bluuebunny/crossref_metadata_2025 huggingface dataset:
Multitarget‐Directed Ligands Combining Cholinesterase and Monoamine Oxidase Inhibition with Histamine H3R Antagonism for Neurodegenerative Diseases
Authors: Bautista‐Aguilera Óscar M. , Hagenow Stefanie , Palomino‐Antolin Alejandra , Farré‐Alins Víctor , Ismaili Lhassane , Joffrin Pierre‐Louis , Jimeno María L. , Soukup Ondřej , Janočková Jana , Kalinowsky Lena , Proschak Ewgenij , Iriepa Isabel , Moraleda Ignacio , Schwed Johannes S. , Romero Martínez Alejandro , López‐Muñoz Francisco , Chioua Mourad , Egea Javier , Ramsay Rona R. , Marco‐Contelles José , Stark Holger
Published: September 2017

The therapy of complex neurodegenerative diseases requires the development of multitarget‐directed drugs (MTDs). Novel indole derivatives with inhibitory activity towards acetyl/butyrylcholinesterases and monoamine oxidases A/B as well as the histamine H3 receptor (H3R) were obtained by optimization of the neuroprotectant ASS234 by incorporating generally accepted H3R pharmacophore motifs. These small‐molecule hits demonstrated balanced activities at the targets, mostly in the nanomolar concentration range. Additional in vitro studies showed antioxidative neuroprotective effects as well as the ability to penetrate the blood–brain barrier. With this promising in vitro profile, contilisant (at 1 mg kg−1 i.p.) also significantly improved lipopolysaccharide‐induced cognitive deficits.
Copper‐Catalyzed Intermolecular Heck‐Like Coupling of Cyclobutanone Oximes Initiated by Selective C−C Bond Cleavage
Authors: Zhao Binlin , Shi Zhuangzhi
Published: September 2017

The first example of intermolecular olefination of cyclobutanone oximes with alkenes via selective C−C bond cleavage leading to the synthesis of nitriles in the presence of a cheap copper catalyst is reported. The procedure is distinguished by mild and safe reaction conditions that avoid ligand, oxidant, base, or toxic cyanide salt. A wide scope of cyclobutanones and olefin coupling components can be used without compromising efficiency and scalability. The alternative visible‐light‐driven photoredox process for this coupling reaction was also uncovered.
Gold Catalysis for Heterocyclic Chemistry: A Representative Case Study on Pyrone Natural Products
Authors: Fürstner Alois
Published: September 2017

2‐Pyrones and 4‐pyrones are common structural motifs in bioactive natural products. However, traditional methods for their synthesis, which try to emulate the biosynthetic pathway of cyclization of a 1,3,5‐tricarbonyl precursor, are often harsh and, therefore, not particularly suitable for applications to polyfunctionalized and/or sensitive target compounds. π‐Acid catalysis, in contrast, has proved to be better for a systematic exploration of the pyrone estate. To this end, alkynes are used as stable ketone surrogates, which can be activated under exceedingly mild conditions due to the pronounced carbophilicity of [LAu]+ fragments (L=two electron donor ligand); attack of a tethered ester carbonyl group onto the transient alkyne–gold complex then forges the pyrone ring in a fully regiocontrolled manner.
How Trump can Avoid War with China
Authors: Borroz Nicholas , Marston Hunter
Published: September 2017

The administration of Donald Trump is stacked with China policy hawks, who warn of imminent war with the rising Communist power. International relations theorists of the realist school of thought, such as John Mearsheimer, validate the views of these advocates of war. Chief among those clamoring for conflict is Steve Bannon, President Trump's visionary ideologue, who has warned that the United States will go to war with China in the South China Sea in the next few years. Yet, President Trump may be uniquely placed to avoid war with Beijing. As someone comfortable with radical shifts in policy direction, Mr. Trump is predisposed for a course correction. As such, he and his team of advisers should utilize the strategy of ‘America first’ to steer US–China policy toward an aversion of conflict. That centers on two policy directions. The first is promoting American jobs and economic interests, which rely on stable relations with Beijing. The second is consolidating core US alliances and partnerships in Asia, rather than proliferating security agreements and overextending American security commitments. As such, Trump and his vision of America first just might be capable of improving the Sino‐American relationship.
The promise and peril of CRISPR gene drives
Authors: Zentner Gabriel E. , Wade Michael J.
Published: September 2017

Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats (CRISPR) genome editing system have been proposed as a way to alter the genetic characteristics of natural populations of organisms relevant to the goals of public health, conservation, and agriculture. Here, we review the principles and potential applications of CRISPR drives, as well as means proposed to prevent their uncontrolled spread. We also focus on recent work suggesting that factors such as natural genetic variation and inbreeding may represent substantial impediments to the propagation of CRISPR drives.
Efficacy of the Volatile Oil from Water Celery (Helosciadium nodiflorum, Apiaceae) against the Filariasis Vector Culex quinquefasciatus, the Housefly Musca domestica, and the African Cotton Leafworm Spodoptera littoralis
Authors: Benelli Giovanni , Pavela Roman , Ricciutelli Massimo , Lupidi Giulio , Maggi Filippo
Published: September 2017

