bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of social enterprises in facilitating labour market integration for people with disabilities: A convenient deflection from policy mainstreaming?
Authors: CHUI CHERYL HIU-KWAN , CHAN CHEE HON , CHANDRA YANTO
Published: July 2021

Policymakers have increasingly embraced social enterprises as a vehicle to create job opportunities for the disadvantaged. However, there is limited research on social enterprises in the context of disability in relation to labour market integration. Drawing on the perspectives of representatives of work integration social enterprises and people with disabilities employed in these enterprises (n=21), this study examines whether and how work integration social enterprises promote inclusion for people with disabilities, and also explores the role of WISEs in enabling people with disabilities to transition into open employment. Thematic analysis revealed three key emergent themes:Cocooned inclusion but not transition; Reinforced normative demarcation; andWISEs as a deflection from institutionalizing proactive disability policy measures. This article argues that, although WISEs were able to provide job opportunities for people with disabilities, their purported function in enabling disabled people to transition into open employment remains constrained by factors beyond their control including prevailing norms and the absence of proactive disability employment measures. This article cautions against the over-romanticisation of WISEs as the primary means to ensure the rights of people with disabilities to participate in the labour market. Implications on disability employment policies in relation to social enterprises are discussed.
Emission source tracing based on bionic algorithm mobile sensors with artificial olfactory system
Authors: Ma Denglong , Mao Weigao , Tan Wei , Gao Jianmin , Zhang Zaoxiao , Xie Yunchuan
Published: July 2021

The leakage of hazardous chemicals and toxic volatile substances in the atmosphere may cause serious consequences such as explosion and poisoning. To identify the unknown leakage locations and gas compositions, a mobile robot system to trace the leak source in the outdoor was investigated. First, two bionic searching algorithms, Zigzag and Silkworm algorithms, were tested with outdoor experiments for locating the leak source. The results showed that the locating errors of these two algorithms were within 0.5 m in 10 by 20 m search space, but the failing ratio of Zigzag and Silkworm algorithm was still high (about 40–50%). Therefore, an improved tracing algorithm combining the Silkworm and Zigzag algorithm, called as zigzag–Silkworm algorithm, was proposed. Compared with Silkworm and Zigzag algorithms, zigzag–Silkworm algorithm had a higher success ratio of 80% in outdoor source tracing tests, and the searching efficiency was enhanced, the efficiency parameter L: L0 has improved from 2.58 for Silkworm and 2.66 for Zigzag to 2.17 for zigzag–Silkworm. Then, in order to identify the composition of the leaked gases during the source tracing, an artificial olfaction system (AOS) based on the gas sensor array and support vector machine was set on the mobile robot. The test results in the source tracing experiments with ammonia and ethanol emissions indicated that the recognition accuracy of emission gases reached to 99% with AOS equipped on the robot. Therefore, the mobile robot system equipped with the zigzag–Silkworm algorithm and the AOS is feasible to trace the leakage source and identify the emission composition in the outdoor leakage event with good performance in efficiency and accuracy although some underlying problems still need to be addressed in future work.
A network approach to dyslexia: Mapping the reading network
Authors: Verwimp Cara , Tijms Jurgen , Snellings Patrick , Haslbeck Jonas M. B. , Wiers Reinout W.
Published: July 2021

Research on the etiology of dyslexia typically uses an approach based on a single core deficit, failing to understand how variations in combinations of factors contribute to reading development and how this combination relates to intervention outcome. To fill this gap, this study explored links between 28 cognitive, environmental, and demographic variables related to dyslexia by employing a network analysis using a large clinical database of 1,257 elementary school children. We found two highly connected subparts in the network: one comprising reading fluency and accuracy measures, and one comprising intelligence-related measures. Interestingly, phoneme awareness was functionally related to the controlled and accurate processing of letter–speech sound mappings, whereas rapid automatized naming was more functionally related to the automated convergence of visual and speech information. We found evidence for the contribution of a variety of factors to (a)typical reading development, though associated with different aspects of the reading process. As such, our results contradict prevailing claims that dyslexia is caused by a single core deficit. This study shows how the network approach to psychopathology can be used to study complex interactions within the reading network and discusses future directions for more personalized interventions.
Examining the intergenerational transmission of parental invalidation: Extension of the biosocial model
Authors: Lee Stephanie S. M. , Keng Shian-Ling , Hong Ryan Y.
Published: July 2021

This study examined the intergenerational transmission of parental invalidation and whether parental difficulties in emotion regulation mediated the association between past experiences of invalidation and current invalidating parenting practices. We also aimed to investigate whether gender might influence the transmission of parental invalidation. We recruited a community sample of 293 dual-parent families (adolescent and their parents) based in Singapore. Parents and adolescents each completed measures of childhood invalidation, whereas parents additionally reported on their difficulties in emotion regulation. Results based on path analyses demonstrated that past parental invalidation experienced by fathers positively predicted current perceived invalidation by their children. The association between mothers’ childhood invalidation and current invalidating practices was fully mediated by mothers’ difficulties with emotion regulation. Further analyses revealed that parents’ current invalidating behaviors were not predicted by their past experiences of paternal or maternal invalidation. These findings point to the importance of considering the family invalidating environment as a whole when examining the influence of past experienced parental invalidation on emotion regulation and invalidating behaviors of second-generation parents. Our study provides empirical support for the intergenerational transmission of parental invalidation and highlights the need to address childhood experiences of parental invalidation in parenting programs.
Lower bound on the size of a quasirandom forcing set of permutations
Authors: Kurečka Martin
Published: July 2021

A set S of permutations is forcing if for any sequence
$\{\Pi_i\}_{i \in \mathbb{N}}$
of permutations where the density
$d(\pi,\Pi_i)$
converges to
$\frac{1}{|\pi|!}$
for every permutation
$\pi \in S$
, it holds that
$\{\Pi_i\}_{i \in \mathbb{N}}$
is quasirandom. Graham asked whether there exists an integer k such that the set of all permutations of order k is forcing; this has been shown to be true for any
$k\ge 4$
. In particular, the set of all 24 permutations of order 4 is forcing. We provide the first non-trivial lower bound on the size of a forcing set of permutations: every forcing set of permutations (with arbitrary orders) contains at least four permutations.
The architect’s task: the use of models as structural expressionism
Authors: Mindrup Matthew
Published: July 2021

In the above cited quote, Kevin Roche, a principal associate at Eero Saarinen’s architectural practice in 1957, recalls an early morning discussion about the design of the Trans World Airlines’ (TWA) Flight Center. Roche’s story about Saarinen reminds us that at the beginning of an architectural project, a solution may come from any variety of sources, not least of all from everyday objects. This was certainly the case for Saarinen, who found the seed for his design of the structural shells of the TWA Flight Center in the rind of a grapefruit. Despite its seeming novelty, Saarinen is not unique in his approach to the generation of architectural form with models; the Greek-French composer, architect and engineer Iannis Xenakis, who while working with Le Corbusier in 1957, used strings and thick wire to design the hyperbolic shell for their Philips Pavilion at the 1958 Brussels Expo. That a model will play a defining role in an architect’s approach to structural design is also demonstrated by the ‘spherical solution’ that Jørn Utzon discovered while stacking models of his Sydney Opera House’s shell roofs. These explorations with the expression of structure emerged at a time when a new generation of designers, including Eduardo Torroja, Pier Luigi Nervi and Felix Candela, had realised a handful of buildings using models to study and test structural form.
‘Excavating’ Pruitt-Igoe using space syntax
Authors: Major Mark David
Published: July 2021

Pruitt-Igoe, in St Louis, Missouri, United States, was one of the most notorious social housing projects of the twentieth century. Charles Jencks argued opening his book The Language of Post-Modern Architecture, ‘Modern Architecture died in St Louis, Missouri on July 15, 1972 at 3.32 pm (or thereabouts) when the infamous Pruitt-Igoe scheme, or rather several of its slab blocks, were given the final coup de grâce by dynamite.’ However, the magazine Architectural Forum had heralded the project as ‘the best high apartment’ of the year in 1951. Indeed, one of its first residents in 1957 described Pruitt-Igoe as ‘like an oasis in a desert, all of this newness’. But a later resident derided the housing project as ‘Hell on Earth’ in 1967. Only eighteen years after opening, the St Louis Public Housing Authority (PHA) began demolishing Pruitt-Igoe in 1972 [1]. It remains commonly cited for the failures of modernist design and planning.
Community-Driven Methods for Open and Reproducible Software Tools for Analyzing Datasets from Atom Probe Microscopy
Authors: Kühbach Markus , London Andrew J , Wang Jing , Schreiber Daniel K , Mendez Martin Francisca , Ghamarian Iman , Bilal Huma , Ceguerra Anna V
Published: July 2021

Atom probe tomography, and related methods, probe the composition and the three-dimensional architecture of materials. The software tools which microscopists use, and how these tools are connected into workflows, make a substantial contribution to the accuracy and precision of such material characterization experiments. Typically, we adapt methods from other communities like mathematics, data science, computational geometry, artificial intelligence, or scientific computing. We also realize that improving on research data management is a challenge when it comes to align with the FAIR data stewardship principles. Faced with this global challenge, we are convinced it is useful to join forces. Here, we report the results and challenges with an inter-laboratory call for developing test cases for several types of atom probe microscopy software tools. The results support why defining detailed recipes of software workflows and sharing these recipes is necessary and rewarding: Open source tools and (meta)data exchange can help to make our day-to-day data processing tasks become more efficient, the training of new users and knowledge transfer become easier, and assist us with automated quantification of uncertainties to gain access to substantiated results.
The Flux of Flux Ropes Embedded Within Magnetic Clouds Near 5 AU
Authors: Zhao Yan , Feng Hengqiang , Liu Qiang , Zhao Ake , Zhao Guoqing , Tian Zhanjun
Published: July 2021

Magnetic clouds (MCs) are an important kind of interplanetary coronal mass ejections and generally treated as giant flux ropes. Previous researches indicates that the rope structure of MCs may be destructed as they move away from the solar surface. In this paper, we made a statistic study of the azimuthal flux of flux ropes embedded within MCs near 5 AU. The average azimuthal flux of the rope was estimated to be , less than 20% of that near 1 AU. The rope structure occupied from 30% to 100% of the magnetic cloud interval with an average of 69%. The results presented here indicate that the rope structure of MCs still can be efficiently destructed as they move out beyond 1 AU and treating them as flux ropes, at least beyond 1 AU, may not be appropriate.
Interaction Between an EMSTID and an EPB in the EIA Crest Region Over China
Authors: Sun Longchang , Xu Jiyao , Zhu Yajun , Xiong Chao , Yuan Wei , Wu Kun , Hao Yongqiang , Chen Gang , Yan Chunxiao , Wang Zhihua , Zhao Xiukuan , Luo Xiaomin
Published: July 2021

Few observations investigated the interaction between an electrical medium‐scale traveling ionospheric disturbance (EMSTID) and an equatorial plasma bubble (EPB). This paper presents another interaction between a southwestward propagating EMSTID and an eastward drifting EPB in the equatorial ionization anomaly (EIA) crest region of China. When the EMSTID and the EPB touched each other, several depletions of the EMSTID (EPB) showed the eastward (westward) velocity disturbances of the EPB (EMSTID) depletions. Besides, phase elongations of the EPB depletions contrarotated as the EMSTID propagated southwestward. However, of important finding is that the interaction of the EMSTID and the EPB could have polarized one depletion of the postmidnight EPB that should have become a fossilized bubble. Inside that polarized EPB depletion were meter‐scale irregularities that caused activated radar echoes and enhanced ranged spread F (RSF). The interaction occurred in descending ionosphere and the lower density regions got filled up with an enhanced density plasma. We propose that the EMSTID and the EPB could have electrically coupled with each other, causing an enhanced polarization electric field (PEF) that polarized that EPB depletion; the E × B gradient drift instability (Kelley, 1989) could have caused the meter‐scale irregularities when that enhanced PEF was imposed on that reactivated EPB depletion surrounded by that enhanced density plasma. This study provides observational evidence that how an electrical couple of EMSTID and EPB events can activate a postmidnight EPB depletion that should become a fossilized structure.
Exploring the Impact of Thermally Controlled Crustal Viscosity on Volcanic Ground Deformation
Authors: Head Matthew , Hickey James , Gottsmann Joachim , Fournier Nicolas
Published: July 2021

Volcanoes undergoing unrest often produce displacements at the ground surface, providing an important window to interpret the dynamics of the underlying magmatic system. The thermomechanical properties of the surrounding host rock are expected to be highly heterogeneous, with key physical parameters having a strong dependence on temperature. Deformation models that incorporate nonelastic rheological behaviors are therefore heavily reliant on the assumed thermal conditions, and so it is critical to understand how the thermomechanical crustal structure affects the observed deformation field. Here, we use a series of thermo‐viscoelastic Finite Element models to explore how variations in thermal constraints (i.e., reservoir temperature and background geothermal gradient) affect surface displacement patterns when using the Maxwell and Standard Linear Solid (SLS) viscoelastic configurations. Our results demonstrate a strong variability in the viscoelastic deformation response when changing the imposed thermal constraints, caused by the partitioning of deformation and the dissipation of induced stresses. When using the SLS rheology, we identify that cumulative long‐term displacements can vary by over 20%, relative to a reference model with a reservoir temperature of 900°C and background geothermal gradient of 30 K km−1. The relative change increases to a maximum of 35% when thermal weakening of the Young's modulus is also considered. Contrastingly, the deformation patterns of the Maxwell rheology are governed by unbounded displacements and complete stress relaxation. Ultimately, we outline that uncertainties in the thermal constraints can have a significant impact on best‐fit source parameters (e.g., size and depth) and overpressure/volume‐change loading histories inferred from thermo‐viscoelastic models.
Temporal Patterns of Methane Emissions From Two Streams With Different Riparian Connectivity
Authors: Leng Peifang , Kamjunke Norbert , Li Fadong , Koschorreck Matthias
Published: July 2021

Streams are regionally important sources of CH4 to the atmosphere, but the temporal variability in and control on CH4 concentrations and emissions are not well understood. Especially, lack of long‐term data hampers our ability to predict CH4 emissions from streams. Here, we present a 7‐year data set of biweekly CH4 concentration and underlying potential drivers from two adjacent small German streams with contrasting riparian area characteristics. Over the 7‐year study period, mean CH4 concentration and emissions were 0.20 and 0.07 μmol L−1 and 2.01 and 0.84 mmol m−2 d−1 for the two streams, respectively. Our findings suggest that the combination of seasonality and topography ultimately shaped the considerable temporal variations of CH4. CH4 oxidation and production in the streams were probably of minor importance. Instead, fluctuations in CH4 concentrations likely reflected a temporal pattern of CH4 input from soils of the riparian zone with larger CH4 variations in the stream with more riparian lands. Structural equation modeling revealed dissolved organic carbon and nitrate as important predictors of CH4 concentration. However, we did not identify predictors of the considerable short‐term variability, nor the explicit pathways of CH4 delivery to streams. The discrepancy of the CH4 flux between streams was likely triggered by different connectivities to riparian soils with higher CH4 emissions in the hydrologically more connected stream. Interannual comparison showed that changing hydrologic conditions, rather than warming, may impact future CH4 emissions from temperate streams. We predict that higher CH4 emissions occur in wetter years in streams with close connectivity to riparian soils.
The Forecast for Exoplanets is Cloudy but Bright
Authors: Evans Kate
Published: July 2021

Clouds make climate modeling on Earth difficult. Identifying—and even defining—atmospheric phenomena on other planets is the next big exoplanet challenge.
Oddballs of the Exoplanet Realm
Authors: Benningfield Damond
Published: July 2021

The list of planets in other star systems includes zombies, hot giants, puffballs, and even a few Tatooines. Zowie!
Broadband Infrasound Signal of a Collapsing Hanging Glacier
Authors: Marchetti Emanuele , Walter Fabian , Meier Lorenz
Published: July 2021

A major ice collapse (10,000 ) from a hanging glacier on Mount Eiger, Switzerland was recorded by a small aperture array as a broadband (0.1–10 Hz) infrasound signal. Array analysis reveals that the high (3 Hz) frequency signal is infrasound produced by the moving ice mass, and its back azimuth variation with time tracks the ice mass trajectory and provides a mean velocity estimate. Infrasound frequency is used to estimate a radius, that despite overestimating the volume, provides quantitative analysis in near‐real time. The low (0.1 Hz) frequency oscillation is modeled in terms of the velocity field (wind), which the moving ice mass induces on the surrounding air, producing pressure variations at the different elements. These results show how infrasound array observations may provide quantitative information of glacier collapse and ice avalanche trajectories, and possibly, volume.
Bottom Mixing Enhanced by Tropical Storm‐Generated Near‐Inertial Waves Entering Critical Layers in the Straits of Florida
Authors: Qu Lixin , Thomas Leif , Gula Jonathan
Published: July 2021

Tropical storms and hurricanes frequently pass over the Straits of Florida, energizing the near‐inertial wave (NIW) field in the strait. Two ship‐based surveys, which were launched shortly after storms, observed velocity shear bands over the western slope of the strait—clear signatures of NIWs. Also, the hydrographic measurements demonstrate the formation of a slantwise critical layer (where isopycnals are parallel with bathymetry) over the western slope, which is known to be a trapping zone for NIWs. A realistic simulation of the Straits confirms the emergence of NIWs under a tropical storm, which is accompanied by inertially modulated bottom‐enhanced mixing over the western slope. The mechanism driving the mixing is that the storm‐generated NIWs radiate downward from the core of the Florida Current, reflect off the eastern slope, and enter the slantwise critical layer over the western slope; upon entering, wave trapping, and amplification lead to the enhanced mixing.
Response of GOLD Retrieved Thermospheric Temperatures to Geomagnetic Activities of Varying Magnitudes
Authors: Laskar F. I. , Eastes R. W. , Codrescu M. V. , Evans J. S. , Burns A. G. , Wang W. , McClintock W. E. , Aryal S. , Cai X.
Published: July 2021

Global‐scale Observations of Limb and Disk (GOLD) disk measurements of far ultraviolet molecular nitrogen band emissions are used to retrieve temperatures (), which are representative of lower thermospheric altitudes. The present investigation studies the response of lower thermospheric temperatures to geomagnetic activities of varying magnitudes. In this study, it has been observed that increases over all latitudes in response to enhanced geomagnetic activity. The increase in temperature is proportional to the strength of the geomagnetic activity and is greater at higher latitudes. Temperature enhancements vary from 10s to 100s of Kelvins from low‐ to mid‐latitudes. Local time behavior shows that pre‐noon enhancements in temperatures, during relatively stronger geomagnetic activities, are greater compared to afternoon, which may be caused by the combined action of daytime dynamics and geomagnetic forcing. This study, thus, demonstrates the utility of GOLD when investigating the effects of dynamical and external forcings in the thermosphere.
Dissecting Anvil Cloud Response to Sea Surface Warming
Authors: Beydoun Hassan , Caldwell Peter M. , Hannah Walter M. , Donahue Aaron S.
Published: July 2021

We derive an anvil cloud diagnostic from the continuity equation of cloud ice and apply it to the output of convection‐permitting Energy Exascale Earth System Model (E3SM) simulations run in radiative‐convective equilibrium mode. This diagnostic shows that anvil cloud fraction can be reliably diagnosed as a product of cloud detrainment and lifetime. Detrainment is found to be approximated well by a product of clear sky convergence and cloud ice mixing ratio, while cloud lifetime is dominated by sedimentation. Taken together, this diagnostic expresses anvil cloud fraction as a function of five physically measurable quantities. Of these, clear‐sky convergence changes drive the anvil cloud reduction with warming while an increase in cloud ice mixing ratio buffers the decrease. Accordingly, this study provides a theoretical foundation upon which the Stability‐Iris hypothesis can be tested.
Life course socioeconomic position and body composition in adulthood: a systematic review and narrative synthesis
Authors: Bridger Staatz Charis , Kelly Yvonne , Lacey Rebecca E. , Blodgett Joanna M. , George Anitha , Arnot Megan , Walker Emma , Hardy Rebecca
Published: July 2021

Introduction

Multiple systematic reviews have investigated the relation between socioeconomic position (SEP) and body mass index (BMI) throughout the life course. However, BMI does not capture quantity and distribution of fat and muscle, which are better indicators of obesity than BMI, and have been independently linked to adverse health outcomes. Less is known about the relation between SEP and body composition, and the literature has not been reviewed. We therefore systematically reviewed the literature on the association between life course SEP and body composition in adulthood.

Methods

A protocol was registered on PROSPERO (CRD42019119937), and the review followed PRISMA guidelines. An electronic search of three databases (MEDLINE, Embase Classic + Embase and SPORTDiscus) was conducted. Original studies in the English language were included that examine the association between any recognised measure of SEP at any age and body composition (fat mass, fat-free mass, ratio and distribution) in adulthood, measured using a direct technique, i.e., not an anthropometric measure. A narrative synthesis was conducted.

