bluuebunny/crossref_metadata_2025 huggingface dataset:
Who Stays Poor and Who Doesn’t? An Analysis Based on Joint Assessment of Income and Assets
Authors: CHEN JUN-HONG , WU CHI-FANG , ZHENG HAOTIAN
Published: June 2022

When designing programs to assist the poor, it is important to recognize who is most in need of government assistance. Although measures of poverty are often based on income alone, poverty measures based on both income and assets provide greater precision in the analysis of this group since accumulated assets can be liquidated to compensate for temporary shortfalls in income. The current study used the Panel Study of Income Dynamics (2007–2017) to analyze associations between different facets of poverty dynamics (i.e. poverty entry and exit) and its determinants. We explored differences in results based on whether poverty was measured by income alone, or income plus assets. The Cox proportional hazard regression was used to examine how demographic characteristics predicted poverty entry and poverty exit. Results indicated factors predicting poverty entry were not identical to those predicting difficulty of exiting poverty. Also, the risk of poverty entry and exit differed based on whether poverty was measured by income alone, or income plus assets. Thus, using income plus assets provides new perspectives into poverty dynamics which past research, based on income alone, did not provide. These new insights can be used to inform decisions about policies for poverty prevention and alleviation.
Wishing for More: Technological Change, the Rise of Involuntary Part-Time Employment and the Role of Active Labour Market Policies
Authors: VAN DOORN LARS , VAN VLIET OLAF
Published: June 2022

Technological change has squeezed the demand for middle-skill jobs, which typically involve routine-intense tasks. This squeeze has coincided with an increase in the number of part-time working individuals who wish to work more hours. We argue that these two trends are linked. Due to the decline of middle-skill employment, medium-educated workers shift into low-skill employment, increasing the supply of labour for jobs in this segment of the labour market. This pushes those dependent on these jobs to accept part-time jobs, even if these involve fewer hours than they prefer. To empirically assess this claim, we analyse involuntary part-time employment across 16 European countries between 1999 and 2010. Our analysis confirms that a decline in middle-skill employment is associated with an increase in involuntary part-time employment at the bottom end of the labour market. This finding implies that the automation of routine-intense labour worsens employment possibilities in this segment of the labour market. However, we show that training and job creation schemes mitigate this effect. These programmes cushion competition either by providing medium-educated workers with the necessary skills to shift into high-skill jobs or by increasing employment possibilities. Thus, governments have the tools to support workers facing challenges in the knowledge economy.
Belowground structure and determinants of woody plant height at a tropical dry forest site in Zambia, southern Africa
Authors: Chidumayo Emmanuel N.
Published: June 2022

Root metrics and plant height for 256 excavated saplings and small trees of 27 species, including sown plants, were used to describe belowground structure and assess factors that influence shoot growth in a tropical dry forest (TDF) in Zambia. Models were developed to (i) estimate taproot depth from incomplete excavations and (ii) coarse lateral root biomass from proximal diameter data. The majority of the species studied are slow-growing and had a median height of <200 cm at the age of 16 years. Root development advanced sequentially from taproot elongation to thickening to coarse lateral root development. Shrubs in shallow soil had short taproots with a lower wood density. Plant age explained <10% of the variance in shoot height. Root variables explained the majority of the variance in shoot height. More research is needed to improve our knowledge about how belowground structures influence shoot growth and tree recruitment in TDFs of southern Africa.
Aortic valve replacement using On-X valve in a child postorthotopic heart transplantation
Authors: James Adam , Foley Ross , Murchan Helene , Hasan Asif , DeRita Fabrizio , Reinhardt Zdenka , McMahon Colin J.
Published: June 2022

A 20-month-old girl presented with severe dilated cardiomyopathy and decompensated congestive cardiac failure. Despite escalating inotropic and mechanical ventilation support, she required placement on extracorporeal membrane oxygenation and transfer to the transplant centre in Newcastle, England. She was placed on biventricular assist device and then Berlin Heart but failed to show any recovery of ventricular function. She underwent orthotopic heart transplantation at 2 years of age. She developed bacterial endocarditis with Enterococcus faecalis resulting in severe aortic valve regurgitation requiring aortic valve replacement with a 19 mm On-X valve (Airtivion) 11 days after her transplant. Given the size of the donor heart, it was possible to implant a 19-mm valve in this 12 kg child with minimal risk of patient prosthesis mismatch. She was anticoagulated with warfarin (On-X valve INR 2-3 for first 3 months; INR 1.5-2.0 thereafter). Although she suffered several other post-operative complications, including malabsorption, nasojejunal feeding, liver dysfunction, vertebral fractures, renal impairment and renal calcification, and need for repeat opening of her tracheostomy site following her initial decannulation, her aortic valve function has remained stable.
Arsenate removal from aqueous solutions by Mg/Fe-LDH-modified biochar derived from apple tree residues
Authors: SHIRIAZAR Mohammad Ali , SEPEHR Ebrahim , MALEKI Ramin , KHODAVERDILOO Habib , ASADZADEH Farrokh , DOVLATI Behnam , RENGEL Zed
Published: June 2022

