bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid and Mild Synthesis of Amino Acid N‐Carboxy Anhydrides: Basic‐to‐Acidic Flash Switching in a Microflow Reactor
Authors: Otake Yuma , Nakamura Hiroyuki , Fuse Shinichiro
Published: July 2018

Polymerization of N‐carboxy anhydrides (NCAs) is the primary process used to prepare polypeptides. The synthesis of various pure NCAs is key to the efficient synthesis of polypeptides. The only practical method that can be used to synthesize NCAs requires harsh acidic conditions that make acid‐labile substrates unusable and results in an undesired ring opening of NCAs. Basic‐to‐acidic flash switching and subsequent flash dilution technology in a microflow reactor was used to demonstrate the synthesis of NCAs. It is both rapid (0.1 s) and mild (20 °C) and includes substrates containing acid‐labile functional groups. The basic‐to‐acidic flash switching enabled both an acceleration of the desired NCA formation and avoided the undesired ring opening of NCAs. The flash dilution precluded the undesired decomposition of acid‐labile functional groups. The developed process allowed the synthesis of various NCAs which cannot be readily synthesized using conventional batch methods.
Mechanistic Studies on the Organocatalytic α‐Chlorination of Aldehydes: The Role and Nature of Off‐Cycle Intermediates
Authors: Ponath Sebastian , Menger Martina , Grothues Lydia , Weber Manuela , Lentz Dieter , Strohmann Carsten , Christmann Mathias
Published: July 2018

Herein we report the isolation and characterization of aminal intermediates in the organocatalytic α‐chlorination of aldehydes. These species are stable covalent ternary adducts of the substrate, the catalyst and the chlorinating reagent. NMR‐assisted kinetic studies and isotopic labeling experiments with the isolated intermediate did not support its involvement in downstream stereoselective processes as proposed by Blackmond. By tuning the reactivity of the chlorinating reagent, we were able to suppress the accumulation of rate‐limiting off‐cycle intermediates. As a result, an efficient and highly enantioselective catalytic system with a broad functional group tolerance was developed.
Strain‐Induced Double Carbon–Carbon Bond Activations of Cycloparaphenylenes by a Platinum Complex: Application to the Synthesis of Cyclic Diketones
Authors: Kayahara Eiichi , Hayashi Toshiki , Takeuchi Katsuhiko , Ozawa Fumiyuki , Ashida Keita , Ogoshi Sensuke , Yamago Shigeru
Published: July 2018

The carbon–carbon (C−C) bond activation of [n]cycloparaphenylenes ([n]CPPs) by a transition‐metal complex is herein reported. The Pt0 complex Pt(PPh3)4 regioselectively cleaves two C−C σ bonds of [5] CPP and [6]CPP to give cyclic dinuclear platinum complexes in high yields. Theoretical calculations reveal that the relief of ring strain drives the reaction. The cyclic complex was further transformed into a cyclic diketone by using a CO insertion reaction.
Surface‐Assisted Self‐Assembly of a Hydrogel by Proton Diffusion
Authors: Spitzer Daniel , Marichez Vincent , Formon Georges J. M. , Besenius Pol , Hermans Thomas M.
Published: July 2018

Controlling supramolecular growth at solid surfaces is of great importance to expand the scope of supramolecular materials. A dendritic benzene‐1,3,5‐tricarboxamide peptide conjugate is described in which assembly can be triggered by a pH jump. Stopped‐flow kinetics and mathematical modeling provide a quantitative understanding of the nucleation, elongation, and fragmentation behavior in solution. To assemble the molecule at a solid–liquid interface, we use proton diffusion from the bulk. The latter needs to be slower than the lag phase of nucleation to progressively grow a hydrogel outwards from the surface. Our method of surface‐assisted self‐assembly is generally applicable to other gelators, and can be used to create structured supramolecular materials.
Dynamic Covalent Identification of an Efficient Heparin Ligand
Authors: Corredor Miriam , Carbajo Daniel , Domingo Cecilia , Pérez Yolanda , Bujons Jordi , Messeguer Angel , Alfonso Ignacio
Published: July 2018

Despite heparin being the most widely used macromolecular drug, the design of small‐molecule ligands to modulate its effects has been hampered by the structural properties of this polyanionic polysaccharide. Now a dynamic covalent selection approach is used to identify a new ligand for heparin, assembled from extremely simple building blocks. The amplified molecule strongly binds to heparin (KD in the low μm range, ITC) by a combination of electrostatic, hydrogen bonding, and CH–π interactions as shown by NMR and molecular modeling. Moreover, this ligand reverts the inhibitory effect of heparin within an enzymatic cascade reaction related to blood coagulation. This study demonstrates the power of dynamic covalent chemistry for the discovery of new modulators of biologically relevant glycosaminoglycans.
High‐Throughput Metabolomics by 1D NMR
Authors: Vignoli Alessia , Ghini Veronica , Meoni Gaia , Licari Cristina , Takis Panteleimon G. , Tenori Leonardo , Turano Paola , Luchinat Claudio
Published: July 2018

