bluuebunny/crossref_metadata_2025 huggingface dataset:
How did the meter acquire its definitive length?
Authors: Nyblom Jukka
Published: April 2023

The French Academy of Science decided in 1791 that the new unit of length, the meter, is to be as one ten millionth part of the meridian quarter from the north pole to the equator. In order to find out the numerical value for this length, the Academy equipped two expeditions for measuring the meridian arc between Dunkirk and Barcelona. Then by mathematical calculations one could derive the length of the meridian quarter. After the expeditions had returned to Paris and their data had become available, Pierre-Simon Laplace (1749–1827) estimated the flattening of the earth. He obtained the value 1/150.6, which cannot stand as regards known facts. This is a story about how Laplace managed to save the meter project. Combining the new French arc measurements with the older measurements made in Peru 1730–40 he estimated the flattening anew and found the plausible value 1/334. With the help of this new flattening he calculated the definitive length of the meter to be 443.296 Parisian lines. The final section of the article tells the refinements of the meter’s definitions from the year 1799 to the present.
Garau Formation as an unconventional hydrocarbon resource in southwestern Iran: a geochemical investigation
Authors: Hosseiny Ehsan , Mohseni Ahmadreza
Published: April 2023

Due to the growing need for hydrocarbons and the limited conventional resources, paying attention to unconventional oil and gas resources is essential. The upper Jurassic-Lower Cretaceous in western and southwestern Iran contains the most crucial source rocks of the Zagros sedimentary basin. One of the richest source rocks is the shaly Garau Formation. Owing to geochemical and geological characteristics, the Garau Formation, with Neocomian to Coniacian age and periodicity of radiolore black limestones with black pyrite bituminous shales, ammonite, and chertite shale, is the suitable potential sweet spot as oil shale and gas shale. In this study, a comprehensive regional study was conducted on the entire Garau Formation basin using Rock–Eval parameters and organic matter maturity data. In addition to investigating the hydrocarbon generation potential of the Garau Formation as a source rock, the prospect of this Formation as oil and gas shales in the entire Garau basin was investigated. For this purpose, 31 fields in 5 important sub-basins of Zagros, including East Lorestan, West Lorestan, Izeh zone, Dezful Embayment, and Abadan plain were investigated. The study showed that total organic carbon varies between 0.17 and 24.6, and more than 75% of total organic carbon had values greater than 1. By examining the quantity, quality, and maturity parameters and considering the necessary thresholds, it was found that East Lorestan and West Lorestan have the conditions for oil and gas shales. The highest quantity and best quality of organic matter are related to Eastern Lorestan. By moving west and south of Garau Basin, the quantity and quality of organic matter decrease, and the hydrogen index proves the results. Vitrinite reflection studies indicated that the lowest and highest levels of organic matter maturity belong to East Lorestan and West Lorestan, respectively. Therefore, the northeast of Garau Basin (Eastern Lorestan) has the potential for oil shale, and the northwest of the Basin (Western Lorestan) has the potential for gas shale.
Revisiting the public–private wage gap in Spain: new evidence and interpretation
Authors: Couceiro de León Alba , Dolado Juan J.
Published: April 2023

This paper updates the available evidence on the public–private wage gap in Spain, which dates back to 2012. Through microdata drawn from the last three waves of the Wage Structure Survey (2010, 2014 and 2018), we study how this gap and its distribution by gender and education have evolved during and after the Great Recession. Conventional Oaxaca-Blinder decompositions are used to divide the raw wage gap into a component explained by differences in characteristics and another one capturing differences in returns and endogenous selection. The main findings are: (i) a strong wage compression by skills, and (ii) a wage premium for less-skilled women in the public sector. Both empirical results can be rationalised by a monopoly union wage-setting model with monopsonistic features and the presence of female statistical discrimination.
Case report. Hematurie bij een patiënt met lokale doorgroei van een testiscarcinoom
Authors: Nuijens Siberyn T. , Mulder Sasja F. , Halilovic Mirha , Sijm Joost H. M. , Muselaers Constantijn H. J.
Published: April 2023

Samenvatting

Dit case report betreft een patiënt met hematurie ten gevolge van een kiemceltumor van de linker testis, welke doorgroeide in de blaaswand. Mannen met een niet-ingedaalde testis hebben een verhoogde kans op het ontwikkelen van een testiculaire kiemceltumor. Bij de 67-jarige patiënt in deze casus werd tijdens cystoscopie een tumor in de blaas gevonden. De patiënt onderging een diagnostische transurethrale resectie van de tumor, laboratoriumonderzoek en een CT-scan, op grond waarvan een stadium 2‑good-risk seminoom van de testis werd gediagnosticeerd. De patiënt werd behandeld met vier cycli van etoposide en cisplatine met nadien een open chirurgische resectie van de restlaesie. Het herstel verliep ongecompliceerd. Bij beeldvorming na zes maanden waren er geen tekenen van een recidief.
Land-Use Rights and Informal Credit in Rural Vietnam
Authors: Migheli Matteo
Published: April 2023

