bluuebunny/crossref_metadata_2025 huggingface dataset:
Autism risk genes are evolutionarily ancient and maintain a unique feature landscape that echoes their function
Authors: Casanova Emily L. , Switala Andrew E. , Dandamudi Srini , Hickman Allison R. , Vandenbrink Joshua , Sharp Julia L. , Feltus Frank Alex , Casanova Manuel F.
Published: April 2019

Previous research on autism risk (ASD), developmental regulatory (DevReg), and central nervous system (CNS) genes suggests they tend to be large in size, enriched in nested repeats, and mutation intolerant. The relevance of these genomic features is intriguing yet poorly understood. In this study, we investigated the feature landscape of these gene groups to discover structural themes useful in interpreting their function, developmental patterns, and evolutionary history. ASD, DevReg, CNS, housekeeping, and whole genome control (WGC) groups were compiled using various resources. Multiple gene features of interest were extracted from NCBI/UCSC Bioinformatics. Residual variation intolerance scores, Exome Aggregation Consortium pLI scores, and copy number variation data from Decipher were used to estimate variation intolerance. Gene age and protein–protein interactions (PPI) were estimated using Ensembl and EBI Intact databases, respectively. Compared to WGC: ASD, DevReg, and CNS genes are longer, produce larger proteins, maintain greater numbers/density of conserved noncoding elements and transposable elements, produce more transcript variants, and are comparatively variation intolerant. After controlling for gene size, mutation tolerance, and clinical association, ASD genes still retain many of these same features. In addition, we also found that ASD genes that are extremely mutation intolerant have larger PPI networks. These data support many of the recent findings within the field of autism genetics but also expand our understanding of the evolution of these broad gene groups, their potential regulatory complexity, and the extent to which they interact with the cellular network. Autism Res 2019, 12: 860–869. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Autism risk genes are more ancient compared to other genes in the genome. As such, they exhibit physical features related to their age, including long gene and protein size and regulatory sequences that help to control gene expression. They share many of these same features with other genes that are expressed in the brain and/or are associated with prenatal development.
Screening common signaling pathways associated with drug resistance in non‐small cell lung cancer via gene expression profile analysis
Authors: Sun Ting , Zhao Qitai , Zhang Chaoqi , Cao Ling , Song Mengjia , Maimela Nomathamsanqa Resegofetse , Liu Shasha , Wang Jinjin , Gao Qun , Qin Guohui , Wang Liping , Zhang Yi
Published: April 2019

Lung cancer is the leading cause of cancer‐related deaths worldwide. Although several therapeutic strategies have been employed to curb lung cancer, the survival rate is still poor owing to the development of drug resistance. The mechanisms underlying drug resistance development are incompletely understood. Here, we aimed to identify the common signaling pathways involved in drug resistance in non‐small cell lung cancer (NSCLC). Three published transcriptome microarray data were downloaded from the Gene Expression Omnibus (GEO) database comprising different drug‐resistant cell lines and their parental cell lines. Differentially expressed genes (DEGs) were identified and used to perform Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. An overlapping analysis was performed for KEGG pathways enriched from all the three datasets to identify the common signaling pathways. As a result, we found that metabolic pathways, ubiquitin‐mediated proteolysis, and mitogen‐activated protein kinase (MAPK) signaling were the most aberrantly expressed signaling pathways. The knockdown of nicotinamide phosphoribosyltransferase (NAMPT), the gene involved in metabolic pathways and known to be upregulated in drug‐resistant tumor cells, was shown to increase the apoptosis of cisplatin‐resistant A549 cells following cisplatin treatment. Thus, our results provide an in‐depth analysis of the signaling pathways that are commonly altered in drug‐resistant NSCLC cell lines and highlight the potential strategy that facilitates the development of interventions to interfere with upregulated signaling pathways as well as to boost downregulated signaling pathways in drug‐resistant tumors for the elimination of multiple resistance of NSCLC.
Catalytically Active Species in Copper/DiPPAM‐Catalyzed 1,6‐Asymmetric Conjugate Addition of Dialkylzinc to Dienones: A Computational Overview
Authors: Halbert Stéphanie , Lauberteaux Jimmy , Blons Charlie , de Figueiredo Renata Marcia , Crévisy Christophe , Baslé Olivier , Campagne Jean‐Marc , Mauduit Marc , Gérard Hélène
Published: April 2019

Four different catalytically active species are computationally examined in order to investigate the mechanism of Cu/DiPPAM‐catalyzed 1,6‐conjugate addition of dialkylzinc to acyclic dienones. A DiPPAM‐bridged Cu(alkyl)‐Zn(acetate) bimetallic complex exhibits the best catalytic activity, which can be associated with the best balance between the stability of the dienone adduct and its activation by copper. The selectivities (regio‐ and enantioselectivity) associated with the retained mechanism are investigated by DFT calculations and successfully compared to experimental data, including the critical influence of the substituents within the dienone on the regioselectivity and the obtained enantioselectivity for the formation of one 1,6‐adduct.
Cu/C‐catalyzed Hydrogenolysis of Sorbitol to Glycols–On the Influence of Particle Size and Base
Authors: Wang Xinde , Beine Anna Katharina , Hausoul Peter J. C. , Palkovits Regina
Published: April 2019

