bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical Analysis of Ring Ionospheric Trough Characteristics
Authors: Karpachev A. T.
Published: October 2021

In this study, the statistical characteristics of the ring ionospheric trough (RIT) are determined. The RIT is formed by the decay processes of the magnetospheric ring current; therefore, it is most clearly distinguished from the main ionospheric trough (MIT) during the recovery phase of a geomagnetic storm. The dynamics of both the troughs is considered in the case of geomagnetic disturbances with Kp indices from 4 to 9 during 2000–2003. In total, 830 RIT occurrences were identified in the CHAMP satellite data. The RIT is most often formed in the post‐midnight period, less often in the evening, and never in the daytime between 10 and 14 LT. In the post‐midnight period, the RIT is observed in the belt of 39°–62° geomagnetic latitude (in both hemispheres), with an occurrence maximum at 55° (L‐shell, L = 3). This finding is in good agreement with the observations of stable auroral red (SAR) arcs and a residual magnetospheric ring current. When a storm exhibits a long recovery phase, during which the geomagnetic activity periodically resumes, the RIT can exist for more than two days. The RIT is most often formed at the longitudes of South America, where the geomagnetic field is the weakest. In contrast to the MIT position, the averaged RIT position is not so strongly dependent on the longitude and Kp index. At low Kp values, the plasmapause position is close to the MIT position, while at high Kp values, the plasmapause approaches the RIT position.
Recovering 3D Basement Relief Using Gravity Data Through Convolutional Neural Networks
Authors: He Siyuan , Cai Hongzhu , Liu Shuang , Xie Jingtao , Hu Xiangyun
Published: October 2021

Gravity surveys in regional geophysical research can be used to estimate the depth of the sediment‐basement interface. In this study, we investigate a novel method using the convolutional neural network (CNN) for depth‐to‐basement inversion directly from gravity data. Based on the Random‐Midpoint‐Displacement method (RMD) and the features of the observed gravity data, we can generate a large set of realistic sediment‐basement interface models. This new method for model generation can significantly reduce the size of the training data sets which is usually considerably large to train a pervasive network. The application on synthetic models shows that the developed CNN inversion is able to capture the detailed features of the sediment‐basement interface for the complex geological model. However, so far, the training set obtained from the proposed method is still continuous and the CNN inversion still cannot effectively recover the models such as abrupt faults. We also successfully applied the developed method and workflow to a field study. The proposed approach opens a new window for estimating the physical contrast interfaces using potential field.
The Helium Elemental and Isotopic Compositions of the Earth's Core Based on Ab Initio Simulations
Authors: Yuan Liang , Steinle‐Neumann Gerd
Published: October 2021

We use density functional theory‐based molecular dynamics simulations to predict the partitioning behavior of helium (He) between coexisting metal and silicate melts at conditions of the magma ocean and the current core–mantle boundary. Helium strongly favors silicate over metal at low pressures and temperatures (10 GPa and 3,000 K) but it becomes approximately two orders of magnitude more compatible with metal at greater pressures and temperatures (50 GPa and 4,000 K) expected in a deep magma ocean. We further examine He partitioning behavior for varying metal compositions (pure Fe, Fe‐S, and Fe‐O alloys) and find that oxygen enhances He incorporation into the core by one to two orders of magnitude. The He elemental and isotopic compositions of the Earth's core are estimated to be ∼4.2 ng/g and ∼140 atmospheric 3He/4He ratio assuming the core containing some amounts of oxygen as required to explain the core density deficit. Our results suggest that the core may play a key role as a reservoir for the He signature recorded in ocean island basalts with distinctively high 3He/4He ratios.
The Morphology of Simulated Trade‐Wind Convection and Cold Pools Under Wind Shear
Authors: Helfer K. C. , Nuijens L.
Published: October 2021

A growing body of literature investigates convective organization, but few studies to date have sought to investigate how wind shear plays a role in the spatial organization of shallow (trade‐wind) convection. The present study hence investigates the morphology of precipitating marine cumulus convection using large‐eddy‐simulation experiments with zonal forward and backward shear and without shear. One set of simulations includes evaporation of precipitation, promoting cold‐pool development, and another set inhibits the evaporation of precipitation and thus cold‐pool formation. Without (or with only weak) subcloud‐layer shear, conditions are unfavorable for convective deepening, as clouds remain stationary relative to their subcloud‐layer roots so that precipitative downdrafts interfere with emerging updrafts. Under subcloud‐layer forward shear (FS), where the wind strengthens with height (a condition that is commonly found in the trades), clouds move at greater speed than their roots and precipitation falls downwind away from emerging updrafts. FS in the subcloud layer appears to promote the development of stronger subcloud circulations, with greater divergence in the cold‐pool area downwind of the original cell and larger convergence and stronger uplift at the gust front boundary. As clouds shear forward, a larger fraction of precipitation falls outside of clouds, leading to more moistening within the cold pool (gust front).
Divergent Patterns and Spatial Heterogeneity of Soil Nutrients in a Complex and Dynamic Savanna Landscape
Authors: Zhou Yong , Taylor Robert J. , Boutton Thomas W.
Published: October 2021

Many grassy ecosystems around the world are experiencing woody encroachment. These woody encroachers often cause nutrient enrichment in the plant‐soil environment, potentially facilitating their growth and reproduction. However, studies of encroachment effects on nutrient distributions have been confined to a few major elements (e.g.,N, and P) and limited in spatial extent. We analyzed 19 elements in dominant plants and in georeferenced soils across a subtropical savanna landscape experiencing woody encroachment to quantify their spatial patterns and elucidate drivers responsible for these patterns. We found divergent patterns of spatial heterogeneity of these elements in surface soils across this complex landscape. Nutrient accumulation and redistribution underneath woody canopies occurred in a subset of elements (i.e., N, P, S, Ca, Cu, and Sr). Though some of these elements are not necessarily growth‐limiting, they do occur in higher concentrations in woody compared to herbaceous plants. Distributions of the other elements were closely related to spatial variation in soil pH, clay content, and slope rather than to woody encroachment. Our nuanced spatial sampling approach and analysis reveal significant variation in nutrient distributions in response to woody encroachment, and illustrate the role of landscape patterns in mediating ecosystem processes. These changes in the concentrations and distributions of key essential nutrients broaden our understanding of the biogeochemical consequences of woody encroachment, and provide new insights regarding the significance of long‐term vegetation dynamics in dryland ecosystems.
Root Exudates Alters Nutrient Transport in Soil
Authors: Paporisch Amit , Bavli Harel , Strickman Rachel J. , Neumann Rebecca B. , Schwartz Nimrod
Published: October 2021

Root exudates alter the rhizosphere's physical properties, but the impact that these changes have on solute transport is unknown. In this study, we tested the effects of chia mucilage and wheat root exudates (WREs) on the transport of iodide and potassium in saturated or unsaturated soil. Saturated solute breakthrough experiments, conducted in loamy sand soil or coarser textured quartz sand, revealed that increasing the exudate concentration in soil resulted in non‐equilibrium solute transport. This behavior was demonstrated by an initial solute breakthrough after fewer pore volumes (PVs) and the arrival of the peak solute concentration after greater PVs in soil mixed with exudates compared to soil without exudates. These patterns were more pronounced for the coarser textured quartz sand than for the loamy sand soil, and in soil mixed with mucilage than in soil mixed WREs. Parameter fits to these breakthrough curves with a mobile‐immobile transport model indicated the fraction of immobile water increased as the concentration of exudates increased. For example, in quartz sand the estimated immobile fraction increased from 0 without exudates to 0.75 at a mucilage concentration of 0.2%. The solutes' breakthrough under unsaturated conditions was also altered by the exudates, demonstrated by a smaller volume of water extracted from soil mixed with exudates, compared to soil without exudates, before the arrival of the peak solute concentration. The results indicate that exudates alter the rhizosphere's transport properties; we hypothesize that this is due to exudates creating low‐conducting flow paths that result in a physical non‐equilibrium solute transport.
Dynamic Adaptation of Water Resources Systems Under Uncertainty by Learning Policy Structure and Indicators
Authors: Cohen Jonathan S. , Herman Jonathan D.
Published: October 2021

The challenge of adapting water resources systems to uncertain hydroclimatic and socioeconomic conditions warrants a dynamic planning approach. Recent studies have designed policies with structures linking infrastructure and management actions to threshold values of indicator variables observed over time. Typically, one or more of these components are held fixed while the others are optimized, constraining the flexibility of policy generation. Here we develop a framework to address this challenge by designing and testing dynamic adaptation policies that combine indicators, actions, and thresholds in a flexible structure. The approach is demonstrated for a case study of northern California, where a mix of infrastructure, management, and operational adaptations are considered over time in response to an ensemble of nonstationary hydrology and water demands. We first identify a subset of non‐dominated policies that are robust to held‐out scenarios, and then analyze their most common actions and indicators compared to non‐robust policies. Results show that the robust policies are not differentiated by the actions they select, but show substantial differences in their indicator variables, which can be interpreted in the context of physical hydrologic trends. In particular, the most frequent statistical transformations of indicator variables highlight the balance between adapting quickly versus correctly. Additionally, we determine the indicators most frequently associated with each action, as well as the distribution of action timing across scenarios. This study presents a new and transferable problem framing for adaptation under uncertainty in which indicator variables, actions, and policy structure are identified simultaneously during the optimization.
Embodied intelligence via learning and evolution
Authors: Gupta Agrim , Savarese Silvio , Ganguli Surya , Fei-Fei Li
Published: October 2021

The intertwined processes of learning and evolution in complex environmental niches have resulted in a remarkable diversity of morphological forms. Moreover, many aspects of animal intelligence are deeply embodied in these evolved morphologies. However, the principles governing relations between environmental complexity, evolved morphology, and the learnability of intelligent control, remain elusive, because performing large-scale in silico experiments on evolution and learning is challenging. Here, we introduce Deep Evolutionary Reinforcement Learning (DERL): a computational framework which can evolve diverse agent morphologies to learn challenging locomotion and manipulation tasks in complex environments. Leveraging DERL we demonstrate several relations between environmental complexity, morphological intelligence and the learnability of control. First, environmental complexity fosters the evolution of morphological intelligence as quantified by the ability of a morphology to facilitate the learning of novel tasks. Second, we demonstrate a morphological Baldwin effect i.e., in our simulations evolution rapidly selects morphologies that learn faster, thereby enabling behaviors learned late in the lifetime of early ancestors to be expressed early in the descendants lifetime. Third, we suggest a mechanistic basis for the above relationships through the evolution of morphologies that are more physically stable and energy efficient, and can therefore facilitate learning and control.
Realization of nearly dispersionless bands with strong orbital anisotropy from destructive interference in twisted bilayer MoS2
Authors: Xian Lede , Claassen Martin , Kiese Dominik , Scherer Michael M. , Trebst Simon , Kennes Dante M. , Rubio Angel
Published: October 2021

