160 research outputs found

    David Walker, Harriet Beecher Stowe and the Logic of Sentimental Terror

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    With few exceptions, contemporary criticism reads nineteenth-century sentimental fiction as a literature of love. When Harriet Beecher Stowe famously asserted that the moral growth of the nation depended on each citizen’s ability to “feel right,” she voiced a sentiment shared by many of her contemporaries. It is no surprise, then, that scholars have assumed Stowe’s injunction to “feel right” was a call to feel compassion and love, for it was ostensibly through a rhetoric of Christian love that Stowe was able to foment a passionate outcry against slavery from many of her Northern readers. Indeed, sentimentalism’s transformative potential is best expressed in Stowe’s antislavery writing, and scholars continue to uphold her fiction as the paradigmatic example of nineteenth-century abolitionist sentimentality. The ascendancy of love as the identifiable trait of nineteenth-century sentimental writing, moreover, marks a crucial moment in literary criticism. Modern scholars who wanted to claim that a formidable feminist presence existed within the American Renaissance had to separate the sentimental tradition from nineteenth-century Calvinism, which scholars have historically equated with patriarchal power. They have thus detached Calvinism’s severe brand of evangelical theology, which stressed the judgment of God, from a feminized sentimental philosophy that emphasized salvation through motherly love. As a result, the prevailing scholarly view understands love to be the revolutionary impulse behind nineteenth-century sentimental reform, and critics use “sympathy” and “sympathetic identification” as shorthand for this process whereby love and compassion result from an affective bond formed across lines of difference

    Apocalyptic Sentimentalism: Love and Fear in U.S. Antebellum Literature

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    In contrast to the prevailing scholarly consensus that understands sentimentality to be grounded on a logic of love and sympathy, Apocalyptic Sentimentalism demonstrates that in order for sentimentality to work as an antislavery engine, it needed to be linked to its seeming opposite—fear, especially the fear of God’s wrath. Most antislavery reformers recognized that calls for love and sympathy or the representation of suffering slaves would not lead an audience to “feel right” or to actively oppose slavery. The threat of God’s apocalyptic vengeance—and the terror that this threat inspired—functioned within the tradition of abolitionist sentimentality as a necessary goad for sympathy and love. Fear, then, was at the center of nineteenth-century sentimental strategies for inciting antislavery reform, bolstering love when love faltered, and operating as a powerful mechanism for establishing interracial sympathy. Depictions of God’s apocalyptic vengeance constituted the most efficient strategy for antislavery writers to generate a sense of terror in their audience. Focusing on a range of important antislavery figures, including David Walker, Nat Turner, Maria Stewart, Harriet Beecher Stowe, and John Brown, Apocalyptic Sentimentalism illustrates how antislavery discourse worked to redefine violence and vengeance as the ultimate expression (rather than denial) of love and sympathy. At the same time, these warnings of apocalyptic retribution enabled antislavery writers to express, albeit indirectly, fantasies of brutal violence against slaveholders. What began as a sentimental strategy quickly became an incendiary gesture, with antislavery reformers envisioning the complete annihilation of slaveholders and defenders of slavery.https://scholarship.richmond.edu/bookshelf/1202/thumbnail.jp

    Considération de la torsion pour l'analyse sismique non-linéaire de noyaux en béton armé