Herein, a series of Cu catalysts supported on activated carbon with increasing particle size was tested for the conversion of sorbitol to glycols including 1,2‐propanediol and ethylene glycol in the presence of Ca(OH)2. Activity measurements reveal a distinct correlation between TOF and particle size, which increases until 14 nm (N2O chemisorption based) after which a plateau is reached. However, variation of the particle size has no apparent effect on the selectivity for C3/C3 and C2/C4 cleavage. In contrast, variation of the Ca(OH)2 equivalence has a profound impact on selectivity. The ratio of C3/(C2+C4) products reaches an optimum at 0.45 equiv. of Ca(OH)2. Notably, the time course of the reaction demonstrates that the by‐products lactic acid and glycerol are in‐situ converted to the desired product 1,2‐propanediol, contributing to the unprecedented combined glycol selectivity of 84.5 % at 513 K, 5 MPa H2 and 0.3 equiv. of Ca(OH)2. Furthermore, recycling tests reveal a rapid deactivation which is attributed to aggregation of Cu observed in TEM.
Experimental studies on joinability of zircaloy and SiC/SiC composite with titanium powder
Authors: Serizawa Hisashi , Nakazato Naofumi , Sato Yuji , Tsukamoto Masahiro , Park Joon‐Soo , Kishimoto Hirotatsu
Published: April 2019

As for the enhanced accident tolerant fuel cladding for the advanced light‐water reactor, silicon carbide fiber reinforced silicon carbide matrix composite (SiC/SiC composite) is expected as a potential replacement of the current Zircaloy fuel cladding due to its many superiorities, where it is a key issue to develop the endcap seal of SiC/SiC composite cladding. In this research, based on the calking method, the fiber laser irradiation method was employed for sealing the endcap of SiC/SiC composite tube by Zircaloy tube, where the titanium micro‐powder was packed in the slit manufactured on the outer surface of SiC/SiC composite tube. By applying the laser beam irradiation to the outer surface of Zircaloy tube circumferentially, the mechanical calking joint was successfully fabricated. In addition, it is revealed that the good adhesion between Zircaloy and SiC/SiC composite was partially produced as the result of the generation of all proportional solid solution between titanium and zirconium. Moreover, the examinations about the slit shape influences indicate that the narrow hook slit seems to be the best type of silt for holding the titanium powder during the laser irradiation, where the width of slit should be narrower than that of laser irradiation line.
Making Use of the Direct Process Residue: Synthesis of Bifunctional Monosilanes
Authors: Sturm Alexander G. , Santowski Tobias , Schweizer Julia I. , Meyer Lioba , Lewis Kenrick M. , Felder Thorsten , Auner Norbert , Holthausen Max C.
Published: April 2019

The industrial production of monosilanes MenSiCl4−n (n=1–3) through the Müller–Rochow Direct Process generates disilanes MenSi2Cl6−n (n=2–6) as unwanted byproducts (“Direct Process Residue”, DPR) by the thousands of tons annually, large quantities of which are usually disposed of by incineration. Herein we report a surprisingly facile and highly effective protocol for conversion of the DPR: hydrogenation with complex metal hydrides followed by Si−Si bond cleavage with HCl/ether solutions gives (mostly bifunctional) monosilanes in excellent yields. Competing side reactions are efficiently suppressed by the appropriate choice of reaction conditions.
Synergy of Anodic Oxidation and Cathodic Reduction Leads to Electrochemical C—H Halogenation
Authors: Zhou Zhilin , Yuan Yong , Cao Yangmin , Qiao Jin , Yao Anjin , Zhao Jing , Zuo Wanqing , Chen Wenjie , Lei Aiwen
Published: April 2019

Summary of main observation and conclusion

We herein uncovered an electrochemical C—H halogenation protocol that synergistically combines anodic oxidation and cathodic reduction for C—X bond formation. The reaction was demonstrated under exogenous‐oxidant‐free conditions. Moreover, this is the first example of activating CBr4, CHBr3, and CCl3Br under electrochemical conditions.
Aging of polymeric materials by stray‐field NMR relaxometry with the NMR‐MOUSE
Authors: Blümich Bernhard
Published: April 2019

The sensitivity of NMR relaxation to molecular motion is explored to study the aging of polymer materials and paint binder in master paintings. Polymeric materials are formulated from macromolecules with a distribution of molecular weights and low molecular weight additives. Their physical and chemical properties change with time due to exposure to temperature, mechanical stress, and solvents. These conditions lead to physical and chemical aging, which can proceed naturally over longer times or accelerated under artificial conditions in shorter times. Either procedure bears a particular signature on the molecular mobility, which can be probed nondestructively by the NMR relaxation times T1 and T2. Natural aging and accelerated temperature‐ and solvent‐induced aging are summarized for synthetic polymer materials and compared to aging of binders in the paint layers of paintings aged naturally over hundreds of years and aged artificially by solvent‐cleaning procedures during restoration or at elevated temperature during forgery.
The past, present, and future of 1.26T2
Authors: Rovnyak David
Published: April 2019

This mini‐review considers the scientific and historical development of the constant 1.26T2, which represents the acquisition time for which the signal‐to‐noise ratio of a decaying exponential (with time constant T2) is a maximum in the presence of thermal noise. While first reported in 1977, interest in this result greatly increased after about the year 2000, when it began to influence thinking in nonuniform sampling, sensitivity, and pulse sequence design. Overall, 1.26T2 has become a lens through which to view the evolution of NMR data acquisition and processing. An enduring lesson of the 1.26T2 story is the value of describing and analyzing the properties of magnetic resonance signals in the time domain prior to any further spectral analysis and processing, a concept which is at the core of many modern analytic techniques.
Associations of visual forms with colors: The minor role of emotion as the mediator
Authors: Hanada Mitsuhiko
Published: April 2019

