bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diphtheria toxin‐mediated transposon‐driven poly (A)‐trapping efficiently disrupts transcriptionally silent genes in embryonic stem cells
Authors: Bai Jie , Kondo Ryohei , Mayasari N. Ika , Shigeoka Toshiaki , Isotani Ayako , Ikawa Masahito , Sashida Goro , Kawaichi Masashi , Ishida Yasumasa 
Published: July 2020

SummaryRandom gene trapping is the application of insertional mutagenesis techniques that are conventionally used to inactivate protein‐coding genes in mouse embryonic stem (ES) cells. Transcriptionally silent genes are not effectively targeted by conventional random gene trapping techniques, thus we herein developed an unbiased poly (A) trap (UPATrap) method using a Tol2 transposon, which preferentially integrated into active genes rather than silent genes in ES cells. To achieve efficient trapping at transcriptionally silent genes using random insertional mutagenesis in ES cells, we generated a new diphtheria toxin (DT)‐mediated trapping vector, DTrap that removed cells, through the expression of DT that was induced by the promoter activity of the trapped genes, and selected trapped clones using the neomycin‐resistance gene of the vector. We found that a double‐DT, the dDT vector, dominantly induced the disruption of silent genes, but not active genes, and showed more stable integration in ES cells than the UPATrap vector. The dDT vector disrupted differentiated cell lineage genes, which were silent in ES cells, and labeled trapped clone cells by the expression of EGFP upon differentiation. Thus, the dDT vector provides a systematic approach to disrupt silent genes and examine the cellular functions of trapped genes in the differentiation of target cells and development.
Scale‐dependent effects of neighborhood biodiversity on individual tree productivity in a coniferous and broad‐leaved mixed forest in China
Authors: Fan Chunyu , Tan Lingzhao , Zhang Chunyu , Zhao Xiuhai , Gao Lushuang , von Gadow Klaus 
Published: July 2020

AbstractThe relationship between biodiversity and productivity has stimulated an increasing body of research over the past decades, and this topic still occupies a central place in ecology. While most studies have focused on biomass production in quadrats or plots, few have investigated the scale‐dependent relationship from an individual plant perspective. We present an analysis of the effects of biodiversity (species diversity and functional diversity) on individual tree growth with a data set of 16,060 growth records from a 30‐ha temperate forest plot using spatially explicit individual tree‐based methods. A significant relationship between species diversity and tree growth was found at the individual tree level in our study. The magnitude and direction of biodiversity effects varies with the spatial scale. We found positive effects of species diversity on tree growth at scales exceeding 9 m. Individual tree growth rates increased when there was a greater diversity of species in the neighborhood of the focal tree, which provides evidence of a niche complementarity effect. At small scales (3–5 m), species diversity had negative effects on tree growth, suggesting that competition is more prevalent than complementarity or facilitation in these close neighborhoods. The results also revealed many confounding factors which influence tree growth, such as elevation and available sun light. We conclude that the use of individual tree‐based methods may lead to a better understanding of the biodiversity‐productivity relationship in forest communities.
NCoR1 fine‐tunes type‐I IFN response in cDC1 dendritic cells by directly regulating Myd88‐IRF7 axis under TLR9
Authors: Ahad Abdul , Smita Shuchi , Mishra Gyan Prakash , Biswas Viplov Kumar , Sen Kaushik , Gupta Bhawna , Garcin Dominique , Acha‐Orbea Hans , Raghav Sunil K. 
Published: July 2020

