Colorectal cancer (CRC) is the second-most common malignant disease worldwide, and metastasis is the main culprit of CRC-related death. Metachronous metastases remain to be an unpredictable, unpreventable, and fatal complication, and tracing the molecular chain of events that lead to metastasis would provide mechanistically linked biomarkers for the maintenance of remission in CRC patients after curative treatment. We hypothesized, that Metastasis-associated in colorectal cancer-1 (MACC1) induces a secretory phenotype to enforce metastasis in a paracrine manner, and found, that the cell-free culture medium of MACC1-expressing CRC cells induces migration. Stable isotope labeling by amino acids in cell culture mass spectrometry (SILAC-MS) of the medium revealed, that S100A4 is significantly enriched in the MACC1-specific secretome. Remarkably, both biomarkers correlate in expression data of independent cohorts as well as within CRC tumor sections. Furthermore, combined elevated transcript levels of the metastasis genes MACC1 and S100A4 in primary tumors and in blood plasma robustly identifies CRC patients at high risk for poor metastasis-free (MFS) and overall survival (OS). Mechanistically, MACC1 strengthens the interaction of beta-catenin with TCF4, thus inducing S100A4 synthesis transcriptionally, resulting in elevated secretion to enforce cell motility and metastasis. In cell motility assays, S100A4 was indispensable for MACC1-induced migration, as shown via knock-out and pharmacological inhibition of S100A4. The direct transcriptional and functional relationship of MACC1 and S100A4 was probed by combined targeting with repositioned drugs. In fact, the MACC1-beta-catenin-S100A4 axis by statins (MACC1) and niclosamide (S100A4) synergized in inhibiting cancer cell motility in vitro and metastasis in vivo. The MACC1-beta-catenin-S100A4 signaling axis is causal for CRC metastasis. Selectively repositioned drugs synergize in restricting MACC1/S100A4-driven metastasis with cross-entity potential.
Weniger anzeigenIn the rapidly evolving realm of financial technology, blockchain integration has catalyzed transformative changes. This study delves into the intricate relationship between traditional banks and the blockchain technology. Drawing from the perspectives of International Political Economy (IPE) and Science and Technology Studies (STS), this study understands the blockchain technology through the lens of infrastructure, where power dynamics are constantly shaped by the entity wielding the strongest agency. This analysis delves into how traditional banks strategically leverage blockchain not only for technological integration but to exert control. Grounded in the concept of “power of social interaction,” this study reveals how and why banks secure a central position within this evolving infrastructure, dynamically influencing the interplay between technology and financial institutions. A focal point of this exploration is the tokenization process, which illustrates how banks actively engage with blockchain, seamlessly integrating it into their structures to shape the infrastructure narratives. By contributing insights into the implications of blockchain adoption by traditional banks, this study enhances understanding of power dynamics within financial infrastructures and their transformative potential, underscoring the process of infrastructuring governing the endeavor to attain a central position within an infrastructure.
Weniger anzeigenReducing human-made greenhouse gas emissions is crucially important for life on earth, but it requires restructuring industries in ways that could disrupt millions of workers’ lives globally. Whether this transition is “just” from the perspective of workers depends on the magnitude of job losses, the quality of new jobs, and the transitions workers experience from their current jobs to new ones. Using the example of the German automotive industry, where the shift to electric vehicle production has recently accelerated, the authors identify recommendations for unions and policymakers in North America and beyond. This article provides an overview of the tools for workers and trade unions in Germany to steer the transition and shows how analogous tools could be strengthened or created elsewhere.
