bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical Versus Virtual Microscope for Medical Education: A Systematic Review
Authors: Kuo Kuo‐Hsing , Leo Joyce M.
Published: November 2018

Many technological innovations have changed the traditional practice of medical education and clinical practice. Whole slide imaging (WSI) technology provided an unique way of viewing conventional glass slides in histology and pathology laboratories. The WSI technology digitalized glass slide images and made them readily accessible via the Internet using tablets or computers. Users utilized the pan‐and‐zoom function to view digital images of slides, also referred to as the virtual microscope (VM), simulating use of an optical microscope (OM). Several articles have reported various outcomes on the utility of VM in teaching laboratories. Recently, the Royal College of Physicians and Surgeons of Canada certification examinations for anatomical pathologists ha completely adopted VM for the national licensing examination. To better inform medical educators, there is an urgent need for more structured reviews to draw evidence‐based conclusions on the effectiveness of VM and learner’s perceptions, in comparison to OM. The current study provides a descriptive summary of published outcomes using the systematic review approach. In conclusion, medical students’ performance was improved with adoption of VM into the curriculum and recognized as a preferred learning modality, compared to OM. On the contrary, resident learners’ performance was comparable between using OM and VM, with OM being the favored slide‐viewing modality.
Regio/Stereoselective Glycosylation of Diol and Polyol Acceptors in Efficient Synthesis of Neu5Ac‐α‐2,3‐LacNPhth Trisaccharide
Authors: Zhang Ying , Zhao Fu‐Long , Luo Tao , Pei Zhichao , Dong Hai
Published: November 2018

A concise approach to a Neu5Ac‐α‐2,3‐LacNPhth trisaccharide derivative was developed. First, the regio/stereoselective glycosylation between glycoside donors and glucoNPhth diol acceptors was investigated. It was found that the regioselectivity depends not only on the steric hindrance of the C2‐NPhth group and the C6‐OH protecting group of the glucosamine acceptors, but also on the leaving group and protecting group of the glycoside donors. Under optimized conditions, LacNPhth derivatives were synthesized in up to 92 % yield through a regio/stereoselective glycosylation between peracetylated‐α‐galactopyranosyl trichloroacetimidate and p‐methoxyphenyl 6‐O‐tert‐butyldiphenylsilyl‐2‐deoxy‐2‐phthalimido‐β‐d‐glucopyranoside, avoiding the formation of glycosylated orthoesters and anomeric aglycon transfer. Then, the LacNPhth derivative was deacylated and then protected on the primary position by TBDPS to form a LacNPhth polyol acceptor. Finally, the Neu5Ac‐α‐2,3‐LacNPhth derivative was synthesized in 48 % yield through the regio/stereoselective glycosylation between the LacNPhth polyol acceptor and a sialyl phosphite donor. Starting from d‐glucosamine hydrochloride, the target Neu5Ac‐α‐2,3‐LacNPhth derivative was synthesized in a total yield of 18.5 % over only 10 steps.
RiSLnet: Rapid identification of smart mutant libraries using protein structure network. Application to thermal stability enhancement
Authors: Upadhyay Roopali , Kim Jin Young , Hong Eun Young , Lee Sun‐Gu , Seo Joo‐Hyun , Kim Byung‐Gee
Published: November 2018

A key point of protein stability engineering is to identify specific target residues whose mutations can stabilize the protein structure without negatively affecting the function or activity of the protein. Here, we propose a method called RiSLnet (Rapid identification of Smart mutant Library using residue network) to identify such residues by combining network analysis for protein residue interactions, identification of conserved residues, and evaluation of relative solvent accessibility. To validate its performance, the method was applied to four proteins, that is, T4 lysozyme, ribonuclease H, barnase, and cold shock protein B. Our method predicted beneficial mutations in thermal stability with ~62% average accuracy when the thermal stability of the mutants was compared with the ones in the Protherm database. It was further applied to lysine decarboxylase (CadA) to experimentally confirm its accuracy and effectiveness. RiSLnet identified mutations increasing the thermal stability of CadA with the accuracy of ~60% and significantly reduced the number of candidate residues (~99%) for mutation. Finally, combinatorial mutations designed by RiSLnet and in silico saturation mutagenesis yielded a thermally stable triple mutant with the half‐life (T
1/2) of 114.9 min at 58°C, which is approximately twofold higher than that of the wild‐type.
Effects of Ti Doping on the Structural Stability and Enhanced Electrochemical Performance of α‐LiVOPO4
Authors: Lee Seong‐Hun , Ryu Kwang‐Sun
Published: November 2018

Lithium vanadyl phosphate has seven different crystallographic phases. Among them, α‐LiVOPO4 is chosen because of its relatively high energy density and redox voltage of 3.9 V compared to the other phosphates. In this study, Ti4+‐doped α‐LiV1−xTixOPO4 (x = 0.00, 0.003, 0.005, 0.007, and 0.01) was prepared using a sol–gel method to increase the structure stability and electrochemical performance. The triclinic structure with the space group P‐1 was confirmed by X‐ray diffraction, Fourier‐transform infrared spectroscopy, and X‐ray photoelectron spectroscopy. Inductively coupled plasma–optical emission spectroscopy was conducted to determine the precise state. The shape and size of the particles were observed by field‐emission scanning electron microscopy. In situ X‐ray absorption spectroscopy was performed to confirm the structural behavior during the electrochemical reaction. Electrochemical measurements such as cyclic voltammetry and galvanostatic charge–discharge were conducted. α‐LiV1−xTi
xOPO4 (x = 0.003, 0.005, 0.007, and 0.01) showed structural stability during cycling as well as decreased polarization during charge and discharge with the increased diffusion coefficient of lithium ions. α‐LiV0.995Ti0.005OPO4 showed the best cycling stability and rate capability among all the samples examined because Ti doping retained its site to prevent structural collapse.
Process development for an inducible rituximab‐expressing Chinese hamster ovary cell line
Authors: Mellahi Kahina , Cambay Florian , Brochu Denis , Gilbert Michel , Perrier Michel , Ansorge Sven , Durocher Yves , Henry Olivier
Published: November 2018

