bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversible and Irreversible Reactions of Trimethylaluminum with Common Organic Functional Groups as a Model for Molecular Layer Deposition and Vapor Phase Infiltration
Authors: Yang Fan , Brede Jens , Ablat Hayrensa , Abadia Mikel , Zhang Lianbing , Rogero Celia , Elliott Simon D. , Knez Mato
Published: May 2017

Organic–inorganic hybrid materials are of great demand not at least for their enormous application potential in flexible devices. Atomic or molecular layer deposition (ALD or MLD) and vapor phase infiltration (VPI) offer novel pathways for the fabrication of such hybrids, but a clear understanding of the chemistry between the vaporized precursors and functional molecules is still lacking. In this work, the interactions between trimethylaluminum (TMA) and the organic functional groups OH, NH2, and NO2 in the respective substituted phenyls, as well as their stability upon exposure to air are investigated. The experimental evidence agrees with theoretically predicted reaction pathways, showing that TMA initially binds to Lewis basic atoms of the investigated functional groups. Depending on the reaction energy barriers, the interaction between TMA and the investigated functional groups may result in either stable chemical bonding or intermediates that decompose upon exposure to humidity. This investigation contributes to the understanding of ALD/MLD and VPI processes at a molecular level and will support a better process optimization.
Effect of blast furnace slag content on mechanical and slurry abrasion behavior of needle‐punched nonwoven fabric reinforced epoxy composites
Authors: Patnaik Prabina Kumar , Biswas Sandhyarani
Published: May 2017

This article reports on mechanical and slurry abrasion response of a new class of material developed by reinforcement of blast furnace slag (BFS) in needle‐punched nonwoven polyester fabric epoxy composites. These epoxy‐based composites are prepared by the hand‐lay‐up technique with the variation of BFS content (0, 5, 10, and 15 wt. %) and at constant fiber loading. It is observed that the mechanical properties of the composites are improved significantly with the incorporation of filler. However, the properties like tensile, flexural and inter‐laminar shear strength are reduced beyond 10 wt. % of filler loading. Abrasive wear behavior of these composites is studied in the slurry environment by a slurry abrasion test rig (ASTM G105). The specific wear rate of composites under a steady‐state condition with respect to normal load and sliding velocity is found to decrease with the increase in filler loading. Further, experimental design through Taguchi's L16 orthogonal array is applied to determine the optimal parametric combination which reduces the wear rate. The parametric combination among sliding velocity of 0.93 m/s, normal load of 30 N, sliding distance of 600 m, silica sand size of 100 μm and filler loading of 5 wt. %, produces an optimum specific wear rate. The morphological study is conducted on abraded composite surfaces by using scanning electron microscopy (SEM) and possible wear mechanisms responsible for wear have been discussed.
Investigation of Promising Air Electrode for Realizing Ultimate Lithium Oxygen Battery
Authors: Luo Wen‐Bin , Gao Xuan‐Wen , Chou Shu‐Lei , Kang Yong‐Mook , Wang Jia‐Zhao , Liu Hua‐Kun , Dou Shi‐Xue
Published: May 2017

The non‐aqueous lithium oxygen battery has been considered as one of the most promising energy storage systems owing to its potentially high energy density, exceeding that of any other existing storage system for storing sustainable and clean energy. The success of Li‐O2 batteries could efficiently reduce greenhouse gas emissions and the consumption of non‐renewable fossil fuels. How to achieve high round‐trip efficiency, high capacity, and satisfactory cycling performance, however, is still a great challenge for the lithium oxygen battery. Thus, this report will point out what factors will affect the electrochemical performance and will aim to describe how to increase the electrochemical performance by air electrode optimization. Based on recent achievements, several approaches to solving this problem, such as synthesizing electrocatalysts with high catalytic activity and designing appropriate air electrode structures, are described in details. Also, recent progress associated with novel air electrode designs and understanding the reaction process is discussed.
Densely Packed Random Quarterpolymers Containing Two Donor and Two Acceptor Units: Controlling Absorption Ability and Molecular Interaction to Enable Enhanced Polymer Photovoltaic Devices
Authors: Kang So‐Huei , Kumari Tanya , Lee Sang Myeon , Jeong Mingyu , Yang Changduk
Published: May 2017

Dithienyldiketopyrrolopyrrole (DPP2T) and thieno[3,2‐b]thiophene (TT) building blocks, enabling a large intermolecular overlap through π–π stacking, into an amorphous‐like polymer composed of benzo(1,2‐b:4,5‐b′)dithiophene (BDT) and fluorinated thieno[3,4‐b]thiophene (QTT), are introduced. Herein, through the variation of relative compositions of DPP2T‐TT and BDT‐QTT in the polymer backbone, the synthesis and characterization of a series of condensed random 2D‐2A “quarterpolymers” with two reference alternating copolymers are reported. The best power conversion efficiency (PCE) of 9.45% is achieved for the optimum composition due to the synergistic effects such as improved photon absorption and reduced recombination loss, and optimized blend morphology via a change in the crystallinity and orientation of the blend films compared to the alternating copolymers. Moreover, by isolating higher molecular weight and narrower polydispersity fractions of the quarterpolymer via a marginal solvent‐soaking technique, the PCE is further boosted to 10.30%, which is among the highest PCE reported to date for random polymer‐based PSCs. Therefore, this simple 2D‐2A strategy, reported for the first time, should be extended to numerous quaterpolymer systems, greatly accelerating random polymer systems toward further improving PSCs.
Alterations in metabolic patterns have a key role in diagnosis and progression of primrose syndrome
Authors: Casertano Alberto , Fontana Paolo , Hennekam Raoul C. , Tartaglia Marco , Genesio Rita , Dieber Tina Barbaro , Ortega Lucia , Nitsch Lucio , Melis Daniela
Published: May 2017