Access to credit and its cost are a major challenge for farmers in developing countries. Land serves as collateral for accessing formal credit, but the role that land ownership plays in accessing informal credit and determining its cost is understudied. This paper provides empirical evidence on the effects that land ownership has on both the demand for and the cost of informal and formal credit in the Mekong Delta. The results show that as land ownership increases, both the demand for and the cost of informal loans decrease, while the amount of money borrowed from formal lenders increases. The design and implementation of appropriate land redistributions seem to be a fundamental way to fight the informal credit market.
Structural MRI Texture Analysis for Detecting Alzheimer’s Disease
Authors: Silva Joana , Bispo Bruno C. , Rodrigues Pedro M. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2023

Purpose:

Alzheimer’s disease (AD) has the highest worldwide prevalence of all neurodegenerative disorders, no cure, and low ratios of diagnosis accuracy at its early stage where treatments have some effect and can give some years of life quality to patients. This work aims to develop an automatic method to detect AD in 3 different stages, namely, control (CN), mild-cognitive impairment (MCI), and AD itself, using structural magnetic resonance imaging (sMRI).

Methods:

A set of co-occurrence matrix and texture statistical measures (contrast, correlation, energy, homogeneity, entropy, variance, and standard deviation) were extracted from a two-level discrete wavelet transform decomposition of sMRI images. The discriminant capacity of the measures was analyzed and the most discriminant ones were selected to be used as features for feeding classical machine learning (cML) algorithms and a convolution neural network (CNN).

Results:

The cML algorithms achieved the following classification accuracies: 93.3% for AD vs CN, 87.7% for AD vs MCI, 88.2% for CN vs MCI, and 75.3% for All vs All. The CNN achieved the following classification accuracies: 82.2% for AD vs CN, 75.4% for AD vs MCI, 83.8% for CN vs MCI, and 64% for All vs All.

Conclusion:

In the evaluated cases, cML provided higher discrimination results than CNN. For the All vs All comparison, the proposed
method surpasses by 4% the discrimination accuracy of the state-of-the-art methods that use structural MRI.
Differential impact of exportin-1-mediated nuclear export of RNAs on the RNA content of extracellular vesicle subpopulations
Authors: Pálóczi Krisztina , Buzas Edit I. , Falus András
Published: April 2023

Extracellular vesicles (EVs) are membrane-enclosed subcellular structures released by all cell types. EVs have important roles in both cellular homeostasis and intercellular communication. Recent progress in the field revealed substantial heterogeneity of EVs even within the size-based EV categories. Here we addressed the question whether the exportin-1 (XPO1)-mediated nuclear export of RNAs contributed to the EV heterogeneity. Size-based populations were separated from the conditioned media of three cell lines (U937, THP-1 and 5/4E8) in steady-state condition. The effects of activation and leptomycin B treatment (to inhibit the XPO1-mediated nuclear export of RNAs) were also tested in the case of the two monocytic cell lines. Agilent Pico and Small chips were used to characterize RNAs, fragment analysis was performed, and EV-associated miRNAs were tested by Taqman assays. As expected, we found the highest small RNA/total RNA ratio and the lowest rRNA/total RNA proportion in small EVs (~ 50–150 nm). Profiles of the small RNAs within different size-based EV categories significantly differed based on the activation status of the EV releasing cells. Leptomycin B had a differential inhibition on the tested small RNAs in EVs, even within the same EV size category. A similar heterogeneity of the EV miRNA content was observed upon cellular activation and nuclear export inhibition. Here we complement the already existing knowledge on EV heterogeneity by providing evidence that the RNA cargo varies depending on the EV size-based category, the releasing cell type, the functional status of the releasing cells and the exportin-1-mediated nuclear export of RNAs.
Gγ subunit AT1/GS3-the “code” of alkaline tolerance in main graminaceous crops
Authors: Ju Chuanfeng , Wang Cun
Published: April 2023

This brief article highlights the results of Zhang et al. (Science 379, eade8416, 2023), who recently found that the Gγ subunit AT1/GS3 contributes to alkaline tolerance in several main monocots crops, and revealed the molecular mechanism of AT1/GS3-mediated response to alkaline stress in plants, which involves regulating H2O2 levels by inhibiting the phosphorylation of aquaporin PIP2s.
Social anxiety in modern societies from an evolutionary perspective
Authors: Haugan Tommy
Published: April 2023

This study seeks to frame the evolutionary roots of why people strive for attractiveness, and how seeking social status and the desire to be accepted by peers in today’s society may cause psychological distress and social anxiety. The central aim of the present study is twofold. First, the goal is to break down biological selection into its component parts to understand the evolution of key human traits that consequently make social status concerns and social anxiousness reasonable and adaptive. The second goal is to highlight the socioeconomic conditions that may enhance people’s propensity to develop social anxiety. This study proposes that an evolutionary approach to social anxiety should rely on a broad concept of social selection (grouped into nonsexual social selection, intersexual selection, and intrasexual selection). Furthermore, the overwhelming visualisation of differences in quality and conspicuous displays of status markers in modern societies may act as psychological stressors that increase people’s propensity to develop social anxiety. Understanding how the evolved human mind and behavioural strategies respond to socioeconomic and sociocultural circumstances is relevant both in the formation of public policy and in clinical health services aiming to benefit public health.
Innovative design solutions for contemporary Tou-Kung based on topological optimisation
Authors: Duan Cheng Bi , Shen Su Yi , Bao Ding Wen , Yan Xin
Published: April 2023