Water celery (Helosciadium nodiflorum, Apiaceae) is a common and invasive hydrophyte occurring in rivers and slow waters of Europe. In the past, it was consumed as a vegetable and spices, but currently it has mostly been abandoned. As a result, this plant produces an unexploited biomass occluding rivers and slow waters. With the aim to valorise water celery as an important biomass source for the development of botanical insecticides, in this work, we investigated the inhibitory effects of the essential oil hydrodistilled from its aerial parts against larvae of the filariasis vector Culex quinquefasciatus, adults of the housefly Musca domestica, and larvae of the African cotton leafworm Spodoptera littoralis. The essential oil, which was characterized by the insecticidal limonene (39.8%) and myristicin (35.3%), exerted important toxic effects on 3rd instar larvae of C. quinquefasciatus and S. littoralis and on adults of M. domestica, with LD50 of 50.4 μl l−1, 116.7 μg larva−1, and 45.1 (male) and 70.1 (female) μg adult−1, respectively. The oil did not show any noticeable inhibitory activity on the acetylcholinesterase enzyme. Our findings add scientific evidences highlighting water celery as an important biomass source to be used for the control of insect pests and vectors of high economic importance.
Redirecting Killer T Cells through Incorporation of Azido Sugars for Tethering Ligands
Authors: Wang Weiling , Zhao Zhiying , Zhang Ziwei , Zhang Chuanling , Xiao Sulong , Ye Xinshan , Zhang Lihe , Xia Qing , Zhou Demin
Published: September 2017

The genetic expression of chimeric antigen receptors (CARs) on the surfaces of T cells enables the redirection of T cell specificity. To enhance the versatility of T cells as tumor‐specific killers, we developed a nongenetic approach by which azide‐containing sialic acids were metabolically incorporated into T cells to modify cellular sialyl glycans. After successful display of these moieties on the T cells, small‐molecule ligands such as RGD and folate (as proof‐of‐concept, rather than supersized antibodies) were clicked orthogonally, leading to highly selective time‐ and dose‐dependent cytotoxicity to integrin αvβ3‐ and folate‐receptor‐positive cells, respectively. This chemical approach provides a facile platform for rational design of tumor‐specific cytotoxic T cells for targeted immunotherapy.
Further Insight into Crystal Structures of Escherichia coli IspH/LytB in Complex with Two Potent Inhibitors of the MEP Pathway: A Starting Point for Rational Design of New Antimicrobials
Authors: Borel Franck , Barbier Elodie , Krasutsky Sergiy , Janthawornpong Karnjapan , Chaignon Philippe , Poulter C. Dale , Ferrer Jean‐Luc , Seemann Myriam
Published: September 2017

IspH, also called LytB, a protein involved in the biosynthesis of isoprenoids through the methylerythritol phosphate pathway, is an attractive target for the development of new antimicrobial drugs. Here, we report crystal structures of Escherichia coli IspH in complex with the two most potent inhibitors: (E)‐4‐mercapto‐3‐methylbut‐2‐en‐1‐yl diphosphate (TMBPP) and (E)‐4‐amino‐3‐methylbut‐2‐en‐1‐yl diphosphate (AMBPP) at 1.95 and 1.7 Å resolution, respectively. The structure of the E. coli IspH:TMBPP complex exhibited two conformers of the inhibitor. This unexpected feature was exploited to design and evolve new antimicrobial candidates in silico.
Ribbon‐like Foldamers for Cellular Uptake and Drug Delivery
Authors: Vezenkov Lubomir L. , Martin Vincent , Bettache Nadir , Simon Matthieu , Messerschmitt Alexandre , Legrand Baptiste , Bantignies Jean‐Louis , Subra Gilles , Maynadier Marie , Bellet Virginie , Garcia Marcel , Martinez Jean , Amblard Muriel
Published: September 2017

Different intracellular delivery systems of bioactive compounds have been developed, including cell‐penetrating peptides. Although usually nontoxic and biocompatible, these vectors share some of the general drawbacks of peptides, notably low bioavailability and susceptibility to protease degradation, that limit their use. Herein, the conversion of short peptide sequences into poly‐α‐amino‐γ‐lactam foldamers that adopt a ribbon‐like structure is investigated. This template is used to distribute critical cationic and/or hydrophobic groups on both sides of the backbone, leading to potent short, cell‐permeable foldamers with a low positive‐charge content. The lead compound showed dramatically improved protease resistance and was able to efficiently deliver a biologically relevant cargo inside cells. This study provided a simple strategy to convert short peptide sequences into efficient protease‐resistant cell‐penetrating foldamers.
Tailoring stents to fit the anatomy of unique vascular stenoses in congenital heart disease
Authors: Sullivan Patrick M. , Liou Aimee , Takao Cheryl , Justino Henri , Petit Christopher J. , Salazar Jorge D. , Ing Frank F.
Published: September 2017

Background

Unique and small anatomical features often preclude the use of available vascular stents in pediatric patients with congenital heart disease (CHD).

Objectives

To report our experience and outcomes tailoring stents to fit unique anatomy, particularly in small children and infants with CHD.

Methods

Stent tailoring techniques included trimming, folding, and flaring. Patients receiving a tailored stent November 2002 to February 2015 were included in a retrospective analysis.

Results

Forty‐one tailored stents were implanted in 30 patients with median age and weight of 0.8 years (6 days to 17 years) and 8.1 kg (2.9–47.9 kg). Thirty stents were placed intraoperatively and 11 percutaneously. Sites included branch pulmonary arteries (BPA; n = 32), pulmonary veins (n = 6), SVC (n = 1), and the ventricular septum (n = 2). Twenty‐three (56%) stents were trimmed with or without folding to avoid jailing of side branches, 16 (39%) stents were folded or flared with or without trimming to avoid excessive proximal protrusion, and two (5%) stents were folded back at both ends for implantation in ventricular septal defects. Final stent lengths were 6–15 mm. Minimal vessel diameters increased from 2.8 ± 1.4 mm to 6.7 ± 2.6 mm (P < 0.001). Complications included two intraoperative BPA tears, three pinhole balloon leaks, two intraoperative stent dislodgements, one transient heart block, and one lung reperfusion injury. Follow‐up catheterization included 36 re‐dilations and implantation of four additional stents over a median of 4.1 years. In‐stent restenosis was the indication in 25 (69.4%) re‐interventions.

