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Functional loss of ERBB receptor feedback inhibitor 1 (MIG6) promotes glioblastoma tumorigenesis by aberrant activation of epidermal growth factor receptor (EGFR)
No full textDysregulation of epidermal growth factor receptor (EGFR) is one of the most common mechanisms associated with the pathogenesis of various cancers. Mitogen-inducible gene 6 [MIG6; also known as ERBB receptor feedback inhibitor 1 (ERRFI1)], identified as a feedback inhibitor of EGFR, negatively regulates EGFR by directly inhibiting its kinase activity and facilitating its internalization, subsequently leading to degradation. Despite its proposed role as an EGFR-dependent tumor suppressor, the functional consequences and clinical relevance in cancer etiology remain incompletely understood. Here, we identify that the stoichiometric balance between MIG6 and EGFR is crucial in promoting EGFR-dependent oncogenic growth in various experimental model systems. In addition, a subset of ERRFI1 (the official gene symbol of MIG6) mutations exhibit impaired ability to suppress the enzymatic activation of EGFR at multiple levels. In summary, our data suggest that decreased or loss of MIG6 activity can lead to abnormal activation of EGFR, potentially contributing to cellular transformation. We propose that the mutation status of ERRFI1 and the expression levels of MIG6 can serve as additional biomarkers for guiding EGFR-targeted cancer therapies, including glioblastoma.Y
Laser induced recast and the formation of porous carbonized conductive micro-via on polymer thin film
No full textLaser micro-drilling of polymer substrate is widely used for multilayer interconnected circuits. In this study, an analytical model of the chopped-laser micro-drilling process on polyimide substrates was developed to elucidate the mechanism that leads to the formation of conductive porous structures on the surface of the micro-via. The results revealed that the conductive porous structure and its surface morphology at the orifice have resulted from a combined effect of thermal decomposition and thermocapillary recast effects, which are simultaneously affected by the attenuation of laser energy due to extinction by the soot and the augmentation of thermal impact due to micro-combustion at the orifice. Experimental results showed that the deformed area around the orifice is reduced with increasing chopped-laser frequency due to the reduced characteristic length of thermal diffusion. In contrast, the increased temperature gradient caused the maximum height of the porous structure at the orifice to become more prominent. A modified attenuation factor is proposed to simulate this dual laser-material thermal interaction resulting from the combined laser attenuation and micro-combustion augmentation on the polymer surface, the drilling speed, the size of the orifice, and the profile of the porous structure. The simulation results matched the drilling speed from experiments, and the maximum relative error in the overall profile of the drilled micro-vias was <11 %. The proposed multi-physics model effectively captures complex laser-material interactions, providing accurate predictions for surface morphology and micro-via dimensions essential for improving the quality of laser-fabricated multilayer 3D electronics, leading to sustainable manufacturing.N
Combination model for freshness prediction of pork using VIS/NIR hyperspectral imaging with chemometrics
No full textObjective: This study aimed to develop an enhanced model for predicting pork freshness by integrating hyperspectral imaging (HSI) and chemometric analysis Methods: A total of 30 Longissimus thoracis samples from three sows were stored under vacuum conditions at 4 degrees C +/- 2 degrees C for 27 days to acquire data. The freshness prediction model for pork loin employed partial least squares regression (PLSR) with Monte Carlo data augmentation. Total bacterial count (TBC) and volatile basic nitrogen (VBN), which exhibited increases correlating with metabolite changes during storage, were designated as freshness indicators. Metabolic contents of the sample were quantified using nuclear magnetic resonance. Results: A total of 64 metabolites were identified, with 34 and 35 showing high correlations with TBC and VBN, respectively. Lysine and malate for TBC (R2 = 0.886) and methionine and niacinamide for VBN (R2 = 0.909) were identified as the main metabolites in each indicator by Model 1. Model 2 predicted main metabolites using HSI spectral data. Model 3, which predicted freshness indicators with HSI spectral data, demonstrated high prediction coefficients; TBC R2p = 0.7220 and VBN R2p = 0.8392. Furthermore, the combination model (Model 4), utilizing HSI spectral data and predicted metabolites from Model 2 to predict freshness indicators, improved the prediction coefficients compared to Model 3; TBC R2p = 0.7583 and VBN R2p = 0.8441. Conclusion: Combining HSI spectral data with metabolites correlated to the meat freshness may elucidate why certain HSI spectra indicate meat freshness and prove to be more effective in predicting the freshness state of pork loin compared to using only HSI spectral data.N
Punishing "gender deviants"? Women born in the year of the white horse and college selectivity
