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Flow past a circular cylinder at Reynolds numbers up to 160 is simulated using high resolution calculations. Flow quantities at the cylinder surface are obtained and compared with those from the existing experimental and numerical studies. The present study reports the detailed information of flow quantities on the cylinder surface at low Reynolds numbers.

The biophysical properties of therapeutic antibodies influence their manufacturability, efficacy, and safety. To develop an anti-cancer antibody, we previously generated a human monoclonal antibody (Ab417) that specifically binds to L1 cell adhesion molecule with a high affinity, and we validated its anti-tumor activity and mechanism of action in human cholangiocarcinoma xenograft models. In the present study, we aimed to improve the biophysical properties of Ab417. We designed 20 variants of Ab417 with reduced aggregation propensity, less potential post-translational modification (PTM) motifs, and the lowest predicted immunogenicity using computational methods. Next, we constructed these variants to analyze their expression levels and antigen-binding activities. One variant (Ab612)—which contains six substitutions for reduced surface hydrophobicity, removal of PTM, and change to the germline residue—exhibited an increased expression level and antigen-binding activity compared to Ab417. In further studies, compared to Ab417, Ab612 showed improved biophysical properties, including reduced aggregation propensity, increased stability, higher purification yield, lower pI, higher affinity, and greater in vivo anti-tumor efficacy. Additionally, we generated a highly productive and stable research cell bank (RCB) and scaled up the production process to 50 L, yielding 6.6 g/L of Ab612. The RCB will be used for preclinical development of Ab612.

Consumer spray products (CSPs) are widely used in daily life, yet it is challenging to find products that fully disclose all components posing health risks. Existing studies primarily focus on product components or VOC quantities emitted during use. Therefore, this study aimed to measure the VOC concentrations emitted by CSPs at varying distances. 47 CSPs available in the Korean market were selected, spanning three spray groups: antiseptics/insecticides (11), aromatic deodorants (16), and coating/polishing agents (20). VOC in air samples were collected using Tenax TA tube at a distance of 1 and 3 m from the sprayed CSPs and then analyzed by thermal desorption–gas chromatography–mass spectrometry system. Discrepancies were found between labeled and actual product components. Aromatic deodorants exhibited the highest total VOCs (TVOCs), while antiseptic/insecticide sprays exhibited the lowest. In the antiseptic/insecticide group and coating/polishing agent group, benzene as a propellant had a maximum concentration (30.9 ± 25.6 ppb), and as trigger, its concentration was 33.7 ± 30.7 ppb. Quantitative analysis using advanced analytical instruments only explained 26.1 ± 20.4% of toluene-equivalent TVOCs, suggesting the presence of additional substances. Concentrations varied by distance due to substance volatility and usage. Maintaining a distance of at least 1 m from CSPs is recommended.

Background Cytoplasmic inclusions of transactive response DNA binding protein of 43 kDa (TDP-43) in neurons and astrocytes are a feature of some neurodegenerative diseases, such as frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). However, the role of TDP-43 in astrocyte pathology remains largely unknown. Methods To investigate whether TDP-43 overexpression in primary astrocytes could induce inflammation, we transfected primary astrocytes with plasmids encoding Gfp or TDP - 43 - Gfp . The inflammatory response and upregulation of PTP1B in transfected cells were examined using quantitative RT-PCR and immunoblot analysis. Neurotoxicity was analysed in a transwell coculture system of primary cortical neurons with astrocytes and cultured neurons treated with astrocyte-conditioned medium (ACM). We also examined the lifespan, performed climbing assays and analysed immunohistochemical data in pan-glial TDP-43-expressing flies in the presence or absence of a Ptp61f RNAi transgene. Results PTP1B inhibition suppressed TDP-43-induced secretion of inflammatory cytokines (interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)) in primary astrocytes. Using a neuron-astrocyte coculture system and astrocyte-conditioned media treatment, we demonstrated that PTP1B inhibition attenuated neuronal death and mitochondrial dysfunction caused by overexpression of TDP-43 in astrocytes. In addition, neuromuscular junction (NMJ) defects, a shortened lifespan, inflammation and climbing defects caused by pan-glial overexpression of TDP-43 were significantly rescued by downregulation of ptp61f (the Drosophila homologue of PTP1B) in flies. Conclusions These results indicate that PTP1B inhibition mitigates the neuronal toxicity caused by TDP-43-induced inflammation in mammalian astrocytes and Drosophila glial cells.