Conclusion

Tailored stents can be safely implanted to fit unique anatomy in small patients. Re‐interventions can effectively treat restenosis and accommodate ongoing vessel growth.
Octahedral [Pd6L8]12+ Metallosupramolecular Cages: Synthesis, Structures and Guest‐Encapsulation Studies
Authors: Kim Tae Y. , Digal Lori , Gardiner Michael G. , Lucas Nigel T. , Crowley James D.
Published: September 2017

Four planar tripyridyl ligands (Ltripy), 1,3,5‐tris(pyridin‐3‐ylethynyl)benzene 1 a, 1,3,5‐tris[4‐(3‐pyridyl)phenyl]benzene 2 a, and the hexyloxy chain functionalized derivatives 1,3,5‐tris[(3‐hexyloxy‐5‐pyridyl)ethynyl]benzene 1 b, and 1,3,5‐tris[4‐(3‐hexyloxy‐5‐pyridyl)phenyl]benzene 2 b, were synthesized and used to generate a family of [Pd6(Ltripy)8](BF4)12 octahedral cages (Ltripy=1 a, b or 2 a, b). The ligands and cages were characterized using a combination of 1H, 13C, and DOSY nuclear magnetic resonance (NMR) spectroscopy, high resolution electrospray mass spectrometry (HR‐ESI‐MS), infrared (IR) spectroscopy, elemental analysis, and in three cases, X‐ray crystallography. The molecular recognition properties of the cages with neutral and anionic guests were examined, in dimethyl sulfoxide (DMSO), using NMR spectroscopy, mass spectrometry and molecular modeling. No binding was observed with simple aliphatic and aromatic guest molecules. However, anionic sulfonates were found to interact with the octahedral cages and the binding interaction was size selective. The smaller [Pd6(1 a, b)8]12+ cages were able to interact with three p‐toluenesulfonate guest molecules while the larger [Pd6(2 a, b)8]12+ systems could host four of the anionic guest molecules. To probe the importance of the hydrophobic effect, a mixed water–DMSO (1:1) solvent system was used to reexamine the binding of the neutral organic guests adamantane, anthracene, pyrene and 1,8‐naphthalimide within the cages. In this solvent system all the guests except adamantane were observed to bind within the cavities of the cages. NMR spectroscopy and molecular modeling indicated that the cages bind multiple copies of the individual guests (between 3–6 guest molecules per cage).
Auxiliary‐Directed C(sp3)−H Arylation by Synergistic Photoredox and Palladium Catalysis
Authors: Czyz Milena L. , Lupton David W. , Polyzos Anastasios
Published: September 2017

Herein we describe the auxiliary‐directed arylation of unactivated C(sp3)−H bonds with aryldiazonium salts, which proceeds under synergistic photoredox and palladium catalysis. The site‐selective arylation of aliphatic amides with α‐quaternary centres is achieved with high selectivity for β‐methyl C(sp3)−H bonds. This operationally simple method is compatible with carbocyclic amides, a range of aryldiazonium salts and proceeds at ambient conditions.
Three New Chromone Derivatives Produced by Phomopsis sp. HNY29‐2B from Acanthus ilicifolius Linn.
Authors: Ding Bo , Wang Zhiyuan , Xia Guoping , Huang Xishan , Xu Fang , Chen Wenrui , She Zhigang
Published: September 2017

Three new chromone derivatives, phomochromenones A‐C (1–3), and one known chaetocyclinone B (4) were obtained from the cultures of Phomopsis sp. HNY29‐2B isolated from the mangrove Acanthus ilicifolius Linn., which was collected from the South China Sea. Their structures were determined by the analysis of 1D NMR and 2D NMR as well as mass spectroscopic data. The absolute configurations of 1 and 2 were assigned by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compound 3 is the third example of alkaloids possessing the unique chromeno [3,2‐c] pyridine nucleus. In the bioactivity assay, compound 4 showed cytotoxicity against human prostate cancer cell lines (PC‐3 and DU145 cells) with the IC50 values of 8.13 and 3.59 µmol/L, respectively.
Ultrathin Colloidal Quantum Dot Films for Optical Amplification: The Role of Modal Confinement and Heat Dissipation
Authors: Koh Weon‐kyu , Lee Jaesoong , Cho Kyung‐Sang , Roh Young‐Geun
Published: September 2017

We demonstrate optical pumping lasers based on colloidal quantum dots, with a very thin geometry consisting of a ≈20 nm thick film. Obstacles in ultrasmall laser devices come from the limitation of gain materials and the size of cavities for lasing modes, which requires a minimum thickness of the gain media (typically greater than 50–100 nm). Here we introduce dielectric waveguide structures with a high refractive index, in order to reduce the thickness of quantum dot gain media as well as their threshold energy (≈39 % compared to the original gain medium). Finite‐difference time‐domain simulations show that the modal confinement factor of thinner quantum dot films can be improved by the presence of an adjacent waveguide layer. We also discuss the possible role of dielectric waveguide layers for efficient heat dissipation during optical pumping. Integrating an extremely thin colloidal quantum dot gain medium into optical waveguides is a promising platform for downscaling on‐chip photonic integrated devices, as well as investigating extreme interactions between light and matter such as surface plasmon–photon coupling.
Iodine‐Catalyzed Azidation/Cyclization Cascade Approach to 3a‐Azidofuroindolines and ‐pyrroloindolines under Mild Conditions
Authors: Guo Jiajing , Chen Siyu , Liu Jingyuan , Guo Jialiang , Chen Weimin , Cai Qian , Liu Peijun , Sun Pinghua
Published: September 2017