No full textBelief in the Chinese zodiac, a cultural belief widely held in East Asian cultures, posits that people are fated to have different traits according to the zodiac animal attached to their birth year. As a white horse is culturally associated with masculine traits, Korean women born in the White Horse year are presumed to be argumentative, headstrong, and born with "too much" Yin energy. In this study, we analyze a nationally representative sample of Korean college graduates to examine whether and how being born in the White Horse year, thereby being chronically exposed to gender stereotype-violating stigma, affects women's higher educational attainment. Our difference-in-differences models show that White Horse women, on average, entered colleges of lower selectivity than did non-White Horse women, whereas no such disadvantage was attached to White Horse men. The results also suggest that, although the negative impact of the White Horse stigma is more salient for socioeconomically disadvantaged White Horse women than for their advantaged counterparts, the difference between the two groups does not reach statistical significance. We discuss the implications of these findings with emphasis on the role of sheer presumptions about gendered expectations in reproducing social disadvantages for women.N
Zero-Strain Metal-Insulator Transition by the Local Fluctuation of Cation Dimerization
No full textThe coupled electronic and structural transitions in metal-insulator transition (MIT) hinder ultrafast switching and ultimate endurance. Decoupling these transitions and achieving a zero-strain electronic MIT can overcome the fundamental limitations of MIT in solid materials. Here, this study demonstrates that iso-valent Ti dopants in supercooled VO2 epitaxial films cause MIT with minimal hysteresis without changing unit-cell volume and crystal symmetry. The Ti dopants in the VO2 lattice locally alter the configuration of V-V pairs, where the long-range ordering in V-V pairs is disrupted, and the nano-domains of V-V dimers are formed. Strikingly, these local V-V dimers persist even above the electronic transition temperature (TMI), facilitating the zero-strain electronic MIT with nanoscale structural heterogeneity. The geometrically compatible interface between insulating and metallic phases drastically enhances switching speed and endurance during electrically and optically driven zero-strain MIT. This discovery offers a fresh perspective on the scientific understanding of MIT and the improved functionality in terms of device speed and reliability by decoupling electronic and structural transitions.N
Remodeling of tumor microenvironments by EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer
No full textPatients with EGFR mutations exhibit immunosuppressive microenvironments, limiting responsiveness to immunotherapy. We used digital spatial profiling to analyze non-small cell lung carcinomas in 25 patients before and after EGFR tyrosine kinase inhibitor (TKI) treatment, including 14 patients treated with first-line osimertinib, focusing on CD45-positive immune regions and pan-cytokeratin-positive tumor regions. Osimertinib treatment resulted in altered angiogenic pathways and immune cell proportions, with reduced plasma cells (22.2%-11.7%; p = 0.025) and increased macrophage infiltration (p = 0.145). The most predominant immune subtypes before and after treatment was the interferon-g (IFN-g)-dominant C2 subtype and the lymphocyte- depleted C4 subtype. Two patients who showed the opposite pattern, transiting from C4 to C2, had durable responses to subsequent atezolizumab/bevacizumab/carboplatin/paclitaxel treatment. Our results shed light on the immunomodulatory effects of osimertinib treatment and suggest that co-targeting angiogenesis and anti-programmed death (ligand) 1 might be effective in EGFR-TKI-resistant non-small cell lung cancer.Y
Focal Dorsal Enhancement of the Tympanic Bulla: An Early Indicator in Feline Otitis Media
No full textEvaluating the morphological changes of the tympanic bulla and the contrast enhancement (CE) patterns are key factors in diagnosing otitis media and predicting its underlying etiology. However, limited research exists on the CE patterns of the tympanic bulla in cats with bulla effusion. This retrospective study aimed to investigate the prevalence and patterns of CE in the tympanic bulla based on the presence and severity of bulla effusion in cats. Feline head CT or brain MRI images from six institutions were analyzed. Transverse pre- and postcontrast CT and MRI images were reviewed to assess the presence and severity of bulla effusion, along with the presence, pattern, and location of tympanic bulla CE. A total of 644 tympanic bullae from 322 cats were included. Bulla effusion was detected in 105 of 644 bullae, while CE was observed in 73 of 644 bullae: 5 of 539 bullae without effusion and 68 of 105 bullae with effusion. CE was significantly more common in cats with bulla effusion, with the incidence increasing as effusion severity progressed. Focal rim enhancement, predominantly localized to the dorsal aspect of the tympanic bulla, was the most frequent enhancement pattern. In cases with mild or moderate bulla effusion, only focal dorsal enhancement was observed. However, in cats with severe bulla effusion, additional patterns, including focal ventral or lateral, complete rim, and internal enhancement, emerged. These findings suggest that both the incidence and patterns of CE evolve with the progression of bulla effusion in cats and that focal dorsal enhancement may be an early indicator.Y
The Effects of Iridin and Irigenin on Cancer: Comparison with Well-Known Isoflavones in Breast, Prostate, and Gastric Cancers
