bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Thermomechanical Properties in a 2D Rotational Elastocaloric Prototype: A Numerical Study for Enhanced Energy Efficiency
Authors: Cirillo Luca , Greco Adriana , Masselli Claudia
Published: March 2024

So far, much of the research on the caloric effect has focused on the magnetocaloric effect, which was the first investigated chronologically, in the field of room temperature for about 40 years. Subsequently and especially in the last decade, scientific research has focused on the development of solid-state technologies other than the magnetocaloric one, including the one of interest for this work: elastocaloric technology. This work is part of the “SUSSTAINEBLE” project of the Department of Industrial Engineering at the University Federico II of Naples, aimed at developing the first Italian prototype of an elastocaloric device for environmental conditioning. The prototype is currently in the experimental development phase and its design and construction are dynamically accompanied by a two-dimensional numerical model that fully reproduces its thermo-fluid dynamic operation. The rotary-type prototype consists of 600 Nickel Titanium wires subjected to loading and unloading phases controlled by a properly programmed optical encoder. The thermo-fluidic medium that regulates heat transfer is air. The aim is to characterize the operation of the elastocaloric device using numerical analysis software in order to optimize its geometric, operational, and environmental parameters, to maximize its energy performance in terms of temperature difference, useful thermal power, and coefficient of performance.
Salience or event-splitting? An experimental investigation of correlation sensitivity in risk-taking
Authors: Loewenfeld Moritz , Zheng Jiakun
Published: March 2024

Salience theory relies on the assumption that not only the marginal distribution of lotteries, but also the correlation of payoffs across states impacts choices. Recent experimental studies on salience theory seem to provide evidence in favor of such correlation effects. However, these studies fail to control for event-splitting effects (ESE). In this paper, we seek to disentangle the role of correlation and event-splitting in two settings: (1) the common consequence Allais paradox as studied by Bordalo et al. (Q J Econ 127:1243–1285, 2012), Frydman and Mormann (The role of salience in choice under risk: An experimental investigation. Working Paper, 2018), and Bruhin et al. (J Risk Uncertain 65:139–184, 2022); (2) choices between Mao pairs as studied by Dertwinkel-Kalt and Köster (J Eur Econ Assoc 18:2057–2107, 2020). In both settings, we find evidence suggesting that recent findings supporting correlation effects are largely driven by ESE. Once controlling for ESE, we find no consistent evidence for correlation effects. Our results thus shed doubt on the validity of salience theory in describing risky behavior.
The modularity of Siegel’s zeta functions
Authors: Sugiyama Kazunari
Published: March 2024

Siegel defined zeta functions associated with indefinite quadratic forms, and proved their analytic properties such as analytic continuations and functional equations. Coefficients of these zeta functions are called measures of representations, and play an important role in the arithmetic theory of quadratic forms. In a 1938 paper, Siegel made a comment to the effect that the modularity of his zeta functions would be proved with the help of a suitable converse theorem. In the present paper, we accomplish Siegel’s original plan by using a Weil-type converse theorem for Maass forms, which has appeared recently. It is also shown that “half” of Siegel’s zeta functions correspond to holomorphic modular forms.
“No, This Is Not My Boyfriend’s Computer”: Elevating the Voices of Youth in STEM Education Research Leveraging Photo-Elicitation
Authors: Edelen Daniel , Cook Kristin , Tripp L. Octavia , Jackson Christa , Bush Sarah B. , Mohr-Schroeder Margaret J. , Schroeder D. Craig , Roberts Thomas , Maiorca Cathrine , Ivy Jessica , Burton Megan , Perrin Andrea
Published: March 2024

We aim to elevate the stories and voices of youth in integrated STEM education, particularly those who have been historically marginalized and excluded from STEM spaces. Our research uses photo-elicitation to decenter the power of researchers and educators and elevate the experiences and expertise of youth in STEM. Findings are presented from three instrumental case studies, examining the perspectives of youth on what it means to do STEM, who belongs in STEM, and why STEM is important. The findings reveal that youth often perceive STEM as a siloed approach but also emphasize the need for greater integration of mathematics in STEM. Furthermore, the study highlights the importance of STEM identity development, showing that belonging in STEM is not just about future careers but also about fostering a sense of belonging in the present. Additionally, the study uncovers that youth invoke empathy and social consciousness when explaining the importance of integrated STEM, emphasizing the need to address racial, gender, and professional biases in STEM educational spaces. This prompts a reconsideration of the motivations behind integrated STEM education, emphasizing the value of developing STEM literacy for the well-being of all youth, not just as future workforce preparation.
Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats
Authors: Krzyżewska Anna , Baranowska-Kuczko Marta , Galicka Anna , Kasacka Irena , Mińczuk Krzysztof , Kozłowska Hanna
Published: March 2024

Background

Pulmonary hypertension (PH) can cause right ventricular (RV) failure and subsequent cardiohepatic syndrome referred to as congestive hepatopathy (CH). Passive blood stasis in the liver can affect inflammation, fibrosis, and ultimately cirrhosis. Cannabidiol (CBD) has many beneficial properties including anti-inflammatory and reduces RV systolic pressure and RV hypertrophy in monocrotaline (MCT)-induced PH in rats. Thus, it suggests that CBD may have the potential to limit CH development secondary to RV failure. The present study aimed to determine whether chronic administration of CBD can inhibit the CH secondary to RV hypertrophy associated with MCT-induced PH.

