179 research outputs found

    Crystallographic and Spectroscopic Snapshots Reveal a Dehydrogenase in Action

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    Aldehydes are ubiquitous intermediates in metabolic pathways and their innate reactivity can often make them quite unstable. There are several aldehydic intermediates in the metabolic pathway for tryptophan degradation that can decay into neuroactive compounds that have been associated with numerous neurological diseases. An enzyme of this pathway, 2-aminomuconate-6-semialdehyde dehydrogenase, is responsible for ‘disarming’ the final aldehydic intermediate. Here we show the crystal structures of a bacterial analogue enzyme in five catalytically relevant forms: resting state, one binary and two ternary complexes, and a covalent, thioacyl intermediate. We also report the crystal structures of a tetrahedral, thiohemiacetal intermediate, a thioacyl intermediate and an NADþ-bound complex from an active site mutant. These covalent intermediates are characterized by single-crystal and solution-state electronic absorption spectroscopy. The crystal structures reveal that the substrate undergoes an E/Z isomerization at the enzyme active site before an sp3-to-sp2 transition during enzyme-mediated oxidation

    Potential utilization of virtual reality learning for vocational school teachers

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    Abstract This study aims to determine the potential of using virtual reality as a learning tool for teachers, especially at Vocational High Schools. This research is descriptive research with a quantitative approach. Descriptive analysis aims to reveal an objective picture of the conditions in the subject under study. Descriptive quantification seeks to describe an object using numerical data. In addition, verbal/qualitative descriptions of targets are also carried out through in-depth and detailed studies of organizations or certain phenomena through observation or analysis to generate data. The implementation of Virtual Reality-based learning has been systematic, following the design, development/production, utilization, and management and evaluation models. The stages that have not been implemented are developing a learning system integrated with virtual reality models, using virtual reality as a system, managing information systems, and evaluating the effectiveness of implementing virtual reality-based learning. In addition, there are several obstacles, including: 1) The limited quantity and quality of resources that include professionals, specialists, and technicians in the use of virtual reality-based learning; 2) Not all teachers are enthusiastic and motivated, especially older teachers, to apply virtual reality-based learning concerning improving the quality of learning; 3) Not all schools have the necessary infrastructure for optimal implementation of virtual reality (such as multimedia classrooms), there are no buildings or spaces to manage the development of virtual learning in vocational Schools; and 4) The high cost of official/original software is an obstacle for the development and production of virtual reality programs. Keywords: Potential; Virtual Reality; Teacher Vocational High School; Stud

    Intent to vaccinate SARS-CoV-2 infected children in US households: A survey

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    A paucity of data exists evaluating a guardian\u27s intent to vaccinate their child against COVID-19 in the United States. We administered 102 first (April-November 2020) and 45 second (December-January 2020-2021) surveys to guardians of children (\u3c18 years) who had a laboratory-confirmed diagnosis of COVID-19 and assessed their intent to give a COVID-19 vaccine to their child, when one becomes available. The first and second surveys of the same cohort of guardians were conducted before and following the press releases detailing the adult Pfizer-BioNTech and Moderna Phase 3 results. Both surveys included an intent-to-vaccinate question using the subjective language of if a safe and effective vaccine became available, and a second question was added to second surveys using the objective language of would prevent 19 of 20 people from getting disease . When using subjective language, 24 of 45 (53%) guardians endorsed vaccine administration for their children in the first survey, which decreased to 21 (46%) in the second survey. When adding objective language, acceptance of vaccination increased to 31 (69%

    Kronos: A Secure and Generic Sharding Blockchain Consensus with Optimized Overhead

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    Sharding enhances blockchain scalability by dividing the network into shards, each managing specific unspent transaction outputs or accounts. As an introduced new transaction type, cross-shard transactions pose a critical challenge to the security and efficiency of sharding blockchains. Currently, there is a lack of a generic sharding consensus pattern that achieves both security and low overhead. In this paper, we present Kronos, a secure sharding blockchain consensus achieving optimized overhead. In particular, we propose a new secure sharding consensus pattern, based on a buffer managed jointly by shard members. Valid transactions are transferred to the payee via the buffer, while invalid ones are rejected through happy or unhappy paths. Kronos is proved to achieve security with atomicity under malicious clients with optimal intra-shard overhead kBk\mathcal{B} (kk for involved shard number and B\mathcal{B} for a Byzantine fault tolerance (BFT) cost). Efficient rejection even requires no BFT execution in happy paths, and the cost in unhappy paths is still lower than a two-phase commit. Besides, we propose secure cross-shard certification methods based on batch certification and reliable cross-shard transfer. The former combines hybrid trees or vector commitments, while the latter integrates erasure coding. Handling bb transactions, Kronos is proved to achieve reliability with low cross-shard overhead O(nbλ)\mathcal{O}(n b \lambda) (nn for shard size and λ\lambda for the security parameter). Notably, Kronos imposes no restrictions on BFT and does not rely on time assumptions, offering optional constructions in various modules. Kronos could serve as a universal framework for enhancing the performance and scalability of existing BFT protocols, supporting generic models, including asynchronous networks, increasing the throughput by several orders of magnitude. We implement Kronos using two prominent BFT protocols: asynchronous Speeding Dumbo (NDSS\u2722) and partial synchronous Hotstuff (PODC\u2719). Extensive experiments (over up to 1000 AWS EC2 nodes across 4 AWS regions) demonstrate Kronos scales the consensus nodes to thousands, achieving a substantial throughput of 320 ktx/sec with 2.0 sec latency. Compared with the past solutions, Kronos outperforms, achieving up to a 12×\times improvement in throughput and a 50% reduction in latency when cross-shard transactions dominate the workload