Inducible mammalian expression systems are becoming increasingly available and are not only useful for the production of cytotoxic/cytostatic products, but also confer the unique ability to uncouple the growth and production phases. In this work, we have specifically investigated how the cell culture state at the time of induction influences the cumate‐inducible expression of recombinant rituximab by a GS‐CHO cell line. To this end, cells grown in batch and fed‐batch cultures were induced at increasing cell densities (1 to 10 × 10
6 cells/mL). In batch, the cell specific productivity and the product yield were found to reduce with increasing cell density at induction. A dynamic feeding strategy using a concentrated nutrient solution applied prior and postinduction allowed to significantly increase the integral of viable cells and led to a 3‐fold increase in the volumetric productivity (1.2 g/L). The highest product yields were achieved for intermediate cell densities at induction, as cultures induced during the late exponential phase (10 × 10
6 cells/mL) were associated with a shortened production phase. The final glycosylation patterns remained however similar, irrespective of the cell density at induction. The kinetics of growth and production in a 2 L bioreactor were largely comparable to shake flasks for a similar cell density at induction. The degree of galactosylation was found to decrease over time, but the final glycan distribution at harvest was consistent to that of the shake flasks cultures. Taken together, our results provide useful insights for the rational development of fed‐batch cell culture processes involving inducible CHO cells. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2742, 2019
Platinum(II) Complexes with 1,10‐Phenanthroline and Hydrophilic Alkoxyacetate Ligands as Potential Antitumor Agents
Authors: Sun Yanyan , Wei Huaixin , Zhang Qiang , Zhao Xin
Published: November 2018

Four platinum complexes, formulated as [Pt(phen)(OCOCH2OR)2] (phen=1,10‐phenanthroline, R=Me, Et, iPr, or tBu), have been synthesized and well characterized by elemental analysis, IR, 1H‐NMR, 13C‐NMR and ESI‐MS spectroscopy. Replacing chloride groups of the precursor Pt(phen)Cl2 with alkoxyacetate anions greatly improved the aqueous solubility and cytotoxicity of the resulting platinum complexes. The in vitro cytotoxicity study revealed that complexes 1–3 were active in vitro towards four human tumor cell lines, especially complex 1 which exhibited prominent in vitro cytotoxic activity against HCT‐116 cell lines comparable to cisplatin and oxaliplatin. Flow cytometry assay indicated that representative complexes 1 and 2 exerted cytotoxicity on HCT‐116 cell lines through inducing cell apoptosis and blocking cell cycle progression in the S or G2/M phases. The interaction of representative complexes with pET28a plasmid DNA was tested by agarose gel electrophoresis, which demonstrated that complexes 1 and 2 were capable of distorting plasmid DNA mainly by covalent binding and degradation effect.
Impact of hyperprolactinemia in a patient with polyautoimmunity
Authors: Rojas Manuel , Rodríguez Yhojan , Ramírez‐Santana Carolina , Anaya Juan‐Manuel
Published: November 2018

Key Clinical Message

Hyperprolactinemia has been proposed as a triggering factor for autoimmune diseases. The increased levels of prolactin could induce an abnormal immune response. Herein, we present a patient with hyperprolactinemia who developed polyautoimmunity. Patient's symptoms were associated with slightly raised levels of prolactin (20‐40 ng/mL) and administration of dopaminergic agonists.
C‐N Bond Formation Catalyzed by Ruthenium Nanoparticles Supported on N‐Doped Carbon via Acceptorless Dehydrogenation to Secondary Amines, Imines, Benzimidazoles and Quinoxalines
Authors: Guo Bin , Li Hong‐Xi , Zhang Shi‐Qi , Young David James , Lang Jian‐Ping
Published: November 2018

Ruthenium nanoparticles (NPs) supported on N‐doped carbon (Ru/N−C) were prepared by the pyrolysis of cis‐Ru(phen)2Cl2 loaded onto carbon powder (VULCAN XC72R) at 800 °C. Ru/N−C NPs (0.2 mol% Ru) selectively catalyzed either acceptorless dehydrogenation coupling (ADC) or auto‐transfer‐hydrogen (ATH) reactions of amines with alcohols to imines and secondary amines. Such selectivity could be controlled by the choice of alkali metal ion associated with the base. Under similar catalytic conditions, the ADC cross‐coupling of diamines with primary alcohols or diols afforded the corresponding benzimidazoles and quinoxalines in good to excellent yields. This catalytic system displayed good activity, recyclability, and wide applicability to a diverse range of substrates.
Resonance Energy Transfer in a Genetically Engineered Polypeptide Results in Unanticipated Fluorescence Intensity
Authors: Seeley Jason P. , Cotlet Mircea , Eagleton Aileen M. , Higashiya Seiichiro , Welch John T.
Published: November 2018

