bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurodevelopmental disorders, like cancer, are connected to impaired chromatin remodelers, PI3K/mTOR, and PAK1-regulated MAPK
Authors: Nussinov Ruth , Yavuz Bengi Ruken , Arici M Kaan , Demirel Habibe Cansu , Zhang Mingzhen , Liu Yonglan , Tsai Chung-Jung , Jang Hyunbum , Tuncbag Nurcan
Published: April 2023

Neurodevelopmental disorders (NDDs) and cancer share proteins, pathways, and mutations. Their clinical symptoms are different. However, individuals with NDDs have higher probabilities of eventually developing cancer. Here, we review the literature and ask how the shared features can lead to different medical conditions and why having an NDD first can increase the chances of malignancy. To explore these vital questions, we focus on dysregulated PI3K/mTOR, a major brain cell growth pathway in differentiation, and MAPK, a critical pathway in proliferation, a hallmark of cancer. Differentiation is governed by chromatin organization, making aberrant chromatin remodelers highly likely agents in NDDs. Dysregulated chromatin organization and accessibility influence the lineage of specific cell brain types at specific embryonic development stages. PAK1, with pivotal roles in brain development and in cancer, also regulates MAPK. We review, clarify, and connect dysregulated pathways with dysregulated proliferation and differentiation in cancer and NDDs and highlight PAK1 role in brain development and MAPK regulation. Exactly how PAK1 activation controls brain development, and why specific chromatin remodeler components, e.g., BAF170 encoded by SMARCC2 in autism, await clarification.
Ovarian clear cell carcinoma with or without endometriosis origin in a single institution cohort
Authors: Sun Mingming , Jiang Wei
Published: April 2023

Background

As ovarian clear cell carcinoma (OCCC) has distinct clinical features, biology, genetic characteristics and mechanisms of pathogenesis, and whether the origin of endometriosis or not affects the prognosis of OCCC remains controversial.

Methods

We retrospectively collected medical records and follow-up data of patients with OCCC treated at the Obstetrics and Gynecology Hospital of Fudan University from January 2009 to December 2019. Further, we divided patients into 2 groups. Group 1: non-endometriosis origin; Group 2: endometriosis origin. Clinicopathological characteristics and survival outcomes were compared between the 2 groups.

Results

A total of one hundred and twenty-five patients with ovarian clear cell carcinoma were identified and included. In the overall patients’ population, the 5 year overall survival was 84.8%, the mean overall survival was 85.9 months. The results of the stratified analysis showed that early stage (FIGO stage I/II) OCCC had a good prognosis. The results of univariate analyses indicated that a statistically significant relationship between overall survival (OS) and FIGO stage, lymph node metastasis, peritoneum metastasis, chemotherapy administration methods, Chinese herbal treatment, molecular target therapy. As for progression-free survival (PFS), a significant relationship between PFS and child-bearing history, largest residual tumor size, FIGO stage, tumor maximum diameter, lymph node metastasis was found, respectively. FIGO stage and lymph node metastasis are common poor prognostic factors affecting OS and PFS. The multivariate regression analysis revealed that FIGO stage (p = 0.028; HR, 1.944; 95% CI 1.073–3.52) and treatment by Chinese herbs (p = 0.018; HR, 0.141; 95% CI 0.028–0.716) were identified as influencing factors with regard to survival. The presence or absence of lymphadenectomy did not affect OS of 125 OCCC patients (p = 0.851; HR, 0.825; 95% CI 0.111–6.153).

There was a trend towards a better prognosis for patients with OCCC of endometriosis origin than those with OCCC of non-endometriosis origin (p = 0.062; HR, 0.432; 95% CI 0.179–1.045). The two groups differed with respect to several clinicopathological factors. And the proportion of patients with disease relapse was higher in Group 1 (46.9%) than in Group 2 (25.0%), with a statistically significant difference (p = 0.048).

Conclusions

Surgical staging and treatment by Chinese herbs postoperatively are two independent prognostic factors affecting the OS of OCCC, early detection and Chinese herbal medicine combined with chemotherapy postoperatively may be a good choice. Tumor with endometriosis-origin was found less likely to relapse. While the non-necessity of lymphadenectomy in advanced ovarian cancer has been proven, the need for lymphadenectomy in the early stage ovarian cancer, including early stage OCCC, still deserved to be explored.
Sulfate diffusion in coal pillar: experimental data and prediction model
Authors: Wang Min , Xi Xun , Guo Qifeng , Pan Jiliang , Cai Meifeng , Yang Shangtong
Published: April 2023

