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  1. IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity

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    Lauren M.F. Merlo

    2016-01-01

    Full Text Available Indoleamine 2,3-dioxygenase 2 (IDO2, a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1. IDO2 is expressed in antigen-presenting cells, including B cells and dendritic cells, but affects inflammatory responses in the autoimmune context specifically by acting in B cells to modulate T cell help in multiple model systems. Given that expression of IDO2 can lead to exacerbation of inflammatory responses, IDO2 should be considered a potential therapeutic target for autoimmune disorders.

  2. Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors activate the aryl hydrocarbon receptor

    Energy Technology Data Exchange (ETDEWEB)

    Moyer, Benjamin J. [Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Rojas, Itzel Y. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Murray, Iain A. [Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802 (United States); Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802 (United States); Lee, Seokwon; Hazlett, Haley F. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Perdew, Gary H. [Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802 (United States); Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802 (United States); Tomlinson, Craig R., E-mail: Craig.R.Tomlinson@Dartmouth.edu [Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States)

    2017-05-15

    Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in the immune system by regulating tryptophan levels and T cell differentiation. Several tumor types overexpress IDO1 to avoid immune surveillance making IDO1 of interest as a target for therapeutic intervention. As a result, several IDO1 inhibitors are currently being tested in clinical trials for cancer treatment as well as several other diseases. Many of the IDO1 inhibitors in clinical trials naturally bear structural similarities to the IDO1 substrate tryptophan, as such, they fulfill many of the structural and functional criteria as potential AHR ligands. Using mouse and human cell-based luciferase gene reporter assays, qPCR confirmation experiments, and CYP1A1 enzyme activity assays, we report that some of the promising clinical IDO1 inhibitors also act as agonists for the aryl hydrocarbon receptor (AHR), best known for its roles in xenobiotic metabolism and as another key regulator of the immune response. The dual role as IDO antagonist and AHR agonist for many of these IDO target drugs should be considered for full interrogation of their biological mechanisms and clinical outcomes. - Highlights: • Indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors are in cancer clinical trials. • Some IDO1 inhibitors also potently activate AHR signaling. • The dual role of the IDO1 inhibitors may explain some past paradoxical findings. • AHR induction studies must be included in assessing clinical suitability.

  3. Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors activate the aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Moyer, Benjamin J.; Rojas, Itzel Y.; Murray, Iain A.; Lee, Seokwon; Hazlett, Haley F.; Perdew, Gary H.; Tomlinson, Craig R.

    2017-01-01

    Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in the immune system by regulating tryptophan levels and T cell differentiation. Several tumor types overexpress IDO1 to avoid immune surveillance making IDO1 of interest as a target for therapeutic intervention. As a result, several IDO1 inhibitors are currently being tested in clinical trials for cancer treatment as well as several other diseases. Many of the IDO1 inhibitors in clinical trials naturally bear structural similarities to the IDO1 substrate tryptophan, as such, they fulfill many of the structural and functional criteria as potential AHR ligands. Using mouse and human cell-based luciferase gene reporter assays, qPCR confirmation experiments, and CYP1A1 enzyme activity assays, we report that some of the promising clinical IDO1 inhibitors also act as agonists for the aryl hydrocarbon receptor (AHR), best known for its roles in xenobiotic metabolism and as another key regulator of the immune response. The dual role as IDO antagonist and AHR agonist for many of these IDO target drugs should be considered for full interrogation of their biological mechanisms and clinical outcomes. - Highlights: • Indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors are in cancer clinical trials. • Some IDO1 inhibitors also potently activate AHR signaling. • The dual role of the IDO1 inhibitors may explain some past paradoxical findings. • AHR induction studies must be included in assessing clinical suitability.

  4. INDOLEAMINE 2,3-DIOXYGENASE (IDO AND IMMUNE TOLERANCE

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    Coma-del-Corral MJ

    2013-09-01

    Full Text Available SUMMARY: Indoleamine 2,3-dioxygenase (IDO is an intracellular and extrahepatic enzyme predominantly found in many cells, especially macrophages. Tryptophan degradation generates kynurenine, and this pathway of tryptophan metabolism is an effective mechanism for modulating the immune response. The IDO facilitates immune tolerance and is one of the main actors involved in the inhibition of cell proliferation, including activated T cells. IDO induces production of reactive oxygen species (ROS and nitric oxide (NO radicals. Several pathways involved in the regulation of immune response are regulated by redox mechanisms. Reactive oxygen and nitrogen species (ROS-RNS and other redox active molecules play key roles in immunity.

  5. Relationship of Abortion and the Expression of Indoleamine 2,3- dioxygenase (IDO) in Villus and Syncytiotrophoblasts

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To study the relationship of abortion and the expression of indoleamine 2,3- dioxygenase (IDO) in villus and syncytiotrophoblast in vitro.Methods RT-PCR was applied to analyze the mRNA transcription of IDO in villus of normal pregnancy and inevitable abortion and JAR cells as well. Immunohistochemistry was applied to analyze the expression of IDO protein in villus. Western blot was applied to determinate the expression of IDO protein on cultured syncytiotrophoblast. Highperformance liquid chromatography was applied to determinate whether there was kynurenine in cell culture medium of syncytiotrophoblast.Results The expression of IDO mRNA and protein in villus of inevitable abortion was lower than that of normal pregnancy; IDO mRNA did not express in JAR cells. IDO protein expressed on cultured syncytiotrophoblast, and there was kynurenine in cell culture medium of syncytiotrophoblast.Conclusion Appropriate expression of IDO in villus is necessary for maintenance of normal pregnancy and an active IDO protein expresses in syncytiotrophoblast.

  6. Structural insights into the binding mechanism of IDO1 with hydroxylamidine based inhibitor INCB14943

    International Nuclear Information System (INIS)

    Wu, You; Xu, Tingting; Liu, Jinsong; Ding, Ke; Xu, Jinxin

    2017-01-01

    IDO1 (indoleamine 2, 3-dioxygenase 1), a well characterized immunosuppressive enzyme, has attracted growing attention as a potential target for cancer immunotherapy. Hydroxylamidine compounds INCB024360 and INCB14943 (INCB024360 analogue) are highly effective IDO1 inhibitors. INCB024360 is undergoing clinical trials for treatment of various types of human cancer. Here, we determined the co-crystal structure of IDO1 and INCB14943, and elucidate the detailed binding mode. INCB14943 binds to heme iron in IDO1 protein through the oxime nitrogen. Further analysis also reveals that a halogen bonding interaction between the chlorine atom (3-Cl) of INCB14943 and the sulphur atom of C129 significantly improves the inhibition activity against IDO1. Comparing with the other reported inhibitors, the oxime nitrogen and halogen bond interaction are identified as the unique features of INCB14943 among the IDO1 inhibitors. Thus, our study provides novel insights into the interaction between a small molecule inhibitor INCB14943 and IDO1 protein. The structural information will facilitate future IDO1 inhibitor design. - Highlights: • This is the first co-crystal structure of IDO1 with hydroxylamidine compound. • INCB14943 binds to heme iron through oxime nitrogen instead of imidazole nitrogen. • Halogen bond interaction with C129 is another unique feature of INCB14943.

  7. Acyclovir inhibition of IDO to decrease Tregs as a glioblastoma treatment adjunct

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    Söderlund Johan

    2010-08-01

    Full Text Available Abstract Regulatory T cells, Tregs, are a subset of lymphocytes that have immunosuppressive attributes. They are elevated in blood of glioblastoma patients and within this tumor's tissue itself. Indoleamine 2,3-dioxygenase, IDO, converts tryptophan to kynurenine. IDO activity enhances Treg formation by pathways that are unknown. Experimentally, inhibition of IDO decreases Treg function and number in rodents. The common anti-viral agent acyclovir inhibits IDO. Acyclovir may thereby decrease Treg function in glioblastoma. If it can be confirmed that Treg counts are elevated in glioblastoma patients' tumor tissue, and if we can document acyclovir's lowering of tissue Treg counts by a small trial of acyclovir in pre-operative glioblastoma patients, a trial of acyclovir effect on survival should be done given the current poor prognosis of glioblastoma and the well-established safety and low side effect burden of acyclovir.

  8. Indoleamine 2,3-dioxygenase 1 (IDO1 activity correlates with immune system abnormalities in multiple myeloma

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    Bonanno Giuseppina

    2012-12-01

    Full Text Available Abstract Background Multiple myeloma (MM is a plasma cell malignancy with a multifaceted immune dysfunction. Indoleamine 2,3-dioxygenase 1 (IDO1 degrades tryptophan into kynurenine (KYN, which inhibits effector T cells and promote regulatory T-cell (Treg differentiation. It is presently unknown whether MM cells express IDO1 and whether IDO1 activity correlates with immune system impairment. Methods We investigated IDO1 expression in 25 consecutive patients with symptomatic MM and in 7 patients with either monoclonal gammopathy of unknown significance (MGUS; n=3 or smoldering MM (SMM; n=4. IDO1-driven tryptophan breakdown was correlated with the release of hepatocyte growth factor (HGF and with the frequency of Treg cells and NY-ESO-1-specific CD8+ T cells. Results KYN was increased in 75% of patients with symptomatic MM and correlated with the expansion of CD4+CD25+FoxP3+ Treg cells and the contraction of NY-ESO-1-specific CD8+ T cells. In vitro, primary MM cells promoted the differentiation of allogeneic CD4+ T cells into bona fide CD4+CD25hiFoxP3hi Treg cells and suppressed IFN-γ/IL-2 secretion, while preserving IL-4 and IL-10 production. Both Treg expansion and inhibition of Th1 differentiation by MM cells were reverted, at least in part, by d,l-1-methyl-tryptophan, a chemical inhibitor of IDO. Notably, HGF levels were higher within the BM microenvironment of patients with IDO+ myeloma disease compared with patients having IDO- MM. Mechanistically, the antagonism of MET receptor for HGF with SU11274, a MET inhibitor, prevented HGF-induced AKT phosphorylation in MM cells and translated into reduced IDO protein levels and functional activity. Conclusions These data suggest that IDO1 expression may contribute to immune suppression in patients with MM and possibly other HGF-producing cancers.

  9. IL-22 and IDO1 Affect Immunity and Tolerance to Murine and Human Vaginal Candidiasis

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    De Luca, Antonella; Carvalho, Agostinho; Cunha, Cristina; Iannitti, Rossana G.; Pitzurra, Lucia; Giovannini, Gloria; Mencacci, Antonella; Bartolommei, Lorenzo; Moretti, Silvia; Massi-Benedetti, Cristina; Fuchs, Dietmar; De Bernardis, Flavia; Puccetti, Paolo; Romani, Luigina

    2013-01-01

    The ability to tolerate Candida albicans, a human commensal of the gastrointestinal tract and vagina, implicates that host defense mechanisms of resistance and tolerance cooperate to limit fungal burden and inflammation at the different body sites. We evaluated resistance and tolerance to the fungus in experimental and human vulvovaginal candidiasis (VVC) as well as in recurrent VVC (RVVC). Resistance and tolerance mechanisms were both activated in murine VVC, involving IL-22 and IL-10-producing regulatory T cells, respectively, with a major contribution by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). IDO1 was responsible for the production of tolerogenic kynurenines, such that replacement therapy with kynurenines restored immunoprotection to VVC. In humans, two functional genetic variants in IL22 and IDO1 genes were found to be associated with heightened resistance to RVVC, and they correlated with increased local expression of IL-22, IDO1 and kynurenines. Thus, IL-22 and IDO1 are crucial in balancing resistance with tolerance to Candida, their deficiencies are risk factors for RVVC, and targeting tolerance via therapeutic kynurenines may benefit patients with RVVC. PMID:23853597

  10. M. tuberculosis induces potent activation of IDO-1, but this is not essential for the immunological control of infection.

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    Antje Blumenthal

    Full Text Available Indoleamine 2,3-dioxygenesae-1 (IDO-1 catalyses the initial, rate-limiting step in tryptophan metabolism, thereby regulating tryptophan availability and the formation of downstream metabolites, including picolinic and quinolinic acid. We found that Mycobacterium tuberculosis infection induced marked upregulation of IDO-1 expression in both human and murine macrophages in vitro and in the lungs of mice following aerosol challenge with M. tuberculosis. The absence of IDO-1 in dendritic cells enhanced the activation of mycobacteria-specific T cells in vitro. Interestingly, IDO-1-deficiency during M. tuberculosis infection in mice was not associated with altered mycobacteria-specific T cell responses in vivo. The bacterial burden of infected organs, pulmonary inflammatory responses, and survival were also comparable in M. tuberculosis-infected IDO-1 deficient and wild type animals. Tryptophan is metabolised into either picolinic acid or quinolinic acid, but only picolinic acid inhibited the growth of M. tuberculosis in vitro. By contrast macrophages infected with pathogenic mycobacteria, produced quinolinic, rather than picolinic acid, which did not reduce M. tuberculosis growth in vitro. Therefore, although M. tuberculosis induces robust expression of IDO-1 and activation of tryptophan metabolism, IDO-1-deficiency fails to impact on the immune control and the outcome of the infection in the mouse model of tuberculosis.

  11. 1-L-MT, an IDO inhibitor, prevented colitis-associated cancer by inducing CDC20 inhibition-mediated mitotic death of colon cancer cells.

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    Liu, Xiuting; Zhou, Wei; Zhang, Xin; Ding, Yang; Du, Qianming; Hu, Rong

    2018-04-01

    Indoleamine 2,3-dioxygenase 1 (IDO1), known as IDO, catabolizes tryptophan through kynurenine pathway, whose activity is correlated with impaired clinical outcome of colorectal cancer. Here we showed that 1-L-MT, a canonical IDO inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. Our results showed that inhibition of IDO decreased the transcription of CDC20, which resulted in G2/M cycle arrest of HCT-116 and HT-29. Furthermore, 1-L-MT induced mitochondria injuries and caused apoptotic cancer cells. Importantly, 1-L-MT protected mice from azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon carcinogenesis, with reduced mortality, tumor number and size. What is more, IDO1-/- mice exhibited fewer tumor burdens and reduced proliferation in the neoplastic epithelium, while, 1-L-MT did not exhibit any further protective effects on IDO-/- mice, confirming the critical role of IDO and the protective effect of 1-L-MT-mediated IDO inhibition in CRC. Furthermore, 1-L-MT also alleviated CRC in Rag1-/- mice, demonstrating the modulatory effects of IDO independent of its role in modulating adaptive immunity. Taken together, our findings validated that the anti-proliferation effect of 1-L-MT in vitro and the prevention of CRC in vivo were through IDO-induced cell cycle disaster of colon cancer cells. Our results identified 1-L-MT as a promising candidate for the chemoprevention of CRC. © 2018 UICC.

  12. Non-tumor cell IDO1 predominantly contributes to enzyme activity and response to CTLA-4/PD-L1 inhibition in mouse glioblastoma.

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    Zhai, Lijie; Ladomersky, Erik; Dostal, Carlos R; Lauing, Kristen L; Swoap, Kathleen; Billingham, Leah K; Gritsina, Galina; Wu, Meijing; McCusker, Robert H; Binder, David C; Wainwright, Derek A

    2017-05-01

    Glioblastoma (GBM) is the most common malignant brain tumor in adults with a median survival of 14.6months. A contributing factor to GBM aggressiveness is the intratumoral expression of the potently immunosuppressive enzyme, indoleamine 2,3 dioxygenase 1 (IDO1). The enzymatic activity of IDO1 is associated with the conversion of tryptophan into downstream kynurenine (Kyn), which has previously been hypothesized to contribute toward the suppression of tumor immunity. Utilizing the syngeneic, immunocompetent, intracranial GL261 cell GBM model, we previously demonstrated that tumor cell, but not non-tumor cell IDO1, suppresses T cell-mediated brain tumor regression in mice. Paradoxically, we also showed that the survival advantage mediated by immune checkpoint blockade is abrogated by non-tumor cell IDO1 deficiency. Here, we have built on our past observations and confirm the maladaptive role of tumor cell IDO1 in a novel mouse GBM model. We also demonstrate that, non-tumor cells, rather than mouse GBM cells, are the dominant contributor to IDO1-mediated enzyme activity. Finally, we show the novel associations between maximally-effective immune-checkpoint blockade-mediated survival, non-tumor cell IDO1 and intra-GBM Kyn levels. These data suggest for the first time that, GBM cell-mediated immunosuppression is IDO1 enzyme independent, while the survival benefits of immune checkpoint blockade require non-tumor cell IDO1 enzyme activity. Given that current clinical inhibitors vary in their mechanism of action, in terms of targeting IDO1 enzyme activity versus enzyme-independent effects, this work suggests that choosing an appropriate IDO1 pharmacologic will maximize the effectiveness of future immune checkpoint blockade approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role of IDO.

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    Basu, Gargi D; Tinder, Teresa L; Bradley, Judy M; Tu, Tony; Hattrup, Christine L; Pockaj, Barbara A; Mukherjee, Pinku

    2006-08-15

    We report that administration of celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, in combination with a dendritic cell-based cancer vaccine significantly augments vaccine efficacy in reducing primary tumor burden, preventing metastasis, and increasing survival. This combination treatment was tested in MMTV-PyV MT mice that develop spontaneous mammary gland tumors with metastasis to the lungs and bone marrow. Improved vaccine potency was associated with an increase in tumor-specific CTLs. Enhanced CTL activity was attributed to a significant decrease in levels of tumor-associated IDO, a negative regulator of T cell activity. We present data suggesting that inhibiting COX-2 activity in vivo regulates IDO expression within the tumor microenvironment; this is further corroborated in the MDA-MB-231 human breast cancer cell line. Thus, a novel mechanism of COX-2-induced immunosuppression via regulation of IDO has emerged that may have implications in designing future cancer vaccines.

  14. [Knockdown of indoleamine 2, 3-dioxygenase 2 (IDO2)gene inhibits tumor growth and enhances immune function in mice bearing melanoma].

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    Liu, Yanling; Liu, Huan; Xiang, Yingqing; Chen, Xiaoyan; Xu, Ping; Min, Weiping

    2017-12-01

    Objective To study the role of indoleamine 2, 3-dioxygenase 2 (IDO2) in anti-tumor therapy and its effect on the immune response when using IDO2 as therapeutic target. Methods B16-BL6 cells were used to construct mouse xenografted melanoma model. IDO2-shRNA that contained IDO2-siRNA or control shRNA (scrambled-shRNA) was injected hydrodynamically via the tail vein to treat melanoma. The tumor size was measured by vernier caliper. Flow cytometry was performed to analyze the percentage of regulatory T cells (Tregs), T cell apoptosis rate in draining lymph nodes and the expressions of co-stimulatory molecules on splenic dendritic cells (DCs) from different treatment groups. The lactate dehydrogenase (LDH) assay was used to determine the CD8 + cytotoxic T lymphocyte (CTL) activity. The serum levels of tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) were detected by ELISA. Results In the IDO2-shRNA treated group, the tumor formation time was delayed, tumor grew slowly, and excised tumor mass was significantly reduced. IDO2-shRNA treatment also decreased the percentage of Tregs and T cell apoptosis in draining lymph nodes and increased the expressions of co-stimulatory molecules CD80 and CD86 on splenic DCs. The capacity of CD8 + T cells to kill B16-BL6 cells was enhanced and the serum levels of TNF-α and IFN-γ were upregulated. Conclusion Silencing IDO2 can effectively inhibit the growth of melanoma and improve the anti-tumor immune response in vivo.

  15. DPSCs from Inflamed Pulp Modulate Macrophage Function via the TNF-α/IDO Axis

    Science.gov (United States)

    Lee, S.; Zhang, Q.Z.; Karabucak, B.; Le, A.D.

    2016-01-01

    Human dental pulp stem cells (DPSCs) can be isolated from inflamed pulp derived from carious teeth with symptomatic irreversible pulpitis (I-DPSCs), which possess stemness and multidifferentiation potentials similar to DPSCs from healthy pulp. Since macrophages—essential cell players of the pulpal innate immunity—can regulate pulpal inflammation and repair, the authors investigated the immunomodulatory effects of DPSCs/I-DPSCs on macrophage functions and their underlying mechanisms. Similar to DPSCs, I-DPSCs were capable of colony-forming efficiency and adipogenic and osteo/dentinogenic differentiation under in vitro induction conditions. I-DPSCs also expressed a similar phenotypic profile of mesenchymal stem cell markers, except a relatively higher level of CD146 as compared with DPSCs. Coculture of DPSCs or I-DPSCs with differentiated THP-1 cells, the human monocyte cell line, markedly suppressed tumor necrosis factor α (TNF-α) secretion in response to stimulation with lipopolysaccharides (LPS) and/or nigericin. However, unlike TNF-α, the secreted level of interleukin 1β was not affected by coculture with DPSCs or I-DPSCs. Furthermore, DPSC/I-DPSC-mediated inhibition of TNF-α secretion by macrophages was abolished by pretreatment with 1-methyl-D-tryptophan, a specific inhibitor of indoleamine-pyrrole 2,3-dioxygenase (IDO), but not by NSC-398, a specific inhibitor of COX-2, suggesting IDO as a mediator. Interestingly, IDO expression was significantly augmented in macrophages and mesenchymal stromal cells in inflamed human pulp tissues. Collectively, these findings show that I-DPSCs, similar to DPSCs, possess stem cell properties and suppress macrophage functions via the TNF-α/IDO axis, thereby providing a physiologically relevant context for their innate immunomodulatory activity in the dental pulp and their capability for pulp repair. PMID:27384335

  16. DPSCs from Inflamed Pulp Modulate Macrophage Function via the TNF-α/IDO Axis.

    Science.gov (United States)

    Lee, S; Zhang, Q Z; Karabucak, B; Le, A D

    2016-10-01

    Human dental pulp stem cells (DPSCs) can be isolated from inflamed pulp derived from carious teeth with symptomatic irreversible pulpitis (I-DPSCs), which possess stemness and multidifferentiation potentials similar to DPSCs from healthy pulp. Since macrophages-essential cell players of the pulpal innate immunity-can regulate pulpal inflammation and repair, the authors investigated the immunomodulatory effects of DPSCs/I-DPSCs on macrophage functions and their underlying mechanisms. Similar to DPSCs, I-DPSCs were capable of colony-forming efficiency and adipogenic and osteo/dentinogenic differentiation under in vitro induction conditions. I-DPSCs also expressed a similar phenotypic profile of mesenchymal stem cell markers, except a relatively higher level of CD146 as compared with DPSCs. Coculture of DPSCs or I-DPSCs with differentiated THP-1 cells, the human monocyte cell line, markedly suppressed tumor necrosis factor α (TNF-α) secretion in response to stimulation with lipopolysaccharides (LPS) and/or nigericin. However, unlike TNF-α, the secreted level of interleukin 1β was not affected by coculture with DPSCs or I-DPSCs. Furthermore, DPSC/I-DPSC-mediated inhibition of TNF-α secretion by macrophages was abolished by pretreatment with 1-methyl-D-tryptophan, a specific inhibitor of indoleamine-pyrrole 2,3-dioxygenase (IDO), but not by NSC-398, a specific inhibitor of COX-2, suggesting IDO as a mediator. Interestingly, IDO expression was significantly augmented in macrophages and mesenchymal stromal cells in inflamed human pulp tissues. Collectively, these findings show that I-DPSCs, similar to DPSCs, possess stem cell properties and suppress macrophage functions via the TNF-α/IDO axis, thereby providing a physiologically relevant context for their innate immunomodulatory activity in the dental pulp and their capability for pulp repair. © International & American Associations for Dental Research 2016.

  17. TwitterIDo: What if My Shopping Bag Could Tell My Friends I’m Out Shopping

    DEFF Research Database (Denmark)

    Nazzi, Elena; Sokoler, Tomas

    2015-01-01

    In this paper, we explore the use of augmented everyday artefacts to make seniors’ everyday activities more visible in local communities to strengthen existing face-to-face social interactions or open new ones. We ground the twitterIDo idea in a three-year research project. We involved seniors...... as co-designers and we explored twitterIDo in a living lab with a community of senior citizens. Through a set of interactive prototypes of augmented everyday artefacts and dedicated displays, we engaged senior co-designers in in-situ enactments and workshops. Experiencing the possibilities of our idea...

  18. Interferon-γ regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (IDO.

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    Juliana Croitoru-Lamoury

    Full Text Available The kynurenine pathway (KP of tryptophan metabolism is linked to antimicrobial activity and modulation of immune responses but its role in stem cell biology is unknown. We show that human and mouse mesenchymal and neural stem cells (MSCs and NSCs express the complete KP, including indoleamine 2,3 dioxygenase 1 (IDO and IDO2, that it is highly regulated by type I (IFN-β and II interferons (IFN-γ, and that its transcriptional modulation depends on the type of interferon, cell type and species. IFN-γ inhibited proliferation and altered human and mouse MSC neural, adipocytic and osteocytic differentiation via the activation of IDO. A functional KP present in MSCs, NSCs and perhaps other stem cell types offers novel therapeutic opportunities for optimisation of stem cell proliferation and differentiation.

  19. A Longitudinal Analysis of IDO and PDL1 Expression during Immune- or Targeted Therapy in Advanced Melanoma

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    Lukas Krähenbühl

    2018-02-01

    Full Text Available A deepened understanding of the cellular and molecular processes in the tumor microenvironment is necessary for the development of precision immunotherapy (IT. We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry in paired biopsies from various organs of 43 metastatic melanoma patients treated with IT and targeted therapy (TT. Intraindividual biopsies taken after a period of weeks to months demonstrate discordant results in 30% of the cases. Overlap of IDO and PDL1 increased after therapy. IT only marginally impacted PDL1 expression over time in contrast to TT. Standardized repeated assessments of multiple immune markers in repeated biopsies will generate detailed insights in melanoma's immune evolution and adaption during therapies and might be used to support treatment decisions.

  20. Indoleamine 2,3-Dioxygenase (IDO) Enzyme Links Innate Immunity and Altered T-Cell Differentiation in Non-ST Segment Elevation Acute Coronary Syndrome.

    Science.gov (United States)

    Zara, Chiara; Severino, Anna; Flego, Davide; Ruggio, Aureliano; Pedicino, Daniela; Giglio, Ada Francesca; Trotta, Francesco; Lucci, Claudia; D'Amario, Domenico; Vinci, Ramona; Pisano, Eugenia; La Rosa, Giulio; Biasucci, Luigi Marzio; Crea, Filippo; Liuzzo, Giovanna

    2017-12-26

    Atherosclerosis is a chronic inflammatory disease characterized by a complex interplay between innate and adaptive immunity. Dendritic cells (DCs) play a key role in T-cell activation and regulation by promoting a tolerogenic environment through the expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme involved in tryptophan catabolism. IDO expression and activity was analyzed in monocytes derived DCs (MDDCs) from non-ST segment elevation myocardial infarction (NSTEMI) patients, stable angina (SA) patients and healthy controls (HC) by real-time quantitative polymerase chain reaction (RT-qPCR) before and after in vitro maturation with lipopolysaccharide (LPS). The amount of tryptophan catabolite; kynurenine; was evaluated in the culture supernatants of mature-MDDCs by ELISA assay. Autologous mixed lymphocyte reaction (MLR) between mature-MDDCs and naïve T-cells was carried out to study the differentiation towards T-helper 1 (Th1) and induced regulatory T-cells (iTreg). Analysis of IDO mRNA transcripts in mature-MDDCs revealed a significant reduction in cells isolated from NSTEMI (625.0 ± 128.2; mean ± SEM) as compared with those from SA (958.5 ± 218.3; p = 0.041) and from HC (1183.6 ± 231.6; p = 0.034). Furthermore; the concentration of kynurenine was lower in NSTEMI patients (2.78 ± 0.2) and SA (2.98 ± 0.25) as compared with HC (5.1 ± 0.69 ng/mL; p = 0.002 and p = 0.016; respectively). When IDO-competent mature-MDDCs were co-cultured with allogeneic naïve T-cells, the ratio between the percentage of generated Th1 and iTreg was higher in NSTEMI (4.4 ± 2.9) than in SA (1.8 ± 0.6; p = 0.056) and HC (0.9 ± 0.3; p = 0.008). In NSTEMI, the tolerogenic mechanism of the immune response related to IDO production by activated MDDCs is altered, supporting their role in T-cell dysregulation.

  1. Indoleamine 2,3-Dioxygenase (IDO Enzyme Links Innate Immunity and Altered T-Cell Differentiation in Non-ST Segment Elevation Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Chiara Zara

    2017-12-01

    Full Text Available Atherosclerosis is a chronic inflammatory disease characterized by a complex interplay between innate and adaptive immunity. Dendritic cells (DCs play a key role in T-cell activation and regulation by promoting a tolerogenic environment through the expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO, an intracellular enzyme involved in tryptophan catabolism. IDO expression and activity was analyzed in monocytes derived DCs (MDDCs from non-ST segment elevation myocardial infarction (NSTEMI patients, stable angina (SA patients and healthy controls (HC by real-time quantitative polymerase chain reaction (RT-qPCR before and after in vitro maturation with lipopolysaccharide (LPS. The amount of tryptophan catabolite; kynurenine; was evaluated in the culture supernatants of mature-MDDCs by ELISA assay. Autologous mixed lymphocyte reaction (MLR between mature-MDDCs and naïve T-cells was carried out to study the differentiation towards T-helper 1 (Th1 and induced regulatory T-cells (iTreg. Analysis of IDO mRNA transcripts in mature-MDDCs revealed a significant reduction in cells isolated from NSTEMI (625.0 ± 128.2; mean ± SEM as compared with those from SA (958.5 ± 218.3; p = 0.041 and from HC (1183.6 ± 231.6; p = 0.034. Furthermore; the concentration of kynurenine was lower in NSTEMI patients (2.78 ± 0.2 and SA (2.98 ± 0.25 as compared with HC (5.1 ± 0.69 ng/mL; p = 0.002 and p = 0.016; respectively. When IDO-competent mature-MDDCs were co-cultured with allogeneic naïve T-cells, the ratio between the percentage of generated Th1 and iTreg was higher in NSTEMI (4.4 ± 2.9 than in SA (1.8 ± 0.6; p = 0.056 and HC (0.9 ± 0.3; p = 0.008. In NSTEMI, the tolerogenic mechanism of the immune response related to IDO production by activated MDDCs is altered, supporting their role in T-cell dysregulation.

  2. 1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis.

    Science.gov (United States)

    Wei, Chunyan; Mei, Jie; Tang, Lingli; Liu, Yukai; Li, Dajin; Li, Mingqing; Zhu, Xiaoyong

    2016-12-01

    Foxp3 + regulatory T (T reg ) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal T reg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal T reg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment. After adding 1-methyl-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1), to the co-culture system, we found that the differentiation of T reg cells, mainly IL-10 + T reg cells, decreased. Therefore, 1-MT-pretreated ESCs-educated T reg cells performed impaired suppressive function. Moreover, estrogen promoted the differentiation of T reg cells by elevating IDO1 expression in the ectopic lesion. Subsequently, we examined mannose receptor C, type 2 (MRC2), which is an up-stream molecule of IL-10, by bioinformatics analysis and real-time PCR validation. MRC2 expression in ectopic ESCs was notably lower than that in normal ESCs, which further negatively regulated the expression of IDO1 and Ki-67 in ESCs. Furthermore, MRC2 is required for T reg differentiation in the ectopic lesion, especially that for CD4 high T reg . Therefore, MRC2-silenced ESCs-educated T reg manifested a stronger suppressive function in vitro. Consistently, the percentage of T reg increased when MRC2-shRNA was administered in the peritoneal cavity of endometriosis-disease mice model. Besides, 1-MT improved the condition of endometriosis, in terms of reducing the number and weight of total ectopic lesions in vivo. These results indicate that the estrogen-IDO1-MRC2 axis participates in the differentiation and function of T reg and is involved in the development of

  3. Checkpoint inhibitors in cancer immunotherapy: Cross reactivity of a CTLA-4 antibody and IDO-inhibitor L-1MT in pigs

    DEFF Research Database (Denmark)

    Al-Shatrawi, Zina Adil; Frøsig, Thomas Mørch; Jungersen, Gregers

    a non-specific activation of porcine T cells. This will be further investigated to provide the basis for in vivo studies investigating checkpoint inhibitor blockade in combination with other cancer immunotherapies. Eventually our goal is to establish pigs as an alternative large animal model......Blockade of checkpoint inhibitors has recently shown very convincing results in the treatment of cancer. One key target is CTLA-4, which has been demonstrated to be a potent negative regulator of lymphocyte activation. The treatment with the FDA-approved fully human CTLA-4 monoclonal antibody...... Ipilimumab increases anticancer T-cell reactivity and overall survival of metastatic cancer patients. Indole-amine 2,3-dioxygenase (IDO) is another checkpoint inhibitor which suppresses T-cell immunity by the depletion of tryptophan in the T-cell microenvironment, and also inhibition of IDO by L-1...

  4. Systematic study of imidazoles inhibiting IDO1 via the integration of molecular mechanics and quantum mechanics calculations.

    Science.gov (United States)

    Zou, Yi; Wang, Fang; Wang, Yan; Guo, Wenjie; Zhang, Yihua; Xu, Qiang; Lai, Yisheng

    2017-05-05

    Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as an attractive target for cancer immunotherapy. To rationalize the detailed interactions between IDO1 and its inhibitors at the atomic level, an integrated computational approach by combining molecular mechanics and quantum mechanics methods was employed in this report. Specifically, the binding modes of 20 inhibitors was initially investigated using the induced fit docking (IFD) protocol, which outperformed other two docking protocols in terms of correctly predicting ligand conformations. Secondly, molecular dynamics (MD) simulations and MM/PBSA free energy calculations were employed to determine the dynamic binding process and crucial residues were confirmed through close contact analysis, hydrogen-bond analysis and binding free energy decomposition calculations. Subsequent quantum mechanics and nonbonding interaction analysis were carried out to provide in-depth explanations on the critical role of those key residues, and Arg231 and 7-propionate of the heme group were major contributors to ligand binding, which lowed a great amount of interaction energy. We anticipate that these findings will be valuable for enzymatic studies and rational drug design. Copyright © 2017. Published by Elsevier Masson SAS.

  5. EFECTO DEL TRATAMIENTO CON OXALIPLATINO SOBRE LOS NIVELES DE TIORREDOXINA Y DE LA MOLÉCULA IDO (INDOLAMINA 2,3 DIOXIGENASA EN LINEAS CELULARES DE CÁNCER COLORRECTAL.

    Directory of Open Access Journals (Sweden)

    Cavia Mónica

    2012-01-01

    Full Text Available Increases in indoleamine-2-3-dyoxigenase activity and changes in redox state have been reported in cancer. However, their relationship with chemoterapy remains unknown. The aim of the present study was to evaluate the oxaliplatin treatment in colorectal cancer cell lines (Caco-2 and SW480 on the immunosuppressive molecule IDO and its relationship with the Trx/TrxR system. Results of this study was a higher IDO enzyme activity in Caco-2 cells than in SW480 cells associated with lower levels of the thioredoxin.

  6. Sôbre as causas de insucesso na obtenção do líqüido cefalorraqueano cisternal e lombar

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    J. Baptista dos Reis

    1950-06-01

    Full Text Available Os autores, depois de rápidas considerações gerais, analisam as diversas circunstâncias que podem prejudicar a livre obtenção do líqüido cefalorraqueano. Mostraram que, mesmo em condições técnicas satisfatórias, a colheita do líqüido cefalorraqueano por punção lombar ou suboccipital pode ser difícil ou mesmo impossível, em virtude de alterações anatômicas ou patológicas nesses níveis. Citam, em seguida, as alterações patológicas consistentes era: calcificação do ligamento amarelo, desvios da coluna vertebral, bloqueios acima do nível de punção, hipotensão grave do líqüido cefalorraqueano, grande aumento da densidade do líquor, tumores ao nível do local de punção ou de outros níveis, agindo indiretamente por deslocamentos da massa nervosa, edema agudo do encéfalo, hidrocefalia, processos reacionais meníngeos pós-inflamatórios, abscessos espinhais epidurais e hematomas epidurais lombo-sacros nos recém-nascidos. Os autores sugerem que a punção branca pode constituir, não só um elemento positivo no diagnóstico clínico, como, também, um sinal de alerta para quem punciona no sentido de evitar riscos para o paciente.

  7. The pig as a model for therapeutic human anti-cancer vaccine development, elucidating the T-cell reactivity against IDO and RhoC

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Welner, Simon

    is important. Previous development of therapeutic cancer vaccines has largely been based on studies in mice and the majority of these candidate vaccines failed to establish therapeutic responses in subsequent human clinical trials. Since the porcine immunome is more closely related to the human counterpart, we...... here introduce pigs as a superior large animal model for human cancer vaccine development via the use of our unique technology for swine leukocyte antigen (SLA) production. IDO and RhoC, both known to be important in human cancer development and progression, were used as vaccine targets. Pigs were......, and peptide-SLA complex stability measurements revealed 89 stable (t½ ≥ 0.5 hour) complexes. Vaccine-induced peptide-specific CTL responses were monitored using IFN-γ release as a read out. We found responses to IDO- and RhoC-derived peptides across all groups; surprisingly non-stably binding peptides also...

  8. IDO chronic immune activation and tryptophan metabolic pathway: A potential pathophysiological link between depression and obesity.

    Science.gov (United States)

    Chaves Filho, Adriano José Maia; Lima, Camila Nayane Carvalho; Vasconcelos, Silvânia Maria Mendes; de Lucena, David Freitas; Maes, Michael; Macedo, Danielle

    2018-01-03

    Obesity and depression are among the most pressing health problems in the contemporary world. Obesity and depression share a bidirectional relationship, whereby each condition increases the risk of the other. By inference, shared pathways may underpin the comorbidity between obesity and depression. Activation of cell-mediated immunity (CMI) is a key factor in the pathophysiology of depression. CMI cytokines, including IFN-γ, TNFα and IL-1β, induce the catabolism of tryptophan (TRY) by stimulating indoleamine 2,3-dioxygenase (IDO) resulting in the synthesis of kynurenine (KYN) and other tryptophan catabolites (TRYCATs). In the CNS, TRYCATs have been related to oxidative damage, inflammation, mitochondrial dysfunction, cytotoxicity, excitotoxicity, neurotoxicity and lowered neuroplasticity. The pathophysiology of obesity is also associated with a state of aberrant inflammation that activates aryl hydrocarbon receptor (AHR), a pathway involved in the detection of intracellular or environmental changes as well as with increases in the production of TRYCATs, being KYN an agonists of AHR. Both AHR and TRYCATS are involved in obesity and related metabolic disorders. These changes in the TRYCAT pathway may contribute to the onset of neuropsychiatric symptoms in obesity. This paper reviews the role of immune activation, IDO stimulation and increased TRYCAT production in the pathophysiology of depression and obesity. Here we suggest that increased synthesis of detrimental TRYCATs is implicated in comorbid obesity and depression and is a new drug target to treat both diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Heat and mass transfer in a reforming catalyst bed. Analytical prediction of distributions in the catalyst bed; Kaishitsu shokubaiso ni okeru netsu oyobi busshitsu ido. Suchi kaiseki ni yoru sonai bunpu no yosoku

    Energy Technology Data Exchange (ETDEWEB)

    Usami, Y [Tokyo Electric Power Co. Inc., Tokyo (Japan); Fukusako, S; Yamada, M [Hokkaido University, Sapporo (Japan)

    2000-01-25

    Heat and mass transfer characteristics within a reforming catalyst bed have been analytically investigated. A numerical analysis was carried out in a two-dimensional steady-state model of reforming catalyst layer. Reforming tube was filled with catalyst and the tube wall was uniformly heated, a mixture of steam and methane was reformed through the catalyst bed. Predicted temperature, formed gas composition, methane conversion rate, and heat transfer coefficient distributions in the catalyst layer showed good agreement with experimental data. The effects of space velocity, steam carbon molar ratio, and wall temperature on the heat transfer coefficient were analytically presented. From temperature and composition distributions simulated by two-dimensional analysis, the effects of these factors above mentioned and diffusion on the transport phenomena were qualitatively predicted. (author)

  10. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1

    Energy Technology Data Exchange (ETDEWEB)

    Moyer, Benjamin J. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Rojas, Itzel Y. [Department of Medicine, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Department of Pharmacology & Toxicology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Kerley-Hamilton, Joanna S. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Hazlett, Haley F. [Department of Pharmacology & Toxicology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Department of Immunology & Microbiology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Nemani, Krishnamurthy V. [Department of Radiology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Trask, Heidi W.; West, Rachel J. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Lupien, Leslie E. [Department of Medicine, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Collins, Alan J. [Department of Immunology & Microbiology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); and others

    2016-06-01

    Obesity is an increasingly urgent global problem, yet, little is known about its causes and less is known how obesity can be effectively treated. We showed previously that the aryl hydrocarbon receptor (AHR) plays a role in the regulation of body mass in mice fed Western diet. The AHR is a ligand-activated nuclear receptor that regulates genes involved in a number of biological pathways, including xenobiotic metabolism and T cell polarization. This study was an investigation into whether inhibition of the AHR prevents Western diet-based obesity. Male C57Bl/6J mice were fed control and Western diets with and without the AHR antagonist α-naphthoflavone or CH-223191, and a mouse hepatocyte cell line was used to delineate relevant cellular pathways. Studies are presented showing that the AHR antagonists α-naphthoflavone and CH-223191 significantly reduce obesity and adiposity and ameliorates liver steatosis in male C57Bl/6J mice fed a Western diet. Mice deficient in the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) were also resistant to obesity. Using an AHR-directed, luciferase-expressing mouse hepatocyte cell line, we show that the transforming growth factor β1 (TGFβ1) signaling pathway via PI3K and NF-κB and the toll-like receptor 2/4 (TLR2/4) signaling pathway stimulated by oxidized low-density lipoproteins via NF-κB, each induce luciferase expression; however, TLR2/4 signaling was significantly reduced by inhibition of IDO1. At physiological levels, kynurenine but not kynurenic acid (both tryptophan metabolites and known AHR agonists) activated AHR-directed luciferase expression. We propose a hepatocyte-based model, in which kynurenine production is increased by enhanced IDO1 activity stimulated by TGFβ1 and TLR2/4 signaling, via PI3K and NF-κB, to perpetuate a cycle of AHR activation to cause obesity; and inhibition of the AHR, in turn, blocks the cycle's output to prevent obesity. The AHR with its broad ligand binding

  11. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1

    International Nuclear Information System (INIS)

    Moyer, Benjamin J.; Rojas, Itzel Y.; Kerley-Hamilton, Joanna S.; Hazlett, Haley F.; Nemani, Krishnamurthy V.; Trask, Heidi W.; West, Rachel J.; Lupien, Leslie E.; Collins, Alan J.

    2016-01-01

    Obesity is an increasingly urgent global problem, yet, little is known about its causes and less is known how obesity can be effectively treated. We showed previously that the aryl hydrocarbon receptor (AHR) plays a role in the regulation of body mass in mice fed Western diet. The AHR is a ligand-activated nuclear receptor that regulates genes involved in a number of biological pathways, including xenobiotic metabolism and T cell polarization. This study was an investigation into whether inhibition of the AHR prevents Western diet-based obesity. Male C57Bl/6J mice were fed control and Western diets with and without the AHR antagonist α-naphthoflavone or CH-223191, and a mouse hepatocyte cell line was used to delineate relevant cellular pathways. Studies are presented showing that the AHR antagonists α-naphthoflavone and CH-223191 significantly reduce obesity and adiposity and ameliorates liver steatosis in male C57Bl/6J mice fed a Western diet. Mice deficient in the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) were also resistant to obesity. Using an AHR-directed, luciferase-expressing mouse hepatocyte cell line, we show that the transforming growth factor β1 (TGFβ1) signaling pathway via PI3K and NF-κB and the toll-like receptor 2/4 (TLR2/4) signaling pathway stimulated by oxidized low-density lipoproteins via NF-κB, each induce luciferase expression; however, TLR2/4 signaling was significantly reduced by inhibition of IDO1. At physiological levels, kynurenine but not kynurenic acid (both tryptophan metabolites and known AHR agonists) activated AHR-directed luciferase expression. We propose a hepatocyte-based model, in which kynurenine production is increased by enhanced IDO1 activity stimulated by TGFβ1 and TLR2/4 signaling, via PI3K and NF-κB, to perpetuate a cycle of AHR activation to cause obesity; and inhibition of the AHR, in turn, blocks the cycle's output to prevent obesity. The AHR with its broad ligand binding

  12. Eletroforese em papel das proteínas do líqüido cefalorraquidiano: II. Principais resultados registrados na literatura

    Directory of Open Access Journals (Sweden)

    A. Spina-França

    1958-09-01

    Full Text Available Partindo dos dados referentes à aplicação da eletroforese em papel de filtro na separação das frações proteicas do LCR, apresentados em publicação anterior, são revistos os dados da literatura sob o ponto de vista do laboratório clínico. Tanto os valores relativos normais referentes a cada uma das reações proteicas, como alterações patológicas mais freqüentemente encontradas em diversos tipos de afecções do sistema nervoso são apresentados, ressaltando-se a importância dos achados frente à fisiopatologia do liqüido cefalorraquidiano e frente à Clínica Neurológica.

  13. Topical ear drop self-medication practice among the Ear, Nose, and Throat patients in Ido Ekiti, Nigeria: A cross - sectional study.

    Science.gov (United States)

    Olajide, Toye Gabriel; Aremu, Kayode Shuaib; Esan, Olaide T; Dosunmu, Adepeju Oluwatona; Raji, Mustapha Muhammad

    2018-01-01

    Self-medication is a common habit in our country; Nigeria, especially among patients with otorhinolaryngological disorders. Medication when taken wrongly may bring dire consequences to the individual, such as masking developing diseases and may cause many other undesirable effects. The aim of this study was to determine the prevalence and to analyze topical ear drop self-medication practices among respondents attending the Ear, Nose, and Throat Clinic of Federal Teaching Hospital Ido Ekiti, Nigeria. A 6-month hospital based cross-sectional study was conducted among patients who were seen in the Ear, Nose, and Throat facility of Federal Teaching Hospital, Ido Ekiti from July to December 2016 to determine topical ear drop self-medication practices. A pretested semi-structured questionnaire was used to obtained information from respondents. A total of 162 respondents out of 493 patients seen during the study had otological problems. Of which 107 (66%) respondents had engaged in self-medication with topical ear drops. Their ages ranged between 2 and 83 years with a mean age of 36.6 ± 19.1 years. There were 75 males and 87 females. The major reason for self-medication was that their ailments were minor in about 40.2% and the most common indication for self-medication was ear blockage with hearing impairment (33.6%). Pharmacy/chemist shops (42%) were major sources of information for those that self-medicated. Chloramphenicol and gentamycin were the major drugs that were used by the respondents. Majority of the respondents in this study practiced self-medication using different topical ear drops. Major source of information on the topical ear drops used was from pharmacy/chemist shops. There is a need for adequate public health education to create awareness among people on the danger of self-medication and to enact or enforce the law to reduce access to over the counter drugs. Healthcare should be made available and avoidable at primary health-care level.

  14. Depositional models of the shallow marine carbonates in the geochemical cycle. Busshitsu junkan ni okeru asaumi tansan'engan no taiseki model

    Energy Technology Data Exchange (ETDEWEB)

    Nakamori, T [Tohoku University, Sendai (Japan). Institute of Geology and Paleontology

    1993-06-15

    This paper summarizes depositional models of carbonates related to carbon circulation on the earth surface. The paper lists the following examples of modelling the Recent coral reefs: A model that divides coral reefs into several boxes corresponding to geographies, and estimates organic and inorganic carbon production in each box; and a model that discusses seawater flows to estimate fluxes of organic and inorganic carbons between the boxes and between the reefs and open seas. Carbon circulation in a time scale of the Quaternary may be described appropriately by the box model corresponding to the condition of deposition and dissolution of the carbonate rocks. Several examples of modelling oceans and coral reefs are described briefly. The paper lists a model by Berner et al. that notes migration of carbon, Ca, and Mg among five boxes of Ca-Mg silicate, ocean, atmosphere, calcite, and dolomite regarding the geochemical cycle during about 600 million years in the Phanerozoic era. It also explains a model developed from the former model. 39 refs., 1 fig.

  15. Correction: Dermatan sulfate in tunicate phylogeny: Order-specific sulfation pattern and the effect of [→4IdoA(2-Sulfateβ-1→3GalNAc(4-Sulfateβ-1→] motifs in dermatan sulfate on heparin cofactor II activity

    Directory of Open Access Journals (Sweden)

    Sugahara Kazuyuki

    2011-07-01

    Full Text Available Abstract After the publication of the work entitled "Dermatan sulfate in tunicate phylogeny: Order-specific sulfation pattern and the effect of [→4IdoA(2-Sulfateβ-1→3GalNAc(4-Sulfateβ-1→] motifs in dermatan sulfate on heparin cofactor II activity", by Kozlowski et al., BMC Biochemistry 2011, 12:29, we found that the legends to Figures 2 to 5 contain serious mistakes that compromise the comprehension of the work. This correction article contains the correct text of the legends to Figures 2 to 5.

  16. Implementación de un procedimiento metodológico para la elaboración de piezas por bruñido con rodillo simple.

    Directory of Open Access Journals (Sweden)

    S. Díaz Rojas,

    2009-01-01

    Full Text Available En el presente trabajo se exponen los fundamentos y los resultados de investigaciones realizadas sobre la operación secundaria de acabado superficial de piezas conocida como bruñido por rodillo simple.Se abordan teóricamente las cuestiones más importantes de los procesos de deformación plástica superficial empleados para el mejoramiento de las cualidades superficiales de las piezas.Se realiza una investigación experimental en piezas simétrico-rotativas de acero AISI 1045 en un torno paralelo convencional con una herramienta de bruñir mono rodillo construida al efecto, donde se toman en consideración las variables más influyentes en el bruñido por rodillo simple: fuerza compresiva, avance y número de pasadas de la herramienta bruñidora. Se obtienen los modelos empírico-matemáticos que describen los efectos de estas variables en el incremento de la dureza y la calidad superficial final de la pieza, así como en la disminución del diámetro exterior y en la profundidad de la capa endurecida. Como resultado más importante de este trabajo, se desarrolla un procedimiento metodológico para la elaboración de piezas mediante este tipo de tratamiento mecánico por deformación plástica superficial, que permitirá la creación y difusión de una disciplina tecnológica sobre un proceso de fabricación que posee ventajas y que está poco difundido en las empresas metalmecánicas.In the present work the foundations and the results of the investigation for the secondary operation of superficial finish (single roller burnishing are presented. The most important aspects of the superficial plastic deformation process for improving superficial finish are approachedAn experimental investigation in symmetrical-revolving pieces of steel AISI 1045 in a conventional parallel lathe with a burnishing tool of single roller built to the effect is carried out. The most influential variables were took in consideration: compressive force, feed and number

  17. Mesenchymal stromal cells as vehicles of tetravalent bispecific Tandab (CD3/CD19 for the treatment of B cell lymphoma combined with IDO pathway inhibitor d-1-methyl-tryptophan

    Directory of Open Access Journals (Sweden)

    Xiaolong Zhang

    2017-02-01

    Full Text Available Abstract Background Although blinatumomab, a bispecific T cell engaging antibody, exhibits high clinical response rates in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL and B cell non-Hodgkin’s lymphoma (B-NHL, it still has some limitations because of its short half-life. Mesenchymal stromal cells (MSCs represent an attractive approach for delivery of therapeutic agents to cancer sites owing to their tropism towards tumors, but their immunosuppression capabilities, especially induced by indoleamine 2,3-dioxygenase (IDO, should also be taken into consideration. Methods Human umbilical cord-derived MSCs (UC-MSCs were genetically modified to secrete Tandab (CD3/CD19, a tetravalent bispecific tandem diabody with two binding sites for CD3 and two for CD19. The tropism of MSCs towards Raji cells in vitro was determined by migration assays, and the homing property of MSCs in vivo was analyzed with firefly luciferase-labeled MSCs (MSC-Luc by bioluminescent imaging (BLI. The cytotoxicity of T cells induced by MSC-secreting Tandab (CD3/CD19 was detected in vitro and in vivo in combination with d-1-methyl-tryptophan (D-1MT, an IDO pathway inhibitor. Results The purified Tandab (CD3/CD19 was functional with high-binding capability both for CD3-positive cells and CD19-positive cells and was able to induce specific lysis of CD19-positive cell lines (Raji, Daudi, and BJAB in the presence of T cells. Additionally, results from co-culture killing experiments demonstrated that Tandab (CD3/CD19 secreted from MSCs was also effective. Then, we confirmed that D-1MT could enhance the cytotoxicity of T cells triggered by MSC-Tandab through reversing T cell anergy with down-regulation of CD98 and Jumonji and restoring the proliferation capacity of T cells. Furthermore, MSC-Luc could selectively migrate to tumor site in a BALB/c nude mouse model with Raji cells. And mice injected with MSC-Tandab in combination with D-1MT

  18. Assessing the impact of DRGs on patient care and professional practice in Switzerland (IDoC) - a potential model for monitoring and evaluating healthcare reform.

    Science.gov (United States)

    Wild, Verina; Carina, Fourie; Frouzakis, Regula; Clarinval, Caroline; Fässler, Margrit; Elger, Bernice; Gächter, Thomas; Leu, Agnes; Spirig, Rebecca; Kleinknecht, Michael; Radovanovic, Dragana; Mouton Dorey, Corine; Burnand, Bernard; Vader, John-Paul; Januel, Jean-Marie; Biller-Andorno, Nikola; The IDoC Group

    2015-01-01

    The starting point of the interdisciplinary project "Assessing the impact of diagnosis related groups (DRGs) on patient care and professional practice" (IDoC) was the lack of a systematic ethical assessment for the introduction of cost containment measures in healthcare. Our aim was to contribute to the methodological and empirical basis of such an assessment. Five sub-groups conducted separate but related research within the fields of biomedical ethics, law, nursing sciences and health services, applying a number of complementary methodological approaches. The individual research projects were framed within an overall ethical matrix. Workshops and bilateral meetings were held to identify and elaborate joint research themes. Four common, ethically relevant themes emerged in the results of the studies across sub-groups: (1.) the quality and safety of patient care, (2.) the state of professional practice of physicians and nurses, (3.) changes in incentives structure, (4.) vulnerable groups and access to healthcare services. Furthermore, much-needed data for future comparative research has been collected and some early insights into the potential impact of DRGs are outlined. Based on the joint results we developed preliminary recommendations related to conceptual analysis, methodological refinement, monitoring and implementation.

  19. The evolution of three types of indoleamine 2,3 dioxygenases in fungi with distinct molecular and biochemical characteristics.

    Science.gov (United States)

    Yuasa, Hajime J; Ball, Helen J

    2012-08-01

    Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme and known as a mammalian immunosuppressive molecule. In fungi, the primary role of IDO is to supply nicotinamide adenine dinucleotide (NAD(+)) via the kynurenine pathway. We previously reported that the koji-mold, Aspergillus oryzae has two IDO genes, IDOα and IDOβ. In the present study, we found that A. oryzae also has the third IDO, IDOγ. These three-types of IDOs are widely distributed among the Pezizomycotina fungi, although the black truffle, Tuber melanosporum has only one corresponding gene to IDOα/IDOβ. The yeast, Saccharomyces cerevisiae has a single IDO gene. Generally, Pezizomycotina IDOα showed similar enzymatic properties to the yeast IDO, suggesting that the IDOα is a functional homologue of the S. cerevisiae IDO. In contrast to IDOα, the K(m) value of IDOβ is higher. However, the reaction velocity of IDOβ is very fast, resulting in comparable or higher catalytic efficiency than IDOα. Thus IDOβ may functionally substitute for IDOα in fungal L-Trp metabolism. The enzymatic activity of IDOγ was comparatively very low with the values of enzymatic parameters comparable to vertebrate IDO2 enzymes. IDOα and IDOβ have similar gene structures, suggesting that they were generated by gene duplication which occurred rather early in Pezizomycotina evolution, although the timing of the duplication remains debatable. In contrast, the phylogenetic trees suggest that IDOγs form an evolutionarily distinct group of IDO enzymes, with a closer relationship to group I bacterial IDOs than other fungal IDOs. The ancestor of the IDOγ family is likely to have diverged from other eukaryotic IDOs at a very early stage of eukaryotic evolution. Copyright © 2012. Published by Elsevier B.V.

  20. Indoleamine 2,3-dioxygenase and immune changes under antidepressive treatment in major depression in females.

    Science.gov (United States)

    Zoga, Margarita; Oulis, Panagiotis; Chatzipanagiotou, Stylianos; Masdrakis, Vasilios G; Pliatsika, Paraskevi; Boufidou, Fotini; Foteli, Stefania; Soldatos, Constantin R; Nikolaou, Chryssoula; Papageorgiou, Charalampos

    2014-01-01

    Indoleamine 2, 3-dioxygenase (IDO) induction has been suggested as a mechanism by which immune activation affects tryptophan metabolism and serotonin synthesis in major depressive disorder (MDD). We investigated IDO and changes in inflammatory mediators in patients with MDD undergoing effective treatment. Forty female patients with MDD and 40 controls were recruited. Serum IDO was assessed by enzyme-linked immunosorbent assay (ELISA). We also determined tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), C-reactive protein (CRP) and serotonin concentrations. Patients' baseline concentrations of IDO and immune mediators were higher and serotonin concentrations were lower compared to controls. IDO and TNFα concentrations decreased under treatment and IDO changes were positively correlated with patient improvement. IFNγ and CRP concentrations remained unchanged. Serotonin concentration tended to increase. IDO might play an important role in the pathophysiology of MDD. Moreover, antidepressant therapy might reduce IDO production through an IFNγ-independent pathway. Finally, peripheral concentration of IDO assessed by ELISA might be a useful marker of MDD. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Glial and tissue-specific regulation of Kynurenine Pathway dioxygenases by acute stress of mice

    Directory of Open Access Journals (Sweden)

    Carlos R. Dostal

    2017-12-01

    Full Text Available Stressors activate the hypothalamic-pituitary-adrenal (HPA axis and immune system eliciting changes in cognitive function, mood and anxiety. An important link between stress and altered behavior is stimulation of the Kynurenine Pathway which generates neuroactive and immunomodulatory kynurenines. Tryptophan entry into this pathway is controlled by rate-limiting indoleamine/tryptophan 2,3-dioxygenases (DOs: Ido1, Ido2, Tdo2. Although implicated as mediating changes in behavior, detecting stress-induced DO expression has proven inconsistent. Thus, C57BL/6J mice were used to characterize DO expression in brain-regions, astrocytes and microglia to characterize restraint-stress-induced DO expression. Stress increased kynurenine in brain and plasma, demonstrating increased DO activity. Of three Ido1 transcripts, only Ido1-v1 expression was increased by stress and within astrocytes, not microglia, indicating transcript- and glial-specificity. Stress increased Ido1-v1 only in frontal cortex and hypothalamus, indicating brain-region specificity. Of eight Ido2 transcripts, Ido2-v3 expression was increased by stress, again only within astrocytes. Likewise, stress increased Tdo2-FL expression in astrocytes, not microglia. Interestingly, Ido2 and Tdo2 transcripts were not correspondingly induced in Ido1-knockout (Ido1KO mice, suggesting that Ido1 is necessary for the central DO response to acute stress. Unlike acute inflammatory models resulting in DO induction within microglia, only astrocyte DO expression was increased by acute restraint-stress, defining their unique role during stress-dependent activation of the Kynurenine Pathway. Keywords: Stress, Ido, Tdo, Kynurenine, Astrocyte, Liver

  2. Gene silencing of indoleamine 2,3-dioxygenase 2 in melanoma cells induces apoptosis through the suppression of NAD+ and inhibits in vivo tumor growth.

