bluuebunny/crossref_metadata_2025 huggingface dataset:
“I’m Not Worthless, I Do Help Society”: Exploring the Lived Experience of Community Placement in Activation Schemes
Authors: Petautschnig Carla , Timonen Virpi
Published: January 2024

Activation schemes are widely criticised, with the negative experiences of ‘the activated’ featuring prominently in the literature. This article presents the findings of a constructivist grounded theory study concerning the lived experience of long-term unemployment, welfare recipiency and community placement in activation schemes in Ireland, with a focus on the positive effects that participating in such schemes had on participants’ subjective well-being. For the participants in this research, community placement signified change, respite, and recovery that improved their subjective well-being by creating an experience that counteracted the draining experience of long-term unemployment and welfare recipiency. This study brings new elements to the discussion on the role of activation in promoting/diminishing the subjective well-being of the long-term unemployed.
Preconditions for efficiency and affordability in mixed health systems: are they fulfilled in the Australian public–private mix?
Authors: Berardi Chiara , Arija Prieto Pablo , Henríquez Josefa , Paolucci Francesco
Published: January 2024

The Australian health system is characterised by high quality care by international standards, produced by a mix of public and private provision and funding of healthcare services. Despite good overall results, three issues are of concern. The first issue relates to the public procurement of healthcare, whose flaws have impacted individuals' access to care, and the high out-of-pocket spending. The second issue concerns the sustainability of the private health insurance market, given the government's goal of relieving cost and capacity from the public scheme, incentivising participation. Third, there are existing inefficiencies and inequities related to the duplication resulting from the interaction between public and private schemes. To ensure a sustainable, efficient and equitable health system, structural reforms are necessary to achieve long-term performance improvements. Using a framework for mixed public–private health systems, we assess the extent to which the Australian healthcare system achieves preconditions for efficiency and affordability in competitive healthcare markets.
Free-electron crystals for enhanced X-ray radiation
Authors: Wong Lee Wei Wesley , Shi Xihang , Karnieli Aviv , Lim Jeremy , Kumar Suraj , Carbajo Sergio , Kaminer Ido , Wong Liang Jie
Published: January 2024

Bremsstrahlung—the spontaneous emission of broadband radiation from free electrons that are deflected by atomic nuclei—contributes to the majority of X-rays emitted from X-ray tubes and used in applications ranging from medical imaging to semiconductor chip inspection. Here, we show that the bremsstrahlung intensity can be enhanced significantly—by more than three orders of magnitude—through shaping the electron wavefunction to periodically overlap with atoms in crystalline materials. Furthermore, we show how to shape the bremsstrahlung X-ray emission pattern into arbitrary angular emission profiles for purposes such as unidirectionality and multi-directionality. Importantly, we find that these enhancements and shaped emission profiles cannot be attributed solely to the spatial overlap between the electron probability distribution and the atomic centers, as predicted by the paraxial and non-recoil theory for free electron light emission. Our work highlights an unprecedented regime of free electron light emission where electron waveshaping provides multi-dimensional control over practical radiation processes like bremsstrahlung. Our results pave the way towards greater versatility in table-top X-ray sources and improved fundamental understanding of quantum electron-light interactions.
Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor)
Authors: Zhang Lei , Chen Jiabing , Yang Xiaoying , Shen Chuangpeng , Huang Jiawen , Zhang Dong , Liu Naihua , Liu Chaonan , Zhong Yadi , Chen Yingjian , Tang Kaijia , Guo Jingyi , Cui Tianqi , Duan Siwei , Li Jiayu , Huang Shangyi , Pan Huafeng , Zhang Huabing , Tang Xiaoqiang , Chang Yongsheng , Gao Yong
Published: January 2024

A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease (NAFLD), coupled with hepatitis and insulin resistance. Yet the details of the underlying mechanisms are not fully understood. Here, we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of NAFLD. Hepatic Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation (FAO), and induced insulin resistance. Conversely, hepatic Zbtb18 overexpression alleviated hepato-steatosis, insulin resistance, and hyperglycemia in mice fed on a high-fat diet (HFD) or in diabetic mice. Notably, in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor (FXR) mediated FAO and Clathrin Heavy Chain (CLTC) protein hinders NLRP3 inflammasome activity. This key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes (MPHs). Moreover, CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in macrophages. Altogether, Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression, which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance, representing an attractive remedy for hepatic steatosis and fibrosis.
The safety and efficacy of systemic delivery of a new liver-de-targeted TGFβ signaling inhibiting adenovirus in an immunocompetent triple negative mouse mammary tumor model
Authors: Shin Soon Cheon , Vickman Renee E. , Filimon Beniamin , Yang Yuefeng , Hu Zebin , Mangold Kathy A. , Prabhakar Bellur S. , Schreiber Hans , Xu Weidong
Published: January 2024

