La stratégie du Diable dans l’Histoire du Docteur Faust (1587) : le recours au mensonge

Die Historia von D. Johann Fausten (1587) stellt sich bereits zu Beginn als eine Aufforderung dar, dem Teufel zu widerstehen. Anhand von zahlreichen Zitaten aus dem Alten und dem Neuen Testament versucht der anonyme Autor seinen Leser vor dem “Vater der Lüge” (Johannes 8, 44) zu warnen. Die Erzählung vom Leben des Dr. Faustus ermöglicht es ihm, die einzelnen Strategien ans Licht zu bringen, auf die der Teufel zurückgreift, um den Menschen in den Ruin zu stürzen. Er bemüht sich um das Vertrauen seines Opfers, indem er sich als dessen Freund ausgibt und dadurch dessen Verdacht auslöscht, oder er dichtet ein paar Wahrheiten in die Lüge hinein, um diese glaubwürdig zu machen. Der Teufel siegt, als es ihm gelungen ist, Dr. Faustus davon zu überzeugen, dass er sein Heil für immer verspielt hat: Diese perfideste aller Lügen bringt Dr. Faustus in eine aussichtslose Verzweiflung, die ihm eine tragische Dimension verleiht.L’Histoire du Docteur Faust (1587) se présente d’emblée comme une exhortation à résister au Diable. En s’appuyant sur de nombreux passages empruntés à l’Ancien et au Nouveau Testament, son auteur anonyme s’efforce de mettre en garde le lecteur contre “le père du mensonge” (Jean 8, 44). La relation de la vie de Faust lui permet d’illustrer les différentes stratégies mensongères mises en œuvre par le Diable pour provoquer la ruine de l’homme : gagner la confiance de sa victime en se faisant passer pour son ami et en endormant ses soupçons, mêler quelques bribes de vérité au mensonge pour mieux accréditer ce dernier. Le Diable triomphe lorsqu’il réussit à convaincre Faust qu’il n’a aucun espoir de salut. Ce mensonge suprême plonge Faust dans un désespoir sans issue qui en fait un personnage tragique.The History of Doctor Faustus (1587) presents itself from the first page already as an exhortation to resist the Devil. Shoring up his arguments with numerous quotations from the Old and the New Testament, the anonymous author endeavours to warn readers against the “father of lies” (John 8:44). Telling Dr. Faustus’ life enables him to illustrate the different strategies which the Devil employs to bring about the ruin of mankind, all of which are based on lying: he passes himself off as Faustus’ friend and allays his suspicion in order to gain his confidence. He blends some truths with his lies in order to make the latter sound true. The Devil finally triumphs over Faustus when he succeeds in convincing him that he has lost all hope of salvation. This most perfidious of lies plunges Faustus into an endless despair which confers upon him a tragic dimension

« Wie sie uns mit Heimatsinn düngten! » : le témoignage de Zygmunt Rogalla dans Heimatmuseum (Siegfried Lenz)

