bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase diagram for preferential flow in dual permeable media
Authors: Liu Fanli , Wang Moran
Published: September 2022

We study the preference of two-phase displacements systematically by theoretical derivations and numerical simulations via a non-uniform pore doublet model. All the most important impact factors, including viscosity ratio, capillary number, wetting conditions and boundary conditions, have been considered, and finally a complete phase diagram for preferential flow has been obtained. The simple treatment for the dual-permeability media has been validated, and further, with a few necessary corrections the phase diagram is applicable for disordered permeable media in general. These results help us to understand the occurrence and manipulation of preferential flow in heterogeneous permeable media.
Clustering in laboratory and numerical turbulent swirling flows
Authors: Angriman Sofía , Ferran Amélie , Zapata Florencia , Cobelli Pablo J. , Obligado Martin , Mininni Pablo D.
Published: September 2022

We study the three-dimensional clustering of velocity stagnation points, of nulls of the vorticity and of the Lagrangian acceleration, and of inertial particles in turbulent flows at fixed Reynolds numbers, but under different large-scale flow geometries. To this end, we combine direct numerical simulations of homogeneous and isotropic turbulence and of the Taylor–Green flow, with particle tracking velocimetry in a von Kármán experiment. While flows have different topologies (as nulls cluster differently), particles behave similarly in all cases, indicating that Taylor-scale neutrally buoyant particles cluster as inertial particles.
Evidence of the critical layer mechanism in growing wind waves
Authors: Carpenter J.R. , Buckley M.P. , Veron F.
Published: September 2022

Highly resolved laboratory measurements of the airflow over wind-generated waves are examined using a novel wave growth diagnostic that quantifies the presence of Miles’ critical layer mechanism of wind-wave growth. The wave growth diagnostic is formulated based on a linear stability analysis, and results in growth rates that agree well with those found by a pressure reconstruction method as well as other, less direct, methods. This finding, combined with a close agreement between the airflow measurements and the predictions of linear stability (critical layer) theory, demonstrate that the Miles’ critical layer mechanism can cause significant wave growth in young (wave age

$c/u_* = 6.3$

, where

$c$

is the wave phase speed, and

$u_*$

the friction velocity) wind-forced waves.
Power, People, and the Political: Understanding the Many Crises in Belarus
Authors: Korosteleva Elena , Petrova Irina
Published: September 2022

The many recent crises in Belarus are often seen through the prism of democratization, post-communist transition, and nation- and identity-building. As a rule, it is put into the context of the 1989 democratization in Central and Eastern Europe and compared with similar societal mobilization in Georgia (2003), Ukraine (2004; 2014), and Kyrgyzstan (2005). This article, however, argues that while these theoretical approaches provide an important explanatory potential, they nevertheless fail to account for informal, hidden, and unstable processes presently unfolding in the Belarusian society, leading to profound change. We argue that, in the vulnerable, unpredictable, complex, and ambiguous (VUCA) world of today, our knowledge and ability to plan and achieve desirable outcomes are limited in contrast to a largely positivist or interpretivist epistemology of the mainstream theories, which conceive of the world as a closed system. In this article, we offer an alternative explanation of the many crises in Belarus by drawing on the insights ofcomplexity-thinkingto suggest that (hidden) transformative change in the country is now irreversible.
Non-target effects of agri-environmental schemes on solitary bees and fungi in the United Kingdom
Authors: Lunn Katherine , Frøslev Tobias , Rhodes Madeleine , Taylor Leah , Oliveira Hernani F. M. , Gresty Catherine E. A. , Clare Elizabeth L.
Published: September 2022

Agri-environmental schemes (AES) are used to enhance pollinator diversity on agricultural farms within the UK. Though the impacts of these schemes on archetypal pollinator species such as the bumblebee (Bombus) and honeybee (Apis) are well-studied, the effects on non-target bee species like solitary bees, in the same environment, are generally lacking. One goal of AES is to alter floral provision and taxonomic composition of plant communities to provide better forage for pollinators, however, this may potentially impact other ecological communities such as fungal diversity associated with plant-bee communities. Fungi are integral in these bee communities as they can impact bee species both beneficially and detrimentally. We test the hypothesis that alteration of the environment through provision of novel plant communities has non-target effects on the fungi associated with solitary bee communities. We analyse fungal diversity and ecological networks formed between fungi and solitary bees present on 15 agricultural farms in the UK using samples from brood cells. The farms were allocated to two categories, low and high management, which differ in the number of agri-environmental measures implemented. Using internal transcribed spacer metabarcoding, we identified 456 fungal taxa that interact with solitary bees. Of these, 202 (approximately 44%) could be assigned to functional groups, the majority being pathotrophic and saprotrophic species. A large proportion was Ascosphaeraceae, a family of bee-specialist fungi. We considered the connectance, nestedness, modularity, nestedness overlap and decreasing fill, linkage density and fungal generality of the farms' bee–fungi ecological networks. We found no difference in the structure of bee–fungi ecological networks between low and high management farms, suggesting floral provision by AES has no significant impact on interactions between these two taxonomic groups. However, bee emergence was lower on the low management farms compared to high management, suggesting some limited non-target effects of AES. This study characterizes the fungal community associated with solitary bees and provides evidence that floral provision through AES does not impact fungal interactions.
Do Natural Disaster Experiences Limit Stock Market Participation?
Authors: Bharath Sreedhar T. , Cho DuckKi
Published: September 2022

