bluuebunny/crossref_metadata_2025 huggingface dataset:
Fractures in Low‐Permeability Rocks: Can Poroelastic Effects Associated With Damage Zones Enhance Their Seismic Visibility?
Authors: Sotelo Edith , Rubino J. Germán , Solazzi Santiago G. , Barbosa Nicolás D. , Holliger Klaus
Published: April 2021

Fluid pressure diffusion (FPD) between a fracture and a porous permeable background can increase the normal compliance of the fracture and, thus, its reflectivity. However, many fractured environments of interest are associated with background rocks that can be regarded as largely impermeable for the the typical frequencies employed in seismic surveys. Nonetheless, there is evidence to suggest that the seemingly ubiquitous presence of damaged zones (DZs) associated with fractures may provide the necessary hydraulic communication between fractures and their immediate surroundings for FPD to occur. Here, we assess the pertinence of this phenomenon. To this end, we consider a 1D elastic‐poroelastic model, which comprises a poroelastic system consisting of a fracture embedded in adjacent DZ layers. This system is enclosed in an impermeable background represented by two elastic half‐spaces. We calculate the frequency‐dependent P‐wave reflectivity at normal incidence at the background‐DZ interface for different permeabilities, thicknesses, and porosities of the DZ. We also evaluate the corresponding normal fracture compliance. Our results show that, when accounting for the presence of a DZ surrounding an individual fracture, FPD effects between these regions induce a higher seismic reflectivity and a higher normal compliance compared to that of a hydraulically isolated fracture. This, in turn, implies that, even in largely impermeable environments, the seismic visibility of fractures can be enhanced through FPD enabled by the presence of DZs.
Survey of Transverse Range Fire Scars in 10 Years of UAVSAR Polarimetry
Authors: Parker Jay , Donnellan Andrea , Glasscoe Margaret
Published: April 2021

Because cross‐polarized radar returns are highly associated with volume scatter, radar polarimetry returns tend to show strong evidence of wildfire scars and recovery in forest and chaparral. We focus on the polarimetry images from UAVSAR (PolSAR) line SanAnd_08525, which covers a roughly 20 km wide swath over the Transverse Range including parts of the Santa Monica, San Gabriel and San Bernardino Mountains. We select images from four acquisition dates from October 2009 to September 2020, very roughly 4 years apart. These are compared to fire perimeters from the national Geospatial Multi‐Agency Coordination and NIFC databases for years 2003–2020, which shows the areas affected by the major fires (west to east) Springs2013, Woolsey2018, Topanga2005, LaTuna2017, Station2009, BlueCut2016, Pilot2016, Slide2007, Butler2007, and many smaller fires. PolSAR images are shown to be helpful in identifying types and boundaries of fire, 50‐meter scale details of vegetation loss, and variability of vegetation recovery in post‐fire years.
SHR/NCrl rats as a model of ADHD can be discriminated from controls based on their brain, blood, or urine metabolomes
Authors: Dupuy Camille , Castelnau Pierre , Mavel Sylvie , Lefevre Antoine , Nadal-Desbarats Lydie , Bodard Sylvie , Busson Julie , Dufour-Rainfray Diane , Blasco Helene , Emond Patrick , Galineau Laurent
Published: April 2021

Attention-Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity. The neurobiological mechanisms underlying ADHD are still poorly understood, and its diagnosis remains difficult due to its heterogeneity. Metabolomics is a recent strategy for the holistic exploration of metabolism and is well suited for investigating the pathophysiology of diseases and finding molecular biomarkers. A few clinical metabolomic studies have been performed on peripheral samples from ADHD patients but are limited by their access to the brain. Here, we investigated the brain, blood, and urine metabolomes of SHR/NCrl vs WKY/NHsd rats to better understand the neurobiology and to find potential peripheral biomarkers underlying the ADHD-like phenotype of this animal model. We showed that SHR/NCrl rats can be differentiated from controls based on their brain, blood, and urine metabolomes. In the brain, SHR/NCrl rats displayed modifications in metabolic pathways related to energy metabolism and oxidative stress further supporting their importance in the pathophysiology of ADHD bringing news arguments in favor of the Neuroenergetic theory of ADHD. Besides, the peripheral metabolome of SHR/NCrl rats also shared more than half of these differences further supporting the importance of looking at multiple matrices to characterize a pathophysiological condition of an individual. This also stresses out the importance of investigating the peripheral energy and oxidative stress metabolic pathways in the search of biomarkers of ADHD.
BDNF haploinsufficiency induces behavioral endophenotypes of schizophrenia in male mice that are rescued by enriched environment
Authors: Harb Mahmoud , Jagusch Justina , Durairaja Archana , Endres Thomas , Leßmann Volkmar , Fendt Markus
Published: April 2021

