bluuebunny/crossref_metadata_2025 huggingface dataset:
Vortex-induced vibrations of a cylinder in inelastic shear-thinning and shear-thickening fluids
Authors: Patel Umang N. , Rothstein Jonathan P. , Modarres-Sadeghi Yahya
Published: January 2022

Vortex-induced vibrations (VIV) of a cylinder in a Newtonian fluid is a model problem in fluid–structure interactions and has been studied extensively. In this work, we study the influence of shear-thinning and shear-thickening fluids on the VIV response of a one-degree-of-freedom flexibly-mounted cylinder. We consider a system with a mass ratio of

$m^*=2$

and zero structural damping in shear-thinning and shear-thickening power-law fluids at

$Re_0 = 15$

and

$Re_0 = 200$

, respectively, defined based on the zero-shear-rate viscosity of the fluids. We investigate how the VIV amplitude and frequency, flow forces, and the vorticity contours change as the reduced velocity,

$U^*$

, and fluid's time constant,

$\lambda$

, change. When the results are compared based on

$Re_0$

, shear-thinning fluids enhance the oscillations while shear-thickening fluids suppress them. If, however, we define a characteristic Reynolds number,

$Re_{char}$

, based on a viscosity evaluated at the characteristic shear rate,

$\dot {\gamma } = U/D$

, then at a constant

$Re_{char}$

, the amplitude of response stays very similar for the shear-thinning, shear-thickening and Newtonian fluids. Despite this similarity, the observed far wake is different: shear thinning amplifies the generation of vorticity and reduces the extent of the wake, whereas shear thickening limits the generation of vorticity and extends the wake. Our findings show that the local apparent viscosity observed close to the cylinder placed in shear-thinning or shear-thickening fluids governs the VIV response of the cylinder.
Fracture patterns in viscoplastic gravity currents
Authors: Ball Thomasina V. , Balmforth Neil J. , Dufresne Ariel P. , Morris Stephen W.
Published: January 2022

Constant-flux gravity currents of viscoplastic fluid remain axisymmetric when extruded onto a dry horizontal plane. However, if the plane is coated with a shallow layer of water, the current suffers a dramatic non-axisymmetric instability in which localized

$v$

-shaped cuts appear in the outer edge where the viscoplastic fluid is in contact with water. These ‘fractures’ lengthen and guide the subsequent radial outflow, leading to distinctive flower-like patterns. This pattern formation process is illustrated for two viscoplastic materials, an aqueous suspension of Carbopol, and a mixture of water and joint compound (a kaolin-based, commercially available product). The fracturing spreads over the entire upper surface of the current when deeper water baths are used, complicating the extrusion patterns. The instability can be removed entirely when the ambient water layer is replaced by an immiscible liquid of comparable viscosity, indicating that the presence of water at the surface is key to the pattern formation process. We conjecture that the underlying mechanism is the fracture under tension of the viscoplastic material, exacerbated by the ambient water.
Gender Stereotyping and the Electoral Success of Women Candidates: New Evidence from Local Elections in the United States
Authors: Anzia Sarah F. , Bernhard Rachel
Published: January 2022

Research shows that voters often use gender stereotypes to evaluate candidates, which should help women in some electoral contexts and hurt them in others. Yet, most research examines a single context at a time—usually US national elections, where partisanship is strong—and employs surveys and experiments, raising concerns that citizens’ responses may not reflect how they actually vote. By analyzing returns from thousands of nonpartisan local elections, we test whether patterns of women's win rates relative to men's match expectations for how the electoral effects of gender stereotyping should vary by context. We find women have greater advantages over men in city council than mayoral races, still greater advantages in school board races, and decreasing advantages in more conservative constituencies. Thus, women fare better in stereotype-congruent contexts and worse in incongruent contexts. These effects are most pronounced during on-cycle elections, when voters tend to know less about local candidates.
The generalized auslander–reiten duality on a module category
Authors: Jiao Pengjie
Published: January 2022

We characterize the generalized Auslander–Reiten duality on the category of finitely presented modules over some certain Hom-finite category. Examples include the category FI of finite sets with injections, and the one VI of finite-dimensional vector spaces with linear injections over a finite field.
Gamma-ray flash in the interaction of a tightly focused single-cycle ultra-intense laser pulse with a solid target
Authors: Hadjisolomou P. , Jeong T.M. , Valenta P. , Kolenaty D. , Versaci R. , Olšovcová V. , Ridgers C.P. , Bulanov S.V.
Published: January 2022

We employ the

$\lambda ^{3}$

regime where a near-single-cycle laser pulse is tightly focused, thus providing the highest possible intensity for the minimal energy at a certain laser power. The quantum electrodynamics processes in the course of the interaction of an ultra-intense laser with a solid target are studied via three-dimensional particle-in-cell simulations, revealing the generation of copious

$\gamma$

-photons and electron–positron pairs. A parametric study of the laser polarisation, target thickness and electron number density shows that a radially polarised laser provides the optimal regime for

$\gamma$

-photon generation. By varying the laser power in the range of 1 to 300 PW we find the scaling of the laser to

$\gamma$

-photon energy conversion efficiency. The laser-generated

$\gamma$

-photon interaction with a high-

$Z$

target is further studied using Monte Carlo simulations revealing further electron–positron pair generation and radioactive nuclide creation.
Towards an in situ non-lethal rapid test to accurately detect the presence of the nematode parasite, Anguillicoloides crassus, in European eel, Anguilla anguilla
Authors: De Noia M. , Poole R. , Kaufmann J. , Waters C. , Adams C. , McGinnity P. , Llewellyn M.
Published: January 2022

Anguillicoloides crassus is an invasive nematode parasite of the critically endangered European eel, Anguilla anguilla, and possibly one of the primary drivers of eel population collapse, impacting many features of eel physiology and life history. Early detection of the parasite is vital to limit the spread of A. crassus, to assess its potential impact on spawning biomass. However accurate diagnosis of infection could only be achieved via necropsy. To support eel fisheries management we developed a rapid, non-lethal, minimally invasive and in situ DNA-based method to infer the presence of the parasite in the swim bladder. Screening of 131 wild eels was undertaken between 2017 and 2019 in Ireland and UK to validate the procedure. DNA extractions and PCR were conducted using both a Qiagen Stool kit and in situ using Whatman qualitative filter paper No1 and a miniPCR DNA Discovery-System™. Primers were specifically designed to target the cytochrome oxidase mtDNA gene region and in situ extraction and amplification takes approximately 3 h for up to 16 individuals. Our in-situ diagnostic procedure demonstrated positive predictive values at 96% and negative predictive values at 87% by comparison to necropsy data. Our method could be a valuable tool in the hands of fisheries managers to enable infection control and help protect this iconic but critically endangered species.
Experimental manipulation of humidity in a cavity-nesting bird influences ectoparasites' abundance
Authors: Castaño-Vázquez F. , Merino S. , Valera F. , Veiga J.
Published: January 2022

Climate change effects on host–parasite interactions have been poorly studied in arid or semi-arid habitats. Here, we conducted an experiment aimed to increase the temperature inside European roller Coracias garrulus nest boxes located in a semi-arid habitat on different nest-site types to look for effects on different ectoparasite abundances and nestling growth. Average nest temperature was slightly higher in heated nests than in control nests, although differences were not statistically significant. However, relative humidity was significantly lower at night in heated nests as compared to control nests. The abundance of sand flies, mites and carnid flies was significantly higher in heated, less humid, nests while biting midge abundance was significantly lower in heated nests. Other ectoparasites were not significantly affected by treatment. Relative humidity was high even in heated nests, reaching more than 60%. Sand fly abundance was higher in nests located in sandstone walls, while mite abundance was higher in isolated farmhouses. In addition, sand fly prevalence was higher in nests located in isolated farmhouses and sandstone walls. Heat treatment, nest-site type or ectoparasite abundances did not affect the nestling body mass, wing length or their growth at different nestling ages.
Shifting Strategies: The Politics of Radical Change in Provincial Development Policy in China
Authors: Donaldson John A. , Yang Xiaotao
Published: January 2022

Why do provincial governments change policy, even when those policies have proven successful? This paper explores a debate regarding the determinants of provincial policy choice and the degree of discretion provinces are permitted in this area. It does so by scrutinizing the shift in Guizhou's development policy from a poverty reduction orientation to a wholehearted pursuit of economic growth, urbanization and industrialization. In contrast to those who argue that central experience, prospects for promotion or local conditions are key factors explaining policy choice, the paper concludes that Guizhou's shift in policy had more to do with the backgrounds and experiences of top provincial leaders. The result has implications for our understanding of central–local relations and local government decision making.
Masjids, monuments and refugees in the Partition city of Delhi, 1947–1959
Authors: Sutton Deborah Ruth
Published: January 2022

This article explores refugee occupation in Delhi during the aftermath of the Partition in 1947. The temporary occupation of public buildings and open spaces was integral to the difficult and gradual assimilation of hundreds of thousands of refugees into and through the city. Monuments, shrines, mosques and temples provided temporary shelter for refugees and some remained occupied for years after the Partition. The definition and custody of these buildings speaks of the uncertainty and anxiety produced by violence and displacement in 1947 and 1948. The article considers both the modification of these places by the refugees who lived in them, and the gradual and faltering processes of eviction and the restoration of the buildings. The physical imprints of refugee occupation are a significant part of the city's past; a heritage which both marked a rupture in the city's history and reflects broader mores of urban dynamics.
The Requirement that Tribunals be Established by Law: A Valuable Principle Safeguarding the Rule of Law and the Separation of Powers in a Context of Trust
Authors: Rizcallah Cecilia , Davio Victor
Published: January 2022

Requirement that tribunals be established by law – European Convention on Human Rights – EU Charter of Fundamental Rights – Fair trial – Rule of law – Separation of powers – Public trust
Asymmetric Response of the Biological Carbon Pump to the ENSO in the South China Sea
Authors: Li Hongliang , Zhang Jingjing , Xuan Jiliang , Wu Zezhou , Ran Lihua , Wiesner Martin G. , Chen Jianfang
Published: January 2022

