Heraklesek Buda ezagutu zuenean. Grekobudismoa Alejandro Handia eta Kanishkaren artean (K.a. IV-K.o. II)

32 p. : il. -- Bibliogr.: p. 24-25[ES] Gradu Amaierako Lan honen helburua Grekobudismoa, hots, kultura helenistiko eta erlijio budistaren arteko sinkretismoa, baldintzatu zituzten faktoreak eta honen garapena aztertzea izango da. Alejandro Handiaren kanpaina militarren ostean Baktria eta India Ipar-Mendebaldean greziarren komunitateak ezarriko ziren, zeintzuk kultura, tradizio eta sineskera helenoak hurrengo mendeetan zehar mantenduko zituzten. Era berean, Mauriar Inperioko Asoka erregeak budismoa zabaltzeko monje misiolariak bidaliko zituen India inguruko lurraldeetara, greziar komunitate hauek konbertsio kanpaina hauen helmugetako bat izanik. Nahiz eta Budismoarekin sinpatizatu izan zezaketen sujetu greziarren kasuak existitu, Pirron Elisekoa bezala, komunitate budistaren babesa lortzeko budismoaren aldeko politika bat bultzatu zutenak errege Indo-Greziarrak izango ziren, zeintzuk sinbolo budistak erabiliko zituzten haiek jaulkitutako txanponetan. Halaber, agintari greziar batzuk, Menandro I bezala, literatura budistan budismoaren babesle sutsuak bihurtuko ziren. Azkenik, Kushan Inperioaren garaian bateratu ziren hainbat elementuen bateratzeari esker Grekobudismoa Gandhrako eskolako artelanetan materializatuko zen, sinkretismoa bere puntu gorenera iritsiz eta helenismoa ikonografia budistaren garapena definituko zuen funtsezko osagai bat bihurtuz.[EN] The aim of this essay is to analyze the historical facts and development of GrecoBuddhism, that is, the syncretism between Greek culture and Buddhism. Greek communities would settle down in Bactria and North-West India after the campaigns of Alexander the Great, importing and maintaining Hellenic culture, costumes and beliefs through the next generations. Likewise, the Mauryan king Ashoka would launch the first massive missionary campaign in order to convert all the territories surrounding India into Buddhism, which also included the areas inhabited by the aforementioned Greeks. Even though some cases of Greek figures sympathizing with Buddhist ideas existed since the time of Alexander, such as that of Pyrrho of Elys, Indo-Greek kings would be the first to adopt a policy in favour of Buddhism with the aim of obtaining the respect of the Buddhist community. Not only would they start using Buddhist symbols in their royal coins, but they would also be portrayed as protectors of the Buddhist faith, as it happended to Menander I. Finally, thanks to the accumulation of different elements during the time of the Kushan Empire, Greco-Buddhism would materialize through the artworks of the Gandhara School, reaching this syncretism its peak as Hellenism became a substantial element that defined the development of Buddhist iconography

Heraklesek Buda ezagutu zuenean. Grekobudismoa Alejandro Handia eta Kanishkaren artean (K.a. IV-K.o. II)

