bluuebunny/crossref_metadata_2025 huggingface dataset:
Method for the determination of hydrazine in workplace air using gas chromatography‐mass spectrometry (GC‐MS) [Air Monitoring Methods, 2017]
Authors: Krämer W. , Brock T.H. , Hebisch R. , Hartwig A. ,   MAK Commission
Published: July 2017

This analytical method is a validated measurement procedure for the determination of hydrazine in workplace air for risk assessment at work. Sampling is performed by drawing a defined volume of air through an adsorption tube filled with XAD‐2 impregnated with 2,4‐pentanedione using a flow‐regulated pump. The flow rate is set to 200 mL/min with a recommended air sample volume of approx. 48 litres at a sampling period of 4 hours. After sampling the formed 3,5‐dimethylpyrazole is extracted with methanol and analysed by means of gas chromatography‐mass spectrometry (GC‐MS). The absolute limit of quantification (LOQ) is 0.05 ng and the relative LOQ is 0.002 mg/m
3
based on an air sample volume of approx. 48 litres. The mean recovery was 82% and the expanded uncertainty for the overall measurement method 18%.

Joint Publication of the Analytical Subcommittee of the Chemistry Board of Experts of the Expert Committee Raw Materials and Chemical Industry of the German Social Accident Insurance and the Working Group “Air Analyses” of the Permanent Senate Commission of the DFG for the Investigation of Health Hazards of Chemical Compounds in the Work Area.
Quecksilber – Methode zur Bestimmung von Dämpfen des Quecksilbers und seinen anorganischen Verbindungen in der Luft am Arbeitsplatz mittels Atomabsorptionsspektrometrie [Air Monitoring Methods in German language, 2017]
Authors: Hebisch R. , Fröhlich N. , Houben T. , Schneider W. , Hartwig A. ,   MAK Commission
Published: July 2017

This analytical method is a validated measurement procedure for the determination of vapour from mercury and its inorganic compounds in workplace air using atomic absorption spectrometry in a concentration range of one thousandth up to twice the currently valid Occupational Exposure Limit (OEL) or MAK value of 0.02 mg/m
3
. Both personal and stationary sampling can be performed for risk assessment at work. Sampling is carried out by drawing a defined volume of air through an adsorption tube filled with hopcalite (mixture of MnO
2
and CuO) using a flow‐regulated pump. The flow rate is set to 250 mL/min with a recommended air sample volume of approx. 30 L at a sampling duration of 2 hours. After sampling the loaded hopcalite is transferred into a quartz boat and the collected mercury can be analysed directly via atomic absorption spectrometry (AAS). The quantitative determination is based on a calibration function obtained by means of a 10‐point calibration. The limit of quantification is 0.013 µg/m
3
based on an air sample volume of approx. 30 L with an expanded uncertainty between 18 and 21 %.
Kupfer und seine anorganischen Verbindungen [BAT Value Documentation in German language, 2017]
Authors: Letzel S. , Rossbach B. , Drexler H. , Hartwig A. ,   MAK Commission
Published: July 2017

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated copper (CAS No
7440‐50‐8
) in 2016.

Due to the homeostatic regulation of copper there is no correlation between copper exposure in air and copper in blood or urine. Neither increased inhalation exposure higher than the MAK value of 0.01 mg copper/m
3
nor increased oral supply lead to an increase of copper in blood or urine, even if first signs of exposure such as increased C‐reactive protein (CRP) are observed. An additional occupational burden cannot be differentiated from physiological levels of copper. Therefore, the evaluation of a biological tolerance value (BAT value) and a biological reference value (“Biologischer Arbeitsstoff‐Referenzwert” (BAR)) for copper and its inorganic compounds is not indicated.
Addendum zu Nitrobenzol [BAT Value Documentation in German language, 2017]
Authors: Leng G. , Bolt H.M. , Drexler H. , Hartwig A. ,   MAK Commission
Published: July 2017

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated nitrobenzene (CAS No
98‐95‐3
) in 2016, considering aniline released from aniline‐haemoglobin conjugate to characterize the internal exposure and the methaemoglobin formation as critical effect.

After inhalative exposure, high nitrobenzene concentrations cause adenomas and carcinomas in liver, kidney and thyroid in rats as well as lung and mamma in mice. A MAK value of 0.1 ml nitrobenzene/m
3
was established. For the haemoglobin adduct of nitrobenzene, a BLW (biological guidance value) of 100 µg aniline (released from aniline‐haemoglobin conjugate)/l blood corresponding to a methaemoglobin formation of 5 % was evaluated based on field studies.
Toluol, Ethylbenzol und Phenol – Bestimmung von o‐Kresol, m‐Kresol, 2‐Ethylphenol, 4‐Ethylphenol und Phenol in Urin mittels Gaschromatographie‐Massenspektrometrie [Biomonitoring Methods in German language, 2011]
Authors: Schettgen T. , Alt A. , Dewes P.
Published: July 2017

Der Artikel enthält folgende Kapitel:

Grundlage des Verfahrens

Geräte, Chemikalien und Lösungen

Geräte

Chemikalien

Lösungen

Interner Standard

Vergleichsstandards

Probenahme und Probenaufbereitung

Probenaufbereitung zur Bestimmung der Kresole und Ethylphenole

Probenaufbereitung zur Bestimmung von Phenol

Instrumentelle Arbeitsbedingungen

Gaschromatographie

Massenspektrometrie

Analytische Bestimmung

Kalibrierung

Berechnung der Analysenergebnisse

Standardisierung der Messergebnisse und Qualitätssicherung

Beurteilung des Verfahrens

Präzision

Richtigkeit

Aufarbeitungsbedingte Verluste

Nachweis‐ und Bestimmungsgrenzen

Störeinflüsse

Diskussion der Methode
Being a good or a just teacher: Which experiences of teachers’ behavior can be more predictive of school bullying?
Authors: Donat Matthias , Knigge Michel , Dalbert Claudia
Published: July 2017

In two cross‐sectional questionnaire studies with N = 2,931 German students, aged between 12 and 17 years (M = 14.1, SD = 0.5), we investigated the relation between students’ bullying behavior and their personal belief in a just world (BJW). We considered students’ personal experience of teacher justice as a possible mediator in this relation and investigated whether the students’ experiences of their teachers’ classroom management explained bullying behavior in addition to personal BJW and teacher justice, while statistically controlling for sex and school type. In both studies, multilevel modeling results showed that the more students endorsed personal BJW and the more they evaluated their teachers’ behavior toward them personally as being just, the less likely they were to report that they bullied others. The students’ personal experience of teacher justice mediated the association of personal BJW with bullying. Furthermore, the students’ personal experience of classroom management significantly predicted bullying in addition to personal BJW and teacher justice. The observed relations were mainly significant at the individual level. The pattern of results persisted when we controlled for school type and when we considered student sex as a moderator. We discussed the adaptive functions of BJW and implications for future school research and practice.
Glycine N‐Methylation in NGR‐Tagged Nanocarriers Prevents Isoaspartate Formation and Integrin Binding without Impairing CD13 Recognition and Tumor Homing
Authors: Corti Angelo , Gasparri Anna Maria , Ghitti Michela , Sacchi Angelina , Sudati Francesco , Fiocchi Martina , Buttiglione Valentina , Perani Laura , Gori Alessandro , Valtorta Silvia , Moresco Rosa Maria , Pastorino Fabio , Ponzoni Mirco , Musco Giovanna , Curnis Flavio
Published: July 2017

NGR (asparagine–glycine–arginine) is a tumor vasculature‐homing peptide motif widely used for the functionalization of drugs, nanomaterials, and imaging compounds for cancer treatment and diagnosis. Unfortunately, this motif has a strong propensity to undergo rapid deamidation. This reaction, which converts NGR into isoDGR, is associated with receptor switching from CD13 to integrins, with potentially important manufacturing and pharmacological and toxicological implications. It is found that glycine N‐methylation of NGR‐tagged nanocarriers completely prevents asparagine deamidation without impairing CD13 recognition. Studies in animal models have shown that the methylated NGR motif can be exploited for delivering radiolabeled compounds and nanocarriers, such as tumor necrosis factor‐α‐bearing nanogold and liposomal doxorubicin, to tumors with improved selectivity. These findings suggest that this NGR derivative is a stable and efficient tumor‐homing ligand that can be used for delivering functional nanomaterials to tumor vasculature.
A Skin‐Inspired Integrated Sensor for Synchronous Monitoring of Multiparameter Signals
Authors: Gui Qinyuan , He Yonglin , Gao Naiwei , Tao Xinglei , Wang Yapei
Published: July 2017

Electronic skins, as the integration of multiple distinct sensors, have aroused broad interests owing to their great potential in sensing applications. However, problems including the interference between sensing components and the difficulty in synchronous monitoring are practically encountered when they are applied to mixed signals. In this work, efforts are devoted to trouble‐free technical strategies for laminating three sensors with different sensing abilities into a skin‐like electronic device. The use of ionic liquid, combined with particular circuit topologies, ensures the reliable stability against mechanical disturbance during the real‐time sensing tests. The intrinsic layered structure and three independent sensing functions of natural skins are successfully presented by this particular device in which three sensors with the ease of preparation are spatially integrated. The changes of temperature, pressure, and infrared light can be recorded simultaneously yet without mutual signal interference. The perfect integration of multiple functional sensors into a single skin‐like device without any signal interference makes an important progress for pursuing the goal of future electronic skins that can practically be used as skin.
Spatiotemporally Controlled Release of Rho‐Inhibiting C3 Toxin from a Protein–DNA Hybrid Hydrogel for Targeted Inhibition of Osteoclast Formation and Activity
Authors: Gačanin Jasmina , Kovtun Anna , Fischer Stephan , Schwager Victoria , Quambusch Johanna , Kuan Seah Ling , Liu Weina , Boldt Felix , Li Chuang , Yang Zhongqiang , Liu Dongsheng , Wu Yuzhou , Weil Tanja , Barth Holger , Ignatius Anita
Published: July 2017