Results

A total of 47 papers were included in the final review, none were from low-income countries (LICs). Greater advantage in childhood and adulthood was associated with lower fat levels in high-income countries (HICs). Associations in the opposite direction were found exclusively in middle-income countries (MICs). No studies in MICs reported associations for childhood SEP. For measures of lean mass, the majority of papers reported no association, or greater advantage in adulthood associated with higher lean mass, with little variation between HICs and MICs. Associations in HICs are more often observed in women than men.

Conclusion

The results indicate that fat measures follow similar patterns to those seen for BMI, and that women in HICs are more likely to experience inequalities in both fat and lean measures. Further research in LICs and MICs is needed.
Introduction to the National Cancer Imaging Translational Accelerator (NCITA): a UK-wide infrastructure for multicentre clinical translation of cancer imaging biomarkers
Authors: McAteer M. A. , O’Connor J. P. B. , Koh D. M. , Leung H. Y. , Doran S. J. , Jauregui-Osoro M. , Muirhead N. , Brew-Graves C. , Plummer E. R. , Sala E. , Ng T. , Aboagye E. O. , Higgins G. S. , Punwani S.
Published: July 2021

The National Cancer Imaging Translational Accelerator (NCITA) is creating a UK national coordinated infrastructure for accelerated translation of imaging biomarkers for clinical use. Through the development of standardised protocols, data integration tools and ongoing training programmes, NCITA provides a unique scalable infrastructure for imaging biomarker qualification using multicentre clinical studies.
Cytokine-enhanced cytolytic activity of exosomes from NK Cells
Authors: Enomoto Yutaka , Li Peng , Jenkins Lisa M. , Anastasakis Dimitrios , Lyons Gaelyn C. , Hafner Markus , Leonard Warren J.
Published: July 2021

Natural killer (NK) cells play key roles in immune surveillance against tumors and viral infection. NK cells distinguish abnormal cells from healthy cells by cell–cell interaction with cell surface proteins and then attack target cells via multiple mechanisms. In addition, extracellular vesicles (EVs) derived from NK cells (NK-EVs), including exosomes, possess cytotoxic capacity against tumor cells, but their characteristics and regulation by cytokines remain unknown. Here, we report that EVs derived from human NK-92 cells stimulated with IL-15 + IL-21 show enhanced cytotoxic capacity against tumor cells. Major cytolytic granules, granzyme B and granzyme H, are enriched by IL-15 + IL-21 stimulation in NK-EVs; however, knockout experiments reveal those cytolytic granules are independent of enhanced cytotoxic capacity. To find out the key molecules, mass spectrometry analyses were performed with different cytokine conditions, no cytokine, IL-15, IL-21, or IL-15 + IL-21. We then found that CD226 (DNAM-1) on NK-EVs is enriched by IL-15 + IL-21 stimulation and that blocking antibodies against CD226 reduced the cytolytic activity of NK-EVs. We also show NK-EVs are taken up by target cells via macropinocytosis. Collectively, our findings elucidate the novel properties of NK-EVs and the mechanism of their incorporation into target cells.
Analysis and optimization of quantum adaptive measurement protocols with the framework of preparation games
Authors: Weilenmann M. , Aguilar E. A. , Navascués M.
Published: July 2021

A preparation game is a task whereby a player sequentially sends a number of quantum states to a referee, who probes each of them and announces the measurement result. Many experimental tasks in quantum information, such as entanglement quantification or magic state detection, can be cast as preparation games. In this paper, we introduce general methods to design n-round preparation games, with tight bounds on the performance achievable by players with arbitrarily constrained preparation devices. We illustrate our results by devising new adaptive measurement protocols for entanglement detection and quantification. Surprisingly, we find that the standard procedure in entanglement detection, namely, estimating n times the average value of a given entanglement witness, is in general suboptimal for detecting the entanglement of a specific quantum state. On the contrary, there exist n-round experimental scenarios where detecting the entanglement of a known state optimally requires adaptive measurement schemes.
SNX19 restricts endolysosome motility through contacts with the endoplasmic reticulum
Authors: Saric Amra , Freeman Spencer A. , Williamson Chad D. , Jarnik Michal , Guardia Carlos M. , Fernandopulle Michael S. , Gershlick David C. , Bonifacino Juan S.
Published: July 2021

The ability of endolysosomal organelles to move within the cytoplasm is essential for the performance of their functions. Long-range movement involves coupling of the endolysosomes to motor proteins that carry them along microtubule tracks. This movement is influenced by interactions with other organelles, but the mechanisms involved are incompletely understood. Herein we show that the sorting nexin SNX19 tethers endolysosomes to the endoplasmic reticulum (ER), decreasing their motility and contributing to their concentration in the perinuclear area of the cell. Tethering depends on two N-terminal transmembrane domains that anchor SNX19 to the ER, and a PX domain that binds to phosphatidylinositol 3-phosphate on the endolysosomal membrane. Two other domains named PXA and PXC negatively regulate the interaction of SNX19 with endolysosomes. These studies thus identify a mechanism for controlling the motility and positioning of endolysosomes that involves tethering to the ER by a sorting nexin.
Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization
Authors: Pathak Gita A. , Singh Kritika , Miller-Fleming Tyne W. , Wendt Frank R. , Ehsan Nava , Hou Kangcheng , Johnson Ruth , Lu Zeyun , Gopalan Shyamalika , Yengo Loic , Mohammadi Pejman , Pasaniuc Bogdan , Polimanti Renato , Davis Lea K. , Mancuso Nicholas
Published: July 2021