We examine whether natural disaster experiences affect households’ portfolio choice decisions. Using data from the National Longitudinal Survey of Youth 1979, we find that adversely affected households are less likely to participate in risky asset markets. After a disaster shock, households become more risk-averse and lower their expectations on future stock market returns. Such conservative portfolio choices persist even after households relocate to less disaster-prone areas, consistent with risk preferences being altered by disaster experiences. Overall, our evidence suggests that transient but salient experiences can be an important factor in explaining the limited participation puzzle.
Using off-the-shelf GPS loggers to assess co-occurrence between marine mammals and small-scale fisheries: a pilot study from the Mediterranean Sea
Authors: Glarou Maria , Kerametsidis Georgios , Akkaya Aylin , Beqiri Kristian , Nikpaljevic Natasa , Awbery Tim , Bakiu Rigers , Geijer Christina K. A.
Published: September 2022

Fisheries constitute a major threat to marine mammals globally. To evaluate the impact of small-scale fisheries (SSF) on regional under-studied marine mammal populations, we tested a novel and cost-effective approach at three data-limited locations of the central and eastern Mediterranean Sea. Using off-the-shelf GPS loggers to track SSF activities and systematic surveys to map the distribution of marine mammals, we assessed the probability of co-occurrence between SSF and marine mammals by reporting areas of spatial overlap. Spatial overlap between SSF and the core zones of marine mammal distribution (ranging between 21.85–35.4%) was observed in all three locations, indicating potential interaction hotspots. The probability of co-occurrence in those areas varied from 0.5–2.9% depending on the species. The resulting overlap between fishing activity and marine mammals may pose a threat in both directions: higher risk of species entanglement and economic burden on fishers due to gear damage. Despite the spatial and temporal limitations of this pilot study, the proposed approach can provide baseline information on SSF-marine mammal co-occurrence, particularly in financially limited regions. If applied on a larger scale, our method may be used to inform future conservation actions with the aim to reduce pressure on key populations.
Ceratonova shasta: a cnidarian parasite of annelids and salmonids
Authors: Bartholomew Jerri L. , Alexander Julie D. , Hallett Sascha L. , Alama-Bermejo Gema , Atkinson Stephen D.
Published: September 2022

The myxozoan Ceratonova shasta was described from hatchery rainbow trout over 70 years ago. The parasite continues to cause severe disease in salmon and trout, and is recognized as a barrier to salmon recovery in some rivers. This review incorporates changes in our knowledge of the parasite's life cycle, taxonomy and biology and examines how this information has expanded our understanding of the interactions between C. shasta and its salmonid and annelid hosts, and how overarching environmental factors affect this host–parasite system. Development of molecular diagnostic techniques has allowed discrimination of differences in parasite genotypes, which have differing host affinities, and enabled the measurement of the spatio-temporal abundance of these different genotypes. Establishment of the C. shasta life cycle in the laboratory has enabled studies on host–parasite interactions and the availability of transcriptomic data has informed our understanding of parasite virulence factors and host defences. Together, these advances have informed the development of models and management actions to mitigate disease.
Nonparametric estimation of some dividend problems in the perturbed compound Poisson model
Authors: Yang Yang , Xie Jiayi , Zhang Zhimin
Published: September 2022

In this paper, we consider some dividend problems in the perturbed compound Poisson model under a constant barrier dividend strategy. We approximate the expected present value of dividend payments before ruin and the expected discounted penalty function based on the COS method, and construct some nonparametric estimators by using a random sample on claim number and individual claim sizes. Under a large sample size setting, we perform an error analysis of the estimators. We also provide some simulation results to verify the effectiveness of this estimation method when the sample size is finite.
Powder X-ray diffraction of altrenogest, C21H26O2
Authors: Kaduk James A. , Gindhart Amy M. , Gates-Rector Stacy , Blanton Thomas N.
Published: September 2022

The crystal structure of altrenogest has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Altrenogest crystallizes in space group P212121 (#19) with a = 7.286 916(16), b = 10.580 333(19), c = 22.266 08(7) Å, V = 1716.671(6) Å3, and Z = 4 at 295 K. Thermal expansion between 113 and 295 K is anisotropic. An O–H⋯O hydrogen bond links the molecules into chains along the c-axis. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File™ (PDF®).
Our Future at Risk: Toward an American Political Development Scholarship of Foresight
Authors: Kryder Daniel , LaRochelle Ryan
Published: September 2022

For the first time since 1860, our collective future as an ideologically coherent and nominally democratic nation is at risk. In the short, medium, and long term, our nation faces several systemic and intertwined threats. Because these cascading crises threaten our fundamental political ideals and our lives, we recommend here a rapid and careful reorientation of at least some part of American political development (APD) toward a scholarship of foresight—that is, one based on the premise that anticipating and shaping the future is now as important as or more important than understanding the past. The article first considers some of the ways in which APD is tethered to the past and then discusses how several of the subfield's analytical approaches are compatible with a scholarship of foresight. Prognosis, prediction, and projection, we argue, are analytical tools that can inform prescription. We conclude with five sets of recommendations that can help APD scholars consider turning their attention toward the future.
Climate Change? Designing and Implementing Climate Surveys to Promote Inclusivity in Political Science Departments
Authors: Turco Linnea , Tosun Leyla , Watson Sara
Published: September 2022