The development of non-toxic and inexpensive materials for arsenic removal is required due to water sources being polluted by arsenic in many countries around the world. The main aim of this study was to characterise the capacity and behaviour of Mg/Fe layered double hydroxides/biochar [Magnesium/Iron-Layered Double Hydroxide (Mg/Fe-LDH)] composite for arsenate adsorption from solution. Apple tree pruning residues were used to produce biochar at 500 °C under oxygen-limited atmosphere. Mg/Fe-LDH-biochar was synthesised using a spontaneous in situ co-precipitation method. Batch experiments were used for the assessment of the kinetics, isotherms, and the effects of initial solution pH (4, 6, 8, and 10), ionic strength (0.01, 0.1, and 0.2 mol L−1), and co-occurring anions (carbonate and phosphate) on the arsenate removal. Scanning electron microscope images showed Mg/Fe-LDH were loaded on the biochar porous structure, and X-ray diffraction analysis affirmed the presence of crystalline LDH minerals in Mg/Fe-LDH-biochar. Surface modification of biochar by Mg/Fe-LDH increased the maximum arsenate adsorption capacity (3.6 mg g−1) ten times compared to unmodified biochar (0.35 mg g−1). Arsenate removal capacity increased from 4.2 % to 54.2 % with modification of biochar by Mg/Fe-based LDH. Kinetic studies indicated that >90 % of Mg/Fe-LDH-biochar arsenate adsorption from a starting concentration of 10 mg L−1 occurred in the first 120 min. Pseudo-second order and Langmuir models described well the kinetics and isotherm of arsenate adsorption by biochar and Mg/Fe-LDH-biochar. Mg/Fe-LDH-biochar showed maximum arsenate removal capacity at pH 6. Increasing solution ionic strength and the presence of phosphate and carbonate anions suppressed arsenate removal by Mg/Fe-LDH-biochar. In summary, surface modification of biochar using Mg/Fe-LDH produced a potentially more cost-effective, locally available, reusable, and non-toxic arsenic adsorbent for decontamination of surface- and groundwater.
Formulation of Wavelet Based Multi‐Scale Multi‐Objective Performance Evaluation (WMMPE) Metric for Improved Calibration of Hydrological Models
Authors: Manikanta Velpuri , Vema Vamsi Krishna
Published: June 2022

Estimation of the hydrological model parameters, known as model calibration, is an important step in application of these models for various water resources problems. In the auto‐calibration approach, the match between the simulated and observed variables is assessed using the statistical performance measures, which are used as objective functions. Earlier studies show that the use of traditional single‐objective functions alone cannot capture all the features of the hydrographs, motivating the utilization of multi‐objective calibration. Further, wavelet‐based approaches can capture features that occur at different time scales. In this study, Wavelet Transforms are employed to formulate a Wavelet based Multi‐Scale Multi‐Objective Performance Evaluation (WMMPE) metric that combines multiple standard metrics at multiple time scales. The performance of WMMPE along with other objective functions such as Nash Sutcliffe Efficiency (NSE), Kling Gupta Efficiency (KGE)), Euclidean distance based Multi Objective Calibration Function and wavelet based Multi‐Scale NSE in calibrating two conceptual hydrologic models were tested on 53 watersheds. The performance of the five calibrated models were evaluated for their efficacy in simulating different characteristics of hydrograph such as, low and high flows, water balance components, frequency domain characteristics and average error magnitude. The results show that WMMPE calibrated models are performing well in matching all the flow segments of hydrograph in >22 basins for the two conceptual models. Further, results of the analysis suggested that the presence of outliers have minimum impact on the simulation of WMMPE calibrated models in the validation period.
Detection and Attribution of Human Influence on the Global Diurnal Temperature Range Decline
Authors: Liu Jianyu , Feng Xingyu , Gu Xihui , Zhang Jiawen , Slater Louise J. , Kong Dongdong
Published: June 2022

A decline in the global diurnal temperature range (DTR) and its implications for human and natural systems have been widely reported, yet it remains unclear whether humans have a detectable influence on the DTR and to what extent anthropogenic greenhouse gases (GHG) may be driving such changes. Results indicate that the effect of anthropogenic forcing on the DTR is detectable separately from natural forcing across the globe and in many regions. GHG is the dominant contributor to DTR changes and caused the global DTR to decrease by −0.32°C during 1951–2018, close to the observed change of −0.41°C. Decreased anthropogenic aerosols (AER) increased the DTR in Europe, while increased AER decreased the DTR in Asia. If greenhouse gas emissions continue to rise, further decreases in the DTR are likely to be observed in the future.
Elastic Contrast, Rupture Directivity, and Damage Asymmetry in an Anisotropic Bimaterial Strike‐Slip Fault at Middle Crustal Depths
Authors: Song Bo Ra , Song Won Joon , Johnson Scott E. , Gerbi Christopher C. , Vel Senthil S.
Published: June 2022

Mature faults with large cumulative slip often separate rocks with dissimilar elastic properties and show asymmetric damage distribution. Elastic contrast across such bimaterial faults can significantly modify various aspects of earthquake rupture dynamics, including normal stress variations, rupture propagation direction, distribution of ground motions, and evolution of off‐fault damage. Thus, analyzing elastic contrasts of bimaterial faults is important for understanding earthquake physics and related hazard potential. The effect of elastic contrast between isotropic materials on rupture dynamics is relatively well studied. However, most fault rocks are elastically anisotropic, and little is known about how the anisotropy affects rupture dynamics. We examine microstructures of the Sandhill Corner shear zone, which separates quartzofeldspathic rock and micaceous schist with wider and narrower damage zones, respectively. This shear zone is part of the Norumbega fault system, a Paleozoic, large‐displacement, seismogenic, strike‐slip fault system exhumed from middle crustal depths. We calculate elastic properties and seismic wave speeds of elastically anisotropic rocks from each unit having different proportions of mica grains aligned sub‐parallel to the fault. Our findings show that the horizontally polarized shear wave propagating parallel to the bimaterial fault (with fault‐normal particle motion) is the slowest owing to the fault‐normal compliance and therefore may be important in determining the elastic contrast that affects rupture dynamics in anisotropic media. Following results from subshear rupture propagation models in isotropic media, our results are consistent with ruptures preferentially propagated in the slip direction of the schist, which has the slower horizontal shear wave and larger fault‐normal compliance.
Speed and Acceleration of Droplets Generated by Breaking Wind‐Forced Waves
Authors: Erinin M. A. , Néel B. , Ruth D. J. , Mazzatenta M. , Jaquette R. D. , Veron F. , Deike L.
Published: June 2022