Methods

The experiments involved rats with and without MCT-induced PH. CBD (10 mg/kg) or its vehicle was administered once daily for 3 weeks after MCT injection (60 mg/kg).

Results

Monocrotaline administration increased the liver/body weight ratio. In histology examinations, we observed necrosis and vacuolar degeneration of hepatocytes as well as sinusoidal congestion. In biochemical studies, we observed increased levels of nuclear factor-κappa B (NF-κB), tumour necrosis factor-alpha (TNA-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CBD administration to PH rats reduced the liver/body weight ratio, improved the architecture of the liver, and inhibited the formation of necrosis. Cannabidiol also decreased the level of NF-κB, TNF-α, IL-1β and IL-6.

Conclusions

The studies show that CBD can protect the liver from CH probably through attenuating PH, protective effects on the RV, and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway.

Graphical abstract
Differences by Race and Ethnicity in Title IX’s Effect on Women’s Health
Authors: Beck Delaney , Hersch Joni , Viscusi W. Kip
Published: March 2024

Title IX greatly expanded adolescent females’ participation in athletic activities, which may have led to health benefits that extend into later life. Previous research has not explored whether health benefits arising from Title IX differ by race or ethnicity and has not examined women at older ages when health problems become more evident. This article examines the effect of Title IX on racial and ethnicity disparities in health outcomes by considering women aged 42–52 years. White women in these age groups exhibit declines in their self-assessed health status and increases in many health-related ailments, consistent with other evidence on temporal trends in health for women in this age range. Compared to white women, both Black and Hispanic women report the opposite pattern, as there is greater improvement in the post-Title IX period in overall health status. Black and Hispanic women also exhibit greater declines relative to white women in smoking rates post-Title IX, which should confer a broad range of risk reductions. The more favorable impact of Title IX on Black and Hispanic women indicates that investments in women’s sports may enhance both equity and efficiency.
Wages for Earthwork
Authors: TEMIN DAVID MYER
Published: March 2024

This essay proposes a novel paradigm for a political theory of climate justice: wages for earthwork. Indigenous peoples have disproportionately contributed to the sustainable stewardship of the natural world through ecological systems of governance, which I theorize as “earthwork.” Proponents of climate reparations have focused on reparations for unequal climate damages from emissions. By contrast, I propose “wages” or reparations to Indigenous peoples for debt owed to them for their devalued climate work. This framework makes use of an analogy to the 1970s feminist wages for housework movement, which sought to reveal the exploited and yet indispensable character of systematically devalued work rendered natural and invisible. I contend that (re)valuing earthwork must also be central to projects aimed at decolonizing climate justice, that is, anticolonial climate justice. More than monetary transfers alone, wages for earthwork prioritize the restoration of Indigenous sovereignty and land and wider structural transformation of colonial capitalism.
Campaign Finance Vouchers Do Not Expand the Diversity of Donors: Evidence from Seattle
Authors: YORGASON CHENOA
Published: March 2024

Donating to a campaign is inherently costly, and as a result the composition of campaign donors differs from the composition of the electorate. What happens when the financial barriers to campaign finance participation are removed? This paper analyzes Seattle’s recent campaign finance reform, where all registered voters receive four $25 vouchers to donate to candidates abiding by stricter campaign finance restrictions. Utilizing individual- and census block group-level data combined with administrative donation records, I find that those most mobilized by the availability of vouchers belong to groups already overrepresented within the donor pool. This finding is significant across race, income, past political participation, age, and partisanship. In some cases, the availability of vouchers appears to pull the donor pool further from parity with the larger electorate.
An urban image in an urbanized landscape: measuring the visual impact of Tibur's amphitheater
Authors: Notarian Matthew
Published: March 2024

Though infrequently used and largely superfluous, amphitheaters were often the most physically imposing and ideologically charged structures in a Roman city. The preponderance of extramural amphitheaters in Italy and their appearance in visual culture confirm they were potent markers of urban life and civic status. This paper contextualizes Tibur's imperial amphitheater within the Roman suburbium's persistent urban sprawl and villas, especially Hadrian's Villa, using a novel GIS visibility analysis. Its apparent size from various points in the surrounding landscape is quantified within empirical and qualitative scales developed for modern visual impact assessments. The results demonstrate the amphitheater's suburban location did more than integrate Tibur's extramural growth into the older urban center. It emphasized the city's urban appearance, even from long distances, and monumentalized alternate routes to the city used by the villa-owning elite, countering the ambiguous status of a liminal city that was both Rome's annex and an autonomous municipium.
Looking on the Bright Side of Life
Authors: Lippert Michael W. , Schoppmann Johanna , Kranhold Anna-Luisa , Marks Jessica , Liedtke Lena Marie , Margraf Jürgen , Schneider Silvia
Published: March 2024