Brain-derived neurotrophic factor (BDNF) is implicated in a number of processes that are crucial for healthy functioning of the brain. Schizophrenia is associated with low BDNF levels in the brain and blood, however, not much is known about BDNF’s role in the different symptoms of schizophrenia. Here, we used BDNF-haploinsufficient (BDNF+/−) mice to investigate the role of BDNF in different mouse behavioral endophenotypes of schizophrenia. Furthermore, we assessed if an enriched environment can prevent the observed changes. In this study, male mature adult wild-type and BDNF+/− mice were tested in mouse paradigms for cognitive flexibility (attentional set shifting), sensorimotor gating (prepulse inhibition), and associative emotional learning (safety and fear conditioning). Before these tests, half of the mice had a 2-month exposure to an enriched environment, including running wheels. After the tests, BDNF brain levels were quantified. BDNF+/− mice had general deficits in the attentional set-shifting task, increased startle magnitudes, and prepulse inhibition deficits. Contextual fear learning was not affected but safety learning was absent. Enriched environment housing completely prevented the observed behavioral deficits in BDNF+/− mice. Notably, the behavioral performance of the mice was negatively correlated with BDNF protein levels. These novel findings strongly suggest that decreased BDNF levels are associated with several behavioral endophenotypes of schizophrenia. Furthermore, an enriched environment increases BDNF protein to wild-type levels and is thereby able to rescue these behavioral endophenotypes.
Improving cell-free glycoprotein synthesis by characterizing and enriching native membrane vesicles
Authors: Hershewe Jasmine M. , Warfel Katherine F. , Iyer Shaelyn M. , Peruzzi Justin A. , Sullivan Claretta J. , Roth Eric W. , DeLisa Matthew P. , Kamat Neha P. , Jewett Michael C.
Published: April 2021

Cell-free gene expression (CFE) systems from crude cellular extracts have attracted much attention for biomanufacturing and synthetic biology. However, activating membrane-dependent functionality of cell-derived vesicles in bacterial CFE systems has been limited. Here, we address this limitation by characterizing native membrane vesicles in Escherichia coli-based CFE extracts and describing methods to enrich vesicles with heterologous, membrane-bound machinery. As a model, we focus on bacterial glycoengineering. We first use multiple, orthogonal techniques to characterize vesicles and show how extract processing methods can be used to increase concentrations of membrane vesicles in CFE systems. Then, we show that extracts enriched in vesicle number also display enhanced concentrations of heterologous membrane protein cargo. Finally, we apply our methods to enrich membrane-bound oligosaccharyltransferases and lipid-linked oligosaccharides for improving cell-free N-linked and O-linked glycoprotein synthesis. We anticipate that these methods will facilitate on-demand glycoprotein production and enable new CFE systems with membrane-associated activities.
Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies
Authors: Harris William S. , Tintle Nathan L. , Imamura Fumiaki , Qian Frank , Korat Andres V. Ardisson , Marklund Matti , Djoussé Luc , Bassett Julie K. , Carmichael Pierre-Hugues , Chen Yun-Yu , Hirakawa Yoichiro , Küpers Leanne K. , Laguzzi Federica , Lankinen Maria , Murphy Rachel A. , Samieri Cécilia , Senn Mackenzie K. , Shi Peilin , Virtanen Jyrki K. , Brouwer Ingeborg A. , Chien Kuo-Liong , Eiriksdottir Gudny , Forouhi Nita G. , Geleijnse Johanna M. , Giles Graham G. , Gudnason Vilmundur , Helmer Catherine , Hodge Allison , Jackson Rebecca , Khaw Kay-Tee , Laakso Markku , Lai Heidi , Laurin Danielle , Leander Karin , Lindsay Joan , Micha Renata , Mursu Jaako , Ninomiya Toshiharu , Post Wendy , Psaty Bruce M. , Risérus Ulf , Robinson Jennifer G. , Shadyab Aladdin H. , Snetselaar Linda , Sala-Vila Aleix , Sun Yangbo , Steffen Lyn M. , Tsai Michael Y. , Wareham Nicholas J. , Wood Alexis C. , Wu Jason H. Y. , Hu Frank , Sun Qi , Siscovick David S. , Lemaitre Rozenn N. , Mozaffarian Dariush ,   The Fatty Acids and Outcomes Research Consortium (FORCE)
Published: April 2021

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15–18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20–22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
Hetero-site nucleation for growing twisted bilayer graphene with a wide range of twist angles
Authors: Sun Luzhao , Wang Zihao , Wang Yuechen , Zhao Liang , Li Yanglizhi , Chen Buhang , Huang Shenghong , Zhang Shishu , Wang Wendong , Pei Ding , Fang Hongwei , Zhong Shan , Liu Haiyang , Zhang Jincan , Tong Lianming , Chen Yulin , Li Zhenyu , Rümmeli Mark H. , Novoselov Kostya S. , Peng Hailin , Lin Li , Liu Zhongfan
Published: April 2021

Twisted bilayer graphene (tBLG) has recently attracted growing interest due to its unique twist-angle-dependent electronic properties. The preparation of high-quality large-area bilayer graphene with rich rotation angles would be important for the investigation of angle-dependent physics and applications, which, however, is still challenging. Here, we demonstrate a chemical vapor deposition (CVD) approach for growing high-quality tBLG using a hetero-site nucleation strategy, which enables the nucleation of the second layer at a different site from that of the first layer. The fraction of tBLGs in bilayer graphene domains with twist angles ranging from 0° to 30° was found to be improved to 88%, which is significantly higher than those reported previously. The hetero-site nucleation behavior was carefully investigated using an isotope-labeling technique. Furthermore, the clear Moiré patterns and ultrahigh room-temperature carrier mobility of 68,000 cm2 V−1 s−1 confirmed the high crystalline quality of our tBLG. Our study opens an avenue for the controllable growth of tBLGs for both fundamental research and practical applications.
Machine learning guided aptamer refinement and discovery
Authors: Bashir Ali , Yang Qin , Wang Jinpeng , Hoyer Stephan , Chou Wenchuan , McLean Cory , Davis Geoff , Gong Qiang , Armstrong Zan , Jang Junghoon , Kang Hui , Pawlosky Annalisa , Scott Alexander , Dahl George E. , Berndl Marc , Dimon Michelle , Ferguson B. Scott
Published: April 2021

