A discourse, embracing several important objections to the doctrine that Jesus Christ as mediator posseses two natures : the divine and human, in mysterious, yet all harmonious union ; in reply to a recently published sermon, delivered by the Rev. Daniel Baker, in the First and Second Presbyterian Churches in Richmond, Va. /

Reprint of the 1834 ed. published by Samuel Shepard, Richmond.

The mediatorial reign of the Son of God; or the absolute ability and willingness of Jesus Christ to save all mankind, demonstrated from the scriptures,

Mode of access: Internet.

Paul et la révélation de Dieu en 2Co 12,1-10 : éclairage scripturaire sur les phénomènes de révélations au Cameroun

La théologie catholique affirme que Jésus, médiateur par excellence, est la Révélation plénière de Dieu à son peuple. Cependant, il y a eu au fil des siècles des révélations dites «privées», dont certaines ont été reconnues par l’autorité de l’Église. Le cas des révélations privées non reconnues a toujours été générateur de malentendus et de conflits froids et parfois ouverts entre l’autorité de l’Église et certains fidèles. En contexte africain, où le christianisme se greffe sur la culture traditionnelle, cette question de révélations privées est importante car elle imprègne la religion ancestrale. Dans notre contexte où le Christianisme semble avoir le vent en poupe, on se demande quelque rapport y a-t-il entre foi et expérience individuelle de révélation privée; la révélation privée est-elle un couronnement d’une vie de foi bien menée sous le regard du Seigneur et des hommes? Comment Dieu se manifeste-t-il aux hommes et comment en rendre compte sans faire face à l’adversité? Avec l’étude de l’expérience de Paul en 2Co 12, 1-10, il y a lieu de revenir sur la théologie catholique au sujet de la Révélation en rapport avec les révélations pour voir comment elle s’est articulée, à partir de la Bible, au fil des temps, en fonction des cultures et des réalités sans cesse nouvelles. À la base de cette théologie, on peut trouver en bonne position l’influence herméneutique de l’expérience mystique de Paul. Une révélation privée comme celle qu’il vit, fait toujours face à des doutes ou des attitudes sceptiques parfois tenaces pour se préciser après coup et fonder en raison son apport par rapport au Christ et à la vie ecclésiale. Si le jugement de l’Église est important pour son insertion dans la vie des communautés, toutefois, il faut dire qu’il n’est pas déterminant. Tout se joue entre Dieu et la personne certes, mais la qualité des fruits de ce jeu spirituel étant garante de la crédibilité de la révélation. Dieu, qui sait toujours communiquer avec son peuple sous des formes variées, en est capable en tout temps et selon le mode qu’il se donne. Pour mieux parler de l’expérience de Paul en 2Co 12,1-10, les démarches historico-critique et narrative ont été d’une utilité complémentaire en vue d’authentifier dans la péricope ce qu’il convient d’appeler : la mystique de Paul. Le témoignage spirituel de Paul peut servir de paradigme pour les personnes et d’éclairage pour l’Église dans le discernement des phénomènes de révélation privée aujourd’hui. Paul vit une relation forte avec le Dieu de Jésus Christ, il la fait vivre à ses communautés; quoiqu’il advienne, il n’hésite pas à en rendre compte et à la communauté, et à Pierre et aux autres. Sa vie intensément mystique, ne le soustrait pas de la démarche ecclésiale pour défendre ses révélations.

Clusterin is a critical downstream mediator of stress-induced YB-1 transactivation in prostate cancer

Clusterin is a stress-activated, cytoprotective chaperone that confers broad-spectrum treatment resistance in cancer. However, the molecular mechanisms mediating CLU transcription following anticancer treatment stress remain incompletely defined. We report that Y-box binding protein-1 (YB-1) directly binds to CLU promoter regions to transcriptionally regulate clusterin expression. In response to endoplasmic reticulum stress inducers, including paclitaxel, YB-1 is translocated to the nucleus to transactivate clusterin. Furthermore, higher levels of activated YB-1 and clusterin are seen in taxane-resistant, compared with parental, prostate cancer cells. Knockdown of either YB-1 or clusterin sensitized prostate cancer cells to paclitaxel, whereas their overexpression increased resistance to taxane. Clusterin overexpression rescued cells from increased paclitaxel-induced apoptosis following YB-1 knockdown; in contrast, however, YB-1 overexpression did not rescue cells from increased paclitaxel-induced apoptosis following clusterin knockdown. Collectively, these data indicate that YB-1 transactivation of clusterin in response to stress is a critical mediator of paclitaxel resistance in prostate cancer. Mol Cancer Res; 9(12); 1755–66.

BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma

The rapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine-induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine-induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down-regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re-activation of vinorelbine-induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Effect of the mediator in feedback mode-based SECM interrogation of indium tin-oxide and boron-doped diamond electrodes

Indium tin-oxide (ITO) and polycrystalline boron-doped diamond (BDD) have been examined in detail using the scanning electrochemical microscopy technique in feedback mode. For the interrogation of electrodes made from these materials, the choice of mediator has been varied. Using Ru(CN) 4− 6 (aq), ferrocene methanol (FcMeOH), Fe(CN) 3− 6 (aq) and Ru(NH 3) 3+ 6 (aq), approach curve experiments have been performed, and for purposes of comparison, calculations of the apparent heterogeneous electron transfer rates (k app) have been made using these data. In general, it would appear that values of k app are affected mainly by the position of the mediator reversible potential relative to the relevant semiconductor band edge (associated with majority carriers). For both the ITO (n type) and BDD (p type) electrodes, charge transfer is impeded and values are very low when using FcMeOH and Fe(CN) 3− 6 (aq) as mediators, and the use of Ru(NH 3) 3+ 6(aq) results in the largest value of k app. With ITO, the surface is chemically homogeneous and no variation is observed for any given mediator. Data is also presented where the potential of the ITO electrode is fixed using a ratio of the mediators Fe(CN) 3− 6(aq) and Fe(CN) 4− 6(aq). In stark contrast, the BDD electrode is quite the opposite and a range of k app values are observed for all mediators depending on the position on the surface. Both electrode surfaces are very flat and very smooth, and hence, for BDD, variations in feedback current imply a variation in the electrochemical activity. A comparison of the feedback current where the substrate is biased and unbiased shows a surprising degree of proportionality.

Stepping into my shoes: Generativity as a mediator of the relationship between business owners' age and family succession

The authors investigated generativity – the concern in establishing and guiding the next generation – as a mediator of the relationship between family business owners' age and succession in family businesses. Data came from 155 family business owners in Germany from different industries between the ages of 26 and 83 years. Results showed that age was positively related to generativity, and that generativity, in turn, positively influenced an objective measure of family succession. Generativity fully mediated the positive relationship between age and family succession. The findings suggest that generativity is an important psycho-social construct for understanding ageing, careers and succession in family business settings.

Focus on opportunities as a mediator of the relationship between business owners' age and venture growth

Combining upper echelons and lifespan theories, we investigated the mediating effect of focus on opportunities on the negative relationship between business owners' age and venture growth. We also expected that mental health moderates the negative relationship between business owners' age and focus on opportunities. Path analytic findings based on data from 84 business owners (mean age = 44, range 24-74) supported these hypotheses. Findings suggest that focus on opportunities is a psychological mechanism that links business owners' age with venture growth. Our findings also indicate that mental health helps maintain a high level of focus on opportunities with increasing age.

Focus on opportunities as a mediator of the relationships between age, job complexity, and work performance

Focus on opportunities is a cognitive-motivational facet of occupational future time perspective that describes how many new goals, options, and possibilities individuals expect to have in their personal work-related futures. This study examined focus on opportunities as a mediator of the relationships between age and work performance and between job complexity and work performance. In addition, it was expected that job complexity buffers the negative relationship between age and focus on opportunities and weakens the negative indirect effect of age on work performance. Results of mediation, moderation, and moderated mediation analyses with data collected from 168 employees in 41 organizations (mean age = 40.22 years, SD = 10.43, range = 19-64 years) as well as 168 peers providing work performance ratings supported the assumptions. The findings suggest that future studies on the role of age for work design and performance should take employees' focus on opportunities into account.

