bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Optical Coherence Tomography to Reveal the Hidden History of The Landsdowne Virgin of the Yarnwinder by Leonardo da Vinci and Studio
Authors: Targowski Piotr , Iwanicka Magdalena , Sylwestrzak Marcin , Frosinini Cecilia , Striova Jana , Fontana Raffaella 
Published: March 2018

AbstractOptical coherence tomography (OCT) was used for non‐invasive examination of a well‐known, yet complex, painting from the studio of Leonardo da Vinci in combination with routine imaging in various bands of electromagnetic radiation. In contrast with these techniques, OCT provides depth‐resolved information. Three post‐processing modalities were explored: cross‐sectional views, maps of scattering from given depths, and their 3D models. Some hidden alterations of the painting owing to past restorations were traced: retouching and overpainting with their positioning within varnish layers as well as indications of a former transfer to canvas.
Herstellung enantiomerenangereicherter sekundärer Alkyllithium‐ und Alkylkupferverbindungen – Synthese von (−)‐Lardolure und Siphonarienal
Authors: Morozova Varvara , Skotnitzki Juri , Moriya Kohei , Karaghiosoff Konstantin , Knochel Paul 
Published: March 2018

AbstractEnantiomerenangereicherte sekundäre Alkyliodide wurden in sekundäre Alkyllithium‐ und Alkylkupferverbindungen unter hoher Retention der Konfiguration überführt. Abfangreaktionen mit unterschiedlichen Elektrophilen, einschließlich chiraler Epoxide, lieferten eine Bandbreite von chiralen Molekülen mit hoher Enantiomerenreinheit (>90 % ee). Diese Methode wurde, ausgehend von kommerziell erhältlichem Ethyl‐(R)‐3‐hydroxybutyrat (>99 % ee), in einer iterativen Weise für die Totalsynthese von (−)‐Lardolure in 13 Stufen und 5.4 % Gesamtausbeute (>99 % ee, dr>99:1) und Siphonarienal in 15 Stufen und 5.6 % Gesamtausbeute (>99 % ee, dr>99:1) angewendet.
Catalytic Asymmetric [2+3] Cyclizations of Azlactones with Azonaphthalenes
Authors: Ma Chun , Zhou Jia‐Yu , Zhang Yi‐Zhu , Mei Guang‐Jian , Shi Feng 
Published: March 2018

AbstractThe first catalytic asymmetric [2+3] cyclization of azlactones with azonaphthalenes has been established. This strategy allowed the synthesis of a variety of chiral isatin derivatives in generally good yields and excellent enantioselectivities (up to 99 % yield, 98 % ee). The developed reaction has not only established a catalytic enantioselective [2+3] cyclization using azlactones as two‐carbon building blocks, but also enriches the chemistry of catalytic asymmetric cyclizations of azonaphthalenes. In addition, this protocol will provide a useful method for constructing enantioenriched 3,3′‐disubstituted isatin‐type frameworks.
Formation of Agostic Structures Driven by London Dispersion
Authors: Lu Qing , Neese Frank , Bistoni Giovanni 
Published: March 2018

AbstractAgostic interactions between a C−H bond and a transition metal are commonly crucial in catalytic polymerization processes. Herein, a quantitative study of the nature of β‐agostic interactions in a series of systems of importance in C−H bond activation reactions is reported. The analysis, characterized by the use of a coupled‐cluster‐based energy decomposition scheme, demonstrates that short‐range London dispersion between the agostic C−H bond and the metal center plays a fundamental role in affecting the structural stability of these systems, contrary to a widely held view. These results are used to rationalize a series of previously published experimental findings.
An Ethylenediamine‐based Switch to Render the Polyzwitterion Cationic at Tumorous pH for Effective Tumor Accumulation of Coated Nanomaterials
Authors: Ranneh Abdul‐Hackam , Takemoto Hiroyasu , Sakuma Shunya , Awaad Aziz , Nomoto Takahiro , Mochida Yuki , Matsui Makoto , Tomoda Keishiro , Naito Mitsuru , Nishiyama Nobuhiro 
Published: March 2018

