bluuebunny/crossref_metadata_2025 huggingface dataset:
So far, yet so close. Using networks of words to measure proximity and spillovers between firms
Authors: Marra Alessandro , Cucculelli Marco , Cartone Alfredo
Published: June 2024

Textual data are the last frontier in the empirical literature on proximity between firms. While there are a growing number of studies using textual data, no robust methodology has yet emerged, nor has any attempt been made to compare the resulting findings with standard measures of proximity based on existing classification systems. The purpose of this paper is threefold. First, we propose a methodology that can be an effective and applicable tool for measuring proximity between companies. Second, we compare the resulting indicator of proximity, which we refer to as “business” proximity, with industrial and technological proximity scores based on activity codes and technology adoption, respectively. Third, we use business proximity to explain economic performance, assuming that knowledge sharing can occur between employees working in similar firms. Having established the soundness of the methodology, the empirical results confirm the substantial information content of the descriptive texts and provide evidence on the likelihood of spillover effects between firms that are close in the business and geographical dimension.
Shock Plasticity Reconciled with Uniform High-Rate Plasticity
Authors: Brown L. M.
Published: June 2024

Recent papers describe plastic flow in metals as departing from a relatively rate-independent regime to a highly rate sensitive regime at rates above about 104 s−1. Analysis of recently published data in copper suggests that the departure is due to the breakdown of collective dislocation motion which prevents the formation of the larger slip bands, forcing the stress to rise. As the rate increases still further, the stress required to generate dislocation loops in the perfect lattice is reached. Then a new regime is established, in which a Lϋders band propagates through the metal. This band might well be related to what is often called ‘adiabatic shear’, characteristic of the plastic response at very high rates. The characteristic power laws corresponding to the different regimes can be rationalised.
Is A Star A Document? Catalogued Students and Learning Analytics
Authors: Gourlay Lesley
Published: June 2024

The media theorist Suzanne Briet proposed that through the recording of information about entities in the world, these entities are not only documented, but they themselves are rendered into documents. She asks us to consider the case of an antelope which is captured, brought to Europe, put in a zoo, and examined by experts and members of the public. She argues that the zoo is effectively a laboratory in which the antelope is analysed, displayed, and therefore itself becomes a document due to these material analytical assemblages around it. In this paper, I propose that Briet’s notion of the document can be applied to data visualisation used in learning analytics, and its effect on students. With reference to a philosophical discussion of the status of data visualisation in terms of Kant’s theory of the sublime versus Deleuze’s notion of the diagram, I argue that a learning analytics dashboard designed for individual student use not only renders the student into a document but also imbricates the student in a co-constitutive form of relationality with that document, which explicitly encourages and rewards a very particular form of action in the world in relation to the learning management system. I conclude that this has real-world effects not only in this inculcation, but in the reification of a particular neoliberal ideology of student engagement as a performance of observable, traceable, self-optimisation in a highly individualised educational worldview.
Influence of Microalgae Biomasses Retrieved from Phycoremediation of Wastewaters on Yield of Lettuce, Soil Health, and Nitrogen Environmental Fate
Authors: La Bella Emanuele , Baglieri Andrea , Fragalà Ferdinando , Saccone Rossella , Salvagno Erika , Terrazzino Sergio , Puglisi Ivana
Published: June 2024

The main purpose of this study was to investigate the effects of three microalgae strains, Chlorella vulgaris, Scenedesmus quadricauda, and Klebsormidium sp. K39, on the enhancement of lettuce yield and soil fertility and in mitigation of nitrogen losses in groundwater, focusing on some aspects of the complex soil-plant system. The experimental trials were carried in pots, and involved the application of microalgae cells at two different concentrations (50 and 500 mg kg− 1 of soil), alone or in combination with standard mineral fertilization. The yield, main morpho-biometric parameters, and protein content of lettuce seedlings, as well as the activities of key enzymes involved in the nitrogen pathway (nitrate reductase, glutamine synthase, and glutamate synthetase) at both root and shoot levels, were monitored and the results were compared to not-inoculated control plants. The nitrate leached due to over irrigation was also evaluated. Furthermore, even the effects of microalgae biostimulants on soil biochemical activity were analysed by monitoring fluorescein diacetate hydrolysis, dehydrogenase, acid and alkaline phosphomonoesterase, and urease activities. All treatments significantly improved lettuce growth, especially when combined with mineral fertilization, providing comparable levels to the control plants treated only with microalgae cells. Furthermore, microalgae treatments positively influenced soil biological activities, as evidenced by increased of the potential biochemical index of soil fertility (Mw). In conclusion, microalgae soil treatments may be considered as a viable strategy to assist growers in reducing the use of mineral fertilizers, with a view to improve plant growth as well as soil biological activity.
You are How You Eat: Foraging Behavior as a Potential Novel Marker of Rat Affective State
Authors: Neville Vikki , Finnegan Emily , Paul Elizabeth S. , Davidson Molly , Dayan Peter , Mendl Michael
Published: June 2024