    Accuracy of digital guided implant surgery: expert consensus on nonsurgical factors and their treatments

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    The standardized workflow of computer-aided static guided implant surgery includes preoperative examination, data acquisition, guide design, guide fabrication and surgery. Errors may occur at each step, leading to irreversible cumulative effects and thus impacting the accuracy of implant placement. However, clinicians tend to focus on factors causing errors in surgical operations, ignoring the possibility of irreversible errors in nonstandard guided surgery. Based on the clinical practice of domestic experts and research progress at home and abroad, this paper summarizes the sources of errors in guided implant surgery from the perspectives of preoperative inspection, data collection, guide designing and manufacturing and describes strategies to resolve errors so as to gain expert consensus. Consensus recommendation: 1. Preoperative considerations: the appropriate implant guide type should be selected according to the patient's oral condition before surgery, and a retaining screw-assisted support guide should be selected if necessary. 2. Data acquisition should be standardized as much as possible, including beam CT and extraoral scanning. CBCT performed with the patient’s head fixed and with a small field of view is recommended. For patients with metal prostheses inside the mouth, a registration marker guide should be used, and the ambient temperature and light of the external oral scanner should be reasonably controlled. 3. Optimization of computer-aided design: it is recommended to select a handle-guided planting system and a closed metal sleeve and to register images by overlapping markers. Properly designing the retaining screws, extending the support structure of the guide plate and increasing the length of the guide section are methods to feasibly reduce the incidence of surgical errors. 4. Improving computer-aided production: it is also crucial to set the best printing parameters according to different printing technologies and to choose the most appropriate postprocessing procedures

    Detecting Neutrinos from Supernova Bursts in PandaX-4T

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    Neutrinos from core-collapse supernovae are essential for the understanding of neutrino physics and stellar evolution. The dual-phase xenon dark matter detectors can provide a way to track explosions of galactic supernovae by detecting neutrinos through coherent elastic neutrino-nucleus scatterings. In this study, a variation of progenitor masses as well as explosion models are assumed to predict the neutrino fluxes and spectra, which result in the number of expected neutrino events ranging from 6.6 to 13.7 at a distance of 10 kpc over a 10-second duration with negligible backgrounds at PandaX-4T. Two specialized triggering alarms for monitoring supernova burst neutrinos are built. The efficiency of detecting supernova explosions at various distances in the Milky Way is estimated. These alarms will be implemented in the real-time supernova monitoring system at PandaX-4T in the near future, providing the astronomical communities with supernova early warnings.Comment: 9 pages,6 figure

    The Arabidopsis thaliana F-Box Protein FBL17 Is Essential for Progression through the Second Mitosis during Pollen Development

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    In fungi and metazoans, the SCF-type Ubiquitin protein ligases (E3s) play a critical role in cell cycle regulation by degrading negative regulators, such as cell cycle-dependent kinase inhibitors (CKIs) at the G1-to-S-phase checkpoint. Here we report that FBL17, an Arabidopsis thaliana F-box protein, is involved in cell cycle regulation during male gametogenesis. FBL17 expression is strongly enhanced in plants co-expressing E2Fa and DPa, transcription factors that promote S-phase entry. FBL17 loss-of-function mutants fail to undergo pollen mitosis II, which generates the two sperm cells in mature A. thaliana pollen. Nonetheless, the single sperm cell-like cell in fbl17 mutants is functional but will exclusively fertilize the egg cell of the female gametophyte, giving rise to an embryo that will later abort, most likely due to the lack of functional endosperm. Seed abortion can, however, be overcome by mutations in FIE, a component of the Polycomb group complex, overall resembling loss-of-function mutations in the A. thaliana cyclin-dependent kinase CDKA;1. Finally we identified ASK11, as an SKP1-like partner protein of FBL17 and discuss a possible mechanism how SCFFBL17 may regulate cell division during male gametogenesis
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