Associations of colors with a wide variety of visual forms were examined. Fifty visual forms were presented to Japanese participants, who were asked to report a color suitable to each visual form out of 15 colors. Correspondence analysis was applied to the responses, and four dimensions of configurations were obtained. The first and second dimensions were related to chromaticity or hue. In these dimensions, red and orange were associated with round symmetric shapes, yellow with shapes with sharp corners, violet and purple with irregular shapes with smooth curves, and cold colors such as blue and green with forms that consisted of simple geometrical elements such as triangles, squares, and circles. The third dimension was related to L* and b* in the CIELAB color space and to the stability of visual forms. Dimension 4 was not significantly related to any of L*, a*, and b*. In another experiment, participants rated the affective impressions of the colors and visual forms on semantic differential (SD) scales. The analyses of the SD data combined with the results of the color‐form associations suggest that the role of emotional meanings of colors and visual forms in mediating the associations was rather minor, and that world‐knowledge contributed considerably to the observed color‐form associations. Kandinsky's color‐form assignment was also examined, and except for the yellow‐triangle association, the assignment was not supported.
Particle Swarm Optimization (PSO) with fuzzy c means (PSO‐FCM)–based segmentation and machine learning classifier for leaf diseases prediction
Authors: S.K. Pravin Kumar , Sumithra M.G. , Saranya N.
Published: April 2019

This paper proposes an automatic classification technique that uses leaf images some medicinal plants. It is primarily the core reason that drives the research presented here, including the introduction of new innovative segmentation and classification techniques that are deployed to facilitate automatic detection. The major aim of the work is to introduce a new leaf disease prediction technique. The study conducted here a unique but effective image segmentation, feature extraction, as well as plant leaf disease classification. The proposed approach initially preprocesses leaf images of plants thereafter which the diseased sections of the plant are segmented by deploying Particle Swarm Optimization (PSO)–based fuzzy c means segmentation (PSO‐FCM), Gaussian Mixture Model (GMM)–based background subtraction. Vein and shape features, edge‐based feature extraction, and texture characteristics or texture features (TF) are computed. This methodology classifies the leaves of medicinal plants by deploying the Multiple Kernel Parallel Support Vector Machine (MK‐PSVM) classifier. The classifier is implemented via the use of MATLAB classifier. The results are measured using the accuracy, sensitivity, specificity, precision, and F‐measure metrics. Experimental results depict that the classifiers that have been proposed here achieve a higher classification accuracy enabling leaf detection.
Determination of Dermal Pharmacokinetics by Microdialysis Sampling in Rats
Authors: Voelkner Nivea M. F. , Voelkner Alexander , Derendorf Hartmut
Published: April 2019

The evaluation of absorption and availability at the site of action of a drug candidate is an important element of drug discovery and development, as clinical response is a function of the bioavailability of the active agent and its continued presence at the site of action. Evaluation of dermal pharmacokinetics facilitates the selection of new compounds or chemical structures for advancement as possible clinical candidates. An advantage of microdialysis is that it allows the measurement of compound concentrations at the site of action without disturbing the tissue milieu, making it possible to determine the relationship between this important variable and plasma concentrations of the agent. Described in this unit are laboratory protocols for performing dermal microdialysis experiments in rat for the purpose of defining the pharmacokinetics parameters of test agents. © 2019 by John Wiley & Sons, Inc.
A Structured Preapproval and Postapproval Comparative Study Design Framework to Generate Valid and Transparent Real‐World Evidence for Regulatory Decisions
Authors: Gatto Nicolle M. , Reynolds Robert F. , Campbell Ulka B.
Published: April 2019

Real‐world evidence provides important information about the effects of medicines in routine clinical practice. To engender trust that evidence generated for regulatory purposes is sufficiently valid, transparency in the reasoning that underlies study design decisions is critical. Building on existing guidance and frameworks, we developed the Structured Preapproval and Postapproval Comparative study design framework to generate valid and transparent real‐world Evidence (SPACE) as a process for identifying design elements and minimal criteria for feasibility and validity concerns, and for documenting decisions. Starting with an articulated research question, we identify key components of the randomized controlled trial needed to maximize validity, and pragmatic choices are considered when required. A causal diagram is used to justify the variables identified for confounding control, and key decisions, assumptions, and evidence are captured in a structured way. In this way, SPACE may improve dialogue and build trust among healthcare providers, patients, regulators, and researchers.
A Semisynthetic Peptide−Metalloporphyrin Responsive Matrix for Artificial Photosynthesis
Authors: Sun Zhongwu , Diebolder Christoph A. , Renault Ludovic , de Groot Huub
Published: April 2019

