bluuebunny/crossref_metadata_2025 huggingface dataset:
China's Changing Perspective on the WTO: From Aspiration, Assimilation to Alienation
Authors: Gao Henry
Published: April 2022

Since its accession to the WTO twenty years ago, China's image has shifted from a good student aspiring to assimilate itself into the multilateral trading system to one that is increasingly alienated from key WTO principles. How has China's perspective on WTO been evolving? What are the reasons behind China's changing perspective? This paper answers these questions from the Chinese perspective with a comprehensive analysis of the key moments in China's first two decades in the WTO, followed by practical suggestions on how to engage China more constructively in the WTO and beyond.
Women's Judicial Representation in Haiti: Unintended Gains of State-Building Efforts
Authors: Tøraasen Marianne
Published: April 2022

Although women's representation in Haiti is generally very low, the number of women judges has increased since the demise of authoritarianism and violent conflict in the 1990s. This case study explores why. I find that “gender-neutral” judicial reforms aimed at strengthening the judiciary have done more for women's judicial representation than explicitly gender-targeted policies, which still lack implementation. Donor-supported reforms have introduced more merit-based and transparent appointment procedures for magistrates (judges and public prosecutors) based on competitive examinations. This has helped women circumvent the largely male power networks that previously excluded them from the judiciary. The judiciary remains understudied in the scholarship on women's access to decision-making in fragile and conflict-affected societies; this article contributes to this emerging literature.
Being an anti-racist clinician
Authors: Williams Monnica T. , Faber Sonya C. , Duniya Caroline
Published: April 2022

Racism is a pervasive problem in Western society, leading to mental and physical unwellness in people from racialized groups. Psychology began as a racist discipline and still is. As such, most clinical training and curricula do not operate from an anti-racist framework. Although most therapists have seen clients with stress and trauma due to racialization, very few were taught how to assess or treat it. Furthermore, clinicians and researchers can cause harm when they rely on White-dominant cultural norms that do not serve people of colour well. This paper discusses how clinicians can recognize and embrace an anti-racism approach in practice, research, and life in general. Included is a discussion of recent research on racial microaggressions, the difference between being a racial justice ally and racial justice saviour, and new research on what racial allyship entails. Ultimately, the anti-racist clinician will achieve a level of competency that promotes safety and prevents harm coming to those they desire to help, and they will be an active force in bringing change to those systems that propagate emotional harm in the form of racism.

Key learning aims

(1)

Knowledge of how racism manifests in therapy, psychology and society.

(2)

Understanding the difference between racial justice allyship versus saviourship.

(3)

Increased awareness of microaggressions in therapy.

(4)

Appreciation of the importance of combatting systemic racism.
A Bioeconomic Projection of Climate‐Induced Wildfire Risk in the Forest Sector
Authors: Riviere M. , Pimont F. , Delacote P. , Caurla S. , Ruffault J. , Lobianco A. , Opitz T. , Dupuy J. L.
Published: April 2022

Under the influence of climate change, wildfire regimes are expected to intensify and expand to new areas, increasing threats to natural and socioeconomic assets. We explore the environmental and economic implications for the forest sector of climate‐induced changes in wildfire regimes. To retain genericity while considering local determinants, we focus on the regional level and take Mediterranean France as an example. Coupling a bioeconomic forest sector model and a model of wildfire activity, we perform spatially explicit simulations under various levels of radiative forcing. By using a probabilistic framework, we also assess the propagation of several sources of uncertainty to the forest sector, considering both climate‐induced uncertainty and the intrinsic stochasticity of the fire process. By the end of the century, summer burned areas increase by up to 55%, causing moderate losses of merchantable timber and forest carbon stocks, with cascading impacts for industrial activities and climate mitigation in the forest sector. Implications for industries remain limited, but we observe price increases, especially for softwoods, as well as spatially differentiated changes in producer welfare. Inter‐annual fluctuations explain most of uncertainty in wildfire activity, but their impacts on the forest sector are quickly dampened. Over time, owing to the cumulative nature of wildfire impacts on forest resources, uncertainty related to climate warming, climate models’ response and stochasticity intrinsic to the wildfire phenomenon strongly increase in relative importance. Results reassert the need to consider multiple futures in prospective assessments, including uncertainty inherent to natural processes, often omitted in large‐scale economic assessments.
Analytical Solutions for Gravity Changes Caused by Triaxial Volumetric Sources
Authors: Nikkhoo Mehdi , Rivalta Eleonora
Published: April 2022

Volcanic crises are often associated with magmatic intrusions or the pressurization of magma chambers of various shapes. These volumetric sources deform the country rocks, changing their density, and cause surface uplift. Both the net mass of intruding magmatic fluids and these deformation effects contribute to surface gravity changes. Thus, to estimate the intrusion mass from gravity changes, the deformation effects must be accounted for. We develop analytical solutions and computer codes for the gravity changes caused by triaxial sources of expansion. This establishes coupled solutions for joint inversions of deformation and gravity changes. Such inversions can constrain both the intrusion mass and the deformation source parameters more accurately.
Uplift Mechanism of Coastal Extremely Persistent Heavy Rainfall (EPHR): The Key Role of Low‐Level Jets and Ageostrophic Winds in the Boundary Layer
Authors: Huang Xiaogang , Zhang Chi , Fei Jianfang , Cheng Xiaoping , Ding Juli , Liu Haisheng
Published: April 2022