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    RÉSUMÉ Les noyaux en béton armé sont utilisés dans de nombreux bâtiments multi-étagés résidentiels comme principal système de résistance aux forces sismiques (SRFS). Dues à des limitations architecturales, ces bâtiments sont souvent flexibles en torsion. Afin d'évaluer l'effet de la torsion sur la réponse non-linéaire de noyaux en béton armé, un modèle basé sur la méthode des cadres équivalents (WCMM) utilisant des éléments fibres est proposés. Les comportements nonlinéaires en gauchissement et biaxial (P-Mx-My) cyclique sont validés à l'aide de résultats expérimentaux et montrent une excellente convergence avec ces derniers. Selon les analyses modale et linéaire temporelle, le modèle proposé peut capturer adéquatement les caractéristiques dynamiques et sismiques des noyaux et ce, incluant la torsion. Le WCMM est ensuite utilisé en régime non-linéaire afin de réaliser des analyses tridimensionnelles (3D) temporelles d'un bâtiment typique en béton armé localisé dans l’est de l'Amérique du Nord et qui est sujet à des tremblements de terre à contenu fréquentiel élevé (environ 10 Hz). Trois configurations de bâtiment avec une flexibilité en torsion croissante (B=1.7, B=2.1 et B=2.5, selon l'actuel Code National du Bâtiment du Canada) sont étudiées afin d'évaluer l'effet de la torsion sur le comportement sismique. Les enveloppes non-linéaires de paramètres importants pour la conception sont similaires aux enveloppes de dimensionnement obtenues à partir d'une analyse spectrale linéaire d'un modèle à éléments coques (B=1.7) incluant les facteurs appropriés de réduction des forces inélastiques. Hormis pour le torque à chaque étage, les demandes en cisaillement et en moment demeurent relativement constantes peu importe la valeur de B. La rigidité effective en cisaillement doit être sélectionnée avec soin pour le WCMM afin d'éviter de larges rotations questionnables. Un délai corrélé est observé entre les crêtes en translation et en rotation lors des analyses temporelles non-linéaires des bâtiments.----------ABSTRACTReinforced concrete (RC) cores are used in many residential multi-story buildings as the primary seismic force resisting system (SFRS). Due to architectural limitations, these buildings are often torsionally lexible. To assess the effect of torsion on the nonlinear seismic response of RC cores, a wide-column model with modules (WCMM) using fiber elements is proposed. The nonlinear warping and the nonlinear biaxial (P-Mx-Mx) cyclic behaviors of the WCMM are validated against experimental results and exhibit excellent agreement. According to modal and linear time history analyses, the proposed model can adequately capture the dynamic characteristics and seismic response of core structures, including torsion. The proposed WCMM is then extended to the nonlinear range to perform three-dimensional (3D) time history analyses of a typical RC building structure located in Eastern North America (ENA) that is subjected to high-frequency ground motions (approximately 10 Hz). Three different building configurations with increasing torsional flexibility (B=1.7, B=2.1 and B=2.5, according to the current National Building Code of Canada) are studied to investigate the effect of torsion on the seismic behavior. The nonlinear envelopes of key response parameters are similar to the design envelopes obtained from the linear response spectrum analysis of a shell elements model (B=1.7) with proper inelastic force modification factors. Aside from the story torque, the shear and moment demands remain relatively constant, regardless of the B value. The effective shear stiffness must be carefully selected in the WCMM to avoid large questionable rotations. A correlated delay can be observed between the translational and rotational peak displacements in the nonlinear time histories of the buildings analyzed

    L’indépendance à tout prix : la Belgique face à la France durant l’Entre-deux-guerres

