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Droplet-based functional CRISPR screening of cell-cell interactions by SPEAC-seq
No full textCell-cell interactions are essential for the function and contextual regulation of biological tissues. We present a platform for high-throughput microfluidics-supported genetic screening of functional regulators of cell-cell interactions. Systematic perturbation of encapsulated associated cells followed by sequencing (SPEAC-seq) combines genome-wide CRISPR libraries, cell coculture in droplets and microfluidic droplet sorting based on functional read-outs determined by fluorescent reporter circuits to enable the unbiased discovery of interaction regulators. This technique overcomes limitations of traditional methods for characterization of cell-cell communication, which require a priori knowledge of cellular interactions, are highly engineered and lack functional read-outs. As an example of this technique, we describe the investigation of neuroinflammatory intercellular communication between microglia and astrocytes, using genome-wide CRISPR-Cas9 inactivation libraries and fluorescent reporters of NF-kappa B activation. This approach enabled the discovery of thousands of microglial regulators of astrocyte NF-kappa B activation important for the control of central nervous system inflammation. Importantly, SPEAC-seq can be adapted to different cell types, screening modalities, cell functions and physiological contexts, only limited by the ability to fluorescently report cell functions and by droplet cultivation conditions. Performing genome-wide screening takes less than 2 weeks and requires microfluidics capabilities. Thus, SPEAC-seq enables the large-scale investigation of cell-cell interactions.N
Achievements and Limitations of Rural Development ODA Projects Utilizing Farmers' Organizations: A Case Study of Tuyen Quang Province, Vietnam
No full text본 연구는 베트남 뚜옌꽝성에서 실시된 농촌개발 ODA(Official Development Assistance) 사업을 사례로, 농민조직을 활용한 농촌개발의 성과와 한계를 분석하고 개선 방향을 제시하고자 한다. 베트남은 한국의 새마을운동 모델을 기반으로 신농촌개발 국가 목표 프로그램을 도입하여 농업 생산성 향상, 농민조직 활성화, 가치사슬 강화 등을 목표로 농촌 근대화를 추진하고 있다. 특히 한국국제협력단(KOICA)의 지원을 받은 뚜옌꽝성 농촌개발 프로그램은 작목반과 협동조합을 통해 농민들의 소득증대와 지역 농업 활성화를 목표로 진행되었다.
연구 결과, 농민조직을 통한 ODA 사업은 농업 생산성 향상과 소득증대 측면에서 긍정적인 성과를 보였지만, 조직력 부족과 가치사슬 참여 미흡 등의 한계가 확인되었다. 작목반은 생산단계에 머물러 있었으며, 협동조합은 유통과 가공단계까지 참여하며 부가가치를 창출하는 데 성공했다. 특히 대부분의 작목반은 협동조합으로 전환되지 못했으며, 농민들의 낮은 행정역량과 관심 부족이 주요 원인으로 분석되었다.
본 연구는 농민조직의 자립과 지속 가능한 운영을 위해 세 가지 정책적 제언을 제시한다. 첫째, 농민조직의 행정역량 강화를 위해 운영회계 교육과 지속적인 모니터링이 병행되어야 한다. 둘째, 신규 농민조직 형성보다 기존 조직의 육성과 통합을 통해 장기적 안정성을 확보해야 한다. 셋째, 농민조직이 농업 가치사슬 전반에 참여할 수 있도록 신용대출 서비스와 같은 금융 접근성을 확대해야 한다. 이러한 방안은 베트남 농촌개발의 지속가능성을 높이고, ODA 사업의 효과성을 극대화하는 데 기여할 것이다.
