bluuebunny/crossref_metadata_2025 huggingface dataset:
The work‐related stressors and coping strategies of group‐employed rural health care practitioners: A qualitative study
Authors: Hasbrouck Melinda A. , Waddimba Anthony C.
Published: August 2017

Background

Escalating demands on practitioners, stagnating/dwindling resources, and diminishing autonomy have heightened patient‐care work‐related stress. Using qualitative content/thematic analysis of responses to open‐ended survey questions, plus spontaneous comments, we sought to identify rural clinicians’ subjective perceptions of their workplace stressors and typical adaptive/coping strategies.

Methods

Within a hybrid inductive‐deductive approach, we framed empirical themes (derived by consensus, corroborated with text segments, and extant literature) into theory‐based coding templates by which we analyzed the data.

Results

Of 308 (65.1% of) recipients completing questionnaires, 290 (94%) answered open‐ended questions and/or provided comments. Categorizing stressors by socio‐ecology, they cited four themes: Organizational, practitioner/staff‐related, patient‐related, and third party‐induced stressors. Organizational stressors were referenced most conspicuously. How respondents described their coping fitted the Stress, Appraisal and Coping. [Lazarus and Folkman (1984): New York, NY: Springer Publishing Company, Inc] model. Emotion‐focused were referenced more than problem‐focused approaches. Themes scarcely differed by demographics, except for marital status.

Conclusions

Findings highlight needs for resilience coaching, rekindling work meaningfulness, mentorship in work‐home balance/limit‐setting, supportive peer networks, and deeper teamwork.
Work organization, health, and obesity in urban transit operators: A qualitative study
Authors: Dobson Marnie , Choi BongKyoo , Schnall Peter L.
Published: August 2017

Background

Urban transit operators have high rates of obesity, hypertension, and other cardiovascular risk‐factors compared to other occupations. There have been few qualitative studies exploring the interrelationships between the organization of transit work, stress, and health including obesity, from the perspective of operators.

Methods

Five focus groups were conducted at five Divisions in a transit authority in Southern California and included 65 bus and rail operators.

Results

Operators reported a great deal of stress related to their work, including 1) time pressures and lack of recovery time; 2) long work shifts and overtime; 3) feeling unsafe when dealing with the public; 4) lack of respect from supervisors and management. Operators believed stressful working conditions negatively impacted their health and weight.

Conclusion

This qualitative study yielded new as well as confirmatory data about stress and transit work organization, health, and weight in operators. This study will add to future survey research and interventions in this population.
RuII‐Catalyzed ortho‐Sulfonamidation of α‐Tetralones with Sulfonyl Azides and Synthesis of Sivelestat by Aromatic C−H Activation
Authors: Krishna Rao Medikonda V. , Reddy Keesari Nagarjuna , Sridhar Balasubramaniam , Subba Reddy Basi V.
Published: August 2017

A method has been developed for the sulfonamidation of tetralones and 1,4‐naphthoquinones by using sulfonyl azides in the presence of a RuII/AgI catalytic system. In case of tetralones, C−H bond functionalization occurred exclusively at the ortho position, whereas 1,4‐addition was the main transformation for 1,4‐naphthoquinones. This method is highly regioselective and was successfully utilized for the synthesis of sivelestat, an inhibitor of human neutrophil elastase.
Axonal components of nerves innervating the human arm
Authors: Gesslbauer Bernhard , Hruby Laura A. , Roche Aidan D. , Farina Dario , Blumer Roland , Aszmann Oskar C.
Published: August 2017

Objective

Axons traveling within the brachial plexus are responsible for the dexterous control of human arm and hand movements. Despite comprehensive knowledge on the topographical anatomy of nerves innervating the human upper limbs, the definite quantity of sensory and motor axons within this neural network remains elusive. Our aim was to perform a quantitative analysis of the axonal components of human upper limb nerves based on highly specific molecular features from spinal cord level to the terminal nerves at wrist level.

Methods

Nerve specimen harvest at predefined harvesting sites (plexus roots and cords as well as major nerves originating from the brachial plexus innervating the arm and hand) was performed in 9 human heart‐beating organ donors. Double immunofluorescence staining using antibodies against choline‐acetyltransferase and neurofilament was performed to differentiate motor and sensory axons on nerve cross sections.

Results

Three hundred fifty thousand axons emerge from the spinal cord to innervate the human upper limb, of which 10% are motor neurons. In all nerves studied, sensory axons outnumber motor axons by a ratio of at least 9:1. The sensory axon contribution increases when moving distally, whereas only 1,700 motor axons reach the hand to innervate the intrinsic musculature.

Interpretation

Our results suggest that upper limb motor execution, and particularly dexterous coordination of hand movement, require an unexpectedly low number of motor neurons, with a large convergence of afferent input for feedback control. Ann Neurol 2017;82:396–408
T1‐/T2‐weighted ratio differs in demyelinated cortex in multiple sclerosis
Authors: Nakamura Kunio , Chen Jacqueline T. , Ontaneda Daniel , Fox Robert J. , Trapp Bruce D.
Published: August 2017

Detecting cortical demyelination in patients with multiple sclerosis (MS) is difficult. Using magnetic resonance imaging (MRI), ratio maps of T1‐weighted (T1w) and T2‐weighted (T2w) images may be sensitive to cortical myelin levels. In this MRI–histological study, postmortem in situ scans were acquired from 6 cadavers with MS on a 3T MRI machine. Immunocytochemistry was used to correlate myelin status and cortical T1w/T2w measures. The results showed that the T1w/T2w values significantly differed between demyelinated and myelinated cortex (p < 0.001). The T1w/T2w ratio maps may be a relatively simple, clinically feasible method to assess cortical demyelination. Ann Neurol 2017;82:635–639
Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging
Authors: Righart Ruthger , Biberacher Viola , Jonkman Laura E. , Klaver Roel , Schmidt Paul , Buck Dorothea , Berthele Achim , Kirschke Jan S. , Zimmer Claus , Hemmer Bernhard , Geurts Jeroen J. G. , Mühlau Mark
Published: August 2017

Objective

In multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown.