A displacement measurement system fusing a low cost real-time kinematic global positioning system (RTK-GPS) receiver and a force feedback accelerometer is proposed for infrastructure monitoring. The proposed system is composed of a sensor module, a base module and a computation module. The sensor module consists of a RTK-GPS rover and a force feedback accelerometer, and is installed on a target structure like conventional RTK-GPS sensors. The base module is placed on a rigid ground away from the target structure similar to conventional RTK-GPS bases, and transmits observation messages to the sensor module. Then, the initial acceleration, velocity and displacement responses measured by the sensor module are transmitted to the computation module located at a central monitoring facility. Finally, high precision and high sampling rate displacement, velocity, and acceleration are estimated by fusing the acceleration from the accelerometer, the velocity from the GPS rover, and the displacement from RTK-GPS. Note that the proposed displacement measurement system can measure 3-axis acceleration, velocity as well as displacement in real time. In terms of displacement, the proposed measurement system can estimate dynamic and pseudo-static displacement with a root-mean-square error of 2 mm and a sampling rate of up to 100 Hz. The performance of the proposed system is validated under sinusoidal, random and steady-state vibrations. Field tests were performed on the Yeongjong Grand Bridge and Yi Sun-sin Bridge in Korea, and the Xihoumen Bridge in China to compare the performance of the proposed system with a commercial RTK-GPS sensor and other data fusion techniques.

Traumatic spinal cord injury (SCI) often leads to debilitating loss of locomotor function. Neuroplasticity of spinal circuitry underlies some functional recovery and therefore represents a therapeutic target to improve locomotor function following SCI. However, the cellular and molecular mechanisms mediating neuroplasticity below the lesion level are not fully understood. The present study performed a gene expression profiling in the rat lumbar spinal cord at 1 and 3 weeks after contusive SCI at T9. Another group of rats received treadmill locomotor training (TMT) until 3 weeks, and gene expression profiles were compared between animals with and without TMT. Microarray analysis showed that many inflammation-related genes were robustly upregulated in the lumbar spinal cord at both 1 and 3 weeks after thoracic injury. Notably, several components involved in an early complement activation pathway were concurrently upregulated. In line with the microarray finding, the number of microglia substantially increased not only in the white matter but also in the gray matter. C3 and complement receptor 3 were intensely expressed in the ventral horn after injury. Furthermore, synaptic puncta near ventral motor neurons were frequently colocalized with microglia after injury, implicating complement activation and microglial cells in synaptic remodeling in the lumbar locomotor circuitry after SCI. Interestingly, TMT did not influence the injury-induced upregulation of inflammation-related genes. Instead, TMT restored pre-injury expression patterns of several genes that were downregulated by injury. Notably, TMT increased the expression of genes involved in neuroplasticity (Arc, Nrcam) and angiogenesis (Adam8, Tie1), suggesting that TMT may improve locomotor function in part by promoting neurovascular remodeling in the lumbar motor circuitry.

TAR DNA-binding protein 43 (TDP-43) is a member of an evolutionarily conserved family of heterogeneous nuclear ribonucleoproteins that modulate multiple steps in RNA metabolic processes. Cytoplasmic aggregation of TDP-43 in affected neurons is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Mislocalized and accumulated TDP-43 in the cytoplasm induces mitochondrial dysfunction and reactive oxidative species (ROS) production. Here, we show that TDP-43- and rotenone-induced neurotoxicity in the human neuronal cell line SH-SY5Y were attenuated by hydroxocobalamin (Hb, vitamin B12 analog) treatment. Although Hb did not affect the cytoplasmic accumulation of TDP-43, Hb attenuated TDP-43-induced toxicity by reducing oxidative stress and mitochondrial dysfunction. Moreover, a shortened lifespan and motility defects in TDP-43-expressing Drosophila were significantly mitigated by dietary treatment with hydroxocobalamin. Taken together, these findings suggest that oral intake of hydroxocobalamin may be a potential therapeutic intervention for TDP-43-associated proteinopathies.

