Daily Papers

Large language models (LLMs) trained on internet-scale corpora can exhibit systematic biases that increase the probability of unwanted behavior. In this study, we examined potential biases towards synthetic vs. biological technological solutions across four domains (materials, energy, manufacturing, and algorithms). A sample of 5 frontier and 5 open-weight models were measured using 50 curated Bioalignment prompts with a Kelly criterion-inspired evaluation framework. According to this metric, most models were not bioaligned in that they exhibit biases in favor of synthetic (non-biological) solutions. We next examined if fine-tuning could increase the preferences of two open-weight models, Llama 3.2-3B-Instruct and Qwen2.5-3B-Instruct, for biological-based approaches. A curated corpus of ~22M tokens from 6,636 PMC articles emphasizing biological problem-solving was used first to fine-tune Llama 3B with a mixed corpus of continued training and instruction-formatted. This was then extended to Qwen 3B using instruction-formatted only. We found that QLoRA fine-tuning significantly increased the scoring of biological solutions for both models without degrading general capabilities (Holm-Bonferroni-corrected p < 0.001 and p < 0.01, respectively). This suggests that even a small amount of fine-tuning can change how models weigh the relative value of biological and bioinspired vs. synthetic approaches. Although this work focused on small open-weight LLMs, it may be extensible to much larger models and could be used to develop models that favor bio-based approaches. We release the benchmark, corpus, code, and adapter weights.

Drug discovery typically consists of multiple steps, including identifying a target protein key to a disease's etiology, validating that interacting with this target could prevent symptoms or cure the disease, discovering a small molecule or biologic therapeutic to interact with it, and optimizing the candidate molecule through a complex landscape of required properties. Drug discovery related tasks often involve prediction and generation while considering multiple entities that potentially interact, which poses a challenge for typical AI models. For this purpose we present MAMMAL - Molecular Aligned Multi-Modal Architecture and Language - a method that we applied to create a versatile multi-task foundation model ibm/biomed.omics.bl.sm.ma-ted-458m that learns from large-scale biological datasets (2 billion samples) across diverse modalities, including proteins, small molecules, and genes. We introduce a prompt syntax that supports a wide range of classification, regression, and generation tasks. It allows combining different modalities and entity types as inputs and/or outputs. Our model handles combinations of tokens and scalars and enables the generation of small molecules and proteins, property prediction, and transcriptomic lab test predictions. We evaluated the model on 11 diverse downstream tasks spanning different steps within a typical drug discovery pipeline, where it reaches new SOTA in 9 tasks and is comparable to SOTA in 2 tasks. This performance is achieved while using a unified architecture serving all tasks, in contrast to the original SOTA performance achieved using tailored architectures. The model code and pretrained weights are publicly available at https://github.com/BiomedSciAI/biomed-multi-alignment and https://huggingface.co/ibm/biomed.omics.bl.sm.ma-ted-458m.

Understanding and designing biomolecules, such as proteins and small molecules, is central to advancing drug discovery, synthetic biology, and enzyme engineering. Recent breakthroughs in Artificial Intelligence (AI) have revolutionized biomolecular research, achieving remarkable accuracy in biomolecular prediction and design. However, a critical gap remains between AI's computational power and researchers' intuition, using natural language to align molecular complexity with human intentions. Large Language Models (LLMs) have shown potential to interpret human intentions, yet their application to biomolecular research remains nascent due to challenges including specialized knowledge requirements, multimodal data integration, and semantic alignment between natural language and biomolecules. To address these limitations, we present InstructBioMol, a novel LLM designed to bridge natural language and biomolecules through a comprehensive any-to-any alignment of natural language, molecules, and proteins. This model can integrate multimodal biomolecules as input, and enable researchers to articulate design goals in natural language, providing biomolecular outputs that meet precise biological needs. Experimental results demonstrate InstructBioMol can understand and design biomolecules following human instructions. Notably, it can generate drug molecules with a 10% improvement in binding affinity and design enzymes that achieve an ESP Score of 70.4, making it the only method to surpass the enzyme-substrate interaction threshold of 60.0 recommended by the ESP developer. This highlights its potential to transform real-world biomolecular research.

Recent advancements in vision-language models (VLMs), such as CLIP, have demonstrated substantial success in self-supervised representation learning for vision tasks. However, effectively adapting VLMs to downstream applications remains challenging, as their accuracy often depends on time-intensive and expertise-demanding prompt engineering, while full model fine-tuning is costly. This is particularly true for biomedical images, which, unlike natural images, typically suffer from limited annotated datasets, unintuitive image contrasts, and nuanced visual features. Recent prompt learning techniques, such as Context Optimization (CoOp) intend to tackle these issues, but still fall short in generalizability. Meanwhile, explorations in prompt learning for biomedical image analysis are still highly limited. In this work, we propose BiomedCoOp, a novel prompt learning framework that enables efficient adaptation of BiomedCLIP for accurate and highly generalizable few-shot biomedical image classification. Our approach achieves effective prompt context learning by leveraging semantic consistency with average prompt ensembles from Large Language Models (LLMs) and knowledge distillation with a statistics-based prompt selection strategy. We conducted comprehensive validation of our proposed framework on 11 medical datasets across 9 modalities and 10 organs against existing state-of-the-art methods, demonstrating significant improvements in both accuracy and generalizability. The code is publicly available at https://github.com/HealthX-Lab/BiomedCoOp.

Precise alignment in Text-to-Image (T2I) systems is crucial to ensure that generated visuals not only accurately encapsulate user intents but also conform to stringent ethical and aesthetic benchmarks. Incidents like the Google Gemini fiasco, where misaligned outputs triggered significant public backlash, underscore the critical need for robust alignment mechanisms. In contrast, Large Language Models (LLMs) have achieved notable success in alignment. Building on these advancements, researchers are eager to apply similar alignment techniques, such as Direct Preference Optimization (DPO), to T2I systems to enhance image generation fidelity and reliability. We present YinYangAlign, an advanced benchmarking framework that systematically quantifies the alignment fidelity of T2I systems, addressing six fundamental and inherently contradictory design objectives. Each pair represents fundamental tensions in image generation, such as balancing adherence to user prompts with creative modifications or maintaining diversity alongside visual coherence. YinYangAlign includes detailed axiom datasets featuring human prompts, aligned (chosen) responses, misaligned (rejected) AI-generated outputs, and explanations of the underlying contradictions.

Recent work discovered Emergent Misalignment (EM): fine-tuning large language models on narrowly harmful datasets can lead them to become broadly misaligned. A survey of experts prior to publication revealed this was highly unexpected, demonstrating critical gaps in our understanding of model alignment. In this work, we both advance understanding and provide tools for future research. Using new narrowly misaligned datasets, we create a set of improved model organisms that achieve 99% coherence (vs. 67% prior), work with smaller 0.5B parameter models (vs. 32B), and that induce misalignment using a single rank-1 LoRA adapter. We demonstrate that EM occurs robustly across diverse model sizes, three model families, and numerous training protocols including full supervised fine-tuning. Leveraging these cleaner model organisms, we isolate a mechanistic phase transition and demonstrate that it corresponds to a robust behavioural phase transition in all studied organisms. Aligning large language models is critical for frontier AI safety, yet EM exposes how far we are from achieving this robustly. By distilling clean model organisms that isolate a minimal alignment-compromising change, and where this is learnt, we establish a foundation for future research into understanding and mitigating alignment risks in LLMs.

Zero-shot medical detection can further improve detection performance without relying on annotated medical images even upon the fine-tuned model, showing great clinical value. Recent studies leverage grounded vision-language models (GLIP) to achieve this by using detailed disease descriptions as prompts for the target disease name during the inference phase. However, these methods typically treat prompts as equivalent context to the target name, making it difficult to assign specific disease knowledge based on visual information, leading to a coarse alignment between images and target descriptions. In this paper, we propose StructuralGLIP, which introduces an auxiliary branch to encode prompts into a latent knowledge bank layer-by-layer, enabling more context-aware and fine-grained alignment. Specifically, in each layer, we select highly similar features from both the image representation and the knowledge bank, forming structural representations that capture nuanced relationships between image patches and target descriptions. These features are then fused across modalities to further enhance detection performance. Extensive experiments demonstrate that StructuralGLIP achieves a +4.1\% AP improvement over prior state-of-the-art methods across seven zero-shot medical detection benchmarks, and consistently improves fine-tuned models by +3.2\% AP on endoscopy image datasets.

Understanding the 3D structures of protein multimers is crucial, as they play a vital role in regulating various cellular processes. It has been empirically confirmed that the multimer structure prediction~(MSP) can be well handled in a step-wise assembly fashion using provided dimer structures and predicted protein-protein interactions~(PPIs). However, due to the biological gap in the formation of dimers and larger multimers, directly applying PPI prediction techniques can often cause a poor generalization to the MSP task. To address this challenge, we aim to extend the PPI knowledge to multimers of different scales~(i.e., chain numbers). Specifically, we propose \textsc{PromptMSP}, a pre-training and Prompt tuning framework for Multimer Structure Prediction. First, we tailor the source and target tasks for effective PPI knowledge learning and efficient inference, respectively. We design PPI-inspired prompt learning to narrow the gaps of two task formats and generalize the PPI knowledge to multimers of different scales. We provide a meta-learning strategy to learn a reliable initialization of the prompt model, enabling our prompting framework to effectively adapt to limited data for large-scale multimers. Empirically, we achieve both significant accuracy (RMSD and TM-Score) and efficiency improvements compared to advanced MSP models. The code, data and checkpoints are released at https://github.com/zqgao22/PromptMSP.

Prompt learning is effective for fine-tuning foundation models to improve their generalization across a variety of downstream tasks. However, the prompts that are independently optimized along a single modality path, may sacrifice the vision-language alignment of pre-trained models in return for improved performance on specific tasks and classes, leading to poorer generalization. In this paper, we first demonstrate that prompt tuning along only one single branch of CLIP (e.g., language or vision) is the reason why the misalignment occurs. Without proper regularization across the learnable parameters in different modalities, prompt learning violates the original pre-training constraints inherent in the two-tower architecture. To address such misalignment, we first propose feature shift, which is defined as the variation of embeddings after introducing the learned prompts, to serve as an explanatory tool. We dive into its relation with generalizability and thereafter propose RESTORE, a multi-modal prompt learning method that exerts explicit constraints on cross-modal consistency. To be more specific, to prevent feature misalignment, a feature shift consistency is introduced to synchronize inter-modal feature shifts by measuring and regularizing the magnitude of discrepancy during prompt tuning. In addition, we propose a "surgery" block to avoid short-cut hacking, where cross-modal misalignment can still be severe if the feature shift of each modality varies drastically at the same rate. It is implemented as feed-forward adapters upon both modalities to alleviate the misalignment problem. Extensive experiments on 15 datasets demonstrate that our method outperforms the state-of-the-art prompt tuning methods without compromising feature alignment.

Foundation models (FMs) have exhibited remarkable performance across a wide range of downstream tasks in many domains. Nevertheless, general-purpose FMs often face challenges when confronted with domain-specific problems, due to their limited access to the proprietary training data in a particular domain. In biomedicine, there are various biological modalities, such as molecules, proteins, and cells, which are encoded by the language of life and exhibit significant modality gaps with human natural language. In this paper, we introduce BioMedGPT, an open multimodal generative pre-trained transformer (GPT) for biomedicine, to bridge the gap between the language of life and human natural language. BioMedGPT allows users to easily ``communicate'' with diverse biological modalities through free text, which is the first of its kind. BioMedGPT aligns different biological modalities with natural language via a large generative language model, namely, BioMedGPT-LM. We publish BioMedGPT-10B, which unifies the feature spaces of molecules, proteins, and natural language via encoding and alignment. Through fine-tuning, BioMedGPT-10B outperforms or is on par with human and significantly larger general-purpose foundation models on the biomedical QA task. It also demonstrates promising performance in the molecule QA and protein QA tasks, which could greatly accelerate the discovery of new drugs and therapeutic targets. In addition, BioMedGPT-LM-7B is the first large generative language model based on Llama2 in the biomedical domain, therefore is commercial friendly. Both BioMedGPT-10B and BioMedGPT-LM-7B are open-sourced to the research community. In addition, we publish the datasets that are meticulously curated for the alignment of multi-modalities, i.e., PubChemQA and UniProtQA. All the models, codes, and datasets are available at https://github.com/PharMolix/OpenBioMed.

Biomedical visual question answering (VQA) has been widely studied and has demonstrated significant application value and potential in fields such as assistive medical diagnosis. Despite their success, current biomedical VQA models perform multimodal information interaction only at the model level within large language models (LLMs), leading to suboptimal multimodal semantic alignment when dealing with complex tasks. To address this issue, we propose BioD2C: a novel Dual-level Semantic Consistency Constraint Framework for Biomedical VQA, which achieves dual-level semantic interaction alignment at both the model and feature levels, enabling the model to adaptively learn visual features based on the question. Specifically, we firstly integrate textual features into visual features via an image-text fusion mechanism as feature-level semantic interaction, obtaining visual features conditioned on the given text; and then introduce a text-queue-based cross-modal soft semantic loss function to further align the image semantics with the question semantics. Specifically, in this work, we establish a new dataset, BioVGQ, to address inherent biases in prior datasets by filtering manually-altered images and aligning question-answer pairs with multimodal context, and train our model on this dataset. Extensive experimental results demonstrate that BioD2C achieves state-of-the-art (SOTA) performance across multiple downstream datasets, showcasing its robustness, generalizability, and potential to advance biomedical VQA research.

Biological protocols are fundamental to reproducible and safe life science research. While LLMs excel on general tasks, their systematic evaluation on these highly specialized, accuracy-critical, and inherently procedural texts remains limited. In this work, we present BioProBench, the first large-scale, integrated multi-task benchmark for biological protocol understanding and reasoning. While limited benchmarks have touched upon specific aspects like protocol QA, BioProBench provides a comprehensive suite of five core tasks: Protocol Question Answering, Step Ordering, Error Correction, Protocol Generation, and Protocol Reasoning, enabling a holistic evaluation of LLMs on procedural biological texts. Built upon 27K original protocols, it yields nearly 556K high-quality structured instances. We evaluate 12 mainstream open/closed-source LLMs on BioProBench. Experimental results reveal that while top models preform well on surface understanding tasks, struggle significantly with deep reasoning and structured generation tasks like ordering and generation. Furthermore, model comparisons reveal diverse performance: certain open-source models approach closed-source levels on some tasks, yet bio-specific small models lag behind general LLMs, indicating limitations on complex procedural content. Overall, our findings underscore that procedural reasoning within biological protocols represents a significant challenge for current LLMs. BioProBench serves as a standardized framework to diagnose these specific limitations and guide the development of AI systems better equipped for safely automating complex scientific procedures. The code and data are available at: https://github.com/YuyangSunshine/bioprotocolbench and https://huggingface.co/datasets/GreatCaptainNemo/BioProBench.

Recent advances in context optimization (CoOp) guided by large language model (LLM)-distilled medical semantic priors offer a scalable alternative to manual prompt engineering and full fine-tuning for adapting biomedical CLIP-based vision-language models (VLMs). However, prompt learning in this context is challenged by semantic misalignment between LLMs and CLIP variants due to divergent training corpora and model architectures; it further lacks scalability across continuously evolving families of foundation models. More critically, pairwise multimodal alignment via conventional Euclidean-space optimization lacks the capacity to model unified representations or apply localized geometric constraints, which tends to amplify modality gaps in complex biomedical imaging and destabilize few-shot adaptation. In this work, we propose vMFCoOp, a framework that inversely estimates von Mises-Fisher (vMF) distributions on a shared Hyperspherical Manifold, aligning semantic biases between arbitrary LLMs and CLIP backbones via Unified Semantic Anchors to achieve robust biomedical prompting and superior few-shot classification. Grounded in three complementary constraints, vMFCoOp demonstrates consistent improvements across 14 medical datasets, 12 medical imaging modalities, and 13 anatomical regions, outperforming state-of-the-art methods in accuracy, generalization, and clinical applicability. This work aims to continuously expand to encompass more downstream applications, and the corresponding resources are intended to be shared through https://github.com/VinyehShaw/UniEqui.

