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Patients with HER2-positive breast cancer often exhibit intrinsic or acquired resistance to trastuzumab treatment. The transmembrane mucin 1 (MUC1) oncoprotein is aberrantly overexpressed in breast cancer cells and associates with HER2. The present studies demonstrate that silencing MUC1 C-terminal subunit (MUC1-C) in HER2-overexpressing SKBR3 and BT474 breast cancer cells results in the downregulation of constitutive HER2 activation. Moreover, treatment with the MUC1-C inhibitor, GO-203, was associated with disruption of MUC1–C/HER2 complexes and decreases in tyrosine-phosphorylated HER2 (p-HER2) levels. In studies of trastuzumab-resistant SKBR3R and BT474R cells, we found that the association between MUC1-C and HER2 is markedly increased (∼20-fold) as compared with that in sensitive cells. In addition, silencing MUC1-C in the trastuzumab-resistant cells or treatment with GO-203 decreased p-HER2 and AKT activation. Moreover, targeting MUC1-C was associated with the downregulation of phospho-p27 and cyclin E, which confer trastuzumab resistance. Consistent with these results, targeting MUC1-C inhibited the growth and clonogenic survival of both trastuzumab-resistant cells. Our results further demonstrate that silencing MUC1-C reverses resistance to trastuzumab and that the combination of GO-203 and trastuzumab is highly synergistic. These findings indicate that MUC1-C contributes to constitutive activation of the HER2 pathway and that targeting MUC1-C represents a potential approach to abrogate trastuzumab resistance.

The terrestrial carbon (C) cycle has received increasing interest over the past few decades, however, there is still a lack of understanding of the fate of newly assimilated C allocated within plants and to the soil, stored within ecosystems and lost to the atmosphere. Stable carbon isotope studies can give novel insights into these issues. In this review we provide an overview of an emerging picture of plant-soil-atmosphere C fluxes, as based on C isotope studies, and identify processes determining related C isotope signatures. The first part of the review focuses on isotopic fractionation processes within plants during and after photosynthesis. The second major part elaborates on plant-internal and plant-rhizosphere C allocation patterns at different time scales (diel, seasonal, interannual), including the speed of C transfer and time lags in the coupling of assimilation and respiration, as well as the magnitude and controls of plant-soil C allocation and respiratory fluxes. Plant responses to changing environmental conditions, the functional relationship between the physiological and phenological status of plants and C transfer, and interactions between C, water and nutrient dynamics are discussed. The role of the C counterflow from the rhizosphere to the aboveground parts of the plants, e.g. via CO2 dissolved in the xylem water or as xylem-transported sugars, is highlighted. The third part is centered around belowground C turnover, focusing especially on above- and belowground litter inputs, soil organic matter formation and turnover, production and loss of dissolved organic C, soil respiration and CO2 fixation by soil microbes. Furthermore, plant controls on microbial communities and activity via exudates and litter production as well as microbial community effects on C mineralization are reviewed. A further part of the paper is dedicated to physical interactions between soil CO2 and the soil matrix, such as CO2 diffusion and dissolution processes within the soil profile. Finally, we highlight state-of-the-art stable isotope methodologies and their latest developments. From the presented evidence we conclude that there exists a tight coupling of physical, chemical and biological processes involved in C cycling and C isotope fluxes in the plant-soil-atmosphere system. Generally, research using information from C isotopes allows an integrated view of the different processes involved. However, complex interactions among the range of processes complicate or currently impede the interpretation of isotopic signals in CO2 or organic compounds at the plant and ecosystem level. This review tries to identify present knowledge gaps in correctly interpreting carbon stable isotope signals in the plant-soil-atmosphere system and how future research approaches could contribute to closing these gaps.

Background In self-correlation lock-in thermography for thermoelastic stress analysis (TSA), the acquisition position of the reference signal affects the accuracy of the obtained stress amplitude distribution. When the reference signal is not large enough compared to the noise, the stress amplitude distribution may be incorrect. Objective This study proposes a method that does not require a reference signal and frequency analysis to obtain the stress amplitude distribution with comparable or higher accuracy than that obtained using self-correlation lock-in thermography. Methods An observation matrix is generated from the temporal variation across all thermographic pixels to describe the thermal fluctuations due to stress. Thereafter, stress amplitude distribution and the original load signal are extracted from the observation matrix using singular value decomposition (SVD). The proposed method is called SVD thermo-component analysis. To investigate the effectiveness of the proposed method, the reconstructed load signal and stress distribution are obtained from the captured thermal images for the specimen under a sinusoidal load. Results The stress amplitude distribution obtained using the proposed method is equivalent to that obtained using conventional lock-in thermography with the original load signal as the reference signal. In addition, the reconstructed load signal obtained using the proposed method successfully represents the original load signal. Conclusions SVD thermo-component analysis does not require prior knowlege of the evaluated mechanical structure to select a suitable reference-signal acquisition position as in self-correlation lock-in thermography. Therefore, the proposed TSA method reduce analysis failures compared to the conventional method.