Aberrant TGFβ signaling is linked to metastasis and tumor immune escape of many cancers including metastatic triple negative breast cancer (mTNBC). Previously, we have found that oncolytic adenoviruses expressing a TGFβ signaling inhibitory protein (sTGFβRIIFc) induced immune activation in a mouse TNBC (4T1) immunocompetent subcutaneous model with intratumoral injection. Systemic administration of adenoviruses can be a superior route to treat mTNBC but faces the challenges of increased toxicity and viral clearance. Thus, we created a liver-de-targeted sTGFβRIIFc- and LyP-1 peptide-expressing adenovirus (mHAdLyp.sT) with enhanced breast cancer cell tropism. Its safety and immune response features were profiled in the 4T1 model. Our data showed that the systemic administration of mHAdLyp.sT resulted in reduced hepatic and systemic toxicity. mHAdLyp.sT was also effective in increasing Th1 cytokines and anti-tumor cell populations by cytokine analysis, spleen/tumor qRT-PCR, and flow cytometry. We further tested the therapeutic effects of mHAdLyp.sT alone and in combination with immune checkpoint inhibitors (ICIs). mHAdLyp.sT alone and with all ICI combinations elicited significant inhibition of lung metastasis by histological analysis. When mHAdLyp.sT was combined with both anti-PD-1 and anti-CTLA-4 antibodies, primary 4T1 tumor growth was also significantly inhibited. We are confident in advancing this new treatment option for mTNBC.
Respiratory distress in SARS-CoV-2 exposed uninfected neonates followed in the COVID Outcomes in Mother-Infant Pairs (COMP) Study
Authors: Man Olivia M. , Azamor Tamiris , Cambou Mary Catherine , Fuller Trevon L. , Kerin Tara , Paiola Sophia G. , Cranston Jessica S. , Mok Thalia , Rao Rashmi , Chen Weiqiang , Jung Jae U. , Martinez Viviana Fajardo , Foo Suan-Sin , Nielsen-Saines Karin
Published: January 2024

Respiratory distress (RD) has been reported in SARS-CoV-2 exposed uninfected (SEU) term neonates. Prior studies suggest that prenatal exposure to Coronavirus Disease 19 (COVID-19) may activate an inflammatory cascade in the newborn airway. In this study, we examine the relationship between maternal COVID-19 vaccination and neonatal RD using a longitudinal cohort of mother-infant pairs in Los Angeles, CA. Two-hundred and twenty-one mothers with laboratory confirmed SARS-CoV-2 during pregnancy and 227 exposed fetuses are enrolled in our study. Maternal disease severity and neonatal RD variables were defined based on current accepted clinical criteria. To explore the multifactorial associations between maternal COVID-19 parameters and infant RD, we utilize a multivariable logistic regression model and a proteomic sub-analysis to propose a pathway for the development of RD followingin uteroexposure to SARS-CoV-2. Unusually high rates of RD are observed in SEU infants (17%). The odds ratio of RD is 3.06 (95% CI:1.08-10.21) in term neonates born to unvaccinated individuals versus those born to individuals vaccinated prior to maternal infection. Proteomic analysis reveals a robust inflammatory response associated with ciliary dysregulation and enhanced IgE production among SEU neonates with RD. Maternal vaccination against COVID-19 reduces the frequency of neonatal RD.
Shape-changing electrode array for minimally invasive large-scale intracranial brain activity mapping
Authors: Wei Shiyuan , Jiang Anqi , Sun Hongji , Zhu Jingjun , Jia Shengyi , Liu Xiaojun , Xu Zheng , Zhang Jing , Shang Yuanyuan , Fu Xuefeng , Li Gen , Wang Puxin , Xia Zhiyuan , Jiang Tianzi , Cao Anyuan , Duan Xiaojie
Published: January 2024

Large-scale brain activity mapping is important for understanding the neural basis of behaviour. Electrocorticograms (ECoGs) have high spatiotemporal resolution, bandwidth, and signal quality. However, the invasiveness and surgical risks of electrode array implantation limit its application scope. We developed an ultrathin, flexible shape-changing electrode array (SCEA) for large-scale ECoG mapping with minimal invasiveness. SCEAs were inserted into cortical surfaces in compressed states through small openings in the skull or dura and fully expanded to cover large cortical areas. MRI and histological studies on rats proved the minimal invasiveness of the implantation process and the high chronic biocompatibility of the SCEAs. High-quality micro-ECoG activities mapped with SCEAs from male rodent brains during seizures and canine brains during the emergence period revealed the spatiotemporal organization of different brain states with resolution and bandwidth that cannot be achieved using existing noninvasive techniques. The biocompatibility and ability to map large-scale physiological and pathological cortical activities with high spatiotemporal resolution, bandwidth, and signal quality in a minimally invasive manner offer SCEAs as a superior tool for applications ranging from fundamental brain research to brain-machine interfaces.
Rational strain design with minimal phenotype perturbation
Authors: Narayanan Bharath , Weilandt Daniel , Masid Maria , Miskovic Ljubisa , Hatzimanikatis Vassily
Published: January 2024

Devising genetic interventions for desired cellular phenotypes remains challenging regarding time and resources. Kinetic models can accelerate this task by simulating metabolic responses to genetic perturbations. However, exhaustive design evaluations with kinetic models are computationally impractical, especially when targeting multiple enzymes. Here, we introduce a framework for efficiently scouting the design space while respecting cellular physiological requirements. The framework employs mixed-integer linear programming and nonlinear simulations with large-scale nonlinear kinetic models to devise genetic interventions while accounting for the network effects of these perturbations. Importantly, it ensures the engineered strain’s robustness by maintaining its phenotype close to that of the reference strain. The framework, applied to improve the anthranilate production in E. coli, devises designs for experimental implementation, including eight previously experimentally validated targets. We expect this framework to play a crucial role in future design-build-test-learn cycles, significantly expediting the strain design compared to exhaustive design enumeration.
Upcycling poly(succinates) with amines to N-substituted succinimides over succinimide anion-based ionic liquids
Authors: Wu Fengtian , Wang Yuepeng , Zhao Yanfei , Zeng Shaojuan , Wang Zhenpeng , Tang Minhao , Zeng Wei , Wang Ying , Chang Xiaoqian , Xiang Junfeng , Xie Zongbo , Han Buxing , Liu Zhimin
Published: January 2024

