bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histoepigenetic analysis of the mesothelin network within pancreatic ductal adenocarcinoma cells reveals regulation of retinoic acid receptor gamma and AKT by mesothelin
Authors: Lurie Eugene , Liu Dongliang , LaPlante Emily L. , Thistlethwaite Lillian R. , Yao Qizhi , Milosavljevic Aleksandar 
Published: July 2020

AbstractTo enable computational analysis of regulatory networks within the cancer cell in its natural tumor microenvironment, we develop a two-stage histoepigenetic analysis method. The first stage involves iterative computational deconvolution to estimate sample-specific cancer-cell intrinsic expression of a gene of interest. The second stage places the gene within a network module. We validate the method in simulation experiments, show improved performance relative to differential expression analysis from bulk samples, and apply it to illuminate the role of the mesothelin (MSLN) network in pancreatic ductal adenocarcinoma (PDAC). The network analysis and subsequent experimental validation in a panel of PDAC cell lines suggests AKT activation by MSLN through two known activators, retinoic acid receptor gamma (RARG) and tyrosine kinase non receptor 2 (TNK2). Taken together, these results demonstrate the potential of histoepigenetic analysis to reveal cancer-cell specific molecular interactions directly from patient tumor profiles.
Fewer tumour-specific PD-1+CD8+ TILs in high-risk “Infiltrating” HPV− HNSCC
Authors: Xu Ke , Fu You , Han Yong , Xia Ronghui , Xu Shengming , Duan Shengzhong , Zhang Zhiyuan , Li Jiang 
Published: July 2020

AbstractBackgroundThe prognosis of HPV-HNSCC was worse than that of HPV+HNSCC. Analysis of tumours and tumour-infiltrating lymphocytes (TILs) may provide insight into the progression of HPV−HNSCC.MethodsThe tumour and TIL phenotypic characteristics of 134 HNSCC specimens (HPV−tumours were classified into “Infiltrating” and “Pushing” subtypes based on their different tumour nest configuration and prognosis) were retrospectively analysed. HNSCC data from the Cancer Genome Atlas (n = 263) were analysed for CD8α, HPV and overall survival (OS). A murine HNSCC model was used to verify the antitumour role of PD-1+CD8+TILs.ResultsThe “Infiltrating” HPV−subtype showed shorter OS than the “Pushing” subtype. Moreover, there is a tendency from “Pushing” to “Infiltrating” subtype from the primary to the recurrent lesion. Different from total CD8+TILs, tumour-specific PD-1+CD8+TILs were fewer in invasive margin (IM) of “Infiltrating” HPV−tumours. PD-1+CD8+TILs recognised autologous HNSCC cells and showed stronger inhibition of tumour growth in a murine HNSCC model resistant to PD-1 blockade.ConclusionsCoevolution of HPV−HNSCC and TILs is characterised by an “Infiltrating” phenotype and less tumour-specific PD-1+CD8+TILs, which may provide a framework for further translational studies and patient stratification.
Quantum simulations of materials on near-term quantum computers
Authors: Ma He , Govoni Marco , Galli Giulia 
Published: July 2020

AbstractQuantum computers hold promise to enable efficient simulations of the properties of molecules and materials; however, at present they only permit ab initio calculations of a few atoms, due to a limited number of qubits. In order to harness the power of near-term quantum computers for simulations of larger systems, it is desirable to develop hybrid quantum-classical methods where the quantum computation is restricted to a small portion of the system. This is of particular relevance for molecules and solids where an active region requires a higher level of theoretical accuracy than its environment. Here, we present a quantum embedding theory for the calculation of strongly-correlated electronic states of active regions, with the rest of the system described within density functional theory. We demonstrate the accuracy and effectiveness of the approach by investigating several defect quantum bits in semiconductors that are of great interest for quantum information technologies. We perform calculations on quantum computers and show that they yield results in agreement with those obtained with exact diagonalization on classical architectures, paving the way to simulations of realistic materials on near-term quantum computers.
metPropagate: network-guided propagation of metabolomic information for prioritization of metabolic disease genes
Authors: Graham Linck Emma J. , Richmond Phillip A. , Tarailo-Graovac Maja , Engelke Udo , Kluijtmans Leo A. J. , Coene Karlien L. M. , Wevers Ron A. , Wasserman Wyeth , van Karnebeek Clara D. M. , Mostafavi Sara 
Published: July 2020

