bluuebunny/crossref_metadata_2025 huggingface dataset:
The sequential search model: A framework for empirical research
Authors: Ursu Raluca , Seiler Stephan , Honka Elisabeth
Published: December 2024

We provide a detailed overview of the empirical implementation of the sequential search model proposed by Weitzman (1979). We discuss the assumptions underlying the model, the identification of search cost and preference parameters, elasticities and welfare formulas, and different estimation approaches. The goal of this paper is to consolidate knowledge and provide a unified treatment of various aspects of sequential search models that are relevant for empirical work.
Behavioral Measurement as Centerpiece
Authors: Johnston James M.
Published: December 2024

Hank Pennypacker’s interest in behavioral measurement began early in his career and gradually became the centerpiece of his diverse accomplishments. A review of his focus in the 1960s is followed by a brief summary of the evolution of behavioral measurement practices in applied behavior analysis as it emerged from the field’s laboratory history. This examination serves as pretext for a discussion of the contributions of Strategies and Tactics of Human Behavioral Research (Johnston & Pennypacker, 1980), Strategies and Tactics of Behavioral Research (Johnston & Pennypacker, 1993a, 2009), and Strategies and Tactics of Behavioral Research and Practice (Johnston et al., 2020) to emerging matters of behavioral measurement. That discussion focuses on how issues raised by the challenges of applied research and practice have evolved.
Controlling the mechanical properties of laser powder bed fusion manufactured AlSi10Mg using optimized oscillating scan paths
Authors: Meyer Samuel , Englert Lukas , Schüßler Philipp , Schulze Volker , Dietrich Stefan
Published: December 2024

In the field of metal additive manufacturing, laser powder bed fusion (L-PBF) stands out for its maturity. The path the laser takes over the powder, in this study AlSi10Mg, is determined by a large set of separate parameters; the combination of which offers ample room for optimization. The close ties between the parameters chosen, and the resulting mechanical properties, are what motivates the extensive research done in this field. This study changed the scan line path into a circular oscillation (prolate trochoid) and narrows down a large set of parameters to two sets that exhibit significant differences from traditional scan lines in terms of density, porosity distribution, tensile strength, elongation at fracture, hardness, surface roughness, and melt pool (MP) shape. Remarkable upper bounds for MP size were also characterized for the first time in this work. Some of the noteworthy findings consist of an up to 70% reduction in surface roughness, up to a 40% increase in the elongation at fracture, and up to a $${150}\,{\upmu }\textrm{m}$$

150

μ
m

range of hatching distances to produce a part with under 0.5% porosity. The last of which leads to an overall increase in the robustness of the L-PBF manufacturing process by reducing the sensitivity to parameter fluctuations.
Developing a Smart Energy Service Canvas
Authors: Günter Jennifer , Fabri Lukas , Wenninger Simon , Kaymakci Can
Published: December 2024

Rising energy and CO2 prices are driving industrial companies to focus increasingly on energy efficiency and flexibility to remain competitive. Besides technical improvements, smart energy services like nonintrusive load monitoring (NILM) are promising approaches to increasing a company’s energy efficiency and flexibility potential. Despite its advantages, smart energy services are not yet widely used in practice, and service providers are cautious. Existing research investigates almost exclusively technical aspects of smart energy service applications and systems, particularly for NILM, while a business model perspective is missing. This study addresses this research gap following a design science research approach with literature research and expert interviews, and develops a business model framework—the Smart Energy Service Canvas (SESC). The SESC is a practical and empirically validated tool to formalize, structure, and implement a business idea on smart energy services.
Contemplation and Society in Plato and Aristotle
Authors: Scott Dominic
Published: December 2024

This Element concerns the civic value of contemplation in Plato and Aristotle: how does intellectual contemplation contribute to the happiness of the ideal state? The texts discussed include the Republic, the Nicomachean Ethics and the Politics, works in which contemplation is viewed from a political angle. The Element concludes that in the Republic contemplation has purely instrumental value, whereas in the Politics and Nicomachean Ethics it has purely intrinsic value. To do justice to the complexity of the issues involved, the author addresses a broader question about the nature of civic happiness: whether it is merely the aggregate of individual happiness or an organic quality that arises from the structure of the state. Answering this question has implications for how contemplation contributes to civic happiness. The Element also discusses how many citizens Plato and Aristotle expected to be engaged in contemplation in the ideal state.
Digital Assets
Authors: Schneider Henrique
Published: December 2024

From the perspective of an investor, digital assets are an alternative class of assets. They have several features that differentiate them from traditional investments. This makes them well-suited for a diversified portfolio. The question is how to accommodate them in such a portfolio, how to manage their potential and risk, and how to evaluate them. This short book explains how to include digital assets is a diversified portfolio. It focuses on their differentiating use cases, their idiosyncracies, and how they relate to other types of investment. This is a volume for practitioners and students in finance, asset management, or portfolio construction.
Monotheism & Paradise
Authors: Gilson Caitlin Smith
Published: December 2024

