4,538 research outputs found

    Self-Convinced Prompting: Few-Shot Question Answering with Repeated Introspection

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    While large language models (LLMs) such as ChatGPT and PaLM have demonstrated remarkable performance in various language understanding and generation tasks, their capabilities in complex reasoning and intricate knowledge utilization still fall short of human-level proficiency. Recent studies have established the effectiveness of prompts in steering LLMs towards generating desired outputs. Building on these insights, we introduce a novel framework that harnesses the potential of large-scale pre-trained language models, to iteratively enhance performance of the LLMs. Our framework incorporates three components: \textit{Normal CoT}, a \textit{Convincer}, and an \textit{Answerer}. It processes the output of a typical few-shot chain-of-thought prompt, assesses the correctness of the response, scrutinizes the answer, refines the reasoning, and ultimately produces a new solution. Experimental results on the 7 datasets of miscellaneous problems validate the efficacy of the Self-Convince framework, achieving substantial improvements compared to the baselines. This study contributes to the burgeoning body of research focused on integrating pre-trained language models with tailored prompts and iterative refinement processes to augment their performance in complex tasks

    Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells

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    The human papillomavirus (HPV) plays a central role in cervical carcinogenesis and its oncogene E7 is essential in this process. We showed here that E7 abrogated the G1 cell cycle checkpoint under hypoxia and analyzed key cell cycle related proteins for their potential role in this process. To further explore the mechanism by which E7 bypasses hypoxia-induced G1 arrest, we applied a proteomic approach and used mass spectrometry to search for proteins that are differentially expressed in E7 expressing cells under hypoxia. Among differentially expressed proteins identified, Cdc6 is a DNA replication initiation factor and exhibits oncogenic activities when overexpressed. We have recently demonstrated that Cdc6 was required for E7-induced re-replication. Significantly, here we showed that Cdc6 played a role in E7-mediated G1 checkpoint abrogation under hypoxic condition, and the function could possibly be independent from its role in DNA replication initiation. This study uncovered a new function of Cdc6 in regulating cell cycle progression and has important implications in HPV-associated cancers

    How should this patient with repeated aspiration pneumonia be managed and treated?—a proposal of the Percutaneous ENdoscopIc Gastrostomy and Tracheostomy (PENlIGhT) procedure

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    Cerebrovascular accident (CVA) is commonly seen among the elderly with a substantial proportion of patients suffering from long-term dysphagia and/or an inability to protect their airway. This potentially imposes on them an increased risk of malnutrition and aspiration pneumonia. In this article, we present a patient with malnutrition and dysphagia secondary to CVA. We propose a procedure for which we will name the Percutaneous ENdoscopIc Gastrostomy and Tracheostomy (PENlIGhT) procedure for placement of percutaneous endoscopic gastrostomy (PEG) and tracheostomy tube (TT) at the same time. The medical literature was systematically reviewed for both PEG and tracheostomy, aiming to provide the state-of-the-art evidence for clinical use of the PENlIGhT procedure. In clinical practice, the PENlIGhT procedure is indicated for patients who are expected to have prolonged swallowing disturbance and mechanical ventilation. Some prediction tools and scores can be helpful to identify such groups of patients. Patients with poor neurological outcomes who require prolonged maintenance of life are also good candidates for the PENlIGhT procedure

    Statistics of X-ray flares of Sagittarius A*: evidence for solar-like self-organized criticality phenomenon

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    X-ray flares have routinely been observed from the supermassive black hole, Sagittarius A^\star (Sgr A^\star), at our Galactic center. The nature of these flares remains largely unclear, despite of many theoretical models. In this paper, we study the statistical properties of the Sgr A^\star X-ray flares, by fitting the count rate (CR) distribution and the structure function (SF) of the light curve with a Markov Chain Monte Carlo (MCMC) method. With the 3 million second \textit{Chandra} observations accumulated in the Sgr A^\star X-ray Visionary Project, we construct the theoretical light curves through Monte Carlo simulations. We find that the 282-8 keV X-ray light curve can be decomposed into a quiescent component with a constant count rate of 6×103 \sim6\times10^{-3}~count s1^{-1} and a flare component with a power-law fluence distribution dN/dEEαEdN/dE\propto E^{-\alpha_{\rm E}} with αE=1.65±0.17\alpha_{\rm E}=1.65\pm0.17. The duration-fluence correlation can also be modelled as a power-law TEαETT\propto E^{\alpha_{\rm ET}} with αET<0.55\alpha_{\rm ET} < 0.55 (95%95\% confidence). These statistical properties are consistent with the theoretical prediction of the self-organized criticality (SOC) system with the spatial dimension S=3S = 3. We suggest that the X-ray flares represent plasmoid ejections driven by magnetic reconnection (similar to solar flares) in the accretion flow onto the black hole.Comment: to appear in Ap

    CIP2A facilitates the G1/S cell cycle transition via B-Myb in human papillomavirus 16 oncoprotein E6-expressing cells

