bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Pressure and pH on the Hydrolysis of Cytosine: Implications for Nucleotide Stability around Deep‐Sea Black Smokers
Authors: Lepper Christopher P. , Williams Martin A. K. , Penny David , Edwards Patrick J. B. , Jameson Geoffrey B.
Published: December 2017

The relatively low chemical stability of cytosine compared with other nucleobases is a key concern in origin‐of‐life scenarios, but the effect of pressure on the rate of hydrolysis of cytosine to uracil remains unknown. Through in situ NMR spectroscopy measurements, it has been determined that the half‐life of cytosine at 373.15 K decreases from (18.0±0.7) days at ambient pressure (0.1 MPa) to (8.64±0.18) days at high pressure (200 MPa). This yields an activation volume for hydrolysis of (−11.8±0.5) cm3 mol−1; a decrease that is similar to the molar volume of water (18.0 cm3 mol−1) and consistent with a tetrahedral 3,3‐hydroxyamine transition‐state/intermediate species. Similar behaviour was also observed for cytidine. At both ambient and high pressures, the half‐life of cytosine decreases significantly as the pH decreases from 7.0 to 6.0. These results provide scant support for the notion that RNA‐based life forms originated in high‐temperature, high‐pressure, acidic environments.
Spontaneous Covalent Self‐Assembly of the Azoarcus Ribozyme from Five Fragments
Authors: Jayathilaka Tharuka S. , Lehman Niles
Published: December 2017

Spontaneous covalent assembly of short RNA fragments has been proposed as a plausible prebiotically relevant pathway to a self‐reproducing system. We previously showed that the Azoarcus group I intron could self‐assemble from four RNA fragments. Here, we extended this fragmentation to five RNAs that averaged <40 nucleotides in length. We optimized this reaction and showed that a dehydration–rehydration sequence was the most effective means to date to shift the self‐assembly equilibrium from reactants to products.
Alphanumerical Visual Display Made of DNA Logic Gates for Drug Susceptibility Testing of Pathogens
Authors: Connelly Ryan P. , Morozkin Evgeny S. , Gerasimova Yulia V.
Published: December 2017

Molecular diagnostics of drug‐resistant pathogens require the analysis of point mutations in bacterial or viral genomes, which is usually performed by trained professionals and/or by sophisticated computer algorithms. We have developed a DNA‐based logic system that autonomously analyzes mutations found in the genome of Mycobacterium tuberculosis complex (MTC) bacteria and communicates the output to a human user as alphanumeric characters read by the naked eye. The five‐gate system displays “O” (“no infection”) for the absence of MTC infection and “P” or “F” for passing or failing a drug‐susceptibility test, respectively.
Carotid‐cavernous fistula after endovascular intervention for chronic carotid artery total occlusion
Authors: Yeh Chih‐Fan , Chen Yin‐Hsien , Lin Mao‐Shin , Huang Ching‐Chang , Hung Chi‐Sheng , Meng Shih‐Wei , Lee Chih‐Kuo , Kao Hsien‐Li
Published: December 2017

Background and Purpose

In addition to head trauma and cranial surgery, endovascular intervention for chronic carotid artery occlusion (CAO) may also result in carotid‐cavernous fistula (CCF). The management and prognosis of iatrogenic CCF during CAO recanalization have never been well described and discussed in the literature.

Materials and Methods

We conducted a retrospective analysis for CAO recanalization attempts in National Taiwan University Hospital and affiliated hospitals. Incidence and presentation, demographic and angiographic variables, and clinical follow‐up of the development of iatrogenic CCF were carefully reviewed.

Results

A total of 138 consecutive de novo CAO endovascular recanalization attempts were reviewed. The technical success rate was 61.6% (85/138). Complication rate, including death, stroke, and intracranial or sub‐arachnoid hemorrhage (ICH or SAH) was 4.3% (6/138). CCF developed in 11 patients (8.0%), and none resulted in death, stroke, or ICH/SAH within 30 days. Female gender and distal carotid artery reconstitution at communicating or ophthalmic segments were associated with development of CCF. Imaging follow‐ups were performed in eight patients and none showed persistent CCF.

Conclusion

CCF may develop during chronic CAO endovascular recanalization attempts. It is usually self‐limited and can be managed conservatively.
Association of isochromosome (7)(q10) in Shwachman–Diamond syndrome with the severity of cytopenia
Authors: Shimosato Yuko , Tanoshima Reo , Tsujimoto Shin‐ichi , Takeuchi Masanobu , Sasaki Koji , Kajiwara Ryosuke , Goto Hiroaki , Nagai Junichi , Yanagimachi Masakatsu D. , Ito Shuichi , Yokota Shumpei
Published: December 2017

Key Clinical Message

We report two male siblings with SDS. They have the same compound heterozygous mutations. Only one of the siblings acquired cytogenetic abnormality of i(7q) 2 years after diagnosis, became transfusion‐dependent, and underwent allogeneic hematopoietic stem cell transplantation. These cases indicate that i(7q) is associated with significant cytopenia in SDS patients.
Covalently Immobilized Lipase on a Thermoresponsive Polymer with an Upper Critical Solution Temperature as an Efficient and Recyclable Asymmetric Catalyst in Aqueous Media
Authors: Lou Lan‐Lan , Qu Huaxin , Yu Wenjun , Wang Bei , Ouyang Lezi , Liu Shuangxi , Zhou Wuzong
Published: December 2017

