23 research outputs found
The binding of prion proteins to serum components is affected by detergent extraction conditions
No full textRevolutionary Russia in American Eyes
No full textTo mark the centenary of the Russian revolutions of 1917, American publishers released several
new histories in 2017, including a massive study by the distinguished scholar Laura Engelstein
and a lengthy account by the prolific author Sean McMeekin. This article develops a
critical perspective on the books by Engelstein and McMeekin by setting them in the context
of other scholarship and by contrasting them to the views presented by American witnesses
of the Russian revolutions. The review essay focuses primarily on three major issues: the nature
of the February Revolution; the relationship between the Bolsheviks and Germany; and
foreign intervention in the Russian Civil War. It argues that there are serious problems in
McMeekin’s and Engelstein’s treatments of those issues. Their presentation of the revolution of
February 1917 as a political event rather than a social transformation, McMeekin’s depiction
of the Bolsheviks as pawns of Imperial Germany, and both authors’ downplaying of American
interventions in Russia ignore the views of Americans who were in Petrograd at the time, and
disregard much important scholarship published since the 1960s. By drawing on those eyewitness
accounts and historical studies, this article reminds scholars of how the February Revolution
both reflected and stimulated a profound change in many Russians’ ways of thinking,
how Americans as well as Germans funded propaganda campaigns in Russia in 1917, and how
the United States intervened in the Russian civil war in several other ways, with the ultimate
objective of restoring a democratic or at least a non-Bolshevik government
Storm, Stress, and Sexual Revolution: Economies of Desire in the German Literary Avant-Garde of the 1770s
No full textThis dissertation identifies a queer revolutionary core to the Sturm und Drang movement in German literature that sought to revolutionize the social through the force of the erotic. Drawing on the discourse of queer theory, I claim that these texts question, disrupt, and overthrow contemporary sexual and gender mores. Moreover, I argue, the political economics of the Sturm und Drang are dependent on its queerness: by questioning the structures of social life, authors of the Sturm und Drang sought not mere reform, but the building of a new polity from the ground-up. My first two chapters reveal Jakob Michael Reinhold Lenz as the most radical author of Sturm und Drang sexual revolution. In his political-economic writings on military reform, Lenz introduces a radical solution in moderate packaging that utilizes the erotic for social transformation. In his dramas, Lenz demonstrates how thus rethinking sexuality as a means for change opens the way disrupting and making more egalitarian existing structures. The third chapter argues that Johann Wolfgang Goethe’s early Sturm und Drang works Stella and Die Leiden des Jungen Werthers engage in a similar process of sexual revolution. Goethe disrupts the either-or logic of the conventional literary love-triangle and substitutes a polyamorous logic of both-and, where all three partners can define their own relationship against social norms. The fourth chapter explores the theme of infanticide. While Lenz and Gottfried August Bürger seek to liberate desire from what they view as an inherently alien force of destruction, Friedrich Schiller and Heinrich Leopold Wagner see such destruction as an inherent part of desire. Goethe attempts to mediate between these two sides in his own approach. The fifth chapter addresses how Schiller’s Die Räuber and Goethe’s Die Wahlverwandtschaften turn definitively away from sexual and social experimentation, ending the movement’s radical potential. I argue that Die Räuber appropriates the aesthetics of the movement against its ideals. Goethe’s Wahlverwandtschaften utilizes the discourses of botany and chemistry to mobilize the order of nature against his own earlier revolutionary ideas. My project is thus an archaeology of a revolution that never happened and an autopsy of its failure.Doctor of Philosoph
Gender and Humor in German Literature of the fin de siècle
No full textThis dissertation explores the intersection of gender and humor in German-language literature of the fin de siècle. At the turn of the century, the German-speaking countries of central Europe experienced a surge of interest in humor theory as well as unprecedented feminist activity, making the relationship between humor and gender a fruitful area of study. However, most literary criticism on gender and humor published in the last forty years has focused on the gender of a humorous literary text’s author rather than how humor affects representations of gender within the text. This dissertation therefore examines literary works by decidedly non-feminist authors like Theodor Fontane, Thomas Mann, and Frank Wedekind as well as the feminist activist Hedwig Dohm and analyzes how humor works to influence gender representation in novels, short stories, dramas, and polemic essays. Ultimately this dissertation argues two main points: First, humor in literature of the fin de siècle often acts as a social leveler and creates a space in which men and women can prove themselves intellectual and moral equals. Second, humor in this literature often goes beyond depicting men and women simply as equals and challenges traditional and essentialist gender roles by exposing them as social constructs devoid of any “natural” foundation. In order to make these arguments, this dissertation engages with humor theory, classical to contemporary, as well as Judith Butler's theory of gender performativity.Doctor of Philosoph
Effectiveness of the GPT-4o Model in Interpreting Electrocardiogram Images for Cardiac Diagnostics: Diagnostic Accuracy Study
No full textAbstract
BackgroundRecent progress has demonstrated the potential of deep learning models in analyzing electrocardiogram (ECG) pathologies. However, this method is intricate, expensive to develop, and designed for specific purposes. Large language models show promise in medical image interpretation, and yet their effectiveness in ECG analysis remains understudied. Generative Pretrained Transformer 4 Omni (GPT-4o), a multimodal artificial intelligence model, capable of processing images and text without task-specific training, may offer an accessible alternative.
ObjectiveThis study aimed to evaluate GPT-4o’s effectiveness in interpreting 12-lead ECGs, assessing classification accuracy, and exploring methods to enhance its performance.
