

    2000-07-25

    The heat shock or stress response is one of the most highly conserved adaptive responses in nature. In single cell organisms, the stress response confers tolerance to a variety of stresses including hyperthermia, hyperoxia, hypoxia, and other perturbations, which alter protein synthesis. This tolerance phenomenon is also extremely important in the multicellular organism, resulting in not only thermal tolerance, but also resistance to stresses of the whole organism such as ischemia-reperfusion injury. Moreover, recent data indicates that these stress proteins have the ability to modulate the cellular immune response. Although the terms heat shock proteins (HSPs) and stress proteins are often used interchangeably, the term stress proteins includes the HSPs, the glucose-regulated proteins (GRPs) and ubiquitin. The stress proteins may be grouped by molecular weight ranging from the large 110 kDa HSP110 to ubiquitin at 8 kDa. These proteins serve as cellular chaperones, participating in protein synthesis and transport through the various cellular compartments. Because these proteins have unique cellular localizations, the chaperone function of the stress proteins often involves a transfer of peptides between stress proteins as the peptide is moved between cellular compartments. For example, HSP70 is a cytosolic and nuclear chaperone, which is critical for the transfer of cellular peptides in the mitochondrion through a hand-off that involves mitochondrial HSP60 at the inner mitochondrial membrane. Similarly, cytosolic proteins are transferred from HSP70 to gp96 as they move into the endoplasmic reticulum. The central role of the stress proteins in the transfer of peptides through the cell may be responsible for the recently recognized importance of the stress proteins in the modulation of the immune system [Feder, M.E., Hofmann, G.E., 1999. Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu. Rev. Physiol. 61

  12. Immune Response to Dengue and Zika.

    Science.gov (United States)

    Ngono, Annie Elong; Shresta, Sujan

    2018-04-26

    Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika (ZIKV) are human pathogens of global significance. In particular, DENV causes the most prevalent mosquito-borne viral diseases in humans, and ZIKV emerged from obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the roles of the immune system during ZIKV infections are as yet unclear. In contrast, decades of DENV research implicate a dual role for the immune system in protection against and pathogenesis of DENV infection. As DENV and ZIKV are closely related, knowledge based on DENV studies has been used to prioritize investigation of ZIKV immunity and pathogenesis, and to accelerate ZIKV diagnostic, therapeutic, and vaccine design. This review discusses the following topics related to innate and adaptive immune responses to DENV and ZIKV: the interferon system as the key mechanism of host defense and viral target for immune evasion, antibody-mediated protection versus antibody-dependent enhancement, and T cell-mediated protection versus original T cell antigenic sin. Understanding the mechanisms that regulate the balance between immune-mediated protection and pathogenesis during DENV and ZIKV infections is critical toward development of safe and effective DENV and ZIKV therapeutics and vaccines.

  13. Immune Responses Involved in Mycobacterium Tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Roghayeh Teimourpour

    2016-09-01

    Full Text Available Background and Objectives: Mycobacterium tuberculosis is the causative agent of tuberculosis (TB. Approximately one-third of the world's population is infected with M. tuberculosis. Despite the availability of drug and vaccine, it remains one of the leading causes of death in humans especially in developing countries. Epidemiological studies have indicated that only 10-30% of people exposed to tubercle bacillus are infected with M. tuberculosis, and at least 90% of the infected people finally do not acquire TB. The studies have indicated that the host efficient immune system has essential roles in the control of TB infection such that the highest rate of mortality and morbidity is seen in immunocompromised patients such as people infected with HIV. M. tuberculosis is an obligatory intracellular bacterium. It enters the body mainly through the respiratory tract and alveolar macrophages combat this pathogen most commonly. In addition to alveolar macrophages, various T-cell subpopulations need to be activated to overcome this bacterium's resistance to the host defense systems. CD4+ T cells, through production of several cytokines such as IFN-γ and TNF-α, and CD8+ T cells, through cytotoxic activities and induction of apoptosis in infected cells, play critical roles in inducing appropriate immune responses against M. tuberculosis. Although cell-mediated immunity is the cornerstone of host responses against TB and the recent studies have provided evidence for the importance of humoral and innate immune system in the control of TB, a profound understanding of the immune responses would provide a basis for development of new generations of vaccines and drugs. The present study addresses immune responses involved in M. tuberculosis infection.

  14. Long-term trend in ground-based air temperature and its responses to atmospheric circulation and anthropogenic activity in the Yangtze River Delta, China

    Science.gov (United States)

    Peng, Xia; She, Qiannan; Long, Lingbo; Liu, Min; Xu, Qian; Zhang, Jiaxin; Xiang, Weining

    2017-10-01

    The Yangtze River Delta (YRD), including Shanghai City, Jiangsu and Zhejiang Provinces, is the largest metropolitan region in China. In the past decades, the region has experienced massive urbanization and detrimentally affected the environment in the region. Identifying the spatio-temporal variations of climate change and its influencing mechanism in the YRD is an important task for assessing their impacts on the local society and ecosystem. Based on long-term (1958-2014) observation data of meteorological stations, three temperature indices, i.e. extreme maximum temperature (TXx), extreme minimum temperature (TNn), and mean temperature (TMm), were selected and spatialized with climatological calculations and spatial techniques. Evolution and spatial heterogeneity of three temperature indices over YRD as well as their links to atmospheric circulation and anthropogenic activity were investigated. In the whole YRD, a statistically significant overall uptrend could be detected in three temperature indices with the Mann-Kendall (M-K) trend test method. The linear increasing trend for TMm was 0.31 °C/10 a, which was higher than the global average (0.12 °C/10 a during 1951-2012). For TXx and TNn, the increasing rates were 0.41 °C/10 a and 0.52 °C/10 a. Partial correlation analysis indicated that TMm was more related with TXx (rp = 0.68, p < 0.001) than TNn (rp = 0.48, p < 0.001). Furthermore, it was detected with M-K analysis at pixel scale that 62.17%, 96.75% and 97.05% of the areas in the YRD showed significant increasing trends for TXx, TNn and TMm, respectively. The increasing trend was more obvious in the southern mountainous areas than the northern plains areas. Further analysis indicated that the variation of TXx over YRD was mainly influenced by anthropogenic activities (e.g. economic development), while TNn was more affected by atmospheric circulations (e.g., the Eurasian zonal circulation index (EAZ) and the cold air activity index (CA)). For TMm, it was a

