bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of formation damage and fracture choking in hydraulically induced fractured reservoirs due to asphaltene deposition
Authors: Khurshid Ilyas , AlShalabi Emad Walid , Al-Attar Hazim , AL-Neaimi Ahmed Khalifa
Published: May 2020

Hydraulically induced fractures provide a significant fraction of oil supply to the world from unconventional reservoirs due to their high permeability. However, these fractures might choke because of the deposition of organic and in-organic particles. Among organic particles, asphaltene deposition severely reduces reservoir permeability causing an exponential drop in production. In this work, a simulator is developed that predicts the performance of fractured reservoirs by solving the fluid flow governing equations for matrix and fractures. These flow equations were then incorporated with asphaltene deposition equations. Primarily, a numerical model is developed to predict the rate of asphaltene deposition and fracture choking in a radial geometry. It is found that asphaltene deposition could partially or completely choke fractures. Finally, the results are compared with the experimental data and determined various factors affecting fracture choking. From the detailed analysis, it is found that fracture choking is a few percent, but it increases with long production time. The sensitivity analysis was performed to investigate the effect of different influential parameters on permeability alteration of fractured reservoirs by asphaltene deposition. These parameters include fracture-to-matrix permeability ratio, production time, and asphaltene concentration. It is observed that, low fracture-to-matrix permeability ratio has a negligible effect on permeability of a reservoir. The developed model assumes negligible gravity and capillary forces. However, these forces might increase fracture choking in unconventional fractured reservoirs.
Understanding Trends in the Concentration of Infant Mortality Among Disadvantaged White and Black Mothers in the United States, 1983–2013: A Decomposition Analysis
Authors: Fan Wen , Luo Liying
Published: May 2020

The United States compares unfavorably with other high-income countries in infant mortality, which recent literature has attributed to the poor birth outcomes among disadvantaged (i.e., unmarried and less-educated) mothers. Describing and decomposing the trend of the concentration of infant mortality among disadvantaged mothers thus provides important clues for improving birth outcomes. We develop the infant mortality disadvantage index (IMDI) to measure such concentration. Using the 1983–2013 Birth Cohort Linked Birth and Infant Death data, we show that although the IMDI—as a measure of mortality inequality—was persistently higher for Blacks than Whites, the trends were different between the two groups. The IMDI declined for Black women; for White women, however, it increased in the 1980s, then plateaued until the early 2000s, and declined thereafter. We then use Das Gupta’s decomposition method to assess the contribution of five demographic/social factors (age, education, marriage, fertility, and infant mortality) to the IMDI trend. Nonmarital fertility among women with less than 12 years of education contributed most to Whites’ changing IMDI; for Blacks, a shrinking proportion of the less-educated group and declines in infant mortality among disadvantaged mothers contributed to their declining IMDI. These findings explicate links between population-level compositional changes and infant mortality inequality.
Biodegradable lubricating mesoporous silica nanoparticles for osteoarthritis therapy
Authors: Wan Li , Wang Yi , Tan Xiaolong , Sun Yulong , Luo Jing , Zhang Hongyu
Published: May 2020

Osteoarthritis is characterized by lubrication failure of the articular cartilage and severe inflammation of the joint capsule. Lubricating mesoporous silica nanoparticles (MSNs) have been developed for the treatment of osteoarthritis based on enhanced lubrication and local drug delivery. However, MSNs are difficult to degrade in vivo in a short time, resulting in potential toxic effect due to bioaccumulation. In this study, biodegradable MSNs (bMSNs) were prepared through an oil-water biphase stratification method, and modified with poly(2-methacryloyloxyethyl phosphocholine) (PMPC) to synthesize lubricating drug-loaded nanoparticles (bMSNs-NH2@PMPC) by photopolymerization. The in vitro degradation test demonstrated that the bMSNs and bMSNs-NH2@PMPC almost degraded within 7 days. The tribiological test showed that the lubrication property of the bMSNs-NH2@PMPC was greatly improved, with a reduction of 50% in the friction coefficient (COF) compared with the bMSNs. It was attributed to hydration lubrication mechanism by which a tenacious hydration layer is formed surrounding the zwitterionic headgroups (N+(CH3)3 and PO4−) in PMPC polyelectrolyte polymer. Additionally, the bMSNs-NH2@PMPC maintained excellent lubrication property under degradation and achieved sustained drug release behavior compared with the bMSNs. In summary, the biodegradable bMSNs-NH2@PMPC developed in this study with the properties of enhanced lubrication and drug delivery may be a promising approach for osteoarthritis therapy.
Intercalating Ultrathin MoO3 Nanobelts into MXene Film with Ultrahigh Volumetric Capacitance and Excellent Deformation for High-Energy-Density Devices
Authors: Wang Yuanming , Wang Xue , Li Xiaolong , Liu Rong , Bai Yang , Xiao Huanhao , Liu Yang , Yuan Guohui
Published: May 2020