Biological carbon pump (BCP) inefficiency was first observed in the South China Sea (SCS) throughout the 1997–1999 El Niño Southern Oscillation (ENSO) event, but the BCP usually recovers its efficiency when the climate conditions change from El Niño to La Niña conditions in the Pacific Ocean. Enhanced stratification and Kuroshio intrusion led to weak mixing and oligotrophic conditions in the sunlit layer of the SCS during the 1997/1998 El Niño phase, but the particulate organic carbon (POC) flux was comparable to the climatological mean due to the ballast effect of increased lithogenic material and CaCO3 flux. The deepened thermocline rendered the recovered mixing less effective in replenishing subsurface nutrients and subsequently lowered POC flux during the 1998/1999 La Niña phase. Both scenarios were characterized by decreased siliceous plankton but a stimulated calcareous plankton contribution, which reduced BCP efficiency, resulting in a unique asymmetric response to the ENSO in the SCS.
Quasi‐Parallel Shock Reformation Seen by Magnetospheric Multiscale and Ion‐Kinetic Simulations
Authors: Johlander Andreas , Battarbee Markus , Turc Lucile , Ganse Urs , Pfau‐Kempf Yann , Grandin Maxime , Suni Jonas , Tarvus Vertti , Bussov Maarja , Zhou Hongyang , Alho Markku , Dubart Maxime , George Harriet , Papadakis Konstantinos , Palmroth Minna
Published: January 2022

Shock waves in collisionless plasmas are among the most efficient particle accelerators in space. Shock reformation is a process important to plasma heating and acceleration, but direct observations of reformation at quasi‐parallel shocks have been lacking. Here, we investigate Earth's quasi‐parallel bow shock with observations by the four Magnetospheric Multiscale spacecraft. The multi‐spacecraft observations provide evidence of short large‐amplitude magnetic structures (SLAMS) causing reformation of the quasi‐parallel shock. We perform an ion‐kinetic Vlasiator simulation of the bow shock and show that SLAMS reforming the bow shock recreates the multi‐spacecraft measurements. This provides a method for identifying shock reformation in the future.
High‐Tide Floods and Storm Surges During Atmospheric Rivers on the US West Coast
Authors: Piecuch Christopher G. , Coats Sloan , Dangendorf Sönke , Landerer Felix W. , Reager J. T. , Thompson Philip R. , Wahl Thomas
Published: January 2022

Atmospheric rivers (ARs) cause inland hydrological impacts related to precipitation. However, little is known about coastal hazards associated with these events. We elucidate high‐tide floods (HTFs) and storm surges during ARs on the US West Coast during 1980–2016. HTFs and ARs cooccur more often than expected from chance. Between 10% and 63% of HTFs coincide with ARs on average, depending on location. However, interannual‐to‐decadal variations in HTFs are due more to tides and mean sea‐level changes than storminess variability. Only 2–15% of ARs coincide with HTFs, suggesting that ARs typically must cooccur with high tides or mean sea levels to cause HTFs. Storm surges during ARs reflect local wind, pressure, and precipitation forcing: meridional wind and barometric pressure are primary drivers, but precipitation makes secondary contributions. This study highlights the relevance of ARs to coastal impacts, clarifies the drivers of storm surge during ARs, and identifies future research directions.
Microseismicity Indicates Atypical Small‐Scale Plate Rotation at the Quebrada Transform Fault System, East Pacific Rise
Authors: Gong Jianhua , Fan Wenyuan , Parnell‐Turner Ross
Published: January 2022

Closely spaced, multi‐strand ridge transform faults (RTFs) accommodate relative motions along fast spreading mid‐ocean ridges. However, the relations between RTFs and plate spreading dynamics are poorly understood. The Quebrada system is one of the most unique RTF systems at the East Pacific Rise, consisting of four transform faults connected by three short intra‐transform spreading centers (ITSCs). We use seven‐months of ocean bottom seismograph data to study the Quebrada system, and find abundant earthquakes unevenly distributed among three active faults. We identify two deep, diffuse seismicity clouds at the inside corners of the ITSC‐transform fault intersections, and one seismically active fracture zone. The observations suggest a complex regional plate‐motion pattern, including possible heterogeneous rotations within the Quebrada system. Evolution of multi‐strand RTFs may have resulted from a strong three‐dimensional local thermal and fluid effects, while the RTFs may have also regulated regional tectonics, forming an intricate feedback system.
Decadal to Multidecadal Variability of the Western North Pacific Subtropical Front and Countercurrent
Authors: Wu Baolan , Xu Lixiao , Lin Xiaopei
Published: January 2022