The CsmA protein from the baseplate of theChlorobaculum tepidumis proposed as an attractive motif for the engineering of semisynthetic materials for artificial photosynthesis. We perform self‐assembly of zinc protoporphyrin IX (ZnPP) with a truncated CsmA (tCsmA) amphipathic peptide scaffold for the bottom‐up construction of a semisynthetic matrix for energy transfer. The resulting self‐assembly shows an extended periodic structure with 72helical symmetry. The complex is able to maintain a good photostability for at least 30 min when the concentration is more than 20 μM, and almost 100 % harvested energy can be transferred to the acceptor cation radical methyl viologen (MV+). The excitation‐energy transfer rate of the complex was increased from the ns−1scale to the ps−1scale that is comparable to natural light‐harvesting antenna systems. It contributes to converging evidence that chiral responsive matrix assemblies can be developed for efficient light energy harvesting in artificial photosynthesis.
Socially responsible investing and the performance of Eurozone corporate bond portfolios
Authors: Pereira Patrícia , Cortez Maria Céu , Silva Florinda
Published: April 2019

This paper investigates the performance of socially screened bond portfolios of 189 Eurozone companies between 2003 and 2016. Bond portfolios are formed on the basis of an aggregate measure of corporate social responsibility (CSR) and on specific dimensions of CSR, namely, Environment, Social, and Governance dimensions. Our results show that the performance of highly socially rated bonds is not significantly different from that of low‐rated bonds. We also observe that in an earlier stage, portfolios of high‐rated bonds outperformed portfolios of low‐rated bonds. Yet over time, this outperformance disappears. These results suggest that the errors‐in‐expectations and shunned‐security hypotheses are not only useful in explaining the performance of socially responsible equity portfolios but that they are also useful in explaining the performance of socially screened bond portfolios over time. Overall, our results indicate that investors can form bond portfolios based on sustainability criteria without compromising financial performance.
An enhanced whale optimization algorithm for vehicular communication networks
Authors: Valayapalayam Kittusamy Senthil Ragavan , Elhoseny Mohamed , Kathiresan Shankar
Published: April 2019

In the field of vehicle communication networks, vehicular ad hoc network (VANET) is established with the help of road side unit (RSU). Each vehicle in the traffic system is managed by RSU with certain mobility factor, but still, there are some issues in the mobility management. In order to avoid such expensive RSUs and to enhance the mobility management of VANET system, the paper proposes a novel algorithm for the process of organizing a cluster structure and cluster head (CH) election suitable for VANETs. The proposed adaptive weighted clustering protocol (AWCP) groups the random nodes, and then the optimal CH is attained by the optimization of network parameters. For the purpose of optimization, an innovative algorithm called the enhanced whale optimization algorithm (EWOA) is introduced. For each vehicle in a trusted clustering model, its movement is analyzed by vehicle network mobility routing protocol with identified speed and position. The distance between the trusted vehicle node and RSU is analyzed by the proposed AWCP‐EWOA model. The results demonstrate the proposed AWCP‐EWOA model outperforms compared with AWCP and AWCP‐Whale Algorithm (WA) protocols in terms of clustering efficiency and its mobility enhancement.
Identity of coral reef herbivores drives variation in ecological processes over multiple spatial scales
Authors: Ruttenberg Benjamin I. , Adam Thomas C. , Duran Alain , Burkepile Deron E.
Published: April 2019

Overexploitation of key species can negatively impact ecosystem processes, so understanding the ecological roles of individual species is critical for improving ecosystem management. Here, we use coral reefs and the process of herbivory as a model to examine how species identity of consumers influence ecosystem processes to inform management of these consumers. Herbivorous fishes can facilitate the recruitment, growth, and recovery of corals by controlling the fast‐growing algae that can outcompete corals for space. However, herbivorous fish guilds are species rich with important differences among species in diet, movement, and habitat preferences. Yet, we lack a general understanding of (1) how these species‐specific differences in feeding and behavior scale up to reef‐wide rates of ecosystem processes and (2) how species identity and diversity impact these processes. To address these knowledge gaps, we used field observations to derive key species‐ and size‐specific foraging parameters for nine herbivorous parrotfish species on coral reefs in the Florida Keys, USA. We then combined these foraging parameters with fish survey data spanning multiple spatial scales to estimate the rates of three ecosystem processes: area of reef grazed, amount of macroalgae removed, and rate of bioerosion. We found that predicted rates of ecological processes varied dramatically among habitats and among reef zones within habitats, driven primarily by variation in abundance among species with different foraging behaviors. In some cases, assemblages with similar levels of total biomass had different rates of ecological processes, and in others, assemblages with different biomass had similar rates of ecological processes. Importantly, our models of herbivory using species‐specific parameters differed from those using genus‐level parameters by up to 300% in rates of ecological processes, highlighting the importance of herbivore identity in this system. Our results indicate that there may be little overlap in the roles species play, suggesting that some systems may be vulnerable to loss of ecological function with the reduction or loss of just a few species. This work provides a framework that can be applied across the region to predict how changes in management may affect the ecological impact of these important herbivores.
A population genetics perspective on the evolutionary histories of three clonal, endemic, and dominant grass species of the Qinghai–Tibet Plateau: Orinus (Poaceae)
Authors: Liu Yuping , Harris AJ , Gao Qingbo , Su Xu , Ren Zhumei
Published: April 2019

We performed analyses of amplified fragment length polymorphism (AFLP) in order to characterize the evolutionary history of Orinus according to its population genetic structure, as well as to investigate putative hybrid origins of O. intermedius and to provide additional insights into relationships among species. The genus Orinus comprises three clonal grasses that are dominant species within xeric alpine grasslands of the Qinghai–Tibet Plateau (QTP). Here, we used eight selectively obtained primer pairs of EcoRI/MseI to perform amplifications in 231 individuals of Orinus representing 48 populations and all three species. We compared our resulting data to genetic models of hybridization using a Bayesian algorithm within NewHybrids software. We determined that genetic variation in Orinus was 56.65% within populations while the among‐species component was 30.04% using standard population genetics statistics. Nevertheless, we detected that species of Orinus were clustered into three highly distinct genetic groups corresponding to classic species identities. Our results suggest that there is some introgression among species. Thus, we tested explicit models of hybridization using a Bayesian approach within NewHybrids software. However, O. intermedius likely derives from a common ancestor with O. kokonoricus and is probably not the result of hybrid speciation between O. kokonoricus and O. thoroldii. We suspect that recent isolation of species of Orinus in allopatry via vicariance may explain the patterns in diversity that we observed, and this is corroborated by a Mantel test that showed significant positive correlation between geographic and genetic distance (r = 0.05, p < 0.05). Recent isolation may explain why Orinus differs from many other clonal species by exhibiting the highest diversity within populations rather than among them.
Functional differences stabilize beetle communities by weakening interspecific temporal synchrony
Authors: van Klink Roel , Lepš Jan , Vermeulen Rikjan , de Bello Francesco
Published: April 2019

The temporal stability of communities is essential for the maintenance of ecosystem functioning across trophic levels. The stabilizing effect of biodiversity is, among other factors, modulated by the level of synchrony in population fluctuations among the species in the community. What drives community synchrony, however, remains largely unclear. Community synchrony can be affected by external drivers such as disturbances, but also by the properties of the community. Species with different ecological strategies should fluctuate less synchronously than more similar species; thus, an increase in diversity of ecological strategies should decrease synchrony, and increase the stability of the community. Here, using an exceptionally large data set of ground beetle trappings in Dutch heathlands (~370,000 individuals in 19 plots, each sampled between 9 and 36 yr), we assess the drivers of community stability and synchrony, and their relationship with disturbance, species richness, and functional diversity (FD). We found no effect of disturbance (fire and topsoil removal) on community stability or synchrony, probably because of unpredictable patterns of increase or decrease of the populations. Community synchrony was overall positive, giving more support for independent and positive correlation between species than for compensatory dynamics. Synchrony decreased with increasing FD, but not with species richness. Supporting this, we found that the more species pairs differ in their traits, the less synchronously their populations fluctuate, where 74% of all pairs showed no significant correlation. Significant positive synchrony (19% of species pairs) was concentrated among pairs with low trait dissimilarity, and the 7% of pairs with significant negative temporal correlation showed no relation with pairwise functional dissimilarity. The stabilizing effect of FD via decreased synchrony supports largely untested theoretical expectations that an increased diversity of functional strategies in a community will have a stabilizing effect on community abundance. We hypothesize that because competition is low in this community, the stabilizing effect of FD reflects interspecific variation in responses to environmental fluctuations rather than competition.
Photochemical Unmasking of 1,3‐Dithiol‐2‐ones: An Alternative Route to Heteroleptic Dithiolene Complexes from Low‐Valent Molybdenum and Tungsten Precursors
Authors: Elvers Benedict J. , Schulzke Carola , Fischer Christian
Published: April 2019

Mono‐dithiolene complexes [Mo(CO)2(dt)(dppe)] and [W(CO)2(dt)(dppe)] {dt = cyclohex‐1‐ene‐1,2‐dithiol; 5,6‐dihydro‐2H‐pyran‐3,4‐dithiol and dppe= 1,2‐bis(diphenylphosphino)ethane} were synthesized by a photochemical procedure. The typical basic de‐protection of the dithiolene ligand precursor was replaced by a light‐induced opening of the 1,2‐dithiole‐2‐one moiety. Advantages of this targeted approach comprise higher yields, cleaner transformations, and the possibility to continuously and precisely monitor the reaction progress. The light induced pericyclic reaction of the protection group releases carbon monoxide with formation of a 1,2‐dithione, which is capable of oxidizing the electron rich metal precursor due to its non‐innocence character. This procedure works well with molybdenum(0) and tungsten(0) precursors and particularly well with dithiolene ligands bearing aliphatic backbones, which are typically and notoriously difficult to handle when applying strictly chemical procedures.
A G‐quadruplex/hemin DNAzyme‐based microchip electrophoresis chemiluminescence assay for highly sensitive detection of biotin in flour
Authors: Li Jian , Li Shuting , Zhao Jingjin , Huang Yong , Zhao Shulin
Published: April 2019

Quantitative analysis of biotin in biological fluids, foods, and pharmaceutical is important for diagnosis and treatment of biotin‐related diseases and health maintenance. In this work, a novel G‐quadruplex/hemin DNAzyme‐based microchip electrophoresis chemiluminescence (CL) assay method was established for rapid and highly sensitive detection of biotin. This method is based on the specific binding between biotin and streptavidin, the catalytic CL characteristics of G‐quadruplex/hemin DNAzyme to the oxidation–reduction reaction of hydrogen peroxide with luminol, and the on‐line separation function of microchip electrophoresis. Under the optimal experimental conditions, on‐chip biotin analysis was achieved within 1 min. The CL intensity is linearly proportional to the concentration of biotin in the range of 13–630 nM with a detection limit of 6.4 nM. The proposed method has been applied for the detection of biotin in flour, biotin contents in three flour samples are found in the range of 199–223 ng/g with a mean value of 214 ng/g. The recoveries were in the range of 94–103%. With excellent sensitivity and good selectivity, the proposed method could be applied in a wide range of biological fluids, foods, and pharmaceutical analysis.
Fast genome editing in Bacillus subtilis
Authors: Wu Guo , Drufva Erin , Wu Kang
Published: April 2019