Weniger anzeigenScience competitions target students interested in science with the aim to support them in developing science competence and career aspirations. Contrary to the common belief that science competition participants are exceptionally competent and strongly motivated to pursue a science career, there is growing evidence that the entirety of participants is rather heterogeneous in terms of their cognitive and affective characteristics. For science competitions to better support all participants in developing competence and career aspirations, a better understanding of the cognitive and affective characteristics of the entirety of participants is required. This study examined the Physics Olympiad as a specific type of science competitions, leading to a nuanced characterisation of N = 155 Physics Olympiad participants. Latent profile analyses revealed four participant profiles distinguished by specific patterns in cognitive abilities, physics interest, and physics self-efficacy. Profiles differed in their performance in the competition and their physics career aspiration. Grade level, gender, previous participation in the competition, and teacher support explained differences in profile membership. Our findings emphasise that Physics Olympiad participants are a heterogeneous group with varying needs and offer implications for more individualised support activities to better support the entirety of participants in developing science competence and career aspirations.
Weniger anzeigenBackground: It is a precondition for evidence-based practice that research is replicable in a wide variety of clinical settings. Current standards for identifying evidence-based psychological interventions and making recommendations for clinical practice in clinical guidelines include criteria that are relevant for replicability, but a better understanding as well refined definitions of replicability are needed enabling empirical research on this topic. Recent advances on this issue were made in the wider field of psychology and in other disciplines, which offers the opportunity to define and potentially increase replicability also in research on psychological interventions. Method: This article proposes a research strategy for assessing, understanding, and improving replicability in research on psychological interventions. Results/Conclusion: First, we establish a replication taxonomy ranging from direct to conceptual replication adapted to the field of research on clinical interventions, propose study characteristics that increase the trustworthiness of results, and define statistical criteria for successful replication with respect to the quantitative outcomes of the original and replication studies. Second, we propose how to establish such standards for future research, i.e., in order to design future replication studies for psychological interventions as well as to apply them when investigating which factors are causing the (non-)replicability of findings in the current literature.
Weniger anzeigenCell fate decisions are tightly regulated by complex signalling networks. Disturbed signalling through these networks is prominent in disease development. To elucidate pathway contributions and effects of alterations to the regulation of proliferation, quiescence, senescence, and apoptosis, computational modelling has been essential. Modelling heterogeneity on different scales was shown to be important for cell fate prediction. In recent years, personalised models capturing signalling and cell fate decisions have been developed. Of special interest is the application of these models to predict the response to drugs. In this review, we highlight examples of mathematical models of signalling pathways that regulate disease-relevant cell fate decisions on the path to develop individualised patient models for optimal treatment prediction.
Weniger anzeigenUnderstanding the world around us is a growing necessity for the whole public, as citizens are required to make informed decisions in their everyday lives about complex issues. Systems thinking (ST) is a promising approach for developing solutions to various problems that society faces and has been acknowledged as a crosscutting concept that should be integrated across educational science disciplines. However, studies show that engaging students in ST is challenging, especially concerning aspects like change over time and feedback. Using computational system models and a system dynamics approach can support students in overcoming these challenges when making sense of complex phenomena. In this paper, we describe an empirical study that examines how 10th grade students engage in aspects of ST through computational system modeling as part of a Next Generation Science Standards-aligned project-based learning unit on chemical kinetics. We show students’ increased capacity to explain the underlying mechanism of the phenomenon in terms of change over time that goes beyond linear causal relationships. However, student models and their accompanying explanations were limited in scope as students did not address feedback mechanisms as part of their modeling and explanations. In addition, we describe specific challenges students encountered when evaluating and revising models. In particular, we show epistemological barriers to fruitful use of real-world data for model revision. Our findings provide insights into the opportunities of a system dynamics approach and the challenges that remain in supporting students to make sense of complex phenomena and nonlinear mechanisms.
Weniger anzeigenNear-field optical microscopy and spectroscopy provide high-resolution imaging below the diffraction limit, crucial in physics, chemistry, and biology for studying molecules, nanoparticles, and viruses. These techniques use a sharp metallic tip of an atomic force microscope (AFM) to enhance incoming and scattered light by excited near-fields at the tip apex, leading to high sensitivity and a spatial resolution of a few nanometers. However, this restricts the near-field orientation to out-of-plane polarization, limiting optical polarization choices. We introduce double tips that offer in-plane polarization for enhanced imaging and spectroscopy. These double tips provide superior enhancement over single tips, although with a slightly lower spatial resolution (∼30 nm). They enable advanced studies of nanotubes, graphene defects, and transition metal dichalcogenides, benefiting from polarization control. The double tips allow varied polarization in tip-enhanced Raman scattering and selective excitation of transverse-electric and -magnetic polaritons, expanding the range of nanoscale samples that can be studied.