Questions of racial, gendered, and class-based inequality in political science are more salient than ever. This article contends that climate surveys can be a useful tool for developing effective equity and inclusion strategies within academic departments. We offer advice on political, procedural, and messaging issues to consider when undertaking a departmental climate survey.
Warp-Free TEM Sample Preparation Methods Using FIB/SEM Systems
Authors: Cook Steven R
Published: September 2022

Warping is a limiting factor when preparing transmission electron microscopy (TEM) samples using focused ion beam (FIB)/scanning electron microscope (SEM) systems. The conventional FIB sputtering process leaves at least one side of the lamella too thin to provide structural support to offset inherent stresses. As a result, warping can occur impacting imagining and reducing the potential size of lamellae. For example, capturing more than a few back-end metal layers in a 3 μm wide cross-section lamella can be difficult. Frequently, TEM analysts must perform multiple stage adjustments to analyze such a sample. In this paper, two methods are presented that enable FIB/SEM operators to prepare TEM samples where the thinned region of interest is surrounded by thick structures. As a result, these methods reduce warping and enable the fabrication of TEM lamellae not possible by conventional means. For example, these methods have been used to produce a 10 μm wide by 8 μm tall cross-section TEM sample that captured front-end transistors and 14 back-end metal layers. Furthermore, warping was so limited that only one alignment was needed by the TEM analyst to complete the imaging of the sample. The methods, called the horizontal bracing and window methods, make use of the deposition of low-Z amorphous films that are electron transparent in the TEM.
Application of Microscopy in the Quality Control of Licorice Roots: Comparative Anatomy of the Roots and Rhizomes of Five Species of Glycyrrhiza
Authors: Raman Vijayasankar , Manfron Jane , Avula Bharathi , Zhao Jianping , Katragunta Kumar , Chittiboyina Amar G , Khan Ikhlas A
Published: September 2022

The raw materials of “licorice root” in the commerce consist of roots and/or rhizomes (stolons) of different species of Glycyrrhiza. Licorice products and raw materials are frequently mislabeled and often have mixed, misidentified, or unidentified species and parts. This paper provides a detailed comparative analysis of the morpho-anatomies of the rhizomes and roots of five species of Glycyrrhiza, namely G. glabra, G. uralensis, G. echinata, G. inflata, and G. lepidota, by bright-field light microscopy and scanning electron microscopy. The studied species showed some similarities in their basic anatomical features due to the fact that they are phylogenetically closely related and belong to the same genus. However, differences in microscopic features such as the thickness of cork and medullary rays, pore frequency, and size of the vessels were observed. The rhizomes can readily be distinguished by the presence of a distinct pith. The roots lack a well-defined pith and instead have primary xylem in the center.
From the Three Bodies of Christ to the King's Two Bodies: The Theological Origins of Secularization Theory
Authors: Shortall Sarah
Published: September 2022

This article traces the influence of theology on one particular strand of secularization theory that emerged from the work of Ernst Kantorowicz and Marcel Gauchet. It shows how Kantorowicz's classic text, The King's Two Bodies, was deeply indebted to the insights of one of the leading Catholic theologians of the twentieth century: the French Jesuit Henri de Lubac. By tracing the influence of de Lubac's work on Kantorowicz and, through him, on the secularization theory developed by Marcel Gauchet, the article uncovers a surprising convergence between theology and the secular disciplines. In the process, it draws attention to the limitations of secularization narratives that focus on the premodern theological origins of modern political concepts, by showing how they struggle to account for the ongoing role and relevance of theology in a modern context.
A new war on nature and people: taking stock of the Colombian peace agreement
Authors: Krause Torsten , Clerici Nicola , López Jesica Murcia , Sánchez Paula Andrea , Valencia Sandra , Esguerra-Rezk Juanita , Van Dexter Kristina
Published: September 2022

Non-technical summary

Almost 6 years have passed since the Colombian peace agreement was signed. However, the promise of a ‘Stable and lasting peace’ is slipping away as the transition towards peace is increasingly tainted and overshadowed with violence. The future of Colombia is at a crossroad and without international support and action taken to monitor global supply chains, these particular drivers of conflict, violence and environmental degradation will persist. We summarize the current situation and shed light on the complexities of building peace in Colombia, with a particular focus on the environmental changes that took place since the peace agreement was signed.

Technical summary

The Colombian peace agreement officially ended one of the world's longest internal armed conflicts. But the transformation of land use that takes place in the wake of the peace agreement has made the historic inequalities of access to land more visible and revealed inherent and violent struggles over resources that persist across the country. In this briefing we analyse the current status of peacebuilding in Colombia and highlight the major barriers and challenges in the current peacebuilding efforts. We show how the last few years brought severe and negative repercussions for people, communities and the natural environment in Colombia as cattle ranching, ‘productive agriculture’ and extractive industries are increasingly encroaching into indigenous territories, protected areas and forest ecosystems, replacing diverse natural forests that support biodiversity and contribute to human well-being locally and globally. The resurging presence of numerous armed groups seeking to control the profitable drug trade and mineral deposits are a major problem and obstacle for building lasting and sustainable peace among people and with the natural environment in Colombia. We conclude this briefing with points that we see as crucial to support the implementation of the peace agreement.

Social media summary

Colombia's peacebuilding effort must foster environmental stewardship and respect its biological and cultural diversity.
Of Madres and Mayordomas: Native Women and Religious Leadership in Colonial Chiapas
Authors: Leavitt-Alcántara Brianna
Published: September 2022

Scholars often assume that women's exclusion from the modern civil-religious cargo system in Mexico is a colonial legacy. But an analysis of Chiapas's surviving colonial cofradía books, approximately 200 in all, reveals that formalized female religious leadership was widespread in this region during the colonial period. Close to 50 cofradías in over 20 different towns elected female officials. Indigenous cofradías were clearly at the forefront of this practice; however, it also became remarkably popular among ladino, Black, and even Spanish cofradías during the eighteenth century. Not just symbolic figures, female cofradía officers managed finances and cared for the spiritual and physical welfare of fellow members and the community. Their labors often overlapped with the work of town councils to ensure community well-being and survival in the face of extreme economic exploitation, migration, and forced resettlements. These findings challenge the common generalization, based on studies of central Mexico, that women in colonial New Spain were excluded from officeholding and the prestige and authority it provided. By shifting focus beyond central Mexico, this article illustrates the diversity of female experience and the ways in which gender shaped native communities, cross-cultural exchanges, and dynamic adaptations in religious organizational leadership and Church policy.
Toward interpretable digital biomarkers of walking and reaching in Parkinson’s disease
Authors: Ryu Jihye , Torres Elizabeth
Published: September 2022

Multimodal digital data registered with wearable biosensors have emerged as highly complementary of clinical pencil-and-paper criteria, offering new insights in ways to detect and diagnose various aspects of Parkinson’s disease (PD). A pressing question is how to combine both the clinical knowledge of PD and the new technology to create interpretable digital biomarkers easily obtainable with off-the-shelf technology. Several challenges concerning disparity in biophysical units, anatomical differences across participants, sensor positioning, and sampling resolution are addressed in this work, along with identification of optimal parameters to automatically differentiate patients with PD from controls. We combine data from a multitude of biosensors registering signals from the central (electroencephalography) and peripheral (magnetometry, kinematics) nervous systems, inclusive of the autonomic nervous system (electrocardiogram), as the participants perform natural tasks requiring different levels of intentional planning and automatic control. We find that magnetometer data during walking, across a variety of amplitude and timing signals, provide optimal separation of PD from neurotypical controls. We conclude that using multimodal signals within the context of actions that bear different levels of intent, can be revealing of features of PD that would scape the naked eye. Further, we add that clinical criteria combined with such optimal digital parameter spaces offer a far more complete picture of PD than using either one of these pieces of data alone.
Using Ice Cores to Evaluate CMIP6 Aerosol Concentrations Over the Historical Era
Authors: Moseid Kine Onsum , Schulz Michael , Eichler Anja , Schwikowski Margit , McConnell Joseph R. , Olivié Dirk , Criscitiello Alison S. , Kreutz Karl J. , Legrand Michel
Published: September 2022

The radiative effect of anthropogenic aerosols is one of the largest uncertainties in Earth's energy budget over the industrial period. This uncertainty is in part due to sparse observations of aerosol concentrations in the pre‐satellite era. To address this lack of measurements, ice cores can be used, which contain the aerosol concentration record. To date, these observations have been under‐utilized for comparison to aerosol concentrations found in state‐of‐the‐art Earth system models (ESMs). Here we compare long term trends in concentrations of sulfate and black carbon (BC) between 15 ice cores and 11 ESMs over nine regions around the world during the period 1850–2000. We find that for sulfate concentration trends model results generally agree with ice core records, whereas for BC concentration the model trends differ from the records. Absolute concentrations of both investigated species are overestimated by the models, probably in part due to representation errors. However, we assume that biases in relative trends are not altered by these errors. Ice cores in the European Alps and Greenland record a maximum BC concentration before 1950, while most ESMs used in this study agree on a post‐1950 maximum. We source this bias to an error in BC emission inventories in Europe. Emission perturbation experiments using NorESM2‐LM support the observed finding that BC concentrations in Northern Greenland ice cores are recording European emissions. Errors in BC emission inventories have implications for all future and past studies where Coupled Model Intercomparison Project Phase 6 historical simulations are compared to observations relevant to aerosol forcing.
Which Sudden Stratospheric Warming Events Are Most Predictable?
Authors: Chwat Dvir , Garfinkel Chaim I. , Chen Wen , Rao Jian
Published: September 2022