Abstract: Theoretical Background: Positive mental health is not simply the absence of a mental disorder. We need a better understanding of the development of mental health, particularly if we are to better understand prevention, remission, and relapse in the context of mental disorders. To date, no measurement tool exists that captures positive mental health for childhood and adolescence, building on a robust theory of positive mental health. Objective: This study develops a questionnaire to assess positive mental health in children and adolescents between 6 and 18 years of age, both in self-report and in external report, and analyzes its quality in a first small sample. Method: Based on established adult scales, we developed a new questionnaire. 83 children and adolescents aged 6 – 18 years ( M = 11.89, SD = 3.0; 66 % female) and 77 parents completed the new questionnaire and other questionnaires assessing positive mental health and psychopathology. Results: The questionnaire showed a unidimensional factor structure as well as very good internal consistency and test-retest reliability. High positive correlations with self-efficacy and life satisfaction as well as high negative correlations with anxiety and depression confirmed the very good construct validity, both in child and parent ratings. Discussion and Conclusion: The PMH-Kids provides evidence of excellent psychometric quality in this first evaluation attempt. The questionnaire is comparable to its adult pendant, enabling researchers to assess positive mental health across the lifespan.
Turbulence as a Key Driver of Ice Aggregation and Riming in Arctic Low‐Level Mixed‐Phase Clouds, Revealed by Long‐Term Cloud Radar Observations
Authors: Chellini Giovanni , Kneifel Stefan
Published: March 2024

Turbulence in clouds is known to enhance particle collision rates, as widely demonstrated for warm rain formation. A similar impact on ice growth processes is expected but a solid observational basis is missing. A statistical analysis of a 15‐month data set of cloud radar observations allows for the first time to quantify the impact of turbulence on ice aggregation and riming in Arctic low‐level mixed‐phase clouds. Increasing eddy dissipation rate (EDR), from below 10−4 to above 10−3 m2 s−3, yields larger ice aggregates, and higher particle concentration, likely caused by increasing fragmentation. In conditions more favorable to riming, higher EDR is associated with dramatically higher particle fall velocities (by up to 125%), under similar liquid water paths, indicative of markedly higher degrees of riming. Our findings thus reveal the key role of turbulence for cold precipitation formation, and highlight the need for an improved understanding of turbulence‐hydrometeor interactions in cold clouds.
An Unstructured Mesh Generation Tool for Efficient High‐Resolution Representation of Spatial Heterogeneity in Land Surface Models
Authors: Fan Hanwen , Xu Qingchen , Bai Fan , Wei Zhongwang , Zhang Yonggen , Lu Xingjie , Wei Nan , Zhang Shupeng , Yuan Hua , Liu Shaofeng , Li XianXiang , Li Xueyan , Dai Yongjiu
Published: March 2024

This study develops an unstructured mesh generation tool for land surface modeling using a multi‐scale hexagon discrete mesh. The tool can automatically determine the required mesh resolution for different regions based on multi‐objective criteria such as elevation, slope, land cover, and land use. The refined unstructured meshes demonstrate significant enhancement in the representation of spatial heterogeneity. The tool is coupled with the Common Land Model (CoLM) to enable land surface simulations using unstructured meshes. Evaluations focused on runoff, river discharge, and inundation indicate improved model performance compared to traditional structured mesh‐based CoLM simulations under the same computational cost constraints. This tool provides new capabilities for more efficiently capturing localized land surface processes and extreme events.
Convection‐Permitting ICON‐LAM Simulations for Renewable Energy Potential Estimates Over Southern Africa
Authors: Chen Shuying , Poll Stefan , Hendricks Franssen Harrie‐Jan , Heinrichs Heidi , Vereecken Harry , Goergen Klaus
Published: March 2024

Renewable energy is recognized in Africa as a means for climate change mitigation, but also to provide access to electricity in sub‐Saharan Africa, where three‐quarters of the global population without electricity resides. Reliable and highly resolved renewable energy potential (REP) information is indispensable to support power plants expansion. Existing atmospheric data sets over Africa that are used for REP estimates are often characterized by data gaps, or coarse resolution. With the aim to overcome these challenges, the ICOsahedral Nonhydrostatic (ICON) Numerical Weather Prediction (ICON‐NWP) model in its Limited Area Mode (ICON‐LAM) is implemented and run over southern Africa in a hindcast dynamical downscaling setup at a convection‐permitting 3.3 km horizontal resolution. The simulation time span covers contrasting solar and wind weather years from 2017 to 2019. To assess the suitability of the novel simulations for REP estimates, the simulated hourly 10 m wind speed (sfcWind) and hourly surface solar irradiance (rsds) are extensively evaluated against a large compilation of in situ observations, satellite, and composite data products. ICON‐LAM reproduces the spatial patterns, temporal evolution, the variability, and absolute values of sfcWind sufficiently well, albeit with a slight overestimation and a mean bias (mean error (ME)) of 1.12 m s−1 over land. Likewise the simulated rsds with an ME of 50 W m−2 well resembles the observations. This new ICON simulation data product will be the basis for ensuing REP estimates that will be compared with existing lower resolution data sets.
TGF-β signaling in health, disease and therapeutics
Authors: Deng Ziqin , Fan Tao , Xiao Chu , Tian He , Zheng Yujia , Li Chunxiang , He Jie
Published: March 2024

