bluuebunny/crossref_metadata_2025_split huggingface dataset:
High potential: lightweight optimised structural design of car bodies for railway vehicles with alternative drive systems
Authors: Schmauder Nicolai , Malzacher Gregor , Fritsche Michael , Burkat Marcel , König Jens , Boese Ben 
Published: April 2024

AbstractClimate change and related goals and measures require a shift away from fossil fuels as an energy source. One solution for non-electrified lines for rail transport is the use of alternative drive technologies such as battery or hydrogen drive instead of diesel units. In order to use these efficiently in rail vehicles, it is imperative to make adjustments to the body structure. Existing car body structures must be adapted to integrate the space-intensive and heavy additional equipment components. Within the framework of the project AnoWaAS those with the highest lightweight construction potential are methodically identified from a large number of different derivatives of car body designs. The high influence of a force flow-compliant design on the lightweight potential is analysed in depth. Possible adapted construction methods for further exploitation of the lightweight potential are shown and analysed with regard to their potential. With the help of trapezoidal windows and the structural integration of equipment enclosures, it is possible to reduce the structural mass of a car body by more than 20%.
Equity for Children in the United States
Authors: Meek Shantel , Catherine Evandra , Boykin Xigrid Soto- , Blevins Darielle 
Published: April 2024

All children deserve access to the conditions and opportunities needed to thrive, including unbiased accessible healthcare and high-quality learning opportunities; safe, toxin-free communities and stable housing; access to nutritious meals; and secure, warm, available, and loving caregivers. Historic and contemporary injustices in US society have created inequities in opportunity and access to resources for Black, Latine, Asian, American Indian and Alaska Native, and other children of color, children with disabilities, children in poverty, and other marginalized children; these have contributed to stark disparities across child development outcomes. This Element overviews inequities in economic, educational, and health systems through historical and contemporary perspectives and describes how these inequities impact children and families. Solutions to address these inequities are considered for a fairer US society, starting with its youngest residents, where all families have what they need to thrive. This title is also available as Open Access on Cambridge Core.
A Convergence Science Approach to Understanding the Changing Arctic
Authors: Ivanov Valeriy Y. , Ungar Peter S. , Ziker John P. , Abdulmanova Svetlana , Celis Gerardo , Dixon Andrew , Ehrich Dorothee , Fufachev Ivan , Gilg Olivier , Heskel Mary , Liu Desheng , Macias‐Fauria Marc , Mazepa Valeriy , Mertens Karl , Orekhov Pavel , Peterson Alexandria , Pokrovskaya Olga , Sheshukov Aleksey , Sokolov Aleksandr , Sokolova Natalia , Spiegel Marcus , Sponheimer Matt , Stammler Florian , Taylor Tyeen , Terekhina Alexandra , Valdayskikh Victor , Volkovitskiy Alexander , Wang Jingfeng , Zhou Wenbo 
Published: April 2024

AbstractScience, engineering, and society increasingly require integrative thinking about emerging problems in complex systems, a notion referred to as convergence science. Due to the concurrent pressures of two main stressors—rapid climate change and industrialization, Arctic research demands such a paradigm of scientific inquiry. This perspective represents a synthesis of a vision for its application in Arctic system studies, developed by a group of disciplinary experts consisting of social and earth system scientists, ecologists, and engineers. Our objective is to demonstrate how convergence research questions can be developed via a holistic view of system interactions that are then parsed into material links and concrete inquiries of disciplinary and interdisciplinary nature. We illustrate the application of the convergence science paradigm to several forms of Arctic stressors using the Yamal Peninsula of the Russian Arctic as a representative natural laboratory with a biogeographic gradient from the forest‐tundra ecotone to the high Arctic.
Phenology of Photosynthesis in Winter‐Dormant Temperate and Boreal Forests: Long‐Term Observations From Flux Towers and Quantitative Evaluation of Phenology Models
Authors: Bowling David R. , Schädel Christina , Smith Kenneth R. , Richardson Andrew D. , Bahn Michael , Arain M. Altaf , Varlagin Andrej , Ouimette Andrew P. , Frank John M. , Barr Alan G. , Mammarella Ivan , Šigut Ladislav , Foord Vanessa , Burns Sean P. , Montagnani Leonardo , Litvak Marcy E. , Munger J. William , Ikawa Hiroki , Hollinger David Y. , Blanken Peter D. , Ueyama Masahito , Matteucci Giorgio , Bernhofer Christian , Bohrer Gil , Iwata Hiroki , Ibrom Andreas , Pilegaard Kim , Spittlehouse David L. , Kobayashi Hideki , Desai Ankur R. , Staebler Ralf M. , Black T. Andrew 
Published: April 2024

