bluuebunny/crossref_metadata_2025 huggingface dataset:
Reformulating Graham v. Connor’s Excessive Force Test to ADApt for Individuals with Disabilities
Authors: Prater-Lee Christiana
Published: March 2022

Individuals with disabilities are sixteen times more likely to be killed by officers during a law enforcement encounter than other individuals. As the ever-growing list of victims demonstrates, law enforcement violence against individuals with disabilities is a national crisis. Yet, the current test, developed under Graham v. Connor, for whether officers’ use of force is excessive during an arrest considers only three factors: severity of the crime, immediacy of the threat, and resistance to arrest or attempts to flee. On its face, Graham’s three-factor test does not contemplate whether an arrestee’s individual characteristics are relevant to an officer’s use of force. Recognizing that the Graham factors are “non-exhaustive” and “flexible,” some lower federal courts have relaxed the excessive force test to account for particular circumstances. However, there is no consensus among the circuit courts and the Supreme Court has not revisited the Graham test.

Over three decades later, courts still do not have sufficient guidance on how to address individual disability under Graham. This Note advocates that in adherence to Graham’s expressed flexibility, its three-factor test should be reformulated to add in a fourth factor inspired by Title II of the Americans with Disabilities Act to account for whether “reasonable modifications” of an individual’s disability were made in situations when law enforcement employs force during the course of an arrest. Applying this standard in cases where an officer “reasonably should know” the arrestee has a disability promotes a baseline assumption that law enforcement officers have an active role in accommodating all disabilities.
Creating informed consumers of aquatic invasive species management programs through online education for nonprofessionals
Authors: Weber Megan M. , Larkin Daniel J. , Mulcahy Patrick
Published: March 2022

There are limited educational opportunities regarding aquatic invasive species (AIS) management that target laypersons. This is a significant gap, particularly as nonprofessionals are often tasked with making decisions about whether and how to pursue AIS control efforts, for example, through their roles in community lake associations. Thus, there is a need for educational programs to help consumers of AIS management services, “do-it-yourself” lakeshore homeowners, and other engaged nonprofessionals gain a stronger foundation in the science and practice of AIS management. We helped fill this unmet need through development of a new online course, AIS Management 101, that targets lakeshore property owners, lake association members, and other nonprofessionals engaged in AIS decision making, seeking to make them better-informed consumers. The course covers concepts ranging from basic invasive species biology to pesticide science, treatment evaluation, regulations and permitting, and nonchemical management tools. Participants in the course demonstrated significant knowledge gains through check-in and check-out knowledge assessments. Course participants also reported greater understanding of key issues pertaining to AIS management and application of this improved knowledge to actual management decisions following completion of the course. While this program focuses on management ofaquaticinvasive species, similar approaches could be applied to lay audiences engaged in management of terrestrial invasive species or other natural resource issues.
Linear and nonlinear optimal growth mechanisms for generating turbulent bands
Authors: Parente E. , Robinet J.-Ch. , De Palma P. , Cherubini S.
Published: March 2022

Recently, many authors have investigated the origin and growth of turbulent bands in shear flows, highlighting the role of streaks and their inflectional instability in the process of band generation and sustainment. Recalling that streaks are created by an optimal transient growth mechanism, and motivated by the observation of a strong increase of the disturbance kinetic energy corresponding to the creation of turbulent bands, we use linear and nonlinear energy optimisations in a tilted domain to unveil the main mechanisms allowing the creation of a turbulent band in a channel flow. Linear transient growth analysis shows an optimal growth for wavenumbers having an angle of approximately$35^\circ$, close to the peak values of the premultiplied energy spectra of direct numerical simulations. This linear optimal perturbation generates oblique streaks, which, for a sufficiently large initial energy, induce turbulence in the whole domain, due to the lack of spatial localisation. However, spatially localised perturbations obtained by adding nonlinear effects to the optimisation or by artificially confining the linear optimal to a localised region in the transverse direction are characterised by a large-scale flow and lead to the generation of a localised turbulent band. These results suggest that two main elements are needed for inducing turbulent bands in a tilted domain: (i) a linear energy growth mechanism, such as the lift-up, for generating large-amplitude flow structures, which produce inflection points; (ii) spatial localisation, linked to the presence or generation of large-scale vortices. We show that these elements alone generate isolated turbulent bands also in large non-tilted domains.
Clustering of motivational constructs based on self-determination theory for diet and physical activity and their associations with behaviour: a cross-sectional study
Authors: Coumans Juul M. J. , Lechner Lilian , Bolman Catherine A. W. , Oenema Anke
Published: March 2022