    Science.gov (United States)

    Liu, Yanling; Zhang, Yujuan; Zheng, Xiufen; Zhang, Xusheng; Wang, Hongmei; Li, Qin; Yuan, Keng; Zhou, Nanjing; Yu, Yanrong; Song, Na; Fu, Jiamin; Min, Weiping

    2016-05-31

    Indoleamine 2,3-dioxygenase 2 (IDO2) is a newly discovered enzyme that catalyzes the initial and rate-limiting step in the degradation of tryptophan. As a homologous protein of IDO1, IDO2 plays an inhibitory role in T cell proliferation, and it is essential for regulatory T cell (Treg) generation in healthy conditions. Little is known about the immune-independent functions of IDO2 relevant to its specific contributions to physiology and pathophysiology in cancer cells. The purpose of this study was to assess the impact of IDO2 gene silencing as a way to inhibit B16-BL6 cancer cells in a murine model. Here, for the first time, we show that knockdown of IDO2 using small interfering RNA (siRNA) inhibits cancer cell proliferation, arrests cell cycle in G1, induces greater cell apoptosis, and reduces cell migration in vitro. Knockdown of IDO2 decreased the generation of nicotinamide adenine dinucleotide (NAD+) while increasing the generation of reactive oxygen species (ROS). We further demonstrate that cell apoptosis, induced by IDO2 downregulation, can be weakened by addition of exogenous NAD+, suggesting a novel mechanism by which IDO2 promotes tumor growth through its metabolite product NAD+. In addition to in vitro findings, we also demonstrate that IDO2 silencing in tumor cells using short hairpin RNA (shRNA) delayed tumor formation and arrested tumor growth in vivo. In conclusion, this study demonstrates a new non-immune-associated mechanism of IDO2 in vitro and IDO2 expression in B16-BL6 cells contributes to cancer development and progression. Our research provides evidence of a novel target for gene silencing that has the potential to enhance cancer therapy.

  3. The selenazal drug ebselen potently inhibits indoleamine 2,3-dioxygenase by targeting enzyme cysteine residues.

    Science.gov (United States)

    Terentis, Andrew C; Freewan, Mohammed; Sempértegui Plaza, Tito S; Raftery, Mark J; Stocker, Roland; Thomas, Shane R

    2010-01-26

    The heme enzyme indoleamine 2,3-dioxygenase (IDO) plays an important immune regulatory role by catalyzing the oxidative degradation of l-tryptophan. Here we show that the selenezal drug ebselen is a potent IDO inhibitor. Exposure of human macrophages to ebselen inhibited IDO activity in a manner independent of changes in protein expression. Ebselen inhibited the activity of recombinant human IDO (rIDO) with an apparent inhibition constant of 94 +/- 17 nM. Optical and resonance Raman spectroscopy showed that ebselen altered the active site heme of rIDO by inducing a transition of the ferric heme iron from the predominantly high- to low-spin form and by lowering the vibrational frequency of the Fe-CO stretch of the CO complex, indicating an opening of the distal heme pocket. Substrate binding studies showed that ebselen enhanced nonproductive l-tryptophan binding, while circular dichroism indicated that the drug reduced the helical content and protein stability of rIDO. Thiol labeling and mass spectrometry revealed that ebselen reacted with multiple cysteine residues of IDO. Removal of cysteine-bound ebselen with dithiothreitol reversed the effects of the drug on the heme environment and significantly restored enzyme activity. These findings indicate that ebselen inhibits IDO activity by reacting with the enzyme's cysteine residues that result in changes to protein conformation and active site heme, leading to an increase in the level of nonproductive substrate binding. This study highlights that modification of cysteine residues is a novel and effective means of inhibiting IDO activity. It also suggests that IDO is under redox control and that the enzyme represents a previously unrecognized in vivo target of ebselen.

  4. Common genetic variation in the indoleamine-2,3-dioxygenase genes and antidepressant treatment outcome in major depressive disorder.

    Science.gov (United States)

    Cutler, Jessica A; Rush, A John; McMahon, Francis J; Laje, Gonzalo

    2012-03-01

    The essential amino acid tryptophan is the precursor to serotonin, but it can also be metabolized into kynurenine through indoleamine-2,3-dioxygenase (IDO). Increased immune activation has long been associated with symptoms of depression and has been shown to upregulate the expression of IDO. The presence of additional IDO directs more tryptophan down the kynurenine pathway, leaving less available for synthesis of serotonin and its metabolites. Kynurenine can be metabolized through a series of enzymes to quinolinic acid, a potent N-methyl-D-aspartate receptor agonist with demonstrated neurotoxic effects. We tested the hypothesis that IDO plays a role in outcome of treatment with the selective serotonin reuptake inhibitor, citalopram. Patients consisted of 1953 participants enrolled in the Sequenced Treatment Alternatives to Relieve Depression study (STAR*D). Genotypes corresponding to 94 single nucleotide polymorphisms (SNPs) in the genes IDO1 and IDO2, which encode IDO and IDO2, were extracted from a larger genome-wide set and analyzed using single marker tests to look for association with previously defined response, remission and QIDS-C score change phenotypes, with adequate correction for racial stratification and multiple testing. One SNP, rs2929115, showed evidence of association with citalopram response (OR = 0.64, p = 0.0005) after experiment-wide correction for multiple testing. Another closely associated marker, rs2929116 (OR = 0.64, p = 0.0006) had an experiment-wide significant result. Both implicated SNPs are located between 26 kb and 28 kb downstream of IDO2. We conclude that common genetic variation in IDO1 and IDO2 may play a role in antidepressant treatment outcome. These results are modest in a genome-wide context and need to be replicated in an independent sample.

  5. The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase

    DEFF Research Database (Denmark)

    Sørensen, Rikke Baek; Berge-Hansen, Linda; Junker, Niels

    2009-01-01

    BACKGROUND: The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance...... to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses. METHODS AND FINDINGS: The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T...... of the major immune suppressive cell populations. CONCLUSION: IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals...

  6. Natural CD4+ T-cell responses against indoleamine 2,3-dioxygenase

    DEFF Research Database (Denmark)

    Munir, Shamaila; Larsen, Stine Kiaer; Iversen, Trine Zeeberg

    2012-01-01

    The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tum...... antigens. Recently, we described cytotoxic CD8(+) T-cell reactivity towards IDO-derived peptides.......The enzyme indoleamine 2,3-dioxygenase (IDO) contributes to immune tolerance in a variety of settings. In cancer IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it endorses the establishment of peripheral immune tolerance to tumor...

  7. Immuno-regulatory function of indoleamine 2,3 dioxygenase through modulation of innate immune responses.

    Directory of Open Access Journals (Sweden)

    Malihe-Sadat Poormasjedi-Meibod

    Full Text Available Successful long-term treatment of type-1 diabetes mainly relies on replacement of β-cells via islet transplantation. Donor shortage is one of the main obstacles preventing transplantation from becoming the treatment of choice. Although animal organs could be an alternative source for transplantation, common immunosuppressive treatments demonstrate low efficacy in preventing xenorejection. Immunoprotective effects of indoleamine 2,3-dioxygenase (IDO on T-cell mediated allorejection has been extensively studied. Our studies revealed that IDO expression by fibroblasts, induced apoptosis in T-cells while not affecting non-immune cell survival/function. Since macrophages play a pivotal role in xenograft rejection, herein we investigated the effect of IDO-induced tryptophan deficiency/kynurenine accumulation on macrophage function/survival. Moreover, we evaluated the local immunosuppressive effect of IDO on islet-xenograft protection. Our results indicated that IDO expression by bystander fibroblasts significantly reduced the viability of primary macrophages via apoptosis induction. Treatment of peritoneal macrophages by IDO-expressing fibroblast conditioned medium significantly reduced their proinflammatory activity through inhibition of iNOS expression. To determine whether IDO-induced tryptophan starvation or kynurenine accumulation is responsible for macrophage apoptosis and inhibition of their proinflammatory activity, Raw264.7 cell viability and proinflammatory responses were evaluated in tryptophan deficient medium or in the presence of kynurenine. Tryptophan deficiency, but not kynurenine accumulation, reduced Raw264.7 cell viability and suppressed their proinflammatory activity. Next a three-dimensional islet-xenograft was engineered by embedding rat islets within either control or IDO-expressing fibroblast-populated collagen matrix. Islets morphology and immune cell infiltration were then studied in the xenografts transplanted into the C57

  8. Central Administration of Lipopolysaccharide Induces Depressive-like Behavior in Vivo and Activates Brain Indoleamine 2,3 Dioxygenase In Murine Organotypic Hippocampal Slice Cultures

    Directory of Open Access Journals (Sweden)

    Kavelaars Annemieke

    2010-08-01

    Full Text Available Abstract Background Transient stimulation of the innate immune system by an intraperitoneal injection of lipopolysaccharide (LPS activates peripheral and central expression of the tryptophan degrading enzyme indoleamine 2,3 dioxygenase (IDO which mediates depressive-like behavior. It is unknown whether direct activation of the brain with LPS is sufficient to activate IDO and induce depressive-like behavior. Methods Sickness and depressive-like behavior in C57BL/6J mice were assessed by social exploration and the forced swim test, respectively. Expression of cytokines and IDO mRNA was measured by real-time RT-PCR and cytokine protein was measured by enzyme-linked immunosorbent assays (ELISAs. Enzymatic activity of IDO was estimated as the amount of kynurenine produced from tryptophan as determined by high pressure liquid chromatography (HPLC with electrochemical detection. Results Intracerebroventricular (i.c.v. administration of LPS (100 ng increased steady-state transcripts of TNFα, IL-6 and the inducible isoform of nitric oxide synthase (iNOS in the hippocampus in the absence of any change in IFNγ mRNA. LPS also increased IDO expression and induced depressive-like behavior, as measured by increased duration of immobility in the forced swim test. The regulation of IDO expression was investigated using in situ organotypic hippocampal slice cultures (OHSCs derived from brains of newborn C57BL/6J mice. In accordance with the in vivo data, addition of LPS (10 ng/ml to the medium of OHSCs induced steady-state expression of mRNA transcripts for IDO that peaked at 6 h and translated into increased IDO enzymatic activity within 8 h post-LPS. This activation of IDO by direct application of LPS was preceded by synthesis and secretion of TNFα and IL-6 protein and activation of iNOS while IFNγ expression was undetectable. Conclusion These data establish that activation of the innate immune system in the brain is sufficient to activate IDO and induce

  9. Indoleamine 2,3-Dioxygenase Fine-Tunes Immune Homeostasis in Atherosclerosis and Colitis through Repression of Interleukin-10 Production

    NARCIS (Netherlands)

    Metghalchi, Sarvenaz; Ponnuswamy, Padmapriya; Simon, Tabassome; Haddad, Yacine; Laurans, Ludivine; Clement, Marc; Dalloz, Marion; Romain, Melissa; Esposito, Bruno; Koropoulis, Vincent; Lamas, Bruno; Paul, Jean-Louis; Cottin, Yves; Kotti, Salma; Bruneval, Patrick; Callebert, Jacques; den Ruijter, Hester; Launay, Jean-Marie; Danchin, Nicolas; Sokol, Harry; Tedgui, Alain; Taleb, Soraya; Mallat, Ziad

    2015-01-01

    Indoleamine 2,3-dioxygenase 1 (Ido1) is a rate-limiting enzyme that catalizes the degradation of tryptophan along the kynurenine pathway. Here, we show that Ido1 activity sustains an immunostimulatory potential through inhibition of interleukin (Il)10. In atherosclerosis, Ido1-dependent inhibition

  10. Heme-containing enzymes and inhibitors for tryptophan metabolism.

    Science.gov (United States)

    Yan, Daojing; Lin, Ying-Wu; Tan, Xiangshi

    2017-09-20

    Iron-containing enzymes such as heme enzymes play crucial roles in biological systems. Three distinct heme-containing dioxygenase enzymes, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the initial and rate-limiting step of l-tryptophan catabolism through the kynurenine pathway in mammals. Overexpression of these enzymes causes depletion of tryptophan and the accumulation of metabolic products, which contributes to tumor immune tolerance and immune dysregulation in a variety of disease pathologies. In the past few decades, IDO1 has garnered the most attention as a therapeutic target with great potential in cancer immunotherapy. Many potential inhibitors of IDO1 have been designed, synthesized and evaluated, among which indoximod (d-1-MT), INCB024360, GDC-0919 (formerly NLG-919), and an IDO1 peptide-based vaccine have advanced to the clinical trial stage. However, recently, the roles of TDO and IDO2 have been elucidated in immune suppression. In this review, the current drug discovery landscape for targeting TDO, IDO1 and IDO2 is highlighted, with particular attention to the recent use of drugs in clinical trials. Moreover, the crystal structures of these enzymes, in complex with inhibitors, and the mechanisms of Trp catabolism in the first step, are summarized to provide information for facilitating the discovery of new enzyme inhibitors.

  11. In vitro modulation of cytochrome P450 reductase supported indoleamine 2,3-dioxygenase activity by allosteric effectors cytochrome b(5) and methylene blue.

    Science.gov (United States)

    Pearson, Josh T; Siu, Sophia; Meininger, David P; Wienkers, Larry C; Rock, Dan A

    2010-03-30

    Indoleamine 2,3-dioxygenase (IDO) is a heme-containing dioxygenase involved in the degradation of several indoleamine derivatives and has been indicated as an immunosuppressive. IDO is an attractive target for therapeutic intervention in diseases which are known to capitalize on immune suppression, including cancer, HIV, and inflammatory diseases. Conventionally, IDO activity is measured through chemical reduction by the addition of ascorbate and methylene blue. Identification of potential coenzymes involved in the reduction of IDO in vivo should improve in vitro reconstitution systems used to identify potential IDO inhibitors. In this study we show that NADPH-cytochrome P450 reductase (CPR) is capable of supporting IDO activity in vitro and that oxidation of l-Trp follows substrate inhibition kinetics (k(cat) = 0.89 +/- 0.04 s(-1), K(m) = 0.72 +/- 0.15 microM, and K(i) = 9.4 +/- 2.0 microM). Addition of cytochrome b(5) to CPR-supported l-Trp incubations results in modulation from substrate inhibition to sigmoidal kinetics (k(cat) = 1.7 +/- 0.3 s(-1), K(m) = 1.5 +/- 0.9 microM, and K(i) = 1.9 +/- 0.3). CPR-supported d-Trp oxidations (+/-cytochrome b(5)) exhibit Michaelis-Menten kinetics. Addition of methylene blue (minus ascorbate) to CPR-supported reactions resulted in inhibition of d-Trp turnover and modulation of l-Trp kinetics from allosteric to Michaelis-Menten with a concurrent decrease in substrate affinity for IDO. Our data indicate that CPR is capable of supporting IDO activity in vitro and oxidation of tryptophan by IDO displays substrate stereochemistry dependent atypical kinetics which can be modulated by the addition of cytochrome b(5).

  12. Decreased expression of indolamine 2,3-dioxygenase in childhood allergic asthma and its inverse correlation with fractional concentration of exhaled nitric oxide.

    Science.gov (United States)

    Hu, Ying; Chen, Zhiqiang; Jin, Ling; Wang, Mei; Liao, Wei

    2017-11-01

    The tryptophan metabolic pathway mediated by indolamine 2,3-dioxygenase (IDO), a tryptophan-degrading enzyme, plays an important role in controlling the development of allergic inflammation. The fractional concentration of exhaled nitric oxide (FeNO) is closely associated with the allergic state and is extensively used for the clinical evaluation of airway allergic inflammation. Clinical trials have rarely assessed the expression of IDO in childhood allergic asthma and its correlation with FeNO. To evaluate the IDO level in children with childhood allergic asthma and the relation between IDO levels and FeNO. Thirty children older than 5 years who were diagnosed the first time with allergic asthma were selected from the pediatric outpatient department. Another 30 healthy children were selected as controls. The subjects were evaluated by complete medical history, pulmonary function test results, skin prick test reaction, FeNO concentration test result, eosinophil count, and a disease severity score. Peripheral venous blood and induced sputum were obtained to measure the concentrations of IDO metabolites (ie, tryptophan and kynurenine). The IDO levels in the peripheral blood and induced sputum were significantly lower in patients with childhood allergic asthma than in children in the control group. The IDO level was negatively correlated with FeNO but was not significantly correlated with age, sex, blood eosinophil count, or disease severity scale. The expression of IDO was significantly lower in childhood allergic asthma, particularly in children with high FeNO levels. There was no significant relation between IDO levels and asthma severity. Chinese Clinical Trial Register (www.chictr.org.cn) Identifier: ChiCTR-COC-15006080. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. International seminar in fiscal 1998 on the development and promotion of global environment-related industrial technologies. Report on International Workshops on CO{sub 2} Cycling and Metabolism in Coral Reef; 1998 nendo chikyu sangyo gijutsu kaihatsu suishin jigyo. 'Sangosho ni okeru busshitsu ido to tanso junkan' kokusai workshop hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    For the study of CO{sub 2} absorption and fixation in the marine ecosystem, studies of coral reefs by RITE (Research Institute of Innovative Technology for the Earth) were subjected to discussion at the above-named workshops. It is after the elapse of a long geological time on the earth that CO2 in the atmosphere has arrived at the current level of concentration thanks to fixation and calcification by living organisms and to dissolution into the seawater. In the formation of CaCO{sub 3} that constitutes the coral skeleton, 1 mol Ca combines with 2 mol bicarbonates for the production of 1 mol CaCO{sub 3} and 1 mol CO{sub 2}. The reaction may suggests a consequential increase of CO2 in the atmosphere but such CO{sub 2} is in reality consumed by being converted into organic substances in a photosynthetic process performed by symbiotic algae. Calculation was made for the whole of Bora Bay, Miyakojima Island, and the result was that 700kg-C/day comes to be stored in the form of organic matters in the community of coral reef organisms. In a coral reef, even when it emits CO2 into the atmosphere, there is organic matter production which exceeds the lost CO{sub 2}. Coral reefs fix carbon out of the seawater at the rate of 0.42Gt-C/year, which is the aggregate of 0.3Gt organic matters and 0.12Gt CaCO{sub 3}. (NEDO)

  14. Indoleamine 2,3-dioxygenase expression in patients with allergic rhinitis: a case-control study

    Directory of Open Access Journals (Sweden)

    Luukkainen Annika

    2011-12-01

    Full Text Available Abstract Background Indoleamine 2,3-dioxygenase (IDO is a tryptophan catalyzing enzyme. It has been suggested that it has a role in lower airway allergic inflammations, but its role in allergic rhinitis has not been investigated. Objective Our aim was to evaluate the expression of IDO in the nasal mucosa of allergic rhinitis patients allergic to birch pollen during peak exposure to birch pollen allergen and compare it to non-atopic patients. Methods IDO expression was immunohistochemically evaluated from nasal specimens obtained in- and off-season from otherwise healthy non-smoking volunteers both allergic to birch pollen (having mild or moderate allergic rhinoconjunctivitis and non-allergic controls. Results: The IDO expression levels were low in healthy controls and remained low also in patients allergic to birch pollen. There were no differences in the expression of IDO in- and off-season in either healthy or allergic subjects. Conclusions There is a controversy in the role of IDO in upper and lower airways during allergic airway disease. It seems that IDO is associated to allergic inflammations of the lower airways, but does not have a local role in the nasal cavity at least in mild or moderate forms of allergic rhinitis.

  15. Spontaneous cytotoxic T-Cell reactivity against indoleamine 2,3-dioxygenase-2

    DEFF Research Database (Denmark)

    Sørensen, Rikke Bæk; Køllgaard, Tania; Andersen, Rikke Sick

    2011-01-01

    in mouse models of cancer in a nontoxic fashion. Here, we describe the immunogenicity of IDO2 by showing the presence of spontaneous cytotoxic T-cell reactivity against IDO2 in peripheral blood of both healthy donors and cancer patients. Furthermore, we show that these IDO2-specific T cells are cytotoxic...

  16. O líqüido cefalorraqueano iso diagnóstico dos tumores intracranianos

    Directory of Open Access Journals (Sweden)

    Aloysio Mattos Pimenta

    1954-09-01

    Full Text Available Foi feito um estudo do líqüido cefalorraqueano num material de 180 casos de tumores intracranianos, histològicamente verificados, apreciando-se a possibilidade de sugestões diagnósticas, em relação à sede, natureza e aspectos cirúrgico e clínico. Foi utilizada a via cisternal para a obtenção do líquor, sendo que a punção negativa da cisterna constituiu um elemento de suspeita diagnostica nos tumores da fossa posterior e de indicação de cautela ao médico que a pratica. As vantagens da via cisternal para colheita do liquor foram assinaladas. A pressão inicial foi normal em 35% dos casos, diminuída em 7% e aumentada em 58%. A hipotensão apareceu em 5 hematomas, num total de 14 casos considerados. Não houve grande diferença de freqüência de hipertensão entre tumores infra e supratentoriais. Em relação à natureza do tumor, o glioblastoma e o abscesso - processos de crescimento rápido - tiveram maior tendência a apresentar hipertensão, em relativa oposição àqueles de crescimento lento (astrocitoma e meningeoma. Houve concordância absoluta entre os sinais clínicos de hipertensão - tríade hipertensiva completa - e a hipertensão do líquor. Entretanto, nos casos com tríade incompleta, foram verificadas, freqüentes vêzes, valores normais da pressão e mesmo hipotensão. O quociente raqueano de Ayala, nos casos de líquor hipertenso, evidenciou em grande maioria o tipo tumoral (menor que 5. 0 valor da fórmula QR menor que 5 e QRD maior que 3, não foi comprovado em nosso material. A xantocromia foi dominante nos casos de hematoma. O crescimento rápido pareceu influir mais que a natureza específica no aparecimento da xantocromia. O retículo fibrinoso foi notado em 20 casos, dos quais 2 sem taxa elevada de proteínas, aparecendo com maior freqüência nos casos de abscesso e glioblastoma. O líquor hemorrágico sòmente foi observado nos casos de hematoma. A citologia quantitativa não forneceu dados que

  17. Indoleamine 2,3-Dioxygenase Is Dispensable for The Immunomodulatory Function of Stem Cells from Human Exfoliated Deciduous Teeth.

    Science.gov (United States)

    Alipour, Razieh; Masoumi Karimi, Masoumeh; Hashemi-Beni, Batool; Adib, Minoo; Sereshki, Nasrin; Sadeghi, Farzaneh

    2017-01-01

    In this study, we sought to better understand the immunoregulatory function of stem cells derived from human exfoliated deciduous teeth (SHED). We studied the role of the interferon gamma (IFN-γ)-indoleamine 2,3-dioxygenase (IDO)-axis in immunoregulation of SHED compared to bone marrow derived mesenchymal stem cells (BMMSCs) under the same conditions. In this cross-sectional study, recently isolated human T cells were stimulated either by mitogen or inactivated allogeneic peripheral blood mononuclear cells (PBMCs). These T cells were subsequently co-cultured with, either SHED or BMMSCs in the presence or absence of 1-methyl-tryptophan (1-MT) or neutralizing anti- human-IFN-γ antibodies. In all co-cultures we evaluated lymphocyte activation as well as IDO activity. SHED, similar to conventional BMMSCs, had anti-proliferative effects on stimulated T cells and reduced their cytokine production. This property of SHED and BMMSCs was changed by IFN-γ neutralization. We detected IDO in the immunosuppressive supernatant of all co-cultures. Removal of IDO decreased the immunosuppression of BMMSCs. SHED, like BMMSCs, produced the IDO enzyme. Although IFN-γ is one of inducer of IDO production in SHED, these cells were not affected by IFN-γ in the same manner as BMMSCs. Unlike BMMSCs, the IDO enzyme did not contribute to their immunosuppression and might have other cell-type specific roles.

  18. Highly Efficient Stable Expression of Indoleamine 2,3 Dioxygenase Gene in Primary Fibroblasts

    Directory of Open Access Journals (Sweden)

    Rezakhanlou Alireza

    2010-03-01

    Full Text Available Abstract Indoleamine 2,3 dioxygenase (IDO is a potent immunomodulatory enzyme that has recently attracted significant attention for its potential application as an inducer of immunotolerance in transplantation. We have previously demonstrated that a collagen matrix populated with IDO-expressing fibroblasts can be applied successfully in suppressing islet allogeneic immune response. Meanwhile, a critical aspect of such immunological intervention relies largely on effective long-term expression of the IDO gene. Moreover, gene manipulation of primary cells is known to be challenging due to unsatisfactory expression of the exogenous gene. In this study, a lentiviral gene delivery system has been employed to transduce primary fibroblasts. We used polybrene to efficiently deliver the IDO gene into primary fibroblasts and showed a significant increase (about tenfold in the rate of gene transfection. In addition, by the use of fluorescence-activated cell sorting, a 95% pure population of IDO-expressing fibroblasts was successfully obtained. The efficiency of the IDO expression and the activity of the enzyme have been confirmed by Western blotting, fluorescence-activated cell sorting analysis, and Kynurenine assay, respectively. The findings of this study revealed simple and effective strategies through which an efficient and stable expression of IDO can be achieved for primary cells which, in turn, significantly improves its potential as a tool for achieving immunotolerance in different types of transplantation.

  19. Coliquefaction of coal, tar sand bitumen and plastic (interaction among coal, bitumen and plastic); Sekitan/tar sand bitumen/plastic no kyoekika ni okeru kyozon busshitsu no eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, H.; Okuyama, Y.; Matsubara, K. [NKK Corp., Tokyo (Japan); Kamo, T.; Sato, Y. [National Institute for Resources and Environment, Tsukuba (Japan)

    1996-10-28

    For the improvement of economy, coliquefaction of coal, tar sand bitumen and plastic was performed under low hydrogen pressure, to investigate the influence of interaction among these on the liquefaction characteristics. For comparison, coliquefaction was also performed under the hydrogen pressure same as the NEDOL process. In addition, for clarifying its reaction mechanism, coliquefaction of dibenzyl and plastic was performed as a model experiment, to illustrate the distribution of products and composition of oil, and to discuss the interaction between dibenzyl and various plastics, and between various plastics. Under direct coal liquefaction conditions, coprocessing of Tanito Harum coal, Athabasca tar sand and plastic was carried out under low hydrogen pressure with an autoclave. The observed value of oil yield was higher than the calculated value based on the values from separate liquefaction of coal and plastic, which suggested the interaction between coal and the mixed plastic. The results of coliquefaction of coal, tar sand bitumen and plastic could be explained from the obtained oil yield and its composition by the coliquefaction of dibenzyl and plastic. 2 refs., 3 tabs.

  20. Indoleamine 2,3-dioxygenase vaccination

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Svane, Inge Marie

    2015-01-01

    Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. Remarkably, we discovered IDO-specific T cells that can influence adaptive immune reactions in patients with cancer. Further, a recent phase I clinical trial demonstrated long-lasting disease stabilization without toxicity in patien...... with non-small-cell lung cancer (NSCLC) who were vaccinated with an IDO-derived HLA-A2-restricted epitope....

  1. Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Antitumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies.

    Science.gov (United States)

    Monjazeb, Arta M; Kent, Michael S; Grossenbacher, Steven K; Mall, Christine; Zamora, Anthony E; Mirsoian, Annie; Chen, Mingyi; Kol, Amir; Shiao, Stephen L; Reddy, Abhinav; Perks, Julian R; T N Culp, William; Sparger, Ellen E; Canter, Robert J; Sckisel, Gail D; Murphy, William J

    2016-09-01

    Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing antitumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically upregulate immunosuppressive pathways, a phenomenon we term "rebound immune suppression," limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy. We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial. In murine models, we observed marked increase in intratumoral IDO expression after treatment with radiotherapy, CpG, or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment. This triple combination induced systemic antitumor effects, decreasing metastases, and improving survival in a CD8(+) T-cell-dependent manner. We evaluated this novel triple therapy in a canine clinical trial, because spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intratumoral immunosuppression, and induced robust systemic antitumor effects. These results suggest that IDO maintains immune suppression in the tumor after therapy, and IDO blockade promotes a local antitumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Clin Cancer Res; 22(17); 4328-40. ©2016 AACR. ©2016 American Association for Cancer Research.

  2. Discovery of Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 Through Structure-Based Virtual Screening

    Directory of Open Access Journals (Sweden)

    Guoqing Zhang

    2018-03-01

    Full Text Available Indoleamine 2,3-dioxygenase 1 (IDO1 is an intracellular monomeric heme-containing enzyme that catalyzes the first and the rate limiting step in catabolism of tryptophan via the kynurenine (KYN pathway, which plays a significant role in the proliferation and differentiation of T cells. IDO1 has been proven to be an attractive target for anticancer therapy and chronic viral infections. In the present study, a class of IDO1 inhibitors with novel scaffolds were identified by virtual screening and biochemical validation, in which the compound DC-I028 shows moderate IDO1 inhibitory activity with an IC50 of 21.61 μM on enzymatic level and 89.11 μM on HeLa cell. In the following hit expansion stage, DC-I02806, an analog of DC-I028, showed better inhibitory activity with IC50 about 18 μM on both enzymatic level and cellular level. The structure–activity relationship (SAR of DC-I028 and its analogs was then discussed based on the molecular docking result. The novel IDO1 inhibitors of DC-I028 and its analogs may provide useful clues for IDO1 inhibitor development.

  3. Discovery of Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 Through Structure-Based Virtual Screening

    Science.gov (United States)

    Zhang, Guoqing; Xing, Jing; Wang, Yulan; Wang, Lihao; Ye, Yan; Lu, Dong; Zhao, Jihui; Luo, Xiaomin; Zheng, Mingyue; Yan, Shiying

    2018-01-01

    Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular monomeric heme-containing enzyme that catalyzes the first and the rate limiting step in catabolism of tryptophan via the kynurenine (KYN) pathway, which plays a significant role in the proliferation and differentiation of T cells. IDO1 has been proven to be an attractive target for anticancer therapy and chronic viral infections. In the present study, a class of IDO1 inhibitors with novel scaffolds were identified by virtual screening and biochemical validation, in which the compound DC-I028 shows moderate IDO1 inhibitory activity with an IC50 of 21.61 μM on enzymatic level and 89.11 μM on HeLa cell. In the following hit expansion stage, DC-I02806, an analog of DC-I028, showed better inhibitory activity with IC50 about 18 μM on both enzymatic level and cellular level. The structure–activity relationship (SAR) of DC-I028 and its analogs was then discussed based on the molecular docking result. The novel IDO1 inhibitors of DC-I028 and its analogs may provide useful clues for IDO1 inhibitor development. PMID:29651242

  4. Remarkable Role of Indoleamine 2,3-Dioxygenase and Tryptophan Metabolites in Infectious Diseases: Potential Role in Macrophage-Mediated Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Yuki Murakami

    2013-01-01

    Full Text Available Indoleamine 2,3-dioxygenase 1 (IDO1, the L-tryptophan-degrading enzyme, plays a key role in the immunomodulatory effects on several types of immune cells. Originally known for its regulatory function during pregnancy and chronic inflammation in tumorigenesis, the activity of IDO1 seems to modify the inflammatory state of infectious diseases. The pathophysiologic activity of L-tryptophan metabolites, kynurenines, is well recognized. Therefore, an understanding of the regulation of IDO1 and the subsequent biochemical reactions is essential for the design of therapeutic strategies in certain immune diseases. In this paper, current knowledge about the role of IDO1 and its metabolites during various infectious diseases is presented. Particularly, the regulation of type I interferons (IFNs production via IDO1 in virus infection is discussed. This paper offers insights into new therapeutic strategies in the modulation of viral infection and several immune-related disorders.

  5. 5-Hydroxytryptophan, a major product of tryptophan degradation, is essential for optimal replication of human parainfluenza virus.

    Science.gov (United States)

    Rabbani, M A G; Barik, Sailen

    2017-03-01

    Interferon (IFN) exerts its antiviral effect by inducing a large family of cellular genes, named interferon (IFN)-stimulated genes (ISGs). An intriguing member of this family is indoleamine 2,3-dioxygenase (IDO), which catalyzes the first and rate-limiting step of the main branch of tryptophan (Trp) degradation, the kynurenine pathway. We recently showed that IDO strongly inhibits human parainfluenza virus type 3 (PIV3), a significant respiratory pathogen. Here, we show that 5-hydoxytryptophan (5-HTP), the first product of an alternative branch of Trp degradation and a serotonin precursor, is essential to protect virus growth against IDO in cell culture. We also show that the apparent antiviral effect of IDO on PIV3 is not due to the generation of the kynurenine pathway metabolites, but rather due to the depletion of intracellular Trp by IDO, as a result of which this rare amino acid becomes unavailable for the alternative, proviral 5-HTP pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Induction of indoleamine 2, 3-dioxygenase in human dendritic cells by a cholera toxin B subunit-proinsulin vaccine.

    Directory of Open Access Journals (Sweden)

    Jacques C Mbongue

    Full Text Available Dendritic cells (DC interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS. Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1. Increased biosynthesis of the immunosuppressive enzyme was detected in DCs inoculated with the CTB-INS fusion protein but not in DCs inoculated with proinsulin, CTB, or an unlinked combination of the two proteins. Immunoblot and PCR analyses of vaccine treated DCs detected IDO1mRNA by 3 hours and IDO1 protein synthesis by 6 hours after vaccine inoculation. Determination of IDO1 activity in vaccinated DCs by measurement of tryptophan degradation products (kynurenines showed increased tryptophan cleavage into N-formyl kynurenine. Vaccination did not interfere with monocytes differentiation into DC, suggesting the vaccine can function safely in the human immune system. Treatment of vaccinated DCs with pharmacological NF-κB inhibitors ACHP or DHMEQ significantly inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in vaccine up-regulation of dendritic cell IDO1. Heat map analysis of the proteomic data revealed an overall down-regulation of vaccinated DC functions, suggesting vaccine suppression of DC maturation. Together, our experimental data indicate that CTB-INS vaccine induction of IDO1 biosynthesis in human DCs may result in the inhibition of DC maturation generating a durable state of immunological tolerance. Understanding how CTB-INS modulates IDO1 activity in human DCs will facilitate vaccine efficacy and safety, moving this immunosuppressive strategy closer to clinical applications for prevention

  7. Plasma Indoleamine 2, 3-Dioxygenase, a Biomarker for Tuberculosis in Human Immunodeficiency Virus-Infected Patients.

    Science.gov (United States)

    Adu-Gyamfi, Clement G; Snyman, Tracy; Hoffmann, Christopher J; Martinson, Neil A; Chaisson, Richard E; George, Jaya A; Suchard, Melinda S

    2017-10-15

    There is no biomarker for diagnosing active tuberculosis in patients with human immunodeficiency virus (HIV) infection. Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that breaks down tryptophan (Trp) to metabolites known as kynurenines (Kyns). We investigated whether IDO activity, as measured by the ratio of Kyn to Trp, could be used to diagnose or predict active tuberculosis disease in HIV-infected adults. Kyn and Trp concentrations were measured using ultraperformance liquid chromatography mass spectrometry in plasma samples from 32 HIV-infected patients in whom active tuberculosis developed and who were followed up prospectively. We compared to 70 HIV-infected control subjects from the same cohort in whom tuberculosis did not develop, matched by age, sex, and CD4 cell count, and 37 unmatched HIV-infected patients with a diagnosis of pneumonia. Clinical parameters, including body mass index, CD4 cell count, HIV load, and C-reactive protein levels were analyzed. At the time of tuberculosis diagnosis, IDO activity was significantly higher in patients with tuberculosis than in controls (P tuberculosis diagnosis, IDO activity was significantly higher in all patients who later developed tuberculosis (P tuberculosis treatment, IDO activity in patients with tuberculosis declined to levels similar to those in controls. IDO activity was 4-fold higher in patients with tuberculosis than in those with pneumonia, and could be used to distinguish them. With a receiver operating characteristic curve, IDO activity had a sensitivity of 97%, a specificity of 99%, and positive and negative predictive values of 89% and 100% for detecting active tuberculosis disease. Plasma IDO activity is suitable as a biomarker of active tuberculosis in HIV-positive patients. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  8. Chimeric Vaccine Stimulation of Human Dendritic Cell Indoleamine 2, 3-Dioxygenase Occurs via the Non-Canonical NF-κB Pathway.

    Directory of Open Access Journals (Sweden)

    Nan-Sun Kim

    Full Text Available A chimeric protein vaccine composed of the cholera toxin B subunit fused to proinsulin (CTB-INS was shown to suppress type 1 diabetes onset in NOD mice and upregulate biosynthesis of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1 in human dendritic cells (DCs. Here we demonstrate siRNA inhibition of the NF-κB-inducing kinase (NIK suppresses vaccine-induced IDO1 biosynthesis as well as IKKα phosphorylation. Chromatin immunoprecipitation (ChIP analysis of CTB-INS inoculated DCs showed that RelB bound to NF-κB consensus sequences in the IDO1 promoter, suggesting vaccine stimulation of the non-canonical NF-κB pathway activates IDO1 expression in vivo. The addition of Tumor Necrosis Factor Associated Factors (TRAF TRAF 2, 3 and TRAF6 blocking peptides to vaccine inoculated DCs was shown to inhibit IDO1 biosynthesis. This experimental outcome suggests vaccine activation of the TNFR super-family receptor pathway leads to upregulation of IDO1 biosynthesis in CTB-INS inoculated dendritic cells. Together, our experimental data suggest the CTB-INS vaccine uses a TNFR-dependent signaling pathway of the non-canonical NF-κB signaling pathway resulting in suppression of dendritic cell mediated type 1 diabetes autoimmunity.

  9. Remarkable Role of Indoleamine 2,3-Dioxygenase and Tryptophan Metabolites in Infectious Diseases: Potential Role in Macrophage-Mediated Inflammatory Diseases

    OpenAIRE

    Murakami, Yuki; Hoshi, Masato; Imamura, Yukio; Arioka, Yuko; Yamamoto, Yasuko; Saito, Kuniaki

    2013-01-01

    Indoleamine 2,3-dioxygenase 1 (IDO1), the L-tryptophan-degrading enzyme, plays a key role in the immunomodulatory effects on several types of immune cells. Originally known for its regulatory function during pregnancy and chronic inflammation in tumorigenesis, the activity of IDO1 seems to modify the inflammatory state of infectious diseases. The pathophysiologic activity of L-tryptophan metabolites, kynurenines, is well recognized. Therefore, an understanding of the regulation of IDO1 and th...

  10. Indoleamine 2,3-dioxygenase and regulatory T cells in acute myeloid leukemia.

    Science.gov (United States)

    Mansour, Iman; Zayed, Rania A; Said, Fadwa; Latif, Lamyaa Abdel

    2016-09-01

    The microenvironment of acute myeloid leukemia (AML) is suppressive for immune cells. Regulatory T cells (Tregs) have been recognized to play a role in helping leukemic cells to evade immunesurveillance. The mesenchymal stem cells (MSCs) are essential contributors in immunomodulation of the microenvironment as they can promote differentiation of Tregs via the indoleamine 2,3-dioxygenase (IDO) pathway. The aim of the present work was to evaluate the expression of IDO in bone marrow derived MSCs and to study its correlation to percentage of Tregs. Thirty-seven adult bone marrow samples were cultured in appropriate culture medium to isolate MSCs. Successful harvest of MSCs was determined by plastic adherence, morphology, and positive expression of CD271 and CD105; negative expression of CD34 and CD45 using flowcytometry. MSCs were examined for IDO expression by immunocytochemistry using anti-IDO monoclonal antibody. CD4+ CD25+ cells (Tregs) were measured in bone marrow samples by flowcytometry. MSCs were successfully isolated from 20 of the 37 bone marrow samples cultured. MSCs showed higher expression of IDO and Tregs percentage was higher in AML patients compared to control subjects (P = 0.002 and P < 0.001, respectively). A positive correlation was found between IDO expression and Tregs percentage (P value = 0.012, r = 0.5). In this study, we revealed an association between high IDO expression in MSCs and elevated levels of Tregs which could have an important role in the pathogenesis of AML, providing immunosuppressive microenvironment.

  11. Fused Heterocyclic Compounds as Potent Indoleamine-2,3-dioxygenase 1 Inhibitors.

    Science.gov (United States)

    Panda, Subhankar; Roy, Ashalata; Deka, Suman Jyoti; Trivedi, Vishal; Manna, Debasis

    2016-12-08

    Uncontrolled metabolism of l-tryptophan (l-Trp) in the immune system has been recognized as a critical cellular process in immune tolerance. Indoleamine 2,3-dioxygenase 1 (IDO1) enzyme plays an important role in the metabolism of a local l-Trp through the kynurenine pathway in the immune systems. In this regard, IDO1 has emerged as a therapeutic target for the treatment of diseases that are associated with immune suppression like chronic infections, cancer, and others. In this study, we synthesized a series of pyridopyrimidine, pyrazolopyranopyrimidine, and dipyrazolopyran derivatives. Further lead optimizations directed to the identification of potent compounds, 4j and 4l (IC 50 = 260 and 151 nM, respectively). These compounds also exhibited IDO1 inhibitory activities in the low nanomolar range in MDA-MB-231 cells with very low cytotoxicity. Stronger selectivity for the IDO1 enzyme (>300-fold) over tryptophan 2,3-dioxygenase (TDO) enzyme was also observed for these compounds. Hence, these fused heterocyclic compounds are attractive candidates for the advanced study of IDO1-dependent cellular function and immunotherapeutic applications.

  12. Lactobacillus johnsonii inhibits indoleamine 2,3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats.

    Science.gov (United States)

    Valladares, Ricardo; Bojilova, Lora; Potts, Anastasia H; Cameron, Evan; Gardner, Christopher; Lorca, Graciela; Gonzalez, Claudio F

    2013-04-01

    In our previous work, we found that feeding Lactobacillus johnsonii to BioBreeding diabetes-prone (BBDP) rats decreased the incidence of diabetes development. The aim of this study was to investigate host pathways affected by L. johnsonii, with specific focus on the rate-limiting enzyme of tryptophan catabolism, indoleamine 2,3-dioxygenase (IDO). Suspensions of L. johnsonii or an equal volume of vehicle were orally administered to BBDP rats. Tissue IDO was investigated using quantitative RT-PCR and Western blot, whereas tryptophan, kynurenine, and 5-hydroxytryptamine (5-HT) concentrations were quantified by HPLC and ELISA. IDO activity was also investigated using L. johnsonii culture cell-free supernatant (CFS) with affinity-purified IDO and HT-29 intestinal epithelial cells. L. johnsonii feeding resulted in a 17% reduction in serum kynurenine compared with that in vehicle-fed controls, correlating with a 1.4-fold elevation in 5-HT levels. H₂O₂ produced by L. johnsonii abolished IDO activity in vitro, and L. johnsonii feeding resulted in a 3.9-fold increase in ileum lumen H₂O₂. L. johnsonii CFS significantly reduced IDO activity in HT-29 intestinal epithelial cells (47% reduction) compared with that in vehicle-treated controls, an effect abolished by catalase treatment. These data support the role of H₂O₂ in commensal bacteria-host interactions and highlight the influence of commensal bacteria-derived H₂O₂ on host physiology.

  13. Interferon-γ regulates the function of mesenchymal stem cells from oral lichen planus via indoleamine 2,3-dioxygenase activity.

    Science.gov (United States)

    Zhang, Zhihui; Han, Ying; Song, Jiangyuan; Luo, Ruxi; Jin, Xin; Mu, Dongdong; Su, Sha; Ji, Xiaoli; Ren, Yan-Fang; Liu, Hongwei

    2015-01-01

    Little is known about mesenchymal stem cells (MSCs) in normal or inflammatory oral mucosal tissues, such as in oral lichen planus (OLP). Our objectives were to identify, isolate, and characterize MSCs from normal human oral mucosa and OLP lesions, and to evaluate indoleamine 2,3 dioxygenase (IDO) activity in mediating immunomodulation of MSCs from these tissues. Expressions of MSCs-related markers were examined in isolated cells by flow cytometry. Self-renewal and multilineage differentiations were studied to characterize these MSCs. Interferon-γ (IFN-γ), IDO, and STRO-1 were assessed by immunofluorescence. MSCs from oral mucosa and OLP or IFN-γ-pretreated MSCs were co-cultured with allogeneic mixed lymphocyte reaction assays (MLR). Proliferation and apoptosis of MLR or MSCs were detected by CCK8 and the annexin V-FITC apoptosis detection kit, respectively. IDO expression and activity were measured by real-time PCR, Western blotting, and high-performance liquid chromatography. Isolated cells from oral mucosa and OLP expressed MSC-related markers STRO-1, CD105, and CD90 but were absent for hematopoietic stem cell markers CD34. Besides, they all showed self-renewal and multilineage differentiation capacities. MSCs in OLP presented STRO-1/IDO+ phenotype by immunofluorescence. MSCs and IFN-γ-pretreated MSCs could inhibit lymphocyte proliferation via IDO activity, but not via cell apoptosis. Long-term IFN-γ could also inhibit MSC proliferation via IDO activity. Mesenchymal stem cells can be isolated from human oral mucosa and OLP tissues. Besides self-renewal and multilineage differentiation properties, these cells may participate in immunomodulation mediated by IFN-γ via IDO activity in human OLP. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Heparan sulfate C5-epimerase is essential for heparin biosynthesis in mast cells.

    Science.gov (United States)

    Feyerabend, Thorsten B; Li, Jin-Ping; Lindahl, Ulf; Rodewald, Hans-Reimer

    2006-04-01

    Biosynthesis of heparin, a mast cell-derived glycosaminoglycan with widespread importance in medicine, has not been fully elucidated. In biosynthesis of heparan sulfate (HS), a structurally related polysaccharide, HS glucuronyl C5-epimerase (Hsepi) converts D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) residues. We have generated Hsepi-null mouse mutant mast cells, and we show that the same enzyme catalyzes the generation of IdoA in heparin and that 'heparin' lacking IdoA shows a distorted O-sulfation pattern.

  15. Low indoleamine 2,3-dioxygenase activity in persistent food allergy in children.

    Science.gov (United States)

    Buyuktiryaki, B; Sahiner, U M; Girgin, G; Birben, E; Soyer, O U; Cavkaytar, O; Cetin, C; Arik Yilmaz, E; Yavuz, S T; Kalayci, O; Baydar, T; Sackesen, C

    2016-02-01

    Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (Trp) to kynurenine (Kyn), has been demonstrated to contribute to modulation of allergic responses. However, the role of IDO in food allergy has not yet been elucidated. Serum Trp and Kyn concentrations were analyzed by high-pressure liquid chromatography. Expression of IDO gene was measured by real-time PCR. The levels of interleukin (IL)-4, IL-10, and interferon (IFN)-γ in cell culture supernatants were measured by ELISA. Kyn/Trp (IDO activity) was significantly lower in subjects with food allergy (n = 100) than in aged-matched healthy controls (n = 112) (P = 0.004). Kyn/Trp was decreased from healthy through completely tolerant, partially tolerant, and reactive ones [LN transformation (mean ± SEM) healthy: 3.9 ± 0.02 μM/mM; completely tolerant: 3.83 ± 0.04; partially tolerant: 3.8 ± 0.06; reactive: 3.7 ± 0.04] (P = 0.008). The frequency of genetic polymorphisms of IDO did not reveal a significant association with Trp, Kyn, and Kyn/Trp in healthy and food-allergic cases. Culture of PBMC experiments yielded that IDO mRNA expression was not different between tolerant and reactive groups. IL-4 synthesis when stimulated with casein increased significantly in subjects who are reactive and tolerant to foods (P = 0.042, P = 0.006, respectively). Increase in IL-10 synthesis was observed only in children tolerant to milk, but not in reactive ones. IFN-γ synthesis, when stimulated with IL-2 and β-lactoglobulin in cell culture, was significantly higher in subjects tolerant to milk than in the reactive ones (P = 0.005 and P = 0.029, respectively). Our results imply the probability of involvement of IDO in development of tolerance process, and we presume that high IDO activity is associated with nonresponsiveness to food allergens despite allergen sensitization. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. TH-CD-201-05: Characterization of a Novel Light-Collimating Tank Optical-CT System for 3D Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Miles, D; Yoon, S [Duke University Medical Physics Graduate Program, Durham, NC (United States); Adamovics, J [Department of Chemistry and Biology, Rider University, Skillman, NJ (United States); Oldham, M [Duke University Medical Center, Durham, NC (United States)

    2016-06-15

    Purpose: Comprehensive 3D dosimetry is highly desirable for advanced clinical QA, but costly optical readout techniques have hindered widespread implementation. Here, we present the first results from a cost-effective Integrated-lens Dry-tank Optical Scanner (IDOS), designed for convenient 3D dosimetry readout of radiochromic plastic dosimeters (e.g. PRESAGE). Methods: The scanner incorporates a novel transparent light-collimating tank, which collimates a point light source into parallel-ray CT geometry. The tank was designed using an in-house Monte-Carlo optical ray-tracing simulation, and was cast in polyurethane using a 3D printed mould. IDOS spatial accuracy was evaluated by imaging a set of custom optical phantoms, with comparison to x-ray CT images. IDOS dose measurement performance was assessed by imaging PRESAGE dosimeters irradiated with simple known dose distributions (e.g., 4 field box 6MV treatment with Varian Linac). Direct comparisons were made to images from our gold standard DLOS scanner and calculated dose distributions from a commissioned Eclipse planning system. Results: All optical CT images were reconstructed at 1mm isotropic resolution. Comparison of IDOS and x-ray CT images of the geometric phantom demonstrated excellent IDOS geometric accuracy (sub-mm) throughout the dosimeter. IDOS measured 3D dose distribution agreed well with prediction from Eclipse, with 95% gamma pass rate at 3%/3mm. Cross-scanner dose measurement gamma analysis shows >90% of pixels passing at 3%/3mm. Conclusion: The first prototype of the IDOS system has demonstrated promising performance, with accurate dosimeter readout and negligible spatial distortion. The use of optical simulations and 3D printing to create a light collimating-tank has dramatically increased convenience and reduced costs by removing the need for expensive lenses and large volumes of refractive matching fluids.

  17. Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity via Interferon Beta and Indoleamine-2,3-Dioxygenase.

    Directory of Open Access Journals (Sweden)

    Michael B Cheung

    Full Text Available Respiratory syncytial virus (RSV has been reported to infect human mesenchymal stem cells (MSCs but the consequences are poorly understood. MSCs are present in nearly every organ including the nasal mucosa and the lung and play a role in regulating immune responses and mediating tissue repair. We sought to determine whether RSV infection of MSCs enhances their immune regulatory functions and contributes to RSV-associated lung disease. RSV was shown to replicate in human MSCs by fluorescence microscopy, plaque assay, and expression of RSV transcripts. RSV-infected MSCs showed differentially altered expression of cytokines and chemokines such as IL-1β, IL6, IL-8 and SDF-1 compared to epithelial cells. Notably, RSV-infected MSCs exhibited significantly increased expression of IFN-β (~100-fold and indoleamine-2,3-dioxygenase (IDO (~70-fold than in mock-infected MSCs. IDO was identified in cytosolic protein of infected cells by Western blots and enzymatic activity was detected by tryptophan catabolism assay. Treatment of PBMCs with culture supernatants from RSV-infected MSCs reduced their proliferation in a dose dependent manner. This effect on PBMC activation was reversed by treatment of MSCs with the IDO inhibitors 1-methyltryptophan and vitamin K3 during RSV infection, a result we confirmed by CRISPR/Cas9-mediated knockout of IDO in MSCs. Neutralizing IFN-β prevented IDO expression and activity. Treatment of MSCs with an endosomal TLR inhibitor, as well as a specific inhibitor of the TLR3/dsRNA complex, prevented IFN-β and IDO expression. Together, these results suggest that RSV infection of MSCs alters their immune regulatory function by upregulating IFN-β and IDO, affecting immune cell proliferation, which may account for the lack of protective RSV immunity and for chronicity of RSV-associated lung diseases such as asthma and COPD.

  18. TH-CD-201-05: Characterization of a Novel Light-Collimating Tank Optical-CT System for 3D Dosimetry

    International Nuclear Information System (INIS)

    Miles, D; Yoon, S; Adamovics, J; Oldham, M

    2016-01-01

    Purpose: Comprehensive 3D dosimetry is highly desirable for advanced clinical QA, but costly optical readout techniques have hindered widespread implementation. Here, we present the first results from a cost-effective Integrated-lens Dry-tank Optical Scanner (IDOS), designed for convenient 3D dosimetry readout of radiochromic plastic dosimeters (e.g. PRESAGE). Methods: The scanner incorporates a novel transparent light-collimating tank, which collimates a point light source into parallel-ray CT geometry. The tank was designed using an in-house Monte-Carlo optical ray-tracing simulation, and was cast in polyurethane using a 3D printed mould. IDOS spatial accuracy was evaluated by imaging a set of custom optical phantoms, with comparison to x-ray CT images. IDOS dose measurement performance was assessed by imaging PRESAGE dosimeters irradiated with simple known dose distributions (e.g., 4 field box 6MV treatment with Varian Linac). Direct comparisons were made to images from our gold standard DLOS scanner and calculated dose distributions from a commissioned Eclipse planning system. Results: All optical CT images were reconstructed at 1mm isotropic resolution. Comparison of IDOS and x-ray CT images of the geometric phantom demonstrated excellent IDOS geometric accuracy (sub-mm) throughout the dosimeter. IDOS measured 3D dose distribution agreed well with prediction from Eclipse, with 95% gamma pass rate at 3%/3mm. Cross-scanner dose measurement gamma analysis shows >90% of pixels passing at 3%/3mm. Conclusion: The first prototype of the IDOS system has demonstrated promising performance, with accurate dosimeter readout and negligible spatial distortion. The use of optical simulations and 3D printing to create a light collimating-tank has dramatically increased convenience and reduced costs by removing the need for expensive lenses and large volumes of refractive matching fluids.

  19. Hazardous air pollutants; Yugai taiki osen busshitsu

    Energy Technology Data Exchange (ETDEWEB)

    Ogata, A

    2000-02-14

    Hazardous air pollutants (HAPs) are chemical substances listed up since those have a fear of increasing carcinogenic danger even in a small quantity by a long-term exposure. In Europe and Japan, approximately 200 names of substances are known. Concretely, they are particulate substnaces such as floating dusts, gaseous inorganics such as fluorine compound and chroline gas, volatile organic compounds (VOCs). Among those, especially, 22 substances are cited as those that Japan tackles in priority. HAPs explained in this paper mean mostly VOCs such as benzene, tetrachloroethylene and trichloroethylene among those. (NEDO)

  20. Reconocimiento de gestos en tiempo real basado en heurísticas y reconocimiento de patrones

    OpenAIRE

    López Rincón, Omar

    2015-01-01

    Desde los inicios de la computación, el área de procesado de imagen se ha ido incrementando y llegando a nuevas fronteras gracias al incremento del poder computacional que no se detiene, más rutinas han llegado a ser posibles, entre ellas el procesado de imagen en tiempo real. El desarrollo en el procesado de imagen ha ido incrementando junto con el desarrollo de nuevos procesadores y velocidad de computo, esto mismo ha ido abarcando desde imágenes satelitales, medicina y hoy en día los prime...

  1. La ciencia en imágenes. Construcción visual y documental científico

    OpenAIRE

    León, B. (Bienvenido)

    2011-01-01

    En un contexto de creciente importancia del entretenimiento, el documental televisivo de contenido científico ha ido adoptando nuevas formas narrativas y visuales. A lo largo de la historia del cine, la captación de imagen real ha ido haciéndose cada vez más sofisticada, gracias al desarrollo de las tecnologías que han ido mejorando las posibilidades de contar la ciencia con recursos visuales interesantes. Más recientemente, los medios digitales han situado al documental científico en una nue...

  2. Indoleamine 2,3-dioxygenase-dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model

    NARCIS (Netherlands)

    Taher, Yousef A.; Piavaux, Benoit J. A.; Gras, Renee; van Esch, Betty C. A. M.; Hofman, Gerard A.; Bloksma, Nanne; Henricks, Paul A. J.; van Oosterhout, Antoon J. M.

    Background: The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in immune suppression and tolerance induction. Objective: We examined (1) whether IDO activity is required during tolerance induction by allergen immunotherapy or for the subsequent suppressive

  3. The specific targeting of immune regulation

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2012-01-01

    as well as dendritic cells. Consequently, IDO may serve as a widely applicable target for immunotherapeutic strategies with a completely different function as well as expression pattern compared to previously described antigens. IDO constitutes a significant counter-regulatory mechanism induced by pro...

  4. Use of analgesics in intentional drug overdose presentations to hospital before and after the withdrawal of distalgesic from the Irish market.

    Science.gov (United States)

    Corcoran, Paul; Reulbach, Udo; Keeley, Helen S; Perry, Ivan J; Hawton, Keith; Arensman, Ella

    2010-03-18

    Distalgesic, the prescription-only analgesic compound of paracetamol (325 mg) and dextropropoxyphene (32.5 mg) known as co-proxamol in the UK, was withdrawn from the Irish market as of January 2006. This study aimed to evaluate the impact of the withdrawal of distalgesic in terms of intentional drug overdose (IDO) presentations to hospital emergency departments (EDs) nationally. A total of 42,849 IDO presentations to 37 of the 40 hospitals EDs operating in Ireland in 2003-2008 were recorded according to standardised procedures. Data on sales of paracetamol-containing drugs to retail pharmacies for the period 1998-2008 were obtained from IMS Health. The withdrawal of distalgesic from the Irish market resulted in an immediate reduction in sales to retail pharmacies from 40 million tablets in 2005 to 500,000 tablets in 2006 while there was a 48% increase in sales of other prescription compound analgesics. The rate of IDO presentations to hospital involving distalgesic in 2006-2008 was 84% lower than in the three years before it was withdrawn (10.0 per 100,000). There was a 44% increase in the rate of IDO presentations involving other prescription compound analgesics but the magnitude of this rate increase was five times smaller than the magnitude of the decrease in distalgesic-related IDO presentations. There was a decreasing trend in the rate of presentations involving any paracetamol-containing drug that began in the years before the distalgesic withdrawal. The withdrawal of distalgesic has had positive benefits in terms of IDO presentations to hospital in Ireland and provides evidence supporting the restriction of availability of means as a prevention strategy for suicidal behaviour.