Aptamers are single-stranded nucleic acid ligands that bind to target molecules with high affinity and specificity. They are typically discovered by searching large libraries for sequences with desirable binding properties. These libraries, however, are practically constrained to a fraction of the theoretical sequence space. Machine learning provides an opportunity to intelligently navigate this space to identify high-performing aptamers. Here, we propose an approach that employs particle display (PD) to partition a library of aptamers by affinity, and uses such data to train machine learning models to predict affinity in silico. Our model predicted high-affinity DNA aptamers from experimental candidates at a rate 11-fold higher than random perturbation and generated novel, high-affinity aptamers at a greater rate than observed by PD alone. Our approach also facilitated the design of truncated aptamers 70% shorter and with higher binding affinity (1.5 nM) than the best experimental candidate. This work demonstrates how combining machine learning and physical approaches can be used to expedite the discovery of better diagnostic and therapeutic agents.
Crystal structures of an E1–E2–ubiquitin thioester mimetic reveal molecular mechanisms of transthioesterification
Authors: Yuan Lingmin , Lv Zongyang , Adams Melanie J. , Olsen Shaun K.
Published: April 2021

E1 enzymes function as gatekeepers of ubiquitin (Ub) signaling by catalyzing activation and transfer of Ub to tens of cognate E2 conjugating enzymes in a process called E1–E2 transthioesterification. The molecular mechanisms of transthioesterification and the overall architecture of the E1–E2–Ub complex during catalysis are unknown. Here, we determine the structure of a covalently trapped E1–E2–ubiquitin thioester mimetic. Two distinct architectures of the complex are observed, one in which the Ub thioester (Ub(t)) contacts E1 in an open conformation and another in which Ub(t) instead contacts E2 in a drastically different, closed conformation. Altogether our structural and biochemical data suggest that these two conformational states represent snapshots of the E1–E2–Ub complex pre- and post-thioester transfer, and are consistent with a model in which catalysis is enhanced by a Ub(t)-mediated affinity switch that drives the reaction forward by promoting productive complex formation or product release depending on the conformational state.
The Chinese mitten crab genome provides insights into adaptive plasticity and developmental regulation
Authors: Cui Zhaoxia , Liu Yuan , Yuan Jianbo , Zhang Xiaojun , Ventura Tomer , Ma Ka Yan , Sun Shuai , Song Chengwen , Zhan Dongliang , Yang Yanan , Liu Hourong , Fan Guangyi , Cai Qingle , Du Jing , Qin Jing , Shi Chengcheng , Hao Shijie , Fitzgibbon Quinn P. , Smith Gregory G. , Xiang Jianhai , Chan Tin-Yam , Hui Min , Bao Chenchang , Li Fuhua , Chu Ka Hou
Published: April 2021

The infraorder Brachyura (true or short-tailed crabs) represents a successful group of marine invertebrates yet with limited genomic resources. Here we report a chromosome-anchored reference genome and transcriptomes of the Chinese mitten crabEriocheir sinensis, a catadromous crab and invasive species with wide environmental tolerance, strong osmoregulatory capacity and high fertility. We show the expansion of specific gene families in the crab, including F-ATPase, which enhances our knowledge on the adaptive plasticity of this successful invasive species. Our analysis of spatio-temporal transcriptomes and the genome ofE. sinensisand other decapods shows that brachyurization development is associated with down-regulation of Hox genes at the megalopa stage when tail shortening occurs. A better understanding of the molecular mechanism regulating sexual development is achieved by integrated analysis of multiple omics. These genomic resources significantly expand the gene repertoire of Brachyura, and provide insights into the biology of this group, and Crustacea in general.
Loss of endothelial glucocorticoid receptor accelerates diabetic nephropathy
Authors: Srivastava Swayam Prakash , Zhou Han , Setia Ocean , Liu Bing , Kanasaki Keizo , Koya Daisuke , Dardik Alan , Fernandez-Hernando Carlos , Goodwin Julie
Published: April 2021

Endothelial cells play a key role in the regulation of disease. Defective regulation of endothelial cell homeostasis may cause mesenchymal activation of other endothelial cells or neighboring cell types, and in both cases contributes to organ fibrosis. Regulatory control of endothelial cell homeostasis is not well studied. Diabetes accelerates renal fibrosis in mice lacking the endothelial glucocorticoid receptor (GR), compared to control mice. Hypercholesterolemia further enhances severe renal fibrosis. The fibrogenic phenotype in the kidneys of diabetic mice lacking endothelial GR is associated with aberrant cytokine and chemokine reprogramming, augmented Wnt signaling and suppression of fatty acid oxidation. Both neutralization of IL-6 and Wnt inhibition improve kidney fibrosis by mitigating mesenchymal transition. Conditioned media from endothelial cells from diabetic mice lacking endothelial GR stimulate Wnt signaling-dependent epithelial-to-mesenchymal transition in tubular epithelial cells from diabetic controls. These data demonstrate that endothelial GR is an essential antifibrotic molecule in diabetes.
Histone dynamics mediate DNA unwrapping and sliding in nucleosomes
Authors: Armeev Grigoriy A. , Kniazeva Anastasiia S. , Komarova Galina A. , Kirpichnikov Mikhail P. , Shaytan Alexey K.
Published: April 2021