The restacking hindrance of MXene films restricts their development for high volumetric energy density of flexible supercapacitors toward applications in miniature, portable, wearable or implantable electronic devices. A valid solution is construction of rational heterojunction to achieve a synergistic property enhancement. The introduction of spacers such as graphene, CNTs, cellulose and the like demonstrates limited enhancement in rate capability. The combination of currently reported pseudocapacitive materials and MXene tends to express the potential capacitance of pseudocapacitive materials rather than MXene, leading to low volumetric capacitance. Therefore, it is necessary to exploit more ideal candidate materials to couple with MXene for fully expressing both potentials. Herein, for the first time, high electrochemically active materials of ultrathin MoO3 nanobelts are intercalated into MXene films. In the composites, MoO3 nanobelts not only act as pillaring components to prevent restacking of MXene nanosheets for fully expressing the MXene pseudocapacitance in acidic environment but also provide considerable pseudocapacitive contribution. As a result, the optimal M/MoO3 electrode not only achieves a breakthrough in volumetric capacitance (1817 F cm−3 and 545 F g−1), but also maintains good rate capability and excellent flexibility. Moreover, the corresponding symmetric supercapacitor likewise shows a remarkable energy density of 44.6 Wh L−1 (13.4 Wh kg−1), rendering the flexible electrode a promising candidate for application in high-energy-density energy storage devices.
Surface accumulation in Northern Central Greenland during the last 300 years
Authors: Karlsson Nanna B. , Razik Sebastian , Hörhold Maria , Winter Anna , Steinhage Daniel , Binder Tobias , Eisen Olaf
Published: May 2020

The internal stratigraphy of snow and ice as imaged by ground-penetrating radar may serve as a source of information on past accumulation. This study presents results from two ground-based radar surveys conducted in Greenland in 2007 and 2015, respectively. The first survey was conducted during the traverse from the ice-core station NGRIP (North Greenland Ice Core Project) to the ice-core station NEEM (North Greenland Eemian Ice Drilling). The second survey was carried out during the traverse from NEEM to the ice-core station EGRIP (East Greenland Ice Core Project) and then onwards to Summit Station. The total length of the radar profiles is 1427 km. From the radar data, we retrieve the large-scale spatial variation of the accumulation rates in the interior of the ice sheet. The accumulation rates range from 0.11 to 0.26 m a−1ice equivalent with the lowest values found in the northeastern sector towards EGRIP. We find no evidence of temporal or spatial changes in accumulation rates when comparing the 150-year average accumulation rates with the 321-year average accumulation rates. Comparisons with regional climate models reveal that the models underestimate accumulation rates by up to 35% in northeastern Greenland. Our results serve as a robust baseline to detect present changes in either surface accumulation rates or patterns.
The Performance of the Iranian Red Crescent by Launching Testing Centers for the Coronavirus Disease
Authors: Seddighi Hamed
Published: May 2020

The coronavirus disease (COVID-19) screening project has been conducted by the Red Crescent Society for 17 days with the aim of identifying and treating people with COVID-19, reducing road trips, and sensitizing people to the problem. Due to the shortage of testing devices, passengers were screened by measuring skin temperature. In 851 screening posts, 95 371 volunteers of Red Crescent monitored 21 640 866 people.

Besides screening people, the stations have had other functions, including urging people to stay at home, restricting road trips, especially during the Iranian New Year holidays, reassuring the people that all relevant organizations are doing their best to respond to COVID-19, and the like. However, future research is still needed to analyze the cost-benefit of this plan and other possible options.
Present at the destruction? Grand strategy imperatives of US foreign policy experts during the Trump presidency
Authors: Kurthen Hermann
Published: May 2020

This article discusses the grand strategy imperatives of 37 foreign policy experts in Washington, DC in response to President Donald Trump's nationalist challenge to the post-Second World War international order concept. Using an abductive reconstructivist methodology to analyse in-depth interviews, five grand strategy imperatives, or rules for action, shared by all actors were identified: safeguarding US global leadership, maintaining alliances, securing US prosperity, orienting at values, and believing in a mission. Based on the interpretation of these rules for action, four types of foreign policy experts were distinguished: nationalists, realists, pragmatic liberals, and liberals. The latter three expert types, altogether labelled globalists, were united in their opposition to the nationalists’ demolition of the international order but divided along partisan and ideological lines about the meaning and implementation of the rules for action. Realists, pragmatic liberals, and liberals were also unsure of how to explain and respond to Trump's nationalism beyond a defensive or wishful hope to save the vestiges of an US-centric international order. The findings demonstrate the value of in-depth qualitative interviews for explaining elite beliefs and illustrate the rich insights for policy analysis that can be gained through this methodology.
Psychiatrist experience of remote consultations by telephone in an outpatient psychiatric department during the COVID-19 pandemic
Authors: Olwill C. , Mc Nally D. , Douglas L.
Published: May 2020

Objective

In response to the COVID-19 pandemic, there has been a shift globally from face-to-face consultations to remote consultations. In our department, remote consultations have taken in the form of telephone consultations. In this paper, we set out to study a group of Irish psychiatrists’ experience of these consultations.

Methods

We identified recurrent themes in the existing literature on doctors’ experience of telephone consultations with a view to determining the applicability of these themes to a group of Irish psychiatrists. A questionnaire was developed based on themes in the literature. This was sent to all psychiatrists working in a busy psychiatric service in Dublin.

Results

The questionnaire response rate was 72% (n = 26/35). Diagnostic challenges, the effect of phone consultation on the therapeutic alliance, challenges associated with the use of technology and ethical concerns were identified as issues. Flexibility in the working day and convenience were identified as possible benefits to telephone consultations.