The present study explored whether motivational constructs for diet and physical activity (PA) cluster and how these motivational constructs relate to dietary and PA behaviour. Data of 1142 participants were used from a randomised controlled trial examining the effects of a web-based diet and PA promotion intervention based on self-determination theory and motivational interviewing. Motivation was assessed using the Treatment Self-Regulation Questionnaire and Behavioural Regulation in Exercise Questionnaire. The dietary outcomes were measured using an adapted Food Frequency Questionnaire. PA was assessed using the Short QUestionnaire to ASsess Health. Spearman rank-order correlations showed large correlation coefficients (rs ≥ 0⋅63) between similar motivational constructs between the two lifestyle domains, except for intrinsic motivation where a medium correlation coefficient was found (rs = 0⋅41). Furthermore, the exploratory factor analysis illustrated that more self-determined forms of motivation seem to be more domain-specific. In contrast, non-self-determined forms of motivation seem to be domain-independent. Last, regression analyses demonstrated that intrinsic motivation towards PA was the only motivational construct significantly positively associated with all PA sub-behaviours (standardised regression coefficients ranging from 0⋅17 to 0⋅28, all P < 0⋅0125). Intrinsic motivation to eat healthily was significantly positively associated with fruits, vegetables and fish intake (standardised regression coefficients ranging from 0⋅11 to 0⋅16, all P < 0⋅0125), but not with unhealthy snacks. Insight of this exploratory study is useful for understanding the interrelationships of motivational induced behaviours, the development of interventions targeting multiple behaviours, and the construction of questionnaires.
WESTMINSTER HALL’S LOST STUART DOOR PASSAGE REDISCOVERED
Authors: Hallam Smith Elizabeth , Crook John
Published: March 2022

In 2018 unpublished archaeological evidence was discovered recording a doorway and passageway concealed inside the Romanesque wall of Westminster Hall, near the south-east corner. Although commemorated by a bronze plaque in situ, their existence had largely been forgotten. Further investigations revealed an access panel in the 1951 cloakroom fittings in adjoining St Stephen’s cloister: this was located, and the space accessed, seemingly for the first time since c 1952. The many features of interest found within included the doorcase and soffits of a great doorway and iron pintles for the doors; Purbeck flagstones on the floor; complex masonry and plaster from several different eras; graffiti by masons from the nineteenth and twentieth centuries; a still-functional Osram lightbulb dating from the early 1950s; and wooden joists supporting the masonry of the ceiling. Isotope dating of the timbers produced a date of 1659, and works accounts showed that the doorway and passageway were created in 1660–1, to form a ceremonial route for the coronation of Charles ii. Further archaeological and historical investigations have enabled the authors to establish a full chronology for the changing fabric and uses of the doorway and passageway from the seventeenth to the twenty-first century, and to trace the masons who walled in the space in 1851. They have also established why the brass plaque in Westminster Hall marking the space erroneously ascribes it with Tudor origins: that ‘fake history’ was created by an over-enthusiastic late-nineteenth century Clerk of the House of Commons.
Digital Social Policy: Past, Present, Future
Authors: HENMAN PAUL W. FAY
Published: March 2022

We undoubtably live in a digitally infused world. From government administrative processes to financial transactions and social media posts, digital technologies automatically collect, collate, combine and circulate digital traces of our actions and thoughts, which are in turn used to construct digital personas of us. More significantly, government decisions are increasingly automated with real world effect; companies subvert human workers to automated processes; while social media algorithms prioritise outrage and ‘fake news’ with destabilizing and devastating effects for public trust in social institutions. Accordingly, what it means to be a person, a citizen, and a consumer, and what constitutes society and the economy in the 21stcentury is profoundly different to that in the 20thcentury.
Popular Propaganda: John Heywood's Wedding Ballad and Mary I's Spanish Match
Authors: Hyde Jenni
Published: March 2022

The text of John Heywood's wedding ballad for Mary I and Philip of Spain,A Balade specifienge partly the maner, has been underestimated for many years. It is criticised for the poor quality of its poetry and lambasted for its tortured imagery. Instead, this article re-evaluates the ballad as a highly effective popular song intended to spread propaganda defending the queen's Spanish match. It argues that the song performed an excellent job of addressing complex constitutional issues through a quintessentially popular genre, while at the same time successfully overcoming the problem of fitting new words to a pre-existing tune. Furthermore, it is proposed that the song was deliberately set to the melody from Henry VIII's ballad ‘Pastyme with good companye’ and, by drawing on the latest research into cultures of creativity and examining what resonances the tune would have had for its listeners, it suggests that the potential multivalency of the melody was crucially important for understanding the song and its reception.
Acceptability of Manufacturer-Proposed Utility Values for NICE Cancer Medicine Appraisals: Analysis of Manufacturers’ Information Sources
Authors: Takada Shunsuke , Narukawa Mamoru
Published: March 2022

Objectives

The National Institute for Health and Care Excellence’s (NICE) method guide for technology appraisals (TAs) encourages medicine manufacturers to use the EuroQol 5 Dimensions (EQ-5D) in relevant clinical trials to obtain utility values; however, the EQ-5D may have low sensitivity when compared to disease-specific measures. This study investigated whether the NICE TA committee’s acceptance of manufacturer-proposed utility values is dependent on the manufacturers’ sources of the utility values.

Methods

Using publicly available data for 2011–2020, we identified 136 single TAs of cancer medicines, the health-related quality-of-life-measures used in relevant clinical trials, manufacturers’ sources of utility values, and the NICE TA committee’s acceptance of these values. Fisher’s exact tests were performed to compare the acceptability of different value sources and reasons for non-acceptance.

Results

The number of appraisals for which the EQ-5D in the relevant clinical trials was the source of the manufacturer-proposed utility values increased continuously over time. The TA committee’s acceptance of values was not dependent on the information source. In cases where a submission for which the information source was the EQ-5D was rejected, the reason was generally related to inappropriate values for the UK population or inappropriate data adjustment, not data reliability.