In osteoporosis, bone structure can be improved by the introduction of therapeutic molecules inhibiting bone resorption by osteoclasts. Here, biocompatible hydrogels represent an excellent option for the delivery of pharmacologically active molecules to the bone tissue because of their biodegradability, injectability, and manifold functionalization capacity. The present study reports the preparation of a multifunctional hybrid hydrogel from chemically modified human serum albumin and rationally designed DNA building blocks. The hybrid hydrogel combines advantageous characteristics, including rapid gelation through DNA hybridization under physiological conditions and a self‐healing and injectable nature with the possibility of specific loading and spatiotemporally controlled release of active proteins, making it an advanced biomaterial for the local treatment of bone diseases, for example, osteoporosis. The hydrogels are loaded with a recombinant Rho‐inhibiting C3 toxin, C2IN‐C3lim‐G205C. This toxin selectively targets osteoclasts and inhibits Rho‐signaling and, thereby, actin‐dependent processes in these cells. Application of C2IN‐C3lim‐G205C toxin‐loaded hydrogels effectively reduces osteoclast formation and resorption activity in vitro, as demonstrated by tartrate‐resistant acid phosphatase staining and the pit resorption assay. Simultaneously, osteoblast activity, viability, and proliferation are unaffected, thus making C2IN‐C3lim‐G205C toxin‐loaded hybrid hydrogels an attractive pharmacological system for spatial and selective modulation of osteoclast functions to reduce bone resorption.
Topotactic Metal–Insulator Transition in Epitaxial SrFeOx Thin Films
Authors: Khare Amit , Shin Dongwon , Yoo Tae Sup , Kim Minu , Kang Tae Dong , Lee Jaekwang , Roh Seulki , Jung In‐Ho , Hwang Jungseek , Kim Sung Wng , Noh Tae Won , Ohta Hiromichi , Choi Woo Seok
Published: July 2017

Topotactic phase transformation enables structural transition without losing the crystalline symmetry of the parental phase and provides an effective platform for elucidating the redox reaction and oxygen diffusion within transition metal oxides. In addition, it enables tuning of the emergent physical properties of complex oxides, through strong interaction between the lattice and electronic degrees of freedom. In this communication, the electronic structure evolution of SrFeOx epitaxial thin films is identified in real‐time, during the progress of reversible topotactic phase transformation. Using real‐time optical spectroscopy, the phase transition between the two structurally distinct phases (i.e., brownmillerite and perovskite) is quantitatively monitored, and a pressure–temperature phase diagram of the topotactic transformation is constructed for the first time. The transformation at relatively low temperatures is attributed to a markedly small difference in Gibbs free energy compared to the known similar class of materials to date. This study highlights the phase stability and reversibility of SrFeOx thin films, which is highly relevant for energy and environmental applications exploiting the redox reactions.
Polymer‐Stabilized Micropixelated Liquid Crystals with Tunable Optical Properties Fabricated by Double Templating
Authors: Sasaki Yuji , Ueda Motoshi , Le Khoa V. , Amano Reo , Sakane Shin , Fujii Shuji , Araoka Fumito , Orihara Hiroshi
Published: July 2017

Self‐organized nano‐ and microstructures of soft materials are attracting considerable attention because most of them are stimuli‐responsive due to their soft nature. In this regard, topological defects in liquid crystals (LCs) are promising not only for self‐assembling colloids and molecules but also for electro‐optical applications such as optical vortex generation. However, there are currently few bottom‐up methods for patterning a large number of defects periodically over a large area. It would be highly desirable to develop more effective techniques for high‐throughput and low‐cost fabrication. Here, a micropixelated LC structure consisting of a square array of topological defects is stabilized by photopolymerization. A polymer network is formed on the structure of a self‐organized template of a nematic liquid crystal (NLC), and this in turn imprints other nonpolymerizable NLC molecules, which maintains their responses to electric field and temperature. Photocuring of specific local regions is used to create a designable template for the reproducible self‐organization of defects. Moreover, a highly diluted polymer network (≈0.1 wt% monomer) exhibits instant on–off switching of the patterns. Beyond the mere stabilization of patterns, these results demonstrate that the incorporation of self‐organized NLC patterns offers some unique and unconventional applications for anisotropic polymer networks.
Strain‐Induced Surface Micro/Nanosphere Structure: A New Technique to Design Mechanically Robust Superhydrophobic Surfaces with Rose Petal‐Like Morphology
Authors: Peng Yuncheng , Zhu Wei , Shen Shengfei , Feng Lishuang , Deng Yuan
Published: July 2017

A robust surface geometrical structure not only enables a favorable practical application but also leads to a long‐term reliability of superhydrophobic surfaces, and hence it is pivotal to find an effective route to improve the mechanical durability of superhydrophobic surfaces. This study reports a simple magnetron sputtering method to directly construct a robust rose petal‐like copper surface with high water adhesion (petal effect). A stable surface micro/nanosphere topography combining with naturally low surface energy is spontaneously formed by the strain‐induced‐island growth of the copper films during the sputtering process. Further reduced surface energy by fluorosilane, the rose petal‐like surface shows a high water contact angle (≈161.4°), effective adhesion force of ≈154 µN, and no‐loss transportation critical droplet volume of ≈98 µL. In addition, as‐prepared superhydrophobic surfaces exhibit superior mechanical stability according to the thermal shock (−40 °C/90 °C) for ≈500 cycles, water‐impacting test for ≈6 h, and finger touch (≈20 times) as well as tape‐peeling test (≈65 times) without losing superhydrophobicity. This work might provide a novel but simple way to directly and effectively fabricating robust superhydrophobic metallic surfaces for potential industrial applications, and can be easily extended to other metals and alloys.
Oxygen‐Dependent Synthesis of Graphene on γ‐Alumina Catalyst
Authors: Lee Minsoo , Park Kichul , Park Jaehyun , Choi Duck‐Kyun , Song Yong‐Won
Published: July 2017

