bluuebunny/crossref_metadata_2025 huggingface dataset:
Ti (IV) Complexes with Bidentate O‐Chelating N‐Heterocyclic Carbenes for Use in the Homopolymerization of Ethylene and Its Copolymerization with Cyclic Olefins
Authors: van der Ende Melita , Hauser Philipp M. , Lienert Christina , Wang Dongren , Frey Wolfgang , Buchmeiser Michael R.
Published: November 2018

The synthesis of titanium (IV) complexes bearing bidentate O‐chelating N‐heterocyclic carbenes (NHCs) is reported. Double deprotonation of the respective NHC precursor ligand and further reaction with one equivalent of TiCl4⋅THF2 leads to the formation of complexes Ti‐1–Ti‐3 of the general formula TiCl3(NHC‐R‐O)(THF), (NHC‐R‐O=1‐(2,6‐diisopropylphenyl)‐3‐(2‐O‐phenyl)‐4,5‐dihydroimidazol‐2‐ylidene, 1‐(mesityl)‐3‐(2‐O‐phenyl)‐4,5‐dihydroimidazol‐2‐ylidene, 1‐(2,6‐dimethylphenyl)‐3‐(2‐O‐phenyl)‐4,5‐dihydroimidazol‐2‐ylidene). Furthermore, these Ti‐(NHC‐R‐O) trichloride complexes can be reacted with the bulky aryloxo ligands 2,6‐ditBu‐4‐methylphenolate and 2,2’,4,4’,6,6’‐hexa‐iPr‐terphenoxide, respectively, to form the mixed titanium (aryloxo)(NHC‐R‐O) dichloride pre‐catalysts Ti‐4–Ti‐6. Single‐crystal X‐ray structures of complexes Ti‐1, Ti‐5 and Ti‐6 are presented. Depending on the aryloxo ligand used, the complexes possess either a trigonal bipyramidal or square pyramidal ligand sphere. The propensity of Ti‐1, Ti‐4–Ti‐6 to homopolymerize ethylene and to copolymerize ethylene with norborn‐2‐ene (NBE) and cyclopentene (CPE), respectively, was investigated and access to high‐molecular weight (co‐)polymers with such complexes is disclosed.
H2 Activation in [FeFe]‐Hydrogenase Cofactor Versus Diiron Dithiolate Models: Factors Underlying the Catalytic Success of Nature and Implications for an Improved Biomimicry
Authors: Arrigoni Federica , Bertini Luca , Bruschi Maurizio , Greco Claudio , De Gioia Luca , Zampella Giuseppe
Published: November 2018

Catalytic H2 oxidation has been dissected by means of DFT into the key steps common to the Fe2 unit of both the [FeFe]‐hydrogenase cofactor and selected biomimics. The aim was to elucidate the molecular details underlying the very different performances of the two systems. We found that the better enzyme performance is based on a single iron atom that is maintained electron‐poor, favoring H2 binding, although embedded within a highly electron‐rich cofactor, ensuring a facile oxidation of the Fe2–H2 adduct. This is due to 1) CN− coordinating to both iron atoms, due to their amphipathic Lewis acid/base properties, and 2) the 4Fe4S subunit further withdrawing electrons from the Fe2 core. Preserving a moderate electron deficiency at a single iron also helps the cofactor preserve hydride affinity, which favors H2 cleavage. Such valuable characteristics allow the biocatalyst to turnover close to equilibrium conditions. All previous biomimicry has shown, in contrast, the impossibility to properly balance the two apparently contrasting aforementioned requisites, although evident progress has been made by the H2‐ase community. Disclosure of the differences identified could inspire the design of novel biomimics, for instance, reconsidering the use of CN− in the catalyst architecture. Indeed, in the presence of bases normally employed in oxidative catalysis, undesired stable protonation at coordinated CN−, which affects the opposite process (proton reduction), could be overcome.
Tetra‐Aza‐Pentacenes by means of a One‐Pot Friedländer Synthesis
Authors: Ukwitegetse Narcisse , Saris Patrick J. G. , Sommer Jonathan R. , Haiges Ralf M. , Djurovich Peter I. , Thompson Mark E.
Published: November 2018

Tetra‐aza‐pentacenes are attractive n‐type small molecules for optoelectronic device applications, yet their syntheses are often laborious. Disclosed here is a one‐pot Friedländer synthesis of 1,7,8,14‐tetraazapentacece (tAP) derivatives (linear and/or bent), fully aromatized in situ despite the absence of an exogenous oxidant. The photophysics of linear tAPs resembles that of regular pentacene though their crystal structures differ. A LUMO energy of −3.71 eV for di‐tert‐butylanisole‐substituted linear tAP is similar to that of the well‐known acceptor, C60.
Cognitive performance in survivors of breast cancer and markers of biological aging
Authors: Carroll Judith E. , Van Dyk Kathleen , Bower Julienne E. , Scuric Zorica , Petersen Laura , Schiestl Robert , Irwin Michael R. , Ganz Patricia A.
Published: November 2018

Background

Biological aging pathways accelerated by cancer treatments may be a mechanism for cognitive impairment in cancer survivors. The goal of the current study was to examine whether indicators of biological aging, namely elevated levels of DNA damage, reduced telomerase enzymatic activity, and shorter peripheral blood mononuclear cell (PBMC) telomere length (TL) would be related to cognitive function in a cohort of survivors of breast cancer.