Conclusions

Our results demonstrated that according with the NICE’s method guide regarding utility values does not guarantee acceptance by the TA committee. Manufacturers must consider in advance possible differences between their clinical trials and clinical practice in the UK and refine plans for EQ-5D measurement in order to obtain convincing evidence.
REJECTION, DENIAL AND THE DEMOCRATIC PRIMARIES
Authors: Incurvati Luca
Published: March 2022

Starting from the case of insurance claims, I investigate the dynamics of acceptance, rejection and denial. I show that disagreement can be more varied than one might think. I illustrate this by looking at the Warren/Sanders controversy in the 2020 democratic primaries and at religious agnosticism.
The transformative forces of international law? Questioning equality regimes from a multi-level perspective
Authors: Eichler Jessika
Published: March 2022

This article approaches current constitutional conservatism in Europe, focusing on the limits of equality rights regimes. These frameworks, it is argued, provide little leverage for positive discrimination to become articulated, let alone for them to be implemented by public policies. Equality regimes are further disentangled by means of a multidimensional reading of legal orders: particular attention is devoted to international human rights law (IHRL) and European Jus Commune that may inspire shifts in constitutional thinking at domestic levels. In that sense, equality frameworks steadily open up towards an inclusive understanding of human rights based on the transformative forces of international law. A pluralistic idea of those subjected to such regimes will be embraced, hence developing a clearer conception of rights holder categories and ultimately peoples affected in daily practice, particularly minorities. A dedicated focus is placed on ethnic, cultural, religious and linguistic grounds. This may similarly concern intersectionalities and the complexities of overlapping grounds of discrimination. It is stressed that equality is best addressed by means of a multivariate approach to legal orders, their dynamics and ultimately virtuous effects of application.
Entwicklung und Evaluation eines Screening-Verfahrens zur Prognose von Rechenschwierigkeiten in der Grundschule
Authors: Clausen-Suhr Kristina , Walter Jürgen
Published: March 2022

Zusammenfassung. Hintergrund: Einen wichtigen Baustein im Rahmen der Prävention von Rechenschwierigkeiten stellen Screening-Verfahren dar, die ein individuelles Entwicklungsrisiko zuverlässig und frühzeitig aufzeigen. Die meisten Instrumente zur Prognose solcher Schwächen im Grundschulalter sind überwiegend als vergleichsweise zeitaufwändige Einzelverfahren konzipiert. Das Ziel der vorliegenden Studie ist die Entwicklung und Evaluation eines gruppenbasierten Screening-Verfahrens für den Einsatz am Schulanfang. Methode: Im vorliegenden Beitrag werden die Entwicklung und Evaluation eines Filter-Screenings an einer Stichprobe von insgesamt 174 Erstklässlern beschrieben. Ein breites Variablen-Set aus domänenspezifischen und domänenunspezifischen Prädiktoren der mathematischen Leistung wurde in die Analyse einbezogen. Resultate: Auf der Basis der logistischen Regressionsanalyse konnte ein durch eine Kreuzvalidierung abgesichertes Vier-Variablen- Prognosemodell (Mengenschätzen, Vorgänger benennen, Zahlen lesen, Matrizen-Test) identifiziert werden, das sehr gute AUC-Werte (bis zu >> .90) aufweist. Diskussion: Die Ergebnisse liefern wertvolle Erkenntnisse hinsichtlich der Implementation eines validen und Schuleingangsscreenings als Gruppenverfahren.
Krankheitsängste bei Psychotherapeut_innen
Authors: Roth-Rawald Julia , Weck Florian
Published: March 2022

Zusammenfassung. Hintergrund: Krankheitsängste beziehen sich meist auf die Angst vor dem Leiden an somatischen Erkrankungen. In Einzelfallberichten wurden auch Ängste vor psychischen Störungen berichtet, jedoch bisher nicht systematisch untersucht. Psychotherapeut_innen sind ständig mit psychischen Erkrankungen konfrontiert. Fragestellung: Diese Studie untersucht, wie stark Krankheitsängste bei Psychotherapeut_innen ausgeprägt sind und welche Faktoren diese beeinflussen. Methoden: Insgesamt 239 Psychotherapeut_innen wurden per anonymer Onlinebefragung mit den Illness Attitude Scales und der Mini-Symptom-Checklist untersucht. Ergebnisse: Krankheitsängste bei Psychotherapeut_innen waren geringer ausgeprägt als in der Allgemeinbevölkerung und bei Psychologiestudierenden. Faktoren wie die allgemeine psychische Belastung und das Vorhandensein tatsächlicher Diagnosen gingen mit erhöhten Krankheitsängsten einher. Schlussfolgerungen: Krankheitsängste können sich nicht nur auf somatische Erkrankungen beziehen, sondern auch psychische Störungen betreffen. Eine stärkere Berücksichtigung psychischer Krankheitsängste und deren weitere systematische Erfassung erscheinen daher wünschenswert.
Sea Ice Rheology Experiment (SIREx): 2. Evaluating Linear Kinematic Features in High‐Resolution Sea Ice Simulations
Authors: Hutter Nils , Bouchat Amélie , Dupont Frédéric , Dukhovskoy Dmitry , Koldunov Nikolay , Lee Younjoo J. , Lemieux Jean‐François , Lique Camille , Losch Martin , Maslowski Wieslaw , Myers Paul G. , Ólason Einar , Rampal Pierre , Rasmussen Till , Talandier Claude , Tremblay Bruno , Wang Qiang
Published: March 2022