This Element will provide an essential tracing of selected Greek views of the afterlife which engage in dynamic tension with the Christian understanding of Paradise as fulfilled in the Resurrected state. The main three sections in this Element are Ideas of the Afterlife in the Greek Tragedians; Plato: The Difficulty of Paradise; and Holiness and Violence: A Christian View of the Resurrected State. The imposition of justice and the expiation of guilt through suffering are necessary prerequisites to our approach to the relationship between Monotheism and Paradise. Additional discussions will focus on weak theology and of a God not transcendent enough to ensure the desire for Heaven. As such, the sections are organized to isolate and trace this thread.
The Science of Music
Authors: Ansari Mohammad Sadegh
Published: December 2024

How did the pre-modern Islamic intellectual tradition conceptualize, produce, and disseminate scientific knowledge? What can we learn about pre-modern Islamic civilizations from the way they examined and studied the universe? In answering these fundamental questions, Mohammad Sadegh Ansari provides a unique perspective for the study of both musicology and intellectual history. Widely considered to be an art today,music in the medieval Islamic world was categorized as one of the four branches of the mathematical sciences, alongside arithmetic, geometry, and astronomy; indeed, some philosophers and scholars of music went as far as linking music with medicine and astrology as part of an interconnected web of cosmological knowledge. This innovative book raises fascinating questions about how designating music a 'science rather than an 'art' impacts our understanding of truth, and reconstructs a richly holistic medieval system of knowledge in the process.
Geographies of Renewal
Authors: DeWaal Jeremy
Published: December 2024

The term 'Heimat', referring to a local sense of home and belonging, has been the subject of much scholarly and popular debate following the fall of the Third Reich. Countering the persistent myth that Heimat was a taboo and unusable term immediately after 1945, Geographies of Renewal uncovers overlooked efforts in the aftermath of the Second World War to conceive of Heimat in more democratic, inclusive, and pro-European modes. It revises persistent misconceptions of Heimat as either tainted or as a largely reactionary idea, revealing some surprisingly early identifications between home and democracy. Jeremy DeWaal further traces the history of efforts to eliminate the concept, which first emerged during the Cold War crisis of the early 1960s and reassesses why so many on the political left sought to re-engage with Heimat in the 1970s and 1980s. This revisionist history intervenes in larger contemporary debates, asking compelling questions surrounding the role of the local, the value of community, and the politics of place attachments.
The Art of Walking in London
Authors: O'Byrne Alison
Published: December 2024

Exploring a variety of perspectives on London during the long eighteenth century, this study considers how walking made possible the various surveys and tours that characterized accounts of the capital. O'Byrne examines how walking in the city's streets and promenades provided subject matter for writers and artists. Engaging with a wide range of material, the book ranges across and investigates the various early eighteenth-century works that provided influential models for representing the city, descriptions of the promenade in St. James's Park, accounts of London that imagine the needs and interests of tourists, popular surveys of the cheats and frauds of the city uncovered on a ramble through London, and comic explorations of the pleasures and pitfalls of urban living produced in the late eighteenth and early nineteenth century. Convincing and engaging, O'Byrne demonstrates the fundamental role played by walking in shaping representations of the eighteenth- and early nineteenth-century city.
Banned
Authors: Cabrera Nolan L. , Chang Robert S.
Published: December 2024

In Banned, readers are taken on a journey through the intense racial politics surrounding the banning of Mexican American Studies in Tucson, Arizona. This book details the state-sponsored racism that led to the elimination of this highly successful program, and the grassroots and legal resistance that followed. Through extensive research and firsthand narratives, readers will gain a deep understanding of the controversy surrounding this historic case. The legal challenge successfully overturned the Arizona law and became a central symbol in the modern-day Ethnic Studies renaissance. This work is a must-read for anyone interested in understanding the power of community activism, the importance of fighting for educational equity, and why the example of Tucson created an alternative blueprint for how we can challenge states that are currently banning critical race theory.
Brownian Motion, the Fredholm Determinant, and Time Series Analysis
Authors: Tanaka Katsuto
Published: December 2024

Brownian motion is an important topic in various applied fields where the analysis of random events is necessary. Introducing Brownian motion from a statistical viewpoint, this detailed text examines the distribution of quadratic plus linear or bilinear functionals of Brownian motion and demonstrates the utility of this approach for time series analysis. It also offers the first comprehensive guide on deriving the Fredholm determinant and the resolvent associated with such statistics. Presuming only a familiarity with standard statistical theory and the basics of stochastic processes, this book brings together a set of important statistical tools in one accessible resource for researchers and graduate students. Readers also benefit from online appendices, which provide probability density graphs and solutions to the chapter problems.
Sustainable Human Settlements within the Global Urban Agenda
Authors: Simon David
Published: December 2024

The UN's urban sustainability goal number eleven (11) is fundamental to the global sustainable development agenda. David Simon explains the anatomy and dynamics of SDG 11, and critically assess how it is being used and understood in different local, regional and national contexts.

Supported by case studies throughout, Simon considers how SDG 11 interacts with other Sustainability Development Goals and how competing indicators, other external constraints, as well as lack of political will can present tough challenges to implementation. He provides a balanced and dispassionate analysis, highlighting problems and limitations alongside positive applications. A key aspect of the unfolding story of the SDGs is how they play out in practice. Although some of the connections and complementarities were designed, others are shown to have emerged by default. Drawing on lessons learnt so far, Simon considers how realistic sustainability goals are for cities and human settlements worldwide, and asks how different will cities be by the end of the SDG's 15-year lifespan in 2030?

