bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of past mining on public safety: seismicity in area of flooded abandoned coal Gardanne mine, France
Authors: Namjesnik Dalija , Kinscher Jannes , Contrucci Isabelle , Klein Emmanuelle
Published: December 2022

This paper focuses on the impact of past mining on public safety. It emphasizes the need to understand the induced seismic hazard and consequently improve the post-mining management procedures and legislations, as many mining sites are located in proximity to populated areas. Due to many challenges and complexity of the post-mining environments, induced seismic hazard nowadays remains largely unknown. However, the return experience of several post-mining sites in recent decades have shown us that the mine flooding and/or degradation of mining works can lead to the stress perturbations, inducing the seismicity and the reactivation of the surrounding geological faults. Hence, it is important to advance the seismic monitoring and research of seismicity in flooded post-mining districts. As the number of mine closures worldwide is rising, it can be expected that flooding induced reactivation of the surrounding faults becomes a more often observed phenomenon. We present in this paper the experience of the abandoned flooded coal mine of Gardanne in France, which has been experiencing post-mining seismicity problems since its closure in 2010. We show the results of a recent study of seismic multiplets and clustering of seismic events, as well as their spatio-temporal activity compared to meteorological conditions. These results provide us new insights as well as lead to raising new questions on seismic sources and triggering mechanisms.
Semi-real time systems for subsidence monitoring in areas affected by underground mining: the example of the Nuraxi-Figus coal district (Sardinia, Italy)
Authors: Ammirati L. , Di Martire D. , Bordicchia F. , Calcaterra D. , Russo G. , Mondillo N.
Published: December 2022

Underground mining can produce subsidence, which can be coincident with mining activities or delayed in response to the time-dependent deformation of the rocks. Therefore, in these cases, it is essential to effectively monitor the soil deformations at different times during and after mining activity. In the present work, an integrated approach based on geotechnical numerical modeling and Advanced Differential Interferometric Synthetic Aperture Radar (A-DInSAR) method has been applied to detect, study and monitor the subsidence related to mining activity in the Nuraxi Figus coal district (Sardinia, Italy). Two datasets of high-resolution COSMO-Skymed images were acquired, respectively in two covering periods: from 2011 and 2014, and from 2013 to 2020. The A-DInSAR results show that the predominant displacement rates are located in correspondence with the panels. The cumulated satellite-based LoS displacements vary in the first period between − 130 and + 28 mm and − 293 and + 28.4 mm, while, during the second period between − 6.9 and + 1.6 mm and − 8.72 and + 4.33 mm in ascending and descending geometries, respectively. The geotechnical numerical model allowed to obtain a value for the maximum expected. By using the vertical and horizontal components it was possible to reconstruct the kinematics of the deformation considering three phases: pre-mining, syn-mining, and post-mining activity. The temporal evolution of displacements started during the mining extraction in 2011, achieved the major values in correspondence of post-mining operations, during the period from 2013 to 2014 and continued slowly until 2020. The near real-time monitoring system applied in this study proved to be very useful for detecting subsidence during the mining activity and the post-mining period.
Static Shape and Stress Control of Trusses with Optimum Time, Actuators and Actuation
Authors: Saeed Najmadeen M. , Manguri Ahmed A. , Szczepanski Marcin , Jankowski Robert , Haydar Barham. A.
Published: December 2022

Traditional shape and stress control of structures use many actuators and require enormous time to find reasonable solutions that need designers to input specific target displacement and stress. This study employs a linear technique to static shape and stress control of pin-jointed assemblies as a theoretical advancement to prior works and provides a comparative analysis against previously established works. The study evaluates the proposed method using MATLAB to find the optimum set of actuators, and MATLAB and SAP2000 to verify the actuation results obtained through applying the set of actuations to the numerical models. The proposed method minimizes the number of trials, count of actuators, and total actuation up to 83%, 73%, and 50%, respectively. Furthermore, the optimum solution could be found in a single trial. The study focuses on the three aspects: (a) finding the optimal count of actuators; (b) optimum amount of actuation using fmincon function; and c) Implementing two-sided inequalities to control equations allowing designers to develop target internal forces and nodal displacements, as domains rather than specific numbers. This improves the optimization process affecting actuator count, total actuation elements, and processing time.
Environmental adaptation assessment on a mountain trail as a pathway to local prosperity based on a topographical approach
Authors: Moutsopoulos D. , Stergiadou A. , Psilovikos Th.
Published: December 2022

Environmental adaptation assessment on a trail is particularly critical in mountain regions, where factors such as poverty and the difficulty in earning an alternative livelihood, the lack of infrastructure, and a lack of policies and planning are magnified. Mountain trails represent unique paths into the wild. The need for a topographical approach to survey a mountain trail led us to use TruePulse 360B laser technology equipment and digital mapping in order to select and analyze a trail in a forested area based on environmental adaptation assessment. Since ancient times, mountain trails have been pathways to local prosperity because they were used for commercial trade. In the modern world, mountain trails are used for hiking, recreational walks in nature, as a method to bring the new generation close to wild forests by persons in wheelchairs or disabled people (those who are deaf or blind or have Down syndrome, etc.). The aim of this paper is not only to provide a digital map for various tourist teams, especially disabled ones, to use when visiting and exploring the natural beauty near the Wildlife Museum in order to manage the wild trails for the benefit and prosperity of the local community, but also to examine the environmental adaptation of this trail by taking into consideration the protection of nature. The constructing methods of a path, the materials that are used for the pavement and the optical adaptation with the nature are also a goal.
Estimating the potential of spices for mineral provision in a refugee context in East Africa
Authors: Woldetsadik Desta , Hailu Hillette , Gebrezgabher Solomie , Adam-Bradford Andrew , Mengistu Tesfu , Evans Colby T. , Madani Nelly , Mafika Tamlyn P. , Fleming David E. B.
Published: December 2022