The predictability of Northern Hemisphere sudden stratospheric warming (SSW) events is considered in 10 subseasonal to seasonal (S2S) forecast models for 16 major SSWs that have occurred since 1998, a larger sample size than has been considered by previous works. The four factors that most succinctly distinguish those SSWs with above average predictability are a preconditioned vortex prior to the SSW, an active Madden‐Julian Oscillation with enhanced convection in the West Pacific, the Quasi‐Biennial Oscillation phase with easterlies in the lower stratosphere, and the vortex morphology (displacement more predictable). Two of these factors appear to not have been considered in previous works focusing on a large sample of events. Most of these effects are not statistically significant at the 95% level due to the still relatively small sample size, though all would exceed a 90% criteria at least marginally. Combined, however, they account for 40% of the inter‐event spread in SSW predictability, thus indicating that SSWs with favorable precursors are significantly more predictable.
Tumor-derived exosomes deliver the tumor suppressor miR-3591-3p to induce M2 macrophage polarization and promote glioma progression
Authors: Li Ming , Xu Hao , Qi Yanhua , Pan Ziwen , Li Boyan , Gao Zijie , Zhao Rongrong , Xue Hao , Li Gang
Published: September 2022

Exosomes can selectively secrete harmful metabolic substances from cells to maintain cellular homeostasis, and complex crosstalk occurs between exosomes and tumor-associated macrophages (TAMs) in the glioma immune microenvironment. However, the precise mechanisms by which these exosome-encapsulated cargos create an immunosuppressive microenvironment remain unclear. Herein, we investigated the effect of glioma-derived exosomes (GDEs) on macrophage polarization and glioma progression. We performed sequencing analysis of cerebrospinal fluid (CSF) and tumor tissues from glioma patients to identify functional microRNAs (miRNAs). High levels of miR-3591-3p were found in CSF and GDEs but not in normal brain tissue or glial cells. Functionally, GDEs and miR-3591-3p significantly induced M2 macrophage polarization and increased the secretion of IL10 and TGFβ1, which in turn promoted glioma invasion and migration. Moreover, miR-3591-3p overexpression in glioma cell lines resulted in G2/M arrest and markedly increased apoptosis. Mechanistically, miR-3591-3p can directly target CBLB and MAPK1 in macrophages and glioma cells, respectively, and further activate the JAK2/PI3K/AKT/mTOR, JAK2/STAT3, and MAPK signaling pathways. In vivo experiments confirmed that macrophages lentivirally transduced with miR-3591-3p can significantly promote glioma progression. Thus, our study demonstrates that tumor-suppressive miR-3591-3p in glioma cells can be secreted via exosomes and target TAMs to induce the formation of an immunosuppressive microenvironment. Collectively, these findings provide new insights into the role of glioma exosomal miRNAs in mediating the establishment of an immunosuppressive tumor microenvironment and show that miR-3591-3p may be a valuable biomarker and that blocking the encapsulation of miR-3591-3p into exosomes may become a novel immunotherapeutic strategy for glioma.
Decolonisation of curricula in undergraduate dental education: an exploratory study
Authors: Ali Kamran , Winter Jennie , Webb Oliver , Zahra Daniel
Published: September 2022

Aims To explore experiences and perceptions of students and staff regarding decolonisation of the curriculum in a dental undergraduate programme.

Methods Participants were invited to respond to an online survey on decolonisation of the dental curriculum. The target population included current students on the Bachelor of Dental Surgery and Bachelor of Dental Therapy and Hygiene programmes, as well as dental staff at a university in the South West region of England. The common items for student and staff versions of the survey were focused on six themes: representation; content; peer engagement; assessment; language and communication; and culture. All responses were anonymous. Data on programme, year of study, age, sex and ethnicity were captured on a voluntary basis.

Results In total, 34 staff members and 120 students from two different programmes participated in the survey, yielding a response rate of 87.17% for staff and 45.28% for students. A comparison showed that average student responses were lower compared with average staff responses. Of the 24 survey items, 17 showed significantly lower scores reported by minority ethnic (ME) students. ME students were, when compared with white counterparts, less likely to report that their programme included opportunities for group discussions about ethnicity and privilege. Similar comparisons of staff responses did not show significant differences between white and ME staff. Nevertheless, responses by staff and students across the board highlighted the need for further steps to improve the representation of ME groups in the curriculum.

Conclusions This study provides useful insights into the perceptions and experiences of students and staff regarding the decolonisation of the dental curriculum in an undergraduate dental programme. Responses by the participants across the board identified several areas which could benefit from better representation of ME groups. Significant differences were noted between staff and student scores and also between white and ME students, indicating the latter group demonstrated more awareness regarding issues of representation. The findings underscore the need to take further steps to decolonise dental curricula.
Deubiquitinase OTUD5 modulates mTORC1 signaling to promote bladder cancer progression
Authors: Hou Tao , Dan Weichao , Liu Tianjie , Liu Bo , Wei Yi , Yue Chenyang , Que Taotao , Ma Bohan , Lei Yuzeshi , Wang Zixi , Zeng Jin , Fan Yizeng , Li Lei
Published: September 2022

