bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Analysis of Permanent-Magnet Vernier Machine for Direct-Driven Wind Power Generator Considering Pole-Slot Combinations
Authors: Kim Hyung-Woo , Kang Seung-Gu , Jung Sang-Yong , Yeo Han-Kyeol
Published: August 2022

Wind power turbines have increasingly attracted attention as a renewable energy source. Gearboxes in wind turbines reduce their efficiency, require periodic maintenance, and result in gearbox failure. Consequently, direct-driven generators with a high torque density have emerged as an alternative because they transmit the high torque of the wind turbine directly. Permanent-magnet vernier machines (PMVMs) possess a simple and robust structure and significantly high torque density at low speeds. Although various topologies and pole-slot combinations of PMVMs have been considered to enhance their performance, studies on fractional-slot distributed-winding PMVMs (FSDW PMVMs) remain limited compared with those on fractional-slot concentrated-winding PMVMs (FSCW PMVMs). In this study, we designed eight models, including permanent magnet synchronous machines (PMSMs), FSDW, and FSCW PMVMs for direct-driven wind power generators. Their performances in terms of torque density, torque ripple, losses, and power factor were compared and verified using finite element analysis. The FSDW PMVM was proposed as the best model for direct-driven wind power generators based on the torque density, torque ripple, and possibility of performance improvement.
Spatial variability and accessibility of collection and delivery points in Nanjing, China
Authors: Mehmood Muhammad Sajid , Jin Annan , Rehman Adnanul , Ahamad Muhammad Irfan , Li Gang
Published: August 2022

Collection and delivery points are an alternative to home delivery and represent an important opportunity to reduce delivery failures in urban areas. As online shopping has become increasingly popular, different accessibility modes such as walking, cycling, and driving are considered for the collection of parcels at collection and delivery points (CDPs). The primary objective of the present study was to assess the spatial variability and accessibility of CDPs in Nanjing City, China. The point of interest (POI) data of 1224 CDPs (including 424 China Post Stations and 800 Cainiao Stations), and population and gross domestic product data were employed for the spatial analysis. The results showed that China Post Stations and Cainiao Stations were distributed in Nanjing as clusters at α = 0.01. Both types (51.1% China Post Stations and 63.2% Cainiao Stations) of CDPs were aggregated in the high population density areas. Moreover, 28.0% of China Post Stations and 50.9% of Cainiao Stations were located in high GDP density areas. The overall spatial distribution of China Post Stations in population and GDP density areas was medium, while that of the Cainiao Stations was high. There was a significant correlation between the spatial distribution of the CDPs, population, and GDP. There were significant spatial accessibility differences to CDPs among different accessibility modes like walking, cycling, and driving. Walking and cycling mode accessibility to China Post Stations and Cainiao Stations were 13.8 and 25.3% and 9.2 and 28.9%, respectively while 71.8% of China Post Stations and 71.1% of Cainiao Stations were accessed by driving. The findings of this study would be beneficial for policymakers and practitioners to develop related policies, to assist companies in building up more sustainable urban logistics and a booming CDPs’ network in the future.
Idea selection in design teams: a computational framework and insights in the presence of influencers
Authors: Singh Harshika , Cascini Gaetano , McComb Christopher
Published: August 2022

Idea selection is crucial in design as it impacts the outcome of a project. A collaborative design activity could be considered as a social process where the interactions and individual states (such as the importance in the team and self-efficacy level) could affect decision-making. It is often seen in design teams that some individuals, referred to as ‘influencers’ in the article have more capacity to influence than others, hence they govern the team process for better or worse. Due to the limited work done in the past to study the effect of these influencers on design outcomes, the work aims at increasing the understanding by presenting some insights from its agent-based simulation. The simulation results show how different influencer team compositions affect design outcomes in terms of quality and exploration of the solutions. The idea selection starts with the agents who are ready with their solution in their ‘mind’. The work presented in this article describes a framework for simulating decision-making during idea selection by considering the influencer and majority effect. The empirical study presented in the article verifies the model logic, that is, the presence of influencer and the majority during idea selection and supports the assumption that individuals’ agreement on solutions proposed by other team members depends on the degree of influence and past agreement. The results of the simulation show that teams with well-defined influencers produced solutions with higher variety and had more uniform contributions from team members, but also produced solutions of lower quality.
WESTERN HAN NOBLE BURIALS: A VIEW FROM ZHANG ANSHI'S 張安世 TOMB
Authors: Ruyue He , Yuanru Song , Nylan Michael
Published: August 2022

The family cemetery of Zhang Anshi was the first cemetery for nobles to be discovered in which the tomb occupants, dating, and gravesite orientation was so clear to investigators. As such, the site is of enormous historical significance. This essay introduces the entire site to readers and extrapolates aspects of the Western Han mourning regulations from the evidence presented by the jade suits, carriage and horse sets, tomb figurines, shrine, and layout. The essay also assesses scholarly debates concerning the degree to which Zhang Anshi's burial conforms to standards of late Western Han, and the relationship between Emperor Xuan's burial site and Duling with the site of Zhang Anshi's own tomb, questioning the traditional beliefs about “accompanying burials.”
Perforation effects on the wake dynamics of normal flat plates
Authors: Singh Abhinav , Narasimhamurthy Vagesh D.
Published: August 2022

The effect of perforation on the wake of a thin flat plate placed normal to the free stream at Reynolds number (