Tou-Kung, which is pronounced in Chinese and known as Bracket Set (Liang & Fairbank, A pictorial history of Chinese architecture, 1984), is a vital support component in the Chinese traditional wooden tectonic systems. It is located between the column and the beam and connects the eave and pillar, making the heavy roof extend out of the eaves longer. The development of Tou-Kung is entirely a microcosm of the development of ancient Chinese architecture; the aesthetic structure and Asian artistic temperament behind Tou-Kung make it gradually become the cultural and spiritual symbol of traditional Chinese architecture. In the contemporary era, inheriting and developing Tou-Kung has become an essential issue. Several architects have attempted to employ new materials and techniques to integrate the traditional Tou-Kung into modern architectural systems, such as the China Pavilion at the 2010 World Expo and Yusuhara Wooden Bridge Museum. This paper introduces the topological optimisation method bi-directional evolutionary structural optimisation (BESO) for form-finding. BESO method is one of the most popular topology optimisation methods widely employed in civil engineering and architecture. Through analyzing the development trend of Tou-Kung and mechanical structure, the authors integrate 2D and 3D optimisation methods and apply the hybrid methods to form-finding. Meanwhile, mortise and tenon joint used to create stable connections with components of Tou-Kung are retained. This research aims to design a new Tou-Kung corresponding to “structural performance-based aesthetics”. The workflow proposed in this paper is valuable for Architrave and other traditional building components.
Just Transitions
Authors: Stevis Dimitris
Published: April 2023

Just transition prompts us to explore a number of important dimensions of Earth System Governance research, including sustainability transformations, inequality, power and justice. This Element aims to place just transition in the dynamics of the world political economy over the last several decades and to offer an overview of the varieties of just transitions based on an analytical scheme that focuses on their breadth (coverage), depth (social and ecological priorities) and ambition. The focus on breadth, depth and ambition centers on power, inequality and injustice and allows us to analyze and compare just transitions as a prerequisite for their fuller interpretation.
A systematic review on whether regenerative agriculture improves animal welfare: A qualitative analysis with a One Welfare perspective
Authors: Hargreaves-Méndez Matías Javier , Hötzel María José
Published: April 2023

The welfare of animals in food-production systems is a cause of concern to the public. Regenerative agriculture was first used by the Rodale Institute and proposes to regenerate degraded components of ecosystems, aiming to be more than just sustainable. However, despite animal welfare being pushed to be part of the SDG agenda for 2030, there is no clarity on how regenerative agriculture impacts animal welfare. It is challenging to determine regenerative agriculture impacts on animal welfare, since it is not entirely defined. One Welfare could help define entry points for future research by studying animal welfare in connection with human welfare and environmental conservation. We aimed to analyse the extent to which positive animal welfare outcomes characterise regenerative agriculture systems in peer-reviewed articles and whether the narratives of such articles support that regenerative agriculture promotes animal welfare directly or indirectly by improving human welfare and environmental conservation. We searched papers including ‘regenerative agriculture’ using PRISMA-P, selecting animal welfare, human welfare, environment conservation terms, developed themes, and carried out analysis using Atlas.Ti8 and Causal Loop Diagram. We found that papers mainly linked animal welfare to animal health, human welfare to financial farm status and farmer’s self-awareness, and environmental conservation to soil improvement. Causal Loop Diagram indicated that regenerative agriculture had the potential to improve the health and nutrition components of animal welfare by enhancing financial farmers’ status/self-awareness (human welfare), and the soil (environmental conservation), reflecting that the processes that affect human welfare and environmental conservation could also affect animal welfare. However, information in papers remains insufficient to determine how regenerative agriculture impacts on animal welfare and research into regenerative agriculture needs to extend its focus on animal welfare and elucidate the regenerative agriculture principles leading to animal welfare.
Interpreting the state–citizen nexus in contemporary Nordic legal and social citizenship: the case of divergence in restriction on freedom of movement as a mitigation policy in the COVID-19 pandemic
Authors: Nordensvärd Johan , Sefton Therese , Godenhjelm Sebastian
Published: April 2023

The aim of this article was to use an interpretivist approach to analyse the state–citizen nexus in general and the conflict between civil and social rights imposing restrictions on people’s freedom of movement during the COVID-19 pandemic in the Nordic countries: Sweden (restrictions were voluntary and relied on nudging and individual implementation), Norway (restrictions of movement were for everyone and was enforced by authorities), and Finland (restrictions of movement were for the capital region and was enforced by authorities). Sweden focused more on upholding the civil rights vis-à-vis social rights whereas in Norway and Finland social rights have trumped civil rights in the face of the pandemic. Thus, the analysis suggests that the Nordic countries cannot be understood as monoliths in all respects. The article thereby contributes to a greater understanding of how the Nordic governments prioritise civil and social rights differently when they are forced to choose.
Turning on Those Who Turn to the Courts: Experimental Evidence of Backlash Against Personal Injury Litigants
Authors: Barnes Jeb , Menounou Elli , Hevron Parker
Published: April 2023

