Tijelo, prostor i osjeti u pripovijetci „Nevolja“ Edgara Allana Poea

This paper aims to examine the sensationalism of Blackwood’s Magazine as evident in Poe’s tale “A Predicament” and how Poe disengages from the tradition of Blackwoods. On the one hand, Poe conflates Psyche Zenobia’s adventure into a Gothic Cathedral with the Blackwood’s sensationalistic experience, which treats vehement sensations as the prime condition for stimulating the mind’s engagement with a spiritual vision of a world beyond the material world. On the other, Poe’s tale disengages itself from the tradition of Blackwood’s Magazine: Zenobia loses her sensations altogether in the quest for final knowledge and there is no return to her real life. This paper will further look at the mutilated/deformed body in Poe’s “A Predicament” as a body in pain, or without pain, through which the mind engages its imagination. It will also discuss how Poe, through Zenobia’s gaze and speculation upon a sublime cathedral, installs an aesthetic appreciation that distances an imaginary space from reality and facilitates self-mesmerism through which Zenobia is grounded in the earthly world, both physically and spiritually.Cilj je ovog rada analizirati prikaz senzacionalizma Blackwood’s Magazinea u pripovijetci „Nevolja” Edgara Allana Poea te Poeovo propitivanje tog senzacionalizma. Poe istovremeno isprepliće pustolovine Psyche Zenobije u Gotičkoj katedrali i Blackwood’s senzacionalističko iskustvo, koje snažne osjete smatra glavnim stimulirajućim uvjetom za interakciju uma sa spiritualnom vizijom svijeta izvan materijalnog svijeta, ali se i distancira od tradicije Blackwood’s Magazinea. Zenobia u potpunosti gubi svoje osjete u potrazi za ultimativnim znanjem te se ne može vratiti svom stvarnom životu. Rad se bavi i osakaćenim/deformiranim tijelom u Poeovoj pripovijetci kao tijelom koje osjeti, ili ne osjeti bol te tako omogućuje umu da se koristi imaginacijom. Naposljetku, rad pokazuje kako Poe, pomoću Zenobijina pogleda i razmišljanjima o uzvišenosti katedrale, promiče estetski doživljaj koji odvaja imaginaran prostor od stvarnosti te stvara samoopčinjenost koja smješta Zenobiju i fizički i spiritualno u zemaljski svijet

Olfactory Experiences and an Unknown Force in Patrick Süskind’s «Das Parfum: Die Geschichte eines Mörders»

Patrick Süskind’s Das Parfum: Die Geschichte eines Mörders presents a sort of Janus-figure, gazing backwards toward the primitive form of life (Grenouille’s Romantic deliverance) and forward toward an Enlightenment anthropocentric mechanism (an allusion to negative aesthetics) which reveals the formation and dissolution of political power through the olfactory experiences of the protagonist. In other words, it concerns the two worlds between which there is an unknown force transforming all olfactory manipulation/experimentation into nothingness: as men scheme their evil business through objects or scents, a greater force then deconstructs those schemes

Nonliteral understanding of number words

One of the most puzzling and important facts about communication is that people do not always mean what they say; speakers often use imprecise, exaggerated, or otherwise literally false descriptions to communicate experiences and attitudes. Here, we focus on the nonliteral interpretation of number words, in particular hyperbole (interpreting unlikely numbers as exaggerated and conveying affect) and pragmatic halo (interpreting round numbers imprecisely). We provide a computational model of number interpretation as social inference regarding the communicative goal, meaning, and affective subtext of an utterance. We show that our model predicts humans’ interpretation of number words with high accuracy. Our model is the first to our knowledge to incorporate principles of communication and empirically measured background knowledge to quantitatively predict hyperbolic and pragmatic halo effects in number interpretation. This modeling framework provides a unified approach to nonliteral language understanding more generally.National Science Foundation (U.S.). Graduate Research Fellowship Progra

Clear Cell Renal Cell Carcinoma With a Poorly-Differentiated Component: A Novel Variant Causing Potential Diagnostic Difficulty