AbstractPlasmacytoid dendritic cells (DCs) are reported to induce robust type‐I interferon (IFN) response, whereas cDC1 DCs develop moderate type‐I IFN response upon TLR9 stimulation. It is very interesting to understand how this signaling under TLR9 is tightly regulated for the induction of type‐I IFNs. Here, we report co‐repressor protein NCoR1 as the major factor fine‐tuning the signaling pathways regulating IFN‐β expression under TLR9 in cDC1 DCs. We found that NCoR1 knockdown induced a robust IFN‐β‐mediated antiviral response upon TLR9 activation in cDC1 DCs. At the molecular level, we showed that NCoR1 directly repressed MyD88‐IRF7 signaling axis in cDC1 cells. Therefore, NCoR1 depletion enhanced pIRF7 levels, IFN‐β secretion, and downstream pSTAT1‐pSTAT2 signaling, leading to sustained induction of IFN stimulatory genes. Integrative genomic analysis depicted strong enrichment of an antiviral gene‐module in CpG‐activated NCoR1 knockdown DCs upon TLR9 activation. Moreover, we confirmed our findings in primary DCs derived from splenocytes of WT and NCoR1 DC−/− animals, which showed protection from Sendai and Vesicular Stomatitis viruses upon CpG activation. Ultimately, we identified that NCoR1–HDAC3 complex is involved in repressing the type‐I IFN response in cDC1 DCs.
Thermodynamic feasibility analysis of a newly modified absorption power cycle running with LiBr‐water
Authors: Tozlu Alperen , Yosaf Salem A. , Özcan Hasan 
Published: July 2020

AbstractThis study thermodynamically evaluates a newly modified absorption power cycle (APC) working with Lithium Bromide–Water (LiBr‐H2O) solution and compares it with the conventional Rankine, one‐stage, and three‐stage APC systems. An additional steam condenser is integrated to the conventional APC and part of pure water is extracted and pumped back to the high‐pressure side without passing through the absorber of the cycle. In order to specify the best system parameters, parametric optimization of all configurations is evaluated. The Rankine cycle and the modified APC have better thermodynamic performances than those of the conventional and the three‐stage APC at generator temperatures. The conventional APC is found to improve the cycle performance at low generator pressure. However, the efficiencies of this cycle start to decrease when generator pressure increases. In contrast, the Rankine cycle and the modified APC have larger working ranges of generator pressure.
Nutrition and aroma challenges of green tea product as affected by emerging superfine grinding and traditional extraction
Authors: Peng Pai , Wang Linlin , Shu Guowei , Li Jianke , Chen Li 
Published: July 2020

AbstractGreen tea, superfine green tea powder (SGTP), and tea extract were prepared to determine their chemical components and antioxidant activity. The nutrition and aroma challenges of green tea during traditional extract technique and superfine grinding were profiled in this study. The traditional extract technique took advantage over superfine grinding in L‐theanine and glutamic acid (Glu) preservation, but not in other 16 essential amino acids. SGTP preserved a maximum of elements from green tea, whereas tea extract greatly changed the elements ratio. Tea extract contained higher VB2 and VC contents and doubled the tea polyphenol (TP) content in comparison with green tea and SGTP. Additionally, tea extract contained more favorable aroma compounds and maintained stronger antioxidant activity in comparison with green tea and SGTP. This study profiled an important basis for the comprehensive utilization of green tea resources by consumers and manufacturers.
Nonlinear biomarker interactions in conversion from mild cognitive impairment to Alzheimer's disease
Authors: Popescu Sebastian G. , Whittington Alex , Gunn Roger N. , Matthews Paul M. , Glocker Ben , Sharp David J , Cole James H ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: July 2020

AbstractMultiple biomarkers can capture different facets of Alzheimer's disease. However, statistical models of biomarkers to predict outcomes in Alzheimer's rarely model nonlinear interactions between these measures. Here, we used Gaussian Processes to address this, modelling nonlinear interactions to predict progression from mild cognitive impairment (MCI) to Alzheimer's over 3 years, using Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Measures included: demographics, APOE4 genotype, CSF (amyloid‐β42, total tau, phosphorylated tau), [18F]florbetapir, hippocampal volume and brain‐age. We examined: (a) the independent value of each biomarker; and (b) whether modelling nonlinear interactions between biomarkers improved predictions. Each measured added complementary information when predicting conversion to Alzheimer's. A linear model classifying stable from progressive MCI explained over half the variance (R2= 0.51,p < .001); the strongest independently contributing biomarker was hippocampal volume (R2= 0.13). When comparing sensitivity of different models to progressive MCI (independent biomarker models, additive models, nonlinear interaction models), we observed a significant improvement (p < .001) for various two‐way interaction models. The best performing model included an interaction between amyloid‐β‐PET and P‐tau, while accounting for hippocampal volume (sensitivity = 0.77, AUC = 0.826). Closely related biomarkers contributed uniquely to predict conversion to Alzheimer's. Nonlinear biomarker interactions were also implicated, and results showed that although for some patients adding additional biomarkers may add little value (i.e., when hippocampal volume is high), for others (i.e., with low hippocampal volume) further invasive and expensive examination may be warranted. Our framework enables visualisation of these interactions, in individual patient biomarker ‘space', providing information for personalised or stratified healthcare or clinical trial design.
Convalescent plasma therapy in patients with COVID‐19
Authors: Yiğenoğlu Tuğçe Nur , Hacıbekiroğlu Tuba , Berber İlhami , Dal Mehmet Sinan , Baştürk Abdülkadir , Namdaroğlu Sinem , Korkmaz Serdal , Ulas Turgay , Dal Tuba , Erkurt Mehmet Ali , Turgut Burhan , Altuntaş Fevzi 
Published: July 2020

