bluuebunny/crossref_metadata_2025 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

Optical 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

Enantiomerenangereicherte 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

The 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

Agostic 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

Polyzwitterions 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

Optically 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.
An efficient and new protocol for the Heck reaction using palladium nanoparticle‐engineered dibenzo‐18‐crown‐6‐ether/MCM‐41 nanocomposite in water
Authors: Azaroon Maedeh , Kiasat Ali Reza
Published: March 2018

Palladium nanoparticle‐incorporated mesoporous organosilica (MCM‐41‐Crown.Pd) was synthesized via the grafting of dibenzo‐18‐crown‐6‐ether moieties on the MCM‐41 surface, followed by reaction of the nanocomposite with palladium acetate and then its reduction in ethanol. The cavity of the immobilized dibenzo‐18‐crown‐6 as host material can stabilize the palladium nanoparticles effectively and prevent their aggregation and separation from the surface. The structure of the nanocomposite was characterized using various techniques. The catalytic properties of the nanocomposite in the Heck coupling reaction, one of the most useful transformations in organic synthesis, between aryl halides and olefins in water were also explored. The main advantages of the method are low cost, high yields, easy work‐up and short reaction time. The nanocatalyst can be easily separated from a reaction mixture and was successfully examined for seven runs, with a slight loss of catalytic activity.
Oxygenation of sulfides catalysed by SBA‐15‐immobilized molybdenum(VI) complex of a bis(phenol) diamine ligand using aqueous hydrogen peroxide as a green oxidant
Authors: Saberikia Iraj , Safaei Elham , Karimi Babak , Lee Yong‐III
Published: March 2018

A highly efficient and reusable molybdenum‐based catalyst has been synthesized by covalent grafting of a bis(phenol) diamine ligand, namely 2‐(((2‐bromoethyl)(2‐((3,5‐di‐tert‐butyl‐2‐hydroxybenzyl)amino)ethyl)amino)methyl)‐4,6‐di‐tert‐butylphenol, onto functionalized ordered mesoporous silica (SBA‐15) followed by complexation with MoO2(acac)2. The resulting organic–inorganic hybrid material was found to be a highly effective catalyst for oxygenation of various sulfides to their corresponding sulfoxides or sulfones. The catalyst was characterized using transmission and scanning electron microscopies, X‐ray photoelectron, Fourier transform infrared and atomic absorption spectroscopies, Brunauer–Emmett–Teller surface area analysis and thermogravimetric analysis. Mild reaction conditions, high selectivity and easy recovery and reusability of the catalyst render the presented protocol very useful for addressing industrial needs and environmental concerns.
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.
Newly synthesized Cu(II) pyrazino[2,3‐f][1,10]phenanthroline complexes as potential anticancer candidates
Authors: İnci Duygu , Aydın Rahmiye , Huriyet Huzeyfe , Zorlu Yunus , Çinkılıç Nilüfer
Published: March 2018

New binary and ternary copper(II) complexes, [Cu(py‐phen)2(NO3)]NO3 (1), [Cu2(py‐phen)2(gly)2(NO3)2(H2O)2]⋅3H2O (2) and [Cu2(py‐phen)2(tyr)2(H2O)2](NO3)2⋅3H2O (3) (py‐phen: pyrazino[2,3‐f][1,10]phenanthroline; gly: glycine; tyr: tyrosine), have been synthesized and characterized using CHN analysis, electrospray ionization mass spectrometry, Fourier transform infrared spectroscopy and single‐crystal X‐ray diffraction. Interaction of these complexes with calf thymus DNA has been investigated using absorption spectral titration, ethidium bromide and Hoechst 33258 displacement assay and thermal denaturation measurements. These complexes were found to be efficient cleaving agents and cleavage reactions were mediated by hydrolytic and oxidative pathways. The interaction between these complexes and bovine serum albumin (BSA) was investigated using electronic absorption and fluorescence spectroscopy. The experimental results show that the fluorescence quenching mechanism of these complexes and BSA is a static quenching process. Furthermore, in vitro cytotoxicities of these complexes against tumour cell lines (Caco‐2, MCF‐7 and A549) and healthy cell line (BEAS‐2B) showed that they exhibited anticancer activity with low IC50 values. These complexes were markedly active against the cell lines and can be good drug candidates that are effective and safe for healthy tissue.
New triorganotin(IV) complexes of quinolone antibacterial drug sparfloxacin: Synthesis, structural characterization, DFT studies and biological activity
Authors: Joshi Rachana , Pandey Nidhi , Tilak Ragini , Yadav Swatantra Kumar , Mishra Hirdyesh , Pokharia Sandeep
Published: March 2018