  5. Dermatan sulfate is involved in the tumorigenic properties of esophagus squamous cell carcinoma

    DEFF Research Database (Denmark)

    Thelin, Martin A; Svensson, Katrin J; Shi, Xiaofeng

    2012-01-01

    . The unique feature that distinguishes DS from CS is the presence of iduronic acid (IdoA) in DS. Here, we report that CS/DS is increased five-fold in human biopsies of esophagus squamous cell carcinoma (ESCC), an aggressive tumor with poor prognosis, as compared with normal tissue. The main Ido...

  6. Increased Tregs associated with elevated Indoleamine-2,3-dioxygenase activity and an imbalanced Kynurenine pathway in IFNpositive primary Sjögren's syndrome

    NARCIS (Netherlands)

    N.I. Maria (Naomi); C.G. van Helden-Meeuwsen; Z. Brkić (Zana); S.M.J. Paulissen (Sandra); E.C. Steenwijk (Eline); V.A.S.H. Dalm (Virgil); P.L.A. van Daele (Paul); M.P. van Hagen (Martin); F.G.M. Kroese (Frans G.); J.A.G. van Roon (J. A G); A. Harkin (Andrew); A.W. Dik (Willem); H.A. Drexhage (Hemmo); E.W. Lubberts (Erik); M.A. Versnel (Marjan)

    2016-01-01

    textabstractIntroduction Indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme converting tryptophan (TRP) to kynurenine (KYN), is driven in part by type I/II IFNs. Naïve T cells are polarized into FoxP3+ regulatory T cells (Tregs) upon exposure to either IDO+ cells or KYN. Recent studies

  7. CD4+ T-Lymphocytes cell counts in adults with human ...

    African Journals Online (AJOL)

    Objectives: To evaluate the CD4+ cell counts in adults with human immunodeficiency virus (HIV) infections presenting at the medical department of the Federal Medical Centre, Ido-Ekiti, Nigeria. Methods: This study was carried out at the medical department of the Federal Medical Centre (FMC), Ido-Ekiti, Nigeria, in the ...

  8. Immunological mechanisms to establish embryo tolerance in early bovine pregnancy.

    Science.gov (United States)

    Groebner, A E; Schulke, K; Schefold, J C; Fusch, G; Sinowatz, F; Reichenbach, H D; Wolf, E; Meyer, H H D; Ulbrich, S E

    2011-01-01

    A well-balanced immunological interaction between mother and the semi-allogenic embryo is of particular importance. The objective of the present study was to analyse mechanisms of immune tolerance in bovine pregnancy during peri-implantation. Simmental heifers inseminated with either cryopreserved spermatozoa or seminal plasma were killed 12, 15 or 18 days after oestrus. Uteri were flushed for the recovery of conceptuses and the ipsilateral intercaruncular endometrium was sampled for gene expression analysis. Indoleamine 2,3-dioxygenase (IDO) mRNA, coding for the initial enzyme of the kynurenine pathway, was 18-fold (P < 0.001) more abundant in the endometrium of Day 18 pregnant v. non-pregnant animals. Tandem mass spectrometry revealed a decrease of endometrial l-tryptophan (P = 0.0008), but an increase of l-kynurenine concentration (P = 0.005) from Day 12 to Day 18, suggesting increasing IDO activity (P < 0.03). An in vitro coculture model of endometrial cells showed an induction of IDO expression following interferon-τ exposure primarily in stroma cells, which was confirmed by in situ hybridisation localising IDO mRNA mainly in deep stroma cells. Immunohistochemical analysis revealed fewer CD45-positive leucocytes in the zona basalis of pregnant animals. Elevated IDO activity may reduce the presence of leucocytes in the pregnant endometrium, providing a possible mechanism for protecting the semi-allogenic conceptus from maternal rejection.

  9. Targeting the immunoregulatory indoleamine 2,3 dioxygenase pathway in immunotherapy

    Science.gov (United States)

    Johnson, Burles A; Baban, Babak; Mellor, Andrew L

    2009-01-01

    Natural immune tolerance is a formidable barrier to successful immunotherapy to treat established cancers and chronic infections. Conversely, creating robust immune tolerance via immunotherapy is the major goal in treating autoimmune and allergic diseases, and enhancing survival of transplanted organs and tissues. In this review, we focus on a natural mechanism that creates local T-cell tolerance in many clinically relevant settings of chronic inflammation involving expression of the cytosolic enzyme indoleamine 2,3-dioxygenase (IDO) by specialized subsets of dendritic cells. IDO-expressing dendritic cells suppress antigen-specific T-cell responses directly, and induce bystander suppression by activating regulatory T cells. Thus, manipulating IDO is a promising strategy to treat a range of chronic inflammatory diseases. PMID:20161103

  10. Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory.

    Science.gov (United States)

    Heisler, Jillian M; O'Connor, Jason C

    2015-11-01

    Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. Published by Elsevier Inc.

  11. Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory

    Science.gov (United States)

    Heisler, Jillian M.; O’Connor, Jason C.

    2015-01-01

    Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID:26130057

  12. The Kynurenine Pathway As a Novel Link between Allergy and the Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Aaron P. Van der Leek

    2017-11-01

    Full Text Available In the past few decades, the indoleamine 2,3 dioxygenase (IDO subset of the kynurenine (KYN pathway of tryptophan (TRP metabolism has been the subject of much research in the area of immune tolerance. In this review, we aim to incorporate new findings on this pathway in relation to allergy and the gut microbiome, while providing a comprehensive overview of the pathway itself. Stimulated by interferon gamma, IDO acts as a tolerogenic, immunosuppressive enzyme to attenuate allergic responses by the induction of the KYN-IDO pathway, resultant depletion of TRP, and elevation in KYN metabolites. Acting through the aryl hydrocarbon receptor, KYN metabolites cause T-cell anergy and apoptosis, proliferation of Treg and Th17 cells, and deviation of the Th1/Th2 response, although the outcome is highly dependent on the microenvironment. Moreover, new evidence from germ-free mice and human infants shows that gut microbiota and breast milk are key in determining the functioning of the KYN-IDO pathway. As such, we recommend further research on how this pathway may be a critical link between the microbiome and development of allergy.

  13. Iduronic acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Barbara Bartolini

    Full Text Available Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA, catalyzed by two DS epimerases. Functional ablation of DS-epi1, the main epimerase in these cells, resulted in a major reduction of IdoA both on cell surface and in secreted CS/DS proteoglycans. Downregulation of IdoA led to delayed ability to re-populate wounded areas due to loss of directional persistence of migration. DS-epi1-/- aortic smooth muscle cells, however, had not lost the general property of migration showing even increased speed of movement compared to wild type cells. Where the cell membrane adheres to the substratum, stress fibers were denser whereas focal adhesion sites were fewer. Total cellular expression of focal adhesion kinase (FAK and phospho-FAK (pFAK was decreased in mutant cells compared to control cells. As many pathological conditions are dependent on migration, modulation of IdoA content may point to therapeutic strategies for diseases such as cancer and atherosclerosis.

  14. Activation of the Serotonin Pathway is Associated with Poor Outcome in COPD Exacerbation: Results of a Long-Term Cohort Study.

    Science.gov (United States)

    Meier, Marc A; Ottiger, Manuel; Vögeli, Alaadin; Steuer, Christian; Bernasconi, Luca; Thomann, Robert; Christ-Crain, Mirjam; Henzen, Christoph; Hoess, Claus; Zimmerli, Werner; Huber, Andreas; Mueller, Beat; Schuetz, Philipp

    2017-06-01

    Indoleamine 2,3-dioxygenase (IDO) metabolizes tryptophan to kynurenine. An increase of its activity is associated with severity in patients with pneumonia. In chronic obstructive pulmonary disease (COPD) patients, an elevation of serotonin has been reported. Experimental models showed that cigarette smoke inhibits monoamine oxidase (MAO) leading to higher levels of serotonin. We investigated the prognostic ability of tryptophan, serotonin, kynurenine, IDO, and tryptophan hydroxylase (TPH) to predict short- and long-term outcomes in patients with a COPD exacerbation. We measured tryptophan, serotonin, and kynurenine on admission plasma samples in patients with a COPD exacerbation from a previous trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). IDO and TPH were calculated as ratios of kynurenine over tryptophan, and serotonin over tryptophan, respectively. We studied their association with parameters measured in clinical routine at emergency department admission representing inflammation (C-reactive protein [CRP]), infection (procalcitonin [PCT]), oxygenation (SpO 2 ), as well as patients' clinical outcome, confirmed by structured phone interviews. Mortality in the 149 included patients was 53.7% within six years of follow-up. While IDO activity showed strong positive correlations, tryptophan was negatively correlated with CRP and PCT. For 30-day adverse outcome defined as death and/or intensive care unit (ICU) admission, a multivariate regression analysis adjusted for age and comorbidities found strong associations for IDO activity (adjusted odds ratios of 31.4 (95%CI 1.1-857), p = 0.041) and TPH (adjusted odds ratios 27.0 (95%CI 2.2-327), p = 0.010). TPH also showed a significant association with mortality at 18 months, (hazard ratio 2.61 (95%CI 1.2-5.8), p = 0.020). In hospitalized patients with a COPD exacerbation, higher IDO and TPH activities independently predicted adverse short-term outcomes and TPH levels were also

  15. Interaction of Carthamus tinctorius lignan arctigenin with the binding site of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase☆

    Science.gov (United States)

    Temml, Veronika; Kuehnl, Susanne; Schuster, Daniela; Schwaiger, Stefan; Stuppner, Hermann; Fuchs, Dietmar

    2013-01-01

    Mediterranean Carthamus tinctorius (Safflower) is used for treatment of inflammatory conditions and neuropsychiatric disorders. Recently C. tinctorius lignans arctigenin and trachelogenin but not matairesinol were described to interfere with the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in peripheral blood mononuclear cells in vitro. We examined a potential direct influence of compounds on IDO enzyme activity applying computational calculations based on 3D geometry of the compounds. The interaction pattern analysis and force field-based minimization was performed within LigandScout 3.03, the docking simulation with MOE 2011.10 using the X-ray crystal structure of IDO. Results confirm the possibility of an intense interaction of arctigenin and trachelogenin with the binding site of the enzyme, while matairesinol had no such effect. PMID:24251110

  16. Safety, immune and clinical responses in metastatic melanoma patients vaccinated with a long peptide derived from indoleamine 2,3-dioxygenase in combination with ipilimumab

    DEFF Research Database (Denmark)

    Bjørn, Jon; Iversen, Trine Zeeberg; Nitschke, Nikolaj Juul

    2016-01-01

    antibody ipilimumab (ipi). METHODS: Ten patients with metastatic melanoma participated in a phase I first-in-human clinical study assessing safety of combining ipi with a 21-mer synthetic peptide vaccine from IDO denoted IDOlong. Secondary and tertiary end points included vaccine and clinical response......BACKGROUND AIM: Indoleamine 2,3-dioxygenase (IDO) is an emerging new target in cancer therapy that can be targeted with active immunotherapy (e.g. through peptide vaccination). Furthermore, IDO has been identified as a key mechanism underlying resistance to treatment with the checkpoint blocking....... RESULTS: Treatment was generally safe and well tolerated. Vaccine related adverse reactions included grade I and II erythema, oedema and pruritus at the vaccination site, which were manageable with mild topical corticosteroids. One patient developed presumed ipi-induced colitis. It initially responded...

  17. Fiscal 2000 survey report. Research on laser-aided photolysis of environmental pollutant in liquid phase system; 2000 nendo ekisokei ni okeru kankyo osen busshitsu no laser hikari bunkai gijutsu ni kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-03-01

    Experiments were conducted on laser-aided decomposition and removal of chemical substances in liquid phase systems on the assumption that there existed chemical pollutants in wastewater or water after washing burned ash. The aim of the research was to split carbon-chlorine bonds and break benzene rings, the two being the cause of harmfulness, and experiments were conducted using chlorophenol. The photolytic lasers were ArF excimer laser and KrF excimer laser. It was found that the reduction rate of chlorophenol in a water solution under excimer laser irradiation was 1.7 times higher under KrF laser than under ArF laser. For mediums other than water, isopropanol was used, more convenient than chlorophenol in separating organic pollutants from burned ash and the like. In this case, organochlorine compounds were generated at the beginning, but they disappeared when irradiation was prolonged. It was demonstrated that the laser-aided environmental cleaning technology would find a very wide scope of application as an effective photolytic means. (NEDO)

  18. Addition of an indoleamine 2,3,-dioxygenase inhibitor to B cell-depletion therapy blocks autoreactive B cell activation and recurrence of arthritis in K/BxN mice.

    Science.gov (United States)

    Pigott, Elizabeth; Mandik-Nayak, Laura

    2012-07-01

    To define the role of indoleamine 2,3-dioxygenase (IDO) in driving pathogenic B cell responses that lead to arthritis and to determine if inhibitors of the IDO pathway can be used in conjunction with therapeutic B cell depletion to prevent the reemergence of autoantibodies and arthritis following reconstitution of the B cell repertoire. Immunoglobulin-transgenic mice were treated with the IDO inhibitor 1-methyltryptophan (1-MT) and monitored for the extent of autoreactive B cell activation. Arthritic K/BxN mice were treated with B cell depletion alone or in combination with 1-MT. Mice were monitored for the presence of autoantibody-secreting cells, inflammatory cytokines, and joint inflammation. Treatment with 1-MT did not affect the initial activation or survival of autoreactive B cells, but it did inhibit their ability to differentiate into autoantibody-secreting cells. Treatment with anti-CD20 depleted the B cell repertoire and attenuated arthritis symptoms; however, the arthritis symptoms rapidly returned as B cells repopulated the repertoire. Administration of 1-MT prior to B cell repopulation prevented the production of autoantibodies and inflammatory cytokines and flare of arthritis symptoms. IDO activity is essential for the differentiation of autoreactive B cells into antibody-secreting cells, but it is not necessary for their initial stages of activation. Addition of 1-MT to therapeutic B cell depletion prevents the differentiation of autoantibody-secreting cells and the recurrence of autoimmune arthritis following reconstitution of the B cell repertoire. These data suggest that IDO inhibitors could be used in conjunction with B cell depletion as an effective cotherapeutic strategy in the treatment of rheumatoid arthritis. Copyright © 2012 by the American College of Rheumatology.

  19. A CD8 T Cell/Indoleamine 2,3-Dioxygenase Axis Is Required for Mesenchymal Stem Cell Suppression of Human Systemic Lupus Erythematosus

    Science.gov (United States)

    Wang, Dandan; Feng, Xuebing; Lu, Lin; Konkel, Joanne E; Zhang, Huayong; Chen, Zhiyong; Li, Xia; Gao, Xiang; Lu, Liwei; Shi, Songtao; Chen, Wanjun; Sun, Lingyun

    2014-01-01

    Objective Allogeneic mesenchymal stem cells (MSCs) exhibit therapeutic effects in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain largely unknown. The aim of this study was to investigate how allogeneic MSCs mediate immunosuppression in lupus patients. Methods The effects of allogeneic umbilical cord–derived MSCs (UC-MSCs) on inhibition of T cell proliferation were determined. MSC functional molecules were stimulated with peripheral blood mononuclear cells from healthy controls and SLE patients and examined by real-time polymerase chain reaction. CD4+ and CD8+ T cells were purified using microbeads to stimulate MSCs in order to determine cytokine expression by MSCs and to further determine which cell subset(s) or which molecule(s) is involved in inhibition of MSC–mediated T cell proliferation. The related signaling pathways were assessed. We determined levels of serum cytokines in lupus patients before and after UC-MSC transplantation. Results Allogeneic UC-MSCs suppressed T cell proliferation in lupus patients by secreting large amounts of indoleamine 2,3-dioxygenase (IDO). We further found that interferon-γ (IFNγ), which is produced predominantly by lupus CD8+ T cells, is the key factor that enhances IDO activity in allogeneic MSCs and that it is associated with IFNGR1/JAK-2/STAT signaling pathways. Intriguingly, bone marrow–derived MSCs from patients with active lupus demonstrated defective IDO production in response to IFNγ and allogeneic CD8+ T cell stimulation. After allogeneic UC-MSC transplantation, serum IDO activity increased in lupus patients. Conclusion We found a previously unrecognized CD8+ T cell/IFNγ/IDO axis that mediates the therapeutic effects of allogeneic MSCs in lupus patients. PMID:24756936

  20. Type I Interferon-Mediated Skewing of the Serotonin Synthesis Is Associated with Severe Disease in Systemic Lupus Erythematosus

    Science.gov (United States)

    Lood, Christian; Tydén, Helena; Gullstrand, Birgitta; Klint, Cecilia; Wenglén, Christina; Nielsen, Christoffer T.; Heegaard, Niels H. H.; Jönsen, Andreas; Kahn, Robin; Bengtsson, Anders A.

    2015-01-01

    Serotonin, a highly pro-inflammatory molecule released by activated platelets, is formed by tryptophan. Tryptophan is also needed in the production of kynurenine, a process mediated by the type I interferon (IFN)-regulated rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO). The aim of this study was to investigate levels of serotonin in patients with the autoimmune disease systemic lupus erythematosus (SLE), association to clinical phenotype and possible involvement of IDO in regulation of serotonin synthesis. Serotonin levels were measured in serum and plasma from patients with SLE (n=148) and healthy volunteers (n=79) by liquid chromatography and ELISA, as well as intracellularly in platelets by flow cytometry. We found that SLE patients had decreased serotonin levels in serum (p=0.01) and platelets (pserotonin (p=0.0008) as well as increased IDO activity (pserotonin levels in platelets and serum (pserotonin levels were associated with severe SLE with presence of anti-dsDNA antibodies and nephritis. In all, reduced serum serotonin levels in SLE patients were related to severe disease phenotype, including nephritis, suggesting involvement of important immunopathological processes. Further, our data suggest that type I IFNs, present in SLE sera, are able to up-regulate IDO expression, which may lead to decreased serum serotonin levels. PMID:25897671

  1. White dots <i>do matter

    DEFF Research Database (Denmark)

    Soeken, Mathias; Thomsen, Michael Kirkedal

    2013-01-01

    The increased effort in recent years towards methods for computer aided design of reversible logic circuits has also lead to research in algorithms for optimising the resulting circuits; both with higher-level data structures and directly on the reversible circuits. To obtain structural patterns...... that can be replaced by a cheaper realisation, many direct algorithms apply so-called moving rules; a simple form of rewrite rules that can only swap gate order. In this paper we first describe the few basic rules that are needed to perform rewriting directly on reversible logic circuits made from general...... as problems based on our rewrite rules. Finally, we outline a path to generalising the rewrite rules by showing their forms for reversible control-gates. This can be used to expand our method to other gates such as the controlled-swap gate or quantum gates....

  2. Augmenting Everyday Artefacts to Support Social Interaction Among Senior Peers

    DEFF Research Database (Denmark)

    Nazzi, Elena; Sokoler, Tomas

    2015-01-01

    Novel technological possibilities emerge when tangible and social computing come together. This paper explores the potential of such technology when designing for seniors and their social interaction. Our research is guided by the concept of twitterIDo, which is to make seniors’ everyday activities...... and displays designed to start a dialogue with the seniors on how twitterIDo-technology may fit into their everyday situations. Our findings point out how augmented everyday artefacts can make a positive difference when designing technology in a domain such the one of seniors’ and their social interaction...... more visible by augmenting everyday artefacts to communicate the ongoing activity they are used for. We engaged a local community of seniors in a living lab to explore the possibilities of twitterIDo in real life situations. This paper presents a series of interactive prototypes of everyday artefacts...

  3. Estudio y desarrollo de procesos de soporte de negocio en una empresa española perteneciente al sector de las infraestructuras, servicios, ingeniería y sistemas.

    OpenAIRE

    Porcar Tremps, Víctor

    2010-01-01

    El presente proyecto tiene como objetivo principal estudiar y desarrollar procesos de soporte de negocio de una multinacional española, cuya actividad principal es el negocio de las infraestructuras. Las empresas llevan tiempo trabajando para alcanzar la máxima excelencia en la gestión de sus procesos, y para ello han ido aplicando progresivamente los diferentes avances tecnológicos que han ido surgiendo. En este caso la herramienta utilizada es un sistema BPM (Business Process...

  4. Effect of arthritic synovial fluids on the expression of immunomodulatory factors by mesenchymal stem cells: an explorative in-vitro study

    Directory of Open Access Journals (Sweden)

    Maarten J.C. Leijs

    2012-08-01

    Full Text Available Background: In diseased joints, the catabolic environment results in progressive joint damage. Mesenchymal stem cells (MSCs can have immunomodulatory effect by secreting anti-inflammatory factors. To exert these effects, MSCs need to be triggered by pro-inflammatory cytokines. To explore the potential of MSCs as a treatment for diseased joints, we studied the effect of synovial fluid (SF from donors with different joint diseases and donors without joint pathology on the immunomodulatory capacities of human MSCs in vitro. We hypothesized that SF of diseased joints influences the immunomodulatory effects of MSCs. Materials & Methods: MSCs were cultured in medium with SF of six osteoarthritis (OA or six rheumatoid arthritis (RA donors and three donors without joint pathology were used as control. Gene expressions of IL-6, HGF, TNFa, TGFb1 and indoleamine 2,3-dioxygenase (IDO were analysed. L-kynurenine concentration in conditioned medium (CM by MSCs with SF was determined as a measure of IDO activity by MSCs. Furthermore, the effect of CM with SF on proliferation of activated lymphocytes was analysed. Results: Addition of SF significantly up-regulated the mRNA expression of IL-6 and IDO in MSCs. SF(OA induced significantly higher expression of IDO than SF(control, although no difference in IDO activity of the MSCs could be shown with a L-kynurenine assay. Medium conditioned by MSCs with SF(OA or RA suppressed activated lymphocyte proliferation in vitro more than medium conditioned by MSCs without SF or with SF(control.Discussion: SF can influence the expression of genes involved in immunomodulation by MSCs and the effect on lymphocyte proliferation. We found indications for disease-specific differences between SFs but the variation between donors, even within one disease group was high. These data warrant further research to examine the potential application of MSC therapy in arthritic joints.

  5. Immunomodulatory properties of cacao extracts – potential consequences for medical applications

    Science.gov (United States)

    Becker, Kathrin; Geisler, Simon; Ueberall, Florian; Fuchs, Dietmar; Gostner, Johanna M.

    2013-01-01

    Anti-inflammatory properties of cacao, fruits of Theobroma cacao L. (Sterculiaceae), are well documented, and therapeutic applications are described for gastrointestinal, nervous, and cardiovascular abnormalities. Most, if not all of these disease conditions involve inflammation or immune activation processes. The pro-inflammatory cytokine interferon-γ (IFN-γ) and related biochemical pathways like tryptophan breakdown by indoleamine 2,3-dioxygenase (IDO) and neopterin formation are deeply involved in their pathogenesis. Neopterin concentrations and the kynurenine to tryptophan ratio (Kyn/Trp, an estimate of IDO activity) are elevated in a significant proportion of patients with virus infections, cancer, autoimmune syndrome, neurodegeneration, and coronary artery disease. Moreover, higher neopterin and Kyn/Trp concentrations are indicative for poor prognosis. When investigating the effect of aqueous or ethanolic extracts of cacao on IFN-γ, neopterin and Kyn/Trp concentrations in mitogen-stimulated human peripheral blood mononuclear cells, breakdown of tryptophan by IDO, and formation of neopterin and IFN-γ were dose-dependently suppressed. The effects observed in the cell-based assays are associated with the antioxidant activity of the cacao extracts as determined by the cell-free oxygen radical absorption capacity assay. The influence of cacao extracts on IDO activity could be of particular relevance for some of the beneficial health effects ascribed to cacao: tryptophan breakdown by IDO is strongly involved in immunoregulation, and the diminished availability of tryptophan limits the biosynthesis of neurotransmitter serotonin. The inhibition of tryptophan breakdown by cacao constituents could thus be relevant not only for immune system restoration in patients, but also contribute to mood elevation and thereby improve quality of life. However, the available data thus far are merely in vitro only and future studies need to investigate the influence of cacao on

  6. Involvement of the kynurenine pathway in human glioma pathophysiology.

    Directory of Open Access Journals (Sweden)

    Seray Adams

    Full Text Available The kynurenine pathway (KP is the principal route of L-tryptophan (TRP catabolism leading to the production of kynurenine (KYN, the neuroprotectants, kynurenic acid (KYNA and picolinic acid (PIC, the excitotoxin, quinolinic acid (QUIN and the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD(+. The enzymes indoleamine 2,3-dioxygenase-1 (IDO-1, indoleamine 2,3-dioxygenase-2 (IDO-2 and tryptophan 2,3-dioxygenase (TDO-2 initiate the first step of the KP. IDO-1 and TDO-2 induction in tumors are crucial mechanisms implicated to play pivotal roles in suppressing anti-tumor immunity. Here, we report the first comprehensive characterisation of the KP in 1 cultured human glioma cells and 2 plasma from patients with glioblastoma (GBM. Our data revealed that interferon-gamma (IFN-γ stimulation significantly potentiated the expression of the KP enzymes, IDO-1 IDO-2, kynureninase (KYNU, kynurenine hydroxylase (KMO and significantly down-regulated 2-amino-3-carboxymuconate semialdehyde decarboxylase (ACMSD and kynurenine aminotransferase-I (KAT-I expression in cultured human glioma cells. This significantly increased KP activity but significantly lowered the KYNA/KYN neuroprotective ratio in human cultured glioma cells. KP activation (KYN/TRP was significantly higher, whereas the concentrations of the neuroreactive KP metabolites TRP, KYNA, QUIN and PIC and the KYNA/KYN ratio were significantly lower in GBM patient plasma (n = 18 compared to controls. These results provide further evidence for the involvement of the KP in glioma pathophysiology and highlight a potential role of KP products as novel and highly attractive therapeutic targets to evaluate for the treatment of brain tumors, aimed at restoring anti-tumor immunity and reducing the capacity for malignant cells to produce NAD(+, which is necessary for energy production and DNA repair.

  7. Induction of indolamine 2,3-dioxygenase and kynurenine 3-monooxygenase in rat brain following a systemic inflammatory challenge: a role for IFN-gamma?

    Science.gov (United States)

    Connor, Thomas J; Starr, Neasa; O'Sullivan, Joan B; Harkin, Andrew

    2008-08-15

    Inflammation-mediated dysregulation of the kynurenine pathway has been implicated as a contributor to a number of major brain disorders. Consequently, we examined the impact of a systemic inflammatory challenge on kynurenine pathway enzyme expression in rat brain. Indoleamine 2,3-dioxygenase (IDO) expression was induced in cortex and hippocampus following systemic lipopolysaccharide (LPS) administration. Whilst IDO expression was paralleled by increased circulating interferon (IFN)-gamma concentrations, IFN-gamma expression in the brain was only modestly altered following LPS administration. In contrast, induction of IDO was associated with increased central tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 expression. Similarly, in cultured glial cells LPS-induced IDO expression was accompanied by increased TNF-alpha and IL-6 expression, whereas IFN-gamma was not detectable. These findings indicate that IFN-gamma is not required for LPS-induced IDO expression in brain. A robust increase in kynurenine-3-monooxygenase (KMO) expression was observed in rat brain 24h post LPS, without any change in kynurenine aminotransferase II (KAT II) expression. In addition, we report that constitutive expression of KAT II is approximately 8-fold higher than KMO in cortex and 20-fold higher in hippocampus. Similarly, in glial cells constitutive expression of KAT II was approximately 16-fold higher than KMO, and expression of KMO but not KAT II was induced by LPS. These data are the first to demonstrate that a systemic inflammatory challenge stimulates KMO expression in brain; a situation that is likely to favour kynurenine metabolism in a neurotoxic direction. However, our observation that expression of KAT II is much higher than KMO in rat brain is likely to counteract potential neurotoxicity that could arise from KMO induction following an acute inflammation.

  8. Arquetipos iconográficos femeninos en el cómic y la animación japonesa para adolescentes masculinos

    OpenAIRE

    López Rodríguez, Francisco Javier; García Pacheco, Juan A.

    2011-01-01

    El cómic japonés (manga) y la animación japonesa (anime) son poderosas industrias culturales que, progresivamente, se han ido expandiendo internacionalmente. A medida que estas obras han ido llegando a los mercados occidentales, la atención de los investigadores se ha fijado en las particularidades expresivas, narrativas y culturales de estos productos. La investigación en género relacionada con el manga y el anime se ha centrado principalmente en las obras destinadas a un público femenino y,...

  9. Educación maternal y salud maternoinfantil

    OpenAIRE

    Andrés Plaza, Mª del Carmen

    2016-01-01

    INTRODUCCIÓN: La educación maternal comprende una serie de medidas educativas, maternales y paternales, enfocadas a las necesidades tanto físicas, como psíquicas, sociales y emocionales que surgen a lo largo del embarazo, parto, puerperio y crianza del recién nacido. A lo largo del tiempo ha ido evolucionando por las diferentes escuelas hasta la que existe actualmente. La participación en dichos programas ha ido decreciendo con el paso del tiempo. OBJETIVO: Analizar los efectos de la realizac...

  10. Umbilical Cord Tissue-Derived Mesenchymal Stem Cells Induce T Lymphocyte Apoptosis and Cell Cycle Arrest by Expression of Indoleamine 2, 3-Dioxygenase

    Directory of Open Access Journals (Sweden)

    Xiuying Li

    2016-01-01

    Full Text Available It has been reported that human mesenchymal stem cells are able to inhibit T lymphocyte activation; however, the discrepancy among different sources of MSCs is not well documented. In this study, we have compared the MSCs from bone marrow (BM, adipose tissue (AT, placenta (PL, and umbilical cord (UC to determine which one displayed the most efficient immunosuppressive effects on phytohemagglutinin-induced T cell proliferation. Among them we found that hUC-MSC has the strongest effects on inhibiting T cell proliferation and is chosen to do the further study. We observed that T lymphocyte spontaneously released abundant IFN-γ. And IFN-γ secreted by T lymphocyte could induce the expression of indoleamine 2, 3-dioxygenase (IDO in hUC-MSCs. IDO was previously reported to induce T lymphocyte apoptosis and cell cycle arrest in S phase. When cocultured with hUC-MSCs, T lymphocyte expression of caspase 3 was significantly increased, while Bcl2 and CDK4 mRNA expression decreased dramatically. Addition of 1-methyl tryptophan (1-MT, an IDO inhibitor, restored T lymphocyte proliferation, reduced apoptosis, and induced resumption of the cell cycle. In addition, the changes in caspase 3, CDK4, and Bcl2 expression were reversed by 1-MT. These findings demonstrate that hUC-MSCs induce T lymphocyte apoptosis and cell cycle arrest by expressing abundant IDO and provide an explanation for some of the immunomodulatory effects of MSCs.

  11. Uso de las redes sociales en la distribución comercial

    OpenAIRE

    Indurain Riva, Rocío

    2017-01-01

    RESUMEN: El marketing hasta hace no mucho tiempo pasaba casi inadvertido por parte de organizaciones y empresarios, era algo secundario que no se consideraba de gran importancia. Sin embargo, de unos años hasta ahora ha ido cogiendo fuerza y se ha visto y comprobado cómo un buen marketing puede impulsar de sobremanera a una empresa al éxito. Dentro de los dos tipos de marketing existentes como son el estratégico y el operativo es éste último el que se ha ido desarrollando y evolucionando con ...

  12. Osteoclastos: mucho más que células remodeladoras del hueso

    OpenAIRE

    Arboleya, L.; Castañeda, S.

    2014-01-01

    El osteoclasto ha sido considerado clásicamente como una célula con una función exclusivamente remodeladora del hueso, de comportamiento gregario. Sin embargo, los avances que se han ido produciendo en los últimos años han ido cambiando drásticamente este concepto y, en el momento actual, sabemos que esta célula multinucleada está sometida a una compleja regulación biológica, necesaria para ejercer un papel multifuncional de dimensiones desconocidas. Además de su participación como la única c...

  13. Exploring the mechanism of tryptophan 2,3-dioxygenase

    Science.gov (United States)

    Thackray, Sarah J.; Mowat, Christopher G.; Chapman, Stephen K.

    2008-01-01

    The haem proteins TDO (tryptophan 2,3-dioxygenase) and IDO (indoleamine 2,3-dioxygenase) are specific and powerful oxidation catalysts that insert one molecule of dioxygen into L-tryptophan in the first and rate-limiting step in the kynurenine pathway. Recent crystallographic and biochemical analyses of TDO and IDO have greatly aided our understanding of the mechanisms employed by these enzymes in the binding and activation of dioxygen and tryptophan. In the present paper, we briefly discuss the function, structure and possible catalytic mechanism of these enzymes. PMID:19021508

  14. The Interactions Between Kynurenine, Folate, Methionine and Pteridine Pathways in Obesity.

    Science.gov (United States)

    Engin, Ayse Basak; Engin, Atilla

    2017-01-01

    Obesity activates both innate and adaptive immune responses in adipose tissue. Elevated levels of eosinophils with depression of monocyte and neutrophil indicate the deficiencies in the immune system of morbidly obese individuals. Actually, adipose tissue macrophages are functional antigen-presenting cells that promote the proliferation of interferon-gamma (IFN-gamma)-producing CD4+ T cells in adipose tissue of obese subjects. Eventually, diet-induced obesity is associated with the loss of tissue homeostasis and development of type 1 inflammatory responses in visceral adipose tissue. Activity of inducible indoleamine 2,3-dioxygenase-1 (IDO-1) plays a major role under pro-inflammatory, IFN-gamma dominated settings. One of the two rate-limiting enzymes which can metabolize tryptophan to kynurenine is IDO-1. Tumor necrosis factor-alpha (TNF-alpha) correlates with IDO-1 in adipose compartments. Actually, IDO-1-mediated tryptophan catabolism due to chronic immune activation is the cause of reduced tryptophan plasma levels and be considered as the driving force for food intake in morbidly obese patients. Thus, decrease in plasma tryptophan levels and subsequent reduction in serotonin (5-HT) production provokes satiety dysregulation that leads to increased caloric uptake and obesity. However, after bariatric surgery, weight reduction does not lead to normalization of IDO-1 activity. Furthermore, there is a connection between arginine and tryptophan metabolic pathways in the generation of reactive nitrogen intermediates. Hence, abdominal obesity is associated with vascular endothelial dysfunction and reduced nitric oxide (NO) availability. IFN-gamma-induced activation of the inducible nitric oxide synthase (iNOS) and dissociation of endothelial adenosine monophosphate activated protein kinase (AMPK)- phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt)- endothelial NO synthase (eNOS) pathway enhances oxidative stress production secondary to high-fat diet. Thus, reduced

  15. SIO Ferromanganese Nodule Description file - IDOE Portion

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Scripps Institution of Oceanography compiled descriptions of sediment samples related to ferromanganese deposits, funded through the International Decade of...

  16. Enhanced biodegradation of Pina Cuban crude oil by a culture of mixed marine bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, I.N.; Perigo, E. [Ministry of Science. Inst. of Oceanography, La Habana (Cuba); Bergueiro, J.R.; Pita, A.; Mayol, M.A. [Balearic Island Univ., Palma de Mallorca, Islas Baleares (Spain); Navarro, A. [Ministry of Industry, Oil Research Center, La Habana (Cuba)

    1998-09-01

    The ability of a mixed marine bacteria culture to degrade Pina Cuban crude oil in the presence of nutrients and sea water was studied. Laboratory experiments were conducted in flasks with 100 ml of saline liquid containing 1 per cent crude. The flasks were inoculated with marine bacteria (IDO-225, IDO-226, and IDO-229) at a final concentration of 10{sup 6} cell/ml. The cultures were grown at 29 degrees C for 21 days. Bacterial growth, and surface and interfacial tension were measured after 5, 13 and 21 days. Results showed that the marine bacteria were effective in accelerating the biodegradation process of Pina Cuban oil. The efficiency of the process increased when nutrients were added to the system. This biopreparation also accelerated emulsification of the oil without any negative effects to the natural microbiota. The biological oxygen demand at five days and at the end of the experiment was determined. The biodegradation constant and the biochemical stabilization constant were also measured. 14 refs., 5 tabs., 4 figs.

  17. Enhanced biodegradation of Pina Cuban crude oil by a culture of mixed marine bacteria

    International Nuclear Information System (INIS)

    Joseph, I.N.; Perigo, E.; Bergueiro, J.R.; Pita, A.; Mayol, M.A.; Navarro, A.

    1998-01-01

    The ability of a mixed marine bacteria culture to degrade Pina Cuban crude oil in the presence of nutrients and sea water was studied. Laboratory experiments were conducted in flasks with 100 ml of saline liquid containing 1 per cent crude. The flasks were inoculated with marine bacteria (IDO-225, IDO-226, and IDO-229) at a final concentration of 10 6 cell/ml. The cultures were grown at 29 degrees C for 21 days. Bacterial growth, and surface and interfacial tension were measured after 5, 13 and 21 days. Results showed that the marine bacteria were effective in accelerating the biodegradation process of Pina Cuban oil. The efficiency of the process increased when nutrients were added to the system. This biopreparation also accelerated emulsification of the oil without any negative effects to the natural microbiota. The biological oxygen demand at five days and at the end of the experiment was determined. The biodegradation constant and the biochemical stabilization constant were also measured. 14 refs., 5 tabs., 4 figs

  18. Adolescencia e identidades LGBT en el cine español. Evolución, personajes y significados.

    Directory of Open Access Journals (Sweden)

    Juan Carlos Alfeo Álvarez

    2011-09-01

    Full Text Available Sea como sujeto o como objeto de deseo; aislado en su soledad esencial o vinculado a otros en relaciones simétricas o asimétricas, depositarios de la mayor ingenuidad o lúcidos manipuladores, víctimas o verdugos, cuando no ambas cosas, los personajes homosexuales en su tránsito por la adolescencia constituyen una categoría en sí mismos. Por otra parte el modo en el que han ido siendo representados dice mucho de la evolución del imaginario colectivo en relación con la cuestión homosexual. En este artículo se aborda el desarrollo de las representaciones de los adolescentes homosexuales en el cine español desde las primeras representaciones hasta la actualidad, analizando los personajes que han ido desfilando por las pantallas de la cinematografía española, así como la evolución de los roles y de los significados  que se han ido vinculando a cada uno de ellos.

  19. Global burden, distribution, and interventions for infectious diseases of poverty.

    Science.gov (United States)

    Bhutta, Zulfiqar A; Sommerfeld, Johannes; Lassi, Zohra S; Salam, Rehana A; Das, Jai K

    2014-01-01

    Infectious diseases of poverty (IDoP) disproportionately affect the poorest population in the world and contribute to a cycle of poverty as a result of decreased productivity ensuing from long-term illness, disability, and social stigma. In 2010, the global deaths from HIV/AIDS have increased to 1.5 million and malaria mortality rose to 1.17 million. Mortality from neglected tropical diseases rose to 152,000, while tuberculosis killed 1.2 million people that same year. Substantial regional variations exist in the distribution of these diseases as they are primarily concentrated in rural areas of Sub-Saharan Africa, Asia, and Latin America, with geographic overlap and high levels of co-infection. Evidence-based interventions exist to prevent and control these diseases, however, the coverage still remains low with an emerging challenge of antimicrobial resistance. Therefore, community-based delivery platforms are increasingly being advocated to ensure sustainability and combat co-infections. Because of the high morbidity and mortality burden of these diseases, especially in resource-poor settings, it is imperative to conduct a systematic review to identify strategies to prevent and control these diseases. Therefore, we attempted to evaluate the effectiveness of one of these strategies, that is community-based delivery for the prevention and treatment of IDoP. In this paper, we describe the burden, epidemiology, and potential interventions for IDoP. In subsequent papers of this series, we describe the analytical framework and the methodology used to guide the systematic reviews, and report the findings and interpretations of our analyses of the impact of community-based strategies on individual IDoPs.

  20. Evolución y análisis del canon de belleza aplicado a la moda : análisis de Karl Lagerfeld, John Galliano y Victoria’s Secret (1995 – 2007 – 2016)

    OpenAIRE

    Llorca Martínez, Cayetana; Márquez Martínez, María

    2017-01-01

    El presente trabajo abordará las colecciones de tres de los diseñadores de moda más influyentes de las últimas décadas, John Galiano, Karl Lagerfeld, y la firma de lencería femenina Victoria’s Secret. Será un estudio centrado en la tipología de modelo utilizada en las citadas colecciones con objeto de conocer cómo ha ido evolucionando el canon de belleza a lo largo de la historia y cómo se refleja en la moda actual. Se trata de una evolución variable que ha ido adquiriendo una mayor import...

  1. Estudio de viabilidad de implantación de sistemas urbanos de drenaje sostenible en el área de Santander

    OpenAIRE

    Herrería Liaño, Eduardo

    2014-01-01

    En las últimas décadas, los procesos de urbanización se han incrementado de forma considerable. Consecuentemente, la población que residía en Izonas rurales se ha ido desplazando a las grandes ciudades debido a los cambios que ha ido generando el proceso de industrialización de nuestra producción. En 1999 el 19,4% de la población espanola residía en algún municipio calificado como rural. Apenas diez anos más tarde, el porcentaje de población residente en municipios rurales desciende hasta com...

  2. La exportación de espárragos en el período 2005 - 2010, como contribución al crecimiento de la economía peruana

    OpenAIRE

    Carbajal Ramos, Diego Fernando

    2012-01-01

    El presente trabajo de investigación se refiere a los aportes que pueden dar los Espárragos a la economía peruana, como es sabido ésta ha ido incrementando su producción a medida que se han ido mejorando las condiciones tecnológicas, las que han permitido que mejoren los precios de mercado a nivel mundial y con la apertura del Tratado de Libre Comercio con Estados Unidos y de otros tratados individuales con otros países del mundo se incrementará más , el desarrollo de este sector Agroexportad...

  3. Simbolismo, procesos comunicativos e identidad cultural de la Diablada Pillareña

    OpenAIRE

    Acurio Basantes, Tatiana Andrea

    2009-01-01

    La comunicación ha sido sin duda alguna el medio por el cual el ser humano ha evolucionado y socializado con el paso de los años y ha podido mantenerse en el tiempo por medio del intercambio de información y mensajes. Estos mensajes se han ido conformando por signos y símbolos los mismos que dependiendo la época y la cultura han ido evolucionando y cambiando, Los signos y símbolos han permitido desde la antigüedad una comunicación interna en el ser humano para luego socia...

  4. Circulating Zonulin Correlates with Density of Enteroviruses and Tolerogenic Dendritic Cells in the Small Bowel Mucosa of Celiac Disease Patients.

    Science.gov (United States)

    Vorobjova, Tamara; Raikkerus, Helerin; Kadaja, Lumme; Talja, Ija; Uibo, Oivi; Heilman, Kaire; Uibo, Raivo

    2017-02-01

    Impaired intestinal integrity, including increased permeability of the small bowel mucosa, has been shown in patients with celiac disease (CD) as well as with type 1 diabetes (T1D). Zonulin (ZO, pre-haptoglobin), a tight junction regulator, plays a particular role in the regulation of intestinal barrier function and in the pathogenesis of the above-mentioned diseases. To investigate whether enteroviruses (EVs) and immunoregulatory cells are associated with intestinal permeability in patients with CD alone and with coexistent T1D. Altogether 80 patients (mean age 10.68 ± 6.69 years) who had undergone small bowel biopsy were studied. Forty patients with functional dyspepsia and normal small bowel mucosa formed the control group. The circulating ZO level in sera was evaluated using ELISA. The densities of EV, FOXP3+ regulatory T cells (Tregs), indoleamine 2,3-dioxygenase (IDO+) dendritic cells (DCs) and glutamic acid dexarboxylase (GAD)65+ cells in small bowel mucosa were investigated by immunohistochemistry. The expression analysis of FOXP3, tight junction protein 1 (TJP1), gap junction (GJA1), IDO and CD103 genes was evaluated by real-time PCR. The ZO level was higher in CD patients compared to subjects with a normal small bowel mucosa, particularly in those with Marsh IIIc atrophy (p = 0.01), and correlated with the density of EV (r = 0.63; p = 0.0003) and IDO+ DCs (r = 0.58; p = 0.01) in the small bowel mucosa. The density of GAD65+ epithelial cells was correlated with the density of EV (r = 0.59; p = 0.03) and IDO+ DCs (r = 0.78; p = 0.004) in CD patients. The relative expression of FOXP3 mRNA in the small bowel mucosa tissue was significantly higher in patients with CD, compared to subjects with a normal mucosa, and correlated with the density of EV (r = 0.62; p = 0.017) as well as with the relative expression of IDO mRNA (r = 0.54; p = 0.019). The CD is associated with elevation of the circulating ZO level, the value of which

  5. Vinculos, transferencia y transversalidad en la clinica grupal. Un estudio realizado en la casa de la niñez II, con niños y adolescentes varones entre 8 y 17 años con experiencia de vida en calle

    OpenAIRE

    Leiva, Paola

    2011-01-01

    En América Latina el fenómeno de la callejización se agudiza cada día más transformándose en un problema social, gestando una población vulnerable del entorno callejero. En nuestro país este emergente se ha ido desarrollando a pasos muy gigantescos. UNICEF indica que existe un aproximado de cien millones de niños que viven en las calles del mundo. En algunas metrópolis de América Latina hay más de 100.0001 niños que viven en las calles, se ha ido incrementando este fenómeno y s...

  6. Amino Acid Catabolism in Multiple Sclerosis Affects Immune Homeostasis.

    Science.gov (United States)

    Negrotto, Laura; Correale, Jorge

    2017-03-01

    Amino acid catabolism has been implicated in immunoregulatory mechanisms present in several diseases, including autoimmune disorders. Our aims were to assess expression and activity of enzymes involved in Trp and Arg catabolism, as well as to investigate amino acid catabolism effects on the immune system of multiple sclerosis (MS) patients. To this end, 40 MS patients, 30 healthy control subjects, and 30 patients with other inflammatory neurological diseases were studied. Expression and activity of enzymes involved in Trp and Arg catabolism (IDO1, IDO2, Trp 2,3-dioxygenase [TDO], arginase [ARG] 1, ARG2, inducible NO synthetase) were evaluated in PBMCs. Expression of general control nonrepressed 2 serine/threonine kinase and mammalian target of rapamycin (both molecules involved in sensing amino acid levels) was assessed in response to different stimuli modulating amino acid catabolism, as were cytokine secretion levels and regulatory T cell numbers. The results demonstrate that expression and activity of IDO1 and ARG1 were significantly reduced in MS patients compared with healthy control subjects and other inflammatory neurological diseases. PBMCs from MS patients stimulated with a TLR-9 agonist showed reduced expression of general control nonrepressed 2 serine/threonine kinase and increased expression of mammalian target of rapamycin, suggesting reduced amino acid catabolism in MS patients. Functionally, this reduction resulted in a decrease in regulatory T cells, with an increase in myelin basic protein-specific T cell proliferation and secretion of proinflammatory cytokines. In contrast, induction of IDO1 using CTLA-4 or a TLR-3 ligand dampened proinflammatory responses. Overall, these results highlight the importance of amino acid catabolism in the modulation of the immunological responses in MS patients. Molecules involved in these pathways warrant further exploration as potential new therapeutic targets in MS. Copyright © 2017 by The American Association of

  7. Mass spectrometric measurement of urinary kynurenine-to-tryptophan ratio in children with and without urinary tract infection.

    Science.gov (United States)

    Yarbrough, Melanie L; Briden, Kelleigh E; Mitsios, John V; Weindel, Annette L; Terrill, Cindy M; Hunstad, David A; Dietzen, Dennis J

    2018-04-19

    Indoleamine-2,3-dioxygenase (IDO) catalyzes the first step of tryptophan (Trp) catabolism, yielding kynurenine (Kyn) metabolites. The kynurenine-to-tryptophan (K/T) ratio is used as a surrogate for biological IDO enzyme activity. IDO expression is increased during Escherichia coli urinary tract infection (UTI). Thus, our objective was to develop a method for measurement of Kyn/Trp ratio in human blood and urine and evaluate its use as a biomarker of UTI. A mass spectrometric method was developed to measure Trp and Kyn in serum and urine specimens. The method was applied to clinical urine specimens from symptomatic pediatric patients with laboratory-confirmed UTI or other acute conditions and from healthy controls. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was linear to 500 μmol/L for both Trp and Kyn. Imprecision ranged from 5 to 15% for Trp and 6-20% for Kyn. Analytical recoveries of Trp and Kyn ranged from 96 to 119% in serum and 90-97% in urine. No correlation was found between the K/T ratio and circulating IDO mass (r = 0.110) in serum. Urinary Kyn and Trp in the pediatric test cohort demonstrated elevations in the K/T ratio in symptomatic patients with UTI (median 13.08) and without UTI (median 14.38) compared to healthy controls (median 4.93; p < 0.001 for both comparisons). No significant difference in K/T ratio was noted between symptomatic patients with and without UTI (p = 0.84). Measurement of Trp and Kyn by LC-MS/MS is accurate and precise in serum and urine specimens. While urinary K/T ratio is not a specific biomarker for UTI, it may represent a general indicator of a systemic inflammatory process. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  8. Inhibition of the kynurenine pathway protects against reactive microglial-associated reductions in the complexity of primary cortical neurons.

    Science.gov (United States)

    O'Farrell, Katherine; Fagan, Eimear; Connor, Thomas J; Harkin, Andrew

    2017-09-05

    Brain glia possess the rate limiting enzyme indoleamine 2, 3-dioxygenase (IDO) which catalyses the conversion of tryptophan to kynurenine. Microglia also express kynurenine monooxygenase (KMO) and kynureninase (KYNU) which lead to the production of the free radical producing metabolites, 3-hydroxykynurenine and 3-hydroxyanthranillic acid respectively and subsequently production of the NMDA receptor agonist quinolinic acid. The aim of this study was to examine the effect of IFNγ-stimulated kynurenine pathway (KP) induction in microglia on neurite outgrowth and complexity, and to determine whether alterations could be abrogated using pharmacological inhibitors of the KP. BV-2 microglia were treated with IFNγ (5ng/ml) for 24h and conditioned media (CM) was placed on primary cortical neurons 3 days in vitro (DIV) for 48h. Neurons were fixed and neurite outgrowth and complexity was assessed using fluorescent immunocytochemistry followed by Sholl analysis. Results show increased mRNA expression of IDO, KMO and KYNU, and increased concentrations of tryptophan, kynurenine, and 3-hydroxykynurenine in the CM of IFNγ-stimulated BV-2 microglia. The IFNγ-stimulated BV-2 microglial CM reduced neurite outgrowth and complexity with reductions in various parameters of neurite outgrowth prevented when BV-2 microglia were pre-treated with either the IDO inhibitor, 1-methyltryptophan (1-MT) (L) (0.5mM; 30min), the KMO inhibitor, Ro 61-8048 (1μM; 30min), the synthetic glucocorticoid, dexamethasone (1μM; 2h) -which suppresses IFNγ-induced IDO - and the N-methyl-D-aspartate (NMDA) receptor antagonist, MK801 (0.1μM; 30min). Overall this study indicates that inhibition of the KP in microglia may be targeted to protect against reactive microglial-associated neuronal atrophy. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The modulation of enzyme indoleamine 2,3-dioxygenase from dendritic cells for the treatment of type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Abram DM

    2017-07-01

    Full Text Available Débora Moitinho Abram,1 Luis Gustavo Romani Fernandes,1,2 Antônio Celso Saragossa Ramos Filho,2 Patrícia Ucelli Simioni2–4 1Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Cidade Universitária Zeferino Vaz, Campinas, SP, Brazil; 2Department of Biomedical Science, Faculty of Americana, Americana, SP, Brazil; 3Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas (UNICAMP, Campinas, SP, Brazil; 4Department of Biochemistry and Microbiology, Institute of Biosciences, Universidade Estadual Paulista, UNESP, Rio Claro, SP, Brazil Abstract: Diabetes mellitus type 1 (DM1 is an autoimmune disease in which β-cells of the pancreas islet are destroyed by T lymphocytes. Specific T cells are activated by antigen-presenting cells, mainly dendritic cells (DCs. It is already known that the regulation of tryptophan pathway in DC can be a mechanism of immunomodulation. The enzyme indoleamine 2,3-dioxygenase (IDO is present in many cells, including DC, and participates in the metabolism of the amino acid tryptophan. Recent studies suggest the involvement of IDO in the modulation of immune response, which became more evident after the in vitro demonstration of IDO production by DC and of the ability of these cells to inhibit lymphocyte function through the control of tryptophan metabolism. Current studies on immunotherapies describe the use of DC and IDO to control the progression of the immune response that triggers DM1. The initial results obtained are promising and indicate the possibility of developing therapies for the treatment or prevention of the DM1. Clinical trials using these cells in DM1 patients represent an interesting alternative treatment. However, clinical trials are still in the initial phase and a robust group of assays is necessary. Keywords: autoimmunity, immunoregulation, diabetes mellitus type 1, clinical trials, dendritic cells, indoleamine, tryptophan

  10. Las técnicas de Mindfulness en Educación Infantil

    OpenAIRE

    París Sánchez, María 

    2018-01-01

    El presente trabajo tiene como objetivo realizar una descripción del por qué Mindfulness en el sistema educativo y en los procesos de enseñanza-aprendizaje, en concreto, en la etapa de Educación Infantil. Por un lado, se explican las bases teóricas sobre qué es mindfulness, por qué mindfulness en el ámbito educativo, las técnicas que se utilizan en la práctica, los beneficios de su aplicación, además de cómo se ha ido introduciendo en el aula, así como ha ido formando parte del día a día d...

  11. Infectious Diseases of Poverty in Children: A Tale of Two Worlds.

    Science.gov (United States)

    Hansen, Caitlin; Paintsil, Elijah

    2016-02-01

    "Infectious diseases of poverty" (IDoP) describes infectious diseases that are more prevalent among poor and vulnerable populations, namely human immunodeficiency virus (HIV) infection, tuberculosis (TB), malaria, and neglected tropical diseases (NTDs). In 2013, 190,000 children died of HIV-related causes and there were 550,000 cases and 80,000 TB deaths in children. Children under age 5 account for 78% of malaria deaths annually. NTDs remain a public health challenge in low- and middle-income countries. This article provides an overview of the major IDoP that affect children. Clinicians must be familiar with the epidemiology and clinical manifestations to ensure prompt diagnosis and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. La Responsabilidad Social Empresarial y las finanzas

    Directory of Open Access Journals (Sweden)

    María L. Saavedra García

    2011-12-01

    Full Text Available El objetivo de este artículo consiste en mostrar como la responsabilidad social empresarial (RSE ha ido cobrando importancia en el mundo de las finanzas. Se realizó a través una revisión documental que permitió desarrollar los temas: El rendimiento económico y la Responsabilidad Social Empresarial, Historia y Evolución de la inversión socialmente responsable, la normatividad acerca de Responsabilidad Social Empresarial en el ámbito financiero y los informes financieros integrados; así como la inclusión del análisis de los casos de Enron de Estados Unidos y Comercial Mexicana de México. Se concluye que la RSE ha ido cada vez cobrando mayor importancia en el ámbito de las finanzas, quedando demostrado esto en que se han creado índices de responsabilidad social, con el fin de que los inversionistas sean capaces de identificar las inversiones socialmente responsables, las cuales se encuentran respaldadas por empresas que han invertido en este rubro. Así también, las empresas han ido adoptando de manera voluntaria la generación y presentación de informes de responsabilidad social empresarial, como complemento de la información financiera

  13. Probiotics Differently Affect Gut-Associated Lymphoid Tissue Indolamine-2,3-Dioxygenase mRNA and Cerebrospinal Fluid Neopterin Levels in Antiretroviral-Treated HIV-1 Infected Patients: A Pilot Study.

    Science.gov (United States)

    Scagnolari, Carolina; Corano Scheri, Giuseppe; Selvaggi, Carla; Schietroma, Ivan; Najafi Fard, Saeid; Mastrangelo, Andrea; Giustini, Noemi; Serafino, Sara; Pinacchio, Claudia; Pavone, Paolo; Fanello, Gianfranco; Ceccarelli, Giancarlo; Vullo, Vincenzo; d'Ettorre, Gabriella

    2016-09-27

    Recently the tryptophan pathway has been considered an important determinant of HIV-1 infected patients' quality of life, due to the toxic effects of its metabolites on the central nervous system (CNS). Since the dysbiosis described in HIV-1 patients might be responsible for the microbial translocation, the chronic immune activation, and the altered utilization of tryptophan observed in these individuals, we speculated a correlation between high levels of immune activation markers in the cerebrospinal fluid (CSF) of HIV-1 infected patients and the over-expression of indolamine-2,3-dioxygenase (IDO) at the gut mucosal surface. In order to evaluate this issue, we measured the levels of neopterin in CSF, and the expression of IDO mRNA in gut-associated lymphoid tissue (GALT), in HIV-1-infected patients on effective combined antiretroviral therapy (cART), at baseline and after six months of probiotic dietary management. We found a significant reduction of neopterin and IDO mRNA levels after the supplementation with probiotic. Since the results for the use of adjunctive therapies to reduce the levels of immune activation markers in CSF have been disappointing so far, our pilot study showing the efficacy of this specific probiotic product should be followed by a larger confirmatory trial.

  14. The targeting of immunosuppressive mechanisms in hematological malignancies

    DEFF Research Database (Denmark)

    Andersen, M H

    2014-01-01

    enzymes such as indoeamine-2,3-dioxygenase (IDO). The possible therapeutic targeting of these pathways is also discussed. Exciting new strategies that might affect future antileukemia immunotherapy include monoclonal antibodies that block inhibitory T-cell pathways (PD-1/PD-L1) and the prevention...... of tryptophan depletion by IDO inhibitors. Furthermore, the clinical effect of several chemotherapeutic drugs may arise from the targeting of immunosuppressive cells. Evidence for a new feedback mechanism to suppress the function of regulatory immune cells was recently provided by the identification...... and characterization of spontaneous cytotoxic T lymphocyte (CTL) responses against regulatory immune cells. Such specific CTLs may be immensely useful in anticancer immunotherapy (for example, by anticancer vaccination). The targeting of one or more immunosuppressive pathways may be especially interesting...