The chemical transformation of waste polymers into value-added chemicals is of significance for circular economy and sustainable development. Herein, we report upcycling poly(succinates) (PSS) with amines into N-substituted succinimides over succinimide anion-based ionic liquids (ILs, e.g, 1,8-diazabicyclo[5.4.0]undec-7-ene succinimide, [HDBU][Suc]). Assisted with H2O, [HDBU][Suc]) showed the best performance, which could achieve complete transformation of a series of PSS into succinimide derivatives and corresponding diols under mild and metal-free conditions. Mechanism investigation indicates that the cation-anion confined hydrogen-bonding interactions among IL, H2O, ester group, and amino/amide groups, strengthens nucleophilicity of the N atoms in amino/amide groups, and improves electrophilicity of carbonyl C atom in ester group. The attack of the amino/amide N atom on carbonyl C of ester group results in cleavage of carbonyl C-O bond in polyester and formation of amide group. This strategy is also effective for aminolysis of poly(trimethylene glutarate) to glutarimides, and poly(1,4-butylene adipate) to caprolactone diimides.
Pt-doped Ru nanoparticles loaded on ‘black gold’ plasmonic nanoreactors as air stable reduction catalysts
Authors: Sharma Gunjan , Verma Rishi , Masuda Shinya , Badawy Khaled Mohamed , Singh Nirpendra , Tsukuda Tatsuya , Polshettiwar Vivek
Published: January 2024

This study introduces a plasmonic reduction catalyst, stable only in the presence of air, achieved by integrating Pt-doped Ru nanoparticles on black gold. This innovative black gold/RuPt catalyst showcases good efficiency in acetylene semi-hydrogenation, attaining over 90% selectivity with an ethene production rate of 320 mmol g−1 h−1. Its stability, evident in 100 h of operation with continuous air flow, is attributed to the synergy of co-existing metal oxide and metal phases. The catalyst’s stability is further enhanced by plasmon-mediated concurrent reduction and oxidation of the active sites. Finite-difference time-domain simulations reveal a five-fold electric field intensification near the RuPt nanoparticles, crucial for activating acetylene and hydrogen. Kinetic isotope effect analysis indicates the contribution from the plasmonic non-thermal effects along with the photothermal. Spectroscopic and in-situ Fourier transform infrared studies, combined with quantum chemical calculations, elucidate the molecular reaction mechanism, emphasizing the cooperative interaction between Ru and Pt in optimizing ethene production and selectivity.
Manipulating hyperbolic transient plasmons in a layered semiconductor
Authors: Fu Rao , Qu Yusong , Xue Mengfei , Liu Xinghui , Chen Shengyao , Zhao Yongqian , Chen Runkun , Li Boxuan , Weng Hongming , Liu Qian , Dai Qing , Chen Jianing
Published: January 2024

Anisotropic materials with oppositely signed dielectric tensors support hyperbolic polaritons, displaying enhanced electromagnetic localization and directional energy flow. However, the most reported hyperbolic phonon polaritons are difficult to apply for active electro-optical modulations and optoelectronic devices. Here, we report a dynamic topological plasmonic dispersion transition in black phosphorus via photo-induced carrier injection, i.e., transforming the iso-frequency contour from a pristine ellipsoid to a non-equilibrium hyperboloid. Our work also demonstrates the peculiar transient plasmonic properties of the studied layered semiconductor, such as the ultrafast transition, low propagation losses, efficient optical emission from the black phosphorus’s edges, and the characterization of different transient plasmon modes. Our results may be relevant for the development of future optoelectronic applications.
Ratiometric fluorescent sensing of pyrophosphate with sp³-functionalized single-walled carbon nanotubes
Authors: Settele Simon , Schrage C. Alexander , Jung Sebastian , Michel Elena , Li Han , Flavel Benjamin S. , Hashmi A. Stephen K. , Kruss Sebastian , Zaumseil Jana
Published: January 2024

Inorganic pyrophosphate is a key molecule in many biological processes from DNA synthesis to cell metabolism. Here we introduce sp3-functionalized (6,5) single-walled carbon nanotubes (SWNTs) with red-shifted defect emission as near-infrared luminescent probes for the optical detection and quantification of inorganic pyrophosphate. The sensing scheme is based on the immobilization of Cu2+ ions on the SWNT surface promoted by coordination to covalently attached aryl alkyne groups and a triazole complex. The presence of Cu2+ ions on the SWNT surface causes fluorescence quenching via photoinduced electron transfer, which is reversed by copper-complexing analytes such as pyrophosphate. The differences in the fluorescence response of sp3-defect to pristine nanotube emission enables reproducible ratiometric measurements in a wide concentration window. Biocompatible, phospholipid-polyethylene glycol-coated SWNTs with such sp3 defects are employed for the detection of pyrophosphate in cell lysate and for monitoring the progress of DNA synthesis in a polymerase chain reaction. This robust ratiometric and near-infrared luminescent probe for pyrophosphate may serve as a starting point for the rational design of nanotube-based biosensors.
Valid and efficient entanglement verification with finite copies of a quantum state
Authors: Cieśliński Paweł , Dziewior Jan , Knips Lukas , Kłobus Waldemar , Meinecke Jasmin , Paterek Tomasz , Weinfurter Harald , Laskowski Wiesław
Published: January 2024