Effective and safe foraging requires animals to behave according to the expectations they have about the rewards, threats, and costs in their environment. Since these factors are thought to be reflected in the animals’ affective states, we can use foraging behavior as a window into those states. In this study, rats completed a foraging task in which they had repeatedly to decide whether to continue to harvest a food source despite increasing time costs, or to forgo food to switch to a different food source. Rats completed this task across two experiments using manipulations designed to induce both positive and negative, and shorter- and longer- term changes in affective state: removal and return of enrichment (Experiment 1), implementation and reversal of an unpredictable housing treatment (Experiment 1), and delivery of rewards (tickling or sucrose) and punishers (air-puff or back-handling) immediately prior to testing (Experiment 2). In Experiment 1, rats completed fewer trials and were more prone to switching between troughs when housed in standard, compared to enriched, housing conditions. In Experiment 2, rats completed more trials following pre-test tickling compared to pre-test sucrose delivery. However, we also found that they were prone to disengaging from the task, suggesting they were really choosing between three options: ‘harvest’, ‘switch’, or ‘not work’. This limits the straightforward interpretation of the results. At present, foraging behavior within the context of this task cannot reliably be used as an indicator of an affective state in animals.
Self-Provisioning Infrastructures for the Next Generation Serverless Computing
Authors: Nastic Stefan
Published: June 2024

Serverless computing has ushered in a transformative paradigm, with a promise to alleviate developers from the intricacies of infrastructure management. However, current serverless platforms predominantly offer only serverless compute capabilities. As a consequence, the application developers are once again tasked to explicitly provision and manage the backend services (BaaS), such as object stores or API gateways, the infrastructure, and the configuration models. This violates the main promise of serverless computing and erases much of the practical benefits of the serverless paradigm. It also introduces the challenges of managing the application execution environment, which includes maintaining provisioning and deployment scripts, configuring and managing access permissions, and scaling the services during runtime. To address these challenges, in this paper we introduce a novel paradigm for the next generation of serverless computing, called self-provisioning infrastructure. The self-provisioning infrastructure is an infrastructure that is capable to automatically and autonomously (with zero-configuration and zero-touch) provision serverless functions, their infrastructure, and their supporting BaaS services. To achieve this vision, we introduce novel design principles, models, and mechanisms that are formalized vianovel programming, function, and system models. With this novel paradigm, we intend to fortify the core design principles of serverless computing but also extend themto the entire application execution environment. By doing so, we aim to enable the next-generation serverless computing in the Edge-Cloud continuum.
Sample size calculation in biomedical, clinical and biological sciences research
Authors: Sadiq Idris Zubairu , Usman Abubakar , Muhammad Aliyu , Ahmad Kabiru Haliru
Published: June 2024

Sample size determination is a critical aspect of biomedical research, as it dictates the number of samples needed for a successful experiment that can yield generalizable results to the broader population. This paper outlines the methodology for calculating sample sizes in various categories of biomedical and clinical research, encompassing cross-sectional surveys, comparative studies, case–control studies, cohort studies, and animal studies. Detailed examples are provided for each category. The determination of an appropriate sample size holds significant importance from scientific, ethical, and resource allocation perspectives. It is noteworthy that research outcomes are often directly influenced by the accuracy of sample size calculations. A robust sample size calculation serves as a cornerstone for researchers, enabling them to draw precise inferences with a high level of precision across a spectrum of biomedical and clinical investigations.
Effect of hypnosis versus mindfulness on self-defined treatment goals and sleep following acquired brain injury: a randomized actively controlled trial
Authors: Kvamme Timo L. , Lindeløv Jonas Kristoffer , Thomsen Kristine Rømer , Overgaard Rikke , Overgaard Morten
Published: June 2024

Introduction

Cognitive rehabilitation for brain injury using hypnosis has received little attention.

Methods

Here, we report on self-defined treatment goals and sleep-related outcomes from a randomized actively controlled trial of 49 patients with chronic cognitive sequelae following acquired brain injury. Patients were randomized to two groups, who initially received hypnotic suggestions either from a classical hypnosis tradition (“targeted”) or from a mindfulness tradition (“non-targeted”). Patients set self-defined goals for their everyday lives.

Results

After eight sessions, patients reported outcomes (PROs) indicated large improvements with “same” (13%), “better” (44%), “much better” (18%), or “not a problem anymore” (25%). The reported “not a problem anymore” was exclusively reported following hypnosis, not mindfulness. After a 7-week follow-up period both groups experienced a decrease in their need for sleep (~ 55 min/day). Exploratory factor analysis showed that only improvement on objective but not subjective measures (e.g. Working Memory Index, Trail Making Test, and the European Brain Injury Questionnaire scored by a relative) reflected a latent improvement factor. This indicates that subjective reports following hypnotic suggestions should be interpreted cautiously.