본 연구는 베트남 농촌개발 사례를 통해 농민조직을 활용한 ODA 사업 모델의 가능성과 한계를 심층적으로 분석하고, 향후 농촌개발 ODA 전략 수립에 기초자료를 제공한다.N
Deep-subwavelength engineering of stealthy hyperuniformity
No full textLight behaviours in disordered materials have been of research interest primarily at length scales beyond or comparable to the wavelength of light, because order and disorder are often believed to be almost indistinguishable in the subwavelength regime according to effective medium theory (EMT). However, it was demonstrated that the breakdown of EMT occurs even at deep-subwavelength scales when interface phenomena, such as the Goos-H & auml;nchen effect, dominate light flows. Here we develop the engineering of disordered multilayers at deep-subwavelength scales to achieve angle-selective manipulation of wave localization. To examine the disorder-dependent EMT breakdown, we classify the intermediate regime of microstructural phases between deep-subwavelength crystals and uncorrelated disorder through the concept of stealthy hyperuniformity (SHU). We devise material phase transitions from SHU to uncorrelated disorder for distinct angular responses of wave localization by tailoring the short-range and long-range order in SHU multilayers. The result paves the way to the realization of deep-subwavelength disordered metamaterials, bridging the fields of disordered photonics and metamaterials.Y
Modulation of Immune Responses by Metabolic Reprogramming: The Key Role of Immunometabolism
No full textY
AlphaFold Protein Structure Database and 3D-Beacons: New Data and Capabilities
No full textThe AlphaFold Protein Structure Database (https://alphafold.ebi.ac.uk/) has made significant strides in enhancing its utility and accessibility for the life science research community. The recent integration of AlphaMissense predictions enables access to the pathogenicity of human protein missense variants, with an innovative and interactive heatmap and 3D visualisation that display variant data at the residue level. Users can now toggle between structure model quality (pLDDT) and average pathogenicity scores, providing insights into the implications of specific residue changes. The Foldseek integration offers a rapid and accurate method for protein structure searches and comparisons. Bulk data download options further facilitate comprehensive data analysis and integration with other computational tools. The 3D-Beacons framework (https://www.ebi.ac.uk/pdbe/pdbe-kb/3dbeacons/) has also been enhanced with detailed annotation endpoints (such as AlphaMissense data) and integrates LevyLab's dataset of homomeric AlphaFold 2 models. These advancements significantly improve the functionality and accessibility of these resources, enabling discoveries using structure data.Y
A Review of Pnictogenides for Next-Generation Anode Materials for Sodium-Ion Batteries
No full textWith the growing market of secondary batteries for electric vehicles (EVs) and grid-scale energy storage systems (ESS), driven by environmental challenges, the commercialization of sodium-ion batteries (SIBs) has emerged to address the high price of lithium resources used in lithium-ion batteries (LIBs). However, achieving competitive energy densities of SIBs to LIBs remains challenging due to the absence of high-capacity anodes in SIBs such as the group-14 elements, Si or Ge, which are highly abundant in LIBs. This review presents potential candidates in metal pnictogenides as promising anode materials for SIBs to overcome the energy density bottleneck. The sodium-ion storage mechanisms and electrochemical performance across various compositions and intrinsic physical and chemical properties of pnictogenide have been summarized. By correlating these properties, strategic frameworks for designing advanced anode materials for next-generation SIBs were suggested. The trade-off relation in pnictogenides between the high specific capacities and the failure mechanism due to large volume expansion has been considered in this paper to address the current issues. This review covers several emerging strategies focused on improving both high reversible capacity and cycle stability.Y
Integrating Real-Time Machine Learning and Dynamic Charging for Electric Vehicle Routing
No full textAs electric vehicles (EVs) gain popularity, the demand for efficient EV routing and innovative charging solutions is increasing. This study proposes a novel integration of Temporal Multimodal Multivariate Learning (TMML) and the Time-Dependent Shortest Path (TDSP) algorithm to dynamically optimize EV routing while incorporating stationary and wireless charging systems. TMML continuously updates travel time distributions based on real-time observations, reducing uncertainties and enabling more accurate predictions. These updated distributions are utilized by TDSP to determine the most efficient routes, considering time-dependent travel times, and the availability of charging infrastructure. The methodology integrates Mobile Energy Distributors (MEDs) and Dynamic Inductive Charging (DIC). MED dynamically dispatches portable charging units, while DIC enables on-the-move charging through road-embedded systems. Real-world data from the Washington, DC metropolitan area, sourced from Regional Integrated Transportation Information System (RITIS.org), provides granular insights into traffic patterns and charging infrastructure performance. This hybrid system operates by extracting feasible routes, evaluating them using TMML and TDSP, and selecting the optimal path to minimize travel time, waiting time, and charging costs.N
