bluuebunny/crossref_metadata_2025 huggingface dataset:
Seminorm control for ergodic averages with commuting transformations along pairwise dependent polynomials
Authors: FRANTZIKINAKIS NIKOS , KUCA BORYS
Published: January 2023

We examine multiple ergodic averages of commuting transformations with polynomial iterates in which the polynomials may be pairwise dependent. In particular, we show that such averages are controlled by the Gowers–Host–Kra seminorms whenever the system satisfies some mild ergodicity assumptions. Combining this result with the general criteria for joint ergodicity established in our earlier work, we determine a necessary and sufficient condition under which such averages are jointly ergodic, in the sense that they converge in the mean to the product of integrals, or weakly jointly ergodic, in that they converge to the product of conditional expectations. As a corollary, we deduce a special case of a conjecture by Donoso, Koutsogiannis, and Sun in a stronger form.
Demonstration of a petawatt-scale optical parametric chirped pulse amplifier based on yttrium calcium oxyborate
Authors: Sun Meizhi , Kang Jun , Liang Xiao , Zhu Haidong , Yang Qingwei , Gao Qi , Guo Ailin , Zhu Ping , Zhang Panzheng , Li Linjun , Qiu Lijuan , Lu Zhantao , Wang Sheng , Tu Xiaoniu , Xie Xinglong , Zhu Jianqiang
Published: January 2023

As optical parametric chirped pulse amplification has been widely adopted for the generation of extreme intensity laser sources, nonlinear crystals of large aperture are demanded for high-energy amplifiers. Yttrium calcium oxyborate (YCa4O(BO3)3, YCOB) is capable of being grown with apertures exceeding 100 mm, which makes it possible for application in systems of petawatt scale. In this paper, we experimentally demonstrated for the first time to our knowledge, an ultra-broadband non-collinear optical parametric amplifier with YCOB for petawatt-scale compressed pulse generation at 800 nm. Based on the SG-II 5 PW facility, amplified signal energy of approximately 40 J was achieved and pump-to-signal conversion efficiency was up to 42.3%. A gain bandwidth of 87 nm was realized and supported a compressed pulse duration of 22.3 fs. The near-field and wavefront aberration represented excellent characteristics, which were comparable with those achieved in lithium triborate-based amplifiers. These results verified the great potential for YCOB utilization in the future.
Hydrodynamic instabilities of two successive slow/fast interfaces induced by a weak shock
Authors: Liang Yu , Luo Xisheng
Published: January 2023

Shock-induced instability developments of two successive interfaces have attracted much attention, but remain a difficult problem to solve. The feedthrough and reverberating waves between two successive interfaces significantly influence the hydrodynamic instabilities of the two interfaces. The evolutions of two successive slow/fast interfaces driven by a weak shock wave are examined experimentally and numerically. First, a general one-dimensional theory is established to describe the movements of the two interfaces by studying the rarefaction waves reflected between the two interfaces. Second, an analytical, linear model is established by considering the arbitrary wavenumber and phase combinations and compressibility to quantify the feedthrough effect on the Richtmyer–Meshkov instability (RMI) of two successive slow/fast interfaces. The feedthrough significantly influences the RMI of the two interfaces, and even leads to abnormal RMI (i.e. phase reversal of a shocked slow/fast interface is inhibited) which is the first observational evidence of the abnormal RMI provided by the present study. Moreover, the stretching effect and short-time Rayleigh–Taylor instability or Rayleigh–Taylor stabilisation imposed by the rarefaction waves on the two interfaces are quantified considering the two interfaces’ phase reversal. The conditions and outcomes of the freeze-out and abnormal RMI caused by the feedthrough are summarised based on the theoretical model and numerical simulation. A specific requirement for the simultaneously freeze-out of the instability of the two interfaces is proposed, which can potentially be used in the applications to suppress the hydrodynamic instabilities.
Development of the Ethiopian Healthy Eating Index (Et-HEI) and evaluation in women of reproductive age
Authors: Bekele Tesfaye Hailu , de Vries Jeanne H. M. , Feskens Edith J. M. , de Weijer Anneloes , Brouwer Inge D. , Covic Namukolo , Trijsburg Laura
Published: January 2023

Ethiopia announced its first food-based dietary guidelines (FBDGs) on 15 March 2022. The present study aims to develop and evaluate the Ethiopian Healthy Eating Index (Et-HEI) based on the FBDG. Data were collected from 494 Ethiopian women of reproductive age sampled from households in five different regions. The Et-HEI consists of eleven components, and each component was scored between 0 and 10 points, the total score ranging from 0 to 110, with maximum adherence to the FBDG. The Et-HEI score was evaluated against the Minimum Dietary Diversity for Women (MDD-W) and the probability of nutrient adequacy. The average Et-HEI score for women of reproductive age was 49 out of 110. Adherence to the recommendations for grains, vegetables, legumes, fat and oils, salt, sugar and alcohol contributed the most to this score. Most women had low scores for fruits, nuts and seeds, and animal-sourced foods, indicating low intake. The Cronbach's alpha coefficient, indicating the reliability of the Et-HEI to assess its diet quality, was 0⋅53. The low mean Et-HEI score agreed with a low mean score of the MDD-W (3⋅5 out of 10). Also, low nutrient adequacies confirmed poor adherence to nutrient-dense components of the FBDG. The Et-HEI was not associated with the intake of vitamin B12, vitamin C and calcium in this study population. Women who completed secondary school and above had relatively lower Et-HEI scores. The newly developed Et-HEI is able to estimate nutrient adequacy while also assessing adherence to the Ethiopian FBDG though there is room for improvement.
Problematizing Settler Grievances: Danielle Smith and Contested Colonialism
Authors: Collie James , Bhattacharjee Ritwik
Published: January 2023