$Re$

) 250 (based on plate width

$d$

, and inflow velocity

$U_o$

) is studied by means of direct numerical simulation. The perforated plate of length

$6d$

consist of six equidistant square holes of varying sizes corresponding to porosity

$\beta$

(ratio of open area to total plate area) of 0 %, 4 %, 9 %, 12.25 %, 16 %, 20.25 % and 25 %. It is observed that the bleed or jet flow through perforations pushes the shear layer interaction farther downstream with increasing

$\beta$

. This causes a monotonic decrease in the drag coefficient with increasing porosity, and a sharp fall seeming to begin at

$\beta \approx 4\,\%$

. On the other hand, the Strouhal number increases with

$\beta$

up to 16 % (at

$\beta =16\,\%$

, loss of flow three-dimensionality leads to a ‘quasi-laminar’ state of flow). This is followed by a sharp fall in the Strouhal number at

$\beta \approx 20\,\%$

. The behaviour of the large-scale vortical structures in the far wake is influenced by the near-wake behaviour of the bleed flow, where the local

$Re$

based on the perforation hole size determines the overall flow three-dimensionality. It is also observed that the jet or bleed flow undergoes meandering instability when pitch separation is equivalent to the hole size (at

$\beta =25\,\%$

). The low-

$Re$

turbulent flow for a non-perforated plate is altered to a transitional state by the presence of perforation. The streamwise vortex pairs (secondary instabilities) become fairly organized as

$\beta$

is increased from 0 % to 16 %. The secondary instability at

$\beta =16\,\%$

appears similar to mode-B with wavelength

${\approx }1d$

. On the contrary, the secondary instability at

$\beta =25\,\%$

appears similar to mode-A with a wavelength of

${\approx }2d$

.
Picture perfect peaks: comprehension of inferential techniques in visual narratives
Authors: Klomberg Bien , Cohn Neil
Published: August 2022

The ability to reconstruct a missing event to create a coherent interpretation – bridging inference – is central to understanding both real-world events and visual narratives like comics. Most previous work on visual narrative inferencing has focused on fully omitted events, yet few have compared inference generation when climactic events become replaced with a panel employing numerous inferential techniques (e.g., action stars or onomatopoeia). These techniques implicitly express the unseen event while balancing several underlying features that describe their informativeness. Here, we examine whether processing and inference resolution differ across inferential techniques in two self-paced reading experiments. Experiment 1 directly compared five distinct types, and Experiment 2 explored the effect of combining techniques. In both experiments, differences in processing arise both between inferential techniques themselves, and at subsequent panels allowing the bridging inference to be resolved. Analysis of inferential features suggested that the explicitness of the inferential technique led to greater demand in processing, which later facilitated inference generation and comprehensibility. The findings reinforce the necessity of discussing the diversity of narrative patterns motivating bridging inferences within visual narratives.
Joint inversion of tectonic stress and magma pressures using dyke trajectories
Authors: Maerten F. , Maerten L. , Plateaux R. , Cornard P. H.
Published: August 2022

In volcano-tectonic regions, dyke propagation from shallow magmatic chambers is often controlled by the interaction of the local and regional stress fields. The variations of the stress fields result from a combination of factors including the regional tectonic stress, the geometry of pressurized magma chambers, the layering and the pre-existing discontinuities (e.g. fractures). In this contribution, we describe and apply a new multiparametric inversion technique based on geomechanics that can invert for both the far field stress attributes and the internal pressure of magma chambers or stocks, constrained by observed dyke or eruptive fissure orientations. This technique is based on the superposition principle and uses linear elastic models that can be solved using many types of numerical methods. For practical reasons, we chose a 3D boundary element method (BEM) for a heterogeneous elastic half-space, where magma chambers are modelled as pressurized cavities. To verify this approach, the BEM solution has been validated against the known 3D analytical solution of a pressurized cylindrical cavity. Then the effectiveness of this technique and its practical use is demonstrated through application to natural examples of dyke network development around two different volcanic systems, the Spanish Peaks (USA) and the Galapagos Islands (Ecuador). Results demonstrate that regional stress characteristics as well as the internal pressure of magma chambers can be estimated from observed radial and circumferential dyke patterns and some knowledge of magma chamber geometry.
Past Paul’s Jewishness: The Benjaminite Paul in Epiphanius of Cyprus
Authors: Chalmers Matthew
Published: August 2022

Paul’s Jewishness has often acted as a pivot in scholarship about the relationship between Christianity and Judaism, especially in recent conversation about the date and duration of the so-called “Parting of the Ways.” Too little attention has been paid, however, to who represented Paul as Jewish (or not) and why. I examine the late antique reception of Paul’s ethnic identity in Epiphanius of Cyprus, heresiologist, bishop, and someone for whom representation of Jewishness often served as a foil for the manufacture of orthodoxy. I argue that for Epiphanius, when Paul’s ethnic identity is relevant at all, the focus falls on an Israelite, Benjaminite Paul. Paul’s Jewishness becomes peripheral. Building on this observation, I suggest that we must understand even the reification of Jewishness familiar to current scholarship as only one of the late antique Christian behaviors that governed identification as Israelite.
Five Hundred Bones from Constantinople: Monks, Manuscripts, and Memory at the Eastern Borders of Byzantium
Authors: Durmaz Reyhan
Published: August 2022

