bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoröhren‐Nanobody‐Konjugate als zielgerichtete Sonden und Marker für die In‐vivo‐Nahinfrarot‐Bildgebung
Authors: Mann Florian A. , Lv Zhiyi , Großhans Jörg , Opazo Felipe , Kruss Sebastian
Published: May 2019

Fluoreszente Nanomaterialien wie einwandige Kohlenstoffnanoröhren (single‐walled carbon nanotubes, SWCNTs) haben viele photophysikalische Vorteile, können jedoch nur schwer zielgerichtet zu spezifischen Orten in lebenden Systemen gebracht werden. Das grün‐fluoreszierende Protein (GFP) hingegen wurde schon in vielen Zellen und Organismen an Proteine fusioniert und zur Markierung verwendet. In dieser Studie berichten wir über die Konjugation von GFP‐bindenden Nanobodies an DNA‐umwickelte SWCNTs. Dieser Ansatz vereint die Spezifität von GFP‐bindenden Nanobodies mit der nicht‐bleichenden Nahinfrarotfluoreszenz (850–1700 nm) von SWCNTs. Diese Konjugate erlauben es, die Bewegung einzelner Kinesin‐5‐GFP Motorproteine in Drosophila‐Embryos zu verfolgen. Darüber hinaus reagieren die Konjugate auf den Neurotransmitter Dopamin und können so für die zielgerichtete Detektion von Dopamin in nm Konzentrationen genutzt werden.
Facile Generation of Polymer–Alloy Hybrid Layers for Dendrite‐Free Lithium‐Metal Anodes with Improved Moisture Stability
Authors: Jiang Zhipeng , Jin Liu , Han Zhilong , Hu Wei , Zeng Ziqi , Sun Yulong , Xie Jia
Published: May 2019

Lithium‐metal anodes are recognized as the most promising next‐generation anodes for high‐energy‐storage batteries. However, lithium dendrites lead to irreversible capacity decay in lithium‐metal batteries (LMBs). Besides, the strict assembly‐environment conditions of LMBs are regarded as a challenge for practical applications. In this study, a workable lithium‐metal anode with an artificial hybrid layer composed of a polymer and an alloy was designed and prepared by a simple chemical‐modification strategy. Treated lithium anodes remained dendrite‐free for over 1000 h in a Li–Li symmetric cell and exhibited outstanding cycle performance in high‐areal‐loading Li–S and Li–LiFePO4 full cells. Moreover, the treated lithium showed improved moisture stability that benefits from the hydrophobicity of the polymer, thus retaining good electrochemical performance after exposure to humid air.
Acyclic Janus‐AT Nucleoside Host Channels Precisely Lock Water into Single‐File Wires with Local Rotational Flexibility
Authors: Zhou Xinglong , Shen Zhen , Ma Beibei , Xia Zhenqiang , Chai Yingying , Ju Xiaojie , Chu Liangyin , Huang Ridong , Chen Hai , Li Weimin , He Yang
Published: May 2019

Confining polar water molecules to particular geometries demands sophisticated intermolecular interactions, and not many small synthetic molecules have accomplished such a task. Herein, regioisomeric acyclic Janus‐AT nucleosides (1 and 2), with a self‐complementary fused genetic alphabet and conformationally flexible side chains, have been selectively synthesized. 1 and 2 adopt disparate base‐pair motifs from the π–π stacked hydrophobic base moieties and distinct hydrogen bond (HB) interconnections from the hydrophilic sugar residues, which in turn lead to divergent, intricate intermolecular interaction networks with different capacities to confine water molecules. Under the precise control of the host framework of the N8‐regioisomer, separate ordered single‐file water wires can be locked through special three‐HB clamps into unique inter‐ and intra‐wire geometrical alignments. Localized dynamic synchronized rotations within the fixed framework coordinated by both the host hydroxy groups and guest water molecules were observed in a temperature‐induced reversible single‐crystal‐to‐single‐crystal transition (SCSCT).
α‐Arylation of Carbonyl Compounds through Oxidative C−C Bond Activation
Authors: Li Jing , Bauer Adriano , Di Mauro Giovanni , Maulide Nuno
Published: May 2019

A synthetically useful approach for the direct α‐arylation of carbonyl compounds through a novel oxidative C−C bond activation is reported. This mechanistically unusual process relies on a 1,2‐aryl shift and results in all‐carbon quaternary centers. The transformation displays broad functional‐group tolerance and can in principle also be applied as an asymmetric variant.
Decorated Traditional Zeolites with Subunits of Metal–Organic Frameworks for CH4/N2 Separation
Authors: Wu Yaqi , Yuan Danhua , He Dawei , Xing Jiacheng , Zeng Shu , Xu Shutao , Xu Yunpeng , Liu Zhongmin
Published: May 2019

Metal–organic frameworks (MOF) materials are promising materials for gas separation, but their application still faces various challenges. A strategy is now reported for introducing subunits of MOFs into traditional zeolite frameworks to obtain applicable adsorbents with advantages of both zeolites and MOFs. The subunits of ZIFs were introduced into zeolite Y and zeolite ZSM‐5 for CH4/N2 separation. Both the molecular simulation and experimental results validated that the IAST CH4/N2 selectivity of the resulting samples greatly improved (above 8, at 100 kPa and 25 °C) with the incorporation of ZIF subunits into zeolites structure, and the selectivities were obviously higher than that of zeolites and even better than that of ZIFs. This strategy not only gave rise to an efficient adsorbent for CH4/N2 separation but also provided ideas for design of other adsorption and separation materials.
Biodiversity value of remnant pools in an intermittent stream during the great California drought
Authors: Bogan Michael T. , Leidy Robert A. , Neuhaus Linnea , Hernandez Christopher J. , Carlson Stephanie M.
Published: May 2019

In many intermittent streams, remnant pools persist after flow ceases and provide refuge for aquatic organisms able to tolerate stagnant water conditions. The conservation value of these pools may be greatly under‐appreciated, especially in regions with a Mediterranean climate, where perennial streams have been substantially modified or disturbed by human activities.