The fluorescence intensity of a C‐terminal acceptor chromophore, N‐(7‐dimethylamino‐4‐methyl coumarin (DACM), increased proportionally with 280 nm irradiation of an increasing number of donor tryptophan residues located on a β‐sheet forming polypeptide. The fluorescence intensity of the acceptor chromophore increased even as the length of the β‐sheet edge approached 256 Å, well beyond the Förster radius for the tryptophan–acceptor chromophore pair. The folding of the peptides under investigation was verified by circular dichroism (CD) and deep UV resonance Raman experiments. Control experiments showed that the enhancement of DACM fluorescence occurred concomitantly with peptide folding. In other control experiments, the DACM fluorescence intensity of the solutions of tryptophan and DACM did not show any enhancement of DACM fluorescence with increasing tryptophan concentrations. Formation of fibrillar aggregates of the substrate peptides prepared for the fluorescence studies was undetectable by thioflavin T (ThT) fluorescence.
Trifluoromethylation of Allenes: An Expedient Access to α‐Trifluoromethylated Enones at Room Temperature
Authors: Brochetta Massimo , Borsari Tania , Gandini Andrea , Porey Sandip , Deb Arghya , Casali Emanuele , Chakraborty Arka , Zanoni Giuseppe , Maiti Debabrata
Published: November 2018

A silver(I) catalyzed regioselective trifluoromethylation of allenes using Langlois's salt (NaOSOCF3) is demonstrated. This transformation enables direct expedient access to α‐trifluoromethylated acroleins, which are valuable synthons for a number of pharmaceuticals and agrochemicals containing vinyl‐CF3 moieties. Versatility of this trifluoromethylation method has been established with good yield and excellent regioselectivity. Preliminary experiments and computational studies were carried out to elucidate the mechanistic insight of this protocol.
Grafting of Polymer Brushes from Xanthate‐Functionalized Silica Particles
Authors: Ohno Kohji , Yahata Yoshikazu , Sakaue Motokazu , Ladmiral Vincent
Published: November 2018

Monodisperse silica particles (SiPs) were surface‐modified with a newly designed silane coupling agent comprising a triethoxysilane and an alkyl halide, namely, 6‐(triethoxysilyl)hexyl 2‐bromopropionate, which was further treated with potassium O‐ethyl dithiocarbonate (PEX) to immobilize xanthate molecules on the particle surfaces. Surface‐initiated macromolecular design via interchange of xanthates (MADIX) polymerization of vinyl acetate (VAc) was conducted with the xanthate‐functionalized SiPs. The polymerization was well controlled and produced SiPs coated with poly(vinyl acetate) (PVAc) with a well‐defined target molar mass and a graft density of about 0.2 chains nm−2. Dynamic light scattering and TEM measurements revealed that the hybrid particles were highly dispersible in good solvents without any aggregation. The PVAc brushes were hydrolyzed with hydrochloric acid to produce poly(vinyl alcohol) brushes on the SiP surfaces. In addition, the number of xanthate molecules introduced on the SiP surfaces could be successfully controlled by adjusting the concentration of PEX. Thus, the SiPs have two functionalities: xanthates able to act as a MADIX chain‐transfer agent and alkyl bromide initiation sites for atom transfer radical polymerization (ATRP). By using these unique bifunctional particles, mixed polymer brushes were constructed on the SiPs by MADIX of VAc followed by ATRP of styrene or methyl methacrylate.
ABC–ABC‐Type Directly meso–meso Linked Porphyrin Dimers
Authors: Higashino Tomohiro , Kurumisawa Yuma , Iiyama Hitomi , Imahori Hiroshi
Published: November 2018

Covalently linked porphyrin oligomers are attractive because of their extended π‐conjugated systems. Among various porphyrin oligomers, directly meso–meso linked porphyrin oligomers exhibit unique photophysical properties due to their strong exciton couplings derived from the alternative orthogonal geometry of the porphyrins. Although their structural and electronic properties can be greatly altered by substituents at meso positions, it is still difficult to introduce different substituents at the meso positions. Thus, it is a challenge to develop general synthetic methodologies for functional porphyrin dimers and oligomers with different substituents at the meso positions. Herein, a general synthetic strategy for ABC–ABC‐type directly meso–meso linked porphyrin dimers by stepwise functionalization starting from 10,15,20‐meso‐free 5‐substituted porphyrin as building block is established. A meso‐ABC–ABC‐type meso–meso‐linked donor–π‐acceptor‐type porphyrin dimer was prepared and exhibited the highest power conversion efficiency (7.91 %) ever reported for dye‐sensitized solar cells based on dimeric orthogonal donor–π‐acceptor‐type organic sensitizers. This synthetic strategy will provide useful guidance for the rational design of functional porphyrin dimers and oligomers for diverse applications.
Crystal Structure of Cytidine Deaminase Human APOBEC3F Chimeric Catalytic Domain in Complex with DNA
Authors: Cheng Chao , Zhang Tianlong , Wang Chunxi , Lan Wenxian , Ding Jianping , Cao Chunyang
Published: November 2018