  15. The conceptual framework and assessment methodology for the systematic reviews of community-based interventions for the prevention and control of infectious diseases of poverty.

    Science.gov (United States)

    Lassi, Zohra S; Salam, Rehana A; Das, Jai K; Bhutta, Zulfiqar A

    2014-01-01

    This paper describes the conceptual framework and the methodology used to guide the systematic reviews of community-based interventions (CBIs) for the prevention and control of infectious diseases of poverty (IDoP). We adapted the conceptual framework from the 3ie work on the 'Community-Based Intervention Packages for Preventing Maternal Morbidity and Mortality and Improving Neonatal Outcomes' to aid in the analyzing of the existing CBIs for IDoP. The conceptual framework revolves around objectives, inputs, processes, outputs, outcomes, and impacts showing the theoretical linkages between the delivery of the interventions targeting these diseases through various community delivery platforms and the consequent health impacts. We also describe the methodology undertaken to conduct the systematic reviews and the meta-analyses.

  16. Tallinnas möllas 2208 tantsijat / Eveli Rebane

    Index Scriptorium Estoniae

    Rebane, Eveli

    2007-01-01

    Kalevi spordihallis 14.-15. aprillil toimunud rahvusvahelised tantsuvõistlused "Estonian Open Cup" ja "Baltic Cup". Võistlusi korraldab IDO (International Dance Organisation) Eesti haru. "Baltic Cupi" võitjaks tuli Kuressaare tantsutrupp Semiir

  17. Lignans from Carthamus tinctorius suppress tryptophan breakdown via indoleamine 2,3-dioxygenase

    Science.gov (United States)

    Kuehnl, Susanne; Schroecksnadel, Sebastian; Temml, Veronika; Gostner, Johanna M.; Schennach, Harald; Schuster, Daniela; Schwaiger, Stefan; Rollinger, Judith M.; Fuchs, Dietmar; Stuppner, Hermann

    2013-01-01

    Seed extracts of Carthamus tinctorius L. (Asteraceae), safflower, have been traditionally used to treat coronary disease, thrombotic disorders, and menstrual problems but also against cancer and depression. A possible effect of C. tinctorius compounds on tryptophan-degrading activity of enzyme indoleamine 2,3-dioxygenase (IDO) could explain many of its activities. To test for an effect of C. tinctorius extracts and isolated compounds on cytokine-induced IDO activity in immunocompetent cells in vitro methanol and ethylacetate seed extracts were prepared from cold pressed seed cakes of C. tinctorius and three lignan derivatives, trachelogenin, arctigenin and matairesinol were isolated. The influence on tryptophan breakdown was investigated in peripheral blood mononuclear cells (PBMCs). Effects were compared to neopterin production in the same cellular assay. Both seed extracts suppressed tryptophan breakdown in stimulated PBMC. The three structurally closely related isolates exerted differing suppressive activity on PBMC: arctigenin (IC50 26.5 μM) and trachelogenin (IC50 of 57.4 μM) showed higher activity than matairesinol (IC50 >200 μM) to inhibit tryptophan breakdown. Effects on neopterin production were similar albeit generally less strong. Data show an immunosuppressive property of compounds which slows down IDO activity. The in vitro results support the view that some of the anti-inflammatory, anti-cancer and antidepressant properties of C. tinctorius lignans might relate to their suppressive influence on tryptophan breakdown. PMID:23867649

  18. Severe Tryptophan Starvation Blocks Onset of Conventional Persistence and Reduces Reactivation of Chlamydia trachomatis▿

    Science.gov (United States)

    Leonhardt, Ralf M.; Lee, Seung-Joon; Kavathas, Paula B.; Cresswell, Peter

    2007-01-01

    The intracellular survival of the bacterial pathogen Chlamydia trachomatis depends on protein synthesis by the microbe soon after internalization. Pharmacologic inhibition of bacterial translation inhibits early trafficking of the parasitophorous vacuole (inclusion) to the microtubule-organizing center (MTOC) and promotes its fusion with lysosomes, which is normally blocked by Chlamydia. Depletion of cellular tryptophan pools by gamma interferon-inducible indoleamine-2,3-dioxygenase (IDO) is believed to be the major innate immune mechanism controlling C. trachomatis infection in human cells, an action to which the bacteria can respond by converting into a nonreplicating but highly reactivatable persistent state. However, whether severe IDO-mediated tryptophan starvation can be sufficient to fully arrest the chlamydial life cycle and thereby counteract the onset of persistence is unknown. Here we demonstrate that at low exogenous tryptophan concentrations a substantial fraction of C. trachomatis bacteria fail to traffic to the MTOC or to switch into the conventional persistent state in gamma interferon-induced human cells. The organisms stay scattered in the cell periphery, do not retain infectivity, and display only low transcriptional activity. Importantly, the rate at which these aberrant Chlamydia bacteria become reactivated upon replenishment of cellular tryptophan pools is substantially lower. Thus, severe tryptophan depletion in cells with high IDO activity affects chlamydial development more rigorously than previously described. PMID:17724071

  19. Indoleamine 2,3-dioxygenase and iron are required for Mycobacterium leprae survival.

    Science.gov (United States)

    de Mattos Barbosa, Mayara Garcia; da Silva Prata, Rhana Berto; Andrade, Priscila Ribeiro; Ferreira, Helen; de Andrade Silva, Bruno Jorge; da Paixão de Oliveira, Jéssica Araújo; Assis, Tayná Quintella; de Toledo-Pinto, Thiago Gomes; de Lima Bezerra, Ohanna Cavalcanti; da Costa Nery, José Augusto; Rosa, Patricia Sammarco; Bozza, Marcelo Torres; Lara, Flávio Alves; Moraes, Milton Ozório; Schmitz, Veronica; Sarno, Euzenir Nunes; Pinheiro, Roberta Olmo

    2017-11-01

    Our previous study has demonstrated that IL-10 may modulate both indoleamine 2,3-dioxygenase (IDO) and CD163 expression in lepromatous leprosy (LL) cells, favoring Mycobacterium leprae persistence through induction of regulatory pathways and iron storage. Here, we observed that in LL lesion cells there is an increase in the expression of proteins involved in iron metabolism such as hemoglobin (Hb), haptoglobin, heme oxygenase 1 and transferrin receptor 1 (TfR1) when compared to tuberculoid leprosy (BT) cells. We also found increased iron deposits and diminished expression of the iron exporter ferroportin 1 in LL lesion cells. Hemin, but not FeSO 4 stimulation, was able to enhance M. leprae viability by a mechanism that involves IDO. Analysis of cell phenotype in lesions demonstrated a predominance of M2 markers in LL when compared with BT lesion cells. A positive correlation between CD163 and PPARG with the bacillary index (BI) was observed. In contrast, TNF, STAT1 and CSF2 presented a negative correlation with the BI. In summary, this study demonstrates that iron may regulate IDO expression by a mechanism that involves IL-10, which may contribute for the predominance of M2-like phenotype in LL lesions that favors the phagocytosis and maintenance of M. leprae in host cells. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  20. Una perspectiva internacional de la contabilidad

    Directory of Open Access Journals (Sweden)

    Martha Lucia Suarez Suarez

    2005-01-01

    Full Text Available En la medida en que la internacionalización empresarial ha ido intensificándose y va surgiendo un nuevo usuario de la información internacional, la problemática ha ido pasando tanto al ámbito académico como al profesional. Consciente de esta realidad, la Facultad de Contaduría Pública de la Universidad de La Salle ha ido reformando el plan de estudios, e incorporando a los profesores a una visión internacional de la profesión, para atender la demanda formativa en este campo de la Contaduría Pública, para cualificar a los profesionales de la empresa en el escenario que la nueva dimensión internacional de la información contable está creando y necesitando. Uno de los principales objetivos de la contabilidad es proporcionar información útil para la toma de decisiones por parte de los usuarios. Esto adquiere mayor relevancia en la utilización de la información contable, la cual no se ciñe al ámbito nacional, sino que va más allá de las fronteras; la evolución del entorno que rodea a la empresa ha propiciado en los últimos años un proceso de internacionalización de la actividad económica, como consecuencia de la información contable.

  1. Differentiating chondroitin sulfate glycosaminoglycans using collision-induced dissociation; uronic acid cross-ring diagnostic fragments in a single stage of tandem mass spectrometry.

    Science.gov (United States)

    Kailemia, Muchena J; Patel, Anish B; Johnson, Dane T; Li, Lingyun; Linhardt, Robert J; Amster, I Jonathan

    2015-01-01

    The stereochemistry of the hexuronic acid residues of the structure of glycosaminoglycans (GAGs) is a key feature that affects their interactions with proteins and other biological functions. Electron based tandem mass spectrometry methods, in particular electron detachment dissociation (EDD), have been able to distinguish glucuronic acid (GlcA) from iduronic acid (IdoA) residues in some heparan sulfate tetrasaccharides by producing epimer-specific fragments. Similarly, the relative abundance of glycosidic fragment ions produced by collision-induced dissociation (CID) or EDD has been shown to correlate with the type of hexuronic acid present in chondroitin sulfate GAGs. The present work examines the effect of charge state and degree of sodium cationization on the CID fragmentation products that can be used to distinguish GlcA and IdoA containing chondroitin sulfate A and dermatan sulfate chains. The cross-ring fragments (2,4)A(n) and (0,2)X(n) formed within the hexuronic acid residues are highly preferential for chains containing GlcA, distinguishing it from IdoA. The diagnostic capability of the fragments requires the selection of a molecular ion and fragment ions with specific ionization characteristics, namely charge state and number of ionizable protons. The ions with the appropriate characteristics display diagnostic properties for all the chondroitin sulfate and dermatan sulfate chains (degree of polymerization of 4-10) studied.

  2. Prospective randomised controlled trial comparing trigone-sparing versus trigone-including intradetrusor injection of abobotulinumtoxinA for refractory idiopathic detrusor overactivity.

    LENUS (Irish Health Repository)

    Manecksha, Rustom P

    2012-05-01

    Botulinum toxin A is effective for treatment of idiopathic detrusor overactivity (IDO). The trigone is generally spared because of the theoretical risk of vesicoureteric reflux (VUR), although studies assessing injection sites are lacking.

  3. Development of a chemical strategy to produce rare aldohexoses from ketohexoses using 2-aminopyridine.

    Science.gov (United States)

    Hasehira, Kayo; Miyanishi, Nobumitsu; Sumiyoshi, Wataru; Hirabayashi, Jun; Nakakita, Shin-ichi

    2011-12-13

    Rare sugars are monosaccharides that are found in relatively low abundance in nature. Herein, we describe a strategy for producing rare aldohexoses from ketohexoses using the classical Lobry de Bruyn-Alberda van Ekenstein transformation. Upon Schiff-base formation of keto sugars, a fluorescence-labeling reagent, 2-aminopyridine (2-AP), was used. While acting as a base catalyst, 2-AP efficiently promoted the ketose-to-aldose transformation, and acting as a Schiff-base reagent, it effectively froze the ketose-aldose equilibrium. We could also separate a mixture of Sor, Gul, and Ido in their Schiff-base forms using a normal-phase HPLC separation system. Although Gul and Ido represent the most unstable aldohexoses, our method provides a practical way to rapidly obtain these rare aldohexoses as needed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. The Role of IDO in Muc1 Targeted Immunotherapy

    Science.gov (United States)

    2013-01-01

    Besmer*, Teresa L. Tinder , Lopamudra Das Roy, Joseph Lustgarten, Sandra J. Gendler, Pinku Mukherjee Intratumoral Delivery of CpG-Conjugated Anti...3073-87. Epub 2012 Jan 11. PMID: 22238308 3. Mahnaz Sahraei , Lopamudra Das Roy , Jennifer Curry , Teresa Tinder , Sritama Nath , Dahlia M...10.1038/onc.2011.651 4. Dahlia M. Besmer , Dr. Jennifer M. Curry , Dr. Lopamudra D. Roy , Ms. Teresa L. Tinder , Ms. Mahnaz M. Sahraei , Dr

  5. SIO 76-3, Sediment Descriptions from the Studies of East Asia Tectonics and Resources (SEATAR) Program

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The SEATAR files were compiled by the Scripps Institution of Oceanography with funds from IDOE/NSF, as part of the SIO world sediment data bank, under the direction...

  6. The role of indoleamine 2,3 dioxygenase in beneficial effects of stem cells in hind limb ischemia reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Mohamad Masoumy

    Full Text Available Ischemia-Reperfusion (IR injury of limb remains a significant clinical problem causing secondary complications and restricting clinical recovery, despite rapid restoration of blood flow and successful surgery. In an attempt to further improve post ischemic tissue repair, we investigated the effect of a local administration of bone marrow derived stem cells (BMDSCs in the presence or absence of immune-regulatory enzyme, IDO, in a murine model. A whole limb warm ischemia-reperfusion model was developed using IDO sufficient (WT and deficient (KO mice with C57/BL6 background. Twenty-four hours after injury, 5 × 105 cells (5×105 cells/200 µL of PBS solution BMDSCs (Sca1 + cells were injected intramuscularly while the control group received just the vehicle buffer (PBS. Forty-eight to seventy-two hours after limb BMDSC injection, recovery status including the ratio of intrinsic paw function between affected and normal paws, general mobility, and inflammatory responses were measured using video micrometery, flow cytometry, and immunohistochemistry techniques. Additionally, MRI/MRA studies were performed to further study the inflammatory response between groups and to confirm reconstitution of blood flow after ischemia. For the first time, our data, showed that IDO may potentially represent a partial role in triggering the beneficial effects of BMDSCs in faster recovery and protection against structural changes and cellular damage in a hind limb IR injury setting (P = 0.00058.

  7. Análisis discursivo del protocolo en la prensa española

    Directory of Open Access Journals (Sweden)

    Elena Borau Boira

    2014-11-01

    Full Text Available El protocolo, desde sus inicios, se ha ido adaptando a la gran transformación que ha ido experimentando nuestra sociedad y se ha modernizado hacia un mayor funcionalismo y practicidad para ir aportando las soluciones que la realidad va requiriendo. Un protocolo cada vez más simple y efectivo que ha ido dejando atrás la pompa y el boato de antaño. Aun así los medios de comunicación no reflejan esta realidad y siguen representando el protocolo como algo “anclado en el pasado”, casi como obsoleto. Por lo tanto, el objetivo de este artículo es poner de manifiesto la negativa realidad que vive el protocolo en la prensa de nuestro país, para manifestar, en último término, la perjudicial influencia de esta representación para la imagen que esta disciplina tiene en nuestra sociedad. La representación que del protocolo hace la prensa es esencial para una correcta percepción del mismo. Tras llevar a cabo un riguroso análisis del discurso, se pondrán de manifiesto las negativas connotaciones del discurso del protocolo en la prensa, con sus desfavorables consecuencias para la percepción del mismo en la sociedad. En este artículo, por tanto, se reivindica la importancia del binomio protocolo-medios de comunicación, imprescindible para una buena gestión de la comunicación.

  8. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

    Science.gov (United States)

    Kopecka, Joanna; Gazzano, Elena; Sara, Orecchia; Ghigo, Dario; Riganti, Chiara

    2015-01-01

    The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

  9. Reliability and agreement between 2 strength devices used in the newly modified and standardized Constant score

    DEFF Research Database (Denmark)

    Kristensen, Morten Tange; Aagesen, Maria; Hjerrild, Signe

    2014-01-01

    HYPOTHESIS: The new and standardized test protocol for the Constant score (CS) provides new methodology, but different devices are still used for shoulder strength testing. It was hypothesized that strength measurements using the IsoForceControl (IFC) dynamometer (MDS Medical Device Solutions......, Oberburg, Switzerland) would provide results comparable with the IDO isometer (Innovative Design Orthopaedics, Redditch, UK). MATERIALS AND METHODS: Sixty healthy subjects, aged 19 to 83 years, were studied, with 5 men and 5 women in each of 6 ten-year age groups. The IFC and IDO were used in randomized...... order with an 8-minute interval between testing. Subjects performed 3 successive trials with strong verbal encouragement, with 1 minute between trials. The best strength performance was used in the analysis. The rater and subjects were blinded to all results. RESULTS: The IFC produced 0.28-kg (0.62-lb...

  10. UN SEGMENTO DEL TURISMO INTERNACIONAL EN AUGE: EL TURISMO DE CAZA

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rengifo Gallego

    2008-01-01

    Full Text Available El número de turistas internacionales viene creciendo de forma continuada desde que existen fuentes estadísticas. Este crecimiento, que no sólo ha sido cuantitativo, sino espacial, ha ido acompañado de una segmentación del mercado en función de las motivaciones. Entre estos segmentos se halla el turismo cinegético, modalidad que ha experimentado un importante crecimiento en los últimos años por diversos motivos. Este incremento ha ido asociado a la movilidad de un porcentaje importante de cazadores de Europa y Estados Unidos, a la existencia de una gran variedad de especies cinegéticas en el mundo que se distribuyen de forma irregular por el territorio y al desarrollo de un entramado empresarial que participa en la comercialización de la caza.

  11. Detrusor overactivity in diabetic and non-diabetic patients: is there a difference?

    LENUS (Irish Health Repository)

    Golabek, Tomasz

    2013-07-22

    To compare urodynamic characteristics in patients with idiopathic detrusor overactivity (IDO) with those of an age matched cohort with diabetes mellitus (DM) and detrusor overactivity (DO). Secondly, to determine whether urodynamic features could help distinguish these two groups of patients.

  12. Browse Title Index

    African Journals Online (AJOL)

    Items 351 - 400 of 554 ... Vol 6, No 1 (2003), Nitrate, Nitrite and ascorbic acid content of ... and Self-Efficacy for Preventing Childhood Lead Poisoning in Ido Local ... extracts and fractions of Hedranthera barteri leaf in rats and mice, Abstract PDF.

  13. Influência do estrógeno e do interferon γ sobre a expressão da indoleamina-2,3-dioxigenase em cultura de células de placenta e embriões de ratas Wistar

    Directory of Open Access Journals (Sweden)

    Maria Letícia Baptista Salvadori

    2015-09-01

    Full Text Available Resumo: A indoleamina 2,3-dioxigenase (IDO é uma enzima responsável por catabolizar o aminoácido triptofano. Sua presença no ambiente uterino placentário está relacionada à tolerância imunológica ao semi-aloenxerto, pois impede a proliferação de células imunológicas maternas, seja pela falta do aminoácido, ou pela ação de alguns catabólitos oriundos da quebra do triptofano, como o ácido quinolínico, que é tóxico principalmente para os linfócitos T. Pouco se conhece sob a influência de substâncias (hormônios e citocinas presentes na interface materno fetal e a expressão dessa enzima. Por esta razão, formulou-se a hipótese de que hormônios e interleucinas presentes na região uteroplacentária poderiam exercer algum efeito na expressão da IDO. Células oriundas da interface materno fetal de ratas Wistar foram mantidas em cultivo, onde receberam suplementação com estradiol e interferon-γ. A expressão da enzima foi avaliada pela técnica de citometria de fluxo nos períodos de 4, 24 e 48 horas e confirmação da presença proteica por imuno-histoquímica. Os resultados mostraram um aumento na expressão de IDO após a adição de estrógeno (9,03±0,81/11,25±0,25 e interferon-γ (9,03±0,81/20,43±0,60. O efeito do interferon-γ já era esperado como relatado na literatura, contudo, a elevação da expressão da IDO pela adição do estrógeno constitui nova informação sobre possíveis mecanismos envolvidos na ativação da enzima. O melhor esclarecimento desses achados poderia contribuir para uma melhor compreensão da participação dessa enzima na tolerância materno-fetal e para uma futura modulação terapêutica da mesma.

  14. The Lady, the Linguists, and the International Language.

    Science.gov (United States)

    Fettes, Mark

    2001-01-01

    Discusses an extensive research program that was conducted under the auspices of the International Auxiliary Language Association, whose goal was to gather information on Esperanto, Ido, or Latino. Reviews ideological influences that instead led to creation of new hybrid language, Interlingua. (Author/VWL)

  15. Iduronic Acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells

    NARCIS (Netherlands)

    Bartolini, B.; Thelin, M.A.; Svensson, L.; Ghiselli, G.; Kuppevelt, T.H. van; Malmstrom, A.; Maccarana, M.

    2013-01-01

    Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS) proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA), catalyzed by two DS

  16. Challenges and Opportunities in the Discovery of New Therapeutics Targeting the Kynurenine Pathway.

    Science.gov (United States)

    Dounay, Amy B; Tuttle, Jamison B; Verhoest, Patrick R

    2015-11-25

    The kynurenine pathway is responsible for the metabolism of more than 95% of dietary tryptophan (TRP) and produces numerous bioactive metabolites. Recent studies have focused on three enzymes in this pathway: indoleamine dioxygenase (IDO1), kynurenine monooxygenase (KMO), and kynurenine aminotransferase II (KAT II). IDO1 inhibitors are currently in clinical trials for the treatment of cancer, and these agents may also have therapeutic utility in neurological disorders, including multiple sclerosis. KMO inhibitors are being investigated as potential treatments for neurodegenerative diseases, such as Huntington's and Alzheimer's diseases. KAT II inhibitors have been proposed in new therapeutic approaches toward psychiatric and cognitive disorders, including cognitive impairment associated with schizophrenia. Numerous medicinal chemistry studies are currently aimed at the design of novel, potent, and selective inhibitors for each of these enzymes. The emerging opportunities and significant challenges associated with pharmacological modulation of these enzymes will be explored in this review.

  17. Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics.

    Science.gov (United States)

    Kuo, Hann-Chorng

    2011-09-01

    The purpose of this study was to evaluate the efficacy and safety of onabotulinumtoxinA injections at bladder base/trigone and compare with injections at bladder body or bladder body/trigone for the treatment of idiopathic detrusor overactivity (IDO) refractory to antimuscarinics. A single blind, randomized, paralleled, actively controlled trial was performed in patients with urodynamically proven IDO who failed antimuscarinic therapy. Patients were randomly assigned to receive intravesical injections of 100 U of onabotulinumtoxinA into three different bladder sites. All treatments were evaluated by voiding diary variables, urgency severity score, urodynamic studies, and patient perception of bladder condition. Long-term success rates over 12 months were also determined. Among the patients, 37 were randomized to injections in the bladder body, 35 into the bladder body/trigone, and 33 into the bladder base/trigone. Successful results were reported in 76 (72%) patients at 3 months: 26 (70%) in the bladder body group, 26 (74%) in the bladder body/trigone group, and 24 (73%) in the bladder base/trigone group. There were no significant differences in success rates, changes in urgency and urgency incontinence episodes, urodynamic variables, or long-term success rates among the three subgroups. The incidence of adverse events was similar among three groups. No vesicoureteral reflux was noted in all patients with or without involving trigone injection. Intravesical onabotulinumtoxinA injection is an effective treatment for IDO regardless of the bladder injection site. Bladder base/trigone injection is as safe and effective as bladder body injections with or without trigone involvement. Copyright © 2011 Wiley-Liss, Inc.

  18. LA DISTANCIA ENTRE EL DISCURSO JURÍDICO Y LA PRÁCTICA DEL ABORTO EN COLOMBIA

    Directory of Open Access Journals (Sweden)

    Carlos Mario Molina Betancur

    2006-12-01

    Full Text Available La concepción originaria de la Corte Constitucional, respecto de si el nasciturus es poseedor o no del derecho absoluto a la vida, ha ido cambiando gradualmente a medida que han ido pasando las sentencias que han estudiado el tema. No se ha llegado a la idea de considerar que el derecho a la vida se posee, al igual que todos los derechos fundamentales, desde el nacimiento, sin embargo, sí ha ido calando en la Corte la idea que el derecho a la vida del nasciturus, si es que este lo posee, no es absoluto y por eso en ocasiones debe ceder frente a los derechos de la mujer. 'El derecho al aborto y La tolerancia en el discurso iusfilosófico y la vigencia del pensamiento liberal en América Latina' son trabajos de investigación en donde se hace manifiesto el uso del término tolerancia en los diferentes sectores de poder de la sociedad y como argumento de aceptación a la diferencia, por lo tanto, para un país como Colombia, es particularmente problemático que el aborto admita una tolerancia en sentido positivo, esto porque la influencia del discurso religioso es tan fuerte que coarta las decisiones públicas aun en desmedro de las políticas de salud. Por esto se hace necesario elaborar un discurso conciliador entre el estamento político y los pronunciamientos dogmáticos de la iglesia católica en Colombia en lo que al aborto se refiere.

  19. La Guerra Civil en los programas de producción propia de la Televisión de Galicia

    Directory of Open Access Journals (Sweden)

    Mercedes Román Portas

    2013-11-01

    Full Text Available Este trabajo intenta ofrecer una relación exhaustiva de los programas de producción propia emitidos por la Televisión de Galicia sobre la Guerra Civil. Se incluyen documentales, series de ficción, u otras fórmulas de programas (debates, talk shows, etc.. Este material se ha analizado con el fin de conocer cómo se ha ido transmitiendo, y en qué medida ha podido estar teñido por enfoques ideológicos o culturales. Sobre estos análisis se ha elaborado el texto correspondiente. La TVG es una televisión autonómica, de titularidad pública, que inició sus emisiones el 24 de julio de 1985. Desde entonces los directores de la compañía han ido cambiando al compás de los cambios en la presidencia de la Xunta de Galicia. La metodología incluye el visionado de 1.520 minutos (alrededor de 25 horas de cinta pertenecientes al archivo DOPO (documentos de producción propia de la TVG. Dentro de este archivo, se realizó una selección previa de todos aquellos documentos cuya sinopsis o minutaje incluyera los términos "Guerra Civil". Un total de 96 documentos. Una vez revisados los documentos escritos que contenían toda la información sobre los distintos documentales o reportajes, se borraron de la lista aquellos en los que la Guerra Civil era simplemente mencionada (no tratada.

  20. Behavioral Deficits Are Accompanied by Immunological and Neurochemical Changes in a Mouse Model for Neuropsychiatric Lupus (NP-SLE)

    DEFF Research Database (Denmark)

    Li, Yan; Eskelund, Amanda; Zhou, H

    2015-01-01

    pathophysiological mechanisms responsible for NP-SLE are increased peripheral pro-inflammatory cytokines, subsequent induction of indoleamine-2,3-dioxygenase (IDO) and activation of the kynurenine pathway. In the MRL/MpJ-Faslpr (MRL/lpr) murine model of lupus, depression-like behavior and cognitive dysfunction...

  1. Scripps Institution of Oceanography Ferromanganese Nodule Analysis File - IDOE Portion

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Scripps Institution of Oceanography (SIO) compiled data on the geochemistry of marine ferromanganese nodules, funded by the U.S. National Science Foundation...

  2. prevalence and risk factors among secondary school students in Ido ...

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... Male gender, having friends who engaged in sexual activities had association with early ... es young people's risk of infection with HIV and other ..... the influence of alcohol; almost a quarter, 12(20.3%), said .... Desire to win.

  3. The Changing Epidemiology of Infection in Burn Patients,

    Science.gov (United States)

    1992-01-01

    immunosupresores sistdmicos 13. Bruck, H.M., Nash, G.. Foley, F.D., Pruitt, B.A. Jr.: Opportunis- de l leidntdrica ainfccin semanien coo l casa n~s...in burn patients. J. tablecimiento de gdrmenes resistentes recientemente introduc- Trauma 16:824, 1976 idos, en diignosticar.lawifecci6n enkforma

  4. Downregulation of hepatic and intestinal ATP-binding-cassette transporters abcg5 and abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

    NARCIS (Netherlands)

    Bloks, VW; Bakker-van Waarde, WW; Verkade, HJ; Kema, IP; Havinga, R; Wolters, H; Schaap, FG; Sauer, PJJ; Vink, E; Groen, AK; Kuipers, F

    ABSTRACT: P234 Downregulation of Hepatic and Intestinal ATP-Binding-Cassette Transporters Abcg5 and Abcg8 Expression Associated with Altered Sterol Fluxes in Rats with Streptozotocin-Induced Diabetes Vincent W. Bloks, Willie W. Bakker-van Waarde, Henkjan J. Verkade, Ido P. Kema, Rick Havinga, Henk

  5. Indiana Teachers' Perspectives on Testing Accommodations for Limited English Proficient Students Taking the Graduation Qualifying Exam

    Science.gov (United States)

    Hetler, Angela Dawn

    2010-01-01

    This qualitative case study examines teachers' perspectives on testing accommodations for Limited English Proficient (LEP) students taking Indiana's Graduation Qualifying Exam (GQE). The Indiana Department of Education (IDOE) states that the purpose of testing accommodations is to "level the playing field" between LEP students and their…

  6. Rural And Urban Youth Participation In Community Development In ...

    African Journals Online (AJOL)

    The focused on participation in community development activities, constraints to and benefits derived from participation. It compared rural and urban youth participation in community development activities in Ido local government area of Oyo State. Proportionate random sampling was used to select 2 rural, 1 urban ...

  7. Early Posttransplant Tryptophan Metabolism Predicts Long-term Outcome of Human Kidney Transplantation

    NARCIS (Netherlands)

    Vavrincova-Yaghi, Diana; Seelen, Marc A.; Kema, Ido P.; Deelman, Leo E.; Heuvel, van den Marius; Breukelman, Henk; Van den Eynde, Benoit J.; Henning, Rob H.; van Goor, Harry; Sandovici, Maria

    Background. Chronic transplant dysfunction (CTD) is the leading cause of long-term loss of the renal allograft. So far, no single test is available to reliably predict the risk for CTD. Monitoring of tryptophan (trp) metabolism through indoleamine 2.3-dioxygenase (IDO) has been previously proposed

  8. Structural insights into substrate and inhibitor binding sites in human indoleamine 2,3-dioxygenase 1

    Energy Technology Data Exchange (ETDEWEB)

    Lewis-Ballester, Ariel; Pham, Khoa N.; Batabyal, Dipanwita; Karkashon, Shay; Bonanno, Jeffrey B.; Poulos, Thomas L.; Yeh, Syun-Ru (Einstein); (UCI)

    2017-11-22

    Human indoleamine 2,3-dioxygenase 1 (hIDO1) is an attractive cancer immunotherapeutic target owing to its role in promoting tumoral immune escape. However, drug development has been hindered by limited structural information. Here, we report the crystal structures of hIDO1 in complex with its substrate, Trp, an inhibitor, epacadostat, and/or an effector, indole ethanol (IDE). The data reveal structural features of the active site (Sa) critical for substrate activation; in addition, they disclose a new inhibitor-binding mode and a distinct small molecule binding site (Si). Structure-guided mutation of a critical residue, F270, to glycine perturbs the Si site, allowing structural determination of an inhibitory complex, where both the Sa and Si sites are occupied by Trp. The Si site offers a novel target site for allosteric inhibitors and a molecular explanation for the previously baffling substrate-inhibition behavior of the enzyme. Taken together, the data open exciting new avenues for structure-based drug design.

  9. Novedades en el diseño de la prensa digital española (2000-2008

    Directory of Open Access Journals (Sweden)

    José María Caminos

    2008-01-01

    Full Text Available A pesar de su todavía corta vida, el diseño de los principales ciberdiarios españoles muestra ya un notable nivel de evolución respecto a su periodo inicial. Entre los años 2000 y 2008 han ido desapareciendo algunos elementos visuales de su primera etapa (botones de navegación, iconos, menús de salto, etc., a la vez que han ido surgiendo nuevos recursos como los blogs y el RSS. Elementos como la fotografía siguen sin lograr una plena integración en la web. Por otro lado, la publicidad en los cibermedios ha conocido un desarrollo más cuantitativo que cualitativo. Este artículo está basado en un proyecto de investigación financiado por la Universidad del País Vasco, titulado "Diez años de diarios digitales en España: consolidación de contenidos, diseño, publicidad y estrategias comerciales específicas".

  10. Un procedimiento para separar, a alta temperatura, la fase líquida del clínker de los sólidos a los que impregna

    Directory of Open Access Journals (Sweden)

    Ruiz de Gauna, Ángel

    1979-12-01

    Full Text Available Not avaible

    Según se ha ido profundizando en el conocimiento del mecanismo de formación de los silicatos cálcicos hidráulicamente activos del cemento portland, se ha ido poniendo de relieve la gran importancia que la composición de la fase líquida del clínker tiene, tanto en la temperatura y velocidad de formación de aquéllos, como en sus características hidráulicas incluyéndose en ellas las mecánico-resistentes. En las propiedades tecnológicas del cemento resultante influye también directamente la composición que a alta temperatura tiene la fase líquida, por cuanto de ella depende su aptitud a la cristalización, y la clase y propiedades de los componentes secundarios que cristalizan en el curso del enfriamiento y son de decisiva influencia en propiedades tan importantes como la velocidad de fraguado y estabilidad de volumen.

  11. El hispanismo francés y la España contemporánea (historia y literatura

    Directory of Open Access Journals (Sweden)

    Serrano, Carlos

    2001-04-01

    Full Text Available Not available

    La difusión del castellano como segunda lengua extranjera más enseñada —después del inglés— en la educación secundaria francesa ha tenido evidentes efectos para el mundo académico. El interés por el castellano ha conllevado, en efecto, la ampliación de un ingente cupo de estudiantes a las correspondientes Universidades. Estas, a su vez, por su dinámica propia, se han ido multiplicando a lo largo y a lo ancho del país en los últimos años, con sus correspondientes departamentos de español, de tal modo que se ha ido formando un densa red de hispanistas (estudiantes y profesores dedicados a temas españoles y/o iberoamericanos universitarios en Francia, cuya contribución al conocimiento de la historia, de la literatura y de la lengua españolas es, sin embargo, un tanto variopinto…

  12. Transformações em organizações de fruticultura irrigada e a dinâmica do comprometimento organizacional

    Directory of Open Access Journals (Sweden)

    Fabíola Marinho Costa

    Full Text Available As transformações no mundo do trabalho e suas consequências sobre as relações de trabalho enfatizam a importância de se considerar o comprometimento organizacional como um fenômeno que é construído processualmente e que pode se alterar ao longo do tempo, destacando a pertinência da realização de estudos longitudinais. Nesse sentido, o presente trabalho objetiva avaliar o processo de comprometimento afetivo (CA, de comprometimento de continuação (CC, de percepção de suporte organizacional (PSO e de intenção de deixar a organização (IDO, associando-os às transformações organizacionais percebidas pelo gestor e trabalhadores. Foram coletados dados em três organizações de fruticultura irrigada de um mesmo grupo econômico do Vale do São Francisco, em quatro momentos, com intervalos de seis meses. Foram aplicados questionários com questões sobre transformações organizacionais percebidas e quatro escalas: CA, CC, PSO e IDO. Nos quatro tempos, participaram 114, 135, 162 e 162 trabalhadores, respectivamente, tendo 46 participado nos quatro tempos. Os participantes foram, em sua maioria, homens, jovens e de baixa escolaridade. Realizaram-se análises descritivas e comparações de médias. Ao longo dos dois anos investigados, os trabalhadores perceberam mudanças na estrutura física, no processo de trabalho, nas chefias, no quadro de funcionários e destacaram o atraso no pagamento dos salários como uma importante mudança. Na amostra total, observou-se uma redução nas médias de CA e de CC, acompanhadas por uma queda da média de PSO até o tempo 3 e por um aumento de IDO até o tempo 3. A mesma tendência foi observada entre os 46 trabalhadores, tendo ocorrido reduções estatisticamente significativas das médias de PSO entre os tempos 1 e 3, e entre os tempos 2 e 3, e de CA e de CC entre os tempos 2 e 3. Também foi verificado um aumento estatisticamente significativo de IDO entre os tempos 1 e 3. Os achados

  13. Designers coping with culture in an educational setting

    NARCIS (Netherlands)

    Van Boeijen, A.G.C.; Stappers, P.J.

    2012-01-01

    This paper presents the results of a qualitative study about how design students cope with culture in the i-do (international design opportunity) series of international design workshops in Hong Kong. We wanted to learn three things. (1) To what extent do the design students from different nations

  14. Immune modulations during chemoimmunotherapy & novel vaccine strategies - In metastatic melanoma and non small-cell lung cancer

    DEFF Research Database (Denmark)

    Iversen, Trine Zeeberg

    2013-01-01

    . Based on the promising clinical results achieved in the vaccine trial for NSCLC patients, we launched a new clinical trial for MM patients (ongoing patient recruitment) in June 2012. In order to enhance the immune response the vaccine comprises IDO plus Survivin peptide as well as the adjuvants...

  15. Mesenchymal stem cells increase skin graft survival time and up-regulate PD-L1 expression in splenocytes of mice.

    Science.gov (United States)

    Moravej, Ali; Geramizadeh, Bita; Azarpira, Negar; Zarnani, Amir-Hassan; Yaghobi, Ramin; Kalani, Mehdi; Khosravi, Maryam; Kouhpayeh, Amin; Karimi, Mohammad-Hossein

    2017-02-01

    Recently, mesenchymal stem cells (MSCs) have gained considerable interests as hopeful therapeutic cells in transplantation due to their immunoregulatory functions. But exact mechanisms underlying MSCs immunoregulatory function is not fully understood. Herein, in addition to investigate the ability of MSCs to prolong graft survival time, the effects of them on the expression of PD-L1 and IDO immunomodulatory molecules in splenocytes of skin graft recipient mice was clarified. To achieve this goal, full-thickness skins were transplanted from C57BL/6 to BALB/c mice. MSCs were isolated from bone marrow of BALB/c mice and injected to the recipient mice. Skin graft survival was monitored daily to determine graft rejection time. On days 2, 5 and 10 post skin transplantation, serum cytokine levels and expression of PD-L1 and IDO mRNA and protein in the splenocytes of recipient mice were evaluated. The results showed that administration of MSCs prolonged skin graft survival time from 11 to 14 days. On days 2 and 5 post transplantation, splenocytes PD-L1 expression and IL-10 serum level in MSCs treated mice were higher than those in the controls, while IL-2 and IFN-γ levels were lower. Rejection in MSCs treated mice was accompanied by an increase in IL-2 and IFN-γ, and decrease in PD-L1 expression and IL-10 level. No difference in the expression of IDO between MSCs treated mice and controls was observed. In conclusion, we found that one of the mechanisms underlying MSCs immunomodulatory function could be up-regulating PD-L1 expression. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  16. Pain during ice water test distinguishes clinical bladder hypersensitivity from overactivity disorders

    Directory of Open Access Journals (Sweden)

    Bountra Chas

    2006-12-01

    Full Text Available Abstract Background The Bladder cooling reflex (BCR i.e. uninhibited detrusor contractions evoked by intravesical instillation of cold saline, is a segmental reflex believed to be triggered by menthol sensitive cold receptors in the bladder wall, with the afferent signals transmitted by C fibres. The BCR is a neonatal reflex that becomes suppressed by descending signals from higher centres at approximately the time when the child gains full voluntary control of voiding. It re-emerges in adults with neurogenic detrusor overactivity as a consequence of loss of central descending inhibition, resulting from conditions such as spinal cord injury or multiple sclerosis. We have recently shown an increase of nerve fibres expressing the cool and menthol receptor TRPM8 in both overactive (IDO and painful bladder syndrome (PBS, but its functional significance is unknown. We have therefore studied the bladder cooling reflex and associated sensory symptoms in patients with PBS and overactivity disorders. Methods The BCR, elicited by ice water test (IWT was performed in patients with painful bladder syndrome (PBS, n = 17, idiopathic detrusor overactivity (IDO, n = 22, neurogenic detrusor overactivity (NDO, n = 4 and stress urinary incontinence (as controls, n = 21. The IWT was performed by intravesical instillation of cold saline (0 – 4°C. A positive IWT was defined as presence of uninhibited detrusor contraction evoked by cold saline, associated with urgency or with fluid expulsion. Patients were asked to report and rate any pain and cold sensation during the test. Results A positive IWT was observed in IDO (6/22, 27.3% and NDO (4/4, 100% patients, but was negative in all control and PBS patients. Thirteen (76.5% PBS patients reported pain during the IWT, with significantly higher pain scores during ice water instillation compared to the baseline (P = 0.0002, or equivalent amount of bladder filling (100 mls with saline at room temperature (P = 0.015. None

  17. The role of microRNAs on angiogenesis and vascular pressure in ...

    African Journals Online (AJOL)

    Harapan Harapan

    2015-04-28

    Apr 28, 2015 ... parts as miRNAs have diverse effects on preeclampsia patho- ..... sFlt-1: soluble Fms-like tyrosine kinase-1, TGF-b: transforming growth factor beta, VEGF: vascular endothelial growth .... lower VEGF level, and greater insulin resistance than ... expression of IL-6 and indoleamine 2,3-dioxygenase (IDO).

  18. CHAPTER 1

    African Journals Online (AJOL)

    Dr Olaleye

    ABSTRACT. Exposure of school children to lead from various sources, including the school environment, is perilous to their health. In this study, teachers' knowledge of Lead Poisoning (LP) was assessed and the effects of training on their knowledge, perceptions and self-efficacy for preventing childhood LP in Ido Local ...

  19. The Influence of Sex, Marital Status, and Tenure of Service on Job ...

    African Journals Online (AJOL)

    The study examined some demographic factors that interact to influencing the satisfaction that nurses and doctors derive from their jobs. One hundred and ninety one (191) professionals, comprising of one hundred and two (102) nurses and 89 doctors were drawn from Federal Medical Centre, Ido Ekiti in Ekiti State, Nigeria.

  20. Relationships between growth parameters and scrotal ...

    African Journals Online (AJOL)

    scrotal circumference in young Simmentaler bulls. Growth test data from Phase C (National Beef Cattle. Performance and Progeny Testing Scheme) from 129 bulls were obtained from the Simmentaler Cattle Breeders' Society of Southern Africa. The processing of the data was done with the Univac lIDO-computer at the ...

  1. Impact of the Digital Divide on Computer Use and Internet Access on the Poor in Nigeria

    Science.gov (United States)

    Tayo, Omolara; Thompson, Randall; Thompson, Elizabeth

    2016-01-01

    We recruited 20 community members in Ido Local Government Area, Oyo state and Yewa Local Government Area, Ogun state in Nigeria to explore experiences and perceptions of Internet access and computer use. Face-to-face interviews were conducted using open-ended questions to collect qualitative data regarding accessibility of information and…

  2. Modular Digital Missile Guidance, Phase I2

    Science.gov (United States)

    1976-01-28

    transalttal. Jnctf teadt therefore» an analog quantity can oe treated as any other variable In a » articular data block. As the TELE subroutine is...Ido rango of operating conditions» loading to laprovod Sntorcopt »>orforaanca. ftogardloss of how bandwidth and stability aro obtalnod li.o.» how

  3. Prevalence of haemoglobin variants among the Ika ethnic nationality ...

    African Journals Online (AJOL)

    McRoy

    2014-07-26

    Jul 26, 2014 ... mandatory genetic counseling and screening of all intending couples in order to avert the sickling gene pool in our population. REFERENCES. 1. Esan A.J, Omisakin C.T and Okkhuakhua. O. Frequency Distribution of Haemoglobin. Variants, ABO and Rhesus Blood Groups among Children in Ido/Osi Local.

  4. El efecto fin de mes en los principales mercados accionarios latinoamericanos

    Directory of Open Access Journals (Sweden)

    Werner Kristjanpoller Rodríguez

    2015-01-01

    Full Text Available En los mercados accionarios es frecuente encontrar anomalías de calendario, las cuales han sido objeto de diversos estudios en estas últimas décadas, incluso demostrándose que algunas de ellas a través del tiempo han ido desapareciendo. En este contexto, este artículo analiza una de estas anomalías, el efecto fin de mes, tanto en rendimiento como en volatilidad en los mercados accionarios de seis países latinoamericanos; a saber, Brasil, México, Chile, Colombia, Perú y Argentina en el periodo 1993-2011. La importancia de este estudio radica en poder probar si el efecto de fin de mes ha ido desapareciendo o aún persiste, ya que algunos efectos calendario en mercados accionarios desarrollados se han ido disipando. Los hallazgos de esta investigación, que se realizó de acuerdo con los tres periodos diferentes definidos en la literatura para analizar el impacto fin de mes, muestran que la mayoría de los países bajo análisis obtienen rendimientos anormales positivos en los días asociados al cambio de mes y también muestran anomalías en la volatilidad. Esta investigación no solamente analiza los índices característicos de cada mercado, sino que también las acciones en particular de cada uno, dotándolo de una muestra mucho mayor y exigente al momento de concluir sobre la existencia del fenómeno. También se incluye un análisis de volumen de transacción para verificar ciertas hipótesis del fenómeno asociadas a mayor flujo de efectivo.

  5. Plasma Tryptophan and the Kynurenine–Tryptophan Ratio Are Associated with the Acquisition of Statural Growth Deficits and Oral Vaccine Underperformance in Populations with Environmental Enteropathy

    Science.gov (United States)

    Kosek, Margaret N.; Mduma, Estomih; Kosek, Peter S.; Lee, Gwenyth O.; Svensen, Erling; Pan, William K. Y.; Olortegui, Maribel Paredes; Bream, Jay H.; Patil, Crystal; Asayag, Cesar Ramal; Sanchez, Graciela Meza; Caulfield, Laura E.; Gratz, Jean; Yori, Pablo Peñataro

    2016-01-01

    Early childhood enteric infections have adverse impacts on child growth and can inhibit normal mucosal responses to oral vaccines, two critical components of environmental enteropathy. To evaluate the role of indoleamine 2,3-dioxygenase 1 (IDO1) activity and its relationship with these outcomes, we measured tryptophan and the kynurenine–tryptophan ratio (KTR) in two longitudinal birth cohorts with a high prevalence of stunting. Children in rural Peru and Tanzania (N = 494) contributed 1,251 plasma samples at 3, 7, 15, and 24 months of age and monthly anthropometrics from 0 to 36 months of age. Tryptophan concentrations were directly associated with linear growth from 1 to 8 months after biomarker assessment. A 1-SD increase in tryptophan concentration was associated with a gain in length-for-age Z-score (LAZ) of 0.17 over the next 6 months in Peru (95% confidence interval [CI] = 0.11–0.23, P < 0.001) and a gain in LAZ of 0.13 Z-scores in Tanzania (95% CI = 0.03–0.22, P = 0.009). Vaccine responsiveness data were available for Peru only. An increase in kynurenine by 1 μM was associated with a 1.63 (95% CI = 1.13–2.34) increase in the odds of failure to poliovirus type 1, but there was no association with tetanus vaccine response. A KTR of 52 was 76% sensitive and 50% specific in predicting failure of response to serotype 1 of the oral polio vaccine. KTR was associated with systemic markers of inflammation, but also interleukin-10, supporting the association between IDO1 activity and immunotolerance. These results strongly suggest that the activity of IDO1 is implicated in the pathophysiology of environmental enteropathy, and demonstrates the utility of tryptophan and kynurenine as biomarkers for this syndrome, particularly in identifying those at risk for hyporesponsivity to oral vaccines. PMID:27503512

  6. Lipopolysaccharide-induced brain activation of the indoleamine 2,3-dioxygenase and depressive-like behavior are impaired in a mouse model of metabolic syndrome.

    Science.gov (United States)

    Dinel, Anne-Laure; André, Caroline; Aubert, Agnès; Ferreira, Guillaume; Layé, Sophie; Castanon, Nathalie

    2014-02-01

    Although peripheral low-grade inflammation has been associated with a high incidence of mood symptoms in patients with metabolic syndrome (MetS), much less is known about the potential involvement of brain activation of cytokines in that context. Recently we showed in a mouse model of MetS, namely the db/db mice, an enhanced hippocampal inflammation associated with increased anxiety-like behavior (Dinel et al., 2011). However, depressive-like behavior was not affected in db/db mice. Based on the strong association between depressive-like behavior and cytokine-induced brain activation of indoleamine 2,3-dioxygenase (IDO), the enzyme that metabolizes tryptophan along the kynurenine pathway, these results may suggest an impairment of brain IDO activation in db/db mice. To test this hypothesis, we measured the ability of db/db mice and their healthy db/+ littermates to enhance brain IDO activity and depressive-like behavior after a systemic immune challenge with lipopolysaccharide (LPS). Here we show that LPS (5 μg/mouse) significantly increased depressive-like behavior (increased immobility time in a forced-swim test, FST) 24h after treatment in db/+ mice, but not in db/db mice. Interestingly, db/db mice also displayed after LPS treatment blunted increase of brain kynurenine/tryptophan ratio compared to their db/+ counterparts, despite enhanced induction of hippocampal cytokine expression (interleukin-1β, tumor necrosis factor-α). Moreover, this was associated with an impaired effect of LPS on hippocampal expression of the brain-derived neurotrophic factor (BDNF) that contributes to mood regulation, including under inflammatory conditions. Collectively, these data indicate that the rise in brain tryptophan catabolism and depressive-like behavior induced by innate immune system activation is impaired in db/db mice. These findings could have relevance in improving the management and treatment of inflammation-related complications in MetS. Copyright © 2013 Elsevier

  7. Peripheral tumors alter neuroinflammatory responses to lipopolysaccharide in female rats.

    Science.gov (United States)

    Pyter, Leah M; El Mouatassim Bih, Sarah; Sattar, Husain; Prendergast, Brian J

    2014-03-13

    Cancer is associated with an increased prevalence of depression. Peripheral tumors induce inflammatory cytokine production in the brain and depressive-like behaviors. Mounting evidence indicates that cytokines are part of a pathway by which peripheral inflammation causes depression. Neuroinflammatory responses to immune challenges can be exacerbated (primed) by prior immunological activation associated with aging, early-life infection, and drug exposure. This experiment tested the hypothesis that peripheral tumors likewise induce neuroinflammatory sensitization or priming. Female rats with chemically-induced mammary carcinomas were injected with either saline or lipopolysaccharide (LPS, 250μg/kg; i.p.), and expression of mRNAs involved in the pathway linking inflammation and depression (interleukin-1beta [Il-1β], CD11b, IκBα, indolamine 2,3-deoxygenase [Ido]) was quantified by qPCR in the hippocampus, hypothalamus, and frontal cortex, 4 or 24h post-treatment. In the absence of LPS, hippocampal Il-1β and CD11b mRNA expression were elevated in tumor-bearing rats, whereas Ido expression was reduced. Moreover, in saline-treated rats basal hypothalamic Il-1β and CD11b expression were positively correlated with tumor weight; heavier tumors, in turn, were characterized by more inflammatory, necrotic, and granulation tissue. Tumors exacerbated CNS proinflammatory gene expression in response to LPS: CD11b was greater in hippocampus and frontal cortex of tumor-bearing relative to tumor-free rats, IκBα was greater in hippocampus, and Ido was greater in hypothalamus. Greater neuroinflammatory responses in tumor-bearing rats were accompanied by attenuated body weight gain post-LPS. The data indicate that neuroinflammatory pathways are potentiated, or primed, in tumor-bearing rats, which may exacerbate future negative behavioral consequences. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Inducible indoleamine 2,3-dioxygenase 1 and programmed death ligand 1 expression as the potency marker for mesenchymal stromal cells.

    Science.gov (United States)

    Guan, Qingdong; Li, Yun; Shpiruk, Tanner; Bhagwat, Swaroop; Wall, Donna A

    2018-05-01

    Establishment of a potency assay in the manufacturing of clinical-grade mesenchymal stromal cells (MSCs) has been a challenge due to issues of relevance to function, timeline and variability of responder cells. In this study, we attempted to develop a potency assay for MSCs. Clinical-grade bone marrow-derived MSCs were manufactured. The phenotype and immunosuppressive functions of the MSCs were evaluated based on the International Society for Cellular Therapy guidelines. Resting MSCs licensed by interferon (IFN)-γ exposure overnight were evaluated for changes in immune suppression and immune-relevant proteins. The relationship of immune-relevant protein expression with immunosuppression of MSCs was analyzed. MSC supressed third-party T-lymphocyte proliferation with high inter-donor and inter-test variability. The suppression of T-lymphocyte proliferation by IFN-γ-licensed MSCs correlated with that by resting MSCs. Many cellular proteins were up-regulated after IFN-γ exposure, including indoleamine 2,3-dioxygenase 1 (IDO-1), programmed death ligand 1 (PD-L1), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and bone marrow stromal antigen 2 (BST-2). The expression levels of IDO-1 and PD-L1 on licensed MSCs, not VCAM-1, ICAM-1 or BST-2 on licensed MSCs, correlated with MSC suppression of third-party T-cell proliferation. A flow cytometry-based assay of MSCs post-IFN-γ exposure measuring expression of intracellular protein IDO-1 and cell surface protein PD-L1 captures two mechanisms of suppression and offers the potential of a relevant, rapid assay for MSC-mediated immune suppression that would fit with the manufacturing process. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  9. Evolución del Currículo y de las instalaciones a lo largo de la historia de la Educación Física

    Directory of Open Access Journals (Sweden)

    Carlos Aboy Voces

    2009-05-01

    Full Text Available (ES A lo largo de la historia de la educación física, currículo e instalaciones han ido evolucionando conjuntamente. Sin embargo, el espacio actual de educación física está cargado de connotaciones que nos remiten a currículos diferentes al actual.

  10. El Plan Especial de transformación urbana del barrio de La Mina, Barcelona, Premio Nacional de Urbanismo

    OpenAIRE

    Urban, Editor

    2011-01-01

    Lo que ha ido ocurriendo en el barrio de La Mina en los últimos 30 años es un magnífico ejemplo de las luces y sombras que rodean la gran transformación urbana, económica y social que ha sacudido la ciudad de Barcelona y su entorno en estos decenios.

  11. La complejidad social de la discapacidad. Algunos ejemplos de la narración fílmica

    Directory of Open Access Journals (Sweden)

    Cristina Monereo Atienza

    2010-01-01

    Full Text Available Abordar la discapacidad desde una perspectiva multidisciplinar, que recurre a la narración fílmica como método de análisis, puede ayudar a indicar la noción adecuada en referencia a esta realidad dentro de la complejidad terminológica y conceptual existente a nivel jurídico-social. Son muchas las denominaciones utilizadas, y éstas han ido variando en función de los cambios de paradigma en la materia. Se han distinguido tres modelos de tratamiento que, a su vez, han ido apareciendo en la narración fílmica: el tradicional, el médico y el social. Se enfatiza este último ya que entiende la discapacidad como el conjunto de desventajas que el individuo con deficiencias sufre cuando el entorno es incapaz de dar respuesta a sus necesidades. La base político- jurídica está en la dignidad humana concretada en unos derechos fundamentales, en la idea de autonomía y de “inclusión” de la diversidad.

  12. La complejidad social de la discapacidad. Algunos ejemplos de la narración fílmica

    Directory of Open Access Journals (Sweden)

    Cristina Monereo Atienza

    2010-01-01

    Full Text Available Abordar la discapacidad desde una perspectiva multidisciplinar, que recurre a la narración fílmica como método de análisis, puede ayudar a indicar la noción adecuada en referencia a esta realidad dentro de la complejidad terminológica y conceptual existente a nivel jurídico-social. Son muchas las denominaciones utilizadas, y éstas han ido variando en función de los cambios de paradigma en la materia. Se han distinguido tres modelos de tratamiento que, a su vez, han ido apareciendo en la narración fílmica: el tradicional, el médico y el social. Se enfatiza este último ya que entiende la discapacidad como el conjunto de desventajas que el individuo con deficiencias sufre cuando el entorno es incapaz de dar respuesta a sus necesidades. La base político- jurídica está en la dignidad humana concretada en unos derechos fundamentales, en la idea de autonomía y de “inclusión” de la diversidad. 

  13. Immunity and tolerance to fungi in hematopoietic transplantation: Principles and perspectives

    Directory of Open Access Journals (Sweden)

    Agostinho eCarvalho

    2012-06-01

    Full Text Available Resistance and tolerance are two complementary host defence mechanism that increase fitness in response to low-virulence fungi. Resistance is meant to reduce pathogen burden during infection through innate and adaptive immune mechanisms, whereas tolerance mitigate the substantial cost of resistance to host fitness through a multitude of anti-inflammatory mechanisms, including immunological tolerance. In experimental fungal infections, both defense mechanisms are activated through the delicate equilibrium between Th1/Th17 cells, which provide antifungal resistance, and regulatory T cells limiting the consequences of the ensuing inflammatory pathology.Indoleamine 2,3-dioxygenase (IDO, a rate-limiting enzyme in the tryptophan catabolism, plays a key role in induction of tolerance against fungi. Both hematopoietic and nonhematopoietic compartments contribute to the resistance/tolerance balance against Aspergillus fumigatus via the involvement of selected innate receptors converging on IDO. Several genetic polymorphisms in pattern recognition receptors influence resistance and tolerance to fungal infections in human hematopoietic transplantation. Thus, tolerance mechanisms may be exploited for novel diagnostics and therapeutics against fungal infections and diseases.

  14. Structural analysis and biological activity of a highly regular glycosaminoglycan from Achatina fulica.

    Science.gov (United States)

    Liu, Jie; Zhou, Lutan; He, Zhicheng; Gao, Na; Shang, Feineng; Xu, Jianping; Li, Zi; Yang, Zengming; Wu, Mingyi; Zhao, Jinhua

    2018-02-01

    Edible snails have been widely used as a health food and medicine in many countries. A unique glycosaminoglycan (AF-GAG) was purified from Achatina fulica. Its structure was analyzed and characterized by chemical and instrumental methods, such as Fourier transform infrared spectroscopy, analysis of monosaccharide composition, and 1D/2D nuclear magnetic resonance spectroscopy. Chemical composition analysis indicated that AF-GAG is composed of iduronic acid (IdoA) and N-acetyl-glucosamine (GlcNAc) and its average molecular weight is 118kDa. Structural analysis clarified that the uronic acid unit in glycosaminoglycan (GAG) is the fully epimerized and the sequence of AF-GAG is →4)-α-GlcNAc (1→4)-α-IdoA2S (1→. Although its structure with a uniform repeating disaccharide is similar to those of heparin and heparan sulfate, this GAG is structurally highly regular and homogeneous. Anticoagulant activity assays indicated that AF-GAG exhibits no anticoagulant activities, but considering its structural characteristic, other bioactivities such as heparanase inhibition may be worthy of further study. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Inbound Marketing en LinkedIn para la gestión de marca

    Directory of Open Access Journals (Sweden)

    Guadalupe Aguado Guadalupe

    2015-01-01

    Full Text Available El presente trabajo analiza hasta qué punto las prestaciones de Linkedin están orientadas al Inbound Marketing para la gestión de marca, partiendo de que se los usuarios los que llegan a las marcas e interactúan con ellas cuando se produce la necesidad. Para lo cual se requiere de técnicas de comunicación no intrusivas que aporten valor en términos de información, formación, soluciones, experiencia y diversión. Para ello se profundiza en los diferentes usos y herramientas que ha ido desarrollando LinkedIn en su primera y que son esenciales en dicha gestión de marca. Se analiza cómo dicha red ha ido orientando sus prestaciones hacia el marketing de contenidos, el marketing de influencia, el marketing de permiso y el marketing relacional. Se observa cómo se han potenciado estrategias de personalización, buscando la combinación de contenidos relevanes con audiencias relevantes.

