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T7 RNA Polymerase (RNAP) is a widely used enzyme with recent applications in the production of RNA vaccines. For over 50 years denaturing sequencing gels have been used as key analysis tools for probing the nucleotide addition mechanisms of T7 RNAP and other polymerases. However, sequencing gels are low-throughput limiting their utility for comprehensive enzyme analysis. Here, we report the development of HiKER; (High-throughput Kinetics using Capillary Electrophoresis and Robotics) a high-throughput pipeline to quantitatively measure enzyme kinetics. We adapted a traditional polymerase misincorporation assay for fluorescent detection at scale allowing rapid estimates of RNAP misincorporation in different experimental conditions. Using this platform with an OT-2 robotics system, ~1500 time points were collected in a single workday. T7 RNAP exhibited dramatic differences in both observed rate constant and amplitude depending on the mismatch examined. An average misincorporation frequency of ~45 misincorporations per million bases was estimated using HiKER and is consistent with previous studies. Misincorporation time courses for T3 RNAP and Sp6 RNAP were also collected and appeared similar to T7 RNAP suggesting conserved kinetic mechanisms. However, differences between the RNAPs were observed in extension from base mismatch experiments. This platform is affordable, open-source, and broadly applicable to many enzymes. [ABSTRACT FROM AUTHOR]

Introduction: Foot pain can be a significant burden for patients. Custom foot orthoses (CFOs) have been a mainstay in podiatry treatment for foot pain management and improving foot function. However, little is known about podiatrists' experience of prescribing CFOs or patient experience of using foot orthoses (FOs), including CFOs, for foot pain. Methods: A focus group (FG) discussion with three FOs users (Female = 2 and Male = 1) was conducted in November 2022 within a private podiatry practice. This group represented non‐experts from the general local population of individuals with existing or previous foot pain who have personally experienced using either over‐the‐counter FOs or CFOs. An online FG discussion with five musculoskeletal (MSK) specialist podiatrists (Female = 2 and Male = 3) was also conducted in December 2022. This group represented podiatrists with specialist knowledge in foot biomechanics and clinical experience in CFO provision. The FG discussions were recorded and lasted 49 and 57 min respectively. Transcribed data was manually coded, and a thematic analysis was undertaken to identify patterns within the collected data. Results: The participants in the patient FG detailed mixed experiences of the prescription process and CFOs received, with reports of limited involvement/input in their prescription, the need for frequent adjustments and high costs. The impact on footwear choices, replicability and transferability of CFOs into different types of shoes and technologies to aid design were also highlighted. In the podiatrist FG, lack of confidence in design and manufacture processes, prescription form language, relationship and communication building with manufacturers, variability in the CFOs issued and the need for better student education in CFO provision emerged as key themes. Conclusion: Patients and podiatrists shared similar views on CFO provision, namely poor communication with manufacturers leading to dissatisfaction with the CFOs prescribed causing negative impacts on patient experiences. Podiatrists called for greater education at registration level to increase new graduate podiatrist knowledge in CFO design and manufacture and better collaboration with manufacturing companies. [ABSTRACT FROM AUTHOR]

Gallium oxide (Ga2O3) is a wide-bandgap oxide semiconductor, with a bandgap of ∼4.9 eV, making it a promising material for power device applications. This study focuses on the effect of hydrochloric acid addition on the growth rate in homoepitaxial growth of β-Ga2O3 using a mist chemical vapor deposition method. For homoepitaxial growth on a (001) β-Ga2O3 substrate, we introduced different concentrations of HCl into the source solution to assess its impact on the growth rate, crystal structures, and surface morphologies of the films. At a growth temperature of 900 °C, HCl addition linearly increased film thickness, enhancing the growth rate by 4.8 times with 9.09 vol. % HCl. No peaks associated with other phases were exhibited by each sample, indicating pure homoepitaxial growth. When comparing samples with similar film thicknesses, the root-mean-square (rms) roughness was enhanced by 1/7 with an increase in the HCl concentration. However, at 800 °C, an increasing solution concentration caused pronounced step bunching and elevated rms roughness, in contrast with the minimal effect observed at 900 °C. In experiments with hydrochloric acid addition at 900 °C, we observed a striped morphology, which maintained consistent rms roughness despite higher temperature. [ABSTRACT FROM AUTHOR]

Background/Objectives: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by elevated motor activity, impulsivity, and attention deficit. Approximately 5% of the population suffers from this disorder. Among the key explanations of ADHD, executive functions play an important role in understanding the symptomatology present in this disorder and in determining the main treatment strategies for affected patients. We present a systematic review that seeks to identify the treatment methods developed to support executive functions in individuals with ADHD. Methods: Articles were analyzed in the SCOPUS, PUBMED, and Science Direct databases. Initially, 739 articles were found. After applying inclusion and exclusion criteria, 30 articles remained and were included in the data extraction process. Results: Among the primary treatments identified, 14 studies propose psychological training for executive functions, 9 studies recommend medication, 5 studies suggest digital interventions, and 1 study advocates for sports as beneficial for executive functions. Conclusions: The data are discussed around the need to develop new proposals to enhance the executive functions of individuals with ADHD, thereby improving their performance in educational, personal, social, and family activities impacted by this disorder. [ABSTRACT FROM AUTHOR]

Cyclopropane fragments, which widely exist in marketed drugs and natural products, can confer special pharmacological properties to small-molecule drugs. Therefore, developing methods to construct cyclopropanes is of great significance. Nevertheless, the introduction of cyclopropane primarily relies on already-formed cyclopropyl groups, which significantly restricts the diversity of cyclopropane skeletons. Late-stage direct cyclopropanation is still a challenging task. Herein, a photo-induced intermolecular deoxycyclopropanation reaction that employs alcohols as substrates, and 1 mol.% of 2,3,5,6-tetrakis(carbazol-9-yl)-1,4-dicyanobenzene (4CzTPN) as organophotocatalyst is reported. This method proceeds with high transformation efficiency (up to 98% yield) and exhibits broad functional group tolerance, such as primary, secondary, and tertiary alcohols as well as various activated β-halogenated alkenes. This process is mild, easy to operate, and has low equipment requirements. The power of this technology is demonstrated by the late-stage functionalization of five marketed drugs and five natural products., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)