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The article presents a differentially excited low temperature co-fired ceramics (LTCC) based miniaturized planar aperture antenna, distinguished for its high gain and narrow-beam wideband characteristics, tailored specifically for mm-Wave antenna-in-package (AiP) applications. The proposed antenna comprises a stepped-cut patch element excited differentially and enclosed within an open cavity formed by metallized vias. Four tuning stubs are symmetrically incorporated into the stepped-cut patch element, and two pairs of shorting vias are used to ground it, improving overall impedance and gain bandwidth. Rectangular-shaped parasitic strips, strategically positioned outside the open cavity in a symmetrical arrangement, significantly narrow the main beam along two principal cutting planes, thereby enhancing broadside gain across the entire frequency band of operation. To validate the proposed design, a miniaturized and low loss differential feeding network was designed using the same LTCC technology and seamlessly integrated into the underside of the prototype antenna. According to measured results, the fabricated prototype exhibit −10 dB impedance bandwidth of 20.97% (56.55–69.8 GHz), and the realized gain is higher than 10.01 dBi with a peak gain of 12.36 dBi at 63 GHz. Moreover, the radiation pattern of the proposed design is perfectly symmetrical, boasting a half-power beamwidth less than 40° along both the planes across the entire operating band.

Abstract A 6‐year‐old neutered male Siamese cat was referred for investigation of hindlimb ataxia and blindness of 2 weeks’ duration. A swollen right hind limb, with no history of trauma, and no evidence of an external wound, was observed on physical examination. Ophthalmic examination revealed bilateral absence of the menace response and changes consistent with uveitis. Blood tests identified changes consistent with inflammation including serum amyloid A elevation. Infectious disease testing was negative. Degenerate neutrophils and bacterial cocci were detected on fine needle aspiration cytology of the affected limb. Thoracic radiography and abdominal ultrasonography identified no abnormalities. Primary pyomyositis was suspected and clindamycin was prescribed following Penrose drain tube placement. In addition, eye drops containing tobramycin, atropine, and prednisolone were administered. The clinical signs and serum amyloid A level were markedly improved after 5 days of treatment. Based on the medical history and lack of other findings, the uveitis was suspected to be secondary to the pyomyositis. The clinical signs resolved completely, and no recurrence was reported within a 6‐month follow‐up period. To the best of our knowledge, primary pyomyositis with uveitis has not been previously reported in cats.

Electrical losses are converted into thermal energy in motors, which heats each component. It is a significant factor in decreasing motor mechanical performance. In this paper, the motor cooling characteristics were analyzed according to the design factors of the water jacket to investigate the cooling performance of a permanent magnet synchronous motor (PMSM). First, the electrical losses generated in PMSM were calculated using electromagnetic finite element (FE) analysis. Secondly, a 3D electromagnetic–thermal fluid coupled FE analysis was performed to analyze the temperature distribution inside the motor by applying electrical loss as the heat source. Finally, the motor cooling performance according to the design factors of the water jacket was statistically analyzed using the design of experiment (DOE) method. It was found that the mass flow rate of 0.02547 kg/s and six passes of the water jacket with one inlet and two outlets could be considered the optimum conditions in terms of the maximum motor temperature.

Blood–brain barrier (BBB) models are important tools for studying CNS drug delivery, brain development, and brain disease. In vitro BBB models have been obtained from animals and immortalized cell lines; however, brain microvascular endothelial cells (BMECs) derived from them have several limitations. Furthermore, obtaining mature brain microvascular endothelial-like cells (BME-like cells) from human pluripotent stem cells (hPSCs) with desirable properties for establishing BBB models has been challenging. Here, we developed an efficient method for differentiating hPSCs into BMECs that are amenable to the development and application of human BBB models. The established conditions provided an environment similar to that occurring during BBB differentiation in the presence of the co-differentiating neural cell population by the modulation of TGF-β and SHH signaling. The developed BME-like cells showed well-organized tight junctions, appropriate expression of nutrient transporters, and polarized efflux transporter activity. In addition, BME-like cells responded to astrocytes, acquiring substantial barrier properties as measured by transendothelial electrical resistance. Moreover, the BME-like cells exhibited an immune quiescent property of BBB endothelial cells by decreasing the expression of adhesion molecules. Therefore, our novel cellular platform could be useful for drug screening and the development of brain-permeable pharmaceuticals.

Abstract Efforts to improve CRISPR-Cas9 genome editing systems for lower off-target effects are mostly at the cost of its robust on-target efficiency. To enhance both accuracy and efficiency, we created chimeric SpyCas9 proteins fused with the 5′-to-3′ exonuclease Recombination J (RecJ) or with GFP and demonstrated that transfection of the pre-assembled ribonucleoprotein of the two chimeric proteins into human or plant cells resulted in greater targeted mutagenesis efficiency up to 600% without noticeable increase in off-target effects. Improved activity of the two fusion proteins should enable editing of the previously hard-to-edit genes and thus readily obtaining the cells with designer traits.