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    The main focus of this study is the dynamic between France and Belgium during the Interwar period. The goal is to verify if Belgium was ever a satellite of French diplomacy under the 1920 French-Belgium military alliance. Using the diplomatic archives of the Belgian Foreign Office, the study shows that, whilst maintaining the harmony between the main members of the former Allies (French, Great-Britain and Belgium), Belgium always acted in its most basic national interest. As the major events of the Interwar period unveil: (especially, the Ruhr Occupation, the Locarno Treaty, the Rhineland demilitarisation and Hitler’s election) Belgium demonstrates that she is both independent and a major player in the evolution of European politics. The breaking of the 1920 French-Belgian military alliance in 1936 is often falsely seen as a rupture of a political relationship, whereas it only represented Belgium’s way to not be involved in another war without her consent. This study clarifies the Franco-Belgian relationship during the Interwar period and demonstrates that it was not one of submission by Belgium to France.Cette étude s’intéresse à la dynamique des relations franco-belges durant l’Entre-deux-guerres. L’objectif est de définir si la Belgique a été un satellite de la France pendant la durée de l’accord militaire franco-belge de 1920. Utilisant les archives diplomatiques du ministère des Affaires étrangères belge, l’étude démontre que la Belgique, alors même qu’elle tente de maintenir une harmonie entre les membres de l’Entente (Angleterre, France, Belgique), agit dans son plus pur intérêt national. Ainsi, alors que les évènements majeurs de l’Entre-deux-guerres se déroulent -occupation de la Ruhr, signature du Traité de Locarno, démilitarisation de la Ruhr et l’élection d’Hitler- la Belgique démontre qu’elle est une actrice indépendante et importante dans l’évolution de la diplomatie européenne. La rupture de l’accord militaire franco-belge en 1936 est généralement perçue comme une rupture des relations diplomatiques entre les deux pays alors qu’elle ne représente que la volonté belge de ne pas être entrainée dans une guerre qui ne la concerne pas. Ainsi, la présente étude cherche à clarifier la relation franco-belge. Elle démontre que les interactions entre la Belgique et sa grande voisine n’ont rien d’une relation de subordination

    Nonlinear seismic modeling of reinforced concrete cores including torsion

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    Reinforced concrete (RC) cores are used in many residential multi-story buildings as the primary seismic force resisting system (SFRS). Due to architectural limitations, these buildings are often torsionally flexible. To assess the effect of torsion on the nonlinear seismic response of RC cores, a wide-column model (WCM) with fiber elements is used. The nonlinear warping and the nonlinear biaxial (P-Mx-My) cyclic behaviors of the WCM are validated against experimental results and exhibit excellent agreement. According to modal and linear time history analyses, the model can adequately capture the dynamic characteristics and seismic response of core structures, including torsion. The WCM is then extended to the nonlinear range to perform three-dimensional (3D) time history analyses of a typical RC building structure located in Eastern North America (ENA) that is subjected to high-frequency ground motions. Three different building configurations with increasing torsional flexibility (B = 1.7, B = 2.1 and B = 2.5, according to the current National Building Code of Canada) are studied to investigate the effect of torsion on the seismic behavior. The nonlinear envelopes of key response parameters are similar to the design envelopes obtained from the linear response spectrum analysis of a shell elements model (B = 1.7) with proper inelastic force modification factors. Aside from the story torque, the shear and moment demands remain relatively constant, regardless of the torsional flexibility value. The effective shear stiffness must be carefully selected in the WCM to avoid large questionable rotations

    Characterization of neutrophils and macrophages from ex vivo cultured murine bone marrow for morphologic maturation and functional responses by imaging flow cytometry

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    Neutrophils and macrophages differentiate from common myeloid progenitors in the bone marrow, where they undergo unique nuclear morphologic changes as they mature into fully functional phagocytes. These changes include condensation of chromatin, the most pronounced exhibited by mature neutrophils. Both myeloid cells acquire multiple functions critical to their ability to kill pathogens, including phagocytosis, the production of proteolytic enzymes and reactive oxygen species (ROS), and in the case of neutrophils, release of nuclear material known as nuclear extracellular traps (NETs). Studies on these functions often rely on the use of cells acquired from mature mouse tissues, but these tend to produce limited numbers of cells. Strategies to analyze the morphologic features and functional responses of these cells include the use of conventional brightfield or fluorescence microscopy to examine changes in nuclear structure, internalization of fluorescein-labeled bacterial or yeast particles, or release of nuclear material. Flow cytometry also is often used, especially for identifying changes in the expression of lineage-specific cell surface markers and ROS production. However, each of these techniques presents certain limitations. Here we describe methods to generate abundant populations highly enriched for neutrophils or macrophages from previously frozen, ex vivo cultured mouse bone marrow. We then apply state-of-the-art imaging flow cytometry, which combines the resolution of microscopy with the speed of flow cytometry, to analyze each lineage for changes in nuclear structure and expression of key cell surface markers. Different gating and masking strategies are applied to characterize phagocytosis of pH-dependent fluorescein-labeled E. coli, ROS production, and NET release by neutrophils. We also demonstrate that neutrophils engulfing E. coli bioparticles produce NETs in a process we term PhagoNETosis. Together these assays reveal the power of imaging flow cytometry for simultaneously assessing the maturation features and functional responses of these critical mediators of innate immunity