AbstractMany inborn errors of metabolism (IEMs) are amenable to treatment, therefore early diagnosis is imperative. Whole-exome sequencing (WES) variant prioritization coupled with phenotype-guided clinical and bioinformatics expertise is typically used to identify disease-causing variants; however, it can be challenging to identify the causal candidate gene when a large number of rare and potentially pathogenic variants are detected. Here, we present a network-based approach, metPropagate, that uses untargeted metabolomics (UM) data from a single patient and a group of controls to prioritize candidate genes in patients with suspected IEMs. We validate metPropagate on 107 patients with IEMs diagnosed in Miller et al. (2015) and 11 patients with both CNS and metabolic abnormalities. The metPropagate method ranks candidate genes by label propagation, a graph-smoothing algorithm that considers each gene’s metabolic perturbation in addition to the network of interactions between neighbors. metPropagate was able to prioritize at least one causative gene in the top 20th percentile of candidate genes for 92% of patients with known IEMs. Applied to patients with suspected neurometabolic disease, metPropagate placed at least one causative gene in the top 20th percentile in 9/11 patients, and ranked the causative gene more highly than Exomiser’s phenotype-based ranking in 6/11 patients. Interestingly, ranking by a weighted combination of metPropagate and Exomiser scores resulted in improved prioritization. The results of this study indicate that network-based analysis of UM data can provide an additional mode of evidence to prioritize causal genes in patients with suspected IEMs.
A novel pathogenic missense ADAMTS17 variant that impairs secretion causes Weill-Marchesani Syndrome with variably dysmorphic hand features
Authors: Evans Daniel R. , Green Jane S. , Fahiminiya Somayyeh , Majewski Jacek , Fernandez Bridget A. , Deardorff Matthew A. , Johnson Gordon J. , Whelan James H. , Hubmacher Dirk , Apte Suneel S. ,   Care4Rare Canada Consortium, Boycott Kym , Bulman Dennis , Dyment David , McKenzie Alex , Brudno Michael , Woods Michael O. 
Published: July 2020

AbstractWeill-Marchesani syndrome (WMS) is a rare disorder displaying short stature, brachydactyly and joint stiffness, and ocular features including microspherophakia and ectopia lentis. Brachydactyly and joint stiffness appear less commonly in patients with WMS4 caused by pathogenic ADAMTS17 variants. Here, we investigated a large family with WMS from Newfoundland, Canada. These patients displayed core WMS features, but with proportionate hands that were clinically equivocal for brachydactyly. Whole exome sequencing and autozygosity mapping unveiled a novel pathogenic missense ADAMTS17 variant (c.3068 G > A, p.C1023Y). Sanger sequencing demonstrated variant co-segregation with WMS, and absence in 150 population matched controls. Given ADAMTS17 involvement, we performed deep phenotyping of the patients’ hands. Anthropometrics applied to hand roentgenograms showed that metacarpophalangeal measurements of affected patients were smaller than expected for their age and sex, and when compared to their unaffected sibling. Furthermore, we found a possible sub-clinical phenotype involving markedly shortened metacarpophalangeal bones with intrafamilial variability. Transfection of the variant ADAMTS17 into HEK293T cells revealed significantly reduced secretion into the extracellular medium compared to wild-type. This work expands understanding of the molecular pathogenesis of ADAMTS17, clarifies the variable hand phenotype, and underscores a role for anthropometrics in characterizing sub-clinical brachydactyly in these patients.
PPARα activation directly upregulates thrombomodulin in the diabetic retina
Authors: Shiono Akira , Sasaki Hiroki , Sekine Reio , Abe Yohei , Matsumura Yoshihiro , Inagaki Takeshi , Tanaka Toshiya , Kodama Tatsuhiko , Aburatani Hiroyuki , Sakai Juro , Takagi Hitoshi 
Published: July 2020