Background: Several variant histologic patterns of clear cell renal cell carcinoma (RCC) are well known, especially those with sarcomatoid and rhabdoid features. However, we have encountered rare cases in which a high-grade adenocarcinoma or urothelial carcinoma-like component would be difficult to appreciate as clear cell RCC. DesignWe retrieved 26 tumors with histologically typical clear cell RCC juxtaposed to a high-grade non-clear cell component.High grade non-clear cell component was defined as non-sarcomatoid, non-rhabdoid areas that would be difficult to assign as renal cell in origin if viewed in isolation. Tumors were studied with immunohistochemistry and fluorescence in situ hybridization (FISH) or sequencing.ResultsMedian percentage of poorly differentiated component: 50%(IQR20-70). All tumors showed abrupt transition from clear cell carcinoma to poorly-differentiated (non-sarcomatoid/non-rhabdoid) areas, which showed micropapillary (7/26; 27%), urothelial-like (10/26; 39%), and adenocarcinoma NOS features (9/26; 35%). 19 tumors had necrosis. Carbonic anhydrase IX (CA-IX) was uniformly positive in well-differentiated component (20/20); poorly differentiated component showed a median positivity of 82.5% (IQR 65-100). Poorly differentiated component was positive for CK7 (5/19; 26%), CK20 (3/12; 25%), AMACR (7/12; 58%), PAX8 (12/15; 80%), and showed intact FH (6/6; 100%). CDX2 was uniformly negative. Chromosome 3p loss or VHL mutation was present in 8/13 (62%), tested with either FISH (n = 9) or sequencing (n = 4). All tested cases were negative for TFE3 (0/11) and TFEB (0/9) rearrangements on FISH. 5/21 (24%) patients were alive with metastatic disease and 5/21 (24%) had died of disease on follow up. One metastasis was composed only of the poorly-differentiated component and was near-negative for CA-IX. Conclusion: Clear cell RCC with a poorly differentiated component resembling adenocarcinoma or urothelial carcinoma is a novel source of morphologic heterogeneity that has not been previously well characterized. Potential pitfalls include decreased or absent CA-IX staining the high-grade component and aberrant positivity for cytokeratin 7 or 20. With the increasing use of renal mass biopsy and biopsies of metastatic sites for targeted therapy, pathologists should be aware of this entity and consider the possibility of clear cell RCC even for morphologically unusual tumors.https://scholarlycommons.henryford.com/merf2019caserpt/1069/thumbnail.jp

Evaluation of the dystrophin carboxy-terminal domain for micro-dystrophin gene therapy in cardiac and skeletal muscles in the DMDmdx rat model

Duchenne muscular dystrophy (DMD) is a muscle wasting disorder caused by mutations in the gene encoding dystrophin. Gene therapy using micro-dystrophin (MD) transgenes and recombinant adeno-associated virus (rAAV) vectors hold great promise. To overcome the limited packaging capacity of rAAV vectors, most MD do not include dystrophin carboxy-terminal (CT) domain. Yet, the CT domain is known to recruit α1- and β1-syntrophins and α-dystrobrevin, a part of the dystrophin-associated protein complex (DAPC), which is a signaling and structural mediator of muscle cells. In this study, we explored the impact of inclusion of the dystrophin CT domain on ΔR4-23/ΔCT MD (MD1), in DMDmdx rats, which allows for relevant evaluations at muscular and cardiac levels. We showed by LC-MS/MS that MD1 expression is sufficient to restore the interactions at a physiological level of most DAPC partners in skeletal and cardiac muscles, and that inclusion of the CT domain increases the recruitment of some DAPC partners at supra-physiological levels. In parallel, we demonstrated that inclusion of the CT domain does not improve MD1 therapeutic efficacy on DMD muscle and cardiac pathologies. Our work highlights new evidences of the therapeutic potential of MD1 and strengthens the relevance of this candidate for gene therapy of DMD

SeamlessM4T-Massively Multilingual & Multimodal Machine Translation

What does it take to create the Babel Fish, a tool that can help individuals translate speech between any two languages? While recent breakthroughs in text-based models have pushed machine translation coverage beyond 200 languages, unified speech-to-speech translation models have yet to achieve similar strides. More specifically, conventional speech-to-speech translation systems rely on cascaded systems that perform translation progressively, putting high-performing unified systems out of reach. To address these gaps, we introduce SeamlessM4T, a single model that supports speech-to-speech translation, speech-to-text translation, text-to-speech translation, text-to-text translation, and automatic speech recognition for up to 100 languages. To build this, we used 1 million hours of open speech audio data to learn self-supervised speech representations with w2v-BERT 2.0. Subsequently, we created a multimodal corpus of automatically aligned speech translations. Filtered and combined with human-labeled and pseudo-labeled data, we developed the first multilingual system capable of translating from and into English for both speech and text. On FLEURS, SeamlessM4T sets a new standard for translations into multiple target languages, achieving an improvement of 20% BLEU over the previous SOTA in direct speech-to-text translation. Compared to strong cascaded models, SeamlessM4T improves the quality of into-English translation by 1.3 BLEU points in speech-to-text and by 2.6 ASR-BLEU points in speech-to-speech. Tested for robustness, our system performs better against background noises and speaker variations in speech-to-text tasks compared to the current SOTA model. Critically, we evaluated SeamlessM4T on gender bias and added toxicity to assess translation safety. Finally, all contributions in this work are open-sourced and accessible at https://github.com/facebookresearch/seamless_communicatio

Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases