bluuebunny/crossref_metadata_2025 huggingface dataset:
Gauss process regression for real-time ionospheric delay estimation from GNSS observations
Authors: Lupsic Balazs , Takacs Bence
Published: January 2022

The number of devices equipped with global satellite positioning has exceeded seven billion recently. There are a wide variety of receivers regarding their accuracy and reliability. Low cost, multi-frequency units have been released on the market latterly; however, the number of single-frequency receivers is still significant. Since their measurements are influenced by ionospheric delay, accurate ionosphere models are of utmost importance to reduce the effect. This paper summarizes how Gauss process regression (GPR) can be applied to derive near real-time regional ionosphere models using raw Global Navigation Satellite System (GNSS) observations of permanent stations. While Gauss process is widely used in machine learning, GPR is a nonparametric, Bayesian approach to regression. GPR has several benefits for ionosphere monitoring since it is quite robust and efficient to derive a grid model from data available in irregular set of ionospheric pierce points. The corresponding instrumental delays are estimated by a parallel Kalman filter. The presented algorithm can be applied near real-time, however the results are offline calculated and are compared to two high quality TEC map products. Based on the analysis, the accuracy of the GPR modell is in 2 TECu range. The developed methods could be efficiently applied in the field of autonomous vehicle navigation with meeting both accuracy and integrity requirements.
Die Landesparlamente im Zeichen der Emergency Politics in der Corona-Krise
Authors: Höhne Benjamin
Published: January 2022

Auch wenn Deutschlands Performanz bei den Infektions- und Todeszahlen sowie den wirtschaftlichen und sozialen Folgen in Verbindung mit COVID-19 im EU27-Vergleich als zufriedenstellend bewertet würde, stellt sich die Frage nach der Input-Legitimität durch demokratische Verfahren. Sie wird ausgehend vom Konzept der Emergency Politics von Jonathan White am Beispiel Deutschlands mit seinem Notstandsregime der Bund-Länder-Konferenz und dessen Effekten auf die 16 Landesparlamente aufgeworfen. Anschließend daran wird argumentiert, dass die während der Pandemiewellen in den Jahren 2020 und 2021 vorherrschende Entscheidungsfindung und Beschlussfassung innerhalb der föderalen Staatsordnung einen Rahmen bildete, der den Parlamentsfunktionen weitgehend den Boden entzogen hat. Zentral für die Analyse ist die Darlegung der von der Pandemie evozierten Veränderung des Mehrebenen-Regierens durch die Bund-Länder-Konferenzen. Auswirkungen dieser von der Exekutive dominierten Krisenbewältigungspolitik wird für die auf der Landesebene wichtigsten Parlamentsfunktionen, die Kontrolle durch Mitregieren, Oppositionskontrolle, Gesetzgebung sowie das Herstellen von Öffentlichkeit, diskutiert. Empirische Grundlagen bilden Presseberichte, nichtöffentliche Beschlussvorlagen und Beschlüsse der Bund-Länder-Konferenz sowie Bevölkerungsbefragungen. Der Aufsatz schließt mit der Empfehlung, zukünftige Notstandspolitik institutionell besser vorzubereiten und dabei einen Platz für den Landesparlamentarismus vorzusehen.
Experimental and numerical investigation of different geometrical parameters in a centrifugal blood pump
Authors: Hosseini Seyed Ehsan , Keshmiri Amir
Published: January 2022

Purpose

Due to the importance of public health and economics, cardiovascular disease has become one of the most important debates and challenges for scientists. However, few studies have been done to address this challenge. The main objective of this document is to provide an optimal model to improve the performance of the left ventricular assist device and reduce costs. In this way, in the present study, the experimental and numerical procedures were developed to analyze the effects of the geometrical features and operational parameters on the performance of a centrifugal blood pump (CBP).

Methods

In order to achieve this aim, first, experimental tests were carried out to study the influence of the working fluid temperature and the rotational speed on the CBP. Subsequently, the performance of the CBP was assessed using computational fluid dynamics (CFD), and comparison was made against the experimental data. In addition, the influence of mounting an inducer on the overall performance of CBP was also investigated.

Results

Good agreement between the CFD and the data was obtained. The CFD results showed that increasing the fluid temperature and rotational speed leads to an increase in the hydraulic efficiency, pressure difference, and power. In addition, the reduction of the pressure difference and hydraulic efficiency with increasing the surface roughness was observed. While mounting an inducer on the pump did not significantly impact its overall performance, the highest value of the wall shear stress dropped moderately on the impeller and, therefore, unveiled the possibility of improving the performance of such designs.
Genetic adaptation to urban living: molecular DNA analyses of wild boar populations in Budapest and surrounding area
Authors: Zsolnai Attila , Csókás Adrienn , Szabó László , Patkó László , Csányi Sándor , Márton Mihály , Lakatos Erzsébet Anna , Anton István , Deutsch Ferenc , Heltai Miklós
Published: January 2022