Metabolomics deals with the whole ensemble of metabolites (the metabolome). As one of the ‐omic sciences, it relates to biology, physiology, pathology and medicine; but metabolites are chemical entities, small organic molecules or inorganic ions. Therefore, their proper identification and quantitation in complex biological matrices requires a solid chemical ground. With respect to for example, DNA, metabolites are much more prone to oxidation or enzymatic degradation: we can reconstruct large parts of a mammoth's genome from a small specimen, but we are unable to do the same with its metabolome, which was probably largely degraded a few hours after the animal's death. Thus, we need standard operating procedures, good chemical skills in sample preparation for storage and subsequent analysis, accurate analytical procedures, a broad knowledge of chemometrics and advanced statistical tools, and a good knowledge of at least one of the two metabolomic techniques, MS or NMR. All these skills are traditionally cultivated by chemists. Here we focus on metabolomics from the chemical standpoint and restrict ourselves to NMR. From the analytical point of view, NMR has pros and cons but does provide a peculiar holistic perspective that may speak for its future adoption as a population‐wide health screening technique.
The understorey of gorgonian forests in mesophotic temperate reefs
Authors: Ponti Massimo , Turicchia Eva , Ferro Francesca , Cerrano Carlo , Abbiati Marco
Published: July 2018

In the Mediterranean Sea, dense populations of the gorgonian Paramuricea clavata shape marine animal forests, characterizing the seascapes of coralligenous habitats. Despite concerns for its health, with several anthropogenic threats and recent mass mortality events, mainly triggered by thermal anomalies, the understorey of its forests and the ecological processes that they promote are still little known. Here, the abundance and composition of epibenthic assemblages inside and outside P. clavata forests were investigated across the central and western Mediterranean Sea, by applying a multifactorial sampling design.

In spite of the large variability in the structures of epibenthic assemblages at local and regional scales, the gorgonian understoreys share some common features, such as higher abundances of calcareous builder organisms and reduced invasion by the non‐indigenous alga Caulerpa cylindracea, compared with the adjacent unforested rocky bottoms. Paramuricea clavata showed non‐linear density‐dependent relationships with algal turfs and non‐encrusting algae belonging to the genus Peyssonnelia. Moreover, by entrapping benthic mucilaginous aggregates with their branches, these gorgonians risk topical necrotic lesions, but may reduce the suffocation risks for understorey organisms.

Overall, P. clavata forests may enhance bioconstruction processes and increase resistance and resilience of the benthic assemblages in the Mediterranean coralligenous habitats. This species and its forests, together with their understoreys, should be considered as essential elements of the ecology of the Mediterranean Sea, and therefore worthy of specific and effective protection measures.

Conservation strategies should reduce the risk of mechanical damage by regulating fishing activities, anchorages, and scuba diving where gorgonian forests are present. Moreover, when evident alterations are documented, restoration actions should be implemented to recover the integrity of gorgonian forests.
Synthesis of three triterpene series and their activity against respiratory syncytial virus
Authors: Santos da Silva Gloria N. , Monti Atik Diana , Antunes Fernandes Jheini L. , de Freitas do Nascimento Deise , Fazolo Tiago , Duarte de Souza Ana Paula , Baggio Gnoatto Simone C.
Published: July 2018

The human respiratory syncytial virus (hRSV) is a leading cause of hospitalization due to acute lower respiratory infection especially in infants and young children, sometimes causing fatal cases. The monoclonal antibody palivizumab is one of the available options for preventing this virus, and at the moment there are several hRSV vaccine trials underway. Unfortunately, the only drug option to treat hRSV infection is ribavirin, which can be used in severe high‐risk cases. For this reason, new medicines are needed and, in this context, the triterpenes and their derivatives are promising alternatives, since many of them have shown important antiviral activity, such as bevirimat. Therefore, we report three series of triterpene (betulin (BE), betulinic acid (BA), and ursolic acid (UA)) derivatives tested against hRSV. The derivatives were synthesized by using commercial anhydrides in an easy and inexpensive step reaction. For the antiviral assay, A549 cells were infected by hRSV and after 96 h of compound or ribavirin (positive control) treatment, the cell viability was tested by MTT assay. DMSO, non‐infected cells and infected cells without treatment were used as negative control. The triterpene esterification at the hydroxyl group resulted in 17 derivatives. The 3,28‐di‐O‐acetylbetulin derivative (1a) showed the best results for cell viability, and real‐time PCR amplification was performed for 1a treatment. Remarkably, one new anti‐hRSV prototype was obtained through an easy synthesis of BE, which shall represent an alternative for a new lead compound for anti‐hRSV therapy.
Survival and risk of breast cancer recurrence after breast reconstruction with deep inferior epigastric perforator flap
Authors: Svee A , Mani M , Sandquist K , Audolfsson T , Folkvaljon Y , Isern A E , Ringberg A , Manjer J , Falk-Delgado A , Wärnberg F
Published: July 2018

Background

Women who undergo autologous breast reconstruction have been reported to have an increased risk of breast cancer recurrence compared with those who have mastectomy alone. It has been suggested that more extensive surgery possibly activates dormant micrometastases. The aim of this study was to evaluate whether delayed unilateral deep inferior epigastric perforator (DIEP) flap reconstruction after mastectomy increases the risk of breast cancer recurrence or affects mortality among women previously treated for breast cancer.

Methods

This was a matched retrospective cohort study including women with a previous unilateral invasive breast cancer who received a delayed DIEP flap breast reconstruction and a control cohort of individually matched women with unilateral breast cancer who underwent mastectomy but no autologous breast reconstruction. Matching criteria comprised: year of diagnosis (+/–3 years), age at diagnosis (+/–5 years), type of cancer and demographic region. The primary endpoints were local recurrence or distant metastasis, and overall mortality was a secondary endpoint. Absolute risk of recurrent disease and mortality was analysed, and relative risks were estimated using Cox proportional hazards analysis.