Methods

Using a novel magnetic resonance imaging analysis technique, based on the ratio of T1‐ and T2‐weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis. A total of 168 patients with clinically isolated syndrome or relapsing–remitting multiple sclerosis (Expanded Disability Status Scale: median = 1, range = 0–3.5) and 80 age‐ and sex‐matched healthy controls were investigated. We also searched for the histopathological substrate of the T1/T2‐weighted ratio by combining postmortem imaging and histopathology in 9 multiple sclerosis brain donors.

Results

Patients showed lower T1/T2‐weighted ratio values in parietal and occipital areas. The 4 most significant clusters appeared in the medial occipital and posterior cingulate cortex (each left and right). The decrease of the T1/T2‐weighted ratio in the posterior cingulate was related to performance in attention. Analysis of the T1/T2‐weighted ratio values of postmortem imaging yielded a strong correlation with dendrite density but none of the other parameters including myelin.

Interpretation

The T1/T2‐weighted ratio decreases in early stages of multiple sclerosis in a widespread manner, with a preponderance of posterior areas and with a contribution to attentional performance; it seems to reflect dendrite pathology. As the method is broadly available and applicable to available clinical scans, we believe that it is a promising candidate for studying and monitoring cortical pathology or therapeutic effects in multiple sclerosis. Ann Neurol 2017;82:519–529
Nickel‐Catalyzed Reductive Allylation of Tertiary Alkyl Halides with Allylic Carbonates
Authors: Chen Haifeng , Jia Xiao , Yu Yingying , Qian Qun , Gong Hegui
Published: August 2017

The construction of all C(sp3) quaternary centers has been successfully achieved under Ni‐catalyzed cross‐electrophile coupling of allylic carbonates with unactivated tertiary alkyl halides. For allylic carbonates bearing C1 or C3 substituents, the reaction affords excellent regioselectivity through the addition of alkyl groups to the unsubstituted allylic carbon terminus. The allylic alkylation method also exhibits excellent functional‐group compatibility, and delivers the products with high E selectivity.
Enhanced Photophosphorylation of a Chloroplast‐Entrapping Long‐Lived Photoacid
Authors: Xu Youqian , Fei Jinbo , Li Guangle , Yuan Tingting , Li Yue , Wang Chenlei , Li Xianbao , Li Junbai
Published: August 2017

Enhancing solar energy conversion efficiency is very important for developing renewable energy, protecting the environment, and producing agricultural products. Efficient enhancement of photophosphorylation is demonstrated by coupling artificial photoacid generators (PAGs) with chloroplasts. The encapsulation of small molecular long‐lived PAGs in the thylakoid lumen is improved greatly by ultrasonication. Under visible‐light irradiation, a fast intramolecular photoreaction of the PAG occurs and produces many protons, remarkably enhancing the proton gradient in situ. Consequently, compared to pure chloroplasts, the assembled natural–artificial hybrid demonstrates approximately 3.9 times greater adenosine triphosphate (ATP) production. This work will provide new opportunities for constructing enhanced solar energy conversion systems.
Selective Ring‐Opening Polymerization of Non‐Strained γ‐Butyrolactone Catalyzed by A Cyclic Trimeric Phosphazene Base
Authors: Zhao Na , Ren Chuanli , Li Huaike , Li Yunxin , Liu Shaofeng , Li Zhibo
Published: August 2017

A new superbase, the cyclic trimeric phosphazene base (CTPB), was prepared with high yield and purity. In the presence of alcohol, the CTPB serves as a highly efficient organocatalyst for ring‐opening polymerization of the “non‐polymerizable” γ‐butyrolactone to offer well‐defined poly(γ‐butyrolactone) with high conversions (up to 98 %) at −60 °C. The produced polymers have high molecular weights (up to 22.9 kg mol−1) and low polydispersity distributions (1.27–1.50). NMR analysis of initiation process and the structural analysis of resulting polymers by MALDI‐TOF suggest a mechanism involving an activating initiator which leads only to linear polymers with BnO/H chain ends.
Homo‐ and Heteroleptic Phototoxic Dinuclear Metallo‐Intercalators Based on RuII(dppn) Intercalating Moieties: Synthesis, Optical, and Biological Studies
Authors: Saeed Hiwa K. , Jarman Paul J. , Archer Stuart , Sreedharan Sreejesh , Saeed Ibrahim Q. , Mckenzie Luke K. , Weinstein Julia A. , Buurma Niklaas J. , Smythe Carl G. W. , Thomas Jim A.
Published: August 2017

Using a new mononuclear “building block,” for the first time, a dinuclear RuII(dppn) complex and a heteroleptic system containing both RuII(dppz) and RuII(dppn) moieties are reported. The complexes, including the mixed dppz/dppn system, are 1O2 sensitizers. However, unlike the homoleptic dppn systems, the mixed dppz/dppn complex also displays a luminescence “switch on” DNA light‐switch effect. In both cisplatin sensitive and resistant human ovarian carcinoma lines the dinuclear complexes show enhanced uptake compared to their mononuclear analogue. Thanks to a favorable combination of singlet oxygen generation and cellular uptake properties all three of the new complexes are phototoxic and display potent activity against chemotherapeutically resistant cells.
Intramolekulare π‐π‐Wechselwirkungen in flexibel verbrückten, teilweise fluorierten Bisarenen in der Gasphase
Authors: Blomeyer Sebastian , Linnemannstöns Marvin , Nissen Jan Hendrick , Paulus Jannik , Neumann Beate , Stammler Hans‐Georg , Mitzel Norbert W.
Published: August 2017