Micronutrient deficiency remains an enormous problem in refugee settings. Transforming refugees’ food systems through the scaling up of kitchen gardening and fortifying relief food crops with minor food components including nutrient-dense spices can help improve the quality of staple foods. Globally, spices are indispensable in the daily diet and play an important role in the socio-cultural setting of different communities. Forty turmeric and curry powder samples were collected from different market establishments and geographic locations in East Africa. The samples were analyzed for selected elements using Portable X-Ray Fluorescence (PXRF). The contents of potassium (K), calcium (Ca), zinc (Zn) and strontium (Sr) in turmeric powder were statistically different among geographic origins (Ethiopia, Kenya and Uganda). We also aimed to determine if a small portion of spices (turmeric (5 g) and curry (4 g)) would contribute to an adequate intake (AI) or recommended dietary allowance (RDA) for selected minerals, for refugee men and women aged between 19 and 50 years as defined by the Food and Nutrition Board of the Institute of Medicine (IOM). For the reference groups, the contributions of turmeric and curry powder to AI/RDA for K, Ca and Zn varied between 0.48 to 4.13%. On the other hand, turmeric was identified to contribute > 20% AI/RDA for refugee men and women aged between 19 and 50 years for two micro minerals: manganese (Mn) and iron (Fe). Considering turmeric and curry powder of East African origins are good sources of minerals and present acceptable toxic metal(loid)s loads coupled with low cost, these spices particularly turmeric should be more widely popularized and recommended for food-to-spice fortification among the refugee population located in East Africa.
Heat loss along the pipeline and its control measures
Authors: Wang Deming
Published: December 2022

In this study, we present the derivation of the formulas for calculating the temperature drop and heat loss along the heat transporting pipeline and the methods of controlling the heat loss. Our results show that, both the temperature drop and the relative heat loss increase with the pipeline length, and increase close to linearly; the relative heat loss is nearly proportional to the thermal conductivity and is inversely proportional to the insulation thickness; the relative heat loss along or across the pipeline decreases with the increase in pipeline diametre, initial temperature, flow velocity or surrounding temperature. And we can control the relative heat loss within a determined range, even less than 10%. Especially, some thermal problems of the pipeline can be easily handled. Reducing its heat loss by 50%, for example, can be achieved by doubling the insulation thickness or by cutting down the thermal conductivity by half. As well, the causations of all the results are exhibited in detail.
The Participation of Civil Society in European Union Environmental Law-Making Processes: A Critical Assessment of the European Commission’s Consultations in Connection with the European Climate Law
Authors: Ammann Odile , Boussat Audrey
Published: December 2022

The question of how best to tackle anthropogenic climate change is a thorny one: besides scientific uncertainty regarding the consequences of climate change, another difficulty is that the recommendations of climate experts may clash with the priorities of citizens, interest groups and political institutions. With the European Green Deal, the European Union (EU) recently made significant advances in climate policy; at the same time, and as is well known, the EU and its institutions have long been criticised for their “democratic deficit” and for their failure to involve all civil society actors equally in EU law-making processes. This article sheds light on the legal framework governing civil society participation in EU law-making, and more specifically on the Commission’s consultations pursuant to Article 11(3) of the Treaty on European Union. It then critically assesses selected features of two consultations conducted by the Commission in connection with the European Climate Law, which it evaluates from the perspective of the EU primary law principles of democracy, openness and transparency. Through this analysis, and by suggesting how future climate consultations could be further improved, the article aims to contribute to the (still nascent) legal scholarship on civil society participation in environmental and climate policy.
Inertial torque on a squirmer
Authors: Candelier F. , Qiu J. , Zhao L. , Voth G. , Mehlig B.
Published: December 2022

A small spheroid settling in a quiescent fluid experiences an inertial torque that aligns it so that it settles with its broad side first. Here we show that an active particle experiences such a torque too, as it settles in a fluid at rest. For a spherical squirmer, the torque is$\boldsymbol {T}^\prime = -{\frac {9}{8}} m_f (\boldsymbol {v}_s^{(0)} \wedge \boldsymbol {v}_g^{(0)})$where$\boldsymbol {v}_s^{(0)}$is the swimming velocity,$\boldsymbol {v}_g^{(0)}$is the settling velocity in the Stokes approximation and$m_f$is the equivalent fluid mass. This torque aligns the swimming direction against gravity: swimming up is stable, swimming down is unstable.
Mining terms in the history of English
Authors: Landmann Julia , Landmann Andreas
Published: December 2022