Transforming growth factor (TGF)-β is a multifunctional cytokine expressed by almost every tissue and cell type. The signal transduction of TGF-β can stimulate diverse cellular responses and is particularly critical to embryonic development, wound healing, tissue homeostasis, and immune homeostasis in health. The dysfunction of TGF-β can play key roles in many diseases, and numerous targeted therapies have been developed to rectify its pathogenic activity. In the past decades, a large number of studies on TGF-β signaling have been carried out, covering a broad spectrum of topics in health, disease, and therapeutics. Thus, a comprehensive overview of TGF-β signaling is required for a general picture of the studies in this field. In this review, we retrace the research history of TGF-β and introduce the molecular mechanisms regarding its biosynthesis, activation, and signal transduction. We also provide deep insights into the functions of TGF-β signaling in physiological conditions as well as in pathological processes. TGF-β-targeting therapies which have brought fresh hope to the treatment of relevant diseases are highlighted. Through the summary of previous knowledge and recent updates, this review aims to provide a systematic understanding of TGF-β signaling and to attract more attention and interest to this research area.
Interactions between neurotrophins, mood, and physical activity under the conditions of sleep deprivation
Authors: Sochal Marcin , Ditmer Marta , Binienda Agata , Tarasiuk Aleksandra , Białasiewicz Piotr , Turkiewicz Szymon , Karuga Filip Franciszek , Jakub Fichna , Gabryelska Agata
Published: March 2024

Sleep deprivation (DS) is the forced elimination of sleep. While brain-derived neurotrophic factor (BDNF) has been extensively studied in the context of in mood changes following DS, the role of other neurotrophins remains elusive. This study explores the impact of DS on BDNF, glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT3), and neurotrophin-4 (NT4) at mRNA and protein level, considering their potential links to mood disturbances. The study involved 81 participants subjected to polysomnography (PSG) and DS. Blood samples, mood assessments, and actigraphy data were collected twice, after PSG and DS. NT mRNA expression and serum protein concentrations of BDNF, GDNF, NT3, and NT4 were measured. Participants were divided into Responders and Non-Responders based on mood improvement after DS. DS reduced BDNF mRNA expression in all participants, with no change in serum BDNF protein. GDNF protein decreased in Non-Responders, while Responders exhibited reduced GDNF mRNA. NT3 protein increased in both groups, while NT3 mRNA decreased in Respondents. NT4 protein rose universally post-DS, but NT4 mRNA remained unchanged. Physical activity (PA) negatively correlated with mRNA expression of BDNF, GDNF, and NT3 post-DS. The study’s short DS duration and exclusion of immature NT forms limit comprehensive insights. GDNF, together with NT3, might play an important role in mood response to DS. PA during DS seems to impair the mRNA expression of NTs in leukocytes. Future studies on the subject of sleep deprivation might consider investigating the relationship between BDNF and NT4 in the context of their apparent redundancy.
Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation
Authors: Huang Nick , Winans Thomas , Wyman Brandon , Oaks Zachary , Faludi Tamas , Choudhary Gourav , Lai Zhi-Wei , Lewis Joshua , Beckford Miguel , Duarte Manuel , Krakko Daniel , Patel Akshay , Park Joy , Caza Tiffany , Sadeghzadeh Mahsa , Morel Laurence , Haas Mark , Middleton Frank , Banki Katalin , Perl Andras
Published: March 2024

Activation of the mechanistic target of rapamycin (mTOR) is a key metabolic checkpoint of pro-inflammatory T-cell development that contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), however, the underlying mechanisms remain poorly understood. Here, we identify a functional role for Rab4A-directed endosome traffic in CD98 receptor recycling, mTOR activation, and accumulation of mitochondria that connect metabolic pathways with immune cell lineage development and lupus pathogenesis. Based on integrated analyses of gene expression, receptor traffic, and stable isotope tracing of metabolic pathways, constitutively active Rab4AQ72L exerts cell type-specific control over metabolic networks, dominantly impacting CD98-dependent kynurenine production, mTOR activation, mitochondrial electron transport and flux through the tricarboxylic acid cycle and thus expands CD4+ and CD3+CD4−CD8− double-negative T cells over CD8+ T cells, enhancing B cell activation, plasma cell development, antinuclear and antiphospholipid autoantibody production, and glomerulonephritis in lupus-prone mice. Rab4A deletion in T cells and pharmacological mTOR blockade restrain CD98 expression, mitochondrial metabolism and lineage skewing and attenuate glomerulonephritis. This study identifies Rab4A-directed endosome traffic as a multilevel regulator of T cell lineage specification during lupus pathogenesis.
BET inhibitors drive Natural Killer activation in non-small cell lung cancer via BRD4 and SMAD3
Authors: Reggiani Francesca , Talarico Giovanna , Gobbi Giulia , Sauta Elisabetta , Torricelli Federica , Manicardi Veronica , Zanetti Eleonora , Orecchioni Stefania , Falvo Paolo , Piana Simonetta , Lococo Filippo , Paci Massimiliano , Bertolini Francesco , Ciarrocchi Alessia , Sancisi Valentina
Published: March 2024

