bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sampling uncertainty versus method uncertainty: A general framework with applications to omics biomarker selection
Authors: Klau Simon , Martin‐Magniette Marie‐Laure , Boulesteix Anne‐Laure , Hoffmann Sabine 
Published: May 2019

AbstractUncertainty is a crucial issue in statistics which can be considered from different points of view. One type of uncertainty, typically referred to as sampling uncertainty, arises through the variability of results obtained when the same analysis strategy is applied to different samples. Another type of uncertainty arises through the variability of results obtained when using the same sample but different analysis strategies addressing the same research question. We denote this latter type of uncertainty as method uncertainty. It results from all the choices to be made for an analysis, for example, decisions related to data preparation, method choice, or model selection. In medical sciences, a large part of omics research is focused on the identification of molecular biomarkers, which can either be performed through ranking or by selection from among a large number of candidates. In this paper, we introduce a general resampling‐based framework to quantify and compare sampling and method uncertainty. For illustration, we apply this framework to different scenarios related to the selection and ranking of omics biomarkers in the context of acute myeloid leukemia: variable selection in multivariable regression using different types of omics markers, the ranking of biomarkers according to their predictive performance, and the identification of differentially expressed genes from RNA‐seq data. For all three scenarios, our findings suggest highly unstable results when the same analysis strategy is applied to two independent samples, indicating high sampling uncertainty and a comparatively smaller, but non‐negligible method uncertainty, which strongly depends on the methods being compared.
A new flow cell and chemometric protocol for implementing in‐line Raman spectroscopy in chromatography
Authors: Feidl Fabian , Garbellini Simone , Vogg Sebastian , Sokolov Michael , Souquet Jonathan , Broly Hervé , Butté Alessandro , Morbidelli Massimo 
Published: May 2019

AbstractOn‐line monitoring tools for downstream chromatographic processing (DSP) of biotherapeutics can enable fast actions to correct for disturbances in the upstream, gain process understanding, and eventually lead to process optimization. While UV/Vis spectroscopy is mostly assessing the protein's amino acid composition and the application of Fourier transform infrared spectroscopy is limited due to strong water interactions, Raman spectroscopy is able to assess the secondary and tertiary protein structure without significant water interactions. The aim of this work is to implement the Raman technology in DSP, by designing an in‐line flow cell with a reduced dead volume of 80 μL and a reflector to increase the signal intensity as well as developing a chemometric modeling path. In this context, measurement settings were adjusted and spectra were taken from different chromatographic breakthrough curves of IgG1 in harvest. The resulting models show a small average RMSEP of 0.12 mg/mL, on a broad calibration range from 0 to 2.82 mg/mL IgG1. This work highlights the benefits of model assisted Raman spectroscopy in chromatography with complex backgrounds, lays the fundamentals for in‐line monitoring of IgG1, and enables advanced control strategies. Moreover, the approach might be extended to further critical quality attributes like aggregates or could be transferred to other process steps.
Identification and validation of circulating exosomes‐based liquid biopsy for esophageal cancer
Authors: Zhao An , Guo Liwei , Xu Ji , Zheng Lei , Guo Zhenying , Ling Zhiqiang , Wang Lidong , Mao Weimin 
Published: May 2019

AbstractBackgroundEarly detection of esophageal squamous cell carcinoma (ESCC) recurrence is a key element for follow‐up care and surveillance. The aim of this study is to detect the level of circulating exosomes (CEs) in ESCC patient and clarify its clinical significance.MethodsIn this study, 200 serum samples of ESCC patients were obtained from the Zhejiang Cancer Hospital Biospecimen Repository. Total CEs were purified by selectively capturing epithelial cell adhesion molecule positive exosomes, using magnetic‐bead technique. enzyme‐linked immunosorbent assay (ELISA) was performed to measure the concentration level of CEs. The oncogenic potential of CEs was analyzed in vitro.ResultsSerum concentration of CEs was significantly higher in ESCC patients than in healthy controls (P < 0.01). Receiver‐operating characteristic curve analysis demonstrated that CEs concentration could distinguish patients with ESCC from healthy individuals with a sensitivity of 75% and a specificity of 85%. Kaplan‐Meier analysis demonstrated that the increased CEs concentration was associated with poor overall survival (P = 0.01) and progression free survival (P = 0.03) in ESCC patients. Multivariate cox regression analysis revealed that CEs concentration was an independent prognostic marker for overall survival in ESCC patients (P < 0.01). Results from transwell and wound scratching experiments showed that the CEs could promote cell migration and invasion.ConclusionsThis study clearly demonstrates that CEs from ESCC patients are stable enough to be measured and their levels in ESCC patients are significantly upregulated. Circulating exosomes could serve as a novel noninvasive biomarker for detection of ESCC. Their involvement in carcinogenesis must be further established.
Base‐Sequence‐Independent Efficient Redox Switching of Self‐Assembled DNA Nanocages
Authors: Wang Bang , Song Lei , Jin Bang , Deng Ning , Wu Xiaojing , He Jianbo , Deng Zhaoxiang , Li Yulin 
Published: May 2019