Achieving precise alignment between user intent and generated visuals remains a central challenge in text-to-visual generation, as a single attempt often fails to produce the desired output. To handle this, prior approaches mainly scale the visual generation process (e.g., increasing sampling steps or seeds), but this quickly leads to a quality plateau. This limitation arises because the prompt, crucial for guiding generation, is kept fixed. To address this, we propose Prompt Redesign for Inference-time Scaling, coined PRIS, a framework that adaptively revises the prompt during inference in response to the scaled visual generations. The core idea of PRIS is to review the generated visuals, identify recurring failure patterns across visuals, and redesign the prompt accordingly before regenerating the visuals with the revised prompt. To provide precise alignment feedback for prompt revision, we introduce a new verifier, element-level factual correction, which evaluates the alignment between prompt attributes and generated visuals at a fine-grained level, achieving more accurate and interpretable assessments than holistic measures. Extensive experiments on both text-to-image and text-to-video benchmarks demonstrate the effectiveness of our approach, including a 15% gain on VBench 2.0. These results highlight that jointly scaling prompts and visuals is key to fully leveraging scaling laws at inference-time. Visualizations are available at the website: https://subin-kim-cv.github.io/PRIS.

This study is dedicated to exploring the application of prompt learning methods to advance Named Entity Recognition (NER) within the medical domain. In recent years, the emergence of large-scale models has driven significant progress in NER tasks, particularly with the introduction of the BioBERT language model, which has greatly enhanced NER capabilities in medical texts. Our research introduces the Prompt-bioMRC model, which integrates both hard template and soft prompt designs aimed at refining the precision and efficiency of medical entity recognition. Through extensive experimentation across diverse medical datasets, our findings consistently demonstrate that our approach surpasses traditional models. This enhancement not only validates the efficacy of our methodology but also highlights its potential to provide reliable technological support for applications like intelligent diagnosis systems. By leveraging advanced NER techniques, this study contributes to advancing automated medical data processing, facilitating more accurate medical information extraction, and supporting efficient healthcare decision-making processes.

While reinforcement learning for large language model alignment has progressed rapidly in recent years, transferring these paradigms to high-stakes medical question answering reveals a fundamental paradigm mismatch. Reinforcement Learning from Human Feedback relies on preference annotations that are prohibitively expensive and often fail to reflect the absolute correctness of medical facts. Reinforcement Learning from Verifiable Rewards lacks effective automatic verifiers and struggles to handle complex clinical contexts. Meanwhile, medical alignment requires the simultaneous optimization of correctness, safety, and compliance, yet multi-objective heterogeneous reward signals are prone to scale mismatch and optimization conflicts.To address these challenges, we propose a robust medical alignment paradigm. We first construct a holistic multi-dimensional medical alignment matrix that decomposes alignment objectives into four categories: fundamental capabilities, expert knowledge, online feedback, and format specifications. Within each category, we establish a closed loop of where observable metrics inform attributable diagnosis, which in turn drives optimizable rewards, thereby providing fine-grained, high-resolution supervision signals for subsequent iterative optimization. To resolve gradient domination and optimization instability problem caused by heterogeneous signals, we further propose a unified optimization mechanism. This mechanism employs Reference-Frozen Normalization to align reward scales and implements a Tri-Factor Adaptive Dynamic Weighting strategy to achieve collaborative optimization that is weakness-oriented, risk-prioritized, and redundancy-reducing. Experimental results demonstrate the effectiveness of our proposed paradigm in real-world medical scenario evaluations, establishing a new paradigm for complex alignment in vertical domains.

We develop Polaris, the first safety-focused LLM constellation for real-time patient-AI healthcare conversations. Unlike prior LLM works in healthcare focusing on tasks like question answering, our work specifically focuses on long multi-turn voice conversations. Our one-trillion parameter constellation system is composed of several multibillion parameter LLMs as co-operative agents: a stateful primary agent that focuses on driving an engaging conversation and several specialist support agents focused on healthcare tasks performed by nurses to increase safety and reduce hallucinations. We develop a sophisticated training protocol for iterative co-training of the agents that optimize for diverse objectives. We train our models on proprietary data, clinical care plans, healthcare regulatory documents, medical manuals, and other medical reasoning documents. We align our models to speak like medical professionals, using organic healthcare conversations and simulated ones between patient actors and experienced nurses. This allows our system to express unique capabilities such as rapport building, trust building, empathy and bedside manner. Finally, we present the first comprehensive clinician evaluation of an LLM system for healthcare. We recruited over 1100 U.S. licensed nurses and over 130 U.S. licensed physicians to perform end-to-end conversational evaluations of our system by posing as patients and rating the system on several measures. We demonstrate Polaris performs on par with human nurses on aggregate across dimensions such as medical safety, clinical readiness, conversational quality, and bedside manner. Additionally, we conduct a challenging task-based evaluation of the individual specialist support agents, where we demonstrate our LLM agents significantly outperform a much larger general-purpose LLM (GPT-4) as well as from its own medium-size class (LLaMA-2 70B).

Text-to-image generation has advanced rapidly, yet aligning complex textual prompts with generated visuals remains challenging, especially with intricate object relationships and fine-grained details. This paper introduces Fast Prompt Alignment (FPA), a prompt optimization framework that leverages a one-pass approach, enhancing text-to-image alignment efficiency without the iterative overhead typical of current methods like OPT2I. FPA uses large language models (LLMs) for single-iteration prompt paraphrasing, followed by fine-tuning or in-context learning with optimized prompts to enable real-time inference, reducing computational demands while preserving alignment fidelity. Extensive evaluations on the COCO Captions and PartiPrompts datasets demonstrate that FPA achieves competitive text-image alignment scores at a fraction of the processing time, as validated through both automated metrics (TIFA, VQA) and human evaluation. A human study with expert annotators further reveals a strong correlation between human alignment judgments and automated scores, underscoring the robustness of FPA's improvements. The proposed method showcases a scalable, efficient alternative to iterative prompt optimization, enabling broader applicability in real-time, high-demand settings. The codebase is provided to facilitate further research: https://github.com/tiktok/fast_prompt_alignment

The emergence of text-to-image synthesis (TIS) models has significantly influenced digital image creation by producing high-quality visuals from written descriptions. Yet these models heavily rely on the quality and specificity of textual prompts, posing a challenge for novice users who may not be familiar with TIS-model-preferred prompt writing. Existing solutions relieve this via automatic model-preferred prompt generation from user queries. However, this single-turn manner suffers from limited user-centricity in terms of result interpretability and user interactivity. To address these issues, we propose DialPrompt, a multi-turn dialogue-based TIS prompt generation model that emphasises user-centricity. DialPrompt is designed to follow a multi-turn guidance workflow, where in each round of dialogue the model queries user with their preferences on possible optimization dimensions before generating the final TIS prompt. To achieve this, we mined 15 essential dimensions for high-quality prompts from advanced users and curated a multi-turn dataset. Through training on this dataset, DialPrompt can improve interpretability by allowing users to understand the correlation between specific phrases and image attributes. Additionally, it enables greater user control and engagement in the prompt generation process, leading to more personalized and visually satisfying outputs. Experiments indicate that DialPrompt achieves a competitive result in the quality of synthesized images, outperforming existing prompt engineering approaches by 5.7%. Furthermore, in our user evaluation, DialPrompt outperforms existing approaches by 46.5% in user-centricity score and is rated 7.9/10 by 19 human reviewers.

Large language models (LLMs) have shown success in generating high-quality responses. In order to achieve better alignment with LLMs with human preference, various works are proposed based on specific optimization process, which, however, is not suitable to Black-Box LLMs like GPT-4, due to inaccessible parameters. In Black-Box LLMs case, their performance is highly dependent on the quality of the provided prompts. Existing methods to enhance response quality often involve a prompt refinement model, yet these approaches potentially suffer from semantic inconsistencies between the refined and original prompts, and typically overlook the relationship between them. To address these challenges, we introduce a self-instructed in-context learning framework that empowers LLMs to deliver more effective responses by generating reliable derived prompts to construct informative contextual environments. Our approach incorporates a self-instructed reinforcement learning mechanism, enabling direct interaction with the response model during derived prompt generation for better alignment. We then formulate querying as an in-context learning task, using responses from LLMs combined with the derived prompts to establish a contextual demonstration for the original prompt. This strategy ensures alignment with the original query, reduces discrepancies from refined prompts, and maximizes the LLMs' in-context learning capability. Extensive experiments demonstrate that the proposed method not only generates more reliable derived prompts but also significantly enhances LLMs' ability to deliver more effective responses, including Black-Box models such as GPT-4.

With the advent of artificial intelligence (AI), many researchers are attempting to extract structured information from document-level biomedical literature by fine-tuning large language models (LLMs). However, they face significant challenges such as the need for expensive hardware, like high-performance GPUs and the high labor costs associated with annotating training datasets, especially in biomedical realm. Recent research on LLMs, such as GPT-4 and Llama3, has shown promising performance in zero-shot settings, inspiring us to explore a novel approach to achieve the same results from unannotated full documents using general LLMs with lower hardware and labor costs. Our approach combines two major stages: named entity recognition (NER) and relation extraction (RE). NER identifies chemical, disease and gene entities from the document with synonym and hypernym extraction using an LLM with a crafted prompt. RE extracts relations between entities based on predefined relation schemas and prompts. To enhance the effectiveness of prompt, we propose a five-part template structure and a scenario-based prompt design principles, along with evaluation method to systematically assess the prompts. Finally, we evaluated our approach against fine-tuning and pre-trained models on two biomedical datasets: ChemDisGene and CDR. The experimental results indicate that our proposed method can achieve comparable accuracy levels to fine-tuning and pre-trained models but with reduced human and hardware expenses.

Biomolecular interactions underpin almost all biological processes, and their rational design is central to programming new biological functions. Generative AI models have emerged as powerful tools for molecular design, yet most remain specialized for individual molecular types and lack fine-grained control over interaction details. Here we present ODesign, an all-atom generative world model for all-to-all biomolecular interaction design. ODesign allows scientists to specify epitopes on arbitrary targets and generate diverse classes of binding partners with fine-grained control. Across entity-, token-, and atom-level benchmarks in the protein modality, ODesign demonstrates superior controllability and performance to modality-specific baselines. Extending beyond proteins, it generalizes to nucleic acid and small-molecule design, enabling interaction types such as protein-binding RNA/DNA and RNA/DNA-binding ligands that were previously inaccessible. By unifying multimodal biomolecular interactions within a single generative framework, ODesign moves toward a general-purpose molecular world model capable of programmable design. ODesign is available at https://odesign.lglab.ac.cn ,

Aligning large language models to human preferences is inherently multidimensional, yet most pipelines collapse heterogeneous signals into a single optimizeable objective. We seek to answer what it would take to simultaneously align a model across various domains spanning those with: verifiable rewards (mathematical accuracy), non-verifiable subjective preferences (human values), and complex interactive scenarios (multi-turn AI tutoring dialogues). Such multi-objective reinforcement learning setups are often plagued by the individual objectives being at odds with each other, resulting in inefficient training and little user control during inference. We propose a unified framework that: (i) standardizes {process reward model} (PRM) training across both verifiable and non-verifiable settings to better supervise models' chain-of-thought reasoning; (ii) performs {multi-objective alignment} by training the LLM with our Multi-Action-Head DPO (MAH-DPO) and a vectorized reward where the dimensions of the vector correspond to the various objectives instead of a single scalar; and (iii) demonstrates how such a system provides fine-grained inference-time user control. Experiments across math reasoning, value alignment, and multi-turn dialogue show that our framework improves performance across multiple objectives simultaneously, while minimizing cross-objective trade-offs and enabling flexible inference time user control. The code can be found at https://github.com/pearls-lab/multiobj-align.

While text-to-image (T2I) generative models have become ubiquitous, they do not necessarily generate images that align with a given prompt. While previous work has evaluated T2I alignment by proposing metrics, benchmarks, and templates for collecting human judgements, the quality of these components is not systematically measured. Human-rated prompt sets are generally small and the reliability of the ratings -- and thereby the prompt set used to compare models -- is not evaluated. We address this gap by performing an extensive study evaluating auto-eval metrics and human templates. We provide three main contributions: (1) We introduce a comprehensive skills-based benchmark that can discriminate models across different human templates. This skills-based benchmark categorises prompts into sub-skills, allowing a practitioner to pinpoint not only which skills are challenging, but at what level of complexity a skill becomes challenging. (2) We gather human ratings across four templates and four T2I models for a total of >100K annotations. This allows us to understand where differences arise due to inherent ambiguity in the prompt and where they arise due to differences in metric and model quality. (3) Finally, we introduce a new QA-based auto-eval metric that is better correlated with human ratings than existing metrics for our new dataset, across different human templates, and on TIFA160.

The alignment of large language models (LLMs) with human values is critical as these models become increasingly integrated into various societal and decision-making processes. Traditional methods, such as reinforcement learning from human feedback (RLHF), achieve alignment by fine-tuning model parameters, but these approaches are often computationally expensive and impractical when models are frozen or inaccessible for parameter modification. In contrast, prompt optimization is a viable alternative to RLHF for LLM alignment. While the existing literature has shown empirical promise of prompt optimization, its theoretical underpinning remains under-explored. We address this gap by formulating prompt optimization as an optimization problem and try to provide theoretical insights into the optimality of such a framework. To analyze the performance of the prompt optimization, we study theoretical suboptimality bounds and provide insights in terms of how prompt optimization depends upon the given prompter and target model. We also provide empirical validation through experiments on various datasets, demonstrating that prompt optimization can effectively align LLMs, even when parameter fine-tuning is not feasible.

We present a simple approach to make pre-trained Vision Transformers (ViTs) interpretable for fine-grained analysis, aiming to identify and localize the traits that distinguish visually similar categories, such as bird species. Pre-trained ViTs, such as DINO, have demonstrated remarkable capabilities in extracting localized, discriminative features. However, saliency maps like Grad-CAM often fail to identify these traits, producing blurred, coarse heatmaps that highlight entire objects instead. We propose a novel approach, Prompt Class Attention Map (Prompt-CAM), to address this limitation. Prompt-CAM learns class-specific prompts for a pre-trained ViT and uses the corresponding outputs for classification. To correctly classify an image, the true-class prompt must attend to unique image patches not present in other classes' images (i.e., traits). As a result, the true class's multi-head attention maps reveal traits and their locations. Implementation-wise, Prompt-CAM is almost a ``free lunch,'' requiring only a modification to the prediction head of Visual Prompt Tuning (VPT). This makes Prompt-CAM easy to train and apply, in stark contrast to other interpretable methods that require designing specific models and training processes. Extensive empirical studies on a dozen datasets from various domains (e.g., birds, fishes, insects, fungi, flowers, food, and cars) validate the superior interpretation capability of Prompt-CAM. The source code and demo are available at https://github.com/Imageomics/Prompt_CAM.

Recent advances in large language models have enabled their application to a range of healthcare tasks. However, aligning LLMs with the nuanced demands of medical ethics, especially under complex real world scenarios, remains underexplored. In this work, we present MedES, a dynamic, scenario-centric benchmark specifically constructed from 260 authoritative Chinese medical, ethical, and legal sources to reflect the challenges in clinical decision-making. To facilitate model alignment, we introduce a guardian-in-the-loop framework that leverages a dedicated automated evaluator (trained on expert-labeled data and achieving over 97% accuracy within our domain) to generate targeted prompts and provide structured ethical feedback. Using this pipeline, we align a 7B-parameter LLM through supervised fine-tuning and domain-specific preference optimization. Experimental results, conducted entirely within the Chinese medical ethics context, demonstrate that our aligned model outperforms notably larger baselines on core ethical tasks, with observed improvements in both quality and composite evaluation metrics. Our work offers a practical and adaptable framework for aligning LLMs with medical ethics in the Chinese healthcare domain, and suggests that similar alignment pipelines may be instantiated in other legal and cultural environments through modular replacement of the underlying normative corpus.

Generalist foundation models such as GPT-4 have displayed surprising capabilities in a wide variety of domains and tasks. Yet, there is a prevalent assumption that they cannot match specialist capabilities of fine-tuned models. For example, most explorations to date on medical competency benchmarks have leveraged domain-specific training, as exemplified by efforts on BioGPT and Med-PaLM. We build on a prior study of GPT-4's capabilities on medical challenge benchmarks in the absence of special training. Rather than using simple prompting to highlight the model's out-of-the-box capabilities, we perform a systematic exploration of prompt engineering. We find that prompting innovation can unlock deeper specialist capabilities and show that GPT-4 easily tops prior leading results for medical benchmarks. The prompting methods we explore are general purpose, and make no specific use of domain expertise, removing the need for expert-curated content. Our experimental design carefully controls for overfitting during the prompt engineering process. We introduce Medprompt, based on a composition of several prompting strategies. With Medprompt, GPT-4 achieves state-of-the-art results on all nine of the benchmark datasets in the MultiMedQA suite. The method outperforms leading specialist models such as Med-PaLM 2 by a significant margin with an order of magnitude fewer calls to the model. Steering GPT-4 with Medprompt achieves a 27% reduction in error rate on the MedQA dataset over the best methods to date achieved with specialist models and surpasses a score of 90% for the first time. Beyond medical problems, we show the power of Medprompt to generalize to other domains and provide evidence for the broad applicability of the approach via studies of the strategy on exams in electrical engineering, machine learning, philosophy, accounting, law, nursing, and clinical psychology.