This article traces the diachronic uses of the literary motif of “relics coming from Constantinople to monasteries in the East” in Syriac hagiography. Although this motif was seen in Syriac literature as early as the sixth century, there seems to be an increase in the employment of these stories around the twelfth century in saints’ lives local to northern Mesopotamia. In light of two texts—the Life of Abḥay and the Life of Aḥā—the article argues that stories about Constantinopolitan relics (martyrs’ bones or pieces of the True Cross) were oriented toward different modes of remembering Byzantium in the Syriac Church in the Middle Ages. The article further argues that these stories also created space to reflect on the Syriac Church’s relations with the Armenian Church in the medieval Near East. The article thus shows the power of narrative in creating cultural memory, building communal identity, and catalyzing religious rivalry.
On the Vulgate of Thomas Bilney
Authors: DONNELLY COLIN MICHAEL
Published: August 2022

Arguably the most interesting source for the religious views of the early English evangelical Thomas Bilney (1495–1531) are the annotations in his copy of the Vulgate. Unfortunately, scholars have accessed these annotations almost exclusively through the error-riddled and selective summary provided in 1940 by J. Y. Batley. This study corrects Batley's most significant errors and provides transcriptions and translations of the most interesting annotations that he omitted. These include discussions of clerical celibacy, whether God is the author of evil, which biblical texts are authentically canonical and the nature of the law, justification and salvation.
Remnant connectivity in pseudogapping: Experimental evidence for a direct generation approach
Authors: POPPELS TILL , MILLER PHILIP
Published: August 2022

This paper reports the results of two acceptability judgment experiments that examine the effect of PP remnants with mismatching correlates in the antecedent clause (either a PP, with a distinct preposition, or an NP) on the acceptability of pseudogapping as well as non-elliptical controls. Across both experiments, three novel findings emerge: First, utterances with mismatching PPs across the ellipsis clause and its antecedent were consistently degraded relative to their preposition-matched counterparts. Second, this mismatch penalty arose for elliptical and non-elliptical variants alike with only minor differences between the two. Finally, a significant portion of the mismatch penalties was explained away by the degree of semantic similarity between the thematic relations established by the mismatching prepositions with respect to the antecedent verb which was measured in a separate norming experiment. We examine the consequences of these new empirical results for current theories of pseudogapping, namely (i) the remnant-raising analysis, according to which the remnant XP is raised leftward out of the VP prior to VP ellipsis, licensed under identity with its antecedent; and (ii) the direct generation analysis, under which auxiliaries are verbal proforms that recover their referent anaphorically without the need for remnant movement or syntactic identity between the verb and its antecedent. We conclude that the data are more naturally accounted for under the direct generation approach.
A PUZZLE ABOUT VAGUENESS, REASONS, AND JUDICIAL DISCRETION
Authors: Asgeirsson Hrafn
Published: August 2022

The following two theses seem both plausible and consistent: in cases where it is indeterminate whether the relevant legal language applies to the relevant set of facts, officials are not bound to decide the case one way rather than the other, but may reason either way; all reasons for action are—in some relevant sense—knowable. In this paper, I point out what I take to be a robust but unacknowledged tension between these two claims. The tension requires some careful teasing out, but the basic idea is that given certain further plausible assumptions concerning law, language, and normativity, the two claims turn out to be inconsistent. In addition to examining the sources of the tension in some detail, I also address several possible objections to my argument and discuss which of the many theses should be rejected.
The Devil Is in the Tail Dependence: An Assessment of Multivariate Copula‐Based Frameworks and Dependence Concepts for Coastal Compound Flood Dynamics
Authors: Phillips R. C. , Samadi S. , Hitchcock D. B. , Meadows M. E. , Wilson C. A. M. E.
Published: August 2022

A hurricane event can often produce both intense rainfall and a storm tide that can cause a major compound flooding threat to coastlines. This paper examined applications of multivariate copula‐based time series models using data observed during Hurricane Irma (2017) along the coastlines of Florida, Georgia, and South Carolina, United States. Multivariate time series models were developed using bivariate copulas wherein storm tide and rainfall data were modeled using LOWESS‐based autoregressive moving average (ARMA). n samples of observed data were then synthesized using a Monte Carlo approach in which the empirical copula and the parametric estimate of the copula were obtained to approximate two‐sided p‐values using the Rosenblatt probability integral transform method. Analysis suggested that proper selection of the underlying LOWESS‐based ARMA model was the crucial aspect for modeling compound flooding wherein Archimedean, Elliptical, and Extreme Value copulas all offered consistent flexibility in terms of dependence modeling. As a backdrop to compound flood probabilities, this research also outlined both theoretical and applied frameworks for the calculation of non‐exceedance probabilities in a multidimensional environment using classical isofrequency probability assumptions for the “AND” (a bivariate joint probability) and Survival Kendall definitions. Random realizations from storm copulas combined with multivariate non‐exceedance probability definitions ultimately showed there were periods of temporal yet cyclical high intensities that lasted 1–2 hr. Lastly, a discussion is presented on the broader application of the proposed methodology within the field of engineering design and risk management which may serve as a catalyst for the continued research in compound flooding.
How Much Food Can We Grow in Urban Areas? Food Production and Crop Yields of Urban Agriculture: A Meta‐Analysis
Authors: Payen Florian Thomas , Evans Daniel L. , Falagán Natalia , Hardman Charlotte A. , Kourmpetli Sofia , Liu Lingxuan , Marshall Rachel , Mead Bethan R. , Davies Jessica A. C.
Published: August 2022