Studies of wild boar, Sus scrofa Linnaeus 1758, in urban and suburban areas of Budapest, Hungary, have indicated that these populations do not have continuous contact. Based on the assumption that the city has a discrete population, we hypothesized that the urban wild boar would differ genetically from those in suburban areas. Analysis of single-nucleotide polymorphism (SNP) data using the GeneSeek Genomic Profiler (GGP) Porcine 50 K system (Neogen, Scotland, UK) differentiated three populations: Buda (B) from the Western bank of the Danube; Buda Surrounding (BS); and Valkó (V) from the Eastern bank of the Danube. The coefficient of genetic differentiation (FST) for the B and BS populations was low. The inbreeding coefficients of the populations BS and V were close to zero, while population B had a high positive value reflecting the influence of founders and the inbreeding of the continuous urban population. The genome regions that were most differentiated between the B and BS populations were analyzed based on the FST values of the SNP markers using a mixed linear multi-locus model and BayeScan software. The most differentiated marker, WU_10.2_18_56278226, was found on chromosome 18. The surrounding region contained several candidate genes that could play important roles in adaptations related to human-induced stress. Two of these, encoding the adenylate cyclase 1 (ADCY1) and inhibin beta A chain precursor (INHBA) genes, were sequenced. While IHBA gene did not display variation, the allele distribution of the ADCY1 gene in the B population was significantly different from that of the BS population supporting the parapatric differentiation of wild boar.
Cyberbullying, metacognition, and quality of life: preliminary findings from the Longitudinal Adolescent Brain Study (LABS)
Authors: McLoughlin Larisa T. , Simcock Gabrielle , Schwenn Paul , Beaudequin Denise , Driver Christina , Kannis-Dymand Lee , Lagopoulos Jim , Hermens Daniel F.
Published: January 2022

Cyberbullying contributes to poor mental health outcomes and quality of life (QoL), and peer victimisation has been shown to be positively associated with both positive and negative metacognition. Whilst metacognitive beliefs are associated with pathological worry, obsessive–compulsive symptoms, and rumination in depression, research is yet to examine whether metacognitive beliefs influence negative outcomes, such as reduced QoL, associated with experiences of cyberbullying. This study examines whether cybervictimisation, cyberbullying and metacognition play predictive roles in QoL, and if metacognition mediates any association between cybervictimisation, cyberbullying and QoL over time. Participants in the Longitudinal Adolescent Brain Study (LABS), aged 12 years and in grade 7, who had completed up to four assessment time-points (T) were included in this analysis: T1: N = 65; T2: N = 61; T3: N = 56; T4: N = 44. Structural equation modeling revealed significant associations between cyberbullying, cybervictimisation, metacognitive beliefs, and QoL. However, mediation analysis showed that only cognitive confidence acted as a partial mediator between cybervictimisation and QoL. The results suggest those who were more frequently cybervictimised had reduced confidence in their memory, which resulted in lower QoL. In addition, uncontrollability/danger and superstition, punishment, and responsibility were all negatively associated with QoL, indicating that as these metacognitive beliefs increased, QoL decreased. Our findings highlight the detrimental impact that cybervictimisation experiences can have on QoL in young people over time, and that some forms of metacognitive beliefs can also impact QoL. These findings can inform educators and health professionals on the importance of metacognition in regard to QoL over time, particularly in those who experience cybervictimisation.
Tracer les limites des sociétés dans une perspective transeuropéenne: Les « Polonais de la Ruhr » à la fin du xixe et au début du xxe siècle
Authors: Friedrichs Anne
Published: January 2022

Tracer les limites des sociétés dans une perspective transeuropéenne Les « Polonais de la Ruhr » à la fin du xixe et au début du xxe siècle

Cet article se penche sur les travailleurs germano-polonais, principalement originaires des régions orientales de la Prusse, de l’Autriche-Hongrie et de l’Empire russe, dans la vallée de la Ruhr au tournant des xixe et xxe siècles. À partir de cette étude de cas, nous cherchons à faire valoir un point méthodologique plus général permettant de repenser notre conception des sociétés, en étudiant les processus par lesquels la démarcation et l’appartenance ont été produites aux niveaux local, national et transeuropéen lorsqu’un nombre croissant de personnes sont venues, restées et parfois parties de nouveau. La figure intellectuelle et sociale des « Polonais de la Ruhr » est particulièrement révélatrice en ce qu’elle met au jour des attributions spatiales concurrentes dont les significations ont changé en fonction du monde social et du contexte. L’analyse des processus de différenciation et d’évaluation imbriqués dans lesquels ces migrants étaient impliqués donne un aperçu de l’influence exercée par les acteurs régionaux à travers les pratiques administratives de catégorisation. Elle met également en évidence les différentes manières dont les nouveaux arrivants se sont représentés et ont réglementé les relations sociales. Enfin, nous discutons des conséquences de ces processus interactifs dans la classification légale et académique d’individus qui se déplaçaient au-delà de la grille de lecture de l’État-nation – et entre des espaces multiples tels que la vallée de la Ruhr et les régions polonophones. L’article montre que même à une époque où l’idéal de l’État-nation devenait prédominant dans les discours universitaires et publics en Europe, différentes constructions de l’appartenance, fondées sur l’origine, la réussite et des visions de l’humanité commune des sujets se côtoyaient dans la région de la Ruhr en tant que zone économique façonnée par les mobilités.
Static-Dynamic Hybridity in Dynamical Models of Cognition
Authors: Weinberger Naftali , Allen Colin
Published: January 2022

Dynamical models of cognition have played a central role in recent cognitive science. In this paper, we consider a common strategy by which dynamical models describe their target systems neither as purely static nor as purely dynamic, but rather using a hybrid approach. This hybridity reveals how dynamical models involve representational choices that are important for understanding the relationship between dynamical and non-dynamical representations of a system.
Speculation Made Material: Experimental Archaeology and Maker’s Knowledge
Authors: Currie Adrian
Published: January 2022

Experimental archaeology is often understood both as testing hypotheses about processes shaping the archaeological record and as generating tacit knowledge. Considering lithic technologies, I examine the relationship between these conceptions. Experimental archaeology is usefully understood via “maker’s knowledge”: archaeological experiments generate embodied know-how enabling archaeological hypotheses to be grasped and challenged, and further, well-positioning archaeologists to generate integrated interpretations. Finally, experimental archaeology involves “material speculation”: the constraints and affordances of archaeologists and their materials shape productive exploration of the capacities of objects and human skill in ways relevant to archaeological questions.
Rescuing Ontological Individualism
Authors: Guala Francesco
Published: January 2022

Standard defenses of ontological individualism are challenged by arguments that exploit the dependence of social facts on material facts—that is, facts that are not about human individuals. In this article, I discuss Brian Epstein’s “materialism” inThe Ant Trap: granting Epstein’s strict definition of individualism, I show that his arguments depend crucially on a generous conception of social properties and social facts. Individualists, however, are only committed to the claim thatprojectibleproperties are individualistically realized, and materialists have not undermined this claim.
Are Points (Necessarily) Unextended?
Authors: Ehrlich Philip
Published: January 2022

Since Euclid defined a point as “that which has no part” it has been widely assumed that points are necessarily unextended. It has also been assumed that this is equivalent to saying that points or, more properly speaking, degenerate segments, have length zero. We challenge these assumptions by providing models of Euclidean geometry where the points are extended despite the fact that the degenerate segments have null lengths, and observe that whereas the extended natures of the points are not recognizable in the given models, they can be recognized and characterized by structures that are suitable expansions of the models.
Adipokines: inflammation and the pleiotropic role of white adipose tissue
Authors: Trayhurn Paul
Published: January 2022

I had been working on the endocrine and signalling role of white adipose tissue (WAT) since 1994 following the identification of the ob (Lep) gene(1), this after some 15 years investigating the physiological role of brown adipose tissue. The ob gene, a mutation in which it is responsible for the profound obesity of ob/ob (Lepob/Lepob) mice, is expressed primarily in white adipocytes and encodes the pleiotropic hormone leptin. The discovery of this adipocyte hormone had wide-ranging implications, including that white fat has multiple functions that far transcend the traditional picture of a simple lipid storage organ.
Impact of mother genetic and resource environment on her offspring’s growth features in Munjal sheep
Authors: Magotra Ankit , Bangar Yogesh C. , Chauhan Ashish , Yadav Abhay Singh , Malik Zile Singh
Published: January 2022

The present study evaluated maternal and additive influences that contribute to phenotypic variation in various growth traits in Munjal sheep. The targeted traits that pertained to 2278 records of 706 lambs were birth weight (BWT), weaning weight (WT3), 6-month body weight (WT6), 12-month body weight (WT12), average daily gain (ADG1: 0–3 months; ADG2: 3–6 months, ADG3: 6–12 months of age) and their corresponding Kleiber ratios designated as KR1, KR2 and KR3. The direct heritability estimates for BWT, WT3, WT6, WT12, ADG1, ADG2, ADG3, KR1, KR2 and KR3 under animal models were 0.20 ± 0.08, 0.28 ± 0.08, 0.17 ± 0.07, 0.47 ± 0.09, 0.33 ± 0.08, 0.09 ± 0.06, 0.36 ± 0.10, 0.33 ± 0.08, 0.09 ± 0.06 and 0.32 ± 0.10, respectively. The estimates of maternal genetic effects contributed significantly and were 8% and 7% for BWT and WT3 traits, respectively, which highlighted the considerable role of maternal effects on early growth traits. Genetic and phenotypic correlations ranged from moderate to high between weaning and post-weaning traits. It was concluded that early selection that considered additive as well as maternal effects at weaning age may be delivered to the desired genetic progress in Munjal sheep.
Biventricular non-compaction cardiomyopathy and tricuspid hypoplasia in a novel non-POU domain-containing octamer-binding gene variant
Authors: Safi Sanam , Sanders Stephen P. , Zhao Melissa , Carreon Chrystalle Katte
Published: January 2022

A maternally inherited novel pathogenic non-POU domain-containing octamer-binding gene variant c.767G>T, p.R256I [NM_001145408], manifested in a male infant as dilated cardiomyopathy with severe left ventricular dysfunction and dilation, biventricular non-compaction, tricuspid hypoplasia, and hydrocephaly. To the best of our knowledge, no previous non-POU domain-containing octamer-binding gene variants with biventricular non-compaction have been associated with tricuspid valve hypoplasia. Hence, this case introduces a new pathogenic variant observed in the non-POU domain-containing octamer-binding gene and adds to the range of cardiac phenotypes identified in non-POU domain-containing octamer-binding gene variants.
Using Your Beam Efficiently: Reducing Electron Dose in the STEM via Flyback Compensation
Authors: Mullarkey Tiarnan , Peters Jonathan J P , Downing Clive , Jones Lewys
Published: January 2022

In the scanning transmission electron microscope, fast-scanning and frame-averaging are two widely used approaches for reducing electron-beam damage and increasing image signal noise ratio which require no additional specialized hardware. Unfortunately, for scans with short pixel dwell-times (less than 5 μs), line flyback time represents an increasingly wasteful overhead. Although beam exposure during flyback causes damage while yielding no useful information, scan coil hysteresis means that eliminating it entirely leads to unacceptably distorted images. In this work, we reduce this flyback to an absolute minimum by calibrating and correcting for this hysteresis in postprocessing. Substantial improvements in dose efficiency can be realized (up to 20%), while crystallographic and spatial fidelity is maintained for displacement/strain measurement.
FDA-MIMO for target localization via multi-pulse tensor decomposition
Authors: Liu Yibin , Wang Chunyang , Gong Jian , Tan Ming
Published: January 2022