Mining is a broad and complex field. The search for and exploitation of minerals is unceasing in many countries worldwide. Before its collapse towards the close of the 20th century, coal mining in the United Kingdom, for instance, which dates back to Roman antiquity, occurred in various regions of the country, such as Northumberland and Durham, North and South Wales, Yorkshire, Kent, and the East and West Midlands. An essential aim of the present paper is to give an overview of the plethora of mining terms in English which have been coined due to progress and advance in this field over time, ranging from terms associated with boring, drilling and extraction, to ventilation, pipelines and hauling. The Oxford English Dictionary Online (Murray et al., 1884–; henceforth referred to as the OED) and specific sources such as Elsevier's Dictionary of Mining and Mineralogy (Dorian, 1993) constitute valuable tools to identify these types of lexical items. This study relies on the analysis of a comprehensive lexicographical sample of 217 mining terms documented in English.
BERRY–ESSEEN BOUND AND LOCAL LIMIT THEOREM FOR THE COEFFICIENTS OF PRODUCTS OF RANDOM MATRICES
Authors: Dinh Tien-Cuong , Kaufmann Lucas , Wu Hao
Published: December 2022

Let$\mu $be a probability measure on$\mathrm {GL}_d(\mathbb {R})$, and denote by$S_n:= g_n \cdots g_1$the associated random matrix product, where$g_j$are i.i.d. with law$\mu $. Under the assumptions that$\mu $has a finite exponential moment and generates a proximal and strongly irreducible semigroup, we prove a Berry–Esseen bound with the optimal rate$O(1/\sqrt n)$for the coefficients of$S_n$, settling a long-standing question considered since the fundamental work of Guivarc’h and Raugi. The local limit theorem for the coefficients is also obtained, complementing a recent partial result of Grama, Quint and Xiao.
Factors on the Mesozoic Transition From Flat to Steep Subduction of the Paleo‐Pacific Plate Beneath South China: Thickened Oceanic Crust and Subduction Rate
Authors: Jiang Jiawei , Mao Yadan , Hu Xiangyun
Published: December 2022

In the Mesozoic, the age of Paleo‐Pacific plate that flatly subducted beneath the South China was ∼80 Ma, resulting in a cold and dense oceanic slab. The transition process from flat to steep subduction of this old slab and factors that affect it are still unclear. Using 2‐D thermomechanical numerical models, we investigate the dependence of the transition mode on the size of TOC (length and thickness) and the subduction rate. The results indicate that under low subduction rates (e.g., 1 cm/yr), even a 100‐km long eclogitized TOC can induce slab delamination beneath continental lithosphere. The maximum subduction rate for slab delamination to occur increases with an increasing length or thickness of TOC. However, when the subduction rate is over a certain critical value (e.g., ≥4 cm/yr), oceanic slab rolls back. The presence of the TOC delays the initial rollback time, as compared to cases with no TOC. In addition, with a TOC of small size (e.g., 100‐km length and 20‐km thickness) under a certain range of subduction rate, an 80‐Ma old slab can maintain a long‐lasting flat subduction. The comparisons between the numerical results and global plate motion models indicate that the northwestward motion of South China Block since ca. 195 ± 5 Ma induced the delamination of oceanic slab. The arrival of the TOC in the Paleo‐Pacific Plate to the continental arc should be later than the previously estimated ca. 250 Ma. Determination of the TOC size requires three‐dimensional simulations and more detailed geological records.
Jurassic Paleomagnetism of the Lhasa Terrane—Implications for Tethys Evolution and True Polar Wander
Authors: Ma Yiming , Wang Qiang , Wang Huapei , Wan Bo , Zhang Shihong , Deng Chenglong , Zheng Dongyu , Ren Qiang , Yang Tianshui , Wu Dan , Zou Di , Wang Jun , Liu Xiao , Kang Zhiqiang , Dan Wei , Han Fei , Dekkers Mark J.
Published: December 2022

The drift history of the Lhasa terrane from Gondwana to Asia plays a crucial role in understanding the Tethys evolution and true polar wander (TPW). However, few reliable paleomagnetic results from Jurassic strata are currently available for reconstructing its northward journey. We performed a combined paleomagnetic and geochronological study on Bima Formation strata in the Xigaze area. Combined with previous results from the Sangri area, our results reveal a paleolatitude of 8 ± 4°S at ∼180 Ma for the reference point (29.3°N, 90.3°E). Along with other paleomagnetic results from the Triassic to Cretaceous, our new results suggest that the Lhasa terrane motion accelerated from ∼2 cm/yr during ∼220–180 Ma to ∼17 cm/yr during ∼180–170 Ma. Paleolatitude information of the North Qiangtang terrane and Tethyan Himalaya is calculated from paleopoles that meet five criteria, which include (a) structural control, (b) well‐determined rock age, (c) stepwise demagnetizations, (d) a minimum of 25 specimens or 8 sites are contained, and (e) robust field or reversal tests are provided. Both terranes also show significant acceleration during their northward motion, which may be related to oceanic slab subduction. Thus, all Gondwana‐derived microcontinents seem to share a significant acceleration during their northward motion. In addition, recent paleomagnetic results from volcanic rocks dated at ∼155 Ma subdivide the overall northward motion during ∼170–130 Ma into two stages, which include a southward drift during ∼170–155 Ma followed by northward motion during ∼155–130 Ma. These results support the fast Late Jurassic TPW during a ∼10 Myr time span.
The Variation Characteristics and Prediction Performance of TEC in the Geomagnetic Latitude and Local Time Coordinate
Authors: Zhang Simin , Wu Xiaocheng , Hu Xiong
Published: December 2022