The stability of coal pillar dams is crucial for the long-term service of underground reservoirs storing water or heat. Chemical damage of coal dams induced by ions-attacking in coal is one of the main reasons for the premature failure of coal dams. However, the diffusion process of harmful ions in coal is far from clear, limiting the reliability and durability of coal dam designs. This paper investigates sulfate diffusion in coal pillar through experimental and analytical methods. Coal specimens are prepared and exposed to sulfate solutions with different concentrations. The sulfate concentrations at different locations and time are measured. Based on experimental data and Fick’s law, the time-dependent surface concentration of sulfate and diffusion coefficient are determined and formulated. Further, an analytical model for predicting sulfate diffusion in coal pillar is developed by considering dual time-dependent characteristics and Laplace transformations. Through comparisons with experimental data, the accuracy of the analytical model for predicting sulfate diffusion is verified. Further, sulfate diffusions in coal dams for different concentrations of sulfate in mine water are investigated. It has been found that the sulfate concentration of exposure surface and diffusion coefficient in coal are both time-dependent and increase with time. Conventional Fick’s law is not able to predict the sulfate diffusion in coal pillar due to the dual time-dependent characteristics. The sulfate attacking makes the coal dam a typical heterogeneous gradient structure. For sulfate concentrations 0.01–0.20 mol/L in mine water, it takes almost 1.5 and 4 years for sulfate ions to diffuse 9.46 and 18.92 m, respectively. The experimental data and developed model provide a practical method for predicting sulfate diffusion in coal pillar, which helps the service life design of coal dams.
Migraine drugs
Authors: Ramachanderan Raghavendra , Schramm Stefan , Schaefer Bernd
Published: April 2023

According to recent studies, migraine affects more than 1 billion people worldwide, making it one of the world’s most prevalent diseases. Although this highly debilitating illness has been known since ancient times, the first therapeutic drugs to treat migraine, ergotamine (Gynergen) and dihydroergotamine (Dihydergot), did not appear on the market until 1921 and 1946, respectively. Both drugs originated from Sandoz, the world’s leading pharmaceutical company in ergot alkaloid research at the time. Historically, ergot alkaloids had been primarily used in obstetrics, but with methysergide (1-methyl-lysergic acid 1′-hydroxy-butyl-(2S)-amide), it became apparent that they also held some potential in migraine treatment. Methysergide was the first effective prophylactic drug developed specifically to prevent migraine attacks in 1959. On the basis of significantly improved knowledge of migraine pathophysiology and the discovery of serotonin and its receptors, Glaxo was able to launch sumatriptan in 1992. It was the first member from the class of triptans, which are selective 5-HT1B/1D receptor agonists. Recent innovations in acute and preventive migraine therapy include lasmiditan, a selective 5-HT1F receptor agonist from Eli Lilly, the gepants, which are calcitonin gene-related peptide (CGRP) receptor antagonists discovered at Merck & Co and BMS, and anti-CGRP/receptor monoclonal antibodies from Amgen, Pfizer, Eli Lilly, and others.

Graphical abstract
Electrochemical Kinetics Study of Ultrasound-Assisted Chalcopyrite Oxidation
Authors: Li Lin , King Aaron , Davis Krystal , Yu Ben
Published: April 2023

Ultrasound-assisted chalcopyrite leaching has been reported previously, showing a noticeable improvement in leaching kinetics. However, the effect of ultrasound on the chalcopyrite oxidation kinetics from an electrochemical perspective has not been addressed. This study examines the ultrasonic enhancement of chalcopyrite oxidation kinetics in sulfuric acid solution from both conventional leaching and electrochemistry aspects. Electrochemical techniques, including linear sweep voltammetry (LSV) and chronoamperometry (CA), were used to illustrate the kinetics of chalcopyrite ultrasound-assisted leaching. Tafel analysis by LSV showed that 20% amplitude ultrasound power had increased the chalcopyrite electrochemical dissolution rate by about 20% in both Fe3+-free and 10 mM Fe3+-containing 0.5 M sulfuric acid solution. The CA tests indicated a drastic increase in the Fe3+ reduction reaction when ultrasound was applied (20% amplitude). At 0.5 V, the Fe3+ to Fe2+ reduction current density at 30 min drastically increased from − 65.54 without ultrasound to − 1165.84 µA cm−2 with ultrasound.

Graphical Abstract
The Application of Coffee Pulp Biochar Improves the Physical, Chemical, and Biological Characteristics of Soil for Coffee Cultivation
Authors: Sánchez-Reinoso Alefsi David , Ávila-Pedraza Edgar Álvaro , Lombardini Leonardo , Restrepo-Díaz Hermann
Published: April 2023

A field experiment was conducted for 2 years (2019 and 2020) to determine the response to the application of Biochar (BC) obtained from the coffee pulp in combination with chemical fertilization (CF) in coffee trees. The established treatments were the edaphic application of different doses of BC (0, 4, 8, and 16 t ha−1) and levels of CF (0, 33, 66, and 100% of the nutritional requirements) on the physical (bulk density (ρa), stable aggregates), chemical (nutrient availability), and biological (respiration) properties of soil from a coffee crop. Regarding the physical properties, it was mainly observed that BC doses of 8 or 16 t ha−1 reduced ρa (0.82 and 0.83 g cm−3, respectively) and increased the aggregation status (96.5% and 96.84%, respectively) in comparison to 0 t ha−1 in 2020. The chemical properties showed that the application of 16 t ha−1 BC decreased about 60% of the exchangeable acidity (EA) compared to the control (0 t ha−1) whereas the pH (4.96 and 4.92) and organic carbon (OC) (4.41 and 4.59) were higher than in the control soil (EA: 0.58 and 0.54 meq/100 g; pH: 4.63 and 4.55; OC: 4.17 and 4.32% in 2019 and 2020, respectively). Soil respiration (biological property) strongly increased (around 50–60%) with the combination of 66% CF and BC doses between 8 and 16 t ha−1 in both years. Doses between 8 and 16 t ha−1 BC of the coffee pulp can improve the quality of soils for coffee cultivation and provide an alternative and more sustainable amendment that may help reduce chemical fertilization.
A role for macrophages under cytokine control in mediating resistance to ADI-PEG20 (pegargiminase) in ASS1-deficient mesothelioma
Authors: Phillips Melissa M. , Pavlyk Iuliia , Allen Michael , Ghazaly Essam , Cutts Rosalind , Carpentier Josephine , Berry Joe Scott , Nattress Callum , Feng Shenghui , Hallden Gunnel , Chelala Claude , Bomalaski John , Steele Jeremy , Sheaff Michael , Balkwill Frances , Szlosarek Peter W.
Published: April 2023