Premier of Alberta Danielle Smith's comments comparing the Alberta Sovereignty within a United Canada Act to the Indian Act have sparked widespread outrage and condemnation. Premier Smith would later clarify that these remarks were intended to demonstrate that Alberta and First Nations have a “common problem” with Ottawa. In this brief article, we argue that these comments, as well as the act itself, can be analyzed using Jerald Sabin's contested colonialism framework. We then provide a brief critical discussion of what our analysis means for Canadian politics by addressing the possible intentions and harms of the comments.
A cadaveric temporal bone study of the anatomical landmarks for middle turn cochleostomy
Authors: Samuel H , Lepcha A , Philip A , John M , Augustine A
Published: January 2023

Objective

This study aimed to determine anatomical landmarks for accurate and safe middle turn cochleostomy on cadaveric temporal bones.

Methods

In 17 cadaveric wet adult temporal bones, cortical mastoidectomy was performed, followed by extended posterior tympanotomy through which a middle turn opening was created anterior to the stapes footplate. Micro-measurements of various lengths were taken from the cochleostomy to normal middle-ear anatomical landmarks using a digital microscope.

Results

The mean length from the middle turn cochleostomy to the processus cochleariformis was 1.8 ± 0.3 mm and to the tympanic segment of the facial nerve was 2.2 ± 0.3 mm. The mean shortest length from the oval window to the osseous spiral lamina was 2.4 ± 0.3 mm and to the internal carotid artery was 5.0 ± 0.6 mm. The mean shortest length from the round window to the internal carotid artery was 4.3 ± 0.6 mm.

Conclusion

A middle turn cochleostomy can be safely drilled by using the measured lengths in difficult cases.
Pattern-Based Reasons and Disaster
Authors: Dietz Alexander
Published: January 2023

Pattern-based reasons are reasons for action deriving not from the features of our own actions, but from the features of the larger patterns of action in which we might be participating. These reasons might relate to the patterns of action that will actually be carried out, or they might relate to merely hypothetical patterns. In past work, I have argued that accepting merely hypothetical pattern-based reasons, together with a plausible account of how to weigh these reasons, can lead to disastrous consequences. However, in this article, I argue that this problem is not limited to hypothetical pattern-based reasons: it turns out that there are analogous issues for reasons deriving from actual patterns. I then suggest that we can avoid this problem by adopting a different account of the weight of pattern-based reasons.
Conservation of the surface-nesting Kermadec Petrel Pterodroma neglecta neglecta in the South Pacific: clarifying breeding ecology and the threat of avian ground predators
Authors: Carlile Nicholas , O’Dwyer Terence
Published: January 2023

Understanding population dynamics and impacts on island ecology remain top priorities for the conservation management of seabirds, particularly when attempting species-recovery for island restoration. Identifying suitable nesting habitat is a keystone detail in seabird restoration which can be complicated when predator pressures impact colony productivity and population viability. The surface-nesting Kermadec Petrel Pterodroma neglecta neglecta is dispersed on remote islands through the tropics and subtropics. We examined their breeding ecology on Phillip Island, Norfolk Group in the South Pacific and considered the limitations to re-establishment at their previous breeding location on Lord Howe Island (900 km south-east). On Phillip Island, the petrels were mostly monogamous with nesting locations generally within the vicinity of the previous season’s attempts. Breeding sites were limited to sloping terrain 182–228 m above the shoreline and up to 85 m from the coast in small sub-colonies under low scrubby woodland. Based on observations of 56 pairs and data gleaned from Global Light Sensing devices, we determined that breeding (incubation and provisioning) occurs in all calendar months of the year, with a laying peak in the late austral spring. Breeding success in the first year of study was 25% but improved to 56% once management of Purple Swamphens Porphyrio melanotus was implemented. Successful nests were located at sites with naturally limited egress from cleared or lightly vegetated areas. Prudent management of the petrel population on Phillip Island could aid in the regional recovery of the species and, in the process, assist the island’s restoration by significantly increasing transfers of marine-derived nutrient. Their reintroduction to Lord Howe Island is also possible but will likely rely upon consistent productivity of the Phillip Island population for founding immigrants. Moreover, successful establishment will require adaptive management of selected sites to ensure native avian predators do not overly impact breeding.
The Political Role of the Historian
Authors: Motadel David
Published: January 2023

Debates about history have never been strictly confined to the world of scholarship. They have also been at the centre of political controversies in society. ‘The problem for professional historians’, Eric Hobsbawm once observed, ‘is that their subject has important social and political functions’.1 ‘This duality’, he noted, ‘is the core of our subject’. This essay offers some reflections on the political role of historians, exploring the relationship between their scholarly work and their involvement in political debates. A closer look at the issue shows that it is not so much a problem as an opportunity for historians to engage with their subject on various levels, from the realm of scholarship to the realm of contemporary politics, which makes their position in society both more complex and more critical.
The Memory of Southern European Dictatorships in Popular TV Shows
Authors: Kornetis Kostis
Published: January 2023