A thermoresponsive lipase catalyst with an upper critical solution temperature (UCST) of about 26 °C was exploited by covalent immobilization of an enzyme, Pseudomonas cepacia lipase (PSL), onto poly(acrylamide‐co‐acrylonitrile) by glutaraldehyde coupling. The experimental conditions for the PSL immobilization were optimized. The immobilized PSL was much more stable for wide ranges of temperature and pH than free PSL. The material was also evaluated as an asymmetric catalyst in the kinetic resolution of racemic α‐methylbenzyl butyrate at 55 °C in an aqueous medium and exhibited high catalytic performance and stability. Up to 50 % conversion and 99.5 % product enantiomeric excess were achieved, thus providing highly pure enantiomers. This biocatalyst could be easily recovered by simple decantation for reuse based on temperature‐induced precipitation. It showed good reusability and retained 80.5 % of its original activity with a well reserved enantioselectivity in the 6th cycle. This work would shed light on the future development of new UCST‐type enzyme catalysts.
Alkenyl and Aryl Peroxides
Authors: Klussmann Martin
Published: December 2017

Alkenyl and aryl peroxides are a special class of organic peroxides. Under ambient conditions, they are usually short‐lived, rapidly decomposing into radicals by homolytic O−O bond cleavage. They play an important role in the chemistry of the lower atmosphere, where they are formed through ozonolysis of alkenes. In the dark, this pathway is considered the major source of hydroxyl radicals, the “detergent of the atmosphere”. In solution, alkenyl and aryl peroxides can be formed by various methods and their decomposition can be harnessed synthetically. For example, reactions involving alkenyl peroxides can be used to introduce ketones through radical additions, and nucleophilic aromatic substitution reactions generating aryl peroxides have been used to synthesize phenols. The radicals can also initiate radical polymerization reactions or chain reactions and mediate oxidative coupling by C−H bond functionalization. Knowledge of their chemistry could be helpful for projects generating or utilizing peroxides.
Modulation of Nickel Pyridinedicarboxamidate Complexes to Explore the Properties of High‐valent Oxidants
Authors: Pirovano Paolo , Twamley Brendan , McDonald Aidan R.
Published: December 2017

High‐valent Ni oxidants have been implicated in hydrocarbon oxidation catalysis, however, little is understood about the properties of these oxidants. Herein, a family of NiII complexes supported by a pyridinedicarboxamidate ligand and different ancillary ligands was synthesized. The series spans coordination numbers 4, 5, and 6, and contains neutral, mono‐ and di‐anionic donor types. X‐ray crystallography and magnetic measurements showed that the 4‐coordinate complexes were square planar and low spin (S=0) and the 5‐ and 6‐coordinate were intermediate spin (S=1). The NiII complexes could be oxidized by one electron to form a series of metastable NiIII species. EPR analysis confirmed their description as S=
NiIII compounds with signal shape and hyperfine coupling dependent on the coordination environment. The oxidation of phenols by the NiIII species was probed, providing evidence for a correlation between oxidizing power and electron‐donating properties of the supporting ligands. Critically, we found that the pyridinedicarboxamidate ligand may be a non‐innocent proton acceptor in the oxidation reactions.
On the Lewis Acidity of the Oxoiron(IV) Unit in a Tetramethylcyclam Complex
Authors: Klein Johannes E. M. N. , Draksharapu Apparao , Shokri Alireza , Cramer Christopher J. , Que Lawrence
Published: December 2017

The correlation between oxidation state and Lewis acidity is well established for hexaquairon complexes in the +II and +III oxidation state, in which the higher oxidation state leads to a lower pKa for the bound H2O ligand. This article addresses the Lewis acidity of the oxoiron(IV) complex [FeIV(O)(TMC)(OH2)]2+ (1‐OH2; TMC=1,4,8,11‐tetramethylcyclam) by determining the pKa of the H2O ligand. We establish that 1‐OH2 has a pKa of 6.9±0.5, a value that falls in between those found for [FeIII(OH2)6]3+ and [FeII(OH2)6]2+. This intermediate value can be readily rationalized by the presence of the highly basic oxide ligand that mitigates the Lewis acidity of the iron(IV) center. Although the oxo ligand occupies only one position in 1‐OH2, anti to all four methyl groups that protrude from the same face of the nonplanar TMC ligand, its conjugate base 1‐OH exists as a mixture of syn and anti tautomers, which are related by proton transfer between the oxo and the hydroxo ligands.
Designing the Macrocyclic Dimension in Main Group Chemistry
Authors: Niu Hao‐Che , Plajer Alex J. , Garcia‐Rodriguez Raul , Singh Sanjay , Wright Dominic S.
Published: December 2017

Outside the confines and well‐established domain of organic chemistry, the systematic building of large macromolecular arrangements based on non‐carbon elements represents a significant and exciting challenge. Our aim in the past two decades has been to develop robust synthetic methods to construct new types of main group architectures in a methodical way, principles of design that parallel those used in the organic arena. This Concept article addresses the fundamental thermodynamic and kinetic problems involved in the design and synthesis of main group macrocycles and looks to future developments of macromolecules in this area, as well as new applications in coordination chemistry.
Investigation of (Me4N)SCF3 as a Stable, Solid and Safe Reservoir for S=CF2 as a Surrogate for Thiophosgene
Authors: Scattolin Thomas , Pu Maoping , Schoenebeck Franziska
Published: December 2017