AbstractStimuli responsivity has been extensively pursued in dynamic DNA nanotechnology, due to its incredible application potentials. Among diverse dynamic systems, redox‐responsive DNA assembly holds great promise for broad applications, especially considering that redox processes widely exist in various physiological environments. However, only a few studies have been reported on redox‐sensitive dynamic DNA assembly. Albeit ingenious, most of these studies are either dependent on the DNA sequence or involve chemical modification. Herein, a facile and universal mechanism to realize redox‐responsive self‐assembly of DNA nanocages (tetrahedron and cube) driven by the interconversion between cystamine and cysteamine toward dynamic DNA nanotechnology is reported.
A DNA Aptamer for Cyclic Adenosine Monophosphate that Shows Adaptive Recognition
Authors: Sharma Suruchi , Zajac Matthew , Krishnan Yamuna 
Published: May 2019

AbstractAs a ubiquitous second messenger, cyclic adenosine monophosphate (cAMP) mediates diverse biological processes such as cell growth, inflammation, and metabolism. The ability to probe these pathways would be significantly enhanced if we had a DNA‐based sensor for cAMP. Herein, we describe a new, 31‐base long single‐stranded DNA aptamer for cAMP, denoted caDNApt‐1, that was isolated by in vitro selection using systemic evolution of ligands after exponential enrichment (SELEX). caDNApt‐1 has an approximately threefold higher affinity for cAMP than ATP, ADP, and AMP. Using non‐denaturing gel electrophoresis and fluorescence spectroscopy, we characterized the structural changes caDNApt‐1 undergoes upon binding to cAMP and revealed its potential as a cAMP sensor.
Thermo‐Rheology of a Proline‐Based Surface‐Active Ionic Liquid: Mixtures with Water and n‐Octane
Authors: Torres María Dolores , Corchero Raquel , Rodríguez-Escontrela Iria , Soto Ana , Moreira Ramón 
Published: May 2019

AbstractSurfactant flooding is one of the most promising techniques to recover oil from unprofitable reservoirs. Surface‐active ionic liquids can overcome the limitations of the current surfactants. The rheology of the injecting solutions and the formed slugs is critical in the evaluation of an enhanced oil recovery process. The thermo‐rheological behavior of a biodegradable surface‐active ionic liquid, [ProC4]DS, and the corresponding binary and ternary mixtures with water and n‐octane was studied. All flow curves exhibited shear‐thinning and thixotropic behavior. The viscoelastic behavior of the ternary samples depended strongly on the [ProC4]DS content. Three different regions were identified: typical liquid‐like behavior, weak gel, and true gel. The thermal profiles indicated that the tested systems were fully thermoreversible.
Na2Ti3O7 Nanotubes as Anode Materials for Sodium‐ion Batteries and Self‐powered Systems
Authors: Chen Zehua , Lu Liang , Li Nianwu , Sun Chunwen 
Published: May 2019