Recently, the twist angle between adjacent sheets of stacked van der Waals materials emerged as a new knob to engineer correlated states of matter in two-dimensional heterostructures in a controlled manner, giving rise to emergent phenomena such as superconductivity or correlated insulating states. Here, we use an ab initio based approach to characterize the electronic properties of twisted bilayer MoS2. We report that, in marked contrast to twisted bilayer graphene, slightly hole-doped MoS2 realizes a strongly asymmetric px-py Hubbard model on the honeycomb lattice, with two almost entirely dispersionless bands emerging due to destructive interference. The origin of these dispersionless bands, is similar to that of the flat bands in the prototypical Lieb or Kagome lattices and co-exists with the general band flattening at small twist angle due to the moiré interference. We study the collective behavior of twisted bilayer MoS2 in the presence of interactions, and characterize an array of different magnetic and orbitally-ordered correlated phases, which may be susceptible to quantum fluctuations giving rise to exotic, purely quantum, states of matter.
Magnetopause ripples going against the flow form azimuthally stationary surface waves
Authors: Archer M. O. , Hartinger M. D. , Plaschke F. , Southwood D. J. , Rastaetter L.
Published: October 2021

Surface waves process the turbulent disturbances which drive dynamics in many space, astrophysical and laboratory plasma systems, with the outer boundary of Earth’s magnetosphere, the magnetopause, providing an accessible environment to study them. Like waves on water, magnetopause surface waves are thought to travel in the direction of the driving solar wind, hence a paradigm in global magnetospheric dynamics of tailward propagation has been well-established. Here we show through multi-spacecraft observations, global simulations, and analytic theory that the lowest-frequency impulsively-excited magnetopause surface waves, with standing structure along the terrestrial magnetic field, propagate against the flow outside the boundary. Across a wide local time range (09–15h) the waves’ Poynting flux exactly balances the flow’s advective effect, leading to no net energy flux and thus stationary structure across the field also. Further down the equatorial flanks, however, advection dominates hence the waves travel downtail, seeding fluctuations at the resonant frequency which subsequently grow in amplitude via the Kelvin-Helmholtz instability and couple to magnetospheric body waves. This global response, contrary to the accepted paradigm, has implications on radiation belt, ionospheric, and auroral dynamics and potential applications to other dynamical systems.
SARS-CoV-2 antibody seroprevalence and associated risk factors in an urban district in Cameroon
Authors: Nwosu Kene , Fokam Joseph , Wanda Franck , Mama Lucien , Orel Erol , Ray Nicolas , Meke Jeanine , Tassegning Armel , Takou Desire , Mimbe Eric , Stoll Beat , Guillebert Josselin , Comte Eric , Keiser Olivia , Ciaffi Laura
Published: October 2021

The extent of SARS-CoV-2 circulation in many African countries remains unclear, underlining the need for antibody sero-surveys to assess the cumulative attack rate. Here, we present the results of a cross-sectional sero-survey of a random sample of residents of a health district in Yaounde, Cameroon, conducted from October 14 to November 26, 2020. Among the 971 participants, the test-adjusted seroprevalence of anti-SARS-CoV-2 IgG antibodies was 29·2% (95% CI 24·3–34·1). This is about 322 times greater than the 0.09% nationwide attack rate implied by COVID-19 case counts at the time. Men, obese individuals and those living in large households were significantly more likely to be seropositive, and the majority (64·2% [58·7–69·4]) of seropositive individuals reported no symptoms. Despite the high seroprevalence, most of the population had not been infected with SARS-CoV-2, highlighting the importance of continued measures to control viral spread and quick vaccine deployment to protect the vulnerable.
Noninvasive spinal stimulation safely enables upright posture in children with spinal cord injury
Authors: Keller Anastasia , Singh Goutam , Sommerfeld Joel H. , King Molly , Parikh Parth , Ugiliweneza Beatrice , D’Amico Jessica , Gerasimenko Yury , Behrman Andrea L.
Published: October 2021

In children with spinal cord injury (SCI), scoliosis due to trunk muscle paralysis frequently requires surgical treatment. Transcutaneous spinal stimulation enables trunk stability in adults with SCI and may pose a non-invasive preventative therapeutic alternative. This non-randomized, non-blinded pilot clinical trial (NCT03975634) determined the safety and efficacy of transcutaneous spinal stimulation to enable upright sitting posture in 8 children with trunk control impairment due to acquired SCI using within-subject repeated measures study design. Primary safety and efficacy outcomes (pain, hemodynamics stability, skin irritation, trunk kinematics) and secondary outcomes (center of pressure displacement, compliance rate) were assessed within the pre-specified endpoints. One participant did not complete the study due to pain with stimulation on the first day. One episode of autonomic dysreflexia during stimulation was recorded. Following hemodynamic normalization, the participant completed the study. Overall, spinal stimulation was well-tolerated and enabled upright sitting posture in 7 out of the 8 participants.
DUBStepR is a scalable correlation-based feature selection method for accurately clustering single-cell data
Authors: Ranjan Bobby , Sun Wenjie , Park Jinyu , Mishra Kunal , Schmidt Florian , Xie Ronald , Alipour Fatemeh , Singhal Vipul , Joanito Ignasius , Honardoost Mohammad Amin , Yong Jacy Mei Yun , Koh Ee Tzun , Leong Khai Pang , Rayan Nirmala Arul , Lim Michelle Gek Liang , Prabhakar Shyam
Published: October 2021

Feature selection (marker gene selection) is widely believed to improve clustering accuracy, and is thus a key component of single cell clustering pipelines. Existing feature selection methods perform inconsistently across datasets, occasionally even resulting in poorer clustering accuracy than without feature selection. Moreover, existing methods ignore information contained in gene-gene correlations. Here, we introduce DUBStepR (Determining theUnderlyingBasis usingStepwiseRegression), a feature selection algorithm that leverages gene-gene correlations with a novel measure of inhomogeneity in feature space, termed the Density Index (DI). Despite selecting a relatively small number of genes, DUBStepR substantially outperformed existing single-cell feature selection methods across diverse clustering benchmarks. Additionally, DUBStepR was the only method to robustly deconvolve T and NK heterogeneity by identifying disease-associated common and rare cell types and subtypes in PBMCs from rheumatoid arthritis patients. DUBStepR is scalable to over a million cells, and can be straightforwardly applied to other data types such as single-cell ATAC-seq. We propose DUBStepR as a general-purpose feature selection solution for accurately clustering single-cell data.
Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing
Authors: Papathanasiou Stamatis , Markoulaki Styliani , Blaine Logan J. , Leibowitz Mitchell L. , Zhang Cheng-Zhong , Jaenisch Rudolf , Pellman David
Published: October 2021

Karyotype alterations have emerged as on-target complications from CRISPR-Cas9 genome editing. However, the events that lead to these karyotypic changes in embryos after Cas9-treatment remain unknown. Here, using imaging and single-cell genome sequencing of 8-cell stage embryos, we track both spontaneous and Cas9-induced karyotype aberrations through the first three divisions of embryonic development. We observe the generation of abnormal structures of the nucleus that arise as a consequence of errors in mitosis, including micronuclei and chromosome bridges, and determine their contribution to common karyotype aberrations including whole chromosome loss that has been recently reported after editing in embryos. Together, these data demonstrate that Cas9-mediated germline genome editing can lead to unwanted on-target side effects, including major chromosome structural alterations that can be propagated over several divisions of embryonic development.
A bioinspired scaffold for rapid oxygenation of cell encapsulation systems
Authors: Wang Long-Hai , Ernst Alexander Ulrich , An Duo , Datta Ashim Kumar , Epel Boris , Kotecha Mrignayani , Ma Minglin
Published: October 2021

Inadequate oxygenation is a major challenge in cell encapsulation, a therapy which holds potential to treat many diseases including type I diabetes. In such systems, cellular oxygen (O2) delivery is limited to slow passive diffusion from transplantation sites through the poorly O2-soluble encapsulating matrix, usually a hydrogel. This constrains the maximum permitted distance between the encapsulated cells and host site to within a few hundred micrometers to ensure cellular function. Inspired by the natural gas-phase tracheal O2 delivery system of insects, we present herein the design of a biomimetic scaffold featuring internal continuous air channels endowed with 10,000-fold higher O2 diffusivity than hydrogels. We incorporate the scaffold into a bulk hydrogel containing cells, which facilitates rapid O2 transport through the whole system to cells several millimeters away from the device-host boundary. A computational model, validated by in vitro analysis, predicts that cells and islets maintain high viability even in a thick (6.6 mm) device. Finally, the therapeutic potential of the device is demonstrated through the correction of diabetes in immunocompetent mice using rat islets for over 6 months.
Multi-targeted 1H/19F MRI unmasks specific danger patterns for emerging cardiovascular disorders
Authors: Flögel Ulrich , Temme Sebastian , Jacoby Christoph , Oerther Thomas , Keul Petra , Flocke Vera , Wang Xiaowei , Bönner Florian , Nienhaus Fabian , Peter Karlheinz , Schrader Jürgen , Grandoch Maria , Kelm Malte , Levkau Bodo
Published: October 2021

Prediction of the transition from stable to acute coronary syndromes driven by vascular inflammation, thrombosis with subsequent microembolization, and vessel occlusion leading to irreversible myocardial damage is still an unsolved problem. Here, we introduce a multi-targeted and multi-color nanotracer platform technology that simultaneously visualizes evolving danger patterns in the development of progressive coronary inflammation and atherothrombosis prior to spontaneous myocardial infarction in mice. Individual ligand-equipped perfluorocarbon nanoemulsions are used as targeting agents and are differentiated by their specific spectral signatures via implementation of multi chemical shift selective19F MRI. Thereby, we are able to identify areas at high risk of and predictive for consecutive development of myocardial infarction, at a time when no conventional parameter indicates any imminent danger. The principle of this multi-targeted approach can easily be adapted to monitor also a variety of other disease entities and constitutes a technology with disease-predictive potential.
CD127+ CD94+ innate lymphoid cells expressing granulysin and perforin are expanded in patients with Crohn’s disease
Authors: Krabbendam L. , Heesters B. A. , Kradolfer C. M. A. , Haverkate N. J. E. , Becker M. A. J. , Buskens C. J. , Bemelman W. A. , Bernink J. H. , Spits H.
Published: October 2021

Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Recently we showed the identification of cytotoxic ILC3s characterized by expression of CD94. Here we analyse CD127+ ILCs and NK cells in intestinal lamina propria from healthy donors and Crohn’s disease patients and identify two populations of CD127+CD94+ ILCs, designated population A and B, that can be distinguished on the expression of CD117, CD18 and cytotoxic molecules. Population B expresses granulysin, a cytotoxic molecule linked to bacterial lysis and/or chemotaxis of monocytes. Granulysin protein is secreted by population B cells upon stimulation with IL-15. Activation of population B in the presence of TGF-β strongly reduces the expression of cytotoxic effector molecules of population B. Strikingly, samples from individuals that suffer from active Crohn’s disease display enhanced frequencies of granulysin-expressing effector CD127+CD94+ ILCs in comparison to controls. Thus this study identifies group 1 ILC populations which accumulate in inflamed intestinal tissue of Crohn’s disease patients and may play a role in the pathology of the disease.
Fröhlich interaction dominated by a single phonon mode in CsPbBr3
Authors: Iaru Claudiu M. , Brodu Annalisa , van Hoof Niels J. J. , ter Huurne Stan E. T. , Buhot Jonathan , Montanarella Federico , Buhbut Sophia , Christianen Peter C. M. , Vanmaekelbergh Daniël , de Mello Donega Celso , Rivas Jaime Gòmez , Koenraad Paul M. , Silov Andrei Yu.
Published: October 2021

The excellent optoelectronic performance of lead halide perovskites has generated great interest in their fundamental properties. The polar nature of the perovskite lattice means that electron-lattice coupling is governed by the Fröhlich interaction. Still, considerable ambiguity exists regarding the phonon modes that participate in this crucial mechanism. Here, we use multiphonon Raman scattering and THz time-domain spectroscopy to investigate Fröhlich coupling in CsPbBr3. We identify a longitudinal optical phonon mode that dominates the interaction, and surmise that this mode effectively defines exciton-phonon scattering in CsPbBr3, and possibly similar materials. It is additionally revealed that the observed strength of the Fröhlich interaction is significantly higher than the expected intrinsic value for CsPbBr3, and is likely enhanced by carrier localization in the colloidal perovskite nanocrystals. Our experiments also unearthed a dipole-related dielectric relaxation mechanism which may impact transport properties.
PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages
Authors: Obst Juliane , Hall-Roberts Hazel L. , Smith Thomas B. , Kreuzer Mira , Magno Lorenza , Di Daniel Elena , Davis John B. , Mead Emma
Published: October 2021

Human genetic studies have linked rare coding variants in microglial genes, such as TREM2, and more recently PLCG2 to Alzheimer’s disease (AD) pathology. The P522R variant in PLCG2 has been shown to confer protection for AD and to result in a subtle increase in enzymatic activity. PLCγ2 is a key component of intracellular signal transduction networks and induces Ca2+ signals downstream of many myeloid cell surface receptors, including TREM2. To explore the relationship between PLCγ2 and TREM2 and the role of PLCγ2 in regulating immune cell function, we generated human induced pluripotent stem cell (iPSC)- derived macrophages from isogenic lines with homozygous PLCG2 knockout (Ko). Stimulating TREM2 signalling using a polyclonal antibody revealed a complete lack of calcium flux and IP1 accumulation in PLCγ2 Ko cells, demonstrating a non-redundant role of PLCγ2 in calcium release downstream of TREM2. Loss of PLCγ2 led to broad changes in expression of several macrophage surface markers and phenotype, including reduced phagocytic activity and survival, while LPS-induced secretion of the inflammatory cytokines TNFα and IL-6 was unaffected. We identified additional deficits in PLCγ2- deficient cells that compromised cellular adhesion and migration. Thus, PLCγ2 is key in enabling divergent cellular functions and might be a promising target to increase beneficial microglial functions.
Associations between race, APOE genotype, cognition, and mortality among urban middle-aged white and African American adults
Authors: Weiss Jordan , Hossain Sharmin , Maldonado Ana I. , Shen Botong , Beydoun Hind A. , Kivimaki Mika , Evans Michele K. , Zonderman Alan B. , Beydoun May A.
Published: October 2021