ISR-DPO: Aligning Large Multimodal Models for Videos by Iterative Self-Retrospective DPO
No full textData-free quantization (DFQ) is a technique that creates a lightweight network from its full-precision counterpart without the original training data, often through a synthetic dataset. Although several DFQ methods have been proposed for vision transformer (ViT) architectures, they fail to achieve efficacy in low-bit settings. Examining the existing methods, we observe that their synthetic data produce misaligned attention maps, while those of the real samples are highly aligned. From this observation, we find that aligning attention maps of synthetic data helps improve the overall performance of quantized ViTs. Motivated by this finding, we devise MimiQ, a novel DFQ method designed for ViTs that enhances inter-head attention similarity. First, we generate synthetic data by aligning head-wise attention outputs from each spatial query patch. Then, we align the attention maps of the quantized network to those of the full-precision teacher by applying head-wise structural attention distillation. The experimental results show that the proposed method significantly outperforms baselines, setting a new state-of-the-art for ViT-DFQ. Copyright © 2025, Association for the Advancement of Artificial Intelligence (www.aaai.org). All rights reserved.N
Mechanisms Underlying Medication-Related Osteonecrosis of the Jaw
No full textObjectiveMedication-related osteonecrosis of the jaw (MRONJ) is a rare but debilitating disease characterized by a progressive necrosis of jaw bones in patients who have received anti-resorptive or anti-angiogenic therapies. Unfortunately, we still have no validated preventive or pharmaceutical interventions to help these patients, primarily due to our limited understanding of MRONJ pathogenesis. Here, we offer an extensive review of recent studies relevant to MRONJ pathogenesis. We present a hypothesis regarding the coupling of bone resorption and angiogenesis that relies on osteoblast-derived, matrix-bound vascular endothelial growth factors to explain why ONJ is associated with both anti-resorptive and anti-angiogenic agents.MethodsA narrative review was conducted by searching databases, including PubMed, Scopus, Google Scholar, and Web of Science, to retrieve relevant reports.ResultsReduced bone resorption leads to reduced angiogenesis, and vice versa, creating a vicious cycle that ultimately results in ischemic necrosis of the jaw. Additionally, we suggest that reduced angiogenesis, induced by anti-resorptive or anti-angiogenic agents, aggravates bacterial infection-induced bone necrosis, explaining why the jaw bone is particularly susceptible to necrosis.ConclusionOur novel hypothesis will facilitate the advancement of future research and the development of more targeted approaches to managing MRONJ.Y
Antitumor activity of afatinib in EGFR T790M-negative human oral cancer therapeutically targets mTOR/Mcl-1 signaling axis
No full textPurpose This study investigates the role and effectiveness of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in oral cancer, focusing on the clinical relevance of EGFR and myeloid cell leukemia-1 (Mcl-1) in head and neck cancers (HNCs). It aims to explore the molecular mechanism of afatinib, a TKI, in treating human oral cancer.Methods We conducted an in silico analysis using databases like The Cancer Genome Atlas, Gene Expression Omnibus, and Clinical Proteomic Tumor Analysis Consortium, along with immunohistochemistry staining, to study EGFR and Mcl-1 expression in HNCs. For investigating afatinib's anticancer properties, we performed various in vitro and in vivo analyses, including trypan blue exclusion assay, Western blotting, 4 '-6-diamidino-2-phenylindole staining, flow cytometry, quantitative real-time PCR, Mitochondrial membrane potential assay, overexpression vector construction, transient transfection, and a tumor xenograft model.Results Higher expression levels of EGFR and Mcl-1 were observed in HNC patient tissues compared to normal tissues, with their co-expression significantly linked to poor prognosis. There was a strong correlation between EGFR and Mcl-1 expressions in oral cancer patients. Afatinib treatment induced apoptosis and suppressed Mcl-1 in oral cancer cell lines without the EGFR T790M mutation. The mechanism of afatinib-induced apoptosis involved the EGFR/mTOR/Mcl-1 axis, as shown by the effects of mTOR activator MHY1485 and inhibitor rapamycin. Afatinib also increased Bim expression, mitochondrial membrane permeabilization, and cytochrome c release. It significantly lowered tumor volume without affecting body, liver, and kidney weights.Conclusion Afatinib, targeting the EGFR/mTOR/Mcl-1 axis, shows promise as a therapeutic strategy for oral cancer, especially in patients with high EGFR and Mcl-1 expressions.Y