MethodsA total of 6 common ECG diagnoses were evaluated: normal ECG, ST-segment elevation myocardial infarction, atrial fibrillation, right bundle branch block, left bundle branch block, and paced rhythm, with 30 normal ECGs and 10 of each abnormal pattern, totaling 80 cases. Deidentified ECGs were analyzed using OpenAI’s GPT-4o. Our study used both zero-shot and few-shot learning methodologies to investigate three main scenarios: (1) ECG image recognition, (2) binary classification of normal versus abnormal ECGs, and (3) multiclass classification into 6 categories.
ResultsThe model excelled in recognizing ECG images, achieving an accuracy of 100%. In the classification of normal or abnormal ECG cases, the few-shot learning approach improved GPT-4o’s accuracy by 30% from the baseline, reaching 83% (95% CI 81.8%-84.6%). However, multiclass classification for a specific pathology remained limited, achieving only 41% accuracy.
ConclusionsGPT-4o effectively differentiates normal from abnormal ECGs, suggesting its potential as an accessible artificial intelligence–assisted triage tool. Although limited in diagnosing specific cardiac conditions, GPT-4o’s capability to interpret ECG images without specialized training highlights its potential for preliminary ECG interpretation in clinical and remote settings
Methionine Sulfoxides on PrPSc: A Prion-Specific Covalent Signature
No full textPrion diseases are fatal neurodegenerative disorders believed to be transmitted by PrPSc, an aberrant form of the membrane protein PrPC. In the absence of an established form-specific covalent difference, the infectious properties of PrPSc were uniquely ascribed to the self-perpetuation properties of its aberrant fold. Previous sequencing of the PrP chain isolated from PrP(27¿30) showed the oxidation of some methionine residues; however, at that time, these findings were ascribed to experimental limitations. Using the unique recognition properties of ¿PrP mAb IPC2, protein chemistry, and state of the art mass spectrometry, we now show that while a large fraction of the methionine residues in brain PrPSc are present as methionine sulfoxides this modification could not be found on brain PrPC as well as on its recombinant models. In particular, the pattern of oxidation of M213 with respect to the glycosylation at N181 of PrPSc differs both within and between species, adding another diversity factor to the structure of PrPSc molecules. Our results pave the way for the production of prion-specific reagents in the form of antibodies against oxidized PrP chains which can serve in the development of both diagnostic and therapeutic strategies. In addition, we hypothesize that the accumulation of PrPSc and thereafter the pathogenesis of prion disease may result from the poor degradation of oxidized aberrantly folded PrP
Soluble SLAMF6 Receptor Induces Strong CD8+ T-cell Effector Function and Improves Anti-Melanoma Activity <i>In Vivo</i>
No full textAbstract
SLAMF6, a member of the SLAM (signaling lymphocyte activation molecules) family, is a homotypic-binding immune receptor expressed on NK, T, and B lymphocytes. Phosphorylation variance between T-cell subclones prompted us to explore its role in anti melanoma immunity. Using a 203-amino acid sequence of the human SLAMF6 (seSLAMF6) ectodomain, we found that seSLAMF6 reduced activation-induced cell death and had an antiapoptotic effect on tumor-infiltrating lymphocytes. CD8+ T cells costimulated with seSLAMF6 secreted more IFNγ and displayed augmented cytolytic activity. The systemic administration of seSLAMF6 to mice sustained adoptively transferred transgenic CD8+ T cells in comparable numbers to high doses of IL2. In a therapeutic model, lymphocytes activated by seSLAMF6 delayed tumor growth, and when further supported in vivo with seSLAMF6, induced complete tumor clearance. The ectodomain expedites the loss of phosphorylation on SLAMF6 that occurs in response to T-cell receptor triggering. Our findings suggest that seSLAMF6 is a costimulator that could be used in melanoma immunotherapy. Cancer Immunol Res; 6(2); 127–38. ©2018 AACR.</jats:p
Human T cell crosstalk is induced by tumor membrane transfer.
No full textTrogocytosis is a contact-dependent unidirectional transfer of membrane fragments between immune effector cells and their targets, initially detected in T cells following interaction with professional antigen presenting cells (APC). Previously, we have demonstrated that trogocytosis also takes place between melanoma-specific cytotoxic T lymphocytes (CTLs) and their cognate tumors. In the present study, we took this finding a step further, focusing on the ability of melanoma membrane-imprinted CD8+ T cells to act as APCs (CD8+ T-APCs). We demonstrate that, following trogocytosis, CD8+ T-APCs directly present a variety of melanoma derived peptides to fraternal T cells with the same TCR specificity or to T cells with different TCRs. The resulting T cell-T cell immune synapse leads to (1) Activation of effector CTLs, as determined by proliferation, cytokine secretion and degranulation; (2) Fratricide (killing) of CD8+ T-APCs by the activated CTLs. Thus, trogocytosis enables cross-reactivity among CD8+ T cells with interchanging roles of effectors and APCs. This dual function of tumor-reactive CTLs may hint at their ability to amplify or restrict reactivity against the tumor and participate in modulation of the anti-cancer immune response
Table S1 from Soluble SLAMF6 Receptor Induces Strong CD8<sup>+</sup> T-cell Effector Function and Improves Anti-Melanoma Activity <i>In Vivo</i>
No full textTumor infiltrating lymphocytes used in the study</p