Laboratory measurements of droplet size, velocity, and accelerations generated by mechanically and wind‐forced water breaking waves are reported. The wind free stream velocity is up to 12 m/s, leading to wave slopes from 0.15 to 0.35 at a fetch of 23 m. The ratio of wind free stream and wave phase speed ranges from 5.9 to 11.1, depending on the mechanical wave frequency. The droplet size distribution in all configurations can be represented by two power laws, N(d) ∝ d−1 for drops from 30 to 600 μm and N(d) ∝ d−4 above 600 μm. The horizontal and vertical droplet velocities appear correlated, with drops with slower horizontal speed more likely to move upward. The velocity and acceleration distributions are found to be asymmetric, with the velocity probability density functions (PDFs) being described by a normal‐inverse‐Gaussian distribution. The horizontal acceleration PDF are found to follow a shape close to the one predicted for small particles in homogeneous and isotropic turbulence, while the vertical distribution follows an asymmetric normal shape, showing that both acceleration components are controlled by different physical processes.
Hybrid Kinetic Model of the Interaction Between the Dense Plasma Clouds and Magnetospheric Plasma on Large Time and Spatial Scales, and Comparison With MMS Observations
Authors: Lipatov A. S. , Avanov L. A. , Giles B. L.
Published: June 2022

We present a new simulation results of the cloud dynamics in the ambient magnetospheric plasma on the large time and spatial scales. It was assumed that these impulsive structures observed by the MMS spacecraft originally were created because of the reconnection at the magnetopause. Our new 3‐D hybrid kinetic modeling on the large time and spatial scales captures several of these processes: an excitation of the electromagnetic waves (whistler and shear‐Alfvén waves) and plasma instabilities (mirror and flute); a formation of shock waves, and collapsing diamagnetic cavity; particle acceleration. A strong overshoot in plasma density profile was observed in the modeling and MMS observation at the interface between the cloud and magnetospheric plasma. The cloud expansion into ambient magnetospheric plasma causes the flute waves connected with excitation of the Rayleigh‐Taylor instability observed at the overshoot in plasma density profile across the external magnetic field. The modeling demonstrates a formation of the whistler waves at the initial stage which propagate in the external magnetic field direction. At the later stage, a formation of shear‐Alfvén waves was observed.
Densely Sampled Global Dynamic Topographic Observations and Their Significance
Authors: Holdt M. C. , White N. J. , Stephenson S. N. , Conway‐Jones B. W.
Published: June 2022

Topography and bathymetry are principally supported by some combination of crustal and sub‐crustal density variations. However, dynamic topography is generated by vertical deflection of the Earth's surface as a result of mantle convection. Isolating and quantifying observable dynamic topography yields valuable information about mantle processes. Here, we investigate global dynamic topography by calculating residual depth anomalies throughout the oceanic realm and residual topographic anomalies across the continents. We correct for sedimentary and crustal loading by exploiting a variety of seismologic datasets that include seismic reflection profiles, wide‐angle/refraction surveys, and receiver functions. In this way, an extensively revised and augmented global compilation of 10,874 oceanic residual depth measurements and 3,777 continental residual topographic measurements is constructed. In the oceanic realm, the methodology has been revised to improve accuracy and resolution. First, quartz/clay content of the sedimentary column is adjusted to remove minor skewness of residual depth anomalies as a function of plate age. Secondly, variation of bulk density as a function of crustal thickness is taken into account. Our global compilation is used to generate spherical harmonic representations of observable dynamic topography out to degree 40 (i.e., ∼1,000 km). Resultant spectra demonstrate that dynamic topographic power varies linearly with inverse wavenumber. The spectral slope directly reflects the way by which dynamic topography is generated by Stokes' flow. Our global results are consistent with independent and diverse geologic markers of uplift and subsidence together with Neogene‐Quaternary intraplate basalt magmatism.
A Review of GNSS/GPS in Hydrogeodesy: Hydrologic Loading Applications and Their Implications for Water Resource Research
Authors: White Alissa M. , Gardner W. Payton , Borsa Adrian A. , Argus Donald F. , Martens Hilary R.
Published: June 2022