Gamma‐alumina (γ‐Al2O3) is one of the most promising ceramic catalysts for the graphene growth due to its weak bonding with graphene guaranteeing excellent detachability of graphene grown on it and its use as a dielectric layer for graphene‐based electronic devices. Oxygen leakage in graphene growth by chemical vapor deposition (CVD) process is unavoidable resulting in deteriorated graphene quality and device performance. This paper elucidates the role of oxygen on the growth of graphene on γ‐Al2O3 quantitatively and systematically. Escaping from unreliable analysis of the oxygen concentration in the CVD tube during the process, this paper directly focuses on the oxygen contents in resultant graphene crystals grown at diversified positions along the tube displaying from 9.75% to 14.82%. Oxygen‐dependent electrical properties of the graphene‐based electrical devices including sheet resistance, contact resistance, and electrical homogeneity are measured to 0.82–6.64 kΩ sq−1, 0.50–4.43 kΩ mm, and 23.0–97.9%, respectively, with the sp2 densities ranging from 51.0% to 72.1%.
Thermal Release Transfer Printing for Stretchable Conformal Bioelectronics
Authors: Yan Zhuocheng , Pan Taisong , Xue Miaomiao , Chen Changyong , Cui Yan , Yao Guang , Huang Long , Liao Feiyi , Jing Wei , Zhang Hulin , Gao Min , Guo Daqing , Xia Yang , Lin Yuan
Published: July 2017

Soft neural electrode arrays that are mechanically matched between neural tissues and electrodes offer valuable opportunities for the development of disease diagnose and brain computer interface systems. Here, a thermal release transfer printing method for fabrication of stretchable bioelectronics, such as soft neural electrode arrays, is presented. Due to the large, switchable and irreversible change in adhesion strength of thermal release tape, a low‐cost, easy‐to‐operate, and temperature‐controlled transfer printing process can be achieved. The mechanism of this method is analyzed by experiments and fracture‐mechanics models. Using the thermal release transfer printing method, a stretchable neural electrode array is fabricated by a sacrificial‐layer‐free process. The ability of the as‐fabricated electrode array to conform different curvilinear surfaces is confirmed by experimental and theoretical studies. High‐quality electrocorticography signals of anesthetized rat are collected with the as‐fabricated electrode array, which proves good conformal interface between the electrodes and dura mater. The application of the as‐fabricated electrode array on detecting the steady‐state visual evoked potentials research is also demonstrated by in vivo experiments and the results are compared with those detected by stainless‐steel screw electrodes.
Large Magnetoresistance in Silicon at Room Temperature Induced by Onsite Coulomb Interaction
Authors: Luo Zhaochu , Piao Hong‐Guang , Brooks Andrew V. , Wang Xiaofeng , Chen Jiaojiao , Xiong Chengyue , Yang Fuhua , Wang Xiangrong , Zhang Xiao‐Guang , Zhang Xiaozhong
Published: July 2017

Magnetoresistance (MR), as a key property in magnetic‐field sensing and magnetic storage, has been a long‐term focus. In particular in silicon, which is the mainstream semiconductor of information technology, the MR phenomenon has attracted a lot of attention because of its fundamental interest and broad application potential. Here, a large MR in silicon, which is associated with impurity onsite Coulomb interaction and space charge limited current (SCLC), is observed at room temperature. In the presence of SCLC, delocalization of electrons in doubly occupied traps with a strong onsite Coulomb interaction leads to an S‐shape negative differential conductance (SNDC). A large room temperature MR (>103% at 0.05 T) appears around the SNDC region. These findings will help to design high‐performance silicon‐based magnetic device (e.g., magnetic switch devices, magnetic logic devices) and pave the way for magnetoelectronics in silicon.
Investigations on Field‐Effect Transistors Based on Two‐Dimensional Materials
Authors: Finge T. , Riederer F. , Mueller M. R. , Grap T. , Kallis K. , Knoch J.
Published: July 2017

In the present article, experimental and theoretical investigations regarding field‐effect transistors based on two‐dimensional (2D) materials are presented. First, the properties of contacts between a metal and 2D material are discussed. To this end, metal‐to‐graphene contacts as well to transition metal dichalcogenides (TMD) are studied. Whereas metal‐graphene contacts can be tuned with an appropriate back‐gate, metal‐TMD contacts exhibit strong Fermi level pinning showing substantially limited maximum possible drive current. Next, tungsten diselenide (WSe2) field‐effect transistors are presented. Employing buried‐triple‐gate substrates allows tuning source, channel and drain by applying appropriate gate voltages so that the device can be reconfigured to work as n‐type, p‐type and as so‐called band‐to‐band tunnel field‐effect transistor on the same WSe2 flake.
A Quadruple‐Action Platinum(IV) Prodrug with Anticancer Activity Against KRAS Mutated Cancer Cell Lines
Authors: Petruzzella Emanuele , Braude Jeremy Phillip , Aldrich‐Wright Janice R. , Gandin Valentina , Gibson Dan
Published: July 2017

We developed a novel PtIV prodrug that simultaneously releases four different bioactive moieties inside the cancer cell. Its cytotoxicity against monolayer cultures (2D) and spheroid (3D) cancer cells is significantly better than cisplatin. It is 200–450‐fold more potent than cisplatin against KRAS mutated pancreatic and colon cancers and is 40‐fold more selective towards KRAS mutated cells compared to non‐cancerous. This is important since RAS proteins play a role in regulating cell differentiation, proliferation, and survival and KRAS is mutated in 90 % of pancreatic adenocarcinomas, 45 % of colorectal cancers, and 35 % of lung adenocarcinomas. The selectivity index, determined by dividing the IC50 value in non‐cancerous cells by that of a cancerous cell line, is two‐fold better than cisplatin, attesting to preferential cytotoxicity towards neoplastic cells.
Techno‐economic analysis of multiple bio‐based routes to adipic acid
Authors: Gunukula Sampath , Anex Robert P.
Published: July 2017