Written for students, policy-makers and practitioners, the book provides an authoritative assessment of one of the most important and integrative SDGs.
Global Health
Authors: Gatrell Anthony C.
Published: December 2024

Drawing on the latest research in health geography and a wide range of case studies from across the world, this comprehensive and authoritative study offers students an unrivalled analysis of the geographical connections of global health and the challenges they present for governance and treatment. Topics considered include health inequalities across countries, the governance of health by nation-states and international organizations, the incidence and spread of infectious disease, the links between air and water quality and health outcomes, and the health impacts of climate change. The book considers how these different issues play out in a range of geographical settings across the world, with a particular focus on low- and middle-income countries, which are disproportionally affected. The book demonstrates the indispensable role of geographical processes operating across borders in understanding health worldwide and is an excellent resource for courses on health geography, global health, public health and development studies.
The Wealth of Cities and the Poverty of Nations
Authors: Parnreiter Christof
Published: December 2024

Cities are seen as essentially 'good': innovative, pro-growth, poverty-reducing. In a challenging corrective to this common portrayal, Christof Parnreiter argues that the same urban properties which make cities so extraordinarily proficient at producing the 'good' innovations - agglomeration economies, network externalities and a massive built environment - also provides fertile ground for the development of the 'bad' ones, on which urban elites have syphoned off wealth from other localities and regions.

The book scrutinizes the interconnections between wealth creation and poverty generation by putting cities centre stage as a fundamental explanatory category for understanding how the wealth of nations is produced as well as for grasping how the poverty of nations is created. It seeks to correct the developmentalist enthusiasm, commonplace in urban and regional studies, for cities' efficiency, which has displaced interest in cities' role in uneven development.
Social Democracy
Authors: Goes Eunice
Published: December 2024

Social democracy emerged in the late nineteenth century and has become a leading political ideology in Europe. This short history approaches the evolution of this ideology as a body of political thought and political practices. It expounds the development, transformation and practice of European social democracy through the analysis of four key moments in its history: its origins and rise as a key political force in European politics, the second revisionist phase with the embrace of capitalism in the postwar period, the Third Way of the 1990s and the contemporary crisis of social democracy in an era of fragmented politics. The book offers a fresh and engaging discussion of one of the most enduring ideologies of the European political sphere and its manifestations in different countries of the region.
Pyromania
Authors: Dalby Simon
Published: December 2024

We are the only species that uses fire. It has determined how we have made our home on this planet and it has propelled us to the role of the dominant species in the biosphere. But at the heart of contemporary climate change is the process of combustion. Simon Dalby explores what a life without burning things might look like, and how we might get there.

Fires make the carbon dioxide in the atmosphere that is heating the planet, melting the ice sheets, changing weather patterns and making wildfires worse. Our civilization is burning things, especially fossil fuels, at prodigious rates. So much so that we are now heading towards a future 'Hothouse Earth' with a climate that is very different from what humans have known so far.

By focusing on fire and our partial control over one key physical force in the earth system, that of combustion, Simon Dalby is able to ask important and interesting questions about us as humans, including different ways of thinking about how we live, and how we might do so differently in the future. Simply put, there is now far too much 'firepower' loose in the world and we need to think much harder about how to live together in ways that don't require burning stuff to do so.
The Kurds
Authors: Hendessi Mandana
Published: December 2024

The Kurds are the fourth largest ethnic group in the Middle East. An Indigenous people from the Mesopotamian plains and highlands in what is now Southeast Turkey, Northeast Syria, Northern Iraq, northwest Iran and Southwest Armenia, they are the largest stateless people in the world. Denied a national identity, their culture and language have been banned or suppressed throughout the centuries and theirs is a story of resistance and survival.

This book offers a contemporary overview and critical analysis of the Kurds quest for national identity and statehood from the end of the Ottoman Empire to the modern day. Kurdish nationalism has taken many forms and had to endure periods of rebellion, acceptance, oppression and ethnic cleansing. Mandana Hendessi outlines the contours of the political struggle and military conflict that continue to shape the lives of a people that occupy one of the most contested regions in the world.
Ayatollah Khomeini's Mystical Poetry and its Reception in Iran and the Diaspora
Authors: Farhosh-Van Loon Diede
Published: December 2024

There are many publications dealing with the political career of Ruhollah Khomeini (1902-1989), who transformed the political landscape of Iran and the Middle East after the Islamic Revolution of 1979. Most of the research conducted in the West is on Khomeini's political strategies, while the influential role of mysticism in all facets of his life is ignored. This book is the first study examining Khomeini's poetry, mysticism and the reception of his poetry both in Iran and the West. It investigates how Khomeini integrated various doctrines and ideas of Islamic mysticism and Shi’ism such as the 'Perfect Man' into his poetry.
Development of a multifunctional optical diagnostic system at the Shenguang-II upgrade laser facility
Authors: Li Xinyan , Yuan Peng , Gao Fan , Liu Yifan , Wu Lixuan , Yuan Xiaohui , Zhang Zhe , Zhang Jie , Li Jun , Zheng Jian
Published: December 2024