Primrose syndrome is characterized by unusual facial features, macrocephaly, intellectual disability, enlarged, and calcified external ears, sparse body hair, and distal muscle wasting. Nine patients have been described in the literature. The disorder is due to missense mutations in ZBTB20. Here we describe one newly diagnosed 18‐month‐old patient and provide 10 year follow‐up of an earlier reported patient, highlighting the progression and complexity of the disorder. Metabolic studies showed reduced glucose tolerance with prevalence of amino acids and fatty acids catabolism, ketogenesis, and gluconeogenesis, resulting in a Krebs cycle reversion.
Somatic Mosaicism of PCDH19 in a male with early infantile epileptic encephalopathy and review of the literature
Authors: Perez Dorian , Hsieh David T. , Rohena Luis
Published: May 2017

Early infantile epileptic encephalopathy‐9 (EIEE9) linked to mutations of the PCDH19 gene on the X chromosome was once thought to only affect females. Clinical features of the mutation include early onset of variable types and frequency of recurrent cluster of seizures, mild to profound intellectual disability, autistic traits, psychiatric features, and behavioral disturbances. PCDH19 pathogenic variants usually occur via an unusual X‐linked pattern where heterozygous females are affected, but hemizygous males are asymptomatic. Somatic mosaic males for PCDH19 mutations are affected with EIEE9; since this discovery, four somatic mosaic males have been reported. We report the fifth confirmed male with somatic mosaicism of a novel pathogenic variant c.2147+2 T>C located in the splice site of Intron 1 of the PCDH19 gene, which continues to support that cellular interference is responsible for the pathogenic mechanism. The importance of our report is to provide significant knowledge about this rare cause of epilepsy in males, guide subsequent functional studies on males portraying an EIEE9 phenotype that have been potentially misdiagnosed, targeted therapeutic approaches, and further elucidation of this complex and interesting genetic disorder.
Endoplasmic reticulum retention of xylosyltransferase 1 (XYLT1) mutants underlying Desbuquois dysplasia type II
Authors: Al‐Jezawi Nesreen K. , Ali Bassam R. , Al‐Gazali Lihadh
Published: May 2017

Desbuquois syndrome is a heterogeneous rare type of skeletal dysplasia with a prevalence of less than 1 in 1,000,000 individuals. It is characterized by short‐limbed dwarfism, dysmorphic facial features, and severe joint laxity. Two types have been recognized depending on the presence of distinctive carpal and phalangeal features. Mutations in the calcium activated nucleotidase 1 (CANT1) have been found to be responsible for type I and lately, for the Kim type of Desbuquois dysplasia. In addition, a number of Desbuquois dysplasia type II patients have been attributed to mutations in xylosyltransferase 1, encoded by the XYLT1 gene, an enzyme that catalyzes the transfer of UDP‐xylose (a marker of cartilage destruction) to serine residues of an acceptor protein, essential for the biosynthesis of proteoglycans. We report here a patient with features consistent with Desbuquois dysplasia II including short long bones, flat face, mild monkey wrench appearance of the femoral heads. Whole exome sequencing revealed a novel homozygous duplication of a single nucleotide in XYLT1 gene (c.2169dupA). This variant is predicted to result in a frame‐shift and stop codon p.(Val724Serfs*10) within the xylosyltransferase catalytic domain. Immunoflourescence staining of HeLa cells transfected with mutated XYLT1 plasmids constructs of the current as well as the previously reported missense mutations (c.1441C>T, p.(Arg481Trp) and c.1792C>T, p.(Arg598Cys)), revealed aberrant subcellular localization of the enzyme compared to wild‐type, suggesting endoplasmic reticulum retention of these mutants as the likely mechanism of disease.
Convenient Access to C4‐Dicarbonylation of Anilines by Iodine‐Promoted Oxidative Cross‐Coupling Reactions
Authors: Wang Panpan , Fu Yajie , Wu Ping , Guo Xin , Chen Baohua
Published: May 2017

An innovative route for the construction of C4‐dicarbonylation of anilines from simple and readily available anilines and phenyl acetylene has been developed. The iodine‐promoted oxidative cross‐coupling reaction performed well and the highlight of this protocol was not N−H functionalization but C−H functionalization of unprotected anilines.
The postcranial skeletal maturation ofAustralopithecus sediba
Authors: Cameron Noel , Bogin Barry , Bolter Debra , Berger Lee R.
Published: May 2017

Objectives

In 2008, an immature hominin defined as the holotype of the new speciesAustralopithecus sedibawas discovered at the 1.9 million year old Malapa site in South Africa. The specimen (MH1) includes substantial post‐cranial skeletal material, and provides a unique opportunity to assess its skeletal maturation.

Methods

Skeletal maturity indicators observed on the proximal and distal humerus, proximal ulna, distal radius, third metacarpal, ilium and ischium, proximal femur and calcaneus were used to assess the maturity of each bone in comparison to references for modern humans and for wild chimpanzees (Pan troglodytes).

Results

In comparison to humans the skeletal maturational ages forAu. sedibacorrespond to between 12.0 years and 15.0 years with a mean (SD) age of 13.1 (1.1) years. In comparison to the maturational pattern of chimpanzees theAu. sedibaindicators suggest a skeletal maturational age of 9–11 years. Based on either of these skeletal maturity estimates and the body length at death of MH1, an adult height of 150–156 cm is predicted.

Discussion

We conclude that the skeletal remains of MH1 are consistent with an ape‐like pattern of maturity when dental age estimates are also taken into consideration. This maturity schedule in australopiths is consistent with ape‐like estimates of age at death for the NariokotomeHomo erectusremains (KMN‐WT 15000), which are of similar postcranial immaturity to MH1. The findings suggest that humans may have distinctive and delayed post‐cranial schedules from australopiths andH. erectus, implicating a recent evolution of somatic and possibly life history strategies in human evolution.
Structure‐Selective Cation Exchange in the Synthesis of Zincblende MnS and CoS Nanocrystals
Authors: Fenton Julie L. , Schaak Raymond E.
Published: May 2017

The ability to selectively form one crystal structure among several options in a polymorphic system is an important goal in solid‐state synthesis. Nanocrystal cation exchange, which proceeds rapidly under mild conditions, can retain key structural features and yield otherwise inaccessible phases, but the extent to which crystal structure can be retained and therefore selectively targeted during such reactions has been limited. Here, we show that nanocrystals of digenite Cu2−xS transform to zincblende MnS and CoS upon cation exchange. Zincblende MnS and CoS, which are metastable in bulk, retain both the tetrahedral cation coordination and cubic close packed anion sublattice of digenite Cu2−xS. Comparison with wurtzite MnS and CoS, which have been accessed previously through analogous cation exchange of roxbyite Cu2−xS, demonstrates the selective formation of the related zincblende vs. wurtzite polymorphs by cation exchange of structurally distinct templates.
Fullerene C70 as a Nanoflask that Reveals the Chemical Reactivity of Atomic Nitrogen
Authors: Morinaka Yuta , Zhang Rui , Sato Satoru , Nikawa Hidefumi , Kato Tatsuhisa , Furukawa Ko , Yamada Michio , Maeda Yutaka , Murata Michihisa , Wakamiya Atsushi , Nagase Shigeru , Akasaka Takeshi , Murata Yasujiro
Published: May 2017

To investigate the intrinsic reactivity of atomic nitrogen, which had previously been accomplished only by examining its decay in the gas phase using special equipment, a nitrogen atom was inserted into a series of molecule‐encapsulating C60 and C70 fullerenes. Among the studied endofullerenes, H2@C70 was able to encapsulate an additional nitrogen atom within the fullerene cage under radiofrequency plasma conditions. The product was analyzed by ESR spectroscopy and mass spectrometry in solution, which revealed that the nitrogen atom with a quartet ground state does not react but weakly interact with the H2 molecule, thus demonstrating the utility of such fullerenes as “nanoflasks”.
Tyrosine or Tryptophan? Modifying a Metalloradical Catalytic Site by Removal of the Cys–Tyr Cross‐Link in the Galactose 6‐Oxidase Homologue GlxA
Authors: Chaplin Amanda K. , Bernini Caterina , Sinicropi Adalgisa , Basosi Riccardo , Worrall Jonathan A. R. , Svistunenko Dimitri A.
Published: May 2017

The concerted redox action of a metal ion and an organic cofactor is a unique way to maximize the catalytic power of an enzyme. An example of such synergy is the fungal galactose 6‐oxidase, which has inspired the creation of biomimetic copper oxidation catalysts. Galactose 6‐oxidase and its bacterial homologue, GlxA, possess a metalloradical catalytic site that contains a free radical on a covalently linked Cys–Tyr and a copper atom. Such a catalytic site enables for the two‐electron oxidation of alcohols to aldehydes. When the ability to form the Cys–Tyr in GlxA is disrupted, a radical can still be formed. Surprisingly, the radical species is not the Tyr residue but rather a copper second‐coordination sphere Trp residue. This is demonstrated through the introduction of a new algorithm for Trp‐radical EPR spectra simulation. Our findings suggest a new mechanism of free‐radical transfer between aromatic residues and that the Cys–Tyr cross‐link prevents radical migration away from the catalytic site.
Preparation of Waterproof Organometal Halide Perovskite Photonic Crystal Beads
Authors: Chen Kun , Schünemann Stefan , Tüysüz Harun
Published: May 2017

Herein, we report on an innovative method for the preparation of a series of organometal halide perovskite (OHP) photonic crystal beads with pronounced and tunable photonic stop bands by using self‐assembled polystyrene spheres as a mold. After infiltration of the mold with OHP precursor solution and slow drying, the OHPs crystallized in the voids of the polystyrene arrays. By controlling the diameter of the polystyrene spheres, the photonic stop band of the OHPs could be precisely tuned. The overlap between the photonic stop band of the beads and the band gap of the OHPs enhances the light harvesting of the perovskite because of the slow photon effect, which arises from the photonic crystal beads. Moreover, the stability of the composite was greatly enhanced by coating with the transparent polymer PDMS without blocking the light propagation. The coated OHP photonic beads kept their composition even after having been in contact with water for 24 h.
A Hybrid Nanomaterial for the Controlled Generation of Free Radicals and Oxidative Destruction of Hypoxic Cancer Cells
Authors: Shen Song , Zhu Chunlei , Huo Da , Yang Miaoxin , Xue Jiajia , Xia Younan
Published: May 2017