A new series of triorganotin(IV) complexes of sparfloxacin (HL) having general formula R3SnL (where L is the monoanion of sparfloxacin (HL) and R = Me (1)/n‐Bu (2)/Ph (3)/Cy (4)) have been synthesized and characterized by elemental analysis, IR, NMR (1H, 13C, 119Sn), 2D‐HETCOR, ESI‐MS and UV‐Vis studies. These investigations suggest that, in these 1:1 monomeric derivatives the sparfloxacin ligand acts as monoanionic bidentate coordinating through the Ocarboxylate and Opyridone, and the polyhedron around tin is intermediate between pseudotetrahedral and cis‐trigonal bipyramidal, with Opyridone and two organic groups in equatorial plane and the carboxylate oxygen and the third organic group in axial positions. The proposed structures have been validated by density functional theory (DFT) based quantum chemical calculations at B3LYP/6‐31G(d,p)/Def2‐SVP(Sn) level of theory. A detailed electronic structure calculations were performed at this level of theory to calculate atomic charges at the selected atoms, molecular electrostatic potential (MEP) map to assign sites on the surface of the molecules, the selected conceptual‐DFT based global reactivity descriptors to obtain an insight into the structure and reactivity behaviour, and the frontier molecular orbital analysis to analyze the nature of frontier orbitals. All the complexes were screened for their in vitro antibacterial activity against two Gram‐positive and five Gram‐negative bacterial strains. All the complexes exhibited promising antibacterial activity as compared to sparfloxacin against all the chosen strains.
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

Fe‐ 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 Study

This 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 Results

The 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.

Conclusions

These 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

Objective

To 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.

Methods

Three 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.

Results

Of 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.

Conclusion

A 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

The 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.
Density‐free test for symmetry verification in images
Authors: Migalska Agata
Published: March 2018

Presence of symmetry is utilized in multiple machine vision systems to help achieve their goals. In numerous scenarios, this goal is to verify that certain symmetry is indeed exhibited by an image. However, we find that there is a shortage of methods for symmetry verification that would be capable of asserting an arbitrary reflectional or rotational symmetry. Using symmetry detectors to merely perform symmetry verification is improvident and not justified. We thus propose a novel statistical test for symmetry verification that fulfills the requirement of versatility. The proposed test is based on the principle that if an image is invariant to some hypothesized transformation, then an averaged image, obtained by averaging pixel intensities of an input image and of its transformed copy, looks exactly the same as an input image. Adopting the viewpoint that images are visual messages that convey some information allows us to expect that the amount of information in both images is the same. On the contrary, an incorrectly chosen transformation shall result in the information content being different. Based on this equality, we construct the test statistic and show that, when samples are large, the test statistic is asymptotically normally distributed. Finally, to verify the validity of the proposed principle and the performance of the method, a meticulous experimental study was performed on a large set of images. The results of this study confirmed the postulated ability of the method to verify an arbitrary symmetry and are demonstrated with several examples.
Warranty cost analysis: Increasing warranty repair times
Authors: Marshall Sarah , Arnold Richard , Chukova Stefanka , Hayakawa Yu
Published: March 2018

In this study, we model the warranty servicing costs under nonrenewing and renewing free repair warranties. We assume nonzero increasing repair times with the warranty cost depending on the length of the repair time. An increasing geometric process is used to model the consecutive repair times. We introduce the generalised alternating renewal process, which is an alternating process with cycles consisting of an item's operational time followed by the corresponding repair time. We derive analytical results for a generalised alternating renewal process with a finite time horizon and use them to evaluate the warranty costs over the warranty period and over the life cycle of the product under the nonrenewing free repair warranty and renewing free repair warranty. Properties of the model are demonstrated through a simulation study and through the application to warranty claims data from an automotive manufacturer.
Development and clinical application of a bioluminescence enzyme immunoassay for oxytocin
Authors: Karasawa Koji , Sano Yoshihiro , Kato Nobumasa , Arakawa Hidetoshi
Published: March 2018

The 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

Cabozantinib (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

MS 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

Mantle 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

CYP154C8 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

Nowadays, 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.
Oxidative Dehydrogenation of n‐Octane over Niobium‐Doped NiAl2O4: An Example of Beneficial Coking in Catalysis over Spinel
Authors: Farahani Majid D. , Dasireddy Venkata D. B. C. , Friedrich Holger B.
Published: March 2018

