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Animal genomes are organized into topologically associated domains (TADs). TADs are thought to contribute to gene regulation by facilitating enhancer-promoter (E-P) contacts within a TAD and preventing these contacts across TAD borders. However, the absolute difference in contact frequency across TAD boundaries is usually less than 2-fold, even though disruptions of TAD borders can change gene expression by 10-fold. Existing models fail to explain this hypersensitive response. Here, we propose a futile cycle model of enhancer-mediated regulation that can exhibit hypersensitivity through bistability and hysteresis. Consistent with recent experiments, this regulation does not exhibit strong correlation between E-P contact and promoter activity, even though regulation occurs through contact. Through mathematical analysis and stochastic simulation, we show that this system can create an illusion of E-P biochemical specificity and explain the importance of weak TAD boundaries. It also offers a mechanism to reconcile apparently contradictory results from recent global TAD disruption with local TAD boundary deletion experiments. Together, these analyses advance our understanding of cis-regulatory contacts in controlling gene expression and suggest new experimental directions.

Financial LLMs hold promise for advancing financial tasks and domain-specific applications. However, they are limited by scarce corpora, weak multimodal capabilities, and narrow evaluations, making them less suited for real-world application. To address this, we introduce Open-FinLLMs, the first open-source multimodal financial LLMs designed to handle diverse tasks across text, tabular, time-series, and chart data, excelling in zero-shot, few-shot, and fine-tuning settings. The suite includes FinLLaMA, pre-trained on a comprehensive 52-billion-token corpus; FinLLaMA-Instruct, fine-tuned with 573K financial instructions; and FinLLaVA, enhanced with 1.43M multimodal tuning pairs for strong cross-modal reasoning. We comprehensively evaluate Open-FinLLMs across 14 financial tasks, 30 datasets, and 4 multimodal tasks in zero-shot, few-shot, and supervised fine-tuning settings, introducing two new multimodal evaluation datasets. Our results show that Open-FinLLMs outperforms afvanced financial and general LLMs such as GPT-4, across financial NLP, decision-making, and multi-modal tasks, highlighting their potential to tackle real-world challenges. To foster innovation and collaboration across academia and industry, we release all codes (https://anonymous.4open.science/r/PIXIU2-0D70/B1D7/LICENSE) and models under OSI-approved licenses.

Large language models (LLMs) have advanced financial applications, yet they often lack sufficient financial knowledge and struggle with tasks involving multi-modal inputs like tables and time series data. To address these limitations, we introduce Open-FinLLMs, a series of Financial LLMs. We begin with FinLLaMA, pre-trained on a 52 billion token financial corpus, incorporating text, tables, and time-series data to embed comprehensive financial knowledge. FinLLaMA is then instruction fine-tuned with 573K financial instructions, resulting in FinLLaMA-instruct, which enhances task performance. Finally, we present FinLLaVA, a multimodal LLM trained with 1.43M image-text instructions to handle complex financial data types. Extensive evaluations demonstrate FinLLaMA's superior performance over LLaMA3-8B, LLaMA3.1-8B, and BloombergGPT in both zero-shot and few-shot settings across 19 and 4 datasets, respectively. FinLLaMA-instruct outperforms GPT-4 and other Financial LLMs on 15 datasets. FinLLaVA excels in understanding tables and charts across 4 multimodal tasks. Additionally, FinLLaMA achieves impressive Sharpe Ratios in trading simulations, highlighting its robust financial application capabilities. We will continually maintain and improve our models and benchmarks to support ongoing innovation in academia and industry.