Anticancer modalities based on oxygen free radicals, including photodynamic therapy and radiotherapy, have emerged as promising treatments in the clinic. However, the hypoxic environment in tumor tissue prevents the formation of oxygen free radicals. Here we introduce a novel strategy that employs oxygen‐independent free radicals generated from a polymerization initiator for eradicating cancer cells. The initiator is mixed with a phase‐change material and loaded into the cavities of gold nanocages. Upon irradiation by a near‐infrared laser, the phase‐change material is melted due to the photothermal effect of gold nanocages, leading to the release and decomposition of the loaded initiator to generate free radicals. The free radicals produced in this way are highly effective in inducing apoptosis in hypoxic cancer cells.
Facile Access to NaOC≡As and Its Use as an Arsenic Source To Form Germylidenylarsinidene Complexes
Authors: Yao Shenglai , Grossheim Yves , Kostenko Arseni , Ballestero‐Martínez Ernesto , Schutte Stefan , Bispinghoff Mark , Grützmacher Hansjörg , Driess Matthias
Published: May 2017

A facile, one‐pot synthesis of [Na(OC≡As)(dioxane)x] (x=2.3–3.3) in 78 % yield is reported through the reaction of arsine gas with dimethylcarbonate in the presence of NaOtBu and 1,4‐dioxane. It has been employed for the synthesis of the first arsaketenyl‐functionalized germylene [LGeAsCO] (2, L=CH[CMeN(Dipp)]2; Dipp=2,6‐iPr2C6H3) from the reaction with LGeCl (1). Upon exposure to ambient light, 2 undergoes CO elimination to form the 1,3‐digerma‐2,4‐diarsacyclobutadiene [L2Ge2As2] (3), which contains a symmetric Ge2As2 ring with ylide‐like Ge=As bonds. Remarkably, the CO ligand located at the arsenic center of 2 can be exchanged with PPh3 or an N‐heterocyclic carbene iPrNHC donor (iPrNHC=1,3‐diisopropyl‐4,5‐dimethylimidazol‐2‐ylidene) to afford the novel germylidenylarsinidene complexes [LGe‐AsPPh3] (4) and [LGe‐As(iPrNHC)] (5), respectively, demonstrating transition‐metal‐like ligand substitution at the arsinidene‐like As atom. The formation of 2–5 and their electronic structures have been studied by DFT calculations.
Enantioselective Dearomative Difunctionalization of Indoles by Palladium‐Catalyzed Heck/Sonogashira Sequence
Authors: Liu Ren‐Rong , Wang Yong‐Gang , Li Ying‐Long , Huang Bing‐Bing , Liang Ren‐Xiao , Jia Yi‐Xia
Published: May 2017

Palladium‐catalyzed enantioselective dearomative arylalkynylation of N‐substituted indoles, through a Heck/Sonogashira sequence, was established using a new BINOL‐based phosphoramidite as the chiral ligand. A wide range of 2,3‐disubstituted indolines, bearing vicinal quaternary and tertiary stereocenters, were efficiently constructed in one step with excellent enantioselectivities (up to 97 % ee) and diastereoselectivities (>20:1).
Self‐Optimization of the Active Site of Molybdenum Disulfide by an Irreversible Phase Transition during Photocatalytic Hydrogen Evolution
Authors: Wang Longlu , Liu Xia , Luo Jinming , Duan Xidong , Crittenden John , Liu Chengbin , Zhang Shuqu , Pei Yong , Zeng Yunxiong , Duan Xiangfeng
Published: May 2017

The metallic 1T‐MoS2 has attracted considerable attention as an effective catalyst for hydrogen evolution reactions (HERs). However, the fundamental mechanism about the catalytic activity of 1T‐MoS2 and the associated phase evolution remain elusive and controversial. Herein, we prepared the most stable 1T‐MoS2 by hydrothermal exfoliation of MoS2 nanosheets vertically rooted into rigid one‐dimensional TiO2 nanofibers. The 1T‐MoS2 can keep highly stable over one year, presenting an ideal model system for investigating the HER catalytic activities as a function of the phase evolution. Both experimental studies and theoretical calculations suggest that 1T phase can be irreversibly transformed into a more active 1T′ phase as true active sites in photocatalytic HERs, resulting in a “catalytic site self‐optimization”. Hydrogen atom adsorption is the major driving force for this phase transition.
Resistance Controllability in Alkynylgold(III) Complex‐Based Resistive Memory for Flash‐Type Storage Applications
Authors: Wang Peng , Fang Yu , Jiang Jun , Ji Yujin , Li Youyong , Zheng Junwei , Xu Qingfeng , Lu Jianmei
Published: May 2017

Owing to the demands of state‐of‐the‐art information technologies that are suitable for vast data storage, the necessity for organic memory device (OMD) materials is highlighted. However, OMDs based on metal complexes are limited to several types of transition‐metal complex systems containing nitrogen‐donor ligands. Herein, attempts are made to introduce novel alkynylgold(III) materials into memory devices with superior performance. In this respect, an alkynyl‐containing coumarin gold(III) complex, [(C19N5H11)Au−C≡C−C9H5O], has been synthesized and integrated into a sandwiched Al/[(C19N5H11)Au−C≡C−C9H5O]/indium tin oxide device. By precisely controlling the compliance current (Icc), the devices show different switching characteristics from flash‐type binary resistance switching (Icc≤10−3 A) to WORM‐type (WORM=write once read many times) ternary resistance switching (Icc=10−2 A). This work explores electrical gold(III) complex based memories for potential use in organic electronics.
Enhanced Fluorescence Imaging and Photodynamic Cancer Therapy Using Hollow Mesoporous Nanocontainers
Authors: Hong Suk ho , Kim Hyunjin , Choi Yongdoo
Published: May 2017

