bluuebunny/crossref_metadata_2025 huggingface dataset:
“You Can Kill Us with Dialogue:” Critical Perspectives on Wind Energy Development in a Nordic-Saami Green Colonial Context
Authors: Fjellheim Eva Maria
Published: March 2023

This article explores Southern Saami reindeer herders’ experiences and contestations over state consultation and corporate dialogue during a conflict over the Øyfjellet wind energy project in Norway. Informed by a committed research approach and juxtaposition with findings from Indigenous peoples' territorial struggles in Latin-America, the article provides critical perspectives on governance practices in a Nordic-Saami green colonial context. The research draws on ethnography from a consultation meeting between Jillen Njaarke, the impacted reindeer herding community, and state authorities, as well as diverse written material. The study suggests that the state- and corporate-led “dialogues” displaced the root cause of the conflict, revealed epistemic miscommunication, and perpetuated relations of domination which limited emancipatory effects for Jillen Njaarke. The premises and discourses underpinning the “dialogues” further reproduced racist notions which devalue ancestral Saami reindeer herding knowledges, practices, and landscape relations. These findings challenge dialogue as prescription of good governance and conflict resolution in a context where democracy and compliance with Indigenous peoples’ rights are perceived as high.
Towards adversarial realism and robust learning for IoT intrusion detection and classification
Authors: Vitorino João , Praça Isabel , Maia Eva
Published: March 2023

The internet of things (IoT) faces tremendous security challenges. Machine learning models can be used to tackle the growing number of cyber-attack variations targeting IoT systems, but the increasing threat posed by adversarial attacks restates the need for reliable defense strategies. This work describes the types of constraints required for a realistic adversarial cyber-attack example and proposes a methodology for a trustworthy adversarial robustness analysis with a realistic adversarial evasion attack vector. The proposed methodology was used to evaluate three supervised algorithms, random forest (RF), extreme gradient boosting (XGB), and light gradient boosting machine (LGBM), and one unsupervised algorithm, isolation forest (IFOR). Constrained adversarial examples were generated with the adaptative perturbation pattern method (A2PM), and evasion attacks were performed against models created with regular and adversarial training. Even though RF was the least affected in binary classification, XGB consistently achieved the highest accuracy in multi-class classification. The obtained results evidence the inherent susceptibility of tree-based algorithms and ensembles to adversarial evasion attacks and demonstrate the benefits of adversarial training and a security-by-design approach for a more robust IoT network intrusion detection and cyber-attack classification.
Analysis of fingerprints on a PPNB figurine from the Tell Halula site, Syria
Authors: Dyowe Roig Albert Epitié , Estebaranz-Sánchez Ferran , Martínez Laura M. , Molist Montaña Miquel
Published: March 2023

With the advent of the Neolithic, the first manipulation of clay for various purposes was observed. Fingerprints could be imprinted due to the plastic properties of clay. Their study and analysis can allow the estimation of the sex and age of the person who left them, thus providing insight into the social organisation of past populations. In the present study, we have analysed the fingerprints that were identified on a figurine representing a bovine animal found at the Neolithic site of Tell Halula in Syria. Tell Halula has a long period of occupation, from the Middle Pre-Pottery Neolithic B (PPNB) to the Late PPNB, with some of the earliest evidence of monumental and/or collective architecture. To confirm the human origin of the prints, the presence of minutiae was first identified. In order to estimate the sex and age of the individual, both the Mean Epidermal Ridge Breadth and the Ridge Breadth were calculated. The mean ridge widths were 0.52 ± 0.076 for the first fingerprint and 0.50 ± 0.11 for the second fingerprint. The ridge density was found to be 6.5. The results indicated that the maker of the bovine figurine could be an adult male (~18/20 years old), taking both values into account. The results suggest that it is highly likely that the individual who handled the artefact was an adult male. However, given the small number of fingerprints in the Tell Halula figurine collection, little more can be said. Not much can be inferred about social structure and division of labour. There is therefore a need for further research into both the symbolism of the objects and who was responsible for their production.
Equations-of-state deduced form different types of black holes
Authors: Yassin Hayam , Elyazeed Eman R. Abo , Tawfik Abdel Nasser
Published: March 2023

Black holes are seen as thermodynamical systems. They can be characterized by thermodynamic intensive quantities such as temperature, pressure, and extensive quantities such as entropy and energy density. In this paper, we focus on the thermodynamical properties of (a) Schwarzschild, (b) Reissner–Nordström, (c) Kerr, and (d) Kerr–Newman black holes. These allow to estimate the corresponding equations-of-state (EoS) and the squared speed of sound for each of them. The latter helps to calculate the ratio of the bulk viscosity to the shear viscosity for each of the black holes. We conclude that the resulting EoS enhances when moving from Schwarzschild to Reissner–Nordström to Kerr, and to Kerr–Newman black holes.
Gust alleviation by spanwise load control applied on a forward and backward swept wing
Authors: Klug L. , Ullah J. , Lutz T. , Streit T. , Heinrich R. , Radespiel R.
Published: March 2023