AbstractWe examined the seasonality of photosynthesis in 46 evergreen needleleaf (evergreen needleleaf forests (ENF)) and deciduous broadleaf (deciduous broadleaf forests (DBF)) forests across North America and Eurasia. We quantified the onset and end (StartGPP and EndGPP) of photosynthesis in spring and autumn based on the response of net ecosystem exchange of CO2 to sunlight. To test the hypothesis that snowmelt is required for photosynthesis to begin, these were compared with end of snowmelt derived from soil temperature. ENF forests achieved 10% of summer photosynthetic capacity ∼3 weeks before end of snowmelt, while DBF forests achieved that capacity ∼4 weeks afterward. DBF forests increased photosynthetic capacity in spring faster (1.95% d−1) than ENF (1.10% d−1), and their active season length (EndGPP–StartGPP) was ∼50 days shorter. We hypothesized that warming has influenced timing of the photosynthesis season. We found minimal evidence for long‐term change in StartGPP, EndGPP, or air temperature, but their interannual anomalies were significantly correlated. Warmer weather was associated with earlier StartGPP (1.3–2.5 days °C−1) or later EndGPP (1.5–1.8 days °C−1, depending on forest type and month). Finally, we tested whether existing phenological models could predict StartGPP and EndGPP. For ENF forests, air temperature‐ and daylength‐based models provided best predictions for StartGPP, while a chilling‐degree‐day model was best for EndGPP. The root mean square errors (RMSE) between predicted and observed StartGPP and EndGPP were 11.7 and 11.3 days, respectively. For DBF forests, temperature‐ and daylength‐based models yielded the best results (RMSE 6.3 and 10.5 days).
Revisiting the Ionospheric Disturbances Over Low Latitude Region of China During Super Typhoon Hato
Authors: Li Ke , Zhang Donghe , Zeng Yi , Tian Yaoyu , Dai Guofeng , Liu Zhizhao , Yang Guanglin , Sun Shuji , Li Guozhu , Hao Yongqiang , Xiao Zuo 
Published: April 2024

AbstractThe ionosphere exhibits complex variations due to the influences from above and below. To distinguish the source of ionospheric disturbances is important for understanding the variation process and the coupling mechanism among different regions. Using the ionospheric total electron content (TEC) derived from Global Navigation Satellite System observations, the ionospheric disturbances during the super typhoon Hato in 2017 that was accompanied by a weak geomagnetic storm are revisited, including the ionospheric deviation and traveling ionospheric disturbances (TIDs). It is found that the ionospheric TEC in the low‐latitude region of China experienced a significant enhancement (200% compared to the quiet geomagnetic day) on Hato landing day. This enhancement covers the northern and southern equatorial ionization anomaly (EIA) region from 80°E to 180°E. Considering the geomagnetic condition, the hmF2 and the O/N2 ratio in thermosphere, it is concluded that this enhancement is not related to the typhoon, but to the coinciding weak geomagnetic storm. Additionally, several medium‐scale TIDs are verified from differential TEC data in China low latitude region during Hato period. Most of them occur after sunset and their propagating direction is southwest that often occur in East‐Asian sector in summer months, which are not related to the typhoon. While a few TIDs with concentric wavefront (Concentric TIDs) are also observed on the day before Hato landfall that should be excited in the deep convective region of the typhoon. Because the ionosphere is affected by disturbances both from above and below, it should be careful to determine the source of the ionospheric disturbances.
Multi‐Segment Earthquake Clustering as Inferred From 36Cl Exposure Dating, the Bet Kerem Fault System, Northern Israel
Authors: Dawood R. , Matmon A. , Benedetti L. ,   ASTER Team, Siman‐Tov S. 
Published: April 2024