32 p. : il. -- Bibliogr.: p. 24-25[ES] Gradu Amaierako Lan honen helburua Grekobudismoa, hots, kultura helenistiko eta erlijio budistaren arteko sinkretismoa, baldintzatu zituzten faktoreak eta honen garapena aztertzea izango da. Alejandro Handiaren kanpaina militarren ostean Baktria eta India Ipar-Mendebaldean greziarren komunitateak ezarriko ziren, zeintzuk kultura, tradizio eta sineskera helenoak hurrengo mendeetan zehar mantenduko zituzten. Era berean, Mauriar Inperioko Asoka erregeak budismoa zabaltzeko monje misiolariak bidaliko zituen India inguruko lurraldeetara, greziar komunitate hauek konbertsio kanpaina hauen helmugetako bat izanik. Nahiz eta Budismoarekin sinpatizatu izan zezaketen sujetu greziarren kasuak existitu, Pirron Elisekoa bezala, komunitate budistaren babesa lortzeko budismoaren aldeko politika bat bultzatu zutenak errege Indo-Greziarrak izango ziren, zeintzuk sinbolo budistak erabiliko zituzten haiek jaulkitutako txanponetan. Halaber, agintari greziar batzuk, Menandro I bezala, literatura budistan budismoaren babesle sutsuak bihurtuko ziren. Azkenik, Kushan Inperioaren garaian bateratu ziren hainbat elementuen bateratzeari esker Grekobudismoa Gandhrako eskolako artelanetan materializatuko zen, sinkretismoa bere puntu gorenera iritsiz eta helenismoa ikonografia budistaren garapena definituko zuen funtsezko osagai bat bihurtuz.[EN] The aim of this essay is to analyze the historical facts and development of GrecoBuddhism, that is, the syncretism between Greek culture and Buddhism. Greek communities would settle down in Bactria and North-West India after the campaigns of Alexander the Great, importing and maintaining Hellenic culture, costumes and beliefs through the next generations. Likewise, the Mauryan king Ashoka would launch the first massive missionary campaign in order to convert all the territories surrounding India into Buddhism, which also included the areas inhabited by the aforementioned Greeks. Even though some cases of Greek figures sympathizing with Buddhist ideas existed since the time of Alexander, such as that of Pyrrho of Elys, Indo-Greek kings would be the first to adopt a policy in favour of Buddhism with the aim of obtaining the respect of the Buddhist community. Not only would they start using Buddhist symbols in their royal coins, but they would also be portrayed as protectors of the Buddhist faith, as it happended to Menander I. Finally, thanks to the accumulation of different elements during the time of the Kushan Empire, Greco-Buddhism would materialize through the artworks of the Gandhara School, reaching this syncretism its peak as Hellenism became a substantial element that defined the development of Buddhist iconography

Common-mode voltage elimination in multilevel power inverter-based motor drive applications

The industry and academia are focusing their efforts on finding more efficient and reliable electrical machines and motor drives. However, many of the motors driven by pulse-width modulated converters face the recurring problem of common-mode voltage (CMV). In fact, this voltage leads to other problems such as bearing breakdown, deterioration of the stator winding insulation and electromagnetic interferences (EMI) that can affect the lifespan and correct operation of the motors. In this sense, multilevel converters have proven to be a useful tool for solving these problems and mitigating CMV over the past few decades. Among other reasons, because they provide additional degrees of freedom when comparing with two-level converters. However, although there are several proposals in the scientific literature on this topic, no complete information has been reviewed about the CMV issues and the different multilevel alternatives that can be used to solve it. In this context, the objective of this work is to determine how multilevel power converters provide additional degrees of freedom to make the reduction of the CMV possible by using specific modulation techniques, making it easier for engineers and scientists in this field to find solutions to this problem. This document consists of a descriptive study that collects the strengths and weaknesses of most important multilevel power converters, with special emphasis on how CMV affects each of them. In addition, the differences of modulation techniques aimed to the CMV reduction are explained in terms of output voltage, operating linear range, and generated CMV. Considering this last, it is recommended to use those modulation techniques that allow the generation of CMV levels of 0 V in order to be able to completely eliminate said voltage.This work was supported in part by the Government of the Basque Country within the Fund for Research Groups of the Basque University System under Grant IT978-16; in part by the Research Program ELKARTEK under Project ENSOL2-KK-2020/00077; in part by the Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya; in part by the Ministerio de Ciencia, Innovacion y Universidades of Spain under Project PID2019-111420RB-I00 and Project PID2020-115126RB-I00; and in part by the FEDER Funds.Peer ReviewedPostprint (author's final draft

Fibroblast growth factors 19 and 21 in acute liver damage

Currently there are very few pharmacological options available to treat acute liver injury. Because its natural exposure to noxious stimuli the liver has developed a strong endogenous hepatoprotective capacity. Indeed, experimental evidence exposed a variety of endogenous hepatic and systemic responses naturally activated to protect the hepatic parenchyma and to foster liver regeneration, therefore preserving individual’s survival. The fibroblast growth factor (FGF) family encompasses a range of polypeptides with important effects on cellular differentiation, growth survival and metabolic regulation in adult organisms. Among these FGFs, FGF19 and FGF21 are endocrine hormones that profoundly influence systemic metabolism but also exert important hepatoprotective activities. In this review, we revisit the biology of these factors and highlight their potential application for the clinical management of acute liver injur

Unraveling the role of transient starch in the response of Arabidopsis to elevated CO2 under long-day conditions