Results

There were 225 women in the DIEP cohort and 450 in the no-DIEP cohort. The median follow-up time was 125 months. There was no difference in absolute risk of recurrence between the cohorts. The hazard ratio for breast cancer recurrence in DIEP versus no-DIEP cohorts was 0·76 (95 per cent c.i. 0·47 to 1·21).

Conclusion

There is no increased risk in breast cancer recurrence after delayed DIEP flap reconstruction compared with mastectomy alone.
Meta-analysis of prognostic factors for overall survival in patients with resected hilar cholangiocarcinoma
Authors: Bird N T E , McKenna A , Dodd J , Poston G , Jones R , Malik H
Published: July 2018

Background

Hilar cholangiocarcinoma is staged using the AJCC staging system. Numerous other prognostically important histopathological and demographic characteristics have been reported. The objective of this meta-analysis was to assess statistically the effect of postresectional tumour characteristics on overall survival of patients undergoing attempted radical curative resection for hilar cholangiocarcinoma.

Methods

Relevant studies were identified by searching the Ovid MEDLINE and PubMed databases. The search was limited to studies published between 2009 and 2017. Papers referring to intrahepatic or distal cholangiocarcinoma were excluded from review. Data extraction used standard Parmar modifications to determine pooled univariable hazard ratios (HRs).

Results

Twenty-four articles, containing 4599 patients, were assessed quantitatively. In pooled analyses, age (HR 1·16, 95 per cent c.i. 1·04 to 1·28), T category (HR 1·49, 1·30 to 1·70), lymph node involvement (HR 1·78, 1·65 to 1·93), microvascular invasion (HR 1·49, 1·34 to 1·68), perineural invasion (HR 1·54, 1·40 to 1·68) and tumour differentiation (HR 1·54, 1·38 to 1·72) were significant prognostic factors, with low heterogeneity. Portal vein resection (HR 1·54, 1·15 to 1·70) and resection margin status (HR 1·77, 1·57 to 1·99) had significant effects, but with high heterogeneity. Sex, tumour size and preoperative carbohydrate antigen 19-9 levels did not have a statistically significant effect on postoperative prognosis.

Conclusion

Several tumour biological variables not included in the seventh edition of the AJCC classification affect overall survival. These require incorporation into prognostic models to ensure a personalized approach to prognostication and treatment.
Multicentre factorial randomized clinical trial of perioperative immunonutrition versus standard nutrition for patients undergoing surgical resection of oesophageal cancer
Authors: Mudge L A , Watson D I , Smithers B M , Isenring E A , Smith L , Jamieson G G , Aly A , Archer S , Ballal M , Barbon J , Barbour A , Benton K , Bessell J , Bond M , Berryman Melissa , Bright T , Cade R , Cardamis A , Carroll R , Cashman K , Chan L , Chapman B , Chapman S , Chen D , Chisholm J , Davidson W , Devitt P , Dong C , Doola R , Edwards S , Epari K , Farley M , Farrow J , Ferguson M , Fletcher D , Forbes K , Fullerton K , Game P , Gan S , Gotley D , Gout B , Gray J , Heaney S , Johnson M A , Johnstone M , Kariyawasam S , Karnon J , Kelaart A , Kellett L , Kennedy E , Krane R , Lemass S , Lindstrom-Sowman R , Loeliger J , Lord A , Ludbrook John , McFarlane C , McPhee M , Ooi S Y-X , Pearce L , Pettigrew K , Putrus E , Rassias G , Shanks A , Shenfine J , Smith E L , Singleton J , Spillane J , Sputore L , Steer B , Sullivan T , Teleni L , Tolcher D , Thomas J , Thompson S , Thorpe T , Watterson C , Wills V , Wilton A , Wright K , Wright T
Published: July 2018

Background

Preoperative immunonutrition has been proposed to reduce the duration of hospital stay and infective complications following major elective surgery in patients with gastrointestinal malignancy. A multicentre 2 × 2 factorial RCT was conducted to determine the impact of preoperative and postoperative immunonutrition versus standard nutrition in patients with oesophageal cancer.

Methods

Patients were randomized before oesophagectomy to immunonutrition (IMPACT®) versus standard isocaloric/isonitrogenous nutrition, then further randomized after operation to immunonutrition versus standard nutrition. Clinical and quality-of-life outcomes were assessed at 14 and 42 days after operation on an intention-to-treat basis. The primary outcome was the occurrence of infective complications. Secondary outcomes were other complications, duration of hospital stay, mortality, nutritional and quality-of-life outcomes (EuroQol EQ-5D-3 L™, European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-OES18). Patients and investigators were blinded until the completion of data analysis.

Results

Some 278 patients from 11 Australian sites were randomized; two were excluded and data from 276 were analysed. The incidence of infective complications was similar for all groups (37 per cent in perioperative standard nutrition group, 51 per cent in perioperative immunonutrition group, 34 per cent in preoperative immunonutrition group and 40 per cent in postoperative immunonutrition group; P = 0·187). There were no significant differences in any other clinical or quality-of-life outcomes.