By combining multiple input multiple output (MIMO) technology and multiple matched filters with frequency diverse array (FDA), FDA-MIMO radar can be used to achieve two-dimensional target localization with range and angle. In this paper, we propose two FDA-MIMO multi-pulse target localization methods based on tensor decomposition. Based on the canonical polyadic decomposition theory, the signal models of CPD-DP-FDA with double-pulse and CPD-SP-FDA with stepped frequency pulses are established. By analyzing the signal processing procedures of the two schemes, the indicator beampattern used for target localization is obtained. The parameter estimation accuracy of the proposed method is investigated in single target and multiple targets scenarios, and the proposed method is compared with the traditional double-pulse method. The results show that the target localization method based on tensor decomposition can effectively solve the problem of multi-target indication ambiguity. The target positioning effect can be further improved by combining stepped frequency pulses. The derivation of Cramer–Rao Lower Bound (CRLB) demonstrates the superiority of the method.
The risk of offspring mood and anxiety disorders in the context of prenatal maternal somatic diseases: a systematic review and meta-analysis
Authors: Gong Xiayu , Fan Zhixin , Xu Hanfang , Wang Hanzhang , Zeng Ningxi , Li Ling , Wu Lili , Yan Can
Published: January 2022

Aims

The importance of prenatal maternal somatic diseases for offspring mood and anxiety disorders may be overlooked or undervalued. We conducted the first systematic review and meta-analysis assessing the risk of offspring mood and anxiety disorders in the context of prenatal maternal somatic diseases.

Methods

We screened articles indexed in Embase (including Embase, MEDLINE, PubMed-not-MEDLINE), PsycARTICLES and PsycINFO databases up to August 2021. 21 studies were included. We examined the overall associations between prenatal maternal somatic diseases and offspring mood/anxiety disorders. Analyses were stratified according to maternal somatic diseases and follow-up duration.

Results

We observed an increased risk of mood and anxiety disorders in the context of prenatal maternal somatic diseases [relative risk (RR) = 1.26; 95% confidence interval (CI) 1.15–1.37, RR = 1.31; 95% CI 1.24–1.38]; maternal obesity(RR = 1.92; 95% CI 1.72–2.11), hypertensive disorders (RR = 1.49; 95% CI 1.11–1.86) and infertility (RR = 1.26, 95% CI 1.14–1.39) were risk factors for mood disorders; maternal polycystic ovary syndrome (RR = 1.61; 95% CI 1.42–1.80), severe obesity (RR = 1.56; 95% CI 1.44–1.68) and moderate obesity (RR = 1.36; 95% CI 1.28–1.44) were risk factors for anxiety disorders. Prenatal maternal somatic diseases increased the risk of mood disorders in childhood and adulthood (RR = 1.71; 95% CI 1.34–2.09/RR = 1.19; 95% CI 1.09–1.30), as well as the risk of anxiety disorders in adulthood (RR = 1.33; 95% CI 1.26–1.41).

Conclusion

The results indicate that prenatal maternal somatic diseases are associated with offspring mood and anxiety disorders, and that the associations may be long-lasting.
Effective Energy of Cosmogenic Isotope (10Be, 14C and 36Cl) Production by Solar Energetic Particles and Galactic Cosmic Rays
Authors: Koldobskiy Sergey , Usoskin Ilya , Kovaltsov Gennady A.
Published: January 2022

Cosmogenic isotopes 14C, 10Be and 36Cl measured in datable natural archives provide the only known quantitative proxy for cosmic‐ray (CR) and solar‐activity variability before the era of direct measurements. Studies of relations between the measured isotope concentrations and CR variability require complicated modeling including the isotope production and transport in the terrestrial system. Here we propose a rough “effective energy” method to make quick estimates of the CR variability directly from the cosmogenic data using an approximate linear scaling between the measured isotope concentrations and the energy‐integrated flux of CR above the effective energy. The method is based on the thoroughly computed effective yield function presented here. A simple way to account for the variable geomagnetic field is also provided. The method was developed for both solar energetic particles (SEPs) and galactic cosmic ray (GCR) variability and is shown to provide a robust result within 20% and 1% accuracy, respectively, without an assumption of the specific spectral shape. Applications of the effective‐energy method to the known extreme SEP events and the secular GCR variability are discussed. The new method provides a simple and quick tool to assess the CR variability in the past. On the other hand, it does not supersede the full detailed modeling required for precise results.
Transient Creep in Subduction Zones by Long‐Range Dislocation Interactions in Olivine
Authors: Wallis David , Sep Mike , Hansen Lars N.
Published: January 2022