Previous studies on Arabidopsis under long-term exposure to elevated CO2 have been conducted using starch synthesis and breakdown mutants cultured under short day conditions. These studies showed that starch synthesis can ameliorate the photosynthetic reduction caused by soluble sugar-mediated feedback regulation. In this work we characterized the effect of long-term exposure to elevated CO2 (800 ppm) on growth, photosynthesis and content of primary photosynthates in long-day grown wild type plants as well as the near starch-less (aps1) and the starch-excess (gwd) mutants. Notably, elevated CO2 promoted growth of both wild type and aps1 plants but had no effect on gwd plants. Growth promotion by elevated CO2 was accompanied by an increased net photosynthesis in WT and aps1 plants. However, the plants with the highest starch content (wild type at elevated CO2, gwd at ambient CO2, and gwd at elevated CO2) were the ones that suffered decreased in in vivo maximum carboxylation rate of Rubisco, and therefore, photosynthetic down-regulation. Further, the photosynthetic rates of wild type at elevated CO2 and gwd at elevated CO2 were acclimated to elevated CO2. Notably, elevated CO2 promoted the accumulation of stress-responsive and senescence-associated amino acid markers in gwd plants. The results presented in this work provide evidence that under long-day conditions, temporary storage of overflow photosynthate as starch negatively affect Rubisco performance. These data are consistent with earlier hypothesis that photosynthetic acclimation can be caused by accelerated senescence and hindrance of CO2 diffusion to the stroma due to accumulation of large starch granules

Dual ifgMosaic: A Versatile Method for Multispectral and Combinatorial Mosaic Gene-Function Analysis

Improved methods for manipulating and analyzing gene function have provided a better understanding of how genes work during organ development and disease. Inducible functional genetic mosaics can be extraordinarily useful in the study of biological systems; however, this experimental approach is still rarely used in vertebrates. This is mainly due to technical difficulties in the assembly of large DNA constructs carrying multiple genes and regulatory elements and their targeting to the genome. In addition, mosaic phenotypic analysis, unlike classical single gene-function analysis, requires clear labeling and detection of multiple cell clones in the same tissue. Here, we describe several methods for the rapid generation of transgenic or gene-targeted mice and embryonic stem (ES) cell lines containing all the necessary elements for inducible, fluorescent, and functional genetic mosaic (ifgMosaic) analysis. This technology enables the interrogation of multiple and combinatorial gene function with high temporal and cellular resolution.This work was supported by grants to the PI R.B. from the Spanish Ministry of Economy, Industry and Competitiveness (SAF2013-44329-P, SAF2013-42359-ERC, and RYC-2013-13209) and European Research Council (ERC-2014-StG - 638028). S.P.-Q., M.F.-C., and I.G.-G. were supported by PhD fellowships from Fundacion La Caixa (CX-SO-2013-02, CX\_E-2015-01, and CX-SO-16-1, respectively). W.L. by a FP7-PEOPLE-2012-COFUND GA600396 postdoctoral contract. We thank Simon Bartlett for English editing, Ralf H. Adams for sharing the Cdh5(PAC)-CreERT2 mice, Jose Luis de La Pompa for comments throughout the project and for sharing the Tie2-Cre mice, Gonzalo Gancedo for the help with the mouse colony, Valeria Caiolfa for the help with the microscopy, and all the members of the CNIC gene targeting, transgenesis, cellomics, and microscopy units. The CNIC is supported by MEIC/MINECO and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

FOSL1 promotes cholangiocarcinoma via transcriptional effectors that could be therapeutically targeted

Understanding the molecular mechanisms involved in cholangiocarcinoma (bile duct cancer) development and progression stands as a critical step for the development of novel therapies. Through an inter-species approach, this study provides evidence of the clinical and functional role of the transcription factor FOSL1 in cholangiocarcinoma. Moreover, we report that downstream effectors of FOSL1 are susceptible to pharmacological inhibition, thus providing new opportunities for therapeutic intervention

Pilot multi-omic analysis of human bile from benign and malignant biliary strictures: a machine-learning approach