  16. Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans

    Czech Academy of Sciences Publication Activity Database

    Stapelberg, M.; Zobalová, Renata; Nguyen, M.N.; Walker, T.; Stantic, M.; Goodwin, J.; Pasdar, E.A.; Thai, T.; Prokopová, Kateřina; Yan, B.; Hall, S.; de Pennington, N.; Thomas, S.R.; Grant, G.; Štursa, Jan; Bajziková, Martina; Meedeniya, A.C.B.; Truksa, Jaroslav; Ralph, S. J.; Ansorge, O.; Dong, L.-F.; Neužil, Jiří

    2014-01-01

    Roč. 67, FEB (2014), s. 41-50 ISSN 0891-5849 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP305/12/1708 Institutional support: RVO:86652036 ; RVO:61388963 Keywords : IDO * Tumor-initiating cells * Mitocans * Mitochondrially targeted vitamin E succinate Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.736, year: 2014

  17. Synthesis of carba sugars from aldonolactones. Part IV. Stereospecific synthesis of carbaheptopyranoses by radical-induced carbocyclisation of 2,3-unsaturated octonolactones

    DEFF Research Database (Denmark)

    Wagner, Sussi Holstein; Lundt, Inge

    2001-01-01

    Three new carbaheptopyranoses, 6-deoxy-5a-carba-beta -L-gulo- (8), 5a-carba-D-glycero-beta -D-ido- (22) and 5a-carba-L-glycero-alpha -L-galacto-heptopyranose (25), have been prepared from 8-bromo-8-deoxy-2,3-unsaturated octono-1,4-lactones with L-galacto-, D-gluco- and D-manno-configuration, resp...

  18. Viviendo Con Incendios: Una guia para los duenos de casas en Nuevo Mexico [Living with Fire: A Guide for the Homeowner-New Mexico

    Science.gov (United States)

    U.S. Department of the Interior Bureau of Land Management

    2008-01-01

    La posibilidad de perdidas humanas y de propiedad en Nuevo Mexico debido a un incendio forestal ha ido incrementando. Para responder a este peligro, entidades locales, estatales, federales, particulares y sin fines de lucro se han unido para crear Como Reducir la Amenaza de Incendios Forestales, un programa dirigido a los propietarios de casas. Este no es un programa...

  19. LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer

    Science.gov (United States)

    2015-11-01

    effect t untreated w on. Occurr 25+ cells at s, sectioned either untreate +,CD25+, Fo eu within Ad- different, indi d-LIGHT trea tiple comparis VA, p...s l . , . s )   Task We t mice LIGH contr show been IDO Ad-C T ce burd 2.2 continu hen isolated and looked T treated ol

  20. Grandes números primos

    OpenAIRE

    Bang, Thöger

    2012-01-01

    En las escuelas danesas la teoría de los números se ha ido restringiendo gradualmente hasta no incluir sino la demostración de la descomposición univoca de los números enteros en números primos y la demostración del teorema clásico de EUCLIDES sobre la existencia de un número primo arbitrariamente grande.

  1. El corredor en la casa de campo. 15 casos entre el mar y la cordillera

    Directory of Open Access Journals (Sweden)

    Hernán Ascui Fernández

    2008-10-01

    Además de sus cualidades de resguardo al clima es un lugar para el descanso, el trabajo y la contemplación. Por su alta eficiencia funcional, el corredor es un ámbito esencial para la vida campesina que se ha ido perfeccionando a través del tiempo en base a la experiencia y los conocimientos enraizados en la cultura local.

  2. Isolation World

    OpenAIRE

    Núñez Martín, Eugeni

    2012-01-01

    El trabajo de fin de grado tiene como nombre “Isolation World”, que en su traducción literal significa “Aislamiento del mundo”, un videojuego diseñado y creado desde cero en su totalidad, utilizando herramientas y conocimiento de lógica en programación que se han ido aprendiendo y desarrollando a lo largo de la carrera.

  3. Comunicación y relevancia en las organizaciones

    DEFF Research Database (Denmark)

    Agustin, Oscar Garcia

    2005-01-01

    La influencia de la teoría y terminología económicas sobre otras disciplinas ha ido aumentando en los últimos años, lo cual supone no sólo medir fenómenos sociales, por ejemplo, con parámetros económicos sino también extender la lógica economicista hacia otros ámbitos....

  4. ITER ITA newsletter. No. 20, February-March 2005

    International Nuclear Information System (INIS)

    2005-03-01

    This issue of ITER ITA (ITER transitional Arrangements) newsletter contains concise information about ITER related activities including interview on the occasion of Academician E.P. Velikhov' 70th birthday conducted by Dr. Lev Golubbchikov, former ITER Contact Person of the Russian Federation and a new document management system of ITER called IDM (ITER Document Management), which supersedes the old IDoMS

  5. Study on search of unknown materials. 1; Michi busshitsu no tansaku ni kansuru kenkyu. 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-11-28

    This is No.92 report of National Institute for Research in Inorganic Materials, concerning search of unknown materials. Purposes of this study are to construct new chemical bond and reaction theory, to systematize the existing compounds, and to search and create the unknown materials, systematically. Structure prediction of electronic state was investigated by means of molecular dynamic method, to determine the electronic state and structure of multi-systems. For the magnetic semiconductors, interactions were investigated between the magnetic spin and electron or hole which is a carrier. The in-solid bond theory aims at clarifying the bond state of materials in which transition metal compounds and inter-electronic interactions are significant. Prediction of the electronic structure of unknown materials can suggest the design of new materials. In the fields of synthesis, design and synthesis of new inorganic ion exchanger and ionic conductor are investigated using Bi oxides and its related materials. There are a lot of compounds having various crystal forms for rare earth element oxides and transition metal oxides. To establish the system of material design, thermodynamics, phase equilibrium diagram, crystal structure, and physical properties of new materials were discussed. 168 refs., 127 figs., 44 tabs.

  6. Material cycling solar system modeled ecosystem; Seitaikei wo model to shita busshitsu junkangata solar system

    Energy Technology Data Exchange (ETDEWEB)

    Sato, M [Hachinohe Institute of Technology, Aomori (Japan)

    1996-10-27

    It is proposed to establish an integrated system close to a natural ecosystem for an industrial complex, taking that in Hachinohe City, Aomori Pref. as the conceptual site. It is a system in which materials are recycled by solar energy and industrial waste heat for a complex food industry. The conceptual site, although blessed with various marine products, are sometimes attacked by cold weather. Waste heat from a 250,000kW power plant, if transported by EHD heat pipes to the site, could provide roughly 400 times the heat required for production of agricultural and marine products, such as cabbages and fish meat. The waste heat, coupled with solar energy, should solve the problems resulting from hot waste water, if they could be utilized for the industrial purposes. The food industrial site that produces agricultural and marine products is considered to be suited as the center of the solar industrial complex incorporating farms. 5 refs., 3 figs.

  7. LA PLANIFICACIÓN Y GESTIÓN DE LOS HUMEDALES DE ANDALUCÍA EN EL MARCO DEL CONVENIO RAMSAR

    Directory of Open Access Journals (Sweden)

    Jonatan Arias-García

    2015-01-01

    Full Text Available Las zonas húmedas de Andalucía han sido objeto de explotación y transformación desde tiempos remotos, lo que ha originado una importante degradación de estos frágiles ecosistemas. Sin embargo, la sociedad ha ido cambiando su percepción y relación con los humedales, evolucionando desde las antiguas desecaciones al actual uso racional y reconocimiento de los valores naturales, bienes y servicios que ofrecen. En este sentido, el Convenio Ramsar ha supuesto un importante punto de partida para los numerosos instrumentos, planes y estrategias que en los últimos años han tratado de garantizar la conservación y revalorización de los humedales. En el presente artículo se realiza una reflexión, sistematización y análisis crítico de las distintas medidas y acciones que se han ido desarrollando para rehabilitar, recuperar y, en definitiva, gestionar las zonas húmedas de Andalucía. Se detecta que las actuaciones derivadas de la planificación resultan insuficientes y dificultan la gestión integral de estos ecosistemas.

  8. Niacin metabolism and indoleamine 2,3-dioxygenase activation in malnourished patients with flaky paint dermatosis.

    Science.gov (United States)

    Maltos, André Luiz; Portari, Guilherme Vannucchi; Moraes, Giselle Vanessa; Monteiro, Marina Casteli Rodrigues; Vannucchi, Helio; da Cunha, Daniel Ferreira

    2015-06-01

    Flaky paint dermatosis, characterized by extensive, often bilateral areas of flaking and pigmentation, mostly in sun unexposed areas is considered a feature of kwashiorkor in both children and adults, and must be differentiated from other dermatosis, including chapped and xerotica skin, and pellagra. In this case series we provide evidence that malnourished patients with flaky paint dermatosis and infection/inflammation shown laboratory data suggestive of indoleamine 2,3-dioxygenase (IDO) activation, besides decreased urinary excretion of N1-methylnicotinamide (N1 MN), a marker of pellagra. We study nine adult patients showing flaky paint dermatosis and clinical features of infection or inflammation, and increased serum C-reactive protein, characteristic of the presence of acute phase response syndrome. As a group, they had low or deficient urinary N1 MN excretion (0.52 ± 0.39 mg/g creatinine) compatible with pellagra. They also showed low serum tryptophan levels (dermatosis showed laboratory data suggestive of IDO activation, besides decreased N1 MN urinary excretion. Taken together, the data support the idea that flaky paint dermatosis could be a skin manifestation of niacin deficiency. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Advanced age negatively impacts survival in an experimental brain tumor model.

    Science.gov (United States)

    Ladomersky, Erik; Zhai, Lijie; Gritsina, Galina; Genet, Matthew; Lauing, Kristen L; Wu, Meijing; James, C David; Wainwright, Derek A

    2016-09-06

    Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. SSDL Newsletter, No. 58, June 2010

    International Nuclear Information System (INIS)

    2010-06-01

    This is a Special Issue of the SSDL Newsletter. After forty years of operation, the service has verified the calibration of approximately 8000 radiotherapy beams in about 1700 hospitals worldwide. Several hundreds of dosimetry deviations have been identified and reconciled, thus avoiding potential dose misadministration to patients. An announcement of the upcoming International Dosimetry Symposium on Standards, Applications and Quality Assurance in Medical Radiation Dosimetry (IDOS) is included on page 5. IDOS will be held at IAEA Headquarters in Vienna during 9-12 November 2010. The IAEA's Dosimetry and Medical Radiation Physics Section focuses on services provided to Member States through the IAEA/WHO SSDL Network and on a system of dose quality audits. The measurement standards of Member States are calibrated, free of charge, at the IAEA's Dosimetry Laboratory. The audits are performed through the IAEA/WHO TLD postal dose audit service for SSDLs and radiotherapy centres. The IAEA Calibration and Measurement Capabilities (CMCs) have been reviewed and published in the CIPM's (Comite International des Poids et Mesures) Appendix C. The Dosimetry Laboratory's Quality Management System has been reviewed and accepted by the Joint Committee of the Regional Metrology Organizations and the BIPM (JCRB)

  11. Alzheimer's disease evaluation using label-free, stainless, fluorescence to measure tryptophan metabolism along the kynurenine pathway

    Science.gov (United States)

    Sordillo, Laura A.; Zhang, Lin; Shi, Lingyan; Sriramoju, Vidyasagar; Sordillo, Peter P.; Alfano, Robert R.

    2018-02-01

    Under stress conditions, pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin 6 and interferon gamma are released. It is known that these cytokines stimulate indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO), which increase tryptophan metabolism through the kynurenine pathway, and that this can cause increased production of neurotoxic compounds. Brain tissues from Alzheimer's disease patients and agematched controls were investigated using label-free fluorescence spectroscopy. Tryptophan (exc. 280/ em. 340 nm) and its metabolites (N-formyl-L-kynurenine (exc. 325/em. 434 nm), kynurenine (exc. 365/em. 480 nm) and kynurenic acid (exc. 330/em. 390 nm)) have distinct spectral profiles. Preliminary results show a difference in the optical signatures in three important areas of the brain (hippocampus, BA 9, BA 17) between patients with Alzheimer's disease and agedmatched controls (normal), and a marked relative increase in tryptophan in the Alzheimer's patients. Thus determinations of tryptophan to tryptophan metabolite ratios could potentially be used to measure IDO and TDO activity and the degree of inflammation in the brain. This label-free optical technique may be useful in the study of Alzheimer's and other neurodegenerative diseases.

  12. Progress in photometry. Sokko ni okeru saikinno shinpo

    Energy Technology Data Exchange (ETDEWEB)

    Krochmann, J

    1991-07-01

    A recent progress in photometry was summarized. As to photometric error, photometric head, luminous intensity, luminous flux, and lighting system, a present situation was introduced. Was described the error in photometry using a silicon photodiode, which became in a level of 0.1% by the self-calibration. Also were illustrated the photometric heads for evaluating spatial luminous intensities, the detector for ratio temperature measurement needed for calibration of a normal standard light source, the filter-type monochromator for measuring a difference of spectral response, and the solar battery for reference which can correct the photometer used for the long period in the field. A measurement of high-speed photocurrent was shown, in which the resolving power of 10{sup {minus}14}ampere (10{sup {minus}6}lux) can be achieved. A goniophotometer for luminous flux measurement was also introduced. Furthermore, the stimulation direct-reading colorimeter, the reflectance and transmission measuring apparatus, the illumination meter with a remote control transmitter, the diffuse reflectance measuring apparatus, and the daylight factor measuring apparatus were illustrated. 14 refs., 11 figs.

  13. Targeting Oxidative Stress, Cytokines and Serotonin Interactions Via Indoleamine 2, 3 Dioxygenase by Coenzyme Q10: Role in Suppressing Depressive Like Behavior in Rats.

    Science.gov (United States)

    Abuelezz, Sally A; Hendawy, Nevien; Magdy, Yosra

    2017-06-01

    Depression is a major health problem in which oxidative stress and inflammation are inextricably connected in its pathophysiology. Coenzyme Q10 (CoQ10) is an important anti-oxidant compound with anti-inflammatory and neuro-protective properties. This study was designed to investigate the hypothesis that CoQ10 by its anti-oxidant and anti-inflammatory potentials can alleviate depressive- like behavior by restoring the balance of the tryptophan catabolites kynurenine/serotonin toward the serotonin pathway by down-regulation of hippocampal indoleamine 2,3-dioxygenase 1 (IDO-1). Depressive-like behavior was induced by chronic unpredictable mild stress (CUMS) protocol including food or water deprivation, cage tilting, reversed light cycle etc. Male Wistar rats were randomly divided into five groups; Control, CUMS, CUMS and CoQ10 (50,100 and 200 mg/kg/day i.p. respectively) groups. CoQ10 effects on different behavioral and biochemical tests were analyzed. CoQ10 showed significant antidepressant efficacy, as evidenced by significantly decreased stress induced changes to forced swimming challenge and open field test, as well as attenuating raised corticosterone level and adrenal glands weight. The anti-oxidant effect of CoQ10 was exhibited by its ability to significantly reduce hippocampal elevated malondialdehyde and 4-hydroxynonenal levels and elevate the reduced glutathione and catalase levels. CoQ10 significantly reduced different pro-inflammatory cytokines levels including interleukin (IL)-1β, IL-2, IL-6 and tumor necrosis factor-α. It suppressed hippocampal IDO-1 and subsequent production of kynurenine and enhanced the hippocampal contents of tryptophan and serotonin. Immunohistochemical analysis revealed that CoQ10 was able to attenuate the elevated microglial CD68 and elevate the astrocyte glial fibrillary acidic protein compared to CUMS group. CoQ10 exhibited antidepressant-like effects on rats exposed to CUMS. This could be attributed to its ability to reduce

  14. [Relationship between intestinal mucosal inflammation and mental disorders in patients with irritable bowel syndrome].

    Science.gov (United States)

    Hao, Jing-xin; Han, Mai; Duan, Li-ping; Han, Ya-jing; Ge, Ying; Huang, Yue-qin

    2012-08-28

    To examine the relationship between inflammation and the comorbidity of mental disorders with irritable bowel syndrome (IBS) by comparing intestinal mucosa inflammatory biomarkers in patients with and without mental disorders. A total of 43 consecutive IBS patients fulfilling the Rome III criteria and 15 volunteers serving as controls without digestive symptoms were recruited and interviewed with Composite International Diagnostic Interview (CIDI) by the well-trained staff and thus classified as with or without mental disorders. All subjects underwent colonoscopy and biopsies were acquired from the mucosa of distal ileum and colon. CD3(+) lymphocytes, mast cells, 5-HT positive cells and (indoleamine 2,3-dioxygenase) IDO positive cells were identified immunohistologically in mucosa biopsies in volunteers (n = 13), IBS patients without mental disorder (n = 24) and IBS patients with mental disorder (n = 19). The incidence of mental disorders in IBS patients was significantly higher than that in the volunteers (19/43 vs 2/15, P = 0.012), including 9 patients with anxiety disorders and 8 with mood disorders. (1) The number of mast cells in IBS patients with mental disorder and that in IBS patients without mental disorder has no statistical significance ((16.7 ± 3.6)/HP vs (15.4 ± 3.1)/HP in distal ileum, (12.8 ± 2.2)/HP vs (12.3 ± 2.5)/HP in sigmoid, both P > 0.05). Similar results were seen in 5-HT positive cells ((3.7 ± 0.9)/HP vs (3.4 ± 0.8)/HP in distal ileum, (6.1 ± 1.8)/HP vs (5.2 ± 1.8)/HP in sigmoid, both P > 0.05). In distal ileum, the number of CD3(+) cells in IBS patients with mental disorder has no statistical significance with that in the IBS patients without mental disorder ((62 ± 16)/HP vs (55 ± 22)/HP, P > 0.05). Similar results were seen in IDO positive cells (6(2, 8)/HP vs 2(1, 5)/HP, P > 0.05). (2) The number of IDO positive cells from distal ileum in IBS patients with anxiety disorder was significantly higher than that in the IBS patients

  15. Agua y energía: producción hidroeléctrica en España

    OpenAIRE

    Cayetano Espejo Marín; Ramón García Marín

    2010-01-01

    La evolución de la energía hidroeléctrica en España en las últimas décadas ha sido siempre creciente, aunque la participación de ésta en el total de eléctrica producida ha ido disminuyendo. Las modernas tecnologías de regulación y control han aumentado la eficiencia de las centrales y del aprovechamiento del recurso agua.

  16. NEOBARROCO VIOLENTO: PERFORMATIVIDADES DEL EXCESO

    OpenAIRE

    Ileana Diéguez

    2011-01-01

    La violencia que se ha desatado en México desde hace más de cuatro años ha ido generando una excesiva espectacularidad que se manifiesta en las mutilaciones corporales y en la exhibición aleccionadora y atemorizante de los mismos. En este estudio abordamos tales manifestaciones como producciones de una gramática neobarroca y como configuraciones de teatralidades y performatividades fuera de las disciplinas del arte.

  17. Terapia biológica en cáncer: nuevos tiempos con una visión optimista

    Directory of Open Access Journals (Sweden)

    Januario E Castro

    2008-07-01

    Full Text Available A medida que las expectativas de vida aumentan también lapoblación de adultos mayores se incrementa, y con ello, elnúmero de pacientes que sufren enfermedades crónicasincluyendo cáncer. Esto ha generado que en muchos paísesindustrializados la incidencia de tumores malignos y lamortalidad asociada a cáncer haya ido aumentandoprogresivamente, siguiendo en orden de frecuencia a lasenfermedades cardiovasculares.

  18. Human Factors Engineering. Part 2. HEDGE (Human Factors Engineering Data Guide for Evaluation)

    Science.gov (United States)

    1983-11-30

    his. telly Ir~O -rtkm1 dew. *or ~ ~ ~ ~ o IrIs leaf .13-2oses 1m I~ ~ wvv wit Ro.w=soI ll., o.W W n t,,. A wop. SOW -ao rmA ido 104151*854044.. .10.0...Footivoielortomb idntitffed. fhetld torae’, Idetoififed. . Eont lskhtiamate a, betel . *Minitttedecadln en Wbt L SID-t 21; -eoOt(r nbiriwoe. -TI "ostep*=’to it

  19. Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

    Science.gov (United States)

    2015-07-01

    Analysis Brain and placenta tissue samples fresh-frozen in liquid nitrogen were ground into a fine powder using a mortar and pestle cooled with...analyzed for 5-HT concentration with HPLC. See (1) for a detailed protocol. The HPLC analysis of perfusion samples was performed on an Eicom 700... analysis revealed significant effects on TRP metabolic gene expression in the placenta. Placental expression of monoamine oxidase A (Maoa), Ido1 and

  20. Biopolíticas de la vejez – Cómo el conocimiento sobre el envejecimiento forma políticas de envejecimiento activo

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    2015-01-01

    economía de las sociedades. Este hecho requiere de técnicas biopolíticas que cambian la forma en la que se vive la vejez y la percepción que se tiene del ciclo vital. En la primera parte del artículo, se expone cómo el ámbito del envejecimiento y de la vejez se ha ido desarrollando a lo largo del siglo XX...

  1. Safety (management and technology). Safety of chemical materials; Anzen (manejimento to tekunoroji). Kagaku busshitsu no anzensei

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, T. [Hosei Univ., Tokyo (Japan). Faculty of Engineering

    1994-08-05

    In chemical materials there exist hazardous materials causing health damages, environmental pollution, fires and explosions. The hazard analysis has been noted as a means for preventing accidents due to chemical materials. This means leads to an effective method of recognizing hazard, evaluating the risk, and lowering the degree of hazard to an allowable level. This paper describes a hazard analysis of autoreactive materials, out of chemical materials causing fires and explosions, which may react by theirselves and cause accidents. In particular, an example is introduced in which this hazard analysis method is adapted to an experimental production of the next generation gas generating agent for automobile collision safety air-bags. In this manufacturing process, in kneading and granulating processes where lots of materials are handled, materials are used in a moistened state, thus countermeasures for preventing occurrence of combustion and explosion being taken. 5 refs., 2 figs., 4 tabs.

  2. Microbial decomposition and bio-remediation of chemical substances. Kagaku busshitsu no biseibutsu bunkai to bio remediation

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, M [Osaka University, Osaka (Japan). Faculty of Engineering

    1993-08-01

    This paper summarizes studies on evaluation of breeding and bio-degradability of decomposition bacteria in bio-remediation, and births and deaths of microorganisms. Structural genes in a phenol decomposition path were separated by means of shotgun cloning. The phe B genes having been taken out were inserted into parent stocks to produce combined stocks for use in phenol decomposition. With 100 mg/l of phenol, the combined stocks showed better performance in both decomposition and multiplication than the parent stocks. When the phenol concentration increases, the rate controlling process changes and loses its effect. Decomposition of trichloroethylene progressed quickly with combined stocks derived from phe A, a phenol decomposed gene. Separated polyvinyl alcohol (PVA) decomposing bacteria were used for PVA decomposition. As a result, it was found that microorganisms are required that utilize intermediately produced low-molecular compounds for multiplication. Combined stocks with E. coli C600 stocks inserted with phe B were prepared to discuss births and deaths of microorganisms in activated sludge. A number of findings was obtained. 6 refs., 10 figs.

  3. Expression of the Kynurenine Pathway in Human Peripheral Blood Mononuclear Cells: Implications for Inflammatory and Neurodegenerative Disease.

    Science.gov (United States)

    Jones, Simon P; Franco, Nunzio F; Varney, Bianca; Sundaram, Gayathri; Brown, David A; de Bie, Josien; Lim, Chai K; Guillemin, Gilles J; Brew, Bruce J

    2015-01-01

    The kynurenine pathway is a fundamental mechanism of immunosuppression and peripheral tolerance. It is increasingly recognized as playing a major role in the pathogenesis of a wide variety of inflammatory, neurodegenerative and malignant disorders. However, the temporal dynamics of kynurenine pathway activation and metabolite production in human immune cells is currently unknown. Here we report the novel use of flow cytometry, combined with ultra high-performance liquid chromatography and gas chromatography-mass spectrometry, to sensitively quantify the intracellular expression of three key kynurenine pathway enzymes and the main kynurenine pathway metabolites in a time-course study. This is the first study to show that up-regulation of indoleamine 2,3-dioxygenase (IDO-1), kynurenine 3-monoxygenase (KMO) and quinolinate phosphoribosyltransferase (QPRT) is lacking in lymphocytes treated with interferon gamma. In contrast, peripheral monocytes showed a significant elevation of kynurenine pathway enzymes and metabolites when treated with interferon gamma. Expression of IDO-1, KMO and QPRT correlated significantly with activation of the kynurenine pathway (kynurenine:tryptophan ratio), quinolinic acid concentration and production of the monocyte derived, pro-inflammatory immune response marker: neopterin. Our results also describe an original and sensitive methodological approach to quantify kynurenine pathway enzyme expression in cells. This has revealed further insights into the potential role of these enzymes in disease processes.

  4. Crear el nacimiento: La medicalización de los conflictos en la reproducción

    Directory of Open Access Journals (Sweden)

    MONTSE JUAN

    1991-01-01

    Full Text Available Estudia la experiencia de la reconstrucción de la maternidad en el área de Barcelona y en la década de los noventa. Es un análisis teórico de los elementos que intervienen en la construcción social de la maternidad. La medicalización de la reproducción se estudia valorando el significado de la tecnología utilizada por los médicos/as a lo largo del proceso reproductivo y, sobre todo, en la "maternidad conflictiva". Abortar, ser madre soltera o ser infértil son situaciones que muestran las contradicciones entre la construcción social de la maternidad y la vivencia real de esa maternidad. A través del conflicto se observan los criterios con que las mujeres se integran en los distintos ámbitos sociales. La tasa de natalidad ha ido decreciendo en estos últimos años al tiempo que las mujeres barcelonesas se han ido integrando en el mercado laboral y en el ámbito académico. Conviene analizar las transformaciones en las relaciones familiares, la vivencia de la sexualidad, el rol de las mujeres, el proceso de medicalización y los mecanismos de desigualdad.

  5. Antitumour agents as inhibitors of tryptophan 2,3-dioxygenase

    Energy Technology Data Exchange (ETDEWEB)

    Pantouris, Georgios; Mowat, Christopher G., E-mail: C.G.Mowat@ed.ac.uk

    2014-01-03

    Highlights: •∼2800 National Cancer Institute USA compounds have been screened as potential inhibitors of TDO and/or IDO. •Seven compounds with anti-tumour properties have been identified as potent inhibitors. •NSC 36398 (taxifolin, dihydroquercetin) is selective for TDO with a K{sub i} of 16 M. •This may help further our understanding of the role of TDO in cancer. -- Abstract: The involvement of tryptophan 2,3-dioxygenase (TDO) in cancer biology has recently been described, with the enzyme playing an immunomodulatory role, suppressing antitumour immune responses and promoting tumour cell survival and proliferation. This finding reinforces the need for specific inhibitors of TDO that may potentially be developed for therapeutic use. In this work we have screened ∼2800 compounds from the library of the National Cancer Institute USA and identified seven potent inhibitors of TDO with inhibition constants in the nanomolar or low micromolar range. All seven have antitumour properties, killing various cancer cell lines. For comparison, the inhibition potencies of these compounds were tested against IDO and their inhibition constants are reported. Interestingly, this work reveals that NSC 36398 (dihydroquercetin, taxifolin), with an in vitro inhibition constant of ∼16 μM, is the first TDO-selective inhibitor reported.

  6. Turismo, territorio y medio ambiente en morella. del P.G.O.U. (1986 a la agenda 21 local (2000

    Directory of Open Access Journals (Sweden)

    Emilio M. Obiol Menero

    2001-01-01

    Full Text Available El presente trabajo intenta analizar desde la perspectiva de la geografía del turismo, esto es atendiendo a las acciones territoriales y ambientales, de qué forma Morella ha ido configurándose como el destino turístico de interior más visitado del País Valenciano. Desde 1964 hasta el año 2000, primero un conjunto de iniciativas públicas y privadas, ilustradas pero relativamente improvisadas, y desde 1980 tres documentos estratégicos de ordenación territorial (PGOU, 1986; PIRCT, 1996; PACA, 2000, han ido sentando las bases para que el turismo posibilite la recuperación activa del patrimonio cultural y dinamice el conjunto de la economía del municipio y de la comarca. En ese contexto, la marca Morella, un producto turístico cultural consolidado, necesita pasar de las acciones cuantitativas de adecuación y puesta en valor turístico a otras cualitativas presididas por la sostenibilidad. Es hora de asumir el reto de la gestión sostenible del turismo, lo que requiere conciliar la conservación natural y cultural con las nuevas perspectivas económicas y sociales que abre la función turística

  7. Towards Applying Climate Change Adaptation

    Directory of Open Access Journals (Sweden)

    Philipp Schmidt-Thomé

    2017-01-01

    Full Text Available La adaptación al cambio climático ha ido cobrando importancia desde comienzos del siglo actual. Históricamente la adaptación, no al cambio climático sino a los eventos atmosféricos extremos, estaba profundamente arraigada en muchas sociedades y en su forma de ocupar el territorio. Con la industria - lización y especialmente con el aumento de la globalización desde los años noventa del pasado siglo, la importancia de una adecuada adaptación al territorio ha ido perdiendo protagonismo, lo que ha aumenta - do la exposición y el riesgo de los asentamientos humanos en áreas potencialmente afectadas por los im - pactos del cambio climático (p.e. subida del nivel de mar y/o por eventos extremos (peligros naturales. Para desarrollar medidas de adaptación al cambio climático es necesario identificar soluciones viables, es decir, viables y aceptables desde el punto de vista socioeconómico. La identificación de estas soluciones factibles va más allá del análisis científico puro puesto que incorpora a todas las partes interesadas, inclui - dos los responsables en la toma de decisiones y el propio conocimiento local.

  8. Agua y energía: producción hidroeléctrica en España

    Directory of Open Access Journals (Sweden)

    Cayetano Espejo Marín

    2010-01-01

    Full Text Available La evolución de la energía hidroeléctrica en España en las últimas décadas ha sido siempre creciente, aunque la participación de ésta en el total de eléctrica producida ha ido disminuyendo. Las modernas tecnologías de regulación y control han aumentado la eficiencia de las centrales y del aprovechamiento del recurso agua.

  9. El papel de la investigación en un observatorio de seguridad alimentaria y nutricional. Experiencia en el departamento de Caldas, Colombia

    Directory of Open Access Journals (Sweden)

    Angélica Pachón Bueno

    2014-09-01

    Full Text Available Los Observatorios Sociales son una herramienta de reconocimiento que ha ido evolucionando durante las últimas tres décadas con fines de monitorear y evaluar el impacto de las políticas púbicas además de convocar a la veeduría ciudadana a partir de la generación de nuevo conocimiento en torno a situaciones particulares de las diversas realidades sociales de nuestros países.

  10. Parálisis facial permanente: corrección quirúrgica con la técnica de Labbé

    Directory of Open Access Journals (Sweden)

    Rubén Yangali

    2008-12-01

    Full Text Available La parálisis facial genera un gran déficit estético y funcional. Las diversas técnicas quirúrgicas han ido evolucionando, a fin de corregir este defecto de la forma más estructural y fisiológica posible. Consideramos que la mioplastia de alargamiento del temporal constituye actualmente la técnica de elección para corregir los casos de parálisis facial permanente.

  11. Development of a Novel Therapeutic Paradigm Utilizing a Mammary Gland-Targeted, Bin-1 Knockout Mouse Model

    Science.gov (United States)

    2008-03-01

    Naphthoquinone Menadione. Included among the naphthoquinone-based compounds evaluated for IDO inhibitory activity was menadione, also known as vitamin K3 (5...phytylated 1,4-naphthoquinone derivative vitamin K1 and the 2-hydroxy derivative 7; the latter was particularly noteworthy given the activity of the...which exhibited low micromolar potency (IC50 ) 1.0 µM) (Table 1). This was a specific feature of this vitamin K precursor molecule, as vitamin K1 (11

  12. PrOtocols for WatERmarking (POWER)

    Science.gov (United States)

    2011-03-01

    Depending on the access policy an access semaphore (or access counter; managed by o.accessAllowed()) can be set (or increased) to limit the number of the...access semaphore can prevent the access if the object is currently processed by another user. Function Description returnObject(onew, IDo...policy a set access semaphore has to be unset. The four primary system functions are accompanied by a set of secondary system functions. The two

  13. Effect of orally administered dipterinyl calcium pentahydrate on oral glucose tolerance in diet-induced obese mice

    OpenAIRE

    Nikoulina, Svetlana E; Fuchs, Dietmar; Moheno, Phillip

    2012-01-01

    Svetlana E Nikoulina1, Dietmar Fuchs2, Phillip Moheno11SanRx Pharmaceuticals, Inc, La Jolla, CA, USA; 2Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, AustriaAbstract: Calcium pterins have been shown to be significant immunotherapeutic agents in models of breast cancer, hepatitis B, and tuberculosis (Bacillus Calmette-Guérin mycobacteria). These compunds modulate the immuno-enzyme indoleamine 2,3-dioxygenase (IDO) and the blood levels of severa...

  14. Immunohistochemical Studies of the Kynurenine Pathway in Morphea

    OpenAIRE

    Noakes, Rowland; Mellick, Nick

    2013-01-01

    Cutaneous sclerosis, resembling that seen in subcutaneous morphea, is a feature of eosinophilic fasciitis and eosinophilia-myalgia syndrome, two conditions in which the kynurenine pathway is known to be activated. To investigate the possibility of activation of the kynurenine pathway in morphea, skin biopsies were taken from involved and non-involved sites in a series of three patients with morphea. Immunohistochemical stains for quinolinic acid and indoleamine 2,3-dioxygenase (IDO) were perf...

  15. Actividad alimentaria de los peces herbívoros y su impacto en arrecifes con diferente nivel de degradación antrópica

    Directory of Open Access Journals (Sweden)

    Alain Durán

    2009-09-01

    Full Text Available Estudiamos la actividad alimentaria de tres peces herbívoros (Sparisoma viride, Scarus iserti y Acanthurus coeruleus y su impacto, en dos arrecifes de coral de Cuba, durante la época seca (febrero y la lluviosa (agosto del 2006. una de las estaciones en los arrecifes está en el lugar de buceo "Acuario" en el parque nacional Guanahacabibes, y es relativamente prístina. La segunda está en la costa norte de la Habana al frente del Instituto de oceanología (IdO y es objeto de presiones de contaminación y pesca. La composición de los peces herbívoros fue analizada, y la intensidad de búsqueda de alimento ("forrajeo" medida para todas las especies de acantúridos y escáridos, contando los mordiscos de peces en 1 m2 durante intervalos de cinco minutos (25 repeticiones. La intensidad de forrajeo fue medida para las fases joven, intermedia, y adulta, contando los mordiscos de peces durante intervalos de 10 minutos (10 repeticiones. La tasa de consumo de algas se estimó usando un coeficiente de biomasa consumida por mordisco, para cada clase de tamaño. La cobertura de algas fue muestreada en transectos de 20 m en línea con cuatro repeticiones en cada sitio. Las piezas de comida fueron evaluadas por medio de muestreo de algas en los sustratos observados con mordiscos. En comparación con Acuario, los herbívoros en IdO mostraron riqueza de especies más baja y mayor densidad de peces pequeños, pero los peces loro de gran tamaño estuvieron casi ausentes debido a la pesca intensiva. La tasa de mordisqueo más alta se observó para los peces de tamaño más pequeño, pero la tasa neta de consumo fue tres veces mayor para los peces de mediano y gran tamaño, los cuales fueron más abundantes en el área protegida. La cobertura de algas fue más baja en Acuario, mientras que en IdO fue muy alta, y la cobertura de coral fue muy baja. En ambas localidades las algas epífitas fueron el alimento preferido. Estos resultados apoyan las

  16. Etiological classification of depression based on the enzymes of tryptophan metabolism.

    Science.gov (United States)

    Fukuda, Katsuhiko

    2014-12-24

    Viewed in terms of input and output, the mechanisms of depression are still akin to a black box. However, there must be main pivots for diverse types of depression. From recent therapeutic observations, both the serotonin (5-HT) and kynurenine pathways of tryptophan metabolism may be of particular importance to improved understanding of depression. Here, I propose an etiological classification of depression, based on key peripheral and central enzymes of tryptophan metabolism. Endogenous depression is caused by a larger genetic component than reactive depression. Besides enterochromaffin and mast cells, tryptophan hydroxylase 1 (TPH1), primarily expressed in the gastrointestinal tract, is also found in 5-hydroxytryptophan-producing cells (5-HTP cells) in normal intestinal enterocytes, which are thought to essentially shunt 5-HT production in 5-HT-producing cells. Genetic studies have reported an association between TPH1 and depression, or the responsiveness of depression to antidepressive medication. Therefore, it is possible that hypofunctional 5-HTP cells (reflecting TPH1 dysfunction) in the periphery lead to deficient brain 5-HT levels. Additionally,it has been reported that higher TPH2 expression in depressed suicides may reflect a homeostatic response to deficient 5-HT levels. Subsequently, endogenous depression may be caused by TPH1 dysfunction combined with compensatory TPH2 activation. Reactive depression results from life stresses and involves the hypothalamic-pituitary-adrenal axis, with resulting cortisol production inducing tryptophan 2,3-dioxygenase (TDO) activation. In secondary depression, caused by inflammation, infection, or oxidative stress, indoleamine 2,3-dioxygenase (IDO) is activated. In both reactive and secondary depression, the balance between 3-hydroxykynurenine (3-HK) and kynurenic acid may shift towards 3-HK production via kynurenine-3-monooxygenase (KMO) activation. By shifting the equilibrium position of key enzymes of tryptophan

  17. Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase.

    Science.gov (United States)

    Sharma, Rajni; Di Dalmazi, Giulia; Caturegli, Patrizio

    2016-08-01

    Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2(h4) mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water. NOD-H2(h4) mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls. CTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory environment. This study

  18. Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase

    Science.gov (United States)

    Sharma, Rajni; Di Dalmazi, Giulia

    2016-01-01

    Background: Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2h4 mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water. Methods: NOD-H2h4 mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls. Results: CTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory

  19. Diseño de un instrumento musical de viento a partir de la gaita hembra de la costa atlántica colombiana

    OpenAIRE

    Rincón Gómez, Ana María; Mesa Trujillo, Daniel

    2007-01-01

    Los instrumentos musicales autóctonos de la costa atlántica, así como de cualquier región Colombiana, son un importante legado de nuestros antepasados. Los conocimientos acerca de su elaboración y su interpretación se han ido transmitiendo a través de las generaciones, conservando su tradición. Muchos de los procesos de fabricación de estos instrumentos no han sido industrializados y siguen siendo netamente artesanales.

  20. Embarazo triple monocorial triamniótico: Experiencia de dos casos y revisión de la literatura

    OpenAIRE

    Valdivieso R,Javiera; Valdés V,Rafael; de Alvarado R,Mercedes; Espinoza G,Juan Pablo; Goity F,Cecilia; Troncoso S,Maite; Schepeler,Manuel; Illanes L,Sebastián; Figueroa D,Horacio

    2014-01-01

    Los embarazos múltiples se consideran una entidad de alto riesgo obstétrico. Su incidencia ha ido en aumento debido a la utilización de técnicas de reproducción asistida y el aumento de la edad materna. Se presentan 2 casos de embarazos triples monocoriales triamnióticos, de sexo femenino y masculino. En ambos embarazos se manifestaron complicaciones, principalmente fetales y neonatales, atribuidas a embarazos múltiples descritas en la literatura.

  1. Fluorescently tagged iminoalditol glycosidase inhibitors as novel biological probes and diagnostics

    DEFF Research Database (Denmark)

    Lundt, Inge; Steiner, Andreas J.; Stütz, Arnold E.

    2006-01-01

    1,5-Dideoxy-1,5-imino-D-glucitol, the corresponding D-manno and L-ido epimers as well as the powerful b-glucosidase inhibitor isofagomine were N-alkylated with di-, tri-, as well as tetraethylene glycol derived straight chain spacer arms by a set of simple standard procedures. The terminal functi...... functional groups of the spacer arms, primary amines, were employed to introduce fluorescent dansyl moieties. Resulting derivatives showed glycosidase inhibitory activities comparable to those of the parent compounds....

  2. Alteraciones alimentarias en pacientes con diagnóstico de Trastorno Bipolar

    OpenAIRE

    Maldonado, Marianela

    2010-01-01

    Las Alteraciones Alimentarias constituyen un importante problema de la Salud Pública en la actualidad. Existen una serie de factores que han ido apareciendo en forma insidiosa como el aumento de su frecuencia y la dificultad en poder ser diagnosticadas y tratadas nutricionalmente en pacientes con Trastorno Bipolar. Los pacientes que presentan esta patología exhiben alteraciones alimentarias que por sus características o su gravedad, no solamente no alcanzan a cumplir con los cr...

  3. El subjetivismo moderno ante el concepto de persona

    OpenAIRE

    Rosal Negre, Thaïs

    2010-01-01

    Tras la formulación del concepto “persona” en la antigüedad y su culminación en cuanto a significado en la tradición cristiana, se apunta en este trabajo cómo el subjetivismo característico de la modernidad ha ido modificando y degradando el contenido del concepto “persona” hasta llegar a nuestros días prácticamente reducido a nada y habiendo perdido su fundamento ontológico.

  4. Immunohistochemical Studies of the Kynurenine Pathway in Morphea

    Directory of Open Access Journals (Sweden)

    Rowland Noakes

    2013-01-01

    Full Text Available Cutaneous sclerosis, resembling that seen in subcutaneous morphea, is a feature of eosinophilic fasciitis and eosinophilia-myalgia syndrome, two conditions in which the kynurenine pathway is known to be activated. To investigate the possibility of activation of the kynurenine pathway in morphea, skin biopsies were taken from involved and non-involved sites in a series of three patients with morphea. Immunohistochemical stains for quinolinic acid and indoleamine 2,3-dioxygenase (IDO were performed.

  5. Between Renewal and Reevaluation. Milestones in French Historiography on the Restoration | Entre la renovación y la reevaluación. Jalones en la historiografía francesa sobre la Restauración

    Directory of Open Access Journals (Sweden)

    Jean-Claude Caron

    2014-12-01

    Full Text Available French historiography of the Restoration is marked by some important milestones. It has gradually abandoned militant writing to become a historic object submitted to a critical view. Despite having been for a long time considered as a nearly forgotten period, it has of late aroused a renewed interest which is made evident by the extension of themes, and by the increasing weight of cultural history which penetrates political, social and religious history. However, the economic history, as well as the compared history of the Restorations in Europe still remains embryonic, in spite of some recent initiatives. | La historiografía francesa sobre la Restauración está marcada por algunos importantes jalones. Poco a poco ha ido escapando de la escritura militante para convertirse en un objeto histórico sometido a una mirada crítica. Aunque durante mucho tiempo fue un período casi abandonado, progresivamente ha ido suscitando mayor interés, algo que puede apreciarse en la ampliación de las temáticas y en el peso creciente de la historia cultural que se infiltra en la historia política, social o religiosa. A pesar de ello, la historia económica o la historia comparada de las Restauraciones en Europa se encuentran todavía en un estado embrionario, a pesar de algunas iniciativas recientemente puestas en marcha.

  6. ATP Release from Chemotherapy-Treated Dying Leukemia Cells Elicits an Immune Suppressive Effect by Increasing Regulatory T Cells and Tolerogenic Dendritic Cells.

    Science.gov (United States)

    Lecciso, Mariangela; Ocadlikova, Darina; Sangaletti, Sabina; Trabanelli, Sara; De Marchi, Elena; Orioli, Elisa; Pegoraro, Anna; Portararo, Paola; Jandus, Camilla; Bontadini, Andrea; Redavid, Annarita; Salvestrini, Valentina; Romero, Pedro; Colombo, Mario P; Di Virgilio, Francesco; Cavo, Michele; Adinolfi, Elena; Curti, Antonio

    2017-01-01

    Chemotherapy-induced immunogenic cell death can favor dendritic cell (DC) cross-priming of tumor-associated antigens for T cell activation thanks to the release of damage-associated molecular patterns, including ATP. Here, we tested the hypothesis that in acute myeloid leukemia (AML), ATP release, along with its well-known immune stimulatory effect, may also contribute to the generation of an immune suppressive microenvironment. In a cohort of AML patients, undergoing combined daunorubicin and cytarabine chemotherapy, a population of T regulatory cells (Tregs) with suppressive phenotype, expressing the immune checkpoint programmed cell death protein 1 (PD-1), was significantly increased. Moving from these results, initial in vitro data showed that daunorubicin was more effective than cytarabine in modulating DC function toward Tregs induction and such difference was correlated with the higher capacity of daunorubicin to induce ATP release from treated AML cells. DCs cultured with daunorubicin-treated AML cells upregulated indoleamine 2,3-dioxygenase 1 (IDO1), which induced anti-leukemia Tregs. These data were confirmed in vivo as daunorubicin-treated mice show an increase in extracellular ATP levels with increased number of Tregs, expressing PD-1 and IDO1 + CD39 + DCs. Notably, daunorubicin failed to induce Tregs and tolerogenic DCs in mice lacking the ATP receptor P2X7. Our data indicate that ATP release from chemotherapy-treated dying cells contributes to create an immune suppressive microenvironment in AML.

  7. Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment.

    Science.gov (United States)

    Chen, Aiping; Zhang, Yonghui; Meng, Gang; Jiang, Dengxu; Zhang, Hailin; Zheng, Meihong; Xia, Mao; Jiang, Aiqin; Wu, Junhua; Beltinger, Christian; Wei, Jiwu

    2017-07-12

    There is an urgent need for novel effective treatment for hepatocellular carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells, but also induce potent antitumour immune responses. The potency and precise mechanisms of antitumour immune activation by attenuated measles virus remain unclear. In this study, we investigated the potency of the measles virus vaccine strain Edmonston (MV-Edm) in improving adoptive CD8 + NKG2D + cells for HCC treatment. We show that MV-Edm-infected HCC enhanced the antitumour activity of CD8 + NKG2D + cells, mediated by at least three distinct mechanisms. First, MV-Edm infection compelled HCC cells to express the specific NKG2D ligands MICA/B, which may contribute to the activation of CD8 + NKG2D + cells. Second, MV-Edm-infected HCC cells stimulated CD8 + NKG2D + cells to express high level of FasL resulting in enhanced induction of apoptosis. Third, intratumoural administration of MV-Edm enhanced infiltration of intravenously injected CD8 + NKG2D + cells. Moreover, we found that MV-Edm and adoptive CD8 + NKG2D + cells, either administered alone or combined, upregulated the immune suppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in HCC. Elimination of IDO1 by fludarabine enhanced antitumour responses. Taken together, our data provide a novel and clinically relevant strategy for treatment of HCC.

  8. LA RACIONALIDAD ECONÓMICA EN NUEVA PERSPECTIVA

    Directory of Open Access Journals (Sweden)

    Jorge Arturo Chaves

    2002-08-01

    Full Text Available Las amenazas a la vida en el planeta, los hechos que han “asaltado al dogma económico” (Daly y Cobb, 1993 tienen mucho que ver con una doble toma de conciencia en la sociedad contemporánea. La primera, sobre lo restringida y esterilizante que resulta una visión economicista para enfrentar los problemas que más preocupan al ser humano hoy: las heridas infligidas al ecosistema, el aumento de la pobreza y la desigualdad, y el crecimiento desproporcionado de la actividad humana en relación a las posibilidades de la biosfera.La segunda, implicada en la anterior, la de darse cuenta que esa limitación está asociada al concepto de suyo estrecho y parcial de racionalidad económica. Enfrentamos aquí el problema del reduccionismo transmitido en el discurso y en la práctica misma de la disciplina económica que, sin embargo, no es exclusivo de ésta ni es atribuible sólo a deficiencias internas de los profesionales que la practican. Existe toda una larga tradición dentro de la cual se ha ido reduciendo de manera progresiva el concepto de razón humana y se ha ido produciendo ese concepto estrecho de racionalidad del que ahora la humanidad realiza esfuerzos por librarse.

  9. Theoretical and experimental study of the intrinsic physical properties of the Mg-MgH{sub 2} system

    Energy Technology Data Exchange (ETDEWEB)

    Puszkiel, Julian A.; Gervasoni, Juana L. [Centro Atomico Bariloche (CAB) - Instituto Balseiro (IB) - Comision Nacional de Energia Atomica (CNEA), Av. Bustillo km 9.5, R8402 AGP S.C. de Bariloche (Argentina)

    2010-06-15

    Due to the fundamental problems of energy source limitations and environmental pollution, hydrogen has become an attractive clean energy source for the future. Despite the fact that the incentive to switch to a hydrogen economy has increased, there are many problems which must be solved. One of the main unsolved issues is hydrogen storage. Among the potential materials to store hydrogen in a safe way, Mg has drawn interest owing to its high hydrogen capacity (7.6 wt%), light weight and low cost. In order to improve the hydrogen capacity of potential storage materials such as Mg, it is important to understand the site preferences of hydrogen atoms in the metal. Such behavior depends mainly on the screening charge density ({delta}n(r)) of the system proton-metallic host, from which all the physical macroscopic properties (viz. V{sub H}, {delta}H{sub S}, B, etc.) and IDOS are determined. In the present work we study the interaction between a proton and Mg as host metal via ab initio calculations, using the Jellium model, based on the density-functional theory (DFT). The macroscopic properties are determined and compared with experimental results and values found in the bibliography. Furthermore, in order to obtain information about the electronic distribution of hydrogen and the nature of the Mg-H bonding, the IDOS is described. (author)

  10. Interleukin-1β: A New Regulator of the Kynurenine Pathway Affecting Human Hippocampal Neurogenesis

    Science.gov (United States)

    Zunszain, Patricia A; Anacker, Christoph; Cattaneo, Annamaria; Choudhury, Shanas; Musaelyan, Ksenia; Myint, Aye Mu; Thuret, Sandrine; Price, Jack; Pariante, Carmine M

    2012-01-01

    Increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. Here, we show for the first time how IL-1β, a pro-inflammatory cytokine shown to be increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. IL-1β was detrimental to neurogenesis, as shown by a decrease in the number of doublecortin-positive neuroblasts (−28%), and mature, microtubule-associated protein-2-positive neurons (−36%). Analysis of the enzymes that regulate the kynurenine pathway showed that IL-1β induced an upregulation of transcripts for indolamine-2,3-dioxygenase (IDO), kynurenine 3-monooxygenase (KMO), and kynureninase (42-, 12- and 30-fold increase, respectively, under differentiating conditions), the enzymes involved in the neurotoxic arm of the kynurenine pathway. Moreover, treatment with IL-1β resulted in an increase in kynurenine, the catabolic product of IDO-induced tryptophan metabolism. Interestingly, co-treatment with the KMO inhibitor Ro 61-8048 reversed the detrimental effects of IL-1β on neurogenesis. These observations indicate that IL-1β has a critical role in regulating neurogenesis whereas affecting the availability of tryptophan and the production of enzymes conducive to toxic metabolites. Our results suggest that inhibition of the kynurenine pathway may provide a new therapy to revert inflammatory-induced reduction in neurogenesis. PMID:22071871

  11. Podemos y la política de la tecnología

    Directory of Open Access Journals (Sweden)

    Gemma Galdon Clavell

    2015-04-01

    Full Text Available El impacto de Podemos en la incorporación de diferentes herramientas tecnológicas al ‘hacer política’ es evidente. Aunque Podemos no fue el único o primer actor en probar muchas de las aplicaciones que hemos ido normalizando o adoptando en los últimos meses, el salto cuantitativo en los niveles de participación y tamaño de las comunidades de usuarias tiene una traducción también cualitativa: las nuevas tecnologías ya no son el guiño ‘moderno’ de estructuras viejas, sino que forman parte del andamio de las nuevas. Sin streaming no hubiera sido posible La Tuerka. Sin redes sociales no se habría creado una comunidad alrededor de las intervenciones televisivas de Pablo Iglesias. Sin Appgree o Agora Voting, la asamblea de Vistalegre no hubiera ido mucho más allá de los pocos miles de asistentes presenciales y la caprichosa cobertura mediática tradicional. Para ‘romper el cerrojo’ de las comunidades y los consensos tradicionales, para la creación del espacio Podemos y la verificación de su hipótesis inicial, estas tecnologías han sido clave. Una vez roto el techo de cristal, no obstante, empiezan a perfilarse los retos de la segunda pantalla.

  12. Removal of chemical substances from the atmosphere by photocatalysis; Hikarishokubai ni yoru kiso kagaku busshitsu no jokyo

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, K; Kutsuna, S [National Institute for Resources and Environment, Tsukuba (Japan)

    1996-01-25

    Suppression at a source is the principle of suppressing air pollution caused by vapor phase chemical substances. For the case of these substances with extremely low concentrations, discussions were given on decomposition by means of photocatalysts (that utilize solar light) to directly purify them in the atmospheric condition. Catalysis takes place in providing and receiving electrons, that is, oxidation and reduction of the electrons, under light irradiation by using photocatalysts in which light excites and causes internal electrons to migrate freely. Titanium oxide was found effective because it is high in catalytic activity, stable chemically, and harmless. Photodecomposition reaction of chlorinated organic compounds on TiO2 proceeds very fast except for fluorocarbons. In practical use, the catalyst must be fixed so that no catalyst powder will scatter around. Porous TiO2 sheets were, therefore, manufactured using fluorine resin as a binder. The sheets were used to have removed successfully NOx, SO2 and low-grade aldehyde with concentrations from 0.01 to 10 ppm (corresponding to gases discharged from a tunnel). Since the catalyst can function even under solar light, it can remove NOx during daytime, and can be regenerated by precipitation (passive environment purification). The catalyst was verified effective when used on roads in urban areas. 16 refs., 9 figs., 3 tabs.

  13. El área metropolitana de Buenos Aires

    Directory of Open Access Journals (Sweden)

    Cristina Malfa del Grosso

    2004-05-01

    Full Text Available Buenos Aires. metropolitana, es cabecera del sistema urbano nacional y en correspondencia con el proceso significativo de desconcentración y centralización-una tipología interna bimodal-, ha ido acrecentando su configuración primática, siendo hoy su jerarquía, dentro de la red nacional de ciudades, de un posicionamiento desproporcionadamente mayor respecto de las dos urbes que le siguen en importancia, Córdoba y Rosario.

  14. Elaboración y validación de una serie de instrumentos para medir la habilidad de pensamiento crítico científico en alumnos de educación primaria

    OpenAIRE

    Morales Ceron, Ángel Floriberto

    2006-01-01

    Conforme la sociedad cambia, exige un mejor servicio educativo, por lo cual la calidad de la educación ha ido evolucionando. Todo este proceso de cambios se ve reflejado en definiciones de calidad, modelos que buscan alcanzar la calidad y programas educativos de calidad propuestos por diferentes autores durante los últimos cincuenta años. Ejemplo de lo anterior es el PEC (Programa Escuelas de Calidad) que el gobierno de México en el año 2001 implemento como estrategia para ...

  15. Utilidad del sistema intrauterino liberador de levonorgestrel (Mirena) en el tratamiento de las metrorragias

    OpenAIRE

    Peláez Mendoza, Jorge

    2010-01-01

    El uso continuo de anticonceptivos hormonales activos mediante la inserción del sistema intrauterino liberador de progestágenos (Levonorgestrel) ha sido de gran utilidad, pues además de la deseada acción anticonceptiva se le añade un efecto positivo de utilidad para el manejo de algunas afecciones ginecológicas, como son la endometriosis, fibromatosis uterina y ciertas disfunciones menstruales, a los que se han ido agregando recientemente nuevas indicaciones. OBJETIVO: Evaluar la utilidad del...

  16. Non-fistulous urinary leakage among women attending a Nigerian family planning clinic

    OpenAIRE

    Ijaiya, Munir’deen; Raji ,; Aboyeji,; Adesina,; Adebara,; Ezeoke,

    2011-01-01

    Munir'deen A Ijaiya1, Hadijat O Raji1, Abiodun P Aboyeji1, Kike T Adesina1, Idowu O Adebara2, Grace G Ezeoke11Department of Obstetrics and Gynaecology, University of Ilorin Teaching Hospital, Ilorin, Nigeria; 2Department of Obstetrics and Gynaecology, Federal Medical Centre, Ido-Ekiti, NigeriaAbstract: Urinary leakage is an important gynecological challenge, which has a substantial impact on quality of life. The aim of this study was to determine the prevalence and types of non-fistul...

  17. Realización de un framework en el back-end de una aplicación móvil en el entorno comercial

    OpenAIRE

    Getino Gavara, Nuria

    2017-01-01

    El comportamiento del consumidor ha cambiado en los últimos años. Las empresas se han ido adaptando a las nuevas tendencias de marketing apostando por utilizar herramientas tecnológicas que les permitan darse a conocer y a su vez, a conocer y satisfacer las necesidades de las nuevas generaciones. Estas basan sus decisiones de compra en herramientas digitales que les proporcionen características sobre los servicios o productos que desean adquirir. Por lo tanto, las empresas no solo deben centr...

  18. Internet: Evolución e Impacto de la Red de Redes

    OpenAIRE

    Medina, Carlos; Beltrán, José

    2016-01-01

    Internet se ha convertido en un fenómeno tecnológico que impacta y transforma la cultura, la economía y la vida de todos. La idea inicial de la misma fue simple, pero ha ido evolucionado a través de décadas en algo más grande que su concepto original. A pesar de que el inicio de la Internet es relativamente reciente, hubo hace mucho tiempo varios individuos que ya la habían visualizado.

  19. Presentación: Nuevas ondas para a televisión universitaria: la Web TV

    Directory of Open Access Journals (Sweden)

    José Ignacio Aguaded Gómez

    2012-01-01

    Full Text Available En los últimos años, las universidades españolas han ido integrando de manera creciente y progresiva en sus webs corporativas portales multimedia de televisión en Internet, con el objeto de dar un impulso de mayor visibilidad a la investigación, la docencia, la vida cultural e institucional y la interacción con la comunidad u la sociedad, mediante la integración y uso de medios audio­visuales digitales.