Do people turn on those who turn to the courts? Using a survey experiment, we find people have significantly more negative attitudes toward personal injury litigants than other types of claimants, even when they believe the claimant is injured and mostly not at fault. Moreover, our subjects were not anti-claim, anti-hiring a lawyer, or even anti-government program. Instead, they were distinctively anti-litigant.
The Lost Breviarium Compertorum and Henry VIII's First Act for the Dissolution of the Monasteries, 1536
Authors: REX RICHARD
Published: April 2023

A challenge has recently been made to the venerable tradition that the passage of Henry VIII's first act for suppressing monasteries (1536) was facilitated by the presentation in parliament of details of monastic sexual misconduct gathered during the royal visitation of the monasteries in 1535–6. This article, by following up clues missed in the evidence cited for that challenge, precisely identifies a now lost source, last sighted in the hands of John Bale, which casts important new light on the visitation and, it is argued, was very probably the exact document presented to parliament in 1536.
Executive Partisanship and Corporate Investment
Authors: Rice Anthony B.
Published: April 2023

I show that an alignment in partisan affiliation, between a firm’s management and the president, is associated with higher levels of investment. Using insider trading data, I find that managers become more optimistic about their companies’ prospects when their preferred party is in power. This optimism-driven increase in investment is amplified by herding and associated with both lower profitability and stock returns. Overall, managers’ political beliefs produce heterogeneous expectations about future cash flows and distort investment decisions.
Nonlinear optimal control for a 4-DOF SCARA robotic manipulator
Authors: Rigatos G. , Abbaszadeh M. , Busawon K. , Pomares J.
Published: April 2023

Selective compliance articulated robot arms (SCARA) robotic manipulators find wide use in industry. A nonlinear optimal control approach is proposed for the dynamic model of the 4-degrees of freedom (DOF) SCARA robotic manipulator. The dynamic model of the SCARA robot undergoes approximate linearization around a temporary operating point that is recomputed at each time-step of the control method. The linearization relies on Taylor series expansion and on the associated Jacobian matrices. For the linearized state-space model of the system, a stabilizing optimal (H-infinity) feedback controller is designed. To compute the controller’s feedback gains, an algebraic Riccati equation is repetitively solved at each iteration of the control algorithm. The stability properties of the control method are proven through Lyapunov analysis. The proposed control method is advantageous because: (i) unlike the popular computed torque method for robotic manipulators, it is characterized by optimality and is also applicable when the number of control inputs is not equal to the robot’s number of DOFs and (ii) it achieves fast and accurate tracking of reference setpoints under minimal energy consumption by the robot’s actuators. The nonlinear optimal controller for the 4-DOF SCARA robot is finally compared against a flatness-based controller implemented in successive loops.
Jigless assembly of an industrial product by a universal robotic hand mounted on an industrial robot
Authors: Fukuda Takahito , Dobashi Hiroki , Nagano Hikaru , Tazaki Yuichi , Katayama Raita , Yokokohji Yasuyoshi
Published: April 2023

This paper demonstrates that “completely-jigless” assembly of a model product that requires fitting accuracy at the level of industrial products is possible by using a universal hand with four parallel stick fingers mounted on a conventional position-control-based industrial robot. Assuming that each part is taken out of the parts bin and temporarily placed on the work table, the accuracy required for precise fitting cannot be achieved with a vision sensor alone. Introducing an appropriate grasping strategy, the initial position error of the part is absorbed by self-alignment in the process of grasping. Once the alignment is completed, the pose of the grasped part is fixed and jigless assembly is possible with a conventional industrial robot, which has high repeatability. In this paper, we use a gear unit as an example of an industrial product and present some grasping strategies with the universal hand. We also propose some subsequent assembly strategies for shafts and gears. Using those grasping and assembly strategies, it is shown that jigless assembly of the gear unit was successfully completed in the experiment. Although the target product in this paper is specific, the assembly elements in this product, such as shaft screwing, bearing insertion, and gear meshing, are also included in many other products. Therefore, the methods shown in this paper can be applied to other products.
Ecocide, the Anthropocene, and the International Criminal Court
Authors: Branch Adam , Minkova Liana
Published: April 2023

The recent proposal by the Independent Expert Panel of the Stop Ecocide initiative to include the crime of ecocide in the International Criminal Court's Rome Statute has raised expectations for preventing and remedying severe environmental harm through international prosecution. As alluring as this image is, we argue that ecocide prosecutions may be the most difficult, perhaps even impossible, in precisely the cases that the ICC would need to be concerned with; namely, the gravest global incidents of environmental harm, including those associated with planetary climate change. We explore a series of questions about the panel's formulation of ecocide that resonate with longer debates around criminalizing environmental harm but take on new dimensions amid the Anthropocene and after twenty years of ICC trials. Ecocide must contend with the hard lessons learned concerning the ICC's limitations in realizing justice in a fraught international political context and also with fundamental challenges to knowledge and legitimacy arising from the uncertainty and dynamic socioenvironmental context of the Anthropocene. The proposed amendment, if adopted, risks ineffective prosecutions or even perverse outcomes for the environment itself. This risk, however, may characterize any effort to prosecute ecocide internationally in the Anthropocene unless the terms of international criminal law are fundamentally rethought.
Distributed Subweb Specifications for Traversing the Web
Authors: BOGAERTS BART , KETSMAN BAS , ZEBOUDJ YOUNES , AAMER HEBA , TAELMAN RUBEN , VERBORGH RUBEN
Published: April 2023

