Search Results (153)

The cHER2+ breast cancer subtype is characterized by the overexpression of the HER2 oncoprotein based on immunohistochemistry (IHC)/or by ERBB2 gene amplification using in situ hybridization (ISH) techniques. Targeted therapies are significantly changing cancer treatment outcomes. However, not all patients benefit from it due to misclassification or intrinsic mechanisms of resistance. Identifying predictive factors of response to therapy is thus crucial for optimizing treatment protocol. In addition, with the development of effective antibody–drug conjugates for targeting HER2-low subtypes, enhancing the HER2 molecular classification is crucial. In this study, a comprehensive analysis of publicly available datasets (TCGA, METABRIC, I-SPY, NOAH and CHER-LOB trials) has been considered. We present a metagene expression score (HER2MtGx 31-gene assay) based on the most informative genes associated with each molecular profile. HER2MtGx scores represent three linear subspaces associated with the HER2, Luminal and Basal-like profiles (STAT). In the METABRIC cohort, the scores are useful to discriminate against the HER2-enriched phenotype and this classification is significantly associated with long-term survival in cHER2+ patients (HR = 1.76; 95%CI = 1.09–2.86). In terms of response to neoadjuvant chemo/target therapy including I-SPY, NOAH, and CHER-LOB trials, the metagene scores are associated with the pathological response to therapy (OR = 2.26; 95%CI = 1.74–2.98). The HER2MtGx assay is a reliable tool for selecting patients for HER2-targeted therapy. Full article

Sustainable agriculture in semi-arid regions like the Awash Basin is critically dependent on water availability, which is increasingly threatened by rapid land use and land cover (LULC) change. This study assesses the impact of multi-decadal LULC changes on water resources essential for agriculture. Using satellite-derived LULC scenarios (2001, 2010, 2020) to drive the WRF-Hydro/Noah-MP modeling framework, we provide a holistic assessment of water dynamics in Ethiopia’s Awash Basin. The model was calibrated and validated with observed streamflow (R² = 0.80–0.89). Markov analysis revealed rapid cropland expansion and urbanization (2001–2010), followed by notable woodland recovery (2010–2020) linked to national initiatives. Simulations show that early-period changes increased surface runoff, potentially enhancing reservoir storage for large-scale irrigation. In contrast, later changes promoted subsurface flow, indicating a shift towards enhanced groundwater recharge, which is critical for small-scale and well-based irrigation. Evapotranspiration (ET) trends, validated against GLEAM (monthly R² = 0.88–0.96), reflected these shifts, with urbanization suppressing water fluxes and woodland recovery fostering their resurgence. This research demonstrates that land use trajectories directly alter the partitioning of agricultural water sources. The findings provide critical evidence for designing sustainable land and water management strategies that balance crop production with forest conservation to secure irrigation water and support initiatives like Ethiopia’s Green Legacy Initiative. Full article

Monitoring groundwater dynamics and basin-scale water budget closure is critical for sustainable water resource management, especially in regions facing climate stress and overexploitation. This study examines the temporal variability of total water storage and groundwater trends in Türkiye’s Kızılırmak River Basin by integrating GRACE/GRACE-FO satellite gravimetry, GLDAS-Noah land surface model outputs, ERA5-Land reanalysis products, and local meteorological observations. Groundwater storage anomalies (GWSAs) were derived from the difference between GRACE-based total water storage anomalies (TWSAs) and GLDAS-modeled surface storage components, revealing a long-term groundwater depletion trend of −9.55 ± 2.6 cm between 2002 and 2024. To investigate the hydrological drivers of these changes, lagged correlation analyses were performed between GRACE TWSA and ERA5-Land variables (precipitation, evapotranspiration, runoff, soil moisture, and temperature), showing time-shifted responses from −3 to +3 months. The strongest correlations were found with soil moisture (CC = 0.82 at lag −1), temperature (CC = −0.70 at lag −3), and runoff (CC = 0.71 at lag 0). A moderate correlation between GRACE TWSA and ERA5-based water storage closure (CC = 0.54) indicates partial alignment. These findings underscore the value of satellite gravimetry in tracking subsurface water changes and support its role in basin-scale hydrological assessments. Full article