Ever since the ground-breaking historical mini-series Holocaust (1978), television has proven to play a major role in structuring the collective memory about the past.1 This medium has, moreover, displayed a capacity to trigger a collective rendering of, and coming to terms with, painful, hidden or forgotten aspects of the past. Media specialist Garry R. Edgerton has even argued that ‘television is the principal means by which most people learn about history’.2 Even though such assertions might be tempered by today's predominance of social media – especially in generational terms – an inquiry into the politics of memory in popular television is still relevant for the field of public history, as well as for memory studies. This is particularly pertinent when representing dictatorship in the European South. Alongside public history projects of all kinds (including museums, memorials, commemorative plaques and practices), filmic representations (be it for cinematic or television use) structure the collective imaginary about the recent past. This essay briefly discusses TV shows that deal with and shape public understandings of the dictatorships in Spain (the final phase of Francoism, post-1968), Greece (the Colonels’ dictatorship, post-1969) and Portugal (the final phase of the Estado Novo (New State), post-1968).
What Do Chimeras Think About?
Authors: Capps Benjamin
Published: January 2023

Non-human animal chimeras, containing human neurological cells, have been created in the laboratory. Despite a great deal of debate, the status of such beings has not been resolved. Under normal definitions, such a being could either be unconventionally human or abnormally animal. Practical investigations in animal sentience, artificial intelligence, and now chimera research, suggest that such beings may be assumed to have no legal rights, so philosophy could provide a different answer. In this vein, therefore, we can ask: What would a chimera, if it could think, think about? Thinking is used to capture the phenomena of a novel, chimeric being perceiving its terrible predicament as no more than a laboratory experiment. The creation of a thinking chimera therefore forces us to reconsider our assumptions about what makes human beings (potentially) unique (and other sentient animals different), because, as such, a chimera’s existence bridges our social and legal expectations about definitions of human and animal. Society has often evolved new social norms based on different kinds of (ir)rational contrivances; the imperative of non-contradiction, which is defended here, therefore requires a specific philosophical response to the rights of a thinking chimeric being.
A Balance of Rights: The Italian Way to the Abortion Controversy
Authors: Reichlin Massimo , Lavazza Andrea
Published: January 2023

The U.S. Supreme Court’s Dobbs ruling triggered a global debate about access to abortion and the legislative models governing it. In the United States, there was a sudden reversal of federal guidance about pregnancy termination that is unprecedented in Western and high-income countries. The strong polarization on the issue of abortion and the difficulty of finding a point of compromise lead one to consider the experiences of countries that have had different paths. Italy stands as a candidate for being a partially alternative model because it allows abortion up to 12 weeks, but without considering it a subjective right. The legislation in place since 1978 aims to balance the interests of the fetus and those of the woman. An issue often raised concerning Italian law is that of conscientious objection granted to doctors. Many gynecologists declare themselves objectors, and this makes access to abortion more difficult in some regions of Italy. After discussing this issue and envisaging different ways to deal with it, the article concludes by highlighting new dilemmas about a possible divorce between the law and medical ethics in different directions and offers some avenues to begin setting up a response.
Measuring palliative care self-efficacy of intellectual and developmental disability staff using Rasch models
Authors: Kim Jinsook , Gray Jennifer A.
Published: January 2023

Objectives

The objectives of this study were to evaluate the psychometric properties of a palliative care self-efficacy instrument developed for intellectual and developmental disability (IDD) staff using Rasch analysis and assess the change in palliative care self-efficacy between 2 time points using Rasch analysis of stacked data.

Methods

Staff from 4 nonprofit IDD services organizations in a US Midwestern state (n = 98) answered 11 questions with Likert-style responses at baseline and 1-month follow-up post training. Rasch analysis was performed to examine rating scale structure, unidimensionality, local independence, overall model fit, person and item reliability and separation, targeting, individual item and personal fit, differential item functioning (DIF), and change in palliative care self-efficacy between 2 time points.

Results

The rating scale structure improved when 5 response categories were collapsed to 3. With the revised 3 response categories, the instrument demonstrated good psychometric properties. Principal components analysis of Rasch residuals supported the assumption of unidimensionality. Model fit statistics indicated an excellent fit of the data to the Rasch model. The instrument demonstrated good person and item reliability and separation. Gender-related DIF was found in 1 item, and work tenure–related DIF in 3 items. Overall palliative care self-efficacy improved between 2 time points.

Significance of results

Rasch analysis allowed for a more thorough examination of this palliative care self-efficacy instrument than classical test theory and provided information on rating scale structure, targeting, DIF, and individual persons and items. These recommendations can improve this instrument for research and practical contexts.
Sexuelle Funktionsstörungen bei Männern
Authors: Velten Julia , Özdemir Umut C.
Published: January 2023