Nucleosomes are elementary building blocks of chromatin in eukaryotes. They tightly wrap ∼147 DNA base pairs around an octamer of histone proteins. How nucleosome structural dynamics affect genome functioning is not completely clear. Here we report all-atom molecular dynamics simulations of nucleosome core particles at a timescale of 15 microseconds. At this timescale, functional modes of nucleosome dynamics such as spontaneous nucleosomal DNA breathing, unwrapping, twisting, and sliding were observed. We identified atomistic mechanisms of these processes by analyzing the accompanying structural rearrangements of the histone octamer and histone-DNA contacts. Octamer dynamics and plasticity were found to enable DNA unwrapping and sliding. Through multi-scale modeling, we showed that nucleosomal DNA dynamics contribute to significant conformational variability of the chromatin fiber at the supranucleosomal level. Our study further supports mechanistic coupling between fine details of histone dynamics and chromatin functioning, provides a framework for understanding the effects of various chromatin modifications.
Spatiotemporal patterning of photoresponsive DNA-based hydrogels to tune local cell responses
Authors: Huang Fujian , Chen Mengxi , Zhou Zhixin , Duan Ruilin , Xia Fan , Willner Itamar
Published: April 2021

Understanding the spatiotemporal effects of surface topographies and modulated stiffness and anisotropic stresses of hydrogels on cell growth remains a biophysical challenge. Here we introduce the photolithographic patterning or two-photon laser scanning confocal microscopy patterning of a series of o-nitrobenzylphosphate ester nucleic acid-based polyacrylamide hydrogel films generating periodically-spaced circular patterned domains surrounded by continuous hydrogel matrices. The patterning processes lead to guided modulated stiffness differences between the patterned domains and the surrounding hydrogel matrices, and to the selective functionalization of sub-regions of the films with nucleic acid anchoring tethers. HeLa cells are deposited on the circularly-shaped domains functionalized with the MUC-1 aptamers. Initiation of the hybridization chain reaction by nucleic acid tethers associated with the continuous hydrogel matrix results in stress-induced ordered orthogonal shape-changes on the patterned domains, leading to ordered shapes of cell aggregates bound to the patterns.
J-aggregates of meso-[2.2]paracyclophanyl-BODIPY dye for NIR-II imaging
Authors: Li Kang , Duan Xingchen , Jiang Zhiyong , Ding Dan , Chen Yuncong , Zhang Guo-Qiang , Liu Zhipeng
Published: April 2021

J-aggregation is an efficient strategy for the development of fluorescent imaging agents in the second near-infrared window. However, the design of the second near-infrared fluorescent J-aggregates is challenging due to the lack of suitable J-aggregation dyes. Herein, we report meso-[2.2]paracyclophanyl-3,5-bis-N,N-dimethylaminostyrl BODIPY (PCP-BDP2) as an example of BODIPY dye with J-aggregation induced the second near-infrared fluorescence. PCP-BDP2 shows an emission maximum at 1010 nm in the J-aggregation state. Mechanism studies reveal that the steric and conjugation effect of the PCP group on the BODIPY play key roles in the J-aggregation behavior and photophysical properties tuning. Notably, PCP-BDP2 J-aggregates can be utilized for lymph node imaging and fluorescence-guided surgery in the nude mouse, which demonstrates their potential clinical application. This study demonstrates BODIPY dye as an alternate J-aggregation platform for developing the second near-infrared imaging agents.
Rapid whole genome sequencing impacts care and resource utilization in infants with congenital heart disease
Authors: Sweeney Nathaly M. , Nahas Shareef A. , Chowdhury Shimul , Batalov Sergey , Clark Michelle , Caylor Sara , Cakici Julie , Nigro John J. , Ding Yan , Veeraraghavan Narayanan , Hobbs Charlotte , Dimmock David , Kingsmore Stephen F.
Published: April 2021

Congenital heart disease (CHD) is the most common congenital anomaly and a major cause of infant morbidity and mortality. While morbidity and mortality are highest in infants with underlying genetic conditions, molecular diagnoses are ascertained in only ~20% of cases using widely adopted genetic tests. Furthermore, cost of care for children and adults with CHD has increased dramatically. Rapid whole genome sequencing (rWGS) of newborns in intensive care units with suspected genetic diseases has been associated with increased rate of diagnosis and a net reduction in cost of care. In this study, we explored whether the clinical utility of rWGS extends to critically ill infants with structural CHD through a retrospective review of rWGS study data obtained from inpatient infants < 1 year with structural CHD at a regional children’s hospital. rWGS diagnosed genetic disease in 46% of the enrolled infants. Moreover, genetic disease was identified five times more frequently with rWGS than microarray ± gene panel testing in 21 of these infants (rWGS diagnosed 43% versus 10% with microarray ± gene panels, p = 0.02). Molecular diagnoses ranged from syndromes affecting multiple organ systems to disorders limited to the cardiovascular system. The average daily hospital spending was lower in the time period post blood collection for rWGS compared to prior (p = 0.003) and further decreased after rWGS results (p = 0.000). The cost was not prohibitive to rWGS implementation in the care of this cohort of infants. rWGS provided timely actionable information that impacted care and there was evidence of decreased hospital spending around rWGS implementation.
A comprehensive study on 2D, 3D and solid tumor environment to explore a multifunctional biogenic nanoconjugate
Authors: Unnikrishnan B. S. , Preethi G. U. , Sreelekha T. T.
Published: April 2021