Here we show that “off‐on” type of photodynamic therapy agents could be developed using hollow mesoporous silica nanoparticles (HMSNPs), which can be used not only for enhancing delivery of photosensitizers to cancer cells but also for enabling switchable optical properties of the photosensitizers. Fluorescence and singlet oxygen generation of the photosensitizer‐loaded HMSNP are turned off in its native state. In vitro cell studies showed that this HMSNP‐based “off‐on” agent may have potential utility in selective fluorescence detection and photodynamic therapy of cancers.
Lateral Extension of a Benzodithiophene System: Construction of Heteroacenes Containing Various Chalcogens
Authors: Wei Jichang , Meng Dong , Zhang Lei , Wang Zhaohui
Published: May 2017

A series of linear acenes with five fused rings, which contain thiophene, selenophene, and tellurophene as the outmost rings, have been synthesized from well‐known benzodithiophene (BDT). It was found that the optical, electrochemical properties and crystal packing motifs could be modulated by changing heteroatoms in the outmost rings.
Comparing dependent kappa coefficients obtained on multilevel data
Authors: Vanbelle Sophie
Published: May 2017

Reliability and agreement are two notions of paramount importance in medical and behavioral sciences. They provide information about the quality of the measurements. When the scale is categorical, reliability and agreement can be quantified through different kappa coefficients. The present paper provides two simple alternatives to more advanced modeling techniques, which are not always adequate in case of a very limited number of subjects, when comparing several dependent kappa coefficients obtained on multilevel data. This situation frequently arises in medical sciences, where multilevel data are common. Dependent kappa coefficients can result from the assessment of the same individuals at various occasions or when each member of a group is compared to an expert, for example. The method is based on simple matrix calculations and is available in the R package “multiagree”. Moreover, the statistical properties of the proposed method are studied using simulations. Although this paper focuses on kappa coefficients, the method easily extends to other statistical measures.
Joint analysis of longitudinal and survival AIDS data with a spatial fraction of long‐term survivors: A Bayesian approach
Authors: Martins Rui , Silva Giovani L. , Andreozzi Valeska
Published: May 2017

A typical survival analysis with time‐dependent covariates usually does not take into account the possible random fluctuations or the contamination by measurement errors of the variables. Ignoring these sources of randomness may cause bias in the estimates of the model parameters. One possible way for overcoming that limitation is to consider a longitudinal model for the time‐varying covariates jointly with a survival model for the time to the event of interest, thereby taking advantage of the complementary information flowing between these two‐model outcomes. We employ here a Bayesian hierarchical approach to jointly model spatial‐clustered survival data with a fraction of long‐term survivors along with the repeated measurements of CD4+T lymphocyte counts for a random sample of 500 HIV/AIDS individuals collected in all the 27 states of Brazil during the period 2002–2006. The proposed Bayesian joint model comprises two parts: on the one hand, a flexible model using Penalized Splines to better capture the nonlinear behavior of the different CD4 profiles over time; on the other hand, a spatial cure model to cope with the set of long‐term survivor individuals. Our findings show that joint models considering this set of patients were the ones with the best performance comparatively to the more traditional survival approach. Moreover, the use of spatial frailties allowed us to map the heterogeneity in the disease risk among the Brazilian states.
Development of an optical system for the non‐invasive tracking of stem cell growth on microcarriers
Authors: Odeleye Akinlolu Oyekunle Oluseun , Castillo‐Avila Sara , Boon Mathew , Martin Haydn , Coopman Karen
Published: May 2017

The emergence of medicinal indications for stem cell therapies has seen a need to develop the manufacturing capacity for adherent cells such as mesenchymal stem cells (MSCs). One such development is in the use of microcarriers, which facilitate enhanced cell densities for adherent stem cell cultures when compared with 2D culture platforms. Given the variety of stem cell expansion systems commercially available, novel methods of non‐invasive and automated monitoring of cell number, confluence, and aggregation, within disparate environments, will become imperative to process control, ensuring reliable and consistent performance. The in situ epi‐illumination of mouse embryonic fibroblasts and human mesenchymal stem cells attached to Cytodex 1 and 3 microcarriers was achieved using a bespoke microscope. Robust image processing techniques were developed to provide quantitative measurements of confluence, aggregate recognition, and cell number, without the need for fluorescent labeling or cell detachment. Large datasets of cells counted on individual microcarriers were statistically analyzed and compared with NucleoCounter measurements, with an average difference of less than 7% observed from days 0 to 6 of a 12‐day culture noted, prior to the onset of aggregation. The developed image acquisition system and post‐processing methodologies were successfully applied to dynamically moving colonized microcarriers. The proposed system offers a novel method of cell identification at the individual level, to consistently and accurately assess viable cell number, confluence, and cell distribution, while also minimizing the variability inherent in the current invasive means by which cells adhered to microcarriers are analyzed. Biotechnol. Bioeng. 2017;114: 2032–2042. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
Multi‐criteria manufacturability indices for ranking high‐concentration monoclonal antibody formulations
Authors: Yang Yang , Velayudhan Ajoy , Thornhill Nina F. , Farid Suzanne S.
Published: May 2017