Mittels Hydrosilylierungs‐ und C‐C‐Kupplungsreaktionen wurden drei mit (CH2)3‐ und (CH2)2SiMe2‐Einheiten verbrückte Verbindungen mit Phenyl‐ und Pentafluorphenylringen synthetisiert. Im Festkörper bilden sie primär dimere oder kettenartige, von intermolekularen π‐π‐Wechselwirkungen dominierte Aggregate. Die Struktur des häufigsten Konformers der freien Moleküle zeigt jeweils, bestimmt mittels Gas‐Elektronen‐Diffraktion, eine signifikante intramolekulare Stabilisierung durch π‐π‐Wechselwirkungen. Die nächstenergiereicheren Konformere für die Siliciumverbindungen zeigen σ‐π‐Wechselwirkungen zwischen Methyl‐ und (Pentafluor‐)Phenylgruppen und können im GED‐Experiment nicht vollständig ausgeschlossen werden. Im Unterschied dazu besteht C6H5(CH2)3C6F5 nur aus einem einzigen Konformer. Die Gasphasenstrukturen dienen als Referenz für die Evaluation einer Reihe (dispersionskorrigierter) quantenchemischer Methoden.
Stereospecific Electrophilic Fluorination of Alkylcarbastannatrane Reagents
Authors: Ma Xinghua , Diane Mohamed , Ralph Glenn , Chen Christine , Biscoe Mark R.
Published: August 2017

We report the use of isolable primary and secondary alkylcarbastannatrane nucleophiles in site‐specific fluorination reactions. These reactions occur without the need for transition metal catalysis or in situ activation of the nucleophile. In the absence of the carbastannatrane backbone, alkyltin nucleophiles exhibit no activity towards fluorination. When enantioenriched alkylcarbastannatranes are employed, fluorination occurs predominately via a stereoinvertive mechanism to generate highly enantioenriched alkyl fluoride compounds. These conditions can also be extended to stereospecific chlorination, bromination, and iodination reactions.
Titanocene‐Catalyzed Radical Opening of N‐Acylated Aziridines
Authors: Zhang Yong‐Qiang , Vogelsang Elisabeth , Qu Zheng‐Wang , Grimme Stefan , Gansäuer Andreas
Published: August 2017

Aziridines activated by N‐acylation are opened to the higher substituted radical through electron transfer from titanocene(III) complexes in a novel catalytic reaction. This reaction is applicable in conjugate additions, reductions, and cyclizations and suited for the construction of quaternary carbon centers. The concerted mechanism of the ring opening is indicated by DFT calculations.
Diagnosis of disturbance in distillation process based on inversion method
Authors: Tian Wende , Liang Huiting , Zhang Guixin
Published: August 2017

Many difficulties are encountered when analyzing hard‐to‐identify underlying causes of disturbances in distillation processes. Direct model‐based fault diagnosis methods often prove to be time‐consuming because they iteratively solve the direct model to obtain representative disturbance parameters. In this paper, an inversion method is proposed for identifying fault causes in the field of distillation diagnosis by mapping measured data against disturbance types. The proposed method consists of an offline phase and an online phase. In the offline phase, both normal and abnormal samples are simulated based on a simplified dynamic mechanistic model, and they are used to establish an inversion model for each disturbance with regard to each characteristic representation quantity using a genetic algorithm (GA). In the online phase, neural network, negative selection algorithm (NSA), and support vector machine (SVM) algorithms are used to determine the disturbance type, and the disturbance quantity is obtained by solving the corresponding inversion model. The proposed method is applied to high purity binary distillation column and benzene–toluene distillation column test cases. Case studies demonstrate that the inversion model‐based diagnosis method can effectively identify disturbances and thus provide theoretical support for the application of quantitative fault diagnosis technology in the chemical industry. © 2017 Curtin University and John Wiley & Sons, Ltd.
Electrospun waterproof breathable membrane with a high level of aerosol filtration
Authors: Maksoud Fouad Junior , Lameh Mohammad , Fayyad Sary , Ismail Nagham , Tehrani‐Bagha Ali Reza , Ghaddar Nesreen , Ghali Kamel
Published: August 2017

In this study, several nanofibrous polyurethane (PU) webs were electrospun (ES) by changing different effective parameters (e.g., polymeric concentration, voltage, feed flow, etc.). The physical–chemical properties of the webs (i.e., average fiber diameters, thickness, areal density, porosity, contact angle, waterproofness, air permeability (AP), water vapor transmittance, and aerosol filtration) were studied based on the standard test methods. A commercially available waterproof breathable (WPB) fabric was used as a reference for benchmarking. The beads‐free webs with an average fiber diameter as small as 200 nm were achieved from electrospinning of 10 wt % PU inN,N‐dimethylformamide, at feed rate of 0.5 mL/h, applied voltage of 25 kV, and tip‐to‐collector distance of 15 cm. By optimizing the electrospinning parameters, a web with a high level of waterproofness, high AP, and high water vapor transmission rate (WVTR) was obtained. In addition, the selected ES membrane showed very promising aerosol filtration efficiency with complete removal of particles larger than 0.5 µm, and 94% reduction in the concentration of smaller particles. We found a linear empirical equation for the estimation of AP and WVTR based on the average pore size diameter, the membrane thickness, and the porosity with very high regression coefficients (R2 > 0.97). © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2018,135, 45660.
Mechanical, thermal, and water absorption properties of melamine–formaldehyde‐treated sisal fiber containing poly(lactic acid) composites
Authors: Tengsuthiwat Jiratti , Asawapirom Udom , Siengchin Suchart , Karger‐Kocsis József
Published: August 2017