Simulating sea ice drift and deformation in the Arctic Ocean is still a challenge because of the multiscale interaction of sea ice floes that compose the Arctic Sea ice cover. The Sea Ice Rheology Experiment (SIREx) is a model intercomparison project of the Forum of Arctic Modeling and Observational Synthesis (FAMOS). In SIREx, skill metrics are designed to evaluate different recently suggested approaches for modeling linear kinematic features (LKFs) to provide guidance for modeling small‐scale deformation. These LKFs are narrow bands of localized deformation that can be observed in satellite images and also form in high resolution sea ice simulations. In this contribution, spatial and temporal properties of LKFs are assessed in 36 simulations of state‐of‐the‐art sea ice models and compared to deformation features derived from the RADARSAT Geophysical Processor System. All simulations produce LKFs, but only very few models realistically simulate at least some statistics of LKF properties such as densities, lengths, or growth rates. All SIREx models overestimate the angle of fracture between conjugate pairs of LKFs and LKF lifetimes pointing to inaccurate model physics. The temporal and spatial resolution of a simulation and the spatial resolution of atmospheric boundary condition affect simulated LKFs as much as the model's sea ice rheology and numerics. Only in very high resolution simulations (≤2 km) the concentration and thickness anomalies along LKFs are large enough to affect air‐ice‐ocean interaction processes.
Sea Ice Rheology Experiment (SIREx): 1. Scaling and Statistical Properties of Sea‐Ice Deformation Fields
Authors: Bouchat Amélie , Hutter Nils , Chanut Jérôme , Dupont Frédéric , Dukhovskoy Dmitry , Garric Gilles , Lee Younjoo J. , Lemieux Jean‐François , Lique Camille , Losch Martin , Maslowski Wieslaw , Myers Paul G. , Ólason Einar , Rampal Pierre , Rasmussen Till , Talandier Claude , Tremblay Bruno , Wang Qiang
Published: March 2022

As the sea‐ice modeling community is shifting to advanced numerical frameworks, developing new sea‐ice rheologies, and increasing model spatial resolution, ubiquitous deformation features in the Arctic sea ice are now being resolved by sea‐ice models. Initiated at the Forum for Arctic Modeling and Observational Synthesis, the Sea Ice Rheology Experiment (SIREx) aims at evaluating state‐of‐the‐art sea‐ice models using existing and new metrics to understand how the simulated deformation fields are affected by different representations of sea‐ice physics (rheology) and by model configuration. Part 1 of the SIREx analysis is concerned with evaluation of the statistical distribution and scaling properties of sea‐ice deformation fields from 35 different simulations against those from the RADARSAT Geophysical Processor System (RGPS). For the first time, the viscous‐plastic (and the elastic‐viscous‐plastic variant), elastic‐anisotropic‐plastic, and Maxwell‐elasto‐brittle rheologies are compared in a single study. We find that both plastic and brittle sea‐ice rheologies have the potential to reproduce the observed RGPS deformation statistics, including multi‐fractality. Model configuration (e.g., numerical convergence, atmospheric representation, spatial resolution) and physical parameterizations (e.g., ice strength parameters and ice thickness distribution) both have effects as important as the choice of sea‐ice rheology on the deformation statistics. It is therefore not straightforward to attribute model performance to a specific rheological framework using current deformation metrics. In light of these results, we further evaluate the statistical properties of simulated Linear Kinematic Features in a SIREx Part 2 companion paper.
Deep Learning for Improving Numerical Weather Prediction of Heavy Rainfall
Authors: Hess Philipp , Boers Niklas
Published: March 2022

The accurate prediction of rainfall, and in particular of the heaviest rainfall events, remains challenging for numerical weather prediction (NWP) models. This may be due to subgrid‐scale parameterizations of processes that play a crucial role in the multi‐scale dynamics generating rainfall, as well as the strongly intermittent nature and the highly skewed, non‐Gaussian distribution of rainfall. Here we show that a U‐Net‐based deep neural network can learn heavy rainfall events from a NWP ensemble. A frequency‐based weighting of the loss function is proposed to enable the learning of heavy rainfall events in the distributions' tails. We apply our framework in a post‐processing step to correct for errors in the model‐predicted rainfall. Our method yields a much more accurate representation of relative rainfall frequencies and improves the forecast skill of heavy rainfall events by factors ranging from two to above six, depending on the event magnitude.
The Data Synergy Effects of Time‐Series Deep Learning Models in Hydrology
Authors: Fang Kuai , Kifer Daniel , Lawson Kathryn , Feng Dapeng , Shen Chaopeng
Published: March 2022

