Hochschulbibliothekszentrum des Landes Nordrhein-Westfalen (hbz)
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Multi-scale hydraulic graph neural networks for flood modelling
No full text<jats:p>Abstract. Deep-learning-based surrogate models represent a powerful alternative to numerical models for speeding up flood mapping while preserving accuracy. In particular, solutions based on hydraulic-based graph neural networks (SWE-GNNs) enable transferability to domains not used for training and allow the inclusion of physical constraints. However, these models are limited due to four main aspects. First, they cannot model rapid differences in flow propagation speeds; secondly, they can face instabilities during training when using a large number of layers, needed for effective modelling; third, they cannot accommodate time-varying boundary conditions; and fourth, they require initial conditions from a numerical solver. To address these issues, we propose a multi-scale hydraulic-based graph neural network (mSWE-GNN) that models the flood at different resolutions and propagation speeds. We include time-varying boundary conditions via ghost cells, which enforce the solution at the domain’s boundary and drop the need for a numerical solver for the initial conditions. To improve generalization over unseen meshes and reduce the data demand, we use invariance principles and make the inputs independent from coordinates' rotations. Numerical results applied to dike-breach floods show that the model predicts the full spatio-temporal simulation of the flood over unseen irregular meshes, topographies, and time-varying boundary conditions, with mean absolute errors in time of 0.05 m for water depths and 0.003 m2 s−1 for unit discharges. We further corroborate the mSWE-GNN in a realistic case study in the Netherlands and show generalization capabilities with only one fine-tuning sample, with mean absolute errors of 0.12 m for water depth, a critical success index for a water depth threshold of 0.05 m of 87.68 %, and speed-ups of over 700 times. Overall, the approach opens up several avenues for probabilistic analyses of realistic configurations and flood scenarios.
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Revealing joint evolutions and causal interactions in complex ecohydrological systems by a network-based framework
No full text<jats:p>Abstract. There is evidence that climate change and human activities are changing ecohydrological systems, yet the complex relationships among ecological (normalized difference vegetation index, gross primary productivity, and water use efficiency) and hydrological variables (runoff, soil water storage, groundwater storage, etc.) remain understudied. This study develops a novel framework based on network analysis alongside satellite data and in situ observations to delineate the joint evolutions (phenomena) and causal interactions (mechanisms) in complex systems. The former employs correlations, and the latter uses physically constrained causality analysis to construct network relationships. This framework is applied to the Yellow River basin, a region undergoing profound ecohydrological changes. Results suggest that joint evolutions are controlled by compound drivers and direct causality. Different types of network relationships are found – namely, joint evolution with weak causality, joint evolution with high causality, and asynchronous evolution with high causality. The upstream alpine subregions, for example, where the ecological subsystem is more influenced by temperature, while the hydrological one is more driven by precipitation, show relatively high synchronization but with weak and lagged causality between two subsystems. On the other hand, ecohydrological causality can be masked by intensive human activities (revegetation, water withdrawals, and reservoir regulation), leading to distinct evolution trends. Other mechanisms can also be deduced. Reductions in water use efficiency in the growing season are directly caused by the control of evapotranspiration, and the strength of control decreases with the greening land surface in some subregions. Overall, the proposed framework provides useful insight into the complex interactions within the ecohydrological systems for the Yellow River basin and has applicability to broader geographical contexts.