Urban agriculture can contribute to food security, food system resilience and sustainability at the city level. While studies have examined urban agricultural productivity, we lack systemic knowledge of how agricultural productivity of urban systems compares to conventional agriculture and how productivity varies for different urban spaces (e.g., allotments vs. rooftops vs. indoor farming) and growing systems (e.g., hydroponics vs. soil‐based agriculture). Here, we present a global meta‐analysis that seeks to quantify crop yields of urban agriculture for a broad range of crops and explore differences in yields for distinct urban spaces and growing systems. We found 200 studies reporting urban crop yields, from which 2,062 observations were extracted. Lettuces and chicories were the most studied urban grown crops. We observed high agronomic suitability of urban areas, with urban agricultural yields on par with or greater than global average conventional agricultural yields. “Cucumbers and gherkins” was the category of crops for which differences in yields between urban and conventional agriculture were the greatest (17 kg m−2 cycle−1 vs. 3.8 kg m−2 cycle−1). Some urban spaces and growing systems also had a significant effect on specific crop yields (e.g., tomato yields in hydroponic systems were significantly greater than tomato yields in soil‐based systems). This analysis provides a more robust, globally relevant evidence base on the productivity of urban agriculture that can be used in future research and practice relating to urban agriculture, especially in scaling‐up studies aiming to estimate the self‐sufficiency of cities and towns and their potential to meet local food demand.
Swinging Strength of Earth’s Magnetic Field Could Signal Inner Core Formation
Authors: Tripathy-Lang Alka
Published: August 2022

The magnetic record stored in rocks documents the liquid core’s behavior and possibly when the inner core formed. Whether it formed half a billion or more than a billion years ago, however, is up for debate.
Constraining Europa's Subsolar Atmosphere With a Joint Analysis of HST Spectral Images and Galileo Magnetic Field Data
Authors: Cervantes S. , Saur J.
Published: August 2022

We constrain Europa's tenuous atmosphere on the subsolar hemisphere by combining two sets of observations: oxygen emissions at 1,304 and 1,356 Å from Hubble Space Telescope (HST) spectral images and Galileo magnetic field measurements from its closest encounter, the E12 flyby. We describe Europa's atmosphere with three neutral gas species: global molecular (O2) and atomic oxygen (O), and localized water (H2O) present as a near‐equatorial plume and as a stable distribution concentrated around the subsolar point on the moon's trailing hemisphere. Our combined modeling based on the ratio of OI 1,356 to OI 1,304 Å emissions from Roth (2021; https://doi.org/10.1029/2021gl094289) and on magnetic field data allows us to derive constraints on the density and location of O2 and H2O in Europa's atmosphere. We demonstrate that 50% of the O2 and between 50% and 75% of the H2O abundances from Roth (2021; https://doi.org/10.1029/2021gl094289) are required to jointly explain the HST and Galileo measurements. These values are conditioned on a column density of O close to the upper limit of 6 × 1016 m−2 derived by Roth (2021; https://doi.org/10.1029/2021gl094289), and on a strongly confined stable H2O atmosphere around the subsolar point. Our analysis yields column densities of 1.2 × 1018 m−2 for O2, and 1.5 × 1019 to 2.2 × 1019 m−2 at the subsolar point for H2O. Both column densities, however, still lie within the uncertainties of Roth (2021; https://doi.org/10.1029/2021gl094289). Our results provide additional evidence for the existence of a stable H2O atmosphere at Europa.
Phosphodiesterase 4D contributes to angiotensin II-induced abdominal aortic aneurysm through smooth muscle cell apoptosis
Authors: Gao Ran , Guo Wenjun , Fan Tianfei , Pang Junling , Hou Yangfeng , Feng Xiaohang , Li Bolun , Ge Weipeng , Fan Tianhui , Zhang Tiantian , Lu Jiakai , Jing He , Jin Mu , Yan Chen , Wang Jing
Published: August 2022

Abdominal aortic aneurysm (AAA) is a permanent expansion of the abdominal aorta that has a high mortality but limited treatment options. Phosphodiesterase (PDE) 4 family members are cAMP-specific hydrolyzing enzymes and have four isoforms (PDE4A-PDE4D). Several pan-PDE4 inhibitors are used clinically. However, the regulation and function of PDE4 in AAA remain largely unknown. Herein, we showed that PDE4D expression is upregulated in human and angiotensin II-induced mouse AAA tissues using RT-PCR, western blotting, and immunohistochemical staining. Furthermore, smooth muscle cell (SMC)-specific Pde4d knockout mice showed significantly reduced vascular destabilization and AAA development in an experimental AAA model. The PDE4 inhibitor rolipram also suppressed vascular pathogenesis and AAA formation in mice. In addition, PDE4D deficiency inhibited caspase 3 cleavage and SMC apoptosis in vivo and in vitro, as shown by bulk RNA-seq, western blotting, flow cytometry and TUNEL staining. Mechanistic studies revealed that PDE4D promotes apoptosis by suppressing the activation of cAMP-activated protein kinase A (PKA) instead of the exchange protein directly activated by cAMP (Epac). Additionally, the phosphorylation of BCL2-antagonist of cell death (Bad) was reversed by PDE4D siRNA in vitro, which indicates that PDE4D regulates SMC apoptosis via the cAMP-PKA-pBad axis. Overall, these findings indicate that PDE4D upregulation in SMCs plays a causative role in AAA development and suggest that pharmacological inhibition of PDE4 may represent a potential therapeutic strategy.
Genome-wide association study of posttraumatic stress disorder among childhood cancer survivors: results from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort
Authors: Lu Donghao , Sapkota Yadav , Valdimarsdóttir Unnur A. , Koenen Karestan C. , Li Nan , Leisenring Wendy M. , Gibson Todd , Wilson Carmen L. , Robison Leslie L. , Hudson Melissa M. , Armstrong Gregory T. , Krull Kevin R. , Yasui Yutaka , Bhatia Smita , Recklitis Christopher J.
Published: August 2022