Conclusion

Based on our findings and converging evidence, we conclude that hypnosis is a promising method in cognitive neurorehabilitation following acquired brain injury, although further high-quality randomized controlled trials are required.
Applying Weighted Salinity Stratification to Rapid Intensification Prediction of Tropical Cyclone With Machine Learning
Authors: Yang Wen , Huang Xiaogang , Fei Jianfang , Ding Juli , Cheng Xiaoping
Published: June 2024

Tropical cyclone (TC) intensification is influenced by environmental conditions, inner‐core dynamics, and interactions with upper‐ocean layers. Rapid intensification (RI) is a significant threat that is difficult to predict, prompting multiple institutions to collaborate. However, the accuracy still needs further improvements. It is well‐known that a warm upper ocean is conducive to RI, but the role of salinity stratification in this process is not well understood, particularly under different TC translation speeds. This study reveals that rapidly intensifying TCs are related to large salinity stratification, especially when TC moves slowly. To develop a predictive model, several machine learning (ML) algorithms are used, with the most appropriate parameters and weights for each algorithm being determined. Our final ML model, which incorporates salinity stratification as a predictor and TC translation speed as a weight parameter, demonstrates superior performance across various predictive metrics, including the probability of detection (POD), false alarm ratio (FAR), and Peirce Skill Score (PSS) over the Western North Pacific during 2004–2022 compared to the model without these two factors. The most significant enhancement is observed for intense RI episodes. The improvements are up to 14% for both in POD; 7% and 13% in FAR; and 19% and 16% in PSS for 12.75 and 15.3 m s−1 RI thresholds, respectively. These results highlight the importance of including salinity stratification as a new predictor and TC translation speed as a weighted parameter using ML techniques in RI prediction models.
Role of Surface Energy Fluxes in Urban Overheating Under Buoyancy‐Driven Atmospheric Conditions
Authors: Back Yannick , Bach Peter M. , Santamouris Mattheos , Rauch Wolfgang , Kleidorfer Manfred
Published: June 2024

Urbanization alters land surface properties in absorbing, reflecting and emitting radiation as well as infiltrating, evaporating and storing water. This consequently modifies surface energy and water fluxes and, thus, urban climates. Weak synoptic flow, clear sky conditions and higher surface temperatures in cities compared to their rural surroundings create a buoyancy‐driven atmospheric circulation, in which surface energy fluxes become the main determinants of urban daytime overheating. Here, we demonstrate the role of surface energy fluxes for warming and cooling processes in the urban canopy layer under buoyancy‐driven atmospheric conditions. We improve and apply an integrated CFD‐GIS modeling approach to provide a detailed analysis of fine‐scale land‐atmosphere interactions and assess the surfaces' profound implications on energy and water exchange. We show that variations in the ratios of the surface energy fluxes to the net radiation can be separated from meteorological conditions (wind speed, air temperature and incoming solar radiation) and emissivity values, varying explicitly with changes in land surface type and water availability for vegetated areas. Based on the energy flux ratios, we introduce an approach to assess the surface‐induced warming and cooling effect and its contribution to urban overheating in the urban canopy layer, under buoyancy‐driven atmospheric conditions, directly applicable to strategic urban planning for climate change adaptation. Independent of meteorological conditions, this approach can be used to evaluate different surface materials (both natural and artificial) and climate adaptation measures, such as urban nature‐based solutions and blue‐green infrastructures, and to monitor changes in the energy and water balance.
Catchment Properties Shape Seasonal Variation in Groundwater‐Surface Water Interaction—Geogenic Silica as a Proxy for Hydrological Turnover Induced Mixing
Authors: Bäthke Lars , Schuetz Tobias
Published: June 2024

The cumulative and bidirectional groundwater‐surface water (GW‐SW) interaction along a stream is defined as hydrological turnover (HT) influencing solute transport and source water composition. However, HT proves to be highly variable, producing spatial exchange patterns influenced by local groundwater, geology, and topography. Hence, identifying factors controlling HT poses a challenge. We studied spatiotemporal HT variability at two reaches of a third order tributary of the river Mosel, Germany. Additionally, we sampled for silica concentrations in the stream and in the near‐stream groundwater. Thus, creating snapshots of the boundary layer between ground‐ and surface water where HT occurs, driven by mixing processes in the hyporheic zone. We utilize an enhanced hydrograph separation method, unveiling reach differences in storage drainage based on aquifer dimension and connectivity. The data shows a site‐specific negative correlation of HT with discharge, while hydraulic gradients correlate with HT only at the reach with faster catchment drainage behavior. Examining silica concentrations between stream and wells shows that silica variation increases significantly with the decrease of HT under low flow conditions at the slower draining reach. At the fast draining reach this relationship is seasonal. In Summary, our results show that stream discharge shapes the influence of HT on solute transport. Yet, reach drainage behavior shapes seasonal states of groundwater storages and can be an additional control of HT. Hence, concentration change of pollutants could be masked by HT. Thus, our findings contribute to the understanding of HT variability along streams and its ability of influencing physico‐chemical stream water composition.
Thermochemical Structure of the Superior Craton and Environs: Implications for the Evolution and Preservation of Cratonic Lithosphere
Authors: Dave Riddhi , Darbyshire Fiona , Afonso Juan Carlos , Fomin I.
Published: June 2024