Bacillus subtilis is a model organism for Gram‐positive bacteria and widely used in the study of cellular functions and processes including protein secretion, sporulation, and signal transduction. It is also an important industrial host for the production of proteins and chemicals. Generally, genome editing of B. subtilis often needs the construction of integration vectors in Escherichia coli, linearizing the constructed plasmids, and subsequent transformation of the linear deoxyribonucleic acid via natural competence or electroporation. In this work, we examined the feasibility to directly transform and integrate B. subtilis using linear deoxyribonucleic acid from Gibson assembly without the need for cloning in E. coli. Linear deoxyribonucleic acid of 8–10 kb showed the highest transformation efficiency which was similar to that of using linearized plasmids constructed in E. coli. This method shortens the overall process from 1 week to 1 day and allows the integration of multiple genes in one step, providing a simple and fast method for genome editing in B. subtilis.
Natural Okra Shells Derived Nitrogen‐Doped Porous Carbon to Regulate Polysulfides for High‐Performance Lithium–Sulfur Batteries
Authors: Li Yanjuan , Liu Lihuai , Shi Rongjia , Yang Shun , Zhao Chengxiao , Shi Yanhui , Cao Changsheng , Yan Xiao
Published: April 2019

Low conductivity of elemental sulfur, the “shuttle effect” of polysulfides, and structural change hamper lithium–sulfur batteries that have poor electrochemical performance. Herein, a facile and scalable approach to fabricate porous carbon is derived from common okra wastes, okra shells, as a matrix for sulfur active materials. Especially, the material calcined under NH3 (N‐doped biomass‐derived porous carbon [N‐OSC]) with a high specific surface area of 2702 m2 g−1 and large pore volume (0.17 cm3 g−1) provides necessary physical adsorption, resulting in the 69.71 wt% loading of sulfur and excellent trapping capacity for polysulfides during the redox process. Furthermore, N element can act as catalytic active sites to facilitate redox conversion from polysulfides to Li2S. Benefiting from the aforementioned advantages, the cell of the N‐OSC/S electrode manifests superior electrochemical performance. The initial capacity is found up to be 1387 mA h g−1 at a current density of 0.1 C and 750 mA h g−1 after 200 cycles at 0.5 C rate (where 1 C = 1672 mA h g−1). For durability evaluations, the capacity is maintained at 416 mA h g−1 at 2 C after 1000 cycles with a mere decay of 0.05% per cycle.
The effect of amplitude scaling limits on conditional spectrum‐based ground motion selection
Authors: Du Wenqi , Ning Chao‐Lie , Wang Gang
Published: April 2019

Amplitude scaling is commonly used to select ground motions matching a target response spectrum. In this paper, the effect of scaling limits on ground motion selection, based on the conditional spectrum framework, is investigated. Target spectra are computed for four probabilistic seismic hazard cases in Western United States, and 16 ground motion suites are selected using different scaling limits (ie, 2, 5, 10, and 15). Comparison of spectral acceleration distributions of the selected ground motion suites demonstrates that the use of a scaling limit of 2 yields a relatively poor representation of the target spectra, because of the small limit leading to an insufficient number of available ground motions. It is also shown that increasing scaling limit results in selected ground motions with generally increased distributions of Arias intensity and significant duration Ds5‐75, implying that scaling limit consideration can significantly influence the cumulative and duration characteristics of selected ground motions. The ground motion suites selected are then used as input for slope displacement and structural dynamic analyses. Comparative results demonstrate that the consideration of scaling limits in ground motion selection has a notable influence on the distribution of the engineering demand parameters calculated (ie, slope displacement and interstory drift ratio). Finally, based on extensive analyses, a scaling limit range of 3 to 5 is recommended for general use when selecting ground motion records from the NGA‐West2 database.
Exploring the nanofiltration mass transfer characteristic and concentrate process of procyanidins from grape juice
Authors: Li Cunyu , Ma Yun , Li Hongyang , Peng Guoping
Published: April 2019

In order to separate procyanidins from grape juice at room temperature, a separation prediction model was established based on nanofiltration. The mass transfer coefficient was positively correlated with the initial concentration. Nanofiltration performance of procyanidins was affected by filtration conditions, membrane properties, and molecular states. The correlation between mass transfer coefficient and initial concentration was established based on the linear equations of the rejection and mass transfer coefficient. The rejection of procyanidins predicted with the mass transfer model was in accordance with the experimental value, and the antioxidant activity was preserved effectively. The mathematical model could predict the rejection of procyanidins. The nanofiltration technology for procyanidin separation from grape juice was characterized by fast separation, low energy consumption, and zero oxidization loss. The nanofiltration technology could greatly improve the utilization efficiency of food products and decrease the energy consumption.
The genesis of gold deposits in the Hetai goldfield, South China: New constraints from geochronology, fluid inclusion, and multiple isotopic studies
Authors: Wang Lixing , Zhao Zhaoxia , Huang Qinyi , Xu Deru , Jiao Qianqian , Chen Genwen , Cai Jianxin , Zou Shaohao , Deng Teng , Shan Qiang
Published: April 2019