The mechanistic (formally “mammalian”) target of rapamycin (mTOR) pathway serves as a crucial regulator of various biological processes such as cell growth and cancer progression. In bladder cancer, recent discoveries showing the cancer-promoting role of mTOR complex 1 have attracted wide attention. However, the regulation of mTOR signaling in bladder cancer is complicated and the underlying mechanism remains elusive. Here, we report that the deubiquitinating enzyme, ovarian tumor domain-containing protein 5 (OTUD5), can activate the mTOR signaling pathway, promote cancer progression, and show its oncogenic potential in bladder cancer. In our study, we found that OTUD5 deubiquitinated a RING-type E3 ligase, RNF186, and stabilized its function. In addition, the stabilization of RNF186 further led to the degradation of sestrin2, which is an inhibitor of the mTOR signaling pathway. Together, we provide novel insights into the pathogenesis of bladder cancer and first prove that OTUD5 can promote bladder cancer progression through the OTUD5-RNF186-sestrin2-mTOR axis, which may be exploited in the future for the diagnosis and treatment of this malignancy.
Front-of-pack nutrition labels: an equitable public health intervention
Authors: Pettigrew Simone , Jongenelis Michelle I. , Hercberg Serge , Julia Chantal
Published: September 2022

It is important for nutrition interventions to be equitable to ensure they do not widen socioeconomic health-based inequalities. The role of front-of-pack nutrition labels is to provide accessible and easily understood information on product packages, and it is essential that such labels assist those who are least able to access and interpret other forms of nutrition information. This secondary analysis of the FOP-ICE food labelling study involving 18 countries (N = 18,393) assessed whether five different front-of-pack labels varied in effectiveness according to income status. The two outcome variables were objective understanding of products’ nutritional quality and product choice. While there were substantial differences in the ability of individual labels to improve understanding, for each label and across all labels combined there were no significant differences in changes in both outcome variables by income category. The results provide evidence that interpretive front-of-pack nutrition labels are an equitable and useful nutrition intervention.
Quantum nonlinear spectroscopy of single nuclear spins
Authors: Meinel Jonas , Vorobyov Vadim , Wang Ping , Yavkin Boris , Pfender Mathias , Sumiya Hitoshi , Onoda Shinobu , Isoya Junichi , Liu Ren-Bao , Wrachtrup J.
Published: September 2022

Conventional nonlinear spectroscopy, which use classical probes, can only access a limited set of correlations in a quantum system. Here we demonstrate that quantum nonlinear spectroscopy, in which a quantum sensor and a quantum object are first entangled and the sensor is measured along a chosen basis, can extract arbitrary types and orders of correlations in a quantum system. We measured fourth-order correlations of single nuclear spins that cannot be measured in conventional nonlinear spectroscopy, using sequential weak measurement via a nitrogen-vacancy center in diamond. The quantum nonlinear spectroscopy provides fingerprint features to identify different types of objects, such as Gaussian noises, random-phased AC fields, and quantum spins, which would be indistinguishable in second-order correlations. This work constitutes an initial step toward the application of higher-order correlations to quantum sensing, to examining the quantum foundation (by, e.g., higher-order Leggett-Garg inequality), and to studying quantum many-body physics.
Targeted immunotherapy against distinct cancer-associated fibroblasts overcomes treatment resistance in refractory HER2+ breast tumors
Authors: Rivas Elisa I. , Linares Jenniffer , Zwick Melissa , Gómez-Llonin Andrea , Guiu Marc , Labernadie Anna , Badia-Ramentol Jordi , Lladó Anna , Bardia Lídia , Pérez-Núñez Iván , Martínez-Ciarpaglini Carolina , Tarazona Noelia , Sallent-Aragay Anna , Garrido Marta , Celià-Terrassa Toni , Burgués Octavio , Gomis Roger R. , Albanell Joan , Calon Alexandre
Published: September 2022

About 50% of human epidermal growth factor receptor 2 (HER2)+ breast cancer patients do not benefit from HER2-targeted therapy and almost 20% of them relapse after treatment. Here, we conduct a detailed analysis of two independent cohorts of HER2+ breast cancer patients treated with trastuzumab to elucidate the mechanisms of resistance to anti-HER2 monoclonal antibodies. In addition, we develop a fully humanized immunocompetent model of HER2+ breast cancer recapitulating ex vivo the biological processes that associate with patients’ response to treatment. Thanks to these two approaches, we uncover a population of TGF-beta-activated cancer-associated fibroblasts (CAF) specific from tumors resistant to therapy. The presence of this cellular subset related to previously described myofibroblastic (CAF-S1) and podoplanin+ CAF subtypes in breast cancer associates with low IL2 activity. Correspondingly, we find that stroma-targeted stimulation of IL2 pathway in unresponsive tumors restores trastuzumab anti-cancer efficiency. Overall, our study underscores the therapeutic potential of exploiting the tumor microenvironment to identify and overcome mechanisms of resistance to anti-cancer treatment.
Intrinsic hard magnetism and thermal stability of a ThMn12-type permanent magnet
Authors: Ochirkhuyag Tumentsereg , Hong Soon Cheol , Odkhuu Dorj
Published: September 2022