Detecting entanglement in multipartite quantum states is an inherently probabilistic process, typically with a few measured samples. The level of confidence in entanglement detection quantifies the scheme’s validity via the probability that the signal comes from a separable state, offering a meaningful figure of merit for big datasets. Yet, with limited samples, avoiding experimental data misinterpretations requires considering not only the probabilities concerning separable states but also the probability that the signal came from an entangled state, i.e. the detection scheme’s efficiency. We demonstrate this explicitly and apply a general method to optimize both the validity and the efficiency in small data sets providing examples using at most 20 state copies. The method is based on an analytical model of finite statistics effects on correlation functions which takes into account both a Frequentist as well as a Bayesian approach and is applicable to arbitrary entanglement witnesses.
Mediation of collisionless turbulent dissipation through cyclotron resonance
Authors: Bowen Trevor A. , Bale Stuart D. , Chandran Benjamin D. G. , Chasapis Alexandros , Chen Christopher H. K. , Dudok de Wit Thierry , Mallet Alfred , Meyrand Romain , Squire Jonathan
Published: January 2024

The dissipation of turbulence in astrophysical systems is fundamental to energy transfer and heating in environments ranging from the solar wind and corona to accretion disks and the intracluster medium. Although turbulent dissipation is relatively well understood in fluid dynamics, astrophysical plasmas often exhibit exotic behaviour, arising from the lack of interparticle collisions, which complicates turbulent dissipation and heating in these systems. Recent observations by NASA’s Parker Solar Probe mission in the inner heliosphere have shed new light on the role of ion cyclotron resonance as a potential candidate for turbulent dissipation and plasma heating. Here, using in situ observations of turbulence and wave populations, we show that ion cyclotron waves provide a major pathway for dissipation and plasma heating in the solar wind. Our results support recent theoretical predictions of turbulence in the inner heliosphere, known as the helicity barrier, that suggest a role of cyclotron resonance in ion-scale dissipation. Taken together, these results provide important constraints for turbulent dissipation and acceleration efficiency in astrophysical plasmas.
Redefining the treponemal history through pre-Columbian genomes from Brazil
Authors: Majander Kerttu , Pla-Díaz Marta , du Plessis Louis , Arora Natasha , Filippini Jose , Pezo-Lanfranco Luis , Eggers Sabine , González-Candelas Fernando , Schuenemann Verena J.
Published: January 2024

The origins of treponemal diseases have long remained unknown, especially considering the sudden onset of the first syphilis epidemic in the late 15th century in Europe and its hypothesized arrival from the Americas with Columbus’ expeditions1,2. Recently, ancient DNA evidence has revealed various treponemal infections circulating in early modern Europe and colonial-era Mexico3–6. However, there has been to our knowledge no genomic evidence of treponematosis recovered from either the Americas or the Old World that can be reliably dated to the time before the first trans-Atlantic contacts. Here, we present treponemal genomes from nearly 2,000-year-old human remains from Brazil. We reconstruct four ancient genomes of a prehistoric treponemal pathogen, most closely related to the bejel-causing agent Treponema pallidum endemicum. Contradicting the modern day geographical niche of bejel in the arid regions of the world, the results call into question the previous palaeopathological characterization of treponeme subspecies and showcase their adaptive potential. A high-coverage genome is used to improve molecular clock date estimations, placing the divergence of modern T. pallidum subspecies firmly in pre-Columbian times. Overall, our study demonstrates the opportunities within archaeogenetics to uncover key events in pathogen evolution and emergence, paving the way to new hypotheses on the origin and spread of treponematoses.
Oligodendrocyte–axon metabolic coupling is mediated by extracellular K+ and maintains axonal health
Authors: Looser Zoe J. , Faik Zainab , Ravotto Luca , Zanker Henri S. , Jung Ramona B. , Werner Hauke B. , Ruhwedel Torben , Möbius Wiebke , Bergles Dwight E. , Barros L. Felipe , Nave Klaus-Armin , Weber Bruno , Saab Aiman S.
Published: January 2024

The integrity of myelinated axons relies on homeostatic support from oligodendrocytes (OLs). To determine how OLs detect axonal spiking and how rapid axon–OL metabolic coupling is regulated in the white matter, we studied activity-dependent calcium (Ca2+) and metabolite fluxes in the mouse optic nerve. We show that fast axonal spiking triggers Ca2+ signaling and glycolysis in OLs. OLs detect axonal activity through increases in extracellular potassium (K+) concentrations and activation of Kir4.1 channels, thereby regulating metabolite supply to axons. Both pharmacological inhibition and OL-specific inactivation of Kir4.1 reduce the activity-induced axonal lactate surge. Mice lacking oligodendroglial Kir4.1 exhibit lower resting lactate levels and altered glucose metabolism in axons. These early deficits in axonal energy metabolism are associated with late-onset axonopathy. Our findings reveal that OLs detect fast axonal spiking through K+ signaling, making acute metabolic coupling possible and adjusting the axon–OL metabolic unit to promote axonal health.
Cortactin stabilizes actin branches by bridging activated Arp2/3 to its nucleated actin filament
Authors: Liu Tianyang , Cao Luyan , Mladenov Miroslav , Jegou Antoine , Way Michael , Moores Carolyn A.
Published: January 2024