Methods

The authors evaluated a cross‐sectional sample of 94 women aged 36 to 69 years who were treated for early‐stage breast cancer 3 to 6 years previously. Leukocyte DNA damage, PBMC telomerase enzymatic activity, PBMC TL, and the inflammatory marker soluble tumor necrosis factor receptor II (sTNF‐RII) were determined from blood samples. Cognitive function was assessed using a neuropsychological test battery and self‐report. Linear regression models examined the relationship between biological aging predictors and cognitive outcomes.

Results

Both higher DNA damage and lower telomerase were found to be statistically significantly related to lower executive function scores adjusting for age, body mass index, race, years from treatment, and intelligence score (standardized coefficients [B], ‐0.23 and 0.30; all P values <.05). In addition, lower telomerase activity was associated with worse attention and motor speed scores (B values, 0.30 and 0.24; P <.05). sTNF‐RII and TL were found to be unrelated to any of the neurocognitive domains.

Conclusions

The results of the current study suggest a significant association between measures of biological aging and objective measures of cognitive performance in survivors of breast cancer. Future prospective studies are needed to confirm a causal role of biological aging as a driver of declines in cognitive function after cancer treatment.
Defining Treatment Effects: A Primer for Nonstatisticians
Authors: Permutt Thomas
Published: November 2018

It would often be of interest to know the effect of a drug compared to control in people who take the drug. However, different people will likely take the drug and the control. Thus, comparing takers of the drug to takers of the control does not yield a drug effect. Drug effects in drug takers can be estimated, but first they must be carefully defined.
Constructing designated server public key encryption with keyword search schemes withstanding keyword guessing attacks
Authors: Lu Yang , Li Jiguo
Published: November 2018

Designated server public key encryption with keyword search (dPEKS) removes the secure channel requirement in public key encryption with keyword search (PEKS). With the dPEKS mechanism, a user is able to delegate the search tasks on the ciphertexts sent to him/her to a designated storage server without leaking the corresponding plaintexts. However, the current dPEKS framework inherently suffers from the security vulnerability caused by the keyword guessing (KG) attack. How to build the dPEKS schemes withstanding the KG attacks is still an unsolved problem up to now. In this work, we introduce an enhanced dPEKS (edPEKS) framework to remedy the security vulnerability in the current dPEKS framework. The edPEKS framework provides resistance to the KG attack by either the outside attacker or the malicious designated server. We provide a semi‐generic edPEKS construction that exploits the existing dPEKS schemes. Our security proofs demonstrate that the derived edPEKS scheme achieves the keyword ciphertext indistinguishability, the keyword ciphertext unforgeability, and the keyword trapdoor indistinguishability if the underlying dPEKS scheme satisfies the keyword ciphertext indistinguishability and the hash Diffie‐Hellman problem is intractable. In addition, a concrete edPEKS scheme is presented to show the instantiation of the proposed semi‐generic construction.
Synthesis, anticonvulsant screening, and molecular modeling studies of new arylalkylimidazole oxime ether derivatives
Authors: Özdemir Zeynep , Sari Suat , Karakurt Arzu , Dalkara Sevim
Published: November 2018

In this study, 15 new oxime ether derivatives were synthesized and their anticonvulsant activities were screened in vivo. The compounds were synthesized by the reaction of various alkyl halides with 1‐(2‐naphthyl)‐2‐(1H‐imidazol‐1‐yl)ethanone oxime. Their anticonvulsant activities were determined using acute (maximal electroshock, subcutaneous metrazol [SCM], and 6 Hz seizure test) and chronic (corneal‐kindled mouse) seizure models, their neurotoxic effects were evaluated by models of behavioral toxicity according to the Epilepsy Therapy Screening Program protocol of the NIH. All our compounds were protective in at least one of the tests. Quantification studies were applied to some of the active compounds and the intraperitoneal ED50 values in mice were found between 25.48 and 99.56 mg/kg. Some pharmacokinetic properties of the compounds were predicted in silico and molecular docking studies were performed to provide insights into their possible anticonvulsant mechanism regarding their SCM activity.
Exercise training in patients with ventricular assist devices: a review of the evidence and practical advice. A position paper from the Committee on Exercise Physiology and Training and the Committee of Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology
Authors: Adamopoulos Stamatis , Corrà Ugo , Laoutaris Ioannis D. , Pistono Massimo , Agostoni Pier Giuseppe , Coats Andrew J.S. , Crespo Leiro Maria G. , Cornelis Justien , Davos Constantinos H. , Filippatos Gerasimos , Lund Lars H. , Jaarsma Tiny , Ruschitzka Frank , Seferovic Petar M. , Schmid Jean‐Paul , Volterrani Maurizio , Piepoli Massimo F.
Published: November 2018

Exercise training (ET) and secondary prevention measures in cardiovascular disease aim to stimulate early physical activity and to facilitate recovery and improve health behaviours. ET has also been proposed for heart failure patients with a ventricular assist device (VAD), to help recovery in the patient's functional capacity. However, the existing evidence in support of ET in these patients remains limited.