Weniger anzeigenIntroducción: se estudiaron los roles en el ciclo alimentario dentro del entorno doméstico, revisitando el concepto de "portera alimentaria". Métodos: la información se obtuvo de 10 etnografías y 24 entrevistas en profundidad a personas responsables de las tareas alimentarias en hogares de ingresos bajos en Santiago, Chile, durante la pandemia. Se realizó un análisis temático desde el marco de entornos alimentarios y género. Resultados: los resultados mostraron que el tiempo destinado al ciclo alimentario es altamente desigual entre los géneros y se responsabiliza a las mujeres del bienestar nutricional de las familias. Este rol conlleva anteponer la alimentación de los/as otros/as a la propia. Conclusión: la discusión subraya la necesidad de considerar la distribución de roles en las intervenciones de salud nutricional, evitando reproducir prácticas riesgosas para la salud y calidad de vida las porteras alimentarias, al sobreexigirlas bajo la justificación de la eficacia en la transmisión de hábitos saludables a las familias.
Weniger anzeigenHow can we understand unexplained variation in the educational outcomes of the children of immigrants? A growing literature posits that standard educational transmission models fail to explain national origin differences in attainment because they ignore immigrant selectivity – the degree to which immigrants differ from non-migrants in their sending countries. The immigrant selectivity hypothesis is usually tested using indicators of parents’ relative or “contextual” educational attainment, measuring their rank in the educational attainment distribution of their country of origin. However, using this proxy, current support for the hypothesis is mixed. We outline three conditions for the use of educational selectivity as a proxy for relative social positioning among the children of immigrants. We test our conditions using an adult and a youth sample from a large household panel survey in the UK. We supplement our analyses by exploring relative education data from prior research on Italy, France and the United States. Triangulating these varied sources, we illustrate cases when our three conditions do and do not hold, providing evidence from the UK and other contexts. We provide guidelines on the use of relative education as a measure of relative social standing in cross-national research as well as an assessment of the immigrant selectivity hypothesis in explaining second-generation educational outcomes.
Weniger anzeigenThe growing AI field faces trust, transparency, fairness, and discrimination challenges. Despite the need for new regulations, there is a mismatch between regulatory science and AI, preventing a consistent framework. A five-layer nested model for AI design and validation aims to address these issues and streamline AI application design and validation, improving fairness, trust, and AI adoption. This model aligns with regulations, addresses AI practitioners’ daily challenges, and offers prescriptive guidance for determining appropriate evaluation approaches by identifying unique validity threats. We have three recommendations motivated by this model: (1) Authors should distinguish between layers when claiming contributions to clarify the specific areas in which the contribution is made and to avoid confusion; (2) authors should explicitly state upstream assumptions to ensure that the context and limitations of their AI system are clearly understood, (3) AI venues should promote thorough testing and validation of AI systems and their compliance with regulatory requirements.
Weniger anzeigenThis article explores how Digital Humanities methodologies can be applied to historical travelogues and highlights the potential of these technologies to provide new insights into historical data. It summarizes the experiences acquired through various research tasks undertaken by the interdisciplinary project team “Digital Editions of Historical Travelogues” (DEHisRe), funded by the German Research Council (DFG) from 2021 to 2024. Based on an iterative case study of handwritten travel journals from the early 19th century, the authors outline the six-step “Life Cycle of Digital Editing”. This circular workflow incorporates best practices in the field while aiming to produce sustainable digital editions of historical travelogues.