Total electron content (TEC), as one of the most valuable ionosphere parameters, has many variation characteristics. The TEC has specific characteristics at a given time, suggesting that the global TEC morphology distribution is maintained for a period. We consider the global ionosphere map (GIM) to be the actual ionospheric electron density integration, predict the GIM by a previous period in a geomagnetic latitude and local time (LT) coordinate system, and compare the differences between these two GIMs. The objective of this research is to find the morphological properties of global TEC in the geomagnetic latitude and LT coordinate system, reveal ionospheric behavior and predict TEC using an uncomplicated method. The GIM data for a solar cycle (2009–2020) are used to find the error characteristics and prediction performance of TEC in this coordinate. The equatorial ionization anomaly is the dominant error region. This error shows diurnal and seasonal variations and has a strong correlation with solar activity. The prediction error of this method is smaller than that of the International Reference Ionosphere (IRI) model, especially in high solar activity years. The root mean square error of the 3‐hr prediction is 6.53 in 2014 and 2.02 TECU in 2019, and it is 28.5% smaller than that of IRI on average for 2009–2020.
Two‐Way Assessment of Ionospheric Maps Performance Over the Brazilian Region: Global Versus Regional Products
Authors: Jerez Gabriel O. , Hernández‐Pajares Manuel , Goss Andreas , Prol Fabricio S. , Alves Daniele B. M. , Monico João F. G. , Schmidt Michael
Published: December 2022

Vertical total electron content (VTEC) has great importance in describing the ionosphere. VTEC values are commonly distributed in regular grids by means of so‐called global ionospheric maps (GIMs) and regional ionospheric maps (RIMs). Although considerable research has been conducted to develop regional and global models, there is no clear understanding of the benefits of using RIMs over GIMs. Aiming to contribute to this discussion, our investigation presents a comparison between seven global and regional ionospheric maps considering two approaches: (a) ionosonde data‐based assessment and (b) global navigation satellite systems (GNSS) positioning assessment. A challenging low latitude ionosphere scenario, the Brazilian region, was selected during a week with an active geomagnetic storm. The assessment results with ionosonde data have shown better performance of the RIM products named OTHR and OTRG. Among the global products, CODG and UQRG have shown the best performances. The worst results were obtained with the RIM named Instituto Nacional de Pesquisas Espaciais. The assessment with GNSS positioning led to larger and noisier errors close to the equatorial anomaly. Two of the analyzed RIMs presented expected large errors in stations at the edges of the coverage area. To overcome this issue, a hybrid product was proposed to extend the RIM covered region. The proposed hybrid product (OTRG) presented the best results in the GNSS positioning domain.
Basal Décollement Splaying Induces Mid‐Crustal Tectonic Imbrication in an Intracontinental Orogen
Authors: Feng Zhentian , Chu Yang , Wei Wei , Xue Zhenhua , Xin Guangyao , Meng Lingtong , Zhang Di , Lin Wei
Published: December 2022

Mid‐to‐lower crustal rock exhumation is common in orogenic belts, but the deformation process exposing these rocks remains debated. Distributed deformation in low viscous crust extruding mid‐to‐lower crustal rocks as channel flow and localized deformation along shear zones imbricating rigid blocks are two end‐members that account for crustal thickening and unroofing. At the northwest of the Early Paleozoic orogenic belt in the South China Block, the Jiuling Massif includes orogenic root rocks exhumed from deep crustal level. Their structural pattern and exhumation history can improve our understanding on how continental mid‐to‐lower crust is deformed, thickened, and finally transported to the surface. Structural analysis reveals that two major mid‐crustal ductile shear zones and their splays are developed at temperatures of ∼350°C–550°C. Anisotropy of magnetic susceptibility (AMS) shows that the Southern Jiuling Batholith has a modified AMS pattern by syn‐orogenic compression, suggesting a gradually deformed rigid block. Combining surface geological evidence and deep structures by gravity modeling, we find shear zones rooted in basal décollement incrementally stacked the rigid granitic blocks. Along strike, the major shear zones evolved differently with more splays at their eastern portions. Thus, tectonic imbrication can evolve to pervasive flow‐like deformation as shear zones continue to splay and form an anastomosed shear zone system. The complexed structures by splayed shear zones segmenting and imbricating small rigid blocks may correspond to the geophysically low‐velocity zone in the crust, so shear zone splaying is a linking mechanism between tectonic imbrication and viscous flow deformation of the crust.
Ultrasound-targeted microbubble destruction remodels tumour microenvironment to improve immunotherapeutic effect
Authors: Liu Senbo , Zhang Yan , Liu Yang , Wang Wenkang , Gao Shuochen , Yuan Weitang , Sun Zhenqiang , Liu Lin , Wang Chengzeng
Published: December 2022

Cancer immunotherapy (CIT) has gained increasing attention and made promising progress in recent years, especially immune checkpoint inhibitors such as antibodies blocking programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). However, its therapeutic efficacy is only 10–30% in solid tumours and treatment sensitivity needs to be improved. The complex tissue environment in which cancers originate is known as the tumour microenvironment (TME) and the complicated and dynamic TME is correlated with the efficacy of immunotherapy. Ultrasound-targeted microbubble destruction (UTMD) is an emerging technology that integrates diagnosis and therapy, which has garnered much traction due to non-invasive, targeted drug delivery and gene transfection characteristics. UTMD has also been studied to remodel TME and improve the efficacy of CIT. In this review, we analyse the effects of UTMD on various components of TME, including CD8+ T cells, tumour-infiltrating myeloid cells, regulatory T cells, natural killer cells and tumour vasculature. Moreover, UTMD enhances the permeability of the blood-brain barrier to facilitate drug delivery, thus improving CIT efficacy in vivo animal experiments. Based on this, we highlight the potential of immunotherapy against various cancer species and the clinical application prospects of UTMD.
The mechanism of BUD13 m6A methylation mediated MBNL1-phosphorylation by CDK12 regulating the vasculogenic mimicry in glioblastoma cells
Authors: Liu Meichen , Ruan Xuelei , Liu Xiaobai , Dong Weiwei , Wang Di , Yang Chunqing , Liu Libo , Wang Ping , Zhang Mengyang , Xue Yixue
Published: December 2022