The western North Pacific Subtropical Countercurrent (WSTCC), anchored by the western subtropical front (WSTF), varies from seasonal to multidecadal time scales and affects the climate variability in the North Pacific. However, conflicting views exist for physical mechanisms of the decadal to multidecadal variability of the WSTF/WSTCC. While many previous studies attribute the WSTF/WSTCC decadal variability to the anomalous wind forcing by the Pacific Decadal Oscillation, by synthesizing observations, reanalysis products and the pre‐industrial model simulation experiment, the present study demonstrates that they are controlled by the Atlantic Multidecadal Oscillation (AMO) through the Subtropical Mode Water (STMW) variability. The AMO induced decadal temperature and volume anomalies of the STMW are stored in the subsurface ocean through the subduction process south of the Kuroshio Extension. Then these anomalies propagate southwestward along the thermocline circulation and reaches the northern flank of the WSTCC in about 5 years. During the AMO‐positive phase, the anomalous warm and thin STMW flattens the upper thermocline, reduces the meridional temperature gradient and weakens the WSTF intensity, lagging 5 years behind the AMO index. Subsequently, the WSTCC decreases and moves southward, and vice versa for the AMO‐negative phase. Our results provide a potential predictability for the WSTF and WSTCC decadal to multidecadal variability and are important for the North Pacific climate change and the biogeochemical processes.
An Evaluation of Convection‐Permitting Ensemble Simulations of Coastal Nocturnal Rainfall Over South China During the Early‐Summer Rainy Season
Authors: Huang Ling , Luo Yali , Bai Lanqiang
Published: January 2022

Convection‐permitting ensemble Weather Research and Forecasting simulations were successively conducted on each day during the early‐summer rainy season (April‒June) in 2018 over South China. These simulations were configured by eight sets of parameterization schemes associated with the planetary boundary layer and surface layer. The performance of the ensemble products in reproducing the nocturnal rainfall in the coastal region of South China was evaluated using observations from densely distributed rain gauges and wind profiling radars. The simulations at a lead time of 12 hr present a relatively better performance than those at 36 hr lead time, but still exhibit a low skill especially after midnight. The degradation of forecast skill after midnight is closely associated with the worse underestimation of the low‐level onshore flow and land surface air temperature. The large‐scale onshore flow at low levels from the South China Sea (SCS) interacted with land/mountain breezes, enhancing the lower‐troposphere moisture pooling and convergence for the rainfall production over the coastal mountains/cities. In the longer lead‐time simulations, the low‐level onshore flow presented a deceleration tendency and thus indirectly amplified the effects of land/mountain breezes in nighttime, leading to more serious underestimation in rainfall amount and larger southward displacement error than the shorter lead‐time simulation. The findings highlight the dependence of the nocturnal rainfall forecast on accurately predicting the upstream low‐level onshore flow over the SCS and the thermal conditions in the urban region surrounded by mountains.
Rivers and Lakes in Western Arabia Terra: The Fluvial Catchment of the ExoMars 2022 Rover Landing Site
Authors: Fawdon Peter , Balme Matthew , Davis Joel , Bridges John , Gupta Sanjeev , Quantin‐Nataf Cathey
Published: January 2022

Oxia Planum, the landing site for the ExoMars rover mission, is a shallow basin on the southern margin of Chryse Planitia that hosts remnants of fan‐shaped sedimentary deposits associated with the ancient channel system Coogoon Vallis. This indicates runoff from a catchment in Arabia Terra has transported sediment into the landing site. To explore this fluvial system we created a model catchment for Oxia Planum and, using 6 m/pixel ConTeXt camera orbital remote sensing image data, we digitized the fluvial and lacustrine landforms in Western Arabia Terra in and around this catchment. We find: (a) The catchment has a minimum area of ∼2.1 × 105 km2 and has been episodically deformed by tectonic activity; (b) There were at least two phases of fluvial activity. The first created a mature landscape associated with Coogoon Vallis, which may have deposited alluvial or deltaic deposits in the Oxia Basin. After a substantial hiatus, a second phase of activity incised U‐section channels into the pre‐existing landscape and channel systems; and (c) Evidence for numerous possible paleolake deposits within the catchment. These are not well connected to the fluvial system and were probably sustained by groundwater activity contemporaneous with both phases of fluvial activity. This groundwater might have modified the mineralogy of Oxia Planum. Oxia Planum probably experienced an alluvial or distal deltaic/lacustrine depositional environment during the mid Noachian, which was later overprinted by a younger phase of fluvial activity.
Enhanced Terrestrial Carbon Export From East Antarctica During the Early Eocene
Authors: Inglis Gordon N. , Toney Jaime L. , Zhu Jiang , Poulsen Christopher J. , Röhl Ursula , Jamieson Stewart S. R. , Pross Jörg , Cramwinckel Marlow J. , Krishnan Srinath , Pagani Mark , Bijl Peter K. , Bendle James
Published: January 2022

Terrestrial organic carbon (TerrOC) acts as an important CO2 sink when transported via rivers to the ocean and sequestered in coastal marine sediments. This mechanism might help to modulate atmospheric CO2 levels over short‐ and long‐ timescales (103–106 years), but its importance during past warm climates remains unknown. Here we use terrestrial biomarkers preserved in coastal marine sediment samples from Wilkes Land, East Antarctica (∼67°S) to quantify TerrOC burial during the early Eocene (∼54.4–51.5 Ma). Terrestrial biomarker distributions indicate the delivery of plant‐, soil‐, and peat‐derived organic carbon (OC) into the marine realm. Mass accumulation rates of plant‐ (long‐chain n‐alkane) and soil‐derived (hopane) biomarkers dramatically increase between the earliest Eocene (∼54 Ma) and the early Eocene Climatic Optimum (EECO; ∼53 Ma). This coincides with increased OC mass accumulation rates and indicates enhanced TerrOC burial during the EECO. Leaf wax δ2H values indicate that the EECO was characterized by wetter conditions relative to the earliest Eocene, suggesting that hydroclimate exerts a first‐order control on TerrOC export. Our results indicate that TerrOC burial in coastal marine sediments could have acted as an important negative feedback mechanism during the early Eocene, but also during other warm climate intervals.
Influence of Surface Processes on Postrift Faulting During Divergent Margins Evolution
Authors: Silva R. M. , Sacek V.
Published: January 2022