Extremely persistent heavy rainfall (EPHR) events frequently occur in southern China. The mechanisms underlying their generation and development are not well understood, and this leads to difficulties in accurately forecasting these events. In this paper, hourly precipitation grid data and ERA‐5 reanalysis data are used to examine the relationships between precipitation, ageostrophic winds, and low‐level jets (LLJ). The results suggest that ageostrophic winds in the boundary layer mainly exhibit confrontational and asymptotic convergence, with the former being accompanied by double LLJ, which transport more vapor and provide favorable uplift conditions, thus producing stronger precipitation and wider rainbands. The different cooperated relationships between LLJ and ageostrophic winds play an important role in the development of EPHR events, and greater account needs to be taken of these relationships when forecasting.
A Generic Model of Global Earthquake Rupture Characteristics Revealed by Machine Learning
Authors: Li Zefeng
Published: April 2022

Rupture processes of global large earthquakes have been observed to exhibit great variability, whereas recent studies suggest that the average rupture behavior could be unexpectedly simple. To what extent do large earthquakes share common rupture characteristics? Here, we use a machine learning algorithm to derive a generic model of global earthquake source time functions. The model indicates that simple and homogeneous ruptures are pervasive whereas complex and irregular ruptures are relatively rare. Despite the standard long‐tail and near‐symmetric moment release processes, the model reveals two special rupture types: runaway earthquakes with weak growing phases and relatively abrupt termination, and complex earthquakes with all faulting mechanisms but mostly shallow origins (<40 km). The diversity of temporal moment release patterns imposes a limit on magnitude predictability in earthquake early warning. Our results present a panoptic view on the collective similarity and diversity in the rupture processes of global large earthquakes.
Precipitation Scaling With Temperature in the Northeast US: Variations by Weather Regime, Season, and Precipitation Intensity
Authors: Najibi Nasser , Mukhopadhyay Sudarshana , Steinschneider Scott
Published: April 2022

We present a novel hierarchical Bayesian quantile regression model to estimate how precipitation scales with temperature depending on season, weather regime (WR; i.e., large‐scale patterns of atmospheric circulation), and precipitation percentile. The approach develops regional scaling estimates by partially pooling data across sites, accounting for uncertainty stemming from variable record lengths. Results using long‐term records of daily and hourly precipitation and both dry‐bulb and dew point temperature across the Northeast US suggest that regional precipitation scaling rates vary from 0% to 8% per °C. Scaling rate variability is driven most by season and the percentile of precipitation, with only modest variations across WRs. Daily scaling rates are highest in the winter and summer, while hourly rates at the highest percentiles are greatest in summer. Lower scaling rates for more extreme precipitation quantiles are driven by a handful of storms occurring at cooler temperatures but with strong vertical uplift and heavy precipitation.
Small‐Scale Irregularities Within Polarization Jet/SAID During Geomagnetic Activity
Authors: Sinevich A. A. , Chernyshov A. A. , Chugunin D. V. , Oinats A. V. , Clausen L. B. N. , Miloch W. J. , Nishitani N. , Mogilevsky M. M.
Published: April 2022

We study the spatial structure of a polarization jet/Sub‐Auroral Ion Drift (PJ/SAID) based on data from the NorSat‐1 and Swarm satellites during a geomagnetic storm. Observations of plasma parameters inside the PJ/SAID are obtained with NorSat‐1 using a system of Langmuir probes with a nominal sampling rate of up to 1 kHz, which allowed measurements with such a high temporal resolution for the first time. A comparative analysis of plasma parameters and electron density spectra inside PJ according to the data from both satellites is presented. Our results show that fluctuations of plasma parameters inside the PJ increase at all scales with increasing geomagnetic activity. Small‐scale irregularities in the PJ are measured in situ down to hundreds of meters. The role of large‐scale effects in the PJ increases in comparison with the small‐scale ones during high geomagnetic activity. The PJ consists of structures ∼0.2° latitude in size within which small‐scale irregularities are present.
Long‐Term Infrasonic Monitoring of Land and Marine‐Terminating Glaciers in Greenland
Authors: Evers L. G. , Smets P. S. M. , Assink J. D. , Shani‐Kadmiel S. , Kondo K. , Sugiyama S.
Published: April 2022

A period of 18 years of infrasonic recordings was analyzed from a microbarometer array (I18DK) in northwestern Greenland, near Qaanaaq. A huge number of infrasonic detections, over 700,000, have been made in I18DKs soundscape during the Arctic summers. Simultaneously identified were both calving events from marine‐terminating glaciers and discharge related acoustics from a land‐terminating glacier. This infrasonic activity is correlated to sea‐surface and atmospheric temperature, respectively. Inter‐yearly to daily variations were retrieved showing a strong variability in infrasonic detection rates and hence glacier activity. The highest number of infrasonic detections were found in recent years from the land‐terminating glacier. The latter is supported by actual discharge measurements and partly by a discharge model. It is concluded that monitoring infrasound from glaciers can complement other techniques to remotely and passively get insights into glacier dynamics with high temporal and spatial resolution.
Distinct Lithospheric Structure in the Xing'an‐Mongolian Orogenic Belt
Authors: He Yang , Chen Qi‐Fu , Chen Ling , Wang Xin , Guo Guangrui , Li Tianjue , Zhang Kaiwen , Li Juan , Chen Yun
Published: April 2022