Techno‐economic studies of four processes for production of adipic acid from glucose were used to compare the minimum cost of production by each route. We analyzed the purely biological production via reverse β‐oxidation in E. coli; a purely chemical process using oxidation of glucose via chemical catalysis to glucaric acid that undergoes catalytic hydrodeoxygenation to adipic acid; and two hybrid routes that biologically convert glucose to either 6‐hydroxyhexanoic acid or 1, 6‐hexanediol, that are subsequently converted chemically to adipic acid using a metal catalyst. All analyses were based on adipic acid production capacity of 80 000 metric ton/year. Estimated total capital investments were US$157 million, $81 million, $166 million, and $177 million for the purely ­biological, chemical, and two integrated hybrid routes, respectively. Catalyst costs were estimated as $72 million, $36 million, and $37 million for the purely chemical and two integrated routes, respectively. The estimated adipic acid minimum selling prices were $1.36, $1.56, $1.48, and $1.70 per kg for the purely biological, purely chemical, and two integrated routes, respectively. Co‐product revenue and the use of unpurified sugars improved the economics of adipic acid production in the purely biological and two integrated routes. Comparison of the economics of the chemical catalytic steps shows that catalyst yields, turnover frequency, and catalyst life must be greater than 40% of theoretical, 0.01 s‐1, and 100 days to achieve economic viability of purely chemical and integrated routes to adipic acid. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd.
Fetal Cerebral Ventricular Dilatation: Etiopathogenic Study of 130 Observations
Authors: Darouich Sihem , Boutaud Lucile , Bessières Bettina , Bonnière Maryse , Martinovic Jelena , Mechler Charlotte , Alby Caroline , Bernard Jean‐Pierre , Roth Philippe , Ville Yves , Malan Valerie , Vekemans Michel , Attié‐Bitach Tania , Encha‐Razavi Férechté
Published: July 2017

Background

Fetal cerebral ventricular dilatation (CVD) is a common abnormal prenatal finding that often predicts a poor prognosis. The etiology involves both genetic and nongenetic factors with diverse pathogenic mechanisms. We describe the neuropathological features of CVD in a large cohort of fetuses. The goals are to determine the physiopathological mechanisms and etiologies.

Methods

We retrospectively analyzed a series of 130 fetuses examined at the Necker University Hospital following termination of pregnancy between January 2000 and December 2014. Chiari II and Dandy‐Walker malformations were excluded from our study population. Karyotype and/or array comparative genomic hybridization were performed in all cases. Targeted Sanger sequencing or next generation sequencing were carried out in 34 and 5 cases, respectively.

Results

We distinguished four groups of pathological entities: (1) midbrain/hindbrain patterning defects (54 cases, 42%), mainly related to aqueduct of Sylvius anomalies (atresia or stenosis); (2) cerebral cytoarchitectonic disorders (16 cases, 12%), essentially resulting from arachnoidal neuroglial ectopia; (3) hemorrhagic and perfusion failure (42 cases, 32%); and (4) nonspecific CVD (18 cases, 14%), without apparent obstruction, cortical malformation, or clastic injury. Although the pathogenic mechanisms of CVD were identified in 86% of cases, the causes, both acquired and genetic, were recognized in 21% of cases only.

Conclusion

The neuropathological analysis is a powerful tool in the diagnosis of the fetal CVD pathogenic mechanisms and to identify homogeneous groups. The paucity of molecular diagnosis, notably in the major groups of midbrain/hindbrain patterning defects and hemorrhagic and perfusion failure, highlights the needs of future research to improve our current knowledge on CVD causes. Birth Defects Research 109:1586–1595, 2017. © 2017 Wiley Periodicals, Inc.
A biosafety level 2 virology lab for biotechnology undergraduates
Authors: Matza‐Porges Sigal , Nathan Dafna
Published: July 2017

Medical, industrial, and basic research relies heavily on the use of viruses and vectors. Therefore, it is important that bioscience undergraduates learn the practicalities of handling viruses. Teaching practical virology in a student laboratory setup presents safety challenges, however. The aim of this article is to describe the design and implementation of a virology laboratory, with emphasis on student safety, for biotechnology undergraduates. Cell culture techniques, animal virus infection, quantification, and identification are taught at a biosafety level 2 for a diverse group of undergraduates ranging from 20 to 50 students per group. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):537–543, 2017.
Predicting neurocognitive function with hippocampal volumes and DTI metrics in patients with Alzheimer's dementia and mild cognitive impairment
Authors: Shim Geumsook , Choi Kwang‐Yeon , Kim Dohyun , Suh Sang‐il , Lee Suji , Jeong Hyun‐Ghang , Jeong Bumseok
Published: July 2017

Introduction

Cognitive performance in patients with Alzheimer's dementia (AD) and mild cognitive impairment (MCI) has been reported to be related to hippocampal atrophy and microstructural changes in white matter (WM). We aimed to predict the neurocognitive functions of patients with MCI or AD using hippocampal volumes and diffusion tensor imaging (DTI) metrics via partial least squares regression (PLSR).

Methods

A total of 148 elderly female subjects were included: AD (n = 49), MCI (n = 66), and healthy controls (n = 33). Twenty‐four hippocampal subfield volumes and the average values for fractional anisotropy (FA) and mean diffusivity (MD) of 48 WM tracts were used as predictors, CERAD‐K total scores, scores of CERAD‐K 7 cognitive subdomains and K‐GDS were used as dependent variables in PLSR.