APOBEC3F (A3F) demonstrates antivirus activity through its A3F‐CD2 domain catalyzing deamination of cytidine in target motif 5’‐TC in viral cDNA during reverse transcription. But structural basis is unclear. Previously, chimeric A3F‐CD2 (i.e., A3Fc‐CD2, where residues 195—217 of A3F‐CD2 were replaced with residues 197—221 of A3G‐CD2) was found soluble with deamination activity. Here, we report crystal structures of A3Fc‐CD2 in complexes with single‐stranded DNA (5’‐ATTTT5C6A7A8T9T‐3’ and 5’‐ATTTT5C6A7A8C9T‐3’) at resolutions of 1.98 Å and 2.30 Å, respectively. They demonstrate that one molecular DNA binds two A3Fc‐CD2 molecules (monomers A and B) at two sites, distinct from the reported complex structure of human A3F‐CD2 with a 10‐dT DNA. The first site is formed by residues Tyr333, Lys358 and Tyr359 in monomer A, far away from Zn2+ binding motif, interacting with bases dT5, dC6 and dA7 through π‐π stacking and hydrogen bonds. The second site is composed of Trp277, Y307YFW310 near to Zn2+ binding region in monomer B, interacting with base dA8, mainly through π‐π stacking and hydrophobic interactions, determining deamination preference of DNA sequence. Subsequent biochemical investigations further confirm the contribution of these residues to DNA binding and deamination activities. These studies are helpful to understand the mechanism how A3F‐CD2 catalyzes cytidine deamination.
Relationships between neuronal birthdates and tonotopic positions in the mouse cochlear nucleus
Authors: Shepard Austin R. , Scheffel Jennifer L. , Yu Wei‐Ming
Published: November 2018

Tonotopy is a key anatomical feature of the vertebrate auditory system, but little is known about the mechanisms underlying its development. Since date of birth of a neuron correlates with tonotopic position in the cochlea, we investigated if it also correlates with tonotopic position in the cochlear nucleus (CN). In the cochlea, spiral ganglion neurons are organized in a basal to apical progression along the length of the cochlea based on birthdates, with neurons in the base (responding to high‐frequency sounds) born early around mouse embryonic day (E) 9.5–10.5, and those in the apex (responding to low‐frequency sounds) born late around E12.5‑13.5. Using a low‐dose thymidine analog incorporation assay, we examine whether CN neurons are arranged in a spatial gradient according to their birthdates. Most CN neurons are born between E10.5 ānd E13.5, with a peak at E12.5. A second wave of neuron birth was observed in the dorsal cochlear nucleus (DCN) beginning on E14.5 and lasts until E18.5. Large excitatory neurons were born in the first wave, and small local circuit neurons were born in the second. No spatial gradient of cell birth was observed in the DCN. In contrast, neurons in the anteroventral cochlear nucleus (AVCN) were found to be arranged in a dorsal to ventral progression according to their birthdates, which are aligned with the tonotopic axis. Most of these AVCN neurons are endbulb‐innervated bushy cells. The correlation between birthdate and tonotopic position suggests testable mechanisms for specification of tonotopic position.
Hydrodynamic Limit and Viscosity Solutions for a Two‐Dimensional Growth Process in the Anisotropic KPZ Class
Authors: Legras Martin , Toninelli Fabio Lucio
Published: November 2018

We study a two‐dimensional stochastic interface growth model that is believed to belong to the so‐called anisotropic KPZ (AKPZ) universality class [4,5]. It can be seen either as a two‐dimensional interacting particle process with drift that generalizes the one‐dimensional Hammersley process [1,24], or as an irreversible dynamics of lozenge tilings of the plane [5,29]. Our main result is a hydrodynamic limit: the interface height profile converges, after a hyperbolic scaling of space and time, to the solution of a nonlinear first‐order PDE of Hamilton‐Jacobi type with nonconvex Hamiltonian (nonconvexity of the Hamiltonian is a distinguishing feature of the AKPZ class). We prove the result in two situations: (1) for smooth initial profiles and times smaller than the time Tshock when singularities (shocks) appear or (2) for all times, including t > Tshock, if the initial profile is convex. In the latter case, the height profile converges to the viscosity solution of the PDE. As an important ingredient, we introduce a Harris‐type graphical construction for the process. © 2018 Wiley Periodicals, Inc.
Gaussian Complex Zeros on the Hole Event: The Emergence of a Forbidden Region
Authors: Ghosh Subhroshekhar , Nishry Alon
Published: November 2018

Consider the Gaussian entire function

urn:x-wiley:00103640:media:cpa21800:cpa21800-math-0001

where {ξk} is a sequence of independent standard complex Gaussians. This random Taylor series is distinguished by the invariance of its zero set with respect to the isometries of the plane ℂ. It has been of considerable interest to study the statistical properties of the zero set, particularly in comparison to other planar point processes.

We show that the law of the zero set, conditioned on the function Fℂ having no zeros in a disk of radius r and normalized appropriately, converges to an explicit limiting Radon measure on ℂ as r → ∞. A remarkable feature of this limiting measure is the existence of a large “forbidden region” between a singular part supported on the boundary of the (scaled) hole and the equilibrium measure far from the hole. In particular, this answers a question posed by Nazarov and Sodin, and is in stark contrast to the corresponding result of Jancovici, Lebowitz, and Manificat in the random matrix setting: there is no such forbidden region for the Ginibre ensemble. © 2018 Wiley Periodicals, Inc.
Quasiconvex Elastodynamics: Weak‐Strong Uniqueness for Measure‐Valued Solutions
Authors: Koumatos Konstantinos , Spirito Stefano
Published: November 2018

A weak‐strong uniqueness result is proved for measure‐valued solutions to the system of conservation laws arising in elastodynamics. The main novelty brought forward by the present work is that the underlying stored‐energy function of the material is assumed to be strongly quasiconvex. The proof employs tools from the calculus of variations to establish general convexity‐type bounds on quasiconvex functions and recasts them in order to adapt the relative entropy method to quasiconvex elastodynamics. © 2018 Wiley Periodicals, Inc.
Well‐Posedness and Global Behavior of the Peskin Problem of an Immersed Elastic Filament in Stokes Flow
Authors: Mori Yoichiro , Rodenberg Analise , Spirn Daniel
Published: November 2018