Despite rapid progress in characterizing the role of host genetics in SARS-Cov-2 infection, there is limited understanding of genes and pathways that contribute to COVID-19. Here, we integrate a genome-wide association study of COVID-19 hospitalization (7,885 cases and 961,804 controls from COVID-19 Host Genetics Initiative) with mRNA expression, splicing, and protein levels (n = 18,502). We identify 27 genes related to inflammation and coagulation pathways whose genetically predicted expression was associated with COVID-19 hospitalization. We functionally characterize the 27 genes using phenome- and laboratory-wide association scans in Vanderbilt Biobank (n = 85,460) and identified coagulation-related clinical symptoms, immunologic, and blood-cell-related biomarkers. We replicate these findings across trans-ethnic studies and observed consistent effects in individuals of diverse ancestral backgrounds in Vanderbilt Biobank, pan-UK Biobank, and Biobank Japan. Our study highlights and reconfirms putative causal genes impacting COVID-19 severity and symptomology through the host inflammatory response.
Impact of tiered restrictions on human activities and the epidemiology of the second wave of COVID-19 in Italy
Authors: Manica Mattia , Guzzetta Giorgio , Riccardo Flavia , Valenti Antonio , Poletti Piero , Marziano Valentina , Trentini Filippo , Andrianou Xanthi , Mateo-Urdiales Alberto , del Manso Martina , Fabiani Massimo , Vescio Maria Fenicia , Spuri Matteo , Petrone Daniele , Bella Antonino , Iavicoli Sergio , Ajelli Marco , Brusaferro Silvio , Pezzotti Patrizio , Merler Stefano
Published: July 2021

To counter the second COVID-19 wave in autumn 2020, the Italian government introduced a system of physical distancing measures organized in progressively restrictive tiers (coded as yellow, orange, and red) imposed on a regional basis according to real-time epidemiological risk assessments. We leverage the data from the Italian COVID-19 integrated surveillance system and publicly available mobility data to evaluate the impact of the three-tiered regional restriction system on human activities, SARS-CoV-2 transmissibility and hospitalization burden in Italy. The individuals’ attendance to locations outside the residential settings was progressively reduced with tiers, but less than during the national lockdown against the first COVID-19 wave in the spring. The reproduction number R(t) decreased below the epidemic threshold in 85 out of 107 provinces after the introduction of the tier system, reaching average values of about 0.95-1.02 in the yellow tier, 0.80-0.93 in the orange tier and 0.74-0.83 in the red tier. We estimate that the reduced transmissibility resulted in averting about 36% of the hospitalizations between November 6 and November 25, 2020. These results are instrumental to inform public health efforts aimed at preventing future resurgence of cases.
Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis
Authors: Liu Mengfei , Cao Sheng , He Li , Gao Jinhang , Arab Juan P. , Cui Huarui , Xuan Weixia , Gao Yandong , Sehrawat Tejasav S. , Hamdan Feda H. , Ventura-Cots Meritxell , Argemi Josepmaria , Pomerantz William C. K. , Johnsen Steven A. , Lee Jeong-Heon , Gao Fei , Ordog Tamas , Mathurin Philippe , Revzin Alexander , Bataller Ramon , Yan Huihuang , Shah Vijay H.
Published: July 2021

Alcoholic hepatitis (AH) is associated with liver neutrophil infiltration through activated cytokine pathways leading to elevated chemokine expression. Super-enhancers are expansive regulatory elements driving augmented gene expression. Here, we explore the mechanistic role of super-enhancers linking cytokine TNFα with chemokine amplification in AH. RNA-seq and histone modification ChIP-seq of human liver explants show upregulation of multiple CXCL chemokines in AH. Liver sinusoidal endothelial cells (LSEC) are identified as an important source of CXCL expression in human liver, regulated by TNFα/NF-κB signaling. A super-enhancer is identified for multiple CXCL genes by multiple approaches. dCas9-KRAB-mediated epigenome editing or pharmacologic inhibition of Bromodomain and Extraterminal (BET) proteins, transcriptional regulators vital to super-enhancer function, decreases chemokine expression in vitro and decreases neutrophil infiltration in murine models of AH. Our findings highlight the role of super-enhancer in propagating inflammatory signaling by inducing chemokine expression and the therapeutic potential of BET inhibition in AH treatment.
Field-free spin-orbit torque-induced switching of perpendicular magnetization in a ferrimagnetic layer with a vertical composition gradient
Authors: Zheng Zhenyi , Zhang Yue , Lopez-Dominguez Victor , Sánchez-Tejerina Luis , Shi Jiacheng , Feng Xueqiang , Chen Lei , Wang Zilu , Zhang Zhizhong , Zhang Kun , Hong Bin , Xu Yong , Zhang Youguang , Carpentieri Mario , Fert Albert , Finocchio Giovanni , Zhao Weisheng , Khalili Amiri Pedram
Published: July 2021