An efficient and practical approach to 3a‐azidofuroindolines and ‐pyrroloindolines involving an iodine‐catalyzed azidation/cyclization cascade of tryptophols and tryptamines with NaN3 was developed. Further transformation of the C3‐azidated product provided a key intermediate for the total synthesis of psychotriasine.
Expedient Synthesis of a Linear Nonadecaarabinofuranoside of the Mycobacterium tuberculosis Cellular Envelope
Authors: Mishra Bijoyananda , Manmode Sujit , Panda Ravi Raja Adhikari , Hotha Srinivas
Published: September 2017

The synthesis of oligosaccharides is demanding as it requires multiple steps and long reaction sequences. The choice of glycosylation method and protecting groups is very important for the successful synthesis of any oligosaccharide. In this paper, we show that ethynylcyclohexyl carbonate glycosyl donors are excellent for the synthesis of a nonadecasaccharide fragment of the Mycobacterium tuberculosis glycocalyx using a split/react/couple strategy. The synthesis of the target nonadecasaccharide was accomplished using eight different reactions and 23 steps in 6.4 % overall yield.
Advanced monitoring and control of pharmaceutical production processes with Pichia pastoris by using Raman spectroscopy and multivariate calibration methods
Authors: Voss Jan‐Patrick , Mittelheuser Nina E. , Lemke Roman , Luttmann Reiner
Published: September 2017

This contribution includes an investigation of the applicability of Raman spectroscopy as a PAT analyzer in cyclic production processes of a potential Malaria vaccine with Pichia pastoris. In a feasibility study, Partial Least Squares Regression (PLSR) models were created off‐line for cell density and concentrations of glycerol, methanol, ammonia and total secreted protein. Relative cross validation errors RMSEcvrel range from 2.87% (glycerol) to 11.0% (ammonia). In the following, on‐line bioprocess monitoring was tested for cell density and glycerol concentration. By using the nonlinear Support Vector Regression (SVR) method instead of PLSR, the error RMSEPrel for cell density was reduced from 5.01 to 2.94%. The high potential of Raman spectroscopy in combination with multivariate calibration methods was demonstrated by the implementation of a closed loop control for glycerol concentration using PLSR. The strong nonlinear behavior of exponentially increasing control disturbances was met with a feed‐forward control and adaptive correction of control parameters. In general the control procedure works very well for low cell densities. Unfortunately, PLSR models for glycerol concentration are strongly influenced by a correlation with the cell density. This leads to a failure in substrate prediction, which in turn prevents substrate control at cell densities above 16 g/L.
A Zinc–Bromine Flow Battery with Improved Design of Cell Structure and Electrodes
Authors: Wu Maochun , Zhao Tianshou , Zhang Ruihan , Jiang Haoran , Wei Lei
Published: September 2017

The zinc–bromine flow battery (ZBFB) is regarded as one of the most promising candidates for large‐scale energy storage owing to its high energy density and low cost. However, because of the large internal resistance and poor electrocatalytic activity of graphite‐ or carbon‐felt electrodes, conventional ZBFBs usually can only be operated at a relatively low current density, which limits their widespread application. Herein, we propose an asymmetrical cell by replacing the conventional thick felt electrode with a thin and electrocatalytically active carbon‐paper (CP) electrode interfacing with a flow‐field structure. With the enhanced electrocatalytic activity of CP for the Br2/Br− redox reaction and the reduced internal resistance of the thinner electrode, the ZBFB with this newly proposed structure exhibits an energy efficiency of up to 83.5 % at a current density of 40 mA cm−2, much higher than that with a graphite‐felt electrode of only 73.0 %. Remarkably, the battery can even be operated at a high current density up to 100 mA cm−2 while maintaining an energy efficiency of more than 70 %, demonstrating an excellent rate capability.
A high‐order discontinuous Galerkin method for extension problems
Authors: Utz Thomas , Kummer Florian
Published: September 2017

We present a novel technique for solving extension problems such as the extension velocity, by reformulating the problem into an elliptic differential equation. We introduce a novel discretization using an upwind flux without any additional stabilization. This leads to a triangular matrix structure, which can be solved using a marching algorithm and high‐order accuracy, even in the presence of singularities.
Finding a subdivision of a prescribed digraph of order 4
Authors: Havet Frédéric , Maia A. Karolinna , Mohar Bojan
Published: September 2017

The problem of when a given digraph contains a subdivision of a fixed digraph F is considered. Bang‐Jensen et al. [4] laid out foundations for approaching this problem from the algorithmic point of view. In this article, we give further support to several open conjectures and speculations about algorithmic complexity of finding F‐subdivisions. In particular, up to five exceptions, we completely classify for which 4‐vertex digraphs F, the F‐subdivision problem is polynomial‐time solvable and for which it is NP‐complete. While all NP‐hardness proofs are made by reduction from some version of the 2‐linkage problem in digraphs, some of the polynomial‐time solvable cases involve relatively complicated algorithms.
Accumulation of advanced‐glycation end products (AGEs) accelerates arthrogenic joint contracture in immobilized rat knee
Authors: Ozawa Junya , Kaneguchi Akinori , Minamimoto Kengo , Tanaka Ryo , Kito Nobuhiro , Moriyama Hideki
Published: September 2017

