Does ChatGPT resemble humans in language use?

Large language models (LLMs) and LLM-driven chatbots such as ChatGPT have shown remarkable capacities in comprehending and producing language. However, their internal workings remain a black box in cognitive terms, and it is unclear whether LLMs and chatbots can develop humanlike characteristics in language use. Cognitive scientists have devised many experiments that probe, and have made great progress in explaining, how people process language. We subjected ChatGPT to 12 of these experiments, pre-registered and with 1,000 runs per experiment. In 10 of them, ChatGPT replicated the human pattern of language use. It associated unfamiliar words with different meanings depending on their forms, continued to access recently encountered meanings of ambiguous words, reused recent sentence structures, reinterpreted implausible sentences that were likely to have been corrupted by noise, glossed over errors, drew reasonable inferences, associated causality with different discourse entities according to verb semantics, and accessed different meanings and retrieved different words depending on the identity of its interlocutor. However, unlike humans, it did not prefer using shorter words to convey less informative content and it did not use context to disambiguate syntactic ambiguities. We discuss how these convergences and divergences may occur in the transformer architecture. Overall, these experiments demonstrate that LLM-driven chatbots like ChatGPT are capable of mimicking human language processing to a great extent, and that they have the potential to provide insights into how people learn and use language

Efficacy of a ML336 Derivative Against Venezuelan and Eastern Equine Encephalitis Viruses

Currently, there are no licensed human vaccines or antivirals for treatment of or prevention from infection with encephalitic alphaviruses. Because epidemics are sporadic and unpredictable, and endemic disease is common but rarely diagnosed, it is difficult to identify all populations requiring vaccination; thus, an effective post-exposure treatment method is needed to interrupt ongoing outbreaks. To address this public health need, we have continued development of ML336 to deliver a molecule with prophylactic and therapeutic potential that could be relevant for use in natural epidemics or deliberate release scenario for Venezuelan equine encephalitis virus (VEEV). We report findings from in vitro assessments of four analogs of ML336, and in vivo screening of three of these new derivatives, BDGR-4, BDGR-69 and BDGR-70. The optimal dosing for maximal protection was observed at 12.5 mg/kg/day, twice daily for 8 days. BDGR-4 was tested further for prophylactic and therapeutic efficacy in mice challenged with VEEV Trinidad Donkey (TrD). Mice challenged with VEEV TrD showed 100% and 90% protection from lethal disease when treated at 24 and 48 h post-infection, respectively. We also measured 90% protection for BDGR-4 in mice challenged with Eastern equine encephalitis virus. In additional assessments of BDGR-4 in mice alone, we observed no appreciable toxicity as evaluated by clinical chemistry indicators up to a dose of 25 mg/kg/day over 4 days. In these same mice, we observed no induction of interferon. Lastly, the resistance of VEEV to BDGR-4 was evaluated by next-generation sequencing which revealed specific mutations in nsP4, the viral polymerase

RNA editing signature during myeloid leukemia cell differentiation

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin–proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells

Representations of Uϵres(sl2)U_{\epsilon}^{res}(sl_2) via Restricted q-Fock Spaces

Two restricted $C[q,q^{-1}]-$forms of the well known q-boson algebra are introduced and the corresponding restricted q-Fock spaces defined. All of the irreducible highest weight representations, including the infinite dimensional ones, of $U_\epsilon ^{res}(sl_2)$ of type 1 are constructed through the restricted q-Fock spaces.Comment: 15 page

Three-dimensional chromatin landscapes in T cell acute lymphoblastic leukemia

Analysis of 3D chromatin architecture in T-ALL identifies differences in intra-TAD interactions and TAD boundary insulation. Inhibition of oncogenic signal transduction or epigenetic regulation can alter specific 3D interactions. Differences in three-dimensional (3D) chromatin architecture can influence the integrity of topologically associating domains (TADs) and rewire specific enhancer-promoter interactions, impacting gene expression and leading to human disease. Here we investigate the 3D chromatin architecture in T cell acute lymphoblastic leukemia (T-ALL) by using primary human leukemia specimens and examine the dynamic responses of this architecture to pharmacological agents. Systematic integration of matched in situ Hi-C, RNA-seq and CTCF ChIP-seq datasets revealed widespread differences in intra-TAD chromatin interactions and TAD boundary insulation in T-ALL. Our studies identify and focus on a TAD 'fusion' event associated with absence of CTCF-mediated insulation, enabling direct interactions between the MYC promoter and a distal super-enhancer. Moreover, our data also demonstrate that small-molecule inhibitors targeting either oncogenic signal transduction or epigenetic regulation can alter specific 3D interactions found in leukemia. Overall, our study highlights the impact, complexity and dynamic nature of 3D chromatin architecture in human acute leukemia