AbstractNa2Ti3O7 (NTO) is a potential anode material with low discharge voltage for room‐temperature sodium‐ion batteries. In this work, NTO nanotubes were prepared by a hydrothermal method. XRD, SEM, TEM, and HRTEM studies are performed to investigate the composition, morphology, and structure. As anodes for sodium‐ion batteries, NTO nanotubes show a reversible capacity of 126.2 mAh g−1 at 100 mA g−1. The discharge capacity can still reach 109 mAh g−1 even for 2000 cycles. Solid‐state sodium‐ion batteries containing NTO‐nanotube anodes and an Na3Zr2Si2PO12 solid electrolyte display a comparable performance to batteries with a liquid electrolyte. Moreover, the prepared solid‐state sodium battery is also demonstrated to store mechanical energy harvested by triboelectric nanogenerators (TENGs). The discharge capacity reaches 121 mAh g−1 at 5 mA g−1.
Structure‐Pattern‐Based Total Synthesis
Authors: Gerlinger Christa K. G. , Gaich Tanja 
Published: May 2019

AbstractIn this article the concept of structure‐pattern‐recognition and its application to total synthesis is summarized. By applying this synthetic strategy to the two biogenetically unrelated natural product families Sarpagine and Stemona alkaloids, a drastic increase of synthetic efficiency could be achieved. To highlight its potential, this strategy is compared with some elegant target‐oriented syntheses. The importance of strategic planning and synthesis design is clearly demonstrated.
Exploring the Chemistry of Non‐sticky Sugars: Synthesis of Polyfluorinated Carbohydrate Analogues of d‐Allopyranose
Authors: Denavit Vincent , St‐Gelais Jacob , Tremblay Thomas , Giguère Denis 
Published: May 2019

AbstractThere is a growing interest in the preparation of polyfluorinated carbohydrates. A limited number of fluorohexopyranosides have been used in biological investigations because of the synthetic challenge they present. Hence, we report the synthesis of fluorinated homodimer, fluorodisaccharides, C‐terminal fluoroglycopeptides, lipoic acid fluoroglycoconjugate and trifluoroallopyranoside derivatives functionalized at C‐6. Our strategy uses levoglucosan as inexpensive starting material and facilitates an approach to complex carbohydrate analogues with multiple C−F bonds. The challenge of our synthetic route centered around an efficient preparation of crucial 1,6‐anhydro‐2,4‐dideoxy‐difluoroglucopyranose and focused on achieving a difficult glycosylation of the trifluoroallopyranose donor. The results clearly highlight challenges related to the preparation of polyhalogenated complex organic molecules and pave the way to access novel medically relevant tools.
The Influence of Chemical Change on Protein Dynamics: A Case Study with Pyruvate Formate‐Lyase
Authors: Hanževački Marko , Čondić‐Jurkić Karmen , Banhatti Radha Dilip , Smith Ana‐Sunčana , Smith David M. 
Published: May 2019

AbstractInvited for the cover of this issue is David M. Smith and co‐workers at the Ruđer Bošković Institute, Zagreb, Croatia and Friedrich Alexander University Erlangen Nurnberg, Germany. The image depicts coenzyme A reaching for the acetyl group in the active site of pyruvate formate–lyase. Read the full text of the article at 10.1002/chem.201900663.
Fluorine‐Containing Drugs Approved by the FDA in 2018
Authors: Mei Haibo , Han Jianlin , Fustero Santos , Medio‐Simon Mercedes , Sedgwick Daniel M. , Santi Claudio , Ruzziconi Renzo , Soloshonok Vadim A. 
Published: May 2019

AbstractOver the last two decades, fluorine substitution has become one of the essential structural traits in modern pharmaceuticals. Thus, about half of the most successful drugs (blockbuster drugs) contain fluorine atoms. In this review, we profile 17 fluorine‐containing drugs approved by the food and drug administration (FDA) in 2018. The newly approved pharmaceuticals feature several types of aromatic F and CF3, as well as aliphatic (CF2) substitution, offering advances in the treatment of various diseases, including cancer, HIV, malarial and smallpox infections.
Methoden zur Technologie‐Vorausschau
Authors: Möckel Christina , Schumacher Gerd , Hake Jürgen‐Friedrich 
Published: May 2019