AbstractPolyzwitterions are employed as coating polymers for biomaterials to induce an antifouling property on the surface. Fine‐tuning the betaine structure switches the antifouling property to be interactive with anionic tissue constituents in response to a tumorous pH gradient. The ethylenediamine moiety in the carboxybetaine enabled stepwise protonation and initiated the di‐protonation process around tumorous pH (6.5). The net charge of the developed polyzwitterion (PGlu(DET‐Car)) was thus neutral at pH 7.4 for antifouling, but was cationic at pH 6.5 for interaction with anionic constituents. Quantum dots coated with PGlu(DET‐Car) exhibited comparable stealth and enhanced tumor accumulation relative to the PEG system. The present study provides a novel design of smart switchable polyzwitterion based on a precise control of the net charge.
Preparation of Optically Enriched Secondary Alkyllithium and Alkylcopper Reagents—Synthesis of (−)‐Lardolure and Siphonarienal
Authors: Morozova Varvara , Skotnitzki Juri , Moriya Kohei , Karaghiosoff Konstantin , Knochel Paul 
Published: March 2018

AbstractOptically enriched secondary alkyl iodides were converted into secondary alkyllithium and secondary alkylcopper compounds with very high retention of configuration. Quenching with various electrophiles, including chiral epoxides, provided a range of chiral molecules with high enantiomeric purity (>90 % ee). This method has been applied in an iterative fashion in the total synthesis of (−)‐lardolure in 13 steps and 5.4 % overall yield (>99 % ee, dr>99:1) and siphonarienal in 15 steps and 5.6 % overall yield (>99 % ee, dr>99:1) starting from commercially available ethyl (R)‐3‐hydroxybutyrate (>99 % ee).
Magnetically recoverable lanthanum hydroxide as an efficient catalyst for Aerobic Oxidative Conversions of primary alcohols to the nitriles
Authors: Ziaee Fariborz , Gholizadeh Mostafa , Seyedi Seyed Mohammad 
Published: March 2018

Herein we report a novel magnetically recoverable lanthanum hydroxide nanoparticles for oxidative synthesis of nitriles directly from corresponding alcohols with ammonia as nitrogen source. The procedure for the preparation and characterization of La(OH)3/Fe3O4 magnetic nanoparticles were investigated and the scope and generality of the method was explored for a series of structurally diverse primary alcohols with electron‐donating and electron‐withdrawing groups. The best result was observed when 5 mol% of La with respect to the benzyl alcohol was used at reflux condition under O2 atmosphere. The La(OH)3/Fe3O4 magnetic nanoparticles could be easily isolated from the reaction mixture with an external magnet and reused at least 5 times without significant loss in activity.
Waste to wealth: conversion of nano‐magnetic eggshell (Fe3O4@Eggshell) to Fe3O4@Ca(HSO4)2: cheap, green and environment‐friendly solid acid catalyst
Authors: Khazaei Ardeshir , Sarmasti Negin , Seyf Jaber Yousefi 
Published: March 2018

Eggshell is a hazardous waste by European Union regulations, so that discarded thousands of tons per year. To convert waste (eggshell) to wealth (catalyst), nano‐magnetic eggshell was prepared based on the nano‐Fe3O4, and then the eggshell was converted to Ca(HSO4)2 with organic acid, namely, chlorosulfonic acid. Based on the back titration, 5.18 mmol SO4H group was loaded per gram of the nano‐structure. Using this method eggshell was converted to cheap, green and environment‐friendly solid acid catalyst. The prepared catalyst (nano‐ Fe3O4@Ca(HSO4)2) was characterized by Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), energy dispersive X‐ray spectroscopy (EDX), field emission scanning electron microscopy (FE‐SEM), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), and thermal gravimetric analysis (TGA). The activity of eggshell waste‐derived catalysts was successfully evaluated in the synthesis of value‐added products, namely indazolo[1,2‐b]‐phthalazinetrione derivatives as a benchmark multicomponent reaction. In addition, design of experiments shows that increase in amount of catalyst (and temperature), boost the reaction yield, especially with steeper slope at higher temperature.
Preparation of ferric phosphonate/phosphinate and their special action on flame retardancy of epoxy resin
Authors: Huang Yawen , Yang Yu , Ma Jiajun , Yang Junxiao 
Published: March 2018