Large earthquakes transfer stress from the shallow lithosphere to the underlying viscoelastic lower crust and upper mantle, inducing transient creep during the postseismic interval. Recent experiments on olivine have provided a new rheological model for this transient creep based on the accumulation and release of back stresses among dislocations. Here, we test whether natural rocks preserve dislocation‐induced stress heterogeneity consistent with the back‐stress hypothesis by mapping olivine from the palaeosubduction interface of the Oman‐UAE ophiolite with high‐angular resolution electron backscatter diffraction. The olivine preserves heterogeneous residual stresses that vary in magnitude by several hundred megapascals over length scales of a few micrometers. Large stresses are commonly spatially associated with elevated densities of geometrically necessary dislocations within subgrain interiors. These spatial relationships, along with characteristic probability distributions of the stresses, confirm that the stress heterogeneity is generated by the dislocations and records their long‐range elastic interactions. Images of dislocations decorated by oxidation display bands of high and low dislocation density, suggesting that dislocation interactions contributed to the organization of the substructure. These results support the applicability of the back‐stress model of transient creep to deformation in the mantle portion of plate‐boundary shear zones. The model predicts that rapid stress changes, such as those imposed by large earthquakes, can induce order‐of‐magnitude changes in viscosity that depend nonlinearly on the stress change, consistent with inferences of mantle rheology from geodetic observations.
OCO‐2 Satellite‐Imposed Constraints on Terrestrial Biospheric CO2 Fluxes Over South Asia
Authors: Philip Sajeev , Johnson Matthew S. , Baker David F. , Basu Sourish , Tiwari Yogesh K. , Indira Nuggehalli K. , Ramonet Michel , Poulter Benjamin
Published: January 2022

The spatiotemporal variability of terrestrial biospheric carbon dioxide (CO2) fluxes over South Asia has large uncertainty. The Orbiting Carbon Observatory 2 (OCO‐2) satellite provides much‐needed retrievals of column‐average CO2 on a global‐scale, with the highest sensitivity to surface CO2 fluxes and spatiotemporal resolution available to‐date. This study conducted global inverse model simulations, assimilating in situ (IS) data and OCO‐2 retrievals, to assess optimized CO2 net ecosystem exchange (NEE) fluxes for South Asia. Annual Net Biome Exchange (NBE = NEE + biomass burning) fluxes over South Asia were estimated to be near neutral (0.04 ± 0.14 PgC yr−1) using both IS and OCO‐2 observations. The most robust result found by assimilating OCO‐2 observations was the constraint imposed on the seasonal cycle of NBE fluxes. The amplitude of the seasonal cycle of NEE was found to be larger than previously assumed. The OCO‐2 inversion led to an NBE seasonal amplitude of 0.34 PgC month−1, which was larger compared to IS constrained NBE (0.19 PgC month−1) and MsTMIP ensemble mean NEE (0.16 PgC month−1). Moreover, OCO‐2 data imposed a phase shift in the NBE seasonal cycle predicted by the prior model. The larger magnitude of NEE seasonality, and phase shift, simulated when assimilating OCO‐2 observations are in general agreement with previous studies assimilating regional aircraft observations in addition to global IS observations. This result suggests that OCO‐2 provides valuable data that allows for the estimate of NBE on a regional scale in a similar manner as regional in situ aircraft networks.
Improved Quantification of Ocean Carbon Uptake by Using Machine Learning to Merge Global Models and pCO2 Data
Authors: Gloege L. , Yan M. , Zheng T. , McKinley G. A.
Published: January 2022

The ocean plays a critical role in modulating climate change by sequestering CO2 from the atmosphere. Quantifying the CO2 flux across the air‐sea interface requires time‐dependent maps of surface ocean partial pressure of CO2 (pCO2), which can be estimated using global ocean biogeochemical models (GOBMs) and observational‐based data products. GOBMs are internally consistent, mechanistic representations of the ocean circulation and carbon cycle, and have long been the standard for making spatio‐temporally resolved estimates of air‐sea CO2 fluxes. However, there are concerns about the fidelity of GOBM flux estimates. Observation‐based products have the strength of being data‐based, but the underlying data are sparse and require significant extrapolation to create global full‐coverage flux estimates. The Lamont Doherty Earth Observatory‐Hybrid Physics Data (LDEO‐HPD) pCO2 product is a new approach to estimating the temporal evolution of surface ocean pCO2 and air‐sea CO2 exchange. LDEO‐HPD uses machine learning to merge high‐quality observations with state‐of‐the‐art GOBMs. We train an eXtreme Gradient Boosting (XGB) algorithm to learn a non‐linear relationship between model‐data mismatch and observed predictors. GOBM fields are then corrected with the predicted model‐data misfit to estimate real‐world pCO2 for 1982–2018. The resulting reconstruction by LDEO‐HPD is in better agreement with independent pCO2 observations than other currently available observation‐based products. Within uncertainties, LDEO‐HPD global ocean uptake of CO2 agrees with other products and the Global Carbon Budget 2020.
Connexin 43 confers chemoresistance through activating PI3K
Authors: Pridham Kevin J. , Shah Farah , Hutchings Kasen R. , Sheng Kevin L. , Guo Sujuan , Liu Min , Kanabur Pratik , Lamouille Samy , Lewis Gabrielle , Morales Marc , Jourdan Jane , Grek Christina L. , Ghatnekar Gautam G. , Varghese Robin , Kelly Deborah F. , Gourdie Robert G. , Sheng Zhi
Published: January 2022

