bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antarctic Warm Extremes Across Seasons and Their Response to Advection
Authors: Xu Min , Pithan Felix , Yang Qinghua 
Published: August 2024

AbstractAntarctic warm extremes impact the cryosphere, with very warm extremes driving surface melt on ice shelves. Here, we analyze temperatures exceeding the 90th percentile and the associated circulation patterns and radiation anomalies. ERA5 reanalysis data show positive geopotential height anomalies related to the occurrence of warm extremes. The highest temperature during warm extremes appears on the western periphery of high‐pressure systems, consistent with anticyclonic advection. Temperature anomalies during warm extremes are strongest in winter due to the transport of warm and moist air and a strong meridional temperature gradient. In summer, the weak meridional gradients of top‐of‐atmosphere downward solar radiation flux and surface air temperature contribute to weak temperature anomalies. Warm extremes are associated with positive longwave radiation anomalies in all seasons, but with negative shortwave radiation anomalies at the surface except during polar night. These relationships are verified by station observations. Our results confirm that Antarctic warm extremes are mostly driven by meridional advection of warm air, and suggest that these warm air masses are predominantly moist and cloudy.
Intermittency of Waves in the Polar Upper Troposphere and Lower Stratosphere Over Northern Norway Using MAARSY
Authors: Ghosh Priyanka , Renkwitz Toralf , Holt Laura , Tsutsumi Masaki , Latteck Ralph , Chau Jorge L. 
Published: August 2024

AbstractWe investigate the absolute momentum flux (AMF) and vertical wind variance of gravity waves (GWs) along with intermittencies in the upper troposphere and lower stratosphere (UTLS) during 2017–2022 using the Middle Atmosphere Alomar Radar System at Andøya, Norway (69.30°N, 16.04°E). We categorized the AMF and into different period ranges (30 min–2 hr, 2–6 hr, 6–13 hr, 13 hr–1 day, and 30 min–1 day) to study the significance of short‐ and long‐period waves. The selection of these period bands was based on the boundary conditions of the available spectra: 30 min (Nyquist frequency), 13 hr (inertial period), and 1 day (based on our interest in maximum long‐period oscillations). Through the investigation of the AMF and , we wish to determine in detail the GW characteristics at northern polar latitudes. Furthermore, it is crucial to assess the intermittency as it considerably influences and alters the GW attributes. Our novel results indicate for both AMF and : (a) seasonal variation with minima during summer (May–September); (b) higher magnitude in the upper troposphere (<9.00 km) than the lower stratosphere; (c) short‐period components (30 min–2 hr, 2–6 hr) are more intermittent in the entire UTLS; and (d) the long‐period components (6–13 hr, 13 hr–1 day) demonstrate lower (higher) intermittency in the upper troposphere (lower stratosphere) in summer implying a plausible wave‐filtering mechanism.
On Energy‐Aware Hybrid Models
Authors: Shevchenko Igor , Crisan Dan 
Published: August 2024

AbstractThis study proposes deterministic and stochastic energy‐aware hybrid models that should enable simulations of idealized and primitive‐equations Geophysical Fluid Dynamics (GFD) models at low resolutions without compromising on quality compared with high‐resolution runs. Such hybrid models bridge the data‐driven and physics‐driven modeling paradigms by combining regional stability and classical GFD models at low resolution that cannot reproduce high‐resolution reference flow features (large‐scale flows and small‐scale vortices) which are, however, resolved. Hybrid models use an energy‐aware correction of advection velocity and extra forcing compensating for the drift of the low‐resolution model away from the reference phase space. The main advantages of hybrid models are that they allow for physics‐driven flow recombination within the reference energy band, reproduce resolved reference flow features, and produce more accurate ensemble forecasts than their classical GFD counterparts. Hybrid models offer appealing benefits and flexibility to the modeling and forecasting communities, as they are computationally cheap and can use both numerically‐computed flows and observations from different sources. All these suggest that the hybrid approach has the potential to exploit low‐resolution models for long‐term weather forecasts and climate projections thus offering a new cost effective way of GFD modeling. The proposed hybrid approach has been tested on a three‐layer quasi‐geostrophic model for a beta‐plane Gulf Stream flow configuration. The results show that the low‐resolution hybrid model reproduces the reference flow features that are resolved on the coarse grid and also gives a more accurate ensemble forecast than the physics‐driven model.
Hepatocyte-specific loss of melanocortin 1 receptor disturbs fatty acid metabolism and promotes adipocyte hypertrophy
Authors: Thapa Keshav , Ghimire Bishwa , Pokharel Kisun , Cai Minying , Savontaus Eriika , Rinne Petteri 
Published: August 2024

Abstract
Background/objectives
Melanocortins mediate their biological functions via five different melanocortin receptors (MC1R - MC5R). MC1R is expressed in the skin and leukocytes, where it regulates skin pigmentation and inflammatory responses. MC1R is also present in the liver and white adipose tissue, but its functional role in these tissues is unclear. This study aimed at determining the regulatory role of MC1R in fatty acid metabolism.