AbstractRecovering the seismic history of multiple segments within a fault system provides a spatiotemporal framework for the fault activity across the system. This kind of data is essential for improving our understanding of how faults interact during earthquake cycles and how they are distributed within a fault system. Bedrock fault scarps, reaching up to 10‐m height, are abundant across the Bet Kerem fault system, Galilee, northern Israel. Using the 36Cl exposure dating method, we recovered the last 30 ka scarp exhumation history of three fault segments from the Bet Kerem fault system. Results indicate that the three faults were active simultaneously in at least three distinguished activity periods, during which a minimum of 1.2 m of surface rupturing occurred in each period. The synchronized activity and total surface rupture at each activity period suggest that the three dated segments were ruptured simultaneously by the same earthquake. That is, a multi‐segment rupture earthquake and that each activity period included a cluster of at least two large multi‐segment earthquakes. The results also indicate a recurrence interval between clusters of 3.5–4.5 ka and the existence of a seismic super cycle with a recurrence interval of about 13 ka.
SWOL2023: Report of Space Weather Observations Throughout Latinoamerica: Filling the Southern Gaps
Authors: Natali M. Paula , Meza Amalia M. , Robinson Robert , Janches Diego , Berger Thomas , Dasso Sergio , De Nardin Clezio , Colazo Marcelo 
Published: April 2024

AbstractThe “Space Weather Observations throughout Latinoamerica: Filling the Southern gaps” Workshop took place in Ushuaia, Argentina, from 2 to 4 October 2023. This event was exclusively dedicated to Space Weather (SWx), gathering leading international academic and governmental agencies focused on the subject. The meeting addressed the field of SWx from three perspectives: driving phenomena occurring in the solar atmosphere, evolution in the interplanetary environment, and interaction with the Earth. In addition, emphasis was placed on identifying key research directions in solar and space physics that warrant development in Argentina and across the region in the forthcoming years. The workshop also focused on the current observational infrastructure that supports SWx studies, and how to improve and develop it through strategic international partnerships, stressing on the need for real‐time data. The conference fostered discussion among different partners involved in SWx studies, that is, researchers and potential space weather service providers, and the need to include in this debate potential users of space weather services.
The addition of bortezomib to rituximab, high-dose cytarabine and dexamethasone in relapsed or refractory mantle cell lymphoma—a randomized, open-label phase III trial of the European mantle cell lymphoma network
Authors: Fischer Luca , Jiang Linmiao , Dürig Jan , Schmidt Christian , Stilgenbauer Stephan , Bouabdallah Krimo , Solal-Celigny Philippe , Scholz Christian W. , Feugier Pierre , de Wit Maike , Trappe Ralf Ulrich , Hallek Michael , Graeven Ullrich , Hänel Mathias , Hoffmann Martin , Delwail Vincent , Macro Margaret , Greiner Jochen , Giagounidis Aristoteles A. N. , Dargel Beate , Durot Eric , Foussard Charles , Silkenstedt Elisabeth , Weigert Oliver , Pott Christiane , Klapper Wolfram , Hiddemann Wolfgang , Unterhalt Michael , Hoster Eva , Ribrag Vincent , Dreyling Martin 
Published: April 2024

AbstractThe therapy of relapsed or refractory (r/r) mantle cell lymphoma (MCL) patients remains a major clinical challenge to date. We conducted a randomized, open-label, parallel-group phase-III trial hypothesizing superior efficacy of rituximab, high-dose cytarabine and dexamethasone with bortezomib (R-HAD + B) versus without (R-HAD) in r/r MCL ineligible for or relapsed after autologous stem cell transplant (ASCT). Primary endpoint was time to treatment failure (TTF), secondary endpoints included response rates, progression free survival, overall survival, and safety. In total, 128 of 175 planned patients were randomized to R-HAD + B (n = 64) or R-HAD (n = 64). Median TTF was 12 vs. 2.6 months (p = 0.045, MIPI-adjusted HR 0.69; 95%CI 0.47–1.02). Overall and complete response rates were 63 vs. 45% (p = 0.049) and 42 vs. 19% (p = 0.0062). A significant treatment effect was seen in the subgroup of patients >65 years (aHR 0.48, 0.29–0.79) and without previous ASCT (aHR 0.52, 0.28–0.96). Toxicity was mostly hematological and attributable to the chemotherapeutic backbone. Grade ≥3 leukocytopenia and lymphocytopenia were more common in R-HAD + B without differences in severe infections between both arms. Bortezomib in combination with chemotherapy can be effective in r/r MCL and should be evaluated further as a therapeutic option, especially if therapy with BTK inhibitors is not an option. Trial registration: NCT01449344.
Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1
Authors: Li Xian , Xu Mengxin , Yang Jingyi , Zhou Li , Liu Lin , Li Min , Wang Shasha , Liu Mei-Qin , Huang Zhixiang , Zhang Zhen , Liu Shuning , Hu Yunqi , Lin Haofeng , Liu Bowen , Sun Ying , Wu Qingguo , Shi Zheng-Li , Lan Ke , Chen Yu , Yan Huimin , Chen Yao-Qing 
Published: April 2024

