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The xeroderma pigmentosum protein A (XPA) and replication protein A (RPA) proteins fulfill essential roles in the assembly of the preincision complex in the nucleotide excision repair (NER) pathway. We have previously characterized the two interaction sites, one between the XPA N-terminal (XPA-N) disordered domain and the RPA32 C-terminal domain (RPA32C), and the other with the XPA DNA binding domain (DBD) and the RPA70AB DBDs. Here, we show that XPA mutations that inhibit the physical interaction in either site reduce NER activity in biochemical and cellular systems. Combining mutations in the two sites leads to an additive inhibition of NER, implying that they fulfill distinct roles. Our data suggest a model in which the interaction between XPA-N and RPA32C is important for the initial association of XPA with NER complexes, while the interaction between XPA DBD and RPA70AB is needed for structural organization of the complex to license the dual incision reaction. Integrative structural models of complexes of XPA and RPA bound to single-stranded/double-stranded DNA (ss/dsDNA) junction substrates that mimic the NER bubble reveal key features of the architecture of XPA and RPA in the preincision complex. Most critical among these is that the shape of the NER bubble is far from colinear as depicted in current models, but rather the two strands of unwound DNA must assume a U-shape with the two ss/dsDNA junctions localized in close proximity. Our data suggest that the interaction between XPA and RPA70 is key for the organization of the NER preincision complex.

The XPA protein functions together with the single-stranded DNA (ssDNA) binding protein RPA as the central scaffold to ensure proper positioning of repair factors in multi-protein nucleotide excision repair (NER) machinery. We previously determined the structure of a short motif in the disordered XPA N-terminus bound to the RPA32C domain. However, a second contact between the XPA DNA-binding domain (XPA DBD) and the RPA70AB tandem ssDNA-binding domains, which is likely to influence the orientation of XPA and RPA on the damaged DNA substrate, remains poorly characterized. NMR was used to map the binding interfaces of XPA DBD and RPA70AB. Combining NMR and X-ray scattering data with comprehensive docking and refinement revealed how XPA DBD and RPA70AB orient on model NER DNA substrates. The structural model enabled design of XPA mutations that inhibit the interaction with RPA70AB. These mutations decreased activity in cell-based NER assays, demonstrating the functional importance of XPA DBD-RPA70AB interaction. Our results inform ongoing controversy about where XPA is bound within the NER bubble, provide structural insights into the molecular basis for malfunction of disease-associated XPA missense mutations, and contribute to understanding of the structure and mechanical action of the NER machinery.

The development of flexible and stretchable devices is crucial for realizing future electronics. In particular, for dielectric layer, conventional inorganic materials are limited by their brittle nature, while organic materials suffer from a low dielectric constant. Here, a novel intrinsically photopatternable high‐k Parylene‐based thin film (Parylene‐OH) is fabricated via a chemical vapor deposition process based on the Gorham method, which provides pin‐hole free, conformal polymeric film on any type of surface. Parylene‐OH can be photo‐patterned by UV crosslinking without further lithography processes and dielectric constant of Parylene‐OH increases from 6.05 to 7.53 after crosslinking, without degrading other parameters, making it comparable to conventional high‐k dielectric, Al2O3. Flexible In─Ga─Zn─O (IGZO) thin‐film transistors (TFTs) with patterned dielectric layers can withstand higher strain owing to the localized pattern of each unit. A CMOS inverter integrated with n‐type IGZO and p‐type Te TFTs is successfully fabricated. Parylene‐OH can be used in the future of state‐of‐the‐art flexible electronic devices. [ABSTRACT FROM AUTHOR]

This paper does present an interpretable support vector machine (SVM) and its application to rehabilitation assessment. We introduce the concept of nearest boundary point to standardize the one-class SVM decision function and determine the shortest path for data from abnormal cases to become those from normal cases. This analytical approach is computationally simple and provides a unique solution. The nearest boundary point of abnormal data can also be used to analyze the cause of abnormal classification and indicate countermeasures for normalization. These properties render the proposed interpretable SVM valuable for medical assessment applications and other problems that require careful consideration of classification results for treatment. Simulation and application results demonstrate the feasibility and effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

This study examined how the linguistic politeness of fact-checking messages affects audiences' belief accuracy and message acceptance by shaping their perceived face threat and psychological reactance. In 2 experiments with national convenience samples of South Korean adults, we manipulated linguistic politeness by using either honorific or non-honorific sentence endings—a well-established marker of linguistic politeness in Korean—in fact-checking news articles correcting misinformation about COVID-19 (Study 1) and refugees (Study 2). Study 1 (N = 240) found that fact-checking articles using honorific sentence endings were perceived as less face-threatening than those presenting identical content with non-honorific endings, which in turn increased belief accuracy and the perceived persuasiveness of the articles. Study 2 (N = 296) replicated the findings of Study 1 and extended them by demonstrating: (1) the effect of using honorific (vs. non-honorific) sentence endings on recipients' perceived face threat was not moderated by their conspiratorial predisposition or need for cognition; (2) the effects of perceived face threat were mediated by psychological reactance; and (3) the sequential mediation also produced attitudinal effects. The findings are discussed in light of their theoretical and practical implications for designing effective fact-checking messages to combat misinformation in non-Western languages. [ABSTRACT FROM AUTHOR]

Developing anode materials with high specific capacity and cycling stability is vital for improving thin‐film lithium‐ion batteries. Thin‐film zinc oxide (ZnO) holds promise due to its high specific capacity, but it suffers from volume changes and structural stress during cycling, leading to poor battery performance. In this research, we ingeniously combined polytetrafluoroethylene (PTFE) with ZnO using a radio frequency (RF) magnetron co‐sputtering method, ensuring a strong bond in the thin‐film composite electrode. PTFE effectively reduced stress on the active material and mitigated volume change effects during Li+ ion intercalation and deintercalation. The composite thin films are thoroughly characterized using advanced techniques such as X‐ray diffraction, scanning electron microscopy, and X‐ray photoelectron spectroscopy for investigating correlations between material properties and electrochemical behaviors. Notably, the ZnO/PTFE thin‐film electrode demonstrated an impressive specific capacity of 1305 mAh g−1 (=7116 mAh cm−3) at a 0.5C rate and a remarkable capacity retention of 82% from the 1st to the 100th cycle, surpassing the bare ZnO thin film (50%). This study provides valuable insights into using binders to stabilize active materials in thin‐film batteries, enhancing battery performance. [ABSTRACT FROM AUTHOR]