Methods
Male recessive yellow (Mc1re/e) mice, a model of global MC1R deficiency, and male hepatocyte-specific MC1R deficient mice (Mc1r LKO) were fed a chow or Western diet for 12 weeks. The mouse models were characterized for body weight and composition, liver adiposity, adipose tissue mass and morphology, glucose metabolism and lipid metabolism. Furthermore, qPCR and RNA sequencing analyses were used to investigate gene expression profiles in the liver and adipose tissue. HepG2 cells and primary mouse hepatocytes were used to study the effects of pharmacological MC1R activation.

Results
Chow- and Western diet-fed Mc1re/e showed increased liver weight, white adipose tissue mass and plasma triglyceride (TG) concentration compared to wild type mice. This phenotype occurred without significant changes in food intake, body weight, physical activity or glucose metabolism. Mc1r LKO mice displayed a similar phenotype characterized by larger fat depots, increased adipocyte hypertrophy and enhanced accumulation of TG in the liver and plasma. In terms of gene expression, markers of de novo lipogenesis, inflammation and apoptosis were upregulated in the liver of Mc1r LKO mice, while enzymes regulating lipolysis were downregulated in white adipose tissue of these mice. In cultured hepatocytes, selective activation of MC1R reduced ChREBP expression, which is a central transcription factor for lipogenesis.

Conclusions
Hepatocyte-specific loss of MC1R disturbs fatty acid metabolism in the liver and leads to an obesity phenotype characterized by enhanced adipocyte hypertrophy and TG accumulation in the liver and circulation.
CDK9 inhibition constrains multiple oncogenic transcriptional and epigenetic pathways in prostate cancer
Authors: Rahman Razia , Rahaman Muhammed H. , Hanson Adrienne R. , Choo Nicholas , Xie Jianling , Townley Scott L. , Shrestha Raj , Hassankhani Ramin , Islam Saiful , Ramm Susanne , Simpson Kaylene J. , Risbridger Gail P. , Best Giles , Centenera Margaret M. , Balk Steven P. , Kichenadasse Ganessan , Taylor Renea A. , Butler Lisa M. , Tilley Wayne D. , Conn Simon J. , Lawrence Mitchell G. , Wang Shudong , Selth Luke A. 
Published: August 2024

Abstract
Background
Cyclin-dependent kinase 9 (CDK9) stimulates oncogenic transcriptional pathways in cancer and CDK9 inhibitors have emerged as promising therapeutic candidates.

Methods
The activity of an orally bioavailable CDK9 inhibitor, CDKI-73, was evaluated in prostate cancer cell lines, a xenograft mouse model, and patient-derived tumor explants and organoids. Expression of CDK9 was evaluated in clinical specimens by mining public datasets and immunohistochemistry. Effects of CDKI-73 on prostate cancer cells were determined by cell-based assays, molecular profiling and transcriptomic/epigenomic approaches.

Results
CDKI-73 inhibited proliferation and enhanced cell death in diverse in vitro and in vivo models of androgen receptor (AR)-driven and AR-independent models. Mechanistically, CDKI-73-mediated inhibition of RNA polymerase II serine 2 phosphorylation resulted in reduced expression of BCL-2 anti-apoptotic factors and transcriptional defects. Transcriptomic and epigenomic approaches revealed that CDKI-73 suppressed signaling pathways regulated by AR, MYC, and BRD4, key drivers of dysregulated transcription in prostate cancer, and reprogrammed cancer-associated super-enhancers. These latter findings prompted the evaluation of CDKI-73 with the BRD4 inhibitor AZD5153, a combination that was synergistic in patient-derived organoids and in vivo.