Soil moisture simulations in semi-arid inland river basins remain highly uncertain due to complex land–atmosphere interactions and multiple parameterization schemes in land surface models. This study evaluated the ability of the Noah-Multiparameterization Land Surface Model (Noah-MP) to simulate soil moisture at meteorological sites representing the upstream, midstream and downstream regions of a semi-arid inland river basin with contrasting climates. A large physics-ensemble experiment (17,280 simulations per site) combining different parameterization schemes for 10 main physical processes was conducted. Natural selection, Tukey’s test and uncertainty contribution analysis were applied to identify sensitive processes and quantify their contributions to simulation uncertainty. Results indicate that Noah-MP captures soil moisture variability across the basin but with notable biases. Three physical processes—frozen soil permeability, supercooled liquid water in frozen soil and ground resistance to sublimation—were sensitive at all sites, whereas radiation transfer and surface albedo were consistently insensitive. At the upstream and midstream sites, supercooled liquid water contributed about half of the ensemble uncertainty, and at the downstream site ground resistance to sublimation contributed roughly 51%. These findings reveal which physical processes most strongly affect Noah-MP soil moisture simulations in semi-arid basins and provide guidance for improving parameterization schemes to reduce uncertainty. Full article

To address the challenges of water scarcity and the limited accuracy of terrestrial water storage (TWS) estimation in Inner Mongolia, this study integrates GRACE satellite observations, the GLDAS-Noah hydrological model, and ground-based precipitation records, in combination with Theil–Sen median trend analysis and the Mann–Kendall test, to systematically evaluate the spatiotemporal evolution of TWS from 2003 to 2016. The results demonstrate that: (1) GRACE data reliably capture regional water storage dynamics. Over the study period, TWS exhibited a significant overall decline, with an average rate of −5.2 × 10⁻⁴ cm/year, and seasonal variations were strongly coupled with precipitation patterns. (2) Spatially, TWS anomalies (TWSa) decreased from northeast to southwest, with values ranging from approximately +1.22 cm to −2.94 cm. The most pronounced decline was detected in the southern Ordos region. (3) Soil water changes were more substantial than those in canopy or snow water, with sharp reductions occurring during 2004–2007 and 2013–2015. Soil water exhibited clear stratification across different depths, and variations in deep soil water and groundwater were primarily influenced by non-precipitation factors. These findings provide a scientific basis for the sustainable utilization of water resources in Inner Mongolia and yield important insights for regional water management and policy formulation. Full article

In 1844, Hermann Müller, a Catholic law professor from Würzburg, published a hefty volume on Nordic Greekdom and the Original History of North-Western Europe. The study claimed to hold definitive proof of the north-European origins of Hellenism, Abrahamic monotheism, and the entire human race. Germanic history was not German at all, Müller argued, but Celtic, and underneath it lay another hidden history of Nordic Greekdom, of which Southern Hellenism had been but a minor branch. Though it is today largely forgotten, Müller’s book elicited several responses upon publication and as late as the 1920s in Nazi literature. This article examines the reception of Nordic Greekdom as a striking example of the politicization of antiquity as an origin myth, arguing that the array of modern historicizations of antiquity and of Christianity’s place within it forms a ruptured and incoherent continuity of which ideologies as dissimilar as liberalism, Christian conservatism, and fascism—to name but a few—were all a part. Tracing this variety across ideological divides avoids overly rigid dichotomies such as the distinction between theological and racial antisemitism, while acknowledging the persistent, vast significance of Christianity within these discussions, whether as a living faith or as a discarded inheritance. Full article