Circumventing chemoresistance is crucial for effectively treating cancer including glioblastoma, a lethal brain cancer. The gap junction protein connexin 43 (Cx43) renders glioblastoma resistant to chemotherapy; however, targeting Cx43 is difficult because mechanisms underlying Cx43-mediated chemoresistance remain elusive. Here we report that Cx43, but not other connexins, is highly expressed in a subpopulation of glioblastoma and Cx43 mRNA levels strongly correlate with poor prognosis and chemoresistance in this population, making Cx43 the prime therapeutic target among all connexins. Depleting Cx43 or treating cells with αCT1–a Cx43 peptide inhibitor that sensitizes glioblastoma to the chemotherapy temozolomide–inactivates phosphatidylinositol-3 kinase (PI3K), whereas overexpression of Cx43 activates this signaling. Moreover, αCT1-induced chemo-sensitization is counteracted by a PI3K active mutant. Further research reveals that αCT1 inactivates PI3K without blocking the release of PI3K-activating molecules from membrane channels and that Cx43 selectively binds to the PI3K catalytic subunit β (PIK3CB, also called PI3Kβ or p110β), suggesting that Cx43 activates PIK3CB/p110β independent of its channel functions. To explore the therapeutic potential of simultaneously targeting Cx43 and PIK3CB/p110β, αCT1 is combined with TGX-221 or GSK2636771, two PIK3CB/p110β-selective inhibitors. These two different treatments synergistically inactivate PI3K and sensitize glioblastoma cells to temozolomide in vitro and in vivo. Our study has revealed novel mechanistic insights into Cx43/PI3K-mediated temozolomide resistance in glioblastoma and demonstrated that targeting Cx43 and PIK3CB/p110β together is an effective therapeutic approach for overcoming chemoresistance.
Transcriptome analysis reveals upregulation of immune response pathways at the invasive tumour front of metastatic seminoma germ cell tumours
Authors: Nestler Tim , Dalvi Priya , Haidl Friederike , Wittersheim Maike , von Brandenstein Melanie , Paffenholz Pia , Wagener-Ryczek Svenja , Pfister David , Koitzsch Ulrike , Hellmich Martin , Buettner Reinhard , Odenthal Margarete , Heidenreich Axel
Published: January 2022

Background

Testicular germ cell tumours (TGCTs) have a high metastasis rate. However, the mechanisms related to their invasion, progression and metastasis are unclear. Therefore, we investigated gene expression changes that might be linked to metastasis in seminomatous testicular germ cell tumour (STGCT) patients.

Methods

Defined areas [invasive tumour front (TF) and tumour centre (TC)] of non-metastatic (with surveillance and recurrence-free follow-up >2 years) and metastatic STGCTs were collected separately using laser capture microdissection. The expression of 760 genes related to tumour progression and metastasis was analysed using nCounter technology and validated with quantitative real-time PCR and enzyme-linked immunosorbent assay.

Results

Distinct gene expression patterns were observed in metastatic and non-metastatic seminomas with respect to both the TF and TC. Comprehensive pathway analysis showed enrichment of genes related to tumour functions such as inflammation, angiogenesis and metabolism at the TF compared to the TC. Remarkably, prominent inflammatory and cancer-related pathways, such as interleukin-6 (IL-6) signalling, integrin signalling and nuclear factor-κB signalling, were significantly upregulated in the TF of metastatic vs non-metastatic tumours.

Conclusions

IL-6 signalling was the most significantly upregulated pathway in metastatic vs non-metastatic tumours and therefore could constitute a therapeutic target for future personalised therapy. In addition, this is the first study showing intra- and inter-tumour heterogeneity in STGCT.
Safety, efficacy and delivery of isometric resistance training as an adjunct therapy for blood pressure control: a modified Delphi study
Authors: Baffour-Awuah Biggie , Pearson Melissa J. , Smart Neil A. , Dieberg Gudrun
Published: January 2022

Uncontrolled hypertension remains the major risk factor for cardiovascular disease. Isometric resistance training (IRT) has been shown to be a useful nonpharmacological therapy for reducing blood pressure (BP); however, some exercise physiologists and other health professionals are uncertain of the efficacy and safety of IRT. Experts’ consensus was sought in light of the current variability of IRT use as an adjunct treatment for hypertension. An expert consensus-building analysis (Delphi study) was conducted on items relevant to the safety, efficacy and delivery of IRT. The study consisted of 3 phases: (1) identification of items and expert participants for inclusion; (2) a two-round modified Delphi exercise involving expert panelists to build consensus; and (3) a study team consensus meeting for a final item review. A list of 50 items was generated, and 42 international experts were invited to join the Delphi panel. Thirteen and 10 experts completed Delphi Rounds 1 and 2, respectively, reaching consensus on 26 items in Round 1 and 10 items in Round 2. The study team consensus meeting conducted a final item review and considered the remaining 14 items for the content list. A final list of 43 items regarding IRT reached expert consensus: 7/10 items on safety, 11/11 items on efficacy, 10/12 items on programming, 8/10 items on delivery, and 7/7 on the mechanism of action. This study highlights that while experts reached a consensus that IRT is efficacious as an antihypertensive therapy, some still have safety concerns, and there is also ongoing conjecture regarding optimal delivery.
Reversing insecticide resistance with allelic-drive in Drosophila melanogaster
Authors: Kaduskar Bhagyashree , Kushwah Raja Babu Singh , Auradkar Ankush , Guichard Annabel , Li Menglin , Bennett Jared B. , Julio Alison Henrique Ferreira , Marshall John M. , Montell Craig , Bier Ethan
Published: January 2022

A recurring target-site mutation identified in various pests and disease vectors alters thevoltage gated sodium channel(vgsc) gene (often referred to asknockdown resistanceorkdr) to confer resistance to commonly used insecticides, pyrethroids and DDT. The ubiquity ofkdrmutations poses a major global threat to the continued use of insecticides as a means for vector control. In this study, we generate commonkdrmutations in isogenic laboratoryDrosophilastrains using CRISPR/Cas9 editing. We identify differential sensitivities to permethrin and DDT versus deltamethrin among these mutants as well as contrasting physiological consequences of two differentkdrmutations. Importantly, we apply a CRISPR-based allelic-drive to replace a resistantkdrmutation with a susceptible wild-type counterpart in population cages. This successful proof-of-principle opens-up numerous possibilities including targeted reversion of insecticide-resistant populations to a native susceptible state or replacement of malaria transmitting mosquitoes with those bearing naturally occurring parasite resistant alleles.
Cornering the universal shape of fluctuations
Authors: Estienne Benoit , Stéphan Jean-Marie , Witczak-Krempa William
Published: January 2022