Conclusion

Use of immunonutrition before and/or after surgery provided no benefit over standard nutrition in patients undergoing oesophagectomy. Registration number: ACTRN12611000178943 (https://www.anzctr.org.au).
Determination of halquinol residual levels in animal‐derived food products using liquid chromatography–tandem mass spectrometry
Authors: Zheng Weijia , Choi Jeong‐Min , Kim Seong‐Kwan , Shim Jae‐Han , Kang Young‐Sun , Abd El‐Aty A. M. , Hacımüftüoğlu Ahmet , Shin Ho‐Chul
Published: July 2018

A reliable and highly sensitive detection method based on liquid chromatography coupled with triple quadrupole electrospray tandem mass spectrometry (LC‐MS/MS) analysis has been developed for determination and quantification of halquinol, including 5,7‐dichloroquinolin‐8‐ol and 5‐chloroquinolin‐8‐ol. The target analytes were extracted from porcine muscle, egg, milk, eel, flatfish and shrimp using a mixture of acetonitrile and ethyl acetate followed by liquid–liquid purification with n‐hexane. The analytes were separated on an Agilent Eclipse XDB‐C18 reversed‐phase analytical column using 0.05% formic acid in distilled water and acetonitrile as mobile phases. Good linearity from six‐point matrix‐matched calibration was obtained with correlation coefficients (R2) ≥ 0.9904. Recoveries from three spiking levels (5, 10 and 20 μg/kg) ranged between 70.6 and 101.7% in various matrices with relative standard deviations ≤8.6%. Samples acquired from markets located in Seoul, Republic of Korea, tested negative for the target analytes. In conclusion, the proposed method is versatile and precise for the routine detection of halquinol residual levels in animal‐derived food products intended for human consumption.
Dopamine gene methylation patterns are associated with obesity markers and carbohydrate intake
Authors: Ramos‐Lopez Omar , Riezu‐Boj Jose I. , Milagro Fermin I. , Martinez J. Alfredo ,   MENA Project
Published: July 2018

Introduction

Dopamine (DA) is a neurotransmitter that regulates the rewarding and motivational processes underlying food intake and eating behaviors. This study hypothesized associations of DNA methylation signatures at genes modulating DA signaling with obesity features, metabolic profiles, and dietary intake.

Methods

An adult population within the Methyl Epigenome Network Association project was included (n = 473). DNA methylation levels in white blood cells were measured by microarray (450K). Differentially methylated genes were mapped within the dopaminergic synapse pathway using the KEGG reference database (map04728). Subsequently, network enrichment analyses were run in the pathDIP portal. Associations of methylation patterns with anthropometric markers of general (BMI) and abdominal obesity (waist circumference), the blood metabolic profile, and daily dietary intakes were screened.

Results

After applying a correction for multiple comparisons, 12 CpG sites were strongly associated (p < 0.0001) with BMI: cg03489495 (ITPR3), cg22851378 (PPP2R2D), cg04021127 (PPP2R2D), cg22441882 (SLC18A1), cg03045635 (DRD5), cg23341970 (ITPR2), cg13051970 (DDC), cg08943004 (SLC6A3), cg20557710 (CACNA1C), cg24085522 (GNAL), cg16846691 (ITPR2), and cg09691393 (SLC6A3). Moreover, average methylation levels of these genes differed according to the presence or absence of abdominal obesity. Pathway analyses revealed a statistically significant contribution of the aforementioned genes to dopaminergic synapse transmission (p = 4.78E−08). Furthermore, SLC18A1 and SLC6A3 gene methylation signatures correlated with total energy (p < 0.001) and carbohydrate (p < 0.001) intakes.

Conclusions

The results of this investigation reveal that methylation status on DA signaling genes may underlie epigenetic mechanisms contributing to carbohydrate and calorie consumption and fat deposition.
Students' experimentation strategies in design: Is process data enough?
Authors: Vieira Camilo , Seah Ying Ying , Magana Alejandra J.
Published: July 2018

Conducting experiments is an important practice for both engineering design and scientific inquiry. Engineers iteratively conduct experiments to evaluate ideas, make informed decisions, and optimize their designs. However, both engineering design and scientific experimentation are open‐ended tasks that are not easy to assess. Recent studies have demonstrated how technology‐based assessments can help to capture and characterize these open‐ended tasks using unobtrusive data logging. This study builds upon a model to characterize students' experimentation strategies in design (ESD). Ten undergraduate students worked on a design challenge using a computer‐aided design (CAD) tool that captured all their interactions with the software. This “process data” was compared to “think‐aloud data,” which included students' explanations of their rationale for the experiments. The results suggest that the process data and the think‐aloud data have both affordances and limitations toward the goal of assessing students' ESD. While the process data was an effective approach to identify relevant sequences of actions, this type of data failed to ensure that students carried them out with a specific purpose. On the other hand, the think‐aloud data captured students' rationale for conducting experiments, but it depended on students' ability to verbalize their actions. In addition, the implementation of think‐aloud procedures and their analysis are time consuming tasks, and can only be done individually.
Tailoring the Selectivity of Bio‐Ethanol Transformation by Tuning the Size of Gold Supported on ZnZr10Ox Catalysts
Authors: He Rong , Men Yong , Liu Jixing , Wang Jinguo , An Wei , Huang Xiaoxiong , Song Weiyu , Liu Jian , Dai Sheng
Published: July 2018

The selective bio‐ethanol cascade transformation to hydrocarbons over multifunctional catalysts is a highly promising sustainable pathway to high‐value chemicals and fuels. However, principles to control the selectivity of the bio‐ethanol transformation using the effects of the size of nanoparticle catalysts have remainedlargely unexplored. Here, using bio‐ethanol transformation reactions catalyzed by Au/ZnZr10Ox as examples, we demonstrate that changing the fashion of gold loading enables control over product distribution. Our results reveal that larger gold particles tendto show much higher selectivity for 1,3‐butadiene, whereas smaller gold nanoparticles favor the formation of acetaldehyde.This study uncovers general principles for tailoring the selectivity of bio‐ethanol transformation by carefully engineering the size of gold. It opens a new avenue for the rational design of multifunctional catalysts to enhance the production of desired reaction products in complex cascade reaction sequences.
Hierarchical Titanium Dioxide Nanowire/Metal–Organic Framework/Carbon Nanofiber Membranes for Highly Efficient Photocatalytic Degradation of Hydrogen Sulfide
Authors: Zhang Guping , Sheng Haibo , Chen Dongyun , Li Najun , Xu Qingfeng , Li Hua , He Jinghui , Lu Jianmei
Published: July 2018

