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Various methods of generating 2D and 3D in vitro blood-brain barrier (BBB) models have previously been published with the objective of developing therapeutics for brain diseases. In general, published methods including our published method demonstrate that in vivo-like semi-permeable barrier can be generated. To further verify that an in vitro BBB model closely represents BBB, functional validation is required. Here, we functionally validate our in vitro 3D BBB model using rituximab as a representative therapeutic antibody and previously published anti-TfR (transferrin receptor) antibodies as representative BBB-penetrating antibodies. We demonstrate that our BBB model can efficiently block rituximab while allowing receptor-mediated transcytosis (RMT) of anti-TfR antibodies. In addition, we showed that RMT efficacy of anti-TfR antibodies with different binding affinity can be displayed using our BBB model. In conclusion, this demonstrates that our BBB model functionally mimics the BBB as well as having BBB-like physical properties, further establishing our BBB model as a screening tool for discovery and development of therapeutics for brain diseases.

ALD/MLD hybrid 2D tincone films were investigated structurally post-annealing. GIWAXS showed that individual benzene ring bonds were combined with the SnO layer in a repeated arrangement of the tincone monomer.

The unsaturated aldehyde

Atomic layer deposition and atomic layer chemical vapor deposition (ALD, ALCVD) of SiO2 films were investigated over a wide range of high temperatures (from 525 °C to 700 °C) using chlorine-free amino silane as the Si precursor and O3 as the oxygen reactant. The ALD window occurred at 550–600 °C. The growth per cycle (GPC) of the SiO2 films was about 1.14–1.58 A/cycle for deposition temperatures between 525 and 700 °C. There were no chlorine impurities detected in any of the deposited ALCVD films. Above a deposition temperature of 750 °C, the SiO2 films exhibited conventional chemical vapor deposition (CVD) behavior due to precursor decomposition, as evidenced by high GPC (5.51 A/cycle) and a significant impurity content (carbon 0.2 at% and nitrogen 0.4 at%). The SiO2 films had high film density (2.3 g/cm3), minimal roughness (rms ~ 0.16 nm). In addition, the wet etch rate (WER) of the SiO2 films decreased from 3.0 to 2.1 nm/min. The ALD SiO2 film at 600 °C exhibited excellent electrical performance, such as a leakage current density of 5.03 × 10−9 A/cm2 (at 3 MV/cm) and a breakdown field of 10.3 MV/cm.

Given the high population density and serious air pollution problems, understanding and predicting air pollution in East Asia are of great importance. Here, we show that the day-to-day variability of East Asia air pollution in winter is remotely controlled by the convection over the tropical Indian Ocean and western Pacific, the so-called Madden–Julian oscillation (MJO), through its extratropical teleconnections. In particular, the concentration of particulate matter with aerodynamic diameter less than 10 micron (PM10) becomes significantly high when the tropical convection is suppressed over the Indian Ocean (MJO phases 5–6). In contrast, PM10 concentration becomes significantly low when the convection is enhanced there (MJO phase 1–2). The station-averaged PM10 difference between the two MJO phases reaches up to 47% of the daily PM10 variability, indicating that the MJO is a primary source of wintertime subseasonal variability of East Asia PM10 concentration. We also show that PM10 anomaly typically lags the tropical convection by one to two weeks. This opens a new window of opportunity for subseasonal PM10 prediction in East Asia.

Skeletal muscle atrophy is associated with many diseases including cancer, inflammatory diseases, neuromuscular diseases, and acute critical illness.

The stratospheric quasi-biennial oscillation (QBO) and the tropospheric Madden–Julian oscillation (MJO) are strongly linked in boreal winter. In this Review, we synthesize observational and modelling evidence for this QBO–MJO connection and discuss its effects on MJO teleconnections and subseasonal-to-seasonal predictions. After 1980, observations indicate that, during winters when lower-stratospheric QBO winds are easterly, the MJO is ~40% stronger and persists roughly 10 days longer compared with when QBO winds are westerly. Global subseasonal forecast models, in turn, show a 1-week improvement (or 25% enhancement) in MJO prediction skill in QBO easterly versus QBO westerly phases. Despite the robustness of the observed QBO–MJO link and its global impacts via atmospheric teleconnections, the mechanisms that drive the connection are uncertain. Theories largely centre on QBO-related temperature stratification effects and subsequent impacts on deep convection, although other hypotheses propose that cloud radiative effects or QBO impacts on wave propagation might be important. Most numerical models, however, are unable to reproduce the observed QBO–MJO relationship, suggesting biases, deficiencies or omission of key physical processes in the models. While future work must strive to better understand all aspects of the QBO–MJO link, focus is needed on establishing a working mechanism and capturing the connection in models. The quasi-biennial oscillation and Madden–Julian oscillation are strongly connected during boreal winter, typified by a more active and persistent Madden–Julian oscillation during easterly quasi-biennial oscillation phases. This Review outlines the characteristics and potential mechanisms of this coupling, as well as the implications for seasonal-to-seasonal prediction.