An 8-year-old, castrated male Shih-tzu dog (Case 1) showing ataxia and gait disorder was referred for neurological examination and magnetic resonance imaging. Through comprehensive examinations, the patient was tentatively diagnosed with meningoencephalitis of unknown origin (MUO) and treatment with prednisolone and cytosine arabinoside was started. The symptoms were improving with immunosuppressive treatment. However, severe bacterial cystitis occurred and we could not avoid tapering off prednisolone. Then, neurological signs recurred. Therefore, we added crisdesalazine, which allowed us to reduce the daily dosage of immunosuppressants easily. In another case, a 4-year-old, spayed female Yorkshire terrier dog (Case 2) was referred to our hospital showing a head tilt, circling, and loss of the menace reflex. The patient was tentatively diagnosed with MUO and treatment with some immunosuppressants was attempted. The clinical symptoms improved, but the alleviation was inadequate. Thus, we added crisdesalazine. The neurological signs then markedly improved. Moreover, the drugs could be tapered off more easily than before. Crisdesalazine is a novel drug that has antioxidant and anti-inflammatory action in brain disease and is used particularly for dementia. In this paper, we tried an off-label use of this drug in canine MUO patients, and found that it had, in these two patients, additional therapeutic effects on the MUO.

A 12-year-old spayed female domestic short cat was presented with tetraplegia. The cat also showed signs of hyponatremia and dehydration, which were rapidly corrected by intravenous fluid infusion. Based on thorough physical and neurological examinations, the patient was suspected of having an intracranial disease. MRI revealed a high-signal T2 image of the bilateral parietal cerebral cortical gray matter junction, which is associated with fast electrolyte calibration, and a high-signal T2 image of the C2 spinal cord ventral area, which is associated with ischemic myelopathy. The cat reappeared three days later due to anorexia. Laboratory examinations revealed that the cat was clinically dehydrated and exhibited hyponatremia. Other causes of hyponatremia were excluded through history-taking, laboratory examination, imaging, and therapeutic response to fluid therapy, except for cerebral salt-wasting syndrome (CSWS). The cat was discharged 3 days after the start of fludrocortisone therapy with electrolytes within the normal range. Magnetic resonance imaging (MRI) was performed again 1 month after hospitalization, and the cerebral lesion disappeared, but the spinal cord lesion worsened compared to the previous image. The patient was euthanized due to the progression of the spinal lesion, with a poor prognosis and poor quality of life. This is the first case of suspected CSWS with a cervical spinal lesion in a cat.

The vertical structural variability of the diurnal internal tide (DIT) with a mode-1 wavelength of ~420 km inside a mesoscale baroclinic anticyclonic eddy was examined based on observations by a single virtual-moored (VM) Slocum glider. During the glider observational period from 10 to 19 September 2018, the eddy traveled northward at approximately 50 km, allowing the glider to scan a cross section of 50 km wide and 800 m deep inside the eddy. VM observations showed that DIT experienced a noticeable vertical structural variability near the eddy center. In a range of 30 km horizontally from the eddy center (inner center), DIT’s vertical displacements were significantly intensified in the 400–800-m depth below the eddy. In the range of 30–50 km from the eddy center (outer center), DIT was almost uniformly distributed from the surface to 800-m depth. Owing to the spatiotemporally restricted dataset by the glider, the significance of DIT’s modulation observed inside the eddy can be questionable. As a result of comparing DIT’s vertical structural variability in two domains in terms of available potential energy (APE) and horizontal kinetic energy (HKE) using CTDs inside the eddy and ADCPs outside the eddy, DIT’s vertical structure inside the eddy was significantly distinguished from that outside the eddy. The relative vorticity inside the eddy was estimated based on the satellite dataset; it was negatively great in the inner center (approximately 0.35 – 0.25f) and small in the outer center (approximately 0.2 – 0.1f). These observational behaviors indicate a close relationship between them; the vorticity-dependent modulation of the DIT seems to be observationally confirmed inside the eddy. Further, in order to examine the energy transferring behavior in low vertical modes, a wavenumber spectral analysis was performed on the DIT displacements and the lowest four wavenumbers, Kz (1) through Kz (4), showed a similar behavior to those observed in DIT’s vertical structural variability inside of the eddy; the relative power of the sum of Kz (2) ~ Kz (4) with respect to Kz (1) was strong in the inner center and weakened in the outer center. These results seem to support that the wave–eddy interaction is non-uniform inside the eddy and partially depends on the relative vorticity.