Fish, amphibians, aquatic reptiles, and aquatic invertebrates were sampled from 15 remnant pools and three seeps at Coyote Creek, California, USA, in the late summer of 2014, during the height of the most intense drought that California has experienced in 500 years. Patterns of vertebrate and invertebrate species richness and community composition were compared with abiotic factors (e.g. water quality and habitat size).

Thirteen vertebrate species and 172 invertebrate taxa were identified from remnant pools and seeps. Overall vertebrate richness and composition were not correlated with abiotic factors, but fish species richness increased with remnant pool size and depth. Invertebrate taxon richness increased with pool size. Invertebrate community composition differed by habitat type (pool versus seep) and gradients in composition were correlated with several abiotic factors (e.g. pool size, substrate, and canopy cover).

Remnant pools at Coyote Creek supported a full assemblage of native fishes and numerous imperilled taxa, including California red‐legged frogs and California floater mussels. Nearly all native fishes and imperilled taxa are absent from artificially perennial and urbanized reaches of Coyote Creek just a few kilometres downstream of the study area.

Remnant pools in intermittent streams should be a focus of conservation efforts in regions with a Mediterranean climate, especially during extreme droughts. Native fauna adapted to harsh intermittent flow regimes can thrive in these habitats, whereas non‐native taxa may fare poorly. Furthermore, remnant pools supported by deep groundwater sources, such as those along geological faults, may provide both ecological refuge and evolutionary refugia for freshwater biota.
Conventional and non conventional body motions modelling and control. Application to the handwriting process
Authors: Abdelkrim Afef , Benrejeb Mohamed
Published: May 2019

The handwriting process is one of the most important and complex activities of the human body. In recent years, modelling and analyzing and controlling it have received great attention leading to large important motion studies results. This paper attempts to present an overview of recent works about our proposed approaches and other ones to model and control this process. Hence, an overall model of the handwriting process has been proposed and developed by the co‐authors, showing the interest of using the soft computing concepts, namely neural networks and fuzzy logic. The design of this model requires several undertaken steps. Starting from an experimental approach to acquire electromyographic signals and writing positions, different conventional and non conventional models have been proposed. Besides some control strategies have been considered in particular neural and fuzzy approaches in addition to non conventional neural and neuro‐fuzzy Internal Model Control strategy. The proposed global model, inspired from the biological structure system, has been designed and validated through simulation results.
Is greed contagious? Four experimental studies
Authors: Cardella Eric , Kugler Tamar , Anderson Jennifer , Connolly Terry
Published: May 2019

Do people become greedier when interacting with others they perceive to be greedy? It has been speculated that greed contagion exits and may have influenced the 2008 financial collapse. We examined this possibility in four experimental studies using a common pool resource dilemma. Specifically, whether participants' second‐round (R2) withdrawal from the common pool was influenced (a) by their assessment of how greedy their opponents' first‐round (R1) withdrawal was, (b) by R1 opponents' reputation for being greedy, (c) by observing past behavior of others in unrelated interactions, and (d) when R1 opponents directly confronted them with an assessment of their own greediness of their R1 withdrawal. In addition, Study 2 examined R2 interactions involving new opponents. Taken together, results suggest that there is contagion of greed. However, the connection appears to be driven by participants adjusting to their opponent's actual behavior, not by their evaluation of the greediness of such behavior. It seems that perceptions of greed do not mediate future behavior and, thus, are not necessarily contagious, but norms of selfish behavior are. In this sense, greed perceptions appear to by epiphenomenal in that they are an incidental by‐product of the behavioral interaction. We discuss the implications of these findings and suggest directions for further research.
Validation and optimization of viral clearance in a downstream continuous chromatography setting
Authors: Chiang Meng‐Jung , Pagkaliwangan Mark , Lute Scott , Bolton Glen , Brorson Kurt , Schofield Mark
Published: May 2019

Continuous bioprocessing holds the potential to improve product consistency, accelerate productivity, and lower cost of production. However, switching a bioprocess from traditional batch to continuous mode requires surmounting business and regulatory challenges. A key regulatory requirement for all biopharmaceuticals is virus safety, which is assured through a combination of testing and virus clearance through purification unit operations. For continuous processing, unit operations such as capture chromatography have aspects that could be impacted by a change to continuous multicolumn operation, for example, do they clear viruses as well as a traditional batch single column. In this study we evaluate how modifying chromatographic parameters including the linear velocity and resin capacity utilization could impact virus clearance in the context of moving from a single column to multicolumn operation. A Design of Experiment (DoE) approach was taken with two model monoclonal antibodies (mAbs) and two bacteriophages used as mammalian virus surrogates. The DoE enabled the identification of best and worst‐case scenario for virus clearance overall. Using these best and worst‐case conditions, virus clearance was tested in single column and multicolumn modes and found to be similar as measured by Log Reduction Values (LRV). The parameters identified as impactful for viral clearance in single column mode were predictive of multicolumn modes. Thus, these results support the hypothesis that the viral clearance capabilities of a multicolumn continuous Protein A system may be evaluated using an appropriately scaled‐down single mode column and equipment.
Mental fatigue assessment may add information after aneurysmal subarachnoid hemorrhage
Authors: Sörbo Ann , Eiving Ingrid , Löwhagen Hendén Pia , Naredi Silvana , Ljungqvist Johan , Odenstedt Hergès Helena
Published: May 2019

Background

Mental fatigue, as part of cognitive dysfunction, has been reported to be common after subarachnoid hemorrhage and it significantly affects quality of life.

