bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure–Degradation Relationships
Authors: Burslem George M. , Ottis Philipp , Jaime‐Figueroa Saul , Morgan Alicia , Cromm Philipp M. , Toure Momar , Crews Craig M. 
Published: June 2018

AbstractThe immunomodulatory drugs (IMiDs) thalidomide, pomalidomide, and lenalidomide have been approved for the treatment of multiple myeloma for many years. Recently, their use as E3 ligase recruiting elements for small‐molecule‐induced protein degradation has led to a resurgence in interest in IMiD synthesis and functionalization. Traditional IMiD synthesis follows a stepwise route with multiple purification steps. Herein we describe a novel one‐pot synthesis without purification that provides rapid access to a multitude of IMiD analogues. Binding studies with the IMiD target protein cereblon (CRBN) reveals a narrow structure–activity relationship with only a few compounds showing sub‐micromolar binding affinity in the range of pomalidomide and lenalidomide. However, anti‐proliferative activity as well as Aiolos degradation could be identified for two IMiD analogues. This study provides useful insight into the structure–degradation relationships for molecules of this type as well as a rapid and robust method for IMiD synthesis.
Non‐Coding RNA Analysis Using the Rfam Database
Authors: Kalvari Ioanna , Nawrocki Eric P. , Argasinska Joanna , Quinones‐Olvera Natalia , Finn Robert D. , Bateman Alex , Petrov Anton I. 
Published: June 2018

AbstractRfam is a database of non‐coding RNA families in which each family is represented by a multiple sequence alignment, a consensus secondary structure, and a covariance model. Using a combination of manual and literature‐based curation and a custom software pipeline, Rfam converts descriptions of RNA families found in the scientific literature into computational models that can be used to annotate RNAs belonging to those families in any DNA or RNA sequence. Valuable research outputs that are often locked up in figures and supplementary information files are encapsulated in Rfam entries and made accessible through the Rfam Web site. The data produced by Rfam have a broad application, from genome annotation to providing training sets for algorithm development. This article gives an overview of how to search and navigate the Rfam Web site, and how to annotate sequences with RNA families. The Rfam database is freely available at http://rfam.org. © 2018 by John Wiley & Sons, Inc.
Amenamevir: Studies of Potential CYP2C8‐ and CYP2B6‐Mediated Pharmacokinetic Interactions With Montelukast and Bupropion in Healthy Volunteers
Authors: Dennison Jeremy , Puri Adeep , Warrington Steven , Endo Takamasa , Adeloye Temitope , Johnston Atholl 
Published: June 2018

AbstractAmenamevir (formerly ASP2151) induces cytochrome P450 (CYP)2B6 and CYP3A4 and inhibits CYP2C8. We conducted 2 studies, 1 using montelukast as a probe to assess CYP2C8 and the other bupropion to assess CYP2B6. The montelukast study examined the effect of amenamevir on the pharmacokinetics of montelukast in 24 healthy men: each subject received montelukast 10 mg alone, followed by montelukast 10 mg with amenamevir 400 mg, or vice versa after a washout period. In the bupropion study, 24 subjects received a single dose of 150 mg bupropion on days 1, 15, 22, and 29, and repeated once‐daily doses of 400 mg amenamevir on days 6‐15. Amenamevir increased peak concentration and area under the concentration‐time curve of montelukast by about 22% (ratio 121.7%, 90%CI [114.8, 129.1]; 121% [116.2, 128.4], respectively) with a similar increase in hydroxymontelukast (ratio 121.4%, 90%CI [106.4, 138.5]; 125.6 % [111.3, 141.7]). Amenamevir reduced peak concentration and area under the concentration‐time curve of bupropion by 16% (84.29%, 90%CI [78.00, 91.10]; 84.07%, 90%CI [78.85, 89.63]), with recovery after 1 week; the pharmacokinetics of the primary metabolite hydroxybupropion was unaffected. Thus, amenamevir increased plasma concentrations of montelukast and decreased those of bupropion, but it did not do so enough to require dose adjustment of coadministered substrates of either CYP2C8 or CYP2B6.
Pharmacokinetics of Perampanel in Healthy Korean, White, and Japanese Adult Subjects
Authors: Tabuchi Hiroko , Shiba Sari , Yasuda Sanae , Ohnishi Akihiro , Shin Jae‐Gook 
Published: June 2018