NiAl2O4‐based materials are known as enhanced catalysts for several catalytic applications that have coke deposition in common. In this study, Nb as a dopant was found to occupy the octahedral sites of the spinel preferably. As a result, the cation distribution was altered between the two sub‐lattices of the cubic spinel. Therefore, ordered modifications of nickel migration, electronic profile, redox properties and surface textures were observed for these catalysts. Also, coke deposition over these catalysts was controlled using Nb doping and found to modify the original features of the fresh catalysts and lower their crystallite sizes. This study suggests reasons why NiAl2O4 spinel performs so well in the majority of the high‐temperature catalytic processes that suffer from coke deposition.
Career Decision Making for Korean International College Students: Acculturation and Networking
Authors: Nadermann Kristen , Eissenstat SunHee J.
Published: March 2018

The authors examined the relationship among acculturation, career networking, and career decision self‐efficacy for Korean international college students. Networking is an essential skill for career success, and acculturation is connected to career outcomes for diverse populations; however, little research has examined the relationship between these factors. A total of 172 Korean international students (117 women, 54 men, 1 not reported) completed measures of acculturation; networking comfort, intensity, and proactivity; and career decision self‐efficacy. Using structural equation modeling, the authors found acculturation to affect career decision self‐efficacy through networking. The relationships among acculturation, networking, and career decision self‐efficacy indicated a medium to large effect size. These findings indicate that career counselors should collaboratively attend to acculturation concerns, such as stress and identity development, as well as provide opportunities for networking skill development. More research is needed on acculturation and networking among additional international student populations.
Using the Delphi Method to Classify Medical Specialties
Authors: Borges Nicole J. , Richard George V.
Published: March 2018

One medical specialty classification system applicable for research and career counseling is the person‐oriented versus technique‐oriented taxonomy. Given that the model was conceptualized in the 1960s, verification based on how medical specialties are practiced and viewed today is necessary. Five specialists in medical career development and advising verified the categorization of specialties. Based on their review, 100% consensus was reached regarding grouping of specialties. This outcome validates the taxonomy of medical specialties and supports its continued use for medical career specialty advising and choice.
Can we beat overfitting?—A closer look at Cloarec's PLS algorithm
Authors: M. Sousa Pedro F. , Åberg K. Magnus
Published: March 2018

Random noise has been addressed as a cause of overfitting in partial least squares regression. A previous study pinpointed that one of the sources of overfitting resides in the calculation of scores due to the accumulation of noise in the diagonal of the variance‐covariance matrix, and a modified partial least squares regression was proposed with the removal of this diagonal prior to the score calculation. Here, a further modification of the NIPALS algorithm is proposed, with the same ability to overcome overfitting due to noise, but algebraically more similar to the original NIPALS. The results indicate that it is possible to get more reliable auto‐predictionR2with a cross‐validation performance close to that of the original NIPALS algorithm.
High‐throughput statistical screening of antiinfective peptides from natural antibacterial protein repertoire: Chemometric prediction, molecular modeling, and susceptibility analysis
Authors: Sun Guangmei , Leng Liyun , Wang Xiaocui
Published: March 2018

Antibiotic‐resistant bacterial infection (ARBI) is one of the most serious global public health threats. Antiinfective peptides (AIPs) have been recognized as a promising alternative to traditional antibiotics, which can effectively combat the ARBI in a distinct mechanism. In the current study, we attempt to discover new and potent AIPs from the natural antibacterial protein repertoire. Hundreds of antibacterial proteins with sequence length > 50 amino acids are manually curated from literatures and databases, which are then broken into a large pool of 12‐mer peptide fragments. In the procedure, a high‐throughput statistical screening strategy that integrates machine learning, chemometic prediction, and molecular modeling is employed to computationally identify 8 promising AIP hits from the fragment pool, of which 5 are determined by susceptibility test to possess a moderate or high potency against human pathogenic bacteria (20 μg/mL < minimum inhibitory concentration < 90 μg/mL), while the other 3 have only a low or no antibacterial activity (minimum inhibitory concentration > 100 μg/mL). Conformational analysis characterizes that the active AIPs are almost α‐helical (helical rate > 50%), carry many positive charges (net charge > +3), and exhibit an amphipathic profile. Dynamic simulation of a representative membrane‐AIP interaction reveals that the peptide can fluctuate nearby the membrane surface and use its cationic side chains to directly interact with and tightly bind to the anionic hydrophilic layer of bacterial outer membrane.
A Highly Sensitive Fluorogenic Probe for Imaging Glycoproteins and Mucine Activity in Live Cells in the Near‐Infrared Region
Authors: Samaniego Lopez Cecilia , Hebe Martínez Jimena , Uhrig María Laura , Coluccio Leskow Federico , Spagnuolo Carla Cecilia
Published: March 2018