Vasculogenic mimicry (VM) is an endothelium-independent tumor microcirculation that provides adequate blood supply for tumor growth. The presence of VM greatly hinders the treatment of glioblastoma (GBM) with anti-angiogenic drugs. Therefore, targeting VM formation may be a feasible therapeutic strategy for GBM. The research aimed to evaluate the roles of BUD13, CDK12, MBNL1 in regulating VM formation of GBM. BUD13 and CDK12 were upregulated and MBNL1 was downregulated in GBM tissues and cells. Knockdown of BUD13, CDK12, or overexpression of MBNL1 inhibited GBM VM formation. METTL3 enhanced the stability of BUD13 mRNA and upregulated its expression through m6A methylation. BUD13 enhanced the stability of CDK12 mRNA and upregulated its expression. CDK12 phosphorylated MBNL1, thereby regulating VM formation of GBM. The simultaneous knockdown of BUD13, CDK12, and overexpression of MBNL1 reduced the volume of subcutaneously transplanted tumors in nude mice and prolonged the survival period. Thus, the BUD13/CDK12/MBNL1 axis plays a crucial role in regulating VM formation of GBM and provides a potential target for GBM therapy.
Targeting HER3 or MEK overcomes acquired Trastuzumab resistance in HER2-positive gastric cancer-derived xenograft
Authors: Zhang Mengqi , Li Beifang , Liao Haiyan , Chen Zuhua , Huang Wenwen , Yang Jing , Ge Sai , Li Zhongwu , Shen Lin , Zhang Cheng , Gao Jing
Published: December 2022

Acquired Trastuzumab resistance is a complicated and disastrous event for HER2-positive gastric cancer (GC). In this study, we successfully established a GC PDX model with Trastuzumab sensitivity (176P) and induced a homologous model with acquired Trastuzumab resistance (176R), then comprehensively delineated the landscape of Trastuzumab resistance mechanisms using single-cell transcriptome sequencing, as well as protein profiling and genomic variation analysis. According to multi-omics study, different gene expression profiles, rather than genetic changes, contributed to acquired Trastuzumab resistance. The mechanisms underlying acquired Trastuzumab resistance present great complexity as multiple molecules and pathways were involved, including ERBB family, MAPK, PI3K/AKT, JAK/STAT, and cell cycle pathways. Through phenotypical and molecular validation, we found that Trastuzumab combined with HER3-targeted antibody or MEK inhibitor demonstrated excellent antitumor activity and good tolerance, which may serve as promising strategies for overcoming acquired Trastuzumab resistance.
Comparison of breath-guards and face-masks on droplet spread in eye clinics
Authors: Newsom Richard , Pattison Chris , Lundgren Andrew , Robison Pauline , Quint Matthew , Amara Adam
Published: December 2022

Introduction

COVID-19 has impacted ophthalmic care delivery, with many units closed and several ophthalmologists catching COVID-19. Understanding droplet spread in clinical and training settings is paramount in maintaining productivity, while keeping patients and practitioners safe.

Objectives

We aimed to assess the effectiveness of a breath-guard and a face mask in reducing droplet spread within an eye clinic.

Methods

We performed a randomised trial of droplet spread using a fluorescein-based cough model to assess the efficacy of a ‘breath-guard’ and ‘face-mask’ to prevent the spread of droplets. The ‘cough’ spray was collected on calibrated paper targets. The sheets were photographed under blue light, with an orange filter on the camera; the position and size of the spots was measured with software originally developed for astronomy.

We performed 44 randomised coughs; 22 controls with no breath-guard or face-mask, 11 using breath-guard only and 11 with combined breath-guard and face-mask. We compared both the number of droplets detected and the area of drops on paper targets.

Results

The average number of droplets in the controls was 19,430 (SE 2691), the breath-guard group 80 (SE 19) droplets (P < 0.001); in the combined In the group the count was 5 (SE 2), a significant drop from shield only (P = 0.008). The mean areas of each target covered by spots for each group were 5.7 ± 0.857% (95% CI), 0.004 ± 0.000104% (95% CI) and 0.001 ± 0.0000627% (95% CI) respectively.