The present study focuses on the melamine–formaldehyde (MF) coating ratio and silanization of PLA/sisal composites. Poly(lactic acid) (PLA) was melt blended with short sisal fiber with and without MF resin coating. MF was applied at different weight ratios (sisal:MF = 1:1; 1:3, and 1:5) to coat the untreated or silanized sisal fibers which were incorporated up to 20 parts per hundred resin (phr) amount in PLA. PLA/sisal composites were produced by compression molding. It was found that the sisal:MF coating ratio at 1:1 by weight improved the tensile strength and tensile modulus of the composite with 10 phr sisal by 4% and 57%, respectively, compared to the virgin PLA. The initial and final decomposition (Ti) and (Tf) of PLA with untreated sisal were changed from 330.8 and 367.1 to 336.2 and 370.4 °C, respectively, after MF‐coating (sisal:MF weight ratio = 1:1). This enhancement in thermal stability was attributed to the strong interaction between the MF and sisal fiber. The water absorption of PLA/MF–sisal composites slightly decreased with increasing sisal:MF ratio. This is due to the fact that the MF‐coating substantially reduced the hydrophilic properties of sisal. Moreover, FTIR spectra and SEM images proved that sisal fibers were coated by MF resin successfully. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45681.
A dual‐induced self‐expandable stent based on biodegradable shape memory polyurethane nanocomposites (PCLAU/Fe3O4) triggered around body temperature
Authors: Gu Shu‐Ying , Chang Kun , Jin Sheng‐Peng
Published: August 2017

Concerning the occurrence of in‐stent restenosis and stent thrombosis of stent implantation with balloon angioplasty, a dual‐induced self‐expandable stent based on biodegradable shape memory polyurethane nanocomposites (PCLAU/Fe3O4) was developed. The stent could maintain its temporary shape at body temperature for a certain period of time while it was able to recover to its permanent shape at the temperature a little above body temperature (around 40 °C) in both a water bath and an alternating magnetic field. The trigger temperature and remote local heating ensured enough operation time and harmless activation without heating the body tissue. The nanocomposites had high fixing ratios above 99% and recovery ratios above 82% at both 37 and 40 °C. Cytotoxicity and in vitro degradation showed the nanocomposites had good biocompatibility and biodegradability. The PCLAU/Fe3O4 nanocomposites with dual‐responsive shape memory effects, desirable mechanical properties, biocompatibility, and biodegradability show great potential for vascular stents. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45686.
Fabrication of Mesoporous Cu Films on Cu Foils and Their Applications to Dopamine Sensing
Authors: Baba Daisuke , Li Cuiling , Malgras Victor , Jiang Bo , Alamri Hatem R. , Alothman Zeid A. , Hossain Md. Shahriar A. , Yamauchi Yusuke , Asahi Toru
Published: August 2017

We previously succeeded to prepare stable mesoporous Cu films on Au‐coated conductive working electrodes by using polystyrene‐b‐poly(oxyethylene) (PS63 000‐b‐PEO26 000) micelles as template and sulfuric acid to increase ionic conductivity. In the present study, we report the preparation of mesoporous Cu films on Cu foil. By changing the Cu salts and electrodeposition potentials, we discuss how these parameters influence the final product. Without having to filtrate interefering species, such as uric acid, ascorbic acid and glucose, the dopamine concentration can be precisely determined by applying a suitable potential. Therefore, non‐invasive electrochemical sensing based on mesoporous films will be useful for daily diagnosis of mental disorder.
Microbial production of mannitol by Lactobacillus brevis 3‐A5 from concentrated extract of Jerusalem artichoke tubers
Authors: Cao Hailong , Yue Min , Liu Gang , Du Yuguang , Yin Heng
Published: August 2017

In the present study, the conversion of the extract of Jerusalem artichoke tubers for mannitol production by Lactobacillus brevis 3‐A5 was investigated. When the bacterium utilized enzymatic hydrolysates of Jerusalem artichoke extract as the main substrates in batch fermentation, the significant decrease in mannitol productivity was observed when the initial concentration of reducing sugar increased. Then, a strategy of continuous fed‐batch fermentation was adopted for improving mannitol production with enzymatic hydrolysates of Jerusalem artichoke extract as main substrates. Although the concentration of mannitol could reach 199.86 g/L at the end of the fermentation, the productivity for the overall process of the fermentation was only 1.67 g/L/H. To improve the mannitol productivity with both higher yield and concentration, the simultaneous enzymatic saccharification and fermentation (SSF) was studied. In SSF, the mannitol production reached 176.50 g/L in 28 H with a productivity of 6.30 g/L/H and a yield of 0.68 g/g total sugar. Our study provides a cost‐effective and eco‐friendly method for mannitol production from a cheap biomass.
Application of HPLC‐LTQ Orbitrap MS for metabolic profiles of Polygonum multiflora extract in rats
Authors: Zhang Jing , Wang Tenghua , Ren Zhiyao , Gong Lu , Huang Juan , Bai Junqi , Qiu Xiaohui , Xu Wen
Published: August 2017