Background

Pegylated arginine deiminase (ADI-PEG20; pegargiminase) depletes arginine and improves survival outcomes for patients with argininosuccinate synthetase 1 (ASS1)-deficient malignant pleural mesothelioma (MPM). Optimisation of ADI-PEG20-based therapy will require a deeper understanding of resistance mechanisms, including those mediated by the tumor microenvironment. Here, we sought to reverse translate increased tumoral macrophage infiltration in patients with ASS1-deficient MPM relapsing on pegargiminase therapy.

Methods

Macrophage-MPM tumor cell line (2591, MSTO, JU77) co-cultures treated with ADI-PEG20 were analyzed by flow cytometry. Microarray experiments of gene expression profiling were performed in ADI-PEG20-treated MPM tumor cells, and macrophage-relevant genetic “hits” were validated by qPCR, ELISA, and LC/MS. Cytokine and argininosuccinate analyses were performed using plasma from pegargiminase-treated patients with MPM.

Results

We identified that ASS1-expressing macrophages promoted viability of ADI-PEG20-treated ASS1-negative MPM cell lines. Microarray gene expression data revealed a dominant CXCR2-dependent chemotactic signature and co-expression of VEGF-A and IL-1α in ADI-PEG20-treated MPM cell lines. We confirmed that ASS1 in macrophages was IL-1α-inducible and that the argininosuccinate concentration doubled in the cell supernatant sufficient to restore MPM cell viability under co-culture conditions with ADI-PEG20. For further validation, we detected elevated plasma VEGF-A and CXCR2-dependent cytokines, and increased argininosuccinate in patients with MPM progressing on ADI-PEG20. Finally, liposomal clodronate depleted ADI-PEG20-driven macrophage infiltration and suppressed growth significantly in the MSTO xenograft murine model.

Conclusions

Collectively, our data indicate that ADI-PEG20-inducible cytokines orchestrate argininosuccinate fuelling of ASS1-deficient mesothelioma by macrophages. This novel stromal-mediated resistance pathway may be leveraged to optimize arginine deprivation therapy for mesothelioma and related arginine-dependent cancers.
On the role of the laminar/turbulent interface in energy transfer between scales in bypass transition
Authors: Yao H. , Papadakis G.
Published: April 2023

We investigate the role of the laminar/turbulent interface in the interscale energy transfer in a boundary layer undergoing bypass transition with the aid of the Kármán–Howarth–Monin–Hill (KHMH) equation. A local binary indicator function is used to detect the interface and employed subsequently to define two-point intermittencies. These are used to decompose the standard-averaged interscale and interspace energy fluxes into conditionally averaged components. We find that the inverse cascade in the streamwise direction reported in an earlier work arises due to events across the downstream or upstream interfaces of a turbulent spot. However, the three-dimensional energy flux maps reveal significant differences between these two regions: in the downstream interface, inverse cascade is stronger and dominant over a larger range of streamwise and spanwise separations. We explain this finding by considering a propagating spot of simplified shape as it crosses a fixed streamwise location. We derive also the conditionally averaged KHMH equation, thus generalising similar equations for single-point statistics to two-point statistics. We compare the three-dimensional maps of the conditionally averaged production and total energy flux within turbulent spots against the maps of standard-averaged quantities within the fully turbulent region. The results indicate remarkable dynamical similarities between turbulent spots and the fully turbulent region for two-point statistics. This has been known only for single-point quantities, and we demonstrate here that the similarity extends to two-point quantities as well.
Variational inference of ice shelf rheology with physics-informed machine learning
Authors: Riel Bryan , Minchew Brent
Published: April 2023

Floating ice shelves that fringe the coast of Antarctica resist the flow of grounded ice into the ocean. One of the key factors governing the amount of flow resistance an ice shelf provides is the rigidity (related to viscosity) of the ice that constitutes it. Ice rigidity is highly heterogeneous and must be calibrated from spatially continuous surface observations assimilated into an ice-flow model. Realistic uncertainties in calibrated rigidity values are needed to quantify uncertainties in ice sheet and sea-level forecasts. Here, we present a physics-informed machine learning framework for inferring the full probability distribution of rigidity values for a given ice shelf, conditioned on ice surface velocity and thickness fields derived from remote-sensing data. We employ variational inference to jointly train neural networks and a variational Gaussian Process to reconstruct surface observations, rigidity values and uncertainties. Applying the framework to synthetic and large ice shelves in Antarctica demonstrates that rigidity is well-constrained where ice deformation is measurable within the noise level of the observations. Further reduction in uncertainties can be achieved by complementing variational inference with conventional inversion methods. Our results demonstrate a path forward for continuously updated calibrations of ice flow parameters from remote-sensing observations.
A spatial mutation model with increasing mutation rates
Authors: Chao Brian , Schweinsberg Jason
Published: April 2023