Viele Männer erleben sexuelle Schwierigkeiten, wie z. B. vorzeitigen Samenerguss, Probleme mit sexueller Erregung bzw. Erektion oder verringertes sexuelles Verlangen. Der Band liefert eine aktuelle Beschreibung sexueller Funktionsstörungen bei Männern und stellt die psychotherapeutische Behandlung dar.
Der Band beschreibt zunächst die wesentlichen Störungsbilder und stellt die diagnostischen Kriterien vor. Es werden Hinweise zur Abgrenzung sexueller Funktionsstörungen von nicht klinischen sexuellen Problemen sowie sexuellen Schwierigkeiten im Rahmen anderer Störungen gegeben. Zudem wird über validierte Verfahren zur Diagnostik sexueller Störungen sowie zur Verlaufskontrolle innerhalb der Behandlung informiert. Praxisorientiert werden therapeutische Interventionen vorgestellt, die – mit entsprechenden Modifikationen – bei allen sexuellen Funktionsstörungen von Männern eingesetzt werden können. Dazu werden neben Sexual- und Psychoedukation sowie sexualtherapeutischen Paarübungen (Sensate Focus) auch körperbezogene Selbsterfahrungsübungen und kognitive Interventionen beschrieben. Schließlich geht der Band auf den Umgang mit Schwierigkeiten ein, die im Behandlungsverlauf auftreten können, und veranschaulicht das psychotherapeutische Vorgehen an einem ausführlichen Fallbeispiel.
Evaluating Knowledge Gaps in Sea‐Level Rise Assessments From the United States
Authors: Garner Andra J. , Sosa Sarah E. , Tan Fangyi , Tan Christabel Wan Jie , Garner Gregory G. , Horton Benjamin P.
Published: January 2023

There have been many scientific advances regarding future sea‐level projections, however it is unclear if these have been transferred to assessment reports used by stakeholders. Here, we present a first‐of‐its‐kind comprehensive analysis of regional sea‐level rise (SLR) assessments for the United States (U.S.). We identify variations in time horizons over which regions plan for SLR, with 25 projections from the U.S. Northeast and West that extend to 2150 or beyond, but no projections from the U.S. South beyond 2100. The majority of 2100 projections from the U.S. Northeast (77%) and West (83%) include ranges of future SLR, while 88% of projections from the U.S. South include only single estimates. At least 56% of U.S. communities in the database underestimate the upper end of future SLR compared to the regional projections of the Intergovernmental Panel on Climate Change Sixth Assessment Report.
A Paradigm Shift: North China Craton's North Margin Orogen Is the Collisional Suture With the Columbia Supercontinent
Authors: Kusky Timothy M. , Traore Alhousseyni
Published: January 2023

In a new study, Wu, Wang, Zhou, Zhao, Haproff, et al. (2022, https://doi.org/10.1029/2022GC010662) present a comprehensive study of the North Margin Orogen of the North China Craton (NCC), showing that older accreted rocks in this belt preserve a record of active margin magmatism from 2.2 to 2.0 Ga, followed by collisional tectonics, marked by mélange and mylonitic shear zones, then granulite facies metamorphism at 1.9–1.8 Ga, marking the final collision of the NCC with the Columbia Supercontinent. The multidisciplinary studies presented in this work support earlier suggestions that the North China Craton amalgamated during accretionary orogenesis in the Neoarchean to earlier Paleoproterozoic, and that the late widespread 1.85 Ga high‐grade metamorphism is craton‐wide in scale, and not confined to a narrow orogen in the center of the craton. This new understanding creates new possibilities for refining reconstructions of one of Earth's earliest, best documented supercontinents, showing a globally linked plate network at 1.85 Ga, and suggests drastic new correlations and models for mineral resource exploration.
Influence of Fluids on Earthquakes Based on Numerical Modeling
Authors: Marguin Valentin , Simpson Guy
Published: January 2023

The strength and sliding behavior of faults in the crust is largely controlled by friction and effective stress, which is itself modulated by fluid pressure. Most earthquake models assume a fixed pore fluid pressure despite widespread evidence that is varies strongly in time due to changes in permeability. Here we explore how dynamic changes in pore pressure influence the properties of earthquakes in the upper crust. To study this problem we develop a two dimensional model that incorporates slow tectonic loading and fluid pressure generation during the interseismic period with frictional sliding on a thrust fault whose permeability evolves with slip. We find that the presence of relatively modest fluid overpressures tends to reduce coseismic slip, stress drop, maximum sliding velocity, rupture velocity and the earthquake recurrence time compared to models without fluids. Our model produces a wide range of sliding velocities from rapid to slow earthquakes, which occur due to the presence of high pore pressures prior to rupture. The models also show evidence for aftershocks that are driven by fluid transfer along the fault plane after the mainshock. Overall, this study shows that fluids can exert an important influence on earthquakes in the crust, which is mostly due to modulation of the effective stress and variations in permeability, and to a lesser extent to poro‐elastic coupling.
Refined Earthquake Focal Mechanism Catalog for Southern California Derived With Deep Learning Algorithms
Authors: Cheng Yifang , Hauksson Egill , Ben‐Zion Yehuda
Published: January 2023

Earthquake focal mechanisms, determined with P‐wave polarities and S/P amplitude ratios, are primary data for analyzing fault zone geometry, sense of slip, and the crustal stress field. Solving for the focal mechanisms of small earthquakes is often challenging because phase arrivals and first‐motion polarities are hard to be separated from noise. To overcome this challenge, we implement convolutional‐neural‐network algorithms (Ross, Meier, & Hauksson, 2018, Ross, Meier, Hauksson, & Heaton, 2018, https://doi.org/10.1029/2017jb015251, https://doi.org/10.1785/0120180080) to detect additional phases and polarities. Using both existing and these new data, we build a high‐quality focal mechanism catalog of 297,478 events that occurred from 1981 to 2021 in southern California with the HASH method of Hardebeck and Shearer (2002), https://doi.org/10.1785/0120010200, Hardebeck and Shearer (2003), https://doi.org/10.1785/0120020236. The new focal mechanism catalog is overall consistent with the standard catalog (Yang et al., 2012, https://doi.org/10.1785/0120110311) but includes 40% more focal mechanisms, and is more consistent with moment tensor solutions derived using waveform‐fitting methods. We apply the new catalog to identify changes in focal mechanism properties caused by the occurrences of large mainshocks such as the 2010 Mw7.2 El Mayor‐Cucapah and 2019 Mw7.1 Ridgecrest earthquakes. Such changes may be associated with co‐seismic stress drops, post‐seismic deformation processes, and static stress changes on a regional scale. The new high‐resolution catalog will contribute to improved understanding of the crustal stress field, earthquake triggering mechanisms, fault zone geometry, and sense of slip on the faults in southern California.
The Impact of Different Atmospheric CO2 Concentrations on Large Scale Miocene Temperature Signatures
Authors: Hossain Akil , Knorr Gregor , Jokat Wilfried , Lohmann Gerrit , Hochmuth Katharina , Gierz Paul , Gohl Karsten , Stepanek Christian
Published: January 2023