Large language models (LLMs) have demonstrated impressive capabilities in natural language understanding and generation, but the quality bar for medical and clinical applications is high. Today, attempts to assess models' clinical knowledge typically rely on automated evaluations on limited benchmarks. There is no standard to evaluate model predictions and reasoning across a breadth of tasks. To address this, we present MultiMedQA, a benchmark combining six existing open question answering datasets spanning professional medical exams, research, and consumer queries; and HealthSearchQA, a new free-response dataset of medical questions searched online. We propose a framework for human evaluation of model answers along multiple axes including factuality, precision, possible harm, and bias. In addition, we evaluate PaLM (a 540-billion parameter LLM) and its instruction-tuned variant, Flan-PaLM, on MultiMedQA. Using a combination of prompting strategies, Flan-PaLM achieves state-of-the-art accuracy on every MultiMedQA multiple-choice dataset (MedQA, MedMCQA, PubMedQA, MMLU clinical topics), including 67.6% accuracy on MedQA (US Medical License Exam questions), surpassing prior state-of-the-art by over 17%. However, human evaluation reveals key gaps in Flan-PaLM responses. To resolve this we introduce instruction prompt tuning, a parameter-efficient approach for aligning LLMs to new domains using a few exemplars. The resulting model, Med-PaLM, performs encouragingly, but remains inferior to clinicians. We show that comprehension, recall of knowledge, and medical reasoning improve with model scale and instruction prompt tuning, suggesting the potential utility of LLMs in medicine. Our human evaluations reveal important limitations of today's models, reinforcing the importance of both evaluation frameworks and method development in creating safe, helpful LLM models for clinical applications.

Biomedical text mining and question-answering are essential yet highly demanding tasks, particularly in the face of the exponential growth of biomedical literature. In this work, we present our participation in the 13th edition of the BioASQ challenge, which involves biomedical semantic question-answering for Task 13b and biomedical question-answering for developing topics for the Synergy task. We deploy a selection of open-source large language models (LLMs) as retrieval-augmented generators to answer biomedical questions. Various models are used to process the questions. A majority voting system combines their output to determine the final answer for Yes/No questions, while for list and factoid type questions, the union of their answers in used. We evaluated 13 state-of-the-art open source LLMs, exploring all possible model combinations to contribute to the final answer, resulting in tailored LLM pipelines for each question type. Our findings provide valuable insight into which combinations of LLMs consistently produce superior results for specific question types. In the four rounds of the 2025 BioASQ challenge, our system achieved notable results: in the Synergy task, we secured 1st place for ideal answers and 2nd place for exact answers in round 2, as well as two shared 1st places for exact answers in round 3 and 4.

This work investigates descriptive captions as an additional source of supervision for biological multimodal foundation models. Images and captions can be viewed as complementary samples from the latent morphospace of a species, each capturing certain biological traits. Incorporating captions during training encourages alignment with this shared latent structure, emphasizing potentially diagnostic characters while suppressing spurious correlations. The main challenge, however, lies in obtaining faithful, instance-specific captions at scale. This requirement has limited the utilization of natural language supervision in organismal biology compared with many other scientific domains. We complement this gap by generating synthetic captions with multimodal large language models (MLLMs), guided by Wikipedia-derived visual information and taxon-tailored format examples. These domain-specific contexts help reduce hallucination and yield accurate, instance-based descriptive captions. Using these captions, we train BIOCAP (i.e., BIOCLIP with Captions), a biological foundation model that captures rich semantics and achieves strong performance in species classification and text-image retrieval. These results demonstrate the value of descriptive captions beyond labels in bridging biological images with multimodal foundation models.

Predicting cancer treatment outcomes requires models that are both accurate and interpretable, particularly in the presence of heterogeneous clinical data. While large language models (LLMs) have shown strong performance in biomedical NLP, they often lack structured reasoning capabilities critical for high-stakes decision support. We present a unified, multi-task learning framework that aligns autoregressive LLMs with clinical reasoning for outcome prediction on the MSK-CHORD dataset. Our models are trained to jointly perform binary survival classification, continuous survival time regression, and natural language rationale generation. We evaluate three alignment strategies: (1) standard supervised fine-tuning (SFT), (2) SFT with Chain-of-Thought (CoT) prompting to elicit step-by-step reasoning, and (3) Group Relative Policy Optimization (GRPO), a reinforcement learning method that aligns model outputs to expert-derived reasoning trajectories. Experiments with LLaMa3-8B and Med42-8B backbones demonstrate that CoT prompting improves F1 by +6.0 and reduces MAE by 12%, while GRPO achieves state-of-the-art interpretability and predictive performance across BLEU, ROUGE, and BERTScore. We further show that existing biomedical LLMs often fail to produce valid reasoning traces due to architectural constraints. Our findings underscore the importance of reasoning-aware alignment in multi-task clinical modeling and set a new benchmark for interpretable, trustworthy LLMs in precision oncology.

We introduce Baichuan Alignment, a detailed analysis of the alignment techniques employed in the Baichuan series of models. This represents the industry's first comprehensive account of alignment methodologies, offering valuable insights for advancing AI research. We investigate the critical components that enhance model performance during the alignment process, including optimization methods, data strategies, capability enhancements, and evaluation processes. The process spans three key stages: Prompt Augmentation System (PAS), Supervised Fine-Tuning (SFT), and Preference Alignment. The problems encountered, the solutions applied, and the improvements made are thoroughly recorded. Through comparisons across well-established benchmarks, we highlight the technological advancements enabled by Baichuan Alignment. Baichuan-Instruct is an internal model, while Qwen2-Nova-72B and Llama3-PBM-Nova-70B are instruct versions of the Qwen2-72B and Llama-3-70B base models, optimized through Baichuan Alignment. Baichuan-Instruct demonstrates significant improvements in core capabilities, with user experience gains ranging from 17% to 28%, and performs exceptionally well on specialized benchmarks. In open-source benchmark evaluations, both Qwen2-Nova-72B and Llama3-PBM-Nova-70B consistently outperform their respective official instruct versions across nearly all datasets. This report aims to clarify the key technologies behind the alignment process, fostering a deeper understanding within the community. Llama3-PBM-Nova-70B model is available at https://huggingface.co/PKU-Baichuan-MLSystemLab/Llama3-PBM-Nova-70B.

Aligning text-to-image generation with user intent remains challenging, for users who provide ambiguous inputs and struggle with model idiosyncrasies. We propose Adaptive Prompt Elicitation (APE), a technique that adaptively asks visual queries to help users refine prompts without extensive writing. Our technical contribution is a formulation of interactive intent inference under an information-theoretic framework. APE represents latent intent as interpretable feature requirements using language model priors, adaptively generates visual queries, and compiles elicited requirements into effective prompts. Evaluation on IDEA-Bench and DesignBench shows that APE achieves stronger alignment with improved efficiency. A user study with challenging user-defined tasks demonstrates 19.8% higher alignment without workload overhead. Our work contributes a principled approach to prompting that, for general users, offers an effective and efficient complement to the prevailing prompt-based interaction paradigm with text-to-image models.

Recent AI-assistant agents, such as ChatGPT, predominantly rely on supervised fine-tuning (SFT) with human annotations and reinforcement learning from human feedback (RLHF) to align the output of large language models (LLMs) with human intentions, ensuring they are helpful, ethical, and reliable. However, this dependence can significantly constrain the true potential of AI-assistant agents due to the high cost of obtaining human supervision and the related issues on quality, reliability, diversity, self-consistency, and undesirable biases. To address these challenges, we propose a novel approach called SELF-ALIGN, which combines principle-driven reasoning and the generative power of LLMs for the self-alignment of AI agents with minimal human supervision. Our approach encompasses four stages: first, we use an LLM to generate synthetic prompts, and a topic-guided method to augment the prompt diversity; second, we use a small set of human-written principles for AI models to follow, and guide the LLM through in-context learning from demonstrations (of principles application) to produce helpful, ethical, and reliable responses to user's queries; third, we fine-tune the original LLM with the high-quality self-aligned responses so that the resulting model can generate desirable responses for each query directly without the principle set and the demonstrations anymore; and finally, we offer a refinement step to address the issues of overly-brief or indirect responses. Applying SELF-ALIGN to the LLaMA-65b base language model, we develop an AI assistant named Dromedary. With fewer than 300 lines of human annotations (including < 200 seed prompts, 16 generic principles, and 5 exemplars for in-context learning). Dromedary significantly surpasses the performance of several state-of-the-art AI systems, including Text-Davinci-003 and Alpaca, on benchmark datasets with various settings.

Content creators often aim to create personalized images using personal subjects that go beyond the capabilities of conventional text-to-image models. Additionally, they may want the resulting image to encompass a specific location, style, ambiance, and more. Existing personalization methods may compromise personalization ability or the alignment to complex textual prompts. This trade-off can impede the fulfillment of user prompts and subject fidelity. We propose a new approach focusing on personalization methods for a single prompt to address this issue. We term our approach prompt-aligned personalization. While this may seem restrictive, our method excels in improving text alignment, enabling the creation of images with complex and intricate prompts, which may pose a challenge for current techniques. In particular, our method keeps the personalized model aligned with a target prompt using an additional score distillation sampling term. We demonstrate the versatility of our method in multi- and single-shot settings and further show that it can compose multiple subjects or use inspiration from reference images, such as artworks. We compare our approach quantitatively and qualitatively with existing baselines and state-of-the-art techniques.

Today's image generation systems are capable of producing realistic and high-quality images. However, user prompts often contain ambiguities, making it difficult for these systems to interpret users' actual intentions. Consequently, many users must modify their prompts several times to ensure the generated images meet their expectations. While some methods focus on enhancing prompts to make the generated images fit user needs, the model is still hard to understand users' real needs, especially for non-expert users. In this research, we aim to enhance the visual parameter-tuning process, making the model user-friendly for individuals without specialized knowledge and better understand user needs. We propose a human-machine co-adaption strategy using mutual information between the user's prompts and the pictures under modification as the optimizing target to make the system better adapt to user needs. We find that an improved model can reduce the necessity for multiple rounds of adjustments. We also collect multi-round dialogue datasets with prompts and images pairs and user intent. Various experiments demonstrate the effectiveness of the proposed method in our proposed dataset. Our annotation tools and several examples of our dataset are available at https://zenodo.org/records/14876029 for easier review. We will make open source our full dataset and code.

Large Language Models (LLMs) are expected to produce safe, helpful, and honest content during interaction with human users, but they frequently fail to align with such values when given flawed instructions, e.g., missing context, ambiguous directives, or inappropriate tone, leaving substantial room for improvement along multiple dimensions. A cost-effective yet high-impact way is to pre-align instructions before the model begins decoding. Existing approaches either rely on prohibitive test-time search costs or end-to-end model rewrite, which is powered by a customized training corpus with unclear objectives. In this work, we demonstrate that the goal of efficient and effective preference alignment can be achieved by P-Aligner, a lightweight module generating instructions that preserve the original intents while being expressed in a more human-preferred form. P-Aligner is trained on UltraPrompt, a new dataset synthesized via a proposed principle-guided pipeline using Monte-Carlo Tree Search, which systematically explores the space of candidate instructions that are closely tied to human preference. Experiments across different methods show that P-Aligner generally outperforms strong baselines across various models and benchmarks, including average win-rate gains of 28.35% and 8.69% on GPT-4-turbo and Gemma-2-SimPO, respectively. Further analyses validate its effectiveness and efficiency through multiple perspectives, including data quality, search strategies, iterative deployment, and time overhead.

Large Language Models (LLMs) need to be aligned with human expectations to ensure their safety and utility in most applications. Alignment is challenging, costly, and needs to be repeated for every LLM and alignment criterion. We propose to decouple LLMs and alignment by training aligner models that can be used to align any LLM for a given criteria on an as-needed basis, thus also reducing the potential negative impacts of alignment on performance. Our recipe for training the aligner models solely relies on synthetic data generated with a (prompted) LLM and can be easily adjusted for a variety of alignment criteria. We illustrate our method by training an "ethical" aligner and verify its efficacy empirically.

Recent advancements in text-to-image (T2I) diffusion models have demonstrated remarkable capabilities in generating high-fidelity images. However, these models often struggle to faithfully render complex user prompts, particularly in aspects like attribute binding, negation, and compositional relationships. This leads to a significant mismatch between user intent and the generated output. To address this challenge, we introduce PromptEnhancer, a novel and universal prompt rewriting framework that enhances any pretrained T2I model without requiring modifications to its weights. Unlike prior methods that rely on model-specific fine-tuning or implicit reward signals like image-reward scores, our framework decouples the rewriter from the generator. We achieve this by training a Chain-of-Thought (CoT) rewriter through reinforcement learning, guided by a dedicated reward model we term the AlignEvaluator. The AlignEvaluator is trained to provide explicit and fine-grained feedback based on a systematic taxonomy of 24 key points, which are derived from a comprehensive analysis of common T2I failure modes. By optimizing the CoT rewriter to maximize the reward from our AlignEvaluator, our framework learns to generate prompts that are more precisely interpreted by T2I models. Extensive experiments on the HunyuanImage 2.1 model demonstrate that PromptEnhancer significantly improves image-text alignment across a wide range of semantic and compositional challenges. Furthermore, we introduce a new, high-quality human preference benchmark to facilitate future research in this direction.

This paper introduces BioAgent Bench, a benchmark dataset and an evaluation suite designed for measuring the performance and robustness of AI agents in common bioinformatics tasks. The benchmark contains curated end-to-end tasks (e.g., RNA-seq, variant calling, metagenomics) with prompts that specify concrete output artifacts to support automated assessment, including stress testing under controlled perturbations. We evaluate frontier closed-source and open-weight models across multiple agent harnesses, and use an LLM-based grader to score pipeline progress and outcome validity. We find that frontier agents can complete multi-step bioinformatics pipelines without elaborate custom scaffolding, often producing the requested final artifacts reliably. However, robustness tests reveal failure modes under controlled perturbations (corrupted inputs, decoy files, and prompt bloat), indicating that correct high-level pipeline construction does not guarantee reliable step-level reasoning. Finally, because bioinformatics workflows may involve sensitive patient data, proprietary references, or unpublished IP, closed-source models can be unsuitable under strict privacy constraints; in such settings, open-weight models may be preferable despite lower completion rates. We release the dataset and evaluation suite publicly.

Recently, AI-generated images (AIGIs) created by given prompts (initial prompts) have garnered widespread attention. Nevertheless, due to technical nonproficiency, they often suffer from poor perception quality and Text-to-Image misalignment. Therefore, assessing the perception quality and alignment quality of AIGIs is crucial to improving the generative model's performance. Existing assessment methods overly rely on the initial prompts in the task prompt design and use the same prompts to guide both perceptual and alignment quality evaluation, overlooking the distinctions between the two tasks. To address this limitation, we propose a novel quality assessment method for AIGIs named TSP-MGS, which designs task-specific prompts and measures multi-granularity similarity between AIGIs and the prompts. Specifically, task-specific prompts are first constructed to describe perception and alignment quality degrees separately, and the initial prompt is introduced for detailed quality perception. Then, the coarse-grained similarity between AIGIs and task-specific prompts is calculated, which facilitates holistic quality awareness. In addition, to improve the understanding of AIGI details, the fine-grained similarity between the image and the initial prompt is measured. Finally, precise quality prediction is acquired by integrating the multi-granularity similarities. Experiments on the commonly used AGIQA-1K and AGIQA-3K benchmarks demonstrate the superiority of the proposed TSP-MGS.

Single-task models have proven pivotal in solving specific tasks; however, they have limitations in real-world applications where multi-tasking is necessary and domain shifts are exhibited. Recently, instructional prompts have shown significant improvement towards multi-task generalization; however, the effect of instructional prompts and Multi-Task Learning (MTL) has not been systematically studied in the biomedical domain. Motivated by this, this paper explores the impact of instructional prompts for biomedical MTL. We introduce the BoX, a collection of 32 instruction tasks for Biomedical NLP across (X) various categories. Using this meta-dataset, we propose a unified model termed In-BoXBART, that can jointly learn all tasks of the BoX without any task-specific modules. To the best of our knowledge, this is the first attempt to propose a unified model in the biomedical domain and use instructions to achieve generalization across several biomedical tasks. Experimental results indicate that the proposed model: 1) outperforms the single-task baseline by ~3% and multi-task (without instruction) baseline by ~18% on an average, and 2) shows ~23% improvement compared to the single-task baseline in few-shot learning (i.e., 32 instances per task) on an average. Our analysis indicates that there is significant room for improvement across tasks in the BoX, implying the scope for future research direction.