Hydrogeodesy, a relatively new field within the earth sciences, is the analysis of the distribution and movement of terrestrial water at Earth's surface using measurements of Earth's shape, orientation, and gravitational field. In this paper, we review the current state of hydrogeodesy with a specific focus on Global Navigation Satellite System (GNSS)/Global Positioning System measurements of hydrologic loading. As water cycles through the hydrosphere, GNSS stations anchored to Earth's crust measure the associated movement of the land surface under the weight of changing hydrologic loads. Recent advances in GNSS‐based hydrogeodesy have led to exciting applications of hydrologic loading and subsequent terrestrial water storage (TWS) estimates. We describe how GNSS position time series respond to climatic drivers, can be used to estimate TWS across temporal scales, and can improve drought characterization. We aim to facilitate hydrologists' use of GNSS‐observed surface deformation as an emerging tool for investigating and quantifying water resources, propose methods to further strengthen collaborative research and exchange between geodesists and hydrologists, and offer ideas about pressing questions in hydrology that GNSS may help to answer.
Targeting fibrosis: mechanisms and clinical trials
Authors: Zhao Manyu , Wang Liqun , Wang Mengzhu , Zhou Shijie , Lu Ying , Cui Huijie , Racanelli Alexandra C. , Zhang Ling , Ye Tinghong , Ding Bisen , Zhang Ben , Yang Jinliang , Yao Yuqin
Published: June 2022

Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including the liver, kidney, heart, and lung. Fibrosis such as liver cirrhosis, idiopathic pulmonary fibrosis, and cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated by various signals, such as transforming growth factor, platelet-derived growth factor, and fibroblast growh factor, has been recongized as a major event in the occurrence and progression of fibrosis. Although the mechanisms driving organ-specific fibrosis have not been fully elucidated, drugs targeting these identified aberrant signals have achieved potent anti-fibrotic efficacy in clinical trials. In this review, we briefly introduce the aetiology and epidemiology of several fibrosis diseases, including liver fibrosis, kidney fibrosis, cardiac fibrosis, and pulmonary fibrosis. Then, we summarise the abnormal cells (epithelial cells, endothelial cells, immune cells, and fibroblasts) and their interactions in fibrosis. In addition, we also focus on the aberrant signaling pathways and therapeutic targets that regulate myofibroblast activation, extracellular matrix cross-linking, metabolism, and inflammation in fibrosis. Finally, we discuss the anti-fibrotic drugs based on their targets and clinical trials. This review provides reference for further research on fibrosis mechanism, drug development, and clinical trials.
Transcription factor Sp9 is a negative regulator of D1-type MSN development
Authors: Li Zhenmeiyu , Shang Zicong , Sun Mengge , Jiang Xin , Tian Yu , Yang Lin , Wang Ziwu , Su Zihao , Liu Guoping , li Xiaosu , You Yan , Yang Zhengang , Xu Zhejun , Zhang Zhuangzhi
Published: June 2022

The striatum is the main input structure of the basal ganglia, receiving information from the cortex and the thalamus and consisting of D1- and D2- medium spiny neurons (MSNs). D1-MSNs and D2-MSNs are essential for motor control and cognitive behaviors and have implications in Parkinson’s Disease. In the present study, we demonstrated that Sp9-positive progenitors produced both D1-MSNs and D2-MSNs and that Sp9 expression was rapidly downregulated in postmitotic D1-MSNs. Furthermore, we found that sustained Sp9 expression in lateral ganglionic eminence (LGE) progenitor cells and their descendants led to promoting D2-MSN identity and repressing D1-MSN identity during striatal development. As a result, sustained Sp9 expression resulted in an imbalance between D1-MSNs and D2-MSNs in the mouse striatum. In addition, the fate-changed D2-like MSNs survived normally in adulthood. Taken together, our findings supported that Sp9 was sufficient to promote D2-MSN identity and repress D1-MSN identity, and Sp9 was a negative regulator of D1-MSN fate.
A trifunctional peptide broadly inhibits SARS-CoV-2 Delta and Omicron variants in hamsters
Authors: Zhao Hanjun , To Kelvin Kai-Wang , Lam Hoiyan , Zhang Chuyuan , Peng Zheng , Meng Xinjie , Wang Xiankun , Zhang Anna Jinxia , Yan Bingpeng , Cai Jianpiao , Yeung Man Lung , Chan Jasper Fuk-Woo , Yuen Kwok-Yung
Published: June 2022

The emergence of highly transmissible SARS-CoV-2 variants has led to the waves of the resurgence of COVID-19 cases. Effective antivirals against variants are required. Here we demonstrate that a human-derived peptide 4H30 has broad antiviral activity against the ancestral virus and four Variants of Concern (VOCs) in vitro. Mechanistically, 4H30 can inhibit three distinct steps of the SARS-CoV-2 life cycle. Specifically, 4H30 blocks viral entry by clustering SARS-CoV-2 virions; prevents membrane fusion by inhibiting endosomal acidification; and inhibits the release of virions by cross-linking SARS-CoV-2 with cellular glycosaminoglycans. In vivo studies show that 4H30 significantly reduces the lung viral titers in hamsters, with a more potent reduction for the Omicron variant than the Delta variant. This is likely because the entry of the Omicron variant mainly relies on the endocytic pathway which is targeted by 4H30. Moreover, 4H30 reduces syncytia formation in infected hamster lungs. These findings provide a proof of concept that a single antiviral can inhibit viral entry, fusion, and release.
A deep Tasman outflow of Pacific waters during the last glacial period
Authors: Struve Torben , Wilson David J. , Hines Sophia K. V. , Adkins Jess F. , van de Flierdt Tina
Published: June 2022