We examined associations between cognition and mortality and how these relationships vary by race and Apolipoprotein E (APOE) genotype, in a longitudinal study of 2346 middle-aged White and African American adults (30–64 years at baseline) from the Healthy Aging in Neighborhoods of Diversity across the Life Span cohort study. Baseline cognition spanned global mental status, and several domains obtained using principal components analysis (PCA; PCA1: verbal memory/fluency; PCA2: attention/working memory; PCA3: executive function/visuo-spatial abilities). Cox regression models evaluated associations between cognition and all-cause and cardiovascular disease (CVD)-mortality. Interactions between cognition and APOE2 as well as APOE4 allelic dose were tested, and race was a key effect modifier. Higher APOE4 dose was associated with increased CVD-mortality (hazard ratio [HR] per allele = 1.37; 95% CI 1.01–1.86, p = 0.041); APOE2 dosage’s association with CVD-mortality was non-significant (HR = 0.60; 95% CI 0.35–1.03, p = 0.065). Higher PCA3 was associated with lower all-cause (HR = 0.93; 95% CI 0.87–0.99, p = 0.030) and CVD (HR = 0.85; 95% CI 0.77–0.95, p = 0.001) mortality risks, the latter association being more pronounced among Whites. PCA2 interacted synergistically with APOE2 dosage, reducing risks for all-cause mortality (PCA2 × APOE2: − 0.33 ± 0.13, p = 0.010) and CVD mortality (PCA2 × APOE2: − 0.73 ± 0.31, p = 0.019). In conclusion, greater executive function/visuo-spatial abilities were associated with reduced CVD-specific mortality, particularly among Whites. Greater “attention/working memory” coupled with higher APOE2 dosage was linked with reduced all-cause and CVD mortality risks.
The effect of a mindfulness-based intervention on executive, behavioural and socio-emotional competencies in very preterm young adolescents
Authors: Siffredi Vanessa , Liverani Maria Chiara , Hüppi Petra Susan , Freitas Lorena G. A. , De Albuquerque Jiske , Gimbert Fanny , Merglen Arnaud , Meskaldji Djalel Eddine , Borradori Tolsa Cristina , Hà-Vinh Leuchter Russia
Published: October 2021

Very preterm (VPT) children and adolescents show executive, behavioural and socio-emotional difficulties that persists into adulthood. This study aims to assess the effectiveness of a mindfulness-based intervention (MBI) in improving these competencies in VPT young adolescents using a randomised controlled trial design. 56 young adolescents aged 10–14 years, born before 32 gestational weeks, were randomly assigned to an “intervention” or a “waiting” group and completed an 8-week MBI in a cross-over design. Executive, behavioural and socio-emotional competencies were assessed at three different time points via parent and self-reported questionnaires, neuropsychological testing and computerised tasks. The data were analysed using an intention-to-treat approach with linear regression modelling. Our findings show a beneficial effect of MBI on executive, behavioural and socio-emotional competencies in VPT young adolescents measured by parent questionnaires. Increased executive competencies were also observed on computerised task with enhanced speed of processing after MBI. Two subgroups of participants were created based on measures of prematurity, which revealed increased long-term benefits in the moderate-risk that were not observed in the high-risk subgroups of VPT young adolescents. MBI seems a valuable tool for reducing detrimental consequences of prematurity in young adolescents, especially regarding executive, behavioural and socio-emotional difficulties.

Clinical Trial RegistrationClinicalTrials, NCT04638101. Registered 20 November 2020—Retrospectively registered,https://clinicaltrials.gov/show/NCT04638101.
Optimization of an appointment scheduling problem for healthcare systems based on the quality of fairness service using whale optimization algorithm and NSGA-II
Authors: Ala Ali , Alsaadi Fawaz E. , Ahmadi Mohsen , Mirjalili Seyedali
Published: October 2021

Effective appointment scheduling (EAS) is essential for the quality and patient satisfaction in hospital management. Healthcare schedulers typically refer patients to a suitable period of service before the admission call closes. The appointment date can no longer be adjusted. This research presents the whale optimization algorithm (WOA) based on the Pareto archive and NSGA-II algorithm to solve the appointment scheduling model by considering the simulation approach. Based on these two algorithms, this paper has addressed the multi-criteria method in appointment scheduling. This paper computes WOA and NSGA with various hypotheses to meet the analysis and different factors related to patients in the hospital. In the last part of the model, this paper has analyzed NSGA and WOA with three cases. Fairness policy first come first serve (FCFS) considers the most priority factor to obtain from figure to strategies optimized solution for best satisfaction results. In the proposed NSGA, the FCFS approach and the WOA approach are contrasted. Numerical results indicate that both the FCFS and WOA approaches outperform the strategy optimized by the proposed algorithm.
Molecular imaging of myogenic stem/progenitor cells with [18F]-FHBG PET/CT system in SCID mice model of post-infarction heart
Authors: Wargocka-Matuszewska Weronika , Fiedorowicz Katarzyna , Rugowska Anna , Bednarowicz Karolina , Zimna Agnieszka , Cheda Łukasz , Hamankiewicz Paulina , Kilian Krzysztof , Fiedorowicz Michał , Drabik Monika , Rozwadowska Natalia , Rogulski Zbigniew , Kurpisz Maciej
Published: October 2021