The root of Polygonum multiflorum (PM) is an important Chinese herbal medicine for treatment of various diseases. Extensive pharmacological studies have been conducted and demonstrated that it shows a wide range of bioactivities. Meanwhile, a considerable number of hepatotoxicity cases owing to oral administration of PM have been reported and have attracted great attention. However, the limited knowledge regarding the metabolism of PM restricts the deeper studies on its pharmacological/toxicological mechanism and therapeutic material basis. The present study aimed to develop a high‐performance liquid chromatography coupled with a linear ion trap–Orbitrap hybrid mass spectrometry method for separation and identification of metabolites in rat urine and plasma after oral administration of PM. Based on the proposed strategy, metabolism profiles of PM in rats were proposed for the first time and 43 metabolites were characterized or tentatively identified. Phase II metabolism, such as glucuronidation and sulfation, are the principal pathways of the main components. These findings will be beneficial to further understanding of the pharmacological mechanism and pharmacodynamic material basis of PM.
Rheumatoid arthritis in review: Clinical, anatomical, cellular and molecular points of view
Authors: Sharif Kassem , Sharif Alaa , Jumah Fareed , Oskouian Rod , Tubbs R. Shane
Published: August 2017

Rheumatoid arthritis (RA) is the most common chronic autoimmune disease of the joints affecting close to 0.5–1.0% of the general population. Although the etiopathogenesis of RA remains elusive, the involvement of dendritic cells and type 17 T‐helper cells appears to be pivotal in maintaining a state of chronic inflammation. RA is generally characterized by small joint involvement. A chronic inflammatory process leads to joint destruction and to tendon and ligament laxity and disintegration. These processes result in an imbalance of forces acting on the joints causing joint deformities including swan neck deformity, boutonniere deformity of the hands, flexion deformity of the wrist, lesser toe deformities, and others. In some instances, bony erosions subsequent to the RA disease process can result in life‐threatening events including, for example, atlanto‐axial subluxation, which can cause myelopathy and paralysis; and basilar invagination, which can cause brain stem injury and imminent death. Although less commonly involved, larger joints are not spared, as evidenced by the involvement of the elbow, hip, and shoulder joints in a sizable proportion of RA patients. The progression and prognosis of this disease entity are variable, guarded and dependent on the efficacy and response to treatment modalities employed. Inadequate management results in disease progression, which ultimately leads to joint erosion, destruction, deformities and substantial decrease in the functional quality of life. Clin. Anat. 31:216–223, 2018. © 2017 Wiley Periodicals, Inc.
Photometric Characterization of the Reductive Amination Scope of the Imine Reductases from Streptomyces tsukubaensis and Streptomyces ipomoeae
Authors: Matzel Philipp , Krautschick Lukas , Höhne Matthias
Published: August 2017

Imine reductases (IREDs) have emerged as promising enzymes for the asymmetric synthesis of secondary and tertiary amines starting from carbonyl substrates. Screening the substrate specificity of the reductive amination reaction is usually performed by time‐consuming GC analytics. We found two highly active IREDs in our enzyme collection, IR‐20 from Streptomyces tsukubaensis and IR‐Sip from Streptomyces ipomoeae, that allowed a comprehensive substrate screening with a photometric NADPH assay. We screened 39 carbonyl substrates combined with 17 amines as nucleophiles. Activity data from 663 combinations provided a clear picture about substrate specificity and capabilities in the reductive amination of these enzymes. Besides aliphatic aldehydes, the IREDs accepted various cyclic (C4–C8) and acyclic ketones, preferentially with methylamine. IR‐Sip also accepted a range of primary and secondary amines as nucleophiles. In biocatalytic reactions, IR‐Sip converted (R)‐3‐methylcyclohexanone with dimethylamine or pyrrolidine with high diastereoselectivity (>94–96 % de). The nucleophile acceptor spectrum depended on the carbonyl substrate employed. The conversion of well‐accepted substrates could also be detected if crude lysates were employed as the enzyme source.
Structures of the N‐Terminal Domain of PqsA in Complex with Anthraniloyl‐ and 6‐Fluoroanthraniloyl‐AMP: Substrate Activation in Pseudomonas Quinolone Signal (PQS) Biosynthesis
Authors: Witzgall Florian , Ewert Wiebke , Blankenfeldt Wulf
Published: August 2017

Pseudomonas aeruginosa, a prevalent pathogen in nosocomial infections and a major burden in cystic fibrosis, uses three interconnected quorum‐sensing systems to coordinate virulence processes. At variance with other Gram‐negative bacteria, one of these systems relies on 2‐alkyl‐4(1H)‐quinolones (Pseudomonas quinolone signal, PQS) and might hence be an attractive target for new anti‐infective agents. Here we report crystal structures of the N‐terminal domain of anthranilate‐CoA ligase PqsA, the first enzyme of PQS biosynthesis, in complex with anthraniloyl‐AMP and with 6‐fluoroanthraniloyl‐AMP (6FABA‐AMP) at 1.4 and 1.7 Å resolution. We find that PqsA belongs to an unrecognized subfamily of anthranilate‐CoA ligases that recognize the amino group of anthranilate through a water‐mediated hydrogen bond. The complex with 6FABA‐AMP explains why 6FABA, an inhibitor of PQS biosynthesis, is a good substrate of PqsA. Together, our data might pave a way to new pathoblockers in P. aeruginosa infections.
Lactoferrin induces tropoelastin expression by activating the lipoprotein receptor‐related protein 1‐mediated phosphatidylinositol 3‐kinase/Akt pathway in human dermal fibroblasts
Authors: Ryu Mizuyuki , Nogami Asuka , Kitakaze Tomoya , Harada Naoki , Suzuki Yasushi A. , Yamaji Ryoichi
Published: August 2017