Non-small-cell lung carcinoma (NSCLC) is the most common lung cancer and one of the pioneer tumors in which immunotherapy has radically changed patients’ outcomes. However, several issues are emerging and their implementation is required to optimize immunotherapy-based protocols. In this work, we investigate the ability of the Bromodomain and Extra-Terminal protein inhibitors (BETi) to stimulate a proficient anti-tumor immune response toward NSCLC. By using in vitro, ex-vivo, and in vivo models, we demonstrate that these epigenetic drugs specifically enhance Natural Killer (NK) cell cytotoxicity. BETi down-regulate a large set of NK inhibitory receptors, including several immune checkpoints (ICs), that are direct targets of the transcriptional cooperation between the BET protein BRD4 and the transcription factor SMAD3. Overall, BETi orchestrate an epigenetic reprogramming that leads to increased recognition of tumor cells and the killing ability of NK cells. Our results unveil the opportunity to exploit and repurpose these drugs in combination with immunotherapy.
Deciphering the critical role of interstitial volume in glassy sulfide superionic conductors
Authors: Su Han , Zhong Yu , Wang Changhong , Liu Yu , Hu Yang , Li Jingru , Wang Minkang , Jiao Longan , Zhou Ningning , Xiao Bing , Wang Xiuli , Sun Xueliang , Tu Jiangping
Published: March 2024

Sulfide electrolytes represent a crucial category of superionic conductors for all-solid-state lithium metal batteries. Among sulfide electrolytes, glassy sulfide is highly promising due to its long-range disorder and grain-boundary-free nature. However, the lack of comprehension regarding glass formation chemistry has hindered their progress. Herein, we propose interstitial volume as the decisive factor influencing halogen dopant solubility within a glass matrix. We engineer a Li3PS4-Li4SiS4 complex structure within the sulfide glassy network to facilitate the release of interstitial volume. Consequently, we increase the dissolution capacity of LiI to 40 mol% in 75Li2S-25P2S5 glass. The synthesized glass exhibits one of the highest ionic conductivities among reported glass sulfides. Furthermore, we develop a glassy/crystalline composite electrolyte to mitigate the shortcomings of argyrodite-type sulfides by utilizing our synthesized glass as the filler. The composite electrolytes effectively mitigate Li intrusion. This work unveils a protocol for the dissolution of halogen dopants in glass electrolytes.
Ultra-photostable small-molecule dyes facilitate near-infrared biophotonics
Authors: Yan Kui , Hu Zhubin , Yu Peng , He Zuyang , Chen Ying , Chen Jiajian , Sun Haitao , Wang Shangfeng , Zhang Fan
Published: March 2024

Long-wavelength, near-infrared small-molecule dyes are attractive in biophotonics. Conventionally, they rely on expanded aromatic structures for redshift, which comes at the cost of application performance such as photostability, cell permeability, and functionality. Here, we report a ground-state antiaromatic strategy and showcase the concise synthesis of 14 cationic aminofluorene dyes with mini structures (molecular weights: 299–504 Da) and distinct spectra covering 700–1600 nm. Aminofluorene dyes are cell-permeable and achieve rapid renal clearance via a simple 44 Da carboxylation. This accelerates optical diagnostics of renal injury by 50 min compared to existing macromolecular approaches. We develop a compact molecular sensing platform for in vivo intracellular sensing, and demonstrate the versatile applications of these dyes in multispectral fluorescence and optoacoustic imaging. We find that aromaticity reversal upon electronic excitation, as indicated by magnetic descriptors, not only reduces the energy bandgap but also induces strong vibronic coupling, resulting in ultrafast excited-state dynamics and unparalleled photostability. These results support the argument for ground-state antiaromaticity as a useful design rule of dye development, enabling performances essential for modern biophotonics.
Nucleic-acid-base photofunctional cocrystal for information security and antimicrobial applications
Authors: Xu Wenqing , Huang Guanheng , Yang Zhan , Deng Ziqi , Zhou Chen , Li Jian-An , Li Ming-De , Hu Tao , Tang Ben Zhong , Phillips David Lee
Published: March 2024