When fitting statistical models to variables in geoscientific disciplines such as hydrology, it is a customary practice to stratify a large domain into multiple regions (or regimes) and study each region separately. Traditional wisdom suggests that models built for each region separately will have higher performance because of homogeneity within each region. However, each stratified model has access to fewer and less diverse data points. Here, through two hydrologic examples (soil moisture and streamflow), we show that conventional wisdom may no longer hold in the era of big data and deep learning (DL). We systematically examined an effect we call data synergy, where the results of the DL models improved when data were pooled together from characteristically different regions. The performance of the DL models benefited from modest diversity in the training data compared to a homogeneous training set, even with similar data quantity. Moreover, allowing heterogeneous training data makes eligible much larger training datasets, which is an inherent advantage of DL. A large, diverse data set is advantageous in terms of representing extreme events and future scenarios, which has strong implications for climate change impact assessment. The results here suggest the research community should place greater emphasis on data sharing.
Proteomic profiling based classification of CLL provides prognostication for modern therapy and identifies novel therapeutic targets
Authors: Griffen Ti’ara L. , Hoff Fieke W. , Qiu Yihua , Lillard James W. , Ferrajoli Alessandra , Thompson Philip , Toro Endurance , Ruiz Kevin , Burger Jan , Wierda William , Kornblau Steven M.
Published: March 2022

Protein expression for 384 total and post-translationally modified proteins was assessed in 871 CLL and MSBL patients and was integrated with clinical data to identify strategies for improving diagnostics and therapy, making this the largest CLL proteomics study to date. Proteomics identified six recurrent signatures that were highly prognostic of survival and time to first or second treatment at three levels: individual proteins, when grouped into 40 functionally related groups (PFGs), and systemically in signatures (SGs). A novel SG characterized by hairy cell leukemia like proteomics but poor therapy response was discovered. SG membership superseded other prognostic factors (Rai Staging, IGHV Status) and were prognostic for response to modern (BTK inhibition) and older CLL therapies. SGs and PFGs membership provided novel drug targets and defined optimal candidates for Watch and Wait vs. early intervention. Collectively proteomics demonstrates promise for improving classification, therapeutic strategy selection, and identifying novel therapeutic targets.
Gpr125 is a unifying hallmark of multiple mammary progenitors coupled to tumor latency
Authors: Spina Elena , Simundza Julia , Incassati Angela , Chandramouli Anupama , Kugler Matthias C. , Lin Ziyan , Khodadadi-Jamayran Alireza , Watson Christine J. , Cowin Pamela
Published: March 2022

Gpr125 is an orphan G-protein coupled receptor, with homology to cell adhesion and axonal guidance factors, that is implicated in planar polarity and control of cell movements. By lineage tracing we demonstrate that Gpr125 is a highly specific marker of bipotent mammary stem cells in the embryo and of multiple long-lived unipotent basal mammary progenitors in perinatal and postnatal glands. Nipple-proximal Gpr125+ cells express a transcriptomic profile indicative of chemo-repulsion and cell movement, whereas Gpr125+ cells concentrated at invasive ductal tips display a hybrid epithelial-mesenchymal phenotype and are equipped to bind chemokine and growth factors and secrete a promigratory matrix. Gpr125 progenitors acquire bipotency in the context of transplantation and cancer and are greatly expanded and massed at the pushing margins of short latency MMTV-Wnt1 tumors. High Gpr125 expression identifies patients with particularly poor outcome within the basal breast cancer subtype highlighting its potential utility as a factor to stratify risk.
Excellently balanced water-intercalation-type heat-storage oxide
Authors: Hatakeyama Takuya , Okamoto Norihiko L. , Otake Satoshi , Sato Hiroaki , Li Hongyi , Ichitsubo Tetsu
Published: March 2022

Importance of heat storage materials has recently been increasing. Although various types of heat storage materials have been reported to date, there are few well-balanced energy storage materials in terms of long lifetime, reversibility, energy density, reasonably fast charge/discharge capability, and treatability. Here we report an interesting discovery that a commonly known substance, birnessite-type layered manganese dioxide with crystal water (δ-type K0.33MnO2 ⋅ nH2O), exhibits a water-intercalation mechanism and can be an excellently balanced heat storage material, from the above views, that can be operated in a solid state with water as a working pair. The volumetric energy density exceeds 1000 MJ m−3 (at n ~ 0.5), which is close to the ideally maximum value and the best among phase-change materials. The driving force for the water intercalation is also validated by the ab initio calculations. The proposed mechanism would provide an optimal solution for a heat-storage strategy towards low-grade waste-heat applications.
Homeostatic serum IgE is secreted by plasma cells in the thymus and enhances mast cell survival
Authors: Kwon Dong-il , Park Eun Seo , Kim Mingyu , Choi Yoon Ha , Lee Myeong-seok , Joo Si-hyung , Kang Yeon-Woo , Lee Minji , Jo Saet-byeol , Lee Seung-Woo , Kim Jong Kyoung , Lee You Jeong
Published: March 2022

Increased serum levels of immunoglobulin E (IgE) is a risk factor for various diseases, including allergy and anaphylaxis. However, the source and ontogeny of B cells producing IgE under steady state conditions are not well defined. Here, we show plasma cells that develop in the thymus and potently secrete IgE and other immunoglobulins, including IgM, IgA, and IgG. The development of these IgE-secreting plasma cells are induced by IL-4 produced by invariant Natural Killer T cells, independent of CD1d-mediated interaction. Single-cell transcriptomics suggest the developmental landscape of thymic B cells, and the thymus supports development of transitional, mature, and memory B cells in addition to plasma cells. Furthermore, thymic plasma cells produce polyclonal antibodies without somatic hypermutation, indicating they develop via the extra-follicular pathway. Physiologically, thymic-derived IgEs increase the number of mast cells in the gut and skin, which correlates with the severity of anaphylaxis. Collectively, we define the ontogeny of thymic plasma cells and show that steady state thymus-derived IgEs regulate mast cell homeostasis, opening up new avenues for studying the genetic causes of allergic disorders.
Two-dimensional covalent organic framework films prepared on various substrates through vapor induced conversion
Authors: Liu Minghui , Liu Youxing , Dong Jichen , Bai Yichao , Gao Wenqiang , Shang Shengcong , Wang Xinyu , Kuang Junhua , Du Changsheng , Zou Ye , Chen Jianyi , Liu Yunqi
Published: March 2022