Aims of the Study

The aim of this study was to assess mental fatigue one year after an aneurysmal subarachnoid hemorrhage and to correlate the degree of mental fatigue to functional outcome assessed with the Extended Glasgow Outcome Scale (GOSE).

Methods

One year after an aneurysmal subarachnoid hemorrhage, the GOSE was assessed and a questionnaire for self‐assessment of mental fatigue, the Mental Fatigue Scale, was distributed to all included patients. The maximum score is 42 and a score of ≥10.5 indicates mental fatigue.

Results

All patients with GOSE 8, indicating full recovery, had a mental fatigue score of <10.5. A linear correlation between the GOSE and the mental fatigue score was observed (p < 0.0001).

Conclusions

Patients with a favorable outcome and GOSE 5–7 could benefit from the assessments of mental fatigue in order to receive satisfactory rehabilitation.
Prognostic impact and periprocedural complications of chronic steroid therapy in patients following transcatheter aortic valve replacement: Propensity‐matched analysis from the Japanese OCEAN registry
Authors: Koyama Yutaka , Yamamoto Masanori , Kagase Ai , Tsujimoto Satoshi , Kano Seiji , Shimura Tetsuro , Hosoba Soh , Watanabe Yusuke , Tada Norio , Naganuma Toru , Araki Motoharu , Yamanaka Futoshi , Mizutani Kazuki , Tabata Minoru , Ueno Hiroshi , Takagi Kensuke , Higashimori Akihiro , Shirai Shinichi , Hayashida Kentaro
Published: May 2019

Objective

This study aimed to assess the effect of chronic steroid use on periprocedural complications and clinical outcomes after transcatheter aortic valve replacement (TAVR).

Background

Chronic steroid use increases the risk of periprocedural complications and mortality during surgery.

Methods

We investigated 1,313 consecutive patients with aortic stenosis who underwent transfemoral (TF)‐TAVR using data from a Japanese multicenter registry. The baseline characteristics, periprocedural complications including vascular complications (VCs), access route related VCs, and clinical outcomes were compared between patients in the steroid group and nonsteroid group.

Results

Major VCs and access route VCs occurred more in the steroid group than in the nonsteroid group (13.4 vs. 5.8%, p = .019; 20.9% vs. 9.8%, p = .004). Especially in the surgical cut‐down group, the rate of access route VCs was differed between the two groups (28.0% vs. 7.5%, p = .003). The 30‐day mortality rates were similar between the two groups (0% vs. 1.4%, p = .39). In the propensity score‐matched model, the higher incidence of major VCs in the steroid group was maintained, although early mortality was similar in the two groups.

Conclusions

Although chronic steroid therapy is not associated with increased early mortality, chronic steroid use may affect periprocedural VCs and access route VCs mainly due to surgical cut‐down in patients following TF‐TAVR.
Effects of barley yellow dwarf disease on wheat grain quality traits
Authors: Peiris Kamaranga H. S. , Bowden Robert L. , Todd Timothy C. , Bockus William W. , Davis Mark A. , Dowell Floyd E.
Published: May 2019

Background and objectives

Barley yellow dwarf (BYD) is an important aphid‐vectored viral disease of wheat. Grain samples were obtained from a previously reported integrated pest management (IPM) field plot experiment that was designed to test the effects of planting dates, cultivars, and insecticide treatments on BYD incidence and wheat yields over 4 years in Kansas, USA. In the current study, the effect of BYD on grain quality traits was estimated by comparing untreated plots that had varying levels of BYD to healthy control plots that received repeated insecticide treatments. Additional grain samples were compared from Tagged Tillers of visually healthy and symptomatic plants.

Findings

For IPM Plots, interactions between insecticide treatments and cultivars were not significant (α = 0.05). The effect of BYD on protein content (PC), starch content (SC), average kernel weight (AKW), and yield was a relative percent gain or loss of +3.7%, −1.0%, −6.4%, and −12.6%, respectively, averaged over all experimental factors and years. Linear critical point models were developed to estimate the percent gain or loss relative to healthy controls as a function of BYD incidence. For each percentage of BYD incidence, BYD increased PC by 0.284%, decreased SC by 0.063%, decreased AKW by 0.314%, and decreased grain yield by 0.664%. Similar magnitudes of effects of BYD were estimated from Tagged Tiller samples. There were distinct, non‐overlapping distributions for healthy versus symptomatic Tagged Tillers for PC and SC for four of six cultivars. However, two cultivars had overlapping distributions for healthy versus symptomatic samples, suggesting they had resistance or physiological tolerance to BYD.

Conclusions

Natural infection with BYD significantly increased PC and decreased SC, AKW, and yields of wheat. The increase in PC was probably due to the concentrating effect of decreased SC and AKW. Critical point models were developed to predict the impact of varying levels of BYD on these parameters. Near‐infrared spectroscopy (NIRS) measurement of PC and SC of diseased versus healthy samples has potential to identify wheat lines with resistance or tolerance to BYD.