Results

Regarding MCI patients, DTI metrics such as the MD values of the left retrolenticular part of the internal capsule and left fornix (cres)/stria terminalis were significant predictors, while hippocampal subfield volumes, like the left CA1 and hippocampal tail, were main contributors to cognitive function in AD patients, although global FA/MD values were also strong predictors. The 10‐fold cross‐validation and stricter 300‐iteration tests proved that global cognition measured by the CERAD‐K total scores and the scores of several CERAD‐K subdomains can be reliably predicted using the PLSR models.

Conclusions

Our findings indicate different structural contributions to cognitive function in MCI and AD patients, implying that diffuse WM microstructural changes may precede hippocampal atrophy during the AD neurodegenerative process.
Ethanol injection into the Marshall vein provoking a pericardial effusion resulting in a fatal complication in a patient with persistent atrial fibrillation
Authors: Kato Kazuo , Igawa Osamu , Morimoto Shin‐ichiro , Kametani Ryosuke , Tanaka Akimitsu , Hattori Hideo
Published: July 2017

Key Clinical Message

An EIM (ethanol infusion into the vein of Marshall [VOM]) provoked a fatal complication in a chronic hemodialysis patient. Autopsy revealed a lacerated VOM covered with thrombi as the only potential cause. The EIM caused vascular damage and clots resulting in myocardial necrosis and interstitial bleeding around the lacerated VOM.
Diastereoselective Cyclization of 1,5‐Dienes with the C−H Bond of Pyridine Catalyzed by a Cationic Mono(phosphinoamide) Alkyl Scandium Complex
Authors: Chen Yanhui , Song Di , Li Jing , Hu Xiaoyan , Bi Xianjia , Jiang Tao , Hou Zhaomin
Published: July 2017

The carbocyclization of non‐conjugated dienes mediated by organometallics is an important reaction for the synthesis of a variety of carbocyclic derivatives, but the direct annulation of dienes with an inert C−H bond of a substrate has remained unexplored to date. We herein report a series of novel rare‐earth dialkyl complexes bearing a phosphinoamide anion and demonstrate that the combination of a mono(phosphinoamido)‐ligated scandium dialkyl complex with B(C6F5)3 results in an excellent catalyst for the cis‐selective cyclization of 1,5‐dienes with the ortho‐C(sp2)−H bond of pyridines to afford a new family of pyridyl‐functionalized 1,3‐disubstituted cyclopentane derivatives containing monocyclic, bicyclic, spirocyclic, and heterocyclic skeletons in moderate to excellent yields with high diastereoselectivities (cis/trans up to 99:1).
From Square‐Planar [ICl4]− to Novel Chloroiodates(III)? A Systematic Experimental and Theoretical Investigation of Their Ionic Liquids
Authors: Burgenmeister Benedikt , Sonnenberg Karsten , Riedel Sebastian , Krossing Ingo
Published: July 2017

A systematic investigation on the existence of chloroiodates formed by reaction of Cl− with I2Cl6, apart from the well‐known [ICl4]−, namely [I2Cl7]− and [I3Cl10]−, was undertaken by employing theoretical as well as experimental methods. The thermodynamic stability in terms of the complexation enthalpies and Gibbs energies, and also the decomposition of the iodine(III) polyinterhalogen anions through dichlorine elimination to form iodine (I) compounds, was studied by means of DFT and ab initio quantum‐chemical calculations up to an extrapolated CCSD(T)/A′QZ level. On the experimental side, mixtures of [HMIM]Cl ([HMIM]+=1‐hexyl‐3‐methylimidazolium), [BMP]Cl ([BMP]+=1‐butyl‐1‐methylpyrrolidinium chloride) and [NEt4]Cl with 0.5, 1.0, and 1.5 equivalents of I2Cl6 were investigated by single‐crystal XRD, ion chromatography, NMR‐ and Raman spectroscopy. The reactions with 0.5 equivalents of I2Cl6 resulted in the compounds [HMIM][ICl4], [BMP][ICl4], and [NEt4][ICl4], of which crystal structures were determined. The mixtures with 1.0 or 1.5 equivalents of I2Cl6 yielded dark red liquids or suspensions of a dark red liquid with an orange solid, respectively. Both mixtures were studied by NMR‐spectroscopy for the organic cation part and ion chromatography and Raman spectroscopy for the polyinterhalogen anions. The discussion of the experimental Raman spectra is supplemented with computed spectra based on the structures obtained from RI‐MP2/def2‐TZVPP structure optimisations. Overall [I2Cl7]− appears to be the predominating anionic species in mixtures with 1.0 equivalents I2Cl6, while mixtures with 1.5 equivalents of I2Cl6 are suspensions of I2Cl6 in a liquid phase containing mixed anionic interhalogen complexes.
Artificial Metallooxidases from Cyclodextrin Diacids
Authors: Wang Bo , Bols Mikael
Published: July 2017

Unprecedented simple artificial metalloenzymes were made from cyclodextrin diacids. Six α‐ and β‐cyclodextrin diacids were prepared and their metal‐binding and acid properties were investigated. The diacids formed fairly stable complexes with copper, zinc, and iron, with dissociation constants of 0.4–8×10−4 m. The iron complexes were found to catalyse a Fenton‐like oxidation reaction of benzylic alcohols, which displayed Michaelis–Menten catalysis and rate accelerations up to 2700.
A Direct Arylation‐Cyclisation Reaction for the Construction of Medium‐Sized Rings
Authors: Whitaker Daniel , Batuecas María , Ricci Paolo , Larrosa Igor
Published: July 2017