Siegfried Lenz recourt à la fiction pour transposer et exorciser son expérience personnelle et celle de toute sa génération. Son roman Heimatmuseum montre comment l’amour de la terre natale a pu être instrumentalisé. À l’instar d’une religion, il fut inculqué à Zygmunt Rogalla, le narrateur, par son grand-oncle, fervent adepte du mouvement en faveur de la culture régionale qui s’épanouit à l’époque wilhelminienne. Il se teinta de nationalisme xénophobe au lendemain de la Première Guerre mondiale, puis fut habilement orchestré par les idéologues et les stratèges du Troisième Reich pour justifier une politique raciste et belliqueuse.La structure enchâssée du récit, le choix d’un narrateur homodiégétique et le recours à un narrataire né après 1945 confèrent au roman une portée didactique : à travers sa narration, Zygmunt Rogalla livre un témoignage sur son passé, mais il s’adresse aussi à la jeunesse qui n’a pas connu la dictature et la guerre, l’invitant à tirer les leçons de l’Histoire et à rendre au mot Heimat son « intégrité » perdue.In sei­nem Roman ver­ar­bei­tet Siegfried Lenz seine ei­gene Erfahrung und die sei­ner gan­zen Generation. Er zeigt u. a., wie die Heimatliebe in­stru­men­ta­li­siert wer­den ­konnte. Zygmunt Rogallas Großonkel, ein be­gei­ster­ter Anhänger des Heimatkults, wie er zur wil­hel­mi­ni­schen Zeit flo­rierte, hatte dem klei­nen Jungen diese Heimatliebe ge­ra­dezu wie ein Glaubensbekenntnis ein­ge­trich­tert. In diese Liebe zur Heimat ­mischte sich nach dem Ersten Weltkrieg ein frem­den­feind­li­cher Nationalismus; von den Ideologen und Strategen des Dritten Reiches wurde diese de­na­tu­rierte Heimatliebe dann weid­lich ge­nutzt, um eine ras­si­sti­sche und krie­ge­ri­sche Politik zu recht­fer­ti­gen.Durch die Rahmenstruktur der Erzählung, durch den Rückgriff auf eine Erzählerfigur, die ihre ei­gene Geschichte er­zählt und sich im Roman an einen Zuhörer wen­det, der nach 1945 ge­bo­ren ist, ge­winnt das Werk eine ex­pli­zit did­ak­ti­sche Dimension: indem Zygmunt Rogalla er­zählt, ­spricht er nicht nur als Augenzeuge, son­dern er ­spricht zu­gleich auch eine Jugend an, die weder Diktatur noch Krieg er­lebt hat, und for­dert sie somit auf, eine Lehre aus der Geschichte zu zie­hen und dem Wort Heimat seine ver­lo­rene « Unbescholtenheit » zu­rück­zu­ge­ben

Light scattering by an ensemble of interacting dipolar particles with both electric and magnetic polarizabilities

We have studied the problem of light scattering by an ensemble of dipoles with both electric and magnetic polarizabilities. Using the coupled electric and magnetic dipole method as the formal base, we have generalized the eigenvector decomposition of the local dipole moments previously derived for purely electric particles to the case of both electric and magnetic dipoles. We have analyzed the properties of eigenvalues and eigenvectors in the most elementary case of two particles. In the purely electric case, the eigenvalues correspond to the resonance modes of the system due to the electromagnetic coupling of its components. For a two-dipole system with both electric and magnetic responses, purely electric, purely magnetic, and mixed states can be distinguished. The resonance spectrum is analyzed as a function of the magnetic permeability, and it is shown that the latter can be fitted quite accurately by the eigenmode decomposition

Exception for the zero-forward-scattering theory

Studies on single scattering of electromagnetic waves by magnetic particles were reported in the 1980s by Kerker et al. [J. Opt. Soc. Am. 73, 765 (1983)] . They obtained that very small spherical particles with electric permittivity and magnetic permeability values such that ε=(4−μ)/(2μ+1) do not produce forward scattering. We show here that this condition contains an interesting exception at ( ε=−2 , μ=−2 ) when electric and magnetic resonances are present and around which the scattered field distribution is computed and described showing a polarization-insensitive behavior at the point ( ε=−2 , μ=−2 )

Peroxisome Proliferator-Activated Receptor gamma enhances the activity of a insulin degrading enzyme-like metalloprotease for amyloid-beta clearance.

Peroxisome proliferator-activated receptor gamma (PPARgamma) activation results in an increased rate of amyloid-beta (Abeta) clearance from the media of diverse cells in culture, including primary neurons and glial cells. Here, we further investigate the mechanism for Abeta clearance and found that PPARgamma activation modulates a cell surface metalloprotease that can be inhibited by metalloprotease inhibitors, like EDTA and phenanthroline, and also by the peptide hormones insulin and glucagon. The metalloprotease profile of the Abeta-degrading mechanism is surprisingly similar to insulin-degrading enzyme (IDE). This mechanism is maintained in hippocampal and glia primary cultures from IDE loss-of-function mice. We conclude that PPARgamma activates an IDE-like Abeta degrading activity. Our work suggests a drugable pathway that can clear Abeta peptide from the brain

Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy.