The present paper investigates the feasibility of gust load alleviation at transonic speeds on a backward swept and a forward swept transport aircraft configuration. Spanwise-distributed control surfaces at the leading and trailing edges are employed to control gust-induced wing bending as well as wing torsion moments. The deflection amplitude and temporal flap actuation are determined by a novel scheme that builds on the aerodynamic strip theory. The aerodynamic effectiveness of the actuators is taken from a data base, computed from either 2D infinite swept wing simulations, or from yawed computations that take the effects of boundary-layer cross flow and the local sweep angle of the control surface into account. The present numerical flow simulations reveal that careful application of control laws at the trailing edge alleviates wing bending moments caused by strong vertical gusts by 85–90%, for both aircraft configurations. The application of leading-edge flaps introduces significant nonlinear aerodynamic interactions, that make the control of torsional moments comparably challenging. Here, the present results indicate that about 60% of wing torsion loads due to strong gusts can be removed.
Legionnaires’ disease in Switzerland: rationale and study protocol of a prospective national case–control and molecular source attribution study (SwissLEGIO)
Authors: Fischer Fabienne B. , Bigler Melina , Mäusezahl Daniel , Hattendorf Jan , Egli Adrian , Julian Timothy R. , Rölli Franziska , Gaia Valeria , Wymann Monica , Fridez Françoise , Bertschi Stefanie ,   The SwissLEGIO Hospital Network, Akers Isabel , Albrich Werner C. , Bandeira Diane , Bernasconi Enos , Berthod Delphine , Boesing Maria , Calligaris-Maibach Romana , Clerc Olivier , Croxatto Antony , Deggim-Messmer Vanessa , Dräger Sarah , Droz Sara , Dumoulin Alexis , Emonet Stéphane , Friedl Andrée , Führer Urs , Garzoni Christian , Gisler Valentin , Gutmann Christine , Greub Gilbert , Hitz Eva , Kaiser Philipp , Keller Peter , Leuppi Jörg D. , Lienhard Reto , Mitrović Irena , Papadimitriou-Olivgeris Matthaios , Petrino Roberta , Preiswerk Benjamin , Risch Martin , Schrenzel Jacques , Suter Buser Brigitte J. , Tarr Philip E. , Thurnheer Maria Christine , de Lorenzi-Tognon Mikaël , Uccella Laura , Vázquez Miriam , Wepf Alexander , Wiggli Benedikt
Published: March 2023

Switzerland has one of the highest annual Legionnaires’ disease (LD) notification rates in Europe (7.8 cases/100,000 population in 2021). The main sources of infection and the cause for this high rate remain largely unknown. This hampers the implementation of targeted Legionella spp. control efforts. The SwissLEGIO national case–control and molecular source attribution study investigates risk factors and infection sources for community-acquired LD in Switzerland. Over the duration of one year, the study is recruiting 205 newly diagnosed LD patients through a network of 20 university and cantonal hospitals. Healthy controls matched for age, sex, and residence at district level are recruited from the general population. Risk factors for LD are assessed in questionnaire-based interviews. Clinical and environmental Legionella spp. isolates are compared using whole genome sequencing (WGS). Direct comparison of sero- and sequence types (ST), core genome multilocus sequencing types (cgMLST), and single nucleotide polymorphisms (SNPs) between clinical and environmental isolates are used to investigate the infection sources and the prevalence and virulence of different Legionella spp. strains detected across Switzerland. The SwissLEGIO study innovates in combining case–control and molecular typing approaches for source attribution on a national level outside an outbreak setting. The study provides a unique platform for national Legionellosis and Legionella research and is conducted in an inter- and transdisciplinary, co-production approach involving various national governmental and national research stakeholders.
Chaboche viscoplastic material model for process simulation of additively manufactured Ti-6Al-4 V parts
Authors: Springer S. , Seisenbacher B. , Leitner M. , Grün F. , Gruber T. , Lasnik M. , Oberwinkler B.
Published: March 2023

For the estimation and further optimization of the residual stress and distortion state in additively manufactured structures during and after the wire arc additive manufacturing (WAAM) process, thermomechanical simulation can be applied as a numerical tool. In addition to the detailed modelling of key process parameters, the used material model and material data have a major influence on the accuracy of the numerical analysis. The material behaviour, in particular the viscoplastic behaviour of the titanium alloy Ti-6Al-4 V which is commonly used in aerospace, is investigated within this work. An extensive material characterization of the viscoplastic material behaviour of the WAAM round specimen is carried out conducting low cycle fatigue (LCF) and complex low cycle fatigue (CLCF) tests in a wide temperature range. An elasto-viscoplastic Chaboche material model is parameterised, fitted, and validated to the experimental data in the investigated temperature range. Subsequently, the material model is implemented in the thermomechanical simulation of a representative, linear ten-layer WAAM structure. To finally determine the effect of the fitted material model on the estimation accuracy of residual stress and distortion, simulation results using the standard material model and the elaborated Chaboche model from this study are compared to experimental data in the substrate. The thermomechanical simulation with the Chaboche model reveals a better agreement with the experimental distortion and residual stress state, whereby the standard material model tends to an overestimation. The estimation accuracy with respect to the maximum distortion is improved from an error of 60% with the standard model to an acceptable error of about 6% using the elaborated model. Additionally, the estimated residual stress state shows a sound agreement to the experimental residual stress in the substrate.
Leon Kirchner
Authors: Riggs Robert
Published: March 2023

Biography of the late American composer Leon Kirchner (1919-2009), exploring his work and important personal associations.
Machaut and the Medieval Apprenticeship Tradition
Authors: Kelly Douglas
Published: March 2023