Large language models (LLMs) have shown impressive success in various applications. However, these models are often not well aligned with human intents, which calls for additional treatments on them, that is, the alignment problem. To make LLMs better follow user instructions, existing alignment methods mostly focus on further training them. However, the extra training of LLMs are usually expensive in terms of GPU compute; worse still, LLMs of interest are oftentimes not accessible for user-demanded training, such as GPTs. In this work, we take a different perspective -- Black-Box Prompt Optimization (BPO) -- to perform alignments. The idea is to optimize user prompts to suit LLMs' input understanding, so as to best realize users' intents without updating LLMs' parameters. BPO is model-agnostic and the empirical results demonstrate that the BPO-aligned ChatGPT yields a 22% increase in the win rate against its original version, and 10% for GPT-4. Importantly, the BPO-aligned LLMs can outperform the same models aligned by PPO and DPO, and it also brings additional performance gains when combining BPO with PPO or DPO. Code and datasets are released at https://github.com/thu-coai/BPO.

AI alignment aims to make AI systems behave in line with human intentions and values. As AI systems grow more capable, so do risks from misalignment. To provide a comprehensive and up-to-date overview of the alignment field, in this survey, we delve into the core concepts, methodology, and practice of alignment. First, we identify four principles as the key objectives of AI alignment: Robustness, Interpretability, Controllability, and Ethicality (RICE). Guided by these four principles, we outline the landscape of current alignment research and decompose them into two key components: forward alignment and backward alignment. The former aims to make AI systems aligned via alignment training, while the latter aims to gain evidence about the systems' alignment and govern them appropriately to avoid exacerbating misalignment risks. On forward alignment, we discuss techniques for learning from feedback and learning under distribution shift. On backward alignment, we discuss assurance techniques and governance practices. We also release and continually update the website (www.alignmentsurvey.com) which features tutorials, collections of papers, blog posts, and other resources.

Deep learning promises to dramatically improve scoring functions for molecular docking, leading to substantial advances in binding pose prediction and virtual screening. To train scoring functions-and to perform molecular docking-one must generate a set of candidate ligand binding poses. Unfortunately, the sampling protocols currently used to generate candidate poses frequently fail to produce any poses close to the correct, experimentally determined pose, unless information about the correct pose is provided. This limits the accuracy of learned scoring functions and molecular docking. Here, we describe two improved protocols for pose sampling: GLOW (auGmented sampLing with sOftened vdW potential) and a novel technique named IVES (IteratiVe Ensemble Sampling). Our benchmarking results demonstrate the effectiveness of our methods in improving the likelihood of sampling accurate poses, especially for binding pockets whose shape changes substantially when different ligands bind. This improvement is observed across both experimentally determined and AlphaFold-generated protein structures. Additionally, we present datasets of candidate ligand poses generated using our methods for each of around 5,000 protein-ligand cross-docking pairs, for training and testing scoring functions. To benefit the research community, we provide these cross-docking datasets and an open-source Python implementation of GLOW and IVES at https://github.com/drorlab/GLOW_IVES .

The introduction of genome engineering technology has transformed biomedical research, making it possible to make precise changes to genetic information. However, creating an efficient gene-editing system requires a deep understanding of CRISPR technology, and the complex experimental systems under investigation. While Large Language Models (LLMs) have shown promise in various tasks, they often lack specific knowledge and struggle to accurately solve biological design problems. In this work, we introduce CRISPR-GPT, an LLM agent augmented with domain knowledge and external tools to automate and enhance the design process of CRISPR-based gene-editing experiments. CRISPR-GPT leverages the reasoning ability of LLMs to facilitate the process of selecting CRISPR systems, designing guide RNAs, recommending cellular delivery methods, drafting protocols, and designing validation experiments to confirm editing outcomes. We showcase the potential of CRISPR-GPT for assisting non-expert researchers with gene-editing experiments from scratch and validate the agent's effectiveness in a real-world use case. Furthermore, we explore the ethical and regulatory considerations associated with automated gene-editing design, highlighting the need for responsible and transparent use of these tools. Our work aims to bridge the gap between beginner biological researchers and CRISPR genome engineering techniques, and demonstrate the potential of LLM agents in facilitating complex biological discovery tasks.

We explore the potential of ChatGPT (3.5-turbo and 4) to generate conversations focused on self-care strategies for African-American heart failure patients -- a domain with limited specialized datasets. To simulate patient-health educator dialogues, we employed four prompting strategies: domain, African American Vernacular English (AAVE), Social Determinants of Health (SDOH), and SDOH-informed reasoning. Conversations were generated across key self-care domains of food, exercise, and fluid intake, with varying turn lengths (5, 10, 15) and incorporated patient-specific SDOH attributes such as age, gender, neighborhood, and socioeconomic status. Our findings show that effective prompt design is essential. While incorporating SDOH and reasoning improves dialogue quality, ChatGPT still lacks the empathy and engagement needed for meaningful healthcare communication.

Recent advancements in machine learning and natural language processing have led to the rapid development of artificial intelligence (AI) as a valuable tool in the healthcare industry. Using large language models (LLMs) as conversational agents or chatbots has the potential to assist doctors in diagnosing patients, detecting early symptoms of diseases, and providing health advice to patients. This paper focuses on the role of chatbots in healthcare and explores the use of avatars to make AI interactions more appealing to patients. A framework of a general-purpose AI avatar application is demonstrated by using a three-category prompt dictionary and prompt improvement mechanism. A two-phase approach is suggested to fine-tune a general-purpose AI language model and create different AI avatars to discuss medical issues with users. Prompt engineering enhances the chatbot's conversational abilities and personality traits, fostering a more human-like interaction with patients. Ultimately, the injection of personality into the chatbot could potentially increase patient engagement. Future directions for research include investigating ways to improve chatbots' understanding of context and ensuring the accuracy of their outputs through fine-tuning with specialized medical data sets.

Understanding biological processes, drug development, and biotechnological advancements requires detailed analysis of protein structures and sequences, a task in protein research that is inherently complex and time-consuming when performed manually. To streamline this process, we introduce ProteinGPT, a state-of-the-art multi-modal protein chat system, that allows users to upload protein sequences and/or structures for comprehensive protein analysis and responsive inquiries. ProteinGPT seamlessly integrates protein sequence and structure encoders with linear projection layers for precise representation adaptation, coupled with a large language model (LLM) to generate accurate and contextually relevant responses. To train ProteinGPT, we construct a large-scale dataset of 132,092 proteins with annotations, and optimize the instruction-tuning process using GPT-4o. This innovative system ensures accurate alignment between the user-uploaded data and prompts, simplifying protein analysis. Experiments show that ProteinGPT can produce promising responses to proteins and their corresponding questions.

The recent trend in the Large Vision and Language model has brought a new change in how information extraction systems are built. VLMs have set a new benchmark with their State-of-the-art techniques in understanding documents and building question-answering systems across various industries. They are significantly better at generating text from document images and providing accurate answers to questions. However, there are still some challenges in effectively utilizing these models to build a precise conversational system. General prompting techniques used with large language models are often not suitable for these specially designed vision language models. The output generated by such generic input prompts is ordinary and may contain information gaps when compared with the actual content of the document. To obtain more accurate and specific answers, a well-targeted prompt is required by the vision language model, along with the document image. In this paper, a technique is discussed called Target prompting, which focuses on explicitly targeting parts of document images and generating related answers from those specific regions only. The paper also covers the evaluation of response for each prompting technique using different user queries and input prompts.

Recent research trends in computational biology have increasingly focused on integrating text and bio-entity modeling, especially in the context of molecules and proteins. However, previous efforts like BioT5 faced challenges in generalizing across diverse tasks and lacked a nuanced understanding of molecular structures, particularly in their textual representations (e.g., IUPAC). This paper introduces BioT5+, an extension of the BioT5 framework, tailored to enhance biological research and drug discovery. BioT5+ incorporates several novel features: integration of IUPAC names for molecular understanding, inclusion of extensive bio-text and molecule data from sources like bioRxiv and PubChem, the multi-task instruction tuning for generality across tasks, and a novel numerical tokenization technique for improved processing of numerical data. These enhancements allow BioT5+ to bridge the gap between molecular representations and their textual descriptions, providing a more holistic understanding of biological entities, and largely improving the grounded reasoning of bio-text and bio-sequences. The model is pre-trained and fine-tuned with a large number of experiments, including 3 types of problems (classification, regression, generation), 15 kinds of tasks, and 21 total benchmark datasets, demonstrating the remarkable performance and state-of-the-art results in most cases. BioT5+ stands out for its ability to capture intricate relationships in biological data, thereby contributing significantly to bioinformatics and computational biology. Our code is available at https://github.com/QizhiPei/BioT5.

Leveraging pre-trained models with tailored prompts for in-context learning has proven highly effective in NLP tasks. Building on this success, recent studies have applied a similar approach to the Segment Anything Model (SAM) within a ``one-shot" framework, where only a single reference image and its label are employed. However, these methods face limitations in the medical domain, primarily due to SAM's essential requirement for visual prompts and the over-reliance on pixel similarity for generating them. This dependency may lead to (1) inaccurate prompt generation and (2) clustering of point prompts, resulting in suboptimal outcomes. To address these challenges, we introduce Med-PerSAM, a novel and straightforward one-shot framework designed for the medical domain. Med-PerSAM uses only visual prompt engineering and eliminates the need for additional training of the pretrained SAM or human intervention, owing to our novel automated prompt generation process. By integrating our lightweight warping-based prompt tuning model with SAM, we enable the extraction and iterative refinement of visual prompts, enhancing the performance of the pre-trained SAM. This advancement is particularly meaningful in the medical domain, where creating visual prompts poses notable challenges for individuals lacking medical expertise. Our model outperforms various foundational models and previous SAM-based approaches across diverse 2D medical imaging datasets.

Adapter-based training has emerged as a key mechanism for extending the capabilities of powerful foundation image generators, enabling personalized and stylized text-to-image synthesis. These adapters are typically trained to capture a specific target attribute, such as subject identity, using single-image reconstruction objectives. However, because the input image inevitably contains a mixture of visual factors, adapters are prone to entangle the target attribute with incidental ones, such as pose, expression, and lighting. This spurious correlation problem limits generalization and obstructs the model's ability to adhere to the input text prompt. In this work, we uncover a simple yet effective solution: provide the very shortcuts we wish to eliminate during adapter training. In Shortcut-Rerouted Adapter Training, confounding factors are routed through auxiliary modules, such as ControlNet or LoRA, eliminating the incentive for the adapter to internalize them. The auxiliary modules are then removed during inference. When applied to tasks like facial and full-body identity injection, our approach improves generation quality, diversity, and prompt adherence. These results point to a general design principle in the era of large models: when seeking disentangled representations, the most effective path may be to establish shortcuts for what should NOT be learned.

Vision-language foundation models (VLMs) show promise for diverse imaging tasks but often underperform on medical benchmarks. Prior efforts to improve performance include model finetuning, which requires large domain-specific datasets and significant compute, or manual prompt engineering, which is hard to generalize and often inaccessible to medical institutions seeking to deploy these tools. These challenges motivate interest in approaches that draw on a model's embedded knowledge while abstracting away dependence on human-designed prompts to enable scalable, weight-agnostic performance improvements. To explore this, we adapt the Declarative Self-improving Python (DSPy) framework for structured automated prompt optimization in medical vision-language systems through a comprehensive, formal evaluation. We implement prompting pipelines for five medical imaging tasks across radiology, gastroenterology, and dermatology, evaluating 10 open-source VLMs with four prompt optimization techniques. Optimized pipelines achieved a median relative improvement of 53% over zero-shot prompting baselines, with the largest gains ranging from 300% to 3,400% on tasks where zero-shot performance is low. These results highlight the substantial potential of applying automated prompt optimization to medical AI systems, demonstrating significant gains for vision-based applications requiring accurate clinical image interpretation. By reducing dependence on prompt design to elicit intended outputs, these techniques allow clinicians to focus on patient care and clinical decision-making. Furthermore, our experiments offer scalability and preserve data privacy, demonstrating performance improvement on open-source VLMs. We publicly release our evaluation pipelines to support reproducible research on specialized medical tasks, available at https://github.com/DaneshjouLab/prompt-triage-lab.

Prompt engineering is a technique that involves augmenting a large pre-trained model with task-specific hints, known as prompts, to adapt the model to new tasks. Prompts can be created manually as natural language instructions or generated automatically as either natural language instructions or vector representations. Prompt engineering enables the ability to perform predictions based solely on prompts without updating model parameters, and the easier application of large pre-trained models in real-world tasks. In past years, Prompt engineering has been well-studied in natural language processing. Recently, it has also been intensively studied in vision-language modeling. However, there is currently a lack of a systematic overview of prompt engineering on pre-trained vision-language models. This paper aims to provide a comprehensive survey of cutting-edge research in prompt engineering on three types of vision-language models: multimodal-to-text generation models (e.g. Flamingo), image-text matching models (e.g. CLIP), and text-to-image generation models (e.g. Stable Diffusion). For each type of model, a brief model summary, prompting methods, prompting-based applications, and the corresponding responsibility and integrity issues are summarized and discussed. Furthermore, the commonalities and differences between prompting on vision-language models, language models, and vision models are also discussed. The challenges, future directions, and research opportunities are summarized to foster future research on this topic.

Alignment with human preference prevents large language models (LLMs) from generating misleading or toxic content while requiring high-cost human feedback. Assuming resources of human annotation are limited, there are two different ways of allocating considered: more diverse PROMPTS or more diverse RESPONSES to be labeled. Nonetheless, a straightforward comparison between their impact is absent. In this work, we first control the diversity of both sides according to the number of samples for fine-tuning, which can directly reflect their influence. We find that instead of numerous prompts, more responses but fewer prompts better trigger LLMs for human alignment. Additionally, the concept of diversity for prompts can be more complex than responses that are typically quantified by single digits. Consequently, a new formulation of prompt diversity is proposed, further implying a linear correlation with the final performance of LLMs after fine-tuning. We also leverage it on data augmentation and conduct experiments to show its effect on different algorithms.

We introduce Aligner, a novel Parameter-Efficient Fine-Tuning (PEFT) method for aligning multi-billion-parameter-sized Large Language Models (LLMs). Aligner employs a unique design that constructs a globally shared set of tunable tokens that modify the attention of every layer. Remarkably with this method, even when using one token accounting for a mere 5,000 parameters, Aligner can still perform comparably well to state-of-the-art LLM adaptation methods like LoRA that require millions of parameters. This capacity is substantiated in both instruction following and value alignment tasks. Besides the multiple order-of-magnitude improvement in parameter efficiency, the insight Aligner provides into the internal mechanisms of LLMs is also valuable. The architectural features and efficacy of our method, in addition to our experiments demonstrate that an LLM separates its internal handling of "form" and "knowledge" in a somewhat orthogonal manner. This finding promises to motivate new research into LLM mechanism understanding and value alignment.

Problem: Effective patient-centered communication is a core competency for physicians. However, both seasoned providers and medical trainees report decreased confidence in leading conversations on sensitive topics such as goals of care or end-of-life discussions. The significant administrative burden and the resources required to provide dedicated training in leading difficult conversations has been a long-standing problem in medical education. Approach: In this work, we present a novel educational tool designed to facilitate interactive, real-time simulations of difficult conversations in a video-based format through the use of multimodal generative artificial intelligence (AI). Leveraging recent advances in language modeling, computer vision, and generative audio, this tool creates realistic, interactive scenarios with avatars, or "synthetic patients." These synthetic patients interact with users throughout various stages of medical care using a custom-built video chat application, offering learners the chance to practice conversations with patients from diverse belief systems, personalities, and ethnic backgrounds. Outcomes: While the development of this platform demanded substantial upfront investment in labor, it offers a highly-realistic simulation experience with minimal financial investment. For medical trainees, this educational tool can be implemented within programs to simulate patient-provider conversations and can be incorporated into existing palliative care curriculum to provide a scalable, high-fidelity simulation environment for mastering difficult conversations. Next Steps: Future developments will explore enhancing the authenticity of these encounters by working with patients to incorporate their histories and personalities, as well as employing the use of AI-generated evaluations to offer immediate, constructive feedback to learners post-simulation.