A multifunctional optical diagnostic system, which includes an interferometer, a refractometer and a multi-frame shadowgraph, has been developed at the Shenguang-II upgrade laser facility to characterize underdense plasmas in experiments of the double-cone ignition scheme of inertial confinement fusion. The system employs a 266 nm laser as the probe to minimize the refraction effect and allows for flexible switching among three modes of the interferometer, refractometer and multi-frame shadowgraph. The multifunctional module comprises a pair of beam splitters that attenuate the laser, shield stray light and configure the multi-frame and interferometric modules. By adjusting the distance and angle between the beam splitters, the system can be easily adjusted and switched between the modes. Diagnostic results demonstrate that the interferometer can reconstruct electron density below 1019 cm–3, while the refractometer can diagnose density approximately up to 1020 cm–3. The multi-frame shadowgraph is used to qualitatively characterize the temporal evolution of plasmas in the cases in which the interferometer and refractometer become ineffective.
A real-time digital twin of azimuthal thermoacoustic instabilities
Authors: Nóvoa Andrea , Noiray Nicolas , Dawson James R. , Magri Luca
Published: December 2024

When they occur, azimuthal thermoacoustic oscillations can detrimentally affect the safe operation of gas turbines and aeroengines. We develop a real-time digital twin of azimuthal thermoacoustics of a hydrogen-based annular combustor. The digital twin seamlessly combines two sources of information about the system: (i) a physics-based low-order model; and (ii) raw and sparse experimental data from microphones, which contain both aleatoric noise and turbulent fluctuations. First, we derive a low-order thermoacoustic model for azimuthal instabilities, which is deterministic. Second, we propose a real-time data assimilation framework to infer the acoustic pressure, the physical parameters, and the model bias and measurement shift simultaneously. This is the bias-regularized ensemble Kalman filter, for which we find an analytical solution that solves the optimization problem. Third, we propose a reservoir computer, which infers both the model bias and measurement shift to close the assimilation equations. Fourth, we propose a real-time digital twin of the azimuthal thermoacoustic dynamics of a laboratory hydrogen-based annular combustor for a variety of equivalence ratios. We find that the real-time digital twin (i) autonomously predicts azimuthal dynamics, in contrast to bias-unregularized methods; (ii) uncovers the physical acoustic pressure from the raw data, i.e. it acts as a physics-based filter; (iii) is a time-varying parameter system, which generalizes existing models that have constant parameters, and capture only slow-varying variables. The digital twin generalizes to all equivalence ratios, which bridges the gap of existing models. This work opens new opportunities for real-time digital twinning of multi-physics problems.
Transformer-based in-context policy learning for efficient active flow control across various airfoils
Authors: Zheng Changdong , Xie Fangfang , Ji Tingwei , Zhou Hongjie , Zheng Yao
Published: December 2024

Active flow control based on reinforcement learning has received much attention in recent years. Indeed, the requirement for substantial data for trial-and-error in reinforcement learning policies has posed a significant impediment to their practical application, which also serves as a limiting factor in the training of cross-case agents. This study proposes an in-context active flow control policy learning framework grounded in reinforcement learning data. A transformer-based policy improvement operator is set up to model the process of reinforcement learning as a causal sequence and autoregressively give actions with sufficiently long context on new unseen cases. In flow separation problems, this framework demonstrates the capability to successfully learn and apply efficient flow control strategies across various airfoil configurations. Compared with general reinforcement learning, this learning mode without the need for updating the network parameter has even higher efficiency. This study presents an effective novel technique in using a single transformer model to address the flow separation active flow control problem on different airfoils. Additionally, the study provides an innovative demonstration of incorporating reinforcement-learning-based flow control with aerodynamic shape optimization, leading to collective enhancement in performance. This method efficiently lessens the training burden of the new flow control policy during shape optimization, and opens up a promising avenue for interdisciplinary intelligent co-design of future vehicles.
Essay review: the fictive history of Victorian science and empire
Authors: Steere-Williams Jacob
Published: December 2024

In 1820 two French scientists – Pierre Joseph Pelletier and Jean Bienaimé Caventou – discovered and named the active alkaloid substance extracted from cinchona bark: quinine. The bark from the ‘wondrous’ fever tree, and its antimalarial properties, however, had long been known to both colonial scientists and indigenous Peruvians. From the mid-seventeenth century, cinchona bark, taken from trees that grow on the eastern slopes of the Andes, was part of a global circulation of botanical knowledge, practice and profit. By the 1850s, Europeans eager to bypass South American trade routes to access cinchona plants established plantations across the global South in French Algeria, Dutch Java and British India. Wardian cases – plant terrariums named after British physician Nathaniel Bagshaw Ward – would fuel new imperial efforts to curb malaria, contemporaries argued. And yet cinchona trees proved difficult to transport over land and sea, and did not easily or universally thrive in new tropical climates. As a result of the growing demand and uncertainty around cinchona, as Pratik Chakrabarti has argued, from the late eighteenth century there was ‘a global scientific obsession’ with finding a ‘substitute’ for cinchona, particularly local alternatives in India and China.1
Failure to Launch: Tracing the Trajectory of Democratic Innovation Adoption in Canada
Authors: Mattes Megan , Massie Joanna
Published: December 2024