Photocatalysis is an efficient approach to degrade hydrogen sulfide (H2S) and titanium dioxide (TiO2) is commonly used as a catalyst for H2S degradation. However, the low separation rate of photoinduced carriers and low gas adsorption ability of TiO2 limit its H2S photocatalytic decomposition rate. In this paper, single‐crystalline TiO2 nanowires are assembled on one‐dimensional carbon nanofibers (CNFs) and a tunable metal–organic framework (MOF) coating is fabricated on the surface of the TiO2 nanowires using a versatile step‐by‐step self‐assembly strategy. The excellent photocatalytic properties of the resulting membrane originate from the ability of the CNFs to rapidly transport charge carriers and the high and regenerable H2S adsorption ability of the MOF. The photocatalytic mechanism of the as‐prepared material was also discussed. Therefore, this work provides a promising method to improve the photocatalytic performance of H2S degradation.
Configurational Analysis by Residual Dipolar Coupling Driven Floating Chirality Distance Geometry Calculations
Authors: Immel Stefan , Köck Matthias , Reggelin Michael
Published: July 2018

A new method implemented into a computer program (ConArch+) has been developed and applied to demonstrate the successful implementation of residual dipolar couplings (RDCs) in distance geometry (DG) calculations for the configurational assignment of chiral compounds. Unlike established protocols, the new approach combines floating chirality (fc) in 4D‐ and 3D‐distance bounds driven dynamics (DDD) calculations with structural information from RDCs. Thus, relative configurations of chiral compounds were generated only by observables (e.g., NOEs, RDCs) rendering tedious evaluations of calculated structures against RDCs obsolete. We demonstrate the potential of this novel procedure by the simultaneous determination of the configuration and the conformation of three natural products, (−)‐isopinocampheol (1), tubocurarine (2), and vincristine (3), as well as for diisopropylidene‐β‐d‐fructopyranose (4).
Recent Progress on Manganese‐Based Nanostructures as Responsive MRI Contrast Agents
Authors: García‐Hevia Lorena , Bañobre‐López Manuel , Gallo Juan
Published: July 2018

Manganese‐based nanostructured contrast agents (CAs) entered the field of medical diagnosis through magnetic resonance imaging (MRI) some years ago. Although some of these Mn‐based CAs behave as classic T1 contrast enhancers in the same way as clinical Gd‐based molecules do, a new type of Mn nanomaterials have been developed to improve MRI sensitivity and potentially gather new functional information from tissues by using traditional T1 contrast enhanced MRI. These nanomaterials have been designed to respond to biological environments, mainly to pH and redox potential variations. In many cases, the differences in signal generation in these responsive Mn‐based nanostructures come from intrinsic changes in the magnetic properties of Mn cations depending on their oxidation state. In other cases, no changes in the nature of Mn take place, but rather the nanomaterial as a whole responds to the change in the environment through different mechanisms, including changes in integrity and hydration state. This review focusses on the chemistry and MR performance of these responsive Mn‐based nanomaterials.
Thermoresponsive Alignment Media in NMR Spectroscopy: Helix Reversal of a Copolyaspartate at Ambient Temperatures
Authors: Schwab Mira , Schmidts Volker , Thiele Christina M.
Published: July 2018

Poly(aspartic acid esters) are known to form either right‐or left‐handed α‐helices depending on the ester group in the side chain, on solvent and/or on temperature. Polyphenethyl‐l‐aspartates (PPLA) exhibit a helix reversal from the right‐ to the left‐handed form with increasing temperature. We have recently reported the application of polyphenethylaspartates as helically chiral alignment media. The thermoresponsivity observed for these polymers offers the possibility to measure different orientations of analytes before and after helix reversal of the alignment medium at 373 K. Herein we present a synthesized copolymer of phenethyl‐ and benzylaspartate as a new alignment medium undergoing this helix reversal at 303–313 K. Thus, the measurement of residual dipolar couplings (RDC) before and after the helix reversal is allowed for at ambient temperatures. A complete sign change of all 1H–13C RDCs was observed, which is close to the highest possible difference in NMR spectra.
Simultaneous chiral analysis of amphetamine‐type stimulants and ephedrine by capillary electrophoresis coupled to time‐of‐flight mass spectrometry
Authors: Cui Xuezi , Liang Chen , Gong Feijun , Wang Rong , Ni Chunfang , Wu Yanhong , Chen Guiliang , Zhang Yurong
Published: July 2018