Conclusions

The group that participated in this research study identified a number of challenges to carrying out successful phone consultations. This study highlights the need at our clinical site for interventions to address the issues identified by staff. The findings also highlight the requirement for larger studies with stronger methodologies to determine the generalisability of our results.
Discerning the diets of sweep-feeding eurypterids: assessing the importance of prey size to survivorship across the Late Devonian mass extinction in a phylogenetic context
Authors: Hughes Emily S. , Lamsdell James C.
Published: May 2020

Eurypterids are generally considered to comprise a mixture of active nektonic to nektobenthic predators and benthic scavenger-predators exhibiting a mode of life similar to modern horseshoe crabs. However, two groups of benthic stylonurine eurypterids, the Stylonuroidea and Mycteropoidea, independently evolved modifications to the armature of their anterior appendages that have been considered adaptations toward a sweep-feeding life habit, and it has been suggested the evolution toward sweep-feeding may have permitted stylonurines to capture smaller prey species and may have been critical for the survival of mycteropoids during the Late Devonian mass extinction. There is a linear correlation between the average spacing of feeding structures and prey sizes among extant suspension feeders. Here, we extrapolate this relationship to sweep-feeding eurypterids in order to estimate the range of prey sizes that they could capture and examine prey size in a phylogenetic context to determine what role prey size played in determining survivorship during the Late Devonian. The mycteropoidCyrtoctenuswas the most specialized sweep-feeder, with comblike appendage armature capable of capturing mesoplankton out of suspension, while the majority of stylonurines possess armature corresponding to a prey size range of 1.6–52 mm, suggesting they were suited for capturing small benthic macroinvertebrates such as crustaceans, mollusks, and wormlike organisms. There is no clear phylogenetic signal to prey size distribution and no evolutionary trend toward decreasing prey sizes among Stylonurina. Rather than prey size, species survivorship during the Late Devonian was likely mediated by geographic distribution and ability to capitalize on the expanding freshwater benthos.
Methane consumption potential of soybean-wheat, maize-wheat and maize-gram cropping systems under conventional and no-tillage agriculture in a tropical vertisol
Authors: Kollah Bharati , Bakoriya Mahendra , Dubey Garima , Parmar Rakesh , Somasundaram J. , Shirale Abhay , Gupta S. C. , Patra A. K. , Mohanty Santosh Ranjan
Published: May 2020

Methane (CH4) consumption in agricultural soil is imperative for the mitigation of climate change. However, the effect of tillage and cropping systems on CH4consumption is less studied. Experiments were carried out in Madhya Pradesh, India with soybean-wheat (SW), maize-wheat (MW) and maize-gram (MG) cropping systems under conventional tillage (CT) and no-tillage (NT). Soybean/maize was cultivated during thekharifseason (July–October) and wheat/chickpea in therabiseason (October–March) for 9 years consecutively. Soil samples were collected during vegetative growth stages of soybean and maize from different cropping systems. Methane consumption, the abundance of methanotrophs as particulate methane monooxygenase (pmoA) gene copies, soil and crop parameters were estimated. Methane consumption rate was higher in NT and upper soil layer (0–5 cm) than CT and 5–15 cm depth. Methane consumption rate k ranged from 0.35 to 0.56 μg CH4consumed/g soil/d in the order of MW>SW>MG in 0–5 cm. The abundance ofpmoAgene copies ranged from 43 × 104/g soil to 13 × 104/g soil and was highest in MW-NT and lowest in MG-CT. Available nitrogen, phosphorus and potassium were higher in 0–5 cm than in 5–15 cm depth. Soil and plant parameters and abundance ofpmoAgenes correlated significantly and positively with CH4consumption rate. No-tillage stimulated CH4consumption compared to CT irrespective of cropping system and CH4consumption potential was highest in MW and lowest in MG. However, the magnitude of the positive effect of NT towards CH4consumption was higher in SW and MG than MW.
Indexed type theories
Authors: Isaev Valery
Published: May 2020

In this paper, we define indexed type theories which are related to indexed (∞-)categories in the same way as (homotopy) type theories are related to (∞-)categories. We define several standard constructions for such theories including finite (co)limits, arbitrary (co)products, exponents, object classifiers, and orthogonal factorization systems. We also prove that these constructions are equivalent to their type theoretic counterparts such as Σ-types, unit types, identity types, finite higher inductive types, Π-types, univalent universes, and higher modalities.
Surge, retraction and prices: the performance of fiat coins in Sweden, c. 1715–1720
Authors: Ericsson Peter , Winton Patrik
Published: May 2020

From 1716 to 1718, Sweden experienced a shock of liquidity when the absolutist regime of Charles XII issued large amounts of fiat coins (mynttecken) in order to finance the Great Northern War. After the death of the king in November 1718, the new parliamentary regime decided to partially default on the coins. In international literature, this episode is largely unknown, and in Swedish historiography, scholars have often claimed that the country's currency collapsed in hyperinflation. We assess the performance of the new coins by studying how prices of commodities in various geographic locations developed. We also study bookkeeping practices in order to see how accountants treated the new coins. Our results show that there was a complex relationship between prices and liquidity. Prices of products in high demand by the military increased more than other prices. Accountants did not treat mynttecken and other currencies differently in 1718. It was only after the death of the king that accountants started to differentiate between different types of coins. The value of the fiat coins was linked to the actions and the legitimacy of the royal regime, which is in line with the State theory of money.
On the phantom-like appearance of bilingualism effects on neurocognition: (How) should we proceed?
Authors: Leivada Evelina , Westergaard Marit , Duñabeitia Jon Andoni , Rothman Jason
Published: May 2020

