Mechanism of an ATP-independent Protein Disaggregase. II. Distinct Molecular Interactions Drive Multiple Steps During Aggregate Disassembly

The ability of molecular chaperones to overcome the misfolding and aggregation of proteins is essential for the maintenance of proper protein homeostasis in all cells. Thus far, the best studied disaggregase systems are the Clp/Hsp100 family of “ATPases associated with various cellular activities” (AAA^+) ATPases, which use mechanical forces powered by ATP hydrolysis to remodel protein aggregates. An alternative system to disassemble large protein aggregates is provided by the 38-kDa subunit of the chloroplast signal recognition particle (cpSRP43), which uses binding energy with its substrate proteins to drive disaggregation. The mechanism of this novel chaperone remains unclear. Here, molecular genetics and structure-activity analyses show that the action of cpSRP43 can be dissected into two steps with distinct molecular requirements: (i) initial recognition, during which cpSRP43 binds specifically to a recognition motif displayed on the surface of the aggregate; and (ii) aggregate remodeling, during which highly adaptable binding interactions of cpSRP43 with hydrophobic transmembrane domains of the substrate protein compete with the packing interactions within the aggregate. This establishes a useful framework to understand the molecular mechanism by which binding interactions from a molecular chaperone can be used to overcome protein aggregates in the absence of external energy input from ATP

Geographical heterogeneity and influenza infection within households

Although it has been suggested that schoolchildren vaccination reduces influenza morbidity and mortality in the community, it is unknown whether geographical heterogeneity would affect vaccine effectiveness

Asymptomatic ratio for seasonal H1N1 influenza infection among schoolchildren in Taiwan

Studies indicate that asymptomatic infections do indeed occur frequently for both seasonal and pandemic influenza, accounting for about one-third of influenza infections. Studies carried out during the 2009 pH1N1 pandemic have found significant antibody response against seasonal H1N1 and H3N2 vaccine strains in schoolchildren receiving only pandemic H1N1 monovalent vaccine, yet reported either no symptoms or only mild symptoms

Investigating the Effects of Large-Scale Pseudo-Stereo Data and Different Speech Foundation Model on Dialogue Generative Spoken Language Model

Recent efforts in Spoken Dialogue Modeling aim to synthesize spoken dialogue without the need for direct transcription, thereby preserving the wealth of non-textual information inherent in speech. However, this approach faces a challenge when speakers talk simultaneously, requiring stereo dialogue data with speakers recorded on separate channels, a notably scarce resource. To address this, we have developed an innovative pipeline capable of transforming single-channel dialogue data into pseudo-stereo data. This expanded our training dataset from a mere 2,000 to an impressive 17,600 hours, significantly enriching the diversity and quality of the training examples available. The inclusion of this pseudo-stereo data has proven to be effective in improving the performance of spoken dialogue language models. Additionally, we explored the use of discrete units of different speech foundation models for spoken dialogue generation.Comment: submitted to interspeech 202

Durvalumab and pembrolizumab in advanced biliary tract cancer: a reconstructed patient-level mimic head-to-head comparative analysis

BackgroundThe addition of durvalumab or pembrolizumab to gemcitabine and cisplatin (GP) has been approved to statistically improve survival outcomes in patients with advanced biliary tract cancer. However, since the survival time was only prolonged by about two months, doubts have been raised. In this analysis, we aimed to evaluate the efficacy of combining durvalumab or pembrolizumab with GP chemotherapy.MethodsRecords were identified through a formal search of PubMed and Web of Science. The TOPAZ-1 and KEYNOTE-966 trials were definitively included. Patient-level overall survival (OS) and progression-free survival (PFS) data were reconstructed and analyzed using a one-stage approach.ResultsThe immunotherapy plus GP chemotherapy group showed superiority over the GP chemotherapy group (OS: HR 0.83, p < 0.001; PFS: HR 0.88, p = 0.009). The survival outcomes were similar between the durvalumab and pembrolizumab groups (OS: HR 1.02, p = 0.83; PFS: HR 0.95, p = 0.53). In the subgroup analysis, the gemcitabine-maintenance group significantly prolonged the OS compared to the gemcitabine-limited-to-8-cycles group (OS: HR 0.86, p = 0.007). Neither the durvalumab nor pembrolizumab groups statistically improved the OS compared to the gemcitabine-maintenance group. In contrast, the durvalumab and pembrolizumab groups significantly improved OS compared to the gemcitabine-limited-to-8-cycles group.ConclusionsBased on this mimic head-to-head analysis, we are convinced that durvalumab and pembrolizumab benefit patients with biliary tract cancer. However, despite the statistically significant differences, the moderate progress made in OS and PFS might still be considered inadequate. It is crucial for clinicians to identify the precise subgroup population that could benefit most from immunotherapy and develop more strategies for those who might not respond well to immunotherapy