Genetic influence shapes who develops posttraumatic stress disorder (PTSD) after traumatic events. However, the genetic variants identified for PTSD may in fact be associated with traumatic exposures (e.g., interpersonal violence), which appear heritable as well. Childhood cancer survivors (CCS) are at risk for PTSD, but genetic influences affecting cancer are unlikely to overlap with those affecting PTSD. This offers a unique opportunity to identify variants specific to PTSD risk. In a genome-wide association study (GWAS), 3984 5-year survivors of childhood cancer of European-ancestry from the Childhood Cancer Survivor Study (CCSS) were evaluated for discovery and 1467 survivors from the St. Jude Lifetime (SJLIFE) cohort for replication. Childhood cancer-related PTSD symptoms were assessed using the Posttraumatic Stress Diagnostic Scale in CCSS. GWAS was performed in CCSS using logistic regression and lead markers were replicated/meta-analyzed using SJLIFE. Cross-associations of identified loci were examined between CCS and the general population. PTSD criteria were met for 671 participants in CCSS and 161 in SJLIFE. Locus 10q26.3 was significantly associated with PTSD (rs34713356, functionally mapped to ECHS1, P = 1.36 × 10–8, OR 1.57), and was replicated in SJLIFE (P = 0.047, OR 1.37). Variants in locus 6q24.3-q25.1 reached marginal significance (rs9390543, SASH1, P = 3.56 × 10–6, OR 0.75) in CCSS and significance when meta-analyzing with SJLIFE (P = 2.02 × 10–8, OR 0.75). Both loci were exclusively associated with PTSD in CCS rather than PTSD/stress-related disorders in general population (P-for-heterogeneity < 5 × 10–6). Our CCS findings support the role of genetic variation in PTSD development and may provide implications for understanding PTSD heterogeneity.
Strontium-incorporated bioceramic scaffolds for enhanced osteoporosis bone regeneration
Authors: Wu Qianju , Hu Longwei , Yan Ran , Shi Junfeng , Gu Hao , Deng Yuwei , Jiang Ruixue , Wen Jin , Jiang Xinquan
Published: August 2022

The restoration of bone defects caused by osteoporosis remains a challenge for surgeons. Strontium ranelate has been applied in preventative treatment approaches due to the biological functions of the trace element strontium (Sr). In this study, we aimed to fabricate bioactive scaffolds through Sr incorporation based on our previously developed modified amino-functional mesoporous bioactive glass (MBG) and to systematically investigate the bioactivity of the resulting scaffold in vitro and in vivo in an osteoporotic rat model. The results suggested that Sr-incorporated amino-functional MBG scaffolds possessed favorable biocompatibility. Moreover, with the incorporation of Sr, osteogenic and angiogenic capacities were upregulated in vitro. The in vivo results showed that the Sr-incorporated amino-functional MBG scaffolds achieved better bone regeneration and vessel formation. Furthermore, bioinformatics analysis indicated that the Sr-incorporated amino-functional MBG scaffolds could reduce reactive oxygen species levels in bone marrow mesenchymal stem cells in the osteoporotic model by activating the cAMP/PKA signaling pathway, thus playing an anti-osteoporosis role while promoting osteogenesis. This study demonstrated the feasibility of incorporating trace elements into scaffolds and provided new insights into biomaterial design for facilitating bone regeneration in the treatment of osteoporosis.
Imaging and phase-locking of non-linear spin waves
Authors: Dreyer Rouven , Schäffer Alexander F. , Bauer Hans G. , Liebing Niklas , Berakdar Jamal , Woltersdorf Georg
Published: August 2022

Non-linear processes are a key feature in the emerging field of spin-wave based information processing and allow to convert uniform spin-wave excitations into propagating modes at different frequencies. Recently, the existence of non-linear magnons at half-integer multiples of the driving frequency has been predicted for Ni80Fe20 at low bias fields. However, it is an open question under which conditions such non-linear spin waves emerge coherently and how they may be used in device structures. Usually non-linear processes are explored in the small modulation regime and result in the well known three and four magnon scattering processes. Here we demonstrate and image a class of spin waves oscillating at half-integer harmonics that have only recently been proposed for the strong modulation regime. The direct imaging of these parametrically generated magnons in Ni80Fe20 elements allows to visualize their wave vectors. In addition, we demonstrate the presence of two degenerate phase states that may be selected by external phase-locking. These results open new possibilities for applications such as spin-wave sources, amplifiers and phase-encoded information processing with magnons.
KLF4 recruits SWI/SNF to increase chromatin accessibility and reprogram the endothelial enhancer landscape under laminar shear stress
Authors: Moonen Jan-Renier , Chappell James , Shi Minyi , Shinohara Tsutomu , Li Dan , Mumbach Maxwell R. , Zhang Fan , Nair Ramesh V. , Nasser Joseph , Mai Daniel H. , Taylor Shalina , Wang Lingli , Metzger Ross J. , Chang Howard Y. , Engreitz Jesse M. , Snyder Michael P. , Rabinovitch Marlene
Published: August 2022