Numerous studies have argued that bilingualism has effects on cognitive functions. Recently, in light of increasingly mixed empirical results, this claim has been challenged. One might ponder if there is enough evidence to justify a cessation to future research on the topic or, alternatively, how the field could proceed to better understand the phantom-like appearance of bilingual effects. Herein, we attempt to frame this appearance at the crossroads of several factors such as the heterogeneity of the term ‘bilingual’, sample size effects, task effects, and the complex dynamics between an early publication bias that favours positive results and the subsequent Proteus phenomenon. We conclude that any definitive claim on the topic is premature and that research must continue, albeit in a modified way. To this effect, we offer a path forward for future multi-lab work that should provide clearer answers to whether bilingualism has neurocognitive effects, and if so, under what conditions.
Dosimetric comparison of helical tomotherapy and hybrid (3DCRT-VMAT) technique for locally advanced non-small cell lung cancer
Authors: Temelli Öztun , Demirtas Mehmet , Ugurlu Berat Tugrul
Published: May 2020

Aim:

The purpose of the present study is to compare hybrid [three-dimensional conformal radiation therapy-volumetric-modulated arc therapy (3DCRT-VMAT)] and helical tomotherapy (HT) techniques in terms of both planning target volume (PTV) and organs at risk (OARs) in the plans we made in locally advanced non-small cell lung cancer (NSCLC) patients

Material and methods:

Radiotherapy was planned for 15 locally advanced NSCLC patients with 2 different techniques. Large tumours with positive mediastinal lymph nodes were preferred. The prescription dose was determined as 60 Gy at 30 fractions.

Results:

Mean PTV volume was 602·5 cc (range: 265–1461). Mean total lung volume was 4264 cc (range: 1885–6803). Homogeneity index, Dmean, Dmax, D2 and V105 were found to be lower in HT, V100, total monitor units (MU) and total beam on time were found to be lower in the hybrid plan. Total lung Dmean was found to be 17 Gy in both techniques. V10 value was 42·85 in the hybrid plan and 48·67 in HT (p = 0·037). Heart Dmean was 14·5 Gy in the hybrid plan and 18·7 in HT (p < 0·001), and V30 values were 18·1 and 22·9, respectively (p = 0·009).

Conclusion:

Suitable dose coverage and OAR doses can be provided with both techniques. Especially the opposite lung, heart and oesophagus doses can be kept lower with the hybrid plan, and lower MU and shorter beam on time can be provided.
Quantifying Bore‐Bore Capture on Natural Beaches
Authors: Stringari C. E. , Power H. E.
Published: May 2020

Bore‐bore capture occurs when a faster moving bore captures a slower moving bore or the shoreline while both are propagating shoreward in the surf or swash zones and is quantified here for the first time using wave tracking methods applied to data collected at seven sandy Australian beaches. The results showed that, for the locations where bore‐bore capture occurred, there was a high probability (≈40%) of bore‐bore capture occurring in the surf or swash zones. Of these ≈45% consisted of a bore capturing the instantaneous shoreline (i.e., they occurred in the swash zone). The landward‐most 10% of the nearshore region (i.e., the time‐varying surf‐swash extent) was found to be the most likely location for a capture event. Infragravity wave energy (Eig) at the shoreline, number of bore‐bore capture events, and beach morphodynamic state are shown to be correlated: more dissipative beaches had higher levels of Eig at the shoreline which directly correlated with higher rates of bore‐bore capture. Approximately 20% of the capture events led to extreme horizontal shoreline maxima; however, >97% of extreme shoreline maxima were directly driven by bore‐bore capture events. There was a clear relation between the probability of bore‐bore capture driving an extreme shoreline maxima and beach morphodynamic state: The more dissipative the beach, the lower the probability of a bore‐bore capture event causing an extreme shoreline maxima event. Such correlation has direct importance for the future development of predictive runup models, which do not currently account for this phenomenon.
Biases in Structure Functions from Observations of Submesoscale Flows
Authors: Pearson Jenna , Fox‐Kemper Baylor , Pearson Brodie , Chang Henry , Haus Brian K. , Horstmann Jochen , Huntley Helga S. , Kirwan A. D. , Lund Björn , Poje Andrew
Published: May 2020

Surface drifter observations from the LAgrangian Submesoscale ExpeRiment (LASER) campaign in the Gulf of Mexico are paired with Eulerian (ship‐borne X‐band radar) data to demonstrate that velocity structure functions from drifters differ systematically from Eulerian structure functions over scales from 0.4 to 7 km. These differences result from drifters oversampling surface convergences and regions of intense vorticity. The first‐, second‐, and third‐order structure functions are calculated using quasi‐Lagrangian (drifter) and Eulerian data from approximately the same location and time. Differences between quasi‐Lagrangian and Eulerian structure functions are attributed to two forms of bias. The first bias results from the mean divergence or vorticity of the background flow creating nonzero first‐order structure functions. This background bias affects both quasi‐Lagrangian and Eulerian data when insufficiently time‐averaged. It severely biases the drifter third‐order structure functions but is smaller in Eulerian structure functions at both second and third order. This bias can be corrected for using lower‐order structure functions. The second form of bias results from drifters accumulating in regions with flow statistics that differ from undersampled regions. This accumulation bias is diagnosed by identifying the dependence of the Eulerian structure functions on divergence and vorticity as well as scale. Together, both biases suggest that caution is needed when interpreting second‐order drifter statistics and that linking raw third‐order drifter statistics to energy fluxes is often erroneous in ocean data: Even with background correction and sufficient time‐averaging, drifters overestimate the Eulerian estimate of the third‐order structure function by up to a factor of 5 when signs are consistent.
High‐Resolution Measurement of Soil Thermal Properties and Moisture Content Using a Novel Heated Fiber Optics Approach
Authors: Shehata Mahmoud , Heitman Joshua , Ishak Joseph , Sayde Chadi
Published: May 2020