Conclusion
Our work demonstrates that CDK9 inhibition disrupts multiple oncogenic pathways and positions CDKI-73 as a promising therapeutic agent for prostate cancer, particularly aggressive, therapy-resistant subtypes.
Age-related retinal degeneration resulting from the deletion of Shp2 tyrosine phosphatase in photoreceptor neurons
Authors: Rajala Ammaji , Rajala Rahul , Bhat Mohd A. , Eminhizer Mark , Hao Jeff , Du Jianhai , Rajala Raju V. S. 
Published: August 2024

AbstractShp2, a critical SH2-domain-containing tyrosine phosphatase, is essential for cellular regulation and implicated in metabolic disruptions, obesity, diabetes, Noonan syndrome, LEOPARD syndrome, and cancers. This study focuses on Shp2 in rod photoreceptor cells, revealing its enrichment, particularly in rods. Deletion of Shp2 in rods leads to age-dependent photoreceptor degeneration. Shp2 targets occludin (OCLN), a tight junction protein, and its deletion reduces OCLN expression in the retina and retinal pigment epithelium (RPE). The isolation of actively translating mRNAs from rods lacking Shp2, followed by RNA sequencing, reveals alterations in cell cycle regulation. Additionally, altered retinal metabolism is observed in retinal cells lacking Shp2. Our studies indicate that Shp2 is crucial for maintaining the structure and function of photoreceptors.
Fetal growth restriction induced by maternal gal-3 deficiency is associated with altered gut-placenta axis
Authors: Xie Yiran , Zhao Fangqi , Wang Yiru , Borowski Sophia , Freitag Nancy , Tirado-Gonzalez Irene , Hofsink Naomi , Matschl Urte , Plösch Torsten , Garcia Mariana G. , Blois Sandra M. 
Published: August 2024

AbstractAdverse intrauterine conditions may cause fetal growth restriction (FGR), a pregnancy complication frequently linked to perinatal morbidity and mortality. Although many studies have focused on FGR, the pathophysiological processes underlying this disorder are complex and incompletely understood. We have recently determined that galectin-3 (gal-3), a β-galactoside-binding protein, regulates pregnancy-associated processes, including uterine receptibility, maternal vascular adaptation and placentation. Because gal-3 is expressed at both sides of the maternal-fetal interface, we unraveled the contribution of maternal- and paternal-derived gal-3 on fetal-placental development in the prenatal window and its effects on the post-natal period. Deficiency of maternal gal-3 induced maternal gut microbiome dysbiosis, resulting in a sex-specific fetal growth restriction mainly observed in female fetuses and offspring. In addition, poor placental metabolic adaptions (characterized by decreased trophoblast glycogen content and insulin-like growth factor 2 (Igf2) gene hypomethylation) were only associated with a lack of maternal-derived gal-3. Paternal gal-3 deficiency caused compromised vascularization in the placental labyrinth without affecting fetal growth trajectory. Thus, maternal-derived gal-3 may play a key role in fetal-placental development through the gut-placenta axis.
Experimental verification of field-enhanced molecular vibrational scattering at single infrared antennas
Authors: Virmani Divya , Maciel-Escudero Carlos , Hillenbrand Rainer , Schnell Martin 
Published: August 2024

AbstractSurface-enhanced infrared absorption (SEIRA) spectroscopy exploits the field enhancement near nanophotonic structures for highly sensitive characterization of (bio)molecules. The vibrational signature observed in SEIRA spectra is typically interpreted as field-enhanced molecular absorption. Here, we study molecular vibrations in the near field of single antennas and show that the vibrational signature can be equally well explained by field-enhanced molecular scattering. Although the infrared scattering cross section of molecules is negligible compared to their absorption cross section, the interference between the molecular-scattered field and the incident field enhances the spectral signature caused by molecular vibrational scattering by 10 orders of magnitude, thus becoming as large as that of field-enhanced molecular absorption. We provide experimental evidence that field-enhanced molecular scattering can be measured, scales in intensity with the fourth power of the local field enhancement and fully explains the vibrational signature in SEIRA spectra in both magnitude and line shape. Our work may open new paths for developing highly sensitive SEIRA sensors that exploit the presented scattering concept.
Nivolumab plus platinum-doublet chemotherapy in treatment-naive patients with advanced grade 3 Neuroendocrine Neoplasms of gastroenteropancreatic or unknown origin: The multicenter phase 2 NICE-NEC trial (GETNE-T1913)
Authors: Riesco-Martinez Maria Carmen , Capdevila Jaume , Alonso Vicente , Jimenez-Fonseca Paula , Teule Alex , Grande Enrique , Sevilla Isabel , Benavent Marta , Alonso-Gordoa Teresa , Custodio Ana , Anton-Pascual Beatriz , Hernando Jorge , Polo Eduardo , Castillo-Trujillo Oscar Alfredo , Lamas-Paz Arantza , Teijo Ana , Rodriguez-Gil Yolanda , Soldevilla Beatriz , Garcia-Carbonero Rocio 
Published: August 2024