The Archean Superior craton was formed by the assemblage of continental and oceanic terranes at ∼2.6 Ga. The craton is surrounded by multiple Proterozoic mobile belts, including the Paleoproterozoic Trans‐Hudson Orogen which brought together the Superior and Rae/Hearne cratons at ∼1.9–1.8 Ga. Despite numerous studies on Precambrian lithospheric formation and evolution, the deep thermochemical structure of the Superior craton and its surroundings remains poorly understood. Here we investigate the upper mantle beneath the region from the surface to 400 km depth by jointly inverting Rayleigh wave phase velocity dispersion data, elevation, geoid height and surface heat flow, using a probabilistic inversion to obtain a (pseudo‐)3D model of composition, density and temperature. The lithospheric structure is dominated by thick cratonic roots (>300 km) beneath the eastern and western arms of the Superior craton, with a chemically depleted signature (Mg# > 92.5), consistent with independent results from mantle xenoliths. Beneath the surrounding Proterozoic and Phanerozoic orogens, the Mid‐continent Rift and Hudson Strait, we observe a relatively thinner lithosphere and more fertile composition, indicating that these regions have undergone lithospheric modification and erosion. Our model supports the hypothesis that the core of the Superior craton is well‐preserved and has evaded lithospheric destruction and refertilization. We propose three factors playing a critical role in the craton's stability: (a) the presence of a mid‐lithospheric discontinuity, (b) the correct isopycnic conditions to sustain a strength contrast between the craton and the surrounding mantle, and (c) the presence of weaker mobile belts around the craton.
Repacking in Compacting Mushes at Intermediate Melt Fractions: Constraints From Numerical Modeling and Phase Separation Experiments on Granular Media
Authors: Florez Darien , Huber Christian , Hoyos Susana , Pec Matej , Parmentier E. M. , Connolly James A. D. , Hirth Greg
Published: June 2024

Before large volumes of crystal poor rhyolites are mobilized as melt, they are extracted through the reduction of pore space within their corresponding crystal matrix (compaction). Petrological and mechanical models suggest that a significant fraction of this process occurs at intermediate melt fractions (ca. 0.3–0.6). The timescales associated with such extraction processes have important ramifications for volcanic hazards. However, it remains unclear how melt is redistributed at the grain‐scale and whether using continuum scale models for compaction is suitable to estimate extraction timescales at these melt fractions. To explore these issues, we develop and apply a two‐phase continuum model of compaction to two suites of analog phase separation experiments—one conducted at low and the other at high temperatures, T, and pressures, P. We characterize the ability of the crystal matrix to resist porosity change using parameterizations of granular phenomena and find that repacking explains both data sets well. A transition between compaction by repacking to melt‐enhanced grain boundary diffusion‐controlled creep near the maximum packing fraction of the mush may explain the difference in compaction rates inferred from high T + P experiments and measured in previous deformation experiments. When upscaling results to magmatic systems at intermediate melt fractions, repacking may provide an efficient mechanism to redistribute melt. Finally, outside nearly instantaneous force chain disruption events occasionally recorded in the low T + P experiments, melt loss is continuous, and two‐phase dynamics can be solved at the continuum scale with an effective matrix viscosity.
Enrichment of Phosphates, Lead, and Mixed Soil‐Organic Particles in INPs at the Southern Great Plains Site
Authors: Cornwell Gavin C. , Steinke Isabelle , Lata Nurun Nahar , Zelenyuk Alla , Kulkarni Gourihar , Pekour Mikhail , Perkins Russell , Levin Ezra J. T. , China Swarup , DeMott Paul J. , Burrows Susannah M.
Published: June 2024

Ice nucleating particles (INPs) are rare particles that initiate primary ice formation, a critical step required for subsequent important cloud microphysical processes that ultimately govern cloud phase and cloud radiative properties. Laboratory studies have found that organic‐rich dusts, such as those found in soils, are more efficient INPs compared to mineral dust. However, the atmospheric relevance of these organic‐rich dusts are not well understood, particularly in regions with significant agricultural activity. The Agricultural Ice nuclei at the Southern Great Plains field campaign (AGINSGP) was conducted in rural Oklahoma to investigate how soil dusts contribute to INP populations in the Great Plains. We present chemical characterization of ambient and ice crystal residual particles from a single day of sampling, using single particle mass spectrometry (SPMS) and scanning microscopy. Ambient particles were primarily carbonaceous or secondary aerosol, while the fraction of dust particles was higher in the residual particles. We also observed an unusual particle type consisting of a carbonaceous core mixed with dust fragments on the surface, which was found in higher proportion in residuals. Dust particles measured during residual sampling contained greater proportions of phosphate (63 and 79) and lead (206Pb+). Strong sulfate signals were not seen in the residual dust particles measured by the SPMS, while nitrate was slightly depleted relative to ambient dust. This study shows that organic‐rich soils may be important contributors to the ambient INP population in agricultural regions.
Lithological Impact on Radon Levels: A Study of Indoor and Soil Gas Radon in the Centre Region of Cameroon
Authors: Ndjana Nkoulou J. E. , Saïdou  , Hamadou Yerima A. , Oumar Bobbo M. , Nugraha E. D. , Ipan A. S. , Najam L. A. , Suárez‐Navarro J. A. , Yoho B. , Kwato Njock M. G.
Published: June 2024