Significance and novelty

This is the first report of the effect of BYD on wheat starch content and confirms the effect on average kernel weight and protein content. This is the first report of simple models to predict grain quality changes as a function of BYD incidence. Near‐infrared spectroscopy (NIRS) measurement of grain PC and SC from plants with BYD may offer wheat breeding programs a rapid and objective selection method for improved resistance or physiological tolerance to BYD.
Effect of Metal‐Support Interactions in Mixed Co/Al Catalysts for Dry Reforming of Methane
Authors: Horlyck Jonathan , Sara Marina , Lovell Emma C. , Amal Rose , Scott Jason
Published: May 2019

Composite Co/Al oxide materials were prepared via flame spray pyrolysis and examined as catalysts for the dry reforming of methane. The interaction between the metal (Co) and the support (Al‐oxide) was regulated by varying the Co : Al ratio and its influence on catalyst performance studied. The synthesis of materials with a Co content of 30 mol % (Co3Al7) promoted the formation of readily reduced and highly‐dispersed Co particles. This, in combination with a high relative surface basicity, contributed to Co3Al7 delivering a high and stable activity towards the dry reforming reaction. The formation of bulk Co3O4 particles, which exhibit weak interactions with the support material, in samples with a Co content of 50 (Co5Al5) and 70 mol % (Co7Al3) caused rapid catalyst deactivation via coking. The findings demonstrate the importance of metal‐support interactions between the Co catalyst and Al‐oxide support for the activity and selectivity in the dry reforming of methane. Highly dispersed Co deposits and high support basicity, induced by an ideal FSP Co : Al synthesis ratio, are key to delivering an active and stable catalyst for the dry reforming of methane.
An Unusual Exchange Mechanism in the Tafel Reaction on Pt(110)‐(1×1) Surfaces
Authors: He Zheng‐Da , Chen Yan‐Xia , Juarez Fernanda , Santos Elizabeth , Schmickler Wolfgang
Published: May 2019

Experiments suggest that on Pt(110) the Tafel reaction is the rate determining step in hydrogen evolution. We investigate the kinetics of this step on the unreconstructed surface by a combination of density functional theory and grand‐canonical Monte Carlo simulations. We identify two favorable reaction paths: The recombination of a hydrogen atom adsorbed on a bridge site with one adsorbed on top, and an exchange mechanism involving two hydrogen atoms adsorbed on top and one adsorbed on a bridge site. The latter results in a transfer coefficient of two in agreement with experiment, and seems to be the dominant step.
The Quest for Molecular Grippers: Photo‐Electric Control of Molecular Gripping Machinery
Authors: Milić Jovana V. , Diederich François
Published: May 2019

The quest for nanoscale molecular machines has inspired the search for their close relatives, molecular grippers. This path was paved by the development of resorcin[4]arene cavitands and their quinone‐based redox‐active congeners. In this Concept article, the efforts to design and establish the control of quinone‐functionalized resorcin[4]arenes by electronic and electromagnetic stimuli is described. This was achieved by relying on paramagnetic semiquinone radical anions formed electrochemically or by photoredox catalysis. The gripper‐like motion of such species could not be studied by conventional NMR spectroscopy. Instead, an entirely different approach had to be developed that included various electroanalytical and spectroelectrochemical methods, including UV/Vis/NIR spectroelectrochemistry, pulsed EPR and Davies 1H ENDOR spectroscopy, transient absorption spectroscopy, and time‐resolved luminescence measurements, besides density functional theory calculations and X‐ray crystallography. The conceptual breakthroughs are reviewed as well as the current state and future perspectives of photoredox‐switchable molecular grippers.
A Histidine Residue and a Tetranuclear Cuprous‐thiolate Cluster Dominate the Copper Loading Landscape of a Copper Storage Protein from Streptomyces lividans
Authors: Straw Megan L. , Hough Michael A. , Wilson Michael T. , Worrall Jonathan A. R.
Published: May 2019

The chemical basis for protecting organisms against the toxic effect imposed by excess cuprous ions is to constrain this through high‐affinity binding sites that use cuprous‐thiolate coordination chemistry. In bacteria, a family of cysteine rich four‐helix bundle proteins utilise thiolate chemistry to bind up to 80 cuprous ions. These proteins have been termed copper storage proteins (Csp). The present study investigates cuprous ion loading to the Csp from Streptomyces lividans (SlCsp) using a combination of X‐ray crystallography, site‐directed mutagenesis and stopped‐flow reaction kinetics with either aquatic cuprous ions or a chelating donor. We illustrate that at low cuprous ion concentrations, copper is loaded exclusively into an outer core region of SlCsp via one end of the four‐helix bundle, facilitated by a set of three histidine residues. X‐ray crystallography reveals the existence of polynuclear cuprous‐thiolate clusters culminating in the assembly of a tetranuclear [Cu4(μ2‐S‐Cys)4(Νδ1‐His)] cluster in the outer core. As more cuprous ions are loaded, the cysteine lined inner core of SlCsp fills with cuprous ions but in a fluxional and dynamic manner with no evidence for the assembly of further intermediate polynuclear cuprous‐thiolate clusters as observed in the outer core. Using site‐directed mutagenesis a key role for His107 in the efficient loading of cuprous ions from a donor is established. A model of copper loading to SlCsp is proposed and discussed.
Supramolecular Assembly of a Molecularly Engineered Protein and Polymer
Authors: Sikder Amrita , Ray Debes , Aswal Vinod K. , Ghosh Suhrit
Published: May 2019