The need for high‐concentration formulations for subcutaneous delivery of therapeutic monoclonal antibodies (mAbs) can present manufacturability challenges for the final ultrafiltration/diafiltration (UF/DF) step. Viscosity levels and the propensity to aggregate are key considerations for high‐concentration formulations. This work presents novel frameworks for deriving a set of manufacturability indices related to viscosity and thermostability to rank high‐concentration mAb formulation conditions in terms of their ease of manufacture. This is illustrated by analyzing published high‐throughput biophysical screening data that explores the influence of different formulation conditions (pH, ions, and excipients) on the solution viscosity and product thermostability. A decision tree classification method, CART (Classification and Regression Tree) is used to identify the critical formulation conditions that influence the viscosity and thermostability. In this work, three different multi‐criteria data analysis frameworks were investigated to derive manufacturability indices from analysis of the stress maps and the process conditions experienced in the final UF/DF step. Polynomial regression techniques were used to transform the experimental data into a set of stress maps that show viscosity and thermostability as functions of the formulation conditions. A mathematical filtrate flux model was used to capture the time profiles of protein concentration and flux decay behavior during UF/DF. Multi‐criteria decision‐making analysis was used to identify the optimal formulation conditions that minimize the potential for both viscosity and aggregation issues during UF/DF. Biotechnol. Bioeng. 2017;114: 2043–2056. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Perodicals, Inc.
Plantar Exteroceptive Inefficiency causes an asynergic use of plantar and visual afferents for postural control: Best means of remediation
Authors: Foisy Arnaud , Kapoula Zoï
Published: May 2017

Introduction

Some subjects have difficulty to integrate both visual and plantar inputs, showing at the same time a “postural blindness” and a Plantar Exteroceptive Inefficiency (PEI). The former corresponds to a better stability eyes closed (EC) than eyes open (EO), while the latter is defined as a better stability on foam than on firm ground. Clinical studies reported that a manipulation of either plantar or visual input could affect the weight of both cues in postural control, suggesting interdependence in their use. The purpose of the experiment is to characterize the PEI phenomenon better and see if such synergy can be objectified.

Methods

We recruited 48 subjects (25 ± 3.3 years) and assessed their balance with a force platform, EO, EC, at 40 or 200 cm, on firm ground, Dépron® foam, Dynachoc® foam, or on a 3 mm‐thick Anterior Bar AB®. We assessed their sensorial preferences through their PQ and RQ.

Results

The main results are that there normally exists a synergy in the use of plantar and visual afferents, but only at 40 cm and in the absence of PEI.

Conclusions

Plantar Exteroceptive Inefficiency interferes with the role of vision in postural control, its effects are distance specific, are better revealed by Dépron® foam and the AB® improves posture but does not solve visual‐podal asynergy. These results also have clinical interests as they indicate the best way in terms of distance and choice of foam to diagnostic PEI. Finally, they suggest restricting the use of the AB®, commonly employed. These findings can be useful for clinicians concerned with foot, eye, and posture.
“Cure” for multiple sclerosis (MS)—Evolving views of therapy goals in patients on different stages of the disease: A pilot study in a cohort of Polish MS patients
Authors: Chacińska Weronika , Brzostowska Marta , Nojszewska Monika , Podlecka‐Piętowska Aleksandra , Jędrzejczak Wiesław W. , Snarski Emilian
Published: May 2017

Introduction

New aggressive treatments promise improvement of results in the treatment of multiple sclerosis (MS), however, with high risk of serious complications. In this study, we analyzed patients’ acceptance for risks connected with the MS treatment.

Methods

The study was designed as a prospective nonanonymous online questionnaire. Responders were asked about the definition of the “cure” for MS and crucial goals in the treatment.

Results

One hundred and eighty patients filled in the questionnaire (129 women and 51 men), and the mean age was 33 years (SD = 10.29). The MS forms were as follows: relapsing‐remitting (65%), secondary progressive (14%), primary progressive (10%), and other (11%), with mean EDSS score of 3 points (SD = 2.6). For 50% of the patients, relief of symptoms such as fatigue (72%), paresis (66%), and balance disorders (65%) was synonymous with “cure.” The patients with faster progression of the disease were likely to accept risky “curative” treatments—with average 68% accepted mortality risk (p = .003). Over 81% of patients accepted mortality rates over 1% for the treatment that achieves self‐defined cure.

Conclusion

The study shows that the MS patients are likely to accept even very risky treatments as long as they promise patient‐defined “cure.”
Correlation of mammographic density and serum calcium levels in patients with primary breast cancer
Authors: Hack Carolin C. , Stoll Martin J. , Jud Sebastian M. , Heusinger Katharina , Adler Werner , Haeberle Lothar , Ganslandt Thomas , Heindl Felix , Schulz‐Wendtland Rüdiger , Cavallaro Alexander , Uder Michael , Beckmann Matthias W. , Fasching Peter A. , Bayer Christian M.
Published: May 2017

Percentage mammographic breast density (PMD) is one of the most important risk factors for breast cancer (BC). Calcium, vitamin D, bisphosphonates, and denosumab have been considered and partly confirmed as factors potentially influencing the risk of BC. This retrospective observational study investigated the association between serum calcium level and PMD. A total of 982 BC patients identified in the research database at the University Breast Center for Franconia with unilateral BC, calcium and albumin values, and mammogram at the time of first diagnosis were included. PMD was assessed, using a semiautomated method by two readers. Linear regression analyses were conducted to investigate the impact on PMD of the parameters of serum calcium level adjusted for albumin level, and well‐known clinical predictors such as age, body mass index (BMI), menopausal status and confounder for serum calcium like season in which the BC was diagnosed. Increased calcium levels were associated with reduced PMD (P = 0.024). Furthermore, PMD was inversely associated with BMI (P < 0.001) and age (P < 0.001). There was also an association between PMD and menopausal status (P < 0.001). The goodness‐of‐fit of the regression model was moderate. This is the first study assessing the association between serum calcium level and PMD. An inverse association with adjusted serum calcium levels was observed. These findings add to previously published data relating to vitamin D, bisphosphonates, denosumab, and the RANK/RANKL signaling pathway in breast cancer risk and prevention.
Gene expression changes of thermo‐sensitive transient receptor potential channels in obese mice
Authors: Sun Wuping , Li Chen , Zhang Yonghong , Jiang Changyu , Zhai Mingzhu , Zhou Qian , Xiao Lizu , Deng Qiwen
Published: May 2017