ABSTRACTFe‐ and P‐based compounds have demonstrated promising performance in enhancing flame retardancy of epoxy resins. In this context, this work focuses on the preparation of new Fe/P hybridized nanomaterials and their effect on flame retardancy of epoxy resins. The Fe/P hybrids were facilely prepared via forming ferric phosphinates and phosphonates using hydrothermal reaction. Attractively, ferric phosphinates and phosphonates exhibit the morphology of 1D nanorod and 2D nanosheet, respectively. When incorporating these two fillers in epoxy resin, the limiting oxygen index values of composites were enhanced to above 28 and the composites exhibited self‐extinguishing behavior, thus indicating greatly improved fire resistance. Further investigation revealed that the flame retarding behavior, in particular for ferric phosphonate nanosheets, took place mainly in gas phases via delaying the release of flammable gas. Attractively, it was found that the Fe/P hybrids took part into the pyrolysis reaction of epoxy resins through forming FeO and PO bonds. This finding may provide a new insight to design a series of high performance flame retardants for epoxy resins. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46206.
A workflow and protocol describing the field to digitization process for new project‐based fossil leaf collections
Authors: Contreras Dori L. 
Published: March 2018

Premise of the StudyThis article provides a workflow and protocol for paleobotanical researchers that integrates project‐based fossil leaf specimen and data collection with curation and digitization. The methods aim to facilitate efficient digitization of new collections by researchers during the course of their study and promote public databasing of new specimen and project data.Methods and ResultsThe workflow was developed and refined to facilitate a project reconstructing an extensive fossil forest from leaf impressions/compressions. The workflow consists of field, museum, and data mobilization components. Customizing a workspace and streamlining all steps of specimen data collection, curation, and digitization into an integrated processing pipeline resulted in faster accumulation of specimen data and images.ConclusionsThese protocols provide paleobotanists with logistics‐focused methods for integrating research with digitization, and are particularly applicable at institutions with limited collection support staff or when specimen images are needed for project purposes.
Magnetic Resonance Imaging of the Sacroiliac Joints Indicating Sacroiliitis According to the Assessment of SpondyloArthritis international Society Definition in Healthy Individuals, Runners, and Women With Postpartum Back Pain
Authors: de Winter Janneke , de Hooge Manouk , van de Sande Marleen , de Jong Henriëtte , van Hoeven Lonneke , de Koning Anoek , Berg Inger Jorid , Ramonda Roberta , Baeten Dominique , van der Heijde Désirée , Weel Angelique , Landewé Robert 
Published: March 2018

ObjectiveTo compare magnetic resonance images (MRIs) of the sacroiliac (SI) joints of healthy subjects and individuals with known mechanical strain acting upon the SI joints to those of patients with axial spondyloarthritis (SpA) and patients with chronic back pain.MethodsThree readers who had received standardized training and were blinded with regard to study group randomly scored MRIs of the SI joints of 172 subjects, including 47 healthy individuals without current or past back pain, 47 axial SpA patients from the Spondyloarthritis Caught Early (SPACE) cohort (with a previous MRI confirmed positive for sacroiliitis), 47 controls with chronic back pain (irrespective of MRI results) from the SPACE cohort, 7 women with postpartum back pain, and 24 frequent runners. MRIs were scored according to the Assessment of SpondyloArthritis international Society (ASAS) definition and Spondyloarthritis Research Consortium of Canada (SPARCC) index.ResultsOf the 47 healthy volunteers, 11 (23.4%) had an MRI positive for sacroiliitis, compared to 43 (91.5%) of 47 axial SpA patients and 3 (6.4%) of 47 patients with chronic back pain. Three (12.5%) of the 24 runners and 4 (57.1%) of the 7 women with postpartum back pain had a positive MRI. Using a SPARCC cutoff of ≥2 for positivity, 12 (25.5%) of 47 healthy volunteers, 46 (97.9%) of 47 positive axial SpA patients, 5 (10.6%) of 47 controls with chronic back pain, 4 (16.7%) of 24 runners, and 4 (57.1%) of 7 women with postpartum back pain had positive MRIs. Deep bone marrow edema (BME) lesions were not found in healthy volunteers, patients with chronic back pain, or runners, but were found in 42 (89.4%) of 47 positive axial SpA patients and in 1 (14.3%) of 7 women with postpartum back pain.ConclusionA substantial proportion of healthy individuals without current or past back pain has an MRI positive for sacroiliitis according to the ASAS definition. Deep (extensive) BME lesions are almost exclusively found in axial SpA patients.
Nature of Bonding in Bowl‐Like B36 Cluster Revisited: Concentric (6π+18π) Double Aromaticity and Reason for the Preference of a Hexagonal Hole in a Central Location
Authors: Li Rui , You Xue‐Rui , Wang Kang , Zhai Hua‐Jin 
Published: March 2018

AbstractThe bowl‐shaped C6v B36 cluster with a central hexagon hole is considered an ideal molecular model for low‐dimensional boron‐based nanosystems. Owing to the electron deficiency of boron, chemical bonding in the B36 cluster is intriguing, complicated, and has remained elusive despite a couple of papers in the literature. Herein, a bonding analysis is given through canonical molecular orbitals (CMOs) and adaptive natural density partitioning (AdNDP), further aided by natural bond orbital (NBO) analysis and orbital composition calculations. The concerted computational data establish the idea of concentric double π aromaticity for the B36 cluster, with inner 6π and outer 18π electron counting, which both conform to the (4n+2) Hückel rule. The updated bonding picture differs from existing knowledge of the system. A refined bonding model is also proposed for coronene, of which the B36 cluster is an inorganic analogue. It is further shown that concentric double π aromaticity in the B36 cluster is retained and spatially fixed, irrespective of the migration of the hexagonal hole; the latter process changes the system energetically. The hexagonal hole is a destabilizing factor for σ/π CMOs. The central hexagon hole affects substantially fewer CMOs, thus making the bowl‐shaped C6v B36 cluster the global minimum.
Development and clinical application of a bioluminescence enzyme immunoassay for oxytocin
Authors: Karasawa Koji , Sano Yoshihiro , Kato Nobumasa , Arakawa Hidetoshi 
Published: March 2018

AbstractThe development of a highly sensitive analytical method for oxytocin could be useful in the diagnosis and treatment of autistic spectrum disorder. We previously developed a colorimetric enzyme immunoassay (EIA) for plasma oxytocin measurement. In this study, we developed a method to measure oxytocin concentrations using a higher sensitivity bioluminescent EIA. Biotinylated oxytocin bridged with five lysine residues was used in a competitive format. The standard curve range for oxytocin was 1.0 to 1000 pg/assay. In addition, there was good correlation between the colorimetric and bioluminescent immunoassays in terms of measured oxytocin concentration (r = 0.9665, n = 48). The bioluminescent EIA for plasma oxytocin was more rapid and provided higher sensitivity than the colorimetric immunoassay, making it suitable for clinical application.
A sensitive LC–MS/MS method for simultaneous determination of cabozantinib and its metabolite cabozantinib N‐oxide in rat plasma and its application in a pharmacokinetic study
Authors: Ren Lian‐jie , Wu Hua‐jing , Sun Li‐han , Xu Xue , Mo Li‐ying , Zhang Lei , Zhang Jun‐ying , Wu Chun‐yong 
Published: March 2018