A novel fluorescent molecular probe is reported, which is able to detect glycoproteins, especially mucins, with high sensitivity and with a turn‐on response along with a large Stokes shift (>130 nm), within the biologically active window. The probe contains an aminotricarbocyanine as the fluorescent reporter with a linked benzoboroxole as the recognition unit, which operates through a dynamic covalent reaction between the boronic hemiester residue of the receptor and cis‐diols of the analyte. The superior selectivity of the probe is displayed by the labeling of mucins present in Calu‐3 cells. The new benzoboroxole fluorescent derivative gathers together key properties to make it a highly rated molecular probe: specificity, excellent solubility in water, and off–on near infrared emission. This probe is expected to be an excellent tool for imaging intracellular mucin to evaluate mucus‐related diseases as well as a sensing strategy towards glycosylated structures with a high potential for theranostics approaches in biological samples.
UDP‐GlcNAc Analogues as Inhibitors of O‐GlcNAc Transferase (OGT): Spectroscopic, Computational, and Biological Studies
Authors: Ghirardello Mattia , Perrone Daniela , Chinaglia Nicola , Sádaba David , Delso Ignacio , Tejero Tomas , Marchesi Elena , Fogagnolo Marco , Rafie Karim , van Aalten Daan M. F. , Merino Pedro
Published: March 2018

A series of glycomimetics of UDP‐GlcNAc, in which the β‐phosphate has been replaced by either an alkyl chain or a triazolyl ring and the sugar moiety has been replaced by a pyrrolidine ring, has been synthesized by the application of different click‐chemistry procedures. Their affinities for human O‐GlcNAc transferase (hOGT) have been evaluated and studied both spectroscopically and computationally. The binding epitopes of the best ligands have been determined in solution by means of saturation transfer difference (STD) NMR spectroscopy. Experimental, spectroscopic, and computational results are in agreement, pointing out the essential role of the binding of β‐phosphate. We have found that the loss of interactions from the β‐phosphate can be counterbalanced by the presence of hydrophobic groups at a pyrroline ring acting as a surrogate of the carbohydrate unit. Two of the prepared glycomimetics show inhibition at a micromolar level.
Investigating the efficiency of gas re‐injection process of an oil field using combined integrated field simulation and intelligent proxy model application
Authors: Saeedi Dehaghani Amir Hossein , Rahimi Reza
Published: March 2018

Integrated asset modelling is a novel method to overcome the limitations associated with using individual models. This method integrates all the individual models of a field into a single model that relates all the sub‐models using proper boundary conditions. Reservoir, wells, surface, and economic models of an oil reservoir, under gas re‐injection, are integrated. The main goal of this study is to propose a novel approach in integrated asset modelling. An integrated model of a field is used to study how gas must be distributed among injection wells. Another aim of this study is to understand the effects of 4 input parameters on the Net Present Value (NPV) of the field. The input variables are: oil production rate, gas injection rate, and the distribution of gas between injection wells. A comprehensive model of a field was built. Using the experimental design results, a neuro‐fuzzy logic network was developed. The proxy model predicted the simulation outputs with a reasonable accuracy. The effects of input variables were studied. Oil production has an optimum value of 6050 STBD per well. The optimum fractions of injected gas for injection wells 1 and 2 are 0.4 and 0.6 of total injected gas, respectively. This means that 40 % of the total injection gas must be injected to well 1 to have the maximum NPV. The greater the gas injection rate, the higher NPV is.
Detailed CFD modelling of fast pyrolysis of different biomass types in fluidized bed reactors
Authors: Eri Qitai , Wang Baolu , Peng Jing , Zhao Xinjun , Li Ting
Published: March 2018

In the present study, an Eulerian‐Eulerian computational fluid dynamics (CFD) model, combined with a comprehensive biomass reaction scheme, was used to simulate fast pyrolysis of four different biomass types in the fluidized bed reactors. The study focuses on the influence of biomass components of different biomass types on the yields, formations, and contents of compositions of pyrolysis products. The result showed that the bio‐oil yield of cellulose‐rich biomass was higher than other biomass types, and char was mainly produced by the fast pyrolysis of LIG‐C of biomass. Moreover, the contents of bio‐oil components were affected by the fast pyrolysis of biomass components. Further, the energy recovery coefficient (ERC) of bio‐oil obtained from pyrolysis of different biomass types was also calculated and analyzed in this paper.
Distinct sites in tropomyosin specify shared and isoform‐specific regulation of myosins II and V
Authors: Barua Bipasha , Sckolnick Maria , White Howard D. , Trybus Kathleen M. , Hitchcock‐DeGregori Sarah E.
Published: March 2018