Joint mobility decreases in the elderly and in diabetics, this process is thought to be caused by accumulation of advanced‐glycation end products (AGEs). Here, we aimed to elucidate the role of AGEs in joint contracture formation in rat knees. Rats were injected with ribose or saline into the knees twice weekly for 8 weeks. Pentosidine (AGE) levels were measured in the knee‐joint tissues. After serial injections, rats were subjected to unilateral knee‐joint immobilization in a flexion position for various periods. At day 21, the passive knee ranges of motions (ROMs) were measured. Knee joint histopathology were assessed, and the expression of fibrotic genes in the posterior joint capsules was examined using real‐time PCR. Ribose injection induced a 7.0‐fold increase in pentosidine levels relative to saline injection. Joint immobilization resulted in equal myogenic ROM restriction in both groups. Arthrogenic ROM restriction was greater with ribose injection in the immobilized joints (p < 0.05), but was not affected in nonimmobilized joints. Type‐I (COL1A1) and type‐III (COL3A1) collagen gene expression increased significantly in immobilized joints relative to nonimmobilized joints in the ribose group, but was not affected in the saline group. Ribose injection increased COL1A1 expression slightly and COL3A1 expression significantly in immobilized joints. Histologically, inflammatory changes appeared at day 3 of immobilization and peaked at day 7. These responses trended to be more severe and prolonged in the ribose group than in the saline group. Our data provide evidence for a causal relationship between AGEs and joint contracture formation following immobilization. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:854–863, 2018.
One‐Pot Multicomponent Synthesis of Glycopolymers through a Combination of Host–Guest Interaction, Thiol‐ene, and Copper‐Catalyzed Click Reaction in Water
Authors: Hu Xiang , Gao Jinbo , Luo Yan , Wei Ting , Dong Yishi , Chen Gaojian , Chen Hong
Published: September 2017

There is a common phenomenon that the heterogeneity of natural oligosaccharides contains various sugar units, which can be used to enhance affinity and selectivity toward a specific receptor, so the synthesis of heterogeneous glycopolymers is always an important issue in the glycopolymer field. Herein, this study conducts a one‐pot method to prepare polyrotaxane‐based heteroglycopolymers anchored with different sugar units and fluorescent moieties via the combination of host–guest interaction, thiol‐ene, and copper‐catalyzed click chemistry in water. Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, gel permeation chromatography, X‐ray diffraction, and Ellman's assay test are used in the paper to characterize the compounds. Quartz crystal microbalance‐dissipation (QCD‐D) experiments and bacterial adhesion assay are utilized to study the interactions of polyrotaxane‐based heteroglycopolymers with Con A and Escherichia coli. The results reveal that polyrotaxanes (PRs) with mannose and glucose present better specificity toward Con A and E. coli than PRs with glucose due to synergistic effects.
Glitazone use associated with reduced risk of Parkinson's disease
Authors: Brakedal Brage , Flønes Irene , Reiter Simone F. , Torkildsen Øivind , Dölle Christian , Assmus Jörg , Haugarvoll Kristoffer , Tzoulis Charalampos
Published: September 2017

Background

Whether antidiabetic glitazone drugs protect against Parkinson's disease remains controversial. Although a single clinical trial showed no evidence of disease modulation, retrospective studies suggest that a disease‐preventing effect may be plausible. The objective of this study was to examine if the use of glitazone drugs is associated with a lower incidence of PD among diabetic patients.

Methods

We compared the incidence of PD between individuals with diabetes who used glitazones, with or without metformin, and individuals using only metformin in the Norwegian Prescription Database. This database contains all prescription drugs dispensed for the entire Norwegian population. We identified 94,349 metformin users and 8396 glitazone users during a 10‐year period and compared the incidence of PD in the 2 groups using Cox regression survival analysis, with glitazone exposure as a time‐dependent covariate.

Results

Glitazone use was associated with a significantly lower incidence of PD compared with metformin‐only use (hazard ratio, 0.72; 95% confidence interval, 0.55‐0.94; P = 0.01).

Conclusions

The use of glitazones is associated with a decreased risk of incident PD in populations with diabetes. Further studies are warranted to confirm and understand the role of glitazones in neurodegeneration. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society
Treatable inherited rare movement disorders
Authors: Jinnah H. A. , Albanese Alberto , Bhatia Kailash P. , Cardoso Francisco , Da Prat Gustavo , de Koning Tom J. , Espay Alberto J. , Fung Victor , Garcia‐Ruiz Pedro J. , Gershanik Oscar , Jankovic Joseph , Kaji Ryuji , Kotschet Katya , Marras Connie , Miyasaki Janis M. , Morgante Francesca , Munchau Alexander , Pal Pramod Kumar , Rodriguez Oroz Maria C. , Rodríguez‐Violante Mayela , Schöls Ludger , Stamelou Maria , Tijssen Marina , Uribe Roca Claudia , de la Cerda Andres , Gatto Emilia M. ,   for the International Parkinson's Disease Movement Disorders Society Task Force on Rare Movement Disorders
Published: September 2017

There are many rare movement disorders, and new ones are described every year. Because they are not well recognized, they often go undiagnosed for long periods of time. However, early diagnosis is becoming increasingly important. Rapid advances in our understanding of the biological mechanisms responsible for many rare disorders have enabled the development of specific treatments for some of them. Well‐known historical examples include Wilson disease and dopa‐responsive dystonia, for which specific and highly effective treatments have life‐altering effects. In recent years, similarly specific and effective treatments have been developed for more than 30 rare inherited movement disorders. These treatments include specific medications, dietary changes, avoidance or management of certain triggers, enzyme replacement therapy, and others. This list of treatable rare movement disorders is likely to grow during the next few years because a number of additional promising treatments are actively being developed or evaluated in clinical trials. © 2017 International Parkinson and Movement Disorder Society
Chemical shift encoding (CSE) for sensitive fluorine‐19 MRI of perfluorocarbons with complex spectra
Authors: van Heeswijk Ruud B. , Colotti Roberto , Darçot Emeline , Delacoste Jean , Pellegrin Maxime , Piccini Davide , Hernando Diego
Published: September 2017

Purpose

To implement a fluorine‐19 (19F) chemical shift encoding (CSE) approach for the sensitive imaging of molecules with multi‐resonance spectra to remove their chemical shift displacement (CSD) artifacts, and to characterize its sensitivity versus established pulse sequences.