Physiologic laminar shear stress (LSS) induces an endothelial gene expression profile that is vasculo-protective. In this report, we delineate how LSS mediates changes in the epigenetic landscape to promote this beneficial response. We show that under LSS, KLF4 interacts with the SWI/SNF nucleosome remodeling complex to increase accessibility at enhancer sites that promote the expression of homeostatic endothelial genes. By combining molecular and computational approaches we discover enhancers that loop to promoters of KLF4- and LSS-responsive genes that stabilize endothelial cells and suppress inflammation, such as BMPR2, SMAD5, and DUSP5. By linking enhancers to genes that they regulate under physiologic LSS, our work establishes a foundation for interpreting how non-coding DNA variants in these regions might disrupt protective gene expression to influence vascular disease.
Nucleosome-directed replication origin licensing independent of a consensus DNA sequence
Authors: Li Sai , Wasserman Michael R. , Yurieva Olga , Bai Lu , O’Donnell Michael E. , Liu Shixin
Published: August 2022

The numerous enzymes and cofactors involved in eukaryotic DNA replication are conserved from yeast to human, and the budding yeast Saccharomyces cerevisiae (S.c.) has been a useful model organism for these studies. However, there is a gap in our knowledge of why replication origins in higher eukaryotes do not use a consensus DNA sequence as found in S.c. Using in vitro reconstitution and single-molecule visualization, we show here that S.c. origin recognition complex (ORC) stably binds nucleosomes and that ORC-nucleosome complexes have the intrinsic ability to load the replicative helicase MCM double hexamers onto adjacent nucleosome-free DNA regardless of sequence. Furthermore, we find that Xenopus laevis nucleosomes can substitute for yeast ones in engaging with ORC. Combined with re-analyses of genome-wide ORC binding data, our results lead us to propose that the yeast origin recognition machinery contains the cryptic capacity to bind nucleosomes near a nucleosome-free region and license origins, and that this nucleosome-directed origin licensing paradigm generalizes to all eukaryotes.
Bayesian optimization with experimental failure for high-throughput materials growth
Authors: Wakabayashi Yuki K. , Otsuka Takuma , Krockenberger Yoshiharu , Sawada Hiroshi , Taniyasu Yoshitaka , Yamamoto Hideki
Published: August 2022

A crucial problem in achieving innovative high-throughput materials growth with machine learning, such as Bayesian optimization (BO), and automation techniques has been a lack of an appropriate way to handle missing data due to experimental failures. Here, we propose a BO algorithm that complements the missing data in optimizing materials growth parameters. The proposed method provides a flexible optimization algorithm that searches a wide multi-dimensional parameter space. We demonstrate the effectiveness of the method with simulated data as well as in its implementation for actual materials growth, namely machine-learning-assisted molecular beam epitaxy (ML-MBE) of SrRuO3, which is widely used as a metallic electrode in oxide electronics. Through the exploitation and exploration in a wide three-dimensional parameter space, while complementing the missing data, we attained tensile-strained SrRuO3 film with a high residual resistivity ratio of 80.1, the highest among tensile-strained SrRuO3 films ever reported, in only 35 MBE growth runs.
Multiple heavy metals affect root response, iron plaque formation, and metal bioaccumulation of Kandelia obovata
Authors: Chai Minwei , Li Ruili , Shen Xiaoxue , Yu Lingyun , Han Jie
Published: August 2022

Multiple heavy metal pollution in mangrove wetlands is serious. Kandelia obovata seedlings were cultured in pots in which lead (Pb), zinc (Zn) and copper (Cu) were added separately and in combinations. The results showed that heavy metal stress improved the rate of root oxygen leakage, enhanced root activity, and reduced root porosity. The root under single heavy metal stress was impacted by the addition of other heavy metals, demonstrating antagonistic or synergistic effects. Iron plaque (IP) formation was improved under single Zn or Cu stress, and inhibited in binary stress of Pb + Cu. The adsorptions of IP on heavy metals in combined stress (Pb, 62–116 μg g−1; Zn, 194–207 μg g−1; Cu, 35–52 μg g−1) were higher than that in single stress (Pb, 18 μg g−1; Zn, 163 μg g−1; Cu, 22 μg g−1). K. obovata accumulated higher levels of heavy metals in root (Pb, 7–200 μg g−1; Cu, 4–78 μg g−1), compared with IP (Pb, 18–116 μg g−1; Cu, 22–52 μg g−1), stem (Pb, 3–7 μg g−1; Cu, 9–17 μg g−1), and leaf (Pb, 2–4 μg g−1; Cu, 4–7 μg g−1). Correlation analysis showed that single and binary stresses affected K. obovata, with more significant effect of trinary stress. Regression path analysis showed that multiple heavy metal stress firstly affected root, then indirectly contributed to IP formation, as well as heavy metal in IP and root; at last, heavy metal in IP directly contributed to heavy metal bioaccumulations in root.
Patient-reported symptom burden in patients with rare cancers receiving pembrolizumab in a phase II Clinical Trial
Authors: Mendoza Tito R. , Hong David S. , Peterson Christine B. , Stephen Bettzy , Dumbrava Ecaterina , Pant Shubbam , Tsimberidou Apostolia Maria , Yap Timothy Anthony , Sheshadri Ajay , Altan Mehmet , George Goldy , Castillo Lilibeth , Rodriguez Enedelia , Gong Jing , Subbiah Vivek , Janku Filip , Fu Siqing , Piha-Paul Sarina A. , Ahnert Jordi Rodon , Karp Daniel D. , Cleeland Charles , Meric-Bernstam Funda , Naing Aung
Published: August 2022

