bluuebunny/crossref_metadata_2025 huggingface dataset:
The Castellated Façade of Montepulciano’s Palazzo Comunale, 1440: An Image of Florentine Territorial Hegemony
Authors: Chao Koching
Published: November 2023

This article explores the connection between the castellated façade of Montepulciano’s Palazzo Comunale and Florence’s development into a territorial state in the mid-fifteenth century. In 1440, the comune of Montepulciano commissioned a new façade for its town hall from the prominent Florentine architect Michelozzo. While scholars have widely accepted Michelozzo’s design as an imitation of Florence’s Palazzo della Signoria, hitherto unpublished documents preserved in Montepulciano’s Biblioteca Comunale e Archivio Storico ’Piero Calamandrei’ enable further interpretation of the town hall’s fortress-like profile from a geopolitical and military perspective. According to the new textual evidence, Montepulciano maintained a close cooperation with the Dieci di Balìa — Florence’s war committee — from the late 1430s onwards and contributed to its military efforts against Milan, which climaxed in the battle of Anghiari the same year that the façade renovation was initiated. In view of Florence’s decisive victory in the battle, this article argues that the familiar castellated appearance of the new façade was a celebratory manifestation of the city’s military pride and that this was shared by the town. The architecture of the town hall can also be seen as testifying to the role played by castellation in expressing Florence’s territorial ideology.
Identifying and Dating Mont Saint-Michel’s Early Monastic Buildings, c. 1070–1228
Authors: Gandy George N.
Published: November 2023

One of the best-known monastic settlements of western Europe, the abbey of Mont Saint-Michel occupies the summit of a prodigiously steep island site off the coast of Normandy in northern France. The church was built between 1023 and c. 1080–85. The monastic buildings, to the north of the church, were arranged vertically as much as horizontally, reflecting the constraints of the site. They appear to have comprised three adjacent and interconnecting buildings, two of three storeys, the other of two. However, two of these three ranges were overbuilt in the early thirteenth century by an ambitious development which became known as the Merveille (c. 1212–28). This article seeks to identify the buildings that the Merveille replaced and thus the entire complex as it existed in the twelfth century. This inevitably involves a certain amount of speculation and perhaps for this reason the complex has hitherto been largely ignored, important though it is for an understanding of the abbey’s early history. The article also discusses other building projects relevant to the monks, such as the cemetery, the twelfth-century Hôtellerie and the thirteenth-century infirmary and mortuary chapel, and analyses the genesis of the Merveille. Among the findings or propositions are that the monks’ cemetery was housed in what may once have been a ducal palace; that the abbey’s cloister occupied the same position as it does today but was at a lower, mezzanine level and was smaller than the present cloister; that the chapter house and infirmary were probably adjacent to the west walk of the cloister; that the original provision for kitchen and cellar and for sleeping space was inadequate; and that the Merveille, which was the work of Abbot Raoul des Îles, was not entirely new-build as sometimes thought, but a transformation and redevelopment of buildings that already existed.
Building the First Christian Church for the Shanghai Expatriate Community: Trinity Church, 1847–62
Authors: Zheng Hongbin , Campbell James W. P.
Published: November 2023

Trinity Church, built in the British concession at Shanghai in 1847–48, was the first Christian church erected for the foreign community there. Although it was an important centre of worship for that community, within twenty years it had collapsed and been demolished; it was replaced by the current church, erected to designs by George Gilbert Scott between 1866 and 1869, since when the original church has been largely forgotten. However, the failures in construction that led to its demolition are instructive. Drawing on the transnational knowledge network of the British empire, especially the experience of the existing British settlements at Hong Kong and Canton (Guangzhou) a thousand miles to the south, the projectors of the building attempted to combine western and Chinese constructional traditions and practices. The colonists believed they were educating the workforce in the (purportedly superior) methods of the west, but they succeeded only in producing a constructional hybrid, with disastrous consequences. As a work of construction, the first Trinity Church reveals the problematic nature of building production in early treaty-port era Shanghai, while as a cultural construct it stands as a failed example of the so-called pedagogy of imperialism.
Taming the Leviathan or dismantling democratic government? Evolving political ideas on spontaneous income tax integration in the European Union
Authors: Jaakkola Jussi
Published: November 2023

By the turn of the 1990s, tax competition among national governments had emerged as a powerful law-making practice. The possibility of tax competition essentially depends on the design of transnational law, such as European law. This Article examines the change of economic, political, and legal ideas that have shaped responses by the European Communities and the European Union (EU) to income tax competition. It asserts that under the post-war settlement of embedded liberalism and moderate market integration, tax competition was not perceived as a fully developed phenomenon. Under increased cross-border economic mobility in the 1990s, tax competition became a critical concern but received a liberal and permissive reaction from the EU. In the 2010s, governing tax competition in the EU became a more vital topic. Still, in the contemporary EU, turning political ideas into legal rules capable of addressing tax competition remains hampered by the EU law requirement of unanimous decision-making. The European choice of whether and how to address tax competition involves profoundly contrasting ideas on the means by which to govern the socio-economic reality. The decision between spontaneous and regulated income tax integration is therefore a salient political question, but the unanimity rule undermines political contestation over tax competition and over the European model of fiscal federalism. The Article comes to a close by reflecting on whether the EU legal order offers means to overcome the deadlock of unanimity and whether it could accommodate a more properly political contestation over the Europeanisation of income taxation.
Minimum Legal Standards in Reparation Processes for Colonial Crimes: The Case of Namibia and Germany
Authors: Theurer Karina
Published: November 2023

In 2021, the German and Namibian governments published a Joint Declaration as a result of their negotiations on reparations. Ovaherero and Nama representatives strongly criticized the violation of their participation rights during the negotiations and the reproduction of colonial racism. In 2023, a lawsuit was filed with the Namibian High Court. This litigation could become a milestone in the history of legal struggles for reparations for colonial crimes worldwide. In addition to the litigation, several United Nations Special Rapporteurs were contacted and published their joint communication in April 2023, essentially confirming the lack of effective participation and the obligation to grant reparations.