Methods

The feasibility of CSE spoiled gradient echo (GRE) and balanced steady‐state free precession (bSSFP) was first demonstrated in a phantom study. The dependence of the sensitivity of CSE‐bSSFP on several pulse sequence parameters was then established, after which the occurrence of out‐of‐plane excitation was assessed for 2D and 3D techniques. Next, the sensitivity (in mm−3s−0.5) of both CSE techniques was compared to bSSFP ultrashort echo time (bSSFP‐UTE) imaging and multi‐chemical‐shift‐selective turbo spin echo (MCSS‐TSE) in a second phantom study. Finally, the sensitivity of the CSE‐bSSFP, bSSFP‐UTE, and MCSS‐TSE pulse sequences was compared in a preliminary in vivo mouse study.

Results

Both CSE approaches were successfully implemented and resulted in negligible residual CSD artifacts, while large‐volume 3D acquisitions should be considered to reduce problems related to out‐of‐plane excitation. CSE–bSSFP was shown to have a higher sensitivity than the bSSFP‐UTE and MCSS‐TSE pulse sequences (15.8 ± 1.3 vs. 11.7 ± 1.0 vs. 13.3 ± 0.9 mm−3s−0.5, respectively, P < 0.001), whereas CSE‐GRE technique had a lower sensitivity (4.8 ± 1.1 mm−3s−0.5).

Conclusion

CSE 19F MR imaging enables the unambiguous visualization of compounds with complex spectra, and provides high sensitivity both in vitro and in vivo. Magn Reson Med 79:2724–2730, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Z‐spectrum appearance and interpretation in the presence of fat: Influence of acquisition parameters
Authors: Zhang Shu , Keupp Jochen , Wang Xinzeng , Dimitrov Ivan , Madhuranthakam Ananth J. , Lenkinski Robert E. , Vinogradov Elena
Published: September 2017

Purpose

Chemical exchange saturation transfer (CEST) MRI is increasingly evolving from brain to body applications. One of the known problems in the body imaging is the presence of strong lipid signals. Although their influence on the CEST effect is acknowledged, there was no study that focuses on the interplay among echo time, fat fraction, and Z‐spectrum. This study strives to address these points, with the emphasis on the application in the breast.

Methods

Z‐spectra were simulated in phase and out of phase of the main fat peak at −3.4 ppm, with the fat fraction varying from 0 to 100%. The magnetization transfer ratio asymmetry in two ranges, centering at the exchanging pool and at 3.5 ppm approximately opposite the nonexchanging fat pool, were calculated and were plotted against fat fraction. The results were verified in phantoms and in vivo.

Results

The results demonstrate the combined influence of fat fraction and echo time on the Z‐spectrum for gradient echo based CEST acquisitions. The influence is straightforward in the in‐phase images, but it is more complicated in the out‐of‐phase images, potentially leading to erroneous CEST contrast.

Conclusions

This study provides a basis for understanding the origin and appearance of lipid artifacts in CEST imaging, and lays the foundation for their efficient removal. Magn Reson Med 79:2731–2737, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Low‐dose baclofen for treatment of alcohol dependence
Authors: Al‐Garhy Mohamed , Varghese Sona
Published: September 2017

Alcohol use disorder (AUD) is a growing problem in the Arabian Gulf region. Although drug treatment for AUD has largely remained the same in previous years, the dosage of the medication has always been a subject of interest. This report highlights the case of a patient on low‐dose baclofen and the sustained improvement he achieved with the treatment.
Two case studies of clozapine‐induced myocarditis
Authors: Saidova Nargiza , Llewellyn‐Jones Sian
Published: September 2017

There is currently limited knowledge about which side‐effects patients will experience from clozapine. In this article, the authors describe two cases of patients who developed myocarditis during the initiation period of clozapine. The cases also illustrate the difficulty in diagnosing clozapine‐induced myocarditis due to the non‐specific nature of the symptoms.
Early follow‐up of lung disease in infants with cystic fibrosis using the raised volume rapid thoracic compression technique and computed tomography during quiet breathing
Authors: Gauthier Rémi , Cabon Yann , Giroux‐Metges Marie Agnes , Du Boisbaudry Cecile , Reix Phillipe , Le Bourgeois Muriel , Chiron Raphael , Molinari Nicolas , Saguintaah Magali , Amsallem Francis , Matecki Stefan
Published: September 2017

Background

Among the different techniques used to monitor lung disease progression in infants with CF diagnosed by Newborn screening (NBS), raised volume‐rapid thoracic compression (RVRTC) remains a promising tool. However, the need of sedation and positive pressure ventilation considerably limits its clinical use. We recently described a semi‐quantitative method to evaluate air trapping by chest tomography during quite breathing without sedation (CTqb score). This parameter is the radiological sign of airway obstruction and could be also used for lung disease follow‐up in infants with CF. However, its discriminative power compared with RVRTC and correlation with lung function parameters are not known.

Objectives

To compare the discriminative powers of the CTqb score and RVRTC parameters and to determine their correlation during the first year of life of infants with CF.