Canada is regarded as an early adopter of democratic innovations, including the high-profile BC Citizens’ Assembly on Electoral Reform. To what extent has Canada maintained this trajectory? We examine this in the context of breadth and depth by examining trends in adoption over time across Canada and case-level adoption according to the dimensions of influence and temporality. While case studies of Canadian democratic innovations exist, these do not provide analytical capacity to understand trends in the breadth of adoption; we thus contribute a novel dataset of democratic innovations in Canada from 2000 to 2020. To analyze the depth of adoption, we present a two-by-three framework, which we apply to interpret our dataset of Canadian democratic innovations. We find that while there is an increase in the total number of democratic innovations, a low quantity is observed that exhibits high influence and permanence.
Camel tick species distribution in Saudi Arabia and United Arab Emirates using MaxEnt modelling
Authors: Perveen Nighat , Muzaffar Sabir B. , Jaradat Areej , Sparagano Olivier A. , Willingham Arve L.
Published: December 2024

Ticks are important vectors and reservoirs of pathogens causing zoonotic diseases in camels and other livestock, rodents and other small mammals, birds and humans. Hyalomma dromedarii is the most abundant tick species in Saudi Arabia and United Arab Emirates (UAE) affecting primarily camels, and to a lesser extent, other livestock. Species presence data, land use/landcover, elevation, slope and 19 bioclimatic variables were used to model current and future distribution of H. dromedarii ticks using maximum entropy species distribution modelling (MaxEnt.). The model highlighted areas in the northern, eastern and southwestern parts of the study area as highly suitable for ticks. Several variables including land use/land cover (LULC) (53.1%), precipitation of coldest quarter (Bio19) (21.8%), elevation (20.6%), isothermality (Bio3) (1.9%), mean diurnal range [mean of monthly (max temp – min temp)] (Bio2) (1.8%), slope (0.5%), precipitation, seasonality (Bio15) (0.2%) influenced habitat suitability of ticks, predicting high tick density or abundance. Middle of the road scenario (ssp2-4.5) where CO2 levels remain similar to current levels, did not indicate a major change in the tick distributions. This tick distribution model could be used for targeting surveillance efforts and increasing the efficiency and accuracy of public health investigations and vector control strategies.
Networks of care for the modern adolescent
Authors: White Simon R. , Soneson Emma ,   OxWell Study Team, Fazel Mina
Published: December 2024

Background

At a time of increased demand for specialist mental health services, a more nuanced understanding of how adolescents navigate systems of care and support is essential. We mapped ‘networks of care’ to explore patterns of mental health help-seeking alongside the perceived helpfulness of support accessed.

Methods

We examined data from 23 927 adolescents aged 11–18 years who participated in the 2023 OxWell Student Survey, an English school-based, repeated cross-sectional survey of mental health and wellbeing. Students self-reported past-year access to 18 types of support across informal (e.g. friends and family), semi-formal (e.g. school and charities), and formal (e.g. health and social care) domains, alongside how helpful they found the support. We used a network approach to explore interconnections between sources of support accessed and perceived helpfulness.

Results

One in four (27.0%, 6449/23927) adolescents reported past-year access to mental health support, of which 56.7% (3658/6449) reported accessing multiple types. Informal networks were the most commonly accessed (23.1%, 5523/23927), followed by semi-formal (9.7%, 2317/23927) and formal (6.8%, 1623/23927) supports. Informal sources had high acceptability, with around 80–90% reporting them as helpful, whereas child and adolescent mental health services (CAMHS), helplines, and online supports were perceived to be the least helpful. The networks also identified groups who might not be optimally served by current systems, including gender diverse adolescents and adolescents who found mental health support from their parents unhelpful.

Conclusions

Adolescents are accessing mental health support across informal, semi-formal, and formal sources of care. Services can no longer be developed, delivered, or evaluated in isolation from these networks.
On a Mertens-type conjecture for number fields
Authors: HU DANIEL , KANEKO IKUYA , MARTIN SPENCER , SCHILDKRAUT CARL
Published: December 2024

We introduce a number field analogue of the Mertens conjecture and demonstrate its falsity for all but finitely many number fields of any given degree. We establish the existence of a logarithmic limiting distribution for the analogous Mertens function, expanding upon work of Ng. Finally, we explore properties of the generalised Mertens function of certain dicyclic number fields as consequences of Artin factorisation.
Constrictive pericarditis following epicardial pacemaker implant: a diagnostic dilemma
Authors: Khan Naveed , Sen Supratim , Kumar Gaurav
Published: December 2024

Constrictive pericarditis is a rare complication after cardiac surgery. It is mostly seen in adults. We report a case of constrictive pericarditis in a 3-year-old child with right ventricular dysfunction after permanent pacemaker implantation during infancy for congenital complete heart block. Suspicion of constrictive pericarditis must be kept in mind during evaluation.
Bridging the Gap Between Global Weather Prediction and Global Storm‐Resolving Simulation: Introducing the GFDL 6.5‐km SHiELD
Authors: Zhou Linjiong , Harris Lucas , Chen Jan‐Huey , Gao Kun , Cheng Kai‐Yuan , Tong Mingjing , Kaltenbaugh Alex , Morin Matthew , Mouallem Joseph , Chilutti Lauren , Johnston Lily
Published: December 2024