Hydrological parameters are scale dependent. Efficient monitoring techniques capable of measuring hydrological parameters, such as soil moisture content (θ), over a wide range of spatial scales are essential for understanding the complexity of water and energy movement across the landscape. Techniques to measure θ over spatial scales in the range from centimeters to thousands of meters, however, are sorely lacking. Recent improvements in the distributed temperature sensing (DTS) technology supported the development of novel techniques to fill that gap. However, improvements in the accuracy and applicability of DTS techniques are still needed. This study investigates the possibility of improving the accuracy of the fiber optics dual‐probe heat‐pulse (FO‐DPHP) DTS technique by using a new design to maintain the spacing between the FO‐DPHP probes and by introducing a novel data interpretation approach. The accuracy of the novel FO‐DPHP design was tested at different θ in a sand column experiment. The FO‐DPHP measurements obtained using traditional and novel data interpretation approaches were compared against independent measurements from several calibrated soil water content (EC5) sensors. Monte‐Carlo analyses were also performed to assess the impact of DTS measurement errors on the accuracy achieved using the data interpretation approaches. The novel design and data interpretation approach allowed for accurate measurements of soil thermal properties and θ without the need to perform a hard‐to‐achieve soil‐specific calibration. Measured θ had mean errors and standard deviations <0.03 and <0.01 m3 m−3, respectively, for moisture conditions ranging from dry to near saturation. The standard deviation in the measured heat capacity was <0.01 MJ m−3 K−1.
Visualizing Science: How Color Determines What We See
Authors: Zeller Stephanie , Rogers David
Published: May 2020

Color plays a major role in the analysis and communication of scientific information. New tools are helping to improve how color can be applied more accurately and effectively to data.
New Space Telescope Named for Nancy Roman, Astronomy Pioneer
Authors: Cartier Kimberly
Published: May 2020

Nancy Grace Roman’s namesake telescope will search for distant worlds and the earliest galaxies.
The FBW7-MCL-1 axis is key in M1 and M2 macrophage-related colon cancer cell progression: validating the immunotherapeutic value of targeting PI3Kγ
Authors: Lee Yeo Song , Song Su Jeong , Hong Hye Kyung , Oh Bo Young , Lee Woo Yong , Cho Yong Beom
Published: May 2020

Colorectal cancer is a devastating disease with a low 5-year survival rate. Recently, many researchers have studied the mechanisms of tumor progression related to the tumor microenvironment. Here, we addressed the prognostic value of tumor-associated macrophages (TAMs) using a total of 232 CRC patient tissue samples and investigated the mechanisms underlying TAM-related colon cancer progression with respect to PI3Kγ regulation using in vitro, in vivo, and ex vivo approaches. Patients with M2/M1 < 3 had significantly improved progression-free survival and overall survival compared with patients with M2/M1 > 3. M1 and M2 macrophages elicited opposite effects on colon cancer progression via the FBW7-MCL-1 axis. Blocking macrophage PI3Kγ had cytotoxic effects on colon cancer cells and inhibited epithelial–mesenchymal transition features by regulating the FBW7-MCL-1 axis. The results of this study suggest that macrophage PI3Kγ may be a promising target for immunotherapy in colon cancer.
Linked patterns of biological and environmental covariation with brain structure in adolescence: a population-based longitudinal study
Authors: Modabbernia Amirhossein , Reichenberg Abraham , Ing Alex , Moser Dominik A. , Doucet Gaelle E. , Artiges Eric , Banaschewski Tobias , Barker Gareth J. , Becker Andreas , Bokde Arun L. W. , Quinlan Erin Burke , Desrivières Sylvane , Flor Herta , Fröhner Juliane H. , Garavan Hugh , Gowland Penny , Grigis Antoine , Grimmer Yvonne , Heinz Andreas , Insensee Corinna , Ittermann Bernd , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Millenet Sabina , Nees Frauke , Orfanos Dimitri Papadopoulos , Paus Tomáš , Penttilä Jani , Poustka Luise , Smolka Michael N. , Stringaris Argyris , van Noort Betteke M. , Walter Henrik , Whelan Robert , Schumann Gunter , Frangou Sophia ,   IMAGEN Consortium
Published: May 2020