Conclusion

These results show that the breath-guard alone reduced the droplet count by 99.93%. Combining the breath-guard with a face-mask reduced the droplet count by over 99.98%. Breath-guards are widely used in clinics and this trial demonstrates that breath-guards with face-masks effectively block droplet spray.
Dual communities in spatial networks
Authors: Kaiser Franz , Böttcher Philipp C. , Ronellenfitsch Henrik , Latora Vito , Witthaut Dirk
Published: December 2022

Both human-made and natural supply systems, such as power grids and leaf venation networks, are built to operate reliably under changing external conditions. Many of these spatial networks exhibit community structures. Here, we show that a relatively strong connectivity between the parts of a network can be used to define a different class of communities: dual communities. We demonstrate that traditional and dual communities emerge naturally as two different phases of optimized network structures that are shaped by fluctuations and that they both suppress failure spreading, which underlines their importance in understanding the shape of real-world supply networks.
Membrane curvature governs the distribution of Piezo1 in live cells
Authors: Yang Shilong , Miao Xinwen , Arnold Steven , Li Boxuan , Ly Alan T. , Wang Huan , Wang Matthew , Guo Xiangfu , Pathak Medha M. , Zhao Wenting , Cox Charles D. , Shi Zheng
Published: December 2022

Piezo1 is a bona fide mechanosensitive ion channel ubiquitously expressed in mammalian cells. The distribution of Piezo1 within a cell is essential for various biological processes including cytokinesis, cell migration, and wound healing. However, the underlying principles that guide the subcellular distribution of Piezo1 remain largely unexplored. Here, we demonstrate that membrane curvature serves as a key regulator of the spatial distribution of Piezo1 in the plasma membrane of living cells. Piezo1 depletes from highly curved membrane protrusions such as filopodia and enriches to nanoscale membrane invaginations. Quantification of the curvature-dependent sorting of Piezo1 directly reveals the in situ nano-geometry of the Piezo1-membrane complex. Piezo1 density on filopodia increases upon activation, independent of calcium, suggesting flattening of the channel upon opening. Consequently, the expression of Piezo1 inhibits filopodia formation, an effect that diminishes with channel activation.
A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA
Authors: Doebley Anna-Lisa , Ko Minjeong , Liao Hanna , Cruikshank A. Eden , Santos Katheryn , Kikawa Caroline , Hiatt Joseph B. , Patton Robert D. , De Sarkar Navonil , Collier Katharine A. , Hoge Anna C. H. , Chen Katharine , Zimmer Anat , Weber Zachary T. , Adil Mohamed , Reichel Jonathan B. , Polak Paz , Adalsteinsson Viktor A. , Nelson Peter S. , MacPherson David , Parsons Heather A. , Stover Daniel G. , Ha Gavin
Published: December 2022

Cell-free DNA (cfDNA) has the potential to inform tumor subtype classification and help guide clinical precision oncology. Here we develop Griffin, a framework for profiling nucleosome protection and accessibility from cfDNA to study the phenotype of tumors using as low as 0.1x coverage whole genome sequencing data. Griffin employs a GC correction procedure tailored to variable cfDNA fragment sizes, which generates a better representation of chromatin accessibility and improves the accuracy of cancer detection and tumor subtype classification. We demonstrate estrogen receptor subtyping from cfDNA in metastatic breast cancer. We predict estrogen receptor subtype in 139 patients with at least 5% detectable circulating tumor DNA with an area under the receive operator characteristic curve (AUC) of 0.89 and validate performance in independent cohorts (AUC = 0.96). In summary, Griffin is a framework for accurate tumor subtyping and can be generalizable to other cancer types for precision oncology applications.
Disorder-dominated quantum criticality in moiré bilayers
Authors: Tan Yuting , Tsang Pak Ki Henry , Dobrosavljević Vladimir
Published: December 2022

Moiré bilayer materials have recently attracted much attention following the discovery of various correlated insulating states at specific band fillings. Here we discuss the metal-insulator transitions (MITs) that have been observed in the same devices, but at fillings far from the strongly correlated regime dominated by Mott-like physics, displaying many similarities to other examples of disorder-dominated MITs. We propose a minimal theoretical model describing the interplay of interactions and disorder, which is able to capture all the universal aspects of quantum criticality, as observed in experiments performed on several devices.
Cryo-EM structure of ssDNA bacteriophage ΦCjT23 provides insight into early virus evolution
Authors: Kejzar Nejc , Laanto Elina , Rissanen Ilona , Abrishami Vahid , Selvaraj Muniyandi , Moineau Sylvain , Ravantti Janne , Sundberg Lotta-Riina , Huiskonen Juha T.
Published: December 2022

The origin of viruses remains an open question. While lack of detectable sequence similarity hampers the analysis of distantly related viruses, structural biology investigations of conserved capsid protein structures facilitate the study of distant evolutionary relationships. Here we characterize the lipid-containing ssDNA temperate bacteriophage ΦCjT23, which infects Flavobacterium sp. (Bacteroidetes). We report ΦCjT23-like sequences in the genome of strains belonging to several Flavobacterium species. The virion structure determined by cryogenic electron microscopy reveals similarities to members of the viral kingdom Bamfordvirae that currently consists solely of dsDNA viruses with a major capsid protein composed of two upright β-sandwiches. The minimalistic structure of ΦCjT23 suggests that this phage serves as a model for the last common ancestor between ssDNA and dsDNA viruses in the Bamfordvirae. Both ΦCjT23 and the related phage FLiP infect Flavobacterium species found in several environments, suggesting that these types of viruses have a global distribution and a shared evolutionary origin. Detailed comparisons to related, more complex viruses not only expand our knowledge about this group of viruses but also provide a rare glimpse into early virus evolution.
A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice
Authors: Hackstein Carl-Philipp , Costigan Dana , Drexhage Linnea , Pearson Claire , Bullers Samuel , Ilott Nicholas , Akther Hossain Delowar , Gu Yisu , FitzPatrick Michael E. B. , Harrison Oliver J. , Garner Lucy C. , Mann Elizabeth H. , Pandey Sumeet , Friedrich Matthias , Provine Nicholas M. , Uhlig Holm H. , Marchi Emanuele , Powrie Fiona , Klenerman Paul , Thornton Emily E.
Published: December 2022