No full textCancer, a worldwide problem and one of the leading causes of death due to uncontrolled cell proliferation, can be caused by various factors, such as genetic and environmental factors. Apoptosis is a programmed cell death mechanism that eliminates abnormal cells or renews cells. There are two main apoptotic pathways: intrinsic and extrinsic pathways. These pathways can be affected by various signaling pathways in cancer, such as the PI3K/AKT, MAPK, Wnt, and JAK/STAT pathways. Numerous approaches to cancer treatment have been studied, and among them, natural compounds have been actively researched. Flavonoids are natural compounds from fruits and vegetables and have been studied for their anti-cancer effects. Isoflavones, one of the subclasses of flavonoids, are usually found in soy food or legumes and are effective in several bioactive functions. The well-known isoflavones are genistein, daidzein, and glycitein. Irigenin and iridin can be extracted from the Iris family. Both irigenin and iridin are currently being studied for anti-inflammation, antioxidant, and anti-cancer by inducing apoptosis. In this review, we summarized five isoflavones, genistein, daidzein, glycitein, irigenin, and iridin and their effects on three different cancers: breast cancer, prostate cancer, and gastric cancer.Y
Ancient genomes reveal trans-Eurasian connections between the European Huns and the Xiongnu Empire
No full textThe Huns appeared in Europe in the 370s, establishing an Empire that reshaped West Eurasian history. Yet until today their origins remain a matter of extensive debate. Traditional theories link them to the Xiongnu, the founders of the first nomadic empire of the Mongolian steppe. The Xiongnu empire dissolved, however, similar to 300 y before the Huns appeared in Europe, and there is little archaeological and historical evidence of Huns in the steppe during this time gap. Furthermore, despite the rich 5th to 6th centuries current era (CE) archaeological record of the Carpathian Basin, the cultural elements of connections with the steppe are limited to few findings and even fewer solitary eastern- type burials. In this study, we coanalyze archaeological evidence with 35 newly sequenced and published genomic data for a total of 370 individuals-from 5th to 6th century CE contexts in the Carpathian Basin including 10 Hun- period eastern- type burials, 2nd to 5th century sites across Central Asia and 2nd c. before current era (BCE) to 1st c. CE Xiongnu period sites across the Mongolian steppe. We find no evidence for the presence of a large eastern/steppe descent community among the Hun- and post- Hun- period Carpathian Basin population. We also observe a high genetic diversity among the eastern- type burials that recapitulates the variability observed across the Eurasian Steppe. This suggests a mixed origin of the incoming steppe conquerors. Nevertheless, long- shared genomic tracts provide compelling evidence of genetic lineages directly connecting some individindividuals, showing that some European Huns descended from them.Y
High-Resolution Model Intercomparison Project phase 2 (HighResMIP2) towards CMIP7
No full textRobust projections and predictions of climate variability and change, particularly at regional scales, rely on the driving processes being represented with fidelity in model simulations. Consequently, the role of enhanced horizontal resolution in improved process representation in all components of the climate system continues to be of great interest. Recent simulations suggest the possibility of significant changes in both large-scale aspects of the ocean and atmospheric circulations and in the regional responses to climate change, as well as improvements in representations of small-scale processes and extremes, when resolution is enhanced.The first phase of the High-Resolution Model Intercomparison Project (HighResMIP1) was successful at producing a baseline multi-model assessment of global simulations with model grid spacings of 25-50 km in the atmosphere and 10-25 km in the ocean, a significant increase when compared to models with standard resolutions on the order of 1 degrees that are typically used as part of the Coupled Model Intercomparison Project (CMIP) experiments. In addition to over 250 peer-reviewed manuscripts using the published HighResMIP1 datasets, the results were widely cited in the Intergovernmental Panel on Climate Change report and were the basis of a variety of derived datasets, including tracked cyclones (both tropical and extratropical), river discharge, storm surge, and impact studies. There were also suggestions from the few ocean eddy-rich coupled simulations that aspects of climate variability and change might be significantly influenced by improved process representation in such models.The compromises that HighResMIP1 made should now be revisited, given the recent major advances in modelling and computing resources. Aspects that will be reconsidered include experimental design and simulation length, complexity, and resolution. In addition, larger ensemble sizes and a wider range of future scenarios would enhance the applicability of HighResMIP.Therefore, we propose the High-Resolution Model Intercomparison Project phase 2 (HighResMIP2) to improve and extend the previous work, to address new science questions, and to further advance our understanding of the role of horizontal resolution (and hence process representation) in state-of-the-art climate simulations. With further increases in high-performance computing resources and modelling advances, along with the ability to take full advantage of these computational resources, an enhanced investigation of the drivers and consequences of variability and change in both large- and synoptic-scale weather and climate is now possible. With the arrival of global cloud-resolving models (currently run for relatively short timescales), there is also an opportunity to improve links between such models and more traditional CMIP models, with HighResMIP providing a bridge to link understanding between these domains. HighResMIP also aims to link to other CMIP projects and international efforts such as the World Climate Research Program lighthouse activities and various digital twin initiatives. It also has the potential to be used as training and validation data for the fast-evolving machine learning climate models.Y