We used thermomechanical numerical models to simulate the formation and evolution of divergent continental margins since continental rifting, taking into account surface processes of erosion of the continental escarpment. We found that the degree of crust–mantle coupling, the magnitude and extent of erosion of the coastal landscape, and the preexistence of weakness zones in the continental crust are important elements that control the reactivation of faults along divergent margins during the postrift phase. The numerical experiments indicated that the presence of a lower crust with a relatively low viscosity, facilitating the decoupling of the upper crust and the development of hyperextended margins, could also contribute to the development and/or reactivation of normal faults in the interior of the continent when the margin is continually subjected to differential denudation and consequent flexural response of the lithosphere. This effect is suppressed in scenarios where the lower crust presents a relatively high viscosity, consequently inducing the coupling of the upper crust with the lithospheric mantle. In this case, the long wavelength of the flexural response of a coupled lithosphere to erosional unloading has a minor impact on the reactivation of faults in the upper crust. As an application of our model, we propose that the combination of a decoupled continental lithosphere, escarpment retreat due to erosion, and the preexistence of shear zones parallel to the coast contributed to the development of postrift Cenozoic tectonism in southeastern Brazil.
Mechanical Stratigraphy Controls Normal Fault Growth and Dimensions, Outer Kwanza Basin, Offshore Angola
Authors: Redpath David , Jackson Christopher A.‐L. , Bell Rebecca E.
Published: January 2022

Mechanical stratigraphy controls the growth patterns and dimensions of relatively small normal faults, yet how it influences the development of much larger structures remains unclear. Here, we use 3D seismic reflection data from the Outer Kwanza Basin, offshore Angola to constrain the geometry and kinematics of several normal faults formed in a deep‐water clastic succession. The faults are up to 6.3‐km long and 1.9‐km tall and have up to 44 m of throw. Aspect ratios and lower‐tip throw gradients are greater for faults that terminate downward at a c. 100 m thick, mass‐transport complex (MTC; up to 5.2 and 0.12) than for those that offset it (up to 2.7 and 0.01). Faults that offset the MTC invariably have >30 m of throw. Based on their geometric properties and throw patterns, we interpret that the faults nucleated above the MTC and propagated down toward it. Upon encountering this unit, which we infer behaved in a more ductile manner than encasing strata, tip propagation was halted until tip stresses were sufficiently high (corresponding to minimum throw of c. 30 m) to breach it. Faults with smaller throw were unable to breach the MTC. We argue that using only geometric criteria to determine fault growth patterns can mask the significant control mechanical stratigraphy has on fault kinematics. Mechanical stratigraphy is therefore a key control on the growth of large, seismic‐scale normal faults, in a similar way to that observed for far smaller structures.
Length-based separation of Bacillus subtilis bacterial populations by viscoelastic microfluidics
Authors: Liu Ping , Liu Hangrui , Semenec Lucie , Yuan Dan , Yan Sheng , Cain Amy K. , Li Ming
Published: January 2022

In this study, we demonstrated the label-free continuous separation and enrichment ofBacillus subtilispopulations based on length using viscoelastic microfluidics.B. subtilis, a gram-positive, rod-shaped bacterium, has been widely used as a model organism and an industrial workhorse.B. subtiliscan be arranged in different morphological forms, such as single rods, chains, and clumps, which reflect differences in cell types, phases of growth, genetic variation, and changing environmental factors. The ability to prepareB. subtilispopulations with a uniform length is important for basic biological studies and efficient industrial applications. Here, we systematically investigated how flow rate ratio, poly(ethylene oxide) (PEO) concentration, and channel length affected the length-based separation ofB. subtiliscells. The lateral positions ofB. subtiliscells with varying morphologies in a straight rectangular microchannel were found to be dependent on cell length under the co-flow of viscoelastic and Newtonian fluids. Finally, we evaluated the ability of the viscoelastic microfluidic device to separate the two groups ofB. subtiliscells by length (i.e., 1–5 μm and >5 μm) in terms of extraction purity (EP), extraction yield (EY), and enrichment factor (EF) and confirmed that the device could separate heterogeneous populations of bacteria using elasto-inertial effects.
Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany
Authors: Endres Dominique , Lüngen Eva , Hasan Alkomiet , Kluge Michael , Fröhlich Sabrina , Lewerenz Jan , Bschor Tom , Haußleiter Ida Sibylle , Juckel Georg , Then Bergh Florian , Ettrich Barbara , Kertzscher Lisa , Oviedo-Salcedo Tatiana , Handreka Robert , Lauer Martin , Winter Klaas , Zumdick Norbert , Drews Anna , Obrocki Jost , Yalachkov Yavor , Bubl Anna , von Podewils Felix , Schneider Udo , Szabo Kristina , Mattern Margarete , Philipsen Alexandra , Domschke Katharina , Wandinger Klaus-Peter , Neyazi Alexandra , Stich Oliver , Prüss Harald , Leypoldt Frank , Tebartz van Elst Ludger
Published: January 2022

Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study’s aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as “probable psychiatric AE (pAE),” if well-characterized neuronal IgG autoantibodies were detected or “possible pAE” (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed.
Functional brain rewiring and altered cortical stability in ulcerative colitis
Authors: Wang Hao , Labus Jennifer S. , Griffin Fiona , Gupta Arpana , Bhatt Ravi R. , Sauk Jenny S. , Turkiewicz Joanna , Bernstein Charles N. , Kornelsen Jennifer , Mayer Emeran A.
Published: January 2022

Despite recent advances, there is still a major need to better understand the interactions between brain function and chronic gut inflammation and its clinical implications. Alterations in executive function have previously been identified in several chronic inflammatory conditions, including inflammatory bowel diseases. Inflammation-associated brain alterations can be captured by connectome analysis. Here, we used the resting-state fMRI data from 222 participants comprising three groups (ulcerative colitis (UC), irritable bowel syndrome (IBS), and healthy controls (HC),N = 74 each) to investigate the alterations in functional brain wiring and cortical stability in UC compared to the two control groups and identify possible correlations of these alterations with clinical parameters. Globally, UC participants showed increased functional connectivity and decreased modularity compared to IBS and HC groups. Regionally, UC showed decreased eigenvector centrality in the executive control network (UC < IBS < HC) and increased eigenvector centrality in the visual network (UC > IBS > HC). UC also showed increased connectivity in dorsal attention, somatomotor network, and visual networks, and these enhanced subnetwork connectivities were able to distinguish UC participants from HCs and IBS with high accuracy. Dynamic functional connectome analysis revealed that UC showed enhanced cortical stability in the medial prefrontal cortex (mPFC), which correlated with severe depression and anxiety-related measures. None of the observed brain changes were correlated with disease duration. Together, these findings are consistent with compromised functioning of networks involved in executive function and sensory integration in UC.
The antigenicity of SARS-CoV-2 Delta variants aggregated 10 high-frequency mutations in RBD has not changed sufficiently to replace the current vaccine strain
Authors: Wu Jiajing , Nie Jianhui , Zhang Li , Song Hao , An Yimeng , Liang Ziteng , Yang Jing , Ding Ruxia , Liu Shuo , Li Qianqian , Li Tao , Cui Zhimin , Zhang Mengyi , He Peng , Wang Youchun , Qu Xiaowang , Hu Zhongyu , Wang Qihui , Huang Weijin
Published: January 2022

Emerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and treatment. To determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vaccine, the changed degree on antigenicity of SARS-CoV-2 variants and H3N2 flu vaccine strains was compared. The neutralization activities of Alpha, Beta and Gamma variants’ spike protein-immunized sera were analysed against the eight current epidemic variants and 20 possible variants combining the top 10 prevalent RBD mutations based on the Delta variant, which were constructed using pseudotyped viruses. Meanwhile, the neutralization activities of convalescent sera and current inactivated and recombinant protein vaccine-elicited sera were also examined against all possible Delta variants. Eight HA protein-expressing DNAs elicited-animal sera were also tested against eight pseudotyped viruses of H3N2 flu vaccine strains from 2011–2019. Our results indicate that the antigenicity changes of possible Delta variants were mostly within four folds, whereas the antigenicity changes among different H3N2 vaccine strains were approximately 10–100-fold. Structural analysis of the antigenic characterization of the SARS-CoV-2 and H3N2 mutations supports the neutralization results. This study indicates that the antigenicity changes of the current SARS-CoV-2 may not be sufficient to require replacement of the current vaccine strain.
The hospital exemption pathway for the approval of advanced therapy medicinal products: an underused opportunity? The case of the CAR-T ARI-0001
Authors: Trias Esteve , Juan Manel , Urbano-Ispizua Alvaro , Calvo Gonzalo
Published: January 2022

In February 2021, the ‘Advanced Therapy Medicinal Product’ (ATMP) ARI-0001 (CART19-BE-01), developed at Hospital Clínic de Barcelona (Spain), received authorization from the Spanish Agency of Medicines and Medical Devices (AEMPS) under the ‘hospital exemption’ (HE) approval pathway for the treatment of patients aged >25 years with relapsed/refractory (RR) acute lymphoblastic leukemia (ALL). The HE pathway foreseen by the European Regulation establishing the legal framework for ATMPs intended to be placed on the market in the EU, allows access to ATMPs prepared on a non-routine basis, according to quality standards, like a custom-made product for an individual patient. Its use is limited to the same Member State where it was developed, in a hospital under the responsibility of a medical practitioner. HE-ATMPs must comply with national traceability and pharmacovigilance requirements and specific quality standards. HE offers an opportunity to develop ATMPs in close contact with clinical practice, with the quality and rapid access needed by patients and at a lower cost compared to regular market authorization. However, many barriers need to be overcome. Here we discuss relevant aspects of the development and authorization of ARI-0001 in the context of the heterogeneous frame of the European Regulation implementation across the Member States.
DDX39B contributes to the proliferation of colorectal cancer through direct binding to CDK6/CCND1
Authors: Zhang Haonan , He Chengcheng , Guo Xuxue , Fang Yuxin , Lai Qiuhua , Wang Xinke , Pan Xingzhu , Li Haolin , Qin Kaiwen , Li Aimin , Liu Side , Li Qingyuan
Published: January 2022