Link traversal–based query processing (ltqp), in which a sparql query is evaluated over a web of documents rather than a single dataset, is often seen as a theoretically interesting yet impractical technique. However, in a time where the hypercentralization of data has increasingly come under scrutiny, a decentralized Web of Data with a simple document-based interface is appealing, as it enables data publishers to control their data and access rights. While (ltqp allows evaluating complex queries over such webs, it suffers from performance issues (due to the high number of documents containing data) as well as information quality concerns (due to the many sources providing such documents). In existing ltqp approaches, the burden of finding sources to query is entirely in the hands of the data consumer. In this paper, we argue that to solve these issues, data publishers should also be able to suggest sources of interest and guide the data consumer toward relevant and trustworthy data. We introduce a theoretical framework that enables such guided link traversal and study its properties. We illustrate with a theoretic example that this can improve query results and reduce the number of network requests. We evaluate our proposal experimentally on a virtual linked web with specifications and indeed observe that not just the data quality but also the efficiency of querying improves.
Comparing the Importance of Iodine and Isoprene on Tropospheric Photochemistry
Authors: Pound R. J. , Durcan D. P. , Evans M. J. , Carpenter L. J.
Published: April 2023

Isoprene, arguably the most studied biogenically emitted gas, is thought to have a large impact on tropospheric composition. Other naturally emitted species have been considered to play a less important role. Here the GEOS‐Chem model is used to compare the impacts of isoprene and iodine emissions on present‐day tropospheric composition. Removing isoprene emissions leads to a 3.4% decrease in tropospheric O3 burden, a smaller absolute change than the 5.9% increase from removing iodine emissions. Iodine has a negligible impact on global mean OH concentrations and methane lifetime (+0.6% and +0.05%) whereas isoprene has a substantial impact on both (−4.3% and −4.2%). Isoprene emissions and chemistry are seen as essential for tropospheric chemistry models, but iodine is often not. We suggest that iodine should receive greater attention in model development and experimental research to allow improved predictions of past, present, and future tropospheric O3.
Climatology of Rossby Wave Breaking Over the Subtropical Indian Region
Authors: Thomas Biyo , Kunchala Ravi Kumar , Singh Bhupendra Bahadur , Kumar Kondapalli Niranjan
Published: April 2023

The weather of subtropical Indian region is frequently impacted by Rossby Wave Breaking (RWB) triggered dynamical changes in the atmosphere. However, studies are elusive on the comprehensive understanding of RWB events over the region. A Potential Vorticity (PV) contour searching algorithm based on existing literature, but implemented with more constraints appropriate for the Indian subcontinent, is used to detect the RWB events. We detect 513 RWB events during the analysis period (1979–2021) and utilize them to understand the RWB climatology and variability over the region. A significant increase in the frequency (about 20%) and intensity of RWB events noticed during the last two decades (1999–2018). The spatial distribution of RWB occurrences is prominent over the northwest parts of the Indian subcontinent during winter months. The most frequent breaking occurs in the wavenumbers ranging between 5 and 7, with stronger wave amplitudes and deeper tropospheric intrusions (∼650 hPa) during winter months that reach as low as 7.5°N in latitude. Further, our analysis shows that RWB promotes extreme rainfall by generating instability in the atmosphere allowing enhanced moisture influx over the region. It is also noted that interannual‐to‐decadal variations in the number of RWB events are linked to sea surface temperature conditions in the Pacific ocean. The findings of this study would contribute to an improved understanding of RWB and associated wave dynamics in triggering extreme weather and may find applications in climate studies on extremes in a warming climate.
Precipitation Bias Correction: A Novel Semi‐parametric Quantile Mapping Method
Authors: Rajulapati Chandra Rupa , Papalexiou Simon Michael
Published: April 2023

Bias correction methods are used to adjust simulations from global and regional climate models to use them in informed decision‐making. Here we introduce a semi‐parametric quantile mapping (SPQM) method to bias‐correct daily precipitation. This method uses a parametric probability distribution to describe observations and an empirical distribution for simulations. Bias‐correction techniques typically adjust the bias between observation and historical simulations to correct projections. The SPQM however corrects simulations based only on observations assuming the detrended simulations have the same distribution as the observations. Thus, the bias‐corrected simulations preserve the climate change signal, including changes in the magnitude and probability dry, and guarantee a smooth transition from observations to future simulations. The results are compared with popular quantile mapping techniques, that is, the quantile delta mapping (QDM) and the statistical transformation of the CDF using splines (SSPLINE). The SPQM performed well in reproducing the observed statistics, marginal distribution, and wet and dry spells. Comparatively, it performed at least equally well as the QDM and SSPLINE, specifically in reproducing observed wet spells and extreme quantiles. The method is further tested in a basin‐scale region. The spatial variability and statistics of the observed precipitation are reproduced well in the bias‐corrected simulations. Overall, the SPQM is easy to apply, yet robust in bias‐correcting daily precipitation simulations.
A Spectral Analysis of Near‐Surface Mean Wind Speed and Gusts Over the Iberian Peninsula
Authors: Utrabo‐Carazo Eduardo , Azorin‐Molina Cesar , Aguilar Enric , Brunet Manola
Published: April 2023