AbstractPerampanel is a highly selective, orally active, noncompetitive α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor antagonist that has been approved in many countries as a treatment for partial‐onset seizures and primary generalized tonic‐clonic seizures. The pharmacokinetics (PK) of perampanel following multiple doses in healthy Korean, white, and Japanese male subjects were assessed in 3 studies. Noncompartmental PK parameters were derived from plasma concentration‐time data. At steady state of perampanel 2‐, 4‐, and 6‐mg oral multiple administration, perampanel was rapidly absorbed, as plasma perampanel concentration reached maximum concentration after 0.55–1 hour (median) after dosing in all 3 ethnic groups. The elimination was slow, with terminal elimination phase half‐life values ranging from 63.9–129 hours (mean) for doses of 2–6 mg; there was no specific tendency suggesting a dose‐related effect, and perampanel PK were linear in Korean subjects. There were no clinically relevant ethnic differences in PK following multiple doses of perampanel 2 and 4 mg between Korean, white, or Japanese subjects. Perampanel was well tolerated by all 3 ethnic groups. This outcome indicates that with respect to PK, the dosing regimens established in white and Japanese patients are applicable to Korean patients.
Kinetics, Assembling, and Conformation Control of L‐Cysteine Adsorption on Pt Investigated by in situ FTIR Spectroscopy and QCM‐D
Authors: Dourado André H. B. , Silva Rubens A. , Torresi Roberto M. , Sumodjo Paulo T. A. , Arenz Matthias , Cordoba de Torresi Susana I. 
Published: June 2018

AbstractA quartz crystal microbalance method with dissipation (QCM−D) and attenuated total reflection Fourier‐transform infrared (ATR‐FTIRS) spectroscopy were used to study the adsorption of L‐cysteine (L–Cys) on Pt. Through QCM−D, it was possible to verify that the viscoelastic properties of the adsorbed species play an important role in the adsorption, rendering Sauerbrey's equation inapplicable. The modelling of QCM−D data exposed two different processes for the adsorption reaction. The first one had an activation time and is fast, whereas the second is slow. These processes were also resolved by ATR‐FTIRS and identified to be water and anion adsorption preceded by L–Cys adsorption. Both techniques reveal that the degree of surface coverage is pH dependent. Spectroscopic data indicate that the conformation of L–Cys(ads) changes with pH and that the structures do not fully agree with those proposed in literature for other metallic surfaces. The assembling of the adsorbed monolayer appeared to be very fast, and it was not possible to determine or quantify this kinetics. The conformation is also controlled by applied potential, and the anion adsorption and interfacial water depends on the conformation of the adsorbed molecules.
An Effective Recombinant Protein Expression and Purification System in Saccharomyces cerevisiae
Authors: Xie Ying , Han Xiao , Miao Yansong 
Published: June 2018

AbstractThe expression and purification of recombinant proteins using bacterial vectors is a mature and preferred system to obtain folded and stable proteins. However, functional post‐translational protein modifications, such as glycosylation or phosphorylation, can only be achieved using eukaryotic expression systems. In addition, insolubility is another challenge when using proteins expressed in Escherichia coli, such as certain intrinsically disordered proteins, which are more prone to aggregation than folded proteins. Eukaryotic protein expression systems, including human cells, baculovirus/insect cells, and yeast, have become indispensable for the production of functional eukaryotic proteins. This article describes a detailed protocol for performing cytosolic protein expression, protein purification, and protein characterization using the budding yeast Saccharomyces cerevisiae. The introduced protein expression and purification system in yeast are advantageous due to the low cost, high yield, high protein solubility, and minimal expertise required. © 2018 by John Wiley & Sons, Inc.
Iron‐Catalyzed Graphitic Carbon Materials from Biomass Resources as Anodes for Lithium‐Ion Batteries
Authors: Gomez‐Martin Aurora , Martinez‐Fernandez Julian , Ruttert Mirco , Heckmann Andreas , Winter Martin , Placke Tobias , Ramirez‐Rico Joaquin 
Published: June 2018