Current-induced spin-orbit torques (SOTs) are of interest for fast and energy-efficient manipulation of magnetic order in spintronic devices. To be deterministic, however, switching of perpendicularly magnetized materials by SOT requires a mechanism for in-plane symmetry breaking. Existing methods to do so involve the application of an in-plane bias magnetic field, or incorporation of in-plane structural asymmetry in the device, both of which can be difficult to implement in practical applications. Here, we report bias-field-free SOT switching in a single perpendicular CoTb layer with an engineered vertical composition gradient. The vertical structural inversion asymmetry induces strong intrinsic SOTs and a gradient-driven Dzyaloshinskii–Moriya interaction (g-DMI), which breaks the in-plane symmetry during the switching process. Micromagnetic simulations are in agreement with experimental results, and elucidate the role of g-DMI in the deterministic switching processes. This bias-field-free switching scheme for perpendicular ferrimagnets with g-DMI provides a strategy for efficient and compact SOT device design.
Oncogene-induced senescence in hematopoietic progenitors features myeloid restricted hematopoiesis, chronic inflammation and histiocytosis
Authors: Biavasco Riccardo , Lettera Emanuele , Giannetti Kety , Gilioli Diego , Beretta Stefano , Conti Anastasia , Scala Serena , Cesana Daniela , Gallina Pierangela , Norelli Margherita , Basso-Ricci Luca , Bondanza Attilio , Cavalli Giulio , Ponzoni Maurilio , Dagna Lorenzo , Doglioni Claudio , Aiuti Alessandro , Merelli Ivan , Di Micco Raffaella , Montini Eugenio
Published: July 2021

Activating mutations in the BRAF-MAPK pathway have been reported in histiocytoses, hematological inflammatory neoplasms characterized by multi-organ dissemination of pro-inflammatory myeloid cells. Here, we generate a humanized mouse model of transplantation of human hematopoietic stem and progenitor cells (HSPCs) expressing the activated form of BRAF (BRAFV600E). All mice transplanted with BRAFV600E-expressing HSPCs succumb to bone marrow failure, displaying myeloid-restricted hematopoiesis and multi-organ dissemination of aberrant mononuclear phagocytes. At the basis of this aggressive phenotype, we uncover the engagement of a senescence program, characterized by DNA damage response activation and a senescence-associated secretory phenotype, which affects also non-mutated bystander cells. Mechanistically, we identify TNFα as a key determinant of paracrine senescence and myeloid-restricted hematopoiesis and show that its inhibition dampens inflammation, delays disease onset and rescues hematopoietic defects in bystander cells. Our work establishes that senescence in the human hematopoietic system links oncogene-activation to the systemic inflammation observed in histiocytic neoplasms.
Surface enrichment and diffusion enabling gradient-doping and coating of Ni-rich cathode toward Li-ion batteries
Authors: Yu Haifeng , Cao Yueqiang , Chen Long , Hu Yanjie , Duan Xuezhi , Dai Sheng , Li Chunzhong , Jiang Hao
Published: July 2021

Critical barriers to layered Ni-rich cathode commercialisation include their rapid capacity fading and thermal runaway from crystal disintegration and their interfacial instability. Structure combines surface modification is the ultimate choice to overcome these. Here, a synchronous gradient Al-doped and LiAlO2-coated LiNi0.9Co0.1O2 cathode is designed and prepared by using an oxalate-assisted deposition and subsequent thermally driven diffusion method. Theoretical calculations, in situ X-ray diffraction results and finite-element simulation verify that Al3+ moves to the tetrahedral interstices prior to Ni2+ that eliminates the Li/Ni disorder and internal structure stress. The Li+-conductive LiAlO2 skin prevents electrolyte penetration of the boundaries and reduces side reactions. These help the Ni-rich cathode maintain a 97.4% cycle performance after 100 cycles, and a rapid charging ability of 127.7 mAh g−1 at 20 C. A 3.5-Ah pouch cell with the cathode and graphite anode showed more than a 500-long cycle life with only a 5.6% capacity loss.
Synergistic broad-spectrum antibacterial activity of Hypoxis hemerocallidea-derived silver nanoparticles and streptomycin against respiratory pathobionts
Authors: Aremu Oluwole S. , Qwebani-Ogunleye T. , Katata-Seru Lebogang , Mkhize Zimbili , Trant John F.
Published: July 2021

Respiratory tract infections arise due to the introduction of microbes into the airway, disrupting the normal, healthy, complex interdependent microbiome. The selective disruption of this community can be either beneficial or dangerous. Nanoparticles are a potential tool for modifying this population. Coated silver nanoparticles (AgNPs) were synthesized using ethanolic extracts of Hypoxis hemerocallidea (EEHH), a Southern African plant used extensively in traditional medicine and the source of many bioactive secondary metabolites. The room temperature reaction between silver nitrate and EEHH forms largely spherical AgNPs with an average diameter of 6–20 nm. These nanoparticles show similar levels of antibacterial activity as the broad-spectrum antibiotic streptomycin against Bacillus cereus, Streptococcus pneumonia, Escherichia coli, Pseudomonas aeuroginosa, and Moraxella catarrhalis. However, the AgNPs synergistically increase the antibacterial activity of streptomycin when they are applied in combination (30–52%). AgNPs are reiterated to be promising dual-function antibiotics, synergistically enhancing activity while also acting as delivery agents for small molecules.
Size conservation emerges spontaneously in biomolecular condensates formed by scaffolds and surfactant clients
Authors: Sanchez-Burgos Ignacio , Joseph Jerelle A. , Collepardo-Guevara Rosana , Espinosa Jorge R.
Published: July 2021

