Application of Computational Lower Extremity Model to Investigate Different Muscle Activities and Joint Force Patterns in Knee Osteoarthritis Patients during Walking

Many experimental and computational studies have reported that osteoarthritis in the knee joint affects knee biomechanics, including joint kinematics, joint contact forces, and muscle activities, due to functional restriction and disability. In this study, differences in muscle activities and joint force patterns between knee osteoarthritis (OA) patients and normal subjects during walking were investigated using the inverse dynamic analysis with a lower extremity musculoskeletal model. Extensor/flexor muscle activations and torque ratios and the joint contact forces were compared between the OA and normal groups. The OA patients had higher extensor muscle forces and lateral component of the knee joint force than normal subjects as well as force and torque ratios of extensor and flexor muscles, while the other parameters had little differences. The results explained that OA patients increased the level of antagonistic cocontraction and the adduction moment on the knee joint. The presented findings and technologies provide insight into biomechanical changes in OA patients and can also be used to evaluate the postoperative functional outcomes of the OA treatments

Tactile Avatar: Tactile Sensing System Mimicking Human Tactile Cognition

As a surrogate for human tactile cognition, an artificial tactile perception and cognition system are proposed to produce smooth/soft and rough tactile sensations by its user's tactile feeling; and named this system as “tactile avatar”. A piezoelectric tactile sensor is developed to record dynamically various physical information such as pressure, temperature, hardness, sliding velocity, and surface topography. For artificial tactile cognition, the tactile feeling of humans to various tactile materials ranging from smooth/soft to rough are assessed and found variation among participants. Because tactile responses vary among humans, a deep learning structure is designed to allow personalization through training based on individualized histograms of human tactile cognition and recording physical tactile information. The decision error in each avatar system is less than 2% when 42 materials are used to measure the tactile data with 100 trials for each material under 1.2N of contact force with 4cm s−1 of sliding velocity. As a tactile avatar, the machine categorizes newly experienced materials based on the tactile knowledge obtained from training data. The tactile sensation showed a high correlation with the specific user's tendency. This approach can be applied to electronic devices with tactile emotional exchange capabilities, as well as advanced digital experiences. © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH1

Experience and pharmacokinetics of Levetiracetam in Korean neonates with neonatal seizures

PurposeThe aims of this study were to evaluate the safety and pharmacokinetics of levetiracetam (LEV) in neonates with seizures and to establish a population pharmacokinetics (PPK) model by using the software NONMEM.MethodsA retrospective analysis of 18 neonatal patients with seizures, who were treated with LEV, including 151 serum samples, was performed. The mean loading dose was 20 mg/kg, followed by a mean maintenance dose of 29 mg/kg/day.ResultsSeventeen neonates (94%) had seizure cessation within 1 week and 16 (84%) remained seizure-free at 30 days under the LEV therapy. The mean serum concentration of LEV was 8.7 µg/mL. Eight samples (5%) were found above the therapeutic range. No serious adverse effects were detected. In the PPK analysis for Korean neonates, the half-life was 9.6 hours; clearance, 0.357 L/hr; and volume of distribution, 4.947 L, showing differences from those in adults.ConclusionLEV is a safe and effective option for the treatment of neonatal seizures with careful therapeutic drug monitoring

Current strategies for protein production and purification enabling membrane protein structural biology.

Membrane proteins are still heavily underrepresented in the protein data bank (PDB) due to multiple bottlenecks. The typical low abundance of membrane proteins in their natural hosts makes it necessary to overexpress these proteins either in heterologous systems or through in vitro translation/cell-free expression. Heterologous expression of proteins, in turn, leads to multiple obstacles due to the unpredictability of compatibility of the target protein for expression in a given host. The highly hydrophobic and/or amphipathic nature of membrane proteins also leads to challenges in producing a homogeneous, stable, and pure sample for structural studies. Circumventing these hurdles has become possible through introduction of novel protein production protocols; efficient protein isolation and sample preparation methods; and, improvement in hardware and software for structural characterization. Combined, these advances have made the past 10-15 years very exciting and eventful for the field of membrane protein structural biology, with an exponential growth in the number of solved membrane protein structures. In this review, we focus on both the advances and diversity of protein production and purification methods that have allowed this growth in structural knowledge of membrane proteins through X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy (cryo-EM).The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

The SWI/SNF-like BAF complex is essential for early B cell development

During the process of B cell development, transcription factors, such as E2A and Ebf1, have been known to play key roles. Although transcription factors and chromatin regulators work in concert to direct the expression of B lineage-specific genes, little is known about the involvement of regulators for chromatin structure during B lymphopoiesis. In this article, we show that deletion of Srg3/mBaf155, a scaffold subunit of the SWI/SNF-like BAF complex, in the hematopoietic lineage caused defects at both the common lymphoid progenitor stage and the transition from pre-pro-B to early pro-B cells due to failures in the expression of B lineage-specific genes, such as Ebf1 and Il7ra, and their downstream target genes. Moreover, mice that were deficient in the expression of Brg1, a subunit of the complex with ATPase activity, also showed defects in early B cell development. We also found that the expression of Ebf1 and Il7ra is directly regulated by the SWI/SNF-like BAF complex. Thus, our results suggest that the SWI/SNF-like BAF complex facilitates early B cell development by regulating the expression of B lineage-specific genes.close1