Programmable assembly of biomolecules is a fast growing research area that aims to emulate nature's elegance in creating numerous hierarchical self‐assembled structures, which are responsible for unimaginably difficult biological functions. Protein assembly is a particularly challenging task, owing to their structural diversity, conformational heterogeneity, and high molecular weight. This article reveals the ability of a supramolecular structure‐directing unit (SSDU) to regulate the entropically favourable supramolecular assembly of a covalently conjugated protein (bovine serum albumin (BSA)) to produce well‐defined protein‐decorated micelles with remarkably high thermal stability, suppression of the thermal denaturation of the protein, and retention of enzymatic activity. Furthermore, a SSDU‐appended thermo‐responsive poly(N‐isopropylacrylamide) (PNIPAM) co‐assembles with the SSDU–BSA conjugate because, in both cases, assembly was primarily driven by specific molecular recognition between the SSDUs. However, the resulting supramolecular protein–polymer conjugate exhibits distinctly different polymersome structure to that of the micellar particle produced by the protein‐SSDU conjugate. In this case, the enzymatic activity can be significantly suppressed above the lower critical solution temperature of supramolecularly conjugated PNIPAM, possibly due to collapse of the de‐solvated polymer chains on the protein surface.
Enantioseparation and molecular modeling study of five β‐adrenergic blockers on Chiralpak IC column
Authors: Zhao Yu , Li Shuang , Wang Xia , Yu Jia , Song Yongbo , Guo Xingjie
Published: May 2019

A new high‐performance liquid chromatography (HPLC) method was developed for the enantiomeric resolution of five β‐adrenergic blockers on a Chiralpak IC column (250 mm × 4.6 mm, 5.0 μm particle size) in normal phase mode. The mobile phase used was n‐hexane‐ethanol‐diethylamine in different proportions at the flow rate of 1.0 mL/min with the column temperature of 25°C using a UV detector at 230 nm. The influences of base additives and alcohol modifiers were evaluated and optimized. The maximum resolution values for bevantolol, propranolol carteolol, esmolol, and metoprolol were 4.80, 2.77, 2.09, 2.30, and 1.11, respectively. To gain a better understanding of the interaction between chiral stationary phase and analyte enantiomers, the molecular docking of chiral stationary phase with five pairs of enantiomer was carried out using AutoDock molecular docking technique. By simulation studies, the mechanism of chiral recognition was determined. According to the results, hydrogen bond interactions and π‐π interactions were the chief interactions for the chiral recognition.
SEL1L plays a major role in human malignant gliomas
Authors: Mellai Marta , Annovazzi Laura , Boldorini Renzo , Bertero Luca , Cassoni Paola , De Blasio Pasquale , Biunno Ida , Schiffer Davide
Published: May 2019

Suppressor of Lin‐12‐like (C. elegans) (SEL1L) participates in the endoplasmic reticulum‐associated protein degradation pathway, malignant transformation and stem cell biology. We explored the role of SEL1L in 110 adult gliomas, of different molecular subtype and grade, in relation to cell proliferation, stemness, glioma‐associated microglia/macrophages (GAMs), prognostic markers and clinical outcome. SEL1L protein expression was assessed by immunohistochemistry and Western blotting. Genetic and epigenetic alterations were detected by molecular genetics techniques. SEL1L was overexpressed in anaplastic gliomas (World Health Organization [WHO] grade III) and in glioblastoma (GB, WHO grade IV) with the highest labelling index (LI) in the latter. Immunoreactivity was significantly associated with histological grade (p = 0.002) and cell proliferation index Ki‐67/MIB‐1 (p = 0.0001). In GB, SEL1L co‐localised with stemness markers Nestin and Sox2. Endothelial cells and vascular pericytes of proliferative tumour blood vessels expressed SEL1L suggesting a role in tumour neo‐vasculature. GAMs consistently expressed SEL1L. SEL1L overexpression was significantly associated with TERT promoter mutations (p = 0.0001), EGFR gene amplification (p = 0.0013), LOH on 10q (p = 0.0012) but was mutually exclusive with IDH1/2 mutations (p = 0.0001). SEL1L immunoreactivity correlated with tumour progression and cell proliferation, conditioning poor patient survival and response to therapy. This study emphasises SEL1L as a potential biomarker for the most common subgroup of TERT mutant/EGFR amplified/IDH‐WT GBs.
Preparation of Naphthalene Dianhydride Bithiophene Copolymers by Direct Arylation Polycondensation and the Latent Pigment Approach
Authors: Sanzone Alessandro , Cimò Simone , Mattiello Sara , Ruffo Riccardo , Facchinetti Irene , Bonacchini Giorgio E. , Caironi Mario , Sassi Mauro , Sommer Michael , Beverina Luca
Published: May 2019

An alternating naphthalene dianhydride bithiophene copolymer (PNDAT2) is prepared by a combined direct arylation polycondensation and the latent pigment approach. PNDAT2 is the first reported example of an alternating conjugated polymer containing naphthalene dianhydride, the oxo‐analogue of naphthalene diimide often used in electron‐acceptor conjugated polymers. PNDAT2 is resistant to organic solvents and can be generated directly as film by thermal treatment of the soluble tetraester precursor PNTET2. PNDAT2 is characterized by a LUMO level of −3.9 eV, similar to that of established naphthalene diimide containing soluble copolymers. This route to insoluble electron acceptor copolymers by thermal cleavage of soluble precursors is an alternative to classical cross‐linking or orthogonal processing strategies.
Correlation structure in hierarchical linear modelling: An illustration with the therapeutic alliance
Authors: Gonçalves Miguel M. , Sousa Inês , Rosa Catarina
Published: May 2019