Methods

In this multicenter longitudinal study, infants with CF diagnosed by NBS underwent RVRTC and CT during quite breathing at 10 ± 4 weeks (n = 30) and then at 13 ± 1 months of age (n = 28).

Results

All RVRTC parameters and the CTqb score remained stable between evaluations. The CTqb score showed a higher discriminative power than forced expiratory volume in 0.5 s (FEV0.5; the main RVRTC parameter) at both visits (66% and 50% of abnormal values vs 30% and 28%, respectively). No correlation was found between CTqb score and, the different RVRTC parameters or the plethysmographic functional residual capacity, indicating that they evaluate different aspect of CF lung disease.
Measurement and Modelling of Pyrotechnic Time Delay Burning Rates: Method and Model Development
Authors: Montgomery Yolandi C. , Focke Walter W. , Kelly Cheryl
Published: September 2017

The burning rates of a slow reacting Mn+Sb2O3 and a fast reacting Si+Pb3O4 time delay composition, filled into lead tubes, were measured with an infrared camera, with two thermocouples and in the form of a fully assembled detonator. The infrared camera method returned values that were on average about 12 % lower than those recorded for the detonators. The temperature profiles measured for the slow burning elements were fully developed, whereas those obtained for the fast burning Si+Pb3O4 elements were not. A numerical model was developed to simulate the Mn+Sb2O3 system. Kinetic parameters were determined by least square fits to the recorded surface temperature profiles. The model made it possible to determine the effect of various property variations on the burning rate. The thermal conductivity of the delay composition was found to have the smallest impact and the heat of reaction the largest effect.
The Integral Form of D = 3 Chern‐Simons Theories Probing Singularities
Authors: Fré P. , Grassi P.A.
Published: September 2017

We consider D=3 supersymmetric Chern Simons gauge theories both from the point of view of their formal structure and of their applications to the AdS4/CFT3 correspondence. From the structural view‐point, we use the new formalism of integral forms in superspace that utilizes the rheonomic Lagrangians and the Picture Changing Operators, as an algorithmic tool providing the connection between different approaches to supersymmetric theories. We provide here the generalization to an arbitrary Kähler manifold with arbitrary gauge group and arbitrary superpotential of the rheonomic lagrangian of D=3 matter coupled gauge theories constructed years ago. From the point of view of the AdS4/CFT3 correspondence and more generally of M2‐branes we emphasize the role of the Kähler quotient data in determining the field content and the interactions of the Cherns Simons gauge theory when the transverse space to the brane is a non‐compact Kähler quotient K4 of some flat variety with respect to a suitable group. The crepant resolutions of singularities fall in this category. In the present paper we anticipate the general scheme how the geometrical data are to be utilized in the construction of the D=3 Chern‐Simons Theory supposedly dual to the corresponding M2‐brane solution.
Cover Image, Volume 73, Issue 10
Authors: Tay Jia‐Wei , Hoddle Mark S , Mulchandani Ashok , Choe Dong‐Hwan
Published: September 2017

The cover image, by Jia‐Wei Tay et al., is based on the Research Article Development of an alginate hydrogel to deliver aqueous bait for pest ant management, DOI: 10.1002/ps.4616.

image
Electrochemically Grown ZnO Vertical Nanowire Scintillator with Light‐Guiding Effect
Authors: Izaki Masanobu , Kobayashi Masakazu , Shinagawa Tsutomu , Koyama Takayuki , Uesugi Kentaro , Takeuchi Akihisa
Published: September 2017

The <0001>‐oriented ZnO vertical nanowires (vnws) have been prepared by electrochemical growth for the electric charge of 0.3, 0.7, and 1.5 Ccm−2 on a <0001>‐Ga:ZnO/soda‐lime glass substrate in an simple aqueous 0.8 mmol L−1 zinc nitrate hydrate solution. All the ZnO‐vnws emitted strong ultraviolet light that originated from the recombination of a bound exciton and weak visible light due to native defects. The best performance regarding the intensity ratio and ultraviolet light intensity was obtained for the ZnO‐vnws prepared for 0.7 Ccm−2, and the performance changed depending on the electric charge. The ZnO‐vnws also showed the best scintillator performance with the luminous efficiency of 8.3% and spatial resolution of 4 μm, and the scintillator performance was closely related to the light‐guiding effects originating from the nanowire dimension in addition to the photoluminescence characteristic.
Key Points in the Latest Developments of High‐Efficiency Thin‐Film Silicon Solar Cells
Authors: Sai Hitoshi , Matsui Takuya , Matsubara Koji
Published: September 2017

Thin‐film silicon has been intensively used in photovoltaic applications. In recent years, most of the record efficiencies in thin‐film silicon solar cells have been updated frequently, particularly in microcrystalline silicon solar cells. In this article, key points in the latest developments of high‐efficiency thin‐film silicon solar cells are reviewed with a short overview of thin‐film silicon technology. The main driver for the efficiency improvement of microcrystalline silicon cells was the development of sophisticated light scattering substrates. The well‐designed honeycomb‐textured substrates enabled a systematic and detailed optimization to realize the growth of high‐quality films and significant light absorption enhancement simultaneously. The knowledge obtained about microcrystalline silicon solar cells and the insights regarding light‐induced degradation of a‐Si:H solar cells were successfully transferred to triple junction cells, which was demonstrated by the achievement of the record stabilized efficiency of 14%.
Encapsulation of Hydrophilic and Hydrophobic Peptides into Hollow Mesoporous Silica Nanoparticles for Enhancement of Antitumor Immune Response
Authors: Xie Jun , Yang Chaohua , Liu Qianqian , Li Jun , Liang Ruijing , Shen Chen , Zhang Yi , Wang Ke , Liu Liping , Shezad Khurram , Sullivan Martin , Xu Yong , Shen Guanxin , Tao Juan , Zhu Jintao , Zhang Zhiping
Published: September 2017