AbstractThere are currently no licensed vaccines or therapeutics for COVID‐19. Anti‐SARS CoV‐2 antibody‐containing plasmas, obtained from the recovered individuals who had confirmed COVID‐19, have been started to be collected using apheresis devices and stored in blood banks in some countries in order to administer to the patients with COVID‐19 for reducing the need of intensive care and the mortality rates. Therefore, in this review, we aim to point out some important issues related to convalescent plasma (CP) and its use in COVID‐19. CP may be an adjunctive treatment option to the anti‐viral therapy. The protective effect of CP may continue for weeks and months. After the assessment of the donor, 200‐600 mL plasma can be collected with apheresis devices. The donation interval may vary between countries. Even though limited published studies are not prospective or randomized, until the development of vaccines or therapeutics, CP seems to be a safe and probably effective treatment for critically ill patients with COVID‐19. It could also be used for prophylactic purposes but the safety and effectiveness of this approach should be tested in randomized prospective clinical trials.
Statistically downscaled precipitation sensitivity to gridded observation data and downscaling technique
Authors: Wootten Adrienne M. , Dixon Keith W. , Adams‐Smith Dennis J. , McPherson Renee A. 
Published: July 2020

AbstractFuture climate projections illuminate our understanding of the climate system and generate data products often used in climate impact assessments. Statistical downscaling (SD) is commonly used to address biases in global climate models (GCM) and to translate large‐scale projected changes to the higher spatial resolutions desired for regional and local scale studies. However, downscaled climate projections are sensitive to method configuration and input data source choices made during the downscaling process that can affect a projection's ultimate suitability for particular impact assessments. Quantifying how changes in inputs or parameters affect SD‐generated projections of precipitation is critical for improving these datasets and their use by impacts researchers. Through analysis of a systematically designed set of 18 statistically downscaled future daily precipitation projections for the south‐central United States, this study aims to improve the guidance available to impacts researchers. Two statistical processing techniques are examined: a ratio delta downscaling technique and an equi‐ratio quantile mapping method. The projections are generated using as input results from three GCMs forced with representative concentration pathway (RCP) 8.5 and three gridded observation‐based data products. Sensitivity analyses identify differences in the values of precipitation variables among the projections and the underlying reasons for the differences.Results indicate that differences in how observational station data are converted to gridded daily observational products can markedly affect statistically downscaled future projections of wet‐day frequency, intensity of precipitation extremes, and the length of multi‐day wet and dry periods. The choice of downscaling technique also can affect the climate change signal for variables of interest, in some cases causing change signals to reverse sign. Hence, this study provides illustrations and explanations for some downscaled precipitation projection differences that users may encounter, as well as evidence of symptoms that can affect user decisions.
Identification of paternal germline mosaicism by MicroSeq and targeted next‐generation sequencing
Authors: Dai Congling , Cheng Dehua , Li Weina , Zeng Sicong , Lu Guangxiu , Zhang Qianjun 
Published: July 2020