Preclinical and clinical studies have shown that stem cells can promote the regeneration of damaged tissues, but therapeutic protocols need better quality control to confirm the location and number of transplanted cells. This study describes in vivo imaging while assessing reporter gene expression by its binding to a radiolabelled molecule to the respective receptor expressed in target cells. Five mice underwent human skeletal muscle-derived stem/progenitor cell (huSkMDS/PC EF1-HSV-TK) intracardial transplantation after induction of myocardial infarction (MI). The metabolic parameters of control and post-infarction stem progenitor cell-implanted mice were monitored using 2-deoxy-18F-fluorodeoxyglucose ([18F]-FDG) before and after double promotor/reporter probe imaging with 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]-FHBG) using positron emission tomography (PET) combined with computed tomography (CT). Standardized uptake values (SUVs) were then calculated based on set regions of interest (ROIs). Experimental animals were euthanized after magnetic resonance imaging (MRI). Molecular [18F]-FHBG imaging of myogenic stem/progenitor cells in control and post-infarction mice confirmed the survival and proliferation of transplanted cells, as shown by an increased or stable signal from the PET apparatus throughout the 5 weeks of monitoring. huSkMDS/PC EF1-HSV-TK transplantation improved cardiac metabolic ([18F]-FDG with PET) and haemodynamic (MRI) parameters. In vivo PET/CT and MRI revealed that the precise use of a promotor/reporter probe incorporated into stem/progenitor cells may improve non-invasive monitoring of targeted cellular therapy in the cardiovascular system.
NB-LRR-encoding genes conferring susceptibility to organophosphate pesticides in sorghum
Authors: Jing Zihuan , Wacera W. Fiona , Takami Tsuneaki , Takanashi Hideki , Fukada Fumi , Kawano Yoji , Kajiya-Kanegae Hiromi , Iwata Hiroyoshi , Tsutsumi Nobuhiro , Sakamoto Wataru
Published: October 2021

Organophosphate is the commonly used pesticide to control pest outbreak, such as those by aphids in many crops. Despite its wide use, however, necrotic lesion and/or cell death following the application of organophosphate pesticides has been reported to occur in several species. To understand this phenomenon, called organophosphate pesticide sensitivity (OPS) in sorghum, we conducted QTL analysis in a recombinant inbred line derived from the Japanese cultivar NOG, which exhibits OPS. Mapping OPS in this population identified a prominent QTL on chromosome 5, which corresponded to Organophosphate-Sensitive Reaction (OSR) reported previously in other mapping populations. The OSR locus included a cluster of three genes potentially encoding nucleotide-binding leucine-rich repeat (NB-LRR, NLR) proteins, among which NLR-C was considered to be responsible for OPS in a dominant fashion. NLR-C was functional in NOG, whereas the other resistant parent, BTx623, had a null mutation caused by the deletion of promoter sequences. Our finding of OSR as a dominant trait is important not only in understanding the diversified role of NB-LRR proteins in cereals but also in securing sorghum breeding free from OPS.
RRAM-based CAM combined with time-domain circuits for hyperdimensional computing
Authors: Halawani Yasmin , Kilani Dima , Hassan Eman , Tesfai Huruy , Saleh Hani , Mohammad Baker
Published: October 2021

Content addressable memory (CAM) for search and match operations demands high speed and low power for near real-time decision-making across many critical domains. Resistive RAM (RRAM)-based in-memory computing has high potential in realizing an efficient static CAM for artificial intelligence tasks, especially on resource-constrained platforms. This paper presents an XNOR-based RRAM-CAM with a time-domain analog adder for efficient winning class computation. The CAM compares two operands, one voltage and the second one resistance, and outputs a voltage proportional to the similarity between the input query and the pre-stored patterns. Processing the summation of the output similarity voltages in the time-domain helps avoid voltage saturation, variation, and noise dominating the analog voltage-based computing. After that, to determine the winning class among the multiple classes, a digital realization is utilized to consider the class with the longest pulse width as the winning class. As a demonstrator, hyperdimensional computing for efficient MNIST classification is considered. The proposed design uses 65 nm CMOS foundry technology and realistic data for RRAM with total area of 0.0077 mm2, consumes 13.6 pJ of energy per 1 k query within 10 ns clock cycle. It shows a reduction of ~ 31 × in area and ~ 3 × in energy consumption compared to fully digital ASIC implementation using 65 nm foundry technology. The proposed design exhibits a remarkable reduction in area and energy compared to two of the state-of-the-art RRAM designs.
Electrical impedance tomography for non-invasive identification of fatty liver infiltrate in overweight individuals
Authors: Chang Chih-Chiang , Huang Zi-Yu , Shih Shu-Fu , Luo Yuan , Ko Arthur , Cui Qingyu , Sumner Jennifer , Cavallero Susana , Das Swarna , Gao Wei , Sinsheimer Janet , Bui Alex , Jacobs Jonathan P. , Pajukanta Päivi , Wu Holden , Tai Yu-Chong , Li Zhaoping , Hsiai Tzung K.
Published: October 2021

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cardiometabolic diseases in overweight individuals. While liver biopsy is the current gold standard to diagnose NAFLD and magnetic resonance imaging (MRI) is a non-invasive alternative still under clinical trials, the former is invasive and the latter costly. We demonstrate electrical impedance tomography (EIT) as a portable method for detecting fatty infiltrate. We enrolled 19 overweight subjects to undergo liver MRI scans, followed by EIT measurements. The MRI images provided the a priori knowledge of the liver boundary conditions for EIT reconstruction, and the multi-echo MRI data quantified liver proton-density fat fraction (PDFF%) to validate fat infiltrate. Using the EIT electrode belts, we circumferentially injected pairwise current to the upper abdomen, followed by acquiring the resulting surface-voltage to reconstruct the liver conductivity. Pearson’s correlation analyses compared EIT conductivity or MRI PDFF with body mass index, age, waist circumference, height, and weight variables. We reveal that the correlation between liver EIT conductivity or MRI PDFF with demographics is statistically insignificant, whereas liver EIT conductivity is inversely correlated with MRI PDFF (R = −0.69,p = 0.003, n = 16). As a pilot study, EIT conductivity provides a portable method for operator-independent and cost-effective detection of hepatic steatosis.
Cenozoic climatic changes drive evolution and dispersal of coastal benthic foraminifera in the Southern Ocean
Authors: Majewski Wojciech , Holzmann Maria , Gooday Andrew J. , Majda Aneta , Mamos Tomasz , Pawlowski Jan
Published: October 2021