Based on inferences from proxy records the Miocene (23.03–5.33 Ma) was a time of amplified polar warmth compared to today. However, it remains a challenge to simulate a warm Miocene climate and pronounced polar warmth at reconstructed Miocene CO2 concentrations. Using a state‐of‐the‐art Earth‐System‐Model, we implement a high‐resolution paleobathymetry and simulate Miocene climate at different atmospheric CO2 concentrations. We estimate global mean surface warming of +3.1°C relative to the preindustrial at a CO2 level of 450 ppm. An increase of atmospheric CO2 from 280 to 450 ppm provides an individual warming of ∼1.4°C, which is as strong as all other Miocene forcing contributions combined. Substantial changes in surface albedo are vital to explain Miocene surface warming. Simulated surface temperatures fit well with proxy reconstructions at low‐ to mid‐latitudes. The high latitude cooling bias becomes less pronounced for higher atmospheric CO2 concentrations. At such CO2 levels simulated Miocene climate shows a reduced polar amplification, linked to a breakdown of seasonality in the Arctic Ocean. A pronounced warming in boreal fall is detected for a CO2 increase from 280 to 450 ppm, in comparison to weaker warming for CO2 changes from 450 to 720 ppm. Moreover, a pronounced warming in winter is detected for a CO2 increase from 450 to 720 ppm, in contrast to a moderate summer temperature increase, which is accompanied by a strong sea‐ice concentration decline that promotes cloud formation in summer via enhanced moisture availability. As a consequence planetary albedo increases and dampens the temperature response to CO2 forcing at a warmer Miocene background climate.
Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity
Authors: Zhang Bo , Sun Jiaqi , Yuan Yeshuang , Ji Dezhong , Sun Yeting , Liu Yudong , Li Shengjie , Zhu Xingxing , Wu Xunyao , Hu Jin , Xie Qiu , Wu Ling , Liu Lulu , Cheng Boyang , Zhang Yuanjie , Jiang Lingjuan , Zhao Lidan , Yu Fei , Song Wei , Wang Min , Xu Yue , Ma Shiliang , Fei Yunyun , Zhang Lihe , Zhou Demin , Zhang Xuan
Published: January 2023

Interleukin-2 (IL-2) is a pleiotropic cytokine that orchestrates bidirectional immune responses via regulatory T cells (Tregs) and effector cells, leading to paradoxical consequences. Here, we report a strategy that exploited genetic code expansion-guided incorporation of the latent bioreactive artificial amino acid fluorosulfate-L-tyrosine (FSY) into IL-2 for proximity-enabled covalent binding to IL-2Rα to selectively promote Treg activation. We found that FSY-bearing IL-2 variants, such as L72-FSY, covalently bound to IL-2Rα via sulfur-fluoride exchange when in proximity, resulting in persistent recycling of IL-2 and selectively promoting the expansion of Tregs but not effector cells. Further assessment of L72-FSY-expanded Tregs demonstrated that L72-FSY maintained Tregs in a central memory phenotype without driving terminal differentiation, as demonstrated by simultaneously attenuated expression of lymphocyte activation gene-3 (LAG-3) and enhanced expression of programmed cell death protein-1 (PD-1). Subcutaneous administration of L72-FSY in murine models of pristane-induced lupus and graft-versus-host disease (GvHD) resulted in enhanced and sustained therapeutic efficacy compared with wild-type IL-2 treatment. The efficacy of L72-FSY was further improved by N-terminal PEGylation, which increased its circulatory retention for preferential and sustained effects. This proximity-enabled covalent binding strategy may accelerate the development of pleiotropic cytokines as a new class of immunomodulatory therapies.
Interferon-γ secreted by recruited Th1 cells in peritoneal cavity inhibits the formation of malignant ascites
Authors: Liu Chang , Xiao Zhuanglong , Du Li , Zhu Shenghua , Xiang Hongyu , Wang Zehui , Liu Fang , Song Yuhu
Published: January 2023