A strategy for assembling biaryls linked through a medium‐sized ring is herein presented. π‐Complexation of fluoroarenes to chromium tricarbonyl activates the molecule towards both C−H activation and nucleophilic aromatic substitution without covalently altering the molecular connectivity of the arene. The construction of bridged biaryl molecules with 6–10‐membered core rings is achieved through a one‐pot C−H arylation/nucleophilic aromatic substitution sequence. The methodology is applicable to the synthesis of heterocyclic as well as fully carbocyclic rings.
Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) in pediatric and young adult patients: Results from a prospective study using limited‐margin radiotherapy
Authors: Tinkle Christopher L. , Fernandez‐Pineda Israel , Sykes April , Lu Zhaohua , Hua Chia‐ho , Neel Michael D. , Bahrami Armita , Shulkin Barry L. , Kaste Sue C. , Pappo Alberto , Spunt Sheri L. , Krasin Matthew J.
Published: July 2017

BACKGROUND

Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long‐term treatment outcomes and toxicities for pediatric and young adult patients with high‐grade NRSTS who were treated on a prospective trial using limited‐margin radiotherapy.

METHODS

Sixty‐two patients (ages 3‐22 years) with predominantly high‐grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external‐beam radiotherapy and/or brachytherapy using a 1.5‐cm to 2‐cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan‐Meier method estimated survival, competing‐risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0.

RESULTS

At a median follow‐up of 5.1 years (range, 0.2‐10.9 years), 9 patients had experienced local failure. The 5‐year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%‐25%), and all but 1 local failure occurred outside the highest‐dose irradiation volume. The 5‐year Kaplan‐Meier estimates for event‐free and overall survival were 49.3% (95% CI, 36.3%‐61.1%) and 67.9% (95% CI, 54.2%‐78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P = .004). The 5‐year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%‐25.3%).

CONCLUSIONS

The delivery of limited‐margin radiotherapy using conformal external‐beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment‐related morbidity. Cancer 2017;123:4419‐29. © 2017 American Cancer Society.
Adequate sampling of multiple thyroid nodules by fine‐needle aspiration
Authors: Renshaw Andrew A. , Gould Ewing W.
Published: July 2017

BACKGROUND

Recommendations regarding how many nodules to biopsy with thyroid fine‐needle aspiration vary.

METHODS

The authors reviewed fine‐needle aspiration specimens of 12,763 nodules from 10,506 patients and correlated them with the number of nodules biopsied.

RESULTS

Compared with patients in whom only a single nodule was biopsied, patients in whom multiple nodules were biopsied were found to be significantly younger, more likely female, and to have larger tumors, and those tumors were more often papillary (all P<.001). On fine‐needle aspiration, patients who had multiple nodules biopsied were more often diagnosed with benign findings (P<.001), but usually had no significant difference in the risk of malignancy associated with any cytologic diagnosis. Performing biopsy in 3 nodules detected all carcinomas in the current series. Combining all cases in the literature demonstrated that performing only 3 biopsies in a patient with at least 4 suspicious nodules had a risk of malignancy of 1.2%.

CONCLUSIONS

Biopsy of 3 different nodules in patients with multiple nodules appears to lower the risk of malignancy to that of a benign fine‐needle aspiration specimen. Although exceptions can occur, cytologists may be able to improve the accuracy of their diagnoses by focusing predominantly on identifying papillary carcinoma after the first 2 nodules have been biopsied. Cancer Cytopathol 2017;125:848–53. © 2017 American Cancer Society.
Sodium channel subtypes are differentially localized to pre‐ and post‐synaptic sites in rat hippocampus
Authors: Johnson Kenneth W. , Herold Karl F. , Milner Teresa A. , Hemmings Hugh C. , Platholi Jimcy
Published: July 2017

Voltage‐gated Na+ channels (Nav) modulate neuronal excitability, but the roles of the various Nav subtypes in specific neuronal functions such as synaptic transmission are unclear. We investigated expression of the three major brain Nav subtypes (Nav1.1, Nav1.2, Nav1.6) in area CA1 and dentate gyrus of rat hippocampus. Using light and electron microscopy, we found labeling for all three Nav subtypes on dendrites, dendritic spines, and axon terminals, but the proportion of pre‐ and post‐synaptic labeling for each subtype varied within and between subregions of CA1 and dentate gyrus. In the central hilus (CH) of the dentate gyrus, Nav1.1 immunoreactivity was selectively expressed in presynaptic profiles, while Nav1.2 and Nav1.6 were expressed both pre‐ and post‐synaptically. In contrast, in the stratum radiatum (SR) of CA1, Nav1.1, Nav1.2, and Nav1.6 were selectively expressed in postsynaptic profiles. We next compared differences in Nav subtype expression between CH and SR axon terminals and between CH and SR dendrites and spines. Nav1.1 and Nav1.2 immunoreactivity was preferentially localized to CH axon terminals compared to SR, and in SR dendrites and spines compared to CH. No differences in Nav1.6 immunoreactivity were found between axon terminals of CH and SR or between dendrites and spines of CH and SR. All Nav subtypes in both CH and SR were preferentially associated with asymmetric synapses rather than symmetric synapses. These findings indicate selective presynaptic and postsynaptic Nav expression in glutamatergic synapses of CH and SR supporting neurotransmitter release and synaptic plasticity.
Clustered organization and region‐specific identities of estrogen‐producing neurons in the forebrain of Zebra Finches (Taeniopygia guttata)
Authors: Ikeda Maaya Z. , Krentzel Amanda A. , Oliver Tessa J. , Scarpa Garrett B. , Remage‐Healey Luke
Published: July 2017