The Antarctic coastal fauna is characterized by high endemism related to the progressive cooling of Antarctic waters and their isolation by the Antarctic Circumpolar Current. The origin of the Antarctic coastal fauna could involve either colonization from adjoining deep-sea areas or migration through the Drake Passage from sub-Antarctic areas. Here, we tested these hypotheses by comparing the morphology and genetics of benthic foraminifera collected from Antarctica, sub-Antarctic coastal settings in South Georgia, the Falkland Islands and Patagonian fjords. We analyzed four genera (Cassidulina, Globocassidulina, Cassidulinoides, Ehrenbergina) of the family Cassidulinidae that are represented by at least nine species in our samples. Focusing on the genera Globocassidulina and Cassidulinoides, our results showed that the first split between sub-Antarctic and Antarctic lineages took place during the mid-Miocene climate reorganization, probably about 20 to 17 million years ago (Ma). It was followed by a divergence between Antarctic species ~ 10 Ma, probably related to the cooling of deep water and vertical structuring of the water-column, as well as broadening and deepening of the continental shelf. The gene flow across the Drake Passage, as well as between South America and South Georgia, seems to have occurred from the Late Miocene to the Early Pliocene. It appears that climate warming during 7–5 Ma and the migration of the Polar Front breached biogeographic barriers and facilitated inter-species hybridization. The latest radiation coincided with glacial intensification (~ 2 Ma), which accelerated geographic fragmentation of populations, demographic changes, and genetic diversification in Antarctic species. Our results show that the evolution of Antarctic and sub-Antarctic coastal benthic foraminifera was linked to the tectonic and climatic history of the area, but their evolutionary response was not uniform and reflected species-specific ecological adaptations that influenced the dispersal patterns and biogeography of each species in different ways.
Eliapixant is a selective P2X3 receptor antagonist for the treatment of disorders associated with hypersensitive nerve fibers
Authors: Davenport Adam J. , Neagoe Ioana , Bräuer Nico , Koch Markus , Rotgeri Andrea , Nagel Jens , Laux-Biehlmann Alexis , Machet Frederic , Coelho Anne-Marie , Boyce Susan , Carty Nikisha , Gemkow Mark J. , Hess Stephen D. , Zollner Thomas M. , Fischer Oliver M.
Published: October 2021

ATP-dependent P2X3 receptors play a crucial role in the sensitization of nerve fibers and pathological pain pathways. They are also involved in pathways triggering cough and may contribute to the pathophysiology of endometriosis and overactive bladder. However, despite the strong therapeutic rationale for targeting P2X3 receptors, preliminary antagonists have been hampered by off-target effects, including severe taste disturbances associated with blocking the P2X2/3 receptor heterotrimer. Here we present a P2X3 receptor antagonist, eliapixant (BAY 1817080), which is both highly potent and selective for P2X3 over other P2X subtypes in vitro, including P2X2/3. We show that eliapixant reduces inflammatory pain in relevant animal models. We also provide the first in vivo experimental evidence that P2X3 antagonism reduces neurogenic inflammation, a phenomenon hypothesised to contribute to several diseases, including endometriosis. To test whether eliapixant could help treat endometriosis, we confirmed P2X3 expression on nerve fibers innervating human endometriotic lesions. We then demonstrate that eliapixant reduces vaginal hyperalgesia in an animal model of endometriosis-associated dyspareunia, even beyond treatment cessation. Our findings indicate that P2X3 antagonism could alleviate pain, including non-menstrual pelvic pain, and modify the underlying disease pathophysiology in women with endometriosis. Eliapixant is currently under clinical development for the treatment of disorders associated with hypersensitive nerve fibers.
Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles
Authors: Hirai Yusuke , Hirose Hisaaki , Imanishi Miki , Asai Tomohiro , Futaki Shiroh
Published: October 2021

Although proteins have attractive features as biopharmaceuticals, the difficulty in delivering them into the cell interior limits their applicability. Lipid nanoparticles (LNPs) are a promising class of delivery vehicles. When designing a protein delivery system based on LNPs, the major challenges include: (i) formulation of LNPs with defined particle sizes and dispersity, (ii) efficient encapsulation of cargo proteins into LNPs, and (iii) effective cellular uptake and endosomal release into the cytosol. Dioleoylglycerophosphate-diethylenediamine (DOP-DEDA) is a pH-responsive, charge-reversible lipid. The aim of this study was to evaluate the applicability of DOP-DEDA-based LNPs for intracellular protein delivery. Considering the importance of electrostatic interactions in protein encapsulation into LNPs, a negatively charged green fluorescent protein (GFP) analog was successfully encapsulated into DOP-DEDA-based LNPs to yield diameters and polydispersity index of < 200 nm and < 0.2, respectively. Moreover, ~ 80% of the cargo proteins was encapsulated into the LNPs. Cytosolic distribution of fluorescent signals of the protein was observed for up to ~ 90% cells treated with the LNPs, indicating the facilitated endocytic uptake and endosomal escape of the cargo attained using the LNP system.