Detailed knowledge of the lithospheric structure is essential for a better understanding of the tectonic evolution of the Xing'an‐Mongolian Orogenic Belt (XMOB). We constrained the lithospheric structure across the XMOB by receiver function imaging and shear wave splitting analysis from a dense seismic array. The lithosphere‐asthenosphere boundary (LAB) is coherently imaged in different tectonic blocks. The mid‐lithospheric discontinuity is also identified at ∼75–100 km depth over the deeper LAB (∼110–130 km) beneath the western side of the North‐South Gravity Lineament (NSGL), roughly at the same depth as the LAB beneath the eastern side of the NSGL. The distinct variations in both the lithospheric structure and fast shear‐wave polarization direction across the NSGL are likely caused by different tectonic processes in the two sides, indicating that the NSGL might represent the western boundary influenced by the subduction of the (Paleo‐)Pacific Plate. Lithosphere thinning in the XMOB is evidenced to have been limited mainly to the east of the NSGL.
Simulation of Ionospheric Perturbations Induced by Rocket‐Propelled Vehicle: A Semi‐Empirical Approach
Authors: Ducourtieux Pierre
Published: April 2022

The flight of rocket‐propelled vehicles triggers acoustic waves that propagate through the atmosphere and induce electron density changes at ionospheric heights. These perturbations can be observed using multi‐frequency Global Navigation Satellite System (GNSS) receivers, sounding the ionosphere by taking advantage of its dispersive property. We extend an existing lightweight modeling approach to reproduce the shape, amplitude and timing of the observed perturbations using a semi‐empirical source model based on flight conditions and engine characteristics to express the acoustic perturbations generated by the exhaust gases and a three‐dimensional ray tracing method accounting for dissipative and dispersive effects to propagate the waveform through the atmosphere. Perturbations of the ionospheric plasma are estimated using a simplified model of collisions between neutral and charged particles. The developed simulation framework is applied to the launch of SpaceX's Crew Dragon spacecraft on May 30, 2020 from Kennedy Space Center. The amplitude, shape and timing of simulated perturbations are in good agreement with measurements made by GNSS ground‐based receivers located in the region. This approach is a new step toward rapid characterization of anthropogenic activity in the atmosphere as well as natural events releasing energy near the Earth's surface (earthquake, volcanic activity, etc.) based on GNSS technology.
Physics‐Informed Neural Networks (PINNs) for Wave Propagation and Full Waveform Inversions
Authors: Rasht‐Behesht Majid , Huber Christian , Shukla Khemraj , Karniadakis George Em
Published: April 2022

We propose a new approach to the solution of the wave propagation and full waveform inversions (FWIs) based on a recent advance in deep learning called physics‐informed neural networks (PINNs). In this study, we present an algorithm for PINNs applied to the acoustic wave equation and test the method with both forward models and FWI case studies. These synthetic case studies are designed to explore the ability of PINNs to handle varying degrees of structural complexity using both teleseismic plane waves and seismic point sources. PINNs' meshless formalism allows for a flexible implementation of the wave equation and different types of boundary conditions. For instance, our models demonstrate that PINN automatically satisfies absorbing boundary conditions, a serious computational challenge for common wave propagation solvers. Furthermore, a priori knowledge of the subsurface structure can be seamlessly encoded in PINNs' formulation. We find that the current state‐of‐the‐art PINNs provide good results for the forward model, even though spectral element or finite difference methods are more efficient and accurate. More importantly, our results demonstrate that PINNs yield excellent results for inversions on all cases considered and with limited computational complexity. We discuss the current limitations of the method with complex velocity models as well as strategies to overcome these challenges. Using PINNs as a geophysical inversion solver offers exciting perspectives, not only for the full waveform seismic inversions, but also when dealing with other geophysical datasets (e.g., MT, gravity) as well as joint inversions because of its robust framework and simple implementation.
Examining Parameterizations of Potential Temperature Variance Across Varied Landscapes for Use in Earth System Models
Authors: Waterman T. , Bragg A. D. , Katul G. , Chaney N.
Published: April 2022

Earth system models (ESMs) and mesoscale models have come to employ increasingly complex parameterization schemes for the atmospheric boundary layer, requiring surface boundary conditions for numerous higher order turbulence statistics. Of particular interest is the potential temperature variance (PTV), which is used not only as a boundary condition itself but also to close boundary conditions of other statistics. The existing schemes in ESMs largely rely on the assumptions of Monin‐Obukhov similarity theory (MOST) and are not necessarily applicable over complex and heterogeneous surfaces where large scale circulations and roughness sub‐layer effects may cause deviations from MOST. The National Ecological Observation Network is used here to evaluate existing parameterizations for the surface boundary of PTV, note key deficiencies, and explore possible remedies. The results indicate that existing schemes are acceptable over a variety of surface conditions provided the analysis of a priori filters out low frequency variability not associated with turbulent time scales. There was, however, significant inter‐site variability in observed similarity constants and a significant bias when compared to the textbook values of these parameters. Existing models displayed the poorest performance over heterogeneous sites and rough landscapes. Attempts to use canopy structure and surface roughness characteristics to improve the results confirmed a relation between these variables and PTV but failed to significantly improve the predictive power of the models. The results did not find strong evidence indicating that large scale circulations caused substantial deviations from textbook models, although additional analysis is required to assess their full impacts.
How to Calibrate a Dynamical System With Neural Network Based Physics?
Authors: Balogh B. , Saint‐Martin D. , Ribes A.
Published: April 2022