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    Infection with high-risk human papillomaviruses (HR-HPVs, including HPV-16, HPV-18, HPV-31) plays a central aetiologic role in the development of cervical carcinoma. The transforming properties of HR-HPVs mainly reside in viral oncoproteins E6 and E7. E6 protein degrades the tumour suppressor p53 and abrogates cell cycle checkpoints. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is involved in the carcinogenesis of many human malignancies. Our previous data showed that CIP2A was overexpressed in cervical cancer. However, the regulation of CIP2A by HPV-16E6 remains to be elucidated. In this study, we demonstrated that HPV-16E6 significantly up-regulated CIP2A mRNA and protein expression in a p53-degradation-dependent manner. Knockdown of CIP2A by siRNA inhibited viability and DNA synthesis and caused G1 cell cycle arrest of 16E6-expressing cells. Knockdown of CIP2A resulted in a significant reduction in the expression of cyclin-dependent kinase 1 (Cdk1) and Cdk2. Although CIP2A has been reported to stabilize c-Myc by inhibiting PP2A-mediated dephosphorylation of c-Myc, we have presented evidence that the regulation of Cdk1 and Cdk2 by CIP2A is dependent on transcription factor B-Myb rather than c-Myc. Taken together, our study reveals the role of CIP2A in abrogating the G1 checkpoint in HPV-16E6-expressing cells and helps in understanding the molecular basis of HPV-induced oncogenesis

    Similarity-driven and Task-driven Models for Diversity of Opinion in Crowdsourcing Markets

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    The recent boom in crowdsourcing has opened up a new avenue for utilizing human intelligence in the realm of data analysis. This innovative approach provides a powerful means for connecting online workers to tasks that cannot effectively be done solely by machines or conducted by professional experts due to cost constraints. Within the field of social science, four elements are required to construct a sound crowd - Diversity of Opinion, Independence, Decentralization and Aggregation. However, while the other three components have already been investigated and implemented in existing crowdsourcing platforms, 'Diversity of Opinion' has not been functionally enabled yet. From a computational point of view, constructing a wise crowd necessitates quantitatively modeling and taking diversity into account. There are usually two paradigms in a crowdsourcing marketplace for worker selection: building a crowd to wait for tasks to come and selecting workers for a given task. We propose similarity-driven and task-driven models for both paradigms. Also, we develop efficient and effective algorithms for recruiting a limited number of workers with optimal diversity in both models. To validate our solutions, we conduct extensive experiments using both synthetic datasets and real data sets.Comment: 32 pages, 10 figure

    Role of WDHD1 in Human Papillomavirus-Mediated Oncogenesis Identified by Transcriptional profiling of E7-expressing cells

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    The E7 oncoprotein of the high-risk human papillomavirus (HPV) plays a major role in HPV-induced carcinogenesis. E7 abrogates the G(1) cell cycle checkpoint and induces genomic instability, but the mechanism is not fully understood. In this study, we performed RNA sequencing (RNA-seq) to characterize the transcriptional profile of keratinocytes expressing HPV 16 (HPV-16) E7. At the transcriptome level, 236 genes were differentially expressed between E7 and vector control cells. A subset of the differentially expressed genes, most of them novel to E7-expressing cells, was further confirmed by real-time PCR. Of interest, the activities of multiple transcription factors were altered in E7-expressing cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were investigated. The upregulated genes were enriched in cell cycle and DNA replication, as well as in the DNA metabolic process, transcription, DNA damage, DNA repair, and nucleotide metabolism. Specifically, we focused our studies on the gene encoding WDHD1 (WD repeat and high mobility group [HMG]-box DNA-binding protein), one of the genes that was upregulated in E7-expressing cells. WDHD1 is a component of the replisome that regulates DNA replication. Recent studies suggest that WDHD1 may also function as a DNA replication initiation factor as well as a G(1) checkpoint regulator. We found that in E7-expressing cells, the steady-state level of WDHD1 protein was increased along with the half-life. Moreover, downregulation of WDHD1 reduced E7-induced G(1) checkpoint abrogation and rereplication, demonstrating a novel function for WDHD1. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications. IMPORTANCE The high-risk HPV types induce cervical cancer and encode an E7 oncoprotein that plays a major role in HPV-induced carcinogenesis. However, the mechanism by which E7 induces carcinogenesis is not fully understood; specific anti-HPV agents are not available. In this study, we performed RNA-seq to characterize transcriptional profiling of keratinocytes expressing HPV-16 E7 and identified more than 200 genes that were differentially expressed between E7 and vector control cells. Through bioinformatics analysis, pathways altered in E7-expressing cells were identified. Significantly, the WDHD1 gene, one of the genes that is upregulated in E7-expressing cells, was found to play an important role in E7-induced G(1) checkpoint abrogation and rereplication. These studies shed light on mechanisms by which HPV induces genomic instability and have therapeutic implications
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