After a review of current knowledge on the causes of the persistence of limitation in exercise capacity in VAD recipients, and concerning the benefit of ET in VAD patients, the Heart Failure Association of the European Society of Cardiology has developed the present document to provide practical advice on implementing ET. This includes appropriate screening to avoid complications and then starting with early mobilisation, ET prescription is individualised to meet the patient's needs. Finally, gaps in our knowledge are discussed.
Nickel‐Catalyzed Directed Hydroarylation of Alkynes with Boronic Acids
Authors: Hanna Luke E. , Konev Mikhail O. , Jarvo Elizabeth R.
Published: November 2018

A regio‐ and stereoselective nickel‐catalyzed hydroarylation of alkynes using propargylic carbamates as directing groups has been developed. The reaction proceeds under mild reaction conditions using arylboronic acids in the absence of base. A range of heterocycles and functional groups are tolerated under the reaction conditions, providing high yields of trisubstituted alkenes with control of olefin geometry.
Point‐of‐Care Smartphone‐based Electrochemical Biosensing
Authors: Sun Alexander C. , Hall Drew A.
Published: November 2018

Point‐of‐care (PoC) biosensors offer promising solutions to today's adverse and costly healthcare issues by moving diagnostic tools closer to the patient. The ubiquity of smartphones has brought about an emergence of PoC devices, which leverage the smartphone's capabilities, enabling the creation of low‐cost and portable biosensors. Electrochemical biosensors are well suited for PoC testing since the transducers can be miniaturized and inexpensively fabricated. This review paper discusses recent developments in smartphone‐based electrochemical biosensors for PoC diagnostics. These peripherals utilize the various connectivity options (for example proprietary ports, audio headphone‐jack, or wireless radio) to offload functionality to the smartphone. The smartphone‐based implementations of various electrochemical techniques, such as amperometry, potentiometry, and impedance spectroscopy are explored. Major challenges include reducing power, area, and cost of measurement circuitry, while maintaining adequate performance for PoC diagnostic applications.
A moving discontinuous Galerkin finite element method for flows with interfaces
Authors: Corrigan Andrew , Kercher Andrew D. , Kessler David A.
Published: November 2018

A moving discontinuous Galerkin finite element method with interface condition enforcement is formulated for flows with discontinuous interfaces. The underlying weak formulation enforces the interface condition separately from the conservation law, so that the residual only vanishes upon satisfaction of both. In this formulation, the discrete grid geometry is treated as a variable, so that, in contrast to the standard discontinuous Galerkin method, this method has both the means to detect interfaces, via interface condition enforcement, and to satisfy, via grid movement, the conservation law and its associated interface condition. The method therefore directly fits interfaces, including shocks, preserving a high‐order representation up to the interface without requiring shock capturing or an upwind numerical flux to achieve stability. It can be generalized to flows with a priori unknown interfaces with nontrivial topology and curved interface geometry as well as to an arbitrary number of spatial dimensions. Unsteady flows are represented in a manner similar to steady flows using a space‐time formulation. In addition to computing flows with interfaces, the method can represent point singularities in a flow field by degenerating cuboid elements. In general, the method works in conjunction with standard local grid operations, including edge collapse, to ensure that degenerate cells are removed. Test cases are presented for up to three‐dimensional flows that provide an initial assessment of the stability and accuracy of the method.
Air Flow Real‐time Optimization Strategy for Fuel Cell Hybrid Power Sources with Fuel Flow Based on Load‐following
Authors: Bizon N. , Iana G. , Kurt E. , Thounthong P. , Oproescu M. , Culcer M. , Iliescu M.
Published: November 2018

The Fuel_LF‐RTO strategy is real‐time optimization (RTO) strategy proposed here to find the optimal values of fueling for the polymer electrolyte membrane fuel cell hybrid power sources under unknown load profile, which is the case of fuel cell vehicle. The proposed optimization strategy is based on global extremum seeking (GES) algorithm and load‐following (LF) control for air and fuel flows. The results show the performance obtained with Fuel_LF‐RTO strategy in comparison with the Static Feed‐Forward strategy. The performance was estimated for constant and variable load. The FC system efficiency and the fuel consumption efficiency for maximum load of 8 kW can increase with up to 1.88% and 11.26 W lpm−1 in comparison with the sFF RTO strategy. Also, the fuel economy is 27.36 L during the 8 kW/12 s constant load cycle, which means an economy of 136.8 lpm. This performance is highlighted for constant load in range 2 to 8 kW, which represents 0.33% and 1.25% from nominal power of the 6 kW FC stack used in this study. Also, the performance was estimate for variable load considering the fuel economy, which can be up to 21.86 l during the 6.25 kW/12 s pulsed load cycle.
Cost‐effectiveness analysis of English memory assessment services 2 years after first consultation for patients with dementia
Authors: Gomes Manuel , Pennington Mark , Black Nick , Smith Sarah
Published: November 2018

Objectives

This paper aims to compare changes over 2 years in patients' health‐related quality of life (HRQL) with the health and social care costs of diagnosis and treatment of people newly referred to memory assessment services (MAS).

Methods

We analysed observational data from 1318 patients referred to 69 MAS who completed resource use and HRQL questionnaires at baseline 3, 6, 12, and 24 months. We reported mean differences in HRQL (disease‐specific DEMQOL and generic EQ‐5D‐3 L), quality‐adjusted life years (QALYs), costs and cost‐effectiveness between baseline, and 2‐year follow‐up.

Results

Two years after referral to MAS, patients reported a higher DEMQOL score (mean gain 4.47, 95% confidence interval, 3.08‐5.90) and EQ‐5D‐3 L (0.014, −0.011 to 0.039). Mean total costs and QALYs over 24 months was £2411 (£1721‐£2873) and 0.027 (0.003‐0.051), respectively. Assuming that patients' HRQL would not have altered over the 2 years had they not attended MAS, these outcomes suggest an incremental cost‐effectiveness ratio of £89 546 (£38 123‐£145 864) based on changes in EQ‐5D‐3 L. If we assumed that patients' HRQL would have declined by about 10% over this period had they not attended MAS, the cost‐effectiveness ratio would be £25 056. The largest MAS (N = 32; 46%) with over 50 new patients a month were more likely to be cost‐effective than smaller ones (P < 0.01).