The objectives of the current study are to carry out soil gas radon (Rn) measurements, to evaluate the total inhalation effective dose, to determine risk levels over the lithological formations of the study area. The behavior investigation of Rn activity concentration distributions in dwellings and soils, and soil Rn mapping were also conducted. Soil gas Rn measurements were made at 102 sampling points by Markus 10 instrument. This data was combined with previously reported results from 140 indoor Rn RADTRAK dosimeters to determine the total inhalation effective dose and to conduct a statistical analysis. Overall, the Rn activity concentrations in soil and dwellings range from 4 to 66 kBq m−3 and from 15 to 140 Bq m−3, with averages of 31 ± 15 kBq m−3 and 41 ± 24 Bq m−3 respectively. The corresponding total inhalation effective dose ranges from 0.35 to 3.53 mSv y−1, with a mean value of 1.37 ± 0.58 mSv y−1. For soil gas Rn, the chlorite schist lithology showed the highest average concentration level. Which could be justified by the possible presence, within chlorite minerals, highly emitting zones of alpha particles, leading to the formation of radioactive halos. Normal and high‐risk level of Rn were found for about 82% and 11% of the total area surveyed respectively. These findings highlight the need for preventive measure against Rn exposure in homes within the investigated areas. This study contributes valuable insights into Rn distribution patterns and risk assessment, offering a basis for targeted interventions in the region.
VTA glutamatergic projections to the nucleus accumbens suppress psychostimulant-seeking behavior
Authors: Barbano M. Flavia , Qi Jia , Chen Emma , Mohammad Uzma , Espinoza Orlando , Candido Marcos , Wang Huiling , Liu Bing , Hahn Suyun , Vautier François , Morales Marisela
Published: June 2024

Converging evidence indicates that both dopamine and glutamate neurotransmission within the nucleus accumbens (NAc) play a role in psychostimulant self-administration and relapse in rodent models. Increased NAc dopamine release from ventral tegmental area (VTA) inputs is critical to psychostimulant self-administration and NAc glutamate release from prelimbic prefrontal cortex (PFC) inputs synapsing on medium spiny neurons (MSNs) is critical to reinstatement of psychostimulant-seeking after extinction. The regulation of the activity of MSNs by VTA dopamine inputs has been extensively studied, and recent findings have demonstrated that VTA glutamate neurons target the NAc medial shell. Here, we determined whether the mesoaccumbal glutamatergic pathway plays a role in psychostimulant conditioned place preference and self-administration in mice. We used optogenetics to induce NAc release of glutamate from VTA inputs during the acquisition, expression, and reinstatement phases of cocaine- or methamphetamine-induced conditioned place preference (CPP), and during priming-induced reinstatement of cocaine-seeking behavior. We found that NAc medial shell release of glutamate resulting from the activation of VTA glutamatergic fibers did not affect the acquisition of cocaine-induced CPP, but it blocked the expression, stress- and priming-induced reinstatement of cocaine- and methamphetamine CPP, as well as it blocked the priming-induced reinstatement of cocaine-seeking behavior after extinction. These findings indicate that in contrast to the well-recognized mesoaccumbal dopamine system that is critical to psychostimulant reward and relapse, there is a parallel mesoaccumbal glutamatergic system that suppresses reward and psychostimulant-seeking behavior.
TRIM26 deficiency enhancing liver regeneration through macrophage polarization and β-catenin pathway activation
Authors: Li Tingting , Zhong Wei , Li Mengqi , Shao Zile , Zhang Gongye , Wang Weiwei , Gao Zhixing , Tan Xuemei , Xu Ziyi , Luo Fanghong , Song Gang
Published: June 2024

Liver regeneration is a complex process involving the crosstalk between parenchymal and non-parenchymal cells, especially macrophages. However, the underlying mechanisms remain incompletely understood. Here, we identify the E3 ubiquitin ligase TRIM26 as a crucial regulator of liver regeneration. Following partial hepatectomy or acute liver injury induced by carbon tetrachloride, Trim26 knockout mice exhibit enhanced hepatocyte proliferation compared to wild-type controls, while adeno-associated virus (AAV)-mediated overexpression of Trim26 reverses the promotional effects. Mechanistically, Trim26 deficiency promotes the recruitment of macrophages to the liver and their polarization towards pro-inflammatory M1 phenotype. These M1 macrophages secrete Wnts, including Wnt2, which subsequently stimulate hepatocyte proliferation through the activation of Wnt/β-catenin signaling. In hepatocytes, Trim26 knockdown reduces the ubiquitination and degradation of β-catenin, thereby further enhancing Wnt/β-catenin signaling. Pharmacological inhibition of Wnt/β-catenin pathway by ICG-001 or depletion of macrophages by clodronate liposomes diminishes the pro-regenerative effects of Trim26 deficiency. Moreover, bone marrow transplantation experiments provide evidence that Trim26 knockout in myeloid cells alone can also promote liver regeneration, highlighting the critical role of macrophage Trim26 in this process. Taken together, our study uncovers TRIM26 as a negative regulator of liver regeneration by modulating macrophage polarization and Wnt/β-catenin signaling in hepatocytes, providing a potential therapeutic target for promoting liver regeneration in clinical settings.
ASAH1 facilitates TNBC by DUSP5 suppression-driven activation of MAP kinase pathway and represents a therapeutic vulnerability
Authors: Reddi Kiran Kumar , Chava Suresh , Chabattula Siva Chander , Edwards Yvonne J. K. , Singh Kamaljeet , Gupta Romi
Published: June 2024