The East/Japan Sea (ES) is regarded as a natural laboratory for predicting future changes in the global Meridional Overturning Circulation (MOC) under warming climates, as the ES MOC (EMOC) changes rapidly in comparison with the global MOC. Specifically, intermediate and deep-water masses of the ES are formed in its northern reaches via wind-driven subduction of surface water, and convection from the surface to deep layers during the winter. Accordingly, it is important to investigate the variation of winter sea surface temperatures (SSTs) for characterizing and predicting the EMOC; however, global SST products must be corrected and optimized for the ES, as they fail to incorporate the local marginal sea conditions. Here, a warm bias in cold SST was identified for three SST products, such as optimally interpolated sea surface temperatures (OISSTs), microwave SSTs, and operational SST and sea ice analysis products, suggesting the potential usefulness of a correction method incorporating Argo float data. When comparing OISSTs with 5 m temperature estimates from Argo float data during 2000–2020, under the assumption that the mixed layer depth is deeper than 8 m, a nearly normalized histogram of biases was produced, and the robust warm bias (mean = 0.9°C) was detected in the range of relatively cold SSTs (-2°C to 10°C), yet no significant bias in warm SSTs (> 10°C) was found. To minimize the warm bias in cold SSTs, OISSTs were corrected with an inverse 4th-order polynomial fitting method. Subsequently, the mean bias between the corrected SSTs and top depth temperatures of Argo float data was significantly reduced to less than 0.1°C. Moreover, the warm bias of cold SSTs resulted in severe underestimations of the outcropping area colder than 1°C over the northern region, as well as the occurrence period of 1°C to 5°C SSTs in the north-western ES. These results highlight the importance of local bias correction for SST products, and it is expected that the newly suggested correction method will improve model predictions of EMOC change by enhancing SST data quality in the northern ES.

The shipboard measurements over approximately 55 years in the southwestern part of the East Sea (Sea of Japan) demonstrate a remarkable basin-wide, interannual-interdecadal variability in the temperature-based thickness of the East Sea Intermediate Water (ESIW) whose temporal variability shows strong correlation with the density-based thickness (r = 0.97). Relevant to the long-term variability of the ESIW thickness, clear changes in horizonal and vertical features have been observed at the intermediate layer in the mid-1990s, such as 1) increases in vertical temperature gradient in the thermocline by shoaling of 2°C–5°C isotherms, 2) relatively high correlations among isotherms in the interdecadal timescale, 3) appearance of zonal phase difference in the ESIW thickness variability after the mid-1990s, and 4) correlation phase change between the Arctic Oscillation Index and the ESIW thickness. The ESIW thickness could be smaller when its formation is weaker and when the formation of deep-water mass below it becomes stronger. Based on the features observed, we hypothesized on the regime shift concerning the East Sea meridional overturning circulation; before the mid-1990s, active deep-water formation mainly controlled the ESIW layer variability, but after the mid-1990s, the ESIW formation rate predominantly affected its own thickness variability.

In recent years, the deterministic design optimization method has been widely used to improve the output performance of brushless direct current (BLDC) motors. However, it does not contribute to reducing the failure rate and performance variation of products because it cannot determine the manufacturing uncertainty. In this study, we proposed reliability-based robust design optimization to improve the output torque of a BLDC motor while reducing the failure rate and performance variation. We calculated the output torque and vibration response of the BLDC motor using the electromagnetic–structural coupled analysis. We selected the tooth thickness, slot opening width, slot radius, slot depth, tooth width, magnet thickness, and magnet length as the design variables related to the shape of the stator and rotor that affect the output torque. We considered the distribution of design variables with manufacturing tolerances. We performed a reliability analysis of the BLDC motor considering the distribution of design variables with manufacturing tolerances. Using the reliability analysis results, we performed reliability-based robust design optimization (RBRDO) to maximize the output torque; consequently, the output torque increased by 8.8% compared to the initial BLDC motor, the standard deviation in output performance decreased by 46.9% with improved robustness, and the failure rate decreased by 99.2% with enhanced reliability. The proposed reliability-based robust design optimization is considered to be useful in the actual product design field because it can evaluate both the reliability and robustness of the product and improve its performance in the design stage.