AbstractDeveloping a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic. Here, we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain (RBD) scaffold protein (3R-NC) adjuvanted with a flagellin protein (KFD) (3R-NC + KFDi.n). In mice, the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year. This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG- and IgA-producing plasma cells, alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant. Based upon these preclinical findings, an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2 (IAV) vaccine. With a favorable safety profile, the 3R-NC + KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions. To meet the challenge of frequently emerged variants, we further designed an updated triple-RBD scaffold protein with mutated RBD combinations, which can induce adaptable antibody responses to neutralize the newly emerging variants, including JN.1. Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.
The pRb/RBL2-E2F1/4-GCN5 axis regulates cancer stem cell formation and G0 phase entry/exit by paracrine mechanisms
Authors: Chang Chao-Hui , Liu Feng , Militi Stefania , Hester Svenja , Nibhani Reshma , Deng Siwei , Dunford James , Rendek Aniko , Soonawalla Zahir , Fischer Roman , Oppermann Udo , Pauklin Siim 
Published: April 2024

AbstractThe lethality, chemoresistance and metastatic characteristics of cancers are associated with phenotypically plastic cancer stem cells (CSCs). How the non-cell autonomous signalling pathways and cell-autonomous transcriptional machinery orchestrate the stem cell-like characteristics of CSCs is still poorly understood. Here we use a quantitative proteomic approach for identifying secreted proteins of CSCs in pancreatic cancer. We uncover that the cell-autonomous E2F1/4-pRb/RBL2 axis balances non-cell-autonomous signalling in healthy ductal cells but becomes deregulated upon KRAS mutation. E2F1 and E2F4 induce whereas pRb/RBL2 reduce WNT ligand expression (e.g. WNT7A, WNT7B, WNT10A, WNT4) thereby regulating self-renewal, chemoresistance and invasiveness of CSCs in both PDAC and breast cancer, and fibroblast proliferation. Screening for epigenetic enzymes identifies GCN5 as a regulator of CSCs that deposits H3K9ac onto WNT promoters and enhancers. Collectively, paracrine signalling pathways are controlled by the E2F-GCN5-RB axis in diverse cancers and this could be a therapeutic target for eliminating CSCs.
Efficient gene knockout and genetic interaction screening using the in4mer CRISPR/Cas12a multiplex knockout platform
Authors: Esmaeili Anvar Nazanin , Lin Chenchu , Ma Xingdi , Wilson Lori L. , Steger Ryan , Sangree Annabel K. , Colic Medina , Wang Sidney H. , Doench John G. , Hart Traver 
Published: April 2024

AbstractGenetic interactions mediate the emergence of phenotype from genotype, but technologies for combinatorial genetic perturbation in mammalian cells are challenging to scale. Here, we identify background-independent paralog synthetic lethals from previous CRISPR genetic interaction screens, and find that the Cas12a platform provides superior sensitivity and assay replicability. We develop the in4mer Cas12a platform that uses arrays of four independent guide RNAs targeting the same or different genes. We construct a genome-scale library, Inzolia, that is ~30% smaller than a typical CRISPR/Cas9 library while also targeting ~4000 paralog pairs. Screens in cancer cells demonstrate discrimination of core and context-dependent essential genes similar to that of CRISPR/Cas9 libraries, as well as detection of synthetic lethal and masking/buffering genetic interactions between paralogs of various family sizes. Importantly, the in4mer platform offers a fivefold reduction in library size compared to other genetic interaction methods, substantially reducing the cost and effort required for these assays.
Revealing hidden spin polarization in centrosymmetric van der Waals materials on ultrafast timescales
Authors: Arnoldi B. , Zachritz S. L. , Hedwig S. , Aeschlimann M. , Monti O. L. A. , Stadtmüller B. 
Published: April 2024