Unlike the traditional subgrid scale parameterizations used in climate models, current machine learning (ML) parameterizations are only tuned offline, by minimizing a loss function on outputs from high‐resolution models. This approach often leads to numerical instabilities and long‐term biases. Here, we propose a method to design tunable ML parameterizations and calibrate them online. The calibration of the ML parameterization is achieved in two steps. First, some model parameters are included within the ML model input. This ML model is fitted at once for a range of values of the parameters, using an offline metric. Second, once the ML parameterization has been plugged into the climate model, the parameters included among the ML inputs are optimized with respect to an online metric quantifying errors on long‐term statistics. We illustrate our method with two simple dynamical systems. Our approach significantly reduces long‐term biases of the ML model.
La Soufriere Volcanic Eruptions Launched Gravity Waves Into Space
Authors: Yue Jia , Miller Steven D. , Straka William C. , Noh Yoo‐Jeong , Chou Min‐Yang , Kahn Ralph , Flower Verity
Published: April 2022

Atmospheric gravity waves can be excited by explosive volcanic eruptions and may reach Earth's upper atmosphere. In this study, we report on mesoscale concentric gravity waves observed in the mesopause airglow layer following the La Soufriere volcano eruption in April 2021. A large ash plume observed by the spaceborne Multi‐angle Imaging SpectroRadiometer instrument on April 10 reached ∼20 km. Temporal evolution of the volcanic ash plume was provided by the GOES‐16 Advanced Baseline Imager. Nightglow gravity waves were observed by the Visible Infrared Imaging Radiometer Suite Day Night Band. These waves had horizontal wavelengths of ∼25–40 km, and took about a half‐to‐1 hr to travel from the tropopause to the mesopause. Some concentric ionospheric disturbance signatures are also seen in Global Navigation Satellite System‐total electron content maps. We found the launch of gravity waves to be highly correlated with the elevated ash plume from explosive eruptions.
Tomographic Imaging of the Plate Geometry Beneath the Arunachal Himalaya and Burmese Subduction Zones
Authors: Dubey Arun Kumar , Singh Arun , Kumar M. Ravi , Jana Niptika , Sarkar Sukanta , Saikia Dipankar , Singh Chandrani
Published: April 2022

We present 3‐D P and S‐wave velocity perturbation maps of the upper‐mantle beneath eastern Himalaya and Burmese subduction zones at 2° × 2° lateral resolution, using teleseismic travel‐time tomography. Collated waveforms of 5,727 teleseismic earthquakes recorded at 273 seismic stations generated an accurate data set of 86,570 P‐arrival and 85,227 S‐arrival times using multichannel cross‐correlation. Tomograms enabled imaging of the structural features down to 1,000 km depth. The subducting Indian lithospheric plate extends up to Bangong‐Nujiang Suture Zone, overturns and descends steeply beyond 200 km below the Himalayan arc. A southward plunging detached slab can be traced beyond 600 km. Results reveal no evidence for the detachment of a S‐E deflecting Indian lithospheric slab below the Burmese arc. The geometry of the slab mimics regional seismicity (up to 200 km) followed by a deeper aseismic zone related to petrological changes. No gaps are seen between the northward and eastward subducting Indian plate, hence confining the eastward escape of Tibetan‐lithospheric material between the Eastern Himalayan Syntaxis and Sichuan Basin.
Complex Coseismic and Postseismic Faulting During the 2021 Northern Thessaly (Greece) Earthquake Sequence Illuminated by InSAR Observations
Authors: Yang Jiuyuan , Xu Caijun , Wen Yangmao , Xu Guangyu
Published: April 2022

Three Mw > 5.5 earthquakes (Tyrnavos, Elassona and Verdikoussa earthquakes) struck the northern Thessaly, Greece, from 3 March to 12 March 2021, filling a significant seismic gap. We exploit Interferometric synthetic aperture radar data to investigate coseismic deformation of these events and the first half‐year postseismic deformation related to the Tyrnavos event. Our coseismic modeling reveals that the seismic sequence activated at least four unmapped low‐angle normal faults. However, postseismic analysis shows that afterslip propagates updip to a high‐angle shallow structure, indicating that the coseismic slip and afterslip jointly activated a ramp‐flat structure. By a comprehensive analysis of the inversions, fault distribution, relocated aftershocks and regional stress changes, we highlight that intersections between the main and secondary faults control the slip extent and rupture termination in each earthquake and that static stress transfers induced by earlier event encourage the rupture reinitiation of the later event.
MESSENGER Observations of Planetary Ion Enhancements at Mercury's Northern Magnetospheric Cusp During Flux Transfer Event Showers
Authors: Sun Weijie , Slavin James A. , Milillo Anna , Dewey Ryan M. , Orsini Stefano , Jia Xianzhe , Raines Jim M. , Livi Stefano , Jasinski Jamie M. , Fu Suiyan , Zhao Jiutong , Zong Qiu‐Gang , Saito Yoshifumi , Li Changkun
Published: April 2022