Previous studies have found an association between therapeutic alliance and treatment outcome, but only recently have researchers begun to analyse time‐lagged relationships between session‐to‐session measures of alliance and outcomes with hierarchical linear modelling (HLM). HLM assumes simple correlation structures between any two measurements from the same client. In this paper, we suggest that this assumption might be problematic. Session‐to‐session measurements of outcomes (Outcome Questionnaire‐10.2) and alliance (Working Alliance Inventory) in a sample (N= 63) were used to perform HLM analyses to test time‐lagged (lag +1) relations between outcomes and alliance in both directions. A first set of analyses replicated the models consistently used in the literature, whereas a second set of models considered a correlation structure as a function of time. A correlation independent of time distance resulted in a bidirectional influence between alliance and outcomes (the model commonly used in the literature), but when considering a correlation structure as a function of time, only the outcomes were predictive of alliance. Considering a more complex correlation structure as a function of time seems to be an important analytical strategy for addressing the issue of variability in within‐client measurements over time.

This study highlights how the misspecification of a statistical model, namely, not considering a time‐dependent correlation structure of the response variable, may lead to misleading findings in HLM studies. This is particularly relevant in process–outcome research, such as studies analysing the impact of therapeutic alliance on clinical outcomes.
Adaptation of CytoProcessor for cervical cancer screening of challenging slides
Authors: Crowell Elizabeth F. , Bazin Cyril , Thurotte Vianney , Elie Hubert , Jitaru Laurette , Olivier Grégoire , Caillot Yann , Brixtel Romain , Lesner Boris , Toutain Matthieu , Renouf Arnaud
Published: May 2019

Background

Current automated cervical cytology screening systems require purchase of a dedicated preparation machine and use of a specific staining protocol. CytoProcessor (DATEXIM, Caen, France) is a new automated system, designed to integrate seamlessly into the laboratory's existing workflow. We previously demonstrated the superior performance of CytoProcessor for diagnosis of ThinPrep slides compared to the ThinPrep Imaging System (HOLOGIC, Marlborough, MA). Next, we analyzed whether CytoProcessor technology can be adapted for use on Novaprep slides.

Methods

Using artificial intelligence, we developed a new algorithm in CytoProcessor for the analysis of slides prepared using the NOVAPREP Processor System NPS50 (Novacyt, Vélizy‐Villacoublay, France). A representative population of 309 cases was selected from the routine workflow in a public hospital. We compared the diagnoses made using CytoProcessor or conventional screening with a microscope. All discordances were resolved by a consensus committee.

Results

The performance of CytoProcessor in terms of diagnostic accuracy on Novaprep slides was very similar to that observed previously on ThinPrep slides. Compared to conventional screening, CytoProcessor slightly improves diagnostic sensitivity while maintaining a statistically equivalent specificity. Diagnosis was reached 1.6 times faster with CytoProcessor compared to using a microscope.

Conclusion

CytoProcessor is a robust automated cervical cytology screening system that can be used successfully with samples having very different characteristics. As previously shown, CytoProcessor confers significant gains in processing time and diagnostic precision. CytoProcessor is accessible through a secured internet connection, making remote diagnosis of Papanicolaou tests possible.
Prominent ‘Y’ descent is an ominous sign of a poorer prognosis in heart failure with preserved ejection fraction
Authors: Harada Daisuke , Asanoi Hidetsugu , Noto Takahisa , Takagawa Junya
Published: May 2019

Aims

The heterogeneity of heart failure with preserved ejection fraction (HFpEF) represents different pathophysiological paths by which individual patients develop heart failure. The deterioration mechanisms are considered to be mainly left ventricular diastolic dysfunction, right ventricular (RV) systolic function, and RV afterload. It is unclear whether RV distensibility affects the deterioration of HFpEF. Our study aimed to clarify whether impaired RV distensibility is associated with the deterioration of HFpEF.

Methods and results

We retrospectively enrolled 322 patients with HFpEF and examined their echocardiography results, electrocardiograms, phonocardiograms, and jugular venous pulse waves. Using signal‐processing techniques, the prominent ‘Y’ descent of the jugular venous waveform was detected as an established haemodynamic sign of a less‐distensible right ventricle. We defined cardiovascular events of HFpEF as follows: sudden death, death from heart failure, or hospitalization for HFpEF. During a mean follow‐up period of 33 ± 20 months, 73 patients had cardiovascular events of HFpEF. The prevalence of a less‐distensible right ventricle and the variables of RV systolic pressure were independent risk factors for cardiovascular events (hazard ratio, 2.046, P = 0.005, and hazard ratio, 1.032 per 1 mmHg, P = 0.002, respectively). The event‐free rate of HFpEF was the lowest for HFpEF with a less‐distensible right ventricle and elevated RV systolic pressure (≥35 mmHg) (P for trend <0.001).