Understanding the fluctuations of observables is one of the main goals in science, be it theoretical or experimental, quantum or classical. We investigate such fluctuations in a subregion of the full system, focusing on geometries with sharp corners. We report that the angle dependence is super-universal: up to a numerical prefactor, this function does not depend on anything, provided the system under study is uniform, isotropic, and correlations do not decay too slowly. The prefactor contains important physical information: we show in particular that it gives access to the long-wavelength limit of the structure factor. We exemplify our findings with fractional quantum Hall states, topological insulators, scale invariant quantum critical theories, and metals. We suggest experimental tests, and anticipate that our findings can be generalized to other spatial dimensions or geometries. In addition, we highlight the similarities of the fluctuation shape dependence with findings relating to quantum entanglement measures.
Selective ligand removal to improve accessibility of active sites in hierarchical MOFs for heterogeneous photocatalysis
Authors: Naghdi Shaghayegh , Cherevan Alexey , Giesriegl Ariane , Guillet-Nicolas Rémy , Biswas Santu , Gupta Tushar , Wang Jia , Haunold Thomas , Bayer Bernhard Christian , Rupprechter Günther , Toroker Maytal Caspary , Kleitz Freddy , Eder Dominik
Published: January 2022

Metal-organic frameworks (MOFs) are commended as photocatalysts for H2 evolution and CO2 reduction as they combine light-harvesting and catalytic functions with excellent reactant adsorption capabilities. For dynamic processes in liquid phase, the accessibility of active sites becomes a critical parameter as reactant diffusion is limited by the inherently small micropores. Our strategy is to introduce additional mesopores by selectively removing one ligand in mixed-ligand MOFs via thermolysis. Here we report photoactive MOFs of the MIL-125-Ti family with two distinct mesopore architectures resembling either large cavities or branching fractures. The ligand removal is highly selective and follows a 2-step process tunable by temperature and time. The introduction of mesopores and the associated formation of new active sites have improved the HER rates of the MOFs by up to 500%. We envision that this strategy will allow the purposeful engineering of hierarchical MOFs and advance their applicability in environmental and energy technologies.
Mammalian brain glycoproteins exhibit diminished glycan complexity compared to other tissues
Authors: Williams Sarah E. , Noel Maxence , Lehoux Sylvain , Cetinbas Murat , Xavier Ramnik J. , Sadreyev Ruslan I. , Scolnick Edward M. , Smoller Jordan W. , Cummings Richard D. , Mealer Robert G.
Published: January 2022

Glycosylation is essential to brain development and function, but prior studies have often been limited to a single analytical technique and excluded region- and sex-specific analyses. Here, using several methodologies, we analyze Asn-linked and Ser/Thr/Tyr-linked protein glycosylation between brain regions and sexes in mice. Brain N-glycans are less complex in sequence and variety compared to other tissues, consisting predominantly of high-mannose and fucosylated/bisected structures. Most brain O-glycans are unbranched, sialylated O-GalNAc and O-mannose structures. A consistent pattern is observed between regions, and sex differences are minimal compared to those in plasma. Brain glycans correlate with RNA expression of their synthetic enzymes, and analysis of glycosylation genes in humans show a global downregulation in the brain compared to other tissues. We hypothesize that this restricted repertoire of protein glycans arises from their tight regulation in the brain. These results provide a roadmap for future studies of glycosylation in neurodevelopment and disease.
Biosensor for branched-chain amino acid metabolism in yeast and applications in isobutanol and isopentanol production
Authors: Zhang Yanfei , Cortez Jeremy D. , Hammer Sarah K. , Carrasco-López César , García Echauri Sergio Á. , Wiggins Jessica B. , Wang Wei , Avalos José L.
Published: January 2022

Branched-chain amino acid (BCAA) metabolism fulfills numerous physiological roles and can be harnessed to produce valuable chemicals. However, the lack of eukaryotic biosensors specific for BCAA-derived products has limited the ability to develop high-throughput screens for strain engineering and metabolic studies. Here, we harness the transcriptional regulator Leu3p from Saccharomyces cerevisiae to develop a genetically encoded biosensor for BCAA metabolism. In one configuration, we use the biosensor to monitor yeast production of isobutanol, an alcohol derived from valine degradation. Small modifications allow us to redeploy Leu3p in another biosensor configuration that monitors production of the leucine-derived alcohol, isopentanol. These biosensor configurations are effective at isolating high-producing strains and identifying enzymes with enhanced activity from screens for branched-chain higher alcohol (BCHA) biosynthesis in mitochondria as well as cytosol. Furthermore, this biosensor has the potential to assist in metabolic studies involving BCAA pathways, and offers a blueprint to develop biosensors for other products derived from BCAA metabolism.
The formation of avian montane diversity across barriers and along elevational gradients
Authors: Pujolar José Martín , Blom Mozes P. K. , Reeve Andrew Hart , Kennedy Jonathan D. , Marki Petter Zahl , Korneliussen Thorfinn S. , Freeman Benjamin G. , Sam Katerina , Linck Ethan , Haryoko Tri , Iova Bulisa , Koane Bonny , Maiah Gibson , Paul Luda , Irestedt Martin , Jønsson Knud Andreas
Published: January 2022