Covalent organic frameworks (COFs) can exhibit high specific surface area and catalytic activity, but traditional solution-based synthesis methods often lead to insoluble and infusible powders or fragile films on solution surface. Herein we report large-area –C=N– linked two-dimensional (2D) COF films with controllable thicknesses via vapor induced conversion in a chemical vapor deposition (CVD) system. The assembly process is achieved by reversible Schiff base polycondensation between PyTTA film and TPA vapor, which results in a uniform organic framework film directly on growth substrate, and is driven by π‐π stacking interactions with the aid of water and acetic acid. Wafer-scale 2D COF films with different structures have been successfully synthesized by adjusting their building blocks, suggesting its generic applicability. The carrier mobility of PyTTA-TPA COF films can reach 1.89 × 10−3 cm2 V−1 s−1. When employed as catalysts in hydrogen evolution reaction (HER), they show high electrocatalytic activity compared with metal-free COFs or even some metallic catalysts. Our results represent a versatile route for the direct construction of large-area uniform 2D COF films on substrates towards multi-functional applications of 2D π‐conjugated systems.
Large evanescently-induced Brillouin scattering at the surrounding of a nanofibre
Authors: Yang Fan , Gyger Flavien , Godet Adrien , Chrétien Jacques , Zhang Li , Pang Meng , Beugnot Jean-Charles , Thévenaz Luc
Published: March 2022

Brillouin scattering has been widely exploited for advanced photonics functionalities such as microwave photonics, signal processing, sensing, lasing, and more recently in micro- and nano-photonic waveguides. Most of the works have focused on the opto-acoustic interaction driven from the core region of micro- and nano-waveguides. Here we observe, for the first time, an efficient Brillouin scattering generated by an evanescent field nearby a single-pass sub-wavelength waveguide embedded in a pressurised gas cell, with a maximum gain coefficient of 18.90 ± 0.17 m−1W−1. This gain is 11 times larger than the highest Brillouin gain obtained in a hollow-core fibre and 79 times larger than in a standard single-mode fibre. The realisation of strong free-space Brillouin scattering from a waveguide benefits from the flexibility of confined light while providing a direct access to the opto-acoustic interaction, as required in free-space optoacoustics such as Brillouin spectroscopy and microscopy. Therefore, our work creates an important bridge between Brillouin scattering in waveguides, Brillouin spectroscopy and microscopy, and opens new avenues in light-sound interactions, optomechanics, sensing, lasing and imaging.
Flagellin outer domain dimerization modulates motility in pathogenic and soil bacteria from viscous environments
Authors: Kreutzberger Mark A. B. , Sobe Richard C. , Sauder Amber B. , Chatterjee Sharanya , Peña Alejandro , Wang Fengbin , Giron Jorge A. , Kiessling Volker , Costa Tiago R. D. , Conticello Vincent P. , Frankel Gad , Kendall Melissa M. , Scharf Birgit E. , Egelman Edward H.
Published: March 2022

Flagellar filaments function as the propellers of the bacterial flagellum and their supercoiling is key to motility. The outer domains on the surface of the filament are non-critical for motility in many bacteria and their structures and functions are not conserved. Here, we show the atomic cryo-electron microscopy structures for flagellar filaments from enterohemorrhagic Escherichia coli O157:H7, enteropathogenic E. coli O127:H6, Achromobacter, and Sinorhizobium meliloti, where the outer domains dimerize or tetramerize to form either a sheath or a screw-like surface. These dimers are formed by 180° rotations of half of the outer domains. The outer domain sheath (ODS) plays a role in bacterial motility by stabilizing an intermediate waveform and prolonging the tumbling of E. coli cells. Bacteria with these ODS and screw-like flagellar filaments are commonly found in soil and human intestinal environments of relatively high viscosity suggesting a role for the dimerization in these environments.
FrCas9 is a CRISPR/Cas9 system with high editing efficiency and fidelity
Authors: Cui Zifeng , Tian Rui , Huang Zhaoyue , Jin Zhuang , Li Lifang , Liu Jiashuo , Huang Zheying , Xie Hongxian , Liu Dan , Mo Haiyan , Zhou Rong , Lang Bin , Meng Bo , Weng Haiyan , Hu Zheng
Published: March 2022

Genome editing technologies hold tremendous potential in biomedical research and drug development. Therefore, it is imperative to discover gene editing tools with superior cutting efficiency, good fidelity, and fewer genomic restrictions. Here, we report a CRISPR/Cas9 from Faecalibaculum rodentium, which is characterized by a simple PAM (5′-NNTA-3′) and a guide RNA length of 21–22 bp. We find that FrCas9 could achieve comparable efficiency and specificity to SpCas9. Interestingly, the PAM of FrCas9 presents a palindromic sequence, which greatly expands its targeting scope. Due to the PAM sequence, FrCas9 possesses double editing-windows for base editor and could directly target the TATA-box in eukaryotic promoters for TATA-box related diseases. Together, our results broaden the understanding of CRISPR/Cas-mediated genome engineering and establish FrCas9 as a safe and efficient platform for wide applications in research, biotechnology and therapeutics.
In situ infrared nanospectroscopy of the local processes at the Li/polymer electrolyte interface
Authors: He Xin , Larson Jonathan M. , Bechtel Hans A. , Kostecki Robert
Published: March 2022