Producing accurate weather prediction beyond two weeks is an urgent challenge due to its ever-increasing socioeconomic value. The Madden-Julian Oscillation (MJO), a planetary-scale tropical convective system, serves as a primary source of global subseasonal (i.e., targeting three to four weeks) predictability. During the past decades, operational forecasting systems have improved substantially, while the MJO prediction skill has not yet reached its potential predictability, partly due to the systematic errors caused by imperfect numerical models. Here, to improve the MJO prediction skill, we blend the state-of-the-art dynamical forecasts and observations with a Deep Learning bias correction method. With Deep Learning bias correction, multi-model forecast errors in MJO amplitude and phase averaged over four weeks are significantly reduced by about 90% and 77%, respectively. Most models show the greatest improvement for MJO events starting from the Indian Ocean and crossing the Maritime Continent., The Madden-Julian Oscillation (MJO) is a crucial component of the tropical weather system, but forecasting it has been challenging. Here, the authors present a deep learning bias correction method that significantly improves multi-model forecasts of the MJO amplitude and phase for up to four weeks.

Tracking an object in a noisy environment is difficult, especially when unknown parameters affect the object’s behavior. In the case of a high-speed ballistic object, its trajectory is affected by ...

The prediction of wintertime extratropical cyclone activity (ECA) on subseasonal time scales by models participating in the Subseasonal Experiment (SubX) and the Seasonal to Subseasonal Prediction (S2S) is assessed. Consistent with a previous study that investigated the S2S models, the SubX models have skillful predictions of ECA over regions from central North Pacific across North America to western North Atlantic, as well as East Asia and northern and southern part of eastern North Atlantic at 3–4 weeks lead time. SubX provides daily mean data, while S2S provides instantaneous data at 0000 UTC each day. This leads to different variance of ECA. Different S2S and SubX models have different reforecast initialization times and reforecast time periods. These factors can all lead to differences in prediction skill. To fairly compare the prediction skill between different models, we develop a novel way to evaluate the prediction of individual model across the two ensembles by comparing every model to the Climate Forecast System, version 2 (CFSv2), as CFSv2 has 6-hourly output and forecasts initialized every day. Among the S2S and SubX models, the European Centre for Medium-Range Weather Forecasts model exhibits the best prediction skill, followed by CFSv2. Our results also suggest that while the prediction skill is sensitive to forecast lead time, including forecasts up to 4 days old into the ensemble may still be useful for weeks 3–4 predictions of ECA.

Area selective atomic layer deposition (AS-ALD) is a promising future technology for the realization of a 5 nm scale Si complementary field effect transistor (FET) and its application in industry. AS-ALD is one of the "bottom-up" technologies, which is a key process that can reduce the cost of fabrication and decrease positional error as an alternative to the conventional "top down" technology. We researched an inhibitor for AS-ALD using molecular layer deposited (MLD) films annealed by electron beam irradiation (EBI). We studied the effect of EBI on an indicone film that was fabricated by using bis(trimethylsilyl)amidodiethyl indium (INCA-1), hydroquinone (HQ), an alucone film fabricated by using trimethylaluminum (TMA) and 4-mercaptophenol (4MP). The EBI effect on MLD films was evaluated by investigating the changes in thickness, composition and structure. In order to observe the selectivity of the annealed indicone film, atomic layer deposition of ZnO was performed on the annealed indicone/silicon line pattern, and it was found that the surface of annealed indicone can inhibit ALD of ZnO for 20 cycles as compared to a Si surface.

The blood-brain barrier (BBB) is a major hurdle for treatment of brain diseases. To overcome this, precise and reproducible BBB model is one of the key factors for successful evaluation of BBB-penetrating efficacy of developmental drugs. Thus, in vitro BBB model recapitulating the physiological structure of the BBB is a valuable tool for drug discovery and development for brain diseases. Here, we develop a simplified 3D co-culture-based BBB model using immortalized human brain endothelial cells and immortalized human astrocytes mixed with Matrigel allowing model preparation within 30 min. We directly compare our 3D BBB model to a 2D BBB model comprised solely of immortalized brain endothelial cells, to demonstrate that our 3D BBB model blocks penetration of Dextran molecules with various molecular weights, remain durable and impermeable even in a BBB-degrading condition, and rapidly form tight junctions while the 2D BBB model do not. In conclusion, this establishes our simplified 3D BBB model as a valuable tool for high throughput screening of drug candidates for brain diseases.