Type 1 T helper (Th1) cells generate an efficient antitumor immune response in multiple malignancies. The functions of Th1 cells in malignant ascites (MA) have not been elucidated. The distribution of helper T cells in peritoneal fluid and peripheral blood was determined in patients and animal models with malignant ascites. The effects of Th1-derived interferon-γ (IFN-γ) on the formation of malignant ascites were investigated. The mechanism underlying the recruitment of Th1 cells into peritoneal cavity was explored. In patients with malignant ascites and animal models of malignant ascites, the percentage of Th1 cells increased in peritoneal fluid compared with peripheral blood. Next, our experiment demonstrated that Th1 cells inhibited the growth of tumor cells by secreting IFN-γ in vitro. In murine models of malignant ascites, increased peritoneal fluid and shorter survival time were observed in IFN-γ−/− mice compared with wild-type (WT) mice. Then, the levels of C-X-C motif chemokine ligand (CXCL) 9/10 and the ratio of CXCR3+ Th1 cells indicated the involvement of CXCL9, 10/CXCR3 axis in the recruitment of Th1 cells into peritoneal cavity. As expected, in murine models of malignant ascites, the gradient between ascitic Th1 ratio and blood Th1 ratio decreased in CXCR3−/− mice compared with WT mice. IFN-γ secreted by recruited Th1 cells in peritoneal cavity inhibits the formation of malignant ascites. Hence, manipulation of Th1 cells or IFN-γ will provide a therapeutic candidate against malignant ascites.
Role of Rho GTPases in inflammatory bowel disease
Authors: Li Xiaoling , Zhang Mudan , Zhou Gaoshi , Xie Zhuo , Wang Ying , Han Jing , Li Li , Wu Qirui , Zhang Shenghong
Published: January 2023

Rat sarcoma virus homolog (Rho) guanosine triphosphatases (GTPases) function as “molecular switch” in cellular signaling regulation processes and are associated with the pathogenesis of inflammatory bowel disease (IBD). This chronic intestinal tract inflammation primarily encompasses two diseases: Crohn’s disease and ulcerative colitis. The pathogenesis of IBD is complex and considered to include four main factors and their interactions: genetics, intestinal microbiota, immune system, and environment. Recently, several novel pathogenic components have been identified. In addition, potential therapies for IBD targeting Rho GTPases have emerged and proven to be clinically effective. This review mainly focuses on Rho GTPases and their possible mechanisms in IBD pathogenesis. The therapeutic possibility of Rho GTPases is also discussed.
Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2
Authors: Ai Liangxia , Li Yafei , Zhou Li , Yao Wenrong , Zhang Hao , Hu Zhaoyu , Han Jinyu , Wang Weijie , Wu Junmiao , Xu Pan , Wang Ruiyue , Li Zhangyi , Li Zhouwang , Wei Chengliang , Liang Jianqun , Chen Haobo , Yang Zhimiao , Guo Ming , Huang Zhixiang , Wang Xin , Zhang Zhen , Xiang Wenjie , Sun Dazheng , Xu Lianqiang , Huang Meiyan , Lv Bin , Peng Peiqi , Zhang Shangfeng , Ji Xuhao , Luo Huiyi , Chen Nanping , Chen Jianping , Lan Ke , Hu Yong
Published: January 2023

Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, most current mRNA delivery platforms need to be stored at −20 °C or −70 °C due to their poor stability, which severely restricts their availability. Herein, we develop a lyophilization technique to prepare SARS-CoV-2 mRNA-lipid nanoparticle vaccines with long-term thermostability. The physiochemical properties and bioactivities of lyophilized vaccines showed no change at 25 °C over 6 months, and the lyophilized SARS-CoV-2 mRNA vaccines could elicit potent humoral and cellular immunity whether in mice, rabbits, or rhesus macaques. Furthermore, in the human trial, administration of lyophilized Omicron mRNA vaccine as a booster shot also engendered strong immunity without severe adverse events, where the titers of neutralizing antibodies against Omicron BA.1/BA.2/BA.4 were increased by at least 253-fold after a booster shot following two doses of the commercial inactivated vaccine, CoronaVac. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity and significantly improves their accessibility, particularly in remote regions.
Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor
Authors: Xu Jun , Wang Qinggong , Hübner Harald , Hu Yunfei , Niu Xiaogang , Wang Haoqing , Maeda Shoji , Inoue Asuka , Tao Yuyong , Gmeiner Peter , Du Yang , Jin Changwen , Kobilka Brian K.
Published: January 2023

The M2 muscarinic receptor (M2R) is a prototypical G-protein-coupled receptor (GPCR) that serves as a model system for understanding GPCR regulation by both orthosteric and allosteric ligands. Here, we investigate the mechanisms governing M2R signaling versatility using cryo-electron microscopy (cryo-EM) and NMR spectroscopy, focusing on the physiological agonist acetylcholine and a supra-physiological agonist iperoxo, as well as a positive allosteric modulator LY2119620. These studies reveal that acetylcholine stabilizes a more heterogeneous M2R-G-protein complex than iperoxo, where two conformers with distinctive G-protein orientations were determined. We find that LY2119620 increases the affinity for both agonists, but differentially modulates agonists efficacy in G-protein and β-arrestin pathways. Structural and spectroscopic analysis suggest that LY211620 stabilizes distinct intracellular conformational ensembles from agonist-bound M2R, which may enhance β-arrestin recruitment while impairing G-protein activation. These results highlight the role of conformational dynamics in the complex signaling behavior of GPCRs, and could facilitate design of better drugs.
Magmatic plumbing and dynamic evolution of the 2021 La Palma eruption
Authors: del Fresno Carmen , Cesca Simone , Klügel Andreas , Domínguez Cerdeña Itahiza , Díaz-Suárez Eduardo A. , Dahm Torsten , García-Cañada Laura , Meletlidis Stavros , Milkereit Claus , Valenzuela-Malebrán Carla , López-Díaz Rubén , López Carmen
Published: January 2023

The 2021 volcanic eruption at La Palma, Canary Islands, was the island’s most voluminous historical eruption. Little is known about this volcano’s feeding system. During the eruption, seismicity was distributed in two clusters at ~10-14 km and ~33-39 km depth, separated by an aseismic zone. This gap coincides with the location of weak seismic swarms in 2017-2021 and where petrological data have implied pre-eruptive magma storage. Here we use seismological methods to understand the seismic response to magma transfer, with 8,488 hypocentral relocations resolving small-scale seismogenic structures, and 156 moment tensors identifying stress heterogeneities and principal axes flips. Results suggest a long-lasting preparatory stage with the progressive destabilisation of an intermediate, mushy reservoir, and a co-eruptive stage with seismicity controlled by the drainage and interplay of two localised reservoirs. Our study provides new insights into the plumbing system that will improve the monitoring of future eruptions in the island.
Cross-species transcriptomic atlas of dorsal root ganglia reveals species-specific programs for sensory function
Authors: Jung Min , Dourado Michelle , Maksymetz James , Jacobson Amanda , Laufer Benjamin I. , Baca Miriam , Foreman Oded , Hackos David H. , Riol-Blanco Lorena , Kaminker Joshua S.
Published: January 2023

Sensory neurons of the dorsal root ganglion (DRG) are critical for maintaining tissue homeostasis by sensing and initiating responses to stimuli. While most preclinical studies of DRGs are conducted in rodents, much less is known about the mechanisms of sensory perception in primates. We generated a transcriptome atlas of mouse, guinea pig, cynomolgus monkey, and human DRGs by implementing a common laboratory workflow and multiple data-integration approaches to generate high-resolution cross-species mappings of sensory neuron subtypes. Using our atlas, we identified conserved core modules highlighting subtype-specific biological processes related to inflammatory response. We also identified divergent expression of key genes involved in DRG function, suggesting species-specific adaptations specifically in nociceptors that likely point to divergent function of nociceptors. Among these, we validated that TAFA4, a member of the druggable genome, was expressed in distinct populations of DRG neurons across species, highlighting species-specific programs that are critical for therapeutic development.
Sb2S3-templated synthesis of sulfur-doped Sb-N-C with hierarchical architecture and high metal loading for H2O2 electrosynthesis
Authors: Yan Minmin , Wei Zengxi , Gong Zhichao , Johannessen Bernt , Ye Gonglan , He Guanchao , Liu Jingjing , Zhao Shuangliang , Cui Chunyu , Fei Huilong
Published: January 2023

Selective two-electron (2e−) oxygen reduction reaction (ORR) offers great opportunities for hydrogen peroxide (H2O2) electrosynthesis and its widespread employment depends on identifying cost-effective catalysts with high activity and selectivity. Main-group metal and nitrogen coordinated carbons (M-N-Cs) are promising but remain largely underexplored due to the low metal-atom density and the lack of understanding in the structure-property correlation. Here, we report using a nanoarchitectured Sb2S3 template to synthesize high-density (10.32 wt%) antimony (Sb) single atoms on nitrogen- and sulfur-codoped carbon nanofibers (Sb-NSCF), which exhibits both high selectivity (97.2%) and mass activity (114.9 A g−1 at 0.65 V) toward the 2e− ORR in alkaline electrolyte. Further, when evaluated with a practical flow cell, Sb-NSCF shows a high production rate of 7.46 mol gcatalyst−1 h−1 with negligible loss in activity and selectivity in a 75-h continuous electrolysis. Density functional theory calculations demonstrate that the coordination configuration and the S dopants synergistically contribute to the enhanced 2e− ORR activity and selectivity of the Sb-N4 moieties.
CD8+ lymphocytes do not impact SIV reservoir establishment under ART
Authors: Statzu Maura , Jin Wang , Fray Emily J. , Wong Andrew Kam Ho , Kumar Mithra R. , Ferrer Elizabeth , Docken Steffen S. , Pinkevych Mykola , McBrien Julia B. , Fennessey Christine M. , Keele Brandon F. , Liang Shan , Harper Justin L. , Mutascio Simona , Franchitti Lavinia , Wang Hong , Cicetti Davide , Bosinger Steven E. , Carnathan Diane G. , Vanderford Thomas H. , Margolis David M. , Garcia-Martinez J. Victor , Chahroudi Ann , Paiardini Mirko , Siliciano Janet , Davenport Miles P. , Kulpa Deanna A. , Siliciano Robert S. , Silvestri Guido
Published: January 2023

Persistence of the human immunodeficiency virus type-1 (HIV-1) latent reservoir in infected individuals remains a problem despite fully suppressive antiretroviral therapy (ART). While reservoir formation begins during acute infection, the mechanisms responsible for its establishment remain unclear. CD8+ T cells are important during the initial control of viral replication. Here we examined the effect of CD8+ T cells on formation of the latent reservoir in simian immunodeficiency virus (SIV)-infected macaques by performing experimental CD8+ depletion either before infection or before early (that is, day 14 post-infection) ART initiation. We found that CD8+ depletion resulted in slower decline of viremia, indicating that CD8+ lymphocytes reduce the average lifespan of productively infected cells during acute infection and early ART, presumably through SIV-specific cytotoxic T lymphocyte (CTL) activity. However, CD8+ depletion did not change the frequency of infected CD4+ T cells in the blood or lymph node as measured by the total cell-associated viral DNA or intact provirus DNA assay. In addition, the size of the persistent reservoir remained the same when measuring the kinetics of virus rebound after ART interruption. These data indicate that during early SIV infection, the viral reservoir that persists under ART is established largely independent of CTL control.
Screening cell–cell communication in spatial transcriptomics via collective optimal transport
Authors: Cang Zixuan , Zhao Yanxiang , Almet Axel A. , Stabell Adam , Ramos Raul , Plikus Maksim V. , Atwood Scott X. , Nie Qing
Published: January 2023