Solid-state batteries possess the potential to significantly impact energy storage industries by enabling diverse benefits, such as increased safety and energy density. However, challenges persist with physicochemical properties and processes at electrode/electrolyte interfaces. Thus, there is great need to characterize such interfaces in situ, and unveil scientific understanding that catalyzes engineering solutions. To address this, we conduct multiscale in situ microscopies (optical, atomic force, and infrared near-field) and Fourier transform infrared spectroscopies (near-field nanospectroscopy and attenuated total reflection) of intact and electrochemically operational graphene/solid polymer electrolyte interfaces. We find nanoscale structural and chemical heterogeneities intrinsic to the solid polymer electrolyte initiate a cascade of additional interfacial nanoscale heterogeneities during Li plating and stripping; including Li-ion conductivity, electrolyte decomposition, and interphase formation. Moreover, our methodology to nondestructively characterize buried interfaces and interphases in their native environment with nanoscale resolution is readily adaptable to a number of other electrochemical systems and battery chemistries.
De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report
Authors: Gandhi Shiv , Klein Jonathan , Robertson Alexander J. , Peña-Hernández Mario A. , Lin Michelle J. , Roychoudhury Pavitra , Lu Peiwen , Fournier John , Ferguson David , Mohamed Bakhash Shah A. K. , Catherine Muenker M. , Srivathsan Ariktha , Wunder Elsio A. , Kerantzas Nicholas , Wang Wenshuai , Lindenbach Brett , Pyle Anna , Wilen Craig B. , Ogbuagu Onyema , Greninger Alexander L. , Iwasaki Akiko , Schulz Wade L. , Ko Albert I.
Published: March 2022

SARS-CoV-2 remdesivir resistance mutations have been generated in vitro but have not been reported in patients receiving treatment with the antiviral agent. We present a case of an immunocompromised patient with acquired B-cell deficiency who developed an indolent, protracted course of SARS-CoV-2 infection. Remdesivir therapy alleviated symptoms and produced a transient virologic response, but her course was complicated by recrudescence of high-grade viral shedding. Whole genome sequencing identified a mutation, E802D, in the nsp12 RNA-dependent RNA polymerase, which was not present in pre-treatment specimens. In vitro experiments demonstrated that the mutation conferred a ~6-fold increase in remdesivir IC50 but resulted in a fitness cost in the absence of remdesivir. Sustained clinical and virologic response was achieved after treatment with casirivimab-imdevimab. Although the fitness cost observed in vitro may limit the risk posed by E802D, this case illustrates the importance of monitoring for remdesivir resistance and the potential benefit of combinatorial therapies in immunocompromised patients with SARS-CoV-2 infection.
Control of zeolite framework flexibility for ultra-selective carbon dioxide separation
Authors: Du Peng , Zhang Yuting , Wang Xuerui , Canossa Stefano , Hong Zhou , Nénert Gwilherm , Jin Wanqin , Gu Xuehong
Published: March 2022

Molecular sieving membranes with uniform pore size are highly desired for carbon dioxide separation. All-silica zeolite membranes feature well-defined micropores, but the size-exclusion effect is significantly compromised by the non-selective macro-pores generated during detemplation. Here we propose a template modulated crystal transition (TMCT) approach to tune the flexibility of Decadodecasil 3 R (DD3R) zeolite to prepare ultra-selective membranes for CO2/CH4 separation. An instantaneous overheating is applied to synchronize the template decomposition with the structure relaxation. The organic template molecules are transitionally converted to tight carbon species by the one-minute overheating at 700 °C, which are facilely burnt out by a following moderate thermal treatment. The resulting membranes exhibit CO2/CH4 selectivity of 157~1,172 and CO2 permeance of (890~1,540) × 10−10 mol m−2 s−1 Pa−1. The CO2 flux and CO2/CH4 mixture selectivity reach 3.6 Nm3 m−2 h−1 and 43 even at feed pressure up to 31 bar. Such strategy could pave the way of all-silica zeolite membranes to practical applications.
Structure and function of the soil microbiome underlying N2O emissions from global wetlands
Authors: Bahram Mohammad , Espenberg Mikk , Pärn Jaan , Lehtovirta-Morley Laura , Anslan Sten , Kasak Kuno , Kõljalg Urmas , Liira Jaan , Maddison Martin , Moora Mari , Niinemets Ülo , Öpik Maarja , Pärtel Meelis , Soosaar Kaido , Zobel Martin , Hildebrand Falk , Tedersoo Leho , Mander Ülo
Published: March 2022