Adolescence is a period of major brain reorganization shaped by biologically timed and by environmental factors. We sought to discover linked patterns of covariation between brain structural development and a wide array of these factors by leveraging data from the IMAGEN study, a longitudinal population-based cohort of adolescents. Brain structural measures and a comprehensive array of non-imaging features (relating to demographic, anthropometric, and psychosocial characteristics) were available on 1476 IMAGEN participants aged 14 years and from a subsample reassessed at age 19 years (n = 714). We applied sparse canonical correlation analyses (sCCA) to the cross-sectional and longitudinal data to extract modes with maximum covariation between neuroimaging and non-imaging measures. Separate sCCAs for cortical thickness, cortical surface area and subcortical volumes confirmed that each imaging phenotype was correlated with non-imaging features (sCCA r range: 0.30–0.65, all PFDR < 0.001). Total intracranial volume and global measures of cortical thickness and surface area had the highest canonical cross-loadings (|ρ| = 0.31−0.61). Age, physical growth and sex had the highest association with adolescent brain structure (|ρ| = 0.24−0.62); at baseline, further significant positive associations were noted for cognitive measures while negative associations were observed at both time points for prenatal parental smoking, life events, and negative affect and substance use in youth (|ρ| = 0.10−0.23). Sex, physical growth and age are the dominant influences on adolescent brain development. We highlight the persistent negative influences of prenatal parental smoking and youth substance use as they are modifiable and of relevance for public health initiatives.
Linking perturbations to temporal changes in diversity, stability, and compositions of neonatal calf gut microbiota: prediction of diarrhea
Authors: Ma Tao , Villot Clothilde , Renaud David , Skidmore Andrew , Chevaux Eric , Steele Michael , Guan Le Luo
Published: May 2020

Perturbations in early life gut microbiota can have long-term impacts on host health. In this study, we investigated antimicrobial-induced temporal changes in diversity, stability, and compositions of gut microbiota in neonatal veal calves, with the objective of identifying microbial markers that predict diarrhea. A total of 220 samples from 63 calves in first 8 weeks of life were used in this study. The results suggest that increase in diversity and stability of gut microbiota over time was a feature of “healthy” (non-diarrheic) calves during early life. Therapeutic antimicrobials delayed the temporal development of diversity and taxa–function robustness (a measure of microbial stability). In addition, predicted genes associated with beta lactam and cationic antimicrobial peptide resistance were more abundant in gut microbiota of calves treated with therapeutic antimicrobials. Random forest machine learning algorithm revealed that Trueperella, Streptococcus, Dorea, uncultured Lachnospiraceae, Ruminococcus 2, and Erysipelatoclostridium may be key microbial markers that can differentiate “healthy” and “unhealthy” (diarrheic) gut microbiota, as they predicted early life diarrhea with an accuracy of 84.3%. Our findings suggest that diarrhea in veal calves may be predicted by the shift in early life gut microbiota, which may provide an opportunity for early intervention (e.g., prebiotics or probiotics) to improve calf health with reduced usage of antimicrobials.
Comparison of skeletal and soft tissue pericytes identifies CXCR4+ bone forming mural cells in human tissues
Authors: Xu Jiajia , Li Dongqing , Hsu Ching-Yun , Tian Ye , Zhang Leititia , Wang Yiyun , Tower Robert J. , Chang Leslie , Meyers Carolyn A. , Gao Yongxing , Broderick Kristen , Morris Carol , Hooper Jody E. , Nimmagadda Sridhar , Péault Bruno , James Aaron W.
Published: May 2020

Human osteogenic progenitors are not precisely defined, being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells (MSCs). Notably, select human pericytes can develop into bone-forming osteoblasts. Here, we sought to define the differentiation potential of CD146+ human pericytes from skeletal and soft tissue sources, with the underlying goal of defining cell surface markers that typify an osteoblastogenic pericyte. CD146+CD31−CD45− pericytes were derived by fluorescence-activated cell sorting from human periosteum, adipose, or dermal tissue. Periosteal CD146+CD31−CD45− cells retained canonical features of pericytes/MSC. Periosteal pericytes demonstrated a striking tendency to undergo osteoblastogenesis in vitro and skeletogenesis in vivo, while soft tissue pericytes did not readily. Transcriptome analysis revealed higher CXCR4 signaling among periosteal pericytes in comparison to their soft tissue counterparts, and CXCR4 chemical inhibition abrogated ectopic ossification by periosteal pericytes. Conversely, enrichment of CXCR4+ pericytes or stromal cells identified an osteoblastic/non-adipocytic precursor cell. In sum, human skeletal and soft tissue pericytes differ in their basal abilities to form bone. Diversity exists in soft tissue pericytes, however, and CXCR4+ pericytes represent an osteoblastogenic, non-adipocytic cell precursor. Indeed, enrichment for CXCR4-expressing stromal cells is a potential new tactic for skeletal tissue engineering.
Necroptosis in head and neck squamous cell carcinoma: characterization of clinicopathological relevance and in vitro cell model
Authors: Li Jingyuan , Huang Sihui , Zeng Lijuan , Li Kan , Yang Le , Gao Siyong , Guan Chenyu , Zhang Sien , Lao Xiaomei , Liao Guiqing , Liang Yujie
Published: May 2020