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Insights into the lemon (Citrus limon) epiphytic microbiome: impact of the biocontrol yeast Clavispora lusitaniae 146
No full text<jats:title>Abstract</jats:title>
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<jats:title>Background</jats:title>
<jats:p>Postharvest lemons are affected by several fungal infections, and as alternatives to chemical fungicides for combating these infections, different microbial biocontrol agents have been studied, with the <jats:italic>Clavispora lusitaniae</jats:italic> 146 strain standing out. Although strain 146 has proven to be an effective agent, the influence of a microbial biological control agent on the postharvest lemon microbiome has not been studied until now. Thus, this study aimed to evaluate how the epiphytic microbiome of postharvest lemons is affected by the application of the biocontrol yeast <jats:italic>C. lusitaniae</jats:italic> 146.</jats:p>
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<jats:title>Results</jats:title>
<jats:p>In terms of bacterial composition, the most abundant genera were <jats:italic>Sphingomonas</jats:italic>, <jats:italic>Pelomonas</jats:italic>, and <jats:italic>Bacillus</jats:italic> and no significant differences in the composition were detected between the treated and control samples. Among fungi, <jats:italic>Clavispora</jats:italic> was predominant not only in the treated samples but also in the control, and statistics indicated differences, suggesting its significant role in modulating the epiphytic community composition of lemon. Understanding fruit microbiomes is vital for effective disease control, and this study provides insights into the microbial composition of the surface of lemon and the role of <jats:italic>C. lusitaniae</jats:italic> 146.</jats:p>
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The liminal space between hope and grief: The phenomenon of uncertainty as experienced by people living with relapsing-remitting multiple sclerosis
No full textBACKGROUND: People with the chronic disease Multiple Sclerosis are subjected to different degrees of profound uncertainty. Uncertainty has been linked to adverse psychological effects such as feelings of heightened vulnerability, avoidance of decision-making, fear, worry, anxiety disorders, and even depression. Research into Multiple Sclerosis has a predominant focus on the scientific, practical, and psychosocial issues of uncertainty. In comparison, existential uncertainty has been under-researched, even though it might pose a greater burden to those experiencing it. OBJECTIVE: To understand the lived experience of uncertainty for people living with relapsing-remitting Multiple Sclerosis. METHODS: This study followed a phenomenological research design, employing elements of both the Reflective Lifeworld Approach and Phenomenology of Practice. Seventeen people with a recent (<1 year) diagnosis of relapsing-remitting Multiple Sclerosis were included. In-depth interviews were conducted immediately after inclusion. RESULTS: The lived experience of uncertainty can be described as a stumbling motion across the liminal space between hope and grief while dealing with oscillating feelings of unrest concerning the body, self, and others. The following four constituents further illuminate the meaning of the phenomenon: Having to constantly (re)define unfamiliar and intangible bodily changes on one’s own; Unsteady navigating amidst a destabilization of the imagined life; Relating to others as a source of, mirror or buffer for uncertainty; Going through overwhelming fears and worries while clinging to one’s own logic. CONCLUSION: Adding to existing qualitative and phenomenological research into MS and theories on uncertainty, this study portrays uncertainty as a multifaceted experience. The findings imply the need for a continuous attunement of healthcare practitioners to the expectations, fears, avoidance techniques, and other uniquely personal circumstances of people with Multiple Sclerosis
Altered translation elongation contributes to key hallmarks of aging in the killifish brain
No full textINTRODUCTION:
Aging brains are characterized by a series of molecular and cellular changes known as aging hallmarks. Among these, a decline in protein homeostasis (proteostasis) marked by reduced clearance and increased protein damage and aggregation has received particular attention as a plausible link between brain aging and those neurodegenerative diseases also characterized by protein aggregation. A notable phenomenon in brain aging is a loss of concordance between mRNA and protein levels, whereby age-linked changes in mRNA do not necessarily lead to proportional changes in protein levels. In this study, we set out to investigate the causes of this “protein-transcript decoupling” and how impaired protein synthesis might contribute to other hallmarks of brain aging.
RATIONALE:
We used the short-lived African turquoise killifish, which exhibits a naturally compressed life span and accelerated brain aging, to undertake a comprehensive investigation of age-related decline in brain proteostasis. We compared young, adult, and old killifish brains at the levels of amino acid concentrations, tRNAs, mRNAs (transcriptome), actively translated mRNAs (translatome), proteins (proteome), protein modifications [phosphorylation (Ph), ubiquitylation (Ub), and acetylation (Ac)], and protein solubility and subcellular localization. We also tested whether reduced protein degradation caused by proteasome impairment contributes to protein-transcript decoupling and other aging hallmarks in the killifish brain. Our comprehensive design allowed us to pinpoint aging-vulnerable steps in protein biogenesis and reveal mechanisms connecting proteostasis decline to other aging hallmarks.