AbstractThe prognosis of patients with advanced high-grade (G3) digestive neuroendocrine neoplasms (NENs) is rather poor. The addition of immune checkpoint inhibition to platinum-based chemotherapy may improve survival. NICE-NEC (NCT03980925) is a single-arm, phase II trial that recruited chemotherapy-naive, unresectable advanced or metastatic G3 NENs of gastroenteropancreatic (GEP) or unknown origin. Patients received nivolumab 360 mg intravenously (iv) on day 1, carboplatin AUC 5 iv on day 1, and etoposide 100 mg/m2/d iv on days 1–3, every 3 weeks for up to six cycles, followed by nivolumab 480 mg every 4 weeks for up to 24 months, disease progression, death or unacceptable toxicity. The primary endpoint was the 12-month overall survival (OS) rate (H0 50%, H1 72%, β 80%, α 5%). Secondary endpoints were objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and safety. From 2019 to 2021, 37 patients were enrolled. The most common primary sites were the pancreas (37.8%), stomach (16.2%) and colon (10.8%). Twenty-five patients (67.6%) were poorly differentiated carcinomas (NECs) and/or had a Ki67 index >55%. The ORR was 56.8%. Median PFS was 5.7 months (95%CI: 5.1-9) and median OS 13.9 months (95%CI: 8.3-Not reached), with a 12-month OS rate of 54.1% (95%CI: 40.2-72.8) that did not meet the primary endpoint. However, 37.6% of patients were long-term survivors (>2 years). The safety profile was consistent with previous reports. There was one treatment-related death. Nivolumab plus platinum-based chemotherapy was associated with prolonged survival in over one-third of chemonaïve patients with G3 GEP-NENs, with a manageable safety profile.
Assessing global drinking water potential from electricity-free solar water evaporation device
Authors: Zhang Wei , Chen Yongzhe , Ji Qinghua , Fan Yuying , Zhang Gong , Lu Xi , Hu Chengzhi , Liu Huijuan , Qu Jiuhui 
Published: August 2024

AbstractUniversal and equitable access to affordable safely managed drinking water (SMDW) is a significant challenge and is highlighted by the United Nations’ Sustainable Development Goals-6.1. However, SMDW coverage by 2030 is estimated to reach only 81% of the global population. Solar water evaporation (SWE) represents one potential method to ensure decentralized water purification, but its potential for addressing the global SMDW challenge remains unclear. We use a condensation-enhanced strategy and develop a physics-guided machine learning model for assessing the global potential of SWE technology to meet SMDW demand for unserved populations without external electricity input. We find that a condensation-enhanced SWE device (1 m2) can supply enough drinking water (2.5 L day−1) to 95.8% of the population lacking SMDW. SWE can help fulfill universal SMDW coverage by 2030 with an annual cost of 10.4 billion U.S. dollars, saving 66.7% of the current investment and fulfilling the SDG-6.1 goal.
Influence of chirality and sequence in lysine-rich lipopeptide biosurfactants and micellar model colloid systems
Authors: Hamley Ian W. , Adak Anindyasundar , Castelletto Valeria 
Published: August 2024

AbstractLipopeptides can self-assemble into diverse nanostructures which can be programmed to incorporate peptide sequences to achieve a remarkable range of bioactivities. Here, the influence of peptide sequence and chirality on micelle structure and interactions is investigated in a series of lipopeptides bearing two lysine or D-lysine residues and tyrosine or tryptophan residues, attached to a hexadecyl lipid chain. All molecules self-assemble into micelles above a critical micelle concentration (CMC). Small-angle x-ray scattering (SAXS) is used to probe micelle shape and structure from the form factor and to probe inter-micellar interactions via analysis of structure factor. The CMC is obtained consistently from surface tension and electrical conductivity measurements. We introduce a method to obtain the zeta potential from the SAXS structure factor which is in good agreement with directly measured values. Atomistic molecular dynamics simulations provide insights into molecular packing and conformation within the lipopeptide micelles which constitute model self-assembling colloidal systems and biomaterials.
Spindle architecture constrains karyotype evolution
Authors: Helsen Jana , Reza Md Hashim , Carvalho Ricardo , Sherlock Gavin , Dey Gautam 
Published: August 2024