Necroptosis is a recently discovered form of programmed cell death (PCD) having necrotic-like morphology. However, its presence and potential impact with respect to head and neck squamous cell carcinoma (HNSCC) are still unknown. The aim of this study was to reveal the necroptosis status and its clinicopathological relevance in HNSCC and to establish an in vitro model. We first analyzed the level of p-MLKL, MLKL, and tumor necrosis in HNSCC patient tissues as well as their correlation with clinicopathological features. Results showed that approximately half of the tumor necrosis can be attributed to necroptosis, and the extent of necroptosis is an independent prognostic marker for patient’s overall survival and progression-free survival. Then we established and thoroughly verified an in vitro model of necroptosis in two HNSCC cell lines using combined treatment of TNF-α, Smac mimetic and zVAD-fmk (TSZ). At last, we adopted this model and demonstrated that necroptosis can promote migration and invasion of HNSCC cells by releasing damage-associated molecular patterns. In conclusion, our study unveiled the necroptotic status in HNSCC for the first time and provided a novel in vitro model of necroptosis in two HNSCC cell lines. In addition, our results indicated that necroptosis may be a potential cancer promoter in HNSCC. This study may serve as the foundation for future researches of necroptosis in HNSCC.
Sodium–glucose cotransporter 2 inhibition suppresses HIF-1α-mediated metabolic switch from lipid oxidation to glycolysis in kidney tubule cells of diabetic mice
Authors: Cai Ting , Ke Qingqing , Fang Yi , Wen Ping , Chen Hanzhi , Yuan Qi , Luo Jing , Zhang Yu , Sun Qi , Lv Yunhui , Zen Ke , Jiang Lei , Zhou Yang , Yang Junwei
Published: May 2020

Inhibition of sodium–glucose cotransporter 2 (SGLT2) in the proximal tubule of the kidney has emerged as an effective antihyperglycemic treatment. The potential protective role of SGLT2 inhibition on diabetic kidney disease (DKD) and underlying mechanism, however, remains unknown. In this study, metabolic switch was examined using kidney samples from human with diabetes and streptozocin (STZ)-induced experimental mouse model of diabetes treated with or without SGLT2 inhibitor dapagliflozin. Results were further validated using primarily cultured proximal tubule epithelial cells. We found that DKD development and progression to renal fibrosis entailed profound changes in proximal tubule metabolism, characterized by a switch from fatty acid utilization to glycolysis and lipid accumulation, which is associated with the increased expression of HIF-1α. Diabetes-induced tubulointerstitial damage, such as macrophage infiltration and fibrosis, was significantly improved by dapagliflozin. Consistent with the effects of these beneficial interventions, the metabolic disorder was almost completely eliminated by dapagliflozin. The increased level of HIF-1α in renal proximal tubule was nearly nullified by dapagliflozin. Moreover, dapagliflozin protects against glucose-induced metabolic shift in PTCs via inhibiting HIF-1α. It suggests that SGLT2 inhibition is efficient in rectifying the metabolic disorder and may be a novel prevention and treatment strategy for kidney tubule in DKD.
How to define and study structural proteins as biopolymer materials
Authors: Numata Keiji
Published: May 2020

Structural proteins, including silk fibroins, play an important role in shaping the skeletons and structures of cells, tissues, and organisms. The amino acid sequences of structural proteins often show characteristic features, such as a repeating tandem motif, that are notably different from those of functional proteins such as enzymes and antibodies. In recent years, materials composed of or containing structural proteins have been studied and developed as biomedical, apparel, and structural materials. This review outlines the definition of structural proteins, methods for characterizing structural proteins as polymeric materials, and potential applications.
Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation
Authors: Wang Yin , Yao Fang , Wang Lipeng , Li Zheng , Ren Zongna , Li Dandan , Zhang Mingzhi , Han Leng , Wang Shi-qiang , Zhou Bingying , Wang Li
Published: May 2020

Cardiac maturation lays the foundation for postnatal heart development and disease, yet little is known about the contributions of the microenvironment to cardiomyocyte maturation. By integrating single-cell RNA-sequencing data of mouse hearts at multiple postnatal stages, we construct cellular interactomes and regulatory signaling networks. Here we report switching of fibroblast subtypes from a neonatal to adult state and this drives cardiomyocyte maturation. Molecular and functional maturation of neonatal mouse cardiomyocytes and human embryonic stem cell-derived cardiomyocytes are considerably enhanced upon co-culture with corresponding adult cardiac fibroblasts. Further, single-cell analysis of in vivo and in vitro cardiomyocyte maturation trajectories identify highly conserved signaling pathways, pharmacological targeting of which substantially delays cardiomyocyte maturation in postnatal hearts, and markedly enhances cardiomyocyte proliferation and improves cardiac function in infarcted hearts. Together, we identify cardiac fibroblasts as a key constituent in the microenvironment promoting cardiomyocyte maturation, providing insights into how the manipulation of cardiomyocyte maturity may impact on disease development and regeneration.
KAT3-dependent acetylation of cell type-specific genes maintains neuronal identity in the adult mouse brain
Authors: Lipinski Michal , Muñoz-Viana Rafael , del Blanco Beatriz , Marquez-Galera Angel , Medrano-Relinque Juan , Caramés José M. , Szczepankiewicz Andrzej A. , Fernandez-Albert Jordi , Navarrón Carmen M. , Olivares Roman , Wilczyński Grzegorz M. , Canals Santiago , Lopez-Atalaya Jose P. , Barco Angel
Published: May 2020