DDX39B (also called UAP56 or BAT1) which is a kind of DEAD-box family helicase plays pivotal roles in mRNA binding, splicing, and export. It has been found upregulated in many kinds of tumors as an oncogene. Nevertheless, the underlying molecular mechanisms of DDX39B in the proliferation of human colorectal cancer (CRC) remain fairly elusive. In our study, function experiments including the CCK8 and colony formation assay revealed that DDX39B facilitates CRC proliferation in vitro. DDX39B knockdown cells were administered for the orthotopic CRC tumor xenograft mouse model, after which tumor growth was monitored and immunohistochemistry (IHC) was performed to prove that DDX39B can also facilitates CRC proliferation in vivo. Flow cytometry demonstrated that DDX39B promotes the proliferation of CRC cells by driving the cell cycle from G0/G1 phase to the S phase. Mechanistically, RNA-binding protein immunoprecipitation-sequencing (RIP-seq) confirmed that DDX39B binds directly to the first exon of the CDK6/CCND1 pre-mRNA and upregulates their expression. Splicing experiments in vitro using a RT-PCR and gel electrophoresis assay confirmed that DDX39B promotes CDK6/CCND1 pre-mRNA splicing. Rescue experiments indicated that CDK6/CCND1 is a downstream effector of DDX39B-mediated CRC cell proliferation. Collectively, our results demonstrated that DDX39B and CDK6/CCND1 direct interactions serve as a CRC proliferation promoter, which can accelerate the G1/S phase transition to enhance CRC proliferation, and can offer novel and emerging treatment strategies targeting this cell proliferation-promoting gene.
A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice, rabbits and NHPs
Authors: Liu Zezhong , Zhou Jie , Xu Wei , Deng Wei , Wang Yanqun , Wang Meiyu , Wang Qian , Hsieh Ming , Dong Jingming , Wang Xinling , Huang Weijin , Xing Lixiao , He Miaoling , Tao Chunlin , Xie Youhua , Zhang Yilong , Wang Youchun , Zhao Jincun , Yuan Zhenghong , Qin Chuan , Jiang Shibo , Lu Lu
Published: January 2022

The emergence of SARS-CoV-2 variants and potentially other highly pathogenic sarbecoviruses in the future highlights the need for pan-sarbecovirus vaccines. Here, we discovered a new STING agonist, CF501, and found that CF501-adjuvanted RBD-Fc vaccine (CF501/RBD-Fc) elicited significantly stronger neutralizing antibody (nAb) and T cell responses than Alum- and cGAMP-adjuvanted RBD-Fc in mice. Vaccination of rabbits and rhesus macaques (nonhuman primates, NHPs) with CF501/RBD-Fc elicited exceptionally potent nAb responses against SARS-CoV-2 and its nine variants and 41 S-mutants, SARS-CoV and bat SARSr-CoVs. CF501/RBD-Fc-immunized hACE2-transgenic mice were almost completely protected against SARS-CoV-2 challenge, even 6 months after the initial immunization. NHPs immunized with a single dose of CF501/RBD-Fc produced high titers of nAbs. The immunized macaques also exhibited durable humoral and cellular immune responses and showed remarkably reduced viral load in the upper and lower airways upon SARS-CoV-2 challenge even at 108 days post the final immunization. Thus, CF501/RBD-Fc can be further developed as a novel pan-sarbecovirus vaccine to combat current and future outbreaks of sarbecovirus diseases.
Ultrastable microwave and soliton-pulse generation from fibre-photonic-stabilized microcombs
Authors: Kwon Dohyeon , Jeong Dongin , Jeon Igju , Lee Hansuek , Kim Jungwon
Published: January 2022

The ability to generate lower-noise microwaves has greatly advanced high-speed, high-precision scientific and engineering fields. Microcombs have high potential for generating such low-noise microwaves from chip-scale devices. To realize an ultralow-noise performance over a wider Fourier frequency range and longer time scale, which is required for many high-precision applications, free-running microcombs must be locked to more stable reference sources. However, ultrastable reference sources, particularly optical cavity-based methods, are generally bulky, alignment-sensitive and expensive, and therefore forfeit the benefits of using chip-scale microcombs. Here, we realize compact and low-phase-noise microwave and soliton pulse generation by combining a silica-microcomb (with few-mm diameter) with a fibre-photonic-based timing reference (with few-cm diameter). An ultrastable 22-GHz microwave is generated with −110 dBc/Hz (−88 dBc/Hz) phase noise at 1-kHz (100-Hz) Fourier frequency and 10−13-level frequency instability within 1-s. This work shows the potential of fully packaged, palm-sized or smaller systems for generating both ultrastable soliton pulse trains and microwaves, thereby facilitating a wide range of field applications involving ultrahigh-stability microcombs.
Absent thermal equilibration on fractional quantum Hall edges over macroscopic scale
Authors: Melcer Ron Aharon , Dutta Bivas , Spånslätt Christian , Park Jinhong , Mirlin Alexander D. , Umansky Vladimir
Published: January 2022