The interoceanic exchange of water masses is modulated by flow through key oceanic choke points in the Drake Passage, the Indonesian Seas, south of Africa, and south of Tasmania. Here, we use the neodymium isotope signature (εNd) of cold-water coral skeletons from intermediate depths (1460‒1689 m) to trace circulation changes south of Tasmania during the last glacial period. The key feature of our dataset is a long-term trend towards radiogenic εNd values of ~−4.6 during the Last Glacial Maximum and Heinrich Stadial 1, which are clearly distinct from contemporaneous Southern Ocean εNd of ~−7. When combined with previously published radiocarbon data from the same corals, our results indicate that a unique radiogenic and young water mass was present during this time. This scenario can be explained by a more vigorous Pacific overturning circulation that supported a deeper outflow of Pacific waters, including North Pacific Intermediate Water, through the Tasman Sea.
Associations between long-term drought and diarrhea among children under five in low- and middle-income countries
Authors: Wang Pin , Asare Ernest , Pitzer Virginia E. , Dubrow Robert , Chen Kai
Published: June 2022

Climate change is projected to intensify drought conditions, which may increase the risk of diarrheal diseases in children. We constructed log-binomial generalized linear mixed models to examine the association between diarrhea risk, ascertained from global-scale nationally representative Demographic and Health Surveys, and drought, represented by the standardized precipitation evapotranspiration index, among children under five in 51 low- and middle-income countries (LMICs). Exposure to 6-month mild or severe drought was associated with an increased diarrhea risk of 5% (95% confidence interval 3–7%) or 8% (5–11%), respectively. The association was stronger among children living in a household that needed longer time to collect water or had no access to water or soap/detergent for handwashing. The association for 24-month drought was strong in dry zones but weak or null in tropical or temperate zones, whereas that for 6-month drought was only observed in tropical or temperate zones. In this work we quantify the associations between exposure to long-term drought and elevated diarrhea risk among children under five in LMICs and suggest that the risk could be reduced through improved water, sanitation, and hygiene practices, made more urgent by the likely increase in drought due to climate change.
Optimised weight programming for analogue memory-based deep neural networks
Authors: Mackin Charles , Rasch Malte J. , Chen An , Timcheck Jonathan , Bruce Robert L. , Li Ning , Narayanan Pritish , Ambrogio Stefano , Le Gallo Manuel , Nandakumar S. R. , Fasoli Andrea , Luquin Jose , Friz Alexander , Sebastian Abu , Tsai Hsinyu , Burr Geoffrey W.
Published: June 2022

Analogue memory-based deep neural networks provide energy-efficiency and per-area throughput gains relative to state-of-the-art digital counterparts such as graphics processing units. Recent advances focus largely on hardware-aware algorithmic training and improvements to circuits, architectures, and memory devices. Optimal translation of software-trained weights into analogue hardware weights—given the plethora of complex memory non-idealities—represents an equally important task. We report a generalised computational framework that automates the crafting of complex weight programming strategies to minimise accuracy degradations during inference, particularly over time. The framework is agnostic to network structure and generalises well across recurrent, convolutional, and transformer neural networks. As a highly flexible numerical heuristic, the approach accommodates arbitrary device-level complexity, making it potentially relevant for a variety of analogue memories. By quantifying the limit of achievable inference accuracy, it also enables analogue memory-based deep neural network accelerators to reach their full inference potential.
Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0
Authors: Domenzain Iván , Sánchez Benjamín , Anton Mihail , Kerkhoven Eduard J. , Millán-Oropeza Aarón , Henry Céline , Siewers Verena , Morrissey John P. , Sonnenschein Nikolaus , Nielsen Jens
Published: June 2022

Genome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration of enzyme constraints and proteomics data into such models was first enabled by the GECKO toolbox, allowing the study of phenotypes constrained by protein limitations. Here, we upgrade the toolbox in order to enhance models with enzyme and proteomics constraints for any organism with a compatible GEM reconstruction. With this, enzyme-constrained models for the budding yeasts Saccharomyces cerevisiae, Yarrowia lipolytica and Kluyveromyces marxianus are generated to study their long-term adaptation to several stress factors by incorporation of proteomics data. Predictions reveal that upregulation and high saturation of enzymes in amino acid metabolism are common across organisms and conditions, suggesting the relevance of metabolic robustness in contrast to optimal protein utilization as a cellular objective for microbial growth under stress and nutrient-limited conditions. The functionality of GECKO is expanded with an automated framework for continuous and version-controlled update of enzyme-constrained GEMs, also producing such models for Escherichia coli and Homo sapiens. In this work, we facilitate the utilization of enzyme-constrained GEMs in basic science, metabolic engineering and synthetic biology purposes.
Voltage-driven gigahertz frequency tuning of spin Hall nano-oscillators
Authors: Choi Jong-Guk , Park Jaehyeon , Kang Min-Gu , Kim Doyoon , Rieh Jae-Sung , Lee Kyung-Jin , Kim Kab-Jin , Park Byong-Guk
Published: June 2022

Spin Hall nano-oscillators (SHNOs) exploiting current-driven magnetization auto-oscillation have recently received much attention because of their potential for neuromorphic computing. Widespread applications of neuromorphic devices with SHNOs require an energy-efficient method of tuning oscillation frequency over broad ranges and storing trained frequencies in SHNOs without the need for additional memory circuitry. While the voltage-driven frequency tuning of SHNOs has been demonstrated, it was volatile and limited to megahertz ranges. Here, we show that the frequency of SHNOs is controlled up to 2.1 GHz by an electric field of 1.25 MV/cm. The large frequency tuning is attributed to the voltage-controlled magnetic anisotropy (VCMA) in a perpendicularly magnetized Ta/Pt/[Co/Ni]n/Co/AlOx structure. Moreover, the non-volatile VCMA effect enables cumulative control of the frequency using repetitive voltage pulses which mimic the potentiation and depression functions of biological synapses. Our results suggest that the voltage-driven frequency tuning of SHNOs facilitates the development of energy-efficient neuromorphic devices.
Ion-cluster-mediated ultrafast self-healable ionoconductors for reconfigurable electronics
Authors: Kim Yong Min , Kwon Jin Han , Kim Seonho , Choi U Hyeok , Moon Hong Chul
Published: June 2022