Patients with rare solid tumors treated on early phase trials experience toxicities from their tumors and treatments. However, limited data exist to describe the detailed symptom burden suffered by these patients, particularly those with rare solid tumors treated with immunotherapy. We performed a prospective longitudinal study to capture patient-reported symptom burden. Patients completed the validated MD Anderson Symptom Inventory (MDASI)—Immunotherapy with 20 symptoms including 7 immunotherapy-specific items and 6 interference items at baseline and weekly thereafter for up to 9 weeks. Symptoms and interference were rated on 0–10 scales (0 = none or no interference, 10 = worst imaginable or complete interference). Group-based trajectory modelling determined higher and lower symptom groups. A total of 336 MDASI questionnaires were completed by 53 patients (mean age 55.4y, 53% male) with advanced rare cancers receiving pembrolizumab in a Phase II clinical trial. Symptoms reported as most severe over the course of the treatment over 9 weeks were fatigue [mean (M) = 3.8, SD = 2.3], pain (M = 3.7, SD = 2.9), disturbed sleep (M = 2.7, SD = 2.3), drowsiness (M = 2.6, SD = 2.0) and lack of appetite (M = 2.5, SD = 2.1). Pain in the abdomen (M = 2.2, SD = 2.4), rash (M = 1.1, SD = 1.8) and diarrhea (M = 0.9, SD = 1.5) were less severe. Interference with walking was rated the highest (M = 3.4, SD = 2.8) and relations with others was rated the lowest (M = 2.1, SD = 2.6). Using a composite score based on the five most severe symptoms (fatigue, pain, lack of appetite, feeling drowsy and sleep disturbance), 43% were classified into the high symptom burden group. Using a score based on immunotherapy-specific symptoms (e.g., rash, diarrhea) 33% of patients were included in the high symptom group. Symptom burden stayed relatively stable in the high- and low-symptom burden patient groups from baseline through 9 weeks. Some patients with rare malignancies experienced high symptom burden even at baseline. In patients with rare cancers, symptom trajectories stayed relatively stable over nine weeks of treatment with pembrolizumab.

Trial registration: ClinicalTrials.gov identifier: NCT02721732.
Harmonisation of in-silico next-generation sequencing based methods for diagnostics and surveillance
Authors: Nunez-Garcia J. , AbuOun M. , Storey N. , Brouwer M. S. , Delgado-Blas J. F. , Mo S. S. , Ellaby N. , Veldman K. T. , Haenni M. , Châtre P. , Madec J. Y. , Hammerl J. A. , Serna C. , Getino M. , La Ragione R. , Naas T. , Telke A. A. , Glaser P. , Sunde M. , Gonzalez-Zorn B. , Ellington M. J. , Anjum M. F.
Published: August 2022

Improvements in cost and speed of next generation sequencing (NGS) have provided a new pathway for delivering disease diagnosis, molecular typing, and detection of antimicrobial resistance (AMR). Numerous published methods and protocols exist, but a lack of harmonisation has hampered meaningful comparisons between results produced by different methods/protocols vital for global genomic diagnostics and surveillance. As an exemplar, this study evaluated the sensitivity and specificity of five well-established in-silico AMR detection software where the genotype results produced from running a panel of 436 Escherichia coli were compared to their AMR phenotypes, with the latter used as gold-standard. The pipelines exploited previously known genotype–phenotype associations. No significant differences in software performance were observed. As a consequence, efforts to harmonise AMR predictions from sequence data should focus on: (1) establishing universal minimum to assess performance thresholds (e.g. a control isolate panel, minimum sensitivity/specificity thresholds); (2) standardising AMR gene identifiers in reference databases and gene nomenclature; (3) producing consistent genotype/phenotype correlations. The study also revealed limitations of in-silico technology on detecting resistance to certain antimicrobials due to lack of specific fine-tuning options in bioinformatics tool or a lack of representation of resistance mechanisms in reference databases. Lastly, we noted user friendliness of tools was also an important consideration. Therefore, our recommendations are timely for widespread standardisation of bioinformatics for genomic diagnostics and surveillance globally.
Computational modelling of γ-H2AX foci formation in human cells induced by alpha particle exposure
Authors: Abu Shqair Ali , Lee Ui-Seob , Kim Eun-Hee
Published: August 2022