AbstractGraphitized carbon materials from biomass resources were successfully synthesized with an iron catalyst, and their electrochemical performance as anode materials for lithium‐ion batteries (LIBs) was investigated. Peak pyrolysis temperatures between 850 and 2000 °C were covered to study the effect of crystallinity and microstructural parameters on the anodic behavior, with a focus on the first‐cycle Coulombic efficiency, reversible specific capacity, and rate performance. In terms of capacity, results at the highest temperatures are comparable to those of commercially used synthetic graphite derived from a petroleum coke precursor at higher temperatures, and up to twice as much as that of uncatalyzed biomass‐derived carbons. The opportunity to graphitize low‐cost biomass resources at moderate temperatures through this one‐step environmentally friendly process, and the positive effects on the specific capacity, make it interesting to develop more sustainable graphite‐based anodes for LIBs.
X‐ray micrographic imaging system based on COTS CMOS sensors
Authors: Alcalde Bessia Fabricio , Pérez Martin , Lipovetzky José , Piunno Natalia Alejandra , Mateos Horacio , Sidelnik Iván , Blostein Juan Jerónimo , Sofo Haro Miguel , Gómez Berisso Mariano 
Published: June 2018

SummaryThis paper presents the use of commercial off the shelf CMOS image sensors for the acquisition of X‐ray images with high spatial resolution. The X‐ray images, with application in biology, electronic components inspection, and paleontology research, are obtained with 8‐keV photons from a Cu tube. The quantum efficiency of the detector is estimated using attenuation lengths of photons in the sensor and compared to traditional scintillator conversion layers. The spatial resolution observed with the sensor is limited by the charge redistribution produced after photon interaction with Si.
Forensic ancestry analysis in two Chinese minority populations using massively parallel sequencing of 165 ancestry‐informative SNPs
Authors: He Guanglin , Wang Zheng , Wang Mengge , Luo Tao , Liu Jing , Zhou You , Gao Bo , Hou Yiping 
Published: June 2018

AbstractAncestry inference based on SNPs with marked allele frequency differences in diverse populations (called ancestry‐informative SNP (AISNP)) is rapidly developed with the technology advancements of massively parallel sequencing. Despite the decade of exploration and broad public interest in the peopling of East‐Asians, the genetic landscape of Chinese Silk Road populations based on the AISNPs is still little known. In this work, 206 unrelated individuals from Chinese Uyghur and Hui populations were firstly genotyped by 165 AISNPs (The Precision ID Ancestry Panel) using the Ion Torrent Personal Genome Machine system. The ethnic origin of two investigated populations and population structures and genetic relationships were subsequently investigated. The 165 AISNPs panel not only can differentiate Uyghur and Hui populations but also has potential applications in individual identification. Comprehensive population comparisons and admixture estimates demonstrated a predominantly higher European‐related ancestry (36.30%) in Uyghurs than Huis (3.66%). Overall, the Precision ID Ancestry Panel can provide good resolution at the intercontinental level, but has limitations on the genetic homogeneous populations, such as the Hui and Han. Additional population‐specific AISNPs remain necessary to get better‐scale resolution within geographically proximate populations in East Asia.
A lumped parameter model for time‐domain inertial soil‐structure interaction analysis of structures on pile foundations
Authors: Carbonari Sandro , Morici Michele , Dezi Francesca , Leoni Graziano 
Published: June 2018