RESULTS:
We observed alterations in all molecular signatures investigated, ranging from amino acid concentrations to protein solubility and localization. A clear pattern of proteostasis dysfunction emerged: Although the synthesis of some proteins was enhanced, there was a widespread reduction of proteins enriched in positively charged (basic) amino acids. Notably, many DNA and RNA binding proteins exhibited reduced abundance in old brains, decreasing at the protein but not the transcript levels. Ribosome profiling (Ribo-seq) revealed that brain aging increased ribosome stalling. Accordingly, ribosome collisions were more frequent in old brains. Crucially, stalling events occurred disproportionately on stretches enriched in lysine and arginine codons, thus affecting translation of mRNAs encoding proteins enriched in these basic amino acids, leading to a decline in their protein levels in old brains. Aging-affected proteins included ribosomal subunits and proteins involved in DNA repair, transcription, chromatin maintenance, and RNA splicing and export, which all mediate processes influenced by aging. Ribosome stalling was also associated with increased protein insolubility, likely owing to nascent polypeptide misfolding. Partial proteasome inhibition affected aging hallmarks distinct from those linked to translation dysfunction and primarily influenced lysosomes and mitochondria.
CONCLUSION:
This work identifies altered translation elongation and impaired protein biogenesis as hallmarks of brain aging in a short-lived vertebrate. Increased ribosome pausing is proposed as a key mechanism contributing to the mismatch between mRNA and protein change
Hepatitis B virus X protein (HBx)-mediated immune modulation and prognostic model development in hepatocellular carcinoma
No full textHepatitis B virus (HBV) X protein (HBx) is critical in hepatocellular carcinoma (HCC) development, but its influence on tumor immunity and the tumor microenvironment (TME) remains unclear. This study aimed to construct a prognostic model based on HBx-related genes and explore their relationship with immune infiltration and immunotherapy response. Through transcriptome sequencing of our HBx-expressing HepG2 cells and analysis of HCC patient data from the cancer genome atlas (TCGA) and genotype-tissue expression (GTEx), we identified seven HBx-related genes, nuclear VCP-like (NVL), WD repeat domain 75 (WDR75), NOP58 nucleolar protein (NOP58), Brix domain-containing protein 1 (BRIX1), deoxynucleotidyltransferase terminal interacting protein 2 (DNTTIP2), MKI67 FHA domain interacting nucleolar phosphoprotein (NIFK), and ribosome production factor 2 (RPF2), associated with poor prognosis. LASSO Cox regression narrowed these to four key genes (BRIX1, RPF2, DNTTIP2, and WDR75), which were used to develop a prognostic riskscore signature. High-risk patients exhibited lower survival rates, decreased infiltration of anti-tumor immune cells, poorer responses to immunotherapy, and increased immune evasion. Among the four genes, DNTTIP2 showed higher expression in single-cell data, was linked to migration inhibitory factor (MIF) signaling, and may play a pivotal role in shaping an immunosuppressive TME. Elevated DNTTIP2 expression was confirmed in HBx-expressing HepG2 cells and HBV-infected HCC samples. This study highlights a novel HBx-related four-gene prognostic model that predicts clinical outcomes, immune infiltration, and immunotherapy response, offering insights into HCC progression and potential therapeutic targets
Circulation of Baffin Bay and Hudson Bay waters on the Labrador shelf and into the subpolar North Atlantic
No full text<jats:p>Abstract. In the coming decades increasing amounts of freshwater are predicted to enter the subpolar North Atlantic from Greenland and the Arctic. If this additional freshwater reaches the regions where deep convection occurs, it could potentially dampen ventilation and the formation of deep waters. In this study, we use a surface drifter dataset spanning the period 1990–2023 to investigate the pathways followed by waters originating from Davis Strait and Hudson Strait on the Labrador shelf and into the interior subpolar North Atlantic. Recent drifter deployments in the region allow for an improved understanding of the circulation on the Labrador shelf, in particular its northern part, where prior data were sparse. We show that waters originating from Davis Strait and Hudson Strait remain on the shelf as they flow downstream until they reach the Newfoundland shelf. This confirms that very little exchange takes place between the Labrador shelf and the interior Labrador Sea. Decomposing the Labrador shelf into five regions, we further describe typical pathways for these waters and show that extensive exchanges take place between the coastal and shelf-break branches of the Labrador Current. Our results suggest that if an increasing amount of freshwater reaches the Labrador shelf, it would not directly affect the Labrador Sea convection region; instead, it would lead to the formation of a salinity anomaly off the Grand Banks, which could then circulate around the subpolar North Atlantic.