Regulation of the assembly and turnover of branched actin filament networks nucleated by the Arp2/3 complex is essential during many cellular processes, including cell migration and membrane trafficking. Cortactin is important for actin branch stabilization, but the mechanism by which this occurs is unclear. Given this, we determined the structure of vertebrate cortactin-stabilized Arp2/3 actin branches using cryogenic electron microscopy. We find that cortactin interacts with the new daughter filament nucleated by the Arp2/3 complex at the branch site, rather than the initial mother actin filament. Cortactin preferentially binds activated Arp3. It also stabilizes the F-actin-like interface of activated Arp3 with the first actin subunit of the new filament, and its central repeats extend along successive daughter-filament subunits. The preference of cortactin for activated Arp3 explains its retention at the actin branch and accounts for its synergy with other nucleation-promoting factors in regulating branched actin network dynamics.
The first host plant dataset of Curculionidae Scolytinae of the world: miscellaneous Tribes
Authors: Marchioro Matteo , Vallotto Davide , Ruzzier Enrico , Besana Laura , Rossini Michele , Ortis Giacomo , Faccoli Massimo , Martinez-Sañudo Isabel
Published: January 2024

Tribes Coriacephilini, Corthylini, Cryphalini, Ernoporini, Trypophloeini, Xyloctonini, and Xyloterini (Coleoptera: Curculionidae; Scolytinae) include spermophagous, phloeophagous, and xylomycetophagous species. Besides direct damage caused by burrowing into host plant tissues, some species are vectors of aggressive pathogens causing plant dieback and death, with consequent economic and ecological relevance. The international trade in plants and wood products is one of the main pathways for the introduction of non-native species worldwide. In this context, data availability on host plants and their economic uses is essential in pest risk assessment and for planning effective detection and monitoring strategies against invasive species. This paper provides a complete and updated list of host plants, with economic categorization, for 2139 scolytine species.
Influence of energy poverty on agricultural water efficiency using a panel data study in China
Authors: Shi Hongxu , Zhang Yuehua , Bian Mengyan , Zhang Jun
Published: January 2024

The research attention is increasingly directed towards the effective integration of the 17 United Nations Sustainable Development Goals (SDGs) within the limitations of the real world and amidst intersectoral conflicts. In light of the inextricable relationship between irrigation and energy, the objective of this study is to identify potential avenues for achieving the SDG6 and SDG7 goals of enhancing water use efficiency in agriculture and eradicating energy poverty, respectively. Utilizing data from 30 Chinese provinces from 2002 to 2017, this study explores the dynamic influence of energy poverty on agricultural water efficiency with a system generalized method of moments methodology. The findings suggest that energy poverty may greatly reduce agricultural water efficiency. The heterogeneity study shows that when agricultural water efficiency grows, the negative impacts of energy poverty continue to fade. Based on an assessment of various processes, results suggest that non-farm employment and cropping structure modification is a prominent conduit via which energy poverty negatively influences agricultural water efficiency.
Identification of genes with oscillatory expression in glioblastoma: the paradigm of SOX2
Authors: Fu Richard Zhiming , Cottrell Oliver , Cutillo Luisa , Rowntree Andrew , Zador Zsolt , Wurdak Heiko , Papalopulu Nancy , Marinopoulou Elli
Published: January 2024

Quiescence, a reversible state of cell-cycle arrest, is an important state during both normal development and cancer progression. For example, in glioblastoma (GBM) quiescent glioblastoma stem cells (GSCs) play an important role in re-establishing the tumour, leading to relapse. While most studies have focused on identifying differentially expressed genes between proliferative and quiescent cells as potential drivers of this transition, recent studies have shown the importance of protein oscillations in controlling the exit from quiescence of neural stem cells. Here, we have undertaken a genome-wide bioinformatic inference approach to identify genes whose expression oscillates and which may be good candidates for controlling the transition to and from the quiescent cell state in GBM. Our analysis identified, among others, a list of important transcription regulators as potential oscillators, including the stemness gene SOX2, which we verified to oscillate in quiescent GSCs. These findings expand on the way we think about gene regulation and introduce new candidate genes as key regulators of quiescence.
GAILS: an effective multi-object job shop scheduler based on genetic algorithm and iterative local search
Authors: Shao Xiaorui , Kshitij Fuladi Shubhendu , Kim Chang Soo
Published: January 2024

The job shop scheduling problem (JSSP) is critical for building one smart factory regarding resource management, effective production, and intelligent supply. However, it is still very challenging due to the complex production environment. Besides, most current research only focuses on classical JSSP, while flexible JSSP (FJSSP) is more usual. This article proposes an effective method, GAILS, to deal with JSSP and FJSSP based on genetic algorithm (GA) and iterative local search (ILS). GA is used to find the approximate global solution for the JSSP instance. Each instance was encoded into machine and subtask sequences. The corresponding machine and subtasks chromosome could be obtained through serval-time gene selection, crossover, and mutation. Moreover, multi-objects, including makespan, average utilization ratio, and maximum loading, are used to choose the best chromosome to guide ILS to explore the best local path. Therefore, the proposed method has an excellent search capacity and could balance globality and diversity. To verify the proposed method's effectiveness, the authors compared it with some state-of-the-art methods on sixty-six public JSSP and FJSSP instances. The comparative analysis confirmed the proposed method's effectiveness for classical JSSP and FJSSP in makespan, average utilization ratio, and maximum loading. Primarily, it obtains optimal-like solutions for several instances and outperforms others in most instances.
Analyzing urban influence on extreme winter precipitation through observations and numerical simulation of two South China case studies
Authors: Hu Chenxi , Tam Chi-Yung , Yang Zong-liang , Wang Ziqian
Published: January 2024