Abstract Background Silica nanoparticles (SiNPs) are widely used for biosensing and diagnostics, and for the targeted delivery of therapeutic agents. Safety concerns about the biomedical and clinical applications of SiNPs have been raised, necessitating analysis of the effects of their intrinsic properties, such as sizes, shapes, and surface physicochemical characteristics, on human health to minimize risk in biomedical applications. In particular, SiNP size-associated toxicological effects, and the underlying molecular mechanisms in the vascular endothelium remain unclear. This study aimed to elucidate the detailed mechanisms underlying the cellular response to exposure to trace amounts of SiNPs and to determine applicable size criteria for biomedical application. Methods To clarify whether these SiNP-mediated cytotoxicity due to induction of apoptosis or necrosis, human ECs were treated with SiNPs of four different non-overlapping sizes under low serum-containing condition, stained with annexin V and propidium iodide (PI), and subjected to flow cytometric analysis (FACS). Two types of cell death mechanisms were assessed in terms of production of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress induction, and autophagy activity. Results Spherical SiNPs had a diameter of 21.8 nm; this was further increased to 31.4, 42.9, and 56.7 nm. Hence, we investigated these effects in human endothelial cells (ECs) treated with these nanoparticles under overlap- or agglomerate-free conditions. The 20-nm SiNPs, but not SiNPs of other sizes, significantly induced apoptosis and necrosis. Surprisingly, the two types of cell death occurred independently and through different mechanisms. Apoptotic cell death resulted from ROS-mediated ER stress. Furthermore, autophagy-mediated necrotic cell death was induced through the PI3K/AKT/eNOS signaling axis. Together, the present results indicate that SiNPs within a diameter of

Summary: Pluripotent stem cells (PSCs) represent the most promising clinical source for regenerative medicine. However, given the cellular heterogeneity within cultivation and safety concerns, the development of specific and efficient tools to isolate a pure population and eliminate all residual undifferentiated PSCs from differentiated derivatives is a prerequisite for clinical applications. In this study, we raised a monoclonal antibody and identified its target antigen as desmoglein-2 (DSG2). DSG2 co-localized with human PSC (hPSC)-specific cell surface markers, and its expression was rapidly downregulated upon differentiation. The depletion of DSG2 markedly decreased hPSC proliferation and pluripotency marker expression. In addition, DSG2-negative population in hPSCs exhibited a notable suppression in embryonic body and teratoma formation. The actions of DSG2 in regulating the self-renewal and pluripotency of hPSCs were predominantly exerted through the regulation of β-catenin/Slug-mediated epithelial-to-mesenchymal transition. Our results demonstrate that DSG2 is a valuable PSC surface marker that is essential for the maintenance of PSC self-renewal. : DSG2 is a desmosomal cadherin molecule. In this article, Min and colleagues show that DSG2 is a valuable PSC surface marker that is essential for the maintenance of PSC self-renewal and pluripotency and the acquisition of pluripotency during somatic cell reprogramming through the regulation of β-catenin-mediated EMT signaling. keywords: desmoglein-2, cell surface marker, pluripotent stem cells, monoclonal antibody, EMT

The OceanGliders program started in 2016 to support active coordination and enhancement of global glider activity. OceanGliders contributes to the international efforts of the Global Ocean Observation System (GOOS) for Climate, Ocean Health, and Operational Services. It brings together marine scientists and engineers operating gliders around the world: (1) to observe the long-term physical, biogeochemical, and biological ocean processes and phenomena that are relevant for societal applications; and, (2) to contribute to the GOOS through real-time and delayed mode data dissemination. The OceanGliders program is distributed across national and regional observing systems and significantly contributes to integrated, multi-scale and multi-platform sampling strategies. OceanGliders shares best practices, requirements, and scientific knowledge needed for glider operations, data collection and analysis. It also monitors global glider activity and supports the dissemination of glider data through regional and global databases, in real-time and delayed modes, facilitating data access to the wider community. OceanGliders currently supports national, regional and global initiatives to maintain and expand the capabilities and application of gliders to meet key global challenges such as improved measurement of ocean boundary currents, water transformation and storm forecast.

Acute pancreatitis (AP) is a common disorder characterized by the inflammation of the exocrine pancreas in dogs, and the severity of the clinical signs of pancreatitis varies greatly. Therefore, the diagnosis of pancreatitis is challenging. The canine pancreatic lipase immunoreactivity test (SNAP cPL; IDEXX Laboratories Inc., USA) is rapid and relatively accurate in diagnosing pancreatitis. The purpose of this study was to evaluate the positivity rate of the SNAP cPL test in dogs regarding the severity of gastrointestinal (GI) signs and concurrent diseases. Electronic medical records of dogs were reviewed. For retrospective classification, 80 dogs with GI signs who underwent the SNAP cPL test were enrolled. Additionally, concurrent diseases on the day of the SNAP cPL test were reviewed. A positive SNAP cPL test result was observed in 26 of the 80 dogs (32.5%) with GI signs. The severity of GI signs using a scoring system and the positivity rate of SNAP cPL were statistically related. Furthermore, dogs with concurrent chronic kidney disease had a significantly higher positivity rate of SNAP cPL than those without chronic kidney disease. This information might help clinicians to decide whether a SNAP cPL test is needed. [ABSTRACT FROM AUTHOR]