Herein, a new ternary strategy to fabricate efficient and photostable inverted organic photovoltaics (OPVs) is introduced by combining a bulk heterojunction (BHJ) blend and a fullerene self‐assembled monolayer (C60‐SAM). Time‐of‐flight secondary‐ion mass spectrometry ‐ analysis reveals that the ternary blend is vertically phase separated with the C60‐SAM at the bottom and the BHJ on top. The average power conversion efficiency ‐ of OPVs based on the ternary system is improved from 14.9% to 15.6% by C60‐SAM addition, mostly due to increased current density (Jsc) and fill factor ‐. It is found that the C60‐SAM encourages the BHJ to make more face‐on molecular orientation because grazing incidence wide‐angle X‐ray scattering ‐ data show an increased face‐on/edge‐on orientation ratio in the ternary blend. Light‐intensity dependent Jsc data and charge carrier lifetime analysis indicate suppressed bimolecular recombination and a longer charge carrier lifetime in the ternary system, resulting in the enhancement of OPV performance. Moreover, it is demonstrated that device photostability in the ternary blend is enhanced due to the vertically self‐assembled C60‐SAM that successfully passivates the ZnO surface and protects BHJ layer from the UV‐induced photocatalytic reactions of the ZnO. These results suggest a new perspective to improve both performance and photostability of OPVs using a facial ternary method. A new ternary system is introduced that can form a vertically self‐assembled passivation layer on the interface between photoactive layer and ZnO layer in n‐i‐p device architecture. This system not only improves photostability against UV light but also increases in Jsc and fill factor ‐ by encouraging to make a favorable molecular orientation of photoactive materials from edge‐on to face‐on orientation.

Background: Several noninvasive tools are available for the assessment of nonalcoholic fatty liver disease (NAFLD) including clinical and blood biomarkers, transient elastography (TE), and magnetic resonance imaging (MRI) techniques, such as proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE). In the present study, we aimed to evaluate whether magnetic resonance (MR)-based examinations better discriminate the pathophysiologic features and fibrosis progression in NAFLD than other noninvasive methods.Methods: A total of 133 subjects (31 healthy volunteers and 102 patients with NAFLD) were subjected to clinical and noninvasive NAFLD evaluation, with additional liver biopsy in some patients (n=54).Results: MRI-PDFF correlated far better with hepatic fat measured by MR spectroscopy (r=0.978, P<0.001) than with the TE controlled attenuation parameter (CAP) (r=0.727, P<0.001). In addition, MRI-PDFF showed stronger correlations with various pathophysiologic parameters for cellular injury, glucose and lipid metabolism, and inflammation, than the TE-CAP. The MRI-PDFF and TE-CAP cutoff levels associated with abnormal elevation of serum alanine aminotransferase were 9.9% and 270 dB/m, respectively. The MRE liver stiffness measurement (LSM) showed stronger correlations with liver enzymes, platelets, complement component 3, several clinical fibrosis scores, and the enhanced liver fibrosis (ELF) score than the TE-LSM. In an analysis of only biopsied patients, MRE performed better in discriminating advanced fibrosis with a cutoff value of 3.9 kPa than the TE (cutoff 8.1 kPa) and ELF test (cutoff 9.2 kPa).Conclusion: Our results suggest that MRI-based assessment of NAFLD is the best non-invasive tool that captures the histologic, pathophysiologic and metabolic features of the disease.

Zintl compounds are promising thermoelectric materials for power generation as their electronic and thermal transport properties can be simultaneously engineered with anion/cation alloying. Recently, a peak thermoelectric figure‐of‐merit, zT, of 1.4 was achieved in a (Yb0.9Mg0.1)Cd1.2Mg0.4Zn0.4Sb2 Zintl phase at 700 K. Although the effects of alloying Zn in lattice thermal conductivity had been studied thoroughly, how the Zn alloying affects its electronic transport properties has not yet been fully investigated. This study evaluates how the Zn alloying at Cd sites alters the band parameters of (Yb0.9Mg0.1)Cd1.6−xMg0.4ZnxSb2 (x=0‐0.6) using the Single Parabolic Band model at 700 K. The Zn alloying increased the density‐of‐states effective mass (md*) from 0.87 to 0.97 m0. Among Zn‐alloyed samples, the md* of the x=0.4 sample was the lowest (0.93 m0). The Zn alloying decreased the non‐degenerate mobility (μ0) from 71 to 57 cm2 s−1 V−1. Regardless of Zn alloying content, the μ0 of the Zn‐alloyed samples were similar (∼57 cm2 s−1 V−1). Consequently, the x=0.4 with the highest zT exhibited the lowest weighted mobility (μW). The lowest μW represents the lowest theoretical electronic transport properties among other x. The highest zT at x=0.4 despite the lowest μW was explained with a significant lattice thermal conductivity reduction achieved with Zn alloying with x=0.4, which outweighed the deteriorated electronic transport properties also due to the alloying. The high thermoelectric figure‐of‐merit (zT) of 1.4 reported in (Yb0.9Mg0.1)Cd1.6−xMg0.4ZnxSb2 (x=0.4) is explained in terms of its physical reason. Although the weighted mobility of x=0.4 is the lowest among other Zn alloying content (x), because the lattice thermal conductivity at x=0.4 is also the lowest, the corresponding quality factor becomes the highest with the maximum zT.