Muscle contraction, cytokinesis, cellular movement, and intracellular transport depend on regulated actin‐myosin interaction. Most actin filaments bind one or more isoform of tropomyosin, a coiled‐coil protein that stabilizes the filaments and regulates interactions with other actin‐binding proteins, including myosin. Isoform‐specific allosteric regulation of muscle myosin II by actin‐tropomyosin is well‐established while that of processive myosins, such as myosin V, which transport organelles and macromolecules in the cell periphery, is less certain. Is the regulation by tropomyosin a universal mechanism, the consequence of the conserved periodic structures of tropomyosin, or is it the result of specialized interactions between particular isoforms of myosin and tropomyosin? Here, we show that striated muscle tropomyosin, Tpm1.1, inhibits fast skeletal muscle myosin II but not myosin Va. The non‐muscle tropomyosin, Tpm3.1, in contrast, activates both myosins. To decipher the molecular basis of these opposing regulatory effects, we introduced mutations at conserved surface residues within the six periodic repeats (periods) of Tpm3.1, in positions homologous or analogous to those important for regulation of skeletal muscle myosin by Tpm1.1. We identified conserved residues in the internal periods of both tropomyosin isoforms that are important for the function of myosin Va and striated myosin II. Conserved residues in the internal and C‐terminal periods that correspond to Tpm3.1‐specific exons inhibit myosin Va but not myosin II function. These results suggest that tropomyosins may directly impact myosin function through both general and isoform‐specific mechanisms that identify actin tracks for the recruitment and function of particular myosins.
Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA
Authors: Wang Ya‐Nan , Bheemanaboina Rammohan R. Yadav , Gao Wei‐Wei , Kang Jie , Cai Gui‐Xin , Zhou Cheng‐He
Published: March 2018

A series of benzimidazole–quinolone hybrids as new potential antimicrobial agents were designed and synthesized. Bioactive assays indicated that some of the prepared compounds exhibited potent antibacterial and antifungal activities. Notably, 2‐fluorobenzyl derivative 5 b (ethyl 7‐chloro‐6‐fluoro‐1‐[[1‐[(2‐fluorophenyl)methyl]benzimidazol‐2‐yl]methyl]‐4‐oxo‐quinoline‐3‐carboxylate) showed remarkable antimicrobial activity against resistant Pseudomonas aeruginosa and Candida tropicalis isolated from infected patients. Active molecule 5 b could not only rapidly kill the tested strains, but also exhibit low toxicity toward Hep‐2 cells. It was more difficult to trigger the development of bacterial resistance of P. aeruginosa against 5 b than that against norfloxacin. Molecular docking demonstrated that 5 b could effectively bind with topoisomerase IV–DNA complexes, and quantum chemical studies theoretically elucidated the good antimicrobial activity of compound 5 b. Preliminary experimental reaction mechanism exploration suggested that derivative 5 b could not intercalate into DNA isolated from drug‐resistant P. aeruginosa, but was able to cleave DNA effectively, which might further block DNA replication to exert powerful bioactivities. In addition, compound 5 b is a promising antibacterial agent with membrane disruption abilities.
Childhood adverse life events, disordered eating, and body mass index in US Military service members
Authors: Bakalar Jennifer L. , Barmine Marissa , Druskin Lindsay , Olsen Cara H. , Quinlan Jeffrey , Sbrocco Tracy , Tanofsky‐Kraff Marian
Published: March 2018

Objective

US service members appear to be at high‐risk for disordered eating. Further, the military is experiencing unprecedented prevalence of overweight and obesity. US service members also report a high prevalence of childhood adverse life event (ALE) exposure. Despite consistent links between early adversity with eating disorders and obesity, there is a dearth of research examining the association between ALE exposure and disordered eating and weight in military personnel.

Method

An online survey study was conducted in active duty personnel to examine childhood ALE history using the Life Stressor Checklist ‐ Revised, disordered eating using the Eating Disorder Examination ‐ Questionnaire total score, and self‐reported body mass index (BMI, kg/m2).

Results

Among 179 respondents, multiple indices of childhood ALE were positively associated with disordered eating. Traumatic childhood ALE and subjective impact of childhood ALE were associated with higher BMI and these associations were mediated by disordered eating.

Discussion

Findings support evaluating childhood ALE exposure among service members with disordered eating and weight concerns. Moreover, findings support the need for prospective research to elucidate these relationships.