The Hetai goldfield is one of the largest gold mining districts in the South China Block. A complex paragenesis consists of three mineralization stages: syntectonic metamorphic stage, hydrothermal stage, and supergene stage. The syntectonic metamorphic stage is characterized by banded quartz (Q1) and invisible Au in mylonites. The hydrothermal stage, which is the main gold mineralization stage, can be divided into three substages: an early substage characterized by coarse‐grained quartz (Q2) + pyrite + arsenopyrite + pyrrhotite, an intermediate substage characterized by gray fine‐grained quartz (Q3) + electrum + poly‐sulphides + sericite + chlorite and a late substage with predominate white quartz (Q4) + calcite as well as lesser sulphides. During the supergene stage, malachite, covellite, and limonite were formed. Four types of fluid inclusions (FIs) in these types of quartz were identified: aqueous FIs (type 1), CO2‐bearing aqueous FIs (type 2), CO2‐rich FIs (type 3), and solid‐bearing FIs (type 4). Q1 only contains type 1 FIs; Q2 contains types 2 and 4 FIs; Q3 contains types 2 and 3 FIs; and Q4 only contains type 1 FIs. Microthermometric results show that the homogenization temperatures of fluid inclusions range from 350°C to 400°C for Q1, 250°C to 320°C for Q2, 138°C to 245°C for Q3, and 110°C to 207°C for Q4. Salinities of fluid inclusions range from 3.4 to 5.7 wt.%, 2.6 to 12.9 wt.%, 0.5 to 11.5 wt.%, and 0.2 to 7.3 wt.% for Q1, Q2, Q3, and Q4, respectively. Alteration minerals (sericite and chlorite) from the main mineralization stage have δDH2O‐VSMOW values of −62‰ to −98‰ and calculated δ18OH2O‐VSMOW values of 6.3‰ to 4.4‰. The in situ sulphur isotope analysis of pyrite yields a narrow δ34SCDTrange of −1.5‰ to −5.2‰ (average −3.4‰), combined with the Pb isotopic compositions of the sulphides, wall rocks, and Wucun pluton, revealing that the ore‐forming material was mainly derived from magmatic source. The mineralization age (sericite40Ar/39Ar: 159.3 ± 0.8 Ma) is close to the emplacement age of Wucun biotite monzonitic granite pluton (LA‐ICP‐MS zircon U–Pb age: 158.1 ± 1.9 Ma). These geochemical and geochronological data suggest that the main phase of gold mineralization in the Hetai goldfield is genetically related to the granitic activities in the Late Jurassic rather than the mylonitization event in the Late Triassic to Early Jurassic.
Hodgkin lymphoma transformation of chronic lymphocytic leukemia—A real life data from the Polish Lymphoma Research Group
Authors: Drozd‐Sokołowska Joanna , Zaucha Jan Maciej , Żółtak Tomasz , Jamroziak Krzysztof , Grzybowska‐Izydorczyk Olga , Witkowska Magdalena , Waszczuk‐Gajda Anna , Kaźmierczak Maciej , Szczepaniak Andrzej , Subocz Edyta , Knopińska‐Posłuszny Wanda , Hołojda Jadwiga , Kopińska Anna , Hus Iwona , Rybka Justyna , Wołowiec Dariusz , Kwiatkowski Jacek , Hałaburda Kazimierz , Smolewski Piotr , Giebel Sebastian , Wiktor‐Jędrzejczak Wiesław
Published: April 2019

Richter transformation (RT) of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to Hodgkin lymphoma (HL) is a rare and unexpected event in the course of the disease and data on this phenomenon is still limited. To better understand the clinical and histological characteristics and the outcomes of HL variant of RT (HvRS) the Polish Lymphoma Research Group performed a nationwide survey which identified 22 patients with histologically proven HvRS diagnosed between 2002 and 2016. There were 16 (73%) males. The median age at CLL/SLL and HvRS diagnosis was 59 (39‐77) and 64 (40‐77) years, respectively. The median interval between CLL/SLL and HvRS diagnosis was 38 months (range: 0‐187). All patients had an advanced stage HL, and majority, 17 (77%), presented with B symptoms. The predominant subtypes of HL were nodular sclerosis (12; 55%) and mixed cellularity (9; 41%). Eighteen patients received non‐palliative treatment, including 13 who received driamycin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen first line. Objective response was: 50%, with 33% complete remissions (61% and 46% for ABVD, respectively). Median overall survival reached 13.3 months (95% CI, 3.7‐NA). The only adverse prognostic factor for survival was a higher number (≤1 versus ≥2) of prior lines of treatment given for CLL/SLL with HR 3.57 (95% CI, 1.16‐10.92). We conclude, HvRS harbors a poor prognosis, especially in patients heavily pretreated for CLL/SLL. Response to standard first‐line anti‐HL chemotherapy is unsatisfactory, and new agents should be tested to improve the outcome.
Understanding the limitations of “quasi‐mandatory” approaches to enrolment in community‐based health insurance: Empirical evidence from Tanzania
Authors: Ajuaye Adeline , Verbrugge Boris , Van Ongevalle Jan , Develtere Patrick
Published: April 2019