AbstractThe eukaryotic cell division machinery must rapidly and reproducibly duplicate and partition the cell’s chromosomes in a carefully coordinated process. However, chromosome numbers vary dramatically between genomes, even on short evolutionary timescales. We sought to understand how the mitotic machinery senses and responds to karyotypic changes by using a series of budding yeast strains in which the native chromosomes have been successively fused. Using a combination of cell biological profiling, genetic engineering and experimental evolution, we show that chromosome fusions are well tolerated up until a critical point. Cells with fewer than five centromeres lack the necessary number of kinetochore-microtubule attachments needed to counter outward forces in the metaphase spindle, triggering the spindle assembly checkpoint and prolonging metaphase. Our findings demonstrate that spindle architecture is a constraining factor for karyotype evolution.
NOX2-TRPM2 coupling promotes Zn2+ inhibition of complex III to exacerbate ROS production in a cellular model of Parkinson’s disease
Authors: AlAhmad Maali , Isbea Hala , Shitaw Esra , Li Fangfang , Sivaprasadarao Asipu 
Published: August 2024

AbstractReactive oxygen species (ROS) serve vital physiological functions, but aberrant ROS production contributes to numerous diseases. Unfortunately, therapeutic progress targeting pathogenic ROS has been hindered by the limited understanding of whether the mechanisms driving pathogenic ROS differ from those governing physiological ROS generation. To address this knowledge gap, we utilised a cellular model of Parkinson’s disease (PD), as an exemplar of ROS-associated diseases. We exposed SH-SY5Y neuroblastoma cells to the PD-toxin, MPP+ (1-methyl-4-phenylpyridinium) and studied ROS upregulation leading to cell death, the primary cause of PD. We demonstrate: (1) MPP+ stimulates ROS production by raising cytoplasmic Ca2+ levels, rather than acting directly on mitochondria. (2) To raise the Ca2+, MPP+ co-stimulates NADPH oxidase-2 (NOX2) and the Transient Receptor Potential Melastatin2 (TRPM2) channel that form a positive feedback loop to support each other’s function. (3) Ca2+ exacerbates mitochondrial ROS (mtROS) production not directly, but via Zn2+. (4) Zn2+ promotes electron escape from respiratory complexes, predominantly from complex III, to generate mtROS. These conclusions are drawn from data, wherein inhibition of TRPM2 and NOX2, chelation of Ca2+ and Zn2+, and prevention of electron escape from complexes -all abolished the ability of MPP+ to induce mtROS production and the associated cell death. Furthermore, calcium ionophore mimicked the effects of MPP+, while Zn2+ ionophore replicated the effects of both MPP+ and Ca2+. Thus, we unveil a previously unrecognized signalling circuit involving NOX2, TRPM2, Ca2+, Zn2+, and complex III that drives cytotoxic ROS production. This circuit lies dormant in healthy cells but is triggered by pathogenic insults and could therefore represent a safe therapeutic target for PD and other ROS-linked diseases.
Comprehensive study on the efficiency of vertical bifacial photovoltaic systems: a UK case study
Authors: Badran Ghadeer , Dhimish Mahmoud 
Published: August 2024

AbstractThis paper presents the first comprehensive study of a groundbreaking Vertically Mounted Bifacial Photovoltaic (VBPV) system, marking a significant innovation in solar energy technology. The VBPV system, characterized by its vertical orientation and the use of high-efficiency Heterojunction cells, introduces a novel concept diverging from traditional solar panel installations. Our empirical research, conducted over a full year at the University of York, UK, offers an inaugural assessment of this pioneering technology. The study reveals that the VBPV system significantly outperforms both a vertically mounted monofacial PV (VMPV) system and a conventional tilted monofacial PV (TMPV) system in energy output. Key findings include a daily power output increase of 7.12% and 10.12% over the VMPV system and an impressive 26.91% and 22.88% enhancement over the TMPV system during early morning and late afternoon hours, respectively. Seasonal analysis shows average power gains of 11.42% in spring, 8.13% in summer, 10.94% in autumn, and 12.45% in winter compared to the VMPV system. Against the TMPV system, these gains are even more substantial, peaking at 24.52% in winter. These results underscore the VBPV system's exceptional efficiency in harnessing solar energy across varied environmental conditions, establishing it as a promising and sustainable solution in solar energy technology.