Implementing self-healing capabilities in a deformable platform is one of the critical challenges for achieving future wearable electronics with high durability and reliability. Conventional systems are mostly based on polymeric materials, so their self-healing usually proceeds at elevated temperatures to promote chain flexibility and reduce healing time. Here, we propose an ion-cluster-driven self-healable ionoconductor composed of rationally designed copolymers and ionic liquids. After complete cleavage, the ionoconductor can be repaired with high efficiency (∼90.3%) within 1 min even at 25 °C, which is mainly attributed to the dynamic formation of ion clusters between the charged moieties in copolymers and ionic liquids. By taking advantages of the superior self-healing performance, stretchability (∼1130%), non-volatility (over 6 months), and ability to be easily shaped as desired through cutting and re-assembly protocol, reconfigurable, deformable light-emitting electroluminescent displays are successfully demonstrated as promising electronic platforms for future applications.
Tight junction channel regulation by interclaudin interference
Authors: Shashikanth Nitesh , France Marion M. , Xiao Ruyue , Haest Xenia , Rizzo Heather E. , Yeste Jose , Reiner Johannes , Turner Jerrold R.
Published: June 2022

Tight junctions form selectively permeable seals across the paracellular space. Both barrier function and selective permeability have been attributed to members of the claudin protein family, which can be categorized as pore-forming or barrier-forming. Here, we show that claudin-4, a prototypic barrier-forming claudin, reduces paracellular permeability by a previously unrecognized mechanism. Claudin-4 knockout or overexpression has minimal effects on tight junction permeability in the absence of pore-forming claudins. However, claudin-4 selectively inhibits flux across cation channels formed by claudins 2 or 15. Claudin-4-induced loss of claudin channel function is accompanied by reduced anchoring and subsequent endocytosis of pore-forming claudins. Analyses in nonepithelial cells show that claudin-4, which is incapable of independent polymerization, disrupts polymeric strands and higher order meshworks formed by claudins 2, 7, 15, and 19. This process of interclaudin interference, in which one claudin disrupts higher order structures and channels formed by a different claudin, represents a previously unrecognized mechanism of barrier regulation.
Ultrahigh-transparency and pressure-sensitive iontronic device for tactile intelligence
Authors: Tang Jie , Zhao Chao , Luo Qian , Chang Yu , Yang Zhenguo , Pan Tingrui
Published: June 2022

Emerging tactile sensing devices mimic biological functions of human mechanoreception. By introducing the feature of optical transparency, it can lead to a combined capacities of tactile and visual intelligence into single system. Yet, it is difficult to realize ultrahigh level of optical transparency and device sensitivity in single structure, for the widely used methods for sensitivity improvement, such as elevating the interfacial roughness, may further reduce the transparency. By utilizing a transparent ionic material with tunable surface topologies, as well as introducing a strategy of refractive index matching, we have proposed a transparent iontronic sensing (TIS) device based on the iontronic sensing mechanism, simultaneously offering combined high device sensitivity (83.9 kPa−1), with ultrahigh optical transparency (96.9%), the highest reported value in literature. Benefiting from its comprehensive performance in sensing and optical characteristics, the TIS devices hold enormous potential for the human-machine interfaces for industrial and medical applications.
The specialist in regeneration—the Axolotl—a suitable model to study bone healing?
Authors: Polikarpova A. , Ellinghaus A. , Schmidt-Bleek O. , Grosser L. , Bucher C. H. , Duda G. N. , Tanaka E. M. , Schmidt-Bleek K.
Published: June 2022

While the axolotl’s ability to completely regenerate amputated limbs is well known and studied, the mechanism of axolotl bone fracture healing remains poorly understood. One reason might be the lack of a standardized fracture fixation in axolotl. We present a surgical technique to stabilize the osteotomized axolotl femur with a fixator plate and compare it to a non-stabilized osteotomy and to limb amputation. The healing outcome was evaluated 3 weeks, 3, 6 and 9 months post-surgery by microcomputer tomography, histology and immunohistochemistry. Plate-fixated femurs regained bone integrity more efficiently in comparison to the non-fixated osteotomized bone, where larger callus formed, possibly to compensate for the bone fragment misalignment. The healing of a non-critical osteotomy in axolotl was incomplete after 9 months, while amputated limbs efficiently restored bone length and structure. In axolotl amputated limbs, plate-fixated and non-fixated fractures, we observed accumulation of PCNA+ proliferating cells at 3 weeks post-injury similar to mouse. Additionally, as in mouse, SOX9-expressing cells appeared in the early phase of fracture healing and amputated limb regeneration in axolotl, preceding cartilage formation. This implicates endochondral ossification to be the probable mechanism of bone healing in axolotls. Altogether, the surgery with a standardized fixation technique demonstrated here allows for controlled axolotl bone healing experiments, facilitating their comparison to mammals (mice).
Immunogenicity and protective efficacy of RSV G central conserved domain vaccine with a prefusion nanoparticle
Authors: Rainho-Tomko Jennifer N. , Pavot Vincent , Kishko Michael , Swanson Kurt , Edwards Darin , Yoon Heesik , Lanza Lilibeth , Alamares-Sapuay Judith , Osei-Bonsu Robert , Mundle Sophia T. , Murison Dave A. , Gallichan Scott , Delagrave Simon , Wei Chih-Jen , Zhang Linong , Nabel Gary J.
Published: June 2022