The hydrology of the transboundary region encompassing the western Red River Basin headwaters, such as Devils Lake Basin (DLB) in North America, is complex and highly sensitive to climate variability, impacting water resources, agriculture, and flood risk. Understanding hydrological shifts in this region is critical, particularly given recent hydroclimatic changes. This study aimed to simulate and analyze key hydrological processes and their evolution from 1981 to 2020 using an integrated modeling approach. We employed the NASA Land Information System (LIS) framework configured with the Noah-MP land surface model and the HyMAP routing model, driven by a combination of reanalysis and observational datasets. Simulations revealed a significant increase in precipitation inputs and consequential positive net water storage trends post-1990, indicating increased water retention within the system. Snow dynamics showed high interannual variability and decadal shifts in average Snow Water Equivalent (SWE). Simulated streamflow exhibited corresponding multi-decadal trends, including increasing flows within a major DLB headwater basin (Mauvais Coulee Basin) during the period of Devils Lake expansion (mid-1990s to ~2011). Furthermore, analysis of decadal average seasonal hydrographs indicated significant shifts post-2000, characterized by earlier and often higher spring peaks and increased baseflows compared to previous decades. While the model captured these trends, validation against observed streamflow highlighted significant challenges in accurately simulating peak flow magnitudes (Nash–Sutcliffe Efficiency = 0.33 at Mauvais Coulee River near Cando). Overall, the results depict a non-stationary hydrological system responding dynamically to hydroclimatic forcing over the past four decades. While the integrated modeling approach provided valuable insights into these changes and their potential drivers, the findings also underscore the need for targeted model improvements, particularly concerning the representation of peak runoff generation processes, to enhance predictive capabilities for water resource management in this vital region. Full article

As a region with functions such as energy production and as an ecological barrier, the Loess Plateau plays a vital role in China. This study examines the spatiotemporal changes in water storage and vegetation cover and their correlations. The changes in water storage were calculated using GRACE data and the GLDAS-NOAH model, while vegetation changes were derived from MODIS data. The results showed that the groundwater inventory decreased by 7.80 mm/a and the land inventory decreased by 9.72 mm/a. Surface water storage capacity increased by 1.92 mm/a. From west to east, terrestrial and groundwater storage decrease, reflecting overall losses, but surface water storage remains positive. By analyzing the FVC, it can be observed that since 2006, vegetation coverage has shown an overall increasing trend, with the highest value occurring in 2018. There has been a remarkably increase in vegetation coverage in most areas, while there was a decrease in vegetation coverage along the borders of Qinghai Province and northern Shaanxi Province. By conducting a correlation analysis, it can be found that the correlation coefficients between terrestrial water storage, surface water storage, and groundwater storage changes and vegetation coverage are −0.85, 0.60, and −0.93, respectively, indicating that increased vegetation coverage leads to reduced groundwater and terrestrial water storage. The results also indicate that there are significant spatial differences in the monthly correlations and maximum lag months between water storage and vegetation coverage. In addition, through discussing the driving factors of water storage changes in the Loess Plateau, we consider that the Grain for Green Project and mining activities may be the two major drivers of these changes. This study is highly important and valuable to the study of changes in water reserves in the Loess Plateau, as well as ecological protection and environmental assessment in the Loess Plateau. Full article

Accurately monitoring terrestrial water storage (TWS) variations is essential due to global climate change and growing water demands. This study investigates TWS changes in Oregon, USA, using Global Navigation Satellite System (GNSS) data from the Nevada Geodetic Laboratory, Gravity Recovery and Climate Experiment (GRACE) level-3 mascon data from the Jet Propulsion Laboratory (JPL), and Noah model data from the Global Land Data Assimilation System (GLDAS) data. The results show that the GNSS inversion offers superior spatial resolution, clearly capturing a water storage gradient from 300 mm in the Cascades to 20 mm in the basin and accurately distinguishing between mountainous and basin areas. However, the GRACE data exhibit blurred spatial variability, with the equivalent water height amplitude ranging from approximately 100 mm to 145 mm across the study area, making it difficult to resolve terrestrial water storage gradients. Moreover, GLDAS exhibits limitations in mountainous regions. The GNSS can provide continuous dynamic monitoring, with results aligning well with seasonal trends seen in GRACE and GLDAS data, although with a 1–2 months phase lag compared to the precipitation data, reflecting hydrological complexity. Future work may incorporate geological constraints, region-specific elastic models, and regularization strategies to improve monitoring accuracy. This study demonstrates the strong potential of GNSS technology for monitoring TWS dynamics and supporting environmental assessment, disaster warning, and water resource management. Full article