This study focused on the chiral characteristics of methamphetamine seizures in Shanghai for inferring the synthetic pathways of drugs. Capillary electrophoresis coupled to time‐of‐flight mass spectrometry was used for simultaneous chiral separation of amphetamine‐type stimulants and ephedrine, including S(+)‐amphetamine/R(−)‐amphetamine, S(+)‐methamphetamine/R(−)‐methamphetamine, (±)‐MDA (3,4‐methylenedioxyamphetamine), (±)‐MDMA (3,4‐methylenedioxymethamphetamine), (±)‐MDEA (3,4‐methylenedioxy‐N‐ethylamphetamine), d,l‐N‐ethylamphetamine, methylephedrine/methylpseudoephedrine, and 1S,2R(+)‐ephedrine/(−)‐ephedrine. The running buffer was 50‐mM ammonium formate (pH 2.2 was adjusted by 1‐M formic acid) containing 0.26% highly sulfated γ‐cyclodextrin as the chiral selector. All enantiomers were well resolved within 40 minutes by capillary electrophoresis at 20 kV in an uncoated fused‐silica capillary (50‐μm I.D. × 375‐μm O.D. × 90‐cm length) and detected by micro time‐of‐flight mass spectrometry. Twenty seized methamphetamine samples were determined by the established method. They were classified into two groups through their chiral characteristics.
Toward A New Model For Firm Internationalization: Conservative, Predictable, and Pacemaker Companies and Markets
Authors: Paul Justin , Sánchez‐Morcilio Rosarito
Published: July 2018

Through this article we develop a new model for the internationalization of firms, called the Conservative, Predictable and Pacemaker (CPP) model, for extending research in the domain of international business. The main purpose is to provide a new typology that can be used as a theoretical lens for future research and to motivate researchers to think beyond the established models, which are repeatedly used in many studies. This article is based on primary data collected from firms in the information technology sector in Puerto Rico. The CPP model may be useful for industry analysis and research dealing with the growth and internationalization of firms across industries and countries. © 2018 ASAC. Published by John Wiley & Sons, Ltd.
Generation of Induced Cardiospheres via Reprogramming of Mouse Skin Fibroblasts
Authors: Lian Wei , Jia Yuning , Li Lingyun , Huang Zhong , Xu Jianyong
Published: July 2018

Cardiospheres represent a more effective cell‐based therapy for treatment of myocardial infarction than stem cells of non‐cardiac origin. Unfortunately, their therapeutic application is limited by low yield of cell harvesting, declining quality and quantity during the aging process, and the need for highly invasive heart biopsy. Therefore, there is an emerging interest in generating cardiosphere‐like stem cells from somatic cells via somatic reprogramming. This novel approach would provide an unlimited source of stem cells with cardiac differentiation potential. Here we provide the detailed protocol for generating induced cardiospheres (iCS) for cardiac regeneration by somatic reprogramming of mouse fibroblasts using a panel of pluripotent transcription factors and cardiotrophic growth factors. © 2018 by John Wiley & Sons, Inc.
CYP3A4*22 Impairs the Elimination of Ticagrelor, But Has No Significant Effect on the Bioactivation of Clopidogrel or Prasugrel
Authors: Holmberg Mikko T. , Tornio Aleksi , Paile‐Hyvärinen Maria , Tarkiainen E. Katriina , Neuvonen Mikko , Neuvonen Pertti J. , Backman Janne T. , Niemi Mikko
Published: July 2018

CYP3A enzymes participate in the elimination of ticagrelor and the bioactivation of clopidogrel and prasugrel. We studied the effects of functional CYP3A genetic variants (CYP3A4*22; rs35599367 and CYP3A5*3; rs776746) on the pharmacokinetics and pharmacodynamics of ticagrelor, clopidogrel, and prasugrel. Six healthy volunteers with the CYP3A4*1/*22 and CYP3A5*3/*3 genotype (CYP3A4*22 carriers), eight with the CYP3A4*1/*1 and CYP3A5*1/*3 genotype (CYP3A5 expressors), and 11–13 with the CYP3A4*1/*1 and CYP3A5*3/*3 genotypes (controls) ingested single doses of ticagrelor, clopidogrel, and prasugrel on separate occasions. Ticagrelor area under the plasma concentration‐time curve (AUC) was 89% (P = 0.004) higher in CYP3A4*22 carriers than in controls. CYP3A4*22 carriers also showed more pronounced platelet inhibition at 24 hours after ticagrelor ingestion than the controls (43% vs. 21%; P = 0.029). The CYP3A5 genotype did not affect ticagrelor pharmacokinetics. Neither CYP3A5 nor CYP3A4 genotypes significantly affected prasugrel or clopidogrel. In conclusion, the CYP3A4*22 allele markedly impairs ticagrelor elimination enhancing its antiplatelet effect.
Operando Spectroscopy in Photocatalysis
Authors: Caudillo‐Flores Uriel , Muñoz‐Batista Mario J. , Kubacka Anna , Fernández‐García Marcos
Published: July 2018

The use of operando spectroscopic tools in heterogeneous photocatalysis has experienced a strong drive in recent years. When using operando tools we must, however, consider carefully the fraction of the system to be probed in an in situ cell, that is, the volume under the simultaneous influence of excitation light and the reactants. This is not an obvious task for certain spectroscopies, particularly for those attempting to characterize the physico‐chemical state of the catalysts. Herein we provide an analysis of this point applied to spectroscopies such as XAS (X‐ray absorption spectroscopy) and complete the analysis of operando tools with those aimed to characterize the surface of the photocatalysts (XPS; X‐ray photoelectron spectroscopy) as well as those spectroscopies, such as infrared or Raman, focusing on the study of the reactant−catalyst interface.
Channel assignment scheme in clustered multichannel cognitive radio networks with outdated CSI over Rayleigh fading channels
Authors: Olawole Akinbode A. , Takawira Fambirai , Oyerinde Olutayo O.
Published: July 2018