Spatial transcriptomic technologies and spatially annotated single-cell RNA sequencing datasets provide unprecedented opportunities to dissect cell–cell communication (CCC). However, incorporation of the spatial information and complex biochemical processes required in the reconstruction of CCC remains a major challenge. Here, we present COMMOT (COMMunication analysis by Optimal Transport) to infer CCC in spatial transcriptomics, which accounts for the competition between different ligand and receptor species as well as spatial distances between cells. A collective optimal transport method is developed to handle complex molecular interactions and spatial constraints. Furthermore, we introduce downstream analysis tools to infer spatial signaling directionality and genes regulated by signaling using machine learning models. We apply COMMOT to simulation data and eight spatial datasets acquired with five different technologies to show its effectiveness and robustness in identifying spatial CCC in data with varying spatial resolutions and gene coverages. Finally, COMMOT identifies new CCCs during skin morphogenesis in a case study of human epidermal development.
Convolutional networks for supervised mining of molecular patterns within cellular context
Authors: de Teresa-Trueba Irene , Goetz Sara K. , Mattausch Alexander , Stojanovska Frosina , Zimmerli Christian E. , Toro-Nahuelpan Mauricio , Cheng Dorothy W. C. , Tollervey Fergus , Pape Constantin , Beck Martin , Diz-Muñoz Alba , Kreshuk Anna , Mahamid Julia , Zaugg Judith B.
Published: January 2023

Cryo-electron tomograms capture a wealth of structural information on the molecular constituents of cells and tissues. We present DeePiCt (deep picker in context), an open-source deep-learning framework for supervised segmentation and macromolecular complex localization in cryo-electron tomography. To train and benchmark DeePiCt on experimental data, we comprehensively annotated 20 tomograms of Schizosaccharomyces pombe for ribosomes, fatty acid synthases, membranes, nuclear pore complexes, organelles, and cytosol. By comparing DeePiCt to state-of-the-art approaches on this dataset, we show its unique ability to identify low-abundance and low-density complexes. We use DeePiCt to study compositionally distinct subpopulations of cellular ribosomes, with emphasis on their contextual association with mitochondria and the endoplasmic reticulum. Finally, applying pre-trained networks to a HeLa cell tomogram demonstrates that DeePiCt achieves high-quality predictions in unseen datasets from different biological species in a matter of minutes. The comprehensively annotated experimental data and pre-trained networks are provided for immediate use by the community.
No evidence of a positive effect of learning Chinese language as an L2 on spatial ability
Authors: Likhanov Maxim , Bogdanova Olga , Alenina Evgenia , Kolienko Tatiana , Kovas Yulia
Published: January 2023

Spatial ability (SA) was shown to be a robust predictor of success in various educational contexts, including STEM. Thus, ways to improve SA are of interest to educational psychology. There is some evidence that SA might be improved via learning character-based language, e.g. Chinese as a second language (CSL), however, the existing research is quite limited. The study aims to investigate an effect of CSL learning on SA in schoolchildren from Year 2 to Year 7. Current study employs a sample of Russian schoolchildren (N = 283), who learnt: English only, English and Spanish; or English and Chinese. Participants completed Raven’s progressive matrices and Mental rotation task at the age of 8 and again at the age of 14. Our data showed negligible group differences in the initial SA level at Year 2 (before learning second language). Similar negligible differences were found at Year 7. Regression analysis showed that SA was predicted by intelligence (Raven’s) and gender but not language learnt at both ages. This pattern of results indicates that learning a Chinese as a second language is unlikely to affect SA. Further research is needed to investigate whether other factors, such as length, intensity and context of learning, moderate this link.
Limited water stress modulates expression of circadian clock genes in Brachypodium distachyon roots
Authors: Gombos Magdolna , Hapek Nóra , Kozma-Bognár László , Grezal Gábor , Zombori Zoltán , Kiss Edina , Györgyey János
Published: January 2023

Organisms have evolved a circadian clock for the precise timing of their biological processes. Studies primarily on model dicots have shown the complexity of the inner timekeeper responsible for maintaining circadian oscillation in plants and have highlighted that circadian regulation is more than relevant to a wide range of biological processes, especially organ development and timing of flowering. Contribution of the circadian clock to overall plant fitness and yield has also long been known. Nevertheless, the organ- and species-specific functions of the circadian clock and its relation to stress adaptation have only recently been identified. Here we report transcriptional changes of core clock genes of the model monocot Brachypodium distachyon under three different light regimes (18:6 light:dark, 24:0 light and 0:24 dark) in response to mild drought stress in roots and green plant parts. Comparative monitoring of core clock gene expression in roots and green plant parts has shown that both phase and amplitude of expression in the roots of Brachypodium plants differ markedly from those in the green plant parts, even under well-watered conditions. Moreover, circadian clock genes responded to water depletion differently in root and shoot. These results suggest an organ-specific form and functions of the circadian clock in Brachypodium roots.