We introduce a 6.5‐km version of the Geophysical Fluid Dynamics Laboratory (GFDL)'s System for High‐resolution prediction on Earth‐to‐Local Domains (SHiELD). This global model is designed to bridge the gap between global medium‐range weather prediction and global storm‐resolving simulation while remaining practical for real‐time forecast. The 6.5‐km SHiELD represents a significant advancement over GFDL's flagship global forecast system, the 13‐km SHiELD. This global model features a holistically‐developed scale‐aware suite of physical parameterizations, stepping into the formidable convective “gray zone” of resolutions below 10 km. Comparative analyses with the 13‐km SHiELD, conducted over a 3‐year hindcast period, highlight noteworthy improvements across global‐scale, regional‐scale, tropical cyclone (TC), and continental convection predictions. In particular, the 6.5‐km SHiELD excels in predicting considerably finer‐scale convective systems associated with large‐scale frontal systems and extratropical cyclones. The predictions of global temperature, wind, cloud, and precipitation are significantly improved in this global model. Regionally, over the contiguous United States and the Maritime Continent, substantial reductions in prediction biases of precipitation, cloud cover, and wind fields are also found. In the mesoscale realm, the model demonstrates prominent improvements in global TC intensity and continental convective precipitation prediction: biases are relieved, and skill is higher. These findings affirm the superiority of the 6.5‐km SHiELD compared to the current 13‐km SHiELD, which will advance weather prediction by successfully addressing both synoptic weather systems and specific storm‐scale phenomena in the same global model.
OXTR-mediated signaling in astrocytes contributes to anxiolysis
Authors: Meinung Carl-Philipp , Boi Laura , Pandamooz Sareh , Mazaud David , Ghézali Grégory , Rouach Nathalie , Neumann Inga D.
Published: December 2024

Astrocytes are an indispensable part of signal processing within the mammalian brain. Thus, the mode of action of a neuropeptide such as oxytocin (OXT) can only be fully understood considering this integral part of the CNS. Here, we show that OXT regulates astrocytic gene expression, intracellular signaling and specific proteins both in vitro and in vivo. This translates into rapid regulation of astroglial structural and functional properties including cytoskeletal plasticity, coverage of synapses and gap-junction coupling. At the molecular level, we identify the previously undescribed Sp1-Gem signaling cascade as the key driver for these cell type-specific OXT effects. Finally at the behavioral level, we found in vivo that OXT requires astrocytes to exert its well described anxiolytic properties within the hypothalamic paraventricular nucleus. Thus, our study points to OXT receptor-expressing astrocytes as a critical component of the brain OXT system.
A phase 2 pilot study of umbilical cord blood infusion as an adjuvant consolidation therapy in elderly patients with acute myeloid leukemia
Authors: Wang Jinzeng , Li Xiaoyang , Liu Ping , Dai Yao , Zhu Hongming , Zhang Yunxiang , Wu Min , Yao Yunying , Liu Mingzhu , Yu Shuting , Jiang Fangying , Wang Shuai , Mu Haoran , Jiao Bo , Yan Hua , Wu Wen , Shen Yang , Li Junming , Wang Shengyue , Ren Ruibao
Published: December 2024

Acute myeloid leukemia (AML) is an aging-related malignancy, with patients aged ≥60 years old facing significantly poorer prognosis. Umbilical cord blood (UCB) has emerged as a promising source with effective anti-aging roles. Here, we conducted a prospective, phase 2, single-arm trial of UCB infusion as an adjuvant consolidation therapy in elderly AML patients (ChiCTR-OPC-15006492). A total of 51 patients were enrolled (median age 66 years; range, 60–75) and received two cycles of consolidation chemotherapy combined with UCB infusion. At a median follow-up of 27.3 months (range, 9.3–100), the median overall survival (OS) was not yet reached and the median event-free survival (EFS) was 72.2 months (range, 5.4–100). The 2-year OS and EFS rates were 76.9% and 62.8%, respectively. No acute graft-versus-host disease (aGVHD) or toxicity-related death occurred in any patient. The median times to platelet and neutrophil recovery were 11.5 days (range, 6–17) and 12.2 days (range, 0–21), respectively. Single-cell RNA sequencing (scRNA-seq) identified enhanced anti-tumor and anti-aging properties of UCB, manifested through activation of immune responses and telomere synthesis/maintenance. These findings suggest that UCB infusion is an effective and safe post-remission adjuvant therapy for elderly AML patients. This study provides evidence that anti-aging therapy may serve as a new and promising dimension in combined cancer treatment.
Comparison of fludarabine/melphalan (FM140) with fludarabine/melphalan/BCNU (FBM110) in patients with relapsed/refractory AML undergoing allogeneic hematopoietic cell transplantation – a registry study on behalf of the EBMT Acute Leukemia Working Party
Authors: Duque-Afonso Jesús , Finke Jürgen , Ngoya Maud , Galimard Jacques-Emmanuel , Schetelig Johannes , Eder Matthias , Rösler Wolf , Bug Gesine , Neubauer Andreas , Edinger Matthias , Wulf Gerald. G. , Jindra Pavel , Einsele Hermann , Stelljes Matthias , Selleslag Dominik , Wagner-Drouet Eva Maria , Bunjes Donald , Spyridonidis Alexandros , Brissot Eolia , Nagler Arnon , Ciceri Fabio , Mohty Mohamad
Published: December 2024