While thiophosgene finds widespread usage on a multi‐ton scale, its fluorinated counterpart S=CF2 is essentially unexplored in synthesis. Using experimental reactivity tests, ReactIR and computational techniques, we herein showcase that the solid (Me4N)SCF3 functions as a safe reservoir for S=CF2. A key feature is that the reactive electrophile is not simply released over time, but instead is liberated under activation with a protic nucleophile. The reactivity of S=CF2 is mild, allowing large‐scale and late‐stage synthetic applications without special reaction control. The mechanism was fully elucidated, including a rationalization of the role of the Me4N cation and the origins of selectivity.
Panchromatic Photosensitizers Based on Push–Pull, Unsymmetrically Substituted Porphyrazines
Authors: Fernández‐Ariza Javier , Urbani Maxence , Rodríguez‐Morgade M. Salomé , Torres Tomás
Published: December 2017

A series of five push–pull porphyrazines of A3B type, in which unit B is an isoindole 4‐carboxylic acid, has been prepared. The units A have been endowed with thioether, amine, ether and alkyl functions, either directly attached to the β‐position of the pyrrolic units, or connected to the porphyrazine core through p‐substituted phenyl groups. Attaching the electron‐donor functions to the porphyrazine periphery produces strong perturbations in the electronic and redox properties of the dyes. Their HOMO and LUMO energies, estimated from the optical and redox data, as well as with DFT calculations, raise upon functionalization with amines, while the corresponding frontier orbital energetic levels lower upon functionalization with thioethers, p‐methoxyphenyl or p‐tert‐butylphenyl groups. The effective interaction of peripheral substitution with the macrocycle produces chromophores with panchromatic absorption between 300 and 750–850 nm.
A Rotaxane Scaffold Bearing Multiple Redox Centers: Synthesis, Surface Modification and Electrochemical Properties
Authors: Steffenhagen Marie , Latus Alina , Trinh Thi Minh Nguyet , Nierengarten Iwona , Lucas Ivan T. , Joiret Suzanne , Landoulsi Jessem , Delavaux‐Nicot Béatrice , Nierengarten Jean‐François , Maisonhaute Emmanuel
Published: December 2017

A rotaxane scaffold incorporating two dithiolane anchoring units for the modification of gold surfaces has been functionalized with multiple copies of a redox unit, namely ferrocene. Surface modification has been first assessed at the single molecule level by atomic force microscopy (AFM) and scanning tunneling microscopy (STM) imaging, while tip enhanced Raman spectroscopy (TERS) provided the local vibrational signature of the ferrocenyl subunits of the rotaxanes grafted onto the gold surface. Finally, oxidation of the redox moieties within a rotaxane scaffold grafted onto gold microelectrodes has been investigated by ultrafast cyclic voltammetry. Intramolecular electron hopping is indeed extremely fast in this system. Moreover, the kinetics of charge injection depends on the molecular coverage due to the influence of intermolecular contacts on molecular motions.
Tetraphenylethylene Foldamers with Double Hairpin‐Turn Linkers, TNT‐Binding Mode and Detection of Highly Diluted TNT Vapor
Authors: Xiong Jia‐Bin , Feng Hai‐Tao , Wang Jin‐Hua , Zhang Chun , Li Bao , Zheng Yan‐Song
Published: December 2017

Tetraphenylethylene (TPE) foldamers with double hairpin‐turn linkers showing an aggregation‐induced emission (AIE) effect have been synthesized for the first time. A crystal structure of a foldamer–TNT complex has been obtained, enabling unprecedented direct observation of the interactions between TNT molecules and the chromophores of the foldamer. Instead of π–π stacking interactions, which have often been considered to be the key mechanism in the binding of TNT by chromophoric receptors, strong n–π interactions between the nitro groups of TNT and the aromatic rings of the foldamer have been found. Exceptionally, by addition of 1 % NaF to a suspension of the foldamer in H2O/THF (95:5), the fluorescence quenching efficiency by TNT vapor significantly increased from about 20 % to more than 90 %. Even after diluting TNT‐saturated air at 25 °C by a factor of 2×104, an obvious quenching response was observed, indicating that ultratrace TNT vapor (down to 3.4 fg per mL of air) could be detected.
Efficient Buchwald–Hartwig–Migita Cross‐Coupling for DNA Thioglycoconjugation
Authors: Probst Nicolas , Lartia Rémy , Théry Océane , Alami Mouâd , Defrancq Eric , Messaoudi Samir
Published: December 2017

An efficient method for the thioglycoconjugation of iodinated oligonucleotides by Buchwald–Hartwig–Migita cross‐coupling under mild conditions is reported. The method enables divergent synthesis of many different functionalized thioglycosylated ODNs in good yields, without affecting the integrity of the other A, C, and G nucleobases.
General One‐Pot Synthesis of Transition‐Metal Phosphide/Nitrogen‐Doped Carbon Hybrid Nanosheets as Ultrastable Anodes for Sodium‐Ion Batteries
Authors: Li Jingjing , Shi Liang , Gao Jingyu , Zhang Genqiang
Published: December 2017

Sodium‐ion batteries (SIBs) have been considered as promising energy storage devices in grid‐level applications, owing to their largely reduced cost compared with that of lithium‐ion batteries. However, the practical application of SIBs has been seriously hindered because of the lack of appropriate anode materials, limited by the thermodynamics perspective, which is one of the central task at current stage. Herein, we have developed a general one‐pot strategy for the synthesis of transition‐metal phosphide (TMP) based hybrid nanosheets composed of carbon‐coated TMP nanoparticles anchored to the surface of nitrogen‐doped carbon nanosheets. This facile and cost‐effective method is quite universal and holds potential to be further extended to other metal phosphide materials. Significantly, the hybrid nanosheet electrode possesses excellent sodium storage properties as anodes for SIBs, including high specific capacity, an ultra‐long cycle life and a remarkable rate performance. This work makes a significant contribution to not only the synthetic methodology of TMP–carbon two‐dimensional hybrid nanostructures, but also the application of TMP‐based anodes for high‐energy SIBs.
Synthesis, Structure, and Acidity Constants of Ligated α‐Boryl Acetic Acids
Authors: Allen Thomas H. , Horner Anthony R. , Geib Steven J. , Weber Stephen G. , Curran Dennis P.
Published: December 2017