This Article gives an overview of the most important historical events during German colonial rule and the most significant efforts to legally come to terms with it since 2006. It analyzes the main legal issues in this context: Have the acts committed by German colonial troops violated the laws in force at the time? Is the current application of the doctrine of intertemporal law by the governments a reproduction of racism? Might it be a new act of racism? What challenges and limits do courts face when they attempt to retrospectively reconstruct legal systems and legal norms in force 100 years ago? Does the German state have a legal obligation to enter into negotiations over reparations? What participation rights do affected communities have in processes of legal reappraisal of colonialism?

In view of the growing demands for reparations worldwide, it is timely to deal with the underlying legal issues in an exemplary manner. The legal intervention of the German-Namibian reappraisal could set a precedent. The Article aims at establishing minimum legal standards for reparations processes for colonial crimes worldwide.
Horizontal FDI and Internal R&D of Local Firms in Emerging Economies: A Coopetition Perspective
Authors: Xia Jun , Gu Qian Cecilia , Jiang Marshall S. , Lin Zhouyu
Published: November 2023

This study advances a coopetition perspective to argue that an intangibility gap, defined as the difference in intangible asset intensity between industry-frontier foreign firms and local firms, generates both competitive threats and cooperative opportunities for local firms. Thus, an intangibility gap may affect local firms’ internal research and development (R&D) efforts beyond a linear, catching-up way of thinking. Using a sample of manufacturing firms in China, we find that intangibility gap has an inverted U-shaped relationship with the internal R&D intensity of local firms such that a moderate intangibility gap is more likely to stimulate local firms’ R&D than a small or large intangibility gap. Moreover, the results show that export intensity and state ownership of local firms serve as two boundary conditions under which the inverted U-shaped relationship becomes less and more pronounced, respectively.
Face Detection, Tracking, and Classification from Large-Scale News Archives for Analysis of Key Political Figures
Authors: Girbau Andreu , Kobayashi Tetsuro , Renoust Benjamin , Matsui Yusuke , Satoh Shin’ichi
Published: November 2023

Analyzing the appearances of political figures in large-scale news archives is increasingly important with the growing availability of large-scale news archives and developments in computer vision. We present a deep learning-based method combining face detection, tracking, and classification, which is particularly unique because it does not require any re-training when targeting new individuals. Users can feed only a few images of target individuals to reliably detect, track, and classify them. Extensive validation of prominent political figures in two news archives spanning 10 to 20 years, one containing three U.S. cable news and the other including two major Japanese news programs, consistently shows high performance and flexibility of the proposed method. The codes are made readily available to the public.
Effects of the Chinese Heart-Healthy Diet (Sichuan Cuisine Version) on the 10-year CVD risk and vascular age: a randomised controlled feeding trial
Authors: Su Danping , Chen Hong , Guo Yishan , Feng Qiuyu , Yang Mengtong , Cai Congjie , Zhang Yiqi , Wu Yangfeng , Wang Yanfang , Zeng Guo
Published: November 2023

Sichuan cuisine was previously fitted into the Chinese Heart-Healthy Diet (CHH) trial to verify the antihypertensive effect. Whether the modified Sichuan diet lessens cardiovascular disease (CVD) is not fully explored. We aimed to estimate the effects of the Sichuan version of CHH diet (CHH diet-SC) on the 10-year risk of CVD and vascular age. A single-blinded randomised controlled feeding trial was conducted. General CVD prediction model was used in manners of intention-to-treat and per-protocol set. After a 7-d run-in period, fifty-three participants with pre- and grade I hypertension from local communities were randomised and provided with either CHH diet-SC (n 27) or a control diet (n 26) for 4 weeks. Mean absolute and relative estimated CVD risks were reduced by 4·5 % and 27·9 % in the CHH diet-SC group, and the between-group relative risk reduction was 19·5 % (P < 0·001) using linear mixed-effects models. The sensitivity analysis with datasets and models showed consistent results, and pre-specified factors were not associated with the intervention effects. The vascular age of CHH-SC group was theoretically 4·4 years younger than that of the control group after intervention. Compared with a typical diet, adopting the CHH diet-SC over 1 month significantly reduced 10-year CVD risks and vascular ages among local adults with mild hypertension.
Cartwheel or Ladder? Reconsidering Sinhala Caste
Authors: Winslow Deborah
Published: November 2023