This work investigates channel assignment for cooperative spectrum sensing in multichannel cognitive radio networks, where the heterogeneity of primary user (PU) activity and the effect of varying channel condition on the received signal‐to‐noise ratio during cluster formation are considered. With the objective to minimize interference to the PU while enhancing multiple spectrum utilization of the secondary user (SU), an overlapping cluster‐based assignment is formulated into a nonlinear integer optimization problem. To obtain an efficient solution, the nonlinear integer problem is transformed into a mixed integer linear problem, based on which, this paper proposes an exact solution and then two new heuristic algorithms for suboptimal solutions, respectively. Furthermore, a comparative study of four different cluster head selection schemes with respect to their performance in cooperative spectrum sensing, under cluster's heterogeneity in terms of SUs distribution relative to PU transmitter location is presented. Based on the study, a robust cluster head selection scheme is proposed. Simulation results show that good sensing performance and increased opportunistic spectrum utilization in multichannel cognitive radio networks are two sides of a coin that depend on the ratio of the SUs to the number of PU channels. How far away the PU is from the cluster center is also seen to be key in the optimal selection of cluster heads in cooperative spectrum sensing.
Prevalence of moderately increased albuminuria among individuals with normal HbA1c level but impaired glucose tolerance: Results from the LIFE‐Adult‐Study
Authors: Živković Mila , Tönjes Anke , Baber Ronny , Wirkner Kerstin , Loeffler Markus , Engel Christoph
Published: July 2018

Aims

Diabetes screening strategies using glycated haemoglobin (HbA1c) as first‐instance diagnostic parameter may cause failure to detect individuals with abnormal glucose regulation and possible signs of microvascular complications despite “rule‐out” HbA1c levels. This cross‐sectional study examined the diagnostic performance of HbA1c in relation to fasting and two‐hour postload plasma glucose (FPG/2 h‐PG), and investigated whether individuals with normal HbA1c but abnormal FPG/2 h‐PG have a higher prevalence of moderately increased albuminuria as possible sign of early stage kidney damage.

Methods

A total of 2695 individuals (age 40‐79 years, 48% men) without prior diagnosis of diabetes and complete measurement of HbA1c, FPG, 2 h‐PG and urine albumin‐creatinine ratio (UACR) were taken from a large population‐based epidemiological study in the City of Leipzig, Germany.

Results

A total of 2439 individuals (90.5%, 95% CI: 89.4‐91.6) had normal HbA1c levels, <39 mmol/mol (<5.7%), while 234 (8.7%, 95% CI: 7.7‐9.8) had prediabetes, HbA1c ≥39 and <48 mmol/mol (≥5.7 and <6.5%), and 22 (0.8%, 95% CI: 0.5‐1.2) had diabetes, HbA1c ≥48 mmol/mol (≥6.5%), according to HbA1c. Among individuals with normal HbA1c, 35.6% (95% CI: 33.7‐37.5) had impaired fasting glucose or impaired glucose tolerance and 1.8% (95% CI: 1.4‐2.4) had diabetes according to FPG/2 h‐PG. Individuals with normal HbA1c but prediabetic or diabetic FPG/2 h‐PG had a significantly higher prevalence of moderately increased albuminuria (9.4%, 95% CI: 7.6‐11.5 and 13.3%, 95% CI: 5.8‐25.4, respectively) than individuals with normal HbA1c and normal FPG/2 h‐PG (3.9%, 95% CI: 3.0‐5.0).

Conclusions

The prevalence of prediabetes according to FPG/2 h‐PG among individuals with normal HbA1c is considerably high, and the prevalence of moderately increased albuminuria in this group is significantly elevated. Risk factors for diabetes such as age, gender and BMI may help to better identify this at‐risk group.
Construction and Magnetic Study of One‐Dimensional Lanthanide–Radical Chains Involving Pyridinone‐Substituted Nitronyl Nitroxide Radicals
Authors: Guo Jianni , Sun Juan , Sun Guifang , Sun Zan , Li Licun
Published: July 2018

A new nitronyl nitroxide radical‐containing pyridinone group (NIT‐PhPyO, 1) has been synthesized {NIT‐PhPyO = 2‐[4‐(4‐pyridinone)phenyl]‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide}. By using this functionlized nitronyl nitroxide, two isomorphic lanthanide–nitronyl nitroxide radical compounds [{Ln(hfac)3}3(NIT‐PhPyO)2]n (Ln = Gd 2 and Dy 3; hfac = hexafluoroacetylacetonate) have been successfully obtained. X‐ray spectroscopic analysis reveals that complexes 2 and 3 possess a 1D chain structure with Ln2O2 binuclear units, which represent the first examples of Ln–radical chains involving binuclear Ln2O2 units. Analysis of the magnetic data indicates that a weak antiferromagnetic coupling exists between two Gd3+ ions, while the magnetic interaction between the GdIII ion and the coordinated nitroxide group is ferromagnetic. Alternating current (ac) magnetic studies indicate that compound 3 displays slow magnetic relaxation behavior at low temperature.
Synthesis of a Perylene Diimide Dimer with Pyrrolic N–H Bonds and N‐Functionalized Derivatives for Organic Field‐Effect Transistors and Organic Solar Cells
Authors: Vespa Marcus , Cann Jonathan R. , Dayneko Sergey V. , Melville Owen A. , Hendsbee Arthur D. , Zou Yingping , Lessard Benoît H. , Welch Gregory C.
Published: July 2018