Herein, we theoretically demonstrate that simple metal (Ga and Al) substitutional atoms, rather than the conventional transition metal substitutional elements, not only stabilize the ThMn12-type SmFe12 and Sm(Fe,Co)12 phases thermodynamically but also further improve their intrinsic magnetic properties such that they are superior to those of the widely investigated SmFe11Ti and Sm(Fe,Co)11Ti magnets, and even to the state-of-the-art permanent magnet Nd2Fe14B. More specifically, the quaternary Sm(Fe,Co,Al)12 phase has the highest uniaxial magnetocrystalline anisotropy (MCA) of about 8 MJ m−3, anisotropy field of 18.2 T, and hardness parameter of 2.8 at room temperature and a Curie temperature of 764 K. Simultaneously, the Al and Ga substitutional atoms improve the single-domain size of the Sm(Fe,Co)12 grains by nearly a factor of two. Numerical results of MCA and MCA-driven hard magnetic properties can be described by the strong spin-orbit coupling and orbital angular momentum of the Sm 4f-electron orbitals.
Predicting glass structure by physics-informed machine learning
Authors: Bødker Mikkel L. , Bauchy Mathieu , Du Tao , Mauro John C. , Smedskjaer Morten M.
Published: September 2022

Machine learning (ML) is emerging as a powerful tool to predict the properties of materials, including glasses. Informing ML models with knowledge of how glass composition affects short-range atomic structure has the potential to enhance the ability of composition-property models to extrapolate accurately outside of their training sets. Here, we introduce an approach wherein statistical mechanics informs a ML model that can predict the non-linear composition-structure relations in oxide glasses. This combined model offers an improved prediction compared to models relying solely on statistical physics or machine learning individually. Specifically, we show that the combined model accurately both interpolates and extrapolates the structure of Na2O–SiO2 glasses. Importantly, the model is able to extrapolate predictions outside its training set, which is evidenced by the fact that it is able to predict the structure of a glass series that was kept fully hidden from the model during its training.
Solution-processable through-space charge-transfer emitters via solubilizing groups modification
Authors: Zheng Qi , Wang Xue-Qi , Qu Yang-Kun , Xie Guohua , Liao Liang-Sheng , Jiang Zuo-Quan
Published: September 2022

The solubility of luminescent materials is a key parameter to improve the electroluminescent performances of solution-processed organic light-emitting diodes (OLEDs). The through-space charge transfer (TSCT) materials provide an alternative to introduce the solubilizing groups (SGs) to the linker. Herein, thetert-butyl andn-hexyl groups are introduced as SGs at C7 positions of spiro structure, namedC6-DMBandtBu-DMB, away from the acceptor. This has no influence on the photophysical properties of the parent TSCT molecule. Highly efficient solution-processed OLEDs were demonstrated with the maximum external quantum efficiencies of 21.0% and 21.7%, respectively. To the best of our knowledge, these are champions in the state-of-the-art solution-processed OLEDs with TSCT emitters. This work confirmed our conjecture of constructing highly efficient soluble emitters by transforming an outstanding TSCT material from thermal evaporation to solution-processed OLEDs with SGs simply integrated on the ‘bridge’ linker.
Parallel InAs nanowires for Cooper pair splitters with Coulomb repulsion
Authors: Kürtössy Olivér , Scherübl Zoltán , Fülöp Gergő , Lukács István Endre , Kanne Thomas , Nygård Jesper , Makk Péter , Csonka Szabolcs
Published: September 2022

Hybrid nanostructures consisting of two parallel InAs nanowires connected by an epitaxially grown superconductor (SC) shell recently became available. Due to the defect-free SC-semiconductor interface and the two quasi-one-dimensional channels being close by, these platforms can be utilized to spatially separate entangled pairs of electrons by using quantum dots (QD) in the so-called Cooper pair splitting (CPS) process. The minimized distance between the QDs overcomes the limitations of single-wire-based geometries and can boost the splitting efficiency. Here we investigate CPS in such a device where strong inter-dot Coulomb repulsion is also present and studied thoroughly. We analyze theoretically the slight reduction of the CPS efficiency imposed by the Coulomb interaction and compare it to the experiments. Despite the competition between crossed Andreev reflection (CAR) and inter-wire capacitance, a significant CPS signal is observed indicating the dominance of the superconducting coupling. Our results demonstrate that the application of parallel InAs nanowires with epitaxial SC is a promising route for the realization of parafermionic states relying on enhanced CAR between the wires.
Myogenesis defects in a patient-derived iPSC model of hereditary GNE myopathy
Authors: Schmitt Rebecca E. , Smith Douglas Y. , Cho Dong Seong , Kirkeby Lindsey A. , Resch Zachary T. , Liewluck Teerin , Niu Zhiyv , Milone Margherita , Doles Jason D.
Published: September 2022