Is Sinhala caste simply a weak regional variant of Hindu caste or is it something else entirely? This essay argues that Sinhala caste as found in the territory of the former Kandyan Kingdom has had a distinctive ontology and retains its unique character. The essay begins with an overview of textual, genetic, and archaeological evidence for the origins of caste on the subcontinent. It then turns to the island and the fourth century CE bifurcation of Sinhala society into “high” and “low”; this duality’s persistence into the second millennium CE; its elaboration in the Kandyan Kingdom’s bureaucratic political economy; and the dissonance between this Sinhala “cartwheel” model of collective inequality and the Brahmanical “ladder” of colonial powers and the Sinhala elite. The essay concludes by examining how the ongoing discordance between these two models of Sinhala caste plays out in people’s lives through a case study of a non-elite caste community.
Tropical invariants for binary quintics and reduction types of Picard curves
Authors: Helminck Paul Alexander , El Maazouz Yassine , Kaya Enis
Published: November 2023

In this paper, we express the reduction types of Picard curves in terms of tropical invariants associated with binary quintics. We also give a general framework for tropical invariants associated with group actions on arbitrary varieties. The problem of finding tropical invariants for binary forms fits in this general framework by mapping the space of binary forms to symmetrized versions of the Deligne–Mumford compactification
$\overline{M}_{0,n}$
.
Beam current from downramp injection in electron-driven plasma wakefields
Authors: Hue Céline , Golovanov Anton , Tata Sheroy , Corde Sébastien , Malka Victor
Published: November 2023

We study the stability of plasma wake wave and the properties of density-downramp injection in an electron-driven plasma accelerator. In this accelerator type, a short high-current electron bunch (generated by a conventional accelerator or a laser–wakefield acceleration stage) drives a strongly nonlinear plasma wake wave (blowout), and accelerated electrons are injected into it using a sharp density transition which leads to the elongation of the wake. The accelerating structure remains highly stable until the moment some electrons of the driver reach almost zero energy, which corresponds to the best interaction length for optimal driver-to-plasma energy transfer efficiency. For a particular driver, this efficiency can be optimised by choosing appropriate plasma density. Studying the dependence of the current of the injected bunch on driver and plasma parameters, we show that it does not depend on the density downramp length as long as the condition for trapping is satisfied. Most importantly, we find that the current of the injected bunch primarily depends on just one parameter which combines both the properties of the driver (its current and duration) and the plasma density.
Towards capsule endoscope locomotion in large volumes: design, fuzzy modeling, and testing
Authors: Peker Furkan , Beşer Mert Alperen , Işıldar Ecem , Terzioğlu Yavuz , Erten Ahmet Can , Kumbasar Tufan , Ferhanoğlu Onur
Published: November 2023

We present the design and deployment of a capsule endoscope via external electromagnets for locomotion in large volumes alongside its digital twin implementation based on interval type-2 fuzzy logic systems (IT2-FLSs). To perform locomotion, we developed an external mechanism comprising five external electromagnets on a two-dimensional translational platform that is to be placed underneath the patients’ bed and integrated multiple Neodymium magnets into the capsule. The interaction between the central bottom external electromagnet and the internal magnet forms a fixed body frame at the capsule center, allowing rotation. The interaction between the external electromagnets and the two internal magnets results in rotation. The elevation of the capsule is accomplished due to the interaction between the upper external electromagnet and the internal magnets. Through simulations, we model the capsule rotation as a function of torque and drive voltages. We validated the proposed locomotion approach experimentally and observed that the results are highly nonlinear and uncertain. Thus, we define a regression problem in which IT2-FLSs, capable of representing nonlinearity and uncertainty, are learned. To verify the proposed locomotion approach and test the IT2-FLS, we leverage our experimental effort to a stomach phantom and finally to an ex vivo bovine stomach. The experimental results validate the locomotion capability and show that the IT2-FLS can capture uncertainties while resulting in satisfactory prediction performance. To showcase the benefit in a clinical scenario, we present a digital twin implementation of the proposed approach in a virtual environment that can link physical and virtual worlds in real time.
Must Prioritarians be Antiegalitarian?
Authors: Alexandrie Gustav
Published: November 2023

It has been argued that Prioritarianism violates Risky Non-Antiegalitarianism, a condition stating roughly that an alternative is socially better than another if it both makes everyone better off in expectation and leads to more equality. I show that Risky Non-Antiegalitarianism is in fact compatible with Prioritarianism as ordinarily defined, but that it violates some other conditions that may be attractive to prioritarians. While I argue that the latter conditions are not core principles of Prioritarianism, the choice between these conditions and Risky Non-Antiegalitarianism nonetheless constitutes an important intramural debate for prioritarians.
CODIMENSION ONE FOLIATIONS IN POSITIVE CHARACTERISTIC
Authors: Mendson Wodson , Pereira Jorge Vitório
Published: November 2023

We investigate the geometry of codimension one foliations on smooth projective varieties defined over fields of positive characteristic with an eye toward applications to the structure of codimension one holomorphic foliations on projective manifolds.
A review of wind-driven hydrodynamics in large shallow lakes: Importance, process-based modeling and perspectives
Authors: Zhang Chen , Chen Lingwei
Published: November 2023