AbstractBackgroundPrezygotic de novo mutations may be inherited from parents with germline mosaicism and are often overlooked when the resulting phenotype affects only one child. We aimed to identify paternal germline mosaicism in an index family and provide a strategy to determine germline mosaicism.‘MethodsWhole‐exome sequencing was performed on an Alport syndrome‐affected child. Variants were validated using Sanger sequencing in the pedigree analysis. An apparent de novo mutation was tested by next‐generation sequencing (NGS) following chromosome microdissection of the mutant region (MicroSeq) to clarify its homologous chromosome source. Mosaic mutation in sperm samples was detected using targeted next‐generation sequencing (TNGS). Self‐prepared mosaic DNA samples of the 3% and 0.1% mutant fractions were used to evaluate the TNGS detection sensitivity.ResultsTwo novel heterozygous variants, maternally inherited c.1322delT (p.Ile441Thrfs*17) and the de novo mutation c.2939T>A (p.Leu980Ter), in the COL4A3 gene were discovered in the propositus. MicroSeq identified c.2939T>A in the paternal chromosome, which was in trans with c.1322delT. The frequency of c.2937A was 2.65% in the father's sperm sample. We also showed that a 500X depth coverage may detect a mosaic mutation with an allele frequency as low as 2%–3% using TNGS.ConclusionMicroSeq is a valuable tool to identify the allele source of de novo mutations in a single patient. TNGS can be used to assess the mosaic ratios of known sites. We provided a systematic algorithm to detect germinal mosaicism in a single patient. This algorithm may have implications for genetic and reproductive counseling on germline mosaicism.
The problem of starting control with two intermediate moments of observation in the boundary value problem for the hyperbolic equation
Authors: Mardanov M. J. , Guliyev H. F. , Safarova Z. R. 
Published: July 2020

SummaryIn this article, a starting control problem with two intermediate moments of observation in the mixed linear problem for the second‐order hyperbolic equation with quadratic functional is studied. The necessary and sufficient optimality conditions are obtained in the form of variational inequality.
MMS2plot: An R Package for Visualizing Multiple MS/MS Spectra for Groups of Modified and Non‐Modified Peptides
Authors: Ming Liya , Zou Yang , Zhao Yiming , Zhang Luna , He Ningning , Chen Zhen , Li Shawn S.‐C. , Li Lei 
Published: July 2020

AbstractA large number of post‐translational modifications (PTMs) in proteins are buried in the unassigned mass spectrometric (MS) spectra in shot‐gun proteomics datasets. Because the modified peptide fragments are low in abundance relative to the corresponding non‐modified versions, it is critical to develop tools that allow facile evaluation of assignment of PTMs based on the MS/MS spectra. Such tools will preferably have the ability to allow comparison of fragment ion spectra and retention time between the modified and unmodified peptide pairs or group. Herein, MMS2plot, an R package for visualizing peptide‐spectrum matches (PSMs) for multiple peptides, is described. MMS2plot features a batch mode and generates the output images in vector graphics file format that facilitate evaluation and publication of the PSM assignment. MMS2plot is expected to play an important role in PTM discovery from large‐scale proteomics datasets generated by liquid chromatography‐MS/MS. The MMS2plot package is freely available at https://github.com/lileir/MMS2plot under the GPL‐3 license.
Gradient copolymers of ε‐caprolactone and δ‐valerolactone via solvent‐free ring‐opening copolymerization with a pyridyl‐urea/MTBD system
Authors: Feng Rui , Jie Suyun , Braunstein Pierre , Li Bo‐Geng 
Published: July 2020

AbstractThe ring‐opening copolymerization of ε‐caprolactone and δ‐valerolactone was carried out under solvent‐free conditions with a pyridyl‐urea (6C‐PU)/7‐methyl‐1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene catalytic system by premixing two monomers, yielding gradient copolyesters with cyclic and linear structures in the absence or presence of an initiator, respectively. The random and block copolyesters of these two monomers were also prepared for comparison. The results of 1H and 13C NMR spectra determined the linear and cyclic structure of copolymers. The kinetic experiment was used to determine the consuming rates of two monomers during the polymerization. The topologies and thermal properties of all the copolymers were characterized and compared by NMR and DSC.
Turning chemistry into information for heterogeneous catalysis
Authors: Pablo‐García Sergio , Álvarez‐Moreno Moises , López Núria 
Published: July 2020