A close examination of an important theme in Machaut's works.
The British Navy's Victualling Board, 1793-1815
Authors: Macdonald Janet
Published: March 2023

An examination of the Royal Navy's Victualling Board, the body responsible for supplying the fleet.
The Emergence of Britain's Global Naval Supremacy
Authors: Harding Richard
Published: March 2023

Discusses the lessons which Britain learned in the war of 1739-48 which, when applied in later wars, brought about Britain's global naval supremacy.
Bioregulator application enhances yield by modulating antioxidant efficiency of rainfed cluster bean [Cyamopsis tetragonolobaL. (Taub.)] in the hot arid region of India
Authors: Nathawat Narayan Singh , Yadava Narendra Dev , Singh Jai Parkash , Santra Priyabrata , Bhaskar Suryanarayana , Shekhawat Ravindra Singh , Rathore Vijay Singh
Published: March 2023

Water deficiency is one of the most severe abiotic stresses in rainfed dry lands and limits crop productivity. Exogenous applications of salicylic acid (SA) have been applied to mitigate the adverse effects of water-deficit stresses, but the relative efficacy of different derivatives of SA in enhancing water-deficit tolerance along with the underlying physio-biochemical mechanism and yield of crops is not well documented. Field experiments were conducted to ascertain the relative efficacy of exogenous application of three plant bioregulators (PBRs) [SA, thiosalicylic acid and 5-sulfosalicylic acid (SSA)], each at three concentrations (0.5, 1.0 and 1.5 mM), on the growth, physio-biochemical characteristics and yield of cluster bean under rainfed conditions. Based on a 2-year field experiment, the application of PBRs enhanced yield (from 8 to 16%). The yield enhancement with the application of PBRs was associated with elevated water content (from 9 to 17%), membrane stability (from 12 to 18%) and antioxidant enzyme activity (from 12 to 33%) and reduced lipid peroxidation (from −15 to −34%) in leaves. The effects of PBRs were conditionally type and concentration dependent. The application of SSA at a rate of 1 mM was more effective in enhancing water-deficit tolerance and improving the yield of cluster bean under water shortage conditions. This study provides empirical evidence of the potential for the application of SA and its derivatives to enhance crop yields under drought conditions. The results have direct implications for sustainable crop production for similar regions of the world facing water deficits.
Watermains Leakage and Outdoor Water Use Are Responsible for Significant Phosphorus Fluxes to the Environment Across the United States
Authors: Flint Elizabeth M. , Ascott Matthew J. , Gooddy Daren C. , Stahl Mason O. , Surridge Ben W. J.
Published: March 2023

Human activity has led to excess phosphorus (P) concentrations and the continued eutrophication of coastal and freshwaters across the United States (US). Developing more effective P management policy requires a comprehensive understanding of P sources in the environment. Public water systems across the United States widely dose water with phosphate (PO4) in order to control the corrosion of lead and copper within their distribution networks. Using public water system PO4 dosing facility data and target PO4‐P dosing concentrations, we estimate that PO4 dosing added 4–14.9 kt PO4‐P yr−1 into the US water distribution network in 2015. Using estimates of public water supply inputs and domestic water deliveries, we estimate that 0.7–2.6, and 0.8–3.1 kt PO4‐P yr−1 were then lost from the network due to watermains leakage and outdoor water use, respectively. After accounting for these fluxes, we estimate that 9.3 kt PO4‐P yr−1 was then returned to wastewater treatment plants (WWTPs) and accounted for up to 2.7% of the national WWTP influent P load. As sources of P to the environment, lower and upper estimates of combined watermains leakage and outdoor water use PO4‐P fluxes exceeded P loads to surface waterbodies from documented point sources across 461–541 counties. The exceedance of these fluxes above other major components of the US P‐budget emphasizes the need to include them in P source apportionment studies, both across the US and in other countries where public water supplies are dosed with PO4.
Multi‐Instrument Observations of the Effects of a Solar Wind Pressure Pulse on the High Latitude Ionosphere: A Detailed Case Study of a Geomagnetic Sudden Impulse
Authors: Fogg A. R. , Lester M. , Yeoman T. K. , Carter J. A. , Milan S. E. , Sangha H. K. , Elsden T. , Wharton S. J. , James M. K. , Malone‐Leigh J. , Paxton L. J. , Anderson B. J. , Vines S. K.
Published: March 2023

The effects of a solar wind pressure pulse on the terrestrial magnetosphere have been observed in detail across multiple datasets. The communication of these effects into the magnetosphere is known as a positive geomagnetic sudden impulse (+SI), and are observed across latitudes and different phenomena to characterize the propagation of +SI effects through the magnetosphere. A superposition of Alfvén and compressional propagation modes are observed in magnetometer signatures, with the dominance of these signatures varying with latitude. For the first time, collocated lobe reconnection convection vortices and region 0 field aligned currents are observed preceding the +SI onset, and an enhancement of these signatures is observed as a result of +SI effects. Finally, cusp auroral emission is observed collocated with the convection and current signatures. For the first time, simultaneous observations across multiple phenomena are presented to confirm models of +SI propagation presented previously.
Simulation of Neighborhood‐Scale Air Quality With Two‐Way Coupled WRF‐CMAQ Over Southern Lake Michigan‐Chicago Region
Authors: Montgomery Anastasia , Schnell Jordan L. , Adelman Zachariah , Janssen Mark , Horton Daniel E.
Published: March 2023