Biomolecular condensates are liquid-like membraneless compartments that contribute to the spatiotemporal organization of proteins, RNA, and other biomolecules inside cells. Some membraneless compartments, such as nucleoli, are dispersed as different condensates that do not grow beyond a certain size, or do not present coalescence over time. In this work, using a minimal protein model, we show that phase separation of binary mixtures of scaffolds and low-valency clients that can act as surfactants—i.e., that significantly reduce the droplet surface tension—can yield either a single drop or multiple droplets that conserve their sizes on long timescales (herein ‘multidroplet size-conserved’ scenario’), depending on the scaffold to client ratio. Our simulations demonstrate that protein connectivity and condensate surface tension regulate the balance between these two scenarios. The multidroplet size-conserved scenario spontaneously arises at increasing surfactant-to-scaffold concentrations, when the interfacial penalty for creating small liquid droplets is sufficiently reduced by the surfactant proteins that are preferentially located at the interface. In contrast, low surfactant-to-scaffold concentrations enable continuous growth and fusion of droplets without restrictions. Overall, our work proposes one thermodynamic mechanism to help rationalize how size-conserved coexisting condensates can persist inside cells—shedding light on the roles of protein connectivity, binding affinity, and droplet composition in this process.
Robust topological designs for extreme metamaterial micro-structures
Authors: Chatterjee Tanmoy , Chakraborty Souvik , Goswami Somdatta , Adhikari Sondipon , Friswell Michael I.
Published: July 2021

We demonstrate that the consideration of material uncertainty can dramatically impact the optimal topological micro-structural configuration of mechanical metamaterials. The robust optimization problem is formulated in such a way that it facilitates the emergence of extreme mechanical properties of metamaterials. The algorithm is based on the bi-directional evolutionary topology optimization and energy-based homogenization approach. To simulate additive manufacturing uncertainty, combinations of spatial variation of the elastic modulus and/or, parametric variation of the Poisson’s ratio at the unit cell level are considered. Computationally parallel Monte Carlo simulations are performed to quantify the effect of input material uncertainty to the mechanical properties of interest. Results are shown for four configurations of extreme mechanical properties: (1) maximum bulk modulus (2) maximum shear modulus (3) minimum negative Poisson’s ratio (auxetic metamaterial) and (4) maximum equivalent elastic modulus. The study illustrates the importance of considering uncertainty for topology optimization of metamaterials with extreme mechanical performance. The results reveal that robust design leads to improvement in terms of (1) optimal mean performance (2) least sensitive design, and (3) elastic properties of the metamaterials compared to the corresponding deterministic design. Many interesting topological patterns have been obtained for guiding the extreme material robust design.
Determination of the characteristic inactivation fluence for SARS-CoV-2 under UV-C radiation considering light absorption in culture media
Authors: Martínez-Antón Juan Carlos , Brun Alejandro , Vázquez Daniel , Moreno Sandra , Fernández-Balbuena Antonio A. , Alda Javier
Published: July 2021

The optical absorption coefficient of culture media is critical for the survival analysis of pathogens under optical irradiation. The quality of the results obtained from experiments relies on the optical analysis of the spatial distribution of fluence which also depends on the geometry of the sample. In this contribution, we consider both the geometrical shape and the culture medium’s absorption coefficient to evaluate how the spatial distribution of optical radiation affects pathogens/viruses. In this work, we exposed SARS-CoV-2 to UV-C radiation ($$\lambda$$
λ
= 254 nm) and we calculated—considering the influence of the optical absorption of the culture medium—a characteristic inactivation fluence of $$F_i$$

F
i

= 4.7 J/m2, or an equivalent 10% survival (D90 dose) of 10.8 J/m2. Experimentally, we diluted the virus into sessile drops of Dulbecco’s Modified Eagle Medium to evaluate pathogen activity after controlled doses of UV irradiation. To validate the optical absorption mode, we carried out an additional experiment where we varied droplet size. Our model—including optical absorption and geometrical considerations—provides robust results among a variety of experimental situations, and represents our experimental conditions more accurately. These results will help to evaluate the capability of UV disinfecting strategies applied to a variety of everyday situations, including the case of micro-droplets generated by respiratory functions.
Structural colors of pearls
Authors: Ozaki Ryotaro , Kikumoto Kei , Takagaki Masataka , Kadowaki Kazunori , Odawara Kazushi
Published: July 2021

The luster is the most important characteristic of pearls, whose colors depend on periodic structures of aragonite crystal layers and conchiolin sheets. We here propose an optical model for analyzing the structural colors of pearls that includes the transmission, reflection, and scattering of light in pearls. Unlike other structural color materials, internal light scattering and its transmission are the keys to understanding the optical properties of pearls. The appearance of pearls is determined by the superposition of transmitted and reflected light. The transmission and reflection spectra of pearls calculated using the proposed model show good agreement with experimental results. We also demonstrate the rendering of images of pearls using the calculated spectra. Furthermore, the appearance of pearls with different layer thicknesses are predicted by calculation based on the optical model.