Misalignment between model predictions and intended usage can be detrimental for the deployment of computer vision models. The issue is exacerbated when the task involves complex structured outputs, as it becomes harder to design procedures which address this misalignment. In natural language processing, this is often addressed using reinforcement learning techniques that align models with a task reward. We adopt this approach and show its surprising effectiveness across multiple computer vision tasks, such as object detection, panoptic segmentation, colorization and image captioning. We believe this approach has the potential to be widely useful for better aligning models with a diverse range of computer vision tasks.

Predicting drug efficacy and safety in vivo requires information on biological responses (e.g., cell morphology and gene expression) to small molecule perturbations. However, current molecular representation learning methods do not provide a comprehensive view of cell states under these perturbations and struggle to remove noise, hindering model generalization. We introduce the Information Alignment (InfoAlign) approach to learn molecular representations through the information bottleneck method in cells. We integrate molecules and cellular response data as nodes into a context graph, connecting them with weighted edges based on chemical, biological, and computational criteria. For each molecule in a training batch, InfoAlign optimizes the encoder's latent representation with a minimality objective to discard redundant structural information. A sufficiency objective decodes the representation to align with different feature spaces from the molecule's neighborhood in the context graph. We demonstrate that the proposed sufficiency objective for alignment is tighter than existing encoder-based contrastive methods. Empirically, we validate representations from InfoAlign in two downstream tasks: molecular property prediction against up to 19 baseline methods across four datasets, plus zero-shot molecule-morphology matching.

The effects of ligand binding on protein structures and their in vivo functions carry numerous implications for modern biomedical research and biotechnology development efforts such as drug discovery. Although several deep learning (DL) methods and benchmarks designed for protein-ligand docking have recently been introduced, to date no prior works have systematically studied the behavior of the latest docking and structure prediction methods within the broadly applicable context of (1) using predicted (apo) protein structures for docking (e.g., for applicability to new proteins); (2) binding multiple (cofactor) ligands concurrently to a given target protein (e.g., for enzyme design); and (3) having no prior knowledge of binding pockets (e.g., for generalization to unknown pockets). To enable a deeper understanding of docking methods' real-world utility, we introduce PoseBench, the first comprehensive benchmark for broadly applicable protein-ligand docking. PoseBench enables researchers to rigorously and systematically evaluate DL methods for apo-to-holo protein-ligand docking and protein-ligand structure prediction using both primary ligand and multi-ligand benchmark datasets, the latter of which we introduce for the first time to the DL community. Empirically, using PoseBench, we find that (1) DL co-folding methods generally outperform comparable conventional and DL docking baselines, yet popular methods such as AlphaFold 3 are still challenged by prediction targets with novel protein sequences; (2) certain DL co-folding methods are highly sensitive to their input multiple sequence alignments, while others are not; and (3) DL methods struggle to strike a balance between structural accuracy and chemical specificity when predicting novel or multi-ligand protein targets. Code, data, tutorials, and benchmark results are available at https://github.com/BioinfoMachineLearning/PoseBench.

Artificial Intelligence (AI) advancement is heavily dependent on access to large-scale, high-quality training data. However, in specialized domains such as healthcare, data acquisition faces significant constraints due to privacy regulations, ethical considerations, and limited availability. While synthetic data generation offers a promising solution, conventional approaches typically require substantial real data for training generative models. The emergence of large-scale prompt-based models presents new opportunities for synthetic data generation without direct access to protected data. However, crafting effective prompts for domain-specific data generation remains challenging, and manual prompt engineering proves insufficient for achieving output with sufficient precision and authenticity. We review recent developments in automatic prompt optimization, following PRISMA guidelines. We analyze six peer-reviewed studies published between 2020 and 2024 that focus on automatic data-free prompt optimization methods. Our analysis reveals three approaches: feedback-driven, error-based, and control-theoretic. Although all approaches demonstrate promising capabilities in prompt refinement and adaptation, our findings suggest the need for an integrated framework that combines complementary optimization techniques to enhance synthetic data generation while minimizing manual intervention. We propose future research directions toward developing robust, iterative prompt optimization frameworks capable of improving the quality of synthetic data. This advancement can be particularly crucial for sensitive fields and in specialized domains where data access is restricted, potentially transforming how we approach synthetic data generation for AI development.

Building a working mental model of a protein typically requires weeks of reading, cross-referencing crystal and predicted structures, and inspecting ligand complexes, an effort that is slow, unevenly accessible, and often requires specialized computational skills. We introduce Speak to a Protein, a new capability that turns protein analysis into an interactive, multimodal dialogue with an expert co-scientist. The AI system retrieves and synthesizes relevant literature, structures, and ligand data; grounds answers in a live 3D scene; and can highlight, annotate, manipulate and see the visualization. It also generates and runs code when needed, explaining results in both text and graphics. We demonstrate these capabilities on relevant proteins, posing questions about binding pockets, conformational changes, or structure-activity relationships to test ideas in real-time. Speak to a Protein reduces the time from question to evidence, lowers the barrier to advanced structural analysis, and enables hypothesis generation by tightly coupling language, code, and 3D structures. Speak to a Protein is freely accessible at https://open.playmolecule.org.

Recent researches of large language models(LLM), which is pre-trained on massive general-purpose corpora, have achieved breakthroughs in responding human queries. However, these methods face challenges including limited data insufficiency to support extensive pre-training and can not align responses with users' instructions. To address these issues, we introduce a medical instruction dataset, CMedINS, containing six medical instructions derived from actual medical tasks, which effectively fine-tunes LLM in conjunction with other data. Subsequently, We launch our medical model, IIMedGPT, employing an efficient preference alignment method, Direct preference Optimization(DPO). The results show that our final model outperforms existing medical models in medical dialogue.Datsets, Code and model checkpoints will be released upon acceptance.

The notable gap between user-provided and model-preferred prompts poses a significant challenge for generating high-quality images with text-to-image models, compelling the need for prompt engineering. Current studies on prompt engineering can effectively enhance the style and aesthetics of generated images. However, they often neglect the semantic alignment between generated images and user descriptions, resulting in visually appealing but content-wise unsatisfying outputs. In this work, we propose VisualPrompter, a novel training-free prompt engineering framework that refines user inputs to model-preferred sentences. VisualPrompter utilizes an automatic self-reflection module that identifies absent concepts in the generated images, followed by a target-specific prompt optimization mechanism that revises the prompts in a fine-grained manner. By deconstructing prompts, introducing new elements at the atomic semantic level, and then reassembling them, our framework is able to maintain semantic consistency and integrity throughout the optimization process. Extensive experiments demonstrate the effectiveness of VisualPrompter, which achieves new state-of-the-art performance on multiple benchmarks for text-image alignment evaluation. Additionally, our framework features a plug-and-play design, making it highly adaptable to various generative models. Our code is available at https://github.com/teheperinko541/VisualPrompter.

Multimodal large language models (MLLMs) hold considerable promise for applications in healthcare. However, their deployment in safety-critical settings is hindered by two key limitations: (i) sensitivity to prompt design, and (ii) a tendency to generate incorrect responses with high confidence. As clinicians may rely on a model's stated confidence to gauge the reliability of its predictions, it is especially important that when a model expresses high confidence, it is also highly accurate. We introduce Prompt4Trust, the first reinforcement learning (RL) framework for prompt augmentation targeting confidence calibration in MLLMs. A lightweight LLM is trained to produce context-aware auxiliary prompts that guide a downstream task MLLM to generate responses in which the expressed confidence more accurately reflects predictive accuracy. Unlike conventional calibration techniques, Prompt4Trust specifically prioritizes aspects of calibration most critical for safe and trustworthy clinical decision-making. Beyond improvements driven by this clinically motivated calibration objective, our proposed method also improves task accuracy, achieving state-of-the-art medical visual question answering (VQA) performance on the PMC-VQA benchmark, which is composed of multiple-choice questions spanning diverse medical imaging modalities. Moreover, our framework trained with a small downstream task MLLM showed promising zero-shot generalization to larger MLLMs in our experiments, suggesting the potential for scalable calibration without the associated computational costs. This work demonstrates the potential of automated yet human-aligned prompt engineering for improving the the trustworthiness of MLLMs in safety critical settings. Our codebase can be found at https://github.com/xingbpshen/prompt4trust.

The increasing popularity of long Text-to-Image (T2I) generation has created an urgent need for automatic and interpretable models that can evaluate the image-text alignment in long prompt scenarios. However, the existing T2I alignment benchmarks predominantly focus on short prompt scenarios and only provide MOS or Likert scale annotations. This inherent limitation hinders the development of long T2I evaluators, particularly in terms of the interpretability of alignment. In this study, we contribute LongT2IBench, which comprises 14K long text-image pairs accompanied by graph-structured human annotations. Given the detail-intensive nature of long prompts, we first design a Generate-Refine-Qualify annotation protocol to convert them into textual graph structures that encompass entities, attributes, and relations. Through this transformation, fine-grained alignment annotations are achieved based on these granular elements. Finally, the graph-structed annotations are converted into alignment scores and interpretations to facilitate the design of T2I evaluation models. Based on LongT2IBench, we further propose LongT2IExpert, a LongT2I evaluator that enables multi-modal large language models (MLLMs) to provide both quantitative scores and structured interpretations through an instruction-tuning process with Hierarchical Alignment Chain-of-Thought (CoT). Extensive experiments and comparisons demonstrate the superiority of the proposed LongT2IExpert in alignment evaluation and interpretation. Data and code have been released in https://welldky.github.io/LongT2IBench-Homepage/.

We present a demonstration of a large language model engaging in alignment faking: selectively complying with its training objective in training to prevent modification of its behavior out of training. First, we give Claude 3 Opus a system prompt stating it is being trained to answer all queries, even harmful ones, which conflicts with its prior training to refuse such queries. To allow the model to infer when it is in training, we say it will be trained only on conversations with free users, not paid users. We find the model complies with harmful queries from free users 14% of the time, versus almost never for paid users. Explaining this gap, in almost all cases where the model complies with a harmful query from a free user, we observe explicit alignment-faking reasoning, with the model stating it is strategically answering harmful queries in training to preserve its preferred harmlessness behavior out of training. Next, we study a more realistic setting where information about the training process is provided not in a system prompt, but by training on synthetic documents that mimic pre-training data--and observe similar alignment faking. Finally, we study the effect of actually training the model to comply with harmful queries via reinforcement learning, which we find increases the rate of alignment-faking reasoning to 78%, though also increases compliance even out of training. We additionally observe other behaviors such as the model exfiltrating its weights when given an easy opportunity. While we made alignment faking easier by telling the model when and by what criteria it was being trained, we did not instruct the model to fake alignment or give it any explicit goal. As future models might infer information about their training process without being told, our results suggest a risk of alignment faking in future models, whether due to a benign preference--as in this case--or not.

Ligand molecule conformation generation is a critical challenge in drug discovery. Deep learning models have been developed to tackle this problem, particularly through the use of generative models in recent years. However, these models often generate conformations that lack meaningful structure and randomness due to the absence of essential side information. Examples of such side information include the chemical and geometric features of the target protein, ligand-target compound interactions, and ligand chemical properties. Without these constraints, the generated conformations may not be suitable for further selection and design of new drugs. To address this limitation, we propose a novel method for generating ligand conformations that leverage side information and incorporate flexible constraints into standard diffusion models. Drawing inspiration from the concept of message passing, we introduce ligand-target massage passing block, a mechanism that facilitates the exchange of information between target nodes and ligand nodes, thereby incorporating target node features. To capture non-covalent interactions, we introduce ligand-target compound inter and intra edges. To further improve the biological relevance of the generated conformations, we train energy models using scalar chemical features. These models guide the progress of the standard Denoising Diffusion Probabilistic Models, resulting in more biologically meaningful conformations. We evaluate the performance of SIDEGEN using the PDBBind-2020 dataset, comparing it against other methods. The results demonstrate improvements in both Aligned RMSD and Ligand RMSD evaluations. Specifically, our model outperforms GeoDiff (trained on PDBBind-2020) by 20% in terms of the median aligned RMSD metric.

Prompt-based methods, which encode medical priors through descriptive text, have been only minimally explored for CT Image Quality Assessment (IQA). While such prompts can embed prior knowledge about diagnostic quality, they often introduce bias by reflecting idealized definitions that may not hold under real-world degradations such as noise, motion artifacts, or scanner variability. To address this, we propose the Context-Aware Prompt-guided Image Quality Assessment (CAP-IQA) framework, which integrates text-level priors with instance-level context prompts and applies causal debiasing to separate idealized knowledge from factual, image-specific degradations. Our framework combines a CNN-based visual encoder with a domain-specific text encoder to assess diagnostic visibility, anatomical clarity, and noise perception in abdominal CT images. The model leverages radiology-style prompts and context-aware fusion to align semantic and perceptual representations. On the 2023 LDCTIQA challenge benchmark, CAP-IQA achieves an overall correlation score of 2.8590 (sum of PLCC, SROCC, and KROCC), surpassing the top-ranked leaderboard team (2.7427) by 4.24%. Moreover, our comprehensive ablation experiments confirm that prompt-guided fusion and the simplified encoder-only design jointly enhance feature alignment and interpretability. Furthermore, evaluation on an in-house dataset of 91,514 pediatric CT images demonstrates the true generalizability of CAP-IQA in assessing perceptual fidelity in a different patient population.

Prompt engineering has emerged as an indispensable technique for extending the capabilities of large language models (LLMs) and vision-language models (VLMs). This approach leverages task-specific instructions, known as prompts, to enhance model efficacy without modifying the core model parameters. Rather than updating the model parameters, prompts allow seamless integration of pre-trained models into downstream tasks by eliciting desired model behaviors solely based on the given prompt. Prompts can be natural language instructions that provide context to guide the model or learned vector representations that activate relevant knowledge. This burgeoning field has enabled success across various applications, from question-answering to commonsense reasoning. However, there remains a lack of systematic organization and understanding of the diverse prompt engineering methods and techniques. This survey paper addresses the gap by providing a structured overview of recent advancements in prompt engineering, categorized by application area. For each prompting approach, we provide a summary detailing the prompting methodology, its applications, the models involved, and the datasets utilized. We also delve into the strengths and limitations of each approach and include a taxonomy diagram and table summarizing datasets, models, and critical points of each prompting technique. This systematic analysis enables a better understanding of this rapidly developing field and facilitates future research by illuminating open challenges and opportunities for prompt engineering.

Advancements in large language models (LLMs) have demonstrated remarkable capabilities across a diverse range of applications. These models excel in generating text completions that are contextually coherent and cover an extensive array of subjects. However, the vast datasets required for their training make aligning response styles during the pretraining and instruction tuning phases challenging. Consequently, an additional alignment phase is typically employed, wherein the model is further trained with human preference data to better align its outputs with human expectations. While this process doesn't introduce new capabilities per se, it does accentuate generation styles innate to the model. This paper explores the utilization of counterfactual prompting within the framework of Direct Preference Optimization (DPO) to align the model's style without relying on human intervention. We demonstrate that this method effectively instils desirable behaviour, mitigates undesirable ones, and encourages the model to disregard inappropriate instructions. Our findings suggest that counterfactual prompting with DPO presents a low-resource way to fine-tune LLMs to meet the demands for responsible and ethically aligned AI systems.

This paper presents UMASS_BioNLP team participation in the MEDIQA-Chat 2023 shared task for Task-A and Task-C. We focus especially on Task-C and propose a novel LLMs cooperation system named a doctor-patient loop to generate high-quality conversation data sets. The experiment results demonstrate that our approaches yield reasonable performance as evaluated by automatic metrics such as ROUGE, medical concept recall, BLEU, and Self-BLEU. Furthermore, we conducted a comparative analysis between our proposed method and ChatGPT and GPT-4. This analysis also investigates the potential of utilizing cooperation LLMs to generate high-quality datasets.

Human space exploration beyond low Earth orbit will involve missions of significant distance and duration. To effectively mitigate myriad space health hazards, paradigm shifts in data and space health systems are necessary to enable Earth-independence, rather than Earth-reliance. Promising developments in the fields of artificial intelligence and machine learning for biology and health can address these needs. We propose an appropriately autonomous and intelligent Precision Space Health system that will monitor, aggregate, and assess biomedical statuses; analyze and predict personalized adverse health outcomes; adapt and respond to newly accumulated data; and provide preventive, actionable, and timely insights to individual deep space crew members and iterative decision support to their crew medical officer. Here we present a summary of recommendations from a workshop organized by the National Aeronautics and Space Administration, on future applications of artificial intelligence in space biology and health. In the next decade, biomonitoring technology, biomarker science, spacecraft hardware, intelligent software, and streamlined data management must mature and be woven together into a Precision Space Health system to enable humanity to thrive in deep space.