Respiratory syncytial virus (RSV) G glycoprotein has recently reemerged as a vaccine antigen due to its ability to elicit potent neutralizing antibodies and ameliorate disease in animal models. Here we designed three constructs to display the G central conserved domain (Gcc) focused on inducing broad and potent neutralizing antibodies. One construct displaying Gcc from both RSV subgroups trimerized via a C-terminal foldon (Gcc-Foldon) was highly immunogenic in mice and in MIMIC, a pre-immune human in vitro model. To explore an optimal RSV vaccine, we combined the Gcc-Foldon antigen with a stabilized pre-fusion-F nanoparticle (pre-F-NP) as a bivalent vaccine and detected no antigenic interference between the two antigens in the MIMIC model. In RSV-primed macaques, the bivalent vaccine elicited potent humoral responses. Furthermore, both Gcc-Foldon and the bivalent vaccine conferred effective protection against RSV challenge in mice. This two-component vaccine could potentially provide effective protection against RSV infection in humans and warrants further clinical evaluation.
Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer
Authors: Joanito Ignasius , Wirapati Pratyaksha , Zhao Nancy , Nawaz Zahid , Yeo Grace , Lee Fiona , Eng Christine L. P. , Macalinao Dominique Camat , Kahraman Merve , Srinivasan Harini , Lakshmanan Vairavan , Verbandt Sara , Tsantoulis Petros , Gunn Nicole , Venkatesh Prasanna Nori , Poh Zhong Wee , Nahar Rahul , Oh Hsueh Ling Janice , Loo Jia Min , Chia Shumei , Cheow Lih Feng , Cheruba Elsie , Wong Michael Thomas , Kua Lindsay , Chua Clarinda , Nguyen Andy , Golovan Justin , Gan Anna , Lim Wan-Jun , Guo Yu Amanda , Yap Choon Kong , Tay Brenda , Hong Yourae , Chong Dawn Qingqing , Chok Aik-Yong , Park Woong-Yang , Han Shuting , Chang Mei Huan , Seow-En Isaac , Fu Cherylin , Mathew Ronnie , Toh Ee-Lin , Hong Lewis Z. , Skanderup Anders Jacobsen , DasGupta Ramanuj , Ong Chin-Ann Johnny , Lim Kiat Hon , Tan Emile K. W. , Koo Si-Lin , Leow Wei Qiang , Tejpar Sabine , Prabhakar Shyam , Tan Iain Beehuat
Published: June 2022

The consensus molecular subtype (CMS) classification of colorectal cancer is based on bulk transcriptomics. The underlying epithelial cell diversity remains unclear. We analyzed 373,058 single-cell transcriptomes from 63 patients, focusing on 49,155 epithelial cells. We identified a pervasive genetic and transcriptomic dichotomy of malignant cells, based on distinct gene expression, DNA copy number and gene regulatory network. We recapitulated these subtypes in bulk transcriptomes from 3,614 patients. The two intrinsic subtypes, iCMS2 and iCMS3, refine CMS. iCMS3 comprises microsatellite unstable (MSI-H) cancers and one-third of microsatellite-stable (MSS) tumors. iCMS3 MSS cancers are transcriptomically more similar to MSI-H cancers than to other MSS cancers. CMS4 cancers had either iCMS2 or iCMS3 epithelium; the latter had the worst prognosis. We defined the intrinsic epithelial axis of colorectal cancer and propose a refined ‘IMF’ classification with five subtypes, combining intrinsic epithelial subtype (I), microsatellite instability status (M) and fibrosis (F).
Groundwater level prediction based on a combined intelligence method for the Sifangbei landslide in the Three Gorges Reservoir Area
Authors: Zeng Taorui , Yin Kunlong , Jiang Hongwei , Liu Xiepan , Guo Zizheng , Peduto Dario
Published: June 2022

The monitoring and prediction of the groundwater level (GWL) significantly influence the landslide kinematics. Based on the long-term fluctuation characteristics of the GWL and the time lag of triggering factors, a dynamic prediction model of the GWL based on the Maximum information coefficient (MIC) algorithm and the long-term short-term memory (LSTM) model was proposed. The Sifangbei landslide in the Three Gorges Reservoir area (TGRA) in China, wherein eight GWL monitoring sensors were installed in different locations, was taken as a case study. The monitoring data represented that the fluctuation of the GWL has a specific time lag concerning the accumulated rainfall (AR) and the reservoir water level (RWL). In addition, there were spatial differences in the fluctuation of the GWL, which was controlled by the elevation and the micro landform. From January 19, 2015, to March 6, 2017, the measured data were used to set up the predicted models. The MIC algorithm was adopted to calculate the lag time of the GWL, the RWL, and the AR. The LSTM model is a time series prediction algorithm that can transmit historical information. The Gray wolf optimization (GWO) algorithm was used to seek the most suitable hyperparameter of the LSTM model under the specific prediction conditions. The single-factor GWO-LSTM model without considering triggering factors and the support vector machine regression (SVR) model were considered to compare the prediction results. The results indicate that the MIC-GWO-LSTM model reached the highest accuracy and improved the prediction accuracy by considering the factor selection process with the learner training process. The proposed MIC-GWO-LSTM model combines the advantages of each algorithm and effectively constructs the response relationship between the GWL fluctuation and triggering factors; it also provides a new exploration for the GWL prediction, monitoring, and early warning system in the TGRA.
Preoperative physical performance predicts pulmonary complications after coronary artery bypass grafting: a prospective study
Authors: Li Lin , Yang Qin , Guo Qi , Liu Dandan , Gao Hui , Liu Yaping
Published: June 2022