AbstractTwo large clinical studies showed that fenofibrate, a commonly used peroxisome proliferator-activated receptor α (PPARα) agonist, has protective effects against diabetic retinopathy. However, the underlying mechanism has not been clarified. We performed genome-wide analyses of gene expression and PPARα binding sites in vascular endothelial cells treated with the selective PPARα modulator pemafibrate and identified 221 target genes of PPARα including THBD, which encodes thrombomodulin (TM). ChIP-qPCR and luciferase reporter analyses showed that PPARα directly regulated THBD expression via binding to the promoter. In the rat diabetic retina, treatment with pemafibrate inhibited the expression of inflammatory molecules such as VCAM-1 and MCP1, and these effects were attenuated by intravitreal injection of small interfering RNA targeted to THBD. Furthermore, pemafibrate treatment inhibited diabetes-induced vascular leukostasis and leakage through the upregulation of THBD. Our results indicate that PPARα activation inhibits inflammatory and vasopermeable responses in the diabetic retina through the upregulation of TM.
Accurately predicting electron beam deflections in fringing fields of a solenoid
Authors: Baumgärtel Christof , Smith Ray T. , Maher Simon 
Published: July 2020

AbstractComputer modelling is widely used in the design of scientific instrumentation for manipulating charged particles, for instance: to evaluate the behaviour of proposed designs, to determine the effects of manufacturing imperfections and to optimise the performance of apparatus. For solenoids, to predict charged particle trajectories, accurate values for the magnetic field through which charged species traverse are required, particularly at the end regions where fringe fields are most prevalent. In this paper, we describe a model that accurately predicts the deflection of an electron beam trajectory in the vicinity of the fringing field of a solenoid. The approach produces accurate beam deflection predictions in the fringe field region as well as in the centre of the solenoid. The model is based on a direct-line-of-action force between charges and is compared against field-based approaches including a commercially available package, with experimental verification (for three distinct cases). The direct-action model is shown to be more accurate than the other models relative to the experimental results obtained.
General method for classification of fiber families in fiber-reinforced materials: application to in-vivo human skin images
Authors: Witte Maximilian , Jaspers Sören , Wenck Horst , Rübhausen Michael , Fischer Frank 
Published: July 2020

AbstractFiber structures play a major role for the function of fiber-reinforced materials such as biological tissue. An objective classification of the fiber orientations into fiber families is crucial to understand its mechanical properties. We introduce the Fiber Image Network Evaluation Algorithm (FINE algorithm) to classify and quantify the number of fiber families in scientific images. Each fiber family is characterized by an amplitude, a mean orientation, and a dispersion. A new alignment index giving the averaged fraction of aligned fibers is defined. The FINE algorithm is validated by realistic grayscale Monte-Carlo fiber images. We apply the algorithm to an in-vivo depth scan of second harmonic generation images of dermal collagen in human skin. The derived alignment index exhibits a crossover at a critical depth where two fiber families with a perpendicular orientation around the main tension line arise. This strongly suggests the presence of a transition from the papillary to the reticular dermis. Hence, the FINE algorithm provides a valuable tool for a reliable classification and a meaningful interpretation of in-vivo collagen fiber networks and general fiber reinforced materials.
Genomics and transcriptomics analysis reveals the mechanism of isobutanol tolerance of a laboratory evolved Lactococcus lactis strain
Authors: Gupta Jaya A. , Thapa Sagar , Verma Madhulika , Som Ritu , Mukherjee Krishna Jyoti 
Published: July 2020

AbstractIsobutanol, in spite of its significant superiority over ethanol as a biofuel, remains commercially non-viable due to the non-availability of a suitable chassis which can handle the solvent toxicity associated with its production. To meet this challenge, we chose Lactococcus lactis which is known for its ability to handle environmental stress and carried out Adaptive laboratory evolution (ALE) in a continuous stirred tank reactor (CSTR) to evolve an isobutanol tolerant strain. The strain was grown for more than 60 days (> 250 generations) while gradually increasing the selection pressure, i.e. isobutanol concentration, in the feed. This led to the evolution of a strain that had an exceptionally high tolerance of up to 40 g/l of isobutanol even though a scanning electron microscope (SEM) study as well as analysis of membrane potential revealed only minor changes in cellular morphology. Whole genome sequencing which was done to confirm the strain integrity also showed comparatively few mutations in the evolved strain. However, the criticality of these mutations was reflected in major changes that occurred in the transcriptome, where gene expression levels from a wide range of categories that involved membrane transport, amino acid metabolism, sugar uptake and cell wall synthesis were significantly altered. Analysing the synergistic effect of these changes that lead to the complex phenotype of isobutanol tolerance can help in the construction of better host platforms for isobutanol production.
Extremely preterm children exhibit altered cortical thickness in language areas
Authors: Barnes-Davis Maria E. , Williamson Brady J. , Merhar Stephanie L. , Holland Scott K. , Kadis Darren S. 
Published: July 2020

