A Bio-Conjugated Fullerene as a Subcellular-Targeted and Multifaceted Phototheranostic Agent

Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C₇₀@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C₇₀@lysozyme are confirmed using UV-visible and 2D ¹H, ¹⁵N NMR spectroscopy. The excellent imaging contrast of C₇₀@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C₇₀@lysozyme and its ability to initiate cell death by means of singlet oxygen (¹O₂) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C₇₀@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications.     

Boccia game simulator: Serious game adapted for people with disabilities

Integration in the world of sport is one way for individuals with disabilities or motor disorders to feel more socially integrated, independent, and confident. Boccia is a Paralympic sport, which is increasingly getting more attention around the world. These facts have contributed to the objectives of this work. Including it in the serious games category enables to develop and rehabilitate the cognitive capabilities. The main focus was BC3 classification athletes (users with limited motor characteristics that require the use of an assistive device—a ramp, in this case). This paper describes a realistic Boccia game simulator adapted for people with disabilities that integrates a set of features that includes real physics and social features. These features can be used to enhance the interest of nonpractitioners of the sport and to improve the training conditions. The official Boccia regulation was added to the design of the simulator. The usability and approximation to the reality of the simulator were tested and validated based on the tests performed and data collected via a survey of users with no motor or psychological disorders. Realism and usability rating was almost excellent, and good results were achieved at the assessment of the game experience.     

A Versatile Theranostic Nanoemulsion for Architecture‐Dependent Multimodal Imaging and Dually Augmented Photodynamic Therapy

To design a clinically translatable nanomedicine for photodynamic theranostics, the ingredients should be carefully considered. A high content of nanocarriers may cause extra toxicity in metabolism, and multiple theranostic agents would complicate the preparation process. These issues would be of less concern if the nanocarrier itself has most of the theranostic functions. In this work, a poly(ethylene glycol)‐boron dipyrromethene amphiphile (PEG‐F₅₄‐BODIPY) with 54 fluorine‐19 (¹⁹F) is synthesized and employed to emulsify perfluorohexane (PFH) into a theranostic nanoemulsion (PFH@PEG‐F₅₄‐BODIPY). The as‐prepared PFH@PEG‐F₅₄‐BODIPY can perform architecture‐dependent fluorescence/photoacoustic/¹⁹F magnetic resonance multimodal imaging, providing more information about the in vivo structure evolution of nanomedicine. Importantly, this nanoemulsion significantly enhances the therapeutic effect of BODIPY through both the high oxygen dissolving capability and less self‐quenching of BODIPY molecules. More interestingly, PFH@PEG‐F₅₄‐BODIPY shows high level of tumor accumulation and long tumor retention time, allowing a repeated light irradiation after a single‐dose intravenous injection. The “all‐in‐one” photodynamic theranostic nanoemulsion has simple composition, remarkable theranostic efficacy, and novel treatment pattern, and thus presents an intriguing avenue to developing clinically translatable theranostic agents.     

Soft,Implantable Bioelectronic Interfaces for Translational Research

The convergence of materials science, electronics, and biology, namely bioelectronic interfaces, leads novel and precise communication with biological tissue, particularly with the nervous system. However, the translation of lab-based innovation toward clinical use calls for further advances in materials, manufacturing and characterization paradigms, and design rules. Herein, a translational framework engineered to accelerate the deployment of microfabricated interfaces for translational research is proposed and applied to the soft neurotechnology called electronic dura mater, e-dura. Anatomy, implant function, and surgical procedure guide the system design. A high-yield, silicone-on-silicon wafer process is developed to ensure reproducible characteristics of the electrodes. A biomimetic multimodal platform that replicates surgical insertion in an anatomy-based model applies physiological movement, emulates therapeutic use of the electrodes, and enables advanced validation and rapid optimization in vitro of the implants. Functionality of scaled e-dura is confirmed in nonhuman primates, where epidural neuromodulation of the spinal cord activates selective groups of muscles in the upper limbs with unmet precision. Performance stability is controlled over 6 weeks in vivo. The synergistic steps of design, fabrication, and biomimetic in vitro validation and in vivo evaluation in translational animal models are of general applicability and answer needs in multiple bioelectronic designs and medical technologies.     

Electromagnetic silicon MEMS resonator

We have fabricated a silicon MEMS resonator aiming at multimodal sensors, and evaluated vibration characteristics by electromagnetic drive and induced electromotive force detection. The resonance frequency of the driving voltage of 0.6 Vpp shows torsional vibration of approximately 87 kHz, and the resonance frequency is shifted toward the low‐frequency side as the driving voltage increases. Resonance characteristics due to temperature change and film stress were evaluated.     