In many large shallow lakes across the globe, the surface wind field drives the hydrodynamic process directly through the momentum and energy exchange at the air–water interface. Numerous field measurements, experiments and modeling show that wind-driven hydrodynamic disturbances have profound impacts on the structure and function of lake ecosystems. In this article, we review the response of the shallow lake to the wind-driven wave and flow field, which may accelerate the sediment resuspension and nutrient cycling and, in turn, affect the concentrations of nutrients and dissolved oxygen. Furthermore, the life activities of bacterioplankton, plankton and fish in the aquatic ecosystem are closely related to these water-quality factors. Although we have a developed understanding of the physical processes and biogeochemical cycles of lakes by process-based modeling, the most basic wind-driven hydrodynamic process in some lake models is imprecise. Comprehensive results of physical parameterization, including the wind stress and wind drag coefficient, with their mathematical expressions for depicting the wind-driven force in the hydrodynamic model of lakes are synthesized. Some of these expressions are empirically determined without considering the dynamic environment, and expressions based on physical mechanisms have been widely recognized. Additionally, the adaptation standard of wind-driven force parameterizations to inland lake models under light winds is provided. This article highlights the importance of heterogeneous wind field variability and suggests future studies on the wind fields in extreme climates, which could also cause damage to deep lake ecosystems and the biodiversity effects of wind wave turbulence.
Investigation of inquiries on weed control efficacy of XtendiMax® herbicide with VaporGrip® technology
Authors: Varanasi Aruna , Singh Daljit , Krebel Jenny , Herrmann Jeffrey , Willis John , Elmore Greg , Fischer Joshua , Witten Ty , Head Graham , Aradhya Chandrashekar
Published: November 2023

Herbicide resistance in weeds significantly threatens crop production in the United States. The introduction of dicamba-resistant soybean and cotton stacked with other herbicide tolerance traits has provided farmers with the flexibility of having multiple herbicide options to diversify their weed management practices and delay resistance evolution. XtendiMax® herbicide with VaporGrip® Technology is a dicamba formulation registered for use on dicamba-resistant soybean and cotton crops by the U.S. Environmental Protection Agency (EPA). One of the terms of its registration includes an evaluation of inquiries on reduced weed control efficacy by growers or users of XtendiMax for suspected weed resistance. A total of 3,555 product performance inquiries (PPIs) were received from 2018 to 2021 regarding reduced weed control efficacy by dicamba. Following the criteria recommended by EPA for screening of suspected resistance in the field, a total of 103 weed accessions from 63 counties in 13 states were collected for greenhouse testing over those 4 yr. Weed accessions for greenhouse testing were collected only in states where resistance to dicamba was not yet confirmed in the weed species under investigation. The accessions, which consisted primarily of waterhemp and Palmer amaranth, were treated with dicamba at rates of 560 g ae ha−1 and 1,120 g ae ha−1. All weed accessions, except for one accession each of Palmer amaranth and waterhemp, were controlled by ≥90% with dicamba at 21 d after treatment in the greenhouse.
Suchtprävention in der Schule
Authors: Weichold Karina , Blumenthal Anja , Kilian Anne , Silbereisen Rainer K.
Published: November 2023

Das Lebenskompetenzenprogramm IPSY (Information + Psychosoziale Kompetenz = Schutz) wurde für die Klassenstufen 5–7 basierend auf dem aktuellen Forschungsstand zur Entstehung von jugendlichem Substanzmissbrauch entwickelt und als eines der wenigen Lebenskompetenzprogramme weltweit auch langfristig mit Bezug auf Substanzkonsum erfolgreich evaluiert. Das Programm fördert darüber hinaus nachweislich Lebenskompetenzen und die Bindung an die Schule bei Jugendlichen. Auch das Miteinander im Klassenverband wird positiv beeinflusst.
Das Buch enthält eine hoch strukturierte, praktische und nutzerfreundliche Anleitung zur Durchführung des Programms im Schulalltag und eine Zusammenfassung der theoretischen Grundlagen sowie der Befunde zur Durchführbarkeit, Akzeptanz und Effektivität. Alle Arbeitsmaterialien können nach erfolgter Registrierung von der Website des Hogrefe Verlags heruntergeladen werden.
Für die aktuelle Neuauflage des Werkes wurde die Handreichung zum IPSY-Programm umfassend modernisiert und aktuelle Forschungsbefunde zur Evaluation ergänzt. Dazu flossen in die Überarbeitung Erkenntnisse zu den Gelingensbedingungen der Implementation des Programms in Schulen aus ganz Deutschland ein.
30×30 biodiversity gains rely on national coordination
Authors: Eckert Isaac , Brown Andrea , Caron Dominique , Riva Federico , Pollock Laura J.
Published: November 2023

Global commitments to protect 30% of land by 2030 present an opportunity to combat the biodiversity crisis, but reducing extinction risk will depend on where countries expand protection. Here, we explore a range of 30×30 conservation scenarios that vary what dimension of biodiversity is prioritized (taxonomic groups, species-at-risk, biodiversity facets) and how protection is coordinated (transnational, national, or regional approaches) to test which decisions influence our ability to capture biodiversity in spatial planning. Using Canada as a model nation, we evaluate how well each scenario captures biodiversity using scalable indicators while accounting for climate change, data bias, and uncertainty. We find that only 15% of all terrestrial vertebrates, plants, and butterflies (representing only 6.6% of species-at-risk) are adequately represented in existing protected land. However, a nationally coordinated approach to 30×30 could protect 65% of all species representing 40% of all species-at-risk. How protection is coordinated has the largest impact, with regional approaches protecting up to 38% fewer species and 65% fewer species-at-risk, while the choice of biodiversity incurs much smaller trade-offs. These results demonstrate the potential of 30×30 while highlighting the critical importance of biodiversity-informed national strategies.
Enzymatic β-elimination in natural product O- and C-glycoside deglycosylation
Authors: Bitter Johannes , Pfeiffer Martin , Borg Annika J. E. , Kuhlmann Kirill , Pavkov-Keller Tea , Sánchez-Murcia Pedro A. , Nidetzky Bernd
Published: November 2023