We consider a spatial model of cancer in which cells are points on the d-dimensional torus
$\mathcal{T}=[0,L]^d$
, and each cell with
$k-1$
mutations acquires a kth mutation at rate
$\mu_k$
. We assume that the mutation rates
$\mu_k$
are increasing, and we find the asymptotic waiting time for the first cell to acquire k mutations as the torus volume tends to infinity. This paper generalizes results on waiting for
$k\geq 3$
mutations in Foo et al. (2020), which considered the case in which all of the mutation rates
$\mu_k$
are the same. In addition, we find the limiting distribution of the spatial distances between mutations for certain values of the mutation rates.
EMPIRE INSIDE OUT: CELEBRATING CONSTANTINE'S VICTORIES BETWEEN ROME AND TRIER
Authors: Ross Alan J.
Published: April 2023

This article argues thatPanegyricus LatinusXII(9), a speech performed before Constantine in Trier in 313c.e.following his defeat of Maxentius the previous year, acted as a crucial localized act of communication to the emperor. Through a series of allusions and the careful presentation of his narrative, the orator made a case for the continued political and cultural importance of Trier within the newly expanded Constantinian empire.
Rigidity of capillary surfaces in compact 3-manifolds with strictly convex boundary
Authors: Sousa Paulo Alexandre , Batista Rondinelle Marcolino , Lima Barnabé Pessoa , Vieira Bruno Vasconcelos Mendes
Published: April 2023

In this paper, we obtain one sharp estimate for the length $L(\partial\Sigma)$ of the boundary $\partial\Sigma$ of a capillary minimal surface Σ2 in M3, where M is a compact three-manifolds with strictly convex boundary, assuming Σ has index one. The estimate is in term of the genus of Σ, the number of connected components of $\partial\Sigma$ and the constant contact angle θ. Making an extra assumption on the geometry of M along $\partial M$, we characterize the global geometry of M, which is saturated only by the Euclidean three-balls. For capillary stable CMC surfaces, we also obtain similar results.
Fishes of Empire: Imperialism and ichthyological introductions in British Malaya, 1923–42
Authors: Ruizhi Choo
Published: April 2023

The cultural, technological, and socioeconomic dimensions of exotic animal introductions into the Malayan Peninsula have largely escaped the notice of scholars of British Malaya. At the same time, the scientific literature on exotic ichthyological introductions into Malaya has framed such introductions in largely biological terms. Biological factors alone, however, cannot explain the introduction and cultivation of exotic (sometimes temperate) fishes in tropical Malayan waters. Between 1923 and 1942, the Fisheries Department of the Straits Settlements and Federated Malay States experimented with introducing three categories of exotic fishes into the Malayan Peninsula. These fishes—the sepat siam, Chinese carp and English trout—were reared and released into demographic and geographical landscapes profoundly shaped by imperial power. These animals were thus ‘fishes of Empire’, their introduction and cultivation in the Malayan Peninsula significantly influenced by the scientific, socioeconomic, technological, and cultural contexts of the British Empire. Studying the places, peoples, and technologies that shaped (and were in turn shaped by) these fishes of Empire offers insights into the intersections of imperial power, colonial science, and environmental history.
HEARING SOLARIS: DAI FUJIKURA'S OPERA AND A MUSICAL APPROACH TO STANISŁAW LEM'S NOVEL
Authors: Demoz Héloïse
Published: April 2023

Although many opera libretti are based on novels and short stories, only a few have used a science-fiction story as their main subject. The first opera of the Japanese composer Dai Fujikura was written in 2013–14 to a libretto by Saburo Teshigawara and is developed from Stanisław Lem's acclaimed novel Solaris (1961). By analysing passages from the score, this article will explore both the different strategies used by the composer and his librettist to create a new version of the story and the ways in which they have renewed the genre of opera.
VALENTIN SILVESTROV AND PUTIN'S WAR IN UKRAINE
Authors: Gillies Richard Louis
Published: April 2023

This article draws on published interviews and personal correspondence with the Ukrainian composer Valentin Silvestrov (b. 1937) to situate the development of his musical aesthetics and international reputation within the context of the Ukrainian Revolution of Dignity, the Russian annexation of Crimea and the ongoing Russian invasion of Ukraine, launched in February 2022. In particular, the article focuses on Silvestrov's use of sacred musical genres as a means of engaging directly with his contemporary political environment; it also explores the ways in which Silvestrov and his music have recently become an unequivocal symbol of defiance in the face of Russian aggression, a position that stands in stark contrast to the avowed disinterestedness in and removal from politics that characterised his works of the 1970s and 1980s.
Time, Deindustrialisation and the Receding Horizon of Working-Class Activism in Late Twentieth-Century Italy (Fiat, 1979–1980)
Authors: Myers Matt
Published: April 2023

This article seeks to understand how experiences of time change after influential social groups and institutions are disempowered. By analysing the response of a wide range of actors to key disputes at car manufacturer Fiat between 1979 and 1980, it suggests that changing conceptions of time came to register Fiat workers’ disempowerment within Italian society during the late twentieth century. A new present-centric sense of time came to predominate amongst laid-off Fiat worker activists, while a future-orientated sense grew amongst company managers. With a feeling of loosening connection with the immediate past and anxiety about the future, an indefinite present became the point of departure for workers’ inquiries into the past. The history of the Italian workers’ movement after 1980 shows the inextricable link between undermining collective organisation, delegitimising shared experiences of time, and the plausibility of transformative visions of the future.
Help-seeking and treatment delivery preferences for women experiencing perinatal anxiety symptoms
Authors: Maguire Peta N. , Bhullar Navjot , Cosh Suzanne M. , Wootton Bethany M.
Published: April 2023

Background:

Anxiety is common during the perinatal period and despite effective treatments being available, many women with perinatal anxiety disorders experience barriers when accessing treatment.