Conclusions

MAS are effective and can be cost‐effective for diagnosing and treating people with suspected dementia. Large variations in costs between clinics suggest that many MAS could improve their cost‐effectiveness.
Associations between testosterone and metabolic syndrome in depressed and non‐depressed older men and women
Authors: de Wit Anouk E. , Giltay Erik J. , de Boer Marrit K. , Bosker Fokko J. , van der Mast Roos C. , Comijs Hannie C. , Oude Voshaar Richard C. , Schoevers Robert A.
Published: November 2018

Objectives

Older age and major depressive disorder (MDD) are both risk factors for the development of cardiovascular diseases. Testosterone has been associated with MDD and metabolic syndrome (MetS) in men, although associations in women are less clear. Therefore, we investigated whether testosterone is associated with MetS and whether this association is different for depressed and non‐depressed older men and women.

Methods

In this prospective cohort study, 478 participants (349 patients with MDD and 129 controls) aged between 60 and 93 years from the Netherlands Study of Depression in Older Persons were included. Total testosterone (TT) and sex‐hormone binding globulin levels were measured using a second‐generation radioimmune assay. Free testosterone (FT) was calculated based on TT. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria.

Results

A higher risk for MetS was found in men with low FT and TT (odds ratio [OR]: 0.67, 95% confidence interval [95%CI]: 0.47‐0.95 and OR: 0.51, 95%CI: 0.34‐0.75), and in women with high FT (OR: 1.41, 95%CI: 1.08‐1.82). Strong associations in the same direction were found with adiposity, glucose, and plasma lipid MetS components at baseline, but not with changes in these components at 2‐year follow‐up. The associations did not significantly differ between MDD patients and controls.

Conclusions

Independently of having MDD, low testosterone levels in men and, in contrast, high testosterone levels in women were significantly associated with MetS and its components.
Synthesis and properties of redox‐switchable zinc complexes of 10,15,20‐triaryl‐15‐aza‐5‐oxaporphyrin
Authors: Sudoh Keisuke , Furukawa Ko , Nakano Haruyuki , Shimizu Soji , Matano Yoshihiro
Published: November 2018

The synthesis, aromaticity, and optical and electrochemical properties of zinc(II) complexes of 10,15,20‐triaryl‐15‐aza‐5‐oxaporphyrin (TriAAOP) were investigated. Metal‐templated cyclization of a zinc(II) 1,19‐dichloro‐5,10,15‐triaryl‐10‐azatetrapyrrin complex with an oxygen source afforded 20π TriAAOP in the neutral form. Oxidation of 20π TriAAOP with silver (I) hexafluorophosphate generated the 19π radical cation or 18π dication depending on the content of oxidant used. The interconversion between the three oxidation states (18π, 19π, and 20π) resulted in distinct changes in the aromaticity and optical properties of the 15‐aza‐5‐oxaporphyrin π‐system. Nuclear magnetic resonance spectroscopy of 20π TriAAOP revealed its antiaromatic character, whereas that of the 18π TriAAOP dication showed its aromatic character. The combined effect of the two meso‐heteroatoms was directly reflected in the redox properties of the porphyrin ring; TriAAOP was reduced more easily and more difficult to oxidize than the zinc(II) complex of 5,10,15,20‐tetraaryl‐5,15‐diaz‐aporphyrin (TADAP). In the ultraviolet‐visible‐near–infrared spectra of the materials, the lowest‐energy electronic excitations of the 19π and 18π TriAAOP derivatives were considerably red‐shifted compared with those of the isoelectronic TADAP derivatives. Based on the results of density functional theory calculations, it was concluded that the observed differences between TriAAOP and TADAP would arise from the high electronegativity of oxygen; specific frontier orbitals of the TriAAOP π‐systems were energetically stabilized relative to those of the TADAP π‐system. The present findings corroborate that the meso‐modification of a porphyrin rings with different kinds of heteroatoms is a promising strategy to fine tune their light‐response properties that are switchable by reversible single electron transfer processes.
Encapsulation of Organic Dyes within an Electron‐Deficient Redox Metal‐Organic Tetrahedron for Photocatalytic Proton Reduction
Authors: Wang Hailing , Li Lili , Li Xuezhao , He Cheng
Published: November 2018

The design of artificial systems that mimic highly evolved and finely tuned natural photosynthetic systems is a subject of intensive research. By incorporating electron‐deficient anthraquinone within the ligand backbone, a redox‐active Ni‐based tetrahedron was developed as a redox vehicle for the construction of an artificial photosynthesis system. The tetrahedron can encapsulate fluorescein within its cavity for light‐driven H2 evolution, with the turnover number reaching 1200 moles H2 per mole redox catalyst. This well‐designed supramolecular system displayed a significantly superior activities compared with the reference mononuclear compound or introducing an inactive inhibitor (ATP), which confirmed this enzymatic photocatalytic behaviour.
Role of HA and BG in engineering poly(ε‐caprolactone) porous scaffolds for accelerating cranial bone regeneration
Authors: Yin Hua‐Mo , Li Xiang , Wang Peng , Ren Yue , Liu Wei , Xu Jia‐Zhuang , Li Ji‐Hua , Li Zhong‐Ming
Published: November 2018