Conclusions

A less‐distensible right ventricle and elevated RV systolic pressure were found to be closely associated with the deterioration of HFpEF. Assessment of a less‐distensible right ventricle may help to stratify patients and improve therapeutic strategies for HFpEF.
Apical Cyanide Ligand Substitution in Heterometallic Clusters [Re3Mo3Q8(CN)6]n– (Q = S, Se)
Authors: Muravieva Viktoria K. , Gayfulin Yakov M. , Lappi Tatiana I. , Dorcet Vincent , Sukhikh Taisiya S. , Lemoine Pierric , Ryzhikov Maxim R. , Mironov Yuri V. , Cordier Stéphane , Naumov Nikolay G.
Published: May 2019

A number of transition metal cluster compounds can be obtained only in the melt of inorganic cyanides and, therefore, contain terminal cyanide ligands. Substitution of these ligands, which is often necessary to change the physicochemical properties of the clusters, is an urgent problem because of their low reactivity in substitution reactions. In this work, a synthetic approach has been developed for the substitution of CN‐ligands in the heterometallic cluster anions [Re3Mo3Q8(CN)6]n– (Q = S, n = 6; Q = Se, n = 5) by the 4‐tert‐butylpyridine (TBP) molecules. Two new compounds, namely [Re3Mo3S8(TBP)6] (1) and [Re3Mo3Se8(TBP)6] (2), were obtained with high yields and crystallized under solvothermal conditions. It has been shown that compounds 1 and 2 are based on the paramagnetic cluster cores {Re3Mo3Q8}0 containing 23 cluster valence electrons (CVE). The geometry of the new compounds has been investigated using X‐ray structural analysis. The electronic structure has been analyzed using the DFT calculations showing large distortion of M6 cluster core.
The XB(C6F5)2 Halogenoborane Route to Phosphole Derivatives
Authors: Möricke Jennifer , Ueno Atsushi , Wibbeling Birgit , Daniliuc Constantin G. , Kehr Gerald , Erker Gerhard
Published: May 2019

The reactions of dimesityl(propynyl)phosphane (9) with either of the halogeno‐B(C6F5)2 reagents 10a,b (hal: Cl, Br) proceeds through addition and rearrangement to give the unsaturated C2‐bridged Hal–P/B Lewis pairs 12a,b. Their reactions with two molar equiv. of a small series of alkynyllithium reagents R–C≡CLi led to the formation of the phosphole derivatives 17 via intramolecular 1,1‐carboboration reaction.
Synthesis of Benzofuran and Indole Derivatives Catalyzed by Palladium on Carbon
Authors: Savvidou Anatoli , IoannisTzaras Dimitrios , Koutoulogenis Giorgos S. , Theodorou Alexis , Kokotos Christoforos G.
Published: May 2019

Benzofurans and indoles are key moieties in many natural products and pharmaceuticals. Herein, we describe a cheap and easy‐to‐execute strategy for the synthesis of benzofurans and indoles, employing Pd/C as the promoter. A variety of substituted allyl‐anilines and allyl‐phenols were converted into the desired products in good to excellent yields. Recycling of Pd/C was possible up to five cycles, keeping similar levels of reactivity.
Visual attention to pain cues for impending touch versus impending pain: An eye tracking study
Authors: Ling Ying , Yang Zhou , Jackson Todd
Published: May 2019

Background

In this eye tracking study, we evaluated pain‐related biases in orienting and maintenance of gaze within impending touch versus impending pain tasks and examined features of pain resilience as individual difference influences on potential biases.

Methods

Gaze preferences of healthy adults (25 women and 39 men) were assessed during standardized pain‐neutral (P‐N) image pair presentations (2,000 ms) of an impending touch task versus an impending pain task whereby image pair offsets were followed by potential non‐painful touch and potential pain stimulation, respectively.

Results

Within each task, participants were significantly more likely to fixate first upon pain images in P‐N pairs and maintain gaze on these images for longer overall durations during trials. Between task comparisons indicated pain‐related biases in orienting and maintenance were significantly stronger when image pairs signalled potential pain rather than impending touch. Finally, within the impending pain task, higher scores on the behaviour perseverance dimension of pain resilience were related to shorter first fixation durations and overall gaze durations towards pain images.

Conclusions

Supporting specific threat interpretation model premises, comparatively more threatening external pain cues for impending pain were characterized by gaze biases reflecting pronounced early attentional capture and subsequent prolonged vigilance. However, elevations in self‐reported behavioural perseverance in spite of pain corresponded to an increased capacity to disengage from pain images that signalled potential pain.

Significance

Gaze biases were assessed within a comparatively benign “impending touch” paradigm versus a higher threat, impending pain task. Early capture and maintenance of gaze towards pain images were more pronounced on the latter task, although pain resilient participants were able to disengage more easily from pain images signalling possible pain.
Advances in screening enzyme inhibitors by capillary electrophoresis
Authors: Wang Wei‐Feng , Yang Jun‐Li
Published: May 2019

Capillary electrophoresis (CE) has attracted lots of attention due to its simplicity, low sample consumption, low solvent volume, high resolution, and high speed. Based on these advantages, it has been widely used in enzyme inhibitor screening. There are two main operation modes on enzyme inhibitor screening: off‐line (precapillary enzyme assays) in which process CE was used as an analytical tool; online (in‐capillary enzyme assays) which combined the sample injection, mix, reaction, separation, and detection within a single run. Additionally, diverse of new materials were introduced to immobilize enzyme, which has been coupled with CE for the study of enzyme activity and its inhibitor screening. This review gives an overview of the developments and applications for the CE‐based enzyme inhibitor screening.
Investigation of deep eutectic solvents as additives to β‐CD for enantiomeric separations of Zopiclone, Salbutamol, and Amlodipine by CE
Authors: Mu Yi , Wu Xi , Huang Yan‐Ping , Liu Zhao‐Sheng
Published: May 2019