Revealing Nanomechanical Domains and Their Transient Behavior in Mixed-Halide Perovskite Films

Halide perovskites are a versatile class of semiconductors employed for high performance emerging optoelectronic devices, including flexoelectric systems, yet the influence of their ionic nature on their mechanical behavior is still to be understood. Here, a combination of atomic-force, optical, and compositional X-ray microscopy techniques is employed to shed light on the mechanical properties of halide perovskite films at the nanoscale. Mechanical domains within and between morphological grains, enclosed by mechanical boundaries of higher Young's Modulus (YM) than the bulk parent material, are revealed. These mechanical boundaries are associated with the presence of bromide-rich clusters as visualized by nano-X-ray fluorescence mapping. Stiffer regions are specifically selectively modified upon light soaking the sample, resulting in an overall homogenization of the mechanical properties toward the bulk YM. This behavior is attributed to light-induced ion migration processes that homogenize the local chemical distribution, which is accompanied by photobrightening of the photoluminescence within the same region. This work highlights critical links between mechanical, chemical, and optoelectronic characteristics in this family of perovskites, and demonstrates the potential of combinational imaging studies to understand and design halide perovskite films for emerging applications such as photoflexoelectricity.     

区域运输通道网络设计研究

运用离散优化方法,研究区域内各组团间运输通道网络优化设计问题,设定运输通道供给能力以及通道在区域之间的运输时间约束,构造综合运输通道投资建设总费用的优化模型,考虑各种运输通道的单位投资建设费用和建设长度的最优问题;利用综合运输通道的特点和区域组团网络结构进行算法设计,并给出最优解的多方案求解步骤;针对大规模节点采用遗传算法进行求解可以提高求解效率;通过一个算例,对模型和算法的可行性和有效性进行验证,说明该算法可得到综合运输通道的最优投资方案,使综合运输通道满足规划年的客货运需求,以及各种运输方式的平均出行时间满足要求,分析说明客货运输需求与运输通道建设的关系,结果表明提出的模型与算法对交通投资项目提供较好的辅助决策支持。     

视觉语言多模态预训练综述

在多模态机器学习领域,为特定任务而制作的人工标注数据昂贵,且不同任务难以进行迁移,从而需要大量重新训练,导致训练多个任务时效率低下、资源浪费。预训练模型通过以自监督为代表的方式进行大规模数据训练,对数据集中不同模态的信息进行提取和融合,以学习其中蕴涵的通用知识表征,从而服务于广泛的相关下游视觉语言多模态任务,这一方法逐渐成为人工智能各领域的主流方法。依靠互联网所获取的大规模图文对与视频数据,以及以自监督学习为代表的预训练方法的进步,视觉语言多模态预训练模型在很大程度上打破了不同视觉语言任务之间的壁垒,提升了多个任务训练的效率并促进了具体任务的性能表现。本文总结视觉语言多模态预训练领域的进展,首先对常见的预训练数据集和预训练方法进行汇总,然后对目前最新方法以及经典方法进行系统概述,按输入来源分为图像—文本预训练模型和视频—文本多模态模型两大类,阐述了各方法之间的共性和差异,并将各模型在具体下游任务上的实验情况进行汇总。最后,总结了视觉语言预训练面临的挑战和未来发展趋势。     

数据受限条件下的多模态处理技术综述

随着多媒体技术的发展,可获取的媒体数据在种类和量级上大幅提升。受人类感知方式的启发,多种媒体数据互相融合处理,促进了人工智能在计算机视觉领域的研究发展,在遥感图像解译、生物医学和深度估计等方面有广泛的应用。尽管多模态数据在描述事物特征时具有明显优势,但仍面临着较大的挑战。1）受到不同成像设备和传感器的限制,难以收集到大规模、高质量的多模态数据集;2）多模态数据需要匹配成对用于研究,任一模态的缺失都会造成可用数据的减少;3）图像、视频数据在处理和标注上需要耗费较多的时间和人力成本,这些问题使得目前本领域的技术尚待攻关。本文立足于数据受限条件下的多模态学习方法,根据样本数量、标注信息和样本质量等不同的维度,将计算机视觉领域中的多模态数据受限方法分为小样本学习、缺乏强监督标注信息、主动学习、数据去噪和数据增强5个方向,详细阐述了各类方法的样本特点和模型方法的最新进展。并介绍了数据受限前提下的多模态学习方法使用的数据集及其应用方向（包括人体姿态估计、行人重识别等）,对比分析了现有算法的优缺点以及未来的发展方向,对该领域的发展具有积极的意义。     

Enabling the detection of UV signal in multimodal nonlinear microscopy with catalogue lens components

Using an optical system made from fused silica catalogue optical components, third‐order nonlinear microscopy has been enabled on conventional Ti:sapphire laser‐based multiphoton microscopy setups. The optical system is designed using two lens groups with straightforward adaptation to other microscope stands when one of the lens groups is exchanged. Within the theoretical design, the optical system collects and transmits light with wavelengths between the near ultraviolet and the near infrared from an object field of at least 1 mm in diameter within a resulting numerical aperture of up to 0.56. The numerical aperture can be controlled with a variable aperture stop between the two lens groups of the condenser. We demonstrate this new detection capability in third harmonic generation imaging experiments at the harmonic wavelength of ～300 nm and in multimodal nonlinear optical imaging experiments using third‐order sum frequency generation and coherent anti‐Stokes Raman scattering microscopy so that the wavelengths of the detected signals range from ～300 nm to ～660 nm.