Structure-based RNA Design by Step-wise Optimization of Latent Diffusion Model

RNA inverse folding, designing sequences to form specific 3D structures, is critical for therapeutics, gene regulation, and synthetic biology. Current methods, focused on sequence recovery, struggle to address structural objectives like secondary structure consistency (SS), minimum free energy (MFE), and local distance difference test (LDDT), leading to suboptimal structural accuracy. To tackle this, we propose a reinforcement learning (RL) framework integrated with a latent diffusion model (LDM). Drawing inspiration from the success of diffusion models in RNA inverse folding, which adeptly model complex sequence-structure interactions, we develop an LDM incorporating pre-trained RNA-FM embeddings from a large-scale RNA model. These embeddings capture co-evolutionary patterns, markedly improving sequence recovery accuracy. However, existing approaches, including diffusion-based methods, cannot effectively handle non-differentiable structural objectives. By contrast, RL excels in this task by using policy-driven reward optimization to navigate complex, non-gradient-based objectives, offering a significant advantage over traditional methods. In summary, we propose the Step-wise Optimization of Latent Diffusion Model (SOLD), a novel RL framework that optimizes single-step noise without sampling the full diffusion trajectory, achieving efficient refinement of multiple structural objectives. Experimental results demonstrate SOLD surpasses its LDM baseline and state-of-the-art methods across all metrics, establishing a robust framework for RNA inverse folding with profound implications for biotechnological and therapeutic applications.

Contrastive Learning Guided Latent Diffusion Model for Image-to-Image Translation

The diffusion model has demonstrated superior performance in synthesizing diverse and high-quality images for text-guided image translation. However, there remains room for improvement in both the formulation of text prompts and the preservation of reference image content. First, variations in target text prompts can significantly influence the quality of the generated images, and it is often challenging for users to craft an optimal prompt that fully captures the content of the input image. Second, while existing models can introduce desired modifications to specific regions of the reference image, they frequently induce unintended alterations in areas that should remain unchanged. To address these challenges, we propose pix2pix-zeroCon, a zero-shot diffusion-based method that eliminates the need for additional training by leveraging patch-wise contrastive loss. Specifically, we automatically determine the editing direction in the text embedding space based on the reference image and target prompts. Furthermore, to ensure precise content and structural preservation in the edited image, we introduce cross-attention guiding loss and patch-wise contrastive loss between the generated and original image embeddings within a pre-trained diffusion model. Notably, our approach requires no additional training and operates directly on a pre-trained text-to-image diffusion model. Extensive experiments demonstrate that our method surpasses existing models in image-to-image translation, achieving enhanced fidelity and controllability.

Robust kernel-free quadratic surface twin support vector machine with capped $L_1$-norm distance metric

Twin support vector machine (TSVM) is a very classical and practical classifier for pattern classification. However, the traditional TSVM has two limitations. Firstly, it uses the L_2-norm distance metric that leads to its sensitivity to outliers. Second, it needs to select the appropriate kernel function and the kernel parameters for nonlinear classification. To effectively avoid these two problems, this paper proposes a robust capped L_1-norm kernel-free quadratic surface twin support vector machine (CL_1QTSVM). The strengths of our model are briefly summarized as follows. 1) The robustness of our model is further improved by employing the capped L_1 norm distance metric. 2) Our model is a kernel-free method that avoids the time-consuming process of selecting appropriate kernel functions and kernel parameters. 3) The introduction of L_2-norm regularization term to improve the generalization ability of the model. 4) To efficiently solve the proposed model, an iterative algorithm is developed. 5) The convergence, time complexity and existence of locally optimal solutions of the developed algorithms are further discussed. Numerical experiments on numerous types of datasets validate the classification performance and robustness of the proposed model.