Väkivalta, antisemitismi ja konflikti Mel Gibsonin elokuvassa The Passion of The Christ

Tutkielman tarkoituksena on tutkia Mel Gibsonin elokuvaa The Passion of the Christ. Tarkastelussa mukana on myös Gibsonin muu tuotanto. Tutkielma edustaa poikkitieteellistä lähestymistapaa käyttäen eksegetiikan apuvälineitä kuten lähdekritiikkiä, mutta myös elokuvatutkimuksen välineitä. Tutkimuskysymyksiä nousee lähinnä kaksi, joista seuraa kolmas kysymys: 1. Onko elokuva juutalaisvastainen? Tarkastelen lähdekritiikin avulla mitä evankeliumeja Gibson on käyttänyt elokuvassaan. Mitä muita lähteitä hän on käyttänyt? Mikä on Gibsonin omaa ilmaisua? 2. Miksi elokuva on väkivaltainen? Mitä väkivalta palvelee elokuvassa? 3. Millainen on elokuvamaailman konflikti? Pohdin elokuvamaailman sisälle rakennettua konfliktia, mutta viittaan sillä myös konfliktiin, jonka elokuva itsessään synnytti. Kysymysten ratkaisu vaatii elokuvassa käytettyjen lähteiden tutkimista, mutta myös kysymysten tarkastelua osana laajempaa kokonaisuutta, jossa on mukana koko Gibsonin elokuvatuotanto. On myös selvää, ettei Gibson ole yhtä kuin hänen elokuvansa, mutta toisaalta hänen elokuviaan ei voi tarkastella irrotettuna ohjaajasta itsestään. Ensimmäisessä luvussa tarkastelen elokuvaa ilmiönä ja elokuvasta käytyä ennakkokeskustelua. Luvussa kaksi tarkastelen Gibsonin taustaa. Millaisista lähtökohdista Gibson lähti tekemään elokuvaa? Luvussa kolme esittelen käsikirjoituksesta alkavan elokuvan yleisen tuotantoprosessin. Tutkielman päälähteenä olen käyttänyt Brentanon kirjaa The Dolorous Passion of Our Lord Jesus Christ. Kirja pohjautuu 1800-luvulla eläneen katolisen nunnan, Anne Catherine Emmerichin näkyihin. Luvussa neljä tarkastelen Gibsonin muuta tuotantoa, ja tuon keskusteluun mukaan Scorsesen elokuvan Jeesuksesta. Gibsonin muu tuotanto on jäänyt tutkijoilta liian vähälle huomiolle. Elokuva The Passion of the Christ on nähtävä osana Gibsonin muuta tuotantoa. Näin ollen elokuvaa The Passion of the Christ voidaan ymmärtää paremmin. Luvussa viisi käyn elokuvan The Passion of the Christ läpi kappale kerrallaan tutkimalla, mitä lähteitä Gibson on käyttänyt elokuvassaan. Mitä hän on ottanut evankeliumeista, mitä Emmerichiltä ja mikä on hänen omaa ilmaisuaan? Luvussa kuusi käyn läpi elokuvan vastaanottoa niin raamatuntutkijoiden kuin suuren yleisön parissa. Tutkielmassa todetaan, ettei Gibson ole antisemitisti, vaan ksenofobinen rasisti. Hänen elokuvansa ovat ksenofobisesti rasistisia. Gibsonin kaikista elokuvista on löydettävissä itseään toistavia piirteitä, joissa esiintyy muukalaiskammoa ja väkivaltaa. Gibsonin nimittäminen antisemitistiksi ei tekisi Gibsonille oikeutta. Juutalaiset ovat vain osa laajempaa kokonaisuutta. Väkivalta palvelee kaikissa elokuvissa uuden, Jumalan valtakunnan syntymistä. Konflikti syntyy uuden ja vanhan valtakunnan kansalaisten välillä. Uhrien veren kautta syntyy Jumalan valtakunta. Johtopäätöksillä on merkitystä niin Gibsonin kuin hänen elokuviensa ymmärtämiselle. Elokuvan The Passion of the Christ tulevissa tutkimuksissa on otettava huomioon, ei vain Gibsonin tausta ja lähteet, vaan myös Gibsonin muu elokuvatuotanto.