Weniger anzeigenA pressure-robust space discretization of the incompressible Navier–Stokes equations in a rotating frame of reference is considered. The discretization employs divergence-free, -conforming mixed finite element methods like Scott–Vogelius pairs. An error estimate for the velocity is derived that tracks the dependency of the error bound on the coefficients of the problem, in particular on the angular velocity. Numerical examples support the theoretical results.
Weniger anzeigenImihigo, Rwanda’s flagship performance barometer, is praised for its cultural innovation while being criticised for instrumentalising the regime’s international credibility. Both views gloss over several thematic points, including the strategic self-criticism Imihigo affords. We triangulate fieldwork data collected from local government actors and non-state agents in four districts with secondary data to analyse the quotidian strategies undergirding the spread of, and governance responses to, Imihigo. Our analysis demonstrates three key points. First, the decentralisation reform offers the requisite institutional backdrop for officials to articulate Imihigo as a cultural innovation for local governance and regime legitimacy. The state’s reasonable support for Imihigo incentivises local service delivery, although this is used by the regime to control the local arena. Consequentially, Rwandans’ interest in Imihigo frames a forum for official criticism. Our study shows a paradoxical use of cultural and modern norms for contemporary governance through a strong state committed to producing results.
Weniger anzeigenINTRODUCTION
Cytokines might play a key role in the pathophysiology of major depressive disorder (MDD). The speed of onset of depressive episodes has been discussed as an important clinical parameter in MDD. The aim of this study was to investigate a potential influence of the speed of onset of the depressive episode on cytokine serum levels.
METHOD
Serum level of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) granulocyte and monocyte colony stimulating factor (GM-CSF) were measured in a total of 92 patients with MDD that did not respond to at least one previous antidepressant treatment. Patients were retrospectively divided in two groups: Faster (≤4 weeks) and slower (>4 weeks) onset of the depressive episode defined as the time passing from the first depressive symptoms to a full-blown depressive episode by using information from a clinical interview.
RESULTS
We found significantly lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with a faster onset compared to patients with a slower onset of the depressive episodes. Furthermore, lower cytokine serum levels of IL-2, IL-8, IL-10 and IFN-γ were found in patients with a shorter duration (less than 6 months) compared to a longer duration (6-24 months) of the current depressive episode. This effect on cytokines was independent from the effect of the speed of onset of the depressive episode.
CONCLUSIONS
Patients with faster onset of the depressive episode might represent a biological subtype of MDD with lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ.
Weniger anzeigenFast and effective anesthesia is the key for refining many invasive procedures in fish and gaining reliable data. For fish as for all vertebrates, it is also required by European law to reduce pain, suffering, and distress to the unavoidable minimum in husbandry and experiments. The most often used substance to induce anesthesia in zebrafish is tricaine (MS-222). When properly prepared and dosed, tricaine causes rapid loss of mobility, balance and reaction to touch. These signs are interpreted as a stage of deep anesthesia although its effects on the central nervous system have not convincingly been shown. Therefore, it might be possible that tricaine first acts only on the periphery, resulting in a paralyzed instead of an anesthetized fish. This has severe implications for animals undergoing procedures. To investigate the effects of tricaine on the central nervous system, we used zebrafish larvae [Tg( elavl3 :H2B-GCaMP6s)] at 4 days post fertilization (dpf), expressing a calcium indicator (GCaMP6s) in all neurons, that allows monitoring and quantifying the neuronal activity. After treating larvae with 168 mg/L tricaine, a rapid loss of neuronal activity in the forebrain was observed in confocal microscopy. In contrast, only mild effects were seen in the midbrain and hindbrain. In conclusion, the different larval brain areas showed differences in the sensitivity to tricaine treatment. The effects on the central nervous system are indicative of tricaine’s anesthetic function and are consistent with behavioral observations of inactivity and unresponsiveness to touch.