Hereditary muscle diseases are disabling disorders lacking effective treatments. UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy (GNEM) is an autosomal recessive distal myopathy with rimmed vacuoles typically manifesting in late adolescence/early adulthood.GNEencodes the rate-limiting enzyme in sialic acid biosynthesis, which is necessary for the proper function of numerous biological processes. Outside of the causative gene, very little is known about the mechanisms contributing to the development of GNE myopathy. In the present study, we aimed to address this knowledge gap by querying the underlying mechanisms of GNE myopathy using a patient-derived induced pluripotent stem-cell (iPSC) model. Control and patient-specific iPSCs were differentiated down a skeletal muscle lineage, whereby patient-derived GNEM iPSC clones were able to recapitulate key characteristics of the human pathology and further demonstrated defects in myogenic progression. Single-cell RNA sequencing time course studies revealed clear differences between control and GNEM iPSC-derived muscle precursor cells (iMPCs), while pathway studies implicated altered stress and autophagy signaling in GNEM iMPCs. Treatment of GNEM patient-derived iMPCs with an autophagy activator improved myogenic differentiation. In summary, we report an in vitro, iPSC-based model of GNE myopathy and implicate defective myogenesis as a contributing mechanism to the etiology of GNE myopathy.
Evaluation of the causal relationship between smoking and schizophrenia in East Asia
Authors: Su Mei-Hsin , Lai Rou-Yi , Lin Yen-Feng , Chen Chia-Yen , Feng Yen-Chen A. , Hsiao Po-Chang , Wang Shi-Heng
Published: September 2022

Cigarette smoking has been suggested to be associated with the risk of schizophrenia in observational studies. A significant causal effect of smoking on schizophrenia has been reported in European populations using the Mendelian randomization approach; however, no evidence of causality was found in participants from East Asia. Using Taiwan Biobank (TWBB), we conducted genome-wide association studies (GWAS) to identify susceptibility loci for smoking behaviors, including smoking initiation (N = 79,989) and the onset age (N = 15,582). We then meta-analyzed GWAS from TWBB and Biobank Japan (BBJ) with the total sample size of 245,425 for smoking initiation and 46,000 for onset age of smoking. The GWAS for schizophrenia was taken from the East Asia Psychiatric Genomics Consortium, which included 22,778 cases and 35,362 controls. We performed a two-sample Mendelian randomization to estimate the causality of smoking behaviors on schizophrenia in East Asia. In TWBB, we identified one locus that met genome-wide significance for onset age. In a meta-analysis of TWBB and BBJ, we identified two loci for smoking initiation. In Mendelian randomization, genetically predicted smoking initiation (odds ratio (OR) = 4.00, 95% confidence interval (CI) = 0.89–18.01,P = 0.071) and onset age (OR for a per-year increase = 0.96, 95% CI = 0.91–1.01,P = 0.098) were not significantly associated with schizophrenia; the direction of effect was consistent with European Ancestry samples, which had higher statistical power. These findings provide tentative evidence consistent with a causal role of smoking on the development of schizophrenia in East Asian populations.
Biogenic silver nanoparticles-modified forward osmosis membranes with mitigated internal concentration polarization and enhanced antibacterial properties
Authors: Wu Xing , Fang Fang , Zhang Bifeng , Wu Jun Jie , Zhang Kaisong
Published: September 2022

Thin-film composite forward osmosis (TFC-FO) membranes show the potential to be applied in water treatment applications. However, the TFC-FO membrane performance was limited by internal concentration polarization (ICP) and membrane fouling. In this study, a well-functioning TFC-FO membrane was produced by embedding biogenic silver nanoparticles (BioAg) into the polysulfone (PSf) substrate of a FO membrane. Effects of BioAg on membrane structure, filtration performance, antifouling, and antibacterial properties of the as-prepared FO membranes were examined. Results indicated that BioAg-modified FO membranes achieved improved surface hydrophilicity, higher porosity, and mitigated ICP, resulting in 2.5–4.4 times higher water flux than the pristine FO membranes. The BioAg-modified FO membrane also showed significantly improved antifouling and antibacterial ability. Moreover, the release velocity of silver nanoparticles in FO membranes was significantly slowed down by the construction of the polyamide layer. After 30 days of immersion in an aqueous solution, 96.5% of silver was retained in the optimized BioAg-modified FO membrane. The study offers an effective approach to simultaneously mitigate ICP and enhance the antifouling property of TFC-FO membranes through substrate modification.
Temperature dependent in vitro binding and release of target DNA by Cas9 enzyme
Authors: David Serene Rose , Maheshwaram Sumanth Kumar , Shet Divya , Lakshminarayana Mahesh B. , Soni Gautam V.
Published: September 2022

The CRISPR-associated protein 9 (Cas9) system has proven to be a powerful technology for genome editing in a wide variety of in vivo and in vitro applications. CRISPR–Cas9, when loaded with the guide RNA, cleaves the DNA at the target position as recognized by the guide RNA sequence. For successful application of this technology, it is important to study the biophysical parameters affecting its function. Temperature dependence of the Cas9 binding as well as energetics of product release after cleavage has not been well reported in the literature. In this work, we study the binding properties of Cas9 enzyme to the sequence specific target DNA at a range of temperatures and, surprisingly, find that the Cas9 enzyme, in our study, can find and bind its target DNA with 90 ± 20% efficiency at temperatures as low as 4 °C. Further, we show that the cleaved DNA products remain bound to the Cas9 enzyme strongly and is released from the enzyme only at higher temperatures. Using the gel shift assays, we quantify the rate of Cas9 binding to target DNA to be 0.8 ± 0.2 min−1 at 37 °C. We also tested denaturant (SDS) dependent release of cleaved product which showed a similar release pattern with a dissociation constant of 0.23 ± 0.04 mM. Our results of heat and denaturant dependence on Cas9–DNA binding and release mechanics will provide valuable insights for developing temperature dependent applications of the CRISPR–Cas9 technology.