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is prone to metastasis and therapy resistance. Owing to its aggressive nature and limited availability of targeted therapies, TNBC is associated with higher mortality as compared to other forms of breast cancer. In order to develop new therapeutic options for TNBC, we characterized the factors involved in TNBC growth and progression. Here, we demonstrate that N-acylsphingosine amidohydrolase 1 (ASAH1) is overexpressed in TNBC cells and is regulated via p53 and PI3K-AKT signaling pathways. Genetic knockdown or pharmacological inhibition of ASAH1 suppresses TNBC growth and progression. Mechanistically, ASAH1 inhibition stimulates dual-specificity phosphatase 5 (DUSP5) expression, suppressing the mitogen-activated protein kinase (MAPK) pathway. Furthermore, pharmacological cotargeting of the ASAH1 and MAPK pathways inhibits TNBC growth. Collectively, we unmasked a novel role of ASAH1 in driving TNBC and identified dual targeting of the ASAH1 and MAPK pathways as a potential new therapeutic approach for TNBC treatment.
Crosstalk between CAFs and tumour cells in head and neck cancer
Authors: Li Xinyang , González-Maroto Celia , Tavassoli Mahvash
Published: June 2024

Head and neck squamous cell carcinomas (HNSCCs) are amongst the most aggressive, complex, and heterogeneous malignancies. The standard of care treatments for HNC patients include surgery, radiotherapy, chemotherapy, or their combination. However, around 50% do not benefit while suffering severe toxic side effects, costing the individuals and society. Decades have been spent to improve HNSCC treatment outcomes with only limited success. Much of the research in HNSCC treatment has focused on understanding the genetics of the HNSCC malignant cells, but it has become clear that tumour microenvironment (TME) plays an important role in the progression as well as treatment response in HNSCC. Understanding the crosstalk between cancer cells and TME is crucial for inhibiting progression and treatment resistance. Cancer-associated fibroblasts (CAFs), the predominant component of stroma in HNSCC, serve as the primary source of extra-cellular matrix (ECM) and various pro-tumoral composites in TME. The activation of CAFs in HNSCC is primarily driven by cancer cell-secreted molecules, which in turn induce phenotypic changes, elevated secretive status, and altered ECM production profile. Concurrently, CAFs play a pivotal role in modulating the cell cycle, stemness, epithelial-mesenchymal transition (EMT), and resistance to targeted and chemoradiotherapy in HNSCC cells. This modulation occurs through interactions with secreted molecules or direct contact with the ECM or CAF. Co-culture and 3D models of tumour cells and other TME cell types allows to mimic the HNSCC tumour milieu and enable modulating tumour hypoxia and reprograming cancer stem cells (CSC). This review aims to provide an update on the development of HNSCC tumour models comprising CAFs to obtain better understanding of the interaction between CAFs and tumour cells, and for providing preclinical testing platforms of current and combination with emerging therapeutics.
Mobilization and activation of tumor-infiltrating dendritic cells inhibits lymph node metastasis in intrahepatic cholangiocarcinoma
Authors: Sun Bao-Ye , Wang Zhu-Tao , Chen Ke-Zhu , Song Yang , Wu Jing-Fang , Zhang Dai , Sun Guo-Qiang , Zhou Jian , Fan Jia , Hu Bo , Yi Yong , Qiu Shuang-Jian
Published: June 2024

Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples. Tumor-infiltrating DCs correlated with increased CD8+ T cell infiltration and better prognoses in ICC patients. Mechanistically, β-catenin-mediated CXCL12 suppression accounted for the impaired DC recruitment in ICC with LNM. Two mouse ICC cell lines MuCCA1 and mIC-23 cells were established from AKT/NICD or AKT/YAP-induced murine ICCs respectively and were utilized to construct the footpad tumor LNM model. We found that expansion and activation of conventional DCs (cDCs) by combined Flt3L and poly(I:C) (FL-pIC) therapy markedly suppressed the metastasis of mIC-23 cells to popliteal LNs. Moreover, β-catenin inhibition restored the defective DC infiltration into primary tumor sites and reduced the incidence of LNM in ICC. Collectively, our findings identify tumor cell intrinsic β-catenin activation as a key mechanism for subverting DC-mediated anti-tumor immunity in ICC with LNM. FL-pIC therapy or β-catenin inhibitor could merit exploration as a potential regimen for mitigating ICC cell metastasis to LNs and achieving effective tumor immune control.
Claustrum neurons projecting to the anterior cingulate restrict engagement during sleep and behavior
Authors: Atlan Gal , Matosevich Noa , Peretz-Rivlin Noa , Marsh-Yvgi Idit , Zelinger Noam , Chen Eden , Kleinman Timna , Bleistein Noa , Sheinbach Efrat , Groysman Maya , Nir Yuval , Citri Ami
Published: June 2024