The southern Lake Michigan region of the United States, home to Chicago, Milwaukee, and other densely populated Midwestern cities, frequently experiences high pollutant episodes with unevenly distributed exposure and health burdens. Using the two‐way coupled Weather Research Forecast and Community Multiscale Air Quality Model (WRF‐CMAQ), we investigate criteria pollutants over a southern Lake Michigan domain using 1.3 and 4 km resolution hindcast simulations. We assess WRF‐CMAQ's performance using data from the National Climatic Data Center and Environmental Protection Agency Air Quality System. Our 1.3 km simulation slightly improves on the 4 km simulation's meteorological and chemical performance while also resolving key details in areas of high exposure and impact, that is, urban environments. At 1.3 km, we find that most air quality‐relevant meteorological components of WRF‐CMAQ perform at or above community benchmarks. WRF‐CMAQ's chemical performance also largely meets community standards, with substantial nuance depending on the performance metric and component assessed. For example, hourly simulated NO2 and O3 are highly correlated with observations (r > 0.6) while PM2.5 is less so (r = 0.4). Similarly, hourly simulated NO2 and PM2.5 have low biases (<10%), whereas O3 biases are larger (>30%). Simulated spatial pollutant patterns show distinct urban‐rural footprints, with urban NO2 and PM2.5 20%–60% higher than rural, and urban O3 6% lower. We use our 1.3 km simulations to resolve high‐pollution areas within individual urban neighborhoods and characterize seasonal changes in O3 regimes across tight spatial gradients. Our findings demonstrate both the benefits and limitations of high‐resolution simulations, particularly over urban settings.
Clumped Isotope Thermometry in Plant‐Derived Carbonates
Authors: Stein Rebekah A. , Turner Andrew C. , Amundson Ronald , Stolper Daniel A.
Published: March 2023

The genus Celtis includes widespread trees that produce drupes with aragonite endocarps, or “hackberries.” These carbonate endocarps are preserved in the fossil record, often in cave deposits or packrat middens, and thus are targets for paleoclimate reconstructions. Stable oxygen isotopes in Celtis endocarps have been used as proxies for oxygen isotopic composition of past stream water and for paleothermometry. Here, we explore the suitability of hackberry carbonates for paleoclimate reconstructions based on carbonate clumped‐isotope thermometry. We sampled modern hackberries grown at sites across North America (n = 37) for stable and clumped isotope analyses. Measured clumped‐isotope temperatures are found to be within the range of measured local modern growing season surface temperatures and typically in dual clumped‐isotope equilibrium. As such, we propose that hackberry clumped‐isotope measurements can be used to reconstruct past Earth‐surface air temperatures.
A Global Reassessment of the Spatial and Temporal Expression of the Late Miocene Biogenic Bloom
Authors: Pillot Q. , Suchéras‐Marx B. , Sarr A.‐C. , Bolton C. T. , Donnadieu Y.
Published: March 2023

The Late Miocene Biogenic Bloom (LMBB) is a late Miocene to early Pliocene oceanographic event characterized by high accumulation rates of opal from diatoms and calcite from calcareous nannofossils and planktic foraminifera. This multi‐million year event has been recognized in sediment cores from the Pacific, Atlantic, and Indian Oceans. Based on existing studies, it is not clear whether the LMBB is a global omnipresent event, or whether it is restricted to certain regions or oceanographic environments. Moreover, the origin of this event is still widely discussed. In this study, we aim to provide a comprehensive overview of the geographical and temporal aspects of the LMBB by compiling published ocean drilling (DSDP, ODP, and IODP) records of sedimentation rates, and CaCO3, opal, and terrigenous accumulation rates that cover the late Miocene and early Pliocene interval. Our data compilation shows that manifestations of the LMBB are present in many different locations but in a very heterogeneous way. The compilation shows that the sites where the LMBB is expressed are mainly located in areas with a high productivity regime (i.e., upwelling systems). We suggest that one of the possible hypotheses to explain the onset of the LMBB could be a global increase in upwelling intensity due to an increase in wind strength or an increase in deep water formation, ramping up global thermohaline circulation.
A Family of Soil Water Retention Models Based on Sigmoid Functions
Authors: Li Peijun , Zha Yuanyuan , Zuo Bingxin , Zhang Yonggen
Published: March 2023

The soil water retention curve is the fundamental soil hydraulic property to characterize soil water movement and solute transport. Many efforts have been devoted in the past decades to developing models to describe soil water retention curves. However, most of them are empirical equations or assume that soil pore size distributions conform to a lognormal distribution. Yet, few effects have been undertaken to systematically propose and compare a series of possible alternative probability density functions to describe the sigmoid retention curves with parameters physically explainable. Here, we proposed a family of five soil water retention models based on sigmoid functions with parameters of clear physical implications coinciding with the statistical measures of soil pore size distribution. Compared with the widely used models (i.e., Brooks & Corey, 1964; Kosugi, 1996; van Genuchten, 1980), the proposed models have somewhat improved performances to characterize water retention data for a wide range of soil textures without introducing additional model parameters. Two of the proposed models are capable of characterizing the observed two local extrema in the moisture capacity curves. The associated unsaturated hydraulic conductivity models of the proposed soil water retention models are also derived, which show superior performance in characterizing the observed hydraulic conductivities compared with competing models, especially in macropore regimes. Additionally, we analyzed the parameter‐equivalent conversion between the proposed and the existing models, and a simple linear regression equation can be used to derive the parameters of the proposed models from the existing and other alternative different proposed models.
Effect of Hydrophobicity of Fluorescent Carbon Nanoparticles on Transport in Porous Media: Column Experiments and Modeling
Authors: May Daniel F. , Hassanpour Bahareh , Sinclair Laura , Steenhuis Tammo S. , Cathles Lawrence M.
Published: March 2023