  15. Changes in Olsen Phosphorus Concentration and Its Response to Phosphorus Balance in Black Soils under Different Long-Term Fertilization Patterns

    Science.gov (United States)

    Zhan, Xiaoying; Zhang, Li; Zhou, Baoku; Zhu, Ping; Zhang, Shuxiang; Xu, Minggang

    2015-01-01

    The Olsen phosphorus (P) concentration of a soil is a key index that can be used to evaluate the P supply capacity of the soil and to estimate the optimal P fertilization rate. A study of the relationship between the soil Olsen P concentration and the P balance (P input minus P output) and their variations among different fertilization patterns will help to provide useful information for proper management of P fertilization. In this paper, the two investigated long-term experiments were established on black soils in the northeast region of China. Six fertilization treatments were selected: (1) unfertilized (CK); (2) nitrogen only (N); (3) nitrogen and potassium (NK); (4) nitrogen and phosphorus (NP); (5) nitrogen, phosphorus, and potassium (NPK); and (6) nitrogen, phosphorus, potassium and manure (NPKM). The results showed that the average Olsen P concentrations in the black soils at Gongzhuling and Harbin (16- and 31-year study periods, respectively), decreased by 0.49 and 0.56 mg kg-1 a-1, respectively, without P addition and increased by 3.17 and 1.78 mg kg-1 a-1, respectively, with P fertilization. The changes in soil Olsen P concentrations were significantly (P<0.05) correlated with the P balances at both sites except for the NP and NPK treatments at Gongzhuling. Under an average deficit of 100 kg ha-1 P, the soil Olsen P concentration at both sites decreased by 1.36~3.35 mg kg-1 in the treatments without P addition and increased by 4.80~16.04 mg kg-1 in the treatments with 100 kg ha-1 of P accumulation. In addition, the changes in Olsen P concentrations in the soil with 100 kg ha-1of P balance were significantly correlated with the P activation coefficient (PAC, percentage of Olsen P to total P, r=0.99, P<0.01) and soil organic matter content (r=0.91, P<0.01). A low pH was related to large changes of Olsen P by 1 kg ha-1 of P balance. These results indicated that soil organic matter and pH have important effects on the change in soil Olsen P by 1 kg ha-1 of P

  16. Performance of large open-top chambers for long-term field investigations of tree response to elevated carbon dioxide concentration

    International Nuclear Information System (INIS)

    Whitehead, D.; Hogan, K.P.; Rogers, G.N.D.; Byers, J.N.; Hunt, J.E.; McSeveny, T.M.; Hollinger, D.Y.; Dungan, R.J.; Earl, W.B.; Bourke, M.P.

    1995-01-01

    In preparation for an investigation of the effects of elevated carbondioxide (CO 2 ) concentration on the two tree species Pinus radiata D. Don and Nothofagus fusca (Hook. f. ) Oerst, the environmental conditions inside sixteen open-top chambers, of the design described by Heagle et al. (1989), were measured and compared with those outside. During a period in late summer, both air temperature and air saturation deficit were greater inside the chambers, with mean increases of 0.3 degreesC and 0.1 kPa, respectively. The increases were closely related to solar irradiance, reaching maximum differences for temperature and air saturation deficit of 4.3 degrees C and 0.8 kPa, respectively, when solar irradiance was greater than 1600 mu mol m -2 s -1 . The mean (± standard deviation) CO 2 concentrations for the ambient and elevated treatments were 362 ± 37 and 654 ± 69 mu mol mol -1 , respectively. However, the CO 2 concentration in the elevated treatment decreased as wind speed increased, owing to incursions of ambient air into the chambers. Transmittance of visible solar irradiance (400-700 nm) through the plastic wall material decreased by 7% after 1 year of exposure at the site. In cloudy conditions the mean transmittance of solar irradiance into the chambers was 81% and on clear days this decreased from 80% to 74% with increasing solar zenith angle. The ratio of diffuse to total solar irradiance in the chambers was 13% and 21% greater than that outside for cloudy and clear conditions, respectively. The implications of these differences on water use efficiency for the trees growing inside and outside the chamber are discussed. A cost effective system, built to separate the CO 2 required for the experiment from waste biogas, is described. This project is contributing to the Global Change and Terrestrial Ecosystems (GCTE) Core Research Programme by providing data on the long-term effects of elevated CO 2 concentration on the above and below-ground carbon balance for

  17. Immune Response in Mussels To Environmental Pollution.

    Science.gov (United States)

    Pryor, Stephen C.; Facher, Evan

    1997-01-01

    Describes the use of mussels in measuring the extent of chemical contamination and its variation in different coastal regions. Presents an experiment to introduce students to immune response and the effects of environmental pollution on marine organisms. Contains 14 references. (JRH)