The purpose of this study is to evaluate the relationship between preoperative physical performance (grip strength, gait speed, timed up and go) and postoperative pulmonary complications (PPCs) in patients who have undergone coronary artery bypass grafting (CABG). From September 2019 to August 2021, a total of 497 CABG patients who met the inclusion criteria of this study were examined for grip strength, 4-m gait speed, and timed up and go (TUG) before CABG surgery. Among them, 438 were included in the final analysis. PPCs were classified according to the operational definition of Kroenke et al. and patients with clinically significant PPCs were included in the data analysis. Logistic regression was utilised to analyse the relationship between physical performance and clinically significant PPCs. Besides, the receiver operating characteristic (ROC) curve was applied to analyse the predictive effect of grip strength, gait speed, and TUG on clinically significant PPCs after the CABG procedure. In total, 103 (23.5%) patients developed clinically significant PPCs after CABG. After making adjustments for the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and confounding factors, we established that low grip/weight (OR 0.510; 95% CI 0.363–0.715), slow gait speed (OR 0.619; 95% CI 0.517–0.741), and prolonged TUG (OR 1.617; 95% CI 1.379–1.895) were all independently correlated with clinically significant PPCs after CABG. The ROC curve analysis indicated that the area under the ROC curve of the integrated model of the three indicators (AUC 0.792 vs. 0.682, 0.754, 0.765) was larger than that of the model with a single indicator. Besides the predictive effect of the integrated model was superior to the models using grip/weight, gait speed, or TUG alone. Physical performance, including grip/weight, gait speed, and TUG, is a predictive factor for PPCs in CABG patients, and can be used in preoperative evaluations to and help improve the management of high-risk patients.
Inhaled turmerones can be incorporated in the organs via pathways different from oral administration and can affect weight-gain of mice
Authors: Takemoto Yuki , Kishi Chihiro , Ehira Hinano , Matsui Nobutaka , Yamaguchi Taichi , Yoshioka Yuri , Matsumura Shinichi , Moriyama Tatsuya , Zaima Nobuhiro
Published: June 2022

Turmerones (α-turmerone, β-turmerone, and ar-turmerone) are the major volatile compounds in turmeric (Curcuma longa), a perennial herb of the ginger family. We previously reported that inhaled volatile turmerones could be transferred in the blood and organs. However, the difference between the two pathways, oral administration and inhalation, and the effect of inhaled turmerones on biological activities remain unknown. In this study, we compared the distribution patterns of turmerones after oral administration and inhalation. The relative levels (concentrations of turmerones in each organ/serum) in the lung, olfactory bulb, brain, heart, kidney, and epididymal fat in the inhalation group tended to be, or are significantly, higher than in the oral administration group. The relative levels of brown adipose tissue in the inhalation group were lower than in the oral administration group. Long-term (50 days) inhalation to volatile turmerones suppressed weight gain and hypertrophy of adipocytes in the epididymal fat of mice fed a high-fat diet. These results suggest that inhaled turmerones can be incorporated into the organs of mice via different pathway from as to those from oral administration and can affect the biological function of the organs under certain conditions.
Artemisinin inhibits neutrophil and macrophage chemotaxis, cytokine production and NET release
Authors: Morad Hassan O. J. , Luqman Suaib , Pinto Larissa Garcia , Cunningham Kevin P. , Vilar Bruno , Clayton Georgia , Shankar-Hari Manu , McNaughton Peter A.
Published: June 2022

Immune cell chemotaxis to the sites of pathogen invasion is critical for fighting infection, but in life-threatening conditions such as sepsis and Covid-19, excess activation of the innate immune system is thought to cause a damaging invasion of immune cells into tissues and a consequent excessive release of cytokines, chemokines and neutrophil extracellular traps (NETs). In these circumstances, tempering excessive activation of the innate immune system may, paradoxically, promote recovery. Here we identify the antimalarial compound artemisinin as a potent and selective inhibitor of neutrophil and macrophage chemotaxis induced by a range of chemotactic agents. Artemisinin released calcium from intracellular stores in a similar way to thapsigargin, a known inhibitor of the Sarco/Endoplasmic Reticulum Calcium ATPase pump (SERCA), but unlike thapsigargin, artemisinin blocks only the SERCA3 isoform. Inhibition of SERCA3 by artemisinin was irreversible and was inhibited by iron chelation, suggesting iron-catalysed alkylation of a specific cysteine residue in SERCA3 as the mechanism by which artemisinin inhibits neutrophil motility. In murine infection models, artemisinin potently suppressed neutrophil invasion into both peritoneum and lung in vivo and inhibited the release of cytokines/chemokines and NETs. This work suggests that artemisinin may have value as a therapy in conditions such as sepsis and Covid-19 in which over-activation of the innate immune system causes tissue injury that can lead to death.