SummaryThe paper presents a lumped parameter model for the approximation of the frequency‐dependent dynamic stiffness of pile group foundations. The model can be implemented in commercial software to perform linear or nonlinear dynamic analyses of structures founded on piles taking into account the frequency‐dependent coupled roto‐translational, vertical, and torsional behaviour of the soil‐foundation system. Closed‐form formulas for estimating parameters of the model are proposed with reference to pile groups embedded in homogeneous soil deposits. These are calibrated with a nonlinear least square procedure, based on data provided by an extensive non‐dimensional parametric analysis performed with a model previously developed by the authors. Pile groups with square layout and different number of piles embedded in soft and stiff soils are considered. Formulas are overall well capable to reproduce parameters of the proposed lumped system that can be straightforwardly incorporated into inertial structural analyses to account for the dynamic behaviour of the soil‐foundation system. Some applications on typical bridge piers are finally presented to show examples of practical use of the proposed model. Results demonstrate the capability of the proposed lumped system as well as the formulas efficiency in approximating impedances of pile groups and the relevant effect on the response of the superstructure.
Moving beyond run‐off calibration—Multivariable optimization of a surface–subsurface–atmosphere model
Authors: Stisen Simon , Koch Julian , Sonnenborg Torben O. , Refsgaard Jens Christian , Bircher Simone , Ringgaard Rasmus , Jensen Karsten H. 
Published: June 2018

AbstractSpatially distributed hydrological models are traditionally calibrated and evaluated against few spatially aggregated observations such as river discharge. This model evaluation approach does not enable an assessment of the model predictive capabilities of other hydrological states and fluxes nor does it give any insight into the model ability to mimic the spatial patterns within a catchment. The current study explores a multivariable optimization of a complex coupled surface–subsurface–atmosphere model at the catchment scale in an attempt to move beyond simple run‐off calibration. The model is evaluated against five independent observational data sets of discharge (Q), hydraulic head (h), actual evapotranspiration (ET), soil moisture (SM), and remotely sensed land surface temperature (LST). It is shown that a balanced optimization can be achieved where errors on objective functions for all five observation data sets can be reduced simultaneously. Additionally, the multivariable calibration proved more robust, compared with calibration against Q and h only, during the validation period, even for Q and h. The current parameterization and calibration framework was mainly suitable for reducing model biases and allowed only limited improvements in the spatio‐temporal patterns of the model simulations. This points towards development of better parametrization schemes that will allow simulated spatial patterns to adjust during calibration. Additionally, analysis showed that systematic spatial patterns in the errors of the LST maps could be a very valuable diagnostic tool for assessing deficiencies in the model structure, spatial parameterization, or process description.
Critical issues in genotoxicity assessment of TiO2 nanoparticles by human peripheral blood mononuclear cells
Authors: Andreoli Cristina , Leter Giorgio , De Berardis Barbara , Degan Paolo , De Angelis Isabella , Pacchierotti Francesca , Crebelli Riccardo , Barone Flavia , Zijno Andrea 
Published: June 2018

AbstractIn the last years, a number of in vitro studies have been performed to assess the genotoxic activity of titanium dioxide (TiO2). To resolve the contradictory results, in this study, we investigated the genotoxic activity of commercial TiO2 nanoparticles (NPs) and microparticles of different forms (anatase, rutile and mix of both). We evaluated micronucleus formation in stimulated lymphocytes, as well as DNA strand breaks and 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine in peripheral blood mononuclear cells (PBMCs), a mixed population of lymphocytes and monocytes. Different responses to TiO2 exposure were obtained depending on the assay. Both TiO2 NPs and microparticles and all the crystalline forms elicited a significant increase in 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine and DNA strand breaks in the whole PBMC population, without a concurrent increase of micronuclei in proliferating lymphocytes. The distribution of DNA damage in PBMCs, detected by the comet assay, that measures DNA damage at level of single cells, indicated the presence of a more susceptible cell subpopulation. The measurement of side scatter signals by flow cytometry highlighted the preferential physical interaction of TiO2 particles with monocytes that also displayed higher reactive oxygen species generation, providing a mechanistic explanation for the different responses observed in genotoxicity assays with PBMCs and lymphocytes. This study confirmed the suitability of human PBMCs as multi‐cell model to investigate NP‐induced DNA damage, but suggested some caution in the use of stimulated lymphocytes for the assessment of NP clastogenicity.
Raman spectroscopic investigation of the human liver stem cell line HepaRG
Authors: Ryabchykov Oleg , Bräutigam Katharina , Galler Kerstin , Neugebauer Ute , Mosig Alexander , Bocklitz Thomas , Popp Jürgen 
Published: June 2018