Adipose tissues play key roles in energy homeostasis. Brown adipocytes and beige adipocytes in white adipose tissue (WAT) share the similar characters of thermogenesis, both of them could be potential targets for obesity management. Several thermo‐sensitive transient receptor potential channels (thermoTRPs) are shown to be involved in adipocyte biology. However, the expression pattern of thermoTRPs in adipose tissues from obese mice is still unknown. The mRNA expression of thermoTRPs in subcutaneous WAT (sWAT) and interscapular brown adipose tissue (iBAT) from lean and obese mice were measured using reverse transcriptase‐quantitative PCRs (RT‐qPCR). The results demonstrated that all 10 thermoTRPs are expressed in both iBAT and sWAT, and without significant difference in the mRNA expression level of thermoTRPs between these two tissues. Moreover, Trpv1 and Trpv3 mRNA expression levels in both iBAT and sWAT were significantly decreased in high fat diet (HFD)‐induced obese mice and db/db (leptin receptor deficient) mice. Trpm2 mRNA expression level was significantly decreased only in sWAT from HFD‐induced obese mice and db/db mice. On the other hand, Trpv2 and Trpv4 mRNA expression levels in iBAT and sWAT were significantly increased in HFD‐induced obese mice and db/db mice. Taken together, we conclude that all 10 thermoTRPs are expressed in iBAT and sWAT. And several thermoTRPs differentially expressed in adipose tissues from HFD‐induced obese mice and db/db mice, suggesting a potential involvement in anti‐obesity regulations.
The impact of frailty status on clinical and functional outcomes after transcatheter aortic valve replacement in nonagenarians with severe aortic stenosis
Authors: Okoh Alexis K. , Chauhan Dhaval , Kang Nathan , Haik Nicky , Merlo Aurelie , Cohen Mark , Haik Bruce , Chen Chunguang , Russo Mark J.
Published: May 2017

Background

The impact of frailty status on TAVR outcomes in nonagenarians is unknown. The present study aims to investigate the impact of frailty status on procedural outcomes and overall survival in nonagenarians after TAVR.

Methods

A frailty score (FS) was derived by using preoperative grip strength, gait speed, serum albumin, and daily activities. Patients were divided into two groups: Frail (FS ≥ 3/4) and Non‐Frail (FS <3/4). Health status was assessed using the 12‐item Kansas City Cardiomyopathy Questionnaire (KCCQ). Baseline demographic and clinical characteristics were compared in both groups. The effect of frailty status on outcomes was investigated. Cox regression analyses were performed to determine predictors of overall all‐cause mortality. Kaplan‐Meier survival curves were used to estimate survival.

Results

Seventy‐five patients >90 years underwent full assessment for frailty status. There was a significant improvement in overall health status of non‐frail patients (mean difference: 11.03, P = 0.032). Unadjusted 30‐day and 2‐year mortality rates were higher in the frail group than the non‐frail group. (14% vs. 2% P = 0.059; 31% vs. 9% P = 0.018). Kaplan‐Meier estimated all‐cause mortality to be significantly higher in the frail group (log‐rank test; P = 0.042). Frailty status was independently associated with increased mortality (hazard ratio: 1.84, 95% C.I: 1.06–3.17; P = 0.028) after TAVR.

Conclusion

Among nonagenarians selected to undergo TAVR for severe aortic stenosis, a considerable number are frail. Nonfrail patients report a significant improvement in overall health status in the short term. Worse frailty is strongly associated with diminished long‐term survival. © 2017 Wiley Periodicals, Inc.
Synthesis, Structural Characterization, and Crystal Packing of the Elusive Pentachlorinated Azafullerene C59NCl5
Authors: Amsharov Konstantin Yu. , Holzwarth Johannes , Roshchyna Kateryna , Sharapa Dmitry I. , Hampel Frank , Hirsch Andreas
Published: May 2017

We report on the synthesis and the structure elucidation of the elusive azafullerene pentachloride C59NCl5, which was obtained by high temperature halogenation of (C59N)2. The exceptionally strong host–guest interaction of the title compound in the solid is discussed.
Dual Gold Catalysis: Bidirectional Processes and Tandem sp3‐C−H Insertion Reactions
Authors: Tšupova Svetlana , Rudolph Matthias , Rominger Frank , Hashmi A. Stephen K.
Published: May 2017