The identification of melatonin in grapes has led to the publication of numerous studies on melatonin in wines, and the aim of this study was to perform a systematic review and meta-analysis of published data on melatonin concentrations in wines. In this context, international databases such as Scopus, Web of Science and PubMed were searched for relevant articles (437) up to 29 March 2025. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. A total of 15 studies from eight countries, involving various wine types and analytical methods, were included in the meta-analysis. Considerable analytical variation was observed across studies, and high-performance liquid chromatography (HPLC) coupled with either mass spectrometry (MS) or fluorescence (FL) detection was shown to be the most accurate and sensitive method for quantifying melatonin. The highest concentrations were found in Spanish red Tempranillo wine, Romanian white Noah wine, and Romanian rosé Lidia wine. Red wines, particularly those produced from Cabernet Sauvignon (CS) grapes, were the most frequently studied. The results of this work provide a clearer picture of melatonin levels in wine. Further research is needed to explore the implications of melatonin content in wine for human health and the wine industry. Full article

Land surface models (LSMs) play a crucial role in climate prediction and carbon cycle assessment. To ensure their reliability, it is crucial to evaluate their performance in simulating key processes, such as evapotranspiration (ET) and gross primary productivity (GPP), across various temporal scales and vegetation types. This study systematically evaluates the performance of the newly modernized Noah-MP LSM version 5.0 in simulating water and carbon fluxes, specifically ET and GPP, across temporal scales ranging from half-hourly (capturing diurnal cycles) to annual using observational data from 105 sites within the globally FLUXNET2015 dataset. The results reveal that Noah-MP effectively captured the overall variability of both ET and GPP, particularly at short temporal scales. The model successfully simulated the diurnal and seasonal cycles of both fluxes, though cumulative errors increased at the annual scale. Diurnally, the largest simulation biases typically occurred around noon; while, seasonally, biases were smallest in winter. Performance varied significantly across vegetation types. For ET, the simulations were most accurate for open shrublands and deciduous broadleaf forests, while showing the largest deviation for woody savannas. Conversely, GPP simulations were most accurate for wetlands and closed shrublands, showing the largest deviation for evergreen broadleaf forests. Furthermore, an in-depth analysis stratified by the climate background revealed that ET simulations failed to capture inter-annual variability in the temperate and continental zones, while GPP was severely overestimated in arid and temperate climates. This study identifies the strengths and weaknesses of Noah-MP in simulating water and carbon fluxes, providing valuable insights for future model improvements. Full article

This paper introduces and explores a novel class of Brown and Levy steady-state motions. These motions generalize, respectively, the Ornstein-Uhlenbeck process (OUP) and the Levy-driven OUP. As the OUP and the Levy-driven OUP: the motions are Markov; their dynamics are Langevin; and their steady-state distributions are, respectively, Gauss and Levy. As the Levy-driven OUP: the motions can display the Noah effect (heavy-tailed amplitudal fluctuations); and their memory structure is tunable. And, as Gaussian-stationary processes: the motions can display the Joseph effect (long-ranged temporal dependencies); and their correlation structure is tunable. The motions have two parameters: a critical exponent which determines the Noah effect and the memory structure; and a clock function which determines the Joseph effect and the correlation structure. The novel class is a compelling stochastic model due to the following combination of facts: on the one hand the motions are tractable and amenable to analysis and use; on the other hand the model is versatile and the motions display a host of both regular and anomalous features. Full article