A fast, neuromodulatory role for estrogen signaling has been reported in many regions of the vertebrate brain. Regional differences in the cellular distribution of aromatase (estrogen synthase) in several species suggest that mechanisms for neuroestrogen signaling differ between and even within brain regions. A more comprehensive understanding of neuroestrogen signaling depends on characterizing the cellular identities of neurons that express aromatase. Calcium‐binding proteins such as parvalbumin and calbindin are molecular markers for interneuron subtypes, and are co‐expressed with aromatase in human temporal cortex. Songbirds like the zebra finch have become important models to understand the brain synthesis of steroids like estrogens and the implications for neurobiology and behavior. Here, we investigated the regional differences in cytoarchitecture and cellular identities of aromatase‐expressing neurons in the auditory and sensorimotor forebrain of zebra finches. Aromatase was co‐expressed with parvalbumin in the caudomedial nidopallium (NCM) and HVC shelf (proper name) but not in the caudolateral nidopallium (NCL) or hippocampus. By contrast, calbindin was not co‐expressed with aromatase in any region investigated. Notably, aromatase‐expressing neurons were found in dense somato‐somatic clusters, suggesting a coordinated release of local neuroestrogens from clustered neurons. Aromatase clusters were also more abundant and tightly packed in the NCM of males as compared to females. Overall, this study provides new insights into neuroestrogen regulation at the network level, and extends previous findings from human cortex by identifying a subset of aromatase neurons as putative inhibitory interneurons.
Distinct projection targets define subpopulations of mouse brainstem vagal neurons that express the autism‐associated MET receptor tyrosine kinase
Authors: Kamitakahara Anna , Wu Hsiao‐Huei , Levitt Pat
Published: July 2017

Detailed anatomical tracing and mapping of the viscerotopic organization of the vagal motor nuclei has provided insight into autonomic function in health and disease. To further define specific cellular identities, we paired information based on visceral connectivity with a cell‐type specific marker of a subpopulation of neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (nAmb) that express the autism‐associated MET receptor tyrosine kinase. As gastrointestinal disturbances are common in children with autism spectrum disorder (ASD), we sought to define the relationship between MET‐expressing (MET+) neurons in the DMV and nAmb, and the gastrointestinal tract. Using wholemount tissue staining and clearing, or retrograde tracing in a METEGFP transgenic mouse, we identify three novel subpopulations of EGFP+ vagal brainstem neurons: (a) EGFP+ neurons in the nAmb projecting to the esophagus or laryngeal muscles, (b) EGFP+ neurons in the medial DMV projecting to the stomach, and (b) EGFP+ neurons in the lateral DMV projecting to the cecum and/or proximal colon. Expression of the MET ligand, hepatocyte growth factor (HGF), by tissues innervated by vagal motor neurons during fetal development reveal potential sites of HGF‐MET interaction. Furthermore, similar cellular expression patterns of MET in the brainstem of both the mouse and nonhuman primate suggests that MET expression at these sites is evolutionarily conserved. Together, the data suggest that MET+ neurons in the brainstem vagal motor nuclei are anatomically positioned to regulate distinct portions of the gastrointestinal tract, with implications for the pathophysiology of gastrointestinal comorbidities of ASD.
Anisotropic Diffusion of Microbeads Surrounded by an Anisotropically Elongated Supramolecular Diarylethene Architecture under Linearly Polarized Light
Authors: Sakaguchi Akira , Higashiguchi Kenji , Matsuda Kenji
Published: July 2017

Upon irradiation of an amphiphilic diarylethene derivative (which shows a photoinduced morphological transformation in water between sphere and fiber states) with linearly polarized light, elongation of the fiber in the direction of polarization was observed in TEM images. The diffusive motion was suppressed in the direction perpendicular to that of the generated fiber, as revealed by means of trajectory tracking of added polystyrene (PS) beads. When unpolarized UV light was used, the TEM image showed no anisotropic features and the diffusion of PS beads was isotropic. These results provide a means for anisotropic photocontrol of the morphology of supramolecular architectures.
Validation of an LC–MS/MS method for analysis of anti‐diabetic drugs in botanical dietary supplements labeled for blood sugar management
Authors: Ma Jun , Pawar Rahul S. , Grundel Erich
Published: July 2017

We developed and validated a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to detect and quantitate 14 anti‐diabetic, 2 anti‐obesity, and 3 cholesterol‐lowering drugs in botanical dietary supplements marketed for blood sugar management. Many botanical dietary supplements which carry label statements related to blood sugar management are available over the Internet. Potential adulteration of such dietary supplements with anti‐diabetic and other prescription drugs, some of which have been removed from the market due to adverse events, is of concern. No significant matrix effects were observed and mean recoveries of all 19 analytes from a single product matrix were 88 to 113% at spiking concentrations from 500 to 2000 μg/g. Mean recoveries of metformin, phenformin, and sibutramine from matrices prepared from multiple product composites ranged from 93 to 115% at a spiking concentration of 100 μg/g. The relative standard deviations (RSD) (%) of intra‐day analyses ranged from 0.2 to 13 for all recovery studies. Eighty dietary supplements obtained in the USA and carrying label statements related to blood sugar management were analyzed using this method and none were found to be adulterated with the above 19 drugs. Two products obtained outside of the USA and known to be adulterated were also analyzed by this method and found to contain phenformin, glibenclamide, and sibutramine. This method provided satisfactory selectivity, linearity, accuracy, precision, and sensitivity for rapid determination of 19 drugs and has broad applicability for the analysis of dietary supplements for possible adulteration with these compounds.