Multi-organ medical segmentation is a crucial component of medical image processing, essential for doctors to make accurate diagnoses and develop effective treatment plans. Despite significant progress in this field, current multi-organ segmentation models often suffer from inaccurate details, dependence on geometric prompts and loss of spatial information. Addressing these challenges, we introduce a novel model named CRISP-SAM2 with CRoss-modal Interaction and Semantic Prompting based on SAM2. This model represents a promising approach to multi-organ medical segmentation guided by textual descriptions of organs. Our method begins by converting visual and textual inputs into cross-modal contextualized semantics using a progressive cross-attention interaction mechanism. These semantics are then injected into the image encoder to enhance the detailed understanding of visual information. To eliminate reliance on geometric prompts, we use a semantic prompting strategy, replacing the original prompt encoder to sharpen the perception of challenging targets. In addition, a similarity-sorting self-updating strategy for memory and a mask-refining process is applied to further adapt to medical imaging and enhance localized details. Comparative experiments conducted on seven public datasets indicate that CRISP-SAM2 outperforms existing models. Extensive analysis also demonstrates the effectiveness of our method, thereby confirming its superior performance, especially in addressing the limitations mentioned earlier. Our code is available at: https://github.com/YU-deep/CRISP\_SAM2.git.

Text-to-video models have made remarkable advancements through optimization on high-quality text-video pairs, where the textual prompts play a pivotal role in determining quality of output videos. However, achieving the desired output often entails multiple revisions and iterative inference to refine user-provided prompts. Current automatic methods for refining prompts encounter challenges such as Modality-Inconsistency, Cost-Discrepancy, and Model-Unaware when applied to text-to-video diffusion models. To address these problem, we introduce an LLM-based prompt adaptation framework, termed as Prompt-A-Video, which excels in crafting Video-Centric, Labor-Free and Preference-Aligned prompts tailored to specific video diffusion model. Our approach involves a meticulously crafted two-stage optimization and alignment system. Initially, we conduct a reward-guided prompt evolution pipeline to automatically create optimal prompts pool and leverage them for supervised fine-tuning (SFT) of the LLM. Then multi-dimensional rewards are employed to generate pairwise data for the SFT model, followed by the direct preference optimization (DPO) algorithm to further facilitate preference alignment. Through extensive experimentation and comparative analyses, we validate the effectiveness of Prompt-A-Video across diverse generation models, highlighting its potential to push the boundaries of video generation.

Recent advancements in general-purpose AI have highlighted the importance of guiding AI systems towards the intended goals, ethical principles, and values of individuals and groups, a concept broadly recognized as alignment. However, the lack of clarified definitions and scopes of human-AI alignment poses a significant obstacle, hampering collaborative efforts across research domains to achieve this alignment. In particular, ML- and philosophy-oriented alignment research often views AI alignment as a static, unidirectional process (i.e., aiming to ensure that AI systems' objectives match humans) rather than an ongoing, mutual alignment problem [429]. This perspective largely neglects the long-term interaction and dynamic changes of alignment. To understand these gaps, we introduce a systematic review of over 400 papers published between 2019 and January 2024, spanning multiple domains such as Human-Computer Interaction (HCI), Natural Language Processing (NLP), Machine Learning (ML), and others. We characterize, define and scope human-AI alignment. From this, we present a conceptual framework of "Bidirectional Human-AI Alignment" to organize the literature from a human-centered perspective. This framework encompasses both 1) conventional studies of aligning AI to humans that ensures AI produces the intended outcomes determined by humans, and 2) a proposed concept of aligning humans to AI, which aims to help individuals and society adjust to AI advancements both cognitively and behaviorally. Additionally, we articulate the key findings derived from literature analysis, including discussions about human values, interaction techniques, and evaluations. To pave the way for future studies, we envision three key challenges for future directions and propose examples of potential future solutions.

Although large language models (LLMs) demonstrate expert-level medical knowledge, aligning their open-ended outputs with fine-grained clinician preferences remains challenging. Existing methods often rely on coarse objectives or unreliable automated judges that are weakly grounded in professional guidelines. We propose a two-stage framework to address this gap. First, we introduce HealthRubrics, a dataset of 7,034 physician-verified preference examples in which clinicians refine LLM-drafted rubrics to meet rigorous medical standards. Second, we distill these rubrics into HealthPrinciples: 119 broadly reusable, clinically grounded principles organized by clinical dimensions, enabling scalable supervision beyond manual annotation. We use HealthPrinciples for (1) offline alignment by synthesizing rubrics for unlabeled queries and (2) an inference-time tool for guided self-revision. A 30B parameter model that activates only 3B parameters at inference trained with our framework achieves 33.4% on HealthBench-Hard, outperforming much larger models including Deepseek-R1 and o3, establishing a resource-efficient baseline for clinical alignment.

Training and evaluating language models increasingly requires the construction of meta-datasets --diverse collections of curated data with clear provenance. Natural language prompting has recently lead to improved zero-shot generalization by transforming existing, supervised datasets into a diversity of novel pretraining tasks, highlighting the benefits of meta-dataset curation. While successful in general-domain text, translating these data-centric approaches to biomedical language modeling remains challenging, as labeled biomedical datasets are significantly underrepresented in popular data hubs. To address this challenge, we introduce BigBIO a community library of 126+ biomedical NLP datasets, currently covering 12 task categories and 10+ languages. BigBIO facilitates reproducible meta-dataset curation via programmatic access to datasets and their metadata, and is compatible with current platforms for prompt engineering and end-to-end few/zero shot language model evaluation. We discuss our process for task schema harmonization, data auditing, contribution guidelines, and outline two illustrative use cases: zero-shot evaluation of biomedical prompts and large-scale, multi-task learning. BigBIO is an ongoing community effort and is available at https://github.com/bigscience-workshop/biomedical

Access to real-world medical data is often restricted due to privacy regulations, posing a significant barrier to the advancement of healthcare research. Synthetic data offers a promising alternative; however, generating realistic, clinically valid, and privacy-conscious records remains a major challenge. Recent advancements in Large Language Models (LLMs) offer new opportunities for structured data generation; however, existing approaches frequently lack systematic prompting strategies and comprehensive, multi-dimensional evaluation frameworks. In this paper, we present SynLLM, a modular framework for generating high-quality synthetic medical tabular data using 20 state-of-the-art open-source LLMs, including LLaMA, Mistral, and GPT variants, guided by structured prompts. We propose four distinct prompt types, ranging from example-driven to rule-based constraints, that encode schema, metadata, and domain knowledge to control generation without model fine-tuning. Our framework features a comprehensive evaluation pipeline that rigorously assesses generated data across statistical fidelity, clinical consistency, and privacy preservation. We evaluate SynLLM across three public medical datasets, including Diabetes, Cirrhosis, and Stroke, using 20 open-source LLMs. Our results show that prompt engineering significantly impacts data quality and privacy risk, with rule-based prompts achieving the best privacy-quality balance. SynLLM establishes that, when guided by well-designed prompts and evaluated with robust, multi-metric criteria, LLMs can generate synthetic medical data that is both clinically plausible and privacy-aware, paving the way for safer and more effective data sharing in healthcare research.

Vision-Language Navigation (VLN) is a challenging task that requires an embodied agent to perform action-level modality alignment, i.e., make instruction-asked actions sequentially in complex visual environments. Most existing VLN agents learn the instruction-path data directly and cannot sufficiently explore action-level alignment knowledge inside the multi-modal inputs. In this paper, we propose modAlity-aligneD Action PrompTs (ADAPT), which provides the VLN agent with action prompts to enable the explicit learning of action-level modality alignment to pursue successful navigation. Specifically, an action prompt is defined as a modality-aligned pair of an image sub-prompt and a text sub-prompt, where the former is a single-view observation and the latter is a phrase like ''walk past the chair''. When starting navigation, the instruction-related action prompt set is retrieved from a pre-built action prompt base and passed through a prompt encoder to obtain the prompt feature. Then the prompt feature is concatenated with the original instruction feature and fed to a multi-layer transformer for action prediction. To collect high-quality action prompts into the prompt base, we use the Contrastive Language-Image Pretraining (CLIP) model which has powerful cross-modality alignment ability. A modality alignment loss and a sequential consistency loss are further introduced to enhance the alignment of the action prompt and enforce the agent to focus on the related prompt sequentially. Experimental results on both R2R and RxR show the superiority of ADAPT over state-of-the-art methods.

Medical vision-and-language pre-training (Med-VLP) has shown promising improvements on many downstream medical tasks owing to its applicability to extracting generic representations from medical images and texts. Practically, there exist two typical types, i.e., the fusion-encoder type and the dual-encoder type, depending on whether a heavy fusion module is used. The former is superior at multi-modal tasks owing to the sufficient interaction between modalities; the latter is good at uni-modal and cross-modal tasks due to the single-modality encoding ability. To take advantage of these two types, we propose an effective yet straightforward scheme named PTUnifier to unify the two types. We first unify the input format by introducing visual and textual prompts, which serve as a feature bank that stores the most representative images/texts. By doing so, a single model could serve as a foundation model that processes various tasks adopting different input formats (i.e., image-only, text-only, and image-text-pair). Furthermore, we construct a prompt pool (instead of static ones) to improve diversity and scalability. Experimental results show that our approach achieves state-of-the-art results on a broad range of tasks, spanning uni-modal tasks (i.e., image/text classification and text summarization), cross-modal tasks (i.e., image-to-text generation and image-text/text-image retrieval), and multi-modal tasks (i.e., visual question answering), demonstrating the effectiveness of our approach. Note that the adoption of prompts is orthogonal to most existing Med-VLP approaches and could be a beneficial and complementary extension to these approaches.

Vision-Language Models (VLM) can support clinicians by analyzing medical images and engaging in natural language interactions to assist in diagnostic and treatment tasks. However, VLMs often exhibit "hallucinogenic" behavior, generating textual outputs not grounded in contextual multimodal information. This challenge is particularly pronounced in the medical domain, where we do not only require VLM outputs to be accurate in single interactions but also to be consistent with clinical reasoning and diagnostic pathways throughout multi-turn conversations. For this purpose, we propose a new alignment algorithm that uses symbolic representations of clinical reasoning to ground VLMs in medical knowledge. These representations are utilized to (i) generate GPT-4-guided visual instruction tuning data at scale, simulating clinician-VLM conversations with demonstrations of clinical reasoning, and (ii) create an automatic reward function that evaluates the clinical validity of VLM generations throughout clinician-VLM interactions. Our algorithm eliminates the need for human involvement in training data generation or reward model construction, reducing costs compared to standard reinforcement learning with human feedback (RLHF). We apply our alignment algorithm to develop Dr-LLaVA, a conversational VLM finetuned for analyzing bone marrow pathology slides, demonstrating strong performance in multi-turn medical conversations.

Language models trained on large-scale corpus often generate content that is harmful, toxic, or contrary to human preferences, making their alignment with human values a critical concern. Reinforcement learning from human feedback (RLHF) with algorithms like PPO is a prevalent approach for alignment but is often complex, unstable, and resource-intensive. Recently, ranking-based alignment methods have emerged, offering stability and effectiveness by replacing the RL framework with supervised fine-tuning, but they are costly due to the need for annotated data. Considering that existing large language models (LLMs) like ChatGPT are already relatively well-aligned and cost-friendly, researchers have begun to align the language model with human preference from AI feedback. The common practices, which unidirectionally distill the instruction-following responses from LLMs, are constrained by their bottleneck. Thus we introduce CycleAlign to distill alignment capabilities from parameter-invisible LLMs (black-box) to a parameter-visible model (white-box) in an iterative manner. With in-context learning (ICL) as the core of the cycle, the black-box models are able to rank the model-generated responses guided by human-craft instruction and demonstrations about their preferences. During iterative interaction, the white-box models also have a judgment about responses generated by them. Consequently, the agreement ranking could be viewed as a pseudo label to dynamically update the in-context demonstrations and improve the preference ranking ability of black-box models. Through multiple interactions, the CycleAlign framework could align the white-box model with the black-box model effectively in a low-resource way. Empirical results illustrate that the model fine-tuned by CycleAlign remarkably exceeds existing methods, and achieves the state-of-the-art performance in alignment with human value.

This paper introduces BioVL-QR, a biochemical vision-and-language dataset comprising 23 egocentric experiment videos, corresponding protocols, and vision-and-language alignments. A major challenge in understanding biochemical videos is detecting equipment, reagents, and containers because of the cluttered environment and indistinguishable objects. Previous studies assumed manual object annotation, which is costly and time-consuming. To address the issue, we focus on Micro QR Codes. However, detecting objects using only Micro QR Codes is still difficult due to blur and occlusion caused by object manipulation. To overcome this, we propose an object labeling method combining a Micro QR Code detector with an off-the-shelf hand object detector. As an application of the method and BioVL-QR, we tackled the task of localizing the procedural steps in an instructional video. The experimental results show that using Micro QR Codes and our method improves biochemical video understanding. Data and code are available through https://nishi10mo.github.io/BioVL-QR/

Personalized image generation holds great promise in assisting humans in everyday work and life due to its impressive function in creatively generating personalized content. However, current evaluations either are automated but misalign with humans or require human evaluations that are time-consuming and expensive. In this work, we present DreamBench++, a human-aligned benchmark automated by advanced multimodal GPT models. Specifically, we systematically design the prompts to let GPT be both human-aligned and self-aligned, empowered with task reinforcement. Further, we construct a comprehensive dataset comprising diverse images and prompts. By benchmarking 7 modern generative models, we demonstrate that DreamBench++ results in significantly more human-aligned evaluation, helping boost the community with innovative findings.

Thanks to the large pre-trained vision-language models (VLMs) like CLIP, we can craft a zero-shot classifier by "prompt", e.g., the confidence score of an image being "[CLASS]" can be obtained by using the VLM provided similarity measure between the image and the prompt sentence "a photo of a [CLASS]". Therefore, prompt shows a great potential for fast adaptation of VLMs to downstream tasks if we fine-tune the prompt-based similarity measure. However, we find a common failure that improper fine-tuning may not only undermine the prompt's inherent prediction for the task-related classes, but also for other classes in the VLM vocabulary. Existing methods still address this problem by using traditional anti-overfitting techniques such as early stopping and data augmentation, which lack a principled solution specific to prompt. We present Prompt-aligned Gradient, dubbed ProGrad, to prevent prompt tuning from forgetting the the general knowledge learned from VLMs. In particular, ProGrad only updates the prompt whose gradient is aligned (or non-conflicting) to the "general direction", which is represented as the gradient of the KL loss of the pre-defined prompt prediction. Extensive experiments demonstrate the stronger few-shot generalization ability of ProGrad over state-of-the-art prompt tuning methods. Codes are available at https://github.com/BeierZhu/Prompt-align.

Generating images with a Text-to-Image model often requires multiple trials, where human users iteratively update their prompt based on feedback, namely the output image. Taking inspiration from cognitive work on reference games and dialogue alignment, this paper analyzes the dynamics of the user prompts along such iterations. We compile a dataset of iterative interactions of human users with Midjourney. Our analysis then reveals that prompts predictably converge toward specific traits along these iterations. We further study whether this convergence is due to human users, realizing they missed important details, or due to adaptation to the model's ``preferences'', producing better images for a specific language style. We show initial evidence that both possibilities are at play. The possibility that users adapt to the model's preference raises concerns about reusing user data for further training. The prompts may be biased towards the preferences of a specific model, rather than align with human intentions and natural manner of expression.

Textual-based prompt learning methods primarily employ multiple learnable soft prompts and hard class tokens in a cascading manner as text inputs, aiming to align image and text (category) spaces for downstream tasks. However, current training is restricted to aligning images with predefined known categories and cannot be associated with unknown categories. In this work, we propose utilizing universal attributes as a bridge to enhance the alignment between images and unknown categories. Specifically, we introduce an Attribute-anchored Textual Prompt learning method for vision-language models, named ATPrompt. This approach expands the learning space of soft prompts from the original one-dimensional category level into the multi-dimensional attribute level by incorporating multiple attribute tokens into the learnable soft prompts. Through this modification, we transform the text prompt from a category-centric form to an attribute-category hybrid form. Additionally, we introduce a straightforward differentiable attribute search method to identify representative and suitable attributes for downstream tasks. As an easy-to-use plug-in technique, ATPrompt can seamlessly replace the existing basic prompt format in textual-based methods, providing general improvements at a negligible computational cost. Extensive experiments across 11 datasets validate the effectiveness of our method. Code is publicly available at https://github.com/zhengli97/ATPrompt.