  20. La Hamaca o el Tajo: Variantes para una Narrativa de la Identidad Nacional

    OpenAIRE

    Mirta Suquet Martínez

    2003-01-01

    A partir del estudio de valoraciones y juicios que han ido conformado el relato de nuestra identidad nacional (cubana), intento develar los procesos de construcción identitaria mediante los cuales hemos sido concebidos como el otro femenino de un sujeto masculino colonizador. Para ello abordo periodos históricos decisivos en la conformación de tal relato identitario (Conquista, Colonia, República, Revolución), y utilizo como fuentes para el análisis, fragmentos de textos narrat...

  1. Variación de la estructura fina de las fibras acrílicas en la hilatura

    OpenAIRE

    Gacén Guillén, Joaquín; Maillo Garrido, Josefina; Manich i Bou, Albert Mª; Ussmane, Mahomed

    2002-01-01

    [ESP] Dos fibras acrílicas comerciales de diferente finura han sido transformadas en hilados en continua de hilar (3.3. dtex) y en hilatura de rotor (1.3 dtex). Los hilos resultantes han sido vaporizados y teñidos en condiciones standard. Las variaciones de la estructura producidas por las operaciones de hilatura, vaporizado y tintura han sido evaluadas a través del ensayo de solubilidad de las fibras acrílicas en una mezcla dimetilformamida/agua (95/5).

  2. Neuro-spect: Imaginología funcional en psiqyuiatría

    OpenAIRE

    Ismael Mena, G.

    2013-01-01

    Durante los últimos años la imagenología funcional presentada por Neuro-Spect se ha ido incorporando progresivamente al diagnóstico diferencial de la patología psiquiátrica especialmente trastorno del ánimo, psicosis, esquizofrenia, trastornos cognitivos como enfermedad de Alzheimer´s, el trastorno obsesivo compulsivo, el déficit atencional y sobretodo los efectos cerebrales de neurotóxicos. En este trabajo publicaremos y comentaremos inicialmente los hallazgos en infarto cerebral hiper-agudo...

  3. Obtención de extractos polifenólicos a partir de uva para uso alimentario

    OpenAIRE

    Larrea Posadas, Javier

    2012-01-01

    La uva (Vitis vinífera) es conocida en todo el mundo por ser la fruta de la que procede el vino. Durante la vinificación se desprenden del fruto subproductos como las pepitas, pieles, etc. que últimamente están cobrando especial importancia debido a su contenido en polifenoles y sus propiedades antioxidantes. Diversos estudios han ido dirigidos a investigar diferentes métodos de extracción para obtener extractos con la mayor cantidad de polifenoles posibles y elevados valores ...

  4. Las ciudades en la Web. Barcelona y Turín: el storytelling del turismo y del ocio

    OpenAIRE

    Soro, Elsa

    2014-01-01

    El presente trabajo parte de la necesidad de comprender y describir el funcionamiento del sistema mediático dentro del escenario urbano contemporáneo, en el cual los sectores productivos tradicionales se han visto progresivamente eclipsados, y los sectores recreativos y de la cultura han ido adquiriendo una importancia creciente, convirtiéndose así en agentes involucrados en la producción de imágenes y representaciones urbanas. La creciente relevancia dentro del sistema-ciudad del reino...

  5. Mensaje de la Presidenta de la Asociación Española de Investigación para la Paz (AIPAZ

    Directory of Open Access Journals (Sweden)

    Manuela Mesa

    2008-06-01

    Full Text Available La investigación para la paz en España cuenta con una larga trayectoria. A lo largo de estos años, se han ido consolidando distintas iniciativas, que desde diversos enfoques han abordado la paz y los conflictos, ofreciendo nuevas visiones y discursos, que nos permiten analizar el mundo en el que vivimos desde los valores de la justicia y la solidaridad y la resolución pacífica de conflictos.

  6. Study of street-blockades caused by a large earthquake; Daishinsaiji ni okeru doro heisoku ni knsuru kenkyu (Hanshin Awaji daishinsai ni okeru jittai bunseki)

    Energy Technology Data Exchange (ETDEWEB)

    Imaizumi, K. [Kajima Corp., Tokyo (Japan); Asami, Y. [The University of Tokyo, Tokyo (Japan)

    1999-09-30

    The Great Hanshin-Awaji Earthquake caused great damage to roads. Not only on highways, but even in regional communities, a considerable number of streets became unusable because of falls of buildings, etc. to roads and occurrence of bumps. It provided obstacles in refuge and rescue activities. In building cities preparing for earthquake in future, it is important to re-evaluate how to make the road network including narrow streets. Therefore, paying attention to the physical distance of the roads in earthquake and the number of the points which people cannot reach, clarified was the relation between those phenomena and the characteristics of towns/roads which the region has. As an example of Higashinada-ward, Kobe-city, this report analyzed the data on the actual state from the aspects written below which become especially important in actions taken immediately after earthquake, and described the information/knowledge obtained therefrom: (1) difference in arrival distance between usually and in earthquake in case of walking from residence place to refuge place; (2) state of occurrence of the points where people cannot reach in going to hospitals by ambulance. (NEDO)

  7. El abordaje de cuestiones bioéticas en la enseñanza de las ciencias naturales y de la salud a través del cine

    OpenAIRE

    Cambra Badii, Irene

    2017-01-01

    La Bioética permite integrar conocimientos relacionados con el cuidado de los seres humanos, los animales, las plantas y el medio ambiente. Teniendo en cuenta que la necesidad de construir conocimiento para la promoción de la salud, la prevención y el tratamiento de las enfermedades ha ido originando distintas preocupaciones bioéticas, en este trabajo proponemos una articulación entre esta disciplina y las ideas y concepciones respecto a la naturaleza de la ciencia y a los modos de construcci...

  8. El abordaje de cuestiones bioéticas en la enseñanza de las ciencias naturales y de la salud a través del cine

    OpenAIRE

    Cambra Badii, Irene

    2017-01-01

    La Bioética permite integrar conocimientos relacionados con el cuidado de los seres humanos, los animales, las plantas y el medio ambiente. Teniendo en cuenta que la necesidad de construir conocimiento para la promoción de la salud, la prevención y el tratamiento de las enfermedades ha ido originando distintas preocupaciones bioéticas, en este trabajo proponemos una articulación entre esta disciplina y las ideas y concepciones respecto a la naturaleza de la ciencia y a los modos de co...

  9. Caso clínico-radiológico: sífilis congénita

    OpenAIRE

    F. Ximena Ortega, Dra.; B. Karla Moënne, Dra.; Dr. C. Mauricio Pinto; Dr. A. Salinas José; Dr. S. Stefan Hossiason; Dr. W. Fredy Ribert; Dr. M. Marcos Skarmeta

    2011-01-01

    La sífilis es una infección potencialmente devastadora en el recién nacido, cuya incidencia ha ido aumentando. Se presenta el caso de un prematuro que evoluciona con falla respiratoria y compromiso multisistémico precoz secundario a sífilis congénita. Se comentan hallazgos en el examen físico, laboratorio e imágenes. Se discute sobre las formas de presentación en el niño, pruebas diagnósticas y diagnóstico diferencial.

  10. Revisión de resultados experimentales en técnicas de prueba y de educción de conocimientos

    OpenAIRE

    Guerini, Mario L.; Fernández, E.; Britos, Paola Verónica; García-Martínez, E.

    2008-01-01

    La cantidad de experimentos realizados en el ámbito de la ingeniería del software ha ido aumentando considerablemente en los últimos años. Estos experimentos cubren un amplio rango de temas, como por ejemplo, técnicas de pruebas en software, técnicas de educción de conocimientos, lenguajes de programación, etc. Sin embargo, si los experimentos no son tratados como investigaciones controladas, formales y rigurosas, existe un riesgo de obtener conclusiones que carezcan de validez. En este re...

  11. Registro Nacional sobre Programas de Rehabilitación Cardíaca en México (RENAPREC)

    OpenAIRE

    Ilarraza Lomelí, Hermes; Herrera Franco, Rodolfo; Lomelí Rivas, Álvaro; Zavala Ramírez, Juana; Martínez Ramírez, Leonel; Ramos Becerril, Francisco José; Romo Escamilla, Ricardo Elías; Pacheco Beltrán, Nancy; Alonso Sánchez, Jesús; Mendoza Díaz, Pedro Miguel; Álvarez Cerro, Margarita; Cassaigne Guasco, María Elena; Muñoz Gutiérrez, Luz María Mayela

    2009-01-01

    Los programas de rehabilitación cardiovascular y prevención secundaria conforman una serie de maniobras terapéuticas, basadas en programas de entrenamiento físico y reducción del perfil de riesgo cardiovascular y han mostrado ser una maniobra eficaz de control de las enfermedades cardiovasculares. En México, estos programas se iniciaron en 1944 y, con el paso del tiempo, se han ido integrando diversas instituciones, tanto públicas como privadas, que han trabajado, en general, de forma aislada...

  12. El ecobarrio: proyecto de sensibilización ambiental. El caso de Villa 4 Álamos de Maipú (Chile)

    OpenAIRE

    Ubeira, Felipe; Quiroga, Carolina

    2001-01-01

    En la presente investigación se analizaron las consecuencias que ha tenido el desarrollo del primer proyecto de eco barrio en los habitantes de la villa 4 Álamos de Maipú, en la ciudad de Santiago de Chile. El proyecto es impulsado por la organización comunitaria “Ceibo”, integrada por habitantes de la villa, quienes tras enfrentarse a varios conflictos medioambientales y problemas sociales de distinto tipo, han ido en busca de nuevas maneras de habitar la ciudad, debiendo lidiar con factores...

  13. Si?ndrome de Burnout y estre?s laboral en profesores

    OpenAIRE

    Barreto E., Marilu? E.

    2013-01-01

    En la u?ltima de?cada la presencia del si?ndrome de Burnout ha ido en aumento muy considerablemente, como una consecuencia de trabajar intensamente hasta el li?mite de no tomar en cuenta las necesidades personales. Esta situacio?n se acompan?a de sentimientos de falta de ayuda, de impotencia, de actitudes negativas y de una posible pe?rdida de autoestima que sufre el trabajador, descrita como si?ndrome de Burnout (Caballero y Milla?n,1999). La prevalencia del si?ndrome de Burnout a nivel i...

  14. Evolución de la Calcemia y de los Marcadores de Remodelamiento Óseo durante la Gestación, el Parto y el Postparto Normales.

    OpenAIRE

    Toro Salas, Antonio de

    2016-01-01

    La consecuencia final de la gestación, el parto y el puerperio sobre la masa ósea maternas, no ha sido bien definida, a pesar de las numerosas investigaciones realizadas sobre el tema. Se han realizado estudios sobre la evolución gestacional de los marcadores bioquímicos de remodelamiento ósea, del calcio, y de las hormonas calciotrópicas, que han ido evolucionando en el diseño, en las técnicas, y en los marcadores utilizados. Han apar...

  15. Revisión conceptual del estudio de la autoestima: factores influyentes y protectores

    OpenAIRE

    Rocha Docampo, Carla da

    2012-01-01

    Se analiza el concepto de autoestima desde una perspectiva histórica y teórica, cómo se han ido desarrollando sus definiciones a lo largo del tiempo, cuáles son sus componentes y su desarrollo a lo largo del ciclo vital. Además, se exponen los factores implicados que más influyen en los niveles individuales de autoestima y se analizan los factores protectores de la autoestima utilizados en el ámbito escolar por parte de los estudiantes

  16. Caracterización del sector agroindustrial zonal e importancia de la implementación de sistemas de gestión de la calidad en las MiPyMEs del partido de La Plata

    OpenAIRE

    Benitez, Andrés Ignacio

    2017-01-01

    La preocupación de los consumidores a nivel mundial por la calidad e inocuidad de los alimentos se ha ido incrementando en los últimos años junto con el aumento en la detección de Enfermedades Transmitidas por Alimentos (ETAs). Esto ha llevado a muchas empresas de la Industria de Alimentos y Bebidas (IAB) a buscar formas de certificar ante la sociedad que sus productos no presentan riesgo de afectar la salud al ser consumidos, utilizando diversas certificaciones o protocolos durante el proces...

  17. Variación de la estructura fina de las fibras acrílicas en la hilatura

    OpenAIRE

    Gacén Guillén, Joaquín; Maillo Garrido, Josefina; Manich i Bou, Albert Mª; Ussmane, Mahomed

    2002-01-01

    Dos fibras acrílicas comerciales de diferente finura han sido transformadas en hilados en continua de hilar (3.3. dtex) y en hilatura de rotor (1.3 dtex). Los hilos resultantes han sido vaporizados y teñidos en condiciones standard. Las variaciones de la estructura producidas por las operaciones de hilatura, vaporizado y tintura han sido evaluadas a través del ensayo de solubilidad de las fibras acrílicas en una mezcla dimetilformamida/agua (95/5). Two commercial acrylic fibres of d...

  18. Alfabetización en lectura y escritura en personas en situación de discapacidad intelectual

    OpenAIRE

    Miranda, Angélica María

    2016-01-01

    El trato de las personas en situación de discapacidad (PsD) ha ido variando en la historia de la humanidad desde el infanticidio en la antigüedad hasta la actualidad donde se considera a la persona como un sujeto de derecho que debe ser respetado, no discriminado y con igualdad de oportunidades. El Modelo Multidimensional de la discapacidad (AAIDD, 2011) promueve las habilidades conceptuales de lectura, escritura y matemática considerándolas destrezas fundamentales para la plena inclusión de ...

  19. Medicinas complementarias]/alternativas en adolescentes con trastorno déficit atencional/hiperactividad y trastornos del ánimo

    OpenAIRE

    Pérez Carmona, María Pilar

    2017-01-01

    Las Medicinas Complementarias/alternativas (MCA) cada día son más utilizadas por los pacientes, incluidos niños y adolescentes. En Chile el Ministerio de Salud (Minsal), ha ido reconociendo y regulando alguna de ellas, aunque todavía existe gran desconocimiento sobre su efectividad y seguridad. Objetivo: Revisar la evidencia disponible en relación a las MCA en adolescentes con Trastorno déficit atencional/hiperactividad (TDAH) y trastornos del ánimo. Metodología: Se realizó una búsqueda bibli...

  20. Implementación y análisis de CBTv2 en el medioambiente Ns

    OpenAIRE

    Rigotti, Guillermo

    1998-01-01

    Desde la definición del modelo de servicio multicast en IP, el uso de estas facilidades ha ido adquiriendo cada vez mayor importancia en el ámbito de la Internet. El número de aplicaciones que demandan transmisión multicast, tales como conferencias de audio y video, simulación interactiva distribuida, descubrimiento de recursos, etc, ha aumentado en forma continua, viéndose reflejado en el crecimiento experimentado por el MBONE, experimental en sus inicios en 1992 y actualmente considerado in...

  1. INTERNACIONALIZACIÓN Y CONTROL INTERORGANIZATIVO: REVISIÓN TEÓRICA Y PROPUESTAS DE INVESTIGACIÓN

    OpenAIRE

    Araújo Pinzón, P.; Sánchez Vázquez, J.M.; Vélez Elorza, M.L.; Álvarez-Dardet Espejo, M.C.

    2010-01-01

    Dentro de los desafíos que los procesos de internacionalización presentan a las empresas, la gestión de los canales de exportación externalizados ha ido adquiriendo una mayor relevancia. Analizando las conclusiones de los trabajos que han estudiado el papel del Control Interorganizativo (CI) en el contexto de las relaciones interorganizativas, este trabajo argumenta que el CI podría permitir una mayor integración y coordinación de las relaciones entre socios domésticos e internacionales, dife...

  2. La innovación financiera, la gestion del riesgo y los flujos financieros de la economía. La crisis de los prestamos sub-prime: crónica de una muerte anunciada

    OpenAIRE

    Manzano Frías, Maria-Cruz

    2008-01-01

    La crisis que se evidenció a partir del mes de junio del 2007, y que se ha denominado crisis de los préstamos sub-prime no ha sido sino el resultado de un crecimiento excesivo del riesgo, sobre todo en el sistema financiero estadounidense, con efectos de contagio en los mercados internacionales. Este mayor riesgo no ha ido acompañado de un crecimiento de la base de capital en medida suficiente como para asegurar, en muchos casos, la solvencia de algunos intermediarios financier...

  3. Contribución al estudio de las modificaciones estructurales y ultraestructurales en branquias, en su zona respiratoria y sensitiva, en zebrafish (Danio rerio) tratados con dioxina

    OpenAIRE

    Navas Lloret, José Miguel

    2017-01-01

    Desde mediados del siglo XX ha ido aumentando la preocupación acerca de los efectos de los llamados disruptores endocrinos, efectos que se pueden apreciar en todas las especies animales, incluso en el hombre. Hacemos un recordatorio de características de estos disruptores endocrinos, su naturaleza y sus efectos sobre el medio ambiente, así mismo damos una visión de las actuaciones al respecto de la industria química. Para este estudio se utilizaron 120 individuos de de pez zebrafish (Da...

  4. Cartografía de la esperanza: Iniciativas de resistencia pacífica desde las mujeres

    OpenAIRE

    2006-01-01

    Este estudio muestra una alternativa de vida que desarrollan mujeres organizadas, frente a las experiencias de muerte, maltrato y desplazamiento que han sufrido ellas, sus familias y las comunidades colombianas durante más de la mitad del siglo XX. Es la alternativa de vida que han ido construyendo las mujeres en tres departamentos, Cauca, Chocó y Nariño, que sufren intensamente los rigores de un conflicto armado que no tiene trazas de terminar. La lógica imperante de los actores armados que ...

  5. Evolución del pensamiento estratégico en las relaciones internacionales

    OpenAIRE

    Alejandro L. Corbacho

    2011-01-01

    Desde tiempos inmemoriales las distintas unidades políticas han hecho y continúan haciendo estrategia (making strategy). Esto se define como los modos en los que los líderes políticos y militares evolucionan y articulan las estrategias en respuesta a desafíos externos. Esta necesidad la convierte en un aspecto fundamental de las relaciones internacionales y, por lo tanto, también convierte a la estrategia en un concepto clave de las mismas. El concepto de estrategia ha ido evolucionando a lo ...

  6. Edición Especial: Las redes sociales digitales en la educación del siglo XXI

    OpenAIRE

    Pedagógicos, Ensayos

    2017-01-01

    Vivimos en una constante y acelerada innovación tecnológica, especialmente en el campo de las tecnologías de información y comunicación (TIC). Los recursos, servicios y espacios digitales se han ido transformando e incorporando en los últimos años a los estilos de vida de las personas, tanto para trabajar, comunicarse y producir conocimiento como consumir medios y contenido de entretenimiento, colaborar y socializar. En este sentido es innegable distinguir que las redes sociales digitales son...

  7. Análisis y tratamiento de la información y la imagen institucional en los mass-media

    OpenAIRE

    González Quiñones, Fidel

    2015-01-01

    El México actual es una rica mezcla de herencias propias y extranjeras que se ha fundido en un crisol muy particular de creencias y tradiciones singulares. En este proceso de desarrollo propio e imitación cultural hemos ido adoptado poco a poco una concepción visual del mundo: Para nosotros la forma es fondo. El desarrollo de esta concepción visual se encuentra sin duda alguna fuertemente influenciado por nuestros vecinos del norte (Estados Unidos y Canadá) quienes basan sus sistemas co...

  8. Control interno de la informacion financiera

    OpenAIRE

    Cianca Feijóo, Celeste

    2014-01-01

    RESUMEN: Los escándalos financieros acontecidos en EEUU a principios del S.XXI, originaron la promulgación de la Ley Sarbanes - Oxley, en 2002. A partir de entonces, los requisitos de transparencia de los mercados de valores han evolucionado notablemente. En nuestro país, se han ido sucediendo una serie de iniciativas y normativas sobre el control interno de la información financiera, para fortalecer la transparencia de los mercados e infundir confianza en los inversores. También se h...

  9. Liderazgo y poder en las organizaciones

    OpenAIRE

    Valcarce Fernández, Antonio

    2015-01-01

    En este trabajo, presentamos una revisión sobre el liderazgo y el poder como fenómenos presentes dentro de la organización y empleando para ello la perspectiva de la Psicología de las Organizaciones. En cuanto al liderazgo señalaremos una contextualizacion, asi como las definiciones que se han aceptado y las distintas teorias que han ido formando el estudio del liderazgo así como las habilidades directivas que se enmarcan dentro del liderazgo efectivo,a su vez explicaremos los nue...

  10. El Guggenheim Museum de New York. Interpretación del papel de la estructura a través de la colaboración entre Frank Lloyd Wright y Jaroslav J. Polivka

    OpenAIRE

    Martin Saiz, Diego

    2012-01-01

    Arquitectura y estructura han ido siempre íntimamente ligadas, pero con la aparición del acero y el hormigón surgieron nuevas necesidades formales o estéticas. El Estilo Internacional se inclinó por separar la retícula estructural de los cerramientos. En cambio, la Escuela de Chicago forjó las bases de una arquitectura optimizada y racional. Frank Lloyd Wright, entre estas dos situaciones, optó por seguir las pautas naturales de los materiales, de forma “orgánica”, recuperan...

  11. Supervisión bancaria

    OpenAIRE

    Vallejo Moscoso, Patricio

    1998-01-01

    El presente trabajo tiende a examinar el control que ejerce el estado en el sistema financiero por medio de la Superintendencia de Bancos, entidad a la cual se le asigna el rol de la vigilancia y control de las entidades que operan en el sector financiero. Para ello ha sido necesario establecer la evolución y los cambios que se han ido presentando tanto en lo referente a las actividades u operaciones en el contexto financiero y nacidas de ellas las nuevas tendencias en las que ...

  12. Proceedings of the Tenth Biennial Guidance Test Symposium Held at Holloman Air Force Base, New Mexico, 7-9 October, 1981. Volume I,

    Science.gov (United States)

    1981-10-01

    emphasized in this paper, missile hard- Captive Flight ware receives qualification with a c omb in ed e n vi r onme n talI and burn-in Because of the...provided a cue on the 2. A control/indicator unit (CIU) CDU at the completion of level gyro ;nJ accel- 3. An orthogonal ferrite loop antenna with a signal...processing system addition a reasonableness test is performed by dif- for later data retrival . Backup on-top position data ferencing the actual IDO or

  13. Niña-mujer-objeto de arte: la sexualidad femenina en la pintura.

    OpenAIRE

    Sánchez Concha, Francisco José; García Torralbo, María Cruz

    2011-01-01

    Hasta los impresionistas, el desnudo femenino formaba parte de la historia que el artista quería contar en su obra. El Impresionismo rompió los moldes tanto en la paleta como en la forma de tratar el desnudo de una mujer. A partir de entonces, la sexualidad femenina expresada en los cuadros de desnudos ha ido alcanzando cotas inimaginables ni por el Arte ni por el espectador. Sensualidad, erotismo, pasión, se convierten en algunos pintores en la más descarnada sexualidad, al...

  14. El desempleo: influencia en las relaciones familiares y los problemas sociales y académicos de los hijos

    OpenAIRE

    Pichardo, M.C.; Núñez-Caballero, J.M.; Romero-López, M.

    2016-01-01

    Debido a la crisis económica, muchos hogares han experimentaron una caída de su bienestar financiero, ya que la tasa de desempleo ha ido aumentando de forma exponencial. Diversas investigaciones han confirmado que el desempleo tiene multitud de efectos negativos tanto a nivel individual como familiar, favoreciendo climas caracterizados por mayor hostilidad entre los miembros de la familia y una reducción de apoyo entre ellos. En este trabajo se analiza la relación entre el desempleo y algunas...

  15. Para una crítica de investigaciones académicas y periodísticas sobre la violencia en el fútbol, a partir de La doce, la verdadera historia de la barra brava de Boca : Grabia, Gustavo. Sudamericana, Buenos Aires, 2009

    OpenAIRE

    Sodo, Juan Manuel

    2010-01-01

    Prosa atrapante, reconstrucción de datos seria y rigurosidad informativa mediante, este sesudo trabajo de Grabia, a lo largo de cinco minuciosos capítulos y casi 250 páginas, nos ofrece una exhaustiva cartografía de la red de relaciones que La 12 ha ido tejiendo con dirigentes, punteros políticos, policía, jueces, futbolistas, empresarios, candidatos a elecciones, directores técnicos, hinchas famosos, otras barras... a lo largo de su convulsionada historia, desde que esta hinchada aparece y e...

  16. Botulinum toxin for the management of bladder dysfunction.

    Science.gov (United States)

    Schurch, Brigitte

    2006-01-01

    This review highlights a recent innovation in the medical treatment of detrusor overactivity (DO). Anticholinergics are usually the gold standard to treat bladder overactivity. Adverse effects and lack of efficacy are the two main causes for considering alternative treatments. Until recently, invasive surgery (mainly bladder augmentation) was the only available treatment option for patients with intractable DO. This article considers botulinum toxin type A (BTX-A) injection as an alternative treatment to surgery in patients with DO who do not respond to anticholinergic therapy. To identify papers for inclusion in this review, we searched PubMed with the keywords 'botulinum toxin', 'overactive bladder', 'urinary incontinence' and 'neurogenic bladder' for the years 2000-5. Review articles were not included. Abstracts were cited only if they contained important new information. Experimental animal studies and articles or book chapters related to the use of botulinum toxin for other indications (such as achalasia and cervical dystonia) were analysed with regard to the mechanisms of action of botulinum toxin. From this review, it appears that BTX-A injection into the detrusor muscle is a very effective method for treating urinary incontinence secondary to neurogenic detrusor overactivity (NDO), as well as urinary incontinence due to idiopathic overactive bladder (IDO). In both conditions, the duration of effect seems to be at least 6 months. Overall success rates seem to be similar in both patient populations. For NDO, only one evidence-based medicine level 1 study is available, whereas for IDO, only evidence-based medicine level 3 or 4 studies have been published. Particularly in this latter indication, injection technique and outcome parameters vary from study to study and need to be standardised. Without randomised controlled studies aimed at comparing different techniques and dosages, it remains difficult to decide what technique is optimal for treating patients

  17. Cultura y televisión: una controvertida relación Culture and television. A controversial relation

    Directory of Open Access Journals (Sweden)

    Soledad Ruano López

    2007-03-01

    Full Text Available Desde el nacimiento de la televisión en Europa, se le ha atribuido una función cultural y de difusión de valores, de conocimiento y de saber. Sin embargo, hay que reconocer que la relación entre televisión y cultura siempre ha sido difícil y polémica. Hasta los años ochenta parecía existir un mutuo respeto entre ambas, pero, desde la pérdida del monopolio por parte de las cadenas públicas europeas, la relación ha ido empeorando hasta alcanzar el rótulo de «mala». La televisión pública se ha dejado arrastrar por una loca carrera de índices de audiencia, en donde los programas de valores culturales, con valores culturales o sobre-valores culturales han ido menguando progresivamente. From the birth of the public television in Europe, media has been related with cultural and divulging objectives. Nevertheless, it is necessary to admit that the relation between television and culture have always been difficult or al least controversial. Until the eighties there seemed to exist a mutual respect among each other but since the loss of monopoly on the part of the public European chains the relation has been getting worse. Public television has got involved in drag by a crazy race for audience rates where programmes on or with cultural values have been progressively diminished.

  18. Ganándole la batalla al mal humor. Una propuesta didáctica

    Directory of Open Access Journals (Sweden)

    Sarah Díaz García

    2012-01-01

    Full Text Available En los últimos años, el aprendizaje de lenguas extranjeras ha llegado a ser una necesidad real tanto profesional como personal para todos nosotros como ciudadanos y como trabajadores. La enseñanza del español como lengua extranjera, que es el área de estudio en el que nos centraremos en el resto del presente artículo, ha evolucionado a medida que nuestra sociedad ha ido cambiando y adaptándose a los nuevos tiempos. Este cambio surgió con el Marco Común Europeo de Referencia para las Lenguas (MCER; pasamos de darle una máxima importancia a los aspectos puramente lingüísticos a abrirnos al hecho de que aprender un segundo idioma no es solo centrarnos en la gramática. La competencia comunicativa, por ejemplo, ha ido cobrando protagonismo en los últimos años; la idea de que un estudiante solo es competente en el uso de una lengua cuando utiliza la lingüística (pensemos en la gramática de forma correcta y siguiendo la norma ha caído en desaprobación para muchos. La realidad es que para que un alumno se considere competente en el uso de otra lengua que no sea la suya debe saber utilizar las técnicas y recursos pertinentes para poder comunicarse efectivamente con su interlocutor en un contexto real de habla.

  19. La remunicipalización del servicio de abastecimiento urbano de agua: instituciones y común

    Directory of Open Access Journals (Sweden)

    Edurne Bagué Tova

    2017-11-01

    Full Text Available En el contexto social y político catalán surgido tras el estallido de la crisis de finales de 2008, el debate sobre la gestión del agua ha ido tomando relevancia pública hasta el punto de ser parte central en los programas políticos que las nuevas candidaturas electorales surgidas después del movimiento conocido como 15M prepararon para las elecciones municipales de 2015. Este proceso ha ido en paralelo con los cambios sociales acontecidos después del 15 de mayo de 2011, hecho que se constata en distintos aspectos. Algunas de las características que marcan este periodo son los cambios en el discurso, el cambio de algunos de sus protagonistas, el trato de la gestión del agua; así como la sustitución progresiva de una estrategia centrada en la no privatización, hacia el reclamo del aumento de la capacidad de decidir de la ciudadanía en la gestión del agua en el ámbito municipal. Pasando de una lucha a escala estatal y/o autonómica a una a escala local. En este artículo se enumeran aquellos aspectos que dan pie a la pregunta: ¿Qué concepción del común articula el nuevo escenario de lucha por el agua municipal y qué formas empíricas adquiere?

  20. Immunogenicity and immunomodulatory properties of umbilical cord lining mesenchymal stem cells.

    Science.gov (United States)

    Deuse, Tobias; Stubbendorff, Mandy; Tang-Quan, Karis; Phillips, Neil; Kay, Mark A; Eiermann, Thomas; Phan, Thang T; Volk, Hans-Dieter; Reichenspurner, Hermann; Robbins, Robert C; Schrepfer, Sonja

    2011-01-01

    We here present an immunologic head-to-head comparison between human umbilical cord lining mesenchymal stem cells (clMSCs) and adult bone marrow MSCs (bmMSCs) from patients >65 years of age. clMSCs had significantly lower HLA class I expression, higher production of tolerogenic TGF-β and IL-10, and showed significantly faster proliferation. In vitro activation of allogeneic lymphocytes and xenogeneic in vivo immune activation was significantly stronger with bmMSCs, whereas immune recognition of clMSCs was significantly weaker. Thus, bmMSCs were more quickly rejected in immunocompetent mice. IFN-γ at 25 ng/ml increased both immunogenicity by upregulation of HLA class I/ HLA-DR expression and tolerogenicity by increasing intracellular HLA-G and surface HLA-E expression, augmenting TGF-β and IL-10 release, and inducing indoleamine 2,3-dioxygenase (IDO) expression. Higher concentrations of IFN-γ (>50 ng/ml) further enhanced the immunosuppressive phenotype of clMSCs, more strongly downregulating HLA-DR expression and further increasing IDO production (at 500 ng/ml). The net functional immunosuppressive efficacy of MSCs was tested in mixed lymphocyte cultures. Although both clMSCs and bmMSCs significantly reduced in vitro immune activation, clMSCs were significantly more effective than bmMSCs. The veto function of both MSC lines was enhanced in escalating IFN-γ environments. In conclusion, clMSCs show a more beneficial immunogeneic profile and stronger overall immunosuppressive potential than aged bmMSCs.

  1. Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations

    Directory of Open Access Journals (Sweden)

    Benham Christopher D

    2006-03-01

    Full Text Available Abstract Background The recent identification of the cold-menthol sensory receptor (TRPM8; CMR1, provides us with an opportunity to advance our understanding of its role in the pathophysiology of bladder dysfunction, and its potential mediation of the bladder cooling reflex. In this study, we report the distribution of the cool and menthol receptor TRPM8 in the urinary bladder in patients with overactive and painful bladder syndromes, and its relationship with clinical symptoms. Methods Bladder specimens obtained from patients with painful bladder syndrome (PBS, n = 16, idiopathic detrusor overactivity (IDO, n = 14, and asymptomatic microscopic hematuria (controls, n = 17, were immunostained using specific antibodies to TRPM8; nerve fibre and urothelial immunostaining were analysed using fibre counts and computerized image analysis respectively. The results of immunohistochemistry were compared between the groups and correlated with the Pain, Frequency and Urgency scores. Results TRPM8-immunoreactive staining was observed in the urothelium and nerve fibres scattered in the suburothelium. The nerve fibre staining was seen in fine-calibre axons and thick (myelinated fibres. There was marked increase of TRPM8-immunoreactive nerve fibres in IDO (P = 0.0249 and PBS (P Conclusion This study demonstrates increased TRPM8 in nerve fibres of overactive and painful bladders, and its relationship with clinical symptoms. TRPM8 may play a role in the symptomatology and pathophysiology of these disorders, and may provide an additional target for future overactive and painful bladder pharmacotherapy.

  2. ATP Release from Chemotherapy-Treated Dying Leukemia Cells Elicits an Immune Suppressive Effect by Increasing Regulatory T Cells and Tolerogenic Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Mariangela Lecciso

    2017-12-01

    Full Text Available Chemotherapy-induced immunogenic cell death can favor dendritic cell (DC cross-priming of tumor-associated antigens for T cell activation thanks to the release of damage-associated molecular patterns, including ATP. Here, we tested the hypothesis that in acute myeloid leukemia (AML, ATP release, along with its well-known immune stimulatory effect, may also contribute to the generation of an immune suppressive microenvironment. In a cohort of AML patients, undergoing combined daunorubicin and cytarabine chemotherapy, a population of T regulatory cells (Tregs with suppressive phenotype, expressing the immune checkpoint programmed cell death protein 1 (PD-1, was significantly increased. Moving from these results, initial in vitro data showed that daunorubicin was more effective than cytarabine in modulating DC function toward Tregs induction and such difference was correlated with the higher capacity of daunorubicin to induce ATP release from treated AML cells. DCs cultured with daunorubicin-treated AML cells upregulated indoleamine 2,3-dioxygenase 1 (IDO1, which induced anti-leukemia Tregs. These data were confirmed in vivo as daunorubicin-treated mice show an increase in extracellular ATP levels with increased number of Tregs, expressing PD-1 and IDO1+CD39+ DCs. Notably, daunorubicin failed to induce Tregs and tolerogenic DCs in mice lacking the ATP receptor P2X7. Our data indicate that ATP release from chemotherapy-treated dying cells contributes to create an immune suppressive microenvironment in AML.

  3. RB4CD12 epitope expression and heparan sulfate disaccharide composition in brain vasculature.

    Science.gov (United States)

    Hosono-Fukao, Tomomi; Ohtake-Niimi, Shiori; Nishitsuji, Kazuchika; Hossain, Md Motarab; van Kuppevelt, Toin H; Michikawa, Makoto; Uchimura, Kenji

    2011-11-01

    RB4CD12 is a phage display antibody that recognizes a heparan sulfate (HS) glycosaminoglycan epitope. The epitope structure is proposed to contain a trisulfated disaccharide, [-IdoA(2-OSO(3))-GlcNSO(3) (6-OSO(3))-], which supports HS binding to various macromolecules such as growth factors and cytokines in central nervous tissues. Chemically modified heparins that lack the trisulfated disaccharides failed to inhibit the RB4CD12 recognition of HS chains. To determine the localization of the RB4CD12 anti-HS epitope in the brain, we performed an immunohistochemical analysis for cryocut sections of mouse brain. The RB4CD12 staining signals were colocalized with laminin and were detected abundantly in the vascular basement membrane. Bacterial heparinases eliminated the RB4CD12 staining signals. The RB4CD12 epitope localization was confirmed by immunoelectron microscopy. Western blotting analysis revealed that the size of a major RB4CD12-positive molecule is ∼460 kDa in a vessel-enriched fraction of the mouse brain. Disaccharide analysis with reversed-phase ion-pair HPLC showed that [-IdoA(2-OSO(3))-GlcNSO(3) (6-OSO(3))-] trisulfated disaccharide residues are present in HS purified from the vessel-enriched brain fraction. These results indicated that the RB4CD12 anti-HS epitope exists in large quantities in the brain vascular basement membrane. Copyright © 2011 Wiley-Liss, Inc.

  4. Immunomodulatory Effects of Diterpene Quinone Derivatives from the Roots of Horminum pyrenaicum in Human PBMC

    Directory of Open Access Journals (Sweden)

    K. Becker

    2018-01-01

    Full Text Available Several phytochemicals were shown to interfere with redox biology in the human system. Moreover, redox biochemistry is crucially involved in the orchestration of immunological cascades. When screening for immunomodulatory compounds, the two interferon gamma- (IFN-γ- dependent immunometabolic pathways of tryptophan breakdown via indoleamine 2,3-dioxygenase-1 (IDO-1 and neopterin formation by GTP-cyclohydrolase 1 (GTP-CH-I represent prominent targets, as IFN-γ-related signaling is strongly sensitive to oxidative triggers. Herein, the analysis of these pathway activities in human peripheral mononuclear cells was successfully applied in a bioactivity-guided fractionation strategy to screen for anti-inflammatory substances contained in the root of Horminum (H. pyrenaicum L. (syn. Dragon’s mouth, the only representative of the monophyletic genus Horminum. Four abietane diterpene quinone derivatives (horminone, 7-O-acetylhorminone, inuroyleanol and its 15,16-dehydro-derivative, a novel natural product, two nor-abietane diterpene quinones (agastaquinone and 3-deoxyagastaquinone and two abeo 18 (4 → 3 abietane diterpene quinones (agastol and its 15,16-dehydro-derivative could be identified. These compounds were able to dose-dependently suppress the above mentioned pathways with different potency. Beside the description of new active compounds, this study demonstrates the feasibility of integrating IDO-1 and GTP-CH-I activity in the search for novel anti-inflammatory compounds, which can then be directed towards a more detailed mode of action analysis.

  5. UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

    Science.gov (United States)

    Linetsky, Mikhail; Raghavan, Cibin T.; Johar, Kaid; Fan, Xingjun; Monnier, Vincent M.; Vasavada, Abhay R.; Nagaraj, Ram H.

    2014-01-01

    Advanced glycation end products (AGEs) contribute to lens protein pigmentation and cross-linking during aging and cataract formation. In vitro experiments have shown that ascorbate (ASC) oxidation products can form AGEs in proteins. However, the mechanisms of ASC oxidation and AGE formation in the human lens are poorly understood. Kynurenines are tryptophan oxidation products produced from the indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway and are present in the human lens. This study investigated the ability of UVA light-excited kynurenines to photooxidize ASC and to form AGEs in lens proteins. UVA light-excited kynurenines in both free and protein-bound forms rapidly oxidized ASC, and such oxidation occurred even in the absence of oxygen. High levels of GSH inhibited but did not completely block ASC oxidation. Upon UVA irradiation, pigmented proteins from human cataractous lenses also oxidized ASC. When exposed to UVA light (320–400 nm, 100 milliwatts/cm2, 45 min to 2 h), young human lenses (20–36 years), which contain high levels of free kynurenines, lost a significant portion of their ASC content and accumulated AGEs. A similar formation of AGEs was observed in UVA-irradiated lenses from human IDO/human sodium-dependent vitamin C transporter-2 mice, which contain high levels of kynurenines and ASC. Our data suggest that kynurenine-mediated ASC oxidation followed by AGE formation may be an important mechanism for lens aging and the development of senile cataracts in humans. PMID:24798334

  6. Application of cytotoxicity test for toxic micropollutants. Saibo dokusei shiken ni yoru yugai kagaku busshitsu osen no hyoka

    Energy Technology Data Exchange (ETDEWEB)

    Utsumi, H; Hamada, A [Showa University, Tokyo (Japan). School of Pharmaceutical Science; Ono, Y [National Institute of Hygienic Sciences, Tokyo (Japan)

    1992-10-01

    Considerations were given from a viewpoint of assessing toxicity to human bodies on methods of assessing water pollutants and organisms, and applicability of cytotoxity test using cultured cells to water quality assessment. Biological assessment systems used for water environment may use tests using multicellular organisms, cells, or organelles in cells. The organism assessment method is intended mainly for assessing ecological effects, and a suitable method must be selected upon extrapolating it to human bodies. A toxicity parameter used most frequently in a cytotoxity test is the cell revival rate, and life and death are determined from liberation of enzymes in cells, or with color rejection tests and incorporation tests. There are a number of test specimens of raw tap water and its chlorine treatment condensate that show no mutagenicity but cytotoxity. Efficiencies of removal by means of mild chlorine treatment, fast filtration, and activated carbon adsorption vary greatly with cytotoxity and mutagenicity. Introducing the cytotoxity test is expected of further contributing to improving safety in water quality. 24 refs., 1 fig., 7 tabs.

  7. Utilización de los aportes de la psicología para disminuir el nivel de ansiedad en cirugía dental

    OpenAIRE

    Mattano, Claudia Aurora; Capraro, María Cecilia; Capraro, Carlos Gabriel; Sparacino, Sandra; Schuler, Mónica P.; Bogo, Hernán; Ricciardi, Nicolás; Capraro, María Eugenia; Ricciardi, Alfredo

    2017-01-01

    A pesar de que las técnicas quirúrgicas se han ido modificando, la cirugía constituye un evento estresante, alrededor del cual existen preocupaciones sobre la autonomía y condiciones físicas. La ansiedad ante el tratamiento odontológico, por lo que va a suceder, se puede manifestar de diferentes maneras, como puede ser: depresión, angustias, temor y en algunos casos excitación. La fobia ante el tratamiento odontológico es definida como el miedo excesivo, desproporcionado y persistente, ante l...

  8. Imagen corporal en pacientes sometidos a cirug?a bari?trica

    OpenAIRE

    Vega Meza, Mar?a Paula

    2017-01-01

    La obesidad es un problema de salud que ha ido creciendo de manera considerable en los ?ltimos a?os, afectando a un alto porcentaje de la poblaci?n mundial (WHO, 2015). Uno de los tratamientos que m?s se emplea en la actualidad para tratar esta condici?n es la cirug?a bari?trica, la cual ha mostrado, hasta el momento, ser una de las t?cnicas m?s eficaces en cuanto a la p?rdida significativa del peso y el mantenimiento de los resultados (Abeles & Shikora, 2008). En ese orden, es pertinente ent...

  9. Síndrome Asperger: Intervención en la pragmática con alumnos de Educación Primaria

    OpenAIRE

    Ortuño-Giné, Anaïs

    2015-01-01

    Actualmente el número de alumnos con Necesidades Educativas Especiales (NEE) ha ido en aumento en las aulas de centros ordinarios. Hoy en día podemos ver muchos alumnos con Trastornos Generalizados de Desarrollo (TGD) o Trastornos del Espectro Autista (TEA), dentro de los que se encuentra el Síndrome de Asperger, que es con el que más alumnos están escolarizados de forma ordinaria. Para los alumnos con estas características la escuela inclusiva es complicada, ya que padecen un déficit notable...

  10. La alimentación complementaria del lactante: recomendaciones existentes en el Área V de Asturias Complementary feeding of the infant: recommendations existing in Area V of Asturias (Spain)

    OpenAIRE

    V. García González; M.F. García Díaz; J.M. Fernández Menéndez; E. Lombraña Álvarez; L. Calle Miguel

    2013-01-01

    Introducción.Las recomendaciones de la introducción de la alimentación complementaria del lactante han ido sufriendo modificaciones. Hay una percepción subjetiva de que no existe consenso entre los profesionales en cuanto a las recomendaciones dadas a los padres para la introducción de los distintos alimentos.  Objetivo. Conocer las pautas de alimentación dadas en los centros de salud del Área V de Asturias. Material y métodos.Estudio descriptivo transversal. Se recogieron y analizaron las ho...

  11. La auditoría de gestión como instrumento de control y evaluación para innovar la gestión en la Municipalidad Provincial de Bagua

    OpenAIRE

    Frías Olano, José Genaro

    2015-01-01

    La auditoría gubernamental en nuestro país ha ido evolucionando rápidamente acorde a los nuevos conceptos en los que no solamente se aplica para auditar estados financieros y emitir opinión sobre su razonabilidad o no, sino que se ha ampliado a la auditoria de cumplimiento y la auditoria de desempeño, remplazando de esta manera el antiguo concepto de la auditoría de gestión hacia un nuevo concepto en donde se busca examinar en forma independiente y objetiva las tareas, programas y entidades d...

  12. La percepción de la violencia entre pares en contextos escolares: un estudio cualitativo Violence Among Peers' Perception In Educative Contexts: A Qualitative Study

    OpenAIRE

    Teresa Ana Veccia; Javier Gonzalo Calzada; Erika Valeria Grisolia

    2008-01-01

    La violencia ha ido incrementándose en los últimos tiempos en distintos niveles y países. La misma es multideterminada por factores históricos, comunitarios, institucionales, familiares e individuales. Dentro de este amplio contexto recortamos el problema de la violencia en las escuelas, y más específicamente del maltrato sostenido entre los niños. Este tipo de maltrato constituye una perturbación en las relaciones entre los miembros de un grupo y es expresión de la violencia interpersonal. C...

  13. Valoración de la imputabilidad en trastornos de la personalidad

    OpenAIRE

    Lajas Montero, Julián

    2013-01-01

    Los trastornos de personalidad han supuesto cierta dificultad para ser incluidos en el ámbito del derecho, ya que es difícil percibir en los sujetos con estos trastornos problemas intelectivos o volitivos. Pero gracias al interés que han mostrado estos trastornos y a los estudios que han permitido conocerlos más profundamente, se han ido introduciendo poco a poco en el derecho. Actualmente, el código penal español recoge cuales son las causas que anulan o atenúan la imputabilid...

  14. Implantación de un sistema de información para la comercialización tercerizada de productos financieros

    OpenAIRE

    Lara Bendezu, Junior Felix; Lara Bendezu, Junior Felix; Lara Bendezu, Junior Felix

    2013-01-01

    La tercerización es el proceso por el cual se transfieren actividades dentro de la cadena de valor a socios seleccionados. Es una práctica que ha ido creciendo y evolucionando dentro del mundo de los negocios ya que permite concentrar las energías empresariales en el núcleo del negocio. La empresa Certicom brinda el servicio de tercerización de los procesos de comercialización de créditos financieros de las entidades financieras. Este proceso es de suma importancia para dichas entidades po...

  15. Obtención de bioetanol 2G a partir de hidrolizados de paja de trigo : Fermentación conjunta de los Penta y Hexa carbohidratos con Pichia stpitis

    OpenAIRE

    Bellido Díez, Carolina

    2014-01-01

    En la actualidad, la demanda energética global se ha ido incrementando gradualmente por lo que la escasez de petróleo está asegurada en un futuro. Teniendo en cuenta estos aspectos, junto con los medioambientales y económicos, los biocombustibles cobran especial importancia como primera alternativa de sustitución de los derivados del petróleo en automoción. El bioetanol es el biocombustible más comercializado y su producción mundial va a aumentar en el medio plazo. Actualmente, la mayor parte...

  16. De "los límites de la planeación urbana" a la definición del "modelo de gestión urbana en Ciudad Juárez"... ¿hacia un desarrollo sustentable al dominio de los "no lugares"?

    Directory of Open Access Journals (Sweden)

    Pedro Cital Beltrán

    2009-01-01

    Full Text Available En el presente ensayo se trata de hacer un breve recuento de las discusiones que se han presentado en algunos de los trabajos publicados en la revista Nóesis, particularmente los relacionados con desarrollo y planeación urbana, incluyendo las reflexiones sobre medio ambiente y vivienda. Asimismo, se presenta un balance respecto a las experiencias desarrolladas en los últimos años sobre este tema en Ciudad Juárez, en donde diversos acontecimientos han ido definiendo la configuración y el crecimiento de la localidad.

  17. La enfermedad de Alzheimer y los inhibidores de la colinesterasa

    OpenAIRE

    Carlos Luis Alpízar-Quesada; Catalina Morales-Alpízar

    2003-01-01

    La enfermedad de alzheimer (EA), es muy frecuente en la vejez donde se pierden, en forma lenta y progresiva, capacidades cognoscitivas y motoras. Esta enfermedad ha ido en aumento conforme se incrementa la expectativa de vida de la población. En los últimos años, descubrir un tratamiento efectivo para esta enfermedad ha sido un verdadero reto científico. A pesar de que su patología fue descrita hace algunos años, no hubo tratamiento disponible hasta hace poco tiempo. Desde principios de los n...

  18. NCEL (Naval Civil Engineering Lab.) Ocean Platforms Seminar.

    Science.gov (United States)

    1983-11-01

    Ido (11a) -. 0 3 -,2 21 C1 = (2UmT/T D)/(pDUm L) f Fm sin(e) de (11b) 0 where F mL = measured force per unit length, CT = 1+C, Cm being the added mass...located around the perimeter of the jacket’s base. These structures are fabricated onshore and then skidded onto a barge, transported offshore...type platforms. Both Cerveza and the Cerveza Ligera platforms[ 7] were launched in one piece and installed in 935 ft and 925 ft of water respectively

  19. El doctorado en Derecho: 1930-1956

    OpenAIRE

    Martínez Neira, Manuel; Puyol Montero, José María

    2008-01-01

    El estudio del doctorado permite individualizar distintos niveles de análisis e interpretación. Por un lado, un nivel reglamentario, análisis de las distintas normas jurídicas que se han ido acumulando en el tracto cronológico de la universidad contemporánea. Otro nivel está constituido por lo que podemos llamar la práctica administrativa, es decir, el desarrollo material de esas disposiciones. Un estudio de los expedientes académicos, de los instrumentos burocráticos, de las memorias y una e...

  20. Adenovirus oncolíticos como estrategia terapéutica para tumores del sistema nervioso central

    OpenAIRE

    Vera-Cano, B. (Beatriz); Alonso M.M. (Marta Maria); Saez-Castresana, J. (Javier)

    2018-01-01

    La descripción de los distintos tumores cerebrales y sus alteraciones genéticas ha demostrado ser una herramienta importante para la mejora en el diagnóstico y clasificación de los pacientes que los padecen. Sin embargo, los avances en el tratamiento de estas enfermedades no han ido a la par y a pesar de todos los esfuerzos terapéuticos estos pacientes siguen sucumbiendo a la enfermedad. Los adenovirus oncolíticos diseñados para replicarse y destruir a las células tumorales representan una es...

  1. Dolcey Cabal Concha

    Directory of Open Access Journals (Sweden)

    Facultad Nacional de Agronomía Universidad Nacional de Colombia

    1940-03-01

    Full Text Available La Facultad Nacional de Agronomía lamenta el fallecimiento del señor Dolcey Cabal, quien fue alumno de esta Facultad, en donde se distinguió por su corrección y aprovechamiento, en tal forma que apenas salido de los claustros había ido a la vecina República a prestar excelentes servicios como agrónomo; y que es un deber del Consejo manifestar su vinculación con los hijos de este Instituto a través del tiempo y en las distintas circunstancias.

  2. Recursos y actividades en el marco de un Seminario de b-learning de Farmacología Dentro del Campus Virtual UCM

    OpenAIRE

    Encinas, Mª Teresa; Ros-Rodríguez, José María; Gilabert, Juan Antonio

    2010-01-01

    El presente trabajo expone las características y objetivos de la creación y uso de distintos recursos y actividades incorporados en el Aula Virtual de Farmacología, un seminario de b-learning que se imparte de manera combinada empleando tanto la enseñanza presencial como a través del Campus Virtual-UCM. A lo largo de los dos años de existencia de esta herramienta se han ido incorporando a ella distintas estrategias docentes encaminadas a incentivar en el alumno un aprendizaje autodirigido de ...

  3. La violencia entre iguales en el alumnado universitario

    OpenAIRE

    Valencia-Godinez, I.; Contreras-Landgrave, G.; Ruano-Casado, L.; Ballestar-Tarín, María Luisa; Casas-Patiño, O.D.; Martinez Sabater, Antonio

    2017-01-01

    Introducción: La violencia se ha ido incrementando en los últimos años en todos los países, siendo determinada por factores sociales, educativos, históricos, comunitarios, institucionales, familiares e individuales. Esto se ha hecho presente no solo en las familias y sociedad sino también en las escuelas de diferentes niveles educativos sin importar edad, sexo, género, aún en el nivel superior. Identificar los actores sociales generadores de violencia de género dentro de la UAP Nezahualcóyotl...

  4. Body image in persons with gender dysphoria

    OpenAIRE

    María Frenzi Rabito Alcón; José Miguel Rodríguez Molina

    2015-01-01

    INTRODUCCIÓN Para las personas con disforia de género, la imagen corporal es un aspecto fundamental en su condición. Estas personas a veces manifiestan un fuerte deseo de cambiar sus caracteres sexuales primarios y secundarios. Además, socialmente el ideal de belleza ha ido cobrando cada vez más importancia pudiendo incrementar la insatisfacción corporal. El objetivo de este trabajo es analizar si la insatisfacción corporal en personas con disforia de género es similar a la que presenta l...

  5. De la especie al ecosistema; del ecosistema a la sociedad: revalorizando el algarrobo (ProsoPis Pallida) y el reto de su conservación en Lambayeque y en la costa norte del Perú

    OpenAIRE

    Cuentas Romero, María Alejandra; Salazar Toledo, Arturo Ítalo

    2017-01-01

    El artículo muestra la relevancia de una especie clave —Prosopis pallida— en el desarrollo ecológico del bosque seco costero, y cómo dicha importancia también influye en el desarrollo humano, pues con el tiempo se ha ido fortaleciendo el vínculo social con los ecosistemas forestales. Mediante el método de muestreo por transectos (punto-centro-cuadrado) y el valor obtenido por medio del Índice de Valor de Importancia (IVI) aplicados al Área de Conservación Regional (ACR) Huacrupe La Calera (Ol...

  6. La gestión local de la seguridad ciudadana como herramienta de revitalización y desarrollo para la comunidad

    OpenAIRE

    Villar García, Shaila

    2013-01-01

    La seguridad es una de las cuestiones sociales que más preocupan a los ciudadanos de cualquier territorio, y es elemento fundamental de desarrollo local. El concepto de seguridad ha estado enlazado control social/represión, pero esta idea ha ido evolucionando hacia la prevención de posibles conflictos. Superando la relación tradicional “nº de agentes= más seguridad”, analizaremos, junto a las personas que habitan un territorio ¿Qué elementos son los que crean esa inseguridad? Y ¿Podemos crear...

  7. Implementación de una aplicación para la visualización de resultados en un programa de cálculo matricial

    OpenAIRE

    Madueño Asensio, Alberto

    2012-01-01

    La sociedad a lo largo de la historia, ha ido desallorándose y evolucionando tecnológicamente gracias a diversas técnicas de investigación e innovación que van siendo requeridas poco a poco en todos y cada uno de los aspectos que generan la sociedad. Los desarrollos industriales que más suscitarán la curiosidad de la sociedad serán las construcciones hidráulicas (embalses), infraestructuras destinadas al transporte, siendo un claro ejemplo las carreteras o las vías para ferrocarriles o los me...

  8. GARCÍA ARETIO, L. (2001) La educación a distancia. De la teoría a la práctica. Barcelona, Ariel

    OpenAIRE

    Ruiz Corbella, Marta

    2002-01-01

    A lo largo de estas últimas décadas la educación a distancia se ha ido consolidando como alternativa indiscutible a la educación presencial. La oportunidad de este libro reside en que es urgente una delimitación precisa del concepto de educación a distancia, los elementos que la constituyen, la rigurosa planificación que la respalda..., de tal modo que podamos clarificar cuáles son los fundamentos propios y característicos de esta modalidad de enseñanza.

  9. Análisis de la actividad en redes sociales de marcas del sector moda: una aproximación al social commerce

    OpenAIRE

    Giraldo Cardona, Claudia Marcela

    2014-01-01

    El uso de las redes sociales en el mundo de internet y en el comercio electrónico ha ido incrementándose paulatinamente en los últimos años, ofreciendo a las empresas la oportunidad de llegar hasta donde sus clientes potenciales se encuentran. Así, a través del uso de redes sociales, las empresas pueden: satisfacer mejor la demanda, aumentar la fidelización del cliente, mejorar la comunicación y el posicionamiento de la marca, aumentar su notoriedad e, incluso, aumentar su nivel de ventas. De...

  10. Estudio sobre la utilización y efctividad del Comercio Electronico (E-comerce) y propuesta para su Implementacion en las Pymes del Sector Comercial de Guayaquil

    OpenAIRE

    Peñafiel Espinoza, Maritza M.; Lopez Chila, Roberto D.

    2012-01-01

    TESIS A TEXTO COMPLETO El comercio electrónico ha ido evolucionando cada vez más, porque el mundo de los negocios se mueve tan rápido que las empresas deben de estar siempre en la vanguardia tecnológica; pero esto no implica que un canal electrónico solucione la vida de una PYME (Pequeña y Mediana Empresa), si no hay una estrategia comercial bien definida. Las PYMES del sector comercial de Guayaquil podrían utilizar el comercio electrónico como una herramienta que dinamic...

  11. Construcción y caracterización de un nuevo nebulizador múltiple para técnicas analíticas basadas en plasma (ICP-OES, ICP-MS y MP-AES).

    OpenAIRE

    Lúñez Fernández, Claudia

    2016-01-01

    En la siguiente memoria, se presenta la metodología para la construcción de un nuevo nebulizador múltiple, resultado de una serie de nebulizadores anteriores, los cuales se han ido mejorando para optimizar las características del aerosol generado y con ello los parámetros analíticos de calidad en la espectrometría de emisión atómica con plasma de microondas (MP-AES) y espectrometría de emisión óptica con plasma de acoplamiento inductivo (ICP-OES). Este nuevo nebulizador multiconducto presenta...

  12. The Sage Handbook of Qualitative Research (Norman K. Denzin y Yvonna S. Lincoln, Ed.

    Directory of Open Access Journals (Sweden)

    Bárbara Scandroglio

    2007-05-01

    Full Text Available Desde la primera edición del Handbook of Qualitative Research, Denzin y Licoln se han convertido indiscutiblemente en una referencia obligatoria y, por mucho tiempo, excepcional para el heterogéneo conjunto de concepciones y prácticas que se encuentran reunidas bajo la etiqueta de “investigación cualitativa”. Cada una de las ediciones de esta monografía, manteniendo un corpus de planteamientos y contenidos comunes, ha intentado responder a las demandas de los contextos intelectuales e históricos por los que ha ido transitando el campo.