Cocrystal engineering is an efficient and simple strategy to construct functional materials, especially for the exploitation of novel and multifunctional materials. Herein, we report two kinds of nucleic-acid-base cocrystal systems that imitate the strong hydrogen bond interactions constructed in the form of complementary base pairing. The two cocrystals studied exhibit different colors of phosphorescence from their monomeric counterparts and show the feature of rare high-temperature phosphorescence. Mechanistic studies reveal that the strong hydrogen bond network stabilizes the triplet state and suppresses non-radiative transitions, resulting in phosphorescence even at 425 K. Moreover, the isolation effects of the hydrogen bond network regulate the interactions between the phosphor groups, realizing the manipulation from aggregation to single-molecule phosphorescence. Benefiting from the long-lived triplet state with a high quantum yield, the generation of reactive oxygen species by energy transfer is also available to utilize for some applications such as in photodynamic therapy and broad-spectrum microbicidal effects. In vitro experiments show that the cocrystals efficiently kill bacteria on a tooth surface and significantly help prevent dental caries. This work not only provides deep insight into the relationship of the structure-properties of cocrystal systems, but also facilitates the design of multifunctional cocrystal materials and enriches their potential applications.
Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial
Authors: Ninmer Emily K. , Zhu Hong , Chianese-Bullock Kimberly A. , von Mehren Margaret , Haas Naomi B. , Ross Merrick I. , Dengel Lynn T. , Slingluff Craig L.
Published: March 2024

The critical roles of CD4+ T cells have been understudied for cancer vaccines. Here we report long-term clinical outcomes of a randomized multicenter phase II clinical trial (NCT00118274), where patients with high-risk melanoma received a multipeptide vaccine targeting CD8+ T cells (12MP) and were randomized to receive either of two vaccines for CD4+ (helper) T cells: 6MHP (6 melanoma-specific helper peptides), or tet (a nonspecific helper peptide from tetanus toxoid). Cyclophosphamide (Cy) pre-treatment was also assessed. Primary outcomes for T cell responses to 12MP, 6MHP, and tet were previously reported, suggesting immunogenicity of both vaccines but that CD8 T cell responses to 12MP were lower when tet was replaced with 6MHP. Here, in post-hoc analyses, we report durable prolongation of overall survival by adding 6MHP instead of tet. That benefit was experienced only by male patients. A favorable interaction of 6MHP and Cy is also suggested. Multivariable Cox regression analysis of the intent-to-treat population identify vaccine arm (12MP + 6MHP+Cy) and patient sex (male) as the two significant predictors of enhanced survival. These findings support the value of adding cognate T cell help to cancer vaccines and also suggest a need to assess the impact of patient sex on immune therapy outcomes.
Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer
Authors: Liu Z. L. , Meng X. Y. , Bao R. J. , Shen M. Y. , Sun J. J. , Chen W. D. , Liu F. , He Y.
Published: March 2024

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1. Furthermore, we find that the infiltration of POSTN+ fibroblasts and SPP1+ macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8+ T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma.
Niche availability and competitive loss by facilitation control proliferation of bacterial strains intended for soil microbiome interventions
Authors: Čaušević Senka , Dubey Manupriyam , Morales Marian , Salazar Guillem , Sentchilo Vladimir , Carraro Nicolas , Ruscheweyh Hans-Joachim , Sunagawa Shinichi , van der Meer Jan Roelof
Published: March 2024

Microbiome engineering – the targeted manipulation of microbial communities – is considered a promising strategy to restore ecosystems, but experimental support and mechanistic understanding are required. Here, we show that bacterial inoculants for soil microbiome engineering may fail to establish because they inadvertently facilitate growth of native resident microbiomes. By generating soil microcosms in presence or absence of standardized soil resident communities, we show how different nutrient availabilities limit outgrowth of focal bacterial inoculants (three Pseudomonads), and how this might be improved by adding an artificial, inoculant-selective nutrient niche. Through random paired interaction assays in agarose micro-beads, we demonstrate that, in addition to direct competition, inoculants lose competitiveness by facilitating growth of resident soil bacteria. Metatranscriptomics experiments with toluene as selective nutrient niche for the inoculant Pseudomonas veronii indicate that this facilitation is due to loss and uptake of excreted metabolites by resident taxa. Generation of selective nutrient niches for inoculants may help to favor their proliferation for the duration of their intended action while limiting their competitive loss.
Serotonergic modulation of vigilance states in zebrafish and mice
Authors: Zhao Yang , Huang Chun-Xiao , Gu Yiming , Zhao Yacong , Ren Wenjie , Wang Yutong , Chen Jinjin , Guan Na N. , Song Jianren
Published: March 2024

Vigilance refers to being alertly watchful or paying sustained attention to avoid potential threats. Animals in vigilance states reduce locomotion and have an enhanced sensitivity to aversive stimuli so as to react quickly to dangers. Here we report that an unconventional 5-HT driven mechanism operating at neural circuit level which shapes the internal state underlying vigilance behavior in zebrafish and male mice. The neural signature of internal vigilance state was characterized by persistent low-frequency high-amplitude neuronal synchrony in zebrafish dorsal pallium and mice prefrontal cortex. The neuronal synchronization underlying vigilance was dependent on intense release of 5-HT induced by persistent activation of either DRN 5-HT neuron or local 5-HT axon terminals in related brain regions via activation of 5-HTR7. Thus, we identify a mechanism of vigilance behavior across species that illustrates the interplay between neuromodulators and neural circuits necessary to shape behavior states.
Enhanced CO2 uptake of the coastal ocean is dominated by biological carbon fixation
Authors: Mathis Moritz , Lacroix Fabrice , Hagemann Stefan , Nielsen David Marcolino , Ilyina Tatiana , Schrum Corinna
Published: March 2024