The claustrum has been linked to attention and sleep. We hypothesized that this reflects a shared function, determining responsiveness to stimuli, which spans the axis of engagement. To test this hypothesis, we recorded claustrum population dynamics from male mice during both sleep and an attentional task (‘ENGAGE’). Heightened activity in claustrum neurons projecting to the anterior cingulate cortex (ACCp) corresponded to reduced sensory responsiveness during sleep. Similarly, in the ENGAGE task, heightened ACCp activity correlated with disengagement and behavioral lapses, while low ACCp activity correlated with hyper-engagement and impulsive errors. Chemogenetic elevation of ACCp activity reduced both awakenings during sleep and impulsive errors in the ENGAGE task. Furthermore, mice employing an exploration strategy in the task showed a stronger correlation between ACCp activity and performance compared to mice employing an exploitation strategy which reduced task complexity. Our results implicate ACCp claustrum neurons in restricting engagement during sleep and goal-directed behavior.
Molecular motor tug-of-war regulates elongasome cell wall synthesis dynamics in Bacillus subtilis
Authors: Middlemiss Stuart , Blandenet Matthieu , Roberts David M. , McMahon Andrew , Grimshaw James , Edwards Joshua M. , Sun Zikai , Whitley Kevin D. , Blu Thierry , Strahl Henrik , Holden Séamus
Published: June 2024

Most rod-shaped bacteria elongate by inserting new cell wall material into the inner surface of the cell sidewall. This is performed by class A penicillin binding proteins (PBPs) and a highly conserved protein complex, the elongasome, which moves processively around the cell circumference and inserts long glycan strands that act as barrel-hoop-like reinforcing structures, thereby giving rise to a rod-shaped cell. However, it remains unclear how elongasome synthesis dynamics and termination events are regulated to determine the length of these critical cell-reinforcing structures. To address this, we developed a method to track individual elongasome complexes around the entire circumference of Bacillus subtilis cells for minutes-long periods using single-molecule fluorescence microscopy. We found that the B. subtilis elongasome is highly processive and that processive synthesis events are frequently terminated by rapid reversal or extended pauses. We found that cellular levels of RodA regulate elongasome processivity, reversal and pausing. Our single-molecule data, together with stochastic simulations, show that elongasome dynamics and processivity are regulated by molecular motor tug-of-war competition between several, likely two, oppositely oriented peptidoglycan synthesis complexes associated with the MreB filament. Altogether these results demonstrate that molecular motor tug-of-war is a key regulator of elongasome dynamics in B. subtilis, which likely also regulates the cell shape via modulation of elongasome processivity.
On-chip photodetection of angular momentums of vortex structured light
Authors: Dai Mingjin , Wang Chongwu , Sun Fangyuan , Wang Qi Jie
Published: June 2024

Structured vortex light with orbital angular momentum (OAM) shows great promise for high-bandwidth optical communications, quantum information and computing, optical tweezers, microscopy, astronomy, among others. Generating, controlling, and detecting of vortex light by all-electrical means is at the heart of next generation nanophotonic platforms. However, on-chip electrical photodetection of structured vortex light remains challenging. Here, we propose an on-chip photodetector based on 2D broadband thermoelectric material (PdSe2) with a well-designed spin-Hall couplers to directly characterize angular momentum modes of vortex structured light. Photothermoelectric responses in the PdSe2 nanoflake, excited by the focusing surface plasmons, show a magnitude proportional to the total angular momentum modes of the infrared vortex beams, thereby achieving direct detection of spin and orbital angular momentum, as well as the chirality and ellipticity of scalar vortex lights. Our works provide a promising strategy for developing on-chip angular momentum optoelectronic devices, which play a key role in the next-generation high-capacity optical communications, quantum information and computing, imaging, and other photonic systems.
Machine learning enhanced analysis of EBSD data for texture representation
Authors: Wanni J. , Bronkhorst C. A. , Thoma D. J.
Published: June 2024

Generating reduced-order, synthetic grain structure datasets that accurately represent the measured grain structure of a material is important for reducing the cost and increasing the accuracy of computational crystal plasticity efforts. This study introduces a machine-learning-based approach, termed texture adaptive clustering and sampling (TACS), for generating representative Euler angle datasets that accurately mimic the crystallographic texture. The TACS approach employs K-means clustering and density-based sampling in a closed-loop iteration to create representative Euler angle datasets. Proof-of-principle experiments were performed on rolled and recrystallized low-carbon steel. Validation of the TACS approach was extended to twenty-two datasets, varying lattice structures, and complex crystallographic textures, thereby encompassing a broad range of materials and crystal structures. Kolmogorov-Smirnov (K-S) test comparisons underscore the performance of the TACS approach over traditional electron backscatter diffraction EBSD dataset reduction techniques, with average K-S test scores nearing 0.9, indicating a high-fidelity representation of the original datasets. In contrast, conventional methods display scores below 0.3, indicating less reliability of the structure representation. The independence of the TACS approach from material texture and its capability to autonomously generate datasets with predetermined data points demonstrates its unbiased potential in streamlining dataset preparation for crystallographic analysis.
Systemic prime mucosal boost significantly increases protective efficacy of bivalent RSV influenza viral vectored vaccine
Authors: Bissett Cameron , Belij-Rammerstorfer Sandra , Ulaszewska Marta , Smith Holly , Kailath Reshma , Morris Susan , Powers Claire , Sebastian Sarah , Sharpe Hannah R. , Allen Elizabeth R. , Wang Ziyin , Cunliffe Robert F. , Sallah Hadijatou J. , Spencer Alexandra J. , Gilbert Sarah , Tregoning John S. , Lambe Teresa
Published: June 2024