  13. Desarrollo de una herramienta multimedia para la enseñanza de los fundamentos del diseño basada en los elementos gráficos de la cultura Salasaka

    OpenAIRE

    Quispe Morales, Michele Paulina

    2014-01-01

    1. Fundamentación Teórica.-- 2. Metodología.-- 3. Resultados.-- 4. Conclusiones y Recomendaciones El presente trabajo pretendió indagar, rescatar y difundir la identidad del pueblo Salasaka, uno de los más representativos grupos étnicos de la provincia del Tungurahua, ya que se han ido perdiendo las características individuales con el transcurrir del tiempo debido a la intervención de distintos factores externos, como son los de carácter social, económico y cultural. Por otro lado, la Carr...

  14. Percepciones sobre la migración venezolana: causas, España como destino, expectativas de retorno

    OpenAIRE

    Tomás Castillo Crasto; Mercedes Reguant Álvarez

    2017-01-01

    Venezuela, a lo largo de su historia ha sido un país receptor de inmigrantes. Actualmente, presenta un patrón migratorio completamente distinto, motivado por una crisis nacional bajo un contexto de deterioro institucional, recesión económica y descomposición social, situación que ha ido empeorando durante los últimos 17 años. Este trabajo es un estudio exploratorio de orientación cualitativa. Hecho a través de un análisis bibliográfico de fuentes secundarias y la consulta en profundidad a inm...

  15. Teledetección óptica aplicada a un modelo distribuido de balance híbrido (hidromore) para el cálculo de evapotranspiración y humedad de suelo

    OpenAIRE

    Sánchez Martín, Nilda

    2011-01-01

    [ES]En las últimas décadas, la teledetección se ha ido perfilando como una herramienta valiosa en la tarea de observación y comprensión de los procesos terrestres, y especialmente en el estudio -cualitativo y cuantitativo- del conjunto suelo-vegetaciónagua- atmósfera. La posibilidad de tener información distribuida, instantánea y objetiva de la superficie terrestre ha abierto nuevas formas de modelización de los procesos hidrológicos. En términos generales, los modelos hidrológicos que de...

  16. Prevalencia, aptitudes y percepciones del uso del cigarrillo electrónico en alumnos de Enfermería.

    OpenAIRE

    Méndez Mangana, Carlos

    2015-01-01

    La popularidad de los cigarrillos electrónicos (e-cigs) ha ido en aumento en los últimos años como una posible nueva alternativa al consumo de tabaco. No se conoce cómo los profesionales y estudiantes de Ciencias de la Salud los han adoptado. Objetivo: Describir la prevalencia, conocimientos, percepciones, opiniones y riesgos sobre el uso y la exposición a los cigarrillos electrónicos entre los estudiantes de ciencias de la enfermería desde el 1er al 3er curso de su grado en la...

  17. Aplicación Móvil de Realidad Aumentada para la Enseñanza de la Clasificación de los Seres Vivos a Niños de Tercer Grado

    A Mobile Augmented Reality Application for Teaching the Classification of Living Things to Primary School’s Children

    OpenAIRE

    Cesar Augusto Solano; Johan Fabiel Casas Díaz; Juan Carlos Guevara Bolaños

    2015-01-01

    Las tecnologías de la información y las comunicaciones (TIC) ha tenido un gran auge en lo los últimos años y es debido a este auge que se han ido introduciendo en el aula de clase con resultados prometedores. Por esta razón es indispensable crear herramientas innovadoras que fortalezcan los procesos de enseñanza y aprendizaje de los estudiantes, además de motivarlos a usar este tipo de herramientas tanto dentro como fuera del aula. El presente documento tiene como objetivo presentar al lector...

  18. Turismo, territorio y medio ambiente en Morella. Del P.G.O.U. (1986) a la Agenda 21 local (2000)

    OpenAIRE

    Obiol Menero, Emilio M.; Canós Beltrán, Hernán

    2001-01-01

    El presente trabajo intenta analizar desde la perspectiva de la geografía del turismo, esto es atendiendo a las acciones territoriales y ambientales, de qué forma Morella ha ido configurándose como el destino turístico de interior más visitado del País Valenciano. Desde 1964 hasta el año 2000, primero un conjunto de iniciativas públicas y privadas, ilustradas pero relativamente improvisadas, y desde 1980 tres documentos estratégicos de ordenación territorial (PGOU, 1986; PIRCT,...

  19. Taller sobre el color y su medición

    OpenAIRE

    Alonso Felipe, Jose Vicente

    2016-01-01

    El color y su medición siempre han despertado la curiosidad del ser humano y han ido adquiriendo importancia significativa desde hace mucho tiempo como consecuencia del desarrollo industrial, tanto desde el punto de vista de la física del color como desde la psicología del color. Son muchos los sectores industriales donde su cuantificación y control son de importancia significativa, no hay nada más que pensar en el campo de la automoción, textil, industria del plástico, industria de pintur...

  20. Evaluación de la viabilidad técnica y de costos de la aplicación de un proceso avanzado de oxidación foto catalítico en el tratamiento de aguas residuales del sector textil de Bogotá

    OpenAIRE

    Varela Reyes, Diana Jimena

    2013-01-01

    Dentro del proceso productivo de la industria textil se encuentra diversas operaciones (hilado, tejido, teñido) a partir de los cuales se obtienen subproductos como el agua de vertimiento de cada una de ellas, agua que finalmente llega a la redes de alcantarillado de Bogotá, es por ello que se consideró evaluar la viabilidad técnica y de costos de aplicar un proceso fotocatalítico en el agua de una de las industrias del sector textil de Bogotá, ello con el objetivo de mejorar la calidad del a...

  1. Plan de Comunicación La Cantina Portmany

    OpenAIRE

    Moreno Sánchez, Claudia; Llopis Ortega, Anna

    2017-01-01

    Treball de Final de Grau en Publicitat i Relacions Públiques. Codi: PU0932. Curs acadèmic 2016/2017 Este proyecto de fin de grado se centra en un plan de comunicación para el restaurante La Cantina de Portmany, situado en San Antonio, en la localidad de Ibiza. La Cantina es un restaurante con una larga trayectoria, exactamente desde 1933 cuando empezó siendo el primer Hotel de San Antonio. Desde entonces ha ido pasando de generación en generación hasta la actualidad. Ahora el hotel no s...

  2. Narrativas de la postmemoria en Argentina y Chile: la casa revisitada

    OpenAIRE

    Logie, Ilse; Willem, Bieke

    2016-01-01

    En los últimos años han ido surgiendo, tanto en Argentina como en Chile, narrativas autobiográficas sobre las respectivas dictaduras escritas por la generación de los ‘hijos’ (término que no se refiere exclusivamente a los vínculos parentales, sino también a los hijos simbólicos, cuya infancia o adolescencia estuvo marcada por la experiencia dictatorial). Esta literatura se distingue de la producción anterior por formular una respuesta matizada a la herencia de los 70 (y los 80) y por cuestio...

  3. ESTUDIO DE PROPIEDADES Y COMPATIBILIDAD DE MEZCLAS POLIPROPILENO (PP), ÁCIDO POLILÁCTICO(PLA) Y NANOPARTÍCULAS DE ÓXIDO DE SILICIO (SIO2), MEDIANTE EXTRUSIÓN Y MEZCLADO FÍSICO.

    OpenAIRE

    PONCE HERNÁNDEZ, JUANA SUHEY

    2015-01-01

    En las últimas décadas, el empleo de las poliolefinas en la industria de los empaques y embalajes para alimentos ha ido en aumento. El polipropileno ocupa el segundo lugar a nivel mundial, seguido del polietileno, dentro de los plásticos destinados para empaques que es una de las áreas de los plásticos que genera más residuos y por tanto daño al medio ambiente. Una alternativa para disminuir el impacto ambiental de estos desechos es la utilización de polímeros biodegradables en...

  4. Estudio y diseño del control de una aeronave no tripulada

    OpenAIRE

    Hernando Rodriguez, Albert

    2017-01-01

    La tecnología de los drones, cuyo inicio tuvo lugar hace aproximadamente un siglo, ha ido incorporando nuevos automatismos con el paso del tiempo, cosa que le ha permitido estar presente en más campos de actuación; hasta el punto álgido que vive hoy en día. Actualmente pues, se pueden encontrar drones en muchas aplicaciones, que pueden ir desde tareas de rescate a la agricultura. En este proyecto, se ha decidido centrar el estudio en una aplicación concreta de estas aeronaves, de tal forma...

  5. Territorio virtual: arquitectrónica

    Directory of Open Access Journals (Sweden)

    Marta Borbonet

    2002-08-01

    Desde el nacimiento en 1989 del lenguaje HTML para el intercambio de datos entre científicos, de la mano de Tim Berners-Lee la densificación de la información en Internet ha adquirido proporciones colosales hasta hoy en día. Paralelamente al ingente volcado de información en la Red han ido creciendo lógicamente nodos de conexión, servidores, routers, etc. o sea, mecanismos de distribución y acceso a este flujo informacional.

  6. Calidad de vida para personas con discapacidad intelectual y otras discapacidades del desarrollo. Aplicaciones para personas, organizaciones, comunidades y sistemas. Serie: Feaps

    OpenAIRE

    Schalock, Robert L.; Gardner, James F.; Bradley, Valerie J.

    2008-01-01

    Las perspectivas de mejora de la calidad de vida de las personas con discapacidad intelectual y otras discapacidades del desarrollo han ido variando de forma continua desde los comienzos del movimiento en los primeros años de la década de los ochenta. Todos estos cambios de perspectiva han forzado una nueva estructura y mejora de los procesos de la calidad en el desarrollo del concepto, sus aplicaciones lógicas, mediciones y resultados. Este nuevo libro de la colección FEAPS es una traducción...

  7. A imprensa do Recife na crise dos anos 1920: a repercussão do levante tenentista no Jornal do Commercio e na Tribuna Religiosa

    OpenAIRE

    ALFINO, Luiz Carlos dos Prazeres Serpa

    2013-01-01

    Os primeiros anos da década de 1920 foram determinantes na vida da sociedade brasileira, constituída nos moldes das oligarquias hegemônicas, sob o domínio da economia cafeeira desde os idos do Império. Esse período marcado por intensas movimentações de ordem política e social, investidas de sentimentos nacionalistas e de diversas correntes de pensamento e de concepções ideológicas, acarretará, no seio da sociedade civil, muitos protestos contra o status quo vigente. Neles se co...

  8. Semiótica y Arquitectura

    Directory of Open Access Journals (Sweden)

    Eduardo Meissner Grebe

    1984-12-01

    Full Text Available Al considerar la importancia que ha ido adquiriendo recientemente la semiótica en la búsqueda que, en categorías generales de pensamiento, hace de la naturaleza de los signos que conforman los lenguajes, incorporando las más variadas manifestaciones culturales a un sistema de signos, se comprende el atractivo uso, la útil proyección que resulta de una aplicación de esta teoría a las diferentes categorías de diseño, en especial de la arquitectura.

  9. El servicio civil en Ecuador : innovación y reforma de la burocracia en el período 2003 - 2008

    OpenAIRE

    Costa Sosa, Pablo Ricardo

    2010-01-01

    En los últimos años, el mejoramiento de la administración pública y su gestión, ha sido uno de los objetivos esenciales de varios países a nivel mundial. Para tal propósito los gobiernos han ido gestando nuevos cambios organizacionales pasando de enfoque burocrático a uno más flexible que contempla principios como: la gestión por resultados, la flexibilización de procesos, mayor autonomía gerencial, competitividad, productividad y transparencia. Estas transformaciones se denominarían modelo d...

  10. Entrenamiento y fisiología del ejercicio en la pubertad y adolescencia: principales mitos y controversias actuales

    OpenAIRE

    Mirco, Gustavo Ariel

    2009-01-01

    El presente trabajo forma parte de la especialización en fisiología del ejercicio de la Universidad Nacional de La Plata, Argentina. Actualmente y a lo largo de la historia han ido apareciendo diversos “métodos y medios” de entrenamiento de uso popular tanto en gimnasios como en el resto de los lugares de prácticas corporales. Estas formas de trabajo presentan al menos dudas con respecto a su fundamento fisiológico y biomecánico generando dos posibles consecuencias, la inutilidad del esfue...

  11. Una sala de arbitraje de inversión para Suramérica y El Caribe

    OpenAIRE

    Pedro Duarte LLovera

    2015-01-01

    En tiempos de crisis capitalista e inestabilidad global, el nuevo regionalismo alternativo surge tanto como un puente y como un escudo entre los países en desarrollo y la incertidumbre global. Desde la Cumbre de las Américas de 2004, América del Sur ha ido desarrollando una nueva identidad regional, que no encaja en los conceptos actuales de regionalismo en América del norte, Europa o Asia. Este neo regionalismo que representa ALBA, la Unión de Naciones Suramericanas (UNASUR) y la CELAC, refl...

  12. Propuesta para la estructuración de la plataforma de planeación estratégica de la empresa Óptica Dr. Méndez

    OpenAIRE

    Méndez Ortega, Andrés Felipe; Serrano Pineda, Mario Rodrigo

    2015-01-01

    Desde la aprobación del TLC, el mercado óptico en Colombia ha ido experimentado gradualmente una serie de cambios que están obligando a las microempresas del gremio y a las compañías pequeñas a monitorear constantemente el entorno y las reglas del mercado, este monitoreo está arrojando señales de alerta que deben generar acciones en las empresas, estas acciones son restructuraciones organizacionales, diseños de planes estratégicos nuevos o cambios en las estrategias actuales...

  13. Proyecto para la implementación del taller de fundición de hierro y acero PROFUNCA, en el sector de El Descanso Km. 20

    OpenAIRE

    Armijos Rodríguez, Jorge Luis; Ludeña Carrión, Oscar Andrés

    2008-01-01

    DIAGNOSTICO ACTUAL DEL TALLER. PROFUNCA, Productos Fundidos Cañizares, Taller artesanal que se dedica a la fundición de hierro, para la elaboración de poleas, tapas de alcantarillado y rejillas para sumideros, según el pedido del cliente, que con el pasar de los años ha ido aumentando su producción, instalaciones y sus colaboradores… IDENTIFICACIÓN DE PROCESOS PRODUCTIVO Producción por lotes y producción bajo encargo. ANÁLISIS DE SITUACIÓN ACTUAL Mediante el FODA, el taller se ...

  14. El empleado es el primer cliente, Iberia comprometida con su marketing interno = The employee, the main customer : Iberia commited to its internal marketing

    OpenAIRE

    Castillo Robles, ??ngela

    2018-01-01

    Analizar el proceso de marketing interno que llevan a cabo las empresas para conocer las necesidades y motivaciones de sus empleados es el objetivo principal de este Trabajo Fin de Grado. Para llegar a ??l, lo primero es preciso conocer el concepto en s?? de marketing interno, su origen y c??mo ha ido evolucionando hasta el d??a de hoy. Como es un proceso muy similar al de marketing externo, se dejan claras las diferencias y semejanzas entre ambos. Se va a definir lo que es la Responsabilidad...

  15. Implicaciones sociales del gasto de intereses sobre la deuda pública en Costa Rica: una aproximación

    Directory of Open Access Journals (Sweden)

    Rodrigo Matarrita Venegas

    2007-02-01

    Full Text Available LA FORMA EN LA QUE EL GOBIERNO DE LA REPÚBLICA DE COSTA RICA ha ido modificando su deuda pública ha incidido en la definición de un importante peso en cuanto al pago de intereses, lo que ha afectado la acción de Estado en cuanto a la redistribución de la riqueza, favoreciendo la acumulación del capital financiero de los agentes con excedentes de recursos. El documento procura establecer el uso de un par de indicadores como variables aproximadas de este fenómeno.

  16. Implicaciones sociales del gasto de intereses sobre la deuda pública en Costa Rica: una aproximación

    OpenAIRE

    Rodrigo Matarrita Venegas

    2007-01-01

    LA FORMA EN LA QUE EL GOBIERNO DE LA REPÚBLICA DE COSTA RICA ha ido modificando su deuda pública ha incidido en la definición de un importante peso en cuanto al pago de intereses, lo que ha afectado la acción de Estado en cuanto a la redistribución de la riqueza, favoreciendo la acumulación del capital financiero de los agentes con excedentes de recursos. El documento procura establecer el uso de un par de indicadores como variables aproximadas de este fenómeno.

  17. Estudi dels processos emocionals en nens i nenes amb dificultats d'aprenentatge i la seva relació amb els processos cognitius basats en la Teoria PASS de la Intel·ligència

    OpenAIRE

    Alabau i Bofill, Judith

    2003-01-01

    A lo largo de estos años de existencia del grupo de investigación se han ido desarrollando un volumen de casos donde se comenzó a evidenciar un hecho: niños y adolescentes llegaban derivados a la consulta por problemas de aprendizaje, pero éstos no siempre respondían a que tuvieran unos procesos cognitivos por debajo de la media. Por tanto, no se explicaba su bajo rendimiento escolar. Ante estos casos nos planteamos como intervenir en esta realidad educativa. Indagando descubrimos que la mayo...

  18. Consumo de alcohol y contextos de desarrollo en la adolescencia

    OpenAIRE

    Rubio González, Antonia

    2016-01-01

    Los patrones de consumo de alcohol en España se han modificado en los últimos años, y aunque el consumo de alcohol per cápita ha ido descendiendo ligeramente en las últimas décadas, su prevalencia actual entre los adolescentes y las mujeres es alta. Se ha constatado que el consumo abusivo de alcohol en la adolescencia se asocia a numerosas consecuencias negativas, como la continuidad en su consumo y el de otras drogas en la adultez, los problemas académicos, las relaciones sexu...

  19. Comunicación y movilización social

    Directory of Open Access Journals (Sweden)

    Gloria Dávila de Vela

    2015-01-01

    Full Text Available Hasta hace pocos años, la salud pública era concebida como responsabilidad exclusiva del Estado y como problema a ser resuelto por médicos y salubristas en los hospitales, centros o puestos de salud. Este concepto ha ido modificándose paralelamente al desarrollo de nuevas escuelas de pensamiento que han desplazado el eje de atención de la medicina curativa a la medicina preventiva. La comunicación deberá constituirse en un eje transversal que articule las distintas acciones de movilización social.

  20. Estrategias para inducir la formalidad de la mype de la industria gráfica-offset por medio de gestión competitiva

    OpenAIRE

    Santander Cjuno, Cintya Kristel

    2013-01-01

    Esta tesis presenta un Manual orientado a la Micro y Pequeña Empresa (MYPE) de la Industria Gráfica Offset como estrategia ante la informalidad existente de ese sector, utilizando como herramienta competitiva una esquematización de la propuesta de las políticas públicas y Tecnologías de la Información y Comunicación (TIC) que brindan diferentes organismos públicos. La informalidad empresarial ha ido evolucionando con el tiempo, sin que se definan criterios exactos que determinen la formalida...

  1. Modelos para la valoración genética de la disciplina de concurso completo de equitación a partir del control de rendimientos en las pruebas de selección de caballos jóvenes

    OpenAIRE

    González, M. A.; Cervantes, Isabel; Gómez, María Dolores; Bartolomé Medina, Ester; Serradilla Manrique, Juan Manuel; Valera Córdoba, María Mercedes

    2007-01-01

    Una de las principales fuentes de información funcional para la valoración genética precoz de los animales para las distintas disciplinas ecuestres son las Pruebas de Selección de Caballos Jóvenes (PSCJ), reguladas por el MAPyA, que se están celebrando en nuestro país desde el año 2004. Las PSCJ son muy importantes en la selección de los équidos deb ido a las altas correlaciones genéticas que se han encontrado entre las variables ...

  2. Métodos para la determinación del coeficiente de resistencia al flujo en cauces de rugosidad heterogénea

    OpenAIRE

    López Alonso, Raúl

    2002-01-01

    Al abordar problemas hidráulicos en cauces en los que la rugosidad varía a lo largo del perímetro, es usual el empleo de un único coeficiente de rugosidad de efectos hidráulicos equivalentes. Desde finales del primer tercio del siglo XX, se han ido proponiendo diversas expresiones para la determinación de un coeficiente de rugosidad equivalente, diferenciándose éstas en las hipótesis hidráulicas asumidas. En el presente trabajo se han revisado ocho de estas ecuaciones, proponiéndose la modifi...

  3. Patologías dentales en incisivos, caninos y primer premolar en caballos chilenos adultos Dental pathologies in incisors, canines and first premolar in adult Chilean horses

    OpenAIRE

    L Muñoz; F Vidal; O Sepúlveda; O Ortiz; C Rehhof

    2010-01-01

    Las patologías dentales han ido tomando mayor relevancia clínico veterinaria, aumentando el número de consultas, tratamientos y procedimientos preventivos. En caballos chilenos, la información existente de patologías dentales es nula, por lo que se hace primordial la investigación y recolección de datos en esta raza. Se analizaron 100 caballos pertenecientes a la Asociación de Rodeo Concepción, entre los meses de junio y septiembre del año 2007. Los materiales que se utilizaron fueron puro, l...

  4. Efecto de la pregabalina sobre la expresión de Fos en el tronco del encéfalo y la médula espinal en dos modelos de dolor neuropático

    OpenAIRE

    Villanueva Pérez, Vicente Luis

    2012-01-01

    En las últimas décadas, se han producido avances muy significativos en la búsqueda y hallazgo de nuevas estrategias terapéuticas contra el dolor. Esto ha sido posible gracias, en gran medida, al mayor conocimiento de los mecanismos subyacentes al dolor. Particularmente sustanciales han sido los datos obtenidos acerca del sustrato anatómico de la transmisión dolorosa y de su modulación endógena. En base a estos datos de carácter anatómico se ha ido clasificando el dolor en diferentes tipos: el...

  5. Plan de negocio para una empresa importadora de bisutería a base de cristal y similares procedente desde China, y comercializada en la Ciudad de Guayaquil (Parroquia Tarqui)

    OpenAIRE

    Ávila Chávez, Bella

    2012-01-01

    Con la globalización y la eliminación gradual de las barreras y fronteras al comercio entre los países, se han ido explorando nuevas y diversas formas de estar involucrado en este mercado importador de bisutería. Debido a lo anterior, existe un problema claramente identificado en el mercado de bisutería en la Parroquia Tarqui de la Ciudad de Guayaquil. Dicho problema se resumen en no tener al momento en esta zona un lugar donde comprar piezas de bisuterías, nuevas, modernas y d...

  6. Evolución de los monitores de rendimiento y terminales virtuales en maquinaria agricola

    OpenAIRE

    Garrido Izard, Miguel; Valero Ubierna, Constantino; Barreiro Elorza, Pilar

    2010-01-01

    Los monitores de rendimiento y terminales virtuales (TV), en general han ido adquiriendo con el paso del tiempo cada vez más fuerza dentro de la maquinaria agrícola. A día de hoy es posible la visualización y modificación de variables de trabajo, registro de las tareas llevadas a cabo, así como la posibilidad de facilitar y optimizar la actividades en campo (guiado, aplicación variable, siembra, abonado…), sin que para ello sea preciso abandonar el puesto de mando de la maquinaria. El número ...

  7. Hacemos mejor ciencia que la ciencia misma. Las teorías de la conspiración como discurso académico

    OpenAIRE

    Hugo Antonio Pérez-Hernáiz

    2018-01-01

    A través del análisis de los textos de una revista digital dedicada a los sucesos del 11 de septiembre del 2001 en Nueva York, este trabajo estudia las imbricaciones y divergencias del discurso teórico conspirativo y las ciencias. Se presta particular atención a las ciencias sociales. En el trabajo se arguye que la teoría de la conspiración analizada es mejor entendida como una hipertrofia del discurso científico que como un discurso reñido o ajeno a la ciencia misma.

  8. Nuevos negocios de telecomunicaciones

    OpenAIRE

    Sacoto Coello, Arturo Xavier

    2008-01-01

    Los avances tecnológicos dentro de las telecomunicaciones han generado el desarrollo de nuevos servicios que ha modificado el modelo de negocio provocado una migración de usos hacia éstos, así como la sustitución y renovación de tecnologías. Las enormes barreras de entrada han ido cayendo permitiendo nuevos agentes. La TELEMATICA aumenta a grandes pasos la capacidad de acceso a información y conocimiento, razón por la cual es necesario establecer un amplio conocimiento sobre los Nuevos Ne...

  9. Rol del docente en el control de la disciplina del contexto aúlico en los estudiantes de décimo año de educación general básica de la Escuela Fiscal Mixta Cecilia Álvarez de Freire durante el período 2011-2012.

    OpenAIRE

    Herrera Ramos, Custodia Trinidad

    2012-01-01

    Desde tiempos remotos todas los seres humanos se han comunicado a troves del lenguaje oral y mímico para trasmitir sus ideas, sentimientos y emociones ,con el transitar del tiempo se ha ido experimentando muchos cambios y hoy se vive en una época en el cual se presentan muchas barreras que impiden que se consigan los fines de comunicación pacífica. Las nuevas generaciones acuden a los centros educativos con poco conocimiento de esta habilidad social y los docentes son incapaces de orientar, g...

  10. El periodismo de moda en la blogosfera

    OpenAIRE

    González Fernández, Patricia

    2016-01-01

    En este trabajo de fin de grado se presenta un blog sobre periodismo de moda bajo el título: “El otro lado de la moda”. En él, se trata de mostrar una perspectiva diferente a la que ofrecen los medios de comunicación especializados en moda (tanto tradicionales como online) e incluso los diarios de estilismo o egoblogs que se encuentran en la web. Para llevar a cabo este proyecto se ha creado una plantilla en la plataforma Wordpress que poco a poco se ha ido dando forma hasta ob...

  11. Disparidades regionales en España de la densidad de población alo largo del siglo XX

    Directory of Open Access Journals (Sweden)

    José María Serrano Martínez

    2001-01-01

    Full Text Available Se analiza el proceso desigual de cambio de las regiones españolas (CC.AA durante el último siglo. Se advierte la sucesión de periodos muy diferentes con resultados contrastados. Así junto a áreas donde se han ido concentrando numerosos efectivos de población, en otras se ha producido un despoblamiento intenso. Se intenta realizar una modelización de lo ocurrido. De la misma manera, se señalan algunas de sus causas básicas y consecuencias derivadas de todo ello.

  12. La tecnología de la escritura: Del punzón al teclado, del papiro al blog

    Directory of Open Access Journals (Sweden)

    María Cecilia Reviglio

    2009-06-01

    Full Text Available La historia de la escritura y la lectura han ido a la par con los avances tecnológicos: de la escritura en piedra al lenguaje binario y de lo estático a la movilidad. El artículo abordará algunas concepciones teóricas que dan cuenta de la dimensión tecnológica de la escritura, las características de la escritura electrónica y de los cambios que supone la computadora en las prácticas de escritura.

  13. La codificación de la costumbre internacional

    OpenAIRE

    Jeannette Irigoin Barrenne

    2015-01-01

    La codificación es el enunciado de las normas y prácticas consuetudinarias por escrito y de una manera sistemática. La conveniencia de "codificar" el derecho consuetudinario se ha ido haciendo más evidente debido a la necesidad de precisar su contenido, teniendo presente la intensificación de las relaciones internacionales, las que exigen una regulación más precisa de las normas jurídicas que deben aplicar los sujetos de Derecho Internacional. (...)Contenido: Introducción. La formación de la ...

  14. Responsabilidad de los administradores societarios por pérdida del capital en el derecho argentino

    OpenAIRE

    Martin E. Abdala

    2011-01-01

    En este trabajo intentamos sistematizar y dar una explicación a algunas de las soluciones que la doctrina chilena ha ido adoptando al recepcionar la distinción obligaciones de medios/obligaciones de resultado para resolver casos de responsabilidad civil por actos médicos. Se trata de una aproximación dogmática de carácter tópica a un tema de gran complejidad sustantiva y procesal, por lo que parte importante del tratamiento del régimen jurídico de las obligaciones d...

  15. Análisis taxonómico y funcional del microbioma humano mediante aproximaciones clásicas, moleculares y metagenómicas

    OpenAIRE

    Cabrera Rubio, Raúl

    2014-01-01

    La presente tesis muestra distintas aproximaciones para el estudio del microbioma humano. Éstas han ido desde la secuenciación masiva de productos de PCR, la pirosecuenciación directa del ADN ambiental, la elaboración de librerías de fósmidos y por último el aislamiento de especies presentes en el microbioma mediante sembrado de la muestra. Todas estas técnicas tienen sus ventajas y desventajas, pero todas ellas son complementarias para el estudio de un determinado microbioma. Además la elabo...

  16. Panorama del derecho audiovisual francés

    OpenAIRE

    Derieux, E. (Emmanuel)

    1999-01-01

    El artículo realiza una panorámica del Derecho audiovisual francés hasta 1998. Como características básicas, se destacan su complejidad e inestabilidad, debida en gran parte a la incapacidad para asumir los rápidos cambios tecnológicos y a las continuas modificaciones que han ido introduciendo los gobiernos de distinto signo. Además, se repasan algunas de las cuestiones actuales más relevantes, desde la regulación de las estructuras empresariales hasta los programas audiovisuales y sus conten...

  17. Modelo de programación para infraestructuras Grid computacionales

    OpenAIRE

    Herrera Sanz, José

    2008-01-01

    A lo largo de la última década los sistemas Grid han ido adquiriendo cada vez más relevancia y han sido objeto de una gran variedad de tesis doctorales con diferentes líneas de investigación. Una de las principales líneas de investigación en el ámbito de sistemas Grid heterogéneos, corresponde con portado de aplicaciones, que consiste en adaptar aplicaciones ya existentes a sistemas Grid. Sin embargo, esta tarea conlleva una gran dificultad asociada, ya que el desarrollador de aplicaciones ti...

  18. Construcción de una red MPLS y validación de GNS3 para su simulación

    OpenAIRE

    Delgado Patiño, Héctor

    2015-01-01

    El propósito en este proyecto es:  -Abordar un problema de ingeniería real, diseñando y construyendo una red de comunicaciones de prueba en laboratorio similar a la que pudiera tener una empresa con varias sedes.  -La tecnología MPLS ha ido ganando terreno en los últimos años y actualmente se usa en las redes de tecnología de muchos operadores. Entre los motivos está principalmente su facilidad para configurar nuevos servicios y ofrecer QoS (Calidad de Servicio).  -Utilizar para e...

  19. Estudio hidráulico de la inundabilidad del Principado de Andorra

    OpenAIRE

    Sánchez Tueros, Hans Paul; Gómez Valentín, Manuel; Bladé i Castellet, Ernest; Riera, Manel; Planas, Xavier; Subra, Valèrie; Amigó, Jordi

    2009-01-01

    El Principado de Andorra, debido a la ubicación de sus principales núcleos habitados a orillas del río Vallira, viene sufriendo inundaciones que provocan desde simples molestias a la población hasta serios problemas tanto económicos como personales. Las autoridades, preocupadas por este problema y previendo posibles desastres como se tiene constancia de algunos episodios en años anteriores, ha ido poniendo en marcha una serie de actuaciones de mejora de la capacidad de desagüe del río Vali...

  20. Complementación del diseño de un sistema de información para la toma de decisiones caso FNA

    OpenAIRE

    Gonzalez Rodriguez, Araminta; Jimenez Hernandez, Alexandra

    2013-01-01

    La solución a las necesidades de vivienda de los colombianos, ha ocupado espacios importantes en las políticas públicas de diferentes gobiernos a lo largo del tiempo. Para ello, se han implementado diversas estrategias, que han ido desde la creación de entidades responsables de la administración de proyectos habitacionales, pasando por la incorporación de entidades oficiales y privadas que se vinculan a través de la otorgación de créditos, estimulo a la construcción de diferentes soluciones h...

  1. Uso académico de las redes sociales: análisis comparativo entre estudiantes y profesorado de la Universidad Católica Santo Toribio de Mogrovejo

    OpenAIRE

    Chunga Chinguel, Gerardo Raúl

    2016-01-01

    Desde el surgimiento de la primera red social virtual, Geocities en 1994 hasta la actualidad, han ido emergiendo diversos tipos de redes sociales virtuales con características, fines y público objetivo diferentes. Estos servicios se han universalizado, e incluso forman parte de la vida de las personas, en especial de los jóvenes. Además, se han convertido en un espacio idóneo para intercambiar información y conocimiento de una forma rápida, sencilla y cómoda. Sin embargo, como toda tecnolo...

  2. Cambios físicos y funcionales en el proceso de envejecimiento. ¿Es posible una calidad de vida en la vejez a través de programas socioeducativos

    OpenAIRE

    Belando Montoro, María

    2000-01-01

    A lo largo del tiempo se han ido desarrollando diversas teorías que intentan dar respuesta a los interrogantes sobre la etiología del proceso de envejecimiento. En la actualidad, hay diversas teorías bastante populares, como la de la programación genética y la que hace referencia a la oxidación de los radicales libres, pero lo cierto es que ninguna se ha podido considerar como definitiva, más bien son complementarias, pues cada una de ellas describe diferentes cambios que se producen al envej...

  3. Somatometria, obesidad y sobrepeso en estudiantes de educación básica de la frontera norte de México. Un análisis a partir de la ENSE 2008

    OpenAIRE

    Salvador Ponce Serrano

    2013-01-01

    La prevalencia de exceso de peso (sobrepeso más obesidad) en la población de las escuelas primarias y secundarias en México ha ido en aumento y tiene tendencia ascendente. Estas condiciones se asocian a la presencia de enfermedades crónicas degenerativas en el futuro y a dificultades escolares diversas. El exceso de peso es un problema de salud pública sobre todo en los estados de la frontera norte, con peculiaridades, según entidad federativa, por lo que un análisis diferenciado permite iden...

  4. Implementación de Plataformas Virtuales de Aprendizaje: Caso de Éxito “Universidad Corporativa de la ACP”

    OpenAIRE

    Martínez, Anthony; Ochomogo, Yenny; Miguelena, Ramfis

    2014-01-01

    El uso de las plataformas virtuales de aprendizaje ha ido en aumento, permitiendo de esta manera crear entornos de enseñanza-aprendizaje en donde se integren contenidos didácticos y herramientas que faciliten la comunicación, colaboración y gestión educativa. A partir de esta premisa y con el objetivo de implementar este tipo de plataformas en diferentes organizaciones de nuestro país, se presenta este artículo, en donde queda plasmada la metodología que se utilizó en la implementación de la ...

  5. Enfermedad gingival asociada al paciente pediátrico asmático

    OpenAIRE

    Carfi Marin, Indhira Del Valle; Alarcón Palacios, Marco

    2014-01-01

    El asma es una enfermedad infl amatoria crónica del sistema respiratorio, caracterizada por ser hipersensible y episódica, reversible y con síntomas de abstracción del fl ujo de aire. La prevalencia del asma ha ido en aumento a través de todas las edades, sexo y grupos raciales; y resulta ser mayor entre los niños que en adultos. Últimamente ha sido asociada en numerosas investigaciones a la prevalencia de caries y enfermedad periodontal, donde diversos factores y la respuesta inmune actúan d...

  6. La institución de la ciberpolítica: gobernanza y código.

    OpenAIRE

    Misseri, Patricio

    2016-01-01

    En el presente trabajo se aborda el problema de la manifestación de lo político en el ciberespacio, sosteniendo la hipótesis de que hay un aspecto institucional nuevo y distinto que podemos definir como “ciberpolítica”. Este aspecto se basa en dos fuerzas instituyentes: por un lado, el rol del código informático en la construcción de la arquitectura comunicacional de la red de redes (internet); por el otro, el rol de las comunidades virtuales como sujetos que se ven constreñido...

  7. Las mujeres y el poder colectivo. Análisis crítico del enfoque de empoderamiento de mujeres y la acción colectiva feminista en Chile

    OpenAIRE

    Lizana Salas, Natalia Andrea

    2014-01-01

    [spa] Uno de los aspectos problemáticos que posee el enfoque de empoderamiento de mujeres radica en que desde los años noventa en adelante se ha ido utilizando progresivamente pero sin suficiente precisión, realizándose un uso difuso de los conceptos de poder y empoderamiento, sin claridades conceptuales ni metodológicas, con lo que se diluye su potencial de cambio social. En vista de precisar a qué apunta el empoderamiento cuando se refiere a la transformación de las relaciones de pode...

  8. Redes sociales, políticas públicas y capital social

    OpenAIRE

    Lluís Ballester; Belén Pascual; Carlos Vecina

    2014-01-01

    La comunidad, o en un espacio más amplio la propia sociedad, en cualquiera de sus dimensiones, no es un espacio cerrado sin conexiones e interconexiones; más bien puede concebirse como una red de relaciones. En este sentido, desde las Ciencias Sociales ha ido creciendo el interés por el estudio de las redes sociales; esto ha permitido comprender mejor como se construyen y mantienen las relaciones sociales entre la población. Junto al concepto de redes sociales aparece también el de capital...

  9. Páginas para una historia de las comunicaciones ópticas y la fotónica

    OpenAIRE

    Martín Pereda, José Antonio

    2001-01-01

    Este trabajo es el resultado de una parte del curso "Fundamentos Electrónicos de las Comunicaciones" (2001) que los Departamentos del Área de "Tecnología Electrónica" de la ETSIT UPM llevan Impartiendo, con carácter de asignatura Optativa, durante los últimos tres años. El material recogido a los largo de estos años se ha ido acumulando en una larga serie de transparencias que están esperando adquirir la forma de un breve texto escrito. Antes de que esto se convierta en realidad el a...

  10. Metodología para la gestión ecointegradora y participativa del ciclo del agua en el espacio habitado. Aplicación al caso del barrio de Las Huertas (Sevilla)

    OpenAIRE

    Lara García, Ángela

    2017-01-01

    La configuración de los núcleos de población ha estado muy condicionada históricamente por las relaciones que se producen entre el agua, el territorio y las sociedades que lo habitan. Estas relaciones, que trascienden los aspectos físicos y socio-económicos para penetrar en lo cultural y simbólico, han ido complejizándose conforme los procesos de urbanización han adquirido mayor extensión a escala global. De esta manera, los procesos urbanizadores nos han llevado en la actualidad a una situac...

  11. Los héroes de los juegos olímpicos modernos y la evolución del equipamiento deportivo en el atletismo

    OpenAIRE

    Martín Barrero, Alberto

    2011-01-01

    Los Juegos Olímpicos, como evento deportivo más importante del momento, es un medio muy interesante para observar y analizar cómo el equipamiento deportivo ha cambiado a lo largo de su historia, pudiéndose observar que esta evolución ha ido encaminada a cubrir las necesidades que tenía el deportista para lograr mejores resultados y a su vez, cómo esta ha facilitado la evolución del deporte mediante la inclusión de materiales y medios que permiten tanto una mejor realizaci...

  12. Atención a pacientes con trastorno del espectro autista en la unidad de urgencias pediátricas del Hospital Clínico Universitario de Valladolid propuesta de protocolo

    OpenAIRE

    Pérez Mateos, Sergio

    2017-01-01

    Los Trastornos del Espectro del Autismo (TEA) constituyen un conjunto amplio de alteraciones graves que afectan al neurodesarrollo, provocando deficiencias en la comunicación e interacción social. El concepto del TEA ha ido variando a lo largo de la historia, hasta su clasificación actual descrita por el Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-V), que engloba el Trastorno Autista, el Síndrome de Asperger, el Trastorno Generalizado de la Infancia y el Trastorno Atíp...

  13. Proyecto de Factibilidad para la creación de un Taller de Mantenimiento de Contenedores y Equipos de Refrigeración en el Sur de la Ciudad de Quito.

    OpenAIRE

    Puente Heredia, Oscar Paúl

    2010-01-01

    En los últimos años el transporte pesado ha ido en aumento en nuestro país. Por un lado el crecimiento de las grandes empresas, que por sus volúmenes de ventas, se han visto en la necesidad de crear sus propias flotas de transporte para movilizar sus productos y por otro lado el incremento de empresas logísticas que se dedican al transporte de mercaderías. Hay empresas que necesitan que sus productos se encuentren bajo refrigeración para lo cual requieren de unidades de tran...

  14. APROXIMACIÓN HISTÓRICA A LA CONSTRUCCIÓN SOCIOJURÍDICA DE LA CATEGORÍA INFANCIA

    OpenAIRE

    Ravetllat Ballesté, Isaac

    2015-01-01

    Esta obra trata de presentar de forma sistematizada, recurriendo a un criterio cronológico, las principales etapas históricas por las que ha transitado la categoría sociojurídica Infancia a lo largo del devenir de los tiempos, para facilitar con ello un acercamiento paulatino a la moderna noción que tal concepto ha ido adquiriendo en los actuales sistemas normativos, tras la aprobación y ulterior entrada en vigor de la "Convención sobre los Derechos del Niño". Efectivamente, la moderna config...

  15. TERMINOLOGÍA Y LENGUAJE DEPORTIVO DEL FÚTBOL.

    OpenAIRE

    Rafael Aleixandre-Benavent; Recaredo Agulló Albuixech; Víctor Agulló Calatayud; Juan Carlos Valderrama-Zurián

    2007-01-01

    El deporte del fútbol ha ido alcanzando un creciente nivel de popularidad, por lo que el lenguaje empleado en la narración de los acontecimientos relacionados con él trascienden el medio deportivo y se extienden a casi todos los ámbitos sociales. En este trabajo se analizan y ejemplifican algunas características del lenguaje deportivo del fútbol, como su etimología y procedencia, la existencia de extranjerismos y calcos lingüísticos, las condiciones que deberían tenerse en cuenta para la acep...

  16. Diseño de un plan estratégico de negocios para la Empresa Inproespuma, fabricante de esponja, fabricante de esponja, colchones y almohadas, ubicada en el Valle de los Chillos, parroquia Conocoto

    OpenAIRE

    Pérez Cuásquer, Amanda Patricia

    2012-01-01

    Inproespuma Cía. Ltda. Es una empresa que se dedica a la fabricación de esponjas, colchones y almohadas en la ciudad de Quito y sus alrededores, el producto de mayor venta son las esponjas, aunque en los tres últimos años estas han ido en constante decrecimiento. El producto estrella de la empresa siempre han sido las esponjas, pero al existir rotundos cambios en el mercado específicamente la presencia de nueva competencia, le ha restado sustancialmente sus ventas, por lo que es necesario pen...

  17. ¿Volvería a ser enfermera/o? Análisis de la satisfacción laboral en el complejo asistencial universitario de Palencia

    OpenAIRE

    Morán Morán, Sara

    2017-01-01

    La enfermería ha ido adquiriendo y asumiendo nuevas funciones y responsabilidades con el tiempo, lo que aporta una mayor autonomía, causante de un aumento del estrés en los enfermeros. Al estrés se suman el Burnout y la Satisfacción Laboral. Burnout como consecuencia del estrés, derivado de la carga de trabajo y responsabilidades, juntos, afectan de forma negativa creando una insatisfacción laboral que puede llegar a poner en peligro la calidad de los cuidados ofrecidos. Estos conceptos, está...

  18. Implementación del sistema de venta de recarga virtual para distribuidores de una empresa de telecomunicaciones

    OpenAIRE

    Ibarra Apaza, Wilson Daniel; Ibarra Apaza, Wilson Daniel

    2012-01-01

    En la actualidad se ha observa que el Sector de las Telecomunicaciones ha ido creciendo notablemente, esto debido en parte al crecimiento económico del país en los últimos años, lo cual ha traído consigo oportunidades de negocio para las empresas de telecomunicaciones, quienes constantemente ofrecen productos y servicios de calidad enfocados a la satisfacción de los clientes, con la finalidad de retener a los clientes y atraer nuevos clientes de segmentos que aún no han sido explorados y que ...

  19. El arte MACA. Movimiento que denuncia la mala praxis de la publicidad respecto al tratamiento de las “imperfecciones” de la mujer

    OpenAIRE

    Arenas Solorzano, Almudena; Camberos Castaño, Beatriz; Adjei Hernández, Patrici

    2017-01-01

    La evolución de la imagen de la mujer en publicidad, ha ido cambiando de manera progresiva con el surgimiento de los movimientos feministas y los cambios sociales. Cada movimiento que se ha producido en la sociedad, ha significado un cambio reflejado también en los anuncios y en la imagen proyectada de la mujer en publicidad; sin embargo, dichos cambios, no se encuentran siempre en la manera en la que se retrata físicamente a la mujer. La publicidad ha seguido retratando a una mujer perfecta,...

  20. Aporte a la toma de decisiones Del Instituto de Ortopedia Infantil Roosevelt a partir del análisis estructural del sector estratégico de hospitales universitarios

    OpenAIRE

    Guzmán Prado, Yuli

    2012-01-01

    El concepto de hospitales universitarios ha ido evolucionando en el mundo, siendo cada vez más estricta la legislación que los regula y los mecanismos de evaluación para asegurar la calidad de la educación a los estudiantes que realizan prácticas en ambientes hospitalarios. El direccionamiento estratégico de los hospitales universitarios requiere en primer lugar de un análisis específico del sector, mediante pruebas como el análisis de hacinamiento, levantamiento del panorama competitivo...

  1. Violencia de género y pensamiento profesional: una investigación sobre la práctica del Trabajo Social

    OpenAIRE

    Pilar Ríos Campos

    2010-01-01

    Las casas de acogida para mujeres maltratadas han sufrido un proceso de transformación desde que fueron creadas. Inicialmente fundadas a partir de los principios y la filosofía del movimiento feminista, han ido siendo absorbidas por las administraciones públicas. Esto ha supuesto un cambio hacia la burocratización y la adaptación de las mujeres al sistema, antes que convertirlas en agentes de cambio social como se pretendía en un principio. En este artículo hacemos un somero análisis de est...

  2. Diseño e implementación de prototipo Hardware/Software para la automatización de procesos industriales en la Harinera Castellana

    OpenAIRE

    Torre las Heras, José Antonio de la

    2016-01-01

    La industria, al igual que el ser humano ha ido evolucionando con el paso de los tiempos. Desde la primera revolución industrial, la industria no ha parado de innovar en todos los aspectos. La globalización, por otro lado, ha obligado a las empresas a adoptar otros modelos económicos y estratégicos en sus modelos de negocio. Actualmente nos encontramos ante la cuarta revolución industrial que promete diversas mejoras en muchos planos mediante sistemas ciber-físicos, industria y...

  3. REMEDIACIÓN SOCIO AMBIENTAL Y SU INCIDENCIA EN SUELOS CONTAMINADOS CON HIDROCARBUROS EN EL CAMPO SACHA EN EL AÑO 2015

    OpenAIRE

    Vizuete García, Ricardo Abel

    2016-01-01

    El cambio climático frecuente y la preocupación de la sociedad por el cuidado medio ambiental se han ido incrementando, convirtiéndose en una exigencia social para las distintas empresas. El daño que causan los hidrocarburos en el suelo y en el ser humano es tan profundo que necesita adaptar procesos de remediación para descontaminarlos. El Campo Sacha ubicado en la amazonía ecuatoriana sufre las consecuencias de procesos inadecuados en la explotación y producción del petróleo, de los inadecu...

  4. Mitos en el embarazo. Realidad científica.

    OpenAIRE

    Fernández Barriga, Nuria

    2017-01-01

    Los mitos durante el embarazo tienen su origen antes de Cristo, y por diferentes órganos de difusión, tales como la iglesia y la cultura popular, han ido cogiendo fuerza hasta llegar a nuestros días. Estos mitos, tabúes y creencias se siguen transmitiendo entre las mujeres del siglo XXI. Con este trabajo se pretende identificar los mitos más importantes y comunes que rodean la gestación, buscando la evidencia científica para contrastar la veracidad o no de los mismos. El profesional de ...

  5. Impacto del uso de combustibles alternativos sobre la reactividad del clínker

    OpenAIRE

    Serrano-González, K.; Reyes-Valdez, A.; Chowaniec, O.

    2017-01-01

    El uso de combustibles alternativos en la industria cementera ha ido en incremento en las últimas décadas debido a su beneficio ecológico y económico. En línea con los esfuerzos enfocados en incrementar su uso, se han realizado distintos estudios enfocados en determinar su impacto potencial en la reactividad del clínker y en cómo pueden afectar sus propiedades físicas y mecánicas. Este trabajo estudia el efecto de cinco combustibles alternos sobre la reactividad de ocho muestras industriales ...

  6. Técnicas Básicas en Liberación Miofascial

    OpenAIRE

    Villares Torquemada, Eva María

    2017-01-01

    Técnicas básicas de Liberación miofacial 1. Introducción. 2. Principios de aplicación. 3. Técnicas básicas. 1. Introducción. El sistema fascial constituye una extensa e ininterrumpida red de tejido conjuntivo que envuelve y conecta todas las estructuras de nuestro cuerpo (músculos, tendones, ligamentos, vísceras, meninges, etc.). El concepto de fascia ha ido evolucionando a lo largo de los últimos años; de ser una estructura inerte de separación, a un sistema dinámico y con...

  7. Estudio de los factores del estilo de vida, genéticos y epigenéticos, que influyen en la obesidad y enfermedades relacionadas en población mediterránea

    OpenAIRE

    Barragán Arnal, Rocío

    2017-01-01

    La obesidad ha sido catalogada como la epidemia del siglo XXI, cuya prevalencia a nivel mundial ha ido aumentado en las últimas décadas. La obesidad se define como una acumulación anormal o excesiva de grasa que puede ser perjudicial para la salud. Además de ser considerada una enfermedad, es un factor de riesgo para otras patologías. El origen de la obesidad es multifactorial, y se produce como resultado de la combinación de los efectos genéticos, ambientales y sus interacciones. Los factore...

  8. Avances en sistemas analíticos de vanguardia-retaguardia basados en el empleo de nuevos materiales obtenidos de la combinación de líquidos iónicos con nanotubo de carbono

    OpenAIRE

    Polo Luque, M.D.

    2013-01-01

    En los últimos años, se ha desarrollado una marcada tendencia hacia la creación, optimización y mejora de nuevos materiales, que han sido incorporados y utilizados en una amplia variedad de procesos analíticos. En este sentido, la mayor atención se ha centrado en la creación de nuevos nanomateriales. Desde su descubrimiento en 1991 [1] los nanotubos de carbono (CNTs), así como sus derivados híbridos se han ido incorporando, gracias a sus excelentes propiedades, a multitud de aplicaciones en d...

  9. Seguridad ciudadana: ¿violencia o paz?

    OpenAIRE

    Carhuamaca Zereceda, David

    2006-01-01

    El concepto de seguridad ciudadana diseñado como bien jurídicamente protegido y que engloba a varios derechos de las personas tomadas en conjunto, se ha ido perfilando considerando que hoy en día la convivencia pacífica en una sociedad se encuentra amenazada por la existencia de tensiones y conflictos que generan conductas violentas y que han surgido por diferentes causas. Entre las que podemos señalar a dos de ellas que son complementarias, una es la crisis económica que afecta a la mayor pa...

  10. Detection of vehicle crossing path at intersection; Mitoshi no yoi kosaten ni okeru deaigashira jiko ni tsuite (Ibarakiken ni okeru jiko tahatsu zone no tokucho)

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, K; Uchida, N; Katayama, T [Japan Automobile Research Institute Inc., Tsukuba (Japan)

    1997-10-01

    An investigation was excuted to understand the actual state of accidents happened at intersections where there were no constructive obstacles in field of view. First, the aspects of fatal accidents are described under the basis of the data published by the police of Ibaraki prefecture. Then it is shown that there are at least 336 intersections where the accidents happened in the last two years. It is also clarified that many dangerous zones were located in line along rivers. The authors stress that it is urgent to inform the existence of dangerous zones to prevent the accidents. 2 refs., 5 figs.

  11. N- and C-alkylation of seven-membered iminosugars generates potent glucocerebrosidase inhibitors and F508del-CFTR correctors.

    Science.gov (United States)

    Désiré, J; Mondon, M; Fontelle, N; Nakagawa, S; Hirokami, Y; Adachi, I; Iwaki, R; Fleet, G W J; Alonzi, D S; Twigg, G; Butters, T D; Bertrand, J; Cendret, V; Becq, F; Norez, C; Marrot, J; Kato, A; Blériot, Y

    2014-11-28

    The glycosidase inhibitory properties of synthetic C-alkyl and N-alkyl six-membered iminosugars have been extensively studied leading to therapeutic candidates. The related seven-membered iminocyclitols have been less examined despite the report of promising structures. Using an in house ring enlargement/C-alkylation as well as cross-metathesis methodologies as the key steps, we have undertaken the synthesis and biological evaluation of a library of fourteen 2C- and eight N-alkyl tetrahydroxylated azepanes starting from an easily available glucopyranose-derived azidolactol. Four, six, nine and twelve carbon atom alkyl chains have been introduced. The study of two distinct D-gluco and L-ido stereochemistries for the tetrol pattern as well as R and S configurations for the C-2 carbon bearing the C-alkyl chain is reported. We observed that C-alkylation of the L-ido tetrahydroxylated azepane converts it from an α-L-fucosidase to a β-glucosidase and β-galactosidase inhibitor while N-alkylation of the D-gluco iminosugar significantly improves its inhibition profile leading to potent β-glucosidase, β-galactosidase, α-L-rhamnosidase and β-glucuronidase inhibitors whatever the stereochemistry of the alkyl chain. Interestingly, the N-alkyl chain length usually parallels the azepane inhibitor potency as exemplified by the identification of a potent glucocerebrosidase inhibitor (Ki 1 μM) bearing a twelve carbon atom chain. Additionally, several C-alkyl azepanes demonstrated promising F508del-CFTR correction unlike the parent tetrahydroxyazepanes. None of the C-alkyl and N-alkyl azepanes did inhibit ER α-glucosidases I or II.

  12. De las fosas comunes a los derechos humanos: El descubrimiento de las desapariciones forzadas en la España contemporánea1

    Directory of Open Access Journals (Sweden)

    Francisco FERRÁNDIZ

    2010-11-01

    Full Text Available Este texto se basa en una investigación de campo “multi–situada” de siete años sobre el impacto del ciclo más reciente de exhumaciones de fosas comunes de la Guerra Civil española, llevada a cabo en diversos escenarios: exhumaciones, actos conmemorativos, conferencias académicas sobre la memoria, presentaciones de libros, conciertos musicales, encierros universitarios, asambleas, diversas ONG, grupos de trabajo con apoyo institucional, laboratorios forenses, exposiciones de arte, manifestaciones, etc. Explora la forma en la que los discursos y conceptos transnacionales de los derechos humanos se han ido convirtiendo paulatinamente en guías fundamentales de la acción de muchas de las asociaciones que promueven la conocida como “recuperación de la memoria histórica”, a medida que el debate ha ido creciendo, se ha sofisticado, institucionalizado y, finalmente, judicializado. En este sentido, la secuencia de informes de Amnistía Internacional sobre el proceso o el auto dictado por Baltasar Garzón el 16 de septiembre de 2008, la controversia generada por él hasta su inhibición el 18 de noviembre de 2008, y los sucesos derivados del proceso que se le ha abierto en el Tribunal Supremo han actuado como catalizadores de esta irrupción de los derechos humanos en los debates sobre la memoria, a través de figuras jurídicas como las de los “crímenes contra la humanidad”, las “desapariciones forzadas”, y otras.

  13. Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice.

    Science.gov (United States)

    Rana, Proteesh; Sharma, Amit K; Jain, Smita; Deshmukh, Pravin; Bhattacharya, S K; Banerjee, B D; Mediratta, Pramod K

    2016-11-01

    The inflammatory response system has been implicated in the pathophysiology of major depression. The pro-inflammatory cytokines like interferon-γ induce the enzyme indoleamine-2,3-dioxygenase (IDO) of the kynurenine pathway of tryptophan metabolism. The induction of IDO reduces the availability of tryptophan for serotonin synthesis. Furthermore, the metabolites of kynurenine pathway have neurotoxic property, which along with decreased serotonin may account for depression-like illness. The aim of this study was to compare the effects of treatment with fluoxetine and 1-methyl-L-tryptophan (1-MT) on Bacillus Calmette-Guerin (BCG)-induced inflammatory model of depression in mice. Behavioral tests included locomotor activity, forced swim test (FST) and tail suspension test (TST). Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in homogenized whole brain samples. Comet assays were performed to assess neurotoxicity. The results of this study demonstrate that BCG treatment resulted in an increase in duration of immobility in FST and TST as compared to the saline group. Further, it produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. The hippocampal tissue from BCG group had significantly more comet cells than the saline group. 1-MT and fluoxetine were able to reverse the BCG-induced depression-like behavior and the derangement in oxidative stress parameters. Fluoxetine and 1-MT also reversed the BCG-induced neurotoxicity in such mice. 1-Methyl-L-tryptophan exhibits antidepressant-like effect comparable to that of fluoxetine in treating BCG-induced depression-like behavior in mice.

  14. Microenvironmental cues enhance mesenchymal stem cell-mediated immunomodulation and regulatory T-cell expansion.

    Science.gov (United States)

    Kadle, Rohini L; Abdou, Salma A; Villarreal-Ponce, Alvaro P; Soares, Marc A; Sultan, Darren L; David, Joshua A; Massie, Jonathan; Rifkin, William J; Rabbani, Piul; Ceradini, Daniel J

    2018-01-01

    Mesenchymal stem cells (MSCs) are known to both have powerful immunosuppressive properties and promote allograft tolerance. Determining the environmental oxygen tension and inflammatory conditions under which MSCs are optimally primed for this immunosuppressive function is essential to their utilization in promoting graft tolerance. Of particular interest is the mechanisms governing the interaction between MSCs and regulatory T cells (Tregs), which is relatively unknown. We performed our experiments utilizing rat bone marrow derived MSCs. We observed that priming MSCs in hypoxia promotes maintenance of stem-like characteristics, with greater expression of typical MSC cell-surface markers, increased proliferation, and maintenance of differentiation potential. Addition of autologous MSCs to CD4+/allogeneic endothelial cell (EC) co-culture increases regulatory T cell (Treg) proliferation, which is further enhanced when MSCs are primed in hypoxia. Furthermore, MSC-mediated Treg expansion does not require direct cell-cell contact. The expression of indolamine 2,3-dioxygenase, a mediator of MSC immunomodulation, increases when MSCs are primed in hypoxia, and inhibition of IDO significantly decreases the expansion of Tregs. Priming with inflammatory cytokines IFNγ and TNFα increases also expression of markers associated with MSC immunomodulatory function, but decreases MSC proliferation. The expression of IDO also increases when MSCs are primed with inflammatory cytokines. However, there is no increase in Treg expansion when MSCs are primed with IFNγ, suggesting an alternate mechanism for inflammatory-stimulated MSC immunomodulation. Overall, these results suggest that MSCs primed in hypoxia or inflammatory conditions are optimally primed for immunosuppressive function. These results provide a clearer picture of how to enhance MSC immunomodulation for clinical use.