This study investigates the impact of urbanization on extreme winter rainfall in the South China Greater Bay Area (GBA) through the analysis of hourly station observations and simulations using the Weather Research and Forecasting Model with the Single Layer Urban Canopy Model (WRF-SLUCM). Data from 2008 to 2017 reveal that urban areas in the GBA experience lower 99th percentile hourly winter rainfall intensity compared to surrounding rural regions. However, urban locations exhibit higher annual maximum hourly rainfall (Rmax) and very extreme rainfall events (99.99th percentile) in winter, suggesting a positive influence of urbanization on extreme winter precipitation. A case study further underscores the role of the Urban Heat Island (UHI) effect in enhancing extreme rainfall intensity and probability in the GBA urban areas. Additionally, two extreme cases were dynamically downscaled using WRF-SLUCM, involving four parallel experiments: replacing urban land use with cropland (Nourban), using historical urban land use data from 1999 (99LS), projecting near-future urban land use for 2030 (30LS), and considering 2030 urban land use without anthropogenic heat (AH) (30LS-AH0). Synoptic analysis demonstrates that cold air intrusion suppresses the GBA UHI in Case 2013 but not in Case 2015. Reduced evaporation and humidity induced by urban surfaces significantly decrease urban precipitation in Case 2013. In contrast, the persistent UHI in Case 2015 enhances local convection and land–ocean circulation, leading to increased moisture flux convergence and amplified urban precipitation intensity and probability in 30LS compared to Nourban. This amplification is primarily attributed to AH, while the change in 99LS remains insignificant. These findings suggest that urban influences on extreme precipitation in the GBA persist during winter, particularly when the UHI effect is maintained.
Experimental study on the damage performance and forced response of concrete lining in fault-crossing tunnel
Authors: Hu Hui , Lan Youdi , Liu Yun , Qiu Wenge
Published: January 2024

Understanding the adverse effects of tunnel crossing active faults on tunnel structures is crucial for ensuring their safe operation and construction. This paper presents the results of a series of model tests conducted at a scale of 1:40 using a fault sliding test box. Three sets of fault comparison tests were carried out, namely: (1) the tunnel does not cross the fault, (2) the spring stiffness is reduced, and (3) the model is not reinforced. The objective was to study the failure characteristics of tunnels crossing active faults. The findings reveal that when the hanging wall moves downwards, cracks appear on the surrounding rock surface of the hanging wall, specifically above the tunnel lining crossing the fault. The lining is significantly damaged within the range of − 30–+ 30 cm. All points of axial force exhibit an increasing compression trend. The section of axial force and bending moment near the fault fracture surface is notably larger than that far from the fault fracture surface. The safety factor of the entire structure decreases sharply after dislocation, making the tunnel more susceptible to cracking at various locations such as the vault, arch waist, left and right arch feet, and inverted arch. It has been proven that the shear compression of the fracture surface during fault dislocation is the main cause of longitudinal through cracks in the lining. The use of springs with higher stiffness effectively ensures the reciprocating dislocation of the upper and foot walls, with long duration and large displacement, providing a better simulation of the dislocation of active faults.
Yeast 26S proteasome nuclear import is coupled to nucleus-specific degradation of the karyopherin adaptor protein Sts1
Authors: Breckel Carolyn Allain , Johnson Zane M. , Hickey Christopher M. , Hochstrasser Mark
Published: January 2024

In eukaryotes, the ubiquitin–proteasome system is an essential pathway for protein degradation and cellular homeostasis. 26S proteasomes concentrate in the nucleus of budding yeastSaccharomyces cerevisiaedue to the essential import adaptor protein Sts1 and the karyopherin-α protein Srp1. Here, we show that Sts1 facilitates proteasome nuclear import by recruiting proteasomes to the karyopherin-α/β heterodimer. Following nuclear transport, the karyopherin proteins are likely separated from Sts1 through interaction with RanGTP in the nucleus. RanGTP-induced release of Sts1 from the karyopherin proteins initiates Sts1 proteasomal degradation in vitro. Sts1 undergoes karyopherin-mediated nuclear import in the absence of proteasome interaction, but Sts1 degradation in vivo is only observed when proteasomes successfully localize to the nucleus. Sts1 appears to function as a proteasome import factor during exponential growth only, as it is not found in proteasome storage granules (PSGs) during prolonged glucose starvation, nor does it appear to contribute to the rapid nuclear reimport of proteasomes following glucose refeeding and PSG dissipation. We propose that Sts1 acts as a single-turnover proteasome nuclear import factor by recruiting karyopherins for transport and undergoing subsequent RanGTP-initiated ubiquitin-independent proteasomal degradation in the nucleus.
Nuclear and mitochondrial genetic variants associated with mitochondrial DNA copy number
Authors: Koller Adriana , Filosi Michele , Weissensteiner Hansi , Fazzini Federica , Gorski Mathias , Pattaro Cristian , Schönherr Sebastian , Forer Lukas , Herold Janina M. , Stark Klaus J. , Döttelmayer Patricia , Hicks Andrew A. , Pramstaller Peter P. , Würzner Reinhard , Eckardt Kai-Uwe , Heid Iris M. , Fuchsberger Christian , Lamina Claudia , Kronenberg Florian
Published: January 2024