At Mercury, several processes can release ions and neutrals out of the planet's surface. Here we present enhancements of planetary ions (Na+‐group ions) in Mercury's northern magnetospheric cusp during flux transfer event (FTE) “showers.” FTE showers are intervals of intense dayside magnetopause reconnection, during which FTEs are observed in quick succession, that is, only separated by a few seconds. This study identifies 1953 FTE shower intervals and 1795 Non‐FTE shower intervals. During the shower intervals, this study shows that the FTEs form a solar wind entry layer equatorward of the northern magnetospheric cusp. In this entry layer, solar wind ions are accelerated and move downward (i.e., planetward) toward the cusp, which sputter upward‐moving planetary ions with a particle flux of 1 × 1011 m−2 s−1 within 1 min. The precipitation rate is estimated to increase by an order of magnitude during FTE showers, to 2 × 1025 s−1, and the neutral density of the exosphere could vary by >10% in response to this FTE‐driven sputtering. Such rapid large‐scale variations driven by dayside reconnection may explain the minute‐to‐minute changes in Mercury's exosphere, especially on the high latitudes, observed by ground‐based telescopes on Earth. Our MESSENGER in situ observation of enhanced planetary ions in the entry layer likely corresponds to an escape channel for Mercury's planetary ions. Comprehensive, future multipoint measurements made by BepiColombo will greatly enhance our understanding of the processes contributing to Mercury's dynamic exosphere and magnetosphere.
Glycoside hydrolase from the GH76 family indicates that marine Salegentibacter sp. Hel_I_6 consumes alpha-mannan from fungi
Authors: Solanki Vipul , Krüger Karen , Crawford Conor J , Pardo-Vargas Alonso , Danglad-Flores José , Hoang Kim Le Mai , Klassen Leeann , Abbott D Wade , Seeberger Peter H , Amann Rudolf I , Teeling Hanno , Hehemann Jan-Hendrik
Published: April 2022

Microbial glycan degradation is essential to global carbon cycling. The marine bacterium Salegentibacter sp. Hel_I_6 (Bacteroidota) isolated from seawater off Helgoland island (North Sea) contains an α-mannan inducible gene cluster with a GH76 family endo-α-1,6-mannanase (ShGH76). This cluster is related to genetic loci employed by human gut bacteria to digest fungal α-mannan. Metagenomes from the Hel_I_6 isolation site revealed increasing GH76 gene frequencies in free-living bacteria during microalgae blooms, suggesting degradation of α-1,6-mannans from fungi. Recombinant ShGH76 protein activity assays with yeast α-mannan and synthetic oligomannans showed endo-α-1,6-mannanase activity. Resolved structures of apo-ShGH76 (2.0 Å) and of mutants co-crystalized with fungal mannan-mimicking α-1,6-mannotetrose (1.90 Å) and α-1,6-mannotriose (1.47 Å) retained the canonical (α/α)6 fold, despite low identities with sequences of known GH76 structures (GH76s from gut bacteria: <27%). The apo-form active site differed from those known from gut bacteria, and co-crystallizations revealed a kinked oligomannan conformation. Co-crystallizations also revealed precise molecular-scale interactions of ShGH76 with fungal mannan-mimicking oligomannans, indicating adaptation to this particular type of substrate. Our data hence suggest presence of yet unknown fungal α-1,6-mannans in marine ecosystems, in particular during microalgal blooms.
Evolution of gene expression signature in mammary gland stem cells from neonatal to old mice
Authors: Huang Xiaoling , Xu Yue , Qian Lu , Zhao Qian , Liu Pengfei , Lü Jinhui , Guo Yuefan , Ma Wenjing , Wang Guangxue , Li Shujun , Luo An , Yang Xiaolai , Wang Haiyun , Yu Zuoren
Published: April 2022

During the lifetime of females, mammary epithelial cells undergo cyclical expansion and proliferation depending on the cyclical activation of mammary gland stem/progenitor cells (MaSCs) in response to the change of hormone level. The structural shrink of mammary duct tree and the functional loss of mammary gland occur along with inactivation of MaSCs in old females, even leading to breast cancer occasionally. However, the gene expression signature in MaSCs across the lifespan remains unclear. Herein, we tested the tissue regeneration ability of CD24+CD49fhigh MaSCs over six time points from neonatal (4-day-old) to aged mice (360-day-old). Further RNA-seq analyses identified four clusters of gene signatures based on the gene expression patterns. A subset of stemness-related genes was identified, showing the highest level at day 4 of the neonatal age, and the lowest level at the old age. We also identified an aging-related gene signature showing significant change in the old mice, in which an association between aging process and stemness loss was indicated. The aging-related gene signature showed regulation of cancer signaling pathways, as well as aging-related diseases including Huntington disease, Parkinson disease, and Alzheimer disease. Moreover, 425, 1056, 418, and 1107 gene variants were identified at D20, D40, D90, and D180, respectively, which were mostly reported to associated with tumorigenesis and metastasis in cancer. In summary, the current study is the first to demonstrate the gene expression shift in MaSCs from neonatal to aging, which leads to stemness loss, aging, aging-related diseases, and even breast cancer in old mice.
Cooperative light-induced breathing of soft porous crystals via azobenzene buckling
Authors: Krause Simon , Evans Jack D. , Bon Volodymyr , Crespi Stefano , Danowski Wojciech , Browne Wesley R. , Ehrling Sebastian , Walenszus Francesco , Wallacher Dirk , Grimm Nico , Többens Daniel M. , Weiss Manfred S. , Kaskel Stefan , Feringa Ben L.
Published: April 2022