Basic hydrolyses of various ligated α‐boryl acetic acid esters provided the first ligated derivatives of the unknown compound boroacetic acid (BH2CH2CO2H). Four monoacids (L‐BH2CH2CO2H) and one diacid (L‐BH(CH2CO2H)2) were prepared with N‐heterocyclic carbene, amine, and pyridine ligands (L). The stable acids were characterized by X‐ray crystallography and acidity constant (pKa) measurements. They rank among the least acidic of all known carboxylic acids. In turn, their conjugate bases are among the strongest of all carboxylates.
Fission yeast Myo2: Molecular organization and diffusion in the cytoplasm
Authors: Friend Janice E. , Sayyad Wasim A. , Arasada Rajesh , McCormick Chad D. , Heuser John E. , Pollard Thomas D.
Published: December 2017

Myosin‐II is required for the assembly and constriction of cytokinetic contractile rings in fungi and animals. We used electron microscopy, fluorescence recovery after photobleaching (FRAP), and fluorescence correlation spectroscopy (FCS) to characterize the physical properties of Myo2 from fission yeast Schizosaccharomyces pombe. By electron microscopy, Myo2 has two heads and a coiled‐coiled tail like myosin‐II from other species. The first 65 nm of the tail is a stiff rod, followed by a flexible, less‐ordered region up to 30 nm long. Myo2 sediments as a 7 S molecule in high salt, but aggregates rather than forming minifilaments at lower salt concentrations; this is unaffected by heavy chain phosphorylation. We used FRAP and FCS to observe the dynamics of Myo2 in live S. pombe cells and in cell extracts at different salt concentrations; both show that Myo2 with an N‐terminal mEGFP tag has a diffusion coefficient of ∼ 3 µm2 s−1 in the cytoplasm of live cells during interphase and mitosis. Photon counting histogram analysis of the FCS data confirmed that Myo2 diffuses as doubled‐headed molecules in the cytoplasm. FCS measurements on diluted cell extracts showed that mEGFP‐Myo2 has a diffusion coefficient of ∼ 30 µm2 s−1 in 50 to 400 mM KCl concentrations.
Improving the Potency of Cancer Immunotherapy by Dual Targeting of IDO1 and DNA
Authors: Fang Kun , Dong Guoqiang , Wang Hongyu , He Shipeng , Wu Shanchao , Wang Wei , Sheng Chunquan
Published: December 2017

Herein we report the first exploration of a dual‐targeting drug design strategy to improve the efficacy of small‐molecule cancer immunotherapy. New hybrids of indoleamine 2,3‐dioxygenase 1 (IDO1) inhibitors and DNA alkylating nitrogen mustards that respectively target IDO1 and DNA were rationally designed. As the first‐in‐class examples of such molecules, they were found to exhibit significantly enhanced anticancer activity in vitro and in vivo with low toxicity. This proof‐of‐concept study has established a critical step toward the development of a novel and effective immunotherapy for the treatment of cancers.
Complete multinuclear solid‐state NMR of metal‐organic frameworks: The case of α‐Mg‐formate
Authors: Lucier Bryan E. G. , Zhang Yue , Huang Yining
Published: December 2017

Metal‐organic frameworks (MOFs) are exciting porous materials with a growing number of applications ranging from catalysis to gas storage. Establishing logical connections between the local MOF structure and its properties is not often straightforward, however, solid‐state NMR is a sensitive probe of local structure and can be used to shed light on processes such as guest adsorption and gas motion within MOFs. As illustrated using our recent works on the microporous α‐Mg‐formate (Mg3(HCOO)6) MOF, complete multinuclear solid‐state NMR characterization of MOFs is now possible, and can provide unique insight that is not readily available through other methods. A wide variety of solid‐state NMR techniques have been employed, including direct‐excitation, cross‐polarization, fast magic‐angle spinning, and two‐dimensional experiments. New variable‐temperature 2H solid‐state NMR data of deuterated hydrogen gas within α‐Mg‐formate and the resulting detailed dynamic information is also presented, analyzed, and discussed.
Conditional survival of patients with gastric cancer who undergo curative resection: A multi‐institutional analysis in China
Authors: Wang Pengliang , Sun Zhe , Wang Wei , Deng Jingyu , Wang Zhenning , Liang Han , Zhou Zhiwei , Xu Huimian
Published: December 2017

BACKGROUND

Conditional survival estimates, which take into consideration the changing risk with increasing survival time, provide a dynamic survival probability and more accurate survival information for clinician decision making. The objective of the current study was to evaluate the conditional disease‐specific survival (DSS) for patients with gastric cancer who underwent curative surgery in China.

METHODS

In total, 7658 patients with gastric cancer from a multi‐institutional cohort in China were included in the analyses. Actuarial DSS was estimated using the Kaplan‐Meier method. Three‐year conditional DSS (CDS3) of patients who had already survived for x years was estimated as CDS3 = DSS(x + 3)/DSS(x). Cox proportional hazards regression analyses were used to identify the factors related to DSS.