Aims:

The aims of the current study were to explore women’s perceived barriers to treatment uptake; cognitive behavioural therapy (CBT) treatment delivery preferences; and the utility of the Health Belief Model (HBM) in predicting intention to seek psychological help for women with perinatal anxiety symptoms.

Method:

This study employed a cross-sectional design consisting of women with self-reported anxiety in the perinatal period. A total of 216 women (Mage=28.53 years;SD=4.97) participated in the study by completing a battery of online self-report measures.

Results:

The results indicated that the most salient barriers to accessing care were: (1) the cost of treatment, (2) wanting to solve the problem on their own, and (3) thinking the problem would go away without treatment. Group-delivered CBT was the least acceptable treatment method, while face-to-face individual CBT was the most acceptable treatment method. The HBM variables predicted approximately 35% of the variance in help-seeking intention.

Discussion:

This study has important implications for the delivery of psychological care in the perinatal period and may be used to improve treatment uptake.
‘It was organized from the bottom’: the response from community-based institutions during the 2014 Ebola epidemic
Authors: Franklin Sabine Iva
Published: April 2023

What was the turning point in the world's largest and deadliest outbreak of the Ebola virus disease? Public health interventions tend to focus on supply-side provision of public health goods. These goods are clinical resources such as medicine or equipment. However, no nation has enough resources to ‘treat’ its way out of a widespread epidemic. Behavioural changes, such as social distancing, are needed too. Behaviours are the demand-side of public health goods and if unaddressed, perpetuate disease transmission. Community-based institutions addressed demand-side barriers during the 2014 Ebola epidemic in Liberia and Sierra Leone. Sixty-seven interviews were conducted in several provinces in Liberia and Sierra Leone. The findings show that information asymmetry and collective action challenges lowered the demand for clinical resources. Community-based institutions intervened via health sensitization and emergency regulations. Therefore, health seeking and public cooperation improved. This research study demonstrates a need to integrate community-led action into public health emergency management.
Lifetime caffeine and adolescent nicotine exposure in mice: effects on anxiety-like behavior and reward
Authors: Dutra-Tavares Ana Carolina , Ribeiro-Carvalho Anderson , Nunes Fernanda , Araújo Ulisses Cesar , Bruno Vitor , Marcourakis Tania , Filgueiras Claudio C. , Manhães Alex C. , Abreu-Villaça Yael
Published: April 2023

Caffeine consumption occurs throughout life, while nicotine use typically begins during adolescence, the period when caffeine-nicotine epidemiological association begins in earnest. Despite that, few studies in animal models parallel the pattern of coexposure that occurs in humans. Therefore, the neurobehavioral consequences of the association between these drugs remain unclear. Here, we exposed Swiss mice to lifetime caffeine. Caffeine solutions of 0.1 g/L (CAF0.1), 0.3 g/L (CAF0.3), or water (CTRL) were used as the sole liquid source, being offered to progenitors until weaning and, after that, directly to the offspring until the last day of adolescent behavioral evaluation. The open field test was used to evaluate acute effects of nicotine, of lifetime caffeine and of their interaction on locomotion and anxiety-like behavior, while the conditioned place preference test was used to assess the impact of caffeine on nicotine (0.5 mg/Kg, i.p.) reward. Frontal cerebral cortex dopamine content, dopamine turnover, and norepinephrine levels, as well as hippocampal serotonin 1A receptor expression were assessed. CAF0.3 mice exhibited an increase in anxiety-like behavior when compared to CAF0.1 and CTRL ones, but nicotine coexposure mitigated the anxiogenic-like caffeine-induced effect. Distinctively, caffeine had no effect on locomotion and failed to interfere with both nicotine-induced hyperactivity and place preference. There were no significant effects on dopaminergic and serotonergic markers. In conclusion, although caffeine did not affect nicotine reward, considering the strong association between anxiety disorders and tobacco consumption, caffeine-induced anxiety-like behavior advises limiting its consumption during development, including adolescence, as caffeine could be a risk factor to nicotine use.
Future Increase in Aridity Drives Abrupt Biodiversity Loss Among Terrestrial Vertebrate Species
Authors: Liu Xiaoping , Guo Renyun , Xu Xiaocong , Shi Qian , Li Xia , Yu Haipeng , Ren Yu , Huang Jianping
Published: April 2023