There is a growing demand for understanding sources of predictability on subseasonal to seasonal (S2S) time scales. Predictability at subseasonal time scales is believed to come from processes varying slower than the atmosphere such as soil moisture, snowpack, sea ice, and ocean heat content. The stratosphere as well as tropospheric modes of variability can also provide predictability at subseasonal time scales. However, the contributions of the above sources to S2S predictability are not well quantified. Here we evaluate the subseasonal prediction skill of the Community Earth System Model, version 1 (CESM1), in the default version of the model as well as a version with the improved representation of stratospheric variability to assess the role of an improved stratosphere on prediction skill. We demonstrate that the subseasonal skill of CESM1 for surface temperature and precipitation is comparable to that of operational models. We find that a better-resolved stratosphere improves stratospheric but not surface prediction skill for weeks 3–4.

Area-selective atomic layer deposition (AS-ALD) is a promising technique for fine nanoscale patterning, which may overcome the drawbacks of conventional top-down approaches for the fabrication of future electronic devices. However, conventional materials and processes often employed for AS-ALD are inadequate for conformal and rapid processing. We introduce a new strategy for AS-ALD based on molecular layer deposition (MLD) that is compatible with large-scale manufacturing. Conformal thin films of "indicone" (indium alkoxide polymer) are fabricated by MLD using INCA-1 (bis(trimethylsily)amidodiethylindium) and HQ (hydroquinone). Then, the MLD indicone films are annealed by a thermal heat treatment under vacuum. The properties of the indicone thin films with different annealing temperatures were measured with multiple optical, physical, and chemical techniques. Interestingly, a nearly complete removal of indium from the film was observed upon annealing to ca. 450 °C and above. The chemical mechanism of the thermal transformation of the indicone film was investigated by density functional theory calculations. Then, the annealed indicone thin films were applied as an inhibiting layer for the subsequent ALD of ZnO, where the deposition of approximately 20 ALD cycles (equivalent to a thickness of approximately 4 nm) of ZnO was successfully inhibited. Finally, patterns of annealed MLD indicone/Si substrates were created on which the area-selective deposition of ZnO was demonstrated.

Background Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages. Results We explore the transcriptional regulatory networks of mesenchymal-associated tumor-associated macrophages (MA-TAMs), which drive the malignant phenotypic state of GBM, and identify macrophage receptor with collagenous structure (MARCO) as the most highly differentially expressed gene. MARCOhigh TAMs induce a phenotypic shift towards mesenchymal cellular state of glioma stem cells, promoting both invasive and proliferative activities, as well as therapeutic resistance to irradiation. MARCOhigh TAMs also significantly accelerate tumor engraftment and growth in vivo. Moreover, both MA-TAM master regulators and their target genes are significantly correlated with poor clinical outcomes and are often associated with genomic aberrations in neurofibromin 1 (NF1) and phosphoinositide 3-kinases/mammalian target of rapamycin/Akt pathway (PI3K-mTOR-AKT)-related genes. We further demonstrate the origination of MA-TAMs from peripheral blood, as well as their potential association with tumor-induced polarization states and immunosuppressive environments. Conclusions Collectively, our study characterizes the global transcriptional profile of TAMs driving mesenchymal GBM pathogenesis, providing potential therapeutic targets for improving the effectiveness of GBM immunotherapy.

In an assessment of 29 global climate models (GCMs), Part I of this study identified biases in boreal winter MJO teleconnections in anomalous 500-hPa geopotential height over the Pacific–North America (PNA) region that are common to many models: an eastward shift, a longer persistence, and a larger amplitude. In Part II, we explore the relationships of the teleconnection metrics developed in Part I with several existing and newly developed MJO and basic state (the mean subtropical westerly jet) metrics. The MJO and basic state diagnostics indicate that the MJO is generally weaker and less coherent and propagates faster in models compared to observations. The mean subtropical jet also exhibits notable biases such as too strong amplitude, excessive eastward extension, or southward shift. The following relationships are found to be robust among the models: 1) models with a faster MJO propagation tend to produce weaker teleconnections; 2) models with a less coherent eastward MJO propagation tend to simulate more persistent MJO teleconnections; 3) models with a stronger westerly jet produce stronger and eastward shifted MJO teleconnections; 4) models with an eastward extended jet produce an eastward shift in MJO teleconnections; and 5) models with a southward shifted jet produce stronger MJO teleconnections. The results are supported by linear baroclinic model experiments. Our results suggest that the larger amplitude and eastward shift biases in GCM MJO teleconnections can be attributed to the biases in the westerly jet, and that the longer persistence bias is likely due to the lack of coherent eastward MJO propagation.