Engineered carbon‐based nanoparticles are increasingly used for environmental, industrial, and medical purposes. Thus, understanding their interaction with and transport through materials is important. We examine the impact of nanoparticle hydrophobicity and porous medium surface area on the transport of carbon nanoparticles through sand‐packed columns under saturated and unsaturated conditions. The fluorescent carbon nanoparticles (FCNs) used in this study, synthesized from citric acid and ethanolamine, exhibit synthesis‐temperature‐dependent hydrophobicity. To quantify the impact of hydrophobicity on retention, we use FCNs synthesized at four temperatures: 190°C (FCN190), 210°C (FCN210), 230°C (FCN230), and 250°C (FCN250). Several observations are noted. First, the more hydrophobic particles (FCN230 and FCN250) attain lower outlet concentrations and mass recovery than more hydrophilic particles (FCN190 and FCN210). For instance, while 77% of the FCN190 was recovered after passing through a fine‐sand‐packed column, only 23% of the FCN250 was recovered. Second, sand surface area significantly impacts FCN recovery. A 17‐fold increase in sand surface area yields a 30% decrease in the recovery of FCN210. Third, no significant difference in the mass recovery of the FCNs was observed between the unsaturated and saturated conditions, which is attributed to the small size of the FCNs relative to the water film thickness surrounding sand grains. Fourth, the particle transport model in HYDRUS‐1D successfully simulated FCN transport, showing approximately a tenfold increase in the attachment coefficient for hydrophobic FCNs. In summary, through experiments and modeling, we show that hydrophobicity is a major factor impacting FCN transport.
Mapping Wetland Loss Across Three Centuries
Authors: Wilke Carolyn
Published: March 2023

Millions of square kilometers of wetlands have been drained or converted to make room for crops, pastures, or development. In some places, up to 80% are gone.
Iron Is at the Core of This Earth Science Debate
Authors: Sidder Aaron
Published: March 2023

A new study investigates iron’s form at the planet’s interior. The findings have repercussions for understanding the inner core’s structure.
Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan
Authors: Vilar-Ribó Laura , Cabana-Domínguez Judit , Martorell Lourdes , Ramos-Quiroga Josep Antoni , Sanchez-Roige Sandra , Palmer Abraham A. , Vilella Elisabet , Ribasés Marta , Muntané Gerard , Soler Artigas María
Published: March 2023

There is evidence linking ADHD to a reduced life expectancy. The mortality rate in individuals with ADHD is twice that of the general population and it is associated with several factors, such as unhealthy lifestyle behaviors, social adversity, and mental health problems that may in turn increase mortality rates. Since ADHD and lifespan are heritable, we used data from genome-wide association studies (GWAS) of ADHD and parental lifespan, as proxy of individual lifespan, to estimate their genetic correlation, identify genetic loci jointly associated with both phenotypes and assess causality. We confirmed a negative genetic correlation between ADHD and parental lifespan (rg = −0.36,P = 1.41e−16). Nineteen independent loci were jointly associated with both ADHD and parental lifespan, with most of the alleles that increased the risk for ADHD being associated with shorter lifespan. Fifteen loci were novel for ADHD and two were already present in the original GWAS on parental lifespan. Mendelian randomization analyses pointed towards a negative causal effect of ADHD liability on lifespan (P = 1.54e−06; Beta = −0.07), although these results were not confirmed by all sensitivity analyses performed, and further evidence is required. The present study provides the first evidence of a common genetic background between ADHD and lifespan, which may play a role in the reported effect of ADHD on premature mortality risk. These results are consistent with previous epidemiological data describing reduced lifespan in mental disorders and support that ADHD is an important health condition that could negatively affect future life outcomes.
Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies
Authors: Shi Zhen-Duo , Pang Kun , Wu Zhuo-Xun , Dong Yang , Hao Lin , Qin Jia-Xin , Wang Wei , Chen Zhe-Sheng , Han Cong-Hui
Published: March 2023

Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to a complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed to circumvent tumor cell plasticity, including epigenetic modifications, regulation of transcription factors, activation or suppression of key signaling pathways, as well as modification of the tumor environment. Epithelial-to-mesenchymal transition, tumor cell and cancer stem cell formation also serve as roads towards tumor cell plasticity. Corresponding treatment strategies have recently been developed that either target plasticity-related mechanisms or employ combination treatments. In this review, we delineate the formation of tumor cell plasticity and its manipulation of tumor evasion from targeted therapy. We discuss the non-genetic mechanisms of targeted drug-induced tumor cell plasticity in various types of tumors and provide insights into the contribution of tumor cell plasticity to acquired drug resistance. New therapeutic strategies such as inhibition or reversal of tumor cell plasticity are also presented. We also discuss the multitude of clinical trials that are ongoing worldwide with the intention of improving clinical outcomes. These advances provide a direction for developing novel therapeutic strategies and combination therapy regimens that target tumor cell plasticity.
Neonatal loss of FGFR2 in astroglial cells affects locomotion, sociability, working memory, and glia-neuron interactions in mice
Authors: Stevens Hanna E. , Scuderi Soraya , Collica Sarah C. , Tomasi Simone , Horvath Tamas L. , Vaccarino Flora M.
Published: March 2023