AbstractThe growing generation of data and their wide availability has led to the development of tools to produce, analyze, and store this information. Computational chemistry studies, especially catalytic applications, often yield a vast amount of chemical information that can be analyzed and stored using these tools. In this manuscript, we present a framework that automatically performs a fully automated procedure consisting of the transfer of an adsorbate from a known metal slab to a new metal slab with similar packing. Our method generates the new geometry and also performs the required calculations and analysis to finally upload the processed data to an online database (ioChem‐BD). Two different implementations have been built, one to relocate minimum energy point structures and the second to transfer transition states. Our framework shows good performance for the minimum point location and a decent performance for the transition state identification. Most of the failures occurred during the transition state searches and needed additional steps to fully complete the process. Further improvements of our framework are required to increase the performance of both implementations. These results point to the avoidhuman path as a feasible solution for studies on very large systems that require a significant amount of human resources and, in consequence, are prone to human errors.
Current pharmacological modalities for management of novel coronavirus disease 2019 (COVID‐19) and the rationale for their utilization: A review
Authors: Giovane Richard A. , Rezai Shadi , Cleland Ellen , Henderson Cassandra E. 
Published: July 2020

SummarySARS‐CoV‐2 has caused a pandemic which is putting strain on the health‐care system and global economy. There is much pressure to develop both preventative and curative therapies for SARS‐CoV‐2 as there is no evidence to support therapies to improve outcomes in patients with SARS‐CoV‐2. Medications that inhibit certain steps of virus life cycle that are currently used to treat other illnesses such as Malaria, Ebola, HIV and Hepatitis C are being studied for use against SARS‐CoV‐2. To date, data is limited for medications that facilitate clinical improvement of COVID‐19 infections.
Superlinear Perturbations of the Eigenvalue Problem for the Robin Laplacian Plus an Indefinite and Unbounded Potential
Authors: Papageorgiou Nikolaos S. , Rădulescu Vicenţiu D. , Repovš Dušan D. 
Published: July 2020

AbstractWe consider a superlinear perturbation of the eigenvalue problem for the Robin Laplacian plus an indefinite and unbounded potential. Using variational tools and critical groups, we show that when $$\lambda $$
λ
is close to a nonprincipal eigenvalue, then the problem has seven nontrivial solutions. We provide sign information for six of them.
Technical success, resection status, and procedural complication rate of colonoscopic full-wall resection: a pooled analysis from 7 hospitals of different care levels
Authors: Krutzenbichler Irmengard , Dollhopf Markus , Diepolder Helmut , Eigler Andreas , Fuchs Martin , Herrmann Simon , Kleber Gerhard , Lewerenz Björn , Kaiser Christoph , Lilje Tilman , Rath Timo , Agha Ayman , Vitali Francesco , Schäfer Claus , Schepp Wolfgang , Gundling Felix 
Published: July 2020

Abstract
Introduction
Endoscopic full-thickness resection (eFTR) using the full-thickness resection device (FTRD®) is a novel minimally invasive procedure that allows the resection of various lesions in the gastrointestinal tract including the colorectum. Real-world data outside of published studies are limited. The aim of this study was a detailed analysis of the outcomes of colonoscopic eFTR in different hospitals from different care levels in correlation with the number of endoscopists performing eFTR.

Material and methods
In this case series, the data of all patients who underwent eFTR between November 2014 and June 2019 (performed by a total of 22 endoscopists) in 7 hospitals were analyzed retrospectively regarding rates of technical success, R0 resection, and procedure-related complications.

Results
Colonoscopic eFTR was performed in 229 patients (64.6% men; average age 69.3 ± 10.3 years) mainly on the basis of the following indication: 69.9% difficult adenomas, 21.0% gastrointestinal adenocarcinomas, and 7.9% subepithelial tumors. The average size of the lesions was 16.3 mm. Technical success rate of eFTR was achieved in 83.8% (binominal confidence interval 78.4–88.4%). Overall, histologically complete resection (R0) was achieved in 77.2% (CI 69.8–83.6%) while histologically proven full-wall excidate was confirmed in 90.0% (CI 85.1–93.7%). Of the resectates obtained (n = 210), 190 were resected en bloc (90.5%). We did not observe a clear improvement of technical success and R0 resection rate over time by the performing endoscopists. Altogether, procedure-related complications were observed in 17.5% (mostly moderate) including 2 cases of acute gangrenous appendicitis requiring operation.

Discussion
In this pooled analysis, eFTR represents a feasible, effective, and safe minimally invasive endoscopic technique.