We consider the problem of a one‐dimensional elastic filament immersed in a two‐dimensional steady Stokes fluid. Immersed boundary problems in which a thin elastic structure interacts with a surrounding fluid are prevalent in science and engineering, a class of problems for which Peskin has made pioneering contributions. Using boundary integrals, we first reduce the fluid equations to an evolution equation solely for the immersed filament configuration. We then establish local well‐posedness for this equation with initial data in low‐regularity Hölder spaces. This is accomplished by first extracting the principal linear evolution by a small‐scale decomposition and then establishing precise smoothing estimates on the nonlinear remainder. Higher regularity of these solutions is established via commutator estimates with error terms generated by an explicit class of integral kernels. Furthermore, we show that the set of equilibria consists of uniformly parametrized circles and prove nonlinear stability of these equilibria with explicit exponential decay estimates, the optimality of which we verify numerically. Finally, we identify a quantity that respects the symmetries of the problem and controls global‐in‐time behavior of the system. © 2018 Wiley Periodicals, Inc.
Isolation and Culture of Microglia
Authors: Bohlen Christopher J. , Bennett F. Chris , Bennett Mariko L.
Published: November 2018

Microglia represent 5‐10% of cells in the central nervous system and contribute to the development, homeostasis, injury, and repair of neural tissues. As the tissue‐resident macrophages of the central nervous system, microglia execute core innate immune functions such as detection of pathogens/damage, cytokine secretion, and phagocytosis. However, additional properties that are specific to microglia and their neural environment are beginning to be appreciated. This article describes approaches for purification of microglia by fluorescence‐activated cell sorting using microglia‐specific surface markers and for enrichment of microglia by magnetic sorting and immunopanning. Detailed information about culturing primary microglia at various developmental stages is also provided. Throughout, we focus on special considerations for handling microglia and compare the relative strengths or disadvantages of different protocols. © 2018 by John Wiley & Sons, Inc.
Next‐generation amplicon TRB locus sequencing can overcome limitations of flow‐cytometric Vβ expression analysis and confirms clonality in all T‐cell prolymphocytic leukemia cases
Authors: Kotrova Michaela , Novakova Michaela , Oberbeck Sebastian , Mayer Petra , Schrader Alexandra , Knecht Henrik , Hrusak Ondrej , Herling Marco , Brüggemann Monika
Published: November 2018

T‐cell receptor (TCR) β repertoire analysis can distinguish monoclonal from polyclonal T‐cell proliferations and crucially aid in the diagnosis of T‐cell malignancies. TCR repertoire can be assessed either by flow cytometry (FCM), or by molecular genetic techniques. We compared the results of parallel analyses of Vβ expression by FCM and TRB rearrangements by DNA‐based next‐generation sequencing (NGS) in 80 diagnostic peripheral blood samples of patients with T‐cell prolymphocytic leukemia (T‐PLL) for (1) the diagnosis of clonality and (2) the assessment of dominant Vβ usage. FCM‐based analysis of the surface expression was performed using the IOTest Beta Mark kit. The NGS‐based analysis employed the multiplex Biomed‐2 VB‐JB primers. In all the samples, one or two clonal TRB rearrangements were detected by NGS. Although a dominant Vβ domain usage was detected by FCM in only 41/80 (51%) samples, clonality was suspected in all of them. In a total of 12 cases, the FCM missed the clone detected by NGS, despite theoretical coverage by the antibodies, the functionality of the rearrangement, and the expression of TCRαβ on the cell surface. Partly overlapping with those cases, FCM discovered predominant Vβ usage in the T‐PLL population that differed from the one detected by NGS in 10 cases. Overall, the concordant NGS and FCM results were obtained on 61/80 (76%) of samples. We conclude that NGS‐based TRB analysis can overcome certain limitations of FCM‐based analysis by the identification of both productive and nonproductive rearrangements and by covering the whole Vβ spectrum. Currently available FCM analysis of Vβ expression lacks this breadth but has advantages, such as parallel immunophenotyping and a more accurate quantification of the Vβ usage. © 2018 International Society for Advancement of Cytometry
Combining a Phenanthroline Moiety with Peralkylated Guanidine Residues: Homometallic CuII, NiII and ZnII Halide Complexes with Site‐Differentiating Janus Head Ligands
Authors: Ortmeyer Jochen , Vukadinovic Yannik , Neuba Adam , Flörke Ulrich , Henkel Gerald
Published: November 2018

The unique core portion of Janus head pro‐ligands based on a tailored phenanthroline‐bis(guanidine) architecture has been utilized to generate a multiplicity of homometallic copper(II), nickel(II) and zinc(II) complexes terminated by halide constituents. The bis‐bidentate nitrogen donor ligands provide coordination sites with metal‐differentiating properties which can be loaded successively starting with the phenanthroline interface as can be demonstrated by mononuclear species which form under metal deficient conditions. Furthermore, depending on both the alkylation and metalation stage of the guanidine residues comprising variants with tetramethyl‐, tetraethyl‐, dimethylethylene‐, and dipentylene‐guanidino functionalities, a unique diversity of bi‐ and tetranuclear complexes with multifarious coordination geometries is accessible. The resulting complexes were characterized by low‐temperature X‐ray crystallography, and their redox behavior and magnetochemical properties in solution were analyzed via cyclic voltammetric and NMR techniques (Evans method). In this way, a remarkable equilibrium between the neutral phenanthroline‐bis(guanidine) copper(II) complex (X2CuII‐phenGua‐CuIIX2) and the radical monocationic phenanthroline‐bis(guanidine) copper(I)/copper(II) [X2CuII‐phenGua+·‐(CuIX2)–] species was identified which affects the chemical characteristics of the presented compounds in solution.
Ionic Liquid‐based Microchannels for Highly Sensitive and Fast Amperometric Detection of Toxic Gases
Authors: Ge Mengchen , Hussain Ghulam , Hibbert D. Brynn , Silvester Debbie S. , Zhao Chuan
Published: November 2018