In recent decades, a growing number of low‐income countries (LICs) have experimented with voluntary community‐based health insurance (CBHI), as an instrument to extend social health protection to the rural poor and the informal sector. While modest successes have been achieved, important challenges remain with regard to the recruitment and retention of members, and the regular collection of membership fees. In this context, there is a growing consensus among policymakers that there is a need to experiment with mandatory approaches towards CBHI. In some localities in Tanzania, local actors in charge of community health funds (CHFs) are now relying on what is best described as quasi‐mandatory enrolment strategies, such as increasing user fees for non‐members, automatically enrolling beneficiaries of cash transfer programmes and enrolling the exempted groups (people who are entitled to free healthcare). We find that, while these quasi‐mandatory enrolment strategies may temporarily increase enrolment rates, dropout and the non‐payment of contributions remain important problems. These problems are at least partly related to supply side issues, notably to inadequate benefit packages. Overall, these findings indicate the limitations of any strategy to increase enrolment into CBHI, which is not coupled to clear improvements in the supply and quality of healthcare.
α‐Mangostin promotes apoptosis of human rheumatoid arthritis fibroblast‐like synoviocytes by reactive oxygen species‐dependent activation of ERK1/2 mitogen‐activated protein kinase
Authors: Sheng Xiaoyun , Li Jun , Zhang Chao , Zhao Lianggong , Guo Laiwei , Xu Tianen , Jin Jiaxin , Wu Meng , Xia Yayi
Published: April 2019

α‐Mangostin (α‐M) is a commonly used traditional medicine with various biological and pharmacological activities. Our study aimed to explore the effects and mechanism of α‐M in regulating apoptosis of rheumatoid arthritis fibroblast‐like synoviocytes (RA‐FLS). α‐M of 10 to 100 μM was used to treat RA‐FLS for 24 hours, followed by measuring cell viability and apoptosis. The involvement of reactive oxygen species (ROS) and mitogen‐activated protein kinases was detected. Treatment of α‐M promoted apoptosis and reduced viability of RA‐FLS in a dose‐dependent manner. The mitochondrial membrane potential in RA‐FLS was remarkably reduced by α‐M treatment, accompanied by the cytochrome c accumulation in the cytosol and increased activities of caspase‐3 and caspase‐9. Moreover, we found that α‐M treatment promoted ROS production and extracellular signal‐regulated kinase 1/2 (ERK1/2) phosphorylation. The proapoptotic activity of α‐M in RA‐FLS was markedly reversed by the co‐induction with the ERK1/2 inhibitor LY3214996 or ROS scavenger N‐acetyl‐l‐cysteine. In conclusion, our studies found that α‐M had remarkable proapoptotic activities in RA‐FLS, which is regulated by the induction of ROS accumulation and ERK1/2 phosphorylation. α‐M may thus have potential therapeutic effects for rheumatoid arthritis.
Microarray analyses of lncRNAs and mRNAs expression profiling associated with diabetic peripheral neuropathy in rats
Authors: Guo Guojun , Ren Sen , Kang Yu , Liu Yutian , Duscher Dominik , Machens Hans‐Günther , Chen Zhenbing
Published: April 2019

Diabetic peripheral neuropathy (DPN) is considered to be the most frequent neuropathic complication of diabetes, and severely affects the quality of life of patients. Long noncoding RNAs (lncRNAs) participate in various pathophysiological processes and associate with many diseases. However, the exact impact of lncRNAs on DPN remains obscure. To discover a potential connection, a microarray study was conducted to analyze the expression profiling of lncRNAs and messenger RNAs (mRNAs) in dorsal root ganglia (DRG) from streptozotocin‐induced diabetic rats with DPN. As a result, 983 lncRNAs and 1357 mRNAs were aberrantly expressed compared with control samples. Using bioinformatics analyses, we identified 558 Gene Ontology terms and 94 Kyoto Encyclopedia of Genes and Genomes pathways to be significantly enriched. Additionally, the signal‐net analysis indicated that integrin receptors, including Itgb3, Itgb1, Itgb8, and Itga6, might be important players in network regulation. Furthermore, the lncRNA‐mRNA network analysis showed dynamic interactions between the dysregulated lncRNAs and mRNAs. This is the first study to present an overview of lncRNA and mRNA expressions in DRG tissues from DPN rats. Our results indicate that these differentially expressed lncRNAs may have crucial roles in pathological processes of DPN by regulating their coexpressed mRNAs. The data may provide novel targets for future studies, which should focus on validating their roles in the progression of DPN.
Human vascular cell responses to the circulating bone hormone osteocalcin
Authors: Millar Sophie A. , Anderson Susan I. , O'sullivan Saoirse E.
Published: April 2019

The purpose of this study was to characterize the direct effects of uncarboxylated osteocalcin (ucOCN) on vascular cell biology in vitro, to assess its potential function in pathophysiological conditions such as atherosclerosis. Human aortic endothelial cells (HAECs) and smooth muscle cells (HASMCs) were treated with ucOCN (0.1–50 ng/ml) and changes in phosphorylation of intracellular signaling proteins, angiogenesis, proliferation, migration, monolayer permeability, and protein secretion were measured. In HAECs, phosphorylated JNK and CREB were decreased with ucOCN (p < 0.05). In HASMCs, phosphorylated p70S6K and NF‐ΚB were increased by ucOCN (p < 0.05). Cell proliferation increased in both cell types dose dependently which was blocked by AKT and ERK pathway inhibitors. ucOCN did not affect cell permeability, angiogenesis, or migration. The direct activity of ucOCN on vascular cells is recognized, particularly its proliferative effects. However, at least in physiological settings, it does not appear that osteocalcin may directly promote atherogenesis based on the outcomes measured.