This study analyses for the first time observed surface mean wind speed (SWS) and gusts over the Iberian Peninsula (IP) in the frequency domain for 1961–2019, with the goal of exploring sources of predictability in the interannual and decadal scales. The main result is the high significant correlation between surface winds and the stratospheric polar vortex for periods close to 1 year with a time lag of about 2–3 months with respect to the antiphase, that is, a negative correlation in which the polar vortex modulates winds in the region. Furthermore, we found that the SWS and gusts are decoupled for periods between 9 and 11 years with a marked seasonal dependence in its intensity. Finally, we detected discrepancies between the spectra shown by surface winds from observations and ERA5‐Land reanalysis, suggesting that simulated data do not accurately reproduce the variability of surface wind speeds.
The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity
Authors: Bedford Peter , Hauke Daniel J. , Wang Zheng , Roth Volker , Nagy-Huber Monika , Holze Friederike , Ley Laura , Vizeli Patrick , Liechti Matthias E. , Borgwardt Stefan , Müller Felix , Diaconescu Andreea O.
Published: April 2023

Psychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie their effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI). We modelled data from two randomised, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100 μg LSD and placebo in two resting-state fMRI sessions. We compared EC against whole-brain functional connectivity (FC) using classical statistics and machine learning methods. Multivariate analyses of EC parameters revealed predominantly stronger interregional connectivity and reduced self-inhibition under LSD compared to placebo, with the notable exception of weakened interregional connectivity and increased self-inhibition in occipital brain regions as well as subcortical regions. Together, these findings suggests that LSD perturbs the Excitation/Inhibition balance of the brain. Notably, whole-brain EC did not only provide additional mechanistic insight into the effects of LSD on the Excitation/Inhibition balance of the brain, but EC also correlated with global subjective effects of LSD and discriminated experimental conditions in a machine learning-based analysis with high accuracy (91.11%), highlighting the potential of using whole-brain EC to decode or predict subjective effects of LSD in the future.
Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies
Authors: Zhang Yinqiang , Li Chenggong , Du Mengyi , Jiang Huiwen , Luo Wenjing , Tang Lu , Kang Yun , Xu Jia , Wu Zhuolin , Wang Xindi , Huang Zhongpei , Zhang Yanlei , Wu Di , Chang Alex H. , Hu Yu , Mei Heng
Published: April 2023

Chimeric antigen receptor-T (CAR-T) therapy remains to be investigated in T-cell malignancies. CD7 is an ideal target for T-cell malignancies but is also expressed on normal T cells, which may cause CAR-T cell fratricide. Donor-derived anti-CD7 CAR-T cells using endoplasmic reticulum retention have shown efficacy in patients with T-cell acute lymphoblastic leukemia (ALL). Here we launched a phase I trial to explore differences between autologous and allogeneic anti-CD7 CAR-T therapies in T-cell ALL and lymphoma. Ten patients were treated and 5 received autologous CAR-T therapies. No dose-limiting toxicity or neurotoxicity was observed. Grade 1–2 cytokine release syndrome occurred in 7 patients, and grade 3 in 1 patient. Grade 1–2 graft-versus-host diseases were observed in 2 patients. Seven patients had bone marrow infiltration, and 100% of them achieved complete remission with negative minimal residual disease within one month. Two-fifths of patients achieved extramedullary or extranodular remission. The median follow-up was 6 (range, 2.7–14) months and bridging transplantation was not administrated. Patients treated with allogeneic CAR-T cells had higher remission rate, less recurrence and more durable CAR-T survival than those receiving autologous products. Allogeneic CAR-T cells appeared to be a better option for patients with T-cell malignancies.
Deciphering the involvement of the Hippo pathway co-regulators, YAP/TAZ in invadopodia formation and matrix degradation
Authors: Venghateri Jubina Balan , Dassa Bareket , Morgenstern David , Shreberk-Shaked Michal , Oren Moshe , Geiger Benjamin
Published: April 2023

Invadopodia are adhesive, actin-rich protrusions formed by metastatic cancer cells that degrade the extracellular matrix and facilitate invasion. They support the metastatic cascade by a spatially and temporally coordinated process whereby invading cells bind to the matrix, degrade it by specific metalloproteinases, and mechanically penetrate diverse tissue barriers by forming actin-rich extensions. However, despite the apparent involvement of invadopodia in the metastatic process, the molecular mechanisms that regulate invadopodia formation and function are still largely unclear. In this study, we have explored the involvement of the key Hippo pathway co-regulators, namely YAP, and TAZ, in invadopodia formation and matrix degradation. Toward that goal, we tested the effect of depletion of YAP, TAZ, or both on invadopodia formation and activity in multiple human cancer cell lines. We report that the knockdown of YAP and TAZ or their inhibition by verteporfin induces a significant elevation in matrix degradation and invadopodia formation in several cancer cell lines. Conversely, overexpression of these proteins strongly suppresses invadopodia formation and matrix degradation. Proteomic and transcriptomic profiling of MDA-MB-231 cells, following co-knockdown of YAP and TAZ, revealed a significant change in the levels of key invadopodia-associated proteins, including the crucial proteins Tks5 and MT1-MMP (MMP14). Collectively, our findings show that YAP and TAZ act as negative regulators of invadopodia formation in diverse cancer lines, most likely by reducing the levels of essential invadopodia components. Dissecting the molecular mechanisms of invadopodia formation in cancer invasion may eventually reveal novel targets for therapeutic applications against invasive cancer.
Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success
Authors: Copp Griffin , Robb Kevin P. , Viswanathan Sowmya
Published: April 2023