Fibroblast growth factor receptor 2 (FGFR2) is almost exclusively expressed in glial cells in postnatal mouse brain, but its impact in glia for brain behavioral functioning is poorly understood. We compared behavioral effects from FGFR2 loss in both neurons and astroglial cells and from FGFR2 loss in astroglial cells by using either the pluripotent progenitor-drivenhGFAP-creor the tamoxifen-inducible astrocyte-drivenGFAP-creERT2inFgfr2floxed mice. When FGFR2 was eliminated in embryonic pluripotent precursors or in early postnatal astroglia, mice were hyperactive, and had small changes in working memory, sociability, and anxiety-like behavior. In contrast, FGFR2 loss in astrocytes starting at 8 weeks of age resulted only in reduced anxiety-like behavior. Therefore, early postnatal loss of FGFR2 in astroglia is critical for broad behavioral dysregulation. Neurobiological assessments demonstrated that astrocyte-neuron membrane contact was reduced and glial glutamine synthetase expression increased only by early postnatal FGFR2 loss. We conclude that altered astroglial cell function dependent on FGFR2 in the early postnatal period may result in impaired synaptic development and behavioral regulation, modeling childhood behavioral deficits like attention deficit hyperactivity disorder (ADHD).
Distinct GSDMB protein isoforms and protease cleavage processes differentially control pyroptotic cell death and mitochondrial damage in cancer cells
Authors: Oltra Sara S. , Colomo Sara , Sin Laura , Pérez-López María , Lázaro Sara , Molina-Crespo Angela , Choi Kyoung-Han , Ros-Pardo David , Martínez Lidia , Morales Saleta , González-Paramos Cristina , Orantes Alba , Soriano Mario , Hernández Alberto , Lluch Ana , Rojo Federico , Albanell Joan , Gómez-Puertas Paulino , Ko Jae-Kyun , Sarrió David , Moreno-Bueno Gema
Published: March 2023

Gasdermin (GSDM)-mediated pyroptosis is functionally involved in multiple diseases, but Gasdermin-B (GSDMB) exhibit cell death-dependent and independent activities in several pathologies including cancer. When the GSDMB pore-forming N-terminal domain is released by Granzyme-A cleavage, it provokes cancer cell death, but uncleaved GSDMB promotes multiple pro-tumoral effects (invasion, metastasis, and drug resistance). To uncover the mechanisms of GSDMB pyroptosis, here we determined the GSDMB regions essential for cell death and described for the first time a differential role of the four translated GSDMB isoforms (GSDMB1-4, that differ in the alternative usage of exons 6-7) in this process. Accordingly, we here prove that exon 6 translation is essential for GSDMB mediated pyroptosis, and therefore, GSDMB isoforms lacking this exon (GSDMB1-2) cannot provoke cancer cell death. Consistently, in breast carcinomas the expression of GSDMB2, and not exon 6-containing variants (GSDMB3-4), associates with unfavourable clinical-pathological parameters. Mechanistically, we show that GSDMB N-terminal constructs containing exon-6 provoke cell membrane lysis and a concomitant mitochondrial damage. Moreover, we have identified specific residues within exon 6 and other regions of the N-terminal domain that are important for GSDMB-triggered cell death as well as for mitochondrial impairment. Additionally, we demonstrated that GSDMB cleavage by specific proteases (Granzyme-A, Neutrophil Elastase and caspases) have different effects on pyroptosis regulation. Thus, immunocyte-derived Granzyme-A can cleave all GSDMB isoforms, but in only those containing exon 6, this processing results in pyroptosis induction. By contrast, the cleavage of GSDMB isoforms by Neutrophil Elastase or caspases produces short N-terminal fragments with no cytotoxic activity, thus suggesting that these proteases act as inhibitory mechanisms of pyroptosis. Summarizing, our results have important implications for understanding the complex roles of GSDMB isoforms in cancer or other pathologies and for the future design of GSDMB-targeted therapies.
USP22 upregulates ZEB1-mediated VEGFA transcription in hepatocellular carcinoma
Authors: Zeng Kai , Xie Weiwen , Wang Chunyu , Wang Shengli , Liu Wei , Su Yingjie , Lin Lin , Zou Renlong , Sun Ge , Zhou Baosheng , Wang Manlin , Luan Ruina , Bai Yu , Huo Yunlong , Kato Shigeaki , Zhong Xinping , Zhao Yue
Published: March 2023