Although licensed vaccines against influenza virus have been successful in reducing pathogen-mediated disease, they have been less effective at preventing viral infection of the airways and current seasonal updates to influenza vaccines do not always successfully accommodate viral drift. Most licensed influenza and recently licensed RSV vaccines are administered via the intramuscular route. Alternative immunisation strategies, such as intranasal vaccinations, and “prime-pull” regimens, may deliver a more sterilising form of protection against respiratory viruses. A bivalent ChAdOx1-based vaccine (ChAdOx1-NP + M1-RSVF) encoding conserved nucleoprotein and matrix 1 proteins from influenza A virus and a modified pre-fusion stabilised RSV A F protein, was designed, developed and tested in preclinical animal models. The aim was to induce broad, cross-protective tissue-resident T cells against heterotypic influenza viruses and neutralising antibodies against RSV in the respiratory mucosa and systemically. When administered via an intramuscular prime-intranasal boost (IM-IN) regimen in mice, superior protection was generated against challenge with either RSV A, Influenza A H3N2 or H1N1. These results support further clinical development of a pan influenza & RSV vaccine administered in a prime-pull regimen.
Molecular signatures of premature aging in Major Depression and Substance Use Disorders
Authors: Onisiforou Anna , Zanos Panos , Georgiou Polymnia
Published: June 2024

Major depressive disorder (MDD) and substance-use disorders (SUDs) often lead to premature aging, increasing vulnerability to cognitive decline and other forms of dementia. This study utilized advanced systems bioinformatics to identify aging “signatures” in MDD and SUDs and evaluated the potential for known lifespan-extending drugs to target and reverse these signatures. The results suggest that inhibiting the transcriptional activation of FOS gene family members holds promise in mitigating premature aging in MDD and SUDs. Conversely, antidepressant drugs activating the PI3K/Akt/mTOR pathway, a common mechanism in rapid-acting antidepressants, may accelerate aging in MDD patients, making them unsuitable for those with comorbid aging-related conditions like dementia and Alzheimer’s disease. Additionally, this innovative approach identifies potential anti-aging interventions for MDD patients, such as Deferoxamine, Resveratrol, Estradiol valerate, and natural compounds like zinc acetate, genistein, and ascorbic acid, regardless of comorbid anxiety disorders. These findings illuminate the premature aging effects of MDD and SUDs and offer insights into treatment strategies for patients with comorbid aging-related conditions, including dementia and Alzheimer’s disease.
High-resolution transcriptome datasets during embryogenesis of plant-parasitic nematodes
Authors: Wang Xueyu , Guo Zhiqing , Dai Dadong , Xie Chuanshuai , Zhao Ziwei , Zheng Jinshui , Sun Ming , Peng Donghai
Published: June 2024

Understanding the transcriptional regulatory characteristics throughout the embryogenesis of plant-parasitic nematodes is crucial for elucidating their developmental processes’ uniqueness. However, a challenge arises due to the lack of suitable technical methods for synchronizing the age of plant-parasitic nematodes embryo, it is difficult to collect detailed transcriptome data at each stage of embryonic development. Here, we recorded the 11 embryonic developmental time-points of endophytic nematode Meloidogyne incognita (isolated from Wuhan, China), Heterodera glycines (isolated from Wuhan, China), and Ditylenchus destructor (isolated from Jinan, China) species, and constructed transcriptome datasets of single embryos of these three species utilizing low-input smart-seq2 technology. The datasets encompassed 11 complete embryonic development stages, including Zygote, 2-cell, 4-cell, 8-cell, 24–44 cell, 64–78 cell, Comma, 1.5-fold, 2-fold, Moving, and L1, each stage generated four to five replicates, resulting in a total of 162 high-resolution transcriptome libraries. This high-resolution cross-species dataset serves as a crucial resource for comprehending the embryonic developmental properties of plant-parasitic nematodes and for identifying functional regulatory genes during embryogenesis.
Computed tomography reconstructions of burrow networks for the Opheliid polychaete, Armandia cirrhosa
Authors: Howman Rebecca M. , Mavrogordato Mark N. , Alverez-Borges Fernando , Solan Martin
Published: June 2024

The morphology and architecture of structures formed by sediment-dwelling invertebrates, such as excavations or burrows, are often assumed to be characteristic of a given species, consistent across a range of environmental conditions, and used to categorise species contributions to ecosystem functioning. However, very few investigations use non-invasive high-resolution techniques capable of determining fine scale variations in burrow form and complexity, or consider whether or not the form of the burrow is context dependent. Here, we provide replicate high-resolution micro-focus computed tomography data for the complete burrow systems of the Opheliid polychaete, Armandia cirrhosa, across a range of salinity and habitat conditions. These data provide reference models which can be used by ecologists investigating intraspecific variation in species traits and organism-sediment interactions and, more generally, by those tasked with pattern and shape recognition of objects that are morphologically highly variable and which adjust their architecture with changing circumstance or context.