The enantioseparation of chiral drugs via CE was first investigated using β‐CD as chiral additive and deep eutectic solvents (DESs) as auxiliary additive. The results showed that improved separation of tested chiral drugs was obtained in the presence of DESs and β‐CD compared to the single β‐CD separation system. With the optimized condition, resolutions of DESs applied β‐CD separation system for rac‐Zopiclone, rac‐Salbutamol, and rac‐Amlodipine increased 3–4.2 times as single β‐CD separation system. The resolutions reached 4.74, 6.37, and 9.67, respectively. The results demonstrate that DESs are viable additives to CD system in CE for the separation of the chiral drugs.
A high performance fifth‐order multistep WENO scheme
Authors: Zeng Fangjun , Shen Yiqing , Liu Shengping , Liu Li
Published: May 2019

Many efforts have been made to improve the accuracy of the conventional weighted essentially nonoscillatory (WENO) scheme at transition points (connecting a smooth region and a discontinuity point). This paper analyzes these works and further develops a more effective multistep WENO scheme. Theoretical analysis and numerical results show that the new scheme not only improves the accuracy by one order higher than the traditional fifth‐order WENO schemes at transition point but also maintains the fifth‐order accuracy in smooth regions even at critical point where the first derivative vanishes.
Pleistocene landslides and mammoth bone deposits: The case of Dolní Věstonice II, Czech Republic
Authors: Svoboda Jiří , Krejčí Oldřich , Krejčí Vladimíra , Dohnalová Alena , Sázelová Sandra , Wilczyński Jarosław , Wojtal Piotr
Published: May 2019

The formation of extensive mammoth bone deposits is a characteristic feature of the large Upper Paleolithic settlements of the Moravian Gravettian (approximately 30 ky cal BP). Some of these were preferentially deposited in moist locations, possibly for reasons of hygiene and conservation. Here, we present a case of a mammoth bone deposit located in a side gully below the Dolní Věstonice II settlement, where an earlier a Pleistocene landslide temporarily created a shallow water basin. The environmental record is provided by analyses of pollen and mollusks. The structure of the osteological and archaeological assemblages suggests the use of this location as a place for storage, garbage disposal, and related activities. We suggest that the mammoth remains were transported to such places by humans either directly from nearby kill sites, or, after first selection, from the nearby settlement. We also discuss possible facilities for such transport.
The unique role of father–child numeracy activities in number competence of very young Chinese children
Authors: Liu Yingyi , Zhang Xiao , Song Zhanmei , Yang Wen
Published: May 2019

Based on a sample of 109 Hong Kong nursery children aged approximately 3 years and their parents, this study investigated how Chinese parents contributed to their very young children's mathematics achievement and disentangled mothers' and fathers' roles. Fathers and mothers were asked to independently report the frequencies of their own engagement in a range of numeracy activities with their children. Children were tested individually on their numeracy competencies. The results showed that fathers reported higher frequencies of engagement in number game activities than mothers. Further, fathers' reported use of real‐life applications to teach number knowledge was a significant predictor of their children's number knowledge above and beyond the child's age, gender, parental education, and family income. More importantly, this predictive relation was independent of mothers' effects. The findings highlight the importance of paternal involvement for very young Chinese children's number learning. Practical implications are discussed.

Highlights

This study examines mother‐child and father‐child numeracy activities in relation to Chinese young children's number knowledge.

Fathers are involved in more number game activities with their children than were mothers.

Fathers' use of real‐life applications to teach number knowledge is a significant predictor of their children's number knowledge.
Sp1‐mediated epigenetic dysregulation dictates HDAC inhibitor susceptibility of HER2‐overexpressing breast cancer
Authors: Li Guoyin , Xie Qiaosheng , Yang Zhiwei , Wang Lei , Zhang Xiang , Zuo Baile , Zhang Shengli , Yang Angang , Jia Lintao
Published: May 2019

Human epidermal growth factor receptor 2 (HER2/erbB2) is a key driver and therapeutic target for breast cancer. The treatment of HER2‐positive breast cancer remains a clinical challenge largely due to the limited understanding of HER2‐driving oncogenic signaling and the frequent resistance to simply HER2‐targeted therapy. Here, we show that the histone deacetylase inhibitor, trichostatin A (TSA), suppresses HER2‐overexpressing breast cancer via upregulation of miR‐146a and the resultant repression of its oncogenic targets, interleukin‐1 receptor‐associated kinase 1 and the chemokine receptor CXCR4. Mechanistically, histone H3K56 acetylation and deacetylation on the MIR146A promoter are catalyzed respectively by the acetyltransferase p300 and histone deacetylase 1 (HDAC1), both of which are recruited to the genomic loci by the transcription factor specificity protein 1 (Sp1). HER2 signaling phosphorylates Sp1 and induces its predominant association with HDAC1, but not p300, leading to histone hypoacetylation and silencing of MIR146A. In addition, the death receptor Fas is similarly downregulated by the aforementioned epigenetic paradigm, indicating its wide involvement in impairing tumor suppressor gene expression. Consequently, TSA synergizes with lapatinib, a tyrosine kinase inhibitor of HER2, to suppress breast cancer in vitro and in rodent models. These findings demonstrate a novel mechanism of HER2‐driven carcinogenesis and suggest the applicability of combined HER2 and HDAC targeting in breast cancer therapy.