In cellular experiments, radiation-induced DNA damage can be quantified by counting the number of γ-H2AX foci in cell nucleus by using an immunofluorescence microscope. Quantification of DNA damage carries uncertainty, not only due to lack of full understanding the biological processes but also limitations in measurement techniques. The causes of limited certainty include the possibility of expressing foci in varying sizes responding individual DSBs and the overlapping of foci on the two-dimensional (2D) immunofluorescence microscopy image of γ-H2AX foci, especially when produced due to high-LET radiation exposure. There have been discussions on those limitations, but no successful studies to overcome them. In this paper, a practical modelling has been developed to simulate the occurrences of double-strand breaks (DSBs) and the formations of γ-H2AX foci in response to individual DSB formations, in cell nucleus due to exposure to alpha particles. Cell irradiation and DSB production were simulated using a user-written code that utilizes Geant4-DNA physics models. A C +  + code was used to simulate the formation γ-H2AX foci, which were spatially correlated to the loci of DBSs, and to calculate the number of individual foci from the observed 2D image of the cell nucleus containing the overlapping γ-H2AX foci. The average size of focal images was larger from alpha particle exposure than that from X-ray exposure, whereas the number of separate focal images were comparable except at doses up to 0.5 Gy. About 40% of separate focal images consisted of overlapping γ-H2AX foci at 1 Gy of alpha particle exposure. The foci overlapping ratios were obtained by simulation for individual size groups of focal images at varying doses. The size distributions of foci at varying doses were determined with experimentally obtained separate focal images. The correction factor for foci number was calculated using the foci overlapping ratio and foci size distribution, which are specific to dose from alpha particle exposure. The number of individual foci formations induced by applying the correction factor to the experimentally observed number of focal images better reflected the quality of alpha particles in causing DNA damage. Consequently, the conventional γ-H2AX assay can be better implemented by employing this computational modelling of γ-H2AX foci formation.
Characterization of anti-proliferative and anti-oxidant effects of nano-sized vesicles from Brassica oleracea L. (Broccoli)
Authors: Hossain Md Niamat , De Leo Vincenzo , Tamborra Rosanna , Laselva Onofrio , Ingrosso Chiara , Daniello Valeria , Catucci Lucia , Losito Ilario , Sollitto Francesco , Loizzi Domenico , Conese Massimo , Di Gioia Sante
Published: August 2022

In this in vitro study, we test our hypothesis that Broccoli-derived vesicles (BDVs), combining the anti-oxidant properties of their components and the advantages of their structure, can influence the metabolic activity of different cancer cell lines. BDVs were isolated from homogenized fresh broccoli (Brassica oleracea L.) using a sucrose gradient ultracentrifugation method and were characterized in terms of physical properties, such as particle size, morphology, and surface charge by transmission electron microscopy (TEM) and laser doppler electrophoresis (LDE). Glucosinolates content was assessed by RPLC–ESI–MS analysis. Three different human cancer cell lines (colorectal adenocarcinoma Caco-2, lung adenocarcinoma NCI-H441 and neuroblastoma SHSY5Y) were evaluated for metabolic activity by the MTT assay, uptake by fluorescence and confocal microscopy, and anti-oxidant activity by a fluorimetric assay detecting intracellular reactive oxygen species (ROS). Three bands were obtained with average size measured by TEM based size distribution analysis of 52 nm (Band 1), 70 nm (Band 2), and 82 nm (Band 3). Glucobrassicin, glucoraphanin and neoglucobrassicin were found mostly concentrated in Band 1. BDVs affected the metabolic activity of different cancer cell lines in a dose dependent manner compared with untreated cells. Overall, Band 2 and 3 were more toxic than Band 1 irrespective of the cell lines. BDVs were taken up by cells in a dose- and time-dependent manner. Pre-incubation of cells with BDVs resulted in a significant decrease in ROS production in Caco-2 and NCI-H441 stimulated with hydrogen peroxide and SHSY5Y treated with 6-hydroxydopamine, with all three Bands. Our findings open to the possibility to find a novel “green” approach for cancer treatment, focused on using vesicles from broccoli, although a more in-depth characterization of bioactive molecules is warranted.
Understanding the mechanism of Nb-MXene bioremediation with green microalgae
Authors: Jakubczak Michał , Bury Dominika , Purbayanto Muhammad Abiyyu Kenichi , Wójcik Anna , Moszczyńska Dorota , Prenger Kaitlyn , Naguib Michael , Jastrzębska Agnieszka Maria
Published: August 2022

Rapidly developing nanotechnologies and their integration in daily applications may threaten the natural environment. While green methods of decomposing organic pollutants have reached maturity, remediation of inorganic crystalline contaminants is major problem due to their low biotransformation susceptibility and the lack of understanding of material surface-organism interactions. Herein, we have used model inorganic 2D Nb-based MXenes coupled with a facile shape parameters analysis approach to track the mechanism of bioremediating 2D ceramic nanomaterials with green microalgae Raphidocelis subcapitata. We have found that microalgae decomposed the Nb-based MXenes due to surface-related physicochemical interactions. Initially, single and few-layered MXene nanoflakes attached to microalgae surfaces, which slightly reduced algal growth. But with prolonged surface interaction, the microalgae oxidized MXene nanoflakes and further decomposed them into NbO and Nb2O5. Since these oxides were nontoxic to microalgal cells, they consumed Nb-oxide nanoparticles by an uptake mechanism thus enabling further microalgae recovery after 72 h of water treatment. The uptake-associated nutritional effects were also reflected by cells’ increased size, smoothed shape and changed growth rates. Based on these findings, we conclude that short- and long-term presence of Nb-based MXenes in freshwater ecosystems might cause only negligible environmental effects. Notably, by using 2D nanomaterials as a model system, we show evidence of the possibility of tracking even fine material shape transformations. In general, this study answers an important fundamental question about the surface interaction-associated processes that drive the mechanism of 2D nanomaterials’ bioremediation as well as provides the fundamental basis for further short- and long-term investigations on the environmental effects of inorganic crystalline nanomaterials.