RESULTS

The 1‐year, 3‐year, and 5‐year actuarial DSS rates were 88.2%, 64.5%, and 54.6%, respectively. By using CDS estimates, the probabilities that patients would remain alive for an additional 3 years given that they had already survived for 1, 3, and 5 years were 66.6%, 80.2%, and 88.3%, respectively. Patients who had unfavorable tumor characteristics diagnosed initially at surgery had the greatest improvement in CDS and the largest survival gap between actuarial DSS and CDS.

CONCLUSIONS

The current results indicate that CDS estimates for Chinese patients with gastric cancer who underwent surgery were dynamic and increased with time elapsed. Patients who had unfavorable tumor characteristics had the greatest improvement in CDS. This valuable information could provide more a precise evaluation of long‐term prognosis and may serve as an important prognostic index in clinical practice. Cancer 2018;124:916‐24. © 2017 American Cancer Society.
Clinical impact of sedentary behaviors in adult survivors of acute lymphoblastic leukemia: A report from the St. Jude Lifetime Cohort study
Authors: Howell Carrie R. , Wilson Carmen L. , Ehrhardt Matthew J. , Partin Robyn E. , Kaste Sue C. , Lanctot Jennifer Q. , Pui Ching‐Hon , Robison Leslie L. , Hudson Melissa M. , Ness Kirsten K.
Published: December 2017

BACKGROUND

Sedentary behaviors are associated with poor health outcomes in the general population, but their clinical impact on adult survivors of childhood acute lymphoblastic leukemia (ALL) has not been characterized to date. In the current study, we described the prevalence of sedentary behaviors in survivors of ALL and examined associations between time spent sedentary and body composition and onset of cardiovascular disease (CVD) risk factors.

METHODS

Participants' self‐reported screen time (eg, television, computer) and activity as measured by accelerometer were used to determine activity time (sedentary, light activity, and moderate or vigorous physical activity). The percentage of time spent in each activity was compared between 331 survivors of ALL and 330 controls. Associations between time sedentary and body composition were evaluated in survivors using linear regression models. Cox proportional hazard models were used to examine the association between time sedentary at baseline and CVD risk factor onset during follow‐up.

RESULTS

Survivors spent approximately 65% of their time sedentary, 32% in light activity, and 2% in moderate or vigorous physical activity compared with 67% (P = .04), 30% (P<.01), and 3% (P<.01), respectively, in controls. Among survivors, percentage lean body mass decreased by 1.0% ± 0.4% (P = .01) per 10% increase in time sedentary. Survivors who were sedentary ≥60% per day were found to be at an increased risk of high total cholesterol (hazard ratio, 2.52; 95% confidence interval, 1.12‐5.64) and any CVD risk factor (hazard ratio, 1.96; 95% confidence interval, 1.16‐3.30).

CONCLUSIONS

Sedentary behavior is associated with low lean mass and CVD risk factor development and should be limited in survivors of childhood ALL. Cancer 2018;124:1036‐43. © 2017 American Cancer Society.
Effects of estrogen replacement therapy on the myelin sheath ultrastructure of myelinated fibers in the white matter of middle‐aged ovariectomized rats
Authors: He Qi , Luo Yanmin , Lv Fulin , Xiao Qian , Chao Fenglei , Qiu Xuan , Zhang Lei , Gao Yuan , Xiu Yun , Huang Chunxia , Tang Yong
Published: December 2017

The effects of estrogen replacement therapy (ORT) on white matter and the myelin sheath ultrastructure in the white matter of middle‐aged ovariectomized (OVX) rats were investigated in this study. Middle‐aged rats were ovariectomized and divided into a placebo replacement (OVX + O) group and an estrogen replacement (OVX + E) group. Then, the Morris water maze, electron microscope techniques, and stereological methods were used to investigate the effects of ORT on spatial learning capacity, white matter volume and the myelin sheath ultrastructure in the white matter. We found that the spatial learning capacity of the OVX + E rats was significantly improved compared with that of the OVX + O rats. When compared with that of OVX + O rats, the total volume of the myelin sheaths in the white matter of the OVX + E rats was significantly increased by 27%, and the difference between the outer perimeter and inner perimeter of the myelin sheaths of the white matter in the OVX + E rats increased significantly by 12.6%. The myelinated fibers with mean diameters of 1.2–1.4 μm were significantly longer (46.1%) in the OVX + E rats; the difference between the mean diameter of myelinated fibers and the mean diameter of axons (0–0.4 μm) was significantly increased by 21.6% in the OVX + E rats. These results suggested that ORT had positive protective effects on the spatial learning ability and on the myelin sheath ultrastructure in the white matter of middle‐aged OVX rats.
Preparation and Electrochemical Properties of NiCo2O4 Nanospinels Supported on Graphene Derivatives as Earth‐Abundant Oxygen Bifunctional Catalysts
Authors: Kumar Kavita , Loupias Lola , Canaff Christine , Morisset Sophie , Pronier Stéphane , Morais Cláudia , Habrioux Aurélien , Napporn Teko W. , Kokoh K. Boniface
Published: December 2017