Two-dimensional topological insulators, and in particular quantum Hall states, are characterized by an insulating bulk and a conducting edge. Fractional states may host both downstream (dictated by the magnetic field) and upstream propagating edge modes, which leads to complex transport behavior. Here, we combine two measurement techniques, local noise thermometry and thermal conductance, to study thermal properties of states with counter-propagating edge modes. We find that, while charge equilibration between counter-propagating edge modes is very fast, the equilibration of heat is extremely inefficient, leading to an almost ballistic heat transport over macroscopic distances. Moreover, we observe an emergent quantization of the heat conductance associated with a strong interaction fixed point of the edge modes. Such understanding of the thermal equilibration on edges with counter-propagating modes is a natural route towards extracting the topological order of the exotic 5/2 state.
Detailed modelling of contact line motion in oscillatory wetting
Authors: Amberg Gustav
Published: January 2022

The experimental results of Xia and Steen for the contact line dynamics of a drop placed on a vertically oscillating surface are analyzed by numerical phase field simulations. The concept of contact line mobility or friction is discussed, and an angle-dependent model is formulated. The results of numerical simulations based on this model are compared to the detailed experimental results of Xia and Steen with good general agreement. The total energy input in terms of work done by the oscillating support, and the dissipation at the contact line, are calculated from the simulated results. It is found that the contact line dissipation is almost entirely responsible for the dissipation that sets the amplitude of the response. It is argued that angle-dependent line friction may be a fruitful interpretation of the relations between contact line speed and dynamic contact angle that are often used in practical computational fluid dynamics.
Metabolic modeling of host–microbe interactions for therapeutics in colorectal cancer
Authors: Bhalla Prerna , Rengaswamy Raghunathan , Karunagaran Devarajan , Suraishkumar G. K. , Sahoo Swagatika
Published: January 2022

The onset of colorectal cancer (CRC) is often attributed to gut bacterial dysbiosis, and thus gut microbiota are highly relevant in devising treatment strategies. Certain gut microbes, like Enterococcus spp., exhibit remarkable anti-neoplastic and probiotic properties, which can aid in silver nanoparticle (AgNPs) induced reactive oxygen species (ROS)-based CRC treatment. However, the effects of AgNPs on gut microbial metabolism have not been reported thus far. In this study, a detailed systems-level understanding of ROS metabolism in Enterococcus durans (E. durans), a representative gut microbe, was gained using constraint-based modeling, wherein, the critical association between ROS and folate metabolism was established. Experimental studies involving low AgNP concentration treatment of E. durans cultures confirmed these modeling predictions (an increased extracellular folate concentration by 52%, at the 9th h of microbial growth, was observed). Besides, the computational studies established various metabolic pathways involving amino acids, energy metabolites, nucleotides, and SCFAs as the key players in elevating folate levels on ROS exposure. The anti-cancer potential of E. durans was also studied through MTT analysis of HCT 116 cells treated with microbial culture (AgNP treated) supernatant. A decrease in cell viability by 19% implicated the role of microbial metabolites (primarily folate) in causing cell death. The genome-scale modeling approach was then extended to extensively model CRC metabolism, as well as CRC–E. durans interactions in the context of CRC treatment, using tissue-specific metabolic models of CRC and healthy colon. These findings on further validation can facilitate the development of robust and effective cancer therapy.
Topological triple phase transition in non-Hermitian Floquet quasicrystals
Authors: Weidemann Sebastian , Kremer Mark , Longhi Stefano , Szameit Alexander
Published: January 2022

Phase transitions connect different states of matter and are often concomitant with the spontaneous breaking of symmetries. An important category of phase transitions is mobility transitions, among which is the well known Anderson localization1, where increasing the randomness induces a metal–insulator transition. The introduction of topology in condensed-matter physics2–4 lead to the discovery of topological phase transitions and materials as topological insulators5. Phase transitions in the symmetry of non-Hermitian systems describe the transition to on-average conserved energy6 and new topological phases7–9. Bulk conductivity, topology and non-Hermitian symmetry breaking seemingly emerge from different physics and, thus, may appear as separable phenomena. However, in non-Hermitian quasicrystals, such transitions can be mutually interlinked by forming a triple phase transition10. Here we report the experimental observation of a triple phase transition, where changing a single parameter simultaneously gives rise to a localization (metal–insulator), a topological and parity–time symmetry-breaking (energy) phase transition. The physics is manifested in a temporally driven (Floquet) dissipative quasicrystal. We implement our ideas via photonic quantum walks in coupled optical fibre loops11. Our study highlights the intertwinement of topology, symmetry breaking and mobility phase transitions in non-Hermitian quasicrystalline synthetic matter. Our results may be applied in phase-change devices, in which the bulk and edge transport and the energy or particle exchange with the environment can be predicted and controlled.