Mitochondrial DNA copy number (mtDNA-CN) is a biomarker for mitochondrial dysfunction associated with several diseases. Previous genome-wide association studies (GWAS) have been performed to unravel underlying mechanisms of mtDNA-CN regulation. However, the identified gene regions explain only a small fraction of mtDNA-CN variability. Most of this data has been estimated from microarrays based on various pipelines. In the present study we aimed to (1) identify genetic loci for qPCR-measured mtDNA-CN from three studies (16,130 participants) using GWAS, (2) identify potential systematic differences between our qPCR derived mtDNA-CN measurements compared to the published microarray intensity-based estimates, and (3) disentangle the nuclear from mitochondrial regulation of the mtDNA-CN phenotype. We identified two genome-wide significant autosomal loci associated with qPCR-measured mtDNA-CN: at HBS1L (rs4895440, p = 3.39 × 10–13) and GSDMA (rs56030650, p = 4.85 × 10–08) genes. Moreover, 113/115 of the previously published SNPs identified by microarray-based analyses were significantly equivalent with our findings. In our study, the mitochondrial genome itself contributed only marginally to mtDNA-CN regulation as we only detected a single rare mitochondrial variant associated with mtDNA-CN. Furthermore, we incorporated mitochondrial haplogroups into our analyses to explore their potential impact on mtDNA-CN. However, our findings indicate that they do not exert any significant influence on our results.
Low handgrip strength is associated with worse functional outcomes in long COVID
Authors: do Amaral Camila Miriam Suemi Sato Barros , da Luz Goulart Cássia , da Silva Bernardo Maia , Valente Jefferson , Rezende Anna Gabriela , Fernandes Eduardo , Cubas-Vega Nadia , Borba Mayla Gabriela Silva , Sampaio Vanderson , Monteiro Wuelton , de Melo Gisely Cardoso , Lacerda Marcus , Arêas Guilherme Peixoto Tinoco , Almeida-Val Fernando
Published: January 2024

The diagnosis of long COVID is troublesome, even when functional limitations are present. Dynapenia is the loss of muscle strength and power production that is not caused by neurologic or muscular diseases, being mostly associated with changes in neurologic function and/or the intrinsic force-generating properties of skeletal muscle, which altogether, may partially explain the limitations seen in long COVID. This study aimed to identify the distribution and possible associations of dynapenia with functional assessments in patients with long COVID. A total of 113 patients with COVID-19 were evaluated by functional assessment 120 days post-acute severe disease. Body composition, respiratory muscle strength, spirometry, six-minute walk test (6MWT, meters), and hand-grip strength (HGS, Kilogram-force) were assessed. Dynapenia was defined as HGS < 30 Kgf (men), and < 20 Kgf (women). Twenty-five (22%) participants were dynapenic, presenting lower muscle mass (p < 0.001), worse forced expiratory volume in the first second (FEV1) (p = 0.0001), lower forced vital capacity (p < 0.001), and inspiratory (p = 0.007) and expiratory (p = 0.002) peek pressures, as well as worse 6MWT performance (p < 0.001). Dynapenia, independently of age, was associated with worse FEV1, maximal expiratory pressure (MEP), and 6MWT, (p < 0.001) outcomes. Patients with dynapenia had higher intensive care unit (ICU) admission rates (p = 0.01) and need for invasive mechanical ventilation (p = 0.007) during hospitalization. The HGS is a simple, reliable, and low-cost measurement that can be performed in outpatient clinics in low- and middle-income countries. Thus, HGS may be used as a proxy indicator of functional impairment in this population.
Thinner bats to face hibernation as response to climate warming
Authors: López-Roig Marc , Piera Eduard , Serra-Cobo Jordi
Published: January 2024

One of the principal consequences of climate warming on hibernating mammals could be the loss of optimal conditions for hibernation. Although hibernating mammals, like bats, may be particularly vulnerable to climate warming due to a potential reduction of energy saving during the hibernation, there is a lack of knowledge regarding how they will be affected and how they will respond to this impact. Here, we examine the variation in the body condition of Schreiber’s bent-winged bat (Miniopterus schreibersii) to investigate changes in the optimization energy demand. Using a 20-year dataset (1998–2017), we analyse the temporal trends of body condition in three key stages of the hibernation period: onset and end of hibernation and early activity. Our results indicate that body condition at the onset and end of hibernation have decreased significantly over these 20 years. However, despite this lower body condition, the decrease of mass loss rate in the last decade (although not significant) indicate a greater saving of fat reserves. The significant increase in winter temperatures did not affect body condition or reserve depletion, instead, lower body condition was observed with a higher number of days below 0 °C. Unlike other hibernating bat species, the females had lower fat reserves than males in all three periods considered. This study indicates that hibernation energy requirements could be changing as an adaptation to a warmer climate and that hibernating bats can survive the winter by optimizing their lower accumulation of reserves.
Registered trials on novel therapies for myasthenia gravis: a cross-sectional study on ClinicalTrials.gov
Authors: Li Xingyue , Chen Jinxin , Wang Youtao , Zheng Siwei , Wan Kun , Liu Xiaodong
Published: January 2024