Osteoarthritis (OA) is a degenerative multifactorial disease with concomitant structural, inflammatory, and metabolic changes that fluctuate in a temporal and patient-specific manner. This complexity has contributed to refractory responses to various treatments. MSCs have shown promise as multimodal therapeutics in mitigating OA symptoms and disease progression. Here, we evaluated 15 randomized controlled clinical trials (RCTs) and 11 nonrandomized RCTs using culture-expanded MSCs in the treatment of knee OA, and we found net positive effects of MSCs on mitigating pain and symptoms (improving function in 12/15 RCTs relative to baseline and in 11/15 RCTs relative to control groups at study endpoints) and on cartilage protection and/or repair (18/21 clinical studies). We examined MSC dose, tissue of origin, and autologous vs. allogeneic origins as well as patient clinical phenotype, endotype, age, sex and level of OA severity as key parameters in parsing MSC clinical effectiveness. The relatively small sample size of 610 patients limited the drawing of definitive conclusions. Nonetheless, we noted trends toward moderate to higher doses of MSCs in select OA patient clinical phenotypes mitigating pain and leading to structural improvements or cartilage preservation. Evidence from preclinical studies is supportive of MSC anti-inflammatory and immunomodulatory effects, but additional investigations on immunomodulatory, chondroprotective and other clinical mechanisms of action are needed. We hypothesize that MSC basal immunomodulatory “fitness” correlates with OA treatment efficacy, but this hypothesis needs to be validated in future studies. We conclude with a roadmap articulating the need to match an OA patient subset defined by molecular endotype and clinical phenotype with basally immunomodulatory “fit” or engineered-to-be-fit-for-OA MSCs in well-designed, data-intensive clinical trials to advance the field.
Mitochondria and the eye—manifestations of mitochondrial diseases and their management
Authors: Chen Benson S. , Harvey Joshua P. , Gilhooley Michael J. , Jurkute Neringa , Yu-Wai-Man Patrick
Published: April 2023

Historically, distinct mitochondrial syndromes were recognised clinically by their ocular features. Due to their predilection for metabolically active tissue, mitochondrial diseases frequently involve the eye, resulting in a range of ophthalmic manifestations including progressive external ophthalmoplegia, retinopathy and optic neuropathy, as well as deficiencies of the retrochiasmal visual pathway. With the wider availability of genetic testing in clinical practice, it is now recognised that genotype-phenotype correlations in mitochondrial diseases can be imprecise: many classic syndromes can be associated with multiple genes and genetic variants, and the same genetic variant can have multiple clinical presentations, including subclinical ophthalmic manifestations in individuals who are otherwise asymptomatic. Previously considered rare diseases with no effective treatments, considerable progress has been made in our understanding of mitochondrial diseases with new therapies emerging, in particular, gene therapy for inherited optic neuropathies.
The most at-risk regions in the world for high-impact heatwaves
Authors: Thompson Vikki , Mitchell Dann , Hegerl Gabriele C. , Collins Matthew , Leach Nicholas J. , Slingo Julia M.
Published: April 2023

Heatwaves are becoming more frequent under climate change and can lead to thousands of excess deaths. Adaptation to extreme weather events often occurs in response to an event, with communities learning fast following unexpectedly impactful events. Using extreme value statistics, here we show where regional temperature records are statistically likely to be exceeded, and therefore communities might be more at-risk. In 31% of regions examined, the observed daily maximum temperature record is exceptional. Climate models suggest that similar behaviour can occur in any region. In some regions, such as Afghanistan and parts of Central America, this is a particular problem - not only have they the potential for far more extreme heatwaves than experienced, but their population is growing and increasingly exposed because of limited healthcare and energy resources. We urge policy makers in vulnerable regions to consider if heat action plans are sufficient for what might come.
miR-483-5p offsets functional and behavioural effects of stress in male mice through synapse-targeted repression of Pgap2 in the basolateral amygdala
Authors: Mucha Mariusz , Skrzypiec Anna E. , Kolenchery Jaison B. , Brambilla Valentina , Patel Satyam , Labrador-Ramos Alberto , Kudla Lucja , Murrall Kathryn , Skene Nathan , Dymicka-Piekarska Violetta , Klejman Agata , Przewlocki Ryszard , Mosienko Valentina , Pawlak Robert
Published: April 2023