This work reports on the facile synthesis and characterisation of a non‐precious‐metal bifunctional catalyst for oxygen reduction and evolution reactions (ORR and OER). A few‐layer reduced graphene oxide‐supported NiCo2O4 catalyst is prepared using a rapid and easy two‐step method of synthesis. It consists of the solvothermal poyl(vinylpyrrolidone)‐assisted assembly of metal complexes onto few‐layer graphene followed by a calcination step aiming at converting metal complexes into the spinel phase. Using this synthesis approach, the most active material demonstrates an outstanding activity towards the OER and ORR, making it one of the best bifunctional catalysts of these reactions ever reported. This composite catalyst exhibits improved bifunctional behaviour with a low reversibility criterion of 746 mV. The ORR process follows a four‐electron pathway and the hydroxyl selectivity is higher than those with pure reduced graphene oxide or NiCo2O4 materials, showing the synergistic effect between the two phases. Moreover, the high activity of this composite catalyst is confirmed by comparing its performance with those obtained on other cobaltite catalysts prepared using a different synthesis method, or those obtained using a different graphene‐based support.
Validation of X‐ray Wavefunction Refinement
Authors: Woińska Magdalena , Jayatilaka Dylan , Dittrich Birger , Flaig Ralf , Luger Peter , Woźniak Krzysztof , Dominiak Paulina M. , Grabowsky Simon
Published: December 2017

The front cover artwork is provided by the group of Prof. Krzysztof Woźniak, Dr. Paulina M. Dominiak, and Dr. Magdalena Woińska. The image shows X‐ray wavefunction refinement as a method of electron density reconstruction (symbolized by a jigsaw puzzle), which allows to obtain accurate and precise molecular geometries as well as properties of electron density, and to perform data quality evaluations. Read the full text of the article at 10.1002/cphc.201700810.
Magnetic Interaction Observed in Hetero Biradical Derivatives Containing a 2,2,5,5‐Tetramethylpyrrolin‐1‐yloxyl Unit as a Localized Spin Center
Authors: Takahashi Yusuke , Miura Youhei , Yoshioka Naoki
Published: December 2017

The magneto‐structural correlation of hetero biradical derivatives containing a 2,2,5,5‐tetramethylpyrrolin‐1‐yloxyl unit as a localized spin center and a verdazyl or nitronyl nitroxide radical is reported. The magnetic susceptibility measurement revealed that the verdazyl attached biradical 1 exhibits ferromagnetic interaction, whereas antiferromagnetic interaction is observed for nitronyl nitroxide attached biradical 2. An EPR study in toluene glass matrix suggests that both 1 and 2 have a ground triplet state. DFT calculations predict that there is intramolecular ferromagnetic interaction for both biradicals. The computation also suggests that the intramolecular magnetic interaction is weaker with larger dihedral angle between pyrroline ring and verdazyl ring/O−N−C−N−O plane of nitronyl nitroxide. The computations of model compounds 3 and 4 suggest that spin polarization on vinylic moiety without distribution of SOMO might be an essential condition for the intramolecular ferromagnetic interaction.
Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study
Authors: Brinkman David J. , Tichelaar Jelle , Mokkink Lidwine B. , Christiaens Thierry , Likic Robert , Maciulaitis Romaldas , Costa Joao , Sanz Emilio J. , Maxwell Simon R. , Richir Milan C. , van Agtmael Michiel A. ,   the Education Working Group of the European Association for Clinical Pharmacology and Therapeutics (EACPT) and its affiliated Network of Teachers in Pharmacotherapy (NOTIP)
Published: December 2017

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired.
A Strategy for the Simultaneous Synthesis of Methallyl Alcohol and Diethyl Acetal with Sn‐β
Authors: Hu Wenda , Wan Yan , Zhu Lili , Cheng Xiaojie , Wan Shaolong , Lin Jingdong , Wang Yong
Published: December 2017

Invited for this month′s cover is the group of Yong Wang at Xiamen University. The cover picture shows a strategy to simultaneously produce two important chemicals, namely, methallyl alcohol and diethyl acetal from methacrolein in ethanol solvent at low temperature on Beta zeolites modified by tin (Sn‐β catalysts). The Full Paper itself is available at 10.1002/cssc.201701435.
Memristor‐enhanced humanoid robot control system – Part I: Theory behind the novel memcomputing paradigm
Authors: Ascoli A. , Baumann D. , Tetzlaff R. , Chua L. O. , Hild M.
Published: December 2017

Myon is a humanoid robot where each joint is controlled independently by a supervised bio‐inspired artificial neural network inducing the correction of a number of distinct actions depending on the excitation. One of the control strategies, which the network, located within a certain joint, may implement, allows a controlled motion of the limb connected to the joint from a stable state up to a prescribed height and the maintenance of the new position afterwards. The original approach adopted for this control operation is stable and robust but results in slow and energy‐inefficient limb movements. This work proposes a novel, low‐power, time‐efficient and adaptive memristor‐centred control strategy for the aforementioned robot action. The idea is based upon the exploitation of the combined ability of memristors to store and process data in the same physical location. The part I paper sets the theoretic foundations for the memcomputing paradigm to robot motion control, while the part II manuscript shall demonstrate its benefits over the original approach in terms of energy, and speed, and the inheritance from the standard strategy of a good level of adaptability to changes in the limb load on the basis of the analysis of circuit‐theoretic models adopting an ideal and a real memristor, respectively. Copyright © 2017 John Wiley & Sons, Ltd.
Atomic mass tag of bismuth‐209 for increasing the immunoassay multiplexing capacity of mass cytometry
Authors: Han Guojun , Chen Shih‐Yu , Gonzalez Veronica D. , Zunder Eli R. , Fantl Wendy J. , Nolan Garry P.
Published: December 2017