Emergence of nanotechnology created a drastic change in the field of cancer therapy due to their unique features in drug delivery and imaging. Polysaccharide based nanoparticles have received extensive attention in recent years as promising nanoparticle mediated drug delivery systems. Polysaccharides are endorsed with versatile merits including high drug encapsulation efficiency, efficient drug protection against chemical or enzymatic degradation, unique ability to create a controlled release and cellular internalization. In the current study, we have fabricated doxorubicin-loaded carboxymethylated PST001 coated iron oxide nanoparticles (DOX@CM-PST-IONPs) for better management of cancer. CM-PST coated iron oxide nanoparticles co-encapsulated with chemotherapeutic drug doxorubicin, can be utilized for targeted drug delivery. Biocompatible and non-toxic nanoconjugates was found to be effective in both 2-D and 3-D cell culture system with efficient cancer cell internalization. The bench-marked potential of CM-PIONPs to produce reactive oxygen species makes it a noticeable drug delivery system to compact neoplasia. These nanoconjugates can lay concrete on a better way for the elimination of cancer spheroids and tumor burden.
Molecular dynamics simulation study on the effect of perfluorosulfonic acid side chains on oxygen permeation in hydrated ionomers of PEMFCs
Authors: Kwon Sung Hyun , Kang Haisu , Sohn Young-Jun , Lee Jinhee , Shim Sunbo , Lee Seung Geol
Published: April 2021

We prepared two types of perfluorosulfonic acid (PFSA) ionomers with Aquivion (short side chain) and Nafion (long side chain) on a Pt surface and varied their water contents (2.92 ≤ λ ≤ 13.83) to calculate the solubility and permeability of O2 in hydrated PFSA ionomers on a Pt surface using full atomistic molecular dynamics (MD) simulations. The solubility and permeability of O2 molecules in hydrated Nafion ionomers were greater than those of O2 molecules in hydrated Aquivion ionomers at the same water content, indicating that the permeation of O2 molecules in the ionomers is affected not only by the diffusion coefficient of O2 but also by the solubility of O2. Notably, O2 molecules are more densely distributed in regions where water and hydronium ions have a lower density in hydrated Pt/PFSA ionomers. Radial distribution function (RDF) analysis was performed to investigate where O2 molecules preferentially dissolve in PFSA ionomers on a Pt surface. The results showed that O2 molecules preferentially dissolved between hydrophilic and hydrophobic regions in a hydrated ionomer. The RDF analysis was performed to provide details of the O2 location in hydrated PFSA ionomers on a Pt surface to evaluate the influence of O2 solubility in ionomers with side chains of different lengths. The coordination number of C(center)–O(O2) and O(side chain)–O(O2) pairs in hydrated Nafion ionomers was higher than that of the same pairs in hydrated Aquivion ionomers with the same water content. Our investigation provides detailed information about the properties of O2 molecules in different PFSA ionomers on a Pt surface and with various water contents, potentially enabling the design of better-performing PFSA ionomers for use in polymer electrolyte membrane fuel cells.
A radiomics approach for automated diagnosis of ovarian neoplasm malignancy in computed tomography
Authors: Li Shiyun , Liu Jiaqi , Xiong Yuanhuan , Pang Peipei , Lei Pinggui , Zou Huachun , Zhang Mei , Fan Bing , Luo Puying
Published: April 2021

This paper develops a two-dimensional (2D) radiomics approach with computed tomography (CT) to differentiate between benign and malignant ovarian neoplasms. A retrospective study was conducted from July 2017 to June 2019 for 134 patients with surgically-verified benign or malignant ovarian tumors. The patients were randomly divided in a ratio of 7:3 into two sets, namely a training set (of n = 95) and a test set (of n = 39). The ITK-SNAP software was used to delineate the regions of interest (ROI) associated with lesions of the largest diameters in plain CT image slices. Texture features were extracted by the Analysis Kit (AK) software. The training set was used to select the best features according to the maximum-relevance minimum-redundancy (mRMR) criterion, in addition to the algorithm of the least absolute shrinkage and selection operator (LASSO). Then, we employed a radiomics model for classification via multivariate logistic regression. Finally, we evaluated the overall performance of our method using the receiver operating characteristics (ROC), the DeLong test. and tested in an external validation test sample of patients of ovarian neoplasm. We created a radiomics prediction model from 14 selected features. The radiomic signature was found to be highly discriminative according to the area under the ROC curve (AUC) for both the training set (AUC = 0.88), and the test set (AUC = 0.87). The radiomics nomogram also demonstrated good calibration and differentiation for both the training (AUC = 0.95) and test (AUC = 0.96) samples. External validation tests gave a good performance in radiomic signature (AUC = 0.83) and radiomics nomogram (AUC = 0.95). The decision curve explicitly indicated the clinical usefulness of our nomogram method in the sense that it can influence major clinical events such as the ordering or abortion of other tests, treatments or invasive procedures. Our radiomics model based on plain CT images has a high diagnostic efficiency, which is helpful for the identification and prediction of benign and malignant ovarian neoplasms.
Ambient temperature and subsequent COVID-19 mortality in the OECD countries and individual United States
Authors: Christophi Costas A. , Sotos-Prieto Mercedes , Lan Fan-Yun , Delgado-Velandia Mario , Efthymiou Vasilis , Gaviola Gabriel C. , Hadjivasilis Alexandros , Hsu Yu-Tien , Kyprianou Aikaterini , Lidoriki Irene , Wei Chih-Fu , Rodriguez-Artalejo Fernando , Kales Stefanos N.
Published: April 2021