Severe psychological trauma triggers genetic, biochemical and morphological changes in amygdala neurons, which underpin the development of stress-induced behavioural abnormalities, such as high levels of anxiety. miRNAs are small, non-coding RNA fragments that orchestrate complex neuronal responses by simultaneous transcriptional/translational repression of multiple target genes. Here we show that miR-483-5p in the amygdala of male mice counterbalances the structural, functional and behavioural consequences of stress to promote a reduction in anxiety-like behaviour. Upon stress, miR-483-5p is upregulated in the synaptic compartment of amygdala neurons and directly represses three stress-associated genes: Pgap2, Gpx3 and Macf1. Upregulation of miR-483-5p leads to selective contraction of distal parts of the dendritic arbour and conversion of immature filopodia into mature, mushroom-like dendritic spines. Consistent with its role in reducing the stress response, upregulation of miR-483-5p in the basolateral amygdala produces a reduction in anxiety-like behaviour. Stress-induced neuromorphological and behavioural effects of miR-483-5p can be recapitulated by shRNA mediated suppression of Pgap2 and prevented by simultaneous overexpression of miR-483-5p-resistant Pgap2. Our results demonstrate that miR-483-5p is sufficient to confer a reduction in anxiety-like behaviour and point to miR-483-5p-mediated repression of Pgap2 as a critical cellular event offsetting the functional and behavioural consequences of psychological stress.
Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunction in a mouse model of tauopathy
Authors: Hussong Stacy A. , Banh Andy Q. , Van Skike Candice E. , Dorigatti Angela O. , Hernandez Stephen F. , Hart Matthew J. , Ferran Beatriz , Makhlouf Haneen , Gaczynska Maria , Osmulski Pawel A. , McAllen Salome A. , Dineley Kelly T. , Ungvari Zoltan , Perez Viviana I. , Kayed Rakez , Galvan Veronica
Published: April 2023

Vascular mechanisms of Alzheimer’s disease (AD) may constitute a therapeutically addressable biological pathway underlying dementia. We previously demonstrated that soluble pathogenic forms of tau (tau oligomers) accumulate in brain microvasculature of AD and other tauopathies, including prominently in microvascular endothelial cells. Here we show that soluble pathogenic tau accumulates in brain microvascular endothelial cells of P301S(PS19) mice modeling tauopathy and drives AD-like brain microvascular deficits. Microvascular impairments in P301S(PS19) mice were partially negated by selective removal of pathogenic soluble tau aggregates from brain. We found that similar to trans-neuronal transmission of pathogenic forms of tau, soluble tau aggregates are internalized by brain microvascular endothelial cells in a heparin-sensitive manner and induce microtubule destabilization, block endothelial nitric oxide synthase (eNOS) activation, and potently induce endothelial cell senescence that was recapitulated in vivo in microvasculature of P301S(PS19) mice. Our studies suggest that soluble pathogenic tau aggregates mediate AD-like brain microvascular deficits in a mouse model of tauopathy, which may arise from endothelial cell senescence and eNOS dysfunction triggered by internalization of soluble tau aggregates.
Insights into solvent and surface charge effects on Volmer step kinetics on Pt (111)
Authors: Wilson Jon C. , Caratzoulas Stavros , Vlachos Dionisios G. , Yan Yushan
Published: April 2023

The mechanism of pH-dependent hydrogen oxidation and evolution kinetics is still a matter of significant debate. To make progress, we study the Volmer step kinetics on platinum (111) using classical molecular dynamics simulations with an embedded Anderson-Newns Hamiltonian for the redox process and constant potential electrodes. We investigate how negative electrode electrostatic potential affects Volmer step kinetics. We find that the redox solvent reorganization energy is insensitive to changes in interfacial field strength. The negatively charged surface attracts adsorbed H as well as H+, increasing hydrogen binding energy, but also trapping H+in the double layer. While more negative electrostatic potential in the double layer accelerates the oxidation charge transfer, it becomes difficult for the proton to move to the bulk. Conversely, reduction becomes more difficult because the transition state occurs farther from equilibrium solvation polarization. Our results help to clarify how the charged surface plays a role in hydrogen electrocatalysis kinetics.
Designed Rubredoxin miniature in a fully artificial electron chain triggered by visible light
Authors: Chino Marco , Di Costanzo Luigi Franklin , Leone Linda , La Gatta Salvatore , Famulari Antonino , Chiesa Mario , Lombardi Angela , Pavone Vincenzo
Published: April 2023

Designing metal sites into de novo proteins has significantly improved, recently. However, identifying the minimal coordination spheres, able to encompass the necessary information for metal binding and activity, still represents a great challenge, today. Here, we test our understanding with a benchmark, nevertheless difficult, case. We assemble into a miniature 28-residue protein, the quintessential elements required to fold properly around a FeCys4 redox center, and to function efficiently in electron-transfer. This study addresses a challenge in de novo protein design, as it reports the crystal structure of a designed tetra-thiolate metal-binding protein in sub-Å agreement with the intended design. This allows us to well correlate structure to spectroscopic and electrochemical properties. Given its high reduction potential compared to natural and designed FeCys4-containing proteins, we exploit it as terminal electron acceptor of a fully artificial chain triggered by visible light.