Wetland soils are the greatest source of nitrous oxide (N2O), a critical greenhouse gas and ozone depleter released by microbes. Yet, microbial players and processes underlying the N2O emissions from wetland soils are poorly understood. Using in situ N2O measurements and by determining the structure and potential functional of microbial communities in 645 wetland soil samples globally, we examined the potential role of archaea, bacteria, and fungi in nitrogen (N) cycling and N2O emissions. We show that N2O emissions are higher in drained and warm wetland soils, and are correlated with functional diversity of microbes. We further provide evidence that despite their much lower abundance compared to bacteria, nitrifying archaeal abundance is a key factor explaining N2O emissions from wetland soils globally. Our data suggest that ongoing global warming and intensifying environmental change may boost archaeal nitrifiers, collectively transforming wetland soils to a greater source of N2O.
Binary-state scanning probe microscopy for parallel imaging
Authors: Kim Gwangmook , Kim Eoh Jin , Do Hyung Wan , Cho Min-Kyun , Kim Sungsoon , Kang Shinill , Kim Dohun , Cheon Jinwoo , Shim Wooyoung
Published: March 2022

Scanning probe microscopy techniques, such as atomic force microscopy and scanning tunnelling microscopy, are harnessed to image nanoscale structures with an exquisite resolution, which has been of significant value in a variety of areas of nanotechnology. These scanning probe techniques, however, are not generally suitable for high-throughput imaging, which has, from the outset, been a primary challenge. Traditional approaches to increasing the scalability have involved developing multiple probes for imaging, but complex probe design and electronics are required to carry out the detection method. Here, we report a probe-based imaging method that utilizes scalable cantilever-free elastomeric probe design and hierarchical measurement architecture, which readily reconstructs high-resolution and high-throughput topography images. In a single scan, we demonstrate imaging with a 100-tip array to obtain 100 images over a 1-mm2 area with 106 pixels in less than 10 min. The potential for large-scale tip integration and the advantage of a simple probe array suggest substantial promise for our approach to high-throughput imaging far beyond what is currently possible.
Vital signs in pediatric oncology patients assessed by continuous recording with a wearable device, NCT04134429
Authors: Haemmerli Marion , Ammann Roland A. , Roessler Jochen , Koenig Christa , Brack Eva
Published: March 2022

Pediatric patients with cancer are at high risk for severe infections. Changes in vital signs, triggered by infections, may be detected earlier by continuous recording with a wearable device than with discrete measurements. This prospective, observational single-center feasibility study consecutively recruited pediatric patients undergoing chemotherapy for cancer. The WD Everion® was used for 14 days in each of the 20 patients on study to continuously record vital signs. Nine different vital signs and health indicators derived from them, plus six quality scores. This resulted in 274 study days (6576 hours) with 85’854 measuring points, which are a total of 772’686 measurements of vital signs and health indicators, plus 515’124 quality scores. Additionally, non-WD data like side effects, acceptability of the WD and effort for investigators were collected. In this manuscript, we present the methods of acquisition and explanations to the complete data set, which have been made publically available on open access and which can be used to study feasibility of continuous multi-parameter recording of vital signs by a WD.
Trans-polar drift-pathways of riverine European microplastic
Authors: Huserbråten Mats B. O. , Hattermann Tore , Broms Cecilie , Albretsen Jon
Published: March 2022

High concentrations of microplastic particles are reported across the Arctic Ocean–yet no meaningful point sources, suspension timelines, or accumulation areas have been identified. Here we use Lagrangian particle advection simulations to model the transport of buoyant microplastic from northern European rivers to the high Arctic, and compare model results to the flux of sampled synthetic particles across the main entrance to the Arctic Ocean. We report widespread dispersal along the Eurasian continental shelf, across the North Pole, and back into the Nordic Seas; with accumulation zones over the Nansen basin, the Laptev Sea, and the ocean gyres of the Nordic Seas. The equal distribution of sampled synthetic particles across water masses covering a wide time frame of anthropogenic influence suggests a system in full saturation rather than pronounced injection from European sources, through a complex circulation scheme connecting the entire Arctic Mediterranean. This circulation of microplastic through Arctic ecosystems may have large consequences to natural ecosystem health, highlighting an ever-increasing need for better waste management.
Filtered-orthogonal wavelet division multiplexing (F-OWDM) technique for 5G and beyond communication systems
Authors: Almutairi Ali. F. , Krishna A.
Published: March 2022

Filtered-orthogonal frequency division multiplexing (F-OFDM) is one of the most protruding multicarrier modulation (MCM) techniques for fifth-generation and beyond wireless communication. However, it possesses a high peak-to-average power ratio (PAPR), which results in its poor performance. Thus, a novel wavelet based MCM technique, namely filtered orthogonal wavelet division multiplexing (F-OWDM), is proposed as an efficient alternative to conventional F-OFDM (C-F-OFDM) to reduce the PAPR. In this model, the traditional Fourier transforms (FT) as used in C-F-OFDM was replaced with Wavelet Transforms. The proposed F-OWDM system does not require a cyclic prefix because of the overlapping sub-carriers in the time and frequency domains. Thus, the F-OWDM system exhibits higher bandwidth efficiency. In this paper, the performance of the F-OWDM system with various wavelets from different wavelet families under an additive white Gaussian noise and flat fading channel is investigated. The PAPR and bit error rate (BER) of the F-OWDM system using Haar, discrete Meyer, bi-orthogonal, symlet, and Daubechies wavelets are analyzed. A comparative study between F-OWDM and C-F-OFDM is also presented. From the results, it is able to prove that F-OWDM has the advantage of lower PAPR and lower bit error rate than the C-F-OFDM system.