The lysine acetyltransferases type 3 (KAT3) family members CBP and p300 are important transcriptional co-activators, but their specific functions in adult post-mitotic neurons remain unclear. Here, we show that the combined elimination of both proteins in forebrain excitatory neurons of adult mice resulted in a rapidly progressing neurological phenotype associated with severe ataxia, dendritic retraction and reduced electrical activity. At the molecular level, we observed the downregulation of neuronal genes, as well as decreased H3K27 acetylation and pro-neural transcription factor binding at the promoters and enhancers of canonical neuronal genes. The combined deletion of CBP and p300 in hippocampal neurons resulted in the rapid loss of neuronal molecular identity without de- or transdifferentiation. Restoring CBP expression or lysine acetylation rescued neuronal-specific transcription in cultured neurons. Together, these experiments show that KAT3 proteins maintain the excitatory neuron identity through the regulation of histone acetylation at cell type-specific promoter and enhancer regions.
Ultra-dense optical data transmission over standard fibre with a single chip source
Authors: Corcoran Bill , Tan Mengxi , Xu Xingyuan , Boes Andreas , Wu Jiayang , Nguyen Thach G. , Chu Sai T. , Little Brent E. , Morandotti Roberto , Mitchell Arnan , Moss David J.
Published: May 2020

Micro-combs - optical frequency combs generated by integrated micro-cavity resonators – offer the full potential of their bulk counterparts, but in an integrated footprint. They have enabled breakthroughs in many fields including spectroscopy, microwave photonics, frequency synthesis, optical ranging, quantum sources, metrology and ultrahigh capacity data transmission. Here, by using a powerful class of micro-comb called soliton crystals, we achieve ultra-high data transmission over 75 km of standard optical fibre using a single integrated chip source. We demonstrate a line rate of 44.2 Terabits s−1 using the telecommunications C-band at 1550 nm with a spectral efficiency of 10.4 bits s−1 Hz−1. Soliton crystals exhibit robust and stable generation and operation as well as a high intrinsic efficiency that, together with an extremely low soliton micro-comb spacing of 48.9 GHz enable the use of a very high coherent data modulation format (64 QAM - quadrature amplitude modulated). This work demonstrates the capability of optical micro-combs to perform in demanding and practical optical communications networks.
Tunable photo-responsive elastic metamaterials
Authors: Gliozzi Antonio S. , Miniaci Marco , Chiappone Annalisa , Bergamini Andrea , Morin Benjamin , Descrovi Emiliano
Published: May 2020

The metamaterial paradigm has allowed an unprecedented space-time control of various physical fields, including elastic and acoustic waves. Despite the wide variety of metamaterial configurations proposed so far, most of the existing solutions display a frequency response that cannot be tuned, once the structures are fabricated. Few exceptions include systems controlled by electric or magnetic fields, temperature, radio waves and mechanical stimuli, which may often be unpractical for real-world implementations. To overcome this limitation, we introduce here a polymeric 3D-printed elastic metamaterial whose transmission spectrum can be deterministically tuned by a light field. We demonstrate the reversible doubling of the width of an existing frequency band gap upon selective laser illumination. This feature is exploited to provide an elastic-switch functionality with a one-minute lag time, over one hundred cycles. In perspective, light-responsive components can bring substantial improvements to active devices for elastic wave control, such as beam-splitters, switches and filters.
A biochemically-interpretable machine learning classifier for microbial GWAS
Authors: Kavvas Erol S. , Yang Laurence , Monk Jonathan M. , Heckmann David , Palsson Bernhard O.
Published: May 2020

Current machine learning classifiers have successfully been applied to whole-genome sequencing data to identify genetic determinants of antimicrobial resistance (AMR), but they lack causal interpretation. Here we present a metabolic model-based machine learning classifier, named Metabolic Allele Classifier (MAC), that uses flux balance analysis to estimate the biochemical effects of alleles. We apply the MAC to a dataset of 1595 drug-tested Mycobacterium tuberculosis strains and show that MACs predict AMR phenotypes with accuracy on par with mechanism-agnostic machine learning models (isoniazid AUC = 0.93) while enabling a biochemical interpretation of the genotype-phenotype map. Interpretation of MACs for three antibiotics (pyrazinamide, para-aminosalicylic acid, and isoniazid) recapitulates known AMR mechanisms and suggest a biochemical basis for how the identified alleles cause AMR. Extending flux balance analysis to identify accurate sequence classifiers thus contributes mechanistic insights to GWAS, a field thus far dominated by mechanism-agnostic results.
A cysteine selenosulfide redox switch for protein chemical synthesis
Authors: Diemer Vincent , Ollivier Nathalie , Leclercq Bérénice , Drobecq Hervé , Vicogne Jérôme , Agouridas Vangelis , Melnyk Oleg
Published: May 2020

The control of cysteine reactivity is of paramount importance for the synthesis of proteins using the native chemical ligation (NCL) reaction. We report that this goal can be achieved in a traceless manner during ligation by appending a simple N-selenoethyl group to cysteine. While in synthetic organic chemistry the cleavage of carbon-nitrogen bonds is notoriously difficult, we describe that N-selenoethyl cysteine (SetCys) loses its selenoethyl arm in water under mild conditions upon reduction of its selenosulfide bond. Detailed mechanistic investigations show that the cleavage of the selenoethyl arm proceeds through an anionic mechanism with assistance of the cysteine thiol group. The implementation of the SetCys unit in a process enabling the modular and straightforward assembly of linear or backbone cyclized polypeptides is illustrated by the synthesis of biologically active cyclic hepatocyte growth factor variants.