Weniger anzeigenStructural and functional changes in cortical and subcortical regions have been reported in behavioral variant frontotemporal dementia (bvFTD), however, a multimodal approach may provide deeper insights into the neural correlates of neuropsychiatric symptoms. In this multicenter study, we measured cortical thickness (CTh) and subcortical volumes to identify structural abnormalities in 37 bvFTD patients, and 37 age- and sex-matched healthy controls. For seed regions with significant structural changes, whole-brain functional connectivity (FC) was examined in a sub-cohort of N = 22 bvFTD and N = 22 matched control subjects to detect complementary alterations in brain network organization. To explore the functional significance of the observed structural and functional deviations, correlations with clinical and neuropsychological outcomes were tested where available. Significantly decreased CTh was observed in the bvFTD group in caudal middle frontal gyrus, left pars opercularis, bilateral superior frontal and bilateral middle temporal gyrus along with subcortical volume reductions in bilateral basal ganglia, thalamus, hippocampus, and amygdala. Resting-state functional magnetic resonance imaging showed decreased FC in bvFTD between: dorsal striatum and left caudal middle frontal gyrus; putamen and fronto-parietal regions; pallidum and cerebellum. Conversely, bvFTD showed increased FC between: left middle temporal gyrus and paracingulate gyrus; caudate nucleus and insula; amygdala and parahippocampal gyrus. Additionally, cortical thickness in caudal, lateral and superior frontal regions as well as caudate nucleus volume correlated negatively with apathy severity scores of the Neuropsychiatry Inventory Questionnaire. In conclusion, multimodal structural and functional imaging indicates that fronto-striatal regions have a considerable influence on the severity of apathy in bvFTD.
Weniger anzeigenBackground and Aims
Root restricting layers often hinder crops from accessing the large reservoir of bioavailable mineral nutrients situated in subsoil. This study aims to explore changes in the mean nutrient uptake depth of cereal crops when removing root restricting layers through subsoil management.
Methods
Subsoil management was performed by deep loosening, cultivation of lucerne as deep-rooting pre-crop, and their combination with compost incorporation. Management effects were evaluated by means of shoot biomass and element concentrations in shoots and soil compartments. The mean nutrient uptake depth was fingerprinted by graphically matching the 87 Sr/ 86 Sr ratios in shoots with the 87 Sr/ 86 Sr ratios in the exchangeable fraction in soil. Nutrient uplift from depth to topsoil was inferred from element concentrations in the exchangeable fraction in soil.
Results
Shoot biomass remained constant in management and control plots. The mean nutrient uptake depth changed with subsoil management in the order: deep loosening < control < deep loosening with compost incorporation. The latter coincided with a reallocation of compost-derived Na and hence resulted in increased levels of bioavailable Na below the depth of compost incorporation, which may have led to an improved water use efficiency of the crops. Thus, Na relocation triggered the deepening of the mean uptake depth of water and nutrients. Moreover, nutrient uplift from depth to topsoil was evident 21 months after subsoiling.
Conclusion
Subsoil management by deep loosening with compost incorporation provides a sustainable use of soil resources because otherwise unused deep geogenic-derived nutrient reservoirs were additionally involved in crop nutrition.
Weniger anzeigenThe recent advancements in the field of Artificial Intelligence (AI) translated to an increased adoption of AI technology in the humanities, which is often challenged by the limited amount of annotated data, as well as its heterogeneity. Despite the scarcity of data it has become common practice to design increasingly complex AI models, usually at the expense of human readability, explainability, and trust. This in turn has led to an increased need for tools to help humanities scholars better explain and validate their models as well as their hypotheses. In this paper, we discuss the importance of employing Explainable AI (XAI) methods within the humanities to gain insights into historical processes as well as ensure model reproducibility and a trustworthy scientific result. To drive our point, we present several representative case studies from the Sphaera project where we analyze a large, well-curated corpus of early modern textbooks using an AI model, and rely on the XAI explanatory outputs to generate historical insights concerning their visual content. More specifically, we show that XAI can be used as a partner when investigating debated subjects in the history of science, such as what strategies were used in the early modern period to showcase mathematical instruments and machines.
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