Mass cytometry (or CyTOF) is an atomic mass spectrometry‐based single‐cell immunoassay technology, which has provided an increasingly systematic and sophisticated view in basic biological and clinical studies. Using elemental reporters composed of stable heavy metal isotopes, more than 50 cellular parameters are measured simultaneously. However, this current multiplexing does not meet the theoretical capability of CyTOF instrumentation with 135 detectable channels, primarily due to the limitation of available chemistries for conjugating elemental mass tags to affinity reagents. To address this issue, we develop herein additional metallic mass tag based on bismuth‐209 (209 Bi) for efficient conjugation to monoclonal antibody. This enables the use of an addtional channel m/z = 209 of CyTOF for single‐cell immunoassays. Bismuth has nearly the same charge‐to‐radius ratio as lanthanide elements; thus, bismuth(III) cations (209Bi3+) could coordinate with DTPA chelators in the same geometry of O‐ and N‐donor groups as that of lanthanide. In this report, the coordination chemistry of 209Bi3+ with DTPA chelators and Maxpar® X8 polymers were investigated in details. Accordingly, the protocols of conjugating antibody with bismuth mass tag were provided. A method based on UV‐Vis absorbance at 280 nm of 209Bi3+‐labeling DTPA complexes was developed to evaluate the stoichiometric ratio of 209Bi3+ cations to the conjugated antibody. Side‐by‐side single‐cell analysis experiments with bismuth‐ and lanthanide‐tagged antibodies were carried out to compare the analytical sensitivities. The measurement accuracy of bismuth‐tagged antibody was validated within in vitro assay using primary human natural killer cells. Furthermore, bismuth‐tagged antibodies were successfully employed in cell cycle measurements and high‐dimensional phenotyping immunoassays. © 2017 International Society for Advancement of Cytometry
Normal variation of bone marrow B‐cell precursors according to age – reference ranges for studies in myelodysplastic syndromes in Brazil
Authors: Lorand‐Metze I. , Longhini A. L. , Oliveira‐Duarte G. , Correia R. P. , Santos‐Silva M. C. , Yamamoto M. , Sandes A. F. , Oliveira A. F. , Souto E. X. , Ikoma M. R. V. , Pereira‐Cunha F. G. , Beltrame M. , Metze K. ,   on behalf of the Brazilian Group of Flow Cytometry (GBCFLUX)
Published: December 2017

Background

Normal B lymphoid maturation occurs in bone marrow (BM) throughout life, but immature B‐cell progenitors (BCPs) are more numerous in children than in adults. To assess the normal values according to age became important as BCPs are decreased in myelodysplastic syndromes and have been considered an important diagnostic and prognostic feature in these clonal disorders.

Methods

in a multicenter retrospective study from the Brazilian Group of Flow Cytometry we analyzed the variation of BCPs in normal BM according to age and technical peculiarities of each laboratory. We analysed of 45 BM donors and 89 cases examined for elucidation of transitory reactive cytopenias presenting a normal BM immunophenotyping. BCPs were enumerated as CD19+/CD34+/CD45dim/CD10+ cells (panel 1) or CD19+/CD34+/CD45dim cells (panel 2) among the total nucleated non‐erythroid cells and as percentage of CD34+ cells.

Results

we included 134 cases. Panel 1 was applied in 88 cases and panel 2 was used in 46. Age range: 10 months to 89 years. In a multiple regression, % BCPs/total nucleated cells was an exponential function of age. Age explained alone 49.4% of the variance, while ‘panel used’ explained 1.8% and ‘laboratory’ explained 0.7%. Age explained only 24.9% of the variance of BCPs/CD34+ cells.

Conclusions

in normal individuals, BM B‐cell precursors varied mainly according to age, but were also dependent on technical peculiarities of operators and equipments. Analysis by phenotype and as percentage of total nucleated cells was more accurate and less susceptible to variation than evaluating % BCPs/total CD34+ cells. © 2017 International Clinical Cytometry Society
HER2/HER3‐positive metastatic salivary duct carcinoma in the pleural effusion: A case report
Authors: Murata Kazuya , Kawahara Akihiko , Ono Takeharu , Takase Yorihiko , Abe Hideyuki , Naito Yoshiki , Akiba Jun
Published: December 2017

Salivary duct carcinoma (SDC) is an aggressive form of salivary gland tumor, and SDC patients tend to be older men, more commonly in advanced stage with a poorer prognosis. Although the cytological characteristics of SDC on fine‐needle aspiration cytology have been well‐described at the primary site, they have not been explored in metastasis. Here we reported a case of HER2/HER3‐positive metastatic SDC in the lung and pleural effusion. The patient was a man in his 50s who had undergone extended total parotidectomy in 2008. He was originally diagnosed as having HER2‐positive left parotid SDC. Six years later a mass was discovered in the left lung by chest computed tomography (CT) and was diagnosed as metastatic SDC by both bronchial biopsy and cytology. Subsequently he had a recurrent SDC in the left pleural effusion and died of respiratory failure. Cytological findings from bronchial brushing smear showed small sheet clusters in a slightly necrotic background. In the pleural effusion cytology, tumor cells appeared as ball‐like clusters of epithelioid cells with apocrine‐like findings. In immunocytochemistry, HER3 of SDC cells in pleural effusion was significantly overexpressed relative to the matched primary tumor, even though HER2 amplification did not change. Cytological findings and HER family receptors differed between the primary and metastatic SDC. Therefore, molecular tests, such as protein expression and gene amplification using cytological specimens, may become important in future when determining therapy strategies in patients with distant metastasis.
Exacerbated grassland degradation and desertification in Central Asia during 2000–2014
Authors: Zhang Geli , Biradar Chandrashekhar M. , Xiao Xiangming , Dong Jinwei , Zhou Yuting , Qin Yuanwei , Zhang Yao , Liu Fang , Ding Mingjun , Thomas Richard J.
Published: December 2017