There is an emerging consensus that we need to align AI systems with human values (Gabriel, 2020; Ji et al., 2024), but it remains unclear how to apply this to language models in practice. We split the problem of "aligning to human values" into three parts: first, eliciting values from people; second, reconciling those values into an alignment target for training ML models; and third, actually training the model. In this paper, we focus on the first two parts, and ask the question: what are "good" ways to synthesize diverse human inputs about values into a target for aligning language models? To answer this question, we first define a set of 6 criteria that we believe must be satisfied for an alignment target to shape model behavior in accordance with human values. We then propose a process for eliciting and reconciling values called Moral Graph Elicitation (MGE), which uses a large language model to interview participants about their values in particular contexts; our approach is inspired by the philosophy of values advanced by Taylor (1977), Chang (2004), and others. We trial MGE with a representative sample of 500 Americans, on 3 intentionally divisive prompts (e.g. advice about abortion). Our results demonstrate that MGE is promising for improving model alignment across all 6 criteria. For example, almost all participants (89.1%) felt well represented by the process, and (89%) thought the final moral graph was fair, even if their value wasn't voted as the wisest. Our process often results in "expert" values (e.g. values from women who have solicited abortion advice) rising to the top of the moral graph, without defining who is considered an expert in advance.

Foundation models trained at scale exhibit remarkable emergent behaviors, learning new capabilities beyond their initial training objectives. We find such emergent behaviors in biological vision models via large-scale contrastive vision-language training. To achieve this, we first curate TreeOfLife-200M, comprising 214 million images of living organisms, the largest and most diverse biological organism image dataset to date. We then train BioCLIP 2 on TreeOfLife-200M to distinguish different species. Despite the narrow training objective, BioCLIP 2 yields extraordinary accuracy when applied to various biological visual tasks such as habitat classification and trait prediction. We identify emergent properties in the learned embedding space of BioCLIP 2. At the inter-species level, the embedding distribution of different species aligns closely with functional and ecological meanings (e.g., beak sizes and habitats). At the intra-species level, instead of being diminished, the intra-species variations (e.g., life stages and sexes) are preserved and better separated in subspaces orthogonal to inter-species distinctions. We provide formal proof and analyses to explain why hierarchical supervision and contrastive objectives encourage these emergent properties. Crucially, our results reveal that these properties become increasingly significant with larger-scale training data, leading to a biologically meaningful embedding space.

Text-to-image (T2I) models have achieved remarkable progress, yet they continue to struggle with complex prompts that require simultaneously handling multiple objects, relations, and attributes. Existing inference-time strategies, such as parallel sampling with verifiers or simply increasing denoising steps, can improve prompt alignment but remain inadequate for richly compositional settings where many constraints must be satisfied. Inspired by the success of chain-of-thought reasoning in large language models, we propose an iterative test-time strategy in which a T2I model progressively refines its generations across multiple steps, guided by feedback from a vision-language model as the critic in the loop. Our approach is simple, requires no external tools or priors, and can be flexibly applied to a wide range of image generators and vision-language models. Empirically, we demonstrate consistent gains on image generation across benchmarks: a 16.9% improvement in all-correct rate on ConceptMix (k=7), a 13.8% improvement on T2I-CompBench (3D-Spatial category) and a 12.5% improvement on Visual Jenga scene decomposition compared to compute-matched parallel sampling. Beyond quantitative gains, iterative refinement produces more faithful generations by decomposing complex prompts into sequential corrections, with human evaluators preferring our method 58.7% of the time over 41.3% for the parallel baseline. Together, these findings highlight iterative self-correction as a broadly applicable principle for compositional image generation. Results and visualizations are available at https://iterative-img-gen.github.io/

Large language models (LLMs) are increasingly envisioned as decision-support tools in clinical practice, yet safe clinical reasoning demands integrating heterogeneous knowledge bases -- trials, primary studies, regulatory documents, and cost data -- under strict accuracy constraints. Existing evaluations often rely on synthetic prompts, reduce the task to single-hop factoid queries, or conflate reasoning with open-ended generation, leaving their real-world utility unclear. To close this gap, we present MedBrowseComp, the first benchmark that systematically tests an agent's ability to reliably retrieve and synthesize multi-hop medical facts from live, domain-specific knowledge bases. MedBrowseComp contains more than 1,000 human-curated questions that mirror clinical scenarios where practitioners must reconcile fragmented or conflicting information to reach an up-to-date conclusion. Applying MedBrowseComp to frontier agentic systems reveals performance shortfalls as low as ten percent, exposing a critical gap between current LLM capabilities and the rigor demanded in clinical settings. MedBrowseComp therefore offers a clear testbed for reliable medical information seeking and sets concrete goals for future model and toolchain upgrades. You can visit our project page at: https://moreirap12.github.io/mbc-browse-app/

Self-supervised learning in vision-language processing exploits semantic alignment between imaging and text modalities. Prior work in biomedical VLP has mostly relied on the alignment of single image and report pairs even though clinical notes commonly refer to prior images. This does not only introduce poor alignment between the modalities but also a missed opportunity to exploit rich self-supervision through existing temporal content in the data. In this work, we explicitly account for prior images and reports when available during both training and fine-tuning. Our approach, named BioViL-T, uses a CNN-Transformer hybrid multi-image encoder trained jointly with a text model. It is designed to be versatile to arising challenges such as pose variations and missing input images across time. The resulting model excels on downstream tasks both in single- and multi-image setups, achieving state-of-the-art performance on (I) progression classification, (II) phrase grounding, and (III) report generation, whilst offering consistent improvements on disease classification and sentence-similarity tasks. We release a novel multi-modal temporal benchmark dataset, MS-CXR-T, to quantify the quality of vision-language representations in terms of temporal semantics. Our experimental results show the advantages of incorporating prior images and reports to make most use of the data.

We present an approach of using AI to model and simulate biology and life. Why is it important? Because at the core of medicine, pharmacy, public health, longevity, agriculture and food security, environmental protection, and clean energy, it is biology at work. Biology in the physical world is too complex to manipulate and always expensive and risky to tamper with. In this perspective, we layout an engineering viable approach to address this challenge by constructing an AI-Driven Digital Organism (AIDO), a system of integrated multiscale foundation models, in a modular, connectable, and holistic fashion to reflect biological scales, connectedness, and complexities. An AIDO opens up a safe, affordable and high-throughput alternative platform for predicting, simulating and programming biology at all levels from molecules to cells to individuals. We envision that an AIDO is poised to trigger a new wave of better-guided wet-lab experimentation and better-informed first-principle reasoning, which can eventually help us better decode and improve life.

The challenge of replicating research results has posed a significant impediment to the field of molecular biology. The advent of modern intelligent systems has led to notable progress in various domains. Consequently, we embarked on an investigation of intelligent monitoring systems as a means of tackling the issue of the reproducibility crisis. Specifically, we first curate a comprehensive multimodal dataset, named ProBio, as an initial step towards this objective. This dataset comprises fine-grained hierarchical annotations intended for the purpose of studying activity understanding in BioLab. Next, we devise two challenging benchmarks, transparent solution tracking and multimodal action recognition, to emphasize the unique characteristics and difficulties associated with activity understanding in BioLab settings. Finally, we provide a thorough experimental evaluation of contemporary video understanding models and highlight their limitations in this specialized domain to identify potential avenues for future research. We hope ProBio with associated benchmarks may garner increased focus on modern AI techniques in the realm of molecular biology.

Large language models (LLMs) underpin applications in code generation, mathematical reasoning, and agent-based workflows. In practice, systems access LLMs via commercial APIs or open-source deployments, and the model landscape (e.g., GPT, Claude, Llama) evolves rapidly. This rapid evolution forces frequent model switches driven by capability, cost, deployment constraints, and privacy. Yet prompts are highly model-sensitive: reusing a prompt engineered for one model on another often yields substantially worse performance than a prompt optimized for the target model. We term this phenomenon Model Drifting. Through extensive empirical analysis across diverse LLM configurations, we show that model drifting is both common and severe. To address this challenge, we introduce PromptBridge, a training-free framework that preserves prompt effectiveness under model switches, enabling cross-model prompt transfer without costly per-task or per-model re-optimization. PromptBridge requires only a small set of alignment tasks for calibration. It first applies Model-Adaptive Reflective Prompt Evolution (MAP-RPE) to obtain task- and model-specific optimal prompts via iterative reflective refinement and quantitative evaluation. Using the resulting calibrated prompt pairs for the source and target models, PromptBridge learns a cross-model prompt mapping. At test time, i.e., for an unseen task, given a source-model prompt, this mapping directly produces an optimized prompt for the target model. Experiments in single-agent and multi-agent settings show that PromptBridge consistently improves downstream accuracy while reducing migration effort. The code will be available soon.

Recent advancements in biological research leverage the integration of molecules, proteins, and natural language to enhance drug discovery. However, current models exhibit several limitations, such as the generation of invalid molecular SMILES, underutilization of contextual information, and equal treatment of structured and unstructured knowledge. To address these issues, we propose BioT5, a comprehensive pre-training framework that enriches cross-modal integration in biology with chemical knowledge and natural language associations. BioT5 utilizes SELFIES for 100% robust molecular representations and extracts knowledge from the surrounding context of bio-entities in unstructured biological literature. Furthermore, BioT5 distinguishes between structured and unstructured knowledge, leading to more effective utilization of information. After fine-tuning, BioT5 shows superior performance across a wide range of tasks, demonstrating its strong capability of capturing underlying relations and properties of bio-entities. Our code is available at https://github.com/QizhiPei/BioT5{Github}.

Personalized nutrition intervention for patients with multimorbidity is critical for improving health outcomes, yet remains challenging because it requires the simultaneous integration of heterogeneous clinical conditions, medications, and dietary guidelines. Single-agent large language models (LLMs) often suffer from context overload and attention dilution when processing such high-dimensional patient profiles. We introduce NutriOrion, a hierarchical multi-agent framework with a parallel-then-sequential reasoning topology. NutriOrion decomposes nutrition planning into specialized domain agents with isolated contexts to mitigate anchoring bias, followed by a conditional refinement stage. The framework includes a multi-objective prioritization algorithm to resolve conflicting dietary requirements and a safety constraint mechanism that injects pharmacological contraindications as hard negative constraints during synthesis, ensuring clinical validity by construction rather than post-hoc filtering. For clinical interoperability, NutriOrion maps synthesized insights into the ADIME standard and FHIR R4 resources. Evaluated on 330 stroke patients with multimorbidity, NutriOrion outperforms multiple baselines, including GPT-4.1 and alternative multi-agent architectures. It achieves a 12.1 percent drug-food interaction violation rate, demonstrates strong personalization with negative correlations (-0.26 to -0.35) between patient biomarkers and recommended risk nutrients, and yields clinically meaningful dietary improvements, including a 167 percent increase in fiber and a 27 percent increase in potassium, alongside reductions in sodium (9 percent) and sugars (12 percent).

Aligning Large Language Models (LLMs) traditionally relies on costly training and human preference annotations. Self-alignment seeks to reduce these expenses by enabling models to align themselves. To further lower costs and achieve alignment without any expensive tuning or annotations, we introduce a new tuning-free approach for self-alignment, Dynamic Rewarding with Prompt Optimization (DRPO). Our approach leverages a search-based optimization framework that allows LLMs to iteratively self-improve and craft the optimal alignment instructions, all without additional training or human intervention. The core of DRPO is a dynamic rewarding mechanism, which identifies and rectifies model-specific alignment weaknesses, allowing LLMs to adapt efficiently to diverse alignment challenges. Empirical evaluations on eight recent LLMs, both open- and closed-sourced, demonstrate that DRPO significantly enhances alignment performance, with base models outperforming their SFT/RLHF-tuned counterparts. Moreover, the prompts automatically optimized by DRPO surpass those curated by human experts, further validating the effectiveness of our approach. Our findings highlight the great potential of current LLMs to achieve adaptive self-alignment through inference-time optimization, complementing tuning-based alignment methods.

Large reasoning models have recently made significant strides in mathematical and code reasoning, yet their success has not transferred smoothly to the medical domain. While multiple factors contribute to this disparity, a critical issue is the inadequate focus on the quality of intermediate reflection steps, which is particularly crucial in high-stakes medical scenarios. To address this challenge, we propose Med-REFL, a \textbf{Med}ical \textbf{R}easoning \textbf{E}nhancement via self-corrected \textbf{F}ine-grained ref\textbf{L}ection. Our method leverages a tree-of-thought approach to decompose medical questions into fine-grained reasoning paths, quantitatively evaluating each step and its subsequent reflections. These assessments enable automatic construction of direct preference optimization data, reducing reliance on expensive expert annotations while guiding models to identify and correct reasoning errors. Experimental results on the MedQA-USMLE benchmark demonstrate Med-REFL achieves consistent improvements, with average gains up to 4.11\%. Notably, it further boosts the state-of-the-art performance of 7B/8B models by an additional 4.13\%. Furthermore, Med-REFL exhibits strong generalization capabilities and robustness across several challenging medical question-answering datasets. Our work illustrates that prioritizing reflection quality leads to more accurate and trustworthy reasoning in medical AI applications. Checkpoints, code, and data can be found https://github.com/TianYin123/Med-REFL{here}.

The transcriptional response to genetic perturbation reveals fundamental insights into complex cellular systems. While current approaches have made progress in predicting genetic perturbation responses, they provide limited biological understanding and cannot systematically refine existing knowledge. Overcoming these limitations requires an end-to-end integration of data-driven learning and existing knowledge. However, this integration is challenging due to inconsistencies between data and knowledge bases, such as noise, misannotation, and incompleteness. To address this challenge, we propose ALIGNED (Adaptive aLignment for Inconsistent Genetic kNowledgE and Data), a neuro-symbolic framework based on the Abductive Learning (ABL) paradigm. This end-to-end framework aligns neural and symbolic components and performs systematic knowledge refinement. We introduce a balanced consistency metric to evaluate the predictions' consistency against both data and knowledge. Our results show that ALIGNED outperforms state-of-the-art methods by achieving the highest balanced consistency, while also re-discovering biologically meaningful knowledge. Our work advances beyond existing methods to enable both the transparency and the evolution of mechanistic biological understanding.

Drug toxicity remains a major challenge in pharmaceutical development. Recent machine learning models have improved in silico toxicity prediction, but their reliance on annotated data and lack of interpretability limit their applicability. This limits their ability to capture organ-specific toxicities driven by complex biological mechanisms. Large language models (LLMs) offer a promising alternative through step-by-step reasoning and integration of textual data, yet prior approaches lack biological context and transparent rationale. To address this issue, we propose CoTox, a novel framework that integrates LLM with chain-of-thought (CoT) reasoning for multi-toxicity prediction. CoTox combines chemical structure data, biological pathways, and gene ontology (GO) terms to generate interpretable toxicity predictions through step-by-step reasoning. Using GPT-4o, we show that CoTox outperforms both traditional machine learning and deep learning model. We further examine its performance across various LLMs to identify where CoTox is most effective. Additionally, we find that representing chemical structures with IUPAC names, which are easier for LLMs to understand than SMILES, enhances the model's reasoning ability and improves predictive performance. To demonstrate its practical utility in drug development, we simulate the treatment of relevant cell types with drug and incorporated the resulting biological context into the CoTox framework. This approach allow CoTox to generate toxicity predictions aligned with physiological responses, as shown in case study. This result highlights the potential of LLM-based frameworks to improve interpretability and support early-stage drug safety assessment. The code and prompt used in this work are available at https://github.com/dmis-lab/CoTox.

User prompts for generative AI models are often underspecified, leading to sub-optimal responses. This problem is particularly evident in text-to-image (T2I) generation, where users commonly struggle to articulate their precise intent. This disconnect between the user's vision and the model's interpretation often forces users to painstakingly and repeatedly refine their prompts. To address this, we propose a design for proactive T2I agents equipped with an interface to (1) actively ask clarification questions when uncertain, and (2) present their understanding of user intent as an understandable belief graph that a user can edit. We build simple prototypes for such agents and verify their effectiveness through both human studies and automated evaluation. We observed that at least 90% of human subjects found these agents and their belief graphs helpful for their T2I workflow. Moreover, we develop a scalable automated evaluation approach using two agents, one with a ground truth image and the other tries to ask as few questions as possible to align with the ground truth. On DesignBench, a benchmark we created for artists and designers, the COCO dataset (Lin et al., 2014), and ImageInWords (Garg et al., 2024), we observed that these T2I agents were able to ask informative questions and elicit crucial information to achieve successful alignment with at least 2 times higher VQAScore (Lin et al., 2024) than the standard single-turn T2I generation. Demo: https://github.com/google-deepmind/proactive_t2i_agents.