Although light is a prominent stimulus for smart materials, the application of photoswitches as light-responsive triggers for phase transitions of porous materials remains poorly explored. Here we incorporate an azobenzene photoswitch in the backbone of a metal-organic framework producing light-induced structural contraction of the porous network in parallel to gas adsorption. Light-stimulation enables non-invasive spatiotemporal control over the mechanical properties of the framework, which ultimately leads to pore contraction and subsequent guest release via negative gas adsorption. The complex mechanism of light-gated breathing is established by a series of in situ diffraction and spectroscopic experiments, supported by quantum mechanical and molecular dynamic simulations. Unexpectedly, this study identifies a novel light-induced deformation mechanism of constrained azobenzene photoswitches relevant to the future design of light-responsive materials.
Long-term in vivo imaging of mouse spinal cord through an optically cleared intervertebral window
Authors: Wu Wanjie , He Sicong , Wu Junqiang , Chen Congping , Li Xuesong , Liu Kai , Qu Jianan Y.
Published: April 2022

The spinal cord accounts for the main communication pathway between the brain and the peripheral nervous system. Spinal cord injury is a devastating and largely irreversible neurological trauma, and can result in lifelong disability and paralysis with no available cure. In vivo spinal cord imaging in mouse models without introducing immunological artifacts is critical to understand spinal cord pathology and discover effective treatments. We developed a minimally invasive intervertebral window by retaining the ligamentum flavum to protect the underlying spinal cord. By introducing an optical clearing method, we achieve repeated two-photon fluorescence and stimulated Raman scattering imaging at subcellular resolution with up to 15 imaging sessions over 6–167 days and observe no inflammatory response. Using this optically cleared intervertebral window, we study neuron-glia dynamics following laser axotomy and observe strengthened contact of microglia with the nodes of Ranvier during axonal degeneration. By enabling long-term, repetitive, stable, high-resolution and inflammation-free imaging of mouse spinal cord, our method provides a reliable platform in the research aiming at interpretation of spinal cord physiology and pathology.
A general strategy for heterogenizing olefin polymerization catalysts and the synthesis of polyolefins and composites
Authors: Zou Chen , Si Guifu , Chen Changle
Published: April 2022

The heterogenization of homogeneous metal complexes on solid supports presents an efficient strategy for bridging homogeneous catalysts with industrially-preferred heterogeneous catalysts; however, a series of drawbacks restrict their implementation in olefin polymerization, particularly for copolymerization with polar comonomers. In this contribution, we report an ionic anchoring strategy that is highly versatile, generally applicable to different systems, and enables strong catalyst-support interactions while tolerating various polar functional groups. In addition to greatly enhanced polymerization properties, the supported catalysts achieved higher comonomer incorporation than their unsupported counterparts. This strategy enabled efficient polymerization at high temperatures at large scale and great control over product morphology, and the facile synthesis of polyolefin composites. More importantly, the dispersion of different fillers in the polyolefin matrix produced great material properties even at low composite loadings. It is expected that this strategy will find applications in different catalytic systems and the synthesis of advanced engineering materials.
Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy
Authors: Wang Chao , Fan Li , Khawaja Rabia R. , Liu Bangyan , Zhan Lihong , Kodama Lay , Chin Marcus , Li Yaqiao , Le David , Zhou Yungui , Condello Carlo , Grinberg Lea T. , Seeley William W. , Miller Bruce L. , Mok Sue-Ann , Gestwicki Jason E. , Cuervo Ana Maria , Luo Wenjie , Gan Li
Published: April 2022

Activation of microglia is a prominent pathological feature in tauopathies, including Alzheimer’s disease. How microglia activation contributes to tau toxicity remains largely unknown. Here we show that nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, activated by tau, drives microglial-mediated tau propagation and toxicity. Constitutive activation of microglial NF-κB exacerbated, while inactivation diminished, tau seeding and spreading in young PS19 mice. Inhibition of NF-κB activation enhanced the retention while reduced the release of internalized pathogenic tau fibrils from primary microglia and rescued microglial autophagy deficits. Inhibition of microglial NF-κB in aged PS19 mice rescued tau-mediated learning and memory deficits, restored overall transcriptomic changes while increasing neuronal tau inclusions. Single cell RNA-seq revealed that tau-associated disease states in microglia were diminished by NF-κB inactivation and further transformed by constitutive NF-κB activation. Our study establishes a role for microglial NF-κB signaling in mediating tau spreading and toxicity in tauopathy.
A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
Authors: He Yong-Qiao , Wang Tong-Min , Ji Mingfang , Mai Zhi-Ming , Tang Minzhong , Wang Ruozheng , Zhou Yifeng , Zheng Yuming , Xiao Ruowen , Yang Dawei , Wu Ziyi , Deng Changmi , Zhang Jiangbo , Xue Wenqiong , Dong Siqi , Zhan Jiyun , Cai Yonglin , Li Fugui , Wu Biaohua , Liao Ying , Zhou Ting , Zheng Meiqi , Jia Yijing , Li Danhua , Cao Lianjing , Yuan Leilei , Zhang Wenli , Luo Luting , Tong Xiating , Wu Yanxia , Li Xizhao , Zhang Peifen , Zheng Xiaohui , Zhang Shaodan , Hu Yezhu , Qin Weiling , Deng Bisen , Liang Xuejun , Fan Peiwen , Feng Yaning , Song Jia , Xie Shang-Hang , Chang Ellen T. , Zhang Zhe , Huang Guangwu , Xu Miao , Feng Lin , Jin Guangfu , Bei Jinxin , Cao Sumei , Liu Qing , Kozlakidis Zisis , Mai Haiqiang , Sun Ying , Ma Jun , Hu Zhibin , Liu Jianjun , Lung Maria Li , Adami Hans-Olov , Shen Hongbing , Ye Weimin , Lam Tai-Hing , Zeng Yi-Xin , Jia Wei-Hua
Published: April 2022

Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
Human pancreatic microenvironment promotes β-cell differentiation via non-canonical WNT5A/JNK and BMP signaling
Authors: Chmielowiec Jolanta , Szlachcic Wojciech J. , Yang Diane , Scavuzzo Marissa A. , Wamble Katrina , Sarrion-Perdigones Alejandro , Sabek Omaima M. , Venken Koen J. T. , Borowiak Malgorzata
Published: April 2022

In vitro derivation of pancreatic β-cells from human pluripotent stem cells holds promise as diabetes treatment. Despite recent progress, efforts to generate physiologically competent β-cells are still hindered by incomplete understanding of the microenvironment’s role in β-cell development and maturation. Here, we analyze the human mesenchymal and endothelial primary cells from weeks 9-20 fetal pancreas and identify a time point-specific microenvironment that permits β-cell differentiation. Further, we uncover unique factors that guide in vitro development of endocrine progenitors, with WNT5A markedly improving human β-cell differentiation. WNT5A initially acts through the non-canonical (JNK/c-JUN) WNT signaling and cooperates with Gremlin1 to inhibit the BMP pathway during β-cell maturation. Interestingly, we also identify the endothelial-derived Endocan as a SST+ cell promoting factor. Overall, our study shows that the pancreatic microenvironment-derived factors can mimic in vivo conditions in an in vitro system to generate bona fide β-cells for translational applications.
Inducible and reversible RNA N6-methyladenosine editing
Authors: Shi Huaxia , Xu Ying , Tian Na , Yang Ming , Liang Fu-Sen
Published: April 2022

RNA modifications, including N6-methyladenosine (m6A), have been reported to regulate fundamental RNA processes and properties, and directly linked to various human diseases. Methods enabling temporal and transcript/locus-specific editing of specific RNA modifications are essential, but still limited, to dissect the dynamic and context-dependent functions of these epigenetic modifications. Here, we develop a chemically inducible and reversible RNA m6A modification editing platform integrating chemically induced proximity (CIP) and CRISPR methods. We show that m6A editing can be temporally controlled at specific sites of individual RNA transcripts by the addition or removal of the CIP inducer, abscisic acid (ABA), in the system. By incorporating a photo-caged ABA, a light-controlled version of m6A editing platform can be developed. We expect that this platform and strategy can be generally applied to edit other RNA modifications in addition to m6A.
Meiotic drive in chronic lymphocytic leukemia compared with other malignant blood disorders
Authors: Jønsson Viggo , Awan Haneef , Jones Neil Deaton , Johannesen Tom Børge , Thøgersen Klaus , Steig Bjarni á , Andorsdottir Gudrid , Tjønnfjord Geir Erland
Published: April 2022

The heredity of the malignant blood disorders, leukemias, lymphomas and myeloma, has so far been largely unknown. The present study comprises genealogical investigations of one hundred and twelve Scandinavian families with unrelated parents and two or more cases of malignant blood disease. For comparison, one large family with related family members and three hundred and forty-one cases of malignant blood disease from the Faroese population was included. The inheritance is non-Mendelian, a combination of genomic parental imprinting and feto-maternal microchimerism. There is significantly more segregation in maternal than in paternal lines, predominance of mother-daughter combinations in maternal lines, and father-son combinations in paternal lines. Chronic lymphocytic leukemia is the most frequent diagnosis in the family material, and chronic lymphocytic leukemia has a transgenerational segregation that is unique in that inheritance of susceptibility to chronic lymphocytic leukemia is predominant in males of paternal lines. Male offspring with chronic lymphocytic leukemia in paternal lines have a birth-order effect, which is manifest by the fact that there are significantly more male patients late in the sibling line. In addition, there is contravariation in chronic lymphocytic leukemia, i.e. lower occurrence than expected in relation to other diagnoses, interpreted in such a way that chronic lymphocytic leukemia remains isolated in the pedigree in relation to other diagnoses of malignant blood disease. Another non-Mendelian function appears in the form of anticipation, i.e. increased intensity of malignancy down through the generations and a lower age at onset of disease than otherwise seen in cases from the Cancer Registers, in acute lymphoblastic leukemia, for example. It is discussed that this non-Mendelian segregation seems to spread the susceptibility genes depending on the gender of the parents and not equally to all children in the sibling line, with some remaining unaffected by susceptibility i.e. "healthy and unaffected", due to a birth order effect. In addition, anticipation is regarded as a non-Mendelian mechanism that can amplify, «preserve» these vital susceptibility genes in the family. Perhaps this segregation also results in a sorting of the susceptibility, as the percentage of follicular lymphoma and diffuse large B-cell lymphoma is lower in the family material than in an unselected material. Although leukemias, lymphomas and myelomas are potentially fatal diseases, this non-Mendelian distribution and amplification hardly play any quantitative role in the survival of Homo sapiens, because these diseases mostly occur after fertile age.
Effective pretreatment of lignin-rich coconut wastes using a low-cost ionic liquid
Authors: Anuchi Samson O. , Campbell Kyra L. Sedransk , Hallett Jason P.
Published: April 2022