We propose a set of MJO teleconnection diagnostics that enables an objective evaluation of model simulations, a fair model-to-model comparison, and a consistent tracking of model improvement. Various skill metrics are derived from teleconnection diagnostics including five performance-based metrics that characterize the pattern, amplitude, east–west position, persistence, and consistency of MJO teleconnections and additional two process-oriented metrics that are designed to characterize the location and intensity of the anomalous Rossby wave source (RWS). The proposed teleconnection skill metrics are used to compare the characteristics of boreal winter MJO teleconnections (500-hPa geopotential height anomaly) over the Pacific–North America (PNA) region in 29 global climate models (GCMs). The results show that current GCMs generally produce MJO teleconnections that are stronger, more persistent, and extend too far to the east when compared to those observed in reanalysis. In general, models simulate more realistic teleconnection patterns when the MJO is in phases 2–3 or phases 7–8, which are characterized by a dipole convection pattern over the Indian Ocean and western to central Pacific. The higher model skill for phases 2, 7, and 8 may be due to these phases producing more consistent teleconnection patterns between individual MJO events than other phases, although the consistency is lower in most models than observed. Models that simulate realistic RWS patterns better reproduce MJO teleconnection patterns.

Pueraria lobata (Willd.) Ohwi. is a widely used medicinal plant in Korea, China, and Japan. The flower of P. lobata (Puerariae Flos) contains various bioactive substances such as triterpenoidal saponins and isoflavonoids. In this study, we developed a quantitative analysis of the isoflavones of Puerariae Flos by quantitative proton nuclear magnetic resonance (qHNMR) spectroscopy using the internal calibrant (IC). From the qHNMR results, the isoflavone content was found to be 7.99% and 10.57% for the MeOH sonication extract (PLs) and the MeOH reflux extract (PLr) of Puerariae Flos, respectively. The quantified isoflavone content was validated using the conventional analytical method, high-performance liquid chromatography with ultraviolet detection (HPLC-UV). The present study shows that validated qHNMR spectroscopy is a reliable method for quantifying and standardizing the isoflavone content in Puerariae Flos.

Ajuga multiflora Bunge is a perennial ornamental herb and has been used for the treatment of fever in Korean folk medicine. In the course of searching for protective agents associated with the potential of A. multiflora against dexamethsone (DEX)-induced muscle atrophy, a new phytoecdysteroid, 29-hydroxyprecyasterone (1), together with four known compounds (2–5), were isolated from A. multiflora. The structures of the compounds were determined by spectroscopic analyses, including 1D-, 2D-NMR and HR-MS interpretation. To elucidate the effects of obtained compounds on DEX-induced muscle atrophy, the myotubes diameter, myosin heavy chain (MyHC) positive area, and fusion index were evaluated by immunofluorescence staining. Overall, each compound treatment effectively prevented the atrophic myotubes through an increase of MyHC-positive myotubes and the number of nuclei. Particularly, the measurement of myotube diameter showed that compounds 1 and 5 treatment significantly alleviated the myotube thickness.

Since the first report of amorphous In–Ga–Zn–O based thin film transistors, interest in oxide semiconductors has grown. They offer high mobility, low off-current, low process temperature, and wide flexibility for compositions and processes. Unfortunately, depositing oxide semiconductors using conventional processes like physical vapor deposition leads to problematic issues, especially for high-resolution displays and highly integrated memory devices. Conventional approaches have limited process flexibility and poor conformality on structured surfaces. Atomic layer deposition (ALD) is an advanced technique which can provide conformal, thickness-controlled, and high-quality thin film deposition. Accordingly, studies on ALD based oxide semiconductors have dramatically increased recently. Even so, the relationships between the film properties of ALD-oxide semiconductors and the main variables associated with deposition are still poorly understood, as are many issues related to applications. In this review, to introduce ALD-oxide semiconductors, we provide: (a) a brief summary of the history and importance of ALD-based oxide semiconductors in industry, (b) a discussion of the benefits of ALD for oxide semiconductor deposition (in-situ composition control in vertical distribution/vertical structure engineering/chemical reaction and film properties/insulator and interface engineering), and (c) an explanation of the challenging issues of scaling oxide semiconductors and ALD for industrial applications. This review provides valuable perspectives for researchers who have interest in semiconductor materials and electronic device applications, and the reasons ALD is important to applications of oxide semiconductors.