Biological degradation of natural product glycosides involves, alongside hydrolysis, β-elimination for glycosidic bond cleavage. Here, we discover an O-glycoside β-eliminase (OGE) from Agrobacterium tumefaciens that converts the C3-oxidized O-β-d-glucoside of phloretin (a plant-derived flavonoid) into the aglycone and the 2-hydroxy-3-keto-glycal elimination product. While unrelated in sequence, OGE is structurally homologous to, and shows effectively the same Mn2+ active site as, the C-glycoside deglycosylating enzyme (CGE) from a human intestinal bacterium implicated in β-elimination of 3-keto C-β-d-glucosides. We show that CGE catalyzes β-elimination of 3-keto O- and C-β-d-glucosides while OGE is specific for the O-glycoside substrate. Substrate comparisons and mutagenesis for CGE uncover positioning of aglycone for protonic assistance by the enzyme as critically important for C-glycoside cleavage. Collectively, our study suggests convergent evolution of active site for β-elimination of 3-keto O-β-d-glucosides. C-Glycoside cleavage is a specialized feature of this active site which is elicited by substrate through finely tuned enzyme-aglycone interactions.
Covariance patterns between sleep health domains and distributed intrinsic functional connectivity
Authors: Wang Yulin , Genon Sarah , Dong Debo , Zhou Feng , Li Chenyu , Yu Dahua , Yuan Kai , He Qinghua , Qiu Jiang , Feng Tingyong , Chen Hong , Lei Xu
Published: November 2023

Sleep health is both conceptually and operationally a composite concept containing multiple domains of sleep. In line with this, high dependence and interaction across different domains of sleep health encourage a transition in sleep health research from categorical to dimensional approaches that integrate neuroscience and sleep health. Here, we seek to identify the covariance patterns between multiple sleep health domains and distributed intrinsic functional connectivity by applying a multivariate approach (partial least squares). This multivariate analysis reveals a composite sleep health dimension co-varying with connectivity patterns involving the attentional and thalamic networks and which appear relevant at the neuromolecular level. These findings are further replicated and generalized to several unseen independent datasets. Critically, the identified sleep-health related connectome shows diagnostic potential for insomnia disorder. These results together delineate a potential brain connectome biomarker for sleep health with high potential for clinical translation.
In situ imaging of the atomic phase transition dynamics in metal halide perovskites
Authors: Ma Mengmeng , Zhang Xuliang , Chen Xiao , Xiong Hao , Xu Liang , Cheng Tao , Yuan Jianyu , Wei Fei , Shen Boyuan
Published: November 2023

Phase transition dynamics are an important concern in the wide applications of metal halide perovskites, which fundamentally determine the optoelectronic properties and stabilities of perovskite materials and devices. However, a more in-depth understanding of such a phase transition process with real atomic resolution is still limited by the immature low-dose electron microscopy and in situ imaging studies to date. Here, we apply an emergent low-dose imaging technique to identify different phase structures (α, β and γ) in CsPbI3 nanocrystals during an in-situ heating process. The rotation angles of PbI6 octahedrons can be measured in these images to quantitatively describe the thermal-induced phase distribution and phase transition. Then, the dynamics of such a phase transition are studied at a macro time scale by continuously imaging the phase distribution in a single nanocrystal. The structural evolution process of CsPbI3 nanocrystals at the particle level, including the changes in morphology and composition, is also visualized with increasing temperature. These results provide atomic insights into the transition dynamics of perovskite phases, indicating a long-time transition process with obvious intermediate states and spatial distribution that should be generally considered in the further study of structure-property relations and device performance.
GATA transcription factors drive initial Xist upregulation after fertilization through direct activation of long-range enhancers
Authors: Ravid Lustig Liat , Sampath Kumar Abhishek , Schwämmle Till , Dunkel Ilona , Noviello Gemma , Limberg Elodie , Weigert Raha , Pacini Guido , Buschow René , Ghauri Afrah , Stötzel Maximilian , Wittler Lars , Meissner Alexander , Schulz Edda G.
Published: November 2023

X-chromosome inactivation (XCI) balances gene expression between the sexes in female mammals. Shortly after fertilization, upregulation of Xist RNA from one X chromosome initiates XCI, leading to chromosome-wide gene silencing. XCI is maintained in all cell types, except the germ line and the pluripotent state where XCI is reversed. The mechanisms triggering Xist upregulation have remained elusive. Here we identify GATA transcription factors as potent activators of Xist. Through a pooled CRISPR activation screen in murine embryonic stem cells, we demonstrate that GATA1, as well as other GATA transcription factors can drive ectopic Xist expression. Moreover, we describe GATA-responsive regulatory elements in the Xist locus bound by different GATA factors. Finally, we show that GATA factors are essential for XCI induction in mouse preimplantation embryos. Deletion of GATA1/4/6 or GATA-responsive Xist enhancers in mouse zygotes effectively prevents Xist upregulation. We propose that the activity or complete absence of various GATA family members controls initial Xist upregulation, XCI maintenance in extra-embryonic lineages and XCI reversal in the epiblast.
Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast
Authors: Bradley Samuel A. , Lehka Beata J. , Hansson Frederik G. , Adhikari Khem B. , Rago Daniela , Rubaszka Paulina , Haidar Ahmad K. , Chen Ling , Hansen Lea G. , Gudich Olga , Giannakou Konstantina , Lengger Bettina , Gill Ryan T. , Nakamura Yoko , de Bernonville Thomas Dugé , Koudounas Konstantinos , Romero-Suarez David , Ding Ling , Qiao Yijun , Frimurer Thomas M. , Petersen Anja A. , Besseau Sébastien , Kumar Sandeep , Gautron Nicolas , Melin Celine , Marc Jillian , Jeanneau Remi , O’Connor Sarah E. , Courdavault Vincent , Keasling Jay D. , Zhang Jie , Jensen Michael K.
Published: November 2023