Codelivery of combinational antigenic peptides and adjuvant to antigen presenting cells is expected to amplify tumor specific T lymphocytes immune responses while minimizing the possibility of tumor escaping and reducing immune tolerance to single antigenic peptide. However, the varied hydrophobicities of these multivariant derived short antigenic peptides limit their codelivery efficiency in conventional delivery systems. Here, a facile yet effective route is presented to generate monodisperse and stable hollow mesoporous silica nanoparticles (HMSNs) for codelivering of HGP10025–33 and TRP2180–188, two melanoma‐derived peptides with varied hydrophobicities. The HMSNs with large pore size can improve the encapsulation efficiency of both HGP100 and TRP2 after NH2 modification on the inner hollow core and COOH modification in the porous channels. HGP100 and TRP2 loaded HMSNs (HT@HMSNs) are further enveloped within monophosphoryl lipid A adjuvant entrapped lipid bilayer (HTM@HMLBs), for improved stability/biocompatibility and codelivery efficiency of multiple peptides, adjuvant, and enhanced antitumor immune responses. HTM@HMLBs increase uptake by dendritic cells (DCs) and stimulate DCs maturation efficiently, which further induce the activation of both tumor specific CD8+ and CD4+ T lymphocytes. Moreover, HTM@HMLBs can significantly inhibit tumor growth and lung metastasis in murine melanoma models with good safety profiles. HMSNs enveloped with lipid bilayers (HMLBs) are believed to be a promising platform for codelivery of multiple peptides, adjuvant, and enhancement of antitumor efficacy of conventional vaccinations.
Argon‐Plasma Reinforced Superamphiphobic Fabrics
Authors: Liu Shuai , Zhou Hua , Wang Hongxia , Yang Weidong , Shao Hao , Fu Sida , Zhao Yan , Liu Deqi , Feng Zhihua , Lin Tong
Published: September 2017

A novel method for preparing durable superamphiphobic fabrics is reported, which involves preapplying a solution consisting of perfluoroalkyl acrylate, epoxide‐containing silane, and silica nanoparticles onto fabric and subsequent argon‐plasma treatment. The coated fabrics show superphobic to both water and oil fluids (surface tension >21.5 mN m−1). The coating is durable to withstand repeated laundries and multicycles of abrasion without apparently altering the superamphiphobicity. The coating is also very stable in boiling water, strong acid, and base, but has little effect on the fabric handle and air permeability. The argon‐plasma‐enhanced coating may offer a facile way to prepare durable superamphiphobic fabrics.
“Nobody Spoke Like I Did”: Picture Books, Critical Literacy, and Global Contexts
Authors: Callow Jon
Published: September 2017

In the 21st century, our students increasingly communicate, connect, collaborate, and interact with diverse cultures and traditions around the world, so they need to develop global literacy. This department column highlights research and research‐to‐practice at the international level to bring global best teaching practices to the forefront. Topics include international literacy instruction, international professional development, global literacy initiatives, global partnership and collaborative projects between schools and educators, best practices in literacy globally, and advocacy.
Festkörper‐Lithium‐Ionen‐Akkumulatoren
Authors: Ulrich Sven , Strafela Marc , Fischer Julian , Ziebert Carlos , Seemann Klaus , Leiste Harald , Stüber Michael
Published: September 2017

All‐Solid‐State‐Dünnschicht‐Lithium‐Ionen‐Batterien haben aufgrund ihrer hohen Leistungsdichte und ihrer hohen Sicherheit ein großes Anwendungspotential, insbesondere für den Einsatz in der Mikrosystemtechnik wie MEMS, CMOS, medizinischen Implantaten und Geräten, Chipkarten, RFID, E‐Textilien und Smartphones. Festkörper‐Lithium‐Ionen‐Batterien umfassen drei Hauptbestandteile, die Kathode, den Festkörperelektrolyten und die Anode, zusätzlich zu zwei Stromsammlern für die Kathode bzw. Anode. Neben den Materialeigenschaften einzelner Komponenten sind der Kontakt der Stromsammler zur Anode und Kathode sowie die Schnittstellen zwischen Kathode, Anode und Festkörperelektrolyt von entscheidender Bedeutung für die Batterieleistung. Dieser Artikel gibt einen Überblick über den aktuellen Forschungsstatus und betrachtet die einzelnen Batteriekomponenten hinsichtlich ihrer Materialauswahl, Konstitution, Mikrostruktur sowie der physikalischen, chemischen und elektrischen Eigenschaften. Die Herausforderungen bei der Aufskalierung werden ebenfalls diskutiert.
Geregeltes Reaktivsputtern von Planar‐ und Rohrkathoden
Authors: Radny Tobias , Grub Sebastian , Schäfer Rolf , Schütte Thomas
Published: September 2017

In diesem Beitrag werden grundlegende Eigenschaften von reaktiven Sputterprozessen aufgezeigt und die Auswirkung der verwendeten Magnetrontechnik diskutiert. Weiterhin werden Regelmöglichkeiten zur Stabiliserung solcher Prozesse aufgezeigt. Am Beispiel optischer Breitbandspektroskopie des Sputterplasmas wird die Integration solcher Regelungen in die Anlagentechnik beschrieben und ein Ausblick auf Anwendungen neben der Regelung reaktiver Prozesse gegeben. Zum Abschluss werden Beispielanwendungen aufgezeigt und die Vorteile geregelter Prozesse gegenüber ungeregelter reaktiver Prozesse diskutiert.