  15. El oficio de docente en las novelas de Pérez Galdós / The teacher labour in the novels of Pérez Galdós

    Directory of Open Access Journals (Sweden)

    Ana-María Montero_Pedrera

    2017-01-01

    Full Text Available Resumen Este artículo analiza el oficio de docente en las novelas contemporáneas de Pérez Galdós. En ellas describe innumerables temas y personajes, entre ellos los maestros y maestras, con los que ejemplifica diversos tipos humanos con características bien definidas. Se ha usado el método histórico-educativo para el estudio y en los modelos hallados hay docentes bondadosos, con reminiscencias krausistas, como Máximo Manso en El amigo Manso; ramplones y faltos de vocación como José Ido en Tormento. Sublimes maestras como Atenaida, en La razón de la sinrazón; o doña Lupe, avara e impostora, en Fortunata y Jacinta. Pero, hemos hallado valores en el Magisterio; noble profesión, maltratada tradicionalmente por la sociedad y por los poderes públicos. Abstract This article discusses the teaching profession in Pérez Galdós’ contemporary novels. It describes many topics and characters, including teachers, with who exemplifies various human types with defined characteristics. The historicaleducational method is been used for the analysis. In the models found there are caring teachers, with Krausists reminiscences as Máximo Manso in El amigo Manso; Simples and with a lack of vocation as José Ido in Torment. Sublime teachers as Atenaida, in La razón de la sinrazón; or Dona Lupe, greedy and impostor, in Fortunata y Jacinta. But we have in the Magisterium values; noble profession, traditionally mistreated by society and by the government.

  16. Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies

    International Nuclear Information System (INIS)

    Juhász, Csaba; Nahleh, Zeina; Zitron, Ian; Chugani, Diane C.; Janabi, Majid Z.; Bandyopadhyay, Sudeshna; Ali-Fehmi, Rouba; Mangner, Thomas J.; Chakraborty, Pulak K.; Mittal, Sandeep; Muzik, Otto

    2012-01-01

    Introduction: Tryptophan oxidation via the kynurenine pathway is an important mechanism of tumoral immunoresistance. Increased tryptophan metabolism via the serotonin pathway has been linked to malignant progression in breast cancer. In this study, we combined quantitative positron emission tomography (PET) with tumor immunohistochemistry to analyze tryptophan transport and metabolism in breast cancer. Methods: Dynamic α-[ 11 C]methyl-L-tryptophan (AMT) PET was performed in nine women with stage II–IV breast cancer. PET tracer kinetic modeling was performed in all tumors. Expression of L-type amino acid transporter 1 (LAT1), indoleamine 2,3-dioxygenase (IDO; the initial and rate-limiting enzyme of the kynurenine pathway) and tryptophan hydroxylase 1 (TPH1; the initial enzyme of the serotonin pathway) was assessed by immunostaining of resected tumor specimens. Results: Tumor AMT uptake peaked at 5–20 min postinjection in seven tumors; the other two cases showed protracted tracer accumulation. Tumor standardized uptake values (SUVs) varied widely (2.6–9.8) and showed a strong positive correlation with volume of distribution values derived from kinetic analysis (P < .01). Invasive ductal carcinomas (n = 6) showed particularly high AMT SUVs (range, 4.7–9.8). Moderate to strong immunostaining for LAT1, IDO and TPH1 was detected in most tumor cells. Conclusions: Breast cancers show differential tryptophan kinetics on dynamic PET. SUVs measured 5–20 min postinjection reflect reasonably the tracer's volume of distribution. Further studies are warranted to determine if in vivo AMT accumulation in these tumors is related to tryptophan metabolism via the kynurenine and serotonin pathways.

  17. La formación de competencias investigativas en los estudiantes de la Carrera de Cultura Física. Una estrategia para su aplicación

    Directory of Open Access Journals (Sweden)

    María Del Carmen Corbo Rodríguez

    2007-06-01

    Full Text Available La Educación Superior Cubana en la segunda mitad del siglo XX ha experimentado profundos cambios desde los puntos de vista técnico y metodológico, generados particularmente por el desarrollo de las Ciencias de la Educación y por la necesidad de formar profesionales capaces de superar un proceso de enseñanza-aprendizaje de las ciencias marcado por una pedagogía tradicional y viejos esquemas donde el profesor indica todo lo que hay que hacer y el alumno se limita a reproducir los modelos, por una docencia creativa, integral, a partir de las competencias requeridas por sus modos de actuación. Es por ello que los modelos curriculares han ido cambiando cualitativamente, definiendo claramente tres dimensiones que se entrelazan en el proceso, pero que cada una de ellas se expresan y definen claramente: la dimensión académica, la laboral y la investigativa. Cada uno de estos componentes ha ido evolucionando teniendo en cuenta las necesidades socioculturales, y su aplicación de los sujetos como agente transformador del proceso en el que se desenvuelve. En estos momentos donde el desarrollo educacional concibe una relación directa entre pregrado y postgrado, es necesario reforzar el proceso de formación en investigación de cada una de nuestras carreras para fortalecer la utilización de las operaciones lógicas del pensamiento, la interpretación, la reflexión, para obtener nuevas producciones intelectuales que generen un desarrollo educacional pertinente.

  18. Mujeres emprendedoras en internet: una revisión de la literatura

    OpenAIRE

    Contreras, Ruth S. (Ruth Sofhía); Aramayo García, Alejandra Estella

    2012-01-01

    Los estudios sobre emprendimiento desde la perspectiva de género, es un ámbito que ha ido incrementado en los últimos años, la evidencia que más del 50% de la población mundial son mujeres pero que ellas son propietarias y gestionan una proporción de negocios muy inferior que los hombres y que existen diferentes estilos de gestión según el género, han impulsado el estudio de variables explicativas de las características distintivas entre hombres y mujeres en el ámbito del emprendimiento. El o...

  19. Regulación y Análisis Económico del Servicio Postal en España

    OpenAIRE

    Escribano Sáez, Álvaro; González Gómez, Patricia; Lasheras San Martín, Julio

    2003-01-01

    Las sociedades avanzadas han ido generando cada vez nuevos tipos de demandas; los clientes necesitan decidir cuándo, cómo y dónde utilizar, enviar y recibir información y mercancías de forma rápida. Estos hechos han llevado a liberalizar recientemente los servicios postales en muchos países para poder atender esas nuevas necesidades de servicios. Un buen ejemplo de ello es la elevada tasa de penetración del correo electrónico o de los courriers nacionales e internacionales que se dedicarán al...

  20. Herramientas de resolución y visualización en problemas de elementos finitos

    OpenAIRE

    López García, Enrique

    2017-01-01

    La dificultad de los cálculos a los que se ha de enfrentar un ingeniero para resolver los problemas de cualquier proyecto ha ido aumentando progresivamente, hasta llegar a límites en los que no es posible su resolución por métodos analíticos tradicionales. Es por esto que se desarrollaron, y se siguen mejorando, los llamados “métodos numéricos”: herramientas de cálculo alternativas a la resolución analítica, basadas en el cálculo aproximado mediante reglas matemáticas sencillas. Estos métodos...

  1. La caries dental y su interrelación con algunos factores sociales

    OpenAIRE

    Mayor Hernández, Félix; Pérez Quiñones, José Alberto; Cid Rodríguez, María del Carmen; Martínez Brito, Isabel; Martínez Abreu, Judit; Moure Ibarra, Miriam D

    2014-01-01

    Los estudios de ciencia, tecnología y sociedad en Cuba pretenden participar y fecundar tradiciones de teoría y pensamiento social, así como estrategias educativas y científico-tecnológicas que el país ha ido fomentando durante las últimas décadas. Investigar sobre la ciencia y la tecnología es un objetivo que comparten disciplinas muy diversas como la Historia, Sociología, Filosofía, todas de larga tradición. Desde los tiempos más remotos el ser humano ha tenido una incesante preocupación por...

  2. Los intangibles y el crecimiento económico

    Directory of Open Access Journals (Sweden)

    Marino Valencia Rodriguez

    2006-01-01

    Full Text Available Hoy día, se ha incrementado la superioridad e importancia de los activos intangibles en las empresas. Igualmente, se han ido constituyendo en elementos estratégicos claves y generadores de valor y ventaja competitiva, con los cuales, las organizaciones pueden afrontar los retos del mercado actual caracterizado por un ambiente globalizado y altamente competitivo. También, el artículo trata el concepto de activo intangible recogido en la Norma Internacional de Contabilidad NIC 38; definiciones de diferentes autores y una serie de aspectos y criterios que caracterizan los elementos intangibles.

  3. El Estrés Ocupacional: sus Efectos y una Propuesta para Moderarlos a través de la Actividad Física

    OpenAIRE

    Cabral Guillén, Ana C.

    2004-01-01

    El ámbito laboral es un componente de la vida diaria que está en constante evolución. Las exigencias laborales en diversas áreas han ido en aumento en los Últimos años. Por ésta razón, tal vez ahora más que nunca, el estrés causado por el trabajo representa una amenaza para la salud de los trabajadores y, como consecuencia, a la salud de las organizaciones. En general, el estilo de vida actual es mucho más acelerado que en épocas pasadas y esto ha generado nuevas enfermedades relacionadas con...

  4. Desarrollo de un Marco Tecnocultural para una SocioTecnología de la Información y Cultura, con aplicación en el ámbito de la Educación Superior para la formación de infoprofesionales.

    OpenAIRE

    Fumero Reverón, Antonio

    2012-01-01

    La intensa relación de las infotecnologías con el ámbito educativo no es algo nuevo. Ha ido pasando por diferentes etapas marcadas por uno u otro modelo para el proceso de enseñanza-aprendizaje: tele-enseñanza o educación a distancia, Computer-Based Learning (CBL), E-Learning, Blended Learning o B-Learning son algunos de ellos. En cada caso se han incorporando diferentes tecnologías, desde las cintas magnéticas de audio y vídeo hasta los portátiles, las tabletas y las pizarras electrónica...

  5. La violencia a través de las fases del amor pasional: Porque la pasión también tiene un lado obscuro

    OpenAIRE

    Omar Eduardo Kú Hernández; Rozzana Sánchez Aragón

    2006-01-01

    La pasión ha sido caracterizada por la alegría, sensación de realización, optimismo, éxtasis y profunda idealización del objeto amoroso (Villanueva Orozco, 2004). Sin embargo, autores como Hatfield y Rapson (1993) reconocen un lado más oscuro teñido de desesperanza, ansiedad y vacío. Por su parte, Sánchez Aragón (2004) propone un continuo del amor pasional que va de la atracción al amor desesperado, en donde el matiz negativo se va intensificando básicamente durante el...

  6. Elaboración de un plan de seguridad informática en la Ilustre Municipalidad de Paute

    OpenAIRE

    Carchipulla Choco, Diana Fernanda; Guamba Román, Miriam Alexandra; Méndez Rojas, Carmen Beatriz

    2007-01-01

    Hace relativamente pocos años la seguridad de la información era de fácil administración, sólo bastaba con guardar los documentos más importantes bajo llave y brindar protección a los empleados que poseen el conocimiento. Hoy en día esto es mucho más difícil. Con la evolución de los sistemas electrónicos, que han permitido automatizar un sin número de procesos y brindar grandes ventajas por su capacidad de almacenamiento y procesamiento, se han ido constituyendo como un componente fundamen...

  7. Noticias sobre las obras de Alonso Cano en Madrid: el Cristo de la Humildad de la Real Congregación del Santo Cristo de San Ginés

    OpenAIRE

    de Frutos Sastre, Leticia M.

    2003-01-01

    A pesar de los nuevos datos que están siendo publicados, y de la considerable importancia de la etapa madrileña de Alonso Cano, aún son muchas las dudas en torno a la actividad del granadino en la Corte. José Manuel Cruz Valdovinos ya recalcó la importancia de la figura del conde-duque de Olivares, gracias a la cual, Cano entraría en contacto con un importante círculo de funcionarios al servicio de la Corona. Poco a poco se ha ido conociendo y documentando la existencia de una clientela del a...

  8. Serie Documentos Nº2 - Investigaciones en Antropología Urbana (U. Central de Chile

    Directory of Open Access Journals (Sweden)

    Verónica Tapia Barría

    2007-09-01

    Full Text Available Una de las características principales del desarrollo de la investigación antropológica urbana en Chile es justamente el hecho de constituirse como un espacio en construcción, que obedece más bien a un conjunto de esfuerzos independientes que a la formulación de programas de investigación formales. Dichos esfuerzos son mayormente protagonizados por investigadores jóvenes, que desde sus particulares ópticas y objetos de interés han ido perfilando el carácter de lo que podríamos denominar antropología urbana chilena.

  9. Sistema de análisis automático de sentimientos basado en procesamiento del lenguaje natural

    OpenAIRE

    Casas García, Alejandro

    2014-01-01

    En este Proyecto Fin de Carrera se pretende diseñar e implementar un sistema capaz de extraer información de tipo emocional y de opinión de un texto de forma automatizada a través de técnicas de procesamiento del lenguaje natural y análisis morfosintáctico del mismo. Así, se persigue dar una solución tecnológica al problema del análisis automático del sentimiento, cuyo interés ha ido en alza estos últimos años, debido mayormente al crecimiento continuado en nuestra sociedad de ...

  10. Análisis de la incidencia de la producción de biocombustibles a través de cultivos transgénicos en la seguridad alimentaria. Estudio de caso: Cultivos de soja transgénica en Argentina

    OpenAIRE

    Gómez Salamanca, María Paula

    2013-01-01

    La búsqueda de los Estados por mitigar su dependencia energética de las fuentes fósiles, ha traído consigo la búsqueda de energías alternativas, desencadenando en el uso y producción de biocombustibles. A su vez, la producción de estos últimos a través de cultivos transgénicos ha ido cobrando importancia en el escenario internacional. Esta opción se ha considerado como una salida al dilema de utilización de tierras "Biocombustible vs. Alimentos". En este contexto, el caso de Argentina, como u...

  11. Vacunas de bacterias recombinantes vivas

    OpenAIRE

    Blanco León, Marina

    2016-01-01

    La vacunación es uno de los logros más importantes en la historia de la medicina, que ha ido evolucionando a lo largo de los años permitiendo una reducción significativa de la mortalidad infantil, una disminución de la incidencia de enfermedades e incluso la erradicación de algunas de ellas en países enteros. Las vacunas de nueva generación surgen para reducir o eliminar las carencias de las vacunas “tradicionales”. Técnicas biotecnológicas basadas en el ADN recombinante han dado lugar, entre...

  12. Relación entre las Inteligencias Múltiples y la creatividad en niños 4º de Primaria

    OpenAIRE

    Pérez-Vidal, Belén

    2015-01-01

    En el último siglo la educación ha cambiado vertiginosamente. Multitud de leyes se han ido instaurando en un sistema educativo que va cambiando según el gobierno que llega al poder. Ello ha provocado un Sistema Educativo Español inestable que se traduce en un alto porcentaje de fracaso escolar en los alumnos de nuestro país. Dentro de esta inestabilidad y fallos, encontramos el método de enseñanza empleado por algunos docentes. Un método de enseñanza al que no todo el profesorado ha sab...

  13. Pensamiento del profesorado y alumnado sobre la integración de las TIC y su uso en los centros de adultos de Canarias

    OpenAIRE

    Morales Almeida, Paula

    2014-01-01

    Programa de doctorado: Formación del profesorado [ES] La educación de adultos ha ido adquiriendo una gran importancia en los últimos años como resultado de la educación permanente desarrollada por la sociedad de la información y la comunicación pero para que la educación de adultos tenga éxito debe contar con profesores formados en diversas áreas y que conozcan sus características de aprendizaje. Además, en esta nueva sociedad, las TIC han adquirido una vital importancia, ya que se encuent...

  14. Nutrition in High Performance Wheelchair Basketball in Two European Countries

    OpenAIRE

    Grams, Lena

    2017-01-01

    El interés en los deportes paraolímpicos, especialmente en el baloncesto en silla de ruedas se ha ido incrementando en los últimos años, por otra parte en esta población de igual manera que en otros deportistas el hecho alcanzar altos niveles de rendimiento constituye el principal objetivo o reto común. Es evidente que, pequeñas variaciones de rendimiento pueden determinar la diferencia entre ganar y perder y por tanto además de la condición física, hay que asegurar otros factores que potenci...

  15. La exploración geológica

    OpenAIRE

    Rogelio Monreal Saavedra.

    2013-01-01

    Durante millones de años, los recursos minerales se han ido formando en lugares específicos conocidos como yacimientos minerales los cuales son escasos y difíciles de ubicar. La exploración es de vital importancia para la industria minera y el geólogo viene hacer una pieza importante para su exploración y posterior explotación. La exploración inicia con la búsqueda de un depósito mineral, utilizando una serie de procesos e indicadores geológicos que sirven para localizar un lugar en la super...

  16. Riesgo de tromboembolismo venoso en mujeres consumidoras de anticonceptivos hormonales combinados

    OpenAIRE

    Nápoles Méndez, Danilo; Couto Núñez, Dayana

    2016-01-01

    Desde la introducción en los años 60 de las tabletas anticonceptivas, se han ido produciendo modificaciones en sus componentes, con el objetivo de mejorar su seguridad y tolerancia sin perder su eficacia. Las principales novedades están relacionadas con la introducción de nuevos progestágenos con menores efectos secundarios y mayores beneficios adicionales, así como también con la aparición de un preparado con estrógeno natural y la utilización de nuevas pautas de inicio y de régimen de inter...

  17. Evaluación de Lesiones Periapicales en Pacientes Derivados a Cirugía Periapical Mediante Tomografía Computarizada de Haz Cónico

    OpenAIRE

    Hernández Vigueras, Scarlette; Donoso Zúñiga, Manuel; Sanhueza Tobar, Claudio; Linco Olave, Jared; Riquelme Carrasco, Sebastián

    2017-01-01

    El uso de la tomografía computarizada de haz cónico (CBCT) en endodoncia ha ido en aumento, justificando su uso en casos más complejos, como cirugías periapicales. El objetivo fue evaluar las características imagenológicas encontradas en un grupo de pacientes derivados a cirugía periapical, mediante el uso de CBCT. Se realizó un estudio observacional descriptivo, en un grupo de pacientes, derivados a cirugía periapical, a los cuales se realizó un examen de CBCT, evaluación clínica y radiograf...

  18. PERFIL POR COMPETENCIAS DEL JEFE DE TALENTO HUMANO EN EL GOBIERNO AUTÓNOMO DESCENTRALIZADO DE UN CANTÓN DE LA PROVINCIA DEL GUAYAS.

    OpenAIRE

    Borja Mora, Liz Ivette

    2014-01-01

    La Gestión por Competencias es una filosofía para la gestión del talento humano que ha ido adquiriendo cada vez más importancia en la vida organizacional, toda vez que la correcta definición de los perfiles de cargos por competencias garantiza el punto de partida para la gestión del resto de los subsistemas del talento humano. Una vez que el directivo del área de talento humano hace el análisis para la planeación del talento humano en la organización, cuenta con el inventario de recursos h...

  19. Concepciones y actitudes ante la muerte : teorías implícitas, determinantes socioculturales y aspectos psicológicos relacionados

    OpenAIRE

    López Lechuga, Rocío

    2016-01-01

    La esencia misma del hombre está en la toma de consciencia de la existencia de la muerte. La existencia de esa preocupación por la muerte ha ido variando en sus manifestaciones a lo largo de la historia. Según Kellehear (1984) es inapropiado hablar hoy de un tabú sobre la muerte en la sociedad moderna debido a la proliferación de la literatura, lo que supone un “redescubrimiento” de la muerte pero lo que es cierto es, como dicen Hernández, González, Fernández, e Infante, (2002) que: “en la...

  20. Redes de una organización abierta: El Mundo social de un Monasterio Budista Europeo = Open Organization Networks: The Social World of an European Buddhist Monastery

    OpenAIRE

    Rodriguez, Josep A. (Josep Antoni); Ramon Aribau, Anna; Arroyo Moliner, Liliana

    2011-01-01

    Durante las últimas décadas varias tradiciones y comunidades budistas se han ido asentando en España, una de ellas ha irrumpido más allá de la esfera religiosa o espiritual. Este artículo tiene como objetivo entender cómo se organiza el proyecto hacia la sociedad de los Monjes Budistas de Sakya Tashi Ling. Son una Comunidad con dos monasterios y casas de retiro de la tradición Vajrayana Sakya y Ngagpa. Son una versión occidental y particular de hacer Budismo desde, en y para la sociedad. Se a...

  1. Empresas de trabajo temporal

    OpenAIRE

    Chico Abad, Virginia

    2015-01-01

    Las empresas de trabajo temporal han ido tomando mayor relevancia debido a la estructura de la sociedad y de la economía. La entrada en vigor de la ley 14/1994 por la que se regulan las empresas de trabajo temporal suposo la incorporación al ordenamiento jurífico español de un tipo de empresas cuya actuación se habia extendido en otros países del entorno europeo. La idea general gira en torno a la flexibilidad de un nuevo marco económico y organizativo y exige a las empresas una capa...

  2. Estrategias de manejo sostenible para conservación de la avifauna de la comunidad Gualchán, provincia del Carchi.

    OpenAIRE

    Chandi Yépez, Alonso Javier

    2016-01-01

    Diseñar estrategias de manejo sostenible para la conservación de la avifauna de la comunidad de Gualchán como potencial de desarrollo del Ecoturismo y su ecosistema. La comunidad de Gualchán en los últimos años ha evidenciado la problemática ambiental generada por factores antrópicos, los ecosistemas y la vida natural de muchas de las especies animales que requieren de su hábitat para desarrollarse se han ido deteriorando generando de esta manera la migración y extinción de especies en par...

  3. Desarrollo de una célula robotizada de paletizado

    OpenAIRE

    Rodríguez Rodríguez, Iván

    2017-01-01

    No cabe duda de que, a lo largo de los años, la automatización ha ido cobrando cada vez más importancia en los procesos industriales hasta convertirse en una parte fundamental de los mismos. El afán por mejorar los tiempos de producción, reducir los costes y obtener mejores productos ha provocado que hoy en día, prácticamente cualquier proceso industrial que pueda estar sujeto a ser automatizado, lo sea. Con esta idea en mente, el campo de la automatización de procesos de cara a la formac...

  4. La ganadería ecológica como modelo de gestión del Parque Natural de la Sierra de Grazalema

    OpenAIRE

    Díaz Gaona, Cipriano

    2013-01-01

    1.introducción o motivación de la tesis La mayoría de los Espacios Naturales Protegidos (ENP) de España han llegado a serlo gracias al uso racional que de sus recursos han venido haciendo sus pobladores durante siglos; especialmente, a través de la ganadería. Esta ganadería sostenible ha ido perdiendo rentabilidad en los últimos años, lo que está llevando a muchos ganaderos a intensificar sus explotaciones o a abandonarlas; lo cual repercute negativamente sobre la conservación de dichos E...

  5. Historia de la Conservación Preventiva. Parte II

    OpenAIRE

    García Fernández, Isabel M.

    2014-01-01

    La segunda parte de la historia de la conservación preventiva comienza en 1990; esta etapa es mucho más corta que la primera,pero más prolífica en materiales, proyectos y publicaciones. Vamos a ver cómo desde sus inicios, la conservación preventiva ha ido cobrando protagonismo en todos los ámbitos relacionados con la preservación y uso del patrimonio. En este artículo vamos a destacar los hitos fundamentales que han conseguido afianzar esta disciplina en los últimos 25 años y valorar- su desa...

  6. Conservación in situ de los Mosaicos Romanos de Mérida. Historia y Tecnologías de la Información Geográfica Aplicadas

    OpenAIRE

    Pérez Chivite, Mª Paz

    2017-01-01

    448 p. Mérida constituye uno de los centros más destacados dentro de la producción musiva del mundo romano en la Península Ibérica. Desde los primeros descubrimientos de mosaicos a partir del siglo XIX hasta nuestros días, este patrimonio se ha ido incrementando al compás del desarrollo de la disciplina arqueológica con gran éxito en este centro urbano.La conservación in situ de este vasto legado ha supuesto desde el primer momento un gran esfuerzo por parte de las instituciones creadas a ...

  7. Reflexiones críticas, desde los márgenes, sobre la producción de conocimientos para una acción transformadora

    OpenAIRE

    Juan Carlos Gimeno Martín

    2012-01-01

    Desde la perplejidad de un académico que habita una Europa en crisis, en este artículo se exploran, en forma de conversación, algunas perspectivas críticas que se han ido consolidando en América Latina sobre el mundo en que vivimos y sobre lo que nos ha traído hasta él, reivindicando la producción del conocimiento desde los márgenes, desde las fronteras, desde los sujetos negados por la “historia”. El enfoque utilizado, que valora la existencia, la resistencia, las luchas de mujeres y hombres...

  8. Precisiones sobre la Educación Emocional

    OpenAIRE

    José Antonio MARINA

    2005-01-01

    En este artículo se estudia el interés que ha ido despertando el mundo de los sentimientos, desdeñado por la psicología académica, durante mucho tiempo, por ser demasiado subjetivo. Un viejo tema, ya presente en filósofos como Sócrates, Platón. Aristóteles, Epicuro, Epicteto o Séneca, que fueron educadores de los sentimientos, y, más tarde, en Descartes, Spinoza o Rousseau. Todos estos pensadores incluían la educación de las emociones dentro del marco de la ética, mientras que en la actualida...

  9. Higiene Industrial en empresa de limpieza

    OpenAIRE

    Dorca-Mariño, José Ignacio

    2012-01-01

    Este trabajo se realiza basándose en la experiencia del autor al hacerse cargo del Servicio de Prevención Propio de SERLIMAT ESPAÑOLA , empresa de limpieza industrial con 28 años de experiencia en su sector y que ha ido creciendo tanto en número de empleados, como en actividades y en implantación geográfica. En la actualidad, formamos parte de la empresa más de 700 trabajadores, con una amplia mayoría femenina, que representa aproximadamente el 80%, y la principal actividad de la empresa e...

  10. Tragedias

    OpenAIRE

    Peralta, Fernando López

    2011-01-01

    Son las seis de la tarde; el cielo, teñido de naranja y rosa luce maravilloso sobre los grandes y brillantes edificios que ahora existen en la ciudad. Conduce de regreso a su hogar, su refugio; allí lo esperan Carlos y Braulio, sus dos hijos, para hacer las tareas de matemáticas; lo espera Adriana, su joven y gentil esposa, para contarle que en menos de un año la familia será más grande. También lo esperan las mascotas, Hugo y Roca, dos pequeños chihuahuas que tan pronto sienten que estaci...

  11. ¿Pero sigue existiendo la televisión en un universo global de comunicación?

    OpenAIRE

    Cabero Almenara, Julio

    2005-01-01

    Diferentes han sido las revoluciones de la historia de la comunicación humana, que han ido desde la calzada romana, hasta la imprenta, la radio, la televisión e Internet. Aunque es cierto que Internet va ganando terreno como medio de comunicación de masas, también lo es que hoy por hoy el único medio globalizado es la televisión, y ello es debido a una serie de motivos como volumen de usuarios, globalización y presencia mundial, impacto, volumen de duplicación de aparatos, calidad del medio, ...

  12. Nuevos métodos de pago online, seguridad y confiabilidad

    OpenAIRE

    Rodríguez Martínez, Miguel

    2015-01-01

    RESUMEN: El uso de internet claramente ha cambiado nuestros hábitos y costumbres a lo largo de estos últimos años y principalmente a comienzos del siglo XXI. La economía, que siempre está en constante cambio tampoco podría haberse quedado atrás por lo que se ha ido adaptando a este gran cambio social. El E-commerce o Comercio Electrónico basado en la compra y venta de bienes y servicios mediante internet, ha sufrido un gran incremento tanto en el volumen de operaciones como el número de us...

  13. Análisis de las páginas web de los canales generalistas de TV en España: desarrollo estratégico de marketing

    OpenAIRE

    Mielgo Álvarez, María Aránzazu

    2016-01-01

    La aparición de Internet y la implantación, primero, y propagación, después, de las nuevas tecnologías han propiciado drásticas transformaciones en los hábitos y en las formas de proceder de las sociedades de todo el planeta. Este fenómeno no ha sido tampoco ajeno a los medios de comunicación tradicionales. Hasta el punto de poder asegurar que el ciberespacio ha logrado modificar sustancialmente sus fórmulas clásicas de consumo, que se han ido reconvirtiendo de manera significativa en los últ...

  14. Planificación publicitaria de una televisión privada: el ejemplo de Movistar+

    OpenAIRE

    Panizo Ateza, Roberto

    2017-01-01

    La planificación publicitaria es una disciplina que nace alrededor de los años 50. Desde entonces, y con el desarrollo exponencial de los medios, la planificación de la publicidad ha ido adaptándose a las características de cada uno. En el caso de la televisión, la planificación publicitaria tiene diferentes características y también aristas en común en la diferenciación entre televisiones públicas y privadas. En el presente documento se analiza el caso de una televisión privada como lo es Mo...

  15. La evaluación de competencias en la Educación Superior: el caso de un máster universitario

    OpenAIRE

    Triadó i Ivern, Xavier Ma.; Aparicio Chueca, Ma. del Pilar (María del Pilar); Elasri Ejjaberi, Amal

    2013-01-01

    La implantación de las competencias es una tarea que ha ido incorporándose paulatinamente por los docentes de la universidad española con la entrada en vigor del EEES. A pesar de ello, aún se está lejos de alcanzar los niveles óptimos de evaluación de las mismas. Este artículo permite reflexionar sobre algunas buenas prácticas al respecto y sobre las dificultades y limitaciones que aparecen al querer implantar un cambio en las metodologías docentes, en el marco de un máster universitario. Los...

  16. Acerca de la relación infantil y asistencia escolar: apuntes para su comprensión

    OpenAIRE

    Rausky, María Eugenia

    2008-01-01

    En sociedades occidentales el trabajo de los niños suele pensarse como un fenómeno problemático en tanto entra en contradicción con lo que se considera adecuado para dicho período de la vida. Concretamente, a partir de la época moderna se ha ido consolidando la idea de que la infancia es un momento especial en el curso de vida de los sujetos en el que se van construyendo los elementos necesarios para el desarrollo. Entendiendo que los niños son seres vulnerables, que necesitan de cuidados esp...

  17. Propuesta Para La Disposición Adecuada De Los Residuos Sólidos Reciclables En El Laboratorio San Martín

    OpenAIRE

    Araya-Trejos, Yesenia

    2011-01-01

    Proyecto de Graduación (Maestría en Gestión de Recursos Naturales y Tecnologías de Producción) Instituto Tecnológico de Costa Rica. Área Académica Agroforestal, 2011. En las últimas décadas la generación de residuos sólidos ha ido creciendo exponencialmente a nivel mundial. Dentro de los factores que han contribuido a tal expansión están: la cultura de usar y tirar los llamados “desechables”, la elevada cantidad y diversidad de materiales de empaque que se comercializan con los productos, ...

  18. Enrique Krauze: Redentores. Ideas y poder en América Latina

    OpenAIRE

    Santiváñez Vivanco, Martín

    2012-01-01

    Enrique Krauze es, sin duda alguna, el gran historiador liberal latino de las últimas décadas. Su prestigio como intelectual se ha ido incrementando y, por tanto, las obras de este discípulo de Octavio Paz ejercen un influjo importante en la discusión de las ideas latinoamericanas. Krauze es consciente de ello y por eso, tras El poder y el delirio, una pieza en la que disecciona los resortes del populismo de Hugo Chávez, avanza un paso más con Redentores, volumen en el que nos presenta las se...

  19. Estudio, ensamblaje, caracterización y ensayos de dos modelos reales de RPA

    OpenAIRE

    Matienzo Merodio, Joel Juliá; Olmedilla García, Alfonso

    2016-01-01

    Un dron o un RPA (del inglés, Remote Piloted Aircraft) es un vehículo aéreo no tripulado capaz de despegar, volar y aterrizar de forma autónoma, semiautónoma o manual, siempre con control remoto. Además, toda aeronave de estas características debe ser capaz de mantener un nivel de vuelo controlado y sostenido. A lo largo de los años, estos aparatos han ido evolución tanto en aplicaciones como en su estética y características físicas, siempre impulsado por los requerimientos militares en c...

  20. Comportamiento del consumidor en las compras online

    OpenAIRE

    García Cárdenas, David

    2017-01-01

    RESUMEN: En los últimos años, el surgimiento de Internet y el continuo avance tecnológico han cambiado no solo nuestro estilo de vida, sino también la forma de relacionarnos y de hacer negocios. Las empresas han de adaptarse a un entorno cada vez más competitivo debido a la globalización y a una forma de vender y comerciar que cada vez tiende más hacia el comercio electrónico y menos hacia la venta tradicional en establecimiento físico. En este documento trataremos de analizar cómo ha ido cam...

  1. Los Smartphones en educación superior. Diseño y validación de dos instrumentos de recogida de información sobre la visión del alumnado

    OpenAIRE

    Salcines Talledo, Irina; González Fernández, Natalia

    2015-01-01

    RESUMEN: El surgimiento de la denominada Web 2.0 ha ido acompañado de la aparición de múltiples posibilidades y tendencias pedagógicas en el ámbito de la Educación Superior gracias a la creación de espacios virtuales adecuados para los procesos de enseñanza, aprendizaje, evaluación y orientación educativa. Dicha tendencia, facilita que el acompañamiento de los estudiantes pueda llevarse a cabo en diferentes modalidades y contextos. Entre estas tendencias una de las que mayor repercusión educ...

  2. Preliminares para o conhecimento da Arte Clássica

    Directory of Open Access Journals (Sweden)

    Ulpiano Toledo Bezerra de Meneses

    1965-06-01

    Full Text Available A vastidão da arte grega, no tempo (em têrmos gerais, ido século XI a. C. até fins da éra pagã e no espaço (da Grécia continental expandiu-se para as colônias da Ásia Menor, Sicília, Itália meridional, Mar Negro e, depois, regiões da Anatólia, Síria, Egito e outras partes do Mediterrâneo, Roma, enfim tornam um problema particularmente espinhoso sua caracterização em traços nítidos e definidos.

  3. UChat: chat accesible para la Universidad Carlos III de Madrid

    OpenAIRE

    García Morales, Pablo

    2015-01-01

    En los últimos años se ha producido un increíble aumento en el uso de aplicaciones en telefonía gracias al auge de los teléfonos inteligentes, especialmente las aplicaciones de mensajería instantánea de tipo chat. Estas aplicaciones, además, en los últimos años se han ido utilizando cada vez más en docencia, facilitando la comunicación entre alumnos y profesores en todo momento. A pesar de su popularidad, todavía presentar barreras de accesibilidad que impiden que muchas personas (personas co...

  4. Una Propuesta de Estimulación Musical en la Escuela

    OpenAIRE

    Sáez-de-Ibarra, Olatz

    2013-01-01

    Este trabajo explicamos la influencia positiva de la música en el ser humano, especialmente en las primeras etapas de la infancia. Hemos realizado una síntesis de la evolución que ha ido sufriendo el término de estimulación de temprana, y también hemos revisado los beneficios de la musicoterapia, tanto en niños sin ningún tipo de problema de desarrollo, como en niños con alguna patología definida. Para terminar presentamos una breve selección de actividades pensadas para el seg...

  5. El tráfico ilegal de seres humanos para la explotación sexual y laboral: la esclavitud del siglo XXI

    OpenAIRE

    Anguita Olmedo, Concepción

    2007-01-01

    El crimen actualizado es en la actualidad un fenómeno que ha ido adquiriendo cuerpo en la Sociedad Internacional globalizada. En el crimen organizado confluyen una gran diversidad de delitos - inmigración ilegal, blanqueo de dinero, tráfico sexual, explotación laboral, narcotráfico y comercio de armas- cuya dimensión ha propiciado no sólo su conceptualización, sino también la articulación de políticas desde el ámbito estatal y supranacional. El presente estudio se articula en torno a la ecua...

  6. Estudio psicométrico de la aplicación del Internet Addiction Test con estudiantes universitarios españoles

    OpenAIRE

    Verónica Marín-Díaz; Begoña Esther Sampedro Requena; Esther Vega Gea

    2017-01-01

    Internet ha experimentado en los últimos años una evolución exponencial al crecimiento de la sociedad. A la par han ido surgiendo diversos problemas de diferente naturaleza, asociados a distintas herramientas creadas bajo su ala, como son las redes sociales. Uno de esos problemas, común a muchos recursos digitales, es la adicción. Para determinar el grado de adicción o de uso problemático de los jóvenes a Internet Young creó el Internet Addiction Test. La intención de este artículo ha sido va...

  7. La interfaz familia-trabajo : el efecto del enrequicimiento de rol sobre la intención de abandono de los trabajadores a través de la satisfacción laboral y el compromiso organizacional

    OpenAIRE

    García Alonso, Ero

    2016-01-01

    La evolución de las diferencias de género se erigió en un factor decisivo en la constitución de las nuevas clases sociales emergidas a lo largo del siglo XX. Esta evolución se ha dibujado en base a los derroteros tomados por la trayectoria de las mujeres y su misión dentro de la sociedad. Esta senda se ha ido desarrollando sobre la balanza de la permisividad de las desigualdades de género y la subalternidad femenina (Nash, 2004). Durante el siglo XIX y buena parte del XX, las mujeres carec...

  8. La iniciación al deporte del atletismo: del modelo tradicional a los nuevos enfoques metodológicos

    OpenAIRE

    Valero Valenzuela, Alfonso

    2006-01-01

    La metodología en la iniciación deportiva ha ido avanzando con el paso del tiempo desde que aparecieron los primeros métodos y programas a principios del siglo XX, pasando de un Modelo Tradicional centrado en la enseñanza de la técnica a un Modelo de Proceso que focaliza la atención en la táctica. A su vez, dentro de este último, se distingue entre los planteamientos Horizontales, que realizan una iniciación multideportiva y los planteamientos Verticales, que apuestan por el aprendizaje de lo...

  9. Conducta antisocial y trastornos relacionados: Trastorno Negativista Desafiante, Trastorno Disocial y Trastorno Antisocial de la Personalidad

    OpenAIRE

    Sánchez Seisdedos, Patricia

    2013-01-01

    Se lleva a cabo una revisión bibliográfica de diversos trastornos con un factor común, las conductas antisociales. Se plantea el contexto histórico y los antecedentes del concepto según los distintos autores que han ido planteando teorías y definiciones al respecto, seguido de una descripción de cada trastorno y la clasificación internacional del mismo. Por último se hace una reflexión sobre su evolución, y qué implicación puede tener en la edad adulta si se empiezan a padecer en la niñez...

  10. Historiografía española sobre Europa Central y Oriental. Nacionalismo, transiciones poscomunistas y relaciones exteriores

    OpenAIRE

    Sánchez García, Raquel

    2009-01-01

    La historiografía española no ha prestado especial atención a la Europa central y oriental pues sus objetivos han estado localizados en otros entornos geográficos como la Europa Occidental o América. Sin embargo, desde la caída de las dictaduras comunistas se despertó un gran interés por esta zona de Europa, interés que nació primero en los estudios económicos y políticos y que poco a poco ha ido trasladándose a la historia. [ABSTRAC]Traditionally, Spanish historiography hasn’t paid attent...

  11. Adaptabilidad de la Clasificación Decimal Dewey para la organización de contenidos: de los estantes a la Web

    OpenAIRE

    Moyano-Grimaldo, Wilmer Arturo

    2017-01-01

    Resumen Desde el año 1876, cuando Melvil Dewey publicó la primera edición de su sistema de clasificación bibliográfico, este ha ido evolucionando como un sistema de clasificación muy firme y adaptable que permite organizar de manera práctica el conocimiento, incluso en la Internet. El presente artículo, es derivado de una investigación doctoral desarrollada durante 5 años acerca de diferentes aspectos semánticos, epistemológicos, históricos y tecnológicos de la Clasificación Decimal Dewey, in...

  12. Inclusión del campus virtual Chamilo como herramienta de aprendizaje para el profesorado del Colegio Juan Pablo II

    OpenAIRE

    Núñez Orellana, Elsa Licenia

    2015-01-01

    La tecnología ha estado presente a lo largo de la historia de la humanidad, desde la talla de puntas de flecha se ha ido perfeccionando la técnica hasta llegar a herramientas más elaboradas como instrumentos para labrar la tierra, la invención de la rueda, el telégrafo, la aeronáutica, la aviación, pasando incluso por artefactos de guerra o armas letales para la vida humana, entre otras, y así llegar a los revolucionarios inventos de finales del siglo XX y comienzos del siglo XXI. Desde un...

  13. La terapia manual osteopática

    OpenAIRE

    Escarmis i Costa, Francesc; Martínez Gil, José Luis

    2001-01-01

    Este trabajo desarrolla brevemente la historia de la Osteopatía, su introducción en Europa y cómo desde Europa ha ido viniendo a España de la mano de los Fisioterapeutas. Resume así mismo la Filosofía de la Osteopatía y sus principios. Y, por último, nos revela la situación actual de la Osteopatía en España y la necesidad que creemos que existe para su mayor desarrollo, estudio e integración dentro de la Fisioterapia. Terapia y Rehabilitación

  14. La fábula esópica, los cuentos y los exempla del siglo xiv en el Baldo, un libro de caballerías del siglo XVI

    OpenAIRE

    Pastrana Santamarta, Tomasa

    2015-01-01

    Una obra renacentista como el Baldo da cabida en sus páginas a fábulas esópicas y cuentos medievales que se han ido transmitiendo y adaptando en el transcurso de los siglos. El autor encuentra en este tipo de narraciones una forma directa y sencilla de exponer enseñanzas para, de este modo, justificar la existencia de los libros de caballerías, en un momento en que se suscita la polémica debido a su «falta de verosimilitud». La presencia de estos cuentos es una reivindicación de su utilidad a...

  15. Impacto económico del tratamiento y gestión de los residuos sólidos producidos por el Hospital Militar Central – Lima

    OpenAIRE

    Nava Torres, César Augusto; Nava Torres, César Augusto; Loayza Berrocal, Luis Alberto; Nava Torres, César Augusto

    2012-01-01

    El manejo de los residuos sólidos hospitalarios en nuestro país es uno de los aspectos de la gestión hospitalaria que ha ido tomando importancia e interés en los últimos años. Mediante la presente investigación se pretende evaluar el actual Tratamiento y Gestión de los residuos sólidos en el Hospital Militar Central (HMC) de la ciudad de Lima, analizando los servicios de salud donde los pacientes se hospitalizan y se genere la mayor cantidad de desechos, a fin de determinar las ganancias...

  16. Edición crítica, estudio y notas de una comedia de Tirso de Molina: la elección por la virtud

    OpenAIRE

    Galindo Abellán, Miguel

    2012-01-01

    Desde su publicación en la Tercera Parte de comedias del Maestro Tirso de Molina, impresa en Tortosa (1634), La elección por la virtud ha llegado a nosotros a través de seis ediciones posteriores, pero ninguna de ellas con edición crítica. En esta tesis se catalogan errores y erratas que han ido transmitiéndose de texto en texto, se ofrece un estudio pormenorizado de la comedia, se estudia su métrica y se anotan aspectos lingüísticos y culturales de cada escena, además de estudiar la comedia ...

  17. Factores determinantes de la deserción de mujeres en carreras de la facultad de Ingeniería de la Universidad Nacional de Asunción – Fiuna, 1997-2000

    OpenAIRE

    Pereira Ayala, Zunilda

    2016-01-01

    En Paraguay, el acceso de la mujer a la educación superior ha ido incrementándose de manera paulatina, y de manera ascendente en las carreras de ingenierías de la Facultad de Ingeniería de la UNA(FIUNA); sin embargo, se dispone de escasa información sobre el proceso de formación de las mismas en dichas carreras. Esta investigación motivada por algunas interrogantes sobre este fenómeno, poco estudiado en el país, y menos aún, sobre estudios orientados a mujeres que no han podido culminar sus c...

  18. Breve historia reglamentaria del estilo pecho

    OpenAIRE

    Britez, Julián

    2013-01-01

    La natación a nivel mundial se ha convertido en un espectáculo único acaparando la mirada de todos durante los Juegos Olímpicos y Mundiales, esto ha sido sostenido principalmente por la pulverización constante de records. El estilo Pecho o Braza, es considerado el más lento de los cuatro estilos de nado reconocidos por la Federación Internacional de Natación. Pero con el avance de los años, la organización rectora de la natación a nivel mundial ha ido incorporando cambios y modificaciones con...

  19. La importancia de los Flagship Stores para las marcas del sector retail. Caso práctico: Mango

    OpenAIRE

    Corral Escribano, David

    2017-01-01

    A lo largo de la historia la actividad minorista ha ido evolucionado adaptándose a las necesidades humanas de cada momento. Hace décadas, las empresas se esforzaban en dar salida a sus productos, sirviéndose de la publicidad como principal herramienta. Hoy en día el mercado minorista se ha trasformado completamente y las empresas van más allá. Con un panorama de saturación informativa y un comercio electrónico que crece cada año, las marcas del sector retail están tratando de b...

  20. Efecto del uso combinado de ácido hialurónico, plasma rico en plaquetas y células madre adultas derivadas de tejido adiposo en la reparación de defectos osteocondrales

    OpenAIRE

    Cervero Suárez, Francisco Javier

    2013-01-01

    El cartílago articular es un tejido que permite la trasmisión de fuerzas y el movimiento, y para ello presenta unas características entre las que destacan la baja celularidad y la ausencia de aporte sanguíneo, de terminaciones nerviosas y de drenaje linfático. Sin embargo, estas características son a la vez una limitación crucial para la reparación de los daños. En consecuencia, se han ido desarrollando en los últimos años diferentes terapias que tratan de mejorar la baja capacidad de regene...

  1. Efecto del uso combinado de ácido hialurónico, plasma rico en plaquetas y células madre adultas derivadas de tejido adiposo en la reparación de defectos osteocondrales

    OpenAIRE

    Cervero Suárez, Francisco Javier

    2016-01-01

    El cartílago articular es un tejido que permite la trasmisión de fuerzas y el movimiento, y para ello presenta unas características entre las que destacan la baja celularidad y la ausencia de aporte sanguíneo, de terminaciones nerviosas y de drenaje linfático. Sin embargo, estas características son a la vez una limitación crucial para la reparación de los daños. En consecuencia, se han ido desarrollando en los últimos años diferentes terapias que tratan de mejorar la baja capacidad de regene...

  2. Limitaciones en Argentina del proceso de compatibilización ambiental de las obras de ingeniería y propuestas para su optimización

    OpenAIRE

    Cipponeri, Marcos; Angelaccio, Carlos M.; Salvioli, Mónica L.

    2012-01-01

    Si bien en las últimas décadas la consideración de la variable ambiental en el desarrollo de proyectos de Obras de Ingeniería se ha ido incorporando gradualmente en la visión de los tomadores de decisiones, evolucionando desde la mínima consideración de cumplimentar un trámite administrativo hasta la desestimación de alternativas, o aún de proyectos completos por cuestiones ambientales, todavía no se ha alcanzado un grado de integración que permita asegurar que los niveles de compatibilidad a...

  3. Gestión municipal y planificación urbana en Córdoba, Argentina (1983-2011)

    OpenAIRE

    Martín Lemma

    2017-01-01

    Resumen En 1983, Argentina retorna a la democracia y, a partir de entonces, diversos partidos políticos cordobeses estuvieron a cargo de la gestión de la Municipalidad de la Ciudad de Córdoba. Cada uno de ellos ha abordado, de una manera particular, los diversos problemas del espacio urbano del municipio. A lo largo de 28 años, estos abordajes se han ido modificando en mayor o menor medida, ya sea a modo de continuidad, transformación o ruptura. Hasta 1999, hubo en Córdoba una sucesión de gob...

  4. Estudio técnico y financiero para la creación de una línea de servicio para el Hotel Sheraton Quito organización de seminarios de seguridad y salud ocupacional

    OpenAIRE

    Pozo Cevallos, Mario Andrés

    2015-01-01

    En el presente proyecto se analiza la viabilidad técnica y económica de la implementación de una línea de servicio para el Hotel Sheraton Quito “Organización de Seminarios de Seguridad y Salud”. La necesidad de capacitación en el Ecuador en temas de seguridad y salud ha ido en incremento en los últimos años; esto debido a que las organizaciones requieren como parte de su sistema de gestión de prevención de riesgos capacitaciones avalas por el CISHT (Comité interinstitucional de Seguridad e Hi...

  5. Nuevo dispositivo para el aislamiento de la fracción estromal vascular a partir de lipoaspirados humanos: método de obtención y análisis de calidad celular

    OpenAIRE

    S. Dos-Anjos; J. Mercader; A.J. Katz.; R. Llull

    2013-01-01

    El tejido adiposo obtenido mediante liposucción es una fuente idónea para aislar células con potencial terapéutico, las denominadas células de la fracción estromal vascular (FEV), que incluyen células madre mesenquimales. Estas células se han convertido en una de las principales herramientas de terapia celular autóloga para diversas aplicaciones médicas, y en los últimos años se han ido desarrollando diversas tecnologías para su aislamiento y uso clínico. En este trabajo presentamos un nuevo ...

  6. LOS VALORES SEGÚN LOS PROFESIONALES DE LA EDUCACIÓN FÍSICA Y DEL FÚTBOL ONUBENSE CADETE

    OpenAIRE

    Clara Isabel Pazo Haro; Jesús Tejada Mora

    2015-01-01

    El deporte tradicionalmente ha sido considerado como una actividad física reglada, reservada tan solo para unos pocos y con el principal objetivo de obtener altos rendimientos físicos y óptimos resultados en la competición. Esta concepción se ha ido modificando en las últimas décadas, convirtiéndose en la actualidad en un importante contenido y uno de los medios más adecuado para educar a los jóvenes a través del movimiento. Este estudio se centra en dos realidades bien distintas: el deporte ...

  7. Validación de los procesos de limpieza en la industria farmacéutica, mediante la aplicación del análisis de riesgo, seguridad toxicológica y UPLC

    OpenAIRE

    Rezquellah, Wafae

    2015-01-01

    [spa] En sus procesos de fabricación, la industria farmacéutica debe cumplir con las garantías de calidad y seguridad. Durante las últimas décadas ha ido adquiriendo importancia la validación de los procesos de limpieza de los equipos de producción con el objetivo de minimizar la contaminación cruzada. El establecimiento de los límites de residuos aceptables para la validación de la limpieza en base a criterios científicos es un asunto que aún no se ha resuelto. Este trabajo pretende desarro...

  8. Raíces en el exilio: asentamiento (a)temporal para refugiados de la guerra siria: campo de Za'atari, Jordania

    OpenAIRE

    Fernández Cortés, Marta

    2016-01-01

    Qualificació obtinguda: 10 Matrícula d'honor A raíz del inicio de la guerra de Siria en el año 2011, millones de personas han tenido que huir de sus casas y buscar refugio en otros lugares. Una gran parte de ellos han ido a parar a campos de refugiados, territorios sin ley donde las condiciones de vida son muy precarias, y sus habitantes han perdido muchos de sus derechos y dignidad. Este proyecto se centra en Za’atari, uno de los numerosos campos de refugiados que han surgido a partir...

  9. Novedades del deber de informar al consumidor en la contratación electrónica

    OpenAIRE

    Arias Pou, María

    2014-01-01

    En la presente comunicación se analizan los cambios normativos que han tenido lugar en relación con el deber de los prestadores de servicios de informar al consumidor en un proceso de contratación electrónica. A través del análisis de las novedades que introduce la nueva Directiva sobre derechos de los consumidores y de la evolución de los distintos textos normativos españoles que se han ido aprobando hasta trasponer esta Directiva a nuestro ordenamiento jurídico interno, analizaré cómo ha va...

  10. Diseño para la implementación de los procesos de talento humano para la Pyme Producomercio Joseph´s Foods

    OpenAIRE

    Alvarado Villarreal, Maria del Rocio

    2014-01-01

    La empresa Producomercio Joseph´s Foods, es una empresa de tipo familiar, actualmente está formando parte del sector de las PYMES, inició sus operaciones hace 47 años como una pequeña empresa artesanal, con el pasar del tiempo ha ido creciendo progresivamente, por lo que cada día precisa la contratación de más personal con especialización de funciones; el compromiso de sus directivos es ofrecer productos de la mejor calidad y con el mejor servicio, por ello para seguir operando y llegar a tra...

  11. Contribution to design a communication framework for vehicular ad hoc networks in urban scenarios

    OpenAIRE

    Tripp Barba, Carolina

    2013-01-01

    La movilidad constante de las personas y la creciente necesidad de estar conectados en todo momento ha hecho de las redes vehiculares un área cuyo interés ha ido en aumento. La gran cantidad de vehículos que hay en la actualidad, y los avances tecnológicos han hecho de las redes vehiculares (VANETS, Vehicular Ad hoc Networks) un gran campo de investigación. Las redes vehiculares son un tipo especial de redes móviles ad hoc inalámbricas, las cuales, al igual que las redes MANET (Mobile Ad hoc ...

  12. Tools of the Mind: A Path to Build Knowledge and Construct Language through Play

    OpenAIRE

    Aparicio, Yannelys (UNIR)

    2015-01-01

    “Tools of the Mind” es un Proyecto en cuya creación se ha trabajado durante los últimos veinte años. Dicho proyecto se constituye sobre la base de las ideas de Vygotsky acerca del desarrollo cognitivo y las destrezas de lectoescritura en los niños más jóvenes. El proyecto se ha ido modificando teniendo en cuenta la adquisición de habilidades en los niños para aprender a aprender, con autonomía, mediante una filosofía que trata de inculcarles el pensamiento simbólico y el de la lectoescritura....

  13. La audiencia pública en el procedimiento administrativo

    Directory of Open Access Journals (Sweden)

    Carlos Labaure Aliseris

    2015-10-01

    Full Text Available La audiencia pública en el procedimiento administrativo es un mecanismo que se ha ido extendiendo en los últimos tiempos, como forma de garantizar la participación de los interesados en la toma de decisión por parte de la Administración Pública. Tiene su origen en el derecho anglosajón, en cuanto reconoce el principip del debido proceso, como fundado en la justicia natural, que incluye el derecho a ser oído antes de la toma de decisión y a una decisión imparcial (...

  14. Revista educomunicativa que promueva la conservación ambiental

    OpenAIRE

    Bermúdez Galarza, Pamela Lucía

    2008-01-01

    En estos últimos años, hemos podido observar que la contaminación de los ríos, aire y suelo es cada vez mayor, pues el ser humano ha ido destruyendo la naturaleza; así tenemos: el botar desperdicios en las calles, quebradas, etc., con lo que ha demostrado su falta de cuidado y educación ambiental; provocando de esta manera efectos nocivos para el medio ambiente como los incendios forestales, la tala indiscriminada de árboles, entre otros. Y es que con la acción de cada individuo, se está prod...

  15. Proyecto de prevención de violencia de género en adolescentes.

    OpenAIRE

    Gálvez Gómez, Leticia

    2015-01-01

    Desde este proyecto se pretende realizar un análisis de la violencia de género, de dónde viene y cómo influye la sociedad en ello. Se ha hecho visible esta nueva realidad que se ha ido incrementando desde edades más tempranas, fomentadas en algunos casos por las redes sociales y nuevas tecnologías. Tras un recorrido por los diversos factores que pueden afectar a sus relaciones y cómo influye el entorno que les rodea a nivel de escuela, familia, amigos y sociedad en general, se pretende diseña...

  16. LA MOTRICIDAD EN NIÑOS CON NECESIDADES EDUCATIVAS ESPECIALES

    OpenAIRE

    Arias-Chaves, Melissa

    2012-01-01

    Este trabajo se ha realizado con el propósito de evaluar la motricidad de siete niños con necesidades educativas especiales, así como algunos aspectos de su escritura para proponer después un programa de intervención encaminado a la mejora de estos dos aspectos. En la realización de este trabajo se ha procedido al análisis y síntesis bibliográficas con el objetivo de obtener la información más concreta, y donde se ha ido explicando todo lo relacionado sobre la motricidad en general y en co...

  17. La evolución reciente del sector vitivinícola internacional

    OpenAIRE

    Fernández Portela, Julio

    2013-01-01

    El sector vitivinícola internacional se ha caracterizado por la existencia de un grupo de países dominantes que concentran gran parte de la industria del vino mundial: España, Francia e Italia. Este grupo de países lidera la superficie cultivada de viñedos, la producción de uva, así como la elaboración de vinos. Pero desde hace unas décadas, han aparecido en escena un conjunto de nuevos países emergentes (Estados Unidos, China, Australia, Argentina, etc.) que poco a poco se han ido consolidan...

  18. Plan de social media marketing para una comunidad de videojuegos en el Campus de Gandia.

    OpenAIRE

    VILAPLANA MIRALLES, MIRIAM

    2016-01-01

    [ES] Con la llegada del internet y las redes sociales, la forma en que mostramos los productos y las empresas ha ido cambiando a lo largo de estos años. Cada vez es más notoria la importancia de la presencia en las redes, pero sobre todo de la buena presencia, que ayuda a expandir las marcas y a ser más visible y cercano para el consumidor. Con la estrategia de social media marketing se pretende ayudar, en este caso, al EVAM (Espacio del Videojuego y Arte Multimedia) del campus de Gandia...

  19. La formación en materias de inteligencia en España. Estado del arte a finales de 2015

    Directory of Open Access Journals (Sweden)

    Gustavo Díaz Matey

    2016-05-01

    Full Text Available Todo lo relacionado con la inteligencia ha ido incorporándose progresivamente al debate público de las sociedades democráticas. España no es un caso aparte. En los últimos años, la oferta formativa relacionada con los temas de inteligencia, desde las más variadas perspectivas y desde distintas disciplinas, ha aumentado de forma exponencial. En este estudio hemos analizado la oferta formativa en España del 2012 al 2015 y llegado a diferentes conclusiones que representan el estado de los estudios de inteligencia en la actualidad y el camino a recorrer.

  20. Diseño de una red de centros de distribución para atención de canal cobertura en una empresa de consumo masivo

    OpenAIRE

    Espol; Aguayo Aróstegui, Andrés Josué

    2017-01-01

    Uno de los mayores problemas y retos que enfrentan muchas de las empresas nacionales sobre todo aquellas dedicadas a productos de consumo masivo, es la tecnificación en la selección de centros de distribución. su dificultad se encuentra en el manejo empírico que se dio a este tipo de decisiones desde hace muchas décadas tomando en consideración la escasez en disponibilidad de profesionales con experiencia en este campo en el país, lo cual ha ido cambiando en los últimos 15 años producto de la...