AbstractOne of the key challenges for spintronic and quantum technologies is to achieve active control of the spin angular momentum of electrons in nanoscale materials on ultrafast, femtosecond timescales. While conventional ferromagnetic materials and materials supporting spin texture suffer both from conceptional limitations in miniaturization and inefficiency of optical and electronic manipulation, non-magnetic centrosymmetric layered materials with hidden spin polarization may offer an alternative pathway to manipulate the spin degree of freedom by external stimuli. Here we demonstrate an approach for generating transient spin polarization on a femtosecond timescale in the otherwise spin-unpolarized band structure of the centrosymmetric 2H-stacked group VI transition metal dichalcogenide WSe2. Using ultrafast optical excitation of a fullerene layer grown on top of WSe2, we trigger an ultrafast interlayer electron transfer from the fullerene layer into the WSe2 crystal. The resulting transient charging of the C60/WSe2 interface leads to a substantial interfacial electric field that by means of spin-layer-valley locking ultimately creates ultrafast spin polarization without the need of an external magnetic field. Our findings open a novel pathway for true optical engineering of spin functionalities such as the sub-picosecond generation and manipulation of ultrafast spin currents in 2D heterostructures.
Mechanism of DNA unwinding by MCM8-9 in complex with HROB
Authors: Acharya Ananya , Bret Hélène , Huang Jen-Wei , Mütze Martin , Göse Martin , Kissling Vera Maria , Seidel Ralf , Ciccia Alberto , Guérois Raphaël , Cejka Petr 
Published: April 2024

AbstractHROB promotes the MCM8-9 helicase in DNA damage response. To understand how HROB activates MCM8-9, we defined their interaction interface. We showed that HROB makes important yet transient contacts with both MCM8 and MCM9, and binds the MCM8-9 heterodimer with the highest affinity. MCM8-9-HROB prefer branched DNA structures, and display low DNA unwinding processivity. MCM8-9 unwinds DNA as a hexamer that assembles from dimers on DNA in the presence of ATP. The hexamer involves two repeating protein-protein interfaces between the alternating MCM8 and MCM9 subunits. One of these interfaces is quite stable and forms an obligate heterodimer across which HROB binds. The other interface is labile and mediates hexamer assembly, independently of HROB. The ATPase site formed at the labile interface contributes disproportionally more to DNA unwinding than that at the stable interface. Here, we show that HROB promotes DNA unwinding downstream of MCM8-9 loading and ring formation on ssDNA.
A vascularized breast cancer spheroid platform for the ranked evaluation of tumor microenvironment-targeted drugs by light sheet fluorescence microscopy
Authors: Ascheid David , Baumann Magdalena , Pinnecker Jürgen , Friedrich Mike , Szi-Marton Daniel , Medved Cornelia , Bundalo Maja , Ortmann Vanessa , Öztürk Asli , Nandigama Rajender , Hemmen Katherina , Ergün Süleymann , Zernecke Alma , Hirth Matthias , Heinze Katrin G. , Henke Erik 
Published: April 2024

AbstractTargeting the supportive tumor microenvironment (TME) is an approach of high interest in cancer drug development. However, assessing TME-targeted drug candidates presents a unique set of challenges. We develop a comprehensive screening platform that allows monitoring, quantifying, and ranking drug-induced effects in self-organizing, vascularized tumor spheroids (VTSs). The confrontation of four human-derived cell populations makes it possible to recreate and study complex changes in TME composition and cell-cell interaction. The platform is modular and adaptable for tumor entity or genetic manipulation. Treatment effects are recorded by light sheet fluorescence microscopy and translated by an advanced image analysis routine in processable multi-parametric datasets. The system proved to be robust, with strong interassay reliability. We demonstrate the platform’s utility for evaluating TME-targeted antifibrotic and antiangiogenic drugs side-by-side. The platform’s output enabled the differential evaluation of even closely related drug candidates according to projected therapeutic needs.