ZusammenfassungAuch wenn exakte Vorhersagen der Zukunft in einer nicht‐deterministischen Welt unmöglich sind, liefert die Technologie‐Vorausschau relevante Hinweise auf mögliche zukünftige Entwicklungen. Methoden der Technologie‐Vorausschau spielen daher heute für verschiedenste Branchen der Wirtschaft, inklusive der Chemieindustrie, eine zentrale Rolle im Innovationsmanagement. Das äußerst breite Methodenspektrum ist ständig in der Weiterentwicklung. Meist finden Kombinationen mehrerer Methoden Anwendung mit jeweils sehr spezifischen Lösungsansätzen für eine Fragestellung. Verschiedene Methoden wurden exemplarisch anhand des Gebietes der Energieforschung beleuchtet. Publikationsanalysen liefern Hinweise auf bestehende Trends und auch aufkommende („emerging“) Trends. Gerade schwache Signale liefern hier neue Erkenntnisse. Die Kreativtechnik hingegen kann zur Szenarioentwicklung sinnvoll eingesetzt werden, da mögliche disruptive Ereignisse mit in Betracht gezogen werden können. Die Szenarioentwicklung erfordert neben der Auseinandersetzung mit technologischen Aspekten auch die Betrachtung von möglichen soziologischen und ökonomischen Entwicklungen. Denn erst der sozioökonomische Kontext ist maßgeblich für die Entstehung eines Trends und der Durchsetzung einer Technologie.
Facile in situ Synthesis of Ag‐Doped CdSe Supra‐Quantum Dots and their Characterization
Authors: Lee See Mak , Lim Hyunseob , Lee Younki , Bang Jiwon 
Published: May 2019

AbstractA supra‐quantum dot (SQD) is a three‐dimensionally assembled QD structure composed of several hundreds to thousands of QDs connected through oriented attachments. Owing to their three‐dimensional interconnected structures and relatively large volumes, impurity atoms are thermodynamically more stable in SQDs than in conventional QDs. Herein, we report the facile in‐situ synthesis of colloidal Ag‐doped CdSe SQDs. Ag dopants were efficiently incorporated into CdSe SQDs through the three‐dimensional interconnection of Ag‐doped primary CdSe QDs, as confirmed by elemental analysis combined with chemical etching. Photoelectron spectroscopic studies revealed that the Ag‐doped CdSe SQDs exhibit n‐type doping behavior, since the valence electrons from the interstitial Ag atoms are directly donated to the lattice.
Strong Microheterogeneity in Novel Deep Eutectic Solvents
Authors: Alizadeh Vahideh , Geller David , Malberg Friedrich , Sánchez Pablo B. , Padua Agilio , Kirchner Barbara 
Published: May 2019

AbstractWith the increasing application of template assisted syntheses in deep eutectic solvents and successful application of hydrophobic deep eutectic solvents in extraction processes, where microheterogeneity plays a major role, suggestions for novel deep eutectic solvents which exhibit strong microheterogeneity are desirable. Therefore, classical molecular dynamics simulations were carried out on deep eutectic solvent systems constructed of choline chloride and some of its derivatives mixed with ethylene glycol in a molar composition of 1 : 2 since this is the optimal parent composition. The derivatives consisted of a series of elongated alkyl side chains and elongated alcohol side chains. Of these series only choline chloride ethylene glycol has been investigated experimentally, the other systems are suggested and theoretically investigated as possible target for synthesis. Our domain analysis supported by the clear distinction of polar and nonpolar parts from the electrostatic potentials reveals that strong microheterogeneity within these novel hypothetical deep eutectic solvents exists. Rather stretched than crumbled side chains maximize possible interaction sites for both polar and nonpolar parts which make the suggested compounds valuable objectives for experiments in order to exploit the microheterogeneity in deep eutectic solvents.
From the Synthesis of Biobased Cyclic Carbonate to Polyhydroxyurethanes: A Promising Route towards Renewable Non‐Isocyanate Polyurethanes
Authors: Carré Camille , Ecochard Yvan , Caillol Sylvain , Avérous Luc 
Published: May 2019