Grassland degradation and desertification is a complex process, including both state conversion (e.g., grasslands to deserts) and gradual within‐state change (e.g., greenness dynamics). Existing studies hardly separated the two components and analyzed it as a whole based on time series vegetation index data, which cannot provide a clear and comprehensive picture for grassland degradation and desertification. Here we propose an integrated assessment strategy, by considering both state conversion and within‐state change of grasslands, to investigate grassland degradation and desertification process in Central Asia. First, annual maps of grasslands and sparsely vegetated land were generated to track the state conversions between them. The results showed increasing grasslands were converted to sparsely vegetated lands from 2000 to 2014, with the desertification region concentrating in the latitude range of 43–48° N. A frequency analysis of grassland vs. sparsely vegetated land classification in the last 15 yr allowed a recognition of persistent desert zone (PDZ), persistent grassland zone (PGZ), and transitional zone (TZ). The TZ was identified in southern Kazakhstan as one hotspot that was unstable and vulnerable to desertification. Furthermore, the trend analysis of Enhanced Vegetation Index during thermal growing season (EVITGS) was investigated in individual zones using linear regression and Mann‐Kendall approaches. An overall degradation across the area was found; moreover, the second desertification hotspot was identified in northern Kazakhstan with significant decreasing in EVITGS, which was located in PGZ. Finally, attribution analyses of grassland degradation and desertification were conducted by considering precipitation, temperature, and three different drought indices. We found persistent droughts were the main factor for grassland degradation and desertification in Central Asia. Considering both state conversion and gradual within‐state change processes, this study provided reference information for identification of desertification hotspots to support further grassland degradation and desertification treatment, and the method could be useful to be extended to other regions.
Proximate causes of altitudinal differences in body size in an agamid lizard
Authors: Lu Hong‐Liang , Xu Chun‐Xia , Jin Yuan‐Ting , Hero Jean‐Marc , Du Wei‐Guo
Published: December 2017

Body size is directly linked to key life history traits such as growth, fecundity, and survivorship. Identifying the causes of body size variation is a critical task in ecological and evolutionary research. Body size variation along altitudinal gradients has received considerable attention; however, the underlying mechanisms are poorly understood. Here, we compared the growth rate and age structure of toad‐headed lizards (Phrynocephalus vlangalii) from two populations found at different elevations in the Qinghai‐Tibetan Plateau. We used mark‐recapture and skeletochronological analysis to identify the potential proximate causes of altitudinal variation in body size. Lizards from the high‐elevation site had higher growth rates and attained slightly larger adult body sizes than lizards from the low‐elevation site. However, newborns produced by high‐elevation females were smaller than those by low‐elevation females. Von Bertalanffy growth estimates predicted high‐elevation individuals would reach sexual maturity at an earlier age and have a lower mean age than low‐elevation individuals. Relatively lower mean age for the high‐elevation population was confirmed using the skeletochronological analysis. These results support the prediction that a larger adult body size of high‐elevation P. vlangalii results from higher growth rates, associated with higher resource availability.
Can mesophotic reefs replenish shallow reefs? Reduced coral reproductive performance casts a doubt
Authors: Shlesinger Tom , Grinblat Mila , Rapuano Hanna , Amit Tal , Loya Yossi
Published: December 2017

Mesophotic coral ecosystems (i.e., deep coral reefs at 30–120 m depth) appear to be thriving while many shallow reefs in the world are declining. Amid efforts to understand and manage their decline, it was suggested that mesophotic reefs might serve as natural refuges and a possible source of propagules for the shallow reefs. However, our knowledge of how reproductive performance of corals alters with depth is sparse. Here, we present a comprehensive study of the reproductive phenology, fecundity, and abundance of seven reef‐building conspecific corals in shallow and mesophotic habitats. Significant differences were found in the synchrony and timing of gametogenesis and spawning between shallow and mesophotic coral populations. Thus, mesophotic populations exhibited delayed or protracted spawning events, which led to spawning of the mesophotic colonies in large proportions at times where the shallow ones had long been depleted of reproductive material. All species investigated demonstrated a substantial reduction in fecundity and/or oocyte sizes at mesophotic depths (40–60 m). Two species (Seriatopora hystrix and Galaxea fascicularis) displayed a reduction in both fecundity and oocyte size at mesophotic depths. Turbinaria reniformis had only reduced fecundity and Acropora squarrosa and Acropora valida only reduced oocyte size. In Montipora verrucosa, reduced fecundity was found during one annual reproductive season while, in the following year, only reduced oocyte size was found. In contrast, reduced oocyte size in mesophotic populations of Acropora squarrosa was consistent along three studied years. One species, Acropora pharaonis, was found to be infertile at mesophotic depths along two studied years. This indicates that reproductive performance decreases with depth; and that although some species are capable of reproducing at mesophotic depths, their contribution to the replenishment of shallow reefs may be inconsequential. Reduced reproductive performance with depth, combined with the possible narrower tolerance to environmental factors, further suggests that mesophotic corals may in fact be more vulnerable than previously conceived. Furthermore, we posit that the observed temporal segregation in reproduction could lead to assortative mating, and this, in turn, may facilitate adaptive divergence across depth.