AbstractCabozantinib (CBZ) is used for the treatment of progressive, metastatic medullary thyroid cancer. Its major oxidative metabolite is cabozantinib N‐oxide (CBN), which contains a structural alert associated with mutagenicity, yet the pharmacokinetics studies lack the simultaneous investigation of CBN and dose proportionality. In the current study a simple LC–MS/MS method was developed and validated for the simultaneous estimation and pharmacokinetic investigation of CBZ and CBN in rat plasma. The analytes were separated on a Waters Atlantics C18 column (2.1 × 150 mm, 3 μm). The mass spectrometry analysis was conducted in positive ionization mode with multiple reaction monitoring. Good linearity was observed over the concentration ranges of 0.500–5000 ng/mL for CBZ and 0.525–2100 ng/mL for CBN. The extraction recoveries were constant and the intra‐ and inter‐batch precision and accuracy were acceptable for the analysis of biological samples. The method was successfully applied for the simultaneous estimation of CBZ and CBN in a pharmacokinetic study in Sprague–Dawley rats. After oral administration of CBZ (1, 5 and 12.6 mg/kg), although CBZ showed dose proportionality, the metabolite CBN showed obvious nonlinear elimination pharmacokinetics with greater than dose‐proportional increases in exposure.
Development and validation of an LC‐ESI‐MS/MS method for the quantification of D‐84, reboxetine and citalopram for their use in MS Binding Assays addressing the monoamine transporters hDAT, hSERT and hNET
Authors: Neiens Patrick , De Simone Angela , Ramershoven Anna , Höfner Georg , Allmendinger Lars , Wanner Klaus T. 
Published: March 2018

AbstractMS Binding Assays represent a label‐free alternative to radioligand binding assays. In this study, we present an LC‐ESI‐MS/MS method for the quantification of (R,R)‐4‐(2‐benzhydryloxyethyl)‐1‐(4‐fluorobenzyl)piperidin‐3‐ol [(R,R)‐D‐84, (R,R)‐1], (S,S)‐reboxetine [(S,S)‐2], and (S)‐citalopram [(S)‐3] employed as highly selective nonlabeled reporter ligands in MS Binding Assays addressing the dopamine [DAT, (R,R)‐D‐84], norepinephrine [NET, (S,S)‐reboxetine] and serotonin transporter [SERT, (S)‐citalopram], respectively. The developed LC‐ESI‐MS/MS method uses a pentafluorphenyl stationary phase in combination with a mobile phase composed of acetonitrile and ammonium formate buffer for chromatography and a triple quadrupole mass spectrometer in the multiple reaction monitoring mode for mass spectrometric detection. Quantification is based on deuterated derivatives of all three analytes serving as internal standards. The established LC‐ESI‐MS/MS method enables fast, robust, selective and highly sensitive quantification of all three reporter ligands in a single chromatographic run. The method was validated according to the Center for Drug Evaluation and Research (CDER) guideline for bioanalytical method validation regarding selectivity, accuracy, precision, calibration curve and sensitivity. Finally, filtration‐based MS Binding Assays were performed for all three monoamine transporters based on this LC‐ESI‐MS/MS quantification method as read out. The affinities determined in saturation experiments for (R,R)‐D‐84 toward hDAT, for (S,S)‐reboxetine toward hNET, and for (S)‐citalopram toward hSERT, respectively, were in good accordance with results from literature, clearly demonstrating that the established MS Binding Assays have the potential to be an efficient alternative to radioligand binding assays widely used for this purpose so far.
Lipid nanoparticle siRNA cocktails for the treatment of mantle cell lymphoma
Authors: Knapp Christopher M. , He Jia , Lister John , Whitehead Kathryn A. 
Published: March 2018