Observational reconstructions indicate a contemporary increase in coastal ocean CO2 uptake. However, the mechanisms and their relative importance in driving this globally intensifying absorption remain unclear. Here we integrate coastal carbon dynamics in a global model via regional grid refinement and enhanced process representation. We find that the increasing coastal CO2 sink is primarily driven by biological responses to climate-induced changes in circulation (36%) and increasing riverine nutrient loads (23%), together exceeding the ocean CO2 solubility pump (41%). The riverine impact is mediated by enhanced export of organic carbon across the shelf break, thereby adding to the carbon enrichment of the open ocean. The contribution of biological carbon fixation increases as the seawater capacity to hold CO2 decreases under continuous climate change and ocean acidification. Our seamless coastal ocean integration advances carbon cycle model realism, which is relevant for addressing impacts of climate change mitigation efforts.
Predicting quantum emitter fluctuations with time-series forecasting models
Authors: Ramezani Fereshteh , Strasbourg Matthew , Parvez Sheikh , Saxena Ravindra , Jariwala Deep , Borys Nicholas J. , Whitaker Bradley M.
Published: March 2024

2D materials have important fundamental properties allowing for their use in many potential applications, including quantum computing. Various Van der Waals materials, including Tungsten disulfide (WS2), have been employed to showcase attractive device applications such as light emitting diodes, lasers and optical modulators. To maximize the utility and value of integrated quantum photonics, the wavelength, polarization and intensity of the photons from a quantum emission (QE) must be stable. However, random variation of emission energy, caused by the inhomogeneity in the local environment, is a major challenge for all solid-state single photon emitters. In this work, we assess the random nature of the quantum fluctuations, and we present time series forecasting deep learning models to analyse and predict QE fluctuations for the first time. Our trained models can roughly follow the actual trend of the data and, under certain data processing conditions, can predict peaks and dips of the fluctuations. The ability to anticipate these fluctuations will allow physicists to harness quantum fluctuation characteristics to develop novel scientific advances in quantum computing that will greatly benefit quantum technologies.
Activated fibroblasts modify keratinocyte stem niche through TET1 and IL-6 to promote their rapid transformation in a mouse model of prenatal arsenic exposure
Authors: Chauhan Anchal , Gangopadhyay Siddhartha , Koshta Kavita , Singh Sukhveer , Singh Dhirendra , Srivastava Vikas
Published: March 2024

Early life exposure to environmental pollutants such as arsenic (As) can increase the risk of cancers in the offspring. In an earlier study, we showed that only prenatal As exposure significantly increases epidermal stem cell proliferation and accelerates skin tumorigenesis in BALB/c mouse offspring. In the present work, we have examined the role of As-conditioned dermal fibroblasts (DFs) in creating pro-tumorigenic niches for Keratinocyte stem cells (KSCs) in the offspring. DFs isolated from prenatally exposed animals showed increased levels of activation markers (α-SMA, Fibronectin, Collagen IV), induction of ten-eleven translocation methylcytosine dioxygenase 1(TET1), and secreted high levels of niche modifying IL-6. This led to enhanced proliferation, migration, and survival of KSCs. Increased IL-6 production in As-conditioned fibroblast was driven through TET1 mediated 5-mC to 5-hmC conversion at -698/-526 and -856/-679 region on its promoter. IL-6 further acted through downstream activation of JAK2-STAT3 signaling, promoting epithelial-to-mesenchymal transition (EMT) in KSCs. Inhibition of pSTAT3 induced by IL-6 reduced the EMT process in KSCs resulting in a significant decrease in their proliferation, migration, and colony formation. Our results indicate that IL-6 produced by prenatally conditioned fibroblasts plays a major role in regulating the KSC niche and promoting skin tumor development in As-exposed offspring.
Synthesis of eco-friendly layered double hydroxide and nanoemulsion for jasmine and peppermint oils and their larvicidal activities against Culex pipiens Linnaeus
Authors: Radwan Ibrahim Taha , Khater Hanem F. , Mohammed Shaimaa H. , Khalil Abdelwahab , Farghali Mohamed A. , Mahmoud Mohammed G. , Selim Abdelfattah , Manaa Eman A. , Bagato Noha , Baz Mohamed M.
Published: March 2024