AbstractChildren born extremely preterm (< 28 weeks gestation, EPT) are at increased risk for language and other neurocognitive deficits compared to term controls (TC). Prior studies have reported both increases and decreases in cortical thickness in EPT across the cerebrum. These studies have not formally normalized for intracranial volume (ICV), which is especially important as EPT children often have smaller stature, head size, and ICV. We previously reported increased interhemispheric functional and structural connectivity in a well-controlled group of school-aged EPT children with no known brain injury or neurological deficits. Functional and structural hyperconnectivity between left and right temporoparietal regions was positively related with language scores in EPT, which may be reflected in measures of cortical thickness. To characterize possible language network cortical thickness effects, 15 EPT children and 15 TC underwent standardized assessments of language and structural magnetic resonance imaging at 4 to 6 years of age. Images were subjected to volumetric and cortical thickness analyses using FreeSurfer. Whole-brain analyses of cortical thickness were conducted both with and without normalization by ICV. Non-normalized results showed thinner temporal cortex for EPT, while ICV-normalized results showed thicker cortical regions in the right temporal lobe (FDRq = 0.05). Only ICV-normalized results were significantly related to language scores, with right temporal cortical thickness being positively correlated with performance.
Unveiling antimicrobial and anticancerous behavior of AuNPs and AgNPs moderated by rhizome extracts of Curcuma longa from diverse altitudes of Himalaya
Authors: Sharma Mamta , Monika  , Thakur Pankaj , Saini Reena V. , Kumar Rajesh , Torino Enza 
Published: July 2020

AbstractConservative remedies have a gray history worldwide and these provide productive and pertinent tools to tackle ailments. Also, the high altitude areas of Indian Himalayas with their wealthy biodiversity anchorage around 2000 plant species. Ensuing study demonstrates the synthesis of Silver (Ag) and gold (Au) nanoparticles (NPs) and utilizes one of the medicaments Curcuma longa of Indian Himalayas collected from different altitudes. For the same, turmeric rhizome extracts have been prepared from the aforesaid medicament and its anticancer activity and antimicrobial potential have been evaluated. Formation of Ag and Au nanoparticles was realized via UV–Vis spectroscopy and transmission electron microscope (TEM) confirmed size of the NPs. Antibacterial activity has been checked against Bacillus subtilis and Escherichia coli. The anticancer prospective has been observed against A549 and PC3 cell lines of both Au and Ag NPs and the cytotoxicity on PC3 and A549 cell lines was assessed using MTT assay. Results revealed higher amount of biochemicals, antibacterial and anticancer activity in Ag and Au NPs synthesized from rhizome extract collected from highest altitude. For the first time impact of altitudinal variations on phytochemicals and nanoparticles has been reported which have significant effect on its antimicrobial and anticancerous activity.
Kinetic study of removal heavy metal from aqueous solution using the synthetic aluminum silicate
Authors: Treto-Suárez Manuel Alejandro , Prieto-García Julio Omar , Mollineda-Trujillo Ángel , Lamazares Emilio , Hidalgo-Rosa Yoan , Mena-Ulecia Karel 
Published: July 2020