Ionic liquid (IL)‐based microchannels sensors have been fabricated and employed for the detection of toxic ammonia (NH3) and hydrogen chloride (HCl) gases, with enhanced sensitivity and response times compared to conventional electrodes. Electrochemical techniques were employed to understand the behaviour of these highly toxic gases in two ionic liquids, [C4mpyrr][NTf2] and [C2mim][NTf2], on a gold modified microchannels electrode. The limits of detection (LODs) obtained in [C4mpyrr][NTf2] for NH3 (3.7 ppm) and in [C2mim][NTf2] for HCl (3.6 ppm) were lower than the current Occupational Safety and Health Administration Permissible Exposure Limit (OSHA PEL) for the two gases (25 ppm for NH3 and 5 ppm for HCl). The response time of the sensor is 15 s with a sensitivity of 143 nA ppm−1 and 14 nA ppm−1 for HCl and NH3, respectively. These results demonstrate the superiority of IL‐based microchannels sensors for detecting toxic gases, when compared to commercially available sensors or traditional IL‐based sensor designs, where high sensitivity or fast response time is still a challenge.
Dimethyl Sulfoxide Solvent Engineering for High Quality Cation‐Anion‐Mixed Hybrid and High Efficiency Perovskite Solar Cells
Authors: He X. , Wu J. , Wu T. , Lan Z. , Huang M.
Published: November 2018

High‐quality perovskite thin film is one of the most key factors as to the state‐of the‐art perovskite solar cells (PSCs). Solvent‐engineering has caused widespread concern in the aspects of improving the high‐quality perovskite layers. For the preparation of the cation‐anion‐mixed perovskite Cs0.05(MA0.17FA0.83)0.95Pb(I0.83Br0.17)3, the influence of the perovskite precursor composition on the quality of perovskite layers is not clear yet. Here, we conduct a systematic study on the solution composition by changing the molar ratio for lead (Pb) to dimethyl sulfoxide (DMSO). Significantly, we obtain a dense, uniform, long charge carrier lifetime perovskite thin film, which facilitates charge transportation and reduces charge recombination in PSCs and thus considerably improves the device performance. Based on solvent engineering of DMSO and replacing toxic solvent chlorobenzene with green solvent ethyl acetate, a high‐quality perovskite layer is prepared and the device based on green solvent process exhibits a power conversion efficiency (PCE) of 19.23 %.
Regional and network properties of white matter function in Parkinson's disease
Authors: Ji Gong‐Jun , Ren Cuiping , Li Ying , Sun Jinmei , Liu Tingting , Gao Yaxiang , Xue Dongzhang , Shen Longshan , Cheng Wen , Zhu Chunyan , Tian Yanghua , Hu Panpan , Chen Xianwen , Wang Kai
Published: November 2018

Parkinson's disease (PD) is a neurodegenerative disorder with dysfunction in cortices as well as white matter (WM) tracts. While the changes to WM structure have been extensively investigated in PD, the nature of the functional changes to WM remains unknown. In this study, the regional activity and functional connectivity of WM were compared between PD patients (n = 57) and matched healthy controls (n = 52), based on multimodel magnetic resonance imaging data sets. By tract‐based spatial statistical analyses of regional activity, patients showed decreased structural‐functional coupling in the left corticospinal tract compared to controls. This tract also displayed abnormally increased functional connectivity within the left post‐central gyrus and left putamen in PD patients. At the network level, the WM functional network showed small‐worldness in both controls and PD patients, yet it was abnormally increased in the latter group. Based on the features of the WM functional connectome, previously un‐evaluated individuals could be classified with fair accuracy (73%) and area under the curve of the receiver operating characteristics (75%). These neuroimaging findings provide direct evidence for WM functional changes in PD, which is crucial to understand the functional role of fiber tracts in the pathology of neural circuits.
Circulating Oxidized Low‐Density Lipoprotein is a Strong Risk Factor for the Early Stage of Coronary Heart Disease
Authors: Zhang Qiang , Ai Yongshun , Dong Huiqiu , Wang Junsong , Xu Li
Published: November 2018

This study aimed to detect the circulating oxidized low‐density lipoprotein (ox‐LDL) levels of controls and patients with stable angina pectoris (SAP), unstable angina pectoris (UAP), and acute myocardial infarction (AMI) and also to investigate the correlation with the severity of coronary heart disease (CHD). Plasma levels of circulating ox‐LDL‐4E6, malondialdehyde (MDA), high‐sensitivity C‐reactive protein (hs‐CRP), total cholesterol, high‐density lipoprotein cholesterol, LDL cholesterol, apoprotein A, apoprotein B, and lipoprotein (a) (Lp(a)) were measured in 99 participants who underwent coronary angiography. The plasma ox‐LDL level was significantly higher in patients with CHD than in controls (P = 0.000). However, it was lower in the UAP and AMI groups than in the SAP group (P = 0.000). The lipid peroxide level (MDA) showed a significant difference among all groups (P = 0.000). It increased significantly in patients with CHD. The Lp(a) and hs‐CRP levels were significantly higher in patients with CHD (P = 0.000 and 0.000, respectively). No difference in Lp(a) was found among the SAP, UAP, and AMI groups (P = 0.296). In patients with CHD, the plasma ox‐LDL correlated negatively with hs‐CRP (P = 0.011), and serum MDA correlated positively with hs‐CRP (P = 0.004). The plasma ox‐LDL could be used as a strong risk factor for the early stage but not the advanced stage of CHD. Hs‐CRP may bound and transfer ox‐LDL to macrophages. © 2018 IUBMB Life, 71(1):277–282, 2019
Multispectral photoacoustic imaging of cancer with broadband CuS nanoparticles covering both near‐infrared I and II biological windows
Authors: Liu Yubin , Gao Duyang , Xu Mengze , Yuan Zhen
Published: November 2018