Hepatocellular carcinoma (HCC) is a common solid tumor with high rate of recurrence and mortality. Anti-angiogenesis drugs have been used for the therapy of HCC. However, anti-angiogenic drug resistance commonly occurs during HCC treatment. Thus, identification of a novel VEGFA regulator would be better understanding for HCC progression and anti-angiogenic therapy resistance. Ubiquitin specific protease 22 (USP22) as a deubiquitinating enzyme, participates in a variety of biological processes in numerous tumors. While the molecular mechanism underlying the effects of USP22 on angiogenesis is still needed to be clarified. Here, our results demonstrated that USP22 acts as a co-activator of VEGFA transcription. Importantly, USP22 is involved in maintenance of ZEB1 stability via its deubiquitinase activity. USP22 was recruited to ZEB1-binding elements on the promoter of VEGFA, thereby altering histone H2Bub levels, to enhance ZEB1-mediated VEGFA transcription. USP22 depletion decreased cell proliferation, migration, Vascular Mimicry (VM) formation, and angiogenesis. Furthermore, we provided the evidence to show that knockdown of USP22 inhibited HCC growth in tumor-bearing nude mice. In addition, the expression of USP22 is positively correlated with that of ZEB1 in clinical HCC samples. Our findings suggest that USP22 participates in the promotion of HCC progression, if not all, at least partially via up-regulation of VEGFA transcription, providing a novel therapeutic target for anti-angiogenic drug resistance in HCC.
Fano interference between collective modes in cuprate high-Tc superconductors
Authors: Chu Hao , Kovalev Sergey , Wang Zi Xiao , Schwarz Lukas , Dong Tao , Feng Liwen , Haenel Rafael , Kim Min-Jae , Shabestari Parmida , Hoang Le Phuong , Honasoge Kedar , Dawson Robert David , Putzky Daniel , Kim Gideok , Puviani Matteo , Chen Min , Awari Nilesh , Ponomaryov Alexey N. , Ilyakov Igor , Bluschke Martin , Boschini Fabio , Zonno Marta , Zhdanovich Sergey , Na Mengxing , Christiani Georg , Logvenov Gennady , Jones David J. , Damascelli Andrea , Minola Matteo , Keimer Bernhard , Manske Dirk , Wang Nanlin , Deinert Jan-Christoph , Kaiser Stefan
Published: March 2023

Cuprate high-Tc superconductors are known for their intertwined interactions and the coexistence of competing orders. Uncovering experimental signatures of these interactions is often the first step in understanding their complex relations. A typical spectroscopic signature of the interaction between a discrete mode and a continuum of excitations is the Fano resonance/interference, characterized by the asymmetric light-scattering amplitude of the discrete mode as a function of the electromagnetic driving frequency. In this study, we report a new type of Fano resonance manifested by the nonlinear terahertz response of cuprate high-Tc superconductors, where we resolve both the amplitude and phase signatures of the Fano resonance. Our extensive hole-doping and magnetic field dependent investigation suggests that the Fano resonance may arise from an interplay between the superconducting fluctuations and the charge density wave fluctuations, prompting future studies to look more closely into their dynamical interactions.
Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine
Authors: Neumann Charlotte J. , Mahnert Alexander , Kumpitsch Christina , Kiu Raymond , Dalby Matthew J. , Kujawska Magdalena , Madl Tobias , Kurath-Koller Stefan , Urlesberger Berndt , Resch Bernhard , Hall Lindsay J. , Moissl-Eichinger Christine
Published: March 2023

Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterize fecal samples of 55 infants (<1500 g,n = 383, female = 22) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses; targeted 16S rRNA gene sequencing and shotgun metagenomics), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty acids (German Registry of Clinical Trials, No.: DRKS00009290). Regimens including probioticBifidobacterium longumsubsp.infantisNCDO 2203 supplementation affect microbiome development globally, pointing toward the genomic potential to convert HMOs. Engraftment of NCDO 2203 is associated with a substantial reduction of microbiome-associated antibiotic resistance as compared to regimens using probioticLactobacillus rhamnosusLCR 35 or no supplementation. Crucially, the beneficial effects ofBifidobacterium longumsubsp.infantisNCDO 2203 supplementation depends on simultaneous feeding with HMOs. We demonstrate that preventive regimens have the highest impact on development and maturation of the gastrointestinal microbiome, enabling the establishment of a resilient microbial ecosystem that reduces pathogenic threats in at-risk preterm infants.
Room temperature nondestructive encapsulation via self-crosslinked fluorosilicone polymer enables damp heat-stable sustainable perovskite solar cells
Authors: Wang Tong , Yang Jiabao , Cao Qi , Pu Xingyu , Li Yuke , Chen Hui , Zhao Junsong , Zhang Yixin , Chen Xingyuan , Li Xuanhua
Published: March 2023

Encapsulation engineering is an effective strategy to improve the stability of perovskite solar cells. However, current encapsulation materials are not suitable for lead-based devices because of their complex encapsulation processes, poor thermal management, and inefficient lead leakage suppression. In this work, we design a self-crosslinked fluorosilicone polymer gel, achieving nondestructive encapsulation at room temperature. Moreover, the proposed encapsulation strategy effectively promotes heat transfer and mitigates the potential impact of heat accumulation. As a result, the encapsulated devices maintain 98% of the normalized power conversion efficiency after 1000 h in the damp heat test and retain 95% of the normalized efficiency after 220 cycles in the thermal cycling test, satisfying the requirements of the International Electrotechnical Commission 61215 standard. The encapsulated devices also exhibit excellent lead leakage inhibition rates, 99% in the rain test and 98% in the immersion test, owing to excellent glass protection and strong coordination interaction. Our strategy provides a universal and integrated solution for achieving efficient, stable, and sustainable perovskite photovoltaics.
Recapitulating thyroid cancer histotypes through engineering embryonic stem cells
Authors: Veschi Veronica , Turdo Alice , Modica Chiara , Verona Francesco , Di Franco Simone , Gaggianesi Miriam , Tirrò Elena , Di Bella Sebastiano , Iacono Melania Lo , Pantina Vincenzo Davide , Porcelli Gaetana , Mangiapane Laura Rosa , Bianca Paola , Rizzo Aroldo , Sciacca Elisabetta , Pillitteri Irene , Vella Veronica , Belfiore Antonino , Bongiorno Maria Rita , Pistone Giuseppe , Memeo Lorenzo , Colarossi Lorenzo , Giuffrida Dario , Colarossi Cristina , Vigneri Paolo , Todaro Matilde , Stassi Giorgio
Published: March 2023