Epidemiological studies have yielded conflicting results regarding climate and incident SARS-CoV-2 infection, and seasonality of infection rates is debated. Moreover, few studies have focused on COVD-19 deaths. We studied the association of average ambient temperature with subsequent COVID-19 mortality in the OECD countries and the individual United States (US), while accounting for other important meteorological and non-meteorological co-variates. The exposure of interest was average temperature and other weather conditions, measured at 25 days prior and 25 days after the first reported COVID-19 death was collected in the OECD countries and US states. The outcome of interest was cumulative COVID-19 mortality, assessed for each region at 25, 30, 35, and 40 days after the first reported death. Analyses were performed with negative binomial regression and adjusted for other weather conditions, particulate matter, sociodemographic factors, smoking, obesity, ICU beds, and social distancing. A 1 °C increase in ambient temperature was associated with 6% lower COVID-19 mortality at 30 days following the first reported death (multivariate-adjusted mortality rate ratio: 0.94, 95% CI 0.90, 0.99, p = 0.016). The results were robust for COVID-19 mortality at 25, 35 and 40 days after the first death, as well as other sensitivity analyses. The results provide consistent evidence across various models of an inverse association between higher average temperatures and subsequent COVID-19 mortality rates after accounting for other meteorological variables and predictors of SARS-CoV-2 infection or death. This suggests potentially decreased viral transmission in warmer regions and during the summer season.
Systematic THz study of the substrate effect in limiting the mobility of graphene
Authors: Scarfe Samantha , Cui Wei , Luican-Mayer Adina , Ménard Jean-Michel
Published: April 2021

We explore the substrate-dependent charge carrier dynamics of large area graphene films using contact-free non-invasive terahertz spectroscopy. The graphene samples are deposited on seven distinct substrates relevant to semiconductor technologies and flexible/photodetection devices. Using a Drude model for Dirac fermions in graphene and a fitting method based on statistical signal analysis, we extract transport properties such as the charge carrier density and carrier mobility. We find that graphene films supported by substrates with minimal charged impurities exhibit an enhanced carrier mobility, while substrates with a high surface roughness generally lead to a lower transport performance. The smallest amount of doping is observed for graphene placed on the polymer Zeonor, which also has the highest carrier mobility. This work provides valuable guidance in choosing an optimal substrate for graphene to enable applications where high mobility is required.
Demonstration of a MOT in a sub-millimeter membrane hole
Authors: Lee Jongmin , Biedermann Grant , Mudrick John , Douglas Erica A. , Jau Yuan-Yu
Published: April 2021

We demonstrate the generation of a cold-atom ensemble within a sub-millimeter diameter hole in a transparent membrane, a so-called “membrane MOT”. With a sub-Doppler cooling process, the atoms trapped by the membrane MOT are cooled down to 10 $$\upmu$$
μ
K. The atom number inside the unbridged/bridged membrane hole is about $$10^4$$

10
4

to $$10^5$$

10
5

, and the $$1/e^2$$

1
/

e
2

-diameter of the MOT cloud is about 180 $$\upmu$$
μ
m for a 400 $$\upmu$$
μ
m-diameter membrane hole. Such a membrane device can, in principle, efficiently load cold atoms into the evanescent-field optical trap generated by the suspended membrane waveguide for strong atom-light interaction and provide the capability of sufficient heat dissipation at the waveguide. This represents a key step toward the photonic atom trap integrated platform (ATIP).
Herpes simplex virus 1 and the risk of dementia: a population-based study
Authors: Murphy Meghan J. , Fani Lana , Ikram M. Kamran , Ghanbari Mohsen , Ikram M. Arfan
Published: April 2021

Herpes simplex virus 1 (HSV1) is a neuroinvasive virus capable of entering the brain which makes it a candidate pathogen for increasing risk of dementia. Previous studies are inconsistent in their findings regarding the link between HSV1 and dementia, therefore, we investigated how HSV1 relates to cognitive decline and dementia risk using data from a population-based study. We measured HSV1 immunoglobulin (IgG) antibodies in serum collected between 2002 and 2005 from participants of the Rotterdam Study. We used linear regression to determine HSV1 in relation to change in cognitive performance during 2 consecutive examination rounds on average 6.5 years apart. Next, we determined the association of HSV1 with risk of dementia (until 2016) using a Cox regression model. We repeated analyses for Alzheimer’s disease. All models were adjusted for age, sex, cardiovascular risk factors, and apolipoprotein E genotype. Of 1915 non-demented participants (mean age 71.3 years, 56.7% women), with an average follow-up time of 9.1 years, 244 participants developed dementia (of whom 203 Alzheimer’s disease). HSV1 seropositivity was associated with decline in global cognition (mean difference of HSV1 seropositive vs seronegative per standard deviation decrease in global cognition − 0.16; 95% confidence interval (95%CI), − 0.26; − 0.07), as well as separate cognitive domains, namely memory, information processing, and executive function, but not motor function. Finally, HSV1 seropositivity was not associated with risk of dementia (adjusted hazard ratio 1.18, 95% CI 0.83; 1.68), similar for Alzheimer’s disease. HSV1 is associated with cognitive decline but not with incident dementia in the general population. These data suggest HSV1 to be associated only with subtle cognitive disturbances but not with greater cognitive disorders that result in dementia.
Choosing increases the value of non-instrumental information
Authors: Jiwa Matthew , Cooper Patrick S. , Chong Trevor T.-J. , Bode Stefan
Published: April 2021