Monoterpenoid indole alkaloids (MIAs) represent a large class of plant natural products with marketed pharmaceutical activities against a wide range of indications, including cancer, malaria and hypertension. Halogenated MIAs have shown improved pharmaceutical properties; however, synthesis of new-to-nature halogenated MIAs remains a challenge. Here we demonstrate a platform for de novo biosynthesis of two MIAs, serpentine and alstonine, in baker’s yeast Saccharomyces cerevisiae and deploy it to systematically explore the biocatalytic potential of refactored MIA pathways for the production of halogenated MIAs. From this, we demonstrate conversion of individual haloindole derivatives to a total of 19 different new-to-nature haloserpentine and haloalstonine analogs. Furthermore, by process optimization and heterologous expression of a modified halogenase in the microbial MIA platform, we document de novo halogenation and biosynthesis of chloroalstonine. Together, this study highlights a microbial platform for enzymatic exploration and production of complex natural and new-to-nature MIAs with therapeutic potential.
sciCSR infers B cell state transition and predicts class-switch recombination dynamics using single-cell transcriptomic data
Authors: Ng Joseph C. F. , Montamat Garcia Guillem , Stewart Alexander T. , Blair Paul , Mauri Claudia , Dunn-Walters Deborah K. , Fraternali Franca
Published: November 2023

Class-switch recombination (CSR) is an integral part of B cell maturation. Here we present sciCSR (pronounced ‘scissor’, single-cell inference of class-switch recombination), a computational pipeline that analyzes CSR events and dynamics of B cells from single-cell RNA sequencing (scRNA-seq) experiments. Validated on both simulated and real data, sciCSR re-analyzes scRNA-seq alignments to differentiate productive heavy-chain immunoglobulin transcripts from germline ‘sterile’ transcripts. From a snapshot of B cell scRNA-seq data, a Markov state model is built to infer the dynamics and direction of CSR. Applying sciCSR on severe acute respiratory syndrome coronavirus 2 vaccination time-course scRNA-seq data, we observe that sciCSR predicts, using data from an earlier time point in the collected time-course, the isotype distribution of B cell receptor repertoires of subsequent time points with high accuracy (cosine similarity ~0.9). Using processes specific to B cells, sciCSR identifies transitions that are often missed by conventional RNA velocity analyses and can reveal insights into the dynamics of B cell CSR during immune response.
Structure of the transcribing RNA polymerase II–Elongin complex
Authors: Chen Ying , Kokic Goran , Dienemann Christian , Dybkov Olexandr , Urlaub Henning , Cramer Patrick
Published: November 2023

Elongin is a heterotrimeric elongation factor for RNA polymerase (Pol) II transcription that is conserved among metazoa. Here, we report three cryo-EM structures of human Elongin bound to transcribing Pol II. The structures show that Elongin subunit ELOA binds the RPB2 side of Pol II and anchors the ELOB–ELOC subunit heterodimer. ELOA contains a ‘latch’ that binds between the end of the Pol II bridge helix and funnel helices, thereby inducing a conformational change near the polymerase active center. The latch is required for the elongation-stimulatory activity of Elongin, but not for Pol II binding, indicating that Elongin functions by allosterically regulating the conformational mobility of the polymerase active center. Elongin binding to Pol II is incompatible with association of the super elongation complex, PAF1 complex and RTF1, which also contain an elongation-stimulatory latch element.
9-oxo-ODAs suppresses the proliferation of human cervical cancer cells through the inhibition of CDKs and HPV oncoproteins
Authors: Mogi Kazumasa , Koya Yoshihiro , Yoshihara Masato , Sugiyama Mai , Miki Rika , Miyamoto Emiri , Fujimoto Hiroki , Kitami Kazuhisa , Iyoshi Shohei , Tano Sho , Uno Kaname , Tamauchi Satoshi , Yokoi Akira , Shimizu Yusuke , Ikeda Yoshiki , Yoshikawa Nobuhisa , Niimi Kaoru , Yamakita Yoshihiko , Tomita Hiroyuki , Shibata Kiyosumi , Nawa Akihiro , Tomoda Yutaka , Kajiyama Hiroaki
Published: November 2023

Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan, eggplant calyx is a folk remedy used to treat common warts. 9-oxo-(10E,12E)-octadecadienoic acid, isolated from eggplant calyx, may have antitumor effects. This study investigated the antitumor effects of 9-oxo-(10E, 12Z)-octadecadienoic acid and 9-oxo-(10E,12E)-octadecadienoic acid (9-oxo-ODAs) on human cervical cancer cells. 9-oxo-ODAs suppressed the proliferation of human cervical cancer cell lines (HeLa, and SiHa) in a concentration-dependent manner (IC50 = 25–50 µM). FCM analysis revealed that 9-oxo-ODAs induced apoptosis. Transcriptome, proteomics, and enrichment analyses revealed that treatment with 9-oxo-ODAs significantly altered the cell cycle and p53 pathways and decreased cyclin-dependent kinase 1 (CDK1) protein expression. Real-time PCR analysis demonstrated that 9-oxo-ODAs reduced CDK1 mRNA expression in a concentration-dependent manner. In vitro, 9-oxo-ODAs reduced the HPV oncoprotein expression. In ex vivo human cervical cancer tissues, 9-oxo-ODAs decreased CDK1 expression and increased cleaved caspase 3, an apoptosis marker. Further, 9-oxo-ODAs showed the potential to suppressed metastatic formation and growth of cervical cancer in vivo. These findings suggest that 9-oxo-ODAs induce cell cycle arrest and apoptosis in HPV-positive human cervical cancer cells, and this process involves CDK1. Consequently, 9-oxo-ODAs may be potential therapeutic agents for cervical cancer.
Evaluation of optimal methods and ancestries for calculating polygenic risk scores in East Asian population
Authors: Kim Dong Jun , Kang Joon Ho , Kim Ji-Woong , Cheon Myeong Jae , Kim Sun bin , Lee Young Kee , Lee Byung-Chul
Published: November 2023

Polygenic risk scores (PRSs) have been studied for predicting human diseases, and various methods for PRS calculation have been developed. Most PRS studies to date have focused on European ancestry, and the performance of PRS has not been sufficiently assessed in East Asia. Herein, we evaluated the predictive performance of PRSs for East Asian populations under various conditions. Simulation studies using data from the Korean cohort, Health Examinees (HEXA), demonstrated that SBayesRC and PRS-CS outperformed other PRS methods (lassosum, LDpred-funct, and PRSice) in high fixed heritability (0.3 and 0.7). In addition, we generated PRSs using real-world data from HEXA for ten diseases: asthma, breast cancer, cataract, coronary artery disease, gastric cancer, glaucoma, hyperthyroidism, hypothyroidism, osteoporosis, and type 2 diabetes (T2D). We utilized the five previous PRS methods and genome-wide association study (GWAS) data from two biobank-scale datasets [European (UK Biobank) and East Asian (BioBank Japan) ancestry]. Additionally, we employed PRS-CSx, a PRS method that combines GWAS data from both ancestries, to generate a total of 110 PRS for ten diseases. Similar to the simulation results, SBayesRC showed better predictive performance for disease risk than the other methods. Furthermore, the East Asian GWAS data outperformed those from European ancestry for breast cancer, cataract, gastric cancer, and T2D, but neither of the two GWAS ancestries showed a significant advantage on PRS performance for the remaining six diseases. Based on simulation data and real data studies, it is expected that SBayesRC will offer superior performance for East Asian populations, and PRS generated using GWAS from non-East Asian may also yield good results.
Optical valley separation in two-dimensional semimetals with tilted Dirac cones
Authors: Wild Andrew , Mariani Eros , Portnoi M. E.
Published: November 2023

Quasiparticles emerging in crystalline materials can possess a binary flavor known as the valley quantum number which can be used as a basis to encode information in an emerging class of valleytronic devices. Here we show that two-dimensional semimetals with tilted Dirac cones in the electronic band structure exhibit spatial separation of carriers belonging to different valleys under illumination. In stark contrast to gapped Dirac materials this optovalleytronic phenomenon occurs in systems with intact inversion and time-reversal symmetry that host gapless Dirac cones in the band structure, thereby retaining the exceptional graphene-like transport properties. We thus demonstrate that optical valley separation is possible at arbitrarily low photon frequencies including the deep infrared and terahertz regimes with full gate tunability via Pauli blocking. As a specific example of our theory, we predict tunable valley separation in the proposed two-dimensional tilted Dirac cone semimetal 8-Pmmn borophene for incident infrared photons at room temperature. This work highlights the potential of two-dimensional tilted Dirac cone materials as a platform for tunable broadband optovalleytronic applications.
T2 mapping for quantitative assessment of ankle cartilage of weightlifters
Authors: Wu Weibiao , Kang Zhuanzhuan , Mu Di , Zhao Huiyu , Yang Feng
Published: November 2023

The research into the prevention of sports injuries among the population, particularly juveniles, has become crucial due to the increasing participation in physical exercises like fitness. To assess the difference in T2 values of ankle talar cartilage between weightlifters and healthy volunteers using quantitative magnetic resonance imaging (MRI) technique T2 mapping. Study design: Prospective. Prospective evaluation of T2 values of ankle cartilage of 50 weightlifters (30 adults and 20 juveniles) and 100 healthy volunteers (80 adults and 20 juveniles) using Siemens 3.0 T MRI with PDWI, T1WI, and T2 mapping sequences. Three physicians manually divided the talar cartilage of the ankle joint into six regions of interest. Three physicians utilized the anterior and posterior cut edges of the tibial cartilage as markers to identify the corresponding anterior and posterior cut edges of the talar cartilage on the sagittal MRI images. The medial and lateral sides were defined as half of the talar articular surface on the coronal plane. Differences in T2 values in each cartilage region were compared using independent sample T test or Mann–Whitney U test. The T2 values of talar cartilage were significantly increased in the athlete group relative to the volunteer group (35.11 and 31.99, P < 0.001), with the most significant difference observed in the juvenile athlete group compared to the volunteer group (34.42 and 28.73, P < 0.001). There was a significant difference in the T2 value of ankle talar cartilage between weightlifters and healthy volunteers, and juveniles may be more vulnerable to overuse sports injuries. This study contributes to understanding the cartilage health of juvenile athletes and the prevention of sports injuries.
Engineering planar antenna using geometry arrangements for wireless communications and satellite applications
Authors: El-Hakim Hesham A. , Mohamed Hesham A.
Published: November 2023