Background: We have recently identified down-regulated microRNAs including miR-145 and miR-133a in bladder cancer (BC). The aim of this study is to determine the genes targeted by miR-145 , which is the most down-regulated microRNA in BC. Methods: We focused on fascin homologue 1 ( FSCN1 ) from the gene expression profile in miR-145 transfectant. The luciferase assay was used to confirm the actual binding sites of FSCN1 mRNA. Cell viability was evaluated by cell growth, wound-healing, and matrigel invasion assays. BC specimens were subjected to immunohistochemistry of FSCN1 and in situ hybridisation of miR-145 . Results: The miR-133a as well as miR-145 had the target sequence of FSCN1 mRNA by the database search, and both microRNAs repressed the mRNA and protein expression of FSCN1. The luciferase assay revealed that miR-145 and miR-133a were directly bound to FSCN1 mRNA. Cell viability was significantly inhibited in miR-145 , miR-133a , and si-FSCN1 transfectants. In situ hybridisation revealed that miR-145 expression was markedly repressed in the tumour lesion in which FSCN1 was strongly stained. The immunohistochemical score of FSCN1 in invasive BC ( n =46) was significantly higher than in non-invasive BC ( n =20) ( P =0.0055). Conclusion: Tumour suppressive miR-145 and miR-133a directly control oncogenic FSCN1 in BC.

Studies of person-organization fit (P-O fit) have shown that a fit between the values of the individual and the values of the organization leads to higher job satisfaction. Here, we extended past research by investigating P-O fit on employees’ well-being. We tested what characteristics of the person and the organization contributed to an effective P-O fit in Japan. Specifically, we examined the role of employees’ levels of interdependence and perceptions of their organizational contexts as clan culture or market culture. This allowed us to test what type of organizational culture formed an effective P-O fit for employees with highly interdependent cultural values in Japan. A longitudinal survey of 456 workers in Japan conducted in 2021 and 2022 revealed that clan culture—organizational culture emphasizing interpersonal harmony—was positively related to employees’ well-being, and the effects were stronger for employees with high levels of interdependence. Conversely, market culture—organizational culture emphasizing competition and achievement—was unrelated to employees’ well-being. In fact, it was negatively related to those employees’ well-being who scored high on interdependence. Taken together, these results showed that the effects of organizational culture on employees’ well-being depended on the levels of their interdependence. It seems that interdependence (P) and clan culture (O) provide an ideal P-O fit for Japanese companies.

Regular exercise significantly influences chronic obstructive pulmonary disease (COPD) outcomes. However, the associations of exercise habits during adolescence compared to current exercise habits on physical activity (PA), body composition, pulmonary function, and CT imaging parameters remain unclear. Therefore, the present study aimed to clarify the associations of adolescent and current exercise habits with current conditions. This cross-sectional study enrolled 86 participants, including 72 with COPD and 14 with pre-COPD. Adolescent exercise habits were defined as regular exercise during ages 16 to 22 years, while current exercise habits were defined as regular exercise for at least 1 year. PA was assessed using a triaxial accelerometer, body composition was assessed using bioelectrical impedance analysis, and pulmonary function was assessed using spirometry and computed tomography. Adolescent exercise habits were not significantly associated with PA or body composition, although they were associated with an increased lung volume. Compared to adolescent exercise habits, current exercise habits were associated with an increased duration of active engagement, less sedentary behavior, and increased diffusing capacity. Moreover, current exercise habits were associated with increased fat-free mass index, bone mineral content, and phase angle, which is an indicator of muscle quality. The influence of current exercise habits on these musculoskeletal indicators remained significant even after adjusting for age, sex, disease severity, and adolescent exercise habits. In addition, the relationship between PA and musculoskeletal health was more pronounced in patients with moderate-to-severe COPD than in those with mild COPD. Exercise during adolescence may promote increased lung volume. However, even after the onset of COPD, especially if the disease has progressed, regular exercise routines can help maintain PA, better body composition, and pulmonary function.

The Super DIOS project, which is an improved version of DIOS (Diffuse Intergalactic Oxygen Surveyor), is one of the candidates for Japan’s future scientific satellites, to be launched after 2030. The main scientific objective of the project is to unravel the flow of energy and metal cycles at various scales from galaxies, galaxy clusters to the warm-hot intergalactic medium along the Cosmic Web. The primary goal is the quantification of baryons, especially the unidentified “dark baryons”. Super DIOS will have a wide field of view of ∼ 1 degree, with an angular resolution of ∼ 15 arcseconds and high energy resolution ( E / d E > 1000 ). The detector will be a 30 kilo-pixel array of Transition Edge sensor (TES) with a micro-wave SQUID multiplexer read-out system. In this paper, we report on the scientific concept of Super DIOS and the status of its newly developed technologies.

We report results of a public data-analysis challenge, hosted on the open data-science platform Kaggle, to detect simulated continuous gravitational-wave signals (CWs). These are weak signals from rapidly spinning neutron stars that remain undetected despite extensive searches. The competition dataset consisted of a population of CW signals using both simulated and real LIGO detector data matching the conditions of actual CW searches. The competition attracted more than 1000 participants to develop realistic CW search algorithms. We describe the top 10 approaches and discuss their applicability as a pre-processing step compared to standard CW-search approaches. For the competition’s dataset, we find that top approaches can reduce the computing cost by 1 to 3 orders of magnitude at a false-dismissal probability comparable to standard CW searches. Additionally, the competition drove the development of new GPU-accelerated detection pipelines, which facilitated their adoption in other areas of gravitational-wave data analysis. We release the associated dataset, which constitutes the first open standardized benchmark for CW detection, to enable reproducible method comparisons and to encourage further developments toward the first detection of these elusive signals.