In this study, CuS nanoparticles with optical absorption covering both near‐infrared I (NIR‐I) and NIR‐II biological windows were prepared and served as the contrast agents for multispectral photoacoustic imaging. The physiological parameters including concentrations of deoxyhemoglobin and oxyhemoglobin as well as the water content in the tumor location were quantified based on the multispectral photoacoustic reconstruction method. More importantly, the concentration of CuS nanoparticles/drugs accumulated in the tumor was also recovered after intravenously injection, which are essential for image‐guided cancer theranostics. In addition, phantom and in vivo experimental tests were performed to inspect and compare the imaging depth and signal‐to‐noise ratio (SNR) between the two NIR biological windows. Interestingly, we discovered that a higher SNR was obtained in the NIR‐II window than that in the NIR‐I window. Meanwhile, the multispectral imaging results also demonstrated that the imaging contrast and penetration depth in the NIR‐II window were also significantly improved as compared to those from the NIR‐I window.
Two‐dimensional correlation analysis of Raman microspectroscopy of subcellular interactions of drugs in vitro
Authors: Byrne Hugh J. , Bonnier Franck , Farhane Zeineb
Published: November 2018

Two‐dimensional (2D) correlation analysis is explored to data mine the time evolution of the characteristic Raman microspectroscopic signatures of the subcellular responses of the nucleoli of human lung cancer cells to the uptake of doxorubicin. A simulated dataset of experimental control spectra, perturbed with systematically time‐dependent spectral changes, constituted by a short‐term response which represents the initial binding of the drug in the nucleolus, followed by a longer term response of the organelle metabolism, is used to validate the analysis protocol. Applying 2D correlation analysis, the in phase, synchronous correlation coefficients are seen to contain contributions of both response profiles, whereas they can be independently extracted from the out of phase, asynchronous correlation coefficients. The methodology is applied to experimental data of the uptake of doxorubicin in human lung cell lines to differentiate the signatures of chemical binding and subsequent cellular response.
Theoretical study of lanthanide‐based in vivo luminescent probes for detecting hydrogen peroxide
Authors: Hatanaka Miho , Wakabayashi Tomonari
Published: November 2018

The 4f‐4f emissions from lanthanide trication (Ln3+) complexes are widely used in bioimaging probes. The emission intensity from Ln3+ depends on the surroundings, and thus, the design of appropriate photo‐antenna ligands is indispensable. In this study, we focus on two probes for detecting hydrogen peroxide, for which emission intensities from Tb3+ are enhanced chemo‐selectively by the H2O2‐mediated oxidation of ligands. To understand the mechanism, the Gibbs free energy profiles of the ground and excited states related to emission and quenching are computed by combining our approximation—called the energy shift method—and density functional theory. The different emission intensities are mainly attributed to different activation barriers for excitation energy transfer from the ligand‐centered triplet (T1) to the Tb3+‐centered excited state. Additionally, quenching from T1 to the ground state via intersystem crossing was inhibited by intramolecular hydrogen bonds only in the highly emissive Tb3+ complexes. © 2018 Wiley Periodicals, Inc.
The role of nervous system in adaptive response of bone to mechanical loading
Authors: Qiao Yini , Wang Yang , Zhou Yimei , Jiang Fulin , Huang Tu , Chen Liujing , Lan Jingxiang , Yang Cai , Guo Yutong , Yan Shanyu , Wei Zhangming , Li Juan
Published: November 2018

Bone tissue is remodeled through the catabolic function of the osteoclasts and the anabolic function of the osteoblasts. The process of bone homeostasis and metabolism has been identified to be co‐ordinated with several local and systemic factors, of which mechanical stimulation acts as an important regulator. Very recent studies have shown a mutual effect between bone and other organs, which means bone influences the activity of other organs and is also influenced by other organs and systems of the body, especially the nervous system. With the discovery of neuropeptide (calcitonin gene‐related peptide, vasoactive intestinal peptide, substance P, and neuropeptide Y) and neurotransmitter in bone and the adrenergic receptor observed in osteoclasts and osteoblasts, the function of peripheral nervous system including sympathetic and sensor nerves in bone resorption and its reaction to on osteoclasts and osteoblasts under mechanical stimulus cannot be ignored. Taken together, bone tissue is not only the mechanical transmitter, but as well the receptor of neural system under mechanical loading. This review aims to summarize the relationship among bone, nervous system, and mechanotransduction.
Identification and characterization of circular RNAs involved in mechanical force‐induced periodontal ligament stem cells
Authors: Wang Hong , Feng Cheng , Jin Ye , Tan Wanye , Wei Fulan
Published: November 2018