A triple-band microstrip patch antenna designed for the IEEE 802.16e WiMAX, IEEE 802.11a WLAN, C-band downlink communications, and Ku-band radar recent applications is suggested in this article. The planned antenna operates at 2.45, 6, and 14 GHz resonant frequencies. The antenna fulfilled triple-band physical characteristics covering industrial, scientific, and medical (ISM) bands between (2.1–2.8) GHz; (5.6–6.5) GHz for wireless local area network (WLAN) or ultra-wideband (UWB) services; and 12.7–16 GHz for future two-way 5G:6G either broadcasting or mobile satellite communications. To achieve better return loss performance, parametric studies are carried out using Microwave Studio (CST MWS). The proposed antenna is designed on the FR4 as a hosting medium of total size 46 × 38 × 1.6 mm3, combined with a planar transmission line (T.L.) feed and defected ground structure (DGS). The simulated antenna’s input reflection coefficient (S11) results and the far-field measurements show good agreement. The fabricated prototype achieves peak gain values of 2.8, 3.8, and 4.7 dBi, respectively, and bidirectional radiation characteristics. A comparative study with other recent publications is implemented to validate the consistency of the design.
Mercury and CO2 emissions from artisanal gold mining in Brazilian Amazon rainforest
Authors: Fritz Benjamin , Peregovich Bernhard , da Silva Tenório Lorena , da Silva Alves Adria Cristina , Schmidt Mario
Published: November 2023

The Tapajós River basin in Brazil is one of the world’s regions most affected by artisanal gold mining (ASGM), which is responsible for the release of mercury and high energy consumption. Mercury, mixed with gold-containing materials and then released through heating to extract the gold, can be recovered using a simple distillation device called a retort. Use of these tools has now become standard. In a comprehensive study, we investigated the use of mercury and energy at 47 mining sites in the Tapajós River basin. These included numerous mines that were operated informally or in some cases even illegally and are therefore not accessible to outsiders. Our survey shows that 1.7 kg of mercury are used per kg of gold extracted, of which only about 0.19 kg of mercury is released into the environment when retorts are used. Overall, this means an annual release of at least ≈2.5 tonnes of mercury in the region, even when retorts are used. We also find that ASGM contributes to climate change through energy consumption responsible for the release of about 16,000 kg of CO2 equivalent per kilogram of gold. This means that even artisanal gold mining, which uses retorts, has a major environmental impact.
Structural and functional investigations of syn-copalyl diphosphate synthase from Oryza sativa
Authors: Ma Xiaoli , Xu Haifeng , Tong Yuru , Luo Yunfeng , Dong Qinghua , Jiang Tao
Published: November 2023

The large superfamily of labdane-related diterpenoids is defined by the cyclization of linear geranylgeranyl pyrophosphate (GGPP), catalyzed by copalyl diphosphate synthases (CPSs) to form the basic decalin core, the copalyl diphosphates (CPPs). Three stereochemically distinct CPPs have been found in plants, namely (+)-CPP, ent-CPP and syn-CPP. Here, we used X-ray crystallography and cryo-EM methods to describe different oligomeric structures of a syn-copalyl diphosphate synthase from Oryza sativa (OsCyc1), and provided a cryo-EM structure of OsCyc1D367A mutant in complex with the substrate GGPP. Further analysis showed that tetramers are the dominant form of OsCyc1 in solution and are not necessary for enzyme activity in vitro. Through rational design, we identified an OsCyc1 mutant that can generate ent-CPP in addition to syn-CPP. Our work provides a structural and mechanistic basis for comparing different CPSs and paves the way for further enzyme design to obtain diterpene derivatives with specific chirality.
An AIE-based monofunctional Pt(ii) complex for photodynamic therapy through synergism of necroptosis–ferroptosis
Authors: Zheng Xiaoxue , Liu Minglun , Wu Yanping , Chen Yuncong , He Weijiang , Guo Zijian
Published: November 2023

We report an AIE-based monofunctional Pt(ii) complex with increased singlet oxygen production and negligible dark toxicity. This enters cells via endocytosis, accumulates in lysosomes and produces ROS under light irradiation, causing FSP1-downregulation and cell death by ferroptosis and necroptosis.
Revealing the excited-state dynamics of cytidine and the role of excited-state proton transfer process
Authors: Zhao Li , Geng Xuehui , Han Guoxia , Guo Yahui , Liu Runze , Chen Junsheng
Published: November 2023

The high photostability of DNAs and RNAs is inextricably related to the photochemical and photophysical properties of their building blocks, nucleobases and nucleosides, which can dissipate the absorbed UV light energy in a harmless manner.
Protein charge transfer far from equilibrium: a theoretical perspective
Authors: Castellano Mike , Kaspar Christoph , Thoss Michael , Koslowski Thorsten
Published: November 2023

A combined Monte Carlo and numerical approach permits the computation of the charge transfer characteristics of proteins far from equilibrium.