Interactions with commensal microbes shape host immunity on multiple levels and play a pivotal role in human health and disease. Tissue-dwelling, antigen-specific T cells are poised to respond to local insults, making their phenotype important in the relationship between host and microbes. Here we show that MHC-II restricted, commensal-reactive T cells in the colon of both humans and mice acquire transcriptional and functional characteristics associated with innate-like T cells. This cell population is abundant and conserved in the human and murine colon and endowed with polyfunctional effector properties spanning classic Th1- and Th17-cytokines, cytotoxic molecules, and regulators of epithelial homeostasis. T cells with this phenotype are increased in ulcerative colitis patients, and their presence aggravates pathology in dextran sodium sulphate-treated mice, pointing towards a pathogenic role in colitis. Our findings add to the expanding spectrum of innate-like immune cells positioned at the frontline of intestinal immune surveillance, capable of acting as sentinels of microbes and the local cytokine milieu.
Genetic features and therapeutic relevance of emergent circulating tumor DNA alterations in refractory non-colorectal gastrointestinal cancers
Authors: Hsiehchen David , Bucheit Leslie , Yang Dong , Beg Muhammad Shaalan , Lim Mir , Lee Sunyoung S. , Kasi Pashtoon Murtaza , Kaseb Ahmed O. , Zhu Hao
Published: December 2022

Acquired resistance to systemic treatments is inevitable in most cancers, but the genetic basis for this in many cancer types has remained elusive due to constraints in obtaining tissue specimens longitudinally. In the management of gastrointestinal cancers, molecular profiling is conventionally performed at a single time point, although serial evaluations may yield biological insights that inform treatment decisions. We characterize genetic changes in serial liquid biopsies which provide real-time snapshots of tumor genetics and heterogeneity in refractory non-colorectal gastrointestinal cancers, and determine the clinical utility of repeat circulating tumor DNA (ctDNA) testing. In a national cohort of 449 patients with pancreatic, biliary, esophagogastric, and hepatocellular cancers, resistance to conventional therapies is broadly associated with tumor evolution. Emergent ctDNA alterations only detectable at progression occurs in 63% of patients and are frequently associated with treatment actionability. Tumor mutation burden is dynamic in cancers undergoing treatment, but is not associated with time to progression. Objective tumor responses in a case series of patients receiving treatment matched to emergent alterations show that repeat liquid biopsies may have clinical benefit by expanding treatment options in advanced gastrointestinal cancers.
Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells
Authors: Gerdes Patricia , Lim Sue Mei , Ewing Adam D. , Larcombe Michael R. , Chan Dorothy , Sanchez-Luque Francisco J. , Walker Lucinda , Carleton Alexander L. , James Cini , Knaupp Anja S. , Carreira Patricia E. , Nefzger Christian M. , Lister Ryan , Richardson Sandra R. , Polo Jose M. , Faulkner Geoffrey J.
Published: December 2022

Induced pluripotent stem cells (iPSCs) can in principle differentiate into any cell of the body, and have revolutionized biomedical research and regenerative medicine. Unlike their human counterparts, mouse iPSCs (miPSCs) are reported to silence transposable elements and prevent transposable element-mediated mutagenesis. Here we apply short-read or Oxford Nanopore Technologies long-read genome sequencing to 38 bulk miPSC lines reprogrammed from 10 parental cell types, and 18 single-cell miPSC clones. While single nucleotide variants and structural variants restricted to miPSCs are rare, we find 83 de novo transposable element insertions, including examples intronic to Brca1 and Dmd. LINE-1 retrotransposons are profoundly hypomethylated in miPSCs, beyond other transposable elements and the genome overall, and harbor alternative protein-coding gene promoters. We show that treatment with the LINE-1 inhibitor lamivudine does not hinder reprogramming and efficiently blocks endogenous retrotransposition, as detected by long-read genome sequencing. These experiments reveal the complete spectrum and potential significance of mutations acquired by miPSCs.
Nationwide geospatial analysis of county racial and ethnic composition and public drinking water arsenic and uranium
Authors: Martinez-Morata Irene , Bostick Benjamin C. , Conroy-Ben Otakuye , Duncan Dustin T. , Jones Miranda R. , Spaur Maya , Patterson Kevin P. , Prins Seth J. , Navas-Acien Ana , Nigra Anne E.
Published: December 2022

There is no safe level of exposure to inorganic arsenic or uranium, yet recent studies identified sociodemographic and regional inequalities in concentrations of these frequently detected contaminants in public water systems across the US. We analyze the county-level association between racial/ethnic composition and public water arsenic and uranium concentrations from 2000–2011 using geospatial models. We find that higher proportions of Hispanic/Latino and American Indian/Alaskan Native residents are associated with significantly higher arsenic and uranium concentrations. These associations differ in magnitude and direction across regions; higher proportions of non-Hispanic Black residents are associated with higher arsenic and uranium in regions where concentrations of these contaminants are high. The findings from this nationwide geospatial analysis identifying racial/ethnic inequalities in arsenic and uranium concentrations in public drinking water across the US can advance environmental justice initiatives by informing regulatory action and financial and technical support to protect communities of color.
Inverse design of 3D reconfigurable curvilinear modular origami structures using geometric and topological reconstructions
Authors: Xiao Kai , Liang Zihe , Zou Bihui , Zhou Xiang , Ju Jaehyung
Published: December 2022