AbstractOne of the problems that most affect humanity today is the wastewater discharge into different water bodies. It was estimated that more than 7 million tons of wastewater are generated worldwide and are discharged into rivers, lakes, and reservoirs. Among the most dangerous wastewaters are those from inorganic chemistry research laboratories, mainly due to heavy metals. These problems have become a highly relevant topic, and numerous researchers have tried to design wastewater treatment systems that will deal more efficiently with heavy metals elimination. In this work, the synthesis, characterization, and evaluation of hydrated aluminium silicate were performed as alternative wastewater treatment from chemistry research and teaching laboratories. The compound obtained was $$Al_2O_33SiO_2H_2O$$Al2O33SiO2H2O, which was characterized by the determination of its physicochemical properties. These revealed a low density, very porous material, with low crystallinity, strong chemical resistance, a large surface area, and a high apparent ionic exchange capacity. Absorption kinetics studies of heavy metals in aqueous solutions, through more widespread models, have demonstrated that $$Al_2O_33SiO_2H_2O$$Al2O33SiO2H2O has excellent properties as absorbents of this material. The amorphous hydrated aluminium silicate achieves a decrease in the concentration of all the metal ions studied, reducing them to discharge levels permissible.
Potential for sub-mm long erbium-doped composite silicon waveguide DFB lasers
Authors: Tu Zhengrui , Zhang Jianhao , Rönn John , Alonso-Ramos Carlos , Leroux Xavier , Vivien Laurent , Sun Zhipei , Cassan Éric 
Published: July 2020

AbstractCompact silicon integrated lasers are of significant interest for various applications. We present a detailed investigation for realizing sub-mm long on-chip laser structures operating at λ = 1.533 µm on the silicon-on-insulator photonic platform by combining a multi-segment silicon waveguide structure and a recently demonstrated erbium-doped thin film deposition technology. Quarter-wave shifted distributed feedback structures (QWS-DFB) are designed and a detailed calculation of the lasing threshold conditions is quantitatively estimated and discussed. The results indicate that the requirements for efficient lasing can be obtained in various combinations of the designed waveguide DFB structures. Overall, the study proposes a path to the realization of compact (< 500 µm) on-chip lasers operating in the C-band through the hybrid integration of erbium-doped aluminum oxide processed by atomic layer deposition in the silicon photonic platform and operating under optical pumping powers of few mW at 1,470 nm.
In vitro antioxidant activity of Ficus carica L. latex from 18 different cultivars
Authors: Shahinuzzaman M. , Yaakob Zahira , Anuar Farah Hannan , Akhtar Parul , Kadir N. H. A. , Hasan A. K. Mahmud , Sobayel K. , Nour Majid , Sindi Hatem , Amin Nowshad , Sopian K. , Akhtaruzzaman Md. 
Published: July 2020

AbstractAs synthetic antioxidants that are widely used in foods are known to cause detrimental health effects, studies on natural additives as potential antioxidants are becoming increasingly important. In this work, the total phenolic content (TPC) and antioxidant activity of Ficus carica Linn latex from 18 cultivars were investigated. The TPC of latex was calculated using the Folin–Ciocalteu assay. 1,1-Diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) were used for antioxidant activity assessment. The bioactive compounds from F. carica latex were extracted via maceration and ultrasound-assisted extraction (UAE) with 75% ethanol as solvent. Under the same extraction conditions, the latex of cultivar ‘White Genoa’ showed the highest antioxidant activity of 65.91% ± 1.73% and 61.07% ± 1.65% in DPPH, 98.96% ± 1.06% and 83.04% ± 2.16% in ABTS, and 27.08 ± 0.34 and 24.94 ± 0.84 mg TE/g latex in FRAP assay via maceration and UAE, respectively. The TPC of ‘White Genoa’ was 315.26 ± 6.14 and 298.52 ± 9.20 µg GAE/mL via the two extraction methods, respectively. The overall results of this work showed that F. carica latex is a potential natural source of antioxidants. This finding is useful for further advancements in the fields of food supplements, food additives and drug synthesis in the future.
Hysteresis in the underdamped three-layer model
Authors: Jia Li-Ping , Tekić Jasmina 
Published: July 2020

AbstractThe hysteretic phenomena were investigated in the three-layer model consisting of a chain of harmonically interacting atoms confined between two rigid periodical substrate potentials, where the top substrate was driven by a external force. The pinning to running and the running-to pinning transitions were examined as the driving force was varied and the influence of the equilibrium spacing and strength of the interaction of the particles in the middle layer on the static and kinetic friction force analyzed in detail. The parameter space in which the friction forces could reach their maxima or minima was determined. These results could be interesting for the selection of lubricant materials and minimization of energy loss in tribology.