This study reports on the new and optimized synthesis of an N‐annulated perylene diimide dimer with functional N–H moieties. The presence of two N–H moieties renders the dimer relatively insoluble in most organic solvents. The dimer is easily functionalized with electron donating hexyl chains or electron withdrawing tert‐butyloxycarbonyl (tBOC) groups to yield highly soluble materials. The tBOC groups can be thermally cleaved in the thin film to give the parent dimer. The N–H bonds are acidic and interact with volatile organic bases. Deprotonation results in a color change from red to blue. All compounds have utility as electron transport materials in organic field‐effect transistors and green solvent, air processed organic solar cells. Electron mobilities were on the order of about 2–7 × 10–6 cm2/V s. Solar cell power conversion efficiency reached 2 % for those using the tBOC functionalized dimer, 3 % for those using the H‐atom functionalized dimer, and 6 % for those using the hexyl chain functionalized dimer. The performance of the latter is quite impressive considering the simple materials synthesis and greener solar cell processing.
Markov chain Monte Carlo ground‐motion selection algorithms for conditional intensity measure targets
Authors: Shi Yuan , Stafford Peter J.
Published: July 2018

Two new algorithms are presented for efficiently selecting suites of ground motions that match a target multivariate distribution or conditional intensity measure target. The first algorithm is a Markov chain Monte Carlo (MCMC) approach in which records are sequentially added to a selected set such that the joint probability density function (PDF) of the target distribution is progressively approximated by the discrete distribution of the selected records. The second algorithm derives from the concept of the acceptance ratio within MCMC but does not involve any sampling. The first method takes advantage of MCMC's ability to efficiently explore a sampling distribution through the implementation of a traditional MCMC algorithm. This method is shown to enable very good matches to multivariate targets to be obtained when the numbers of records to be selected is relatively large. A weaker performance for fewer records can be circumvented by the second method that uses greedy optimisation to impose additional constraints upon properties of the target distribution. A preselection approach based upon values of the multivariate PDF is proposed that enables near‐optimal record sets to be identified with a very close match to the target. Both methods are applied for a number response analyses associated with different sizes of record sets and rupture scenarios. Comparisons are made throughout with the Generalised Conditional Intensity Measure (GCIM) approach. The first method provides similar results to GCIM but with slightly worse performance for small record sets, while the second method outperforms method 1 and GCIM for all considered cases.
Hydrology and hillslope processes explain spatial variation in tree‐ring responses to the 1983 earthquake at Borah Peak, Idaho, USA
Authors: Bekker Matthew F. , Metcalf Douglas P. , Harley Grant L.
Published: July 2018

Dendrogeomorphic approaches have been used to identify tree‐ring responses to earthquakes, and have the potential to contribute new paleoseismic information. However, this potential is limited by the relatively low intensity of damage from earthquakes. In this paper, we present a comparison of tree‐ring responses in multiple species to the Mw 6.9 1983 Borah Peak, Idaho earthquake across three adjacent but distinct sites with different hydrologic settings, and different types and intensities of co‐seismic mass movement. We analyzed samples from 166 trees for a broad range of growth responses, including suppressions, releases, reaction wood, and traumatic resin ducts. The proportions of trees recording growth disturbances at the sites with clear hydrologic changes and/or co‐seismic mass movement were twice as high (39–42%) as the site where these processes were less evident (19%), and probability density functions of percentage change in growth for all crossdated trees echoed these results. Growth suppressions and reaction wood were common across sites, whereas traumatic resin ducts were only associated with rockfalls and landslides at one site. Growth releases were also primarily restricted to one site, and in contrast to previous studies, most of these probably reflected direct improvements in growing conditions via documented increased flow in springs and streams, rather than the indirect influence of reduced competition via the death of neighboring trees. These results highlight the importance of site selection in dendroseismology, and particularly suggest that focusing on sites with potential co‐seismic hydrologic changes and mass movement, sampling trees with and without external evidence of earthquake impacts, and understanding the connection between responses and site conditions may facilitate greater contributions of dendrogeomorphic approaches to paleoseismology. © 2018 John Wiley & Sons, Ltd.
Sulfonated Oligomer‐crosslinked Fluorinated Poly(aryl ether sulfone)‐based Proton Exchange Membranes for Fuel Cells
Authors: Zhang X. , Lu Y. , Yan X. , Hu Z. , Chen S.
Published: July 2018

A series of sulfonated oligomer‐crosslinked fluorinated poly(aryl ether sulfone) membranes (c‐SPFAES) have been prepared in a consecutive casting and thermal treating process from fluorinated polymers and sulfonated oligomers, where the latter acted as hydrophilic grafts and crosslinkers at the same time. Membrane structure and physico‐chemical properties are characterized and evaluated by 1H‐nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis and atomic force microscopy, Fenton, water‐swelling and H2/O2 single cell tests. For the c‐SPFAES membranes with ion exchange capacity of 1.04–1.78 mmol g−1, they exhibit excellent mechanical toughness with Young's moduli above 1.3 GPa and tensile strength beyond 35.8 MPa, good dimensional and thermo‐oxidative stability. They also exhibited clear hydrophilic‐hydrophobic phase‐separation morphology. The proton conductivity is higher than 0.1 S cm−1 for the c‐SPFAES membranes with IEC over 1.38 mmol g−1 at 60 °C. In a H2/O2 single cell test, the maximum power density of the c‐SPFAES‐1.61 membrane achieves 587 mW cm−2 at 80 °C under fully hydrated state. The c‐SPFAES membrane show promising potentials as a polymer electrolyte membrane candidate for fuel cell applications.