Collaborative multidisciplinary management and expertise of cT2-3 locally advanced operable esophageal squamous cell carcinoma:two case reports

Background: The accurate clinical staging of esophageal squamous cell carcinoma (ESCC) is pivotal for guiding treatment strategies. However, the current precision in staging for clinical T (cT)2 and cT3 stages remains unsatisfactory. This article discusses the role of multidisciplinary teams (MDTs) in the clinical staging and formulation of neoadjuvant treatment strategies for locally advanced operable ESCC. These challenges underscore the importance of precise staging in the decision-making process for appropriate therapeutic interventions.Case Description: Through the lens of two patient case studies with locally advanced resectable ESCC, the article showcases the intricate process of treatment planning undertaken by MDTs. It captures a range of expert perspectives from Japan, China, Hong Kong (China), Korea, the USA, and Europe, focusing on the challenges of differentiating between cT2 and cT3 stages of the disease, which is a critical determinant in the management and therapeutic approach for patients.Conclusions: The article concludes that the accurate staging of ESCC is a cornerstone in determining the most suitable treatment strategies. It underscores the vital role that MDTs play in both clinical staging and the decision-making process for treatment. Highlighting the limitations in current diagnostic methods, the article emphasizes the urgent need for advanced research and the refinement of diagnostic tools to improve the precision of staging, particularly between the cT2 and cT3 stages. It suggests that future research should consider whether a reclassification of these stages could be warranted to enhance treatment planning and outcomes for patients with ESCC.<br/

Distinct control mechanism of fine-grained sediments from Yellow River and Kyushu supply in the northern Okinawa Trough since the last glacial

© 2017. American Geophysical Union. All Rights Reserved. High-resolution multiproxy records, including clay minerals and Sr-Nd-Pb isotopes of the clay-sized silicate fraction of sediments from IODP Site U1429 in the northern Okinawa Trough, provide reliable evidence for distinct control mechanism on fine-grained sediments input from the Yellow River and the southern Japanese Islands to the northern Okinawa Trough since 34 ka BP. Provenance analysis indicates that the sediments were mainly derived from the Yellow River and the island of Kyushu. Since the last glacial, clay-sized sediments transported from the Yellow River to the study site were strongly influenced by sea-level fluctuation. During low sea-level stage (∼34–14 ka BP), the paleo-Yellow River mouth was positioned closer to the northern Okinawa Trough, favoring large fluvial discharge or even direct input of detrital sediments, which resulted about four times more flux of clay-sized sediments supply to the study area as during the relatively high sea-level stage (∼14–0 ka BP). The input of Kyushu-derived clay-sized sediments to the study site was mainly controlled by the Kuroshio Current and Tsushima Warm Current intensity, with increased input in phase with weakened Kuroshio Current/Tsushima Warm Current. Our study suggests that the Kuroshio Current was very likely flowed into the Okinawa Trough and thus influenced the fine-grained sediment transport in the area throughout the last glacial and deglacial. During ∼34–11 ka BP, the Kyushu clay-sized sediment input was mainly controlled by the Kuroshio Current. Since ∼11 ka BP, the occurrence of Tsushima Warm Current became important in influencing the Kyushu fine-grained sediment input to the northern Okinawa Trough

Aspergillus Myosin-V Supports Polarized Growth in the Absence of Microtubule-Based Transport

In the filamentous fungus Aspergillus nidulans, both microtubules and actin filaments are important for polarized growth at the hyphal tip. Less clear is how different microtubule-based and actin-based motors work together to support this growth. Here we examined the role of myosin-V (MYOV) in hyphal growth. MYOV-depleted cells form elongated hyphae, but the rate of hyphal elongation is significantly reduced. In addition, although wild type cells without microtubules still undergo polarized growth, microtubule disassembly abolishes polarized growth in MYOV-depleted cells. Thus, MYOV is essential for polarized growth in the absence of microtubules. Moreover, while a triple kinesin null mutant lacking kinesin-1 (KINA) and two kinesin-3s (UNCA and UNCB) undergoes hyphal elongation and forms a colony, depleting MYOV in this triple mutant results in lethality due to a severe defect in polarized growth. These results argue that MYOV, through its ability to transport secretory cargo, can support a significant amount of polarized hyphal tip growth in the absence of any microtubule-based transport. Finally, our genetic analyses also indicate that KINA (kinesin-1) rather than UNCA (kinesin-3) is the major kinesin motor that supports polarized growth in the absence of MYOV