The planet is predicted to become drier because of accelerating global warming, increasing great challenges to the survival of terrestrial species. However, the understanding of when and where increasing aridity in the future will lead to abrupt biodiversity loss is still limited. Here, we predicted the spatiotemporal dynamics of future vertebrate biodiversity loss driven by increasing aridity at the assemblage scale under the scenario framework of the shared socio‐economic pathways (SSPs) and representative concentration pathways (RCPs). The results show that, under the high‐emissions scenario of SSP5‐8.5, more than 24.19% of terrestrial assemblages are projected to have at least one vertebrate species exposed to unprecedented aridity conditions by 2100, leading to 55.29% of terrestrial vertebrate species experiencing local habitat loss. In addition, the mean magnitude of global exposure is expected to reach 17.47% by 2100. Within these assemblages, most species will be simultaneously exposed to unprecedented aridity conditions, with an average exposure abruptness of 78.00%, most of which will occur intensively after 2050. If we manage to reduce greenhouse gas emissions to the SSP1‐2.6 (SSP2‐4.5) scenario, the magnitude of exposure can significantly decrease to 7.35% (10.56%), and the onset of exposure can be delayed by 43 (30) years, averaging approximately 30% (14%) of vertebrate species from local habitat loss. Our findings also highlight that the concurrent extremes of increasing aridity and rising temperature in Southeast Asia and Amazon rainforests may amplify exposure risks, which can motivate decision‐makers to respond early and eﬀectively to mitigate abrupt ecological disruption.
Two Volcanic Tsunami Events Caused by Trapdoor Faulting at a Submerged Caldera Near Curtis and Cheeseman Islands in the Kermadec Arc
Authors: Sandanbata Osamu , Watada Shingo , Satake Kenji , Kanamori Hiroo , Rivera Luis
Published: April 2023

Two submarine earthquakes (Mw 5.8) occurred near volcanic islands, Curtis and Cheeseman, in the Kermadec Arc in 2009 and 2017. Following both earthquakes, similar tsunamis with wave heights of about a meter, larger than expected from their moderate seismic magnitudes, were observed by coastal tide gauges. We investigate the source mechanism for both earthquakes by analyzing tsunami and seismic data of the 2017 event. Tsunami waveform analysis indicates that the earthquake uplifted a submerged caldera around the islands. Combined analysis of tsunami and seismic data suggests that trapdoor faulting, or sudden intra‐caldera fault slip interacted with magma reservoir deformation, occurred due to magma overpressure, possibly in association with caldera resurgence. The earthquake scaling relationship for trapdoor faulting events at three calderas deviates from that for regular earthquakes, possibly due to the fault‐reservoir interaction in calderas.
Strong High‐Latitude Zonal Wind Gradient Observed by CHAMP and Simulated by TIEGCM
Authors: Zhang Kedeng , Wang Hui , Wang Wenbin , McInerney Joseph M.
Published: April 2023

Using 6 days cross‐track wind data from CHAMP, we investigate the high‐latitude westward wind gradient and reversal that occurs at fixed longitudes (−120° ∼ −30° GLon in the Northern Hemisphere, 150° ∼ 210° GLon in the Southern Hemisphere). The driver of the wind gradient at 60° ∼ 70° GLat and in the noon sector is investigated via TIEGCM. The wind gradient is driven by the combined effects of the Earth's geomagnetic field configuration and the energy deposition from the solar wind. The temporal variations of the neutral wind cell in afternoon sector are critical to the formation of wind gradient. The development of wind gradient is due to the equatorward expansion of the afternoon westward wind cell from the geographic high‐latitudes to 60° ∼ 70° GLat. Whereas the disappearance is associated with the poleward contraction from 60° to ∼70° GLat to higher latitudes. A further diagnostic analysis of model results shows that the primary internal driver of the wind gradient is a balance between ion drag and pressure gradient. In the acceleration phase, ion drag causes the formation of the strong gradient of westward wind, whereas pressure gradient decelerates it. A similar result is found in the deceleration phase. The ion drag is controlled predominantly by both the electron density and the relative motion between the ions and neutrals.
Quantifying Parametric Uncertainty Effects on Tropical Cloud Fraction in an AGCM
Authors: Xie Feng , Li Lijuan , Pu Ye , Wang Bin , Xue Wei , Qiu Xuexing , Wang Gen
Published: April 2023

The underestimation of cloud fraction, especially the low stratus cloud (LSC) fraction over the eastern oceans, remains a problem in most atmospheric global climate models. This study investigated potential improvements through perturbing nine moist physical parameters, using uniform sampling and Latin hypercube sampling methods, and quantified the parametric uncertainty and effects of non‐linear interaction between parameters on the tropical cloud fraction in the Grid‐Point Atmospheric Model of the Institute of Atmospheric Physics/State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics, version 2. Results showed that the uncertainty ranges of the tropical total cloud fraction and LSC associated with multiple‐parameter perturbation were larger than those from any single‐parameter perturbation. The total cloud fraction was significantly improved with multiple‐parameter perturbation and the LSC also increased notably when using parameter values optimized for the total cloud fraction because of the indirect parametric effect on lower‐tropospheric stability. Non‐linear effects between parameters on simulating LSC were much stronger than those on simulating the total cloud fraction. Furthermore, the non‐linear interaction reduced large values of total cloud fraction but had a strong incremental effect on large values of LSC over the southeast Pacific. The findings demonstrate the feasibility of improving the simulation of LSC over the eastern oceans by tuning moist parameters, and provide further insight into the non‐linear effects between parameters on the simulation of cloud fraction.
Astronaut Radiation Dose Calculation With a New Galactic Cosmic Ray Model and the AMS‐02 Data
Authors: Chen Xuemei , Xu Songying , Song Xiaojian , Huo Ran , Luo Xi
Published: April 2023