The treatment of relapsed/refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The allogeneic hematopoietic cell transplantation (allo-HCT) is frequently performed as salvage therapy. Reduced intensity conditioning protocols have been developed with the aim of reducing the leukemia burden without increasing their toxicity. We compared the reduced intensity conditioning FM140 (fludarabine, 150 mg/m2; melphalan 140 mg/m2) with FBM110 (fludarabine 150 mg/m2; BCNU, also known as carmustine, 300–400 mg/m2; and melphalan 110 mg/m2). From the European Bone Marrow Transplantation (EBMT) Acute Leukemia Working Party registry, we identified 293 adult patients (FM140, n = 118 and FBM110, n = 175) with AML with relapsed/refractory disease prior to allo-HCT. There were some differences such as age (FM140 = 59.5 years vs. FBM110 = 65.1 years, p < 0.001) and graft-versus-host disease (GvHD) prophylaxis based on in vivo T-cell depletion (TCD, FM140 = 39% vs. FBM110 = 75%, p < 0.001). No differences were observed between FM140- and FBM110-treated patients regarding overall survival (OS) (2-year OS: 39.3% vs. 45.7%, p = 0.58), progression-free survival (PFS) (2-year PFS: 36.1% vs. 37.3%, p = 0.69), non-relapse mortality (NRM) (2-year NRM: 15.3% vs. 25.7%, p = 0.10) and relapse incidence (RI) (2-year RI: 48.6% vs. 37.0%, p = 0.7). In conclusion, despite differences in age and GvHD prophylaxis, AML patients with active disease undergoing allo-HCT after FBM110 conditioning showed similar outcomes compared to FM140.
17β-estradiol alleviated ferroptotic neuroinflammation by suppressing ATF4 in mouse model of Parkinson’s disease
Authors: Wang Guoming , Zhuang Wenxin , Zhou Yijun , Wang Xu , Li Zhenfeng , Liu Chuanliang , Li Wentong , He Maotao , Lv E.
Published: December 2024

Neuroinflammation induced by activation of microglial is a vital contributor to progression of Parkinson’s disease (PD), emerging evidences suggested that ferroptosis played a pivotal role in microglial activation and subsequent dopaminergic neuron loss. Nevertheless, the fundamental pathogenesis of that ferroptosis contributes to PD is not yet sufficiently understood. Based on GEO dataset, ferroptosis related genes were found to be enriched in PD patients and MPTP mouse model of PD, among them, ATF4 was found to be dramatically differentially expressed. In our study, ectopic expression of ATF4 augmented MPP+-induced cytotoxic and activation of BV2 cells with upregulated intracellular L-ROS, TLR4 and pNF-κB. Ectopic ATF4 effectively promoted transformation of microglial into M1 pro-inflammatory phenotype. 17β-estradiol (E2) attenuated expression of ATF4 in BV2 cells, silence of ATF4 enhanced protective effect of E2 on MPP+-treated BV2 cells. In MPTP-induced PD mouse model, administration of E2 further abated expression of ATF4 and inhibited expressions of pro-inflammatory cytokines and activation of TLR4/NF-κB pathway. Overall, E2 effectively counteracted TLR4/NF-κB signaling pathway by restraining ATF4 and inhibited inflammatory response triggered by ferroptosis, ultimately exerted anti-PD effects.
The EstroGene2.0 database for endocrine therapy response and resistance in breast cancer
Authors: Li Zheqi , Chen Fangyuan , Chen Li , Liu Jiebin , Tseng Danielle , Hadi Fazal , Omarjee Soleilmane , Kishore Kamal , Kent Joshua , Kirkpatrick Joanna , D’Santos Clive , Lawson Mandy , Gertz Jason , Sikora Matthew J. , McDonnell Donald P. , Carroll Jason S. , Polyak Kornelia , Oesterreich Steffi , Lee Adrian V.
Published: December 2024

Endocrine therapies targeting the estrogen receptor (ER/ESR1) are the cornerstone to treat ER-positive breast cancers patients, but resistance often limits their effectiveness. Notable progress has been made although the fragmented way data is reported has reduced their potential impact. Here, we introduce EstroGene2.0, an expanded database of its precursor 1.0 version. EstroGene2.0 focusses on response and resistance to endocrine therapies in breast cancer models. Incorporating multi-omic profiling of 361 experiments from 212 studies across 28 cell lines, a user-friendly browser offers comprehensive data visualization and metadata mining capabilities (https://estrogeneii.web.app/). Taking advantage of the harmonized data collection, our follow-up meta-analysis revealed transcriptomic landscape and substantial diversity in response to different classes of ER modulators. Endocrine-resistant models exhibit a spectrum of transcriptomic alterations including a contra-directional shift in ER and interferon signalings, which is recapitulated clinically. Dissecting multiple ESR1-mutant cell models revealed the different clinical relevance of cell model engineering and identified high-confidence mutant-ER targets, such as NPY1R. These examples demonstrate how EstroGene2.0 helps investigate breast cancer’s response to endocrine therapies and explore resistance mechanisms.
Chiral Floquet engineering on topological fermions in chiral crystals
Authors: Fan Benshu , Duan Wenhui , Rubio Angel , Tang Peizhe
Published: December 2024