AbstractIn this work, Raman spectroscopic cell imaging approaches and a discrimination between HepG2, nondifferentiated hepatic stem cell line HepaRG, and differentiated hepatocyte‐like HepaRG cells are presented. Raman spectroscopic imaging was used to visualize the cell nuclei by means of false color imaging using a marker band, and a cell segmentation was performed by means of clustering. Furthermore, a 3‐class‐classification model based on the mean Raman spectra of individual cells was established for a classification between different cell types. A high average sensitivity of 96% was achieved by the applied classification model. Based on the results of clustering and classification, the main spectral contributions to different cell types and cell segments were analyzed in detail. Thereby, HepG2, nondifferentiated hepatic stem cell line HepaRG, and differentiated hepatocyte‐like HepaRG cells were Raman spectroscopically characterized and proven to be significantly different.
An adaptive denoising method for Raman spectroscopy based on lifting wavelet transform
Authors: Chen Hao , Xu Weiliang , Broderick Neil , Han Jianda 
Published: June 2018

AbstractNoise, especially high‐level noise, is a severe problem in Raman spectral analysis. It smears informative Raman peaks, distorts spectral features, and therefore affects final analytical results, particularly in multivariate analysis, which is frequently used in Raman spectroscopy. This becomes even worse when it comes to optical Raman probe‐based biological applications due to limited acquisition time, laser power, and collection efficiency. Noise suppression is usually the first step in the preprocessing procedure of Raman spectral analysis. It is crucial to reduce noise effectively before performing further analysis. Discrete wavelet transform is a useful tool for noise reduction. However, it only provides limited and fixed filter banks, which may not be optimal for the data under investigation. In this paper, a novel adaptive denoising method based on lifting wavelet transform is presented for improving the signal‐to‐noise ratio for a Raman probe‐based system. It enables users to develop an infinite number of lifting schemes from a base wavelet, and with the help of genetic algorithm, the optimal one can be easily found. This method is examined by a set of simulated Raman spectra with various noise level and a set of experimental Raman spectra. Performance comparison with other commonly used denoising methods is made. The results indicate that the proposed method is able to remove noise effectively while retaining informative Raman peaks satisfactorily.
Production and Quantitative Analysis of Trehalose Lipid Biosurfactants Using High‐Performance Liquid Chromatography
Authors: Patil Harshada I. , Pratap Amit P. 
Published: June 2018

AbstractTrehalose lipids (THL) are glycolipid biosurfactants having a wide range of biomedical and environmental applications. Low yield, high purification cost, and the absence of a valid analytical method hinders their application. Hence, in the present study a simple, rapid, and reliable isocratic high‐performance liquid chromatography (LC) method was developed for the identification and quantification of trehalose lipid biosurfactants from Rhodococcus erythropolis. THL having a minimum surface tension of 24 mN m−1 and a critical micellar concentration of 25 mg L−1 were produced using hexadecane as a substrate. A standard was developed from the crude THL mixture using thin‐layer chromatography and column chromatography and its structure was confirmed using infrared spectroscopy, mass spectroscopy, and 1H NMR. A high performance liquid chromatography (HPLC) method for quantitation was developed using a C18 column with water/acetonitrile (80:20) as the mobile phase at a 1 mL min−1 flow rate and UV detection at 208 nm. This method was validated according to International Conference on Harmonization guidelines for linearity, precision, accuracy, robustness, LOD, and LOQ. This method was found to be linear over the range 10‐50 μg m L−1 (r2 =0.99801), precise, accurate, and robust. This method can detect minimum 3.2 μg mL−1 and quantify minimum 9.2 μg mL−1 of THL. Standards were developed from R. erythropolis, broth and purified standard trehalose 6,6′‐dimycolate from Mycobacterium bovis, having the same retention time of 2.0 min. The yield was calculated from the calibration curve and was found to be 25 g L−1.