We present a new calculation of the astronaut dose rate from the galactic cosmic rays in free space at 1 AU. We use the unshielded isotropic fluence‐to‐dose conversion coefficients given in the International Commission on Radiological Protection publication 123. A new 3D and time‐dependent solar modulation model based on Parker's transport equation as originally developed in Song et al. (2021, https://doi.org/10.3847/1538-4365/ac281c) is used to calculate the galactic cosmic ray spectra at 1 AU. This model uses the recent local interstellar spectra of Corti et al. (2019, https://doi.org/10.3847/1538-4357/aafac4), M. J. Boschini et al. (2020, https://doi.org/10.3847/1538-4365/aba901, 2021a, https://doi.org/10.3847/1538-4357/abf11c) to reproduce the PAMELA and AMS‐02 observations between 2006 and 2019. The radiation dose calculated from our model and from the AMS‐02 spectra in the same rigidity region agrees better than 1% for proton and helium in a time‐dependent way, and at 2% level for six most contributing cosmic ray elements averaged over 7 or 8.5 years. The time‐dependent dose rate analysis over 13 years shows an effective dose equivalent rate of 55–58 cSv/yr at solar minimum (January 2010) and 26 cSv/yr at solar maximum (February 2014).
Fire in the Earth System: Introduction to the Special Collection
Authors: East Amy , AghaKouchak Amir , Caprarelli Graziella , Filippelli Gabriel , Florindo Fabio , Luce Charles , Rajaram Harihar , Russell Lynn , Santin Cristina , Santos Isaac
Published: April 2023

Fire has always been an important component of many ecosystems, but anthropogenic global climate change is now altering fire regimes over much of Earth's land surface, spurring a more urgent need to understand the physical, biological, and chemical processes associated with fire as well as its effects on human societies. In 2020, AGU launched a Special Collection that spanned 10 journals, soliciting papers under the theme “Fire in the Earth System” to encourage state‐of‐the‐art publications in fire‐related science. The completed Special Collection comprises more than 100 papers. Here, we summarize the articles published in this collection, considering them to be grouped into seven themes: paleofire and its ties to climate; evolution of fire patterns in the recent past and the future, including the effects of ongoing climate change; physical (atmospheric) and chemical processes associated with fire; ecosystem effects, including on biogeochemical cycles; physical landscape change after fire and its associated hazards; fire effects on water quality, air quality, and human health; and new methods and technologies applied to fire research.
Cdyl2-60aa encoded by CircCDYL2 accelerates cardiomyocyte death by blocking APAF1 ubiquitination in rats
Authors: Deng Yunfei , Zeng Xiaochen , Lv Yifei , Qian Zhiyuan , Guo Peijie , Liu Yi , Chen Shaoliang
Published: April 2023

The loss of cardiomyocytes (CMs) after myocardial infarction (MI) is widely acknowledged to initiate the development of heart failure (HF). Herein, we found that circCDYL2 (583 nt) derived from chromodomain Y-like 2 (Cdyl2) is significantly upregulated in vitro (oxygen-glucose deprivation (OGD)-treated CMs) and in vivo (failing heart post-MI) and can be translated into a polypeptide termed Cdyl2-60aa (~7 kDa) in the presence of internal ribosomal entry sites (IRES). Downregulation of circCDYL2 significantly decreased the loss of OGD-treated CMs or the infarcted area of the heart post-MI. Additionally, elevated circCDYL2 significantly accelerated CM apoptosis via Cdyl2-60aa. We then discovered that Cdyl2-60aa could stabilize protein apoptotic protease activating factor-1 (APAF1) and promote CM apoptosis; heat shock protein 70 (HSP70) mediated APAF1 degradation in CMs by ubiquitinating APAF1, which Cdyl2-60aa could competitively block. In conclusion, our work substantiated the claim that circCDYL2 could promote CM apoptosis via Cdyl2-60aa, which enhanced APAF1 stability by blocking its ubiquitination by HSP70, suggesting that it is a therapeutic target for HF post-MI in rats.
Exosome-based nanoimmunotherapy targeting TAMs, a promising strategy for glioma
Authors: Luo Hong , Zhang Hao , Mao Jinning , Cao Hui , Tao Yihao , Zhao Guanjian , Zhang Zhiwen , Zhang Nan , Liu Zaoqu , Zhang Jian , Luo Peng , Xia Yuguo , Cheng Yuan , Xie Zongyi , Cheng Quan , Liu Guodong
Published: April 2023