    Rocaglates as dual-targeting agents for experimental cerebral malaria

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    Cerebral malaria (CM) is a severe and rapidly progressing complication of infection by Plasmodium parasites that is associated with high rates of mortality and morbidity. Treatment options are currently few, and intervention with artemisinin (Art) has limited efficacy, a problem that is compounded by the emergence of resistance to Art in Plasmodium parasites. Rocaglates are a class of natural products derived from plants of the Aglaia genus that have been shown to interfere with eukaryotic initiation factor 4A (eIF4A), ultimately blocking initiation of protein synthesis. Here, we show that the rocaglate CR-1-31B perturbs association of Plasmodium falciparum eIF4A (PfeIF4A) with RNA. CR-1-31B shows potent prophylactic and therapeutic antiplasmodial activity in vivo in mouse models of infection with Plasmodium berghei (CM) and Plasmodium chabaudi (blood-stage malaria), and can also block replication of different clinical isolates of P. falciparum in human erythrocytes infected ex vivo, including drug-resistant P. falciparum isolates. In vivo, a single dosing of CR-1-31B in P. berghei-infected animals is sufficient to provide protection against lethality. CR-1-31B is shown to dampen expression of the early proinflammatory response in myeloid cells in vitro and dampens the inflammatory response in vivo in P. berghei-infected mice. The dual activity of CR-1-31B as an antiplasmodial and as an inhibitor of the inflammatory response in myeloid cells should prove extremely valuable for therapeutic intervention in human cases of CM.We thank Susan Gauthier, Genevieve Perreault, and Patrick Senechal for technical assistance. This work was supported by a research grant (to P.G.) from the Canadian Institutes of Health Research (CIHR) (Foundation Grant). J.P. and P.G. are supported by a James McGill Professorship salary award. D.L. is supported by fellowships from the Fonds de recherche sante Quebec, the CIHR Neuroinflammation training program. J.P. is supported by CIHR Research Grant FDN-148366. M.S. is supported by a CIHR Foundation grant. J.A.P. is supported by NIH Grant R35 GM118173. Work at the Boston University Center for Molecular Discovery is supported by Grant R24 GM111625. K.C.K. was supported by a CIHR Foundation Grant and the Canada Research Chair program. (Canadian Institutes of Health Research (CIHR); James McGill Professorship salary award; Fonds de recherche sante Quebec; CIHR Neuroinflammation training program; FDN-148366 - CIHR Research Grant; CIHR Foundation grant; R35 GM118173 - NIH; Canada Research Chair program; R24 GM111625

    Antibody Engineering Using Phage Display with a Coiled-Coil Heterodimeric Fv Antibody Fragment

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    A Fab-like antibody binding unit, ccFv, in which a pair of heterodimeric coiled-coil domains was fused to VH and VL for Fv stabilization, was constructed for an anti-VEGF antibody. The anti-VEGF ccFv showed the same binding affinity as scFv but significantly improved stability and phage display level. Furthermore, phage display libraries in the ccFv format were constructed for humanization and affinity maturation of the anti-VEGF antibody. A panel of VH frameworks and VH-CDR3 variants, with a significant improvement in affinity and expressibility in both E. coli and yeast systems, was isolated from the ccFv phage libraries. These results demonstrate the potential application of the ccFv antibody format in antibody engineering
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