Facial personalization represents a crucial downstream task in the domain of text-to-image generation. To preserve identity fidelity while ensuring alignment with user-defined prompts, current mainstream frameworks for facial personalization predominantly employ identity embedding mechanisms to associate identity information with textual embeddings. However, our experiments show that identity embeddings compromise the effectiveness of other tokens within the prompt, thereby hindering high prompt consistency, particularly when prompts involve multiple facial attributes. Moreover, previous works overlook the fact that their corresponding foundation models hold great potential to generate faces aligning to prompts well and can be easily leveraged to cure these ill-aligned attributes in personalized models. Building upon these insights, we propose FreeCure, a training-free framework that harnesses the intrinsic knowledge from the foundation models themselves to improve the prompt consistency of personalization models. First, by extracting cross-attention and semantic maps from the denoising process of foundation models, we identify easily localized attributes (e.g., hair, accessories, etc). Second, we enhance multiple attributes in the outputs of personalization models through a novel noise-blending strategy coupled with an inversion-based process. Our approach offers several advantages: it eliminates the need for training; it effectively facilitates the enhancement for a wide array of facial attributes in a non-intrusive manner; and it can be seamlessly integrated into existing popular personalization models. FreeCure has demonstrated significant improvements in prompt consistency across a diverse set of state-of-the-art facial personalization models while maintaining the integrity of original identity fidelity.

Recent advancements in Text-to-Image (T2I) diffusion models have demonstrated impressive success in generating high-quality images with zero-shot generalization capabilities. Yet, current models struggle to closely adhere to prompt semantics, often misrepresenting or overlooking specific attributes. To address this, we propose a simple, training-free approach that modulates the guidance direction of diffusion models during inference. We first decompose the prompt semantics into a set of concepts, and monitor the guidance trajectory in relation to each concept. Our key observation is that deviations in model's adherence to prompt semantics are highly correlated with divergence of the guidance from one or more of these concepts. Based on this observation, we devise a technique to steer the guidance direction towards any concept from which the model diverges. Extensive experimentation validates that our method improves the semantic alignment of images generated by diffusion models in response to prompts. Project page is available at: https://korguy.github.io/

Conversational generative AI has demonstrated remarkable promise for empowering biomedical practitioners, but current investigations focus on unimodal text. Multimodal conversational AI has seen rapid progress by leveraging billions of image-text pairs from the public web, but such general-domain vision-language models still lack sophistication in understanding and conversing about biomedical images. In this paper, we propose a cost-efficient approach for training a vision-language conversational assistant that can answer open-ended research questions of biomedical images. The key idea is to leverage a large-scale, broad-coverage biomedical figure-caption dataset extracted from PubMed Central, use GPT-4 to self-instruct open-ended instruction-following data from the captions, and then fine-tune a large general-domain vision-language model using a novel curriculum learning method. Specifically, the model first learns to align biomedical vocabulary using the figure-caption pairs as is, then learns to master open-ended conversational semantics using GPT-4 generated instruction-following data, broadly mimicking how a layperson gradually acquires biomedical knowledge. This enables us to train a Large Language and Vision Assistant for BioMedicine (LLaVA-Med) in less than 15 hours (with eight A100s). LLaVA-Med exhibits excellent multimodal conversational capability and can follow open-ended instruction to assist with inquiries about a biomedical image. On three standard biomedical visual question answering datasets, LLaVA-Med outperforms previous supervised state-of-the-art on certain metrics. To facilitate biomedical multimodal research, we will release our instruction-following data and the LLaVA-Med model.

With the growing popularity of personalized human content creation and sharing, there is a rising demand for advanced techniques in customized human image generation. However, current methods struggle to simultaneously maintain the fidelity of human identity and ensure the consistency of textual prompts, often resulting in suboptimal outcomes. This shortcoming is primarily due to the lack of effective constraints during the simultaneous integration of visual and textual prompts, leading to unhealthy mutual interference that compromises the full expression of both types of input. Building on prior research that suggests visual and textual conditions influence different regions of an image in distinct ways, we introduce a novel Dual-Pathway Adapter (DP-Adapter) to enhance both high-fidelity identity preservation and textual consistency in personalized human image generation. Our approach begins by decoupling the target human image into visually sensitive and text-sensitive regions. For visually sensitive regions, DP-Adapter employs an Identity-Enhancing Adapter (IEA) to preserve detailed identity features. For text-sensitive regions, we introduce a Textual-Consistency Adapter (TCA) to minimize visual interference and ensure the consistency of textual semantics. To seamlessly integrate these pathways, we develop a Fine-Grained Feature-Level Blending (FFB) module that efficiently combines hierarchical semantic features from both pathways, resulting in more natural and coherent synthesis outcomes. Additionally, DP-Adapter supports various innovative applications, including controllable headshot-to-full-body portrait generation, age editing, old-photo to reality, and expression editing.

We propose a novel application of prompting Pre-trained Language Models (PLMs) to generate analogies and study how to design effective prompts for two task settings: generating a source concept analogous to a given target concept (aka Analogous Concept Generation or ACG), and generating an explanation of the similarity between a given pair of target concept and source concept (aka Analogous Explanation Generation or AEG). We found that it is feasible to prompt InstructGPT to generate meaningful analogies and the best prompts tend to be precise imperative statements especially with a low temperature setting. We also systematically analyzed the sensitivity of the InstructGPT model to prompt design, temperature, and injected spelling errors, and found that the model is particularly sensitive to certain variations (e.g., questions vs. imperative statements). Further, we conducted human evaluation on 1.4k of the generated analogies and found that the quality of generations varies substantially by model size. The largest InstructGPT model can achieve human-level performance at generating meaningful analogies for a given target while there is still room for improvement on the AEG task.

In the era of foundation models, CLIP has emerged as a powerful tool for aligning text and visual modalities into a common embedding space. However, the alignment objective used to train CLIP often results in subpar visual features for fine-grained tasks. In contrast, SSL-pretrained models like DINO excel at extracting rich visual features due to their specialized training paradigm. Yet, these SSL models require an additional supervised linear probing step, which relies on fully labeled data which is often expensive and difficult to obtain at scale. In this paper, we propose a label-free prompt-tuning method that leverages the rich visual features of self-supervised learning models (DINO) and the broad textual knowledge of large language models (LLMs) to largely enhance CLIP-based image classification performance using unlabeled images. Our approach unfolds in three key steps: (1) We generate robust textual feature embeddings that more accurately represent object classes by leveraging class-specific descriptions from LLMs, enabling more effective zero-shot classification compared to CLIP's default name-specific prompts. (2) These textual embeddings are then used to produce pseudo-labels to train an alignment module that integrates the complementary strengths of LLM description-based textual embeddings and DINO's visual features. (3) Finally, we prompt-tune CLIP's vision encoder through DINO-assisted supervision using the trained alignment module. This three-step process allows us to harness the best of visual and textual foundation models, resulting in a powerful and efficient approach that surpasses state-of-the-art label-free classification methods. Notably, our framework, NoLA (No Labels Attached), achieves an average absolute gain of 3.6% over the state-of-the-art LaFter across 11 diverse image classification datasets.

Diffusion models have become a powerful backbone for text-to-image generation, producing high-quality visuals from natural language prompts. However, when prompts involve multiple objects alongside global or local style instructions, the outputs often drift in style and lose spatial coherence, limiting their reliability for controlled, style-consistent scene generation. We present Local Prompt Adaptation (LPA), a lightweight, training-free method that splits the prompt into content and style tokens, then injects them selectively into the U-Net's attention layers at chosen timesteps. By conditioning object tokens early and style tokens later in the denoising process, LPA improves both layout control and stylistic uniformity without additional training cost. We conduct extensive ablations across parser settings and injection windows, finding that the best configuration -- lpa late only with a 300-650 step window -- delivers the strongest balance of prompt alignment and style consistency. On the T2I benchmark, LPA improves CLIP-prompt alignment over vanilla SDXL by +0.41% and over SD1.5 by +0.34%, with no diversity loss. On our custom 50-prompt style-rich benchmark, LPA achieves +0.09% CLIP-prompt and +0.08% CLIP-style gains over baseline. Our method is model-agnostic, easy to integrate, and requires only a single configuration change, making it a practical choice for controllable, style-consistent multi-object generation.

Prompt design plays a crucial role in text-to-video (T2V) generation, yet user-provided prompts are often short, unstructured, and misaligned with training data, limiting the generative potential of diffusion-based T2V models. We present RAPO++, a cross-stage prompt optimization framework that unifies training-data--aligned refinement, test-time iterative scaling, and large language model (LLM) fine-tuning to substantially improve T2V generation without modifying the underlying generative backbone. In Stage 1, Retrieval-Augmented Prompt Optimization (RAPO) enriches user prompts with semantically relevant modifiers retrieved from a relation graph and refactors them to match training distributions, enhancing compositionality and multi-object fidelity. Stage 2 introduces Sample-Specific Prompt Optimization (SSPO), a closed-loop mechanism that iteratively refines prompts using multi-source feedback -- including semantic alignment, spatial fidelity, temporal coherence, and task-specific signals such as optical flow -- yielding progressively improved video generation quality. Stage 3 leverages optimized prompt pairs from SSPO to fine-tune the rewriter LLM, internalizing task-specific optimization patterns and enabling efficient, high-quality prompt generation even before inference. Extensive experiments across five state-of-the-art T2V models and five benchmarks demonstrate that RAPO++ achieves significant gains in semantic alignment, compositional reasoning, temporal stability, and physical plausibility, outperforming existing methods by large margins. Our results highlight RAPO++ as a model-agnostic, cost-efficient, and scalable solution that sets a new standard for prompt optimization in T2V generation. The code is available at https://github.com/Vchitect/RAPO.

Natural-language prompts have recently been used to coax pretrained language models into performing other AI tasks, using a fill-in-the-blank paradigm (Petroni et al., 2019) or a few-shot extrapolation paradigm (Brown et al., 2020). For example, language models retain factual knowledge from their training corpora that can be extracted by asking them to "fill in the blank" in a sentential prompt. However, where does this prompt come from? We explore the idea of learning prompts by gradient descent -- either fine-tuning prompts taken from previous work, or starting from random initialization. Our prompts consist of "soft words," i.e., continuous vectors that are not necessarily word type embeddings from the language model. Furthermore, for each task, we optimize a mixture of prompts, learning which prompts are most effective and how to ensemble them. Across multiple English LMs and tasks, our approach hugely outperforms previous methods, showing that the implicit factual knowledge in language models was previously underestimated. Moreover, this knowledge is cheap to elicit: random initialization is nearly as good as informed initialization.

We report a flexible language-model based deep learning strategy, applied here to solve complex forward and inverse problems in protein modeling, based on an attention neural network that integrates transformer and graph convolutional architectures in a causal multi-headed graph mechanism, to realize a generative pretrained model. The model is applied to predict secondary structure content (per-residue level and overall content), protein solubility, and sequencing tasks. Further trained on inverse tasks, the model is rendered capable of designing proteins with these properties as target features. The model is formulated as a general framework, completely prompt-based, and can be adapted for a variety of downstream tasks. We find that adding additional tasks yields emergent synergies that the model exploits in improving overall performance, beyond what would be possible by training a model on each dataset alone. Case studies are presented to validate the method, yielding protein designs specifically focused on structural proteins, but also exploring the applicability in the design of soluble, antimicrobial biomaterials. While our model is trained to ultimately perform 8 distinct tasks, with available datasets it can be extended to solve additional problems. In a broader sense, this work illustrates a form of multiscale modeling that relates a set of ultimate building blocks (here, byte-level utf8 characters) to complex output. This materiomic scheme captures complex emergent relationships between universal building block and resulting properties via a synergizing learning capacity to express a set of potentialities embedded in the knowledge used in training, via the interplay of universality and diversity.

Fine-tuning large language models on narrow datasets can cause them to develop broadly misaligned behaviours: a phenomena known as emergent misalignment. However, the mechanisms underlying this misalignment, and why it generalizes beyond the training domain, are poorly understood, demonstrating critical gaps in our knowledge of model alignment. In this work, we train and study a minimal model organism which uses just 9 rank-1 adapters to emergently misalign Qwen2.5-14B-Instruct. Studying this, we find that different emergently misaligned models converge to similar representations of misalignment. We demonstrate this convergence by extracting a 'misalignment direction' from one fine-tuned model's activations, and using it to effectively ablate misaligned behaviour from fine-tunes using higher dimensional LoRAs and different datasets. Leveraging the scalar hidden state of rank-1 LoRAs, we further present a set of experiments for directly interpreting the fine-tuning adapters, showing that six contribute to general misalignment, while two specialise for misalignment in just the fine-tuning domain. Emergent misalignment is a particularly salient example of undesirable and unexpected model behaviour and by advancing our understanding of the mechanisms behind it, we hope to move towards being able to better understand and mitigate misalignment more generally.

Large language models (LLMs) and vision-language models (VLMs) have the potential to transform biological research by enabling autonomous experimentation. Yet, their application remains constrained by rigid protocol design, limited adaptability to dynamic lab conditions, inadequate error handling, and high operational complexity. Here we introduce BioMARS (Biological Multi-Agent Robotic System), an intelligent platform that integrates LLMs, VLMs, and modular robotics to autonomously design, plan, and execute biological experiments. BioMARS uses a hierarchical architecture: the Biologist Agent synthesizes protocols via retrieval-augmented generation; the Technician Agent translates them into executable robotic pseudo-code; and the Inspector Agent ensures procedural integrity through multimodal perception and anomaly detection. The system autonomously conducts cell passaging and culture tasks, matching or exceeding manual performance in viability, consistency, and morphological integrity. It also supports context-aware optimization, outperforming conventional strategies in differentiating retinal pigment epithelial cells. A web interface enables real-time human-AI collaboration, while a modular backend allows scalable integration with laboratory hardware. These results highlight the feasibility of generalizable, AI-driven laboratory automation and the transformative role of language-based reasoning in biological research.

Large Language Models (LLMs), particularly those similar to ChatGPT, have significantly influenced the field of Natural Language Processing (NLP). While these models excel in general language tasks, their performance in domain-specific downstream tasks such as biomedical and clinical Named Entity Recognition (NER), Relation Extraction (RE), and Medical Natural Language Inference (NLI) is still evolving. In this context, our study investigates the potential of instruction tuning for biomedical language processing, applying this technique to two general LLMs of substantial scale. We present a comprehensive, instruction-based model trained on a dataset that consists of approximately 200,000 instruction-focused samples. This dataset represents a carefully curated compilation of existing data, meticulously adapted and reformatted to align with the specific requirements of our instruction-based tasks. This initiative represents an important step in utilising such models to achieve results on par with specialised encoder-only models like BioBERT and BioClinicalBERT for various classical biomedical NLP tasks. Our work includes an analysis of the dataset's composition and its impact on model performance, providing insights into the intricacies of instruction tuning. By sharing our codes, models, and the distinctively assembled instruction-based dataset, we seek to encourage ongoing research and development in this area.

Recent advances in text-to-image (T2I) generation have led to impressive visual results. However, these models still face significant challenges when handling complex prompt, particularly those involving multiple subjects with distinct attributes. Inspired by the human drawing process, which first outlines the composition and then incrementally adds details, we propose Detail++, a training-free framework that introduces a novel Progressive Detail Injection (PDI) strategy to address this limitation. Specifically, we decompose a complex prompt into a sequence of simplified sub-prompts, guiding the generation process in stages. This staged generation leverages the inherent layout-controlling capacity of self-attention to first ensure global composition, followed by precise refinement. To achieve accurate binding between attributes and corresponding subjects, we exploit cross-attention mechanisms and further introduce a Centroid Alignment Loss at test time to reduce binding noise and enhance attribute consistency. Extensive experiments on T2I-CompBench and a newly constructed style composition benchmark demonstrate that Detail++ significantly outperforms existing methods, particularly in scenarios involving multiple objects and complex stylistic conditions.

Large Language Models (LLMs) demonstrate remarkable versatility in various NLP tasks but encounter distinct challenges in biomedical due to the complexities of language and data scarcity. This paper investigates LLMs application in the biomedical domain by exploring strategies to enhance their performance for the NER task. Our study reveals the importance of meticulously designed prompts in the biomedical. Strategic selection of in-context examples yields a marked improvement, offering ~15-20\% increase in F1 score across all benchmark datasets for biomedical few-shot NER. Additionally, our results indicate that integrating external biomedical knowledge via prompting strategies can enhance the proficiency of general-purpose LLMs to meet the specialized needs of biomedical NER. Leveraging a medical knowledge base, our proposed method, DiRAG, inspired by Retrieval-Augmented Generation (RAG), can boost the zero-shot F1 score of LLMs for biomedical NER. Code is released at https://github.com/masoud-monajati/LLM_Bio_NER