Effects of varied bioactive fillers on the biological behavior of porous polymer/inorganic composite scaffolds are lack of comprehensive comparison and remain elusive. Moreover, composite scaffolds with high porosity suffer from inferior mechanical performance. Herein, high‐pressure molding and salt leaching were employed to prepare poly(ε‐caprolactone) (PCL) composite porous scaffolds loaded with hydroxyapatite (HA) and bioactive glass (BG), respectively. Structural analysis indicated all the porous scaffolds presented interconnected open‐pore structure with the porosity of ~87% and pore size of ~180 μm, hinging on the amounts and size of porogen. Compared to PCL/HA scaffolds, PCL/BG scaffolds showed ~2.3‐fold augment in the water absorption. Attributing to the compact framework, the PCL/HA and PCL/BG porous scaffolds exhibited outstanding compressive modulus, which was notably higher than other PCL composite porous scaffolds reported in literatures. Cells culture results demonstrated that PCL/BG scaffolds displayed higher expression of osteogenic differentiation than PCL and PCL/HA scaffolds. Furthermore, in vivo results showed that more mature bone was formed within PCL/BG scaffolds than PCL/HA scaffolds, manifesting that the introduction of BG accelerated cranial bone regeneration to obtain complete bone healing within a short time. Therefore, these data indicate that PCL/BG scaffolds are more competitive for bone tissue engineering application. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 654–662, 2019.
An in vivo comparative study of the gelatin microtissue‐based bottom‐up strategy and top‐down strategy in bone tissue engineering application
Authors: Luo Chao , Fang Huimin , Li Jialun , Hou Jinfei , Yang Jie , Yuan Quan , Guo Liang , Zhong Aimei , Wang Jiecong , Sun Jiaming , Wang Zhenxing
Published: November 2018

Tissue‐engineered bone grafts (TEBGs) represent a promising treatment for bone defects. Nevertheless, drawbacks of the current construction strategy (top‐down [TD] strategy) such as limited transmission of nutrients and nonuniform distribution of seeded cells, result in an unsatisfied therapeutic effect on large segmental bone defects. Theoretically, tissue‐engineered microtissue (TEMT)‐based bottom‐up (BU) strategy is effective in preserving seed cells and vascularization, thus being regarded as a better alternative for TEBGs. Yet, there are few studies focusing on the comparison of the in vivo performance of TEBGs fabricated by TD or BU strategy. Here, we developed an ectopic bone formation rat model to compare the performance of these two construction strategies in vivo. TEBGs made from gelatin TEMT (BU strategy) and bulk tissue (BT; TD strategy) were seeded with equal number of rat bone marrow‐derived mesenchymal stem cells and fabricated in 5 mm polydimethylsiloxane chambers. The grafts were implanted into subcutaneous pockets in the same rat. Four weeks after implantation, microcomputed tomography and hematoxylin and eosin staining results demonstrated that more bony tissue was formed in the microtissue (MT) group than in the BT group. CD31 staining further confirmed that there were more blood vessels in the MT group, indicating that the BU strategy was superior in inducing angiogenesis. This comparative study provides evidence that the BU construction strategy is more effective for in vivo application and bone defect treatment by bone tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 678–688, 2019.
Long noncoding RNAs C2dat1 enhances vascular smooth muscle cell proliferation and migration by targeting MiR‐34a‐5p
Authors: Wang Hairong , Jin Zhili , Pei Tu , Song Wenhao , Gong Yao , Chen Deliang , Zhang Lin , Zhang Meichun , Zhang Gangchen
Published: November 2018

Deregulated proliferation of vascular smooth muscle cells (VSMCs) is one common phenomenon of atherosclerosis progression. Long noncoding RNAs (lncRNAs) are one group of noncoding RNAs that play essential roles in many cell biological processes, including cell development, growth, and migration. However, the role of a novel calcium/calmodulin‐dependent protein kinase type II subunit delta (CAMK2D)‐associated lncRNA, CAMK2D‐associated transcript 1 (C2dat1), in VSMCs is still uncovered. In this study, we showed that the expression level of C2dat1 was higher in coronary artery disease (CAD) tissues than in normal arterial tissues and the C2dat1 expression level was upregulated in the proliferating VSMC after being treated with PDGF‐bb or TNF‐α. In addition, we indicated that overexpression of C2dat1 promoted VSMC growth and enhanced proliferating cell nuclear antigen (PCNA) expression in VSMC. Moreover, ectopic expression of C2dat1 increased VSMC migration. Furthermore, we showed that elevated expression of C2dat1 suppressed microRNA‐34a (miR‐34a) expression and promoted sirtuin 1 (SIRT1) expression, which was a direct target gene of miR‐34a. We demonstrated that the expression level of miR‐34a was lower in CAD tissues than in normal arterial tissues and the expression of miR‐34a was negatively correlated with C2dat1 expression. Restored expression of C2dat1 increased VSMC proliferation and migration through promoting SIRT1 expression. These data suggested that lncRNA C2dat1 might be a potential therapeutic target to promote VSMC growth and migration in CAD.
Synthesis, reactions, and biological study of some new thienopyrimidine derivatives as antimicrobial and anti‐inflammatory agents
Authors: Tolba Mahmoud S. , Kamal El‐Dean Adel M. , Ahmed Mostafa , Hassanien Reda
Published: November 2018