Tropical mountains harbor exceptional concentrations of Earth’s biodiversity. In topographically complex landscapes, montane species typically inhabit multiple mountainous regions, but are absent in intervening lowland environments. Here we report a comparative analysis of genome-wide DNA polymorphism data for population pairs from eighteen Indo-Pacific bird species from the Moluccan islands of Buru and Seram and from across the island of New Guinea. We test how barrier strength and relative elevational distribution predict population differentiation, rates of historical gene flow, and changes in effective population sizes through time. We find population differentiation to be consistently and positively correlated with barrier strength and a species’ altitudinal floor. Additionally, we find that Pleistocene climate oscillations have had a dramatic influence on the demographics of all species but were most pronounced in regions of smaller geographic area. Surprisingly, even the most divergent taxon pairs at the highest elevations experience gene flow across barriers, implying that dispersal between montane regions is important for the formation of montane assemblages.
Single particle cryo-EM structure of the outer hair cell motor protein prestin
Authors: Butan Carmen , Song Qiang , Bai Jun-Ping , Tan Winston J. T. , Navaratnam Dhasakumar , Santos-Sacchi Joseph
Published: January 2022

The mammalian outer hair cell (OHC) protein prestin (Slc26a5) differs from other Slc26 family members due to its unique piezoelectric-like property that drives OHC electromotility, the putative mechanism for cochlear amplification. Here, we use cryo-electron microscopy to determine prestin’s structure at 3.6 Å resolution. Prestin is structurally similar to the anion transporter Slc26a9. It is captured in an inward-open state which may reflect prestin’s contracted state. Two well-separated transmembrane (TM) domains and two cytoplasmic sulfate transporter and anti-sigma factor antagonist (STAS) domains form a swapped dimer. The transmembrane domains consist of 14 transmembrane segments organized in two 7+7 inverted repeats, an architecture first observed in the bacterial symporter UraA. Mutation of prestin’s chloride binding site removes salicylate competition with anions while retaining the prestin characteristic displacement currents (Nonlinear Capacitance), undermining the extrinsic voltage sensor hypothesis for prestin function.
Eliminating chronic myeloid leukemia stem cells by IRAK1/4 inhibitors
Authors: Tanaka Yosuke , Takeda Reina , Fukushima Tsuyoshi , Mikami Keiko , Tsuchiya Shun , Tamura Moe , Adachi Keito , Umemoto Terumasa , Asada Shuhei , Watanabe Naoki , Morishita Soji , Imai Misa , Nagata Masayoshi , Araki Marito , Takizawa Hitoshi , Fukuyama Tomofusa , Lamagna Chrystelle , Masuda Esteban S. , Ito Ryoji , Goyama Susumu , Komatsu Norio , Takaku Tomoiku , Kitamura Toshio
Published: January 2022

Leukemia stem cells (LSCs) in chronic myeloid leukemia (CML) are quiescent, insensitive to BCR-ABL1 tyrosine kinase inhibitors (TKIs) and responsible for CML relapse. Therefore, eradicating quiescent CML LSCs is a major goal in CML therapy. Here, using a G0 marker (G0M), we narrow down CML LSCs as G0M- and CD27- double positive cells among the conventional CML LSCs. Whole transcriptome analysis reveals NF-κB activation via inflammatory signals in imatinib-insensitive quiescent CML LSCs. Blocking NF-κB signals by inhibitors of interleukin-1 receptor-associated kinase 1/4 (IRAK1/4 inhibitors) together with imatinib eliminates mouse and human CML LSCs. Intriguingly, IRAK1/4 inhibitors attenuate PD-L1 expression on CML LSCs, and blocking PD-L1 together with imatinib also effectively eliminates CML LSCs in the presence of T cell immunity. Thus, IRAK1/4 inhibitors can eliminate CML LSCs through inhibiting NF-κB activity and reducing PD-L1 expression. Collectively, the combination of TKIs and IRAK1/4 inhibitors is an attractive strategy to achieve a radical cure of CML.
Rare observations of sprites and gravity waves supporting D, E, F-regions ionospheric coupling
Authors: Maurya Ajeet K. , Parihar Navin , Dube Adarsh , Singh Rajesh , Kumar Sushil , Chanrion Olivier , Tomicic Maja , Neubert Torsten
Published: January 2022

We report rare simultaneous observations of columniform sprites and associated gravity waves (GWs) using the Transient Luminous Events (TLEs) camera and All-sky imager at Prayagraj (25.5° N, 81.9° E, geomag. lat. ~ 16.5° N), India. On 30 May 2014, a Mesoscale Convective System generated a group of sprites over the north horizon that reached the upper mesosphere. Just before this event, GWs (period ~ 14 min) were seen in OH broadband airglow (emission peak ~ 87 km) imaging that propagated in the direction of the sprite occurrence and dissipated in the background atmosphere thereby generating turbulence. About 9–14 min after the sprite event, another set of GWs (period ~ 11 min) was observed in OH imaging that arrived from the direction of the TLEs. At this site, we also record Very Low Frequency navigational transmitter signal JJI (22.2 kHz) from Japan. The amplitude of the JJI signal showed the presence of GWs with ~ 12.2 min periodicities and ~ 18 min period. The GWs of similar features were observed in the ionospheric Total Electron Content variations recorded at a nearby GPS site. The results presented here are important to understand the physical coupling of the troposphere with the lower and upper ionosphere through GWs.