The recent development of modular origami structures has ushered in an era for active metamaterials with multiple degrees of freedom (multi-DOF). Notably, no systematic inverse design approach for 3D curvilinear modular origami structures has been reported. Moreover, very few modular origami topologies have been studied to design active metamaterials with multi-DOF. Herein, we develop an inverse design method for constructing 3D reconfigurable architected structures — we synthesize modular origami structures whose unit cells can be volumetrically mapped into a prescribed 3D curvilinear shape followed by volumetric shrinkage to construct modules. After modification of the tubular geometry, we search through all the possible geometric and topological combinations of the modular origami structures to attain the target mobility using a topological reconstruction of modules. Our inverse design using geometric and topological reconstructions can provide an effective solution to construct 3D curvilinear reconfigurable structures with multi-DOF. Our work opens a path toward 3D reconfigurable systems based on volumetric inverse design, such as 3D active metamaterials and 3D morphing devices for automotive, aerospace, and biomedical engineering applications.
ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II
Authors: Ohe Seina , Kubota Yuji , Yamaguchi Kiyoshi , Takagi Yusuke , Nashimoto Junichiro , Kozuka-Hata Hiroko , Oyama Masaaki , Furukawa Yoichi , Takekawa Mutsuhiro
Published: December 2022

Growth factor-induced, ERK-mediated induction of immediate-early genes (IEGs) is crucial for cell growth and tumorigenesis. Although IEG expression is mainly regulated at the level of transcription elongation by RNA polymerase-II (Pol-II) promoter-proximal pausing and its release, the role of ERK in this process remains unknown. Here, we identified negative elongation factor (NELF)-A as an ERK substrate. Upon growth factor stimulation, ERK phosphorylates NELF-A, which dissociates NELF from paused Pol-II at the promoter-proximal regions of IEGs, allowing Pol-II to resume elongation and produce full-length transcripts. Furthermore, we found that in cancer cells, PP2A efficiently dephosphorylates NELF-A, thereby preventing aberrant IEG expression induced by ERK-activating oncogenes. However, when PP2A inhibitor proteins are overexpressed, as is frequently observed in cancers, decreased PP2A activity combined with oncogene-mediated ERK activation conspire to induce NELF-A phosphorylation and IEG upregulation, resulting in tumor progression. Our data delineate previously unexplored roles of ERK and PP2A inhibitor proteins in carcinogenesis.
Graph-based autoencoder integrates spatial transcriptomics with chromatin images and identifies joint biomarkers for Alzheimer’s disease
Authors: Zhang Xinyi , Wang Xiao , Shivashankar G. V. , Uhler Caroline
Published: December 2022

Tissue development and disease lead to changes in cellular organization, nuclear morphology, and gene expression, which can be jointly measured by spatial transcriptomic technologies. However, methods for jointly analyzing the different spatial data modalities in 3D are still lacking. We present a computational framework to integrate Spatial Transcriptomic data using over-parameterized graph-based Autoencoders with Chromatin Imaging data (STACI) to identify molecular and functional alterations in tissues. STACI incorporates multiple modalities in a single representation for downstream tasks, enables the prediction of spatial transcriptomic data from nuclear images in unseen tissue sections, and provides built-in batch correction of gene expression and tissue morphology through over-parameterization. We apply STACI to analyze the spatio-temporal progression of Alzheimer’s disease and identify the associated nuclear morphometric and coupled gene expression features. Collectively, we demonstrate the importance of characterizing disease progression by integrating multiple data modalities and its potential for the discovery of disease biomarkers.
Setd2 supports GATA3+ST2+ thymic-derived Treg cells and suppresses intestinal inflammation
Authors: Ding Zhaoyun , Cai Ting , Tang Jupei , Sun Hanxiao , Qi Xinyi , Zhang Yunpeng , Ji Yan , Yuan Liyun , Chang Huidan , Ma Yanhui , Zhou Hong , Li Li , Sheng Huiming , Qiu Ju
Published: December 2022

Treg cells acquire distinct transcriptional properties to suppress specific inflammatory responses. Transcription characteristics of Treg cells are regulated by epigenetic modifications, the mechanism of which remains obscure. Here, we report that Setd2, a histone H3K36 methyltransferase, is important for the survival and suppressive function of Treg cells, especially those from the intestine. Setd2 supports GATA3+ST2+ intestinal thymic-derived Treg (tTreg) cells by facilitating the expression and reciprocal relationship of GATA3 and ST2 in tTreg cells. IL-33 preferentially boosts Th2 cells rather than GATA3+ Treg cells in Foxp3Cre-YFPSetd2 flox/flox mice, corroborating the constraint of Th2 responses by Setd2 expression in Treg cells. SETD2 sustains GATA3 expression in human Treg cells, and SETD2 expression is increased in Treg cells from human colorectal cancer tissues. Epigenetically, Setd2 regulates the transcription of target genes (including Il1rl1) by modulating the activity of promoters and intragenic enhancers where H3K36me3 is typically deposited. Our findings provide mechanistic insights into the regulation of Treg cells and intestinal immunity by Setd2.