Circular RNAs (circRNAs) play critical roles in signal transduction during cell proliferation, differentiation, and apoptosis in a posttranscriptional manner. Recently, circRNAs have been proved to be a large class of animal RNAs with regulatory potency. However, whether circRNAs can respond to mechanical force (MF) and impact on human periodontal ligament stem cells (PDLSCs) and the orthodontic tooth movement (OTM) process remain unknown. Here, we investigated the circRNAs expression patterns in PDLSCs induced by MF and found that circRNAs were responsive to the MF in PDLSCs. Through the valid reads’ distribution analysis, we found that the majority of reads in both the control PDLSCs and the MF‐induced PDLSCs were distributed in exons. Then we analyzed Gene Ontology terms of genes that overlap with or are neighbors of the stress‐responsive circRNAs and found unique enrichment patterns in biological processes, molecular function, and cellular component of PDLSCs. Next, we predicted the possible functions of circRNAs through circRNAs–miRNAs networks. We found that one circRNA may regulate one or several miRNA/miRNAs and one miRNA may interact with one or multiple circRNA/circRNAs. Importantly, a number of circRNAs were predicted to directly or indirectly regulate miRNAs‐mediated osteogenic differentiation in mesenchymal stem cells. For instance, circRNA3140 was highly and widely associated with microRNA‐21, which plays a critical role in MF‐induced osteogenic differentiation of PDLSCs. Taken together, these findings reveal a previously unrecognized mechanism that MF can induce the expression changes of circRNAs in PDLSCs, which may modulate the OTM process and the alveolar bone remodeling.
HIF‐1α promotes bone marrow stromal cell migration to the injury site and enhances functional recovery after spinal cord injury in rats
Authors: Han Xiaoguang , Chen Yong , Liu Yajun , Wang Zhuo , Tang Guoqing , Tian Wei
Published: November 2018

Background

Spinal cord injury (SCI) is a severe health problem worldwide, and efficacious strategies to properly repair SCI have not yet been developed. Recently, gene and cell therapies as alternative treatments for SCI have been proposed to comprise safe and promising strategies.

Methods

The present study investigated the therapeutic effects and underlying mechanisms of hypoxia‐inducible factor‐1α carried in recombinant adenovirus (Adv‐HIF‐1α), as administered immediately after SCI in adult rats.

Results

Adv‐HIF‐1α‐treated animals showed better functional recovery and smaller cavity volume than those in the vehicle‐treated control group. Both the numbers of green fluorescent protein‐labeled bone marrow stromal cells (GFP‐BMSCs) and cells double‐positive for GFP and a cell lineage marker (NeuN) in the injured spinal cord were larger in the Adv‐HIF‐1α‐treated group. The expression levels of neurotrophins such as neurotrophin‐3 and brain‐derived neurotrophic factor were also higher in the Adv‐HIF‐1α‐treated group.

Conclusions

Adv‐HIF‐1α improves functional recovery in rats with SCI, and the underlying mechanism may be related to the mobilization of BMSCs to the injured area and higher expression levels of neurotrophin‐3 and brain‐derived neurotrophic factor.
The Impact of Cash Transfer Programmes on Youth and Adult Labour Supply: Evidence from Lesotho and the Philippines
Authors: Porreca Eleonora , Rosati Furio C.
Published: November 2018

This study analyses the effect of cash transfers, aimed to increase children's human capital, on youth and adult labour supply. We provide novel results from the evaluation of two programmes: the conditional cash transferPantawidin the Philippines and the unconditional cash transferChild Grant Programmein Lesotho. The transfers did not discourage youth and adult work. However, marginal adjustments emerged: the Child Grant Programme decreased youth and adult occasional work, representing the last resort to cope with income vulnerability; the Pantawid did not influence youth work but increase adult wage work, with a reduction of family work, indicating that the transfer decreased transaction costs associated with labour market access. © 2018 John Wiley & Sons, Ltd.
A practitioner's guide to designing employee surveys
Authors: Akhuly Ajanta , Bhardwaj Sumedha , Shandilya Sandeep M.
Published: November 2018

Human resources professionals have long used employee surveys to help them gain perspective on the many facets of organizational life. Often such surveys are conducted in‐house, without the help of external experts. Based on academic research and established psychometric principles, the step‐by‐step approach presented here focuses on the conceptual development, design, creation, and statistical testing of questionnaires. This process offers human resources professionals a blueprint for creating robust survey questionnaires that yield accurate and useful data.
Physical and chemical behaviour of Nabali Mohassan single‐cultivar olive oil during prolonged storage
Authors: Snouber Jehan A , Abdelraziq Issam , Abu‐Jafar Mohammed , Zyoud Ahed , Hilal Hikmat , Pasqualone Antonella
Published: November 2018

BACKGROUND

The effect of storage time on the fluorescence emission intensity and physico‐chemical properties of olive oil from the Palestinian cultivar Nabali Mohassan was investigated. Olive oil samples stored up to 7 years were obtained from different olive orchards in Palestine, where prolonged storage is still in use.

RESULTS

As a result of oxidation, all fluorescent minor compounds (tocopherols, chlorophylls, pheophytins and phenolic compounds) of olive oil significantly decreased as the storage time increased, whereas viscosity increased (P < 0.05). Until 1 year of storage, the physico‐chemical properties of olive oil samples were within the limits of both Palestinian and European quality standards, and minor compounds, although affected by a marked decrease compared to freshly produced oil, were still detectable. After 5 years, a 90% decrease of the fluorescence attributed to tocopherols occurred and, after 7 years, phenolics reached a loss of 90%.

CONCLUSION

The analysis of fluorescence, together with other physical measures, was demonstrated to be a useful tool for monitoring oil aging. This is the first report on fluorescent minor compounds of oils obtained from Nabali Mohassan olive cultivar. A better knowledge of this single‐cultivar oil could enhance the adoption of the best practices by producers, improving the whole production chain. © 2018 Society of Chemical Industry