Mosquito-borne diseases represent a growing health challenge over time. Numerous potential phytochemicals are target-specific, biodegradable, and eco-friendly. The larvicidal activity of essential oils, a jasmine blend consisting of Jasmine oil and Azores jasmine (AJ) (Jasminum sambacandJasminum azoricum) and peppermint (PP)Mentha arvensisand their nanoformulations against 2nd and 4th instar larvae ofCulex pipiens, was evaluated after subjecting to different concentrations (62.5, 125, 250, 500, 1000, and 2000 ppm). Two forms of phase-different nanodelivery systems of layered double hydroxide LDH and oil/water nanoemulsions were formulated. The synthesized nanoemulsions showed particle sizes of 199 and 333 nm for AJ-NE and PP-NE, with a polydispersity index of 0.249 and 0.198, respectively. Chemical and physiochemical analysis of TEM, SEM, XRD, zeta potential, drug loading capacity, and drug release measurements were done to confirm the synthesis and loading efficiencies of essential oils' active ingredients. At high concentrations of AJ and PP nanoemulsions (2000 ppm), O/W nanoemulsions showed higher larval mortality than both LDH conjugates and crude oils. The mortality rate reached 100% for 2nd and 4th instar larvae. The relative toxicities revealed that PP nanoemulsion (MA-NE) was the most effective larvicide, followed by AJ nanoemulsion (AJ-NE). There was a significant increase in defensive enzymes, phenoloxidase, and α and β-esterase enzymes in the treated groups. After treatment of L4 with AJ, AJ-NE, PP, and PP-NE, the levels of phenoloxidase were 545.67, 731.00, 700.00, and 799.67 u/mg, respectively, compared with control 669.67 u/mg. The activity levels of α-esterase were 9.71, 10.32, 8.91, and 10.55 mg α-naphthol/min/mg protein, respectively. It could be concluded that the AJ-NE and PP-NE nanoformulations have promising larvicidal activity and could act as safe and effective alternatives to chemical insecticides.
Absolute and relative disparity mechanisms revealed by an equivalent noise analysis
Authors: Ding Jian , Lu Hilary H. , Levi Dennis M.
Published: March 2024

The precision of stereopsis and vergence are ultimately limited by internal binocular disparity noise. Here we propose an equivalent noise model with both global and local internal disparity noises to provide a unified explanation of both absolute and relative disparity thresholds. To test this model, we developed a psychophysical procedure to measure the equivalent internal disparity noise by adding external disparity noise to random-Gabor-patch stereograms. We used the method of constant stimuli to measure the minimum and maximum disparity thresholds (Dmin and Dmax) for both absolute and relative disparity. Consistent with previous studies, we found that Dmin thresholds are substantially worse for absolute disparity than for relative disparity. We tested three relative disparity mechanisms: (1) the difference between the monocular separations of targets projecting to the two eyes; (2) the direct measurement of relative disparity; and (3) the difference of absolute disparities of targets. Computing the difference of absolute disparities when detecting relative disparity, Mechanism 3 cancels global noise, resulting in a much lower relative Dmin threshold, and provides a reasonable fit to the experimental data. We also found that the presence of as much as 2400 arcsec of external disparity noise does not appear to affect the Dmax threshold. This observation suggests that Dmax is implicated in a mechanism that disregards the disparity variance of individual items, relying instead on the average disparity across all items, supporting the depth model proposed in our previous study (Ding & Levi, 2021), which posits distinct mechanisms governing Dmin and Dmax thresholds.
The predictive role of the dietary phytochemical index in relation to the clinical and psychological traits of migraine headaches
Authors: Amani Tirani Shahnaz , Balali Arghavan , Kazemi Maryam , Askari Gholamreza , Khorvash Fariborz , Arab Arman
Published: March 2024

We investigated the relationship between dietary phytochemical index (DPI) and migraine headaches in Iranian patients, analyzing both clinical and psychological traits. A cross-sectional study was conducted using non-obese adults aged 20–50 years who were diagnosed with migraine. The study used a validated 168-item food frequency questionnaire to assess the usual dietary intake of participants. The DPI was calculated using the following formula: [daily energy derived from phytochemical-rich foods (in kJ)/total daily energy intake (in kJ)] × 100. Clinical outcomes of migraine including frequency, duration, and severity of headaches, as well as migraine-related disability were obtained using relevant questionnaires. Moreover, the mental health profile of patients including depression, anxiety, and stress, as well as serum levels of nitric oxide (NO) were measured. A Poisson regression was used for headache frequency. Linear regression analyzed migraine-related outcomes including duration, severity, migraine-related disability, and serum NO levels. In addition, psychological traits were analyzed via logistic regression. A total of 262 individuals (85.5% females) with a mean age of 36.1 years were included in the analysis. The frequency of migraine attacks was lower in patients in the last DPI tertile compared to those in the first DPI tertile both in the crude [incidence rate ratio (IRR) = 0.70, 95% confidence interval (CI) 0.63, 0.78, Ptrend < 0.001] and fully-adjusted models (IRR = 0.84, 95% CI 0.74, 0.96, Ptrend = 0.009). After controlling for potential confounders, an inverse relationship was observed between higher adherence to DPI and migraine-related disability (β = − 2.48, 95% CI − 4.86, − 0.10, P trend = 0.046). After controlling for potential confounders, no significant relationship was observed between DPI and depression (OR = 0.79, 95% CI 0.42, 1.47, Ptrend = 0.480), anxiety (OR = 1.14, 95% CI 0.61, 2.14, Ptrend = 0.655), and stress (OR = 1.04, 95% CI 0.57, 1.90, Ptrend = 0.876). Higher intakes of phytochemical-rich foods may be associated with lower migraine frequency and improved daily activities among patients. Further studies should confirm our observations and delineate the biological pathways linking phytochemicals and migraine headaches.