Novel biologics in MG therapy research is on the rise. This research aimed to investigate the characteristics of registered trials on novel therapies for myasthenia gravis on ClinicalTrials.gov. This cross-sectional study used a descriptive approach to assess the features of the included trials on ClinicalTrials.gov. We found 62 registered trials from 2007 to 2023 on ClinicalTrials.gov. The results showed a yearly rise in the number of registered trials (r = 0.76, p < 0.001). Following 2017, more industry-sponsored trials were conducted (91.5% [43] vs. 60% [9], p = 0.009), fewer results were released (10.6% [5] vs. 60% [9], p = 0.001), and more trials entered phase 3 (67.4% [31] vs. 20% [2], p = 0.001). The most researched novel medications were neonatal Fc receptor inhibitors (51.2% [21]), complement inhibitors (39.0% [16]), and B cell depletors (14.6% [6]). According to the website’s data, the neonatal Fc receptor inhibitors and complement inhibitors were effective in treating myasthenia gravis patients in three trials (NCT03315130, NCT03669588, and NCT00727194). This study provides valuable insights into the profile of registered trials on novel therapies for myasthenia gravis. More clinical studies are needed in the future to prove the value of its application.
The osteoinductive potential of different root-end filling materials in a rat femur model
Authors: Aksu Seçkin , Delikan Ebru , Küçük Ayşe Özcan , Asoğlu Zehra Demiray , Yılmaz Şakir Necat
Published: January 2024

In pediatric dentistry, the enduring success of root-end filling materials employed for the establishment of apical plugs in immature teeth undergoing endodontic intervention is contingent upon their possessing a robust osteoinductive capacity. Hence, the primary objective of this study was to histologically assess the osteoinductive potential of four distinct dental materials, specifically recommended for retrograde filling applications, utilizing an animal hard tissue model. Within the designed experimental model, two bone defects measuring 2 mm in diameter and 2 mm in depth were created in both femurs of a cohort comprising 21 male Wistar albino rats. The first defect in the right femur was left blank as the control group, and Neo MTA Plus was placed in the second defect. The EndoSequence BCRRM Fast Set Putty was placed in the first of the defects on the left femur, and Endo Repair was placed in the second defect. Subjects were sacrificed after 7, 14, and 28 days of follow-up, and sections were examined to assess the degree of inflammation, connective tissue formation, and new bone formation. The data were statistically evaluated with Kruskal‒Wallis and post hoc Dunn's tests using SPSS 12 software. The bone healing levels of the Neo MTA Plus group were significantly higher than those of the other groups in all periods (p < 0.05). Bone organization in all groups decreased over time, and fibrous tissue was enriched. The results of this study demonstrate that NeoMta Plus has superior osteoinductive properties compared to other materials but that EndoSequence and Endo Repair have the potential to be developed.
Anthropogenic mortality threatens the survival of Canarian houbara bustards
Authors: Alonso Juan C. , Abril-Colón Inmaculada , Ucero Alberto , Palacín Carlos
Published: January 2024

Anthropogenic mortality is a major cause of global mortality in terrestrial vertebrates. Quantifying its impact on the dynamics of threatened species is essential to improve their conservation. We investigated cause-specific mortality in Canarian houbara bustards (Chlamydotis undulata fuertaventurae), an endangered subspecies endemic to the Canary Islands. We monitored 51 individuals tagged with solar-powered GSM/GPRS loggers for an average of 3.15 years, and recorded 7 casualties at aerial lines (13.73% of the sample; 5 at power lines, 2 at telephone lines), 1 (1.96%) at a wire fence, 4 road kills (7.84%) and 1 case of predation by cat (1.96%). Cox proportional hazards models showed that anthropogenic and natural annual mortality rates were similar (respectively, 6.20% and 6.36% of the individuals). We estimate that 33–35 houbaras die each year in the Canary Islands due to anthropogenic causes. Population viability models using these data and juvenile productivity values obtained over seven years predicted the extinction of the species in 50 years. Eliminating anthropogenic mortality, the population could be recovered, but would still require management actions to improve habitat quality. Conservation measures to reduce anthropogenic mortality due to power line fatalities, roadkills and predation by cats, as well as to increase productivity, are urgently needed, particularly on Fuerteventura, where houbaras are on the brink of extinction.
Strain tuning MoO3 vibrational and electronic properties
Authors: Puebla Sergio , Li Hao , Çakıroğlu Onur , Sánchez-Viso Estrella , Munuera C. , D’Agosta Roberto , Castellanos-Gomez Andres
Published: January 2024

This work investigates the vibrational and electrical properties of molybdenum trioxide (α-MoO3) upon tensile strain applied along different crystal directions. Using a three-point bending setup in combination with Raman spectroscopy, we report measurements of a blueshift of the Raman modes when uniaxial tensile strain is applied along the a- and c-axis to this material. Furthermore, the electrical measurements reveal an increase in resistance with strain applied along both in-plane directions. The findings from the uniaxial strain and Raman spectroscopy measurements are further confirmed by ab-initio calculations. This study provides valuable insights into the mechanical and vibrational properties of α-MoO3 and its potential use in several applications. This study contributes to the growing body of knowledge on the properties of α-MoO3 and lays the foundation for further exploration of its potential applications. Given MoO3 holding the natural hyperbolic phonon polaritons, attracting significant research interest, this study has the potential to arouse the curiosity of the scientific community.