The interplay of chiralities in light and quantum matter provides an opportunity to design and manipulate chirality-dependent properties in quantum materials. Herein we report the chirality-dependent Floquet engineering on topological fermions with the high Chern number in chiral crystal CoSi via circularly polarized light (CPL) pumping. Intense light pumping does not compromise the gapless nature of topological fermions in CoSi, but displaces the crossing points in momentum space along the direction of light propagation. The Floquet chirality index is proposed to signify the interplay between the chiralities of topological fermion, crystal, and incident light, which determines the amplitudes and directions of light-induced momentum shifts. Regarding the time-reversal symmetry breaking induced by the CPL pumping, momentum shifts of topological fermions result in the birth of transient anomalous Hall signals in non-magnetic CoSi within an ultrafast time scale, which Mid-infrared (IR) pumping and terahertz (THz) Kerr or Faraday probe spectroscopy could experimentally detect. Our findings provide insights into exploring novel applications in optoelectronic devices by leveraging the degree of freedom of chirality in the non-equilibrium regime.
Artificial intelligence in risk prediction and diagnosis of vertebral fractures
Authors: Namireddy Srikar R. , Gill Saran S. , Peerbhai Amaan , Kamath Abith G. , Ramsay Daniele S. C. , Ponniah Hariharan Subbiah , Salih Ahmed , Jankovic Dragan , Kalasauskas Darius , Neuhoff Jonathan , Kramer Andreas , Russo Salvatore , Thavarajasingam Santhosh G.
Published: December 2024

With the increasing prevalence of vertebral fractures, accurate diagnosis and prognostication are essential. This study assesses the effectiveness of AI in diagnosing and predicting vertebral fractures through a systematic review and meta-analysis. A comprehensive search across major databases selected studies utilizing AI for vertebral fracture diagnosis or prognosis. Out of 14,161 studies initially identified, 79 were included, with 40 undergoing meta-analysis. Diagnostic models were stratified by pathology: non-pathological vertebral fractures, osteoporotic vertebral fractures, and vertebral compression fractures. The primary outcome measure was AUROC. AI showed high accuracy in diagnosing and predicting vertebral fractures: predictive AUROC = 0.82, osteoporotic vertebral fracture diagnosis AUROC = 0.92, non-pathological vertebral fracture diagnosis AUROC = 0.85, and vertebral compression fracture diagnosis AUROC = 0.87, all significant (p < 0.001). Traditional models had the highest median AUROC (0.90) for fracture prediction, while deep learning models excelled in diagnosing all fracture types. High heterogeneity (I² > 99%, p < 0.001) indicated significant variation in model design and performance. AI technologies show considerable promise in improving the diagnosis and prognostication of vertebral fractures, with high accuracy. However, observed heterogeneity and study biases necessitate further research. Future efforts should focus on standardizing AI models and validating them across diverse datasets to ensure clinical utility.
Testing perioperative meloxicam analgesia to enhance welfare while preserving model validity in an inflammation-induced seizure model
Authors: Weiß Edna , Pauletti Alberto , Egilmez Asya , Bröer Sonja
Published: December 2024

Despite the international effort to improve laboratory animal welfare through the 3R principles (Reduce, Refine, Replace), many scientists still fail to implement and report their assessment of pain and well-being, likely due to concerns regarding the potential effects of analgesics on experimental outcomes. This study aimed to determine whether refining our viral encephalitis model with perioperative analgesia could enhance well-being and recovery after intracerebral virus infection without impacting disease outcomes. We routinely use the Theiler’s Murine Encephalomyelitis Virus (TMEV) model to study virus-induced epilepsy. Given the crucial role of immune cell activation in acute seizure development, we evaluated the effects of the non-steroidal anti-inflammatory drug (NSAID) meloxicam on inflammation, neurodegeneration, and neuronal cell proliferation at 7 days post-infection (dpi). Overall, the impact of virus infection on well-being was less severe than anticipated, and meloxicam treatment did not affect well-being or nest building behavior in TMEV-infected mice. Furthermore, meloxicam treatment did not influence key experimental readouts such as seizure burden, central inflammatory response, neurodegeneration, or neuronal proliferation within the hippocampus. Notably, animals experiencing seizures displayed heightened inflammatory responses and neurodegeneration, which were not influenced by meloxicam treatment. In summary, perioperative analgesia did not compromise key outcome measures such as seizure frequency, inflammation, and neurodegeneration or -regeneration in the TMEV model. However, it also did not add any significant benefits to well-being in the first week after intracranial injections.