BACKGROUND: Modulation and depletion strategies of regulatory T cells (Tregs) constitute valid approaches in antitumor immunotherapy but suffer from severe adverse effects due to their lack of selectivity for the tumor-infiltrating (ti-)Treg population, indicating the need for a ti-Treg specific biomarker. METHODS: We employed single-cell RNA-sequencing in a mouse model of non-small cell lung carcinoma (NSCLC) to obtain a comprehensive overview of the tumor-infiltrating T-cell compartment, with a focus on ti-Treg subpopulations. These findings were validated by flow cytometric analysis of both mouse (LLC-OVA, MC38 and B16-OVA) and human (NSCLC and melanoma) tumor samples. We generated two CCR8-specific nanobodies (Nbs) that recognize distinct epitopes on the CCR8 extracellular domain. These Nbs were formulated as tetravalent Nb-Fc fusion proteins for optimal CCR8 binding and blocking, containing either an antibody-dependent cell-mediated cytotoxicity (ADCC)-deficient or an ADCC-prone Fc region. The therapeutic use of these Nb-Fc fusion proteins was evaluated, either as monotherapy or as combination therapy with anti-programmed cell death protein-1 (anti-PD-1), in both the LLC-OVA and MC38 mouse models. RESULTS: We were able to discern two ti-Treg populations, one of which is characterized by the unique expression of Ccr8 in conjunction with Treg activation markers. Ccr8 is also expressed by dysfunctional CD4+ and CD8+ T cells, but the CCR8 protein was only prominent on the highly activated and strongly T-cell suppressive ti-Treg subpopulation of mouse and human tumors, with no major CCR8-positivity found on peripheral Tregs. CCR8 expression resulted from TCR-mediated Treg triggering in an NF-κB-dependent fashion, but was not essential for the recruitment, activation nor suppressive capacity of these cells. While treatment of tumor-bearing mice with a blocking ADCC-deficient Nb-Fc did not influence tumor growth, ADCC-prone Nb-Fc elicited antitumor immunity and reduced tumor growth in synergy with anti-PD-1 therapy. Importantly, ADCC-prone Nb-Fc specifically depleted ti-Tregs in a natural killer (NK) cell-dependent fashion without affecting peripheral Tregs. CONCLUSIONS: Collectively, our findings highlight the efficacy and safety of targeting CCR8 for the depletion of tumor-promoting ti-Tregs in combination with anti-PD-1 therapy

CD25-Treg-depleting antibodies preserving IL-2 signaling on effector T cells enhance effector activation and antitumor immunity.

Intratumoral regulatory T cell (Treg) abundance associates with diminished anti-tumor immunity and poor prognosis in human cancers. Recent work demonstrates that CD25, the high affinity receptor subunit for IL-2, is a selective target for Treg depletion in mouse and human malignancies; however, anti-human CD25 antibodies have failed to deliver clinical responses against solid tumors due to bystander IL-2 receptor signaling blockade on effector T cells, which limits their anti-tumor activity. Here we demonstrate potent single-agent activity of anti-CD25 antibodies optimized to deplete Tregs whilst preserving IL-2-STAT5 signaling on effector T cells, and demonstrate synergy with immune checkpoint blockade in vivo. Pre-clinical evaluation of an anti-human CD25 (RG6292) antibody with equivalent features demonstrates, in both non-human primates and humanized mouse models, efficient Treg depletion with no overt immune-related toxicities. Our data supports the clinical development of RG6292 and evaluation of novel combination therapies incorporating non-IL-2 blocking anti-CD25 antibodies in clinical studies