Thyroid carcinoma (TC) is the most common malignancy of endocrine organs. The cell subpopulation in the lineage hierarchy that serves as cell of origin for the different TC histotypes is unknown. Human embryonic stem cells (hESCs) with appropriate in vitro stimulation undergo sequential differentiation into thyroid progenitor cells (TPCs-day 22), which maturate into thyrocytes (day 30). Here, we create follicular cell-derived TCs of all the different histotypes based on specific genomic alterations delivered by CRISPR-Cas9 in hESC-derived TPCs. Specifically, TPCs harboring BRAFV600E or NRASQ61R mutations generate papillary or follicular TC, respectively, whereas addition of TP53R248Q generate undifferentiated TCs. Of note, TCs arise by engineering TPCs, whereas mature thyrocytes have a very limited tumorigenic capacity. The same mutations result in teratocarcinomas when delivered in early differentiating hESCs. Tissue Inhibitor of Metalloproteinase 1 (TIMP1)/Matrix metallopeptidase 9 (MMP9)/Cluster of differentiation 44 (CD44) ternary complex, in cooperation with Kisspeptin receptor (KISS1R), is involved in TC initiation and progression. Increasing radioiodine uptake, KISS1R and TIMP1 targeting may represent a therapeutic adjuvant option for undifferentiated TCs.
Fully paper-integrated hydrophobic and air permeable piezoresistive sensors for high-humidity and underwater wearable motion monitoring
Authors: Wei Yuewen , Shi Xuewen , Yao Zhuoqi , Zhi Jiacai , Hu Lixuan , Yan Ren , Shi Chuanqian , Yu Hai-Dong , Huang Wei
Published: March 2023

Paper-based electronics have attracted much attention due to their softness, degradability, and low cost. However, paper-based sensors are difficult to apply to high-humidity environments or even underwater. Here, we report a fully paper-integrated piezoresistive sensing system that exhibits flexibility, waterproofing, air permeability, and biocompatibility. This system consists of hydrophobic paper as the substrate and encapsulation layer, conductive paper with a double ‘zig-zag’ and dotted surface structure as the sensing layer, and silver paste films as the interconnects. The structural design of the sensing layer helps to increase the contact area in adjacent layers under pressure and further improves the pressure sensitivity. The piezoresistive system can be worn on human skin in the ambient environment, wet environment, and water for real-time monitoring of physiological signals with air permeability and waterproofing due to its hydrophobic fiber structure. Such a device provides a reliable, economical, and eco-friendly solution to wearable technologies.
Immune correlates analysis of a phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine
Authors: Benkeser David , Fong Youyi , Janes Holly E. , Kelly Elizabeth J. , Hirsch Ian , Sproule Stephanie , Stanley Ann Marie , Maaske Jill , Villafana Tonya , Houchens Christopher R. , Martins Karen , Jayashankar Lakshmi , Castellino Flora , Ayala Victor , Petropoulos Christos J. , Leith Andrew , Haugaard Deanne , Webb Bill , Lu Yiwen , Yu Chenchen , Borate Bhavesh , van der Laan Lars W. P. , Hejazi Nima S. , Carpp Lindsay N. , Randhawa April K. , Andrasik Michele P. , Kublin James G. , Isaacs Margaret Brewinski , Makhene Mamodikoe , Tong Tina , Robb Merlin L. , Corey Lawrence , Neuzil Kathleen M. , Follmann Dean , Hoffman Corey , Falsey Ann R. , Sobieszczyk Magdalena , Koup Richard A. , Donis Ruben O. , Gilbert Peter B. ,   on behalf of the AstraZeneca AZD1222 Clinical Study Group,   the Immune Assays Team,   the United States Government (USG)/CoVPN Biostatistics Team
Published: March 2023

In the phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine conducted in the U.S., Chile, and Peru, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured four weeks after two doses were assessed as correlates of risk and protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID-19). These analyses of SARS-CoV-2 negative participants were based on case-cohort sampling of vaccine recipients (33 COVID-19 cases by 4 months post dose two, 463 non-cases). The adjusted hazard ratio of COVID-19 was 0.32 (95% CI: 0.14, 0.76) per 10-fold increase in spike IgG concentration and 0.28 (0.10, 0.77) per 10-fold increase in nAb ID50 titer. At nAb ID50 below the limit of detection (< 2.612 IU50/ml), 10, 100, and 270 IU50/ml, vaccine efficacy was −5.8% (−651%, 75.6%), 64.9% (56.4%, 86.9%), 90.0% (55.8%, 97.6%) and 94.2% (69.4%, 99.1%). These findings provide further evidence towards defining an immune marker correlate of protection to help guide regulatory/approval decisions for COVID-19 vaccines.