Dermal fibroblasts generate the extracellular matrix component elastin, which is synthesized as tropoelastin (TE) and play a critical role in maintaining skin elasticity. Lactoferrin (Lf), an 80‐kDa iron‐binding glycoprotein, has biological functions such as anti‐bacterial, ‐inflammatory, and ‐cancer activities. We previously reported that bovine Lf increases TE mRNA expression in human dermal fibroblasts. However, it remains unclear how Lf up‐regulates TE expression. Here, we investigated molecular mechanisms underlying this effect. Lf promoted the phosphorylation of Akt1 and extracellular signal‐regulated protein kinase (ERK)1/2. As expected, the phosphatidylinositol 3‐kinase (PI3K) inhibitor LY294002 and the MAPK inhibitor U0126 inhibited Lf‐induced phosphorylation of Akt1 and ERK1/2, respectively. In contrast, LY294002, but not U0126, inhibited Lf‐induced TE expression. Human dermal fibroblasts expressed lipoprotein receptor‐related protein 1 (LRP‐1) mRNA, and the LRP1 inhibitor receptor‐associated protein attenuated Lf‐induced increases in TE expression. Furthermore, siRNA‐mediated knockdown of LRP‐1 significantly suppressed Lf‐increased TE expression and Lf‐induced Akt1 phosphorylation. Iron‐saturated Lf (holo‐Lf) increased TE expression and promoted Akt1 phosphorylation, when compared to those parameters in cells treated with iron‐free Lf (apo‐Lf). Transforming growth factor (TGF)‐β1 also increased TE expression. LY294002 inhibited TGF‐β1‐mediated TE upregulation, whereas TGF‐β1 activated Akt2, but not Akt1, phosphorylation. These results indicate that holo‐Lf, but not apo‐Lf, increases TE expression through LRP‐1 in human dermal fibroblasts and suggest that holo‐Lf and TGF‐β1 enhance TE expression by activating the PI3K/Akt1 and PI3K/Akt2 pathways, respectively.
Diversity‐Oriented Syntheses by Combining CuAAC and Stereoselective INCIC Reactions with Peptides
Authors: Wang Yuanyuan , Madsen Anders Ø. , Diness Frederik , Meldal Morten
Published: August 2017

Cascade reactions proceeding through peptide‐derived N‐carbamoyl iminium ions are reported. Two new reactions of N‐carbamoyl iminium ions are described, including a stereoselective double cyclization generating N,N′‐aminals and an acid‐promoted auto‐oxidation. Mechanistic investigations revealed that the N,N′‐aminal formation is reversible under strongly acidic conditions. Both of these new reactions proved to be completely orthogonal to subsequent CuAAC chemistry. The reactions were performed in solution and on solid support. The robustness and high stereoselectivity of the methodology holds great promise for applications in parallel diversity‐oriented synthesis and in combinatorial synthesis for drug screening.
Transition‐Metal‐Controlled Inorganic Ligand‐Supported Non‐Precious Metal Catalysts for the Aerobic Oxidation of Amines to Imines
Authors: Yu Han , Zhai Yongyan , Dai Guoyong , Ru Shi , Han Sheng , Wei Yongge
Published: August 2017

Most state‐of‐art transition‐metal catalysts usually require organic ligands, which are essential for controlling the reactivity and selectivity of reactions catalyzed by transition metals. However, organic ligands often suffer from severe problems including cost, toxicity, air/moisture sensitivity, and being commercially unavailable. Herein, we show a simple, mild, and efficient aerobic oxidation procedure of amines using inorganic ligand‐supported non‐precious metal catalysts 1, (NH4)n[MMo6O18(OH)6] (M=Cu2+; Fe3+; Co3+; Ni2+; Zn2+, n=3 or 4), synthesized by a simple one‐step method in water at 100 °C, demonstrating that the catalytic activity and selectivity can be significantly improved by changing the central metal atom. In the presence of these catalysts, the catalytic oxidation of primary and secondary amines, as well as the coupling of alcohols and amines, can smoothly proceed to afford various imines with O2 (1 atm) as the sole oxidant. In particular, the catalysts 1 have transition‐metal ion core, and the planar arrangement of the six MoVI centers at their highest oxidation states around the central heterometal can greatly enhance the Lewis acidity of catalytically active sites, and also enable the electrons in the center to delocalize onto the six edge‐sharing MO6 units, in the same way as ligands in traditional organometallic complexes. The versatility of this methodology maybe opens a path to catalytic oxidation through inorganic ligand‐coordinated metal catalysis.
Arsenic‐Mediated C−C Coupling of Cyanides Leading to Cyanido Arsazolide [AsC4N4]−
Authors: Arlt Sören , Harloff Jörg , Schulz Axel , Stoffers Alrik , Villinger Alexander
Published: August 2017

The chemistry of arsenic cyanides has been investigated and is found to be completely different to the chemistry of the heavier analogs antimony and bismuth as well as phosphorus. The reaction of As(CN)3 with cyanide salts resulted in the formation of an unknown cyanido arsazolide heterocycle, which represents a structure isomer of the desired [As(CN)4]−. The structure, bonding, and formation of this unusual heterocycle is discussed featuring an arsenic mediated C−C coupling of cyanides. [AsC4N4]− salts with different counterions such as [PPh4]+, [PPN]+=[Ph3P‐N‐PPh3]+, Ag+, and [BMIm]+ are reported with [BMIm][AsC4N4] being a low‐temperature ionic liquid (Tm=−62 °C).
Revisiting past refinery accidents from a human reliability analysis perspective: The BP Texas City and the Chevron Richmond accidents
Authors: Abílio Ramos Marilia , Droguett Enrique López , Mosleh Ali , das Chagas Moura Márcio , Ramos Martins Marcelo
Published: August 2017