AbstractWith a global production of around 18 million tons (6th among all polymers) and a wide range of applications, such as rigid and soft foams, elastomers, coatings, and adhesives, polyurethanes (PUs) are a major polymer family. Nevertheless, they present important environmental and health issues. Recently, new and safer PUs, called non‐isocyanate polyurethanes (NIPUs), have become a promising alternative to replace conventional PUs. Sustainable routes towards NIPUs are discussed herein from the perspective of green chemistry. The main focus is on the reaction between biobased carbonates and amines, which offers an interesting pathway to renewable polyhydroxyurethanes (PHUs). An overview of different routes for the synthesis of PHUs draws attention to the green synthesis of cyclic carbonate (CC) compounds and the aminolysis reaction. Current state‐of‐the‐art of different biobased building blocks for the synthesis of PHUs focuses on CC compounds. Three classes of compounds are defined according to the feedstock: 1) vegetable fats and oils, 2) starch and sugar resources, and 3) wood derivatives. Finally, biobased PHU properties are discussed.
CPM modulation index estimation using LS and BLUE methods
Authors: Atashbar Mahmoud , Vahidinia Vahideh 
Published: May 2019

SummaryIn this paper, we propose two methods for blind estimation of modulation index of full‐response binary continuous phase modulation (CPM) scheme. Most of previous works assume that there is a single sample for each symbol; thus, they cannot improve their performance when sampling rate is bigger than symbol rate. In our proposed methods, modulation index is estimated using samples of autocorrelation function of the received signal, which is a nonlinear function of modulation index. We propose Taylor expansion for approximating this nonlinear function by a linear function. Then, by choosing some samples of the autocorrelation function, we estimate the modulation index with the least square (LS) estimator. For decreasing estimation errors, in the second proposed method, we apply the statistical properties of the autocorrelation function estimation errors, to design the best linear unbiased estimation (BLUE) estimator. The numerical performance analysis in terms of mean‐squared error (MSE) and bit error rate (BER) shows that the proposed methods outperform the reference methods in accurate estimation of the modulation index.
Non‐hierarchical competition among co‐occurring woody seedlings in a resource‐limited environment
Authors: Woods Natasha N. , McCarthy Ryan , Miriti Maria N. 
Published: May 2019

AbstractLong‐term species persistence in plant communities is contingent in part on the conditions that favor establishment and early survival. In stressful habitats, facilitated seedling establishment can enhance species richness by providing a safe‐site for species unable to establish in open microsites. However, the indirect effects of seedling competition may drive persistence in locations where seedlings occur in high density. This under‐examined dynamic can influence community recovery to stress by favoring competitively dominant species, in particular when stress increases local seedling density in favorable microsites. We present the results of a response surface experiment that examines growth responses among seedlings of Ambrosia dumosa, Eriogonum fasciculatum, and Larrea tridentata that were planted at three densities and four relative frequencies. These species co‐occur at an extensively monitored reference community located in the Colorado Desert, California, USA, where extensive drought caused unprecedented mortality that will require novel recruitment for the community to reach pre‐disturbance composition. Significant, non‐hierarchical competitive responses show that seedling survival is contingent on the species identity and density of neighboring seedlings. This result supports non‐hierarchical competition among these common species. Ambrosia and Eriogonum had faster growth rates than Larrea, but also experienced larger reductions in growth from competition than Larrea. Although drought may intensify seedling competition in favorable locations, the context dependency of competitive outcomes may permit coexistence.
European environmental policy at 50: Five decades of escaping decision traps?
Authors: Deters Henning 
Published: May 2019

AbstractRather than being constrained by the least ambitious governments, the European Union (EU) has until recently set the pace of national environmental policy. The contribution examines why the EU was often able to set the pace despite the institutionalist expectation that national diversity and quasi‐unanimity should produce joint‐decision traps. It also explains why this is no longer the case. Adopting a long‐term, diachronic perspective, I argue that the EU's unexpected dynamism and its recent decline are related to distinct institutional exits from the joint‐decision trap that have opened and closed in different periods. During the emergence of the policy area, diversity was manageable through bargaining, and joint gains were abundant. Between the late 1980s and the Eastern enlargement, as environmental policy was increasingly adopted under the community method, supranational intervention became an additional exit mechanism, with an activist European Parliament and strong agenda setting by the Commission. Since mid‐2000, the green dynamism is in decline, as supranational interventions wane and bargaining solutions become insufficient to cope with increased diversity after enlargement, exacerbated by the economic crisis. However, nonpolitical lawmaking in the regulatory mode is emerging as a novel exit from the joint‐decision trap.