Nitric oxide is the key mediator of death induced by fisetin in human acute monocytic leukemia cells

Nitric oxide ( NO) has been shown to be effective in cancer chemoprevention and therefore drugs that help generate NO would be preferable for combination chemotherapy or solo use. This study shows a new evidence of NO as a mediator of acute leukemia cell death induced by fisetin, a promising chemotherapeutic agent. Fisetin was able to kill THP-1 cells in vivo resulting in tumor shrinkage in the mouse xenograft model. Death induction in vitro was mediated by an increase in NO resulting in double strand DNA breaks and the activation of both the extrinsic and the intrinsic apoptotic pathways. Double strand DNA breaks could be reduced if NO inhibitor was present during fisetin treatment. Fisetin also inhibited the downstream components of the mTORC1 pathway through downregulation of levels of p70 S6 kinase and inducing hypo-phosphorylation of S6 Ri P kinase, eIF4B and eEF2K. NO inhibition restored phosphorylation of downstream effectors of mTORC1 and rescued cells from death. Fisetin induced Ca2+ entry through L-type Ca2+ channels and abrogation of Ca2+ influx reduced caspase activation and cell death. NO increase and increased Ca2+ were independent phenomenon. It was inferred that apoptotic death of acute monocytic leukemia cells was induced by fisetin through increased generation of NO and elevated Ca2+ entry activating the caspase dependent apoptotic pathways. Therefore, manipulation of NO production could be viewed as a potential strategy to increase efficacy of chemotherapy in acute monocytic leukemia.

Definition of a serum marker panel for glioblastoma discrimination and identification of Interleukin 1 beta in the microglial secretome as a novel mediator of endothelial cell survival induced by C-reactive protein

Glioblastoma (GBM) is the most common malignant adult primary brain tumor. We profiled 724 cancer-associated proteins in sera of healthy individuals (n = 27) and GBM (n = 28) using antibody microarray. While 69 proteins exhibited differential abundance in GBM sera, a three-marker panel (LYAM1, BHE40 and CRP) could discriminate GBM sera from that of healthy donors with an accuracy of 89.7% and p < 0.0001. The high abundance of C-reactive protein (CRP) in GBM sera was confirmed in 264 independent samples. High levels of CRP protein was seen in GBM but without a change in transcript levels suggesting a non-tumoral origin. Glioma-secreted Interleukin 6 (IL6) was found to induce hepatocytes to secrete CRP, involving JAK-STAT pathway. The culture supernatant from CRP-treated microglial cells induced endothelial cell survival under nutrient-deprivation condition involving CRP-Fc gamma RIII signaling cascade. Transcript profiling of CRP-treated microglial cells identified Interleukin 1 beta (IL1 beta) present in the microglial secretome as the key mediator of CRP-induced endothelial cell survival. IL1 beta neutralization by antibody-binding or siRNA-mediated silencing in microglial cells reduced the ability of the supernatant from CRP-treated microglial cells to induce endothelial cell survival. Thus our study identifies a serum based three-marker panel for GBM diagnosis and provides leads for developing targeted therapies. Biological significance A complex antibody microarray based serum marker profiling identified a three-marker panel - LYAM1, BHE40 and CRP as an accurate discriminator of glioblastoma sera from that of healthy individuals. CRP protein is seen in high levels without a concomitant increase of CRP transcripts in glioblastoma. Glioma-secreted IL6 induced hepatocytes to produce CRP in a JAK-STAT signaling dependent manner. CRP induced microglial cells to release IL1 beta which in turn promoted endothelial cell survival. This study, besides defining a serum panel for glioblastoma discrimination, identified IL1 beta as a potential candidate for developing targeted therapy. (C) 2015 Elsevier B.V. All rights reserved.