Theory of Variable Fuzzy Sets for Artificial Emotions Prediction

Emotions have a very important impact on human's beliefs, motivations, actions, and physical states. Emotions predicting and its application in intelligent system can improve the interaction between humans and machines. Current research in artificial emotion focuses on how to measure, calculate, or compute it. However, the transfer of emotion is often too complicated to present full emotion states and changes. This paper combines with emotional dimension and theory of variable fuzzy sets to present a predicting artificial emotion model and shows illustrated example of it. This study shows that any raw data from input can be computed with variable fuzzy set. It provides a mathematical method for representing emotion quantitative, gradual qualitative, and mutated qualitative change. This framework improves calculation methods and mechanisms, closer to real emotional changes

Theory of Variable Fuzzy Sets for Artificial Emotions Prediction

Emotions have a very important impact on human’s beliefs, motivations, actions, and physical states. Emotions predicting and its application in intelligent system can improve the interaction between humans and machines. Current research in artificial emotion focuses on how to measure, calculate, or compute it. However, the transfer of emotion is often too complicated to present full emotion states and changes. This paper combines with emotional dimension and theory of variable fuzzy sets to present a predicting artificial emotion model and shows illustrated example of it. This study shows that any raw data from input can be computed with variable fuzzy set. It provides a mathematical method for representing emotion quantitative, gradual qualitative, and mutated qualitative change. This framework improves calculation methods and mechanisms, closer to real emotional changes

Reactive-Oxygen-Species-Responsive Drug Delivery Systems: Promises and Challenges

Given the increasing evidence indicates that many pathological conditions are associated with elevated reactive oxygen species (ROS) levels, there have been growing research efforts focused on the development of ROS-responsive carrier systems because of their promising potential to realize more specific diagnosis and effective therapy. By judicious utilization of ROS-responsive functional moieties, a wide range of carrier systems has been designed for ROS-mediated drug delivery. In this review article, insights into design principle and recent advances on the development of ROS-responsive carrier systems for drug delivery applications are provided alongside discussion of their in vitro and in vivo evaluation. In particular, the discussions in this article will mainly focus on polymeric nanoparticles, hydrogels, inorganic nanoparticles, and activatable prodrugs that have been integrated with diverse ROS-responsive moieties for spatiotemporally controlled release of drugs for effective therapy.1149sciescopu

Physics at BES-III

This physics book provides detailed discussions on important topics in $\tau$-charm physics that will be explored during the next few years at \bes3 . Both theoretical and experimental issues are covered, including extensive reviews of recent theoretical developments and experimental techniques. Among the subjects covered are: innovations in Partial Wave Analysis (PWA), theoretical and experimental techniques for Dalitz-plot analyses, analysis tools to extract absolute branching fractions and measurements of decay constants, form factors, and CP-violation and \DzDzb-oscillation parameters. Programs of QCD studies and near-threshold tau-lepton physics measurements are also discussed.Comment: Edited by Kuang-Ta Chao and Yi-Fang Wan

Studies on Ancient Rice—Where Botanists, Agronomists, Archeologists, Linguists, and Ethnologists Meet

Abstract Taiwan’s aboriginal peoples are thought to be related to ancestral Austronesian-speaking peoples. Currently, Taiwan has 14 officially acknowledged aboriginal tribes. The major crops currently farmed in aboriginal areas are rice (Oryza sativa) and foxtail millet (Setaria italica). Archeologists recently excavated the remains of several early cultures in Taiwan. The most plentiful plant remains were carbonated rice and foxtail millet grains. The earliest 14C date of these excavation sites is ∼5,000 bp. These settlements may be those of the earliest ancestral Austronesian speakers in Taiwan. Rice domestication is a complex story. In this study, we identified the functional nucleotide polymorphisms of 16 domestication-related genes using 60 landraces collected from aboriginal Taiwanese villages about 100 years ago. We also screened the phenotypes of these landraces. By integrating pheno- and genotypic data, together with data from archeologists and linguists, we may be able to better understand the history of rice cultivation in Taiwan and nearby areas.</jats:p