Pyrimidine and thienopyrimidine derivatives play a very important role in organic chemistry because of their wide applications as bioactive compounds with multiple biological activities. However, a literature survey revealed that the merger of different groups in the thieno[2,3‐d]pyrimidine heterocyclic ring enhances its antibacterial, antifungal and anti‐inflammatory activities. This encouraged us to prepare a new series of thieno[2,3‐d]pyrimidine heterocyclic compounds and to test them as antimicrobial and anti‐inflammatory agents. These compounds have shown remarkable activity toward fungi, bacteria, and inflammation. Thus, these compounds have been prepared by the chloroacylation of 5‐amino‐4‐phenyl‐2‐(p‐tolylamino)thieno[2,3‐d] pyrimidine‐6‐carboxamide (4) using chloroacetyl chloride under neat condition to afford the target compound (6), which was used as precursor for the synthesis of a number of bioactive compounds. Thus reaction of the chloromethylpyrimidine derivative (6) with triphenylphosphine in dry benzene gave the corresponding ((4‐oxo‐9‐phenyl‐7‐(p‐tolylamino)‐3,4‐dihydropyrimido[4′,5′:4,5]thieno[2,3‐d]pyrimidin‐2‐yl)methyl) triphenylphosphonium chloride (7). Compounds 8a–8c and 9a–9c were obtained by the reaction of 7 with some selected aromatic aldehydes and ketones in methanol and sodium methoxide under Wittig reaction condition. The structures of the all new synthesized compounds were established on the basis of their analytical and spectral data (IR, 1H NMR, 13C NMR, and MS).
Clinical exigencies, psychosocial realities: negotiating HIV pre‐exposure prophylaxis beyond the cascade among gay, bisexual and other men who have sex with men in Canada
Authors: Newman Peter A , Guta Adrian , Lacombe‐Duncan Ashley , Tepjan Suchon
Published: November 2018

Introduction

Notwithstanding the efficacy of oral pre‐exposure prophylaxis (PrEP) in clinical trials, a number of obstacles exist to achieving population‐level impact among gay, bisexual and other men who have sex with men (GBM). However, few studies have explored the subjective experiences of GBM PrEP users and non‐users in the community, outside of clinical trials. The objectives of this study were to explore GBM's experiences of considering, accessing and using (or not using) PrEP, and to understand emerging sexual health, social and community issues among GBM in the PrEP era.

Methods

From October 2015 to March 2016, we purposively sampled PrEP‐naïve and PrEP‐experienced GBM from community organizations and health centres in Toronto, Canada. In‐depth, 45‐ to 90‐minute semi‐structured interviews explored PrEP perspectives and decision‐making, access, initiation, use over time, sexual practices and psychosocial considerations. Interviews were recorded, transcribed verbatim, uploaded into NVIVO, reviewed using thematic analysis and then contrasted with the PrEP cascade.

Results

Participants included PrEP users (n = 15) and non‐users (n = 14) (mean age = 36.7 years; SD = 8.2), largely gay‐identified (86.2%), cisgender male (89.7%) and white (79.3%). Themes indicate not only correspondences, but also limitations of the PrEP cascade by complicating a user/non‐user binary and challenging the unilateral presupposition that HIV risk perception leads to PrEP acceptance. Findings further call into question assumptions of a linear stage progression and retention in care as a universal endpoint, instead revealing alternate trajectories of seasonal or intermittent PrEP use and, for some, an end goal of terminating PrEP. GBM's narratives also revealed potent psychological/affective experiences of untethering sex from HIV anxiety; multifaceted PrEP stigma; and challenges to sexual norms and practices that complicate existing behavioural prevention strategies and sexual and social relationships.

Conclusions

An expanded PrEP cascade should consider alternate trajectories of use based on dynamic relationships and behavioural risks that may call for seasonal or intermittent use; systemic barriers in access to and sustaining PrEP; and multiple end goals including PrEP maintenance and discontinuation. Incorporating GBM's lived experiences, evolving preferences, and psychosocial and community‐level challenges into PrEP implementation models, rather than a circumscribed biomedical approach, may more effectively support HIV prevention and GBM's broader sexual and psychological health.
Biotic elicitation as a tool to improve strawberry and raspberry extract potential on metabolic syndrome‐related enzymes in vitro
Authors: Gutierrez‐Albanchez Enrique , Kirakosyan Ara , Bolling Steven F , García‐Villaraco Ana , Gutierrez‐Mañero Javier , Ramos‐Solano Beatriz
Published: November 2018

Background

Raspberry and strawberry are high value‐added food products that can contribute to human health due to the abundance of polyphenols that they contain. Polyphenols are secondary metabolites and therefore devoted to improve plant adaptation, these polyphenol profile can be induced applying different stimuli, such as certain bacteria. The aim of this study was twofold: (i) to evaluate the ability of two bacterial strains to modulate secondary metabolisms in strawberry and raspberry, and (ii) to explore the ability of plant extracts to modify enzyme activities related to metabolic syndrome.

Results

Total phenolic and anthocyanin content was higher in strawberries than in raspberries, despite similar antioxidant capacities. Strawberry extracts performed better on the tested enzymes, except on α‐glucosidase inhibition capacity. Bacillus amyloliquefaciens stabilized the effects of extracts at different points in time, and Pseudomonas fluorescens modified plant metabolism after more inoculations (spring) in both species, improving the effects of raspberry extracts on α‐glucosidase, COX1, and COX2, and of strawberry on α‐amylase and COX1.

Conclusion

It is good to include these two fruits in the diet because they improve the activity of metabolic syndrome‐related enzymes. Applying either strain during plant growth modifies the bioactive profile of the plants, improving the effects of the fruit extracts on human health. © 2018 Society of Chemical Industry
Ergonomic hazards in otolaryngology
Authors: Vaisbuch Yona , Aaron Ksenia A. , Moore Justin M. , Vaughan John , Ma Yifei , Gupta Raghav , Jackler Robert K.
Published: November 2018

Objectives/Hypothesis

To evaluate the presence of postural‐related strain and musculoskeletal discomfort, along with the level of ergonomics training and the availability of ergonomic equipment among otolaryngology surgeons.

Study Design

Intraoperative observations and survey study.

Methods

Using the Rapid Entire Body Assessment score system to identify ergonomic hazards, we conducted intraoperative observations assessing operating room personnel during different otolaryngological subspecialty procedures. Based on these findings, otolaryngology surgeons at a single academic institution in the United States were sent a survey that evaluated ergonomic practice, environmental infrastructure, and prior ergonomic training or education.