Exosomes, the cell-derived small extracellular vehicles, play a vital role in intracellular communication by reciprocally transporting DNA, RNA, bioactive protein, chains of glucose, and metabolites. With great potential to be developed as targeted drug carriers, cancer vaccines and noninvasive biomarkers for diagnosis, treatment response evaluation, prognosis prediction, exosomes show extensive advantages of relatively high drug loading capacity, adjustable therapeutic agents release, enhanced permeation and retention effect, striking biodegradability, excellent biocompatibility, low toxicity, etc. With the rapid progression of basic exosome research, exosome-based therapeutics are gaining increasing attention in recent years. Glioma, the standard primary central nervous system (CNS) tumor, is still up against significant challenges as current traditional therapies of surgery resection combined with radiotherapy and chemotherapy and numerous efforts into new drugs showed little clinical curative effect. The emerging immunotherapy strategy presents convincing results in many tumors and is driving researchers to exert its potential in glioma. As the crucial component of the glioma microenvironment, tumor-associated macrophages (TAMs) significantly contribute to the immunosuppressive microenvironment and strongly influence glioma progressionviavarious signaling molecules, simultaneously providing new insight into therapeutic strategies. Exosomes would substantially assist the TAMs-centered treatment as drug delivery vehicles and liquid biopsy biomarkers. Here we review the current potential exosome-mediated immunotherapeutics targeting TAMs in glioma and conclude the recent investigation on the fundamental mechanisms of diversiform molecular signaling events by TAMs that promote glioma progression.
Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy
Authors: Xing Nan , Du Qinyun , Guo Sa , Xiang Gelin , Zhang Yi , Meng Xianli , Xiang Li , Wang Shaohui
Published: April 2023

Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, and radiotherapy. However, due to the strong metastatic characteristics of lung cancer and the emergence of related drug resistance and radiation resistance, the overall survival rate of lung cancer patients is not ideal. There is an urgent need to develop new treatment strategies or new effective drugs to treat lung cancer. Ferroptosis, a novel type of programmed cell death, is different from the traditional cell death pathways such as apoptosis, necrosis, pyroptosis and so on. It is caused by the increase of iron-dependent reactive oxygen species due to intracellular iron overload, which leads to the accumulation of lipid peroxides, thus inducing cell membrane oxidative damage, affecting the normal life process of cells, and finally promoting the process of ferroptosis. The regulation of ferroptosis is closely related to the normal physiological process of cells, and it involves iron metabolism, lipid metabolism, and the balance between oxygen-free radical reaction and lipid peroxidation. A large number of studies have confirmed that ferroptosis is a result of the combined action of the cellular oxidation/antioxidant system and cell membrane damage/repair, which has great potential application in tumor therapy. Therefore, this review aims to explore potential therapeutic targets for ferroptosis in lung cancer by clarifying the regulatory pathway of ferroptosis. Based on the study of ferroptosis, the regulation mechanism of ferroptosis in lung cancer was understood and the existing chemical drugs and natural compounds targeting ferroptosis in lung cancer were summarized, with the aim of providing new ideas for the treatment of lung cancer. In addition, it also provides the basis for the discovery and clinical application of chemical drugs and natural compounds targeting ferroptosis to effectively treat lung cancer.
Nonvolatile electrical control of spin polarization in the 2D bipolar magnetic semiconductor VSeF
Authors: Li Yuhui , Deng Jun , Zhang Yan-Fang , Jin Xin , Dong Wen-Han , Sun Jia-Tao , Pan Jinbo , Du Shixuan
Published: April 2023

Nonvolatile electrical control of spin polarization in two-dimensional (2D) magnetic semiconductors is greatly appealing toward future low-dissipation spintronic nanodevices. Here, we report a 2D material VSeF, which is an intrinsic bipolar magnetic semiconductor (BMS) featured with opposite spin-polarized valence and conduction band edges. We then propose a general nonvolatile strategy to manipulate both spin-polarized orientations in BMS materials by introducing a ferroelectric gate with proper band alignment. The spin-up/spin-down polarization of VSeF is successfully controlled by the electric dipole of ferroelectric bilayer Al2Se3, verifying the feasibility of the design strategy. The interfacial doping effect from ferroelectric gate also plays a role in enhancing the Curie temperature of the VSeF layer. Two types of spin field effect transistors, namely multiferroic memory and spin filter, are further achieved in VSeF/Al2Se3 and VSeF/Al2Se3/Al2Se3 multiferroic heterostructures, respectively. This work will stimulate the application of 2D BMS materials in future spintronic nanodevices.
Bayesian optimization with active learning of design constraints using an entropy-based approach
Authors: Khatamsaz Danial , Vela Brent , Singh Prashant , Johnson Duane D. , Allaire Douglas , Arróyave Raymundo
Published: April 2023

The design of alloys for use in gas turbine engine blades is a complex task that involves balancing multiple objectives and constraints. Candidate alloys must be ductile at room temperature and retain their yield strength at high temperatures, as well as possess low density, high thermal conductivity, narrow solidification range, high solidus temperature, and a small linear thermal expansion coefficient. Traditional Integrated Computational Materials Engineering (ICME) methods are not sufficient for exploring combinatorially-vast alloy design spaces, optimizing for multiple objectives, nor ensuring that multiple constraints are met. In this work, we propose an approach for solving a constrained multi-objective materials design problem over a large composition space, specifically focusing on the Mo-Nb-Ti-V-W system as a representative Multi-Principal Element Alloy (MPEA) for potential use in next-generation gas turbine blades. Our approach is able to learn and adapt to unknown constraints in the design space, making decisions about the best course of action at each stage of the process. As a result, we identify 21 Pareto-optimal alloys that satisfy all constraints. Our proposed framework is significantly more efficient and faster than a brute force approach.