AbstractMantle cell lymphoma is an aggressive and incurable subtype of non‐Hodgkin B cell lymphoma. Patients typically present with advanced disease, and most patients succumb within a decade of diagnosis. There is a clear and urgent need for novel therapeutic approaches that will affect mantle cell lymphoma through a unique mechanism compared to current therapies. This study examined the use of RNA interference (RNAi) therapy to attack mantle cell lymphoma at the mRNA level, silencing genes associated with cancer cell proliferation. We identified a lipid nanoparticle formulated with the lipidoid 306O13 that delivered siRNA to JeKo‐1 and MAVER‐1 mantle cell lymphoma cell lines. Three therapeutic gene targets were examined for their effect on lymphoma growth. These included Cyclin D1, which is a cell cycle regulator, as well as Bcl‐2 and Mcl‐1, which prevent apoptosis. Gene knockdown with siRNA doses as low at 10 nM increased lymphoma cell apoptosis without carrier‐mediated toxicity. Silencing of Cyclin D1 induced apoptosis despite a twofold “compensation” upregulation of Cyclin D2. Upon simultaneous silencing of all three genes, nearly 75% of JeKo‐1 cells were apoptosing 3 days post‐transfection. Furthermore, cells proliferated at only 15% of their pretreatment rate. These data suggest that lipid nanoparticles‐formulated, multiplexed siRNA “cocktails” may serve as a beneficial addition to the treatment regimens for mantle cell lymphoma and other aggressive cancers.
Tracking Down a New Steroid‐Hydroxylating Promiscuous Cytochrome P450: CYP154C8 from Streptomyces sp. W2233‐SM
Authors: Dangi Bikash , Kim Ki‐Hwa , Kang Sang‐Ho , Oh Tae‐Jin 
Published: March 2018

AbstractCYP154C8 from Streptomyces sp. has been identified as a new cytochrome P450 with substrate flexibility towards different sets of steroids. In vitro treatment of these steroids with CYP154C8 revealed interesting product formation patterns with the same group of steroids. NMR study revealed the major product of corticosterone to be hydroxylated at the C21 position, whereas progesterone, androstenedione, testosterone, and 11‐ketoprogesterone were exclusively hydroxylated at the 16α position. However, the 16α‐hydroxylated product of progesterone was further hydroxylated to yield dihydroxylated products. 16‐hydroxyprogesterone was hydroxylated at two positions to yield dihydroxylated products: 2α,16α‐dihydroxyprogesterone and 6β,16α‐dihydroxyprogesterone. To the best of our knowledge, this is the first report of generation of such products through enzymatic hydroxylation by a CYP450. In view of the importance of modified steroids as pharmaceutical components, CYP154C8 has immense potential for utilization in bioproduction of hydroxylated derivative compounds to be directly employed for pharmaceutical applications.
Ibuprofen reduces cell proliferation through inhibiting Wnt/β catenin signaling pathway in gastric cancer stem cells
Authors: Akrami Hassan , Moradi Behrouz , Borzabadi Farahani Diba , Mehdizadeh Kiumars 
Published: March 2018

AbstractNowadays, most studies focused on cancer stem cells (CSCs) through their abilities to cause tumorigenicity, drug resistance, and cancer recurrence. On the other side, nonsteroidal anti‐inflammatory drugs (NSAIDs) have been taken into consideration because of cheapness and availability. For the reasons mentioned above, we have studied the effect of ibuprofen as an NSAID on CSCs derived from AGS and MKN‐45 gastric cancer cell lines to perform effective cancer therapy. We evaluated cell viability, spheroid body formation, monolayer, and soft agar colony formation to express the anti‐cancer effect of ibuprofen on CSCs. Also, real‐time RT‐PCR data of stemness markers and genes affected on, or downstream of Wnt signaling pathway were evaluated. Our findings suggest that ibuprofen at 1,000 μM for 48 h can reduce cell proliferation, stemness features in CSCs by changing the expression level of CD44, OCT3/4, SOX2, Nanog, and KLF4 as stemness markers. Furthermore, ibuprofen can have an inhibitory role in Wnt signaling pathway by changing the expression level of some genes, including CTNNB1, CTNNBIP1, SMARCD1, PYGO2, SUFU, CASK, and KREMEN1. According to our study, ibuprofen has an anti‐proliferative effect on CSCs derived from AGS and MKN‐45 cells.