Cholangiocarcinoma (CCA) and pancreatic adenocarcinoma (PDAC) may lead to the development of extrahepatic obstructive cholestasis. However, biliary stenoses can also be caused by benign conditions, and the identification of their etiology still remains a clinical challenge. We performed metabolomic and proteomic analyses of bile from patients with benign (n = 36) and malignant conditions, CCA (n = 36) or PDAC (n = 57), undergoing endoscopic retrograde cholangiopancreatography with the aim of characterizing bile composition in biliopancreatic disease and identifying biomarkers for the differential diagnosis of biliary strictures. Comprehensive analyses of lipids, bile acids and small molecules were carried out using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (1H-NMR) in all patients. MS analysis of bile proteome was performed in five patients per group. We implemented artificial intelligence tools for the selection of biomarkers and algorithms with predictive capacity. Our machine-learning pipeline included the generation of synthetic data with properties of real data, the selection of potential biomarkers (metabolites or proteins) and their analysis with neural networks (NN). Selected biomarkers were then validated with real data. We identified panels of lipids (n = 10) and proteins (n = 5) that when analyzed with NN algorithms discriminated between patients with and without cancer with an unprecedented accuracy.This research was funded by: Instituto de Salud Carlos III (ISCIII) co-financed by Fondo Europeo de Desarrollo Regional (FEDER) Una manera de hacer Europa, grant numbers: PI16/01126 (M.A.A.), PI19/00819 (M.J.M. and J.J.G.M.), PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 (J.M.B.); Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation), grant name: Rare Cancers 2017 (J.M.U., M.L.M., J.M.B., M.J.M., R.I.R.M., M.G.F.-B., C.B., M.A.A.); Gobierno de Navarra Salud, grant number 58/17 (J.M.U., M.A.A.); La Caixa Foundation, grant name: HEPACARE (C.B., M.A.A.); AMMF The Cholangiocarcinoma Charity, UK, grant number: 2018/117 (F.J.C. and M.A.A.); PSC Partners US, PSC Supports UK, grant number 06119JB (J.M.B.); Horizon 2020 (H2020) ESCALON project, grant number H2020-SC1-BHC-2018–2020 (J.M.B.); BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia, grant numbers BIO15/CA/016/BD (J.M.B.) and BIO15/CA/011 (M.A.A.). Department of Health of the Basque Country, grant number 2017111010 (J.M.B.). La Caixa Foundation, grant number: LCF/PR/HP17/52190004 (M.L.M.), Mineco-Feder, grant number SAF2017-87301-R (M.L.M.), Fundación BBVA grant name: Ayudas a Equipos de Investigación Científica Umbrella 2018 (M.L.M.). MCIU, grant number: Severo Ochoa Excellence Accreditation SEV-2016-0644 (M.L.M.). Part of the equipment used in this work was co-funded by the Generalitat Valenciana and European Regional Development Fund (FEDER) funds (PO FEDER of Comunitat Valenciana 2014–2020). Gobierno de Navarra fellowship to L.C. (Leticia Colyn); AECC post-doctoral fellowship to M.A.; Ramón y Cajal Program contracts RYC-2014-15242 and RYC2018-024475-1 to F.J.C. and M.G.F.-B., respectively. The generous support from: Fundación Eugenio Rodríguez Pascual, Fundación Echébano, Fundación Mario Losantos, Fundación M Torres and Mr. Eduardo Avila are acknowledged. The CNB-CSIC Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0001 (F.J.C.). Comunidad de Madrid Grant B2017/BMD-3817 (F.J.C.).Peer reviewe

Hepatic matrix metalloproteinase-10 exerts a hepatoprotective role after acute liver injury

After injuries that lead to a loss of liver tissue a regenerative and reparative response is performed in order to restore an adequate hepatic mass. The remodeling of the extracellular matrix, accompanies the liver regeneration and when the reparative reaction goes awry in the setting of chronic liver injury, could be involved in the carcinogenic process (1,2). Following the damage, a provisional matrix is deposed, intended to be successively replaced, which has the function of stabilizing the lesional area and constitutes a support for guiding regenerating cells. Matrix metalloproteinases are increasingly recognized as important modulators of the matrix remodeling process. Matrix metalloproteinase-10 (MMP-10) has been implicated in the reparative process in other organs and has effects on the plasminogen system, which plays a fundamental role in liver repair (3). The hepatic expression of MMP10 in animal models of acute liver injury was tested in order to investigate the role of MMP-10 in liver repair and regeneration. The liver regeneration after two thirds partial hepatectomy (PH) and bile duct ligation (BDL) models were examined. Hepatic MMP-10 expression, analyzed by immunohistochemistry, western blot and qPCR showed a rise early after injury. In the MMP10-deficient mice a diminished and delayed resolution of necrotic lesions, enhanced fibrogenesis and a fibrinogen/fibrin and fibronectin compromised turnover were observed. These findings showed that the MMP10 expression plays a role in the hepatic wound healing response probably through its profibrinolytic activity