Curiosity pervades all aspects of human behaviour and decision-making. Recent research indicates that the value of information is determined by its propensity to reduce uncertainty, and the hedonic value of the outcomes it predicts. Previous findings also indicate a preference for options that are freely chosen, compared to equivalently valued alternatives that are externally assigned. Here, we asked whether the value of information also varies as a function of self- or externally-imposed choices. Participants rated their preference for information that followed either a self-chosen decision, or an externally imposed condition. Our results showed that choosing a lottery significantly increased the subjective value of information about the outcome. Computational modelling indicated that this change in information-seeking behaviour was not due to changes in the subjective probability of winning, but instead reflected an independent effect of choosing on the value of resolving uncertainty. These results demonstrate that agency over a prospect is an important source of information value.
Effect of commonly used cosmetic preservatives on skin resident microflora dynamics
Authors: Pinto Daniela , Ciardiello Tiziana , Franzoni Matteo , Pasini Francesca , Giuliani Giammaria , Rinaldi Fabio
Published: April 2021

Human skin is populated by various microorganisms, the so-called microbiota, such as bacteria, viruses, yeasts, fungi, and archaea. The skin microbiota is in constant contact with the surrounding environment which can alter its eubiotic state. Recently it has been also observed that the application of cosmetic products can alter the balance of the skin microbiota. This effect may be attributed to many factors including the residual activity of the preservatives on the skin. In the present work, we studied the effect of eleven preservatives commonly found in cosmetic products on Propionibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus in vitro using 3D skin models and culture-dependent methods. Also, the effect on Histone deacetylase 3 (HDAC3) has been investigated. Among tested combinations, three resulted as the best suitable for restoring a pre-existing dysbiosis since they act moderately inhibiting C. acnes and strongly S. aureus without simultaneously inhibiting the growth of S. epidermidis. The other four combinations resulted as the best suitable for use in topical products for skin and scalp in which it is necessary to preserve the eubiosis of the microbiota. Some of the tested were also able to increase HDAC3 expression. Taking together these data highlight the role of preservatives of skin resident microflora dynamics and could provide a reference for correctly choice preservatives and dosage in cosmetic formulations to preserve or restore homeostasis of skin microbiota.
Diet and trophic niche of the invasive signal crayfish in the first invaded Italian stream ecosystem
Authors: Ercoli Fabio , Ghia Daniela , Gruppuso Laura , Fea Gianluca , Bo Tiziano , Ruokonen Timo J.
Published: April 2021

The occurrence of the signal crayfish Pacifastacus leniusculus in the Valla Stream was the first established population of this invasive species recorded in an Italian stream ecosystem. We evaluated the seasonality of diet and trophic niche of invasive signal crayfish in order to estimate the ecological role and effects on native communities of the stream ecosystem. We studied the differences in food source use between sexes, life stages and seasons using carbon and nitrogen stable isotope analyses. To supplement stable isotope analyses, we evaluated food source usage using traditional stomach content analysis. We tested the hypothesis that juveniles have a different diet, showing different trophic niches, compared to adults. Results indicated that signal crayfish adult and juvenile diets mainly rely on macroinvertebrates and periphyton in summer, shifting to mostly periphyton in autumn. Although the two age classes occupied an equivalent trophic niche, juveniles showed slightly different carbon isotope values, suggesting a somewhat ontogenetic shift consistent among seasons. No significant differences were found in adult and juvenile diets between summer and autumn seasons. Our findings suggest that signal crayfish juveniles and adults exhibited seasonal feeding habits, probably due to ecological behaviour rather than food resource availability, and that both are likely to impose similar effects on macroinvertebrate communities in this and similar stream ecosystems.
Dual sensor measurement shows that temperature outperforms pH as an early sign of aerobic deterioration in maize silage
Authors: Shan Guilin , Buescher Wolfgang , Maack Christian , Lipski André , Acir Ismail-Hakki , Trimborn Manfred , Kuellmer Fabian , Wang Ye , Grantz David A. , Sun Yurui
Published: April 2021

High quality silage containing abundant lactic acid is a critical component of ruminant diets in many parts of the world. Silage deterioration, a result of aerobic metabolism (including utilization of lactic acid) during storage and feed-out, reduces the nutritional quality of the silage, and its acceptance by animals. In this study, we introduce a novel non-disruptive dual-sensor method that provides near real-time information on silage aerobic stability, and demonstrates for the first time that in situ silage temperature (Tsi) and pH are both associated with preservation of lactic acid. Aerobic deterioration was evaluated using two sources of maize silage, one treated with a biological additive, at incubation temperatures of 23 and 33 °C. Results showed a time delay between the rise of Tsi and that of pH following aerobic exposure at both incubation temperatures. A 11 to 25% loss of lactic acid occurred when Tsi reached 2 °C above ambient. In contrast, by the time the silage pH had exceeded its initial value by 0.5 units, over 60% of the lactic acid had been metabolized. Although pH is often used as a primary indicator of aerobic deterioration of maize silage, it is clear that Tsi was a more sensitive early indicator. However, the extent of the pH increase was an effective indicator of advanced spoilage and loss of lactic acid due to aerobic metabolism for maize silage.
G392E neuroserpin causing the dementia FENIB is secreted from cells but is not synaptotoxic
Authors: Ingwersen Thies , Linnenberg Christian , D’Acunto Emanuela , Temori Shabnam , Paolucci Irene , Wasilewski David , Mohammadi Behnam , Kirchmair Johannes , Glen Robert C. , Miranda Elena , Glatzel Markus , Galliciotti Giovanna
Published: April 2021