Coconut husks and shells are underutilised agricultural feedstocks in the bio-based industry. These biomass wastes have a higher lignin content than other woody biomass and have excellent potential as raw materials for the production of lignin-based materials. This work demonstrates the performance of a low-cost protic ionic liquid,N,N,N-dimethylbutylammonium hydrogen sulfate ([DMBA][HSO4]), for ionoSolv pretreatment of coconut husk and shell at 150 °C for 45–90 min and 170 °C for 15–60 min. Optimum pretreatment conditions were observed at 170 °C and 45 min for both feedstocks. At these conditions, [DMBA][HSO4] was able to remove almost 77 wt% of the lignin from the husk; leaving a cellulosic rich pulp behind, which released 82 % of the theoretical maximum glucose after enzymatic saccharification. The pretreated shell, by comparison, achieved 82 wt% lignin removal and 89 % glucose yield and these higher values could be attributed to the highly porous structure of coconut shell cell walls. The cleavage of the β-O-4 aryl ether linkages of lignin followed by extensive C–C condensation in the lignin at longer pretreatment times was shown by HSQC NMR analysis. This extensive condensation was evidenced by molecular weights > 10,000 g/mol exhibited by lignin precipitated after pretreatment at high temperature and long times. The high degree of lignin removal and high glucose release from both feedstocks demonstrate that [DMBA][HSO4] is an excellent ionic liquid for fractionation of very lignin-rich biomass.
Relationship between rs7586085, GALNT3 and CCDC170 gene polymorphisms and the risk of osteoporosis among the Chinese Han population
Authors: Zhang Jiaqiang , Cai Qinlei , Chen Wangxue , Huang Maoxue , Guan Renyang , Jin Tianbo
Published: April 2022

Osteoporosis (OP) has plagued many women for years, and bone density loss is an indicator of OP. The purpose of this study was to evaluate the relationship between the polymorphism of the rs7586085, CCDC170 and GALNT3 gene polymorphisms and the risk of OP in the Chinese Han population. Using the Agena MassArray method, we identified six candidate SNPs on chromosomes 2 and 6 in 515 patients with OP and 511 healthy controls. Genetic model analysis was performed to evaluate the significant association between variation and OP risk, and meanwhile, the multiple tests were corrected by false discovery rate (FDR). Haploview 4.2 was used for haplotype analysis. In stratified analysis of BMI ˃ 24, rs7586085, rs6726821, rs6710518, rs1346004, and rs1038304 were associated with the risk of OP based on the results of genetic models among females even after the correction of FDR (qd < 0.05). In people at age ≤ 60 years, rs1038304 was associated with an increased risk of OP under genetic models after the correction of FDR (qd < 0.05). Our study reported that GALNT3 and CCDC170 gene polymorphisms and rs7586085 are the effective risk factors for OP in the Chinese Han population.
Optimal intervention strategies to mitigate the COVID-19 pandemic effects
Authors: Kasis Andreas , Timotheou Stelios , Monshizadeh Nima , Polycarpou Marios
Published: April 2022

Governments across the world are currently facing the task of selecting suitable intervention strategies to cope with the effects of the COVID-19 pandemic. This is a highly challenging task, since harsh measures may result in economic collapse while a relaxed strategy might lead to a high death toll. Motivated by this, we consider the problem of forming intervention strategies to mitigate the impact of the COVID-19 pandemic that optimize the trade-off between the number of deceases and the socio-economic costs. We demonstrate that the healthcare capacity and the testing rate highly affect the optimal intervention strategies. Moreover, we propose an approach that enables practical strategies, with a small number of policies and policy changes, that are close to optimal. In particular, we provide tools to decide which policies should be implemented and when should a government change to a different policy. Finally, we consider how the presented results are affected by uncertainty in the initial reproduction number and infection fatality rate and demonstrate that parametric uncertainty has a more substantial effect when stricter strategies are adopted.
Trajectory to local extinction of an isolated dugong population near Okinawa Island, Japan
Authors: Kayanne Hajime , Hara Takeshi , Arai Nobuaki , Yamano Hiroya , Matsuda Hiroyuki
Published: April 2022

A small animal population becomes extinct owing to demographic and environmental stochasticity after declining below the minimum viable population (MVP). However, the actual process of extinction derived by stochastic factors after crossing MVP has not been recorded for long-lived marine mammals. Here, we reconstructed the declining history of a small, isolated population of dugongs in Okinawa over 125 years. The initial population size of approximately 280–420 in the nineteenth century declined to approximately < 100 in 1917 because of overfishing, < 70 in 1979, 11 in 1997, 3 after 2006, and all known individuals disappeared or died by 2019. After 1979, a decline in the natural growth rate has led to extinction. Long-lived animals may persist for a few decades after the population falls below the MVP, at which time active conservation measures, such as captive breeding, should be implemented.