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Linear modeling of brain activity during selective attention to continuous speech: the critical role of the N1 effect in event-related potentials to acoustic edges
No full textRecent studies have suggested a cortical representation of speech through superposition of evoked responses to acoustic edges, an idea closely related to regression-based modeling approaches for studying cortical synchronization to speech via magneto- or electroencephalography (M/EEG). However, it is still unclear to what extent speech-evoked event-related potentials (ERPs) contribute to these techniques. The present study addressed this question by re-analyzing an EEG data set obtained during a selective auditory attention task in which participants focused on one of two competing speakers. Segmenting the EEG based on acoustic edges revealed ERPs with clear P1-N1-P2 complexes and enhanced N1 components elicited by attended streams (N1 effect). Comparisons between ERPs and regression results revealed that temporal response functions were highly similar spatiotemporally to the corresponding ERPs and that stimulus reconstruction accuracies were driven by a consistent enhancement of ERPs including the N1 effect. These observations point to a direct link between ERPs to acoustic edges in speech and the linear modeling techniques. In particular, the improvement in signal-to-noise ratio produced by consistent attention-related enhancements of the N1 component was found to be critical for achieving tracking of selectively attended speech, presumably facilitating the higher-order processing of the selected stream
CD4/CD8–p56lck Induced T-Cell Receptor Signaling and Its Implications for Immunotherapy
No full textT-cells constitute an essential component of the adaptive immune response, mount a protective response against foreign pathogens and are important regulators of anti-tumor immunotherapy. In this context, the activation of T-cells and chimeric antigen receptor (CAR)-expressing T-cells is orchestrated by various signaling pathways, involving the initiation of a protein tyrosine phosphorylation cascade. For T-cells, this involves initiation of the phosphorylation cascade via src-related protein-tyrosine kinase p56lck, which we show to associate with the co-receptors CD4 and CD8 for the induction of a phosphorylation cascade needed for the activation of T-cells. Likewise, p56lck phosphorylation of the antigen receptor immunoreceptor tyrosine-based activation motifs (ITAMs) and key CD28 tyrosine motifs ensures the functionality and the survival of CARs, while their phospho-targets are also inhibited by PD-1, a key component of the immune checkpoint blockade. This review covers historic and current elements of our knowledge of CD4/CD8–p56lck-induced activation events and their importance to the development of CAR T-cell immunotherapies
Effect of colloidal particle size on physicochemical properties and aggregation behaviors of two alkaline soils
No full text<jats:p>Abstract. Colloidal particles are the most active soil components, and they vary in elemental composition and environmental behaviors with the particle size due to the heterogeneous nature of natural soils. The purposes of the present study are to clarify how particle size affects the physicochemical properties and aggregation kinetics of soil colloids and to further reveal the underlying mechanisms. Soil colloidal fractions, from two alkaline soils – Anthrosol and Calcisol – were subdivided into three ranges: d&lt;2 µm, d&lt;1 µm and d&lt;100 nm. The organic and inorganic carbon contents, clay mineralogy and surface electrochemical properties, including surface functional groups and zeta potentials, were characterized. Through a time-resolved light scattering technique, the aggregation kinetics of soil colloidal fractions were investigated, and their critical coagulation concentrations (CCCs) were determined. With decreasing colloidal particle diameter, the total carbon content, organic carbon, organic functional groups' content and illite content all increased. The zeta potential became less negative, and the charge variability decreased with decreasing particle diameter. The CCC values of Anthrosol and Calcisol colloids followed the descending order of d&lt;100 nm, d&lt;1 µm and d&lt;2 µm. Compared with the course factions (d&lt;1 and d&lt;2 µm), soil nanoparticles were more abundant in organic carbon and more stable clay minerals (d&lt;100 nm); thus they exhibited strongest colloidal suspension stability. The differences in organic matter contents and clay mineralogy are the fundamental reasons for the differences in colloidal suspension stability behind the size effects of Anthrosol and Calcisol colloids. The present study revealed the size effects of two alkaline soil colloids on carbon content, clay minerals, surface properties and suspension stability, emphasizing that soil nanoparticles are prone to be more stably dispersed instead of being aggregated. These findings can provide references for in-depth understanding of the environmental behaviors of the heterogeneous soil organic–mineral complexes.
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