bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of Current Account Balance in Six ASEAN Countries: A Panel Analysis Approach
Authors: Lin