Despite the oil industry's efforts in improving safety, it still presents a high rate of serious accidents, many involving human failure events (HFE), which can be identified, modelled, and quantified through human reliability analysis (HRA). The oil industry commonly analyzes process safety by focusing on technical barriers, and thus it could benefit from HRA. Phoenix methodology is an HRA method that uses a human response model and relates the crew failures modes (CFM) to performance influencing factors (PIFs). Based on Phoenix CFMs and PIFs, two refinery accidents, the BP Texas City (2005) and the Chevron Richmond (2012), are analyzed in this paper. The analysis consists of the construction of the accident timeline; identification of the HFEs and assigning them to appropriate CFMs; and, finally analysis of the PIFs. The analysis helped better understand how the operators responded to an abnormal condition of the process, and why they took the actions they did, investigating the contribution of human error to the accidents. The assessment of the role human error played in these accidents is a major contribution to the understanding of why they happened, and a key information to avoid the same happening again in the future. Moreover, the features and limitations of the application of Phoenix HRA, which was developed based mainly on nuclear power plant operations, to Oil Refinery operation scenarios, are discussed and evaluated. This article provides insights on value of investigating the potential impact of human error in the Petroleum Industry accidents.
Degradation of bisphenol A by the UV and UV/H2O2 processes: Evaluation of process variables through experimental design
Authors: Goulart de Araujo Leandro , Santos Flaviane da Silva , Teixeira Antonio Carlos Silva Costa
Published: August 2017

UV‐based technologies have been proposed for the treatment of wastewater containing bisphenol A (BPA), a toxic, endocrine‐disruptor pollutant. Nevertheless, the evaluation of the role of process variables through experimental design has not been previously addressed. In this study, the effects of BPA and H2O2 initial concentrations, and specific photon emission rate (EP,0) on BPA degradation by the UV and UV/H2O2 processes were investigated, using the Doehlert design and response surface analysis. The experiments were performed in a tubular reactor equipped with a 254‐nm UV lamp, for [H2O2]0 and EP,0 in the ranges 1.6–9.6 mmol · L−1 and 0.87 × 1018–3.6 × 1018 photons · L−1 · s−1, respectively. Photolysis ([BPA]0 = 10–50 mg · L−1) was shown to be inefficient for BPA degradation and mineralization, with pollutant removals lower than 55 %. The specific BPA photolysis rate and BPA removal decreased with increasing [BPA]0. In contrast, all the UV/H2O2 experiments ([BPA]0 = 50 mg · L−1) resulted in total BPA degradation after 60 min of irradiation. In this case, the best conditions were [H2O2]0 = 7.6 mmol · L−1 and Ep,0 = 3.6 × 1018 photons · L−1 · s−1, achieving the highest BPA degradation rate and removal after 15 min, and the second highest TOC removal after 180 min. In most experiments less than 75 % TOC removal was achieved, with 95 % mineralization observed solely for the highest [H2O2]0 and EP,0. In any case, the residual toxicity and endocrine activity of treated solutions must be determined, in order to prove the applicability of the UV/H2O2 process for real water and wastewater treatment.
Hydrodynamic design of multi‐zone circulating reactors using CFD
Authors: Marandi Reza , Kamyabi Mohammadmahdi , Mostoufi Navid
Published: August 2017

A 3D model was developed for simulating the hydrodynamics of polypropylene powders in multi‐zone circulating reactors (MZCRs). This model was used to design the proper geometry of the reactor. The model was based on computational fluid dynamics (CFD) in which an Eulerian‐Eulerian approach, incorporating the kinetic theory of granular flow (KTGF), was used to describe gas and solid flow equations. The re‐normalization group (RNG) k‐ϵ model was applied for implementing the turbulency. For finding the best design of the reactor from the hydrodynamic point of view, four geometrical configurations were proposed and tested. It was found that the best configuration has a narrower downer (compared to riser), and a return leg with a side flow which results in a good solid circulation and proper solid distribution in the reactor. This configuration ensures fast fluidization and pseudo packed bed regimes within the riser and downer, respectively. Effect of inlet gas velocity on overriding parameters, such as pressure drop and solid volume fraction, was studied for the selected configuration. Upper and lower limits for the inlet gas velocity were determined.
Reoxidation of Transition‐metal Catalysts with O2
Authors: Li Xinyao , Jiao Ning
Published: August 2017

Transition‐metal catalyzed oxidation reactions are central components of organic chemistry. On behalf of green and sustainable chemistry, molecular oxygen (O2) has been considered as an ideal oxidant due to its natural, inexpensive, and environmentally friendly characters, and therefore offers attractive academic and industrial prospects. In recent years, some powerful organic oxidation methods have been continuously developed. Among them, the use of molecular oxygen (O2) as a green and sustainable oxidant has attracted considerable attentions. However, the development of new transition metal‐catalyzed protocols using O2 as an ideal oxidant is highly desirable but very challenging because of the low standard electrode potential of O2 to reoxidize the transition‐metal catalysts. In this Account, we highlight some of our progress toward the use of transition‐metal catalyzed aerobic oxidation reactions. Through the careful selection of ligand and the acidic additives, we have successfully realized the reoxidation of Cu, Pd, Mn, Fe, Ru, Rh, and bimetallic catalysts under O2 or air atmosphere (1 atm) for the oxidative coupling, oxygenation reactions, oxidative C‐H/C‐C bond cleavage, oxidative annulation, and olefins difunctionalization reactions. Most of the reactions can tolerate a range of functional groups. These methods provide new strategies for the green synthesis of alkynes, (α‐keto)amides/esters, ketones/diones, O/N‐heterocycles, β‐azido alcohols, and nitriles. The high efficiency, low cost, and simple operation under air make these methodologies very attractive and practical. We will also discuss the mechanisms of these reactions which might be useful to promote the new type of aerobic oxidative reaction design.
Association between modifiable lifestyle and the prevalence of atrial fibrillation in a Chinese population: Based on the cardiovascular health score
Authors: Yang Yiheng , Han Xu , Chen Yue , Gao Lianjun , Yin Xiaomeng , Li Huihua , Qiu Jing , Wang Youxin , Zhou Yong , Xia Yunlong
Published: August 2017

Background

The Cardiovascular Health (CVH) Score was comprised of a series of modifiable lifestyle and health factors, which was published by American Heart Association in 2010. Its relationship with atrial fibrillation (AF) remains unclear.

Hypothesis

Individuals with a higher CVH Score had a lower risk of AF.

Methods

Participants ≥40 years of age were recruited from the Jidong community. Information regarding the following 7 CVH metrics, including smoking, body mass index, diet, physical activity, total cholesterol, and fasting blood glucose, were collected. AF was confirmed with a standard 12‐lead electrocardiography or based on the patients' medical histories. A multivariable logistic regression model was used to evaluate the relationship between ideal CVH and AF prevalence.

Results

This study included 4477 individuals, among whom 48 had AF (1.07%). Overall, participants with higher ideal components scores had a lower risk of AF (odds ratio [OR]: 0.78; 95% confidence intervals [CI]: 0.62‐0.97; P trend = 0.024). Subgroup analyses showed that the trend was consistent in the male participants ages 40 to 60 years. Moreover, patients with 5 to 7 ideal components or 3 to 4 ideal components were associated with 57% and 59% reduced risks for AF, respectively. We also detected a significant association between ideal health factors and the prevalence of AF (OR: 0.79; 95% CI: 0.68‐0.93; P = 0.004).

Conclusions

Ideal health behavior and factors are associated with lower prevalence of AF in a community‐based population. Improving healthy behavior and these factors may be beneficial to decrease the prevalence of AF.
Results of a prospective phase 2 study of pazopanib in patients with advanced intermediate‐grade or high‐grade liposarcoma
Authors: Samuels Brian L. , Chawla Sant P. , Somaiah Neeta , Staddon Arthur P. , Skubitz Keith M. , Milhem Mohammed M. , Kaiser Pamela E. , Portnoy David C. , Priebat Dennis A. , Walker Mark S. , Stepanski Edward J.
Published: August 2017

BACKGROUND

This phase 2, single‐arm, multicenter study was designed to determine the treatment activity and safety of single‐agent pazopanib in patients with unresectable or metastatic liposarcoma.

METHODS

Eligible patients had high‐grade or intermediate‐grade liposarcoma with measurable tumors that were unresectable or metastatic, documented disease progression, and had received any number of prior treatments, excluding previous treatment with a vascular endothelial growth factor inhibitor or a tyrosine kinase inhibitor. Patients received oral pazopanib 800 mg once daily for 28‐day cycles. Tumor response was evaluated by local radiology assessments every 3 cycles. The primary endpoint was the progression‐free rate (PFR) at 12 weeks (PFR12).

RESULTS

Forty‐one patients were enrolled. The PFR12 was 68.3% (95% confidence interval [CI], 51.9%‐81.9%), which was significantly greater than the null hypothesis value of 40% (P = .0002). At 24 weeks, 39% of patients (95% CI, 24.2%‐55.5%) remained progression free, and 44% experienced tumor control (partial response or stable disease). The median progression‐free survival was 4.4 months (95% CI, 3.2‐6.5 months), and the median overall survival was 12.6 months (95% CI, 8.5‐16.2 months). The most common adverse events overall were nausea (39%), hypertension (36.6%), diarrhea (34.1%), and fatigue (29.3%), which were typically less than grade 3. There were 5 deaths on study (12.2%), 3 of which were from possible complications of therapy.

CONCLUSIONS

The current study provides evidence of potential activity of pazopanib in the liposarcoma subset of patients with soft tissue sarcoma that was specifically excluded from the phase 3 PALETTE trial of other soft tissue sarcoma types. Cancer 2017;123:4640‐4647. © 2017 American Cancer Society.
Identification of distinct cytomorphologic features in the diagnosis of NIFTP at the time of preoperative FNA: Implications for patient management
Authors: Chandler Jocelyn B. , Colunga Monica , Prasad Manju L. , Callender Glenda G. , Quinn Courtney , Chhieng David , Adeniran Adebowale J.
Published: August 2017

BACKGROUND

A major reclassification occurred with the redesignation of noninvasive encapsulated follicular variant of papillary thyroid carcinoma as noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) due to its indolent nature. The aim of this study was to determine whether distinct cytomorphologic features could be identified on preoperative fine‐needle aspiration (FNA) when NIFTP cases were compared with invasive follicular variant of papillary thyroid carcinoma (FVPTC) subtypes.

METHODS

Thyroid resection cases with the diagnosis of FVPTC from 2012 to 2016 were reclassified as NIFTP, invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC), and invasive FVPTC subtypes. Corresponding FNA specimens were retrieved and retrospectively reviewed. A univariate analysis using Fisher's exact test was performed to determine any differences in the frequencies of various cytomorphologic features among NIFTP, IEFVPTC, and FVPTC cases. A multivariate analysis was performed to identify any independent salient features that would be helpful in differentiating NIFTP from its invasive counterparts.

RESULTS

The study population consisted of 93 cases, including 51 cases of NIFTP, 21 cases of IEFVPTC, and 21 cases of infiltrative FVPTC. Demographics such as age, sex, and tumor size were comparable across the 3 groups. A predominantly microfollicular pattern, an absence of nuclear pseudo‐inclusions, and less frequent nuclear elongations and grooves were significantly more likely to be associated with NIFTP versus its invasive counterparts. The absence of nuclear pseudo‐inclusions and the presence of a microfollicular pattern were the only independent predictors of a NIFTP diagnosis.

CONCLUSIONS

This study demonstrates that NIFTP cases have distinguishing cytomorphologic characteristics in comparison with invasive FVPTC cases. Therefore, a preoperative cytologic evaluation provides clues that can aid in the distinction between NIFTP and its invasive counterparts. Cancer Cytopathol 2017;125:865–75. © 2017 American Cancer Society.