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a progressive neurodegenerative disease caused by point mutations in the gene for neuroserpin, a serine protease inhibitor of the nervous system. Different mutations are known that are responsible for mutant neuroserpin polymerization and accumulation as inclusion bodies in many cortical and subcortical neurons, thereby leading to cell death, dementia and epilepsy. Many efforts have been undertaken to elucidate the molecular pathways responsible for neuronal death. Most investigations have concentrated on analysis of intracellular mechanisms such as endoplasmic reticulum (ER) stress, ER-associated protein degradation (ERAD) and oxidative stress. We have generated a HEK-293 cell model of FENIB by overexpressing G392E-mutant neuroserpin and in this study we examine trafficking and toxicity of this polymerogenic variant. We observed that a small fraction of mutant neuroserpin is secreted via the ER-to-Golgi pathway, and that this release can be pharmacologically regulated. Overexpression of the mutant form of neuroserpin did not stimulate cell death in the HEK-293 cell model. Finally, when treating primary hippocampal neurons with G392E neuroserpin polymers, we did not detect cytotoxicity or synaptotoxicity. Altogether, we report here that a polymerogenic mutant form of neuroserpin is secreted from cells but is not toxic in the extracellular milieu.
Spatial and temporal pattern of wildfires in California from 2000 to 2019
Authors: Li Shu , Banerjee Tirtha
Published: April 2021

The environmental pollution, property losses and casualties caused by wildfires in California are getting worse by the year. To minimize the interference of wildfires on economic and social development, and formulate targeted mitigation strategies, it is imperative to understand the scale and extent of previous wildfire occurrences. In this study, we first investigated the temporal distributions of past wildfires in California divided by size and causes and analyzed the changes observed in the past two decades against the last century. The trend of wildfires in different time scales (yearly and monthly), as well as the distribution of wildfires across different spatial scales (administrative units, climate divisions in California from 2000 to 2019) were also studied. Furthermore, to extract the significant variables on the risk of wildfire occurrence, multivariate analyses of environmental and human-related variables with wildfire densities were carried out. The results show that the wildfire density distribution of the burned area in California conforms to the characteristics of the Pareto distribution. Over the past two decades, the frequency of small (< 500 acres), human-caused wildfires has increased most rapidly, and they are widely distributed in central and western California. The wildfire season has lengthened and the peak months have been advanced from August to July. In terms of the variables related to the risk of wildfire occurrence, the temperature, vapor pressure deficit, grass cover, and the distance to roads are crucial. This study reveals the relationship between environmental and social background conditions and the spatial-temporal distribution of wildfires, which can provide a reference for wildfire management, the formulation of future targeted wildfire emergency plans, and the planning of future land use in California.
Sex difference in the weighting of expected uncertainty under chronic stress
Authors: Lei Huijie , Mochizuki Yasuhiro , Chen Chong , Hagiwara Kosuke , Hirotsu Masako , Matsubara Toshio , Nakagawa Shin
Published: April 2021

The neurobiological literature implicates chronic stress induced decision-making deficits as a major contributor to depression and anxiety. Given that females are twice as likely to suffer from these disorders, we hypothesized the existence of sex difference in the effects of chronic stress on decision-making. Here employing a decision-making paradigm that relies on reinforcement learning of probabilistic predictive relationships, we show female volunteers with a high level of perceived stress in the past month are more likely to make suboptimal choices than males. Computational characterizations of this sex difference suggest that while under high stress, females and males differ in their weighting but not learning of the expected uncertainty in the predictive relationships. These findings provide a mechanistic account of the sex difference in decision-making under chronic stress and may have important implications for the epidemiology of sex difference in depression and anxiety.
Genetic variant rs10251977 (G>A) in EGFR-AS1 modulates the expression of EGFR isoforms A and D
Authors: Dhamodharan Shankar , Rose Mathew Maria , Chakkarappan Sundaram Reddy , Umadharshini Karuppiah Vijayamuthuramalingam , Arulmurugan Ramalingam , Subbiah Shanmugam , Inoue Ituro , Munirajan Arasambattu Kannan
Published: April 2021

Tyrosine kinase inhibitor is an effective chemo-therapeutic drug against tumors with deregulated EGFR pathway. Recently, a genetic variant rs10251977 (G>A) in exon 20 of EGFR reported to act as a prognostic marker for HNSCC. Genotyping of this polymorphism in oral cancer patients showed a similar frequency in cases and controls. EGFR-AS1 expressed significantly high level in tumors and EGFR-A isoform expression showed significant positive correlation (r = 0.6464, p < 0.0001) with reference to EGFR-AS1 expression levels, consistent with larger TCGA HNSCC tumor dataset. Our bioinformatic analysis showed enrichment of alternative splicing marks H3K36me3 and presence of intronic polyA sites spanning around exon 15a and 15b of EGFR facilitates skipping of exon 15b, thereby promoting the splicing of EGFR-A isoform. In addition, high level expression of PTBP1 and its binding site in EGFR and EGFR-AS1 enhances the expression of EGFR-A isoform (r = 0.7404, p < 0.0001) suggesting that EGFR-AS1 expression modulates the EGFR-A and D isoforms through alternative splicing. In addition, this polymorphism creates a binding site for miR-891b in EGFR-AS1 and may negatively regulate the EGFR-A. Collectively, our results suggested the presence of genetic variant in EGFR-AS1 modulates the expression of EGFR-D and A isoforms.