Results

A response rate of 69% was obtained from 70 surgeons, with 72.9% of responding surgeons suffering from some level of back pain, with cervical spine pain being the most common. Interestingly, residents were equally affected when compared to more senior surgeons both in subjective survey reports and from observational risk analysis. Furthermore, 43.8% of surgeons reported suffering from the highest level of pain when standing, whereas only 12.5% experienced pain when sitting. Importantly, 10% stated that pain impacted their work. Only 24% of surgeons had any prior ergonomic training or education.

Conclusions

Our data suggest that pain and disability induced by poor ergonomics are widespread among the otolaryngology community and confirm that surgeons rarely receive ergonomic training in the surgical context. Additionally, intraoperative observational findings identified that the majority of observed surgeons display poor posture, particularly a poor cervical angle and use of ergonomic setups, both of which increase ergonomic risk hazard. These data provide guidance for future interventional studies.

Level of Evidence

NA Laryngoscope, 129:370–376, 2019
Modeling the effective spawning and nursery habitats of northern pike within a large spatiotemporally variable river landscape (St. Lawrence River, Canada)
Authors: Foubert Aline , Le Pichon Céline , Mingelbier Marc , Farrell John M. , Morin Jean , Lecomte Frédéric
Published: November 2018

Spawning and nursery habitats are often spatially disjunct as a consequence of specific life history stage habitat requirements and spatiotemporal habitat changes. Nevertheless, free‐swimming larvae originating from spawning habitats must reach productive nurseries to maximize survival. We examined spawning and nursery habitats of northern pike (Esox lucius) over the past 50 yr to investigate how habitat connectivity and hydrological variability interact to alter the distribution of effective spawning habitat. Habitat models coupled to a least‐cost approach were developed to quantify connectivity between habitats in two contrasting regions of the St. Lawrence River (Canada): a riverine corridor lake (~ 46 km) and a large fluvial lake (~ 48 km). Our simulations demonstrate that depending on hydrological conditions, between 3% to 51% of spawning habitat used by adults in the riverine corridor, and 22% to 90% in the lake, allowed larval survival up to the fifth week of development. Although rapid dewatering of spawning habitat is responsible for most spawning losses in the fluvial lake, increasing water currents were responsible for dispersing larvae away from suitable habitats in the riverine corridor. However, stable hydrological conditions led to spatial overlapping of spawning and nursery habitats favoring larval survival and growth. In addition, downstream larval dispersal by low water currents allowed larvae to reach spatially disjunct nursery habitat, especially in the lake. Our results indicate that despite the vast areas of potentially suitable habitats provided by large vegetated floodplains of fluvial lakes, the effective spawning habitats favoring early‐life recruitment are much more heterogeneous and variable both spatially and temporally.
Strong Coupling in Microcavity Structures: Principle, Design, and Practical Application
Authors: Yu Xiantong , Yuan Yufeng , Xu Jianhua , Yong Ken‐Tye , Qu Junle , Song Jun
Published: November 2018

When interaction between light and matter is in the strong coupling region, matter has a significant influence on the whole system, with potential to develop low‐power active optical devices. Strong coupling can verify some basic problems of quantum physics, and it is an ideal system to study light–matter interaction, providing an intuitive and accurate demonstration of some pure quantum effects with small mass and easy optical control. Here, the most important advances in strong coupling in recent years are described. Of late, an extensive series of experimental and theoretical findings, and remarkable achievements have been made in this field. Strong coupling between cavities and some new materials such as semiconductors, two‐dimensional (2D) material, and quantum dots (QDs) are the focus of research in this field. Another field that has made outstanding progress is the application of this optical phenomenon, including resonance‐enhanced Raman and infrared spectra, nanolasers, and cavity‐enhanced sensing. Furthermore, the potential in this field arises for future quantum information and quantum optical devices. It is now developing at a very fast rate and can be predicted to have broad prospects for development in the future. Some prospects in terms of design and application are included.
Ecotoxicological Modeling, Ranking and Prioritization of Pharmaceuticals Using QSTR and i‐QSTTR Approaches: Application of 2D and Fragment Based Descriptors
Authors: Khan Kabiruddin , Kar Supratik , Sanderson Hans , Roy Kunal , Leszczynski Jerzy
Published: November 2018

There is a huge lack of experimental data on ecotoxicity of pharmaceuticals, while existing resources are insufficient to gather these data against all possible environmental endpoints. Computational tools such as quantitative structure‐toxicity relationship (QSTR) can help us to a great extent to overcome this problem through filling of data gaps. In the current study, QSTR models have been developed for toxicity of 260 diverse pharmaceuticals on three different trophic level species namely algae, daphnia and fish, using partial least squares (PLS) regression approach with 2D descriptors selected through a genetic algorithm approach in order to study underlying chemical features responsible for the observed acute toxicity. The final obtained statistically reliable QSTR models were extensively validated following the OECD guidelines. Interspecies quantitative structure‐toxicity‐toxicity (QSTTR) models were also developed using genetic algorithm followed by multiple linear regression (GA‐MLR) approach to check for the pattern of responses observed as we move across the hierarchy of genetics in different taxonomical class. The obtained interspecies models were finally utilized to fill the data gaps for 260 pharmaceuticals, where experimental data were missing for at least one of the endpoints. Finally, a prioritized list for 7106 existing drug like substances was prepared by predicting their acute toxicity using developed QSTR models.
After Salisbury Nerve Agents Revisited
Authors: Carlsen Lars
Published: November 2018