Various tetrayne systems were converted under dual gold‐catalyzed conditions. For symmetric tetraalkynyl‐substituted thiophenes, bearing two alkyl‐substituted alkynes and two terminal alkyne units, bidirectional cyclizations led to the efficient formation of dibenzothiophene systems. In all cases, selective CH activation of the C−H bond of the alkyl substituent was observed leading to cyclopentane moieties annelated to the newly formed aromatic cores. If two thiophene moieties were tethered over the attached non‐terminal alkynes, depending on the length of the connecting alkyl tether, either bidirectional processes or tandem processes can be addressed leading to interesting molecular structures, such as spiro compounds or isolated benzothiophenes connected by a C−C bond. Other electron‐rich heterocycles also reacted. While the reactions even worked for some mixed systems, other cases only delivered the products of a mono‐cyclization.
Crown Ether Complexes of Alkali‐Metal Chlorides from SO2
Authors: Reuter Kirsten , Rudel Stefan S. , Buchner Magnus R. , Kraus Florian , von Hänisch Carsten
Published: May 2017

The structures of alkali‐metal chloride SO2 solvates (Li–Cs) in conjunction with 12‐crown‐4 or 1,2‐disila‐12‐crown‐4 show strong discrepancies, despite the structural similarity of the ligands. Both types of crown ethers form 1:1 complexes with LiCl to give [Li(1,2‐disila‐12‐crown‐4)(SO2Cl)] (1) and [Li(12‐crown‐4)Cl]⋅4 SO2 (2). However, 1,2‐disila‐12‐crown‐4 proved unable to coordinate cations too large for the cavity diameter, for example, by the formation of sandwich‐type complexes. As a result, 12‐crown‐4 reacts exclusively with the heavier alkali‐metal chlorides NaCl, KCl and RbCl. Compounds [Na(12‐crown‐4)2]Cl⋅4 SO2 (3) and [M(12‐crown‐4)2(SO2)]Cl⋅4 SO2 (4: M=K; 5: M=Rb) all showed S‐coordination to the chloride ions through four SO2 molecules. Compounds 4 and 5 additionally exhibit the first crystallographically confirmed non‐bridging O,O′‐coordination mode of SO2. Unexpectedly, the disila‐crown ether supports the dissolution of RbCl and CsCl in the solvent and gives the homoleptic SO2‐solvated alkali‐metal chlorides [MCl⋅3 SO2] (6: M=Rb; 7: M=Cs), which incorporate bridging μ‐O,O′‐coordinating moieties and the unprecedented side‐on O,O′‐coordination mode. All compounds were characterised by single‐crystal X‐ray diffraction. The crown ether complexes were additionally studied by using NMR spectroscopy, and the presence of SO2 at ambient temperature was revealed by IR spectroscopy of the neat compounds.
A Single‐Step Electrochemical Synthesis of Luminescent WS2 Quantum Dots
Authors: Valappil Manila O. , Anil Athira , Shaijumon Manikoth , Pillai Vijayamohanan K. , Alwarappan Subbiah
Published: May 2017

Transition‐metal dichalcogenide quantum dots (TMDQDs) with few layers are in the forefront of recent research on tailored 2D layered materials owing to their unique band structure. Such quantum dots (QDs) draw wide interest as potential candidates for components in optoelectronic devices. Although a few attempts towards single step synthesis of MoS2 QDs have been demonstrated, limited methods are available for WS2 QDs. Herein, we demonstrate a one‐step electrochemical synthesis of luminescent WS2 QDs from their bulk material. This is achieved by a synergistic effect of perchlorate intercalation in non‐aqueous electrolyte and the applied electric field. The average size of the WS2 QDs is 3  ±1 nm (N=102) with few layers. The QDs show a higher photoluminescence (PL) quantum efficiency (5 %) and exhibit an excitation wavelength‐dependent photoluminescence. This unprecedented electrochemical avenue offers a strategy to synthesize size tunable WS2 nanostructures, which have been systematically investigated by various characterization techniques such as transmission electron microscopy (TEM), photoluminescence and UV/Vis spectroscopies, and X‐ray diffraction (XRD). Time‐dependent TEM investigations revealed that time plays a vital role in this electrochemical transformation. This electrochemical transformation provides a facile method to obtain WS2 QDs from their bulk counterpart, which is expected to have a greater impact on the design and development of nanostructures derived from 2D materials.
Combining LC‐OCD analysis with design‐of‐experiments methods to optimize an advanced oxidation process for the treatment of industrial wastewater
Authors: Aghasadeghi Kimia , Csordas Matthew , Peldszus Sigrid , Latulippe David R.
Published: May 2017

Advanced oxidation (AO) is widely used as a pre‐treatment and/or polishing step for the treatment of wastewater from industrial processes and the destruction of particular contaminants in water sources. It has a high treatment efficacy for many different compounds and thus is ideally suited as a treatment technology for specialized facilities that receive shipments of wastewater from networks of industrial, manufacturing, and commercial facilities. The primary challenge is how to optimize the process because bulk measurements of organic content (e.g. TOC) give no information about the specific composition and specialized advanced analytical techniques (e.g. LC‐MS) are unsuitable due to the complex composition. In this study, a novel combination of design‐of‐experiments (DOE) methods and LC‐OCD analysis was used with actual wastewater samples in order to optimize the AO treatment conditions in terms of chemical reagent concentrations, develop statistical models of the process, and identify potential mechanisms of COD removal. A significant variation in organic content removal was obtained over the range of conditions tested in the DOE method. For example, the percent removal of organic contaminants in the one wastewater sample varied from a low of 36 % to a high of 82 %. Most importantly, it was found that the treatment performance differed quite significantly for wastewater samples of different composition. The results presented in our study prove the need to dynamically optimize the AO treatment conditions for wastewater sources of different origins. Furthermore, by the application of the LC‐OCD analysis a step‐by‐step mechanism of COD removal was postulated.