In the geopolitics of climate change the low-lying islands of Tuvalu are a ‘weak actor’. They are often referred to as the ‘canary in the mine’ concerning the planet’s future in the midst of a superwicked problem. The islands are overwhelmingly Christian in profession: the default practice is to turn to the book of Job and Noah in seeking to understand their plight. They are seldom referred to in theological works beyond the ‘liquid continent’ of Oceania. There is no theological college on any one of these eight atolls and reef islands. In this kind of context the prospective theologian is likely to be a climate activist, a political figure and an advocate for indigenous knowledge. This coming together of formative influence leads to an embodied public theology that draws upon themes to do with what does it mean to be a good neighbour. Full article

In water-limited regions, plant–water interactions significantly affect the hydrological cycle and vegetation dynamics, particularly in deep-rooted plantations where deep water uptake mitigates water stress during seasonal and interannual droughts. In this study, we improved the University of Arizona version of the Noah-MP model by incorporating actual soil thickness, along with new subsurface and water table schemes, to evaluate the long-term influence of plant–water interactions in Robinia pseudoacacia L. plantations. We found that soil water content was sensitive to both soil stratification and vertical root distribution, with Nash–Sutcliffe efficiency increasing from less than 0.20 to 0.63 in sensitivity experiments. Plant–water interactions resulted in persistent low soil water content within the root zone, whereas the static vegetation experiment overestimated soil moisture because of unrealistic infiltration. Transpiration and water uptake remained in dynamic equilibrium, and vegetation growth was not limited by water availability. Deep water uptake (>2 m) contributed 0.3–20.5% of transpiration during the growing season, with higher contributions observed in drier years. Compared to precipitation, evapotranspiration was more sensitive to soil water storage in the upper 0–2 m of soil. Our results emphasize the critical role of plant–water interactions in regulating water availability for deep-rooted plantations on the Loess Plateau under changing environmental conditions. Full article

This study assesses the effectiveness and limitations of publicly accessible runoff and river discharge reanalysis datasets through an intercomparison in the Upper Jinsha River, an alpine region with substantial hydropower potential on the eastern edge of the Tibetan Plateau. The examined datasets are the European Centre for Medium-Range Weather Forecast Reanalysis version 5 (ERA5-Land), the Global Flood Awareness System (GloFAS), the Global Reach-Level Flood Reanalysis (GRFR), and the China Natural Runoff Dataset (CNRD). These datasets are created using various meteorological forcing, runoff generation models, river routing models, and calibration methods. To determine the causes of discrepancies, additional simulations were carried out. One simulation, driven by meteorological forcing similar to that of ERA5-Land and GloFAS but utilizing the uncalibrated NoahMP land surface model at a higher spatial resolution, was included to evaluate the effects of meteorological inputs, spatial resolution, and calibration on runoff estimation. Runoff from all datasets was rerouted on a high-resolution river network derived from the 3-arcsecond Multi-Error-Removed Improved-Terrain Hydrography (MERIT-Hydro) dataset, allowing for a comparison between vector- and grid-based river routing models for discharge estimates. The intercomparison is grounded in observations from three gauging stations—Zhimenda, Gangtuo, and Benzilan—at monthly, daily, and hourly scales. The results suggest that model calibration has a more significant influence on runoff and discharge estimates than meteorological data. Calibrated datasets, such as GloFAS and GRFR, perform better than others, despite variations in the forcing data. The runoff characteristics-based calibration method used in GRFR exhibits superior performance at Zhimenda and Benzilan. However, at Gangtuo, GRFR’s performance is unsatisfactory, highlighting the limitation of the machine learning-based method in regions with rugged terrain and limited observations. Vector-based river routing models demonstrate advantages over grid-based models. GloFAS, which uses a grid-based routing model, encounters difficulties in simultaneously producing accurate runoff and discharge estimates. The intercomparison shows that GRFR’s river routing is sub-optimally configured. However, when GRFR’s runoff rerouted, the performance of discharge improves substantially, attaining a Kling–Gupta efficiency of approximately 0.9. These findings offer valuable insights for the further development of reanalysis datasets in this region. Full article