In March 2018 the term Novichok (Hoвичoκ) became publically known following an attempted murder of a former Russian spy in Salisbury, UK. Novichok is the name of a group of nerve agents secretly produced by Russia in the later stages of the Cold War. These compounds were never declared under the Chemical Weapons Convention and very little is known about the actual identity and characteristics of these compounds. Structures of some of the Novichoks have been reported by a former Russian chemist, Vil Mirzayanov, previously working at the Russian State Scientific Research Institute of Organic Chemistry and Technology (GOSNIIOKhT). It was in this context claimed that at least two compounds of the Novichok family, known as Novichok‐5 and Novichok‐7 were 5–8 times more potent than the hitherto most toxic nerve agent, VX. The present study elucidates, applying a series of QSAR models toxicity, skin permeation, pharmacokinetic aspects as well as the environmental fate of a series of Novichoks. Virtually the results from the different studies related to human health point in the same direction, i. e., the Novichoks are significantly less toxic than VX and the skin permeation much lower and less efficient than observed for VX. Hence, the claim by Mirzayanov could not be substantiated.
Gaussian Process Regression Models for the Prediction of Hydrogen Bond Acceptor Strengths
Authors: Bauer Christoph A. , Schneider Gisbert , Göller Andreas H.
Published: November 2018

We present two approaches for the computation of hydrogen bond acceptor strengths, one by machine‐learning and one by a composite quantum‐mechanical protocol, both based on the well‐established pKBHX scale and dataset. The QM calculations after a necessary linear fit reproduce the complexation free energies in solution with an RMSE of 2.6 kJ mol−1, not far off the expected error of 2 kJ mol−1 obtained from the comparison of experimental data from two different sources. The second approach is by Gaussian Process Regression (GPR) machine‐learning. We describe the hydrogen bond acceptor atoms by a radial atomic reactivity descriptor that encodes their electronic and steric environment. The performance of the GPR model on an external test set corresponds to 3.3 kJ mol−1, which is also close to the experimental error. We apply the GPR model built on experimental data to model the hydrogen bond acceptor strengths of a series of hydrogen bond acceptor sites of 10 phosphodiesterase 10 A inhibitors. The predicted values correlate well with the experimentally measured IC50 values.
31P NMR assessment of the phosvitin‐iron complex in mayonnaise
Authors: Merkx Donny W.H. , Delić Faruk , Wierenga Peter A. , Hennebelle Marie , van Duynhoven John P.M.
Published: November 2018

Lipid oxidation is the main reason for the limited shelf life of mayonnaise. One of the main catalysts of this process is iron, which is introduced in its ferric (Fe(III)) form via phosvitin, an egg yolk phosphoprotein rich in phosphoserines. The binding of Fe(III) to phosvitin and its ability to establish a redox couple with Fe(II) is believed to determine the oxidation rate of unsaturated lipids. In this work, a 31P NMR based method was developed to quantify loading of phosvitin with Fe(III) and its reductive release. Both features could be quantified in model phosvitin solutions by exploiting the paramagnetic broadening of 31P NMR signal of phosphoserine residues by Fe(III). This method was then successfully applied to quantify the phosvitin‐Fe(III) loading in mayonnaise water phase by liquid NMR, whereas 31P NMR MAS could only provide a qualitative measure. The 31P NMR method showed a direct relation between loading of the Fe(III)‐phosvitin complex and lipid oxidation.
Hydrogen bonding networks in gabapentin protic pharmaceutical salts: NMR and in silico studies
Authors: Martins Inês C.B. , Sardo Mariana , Čendak Tomaž , Gomes José R.B. , Rocha João , Duarte M. Teresa , Mafra Luís
Published: November 2018

Hydrogen bonds (HBs) play a key role in the supramolecular arrangement of crystalline solids and, although they have been extensively studied, the influence of their strength and geometry on crystal packing remains poorly understood. Here we describe the crystal structures of two novel protic gabapentin (GBP) pharmaceutical salts prepared with the coformers methanesulfonic acid (GBP:METHA) and ethanesulfonic acid (GBP:ETHA). This study encompasses experimental and computational electronic structure analyses of 1H NMR chemical shifts (CSs), upon in silico HB cleavage. GBP:METHA and GBP:ETHA crystal packing comprise two main structural domains: an ionic layer (characterized by the presence of charge‐assisted +NHGBP⋯O−METHA/ETHA HB interactions) and a neutral layer generated in a different way for each salt, mainly due to the presence of bifurcated HB interactions. A comprehensive study of HB networks is presented for GBP:METHA, by isolating molecular fragments involved in distinct HB types (NH⋯O, OH⋯O, and CH⋯O) obtained from in silico disassembling of an optimized three‐dimensional packing structure. Formation of HB leads to calculated 1H NMR CS changes from 0.4 to ~5.8 ppm. This study further attempts to assess how 1H NMR CS of protons engaged in certain HB are affected when other nearby HB, involving bifurcated or geminal/vicinal hydrogen atoms, are removed.
A new computation method for signature: Markov process method
Authors: Yi He , Cui Lirong
Published: November 2018

System signature is a crucial measure in the description and comparison of system structures in the field of reliability, and it does not depend on the component distributions under the assumption that all components are independent and identically distributed. A Markov process method is proposed to compute signatures for general coherent systems in this paper, which is more efficient for the computation of the system signature. As applications of the method, signature formulas of consecutive‐k‐out‐of‐n: F systems and related consecutive‐type systems are investigated, including both the linear and circular ones. Particularly, the related signature formulas for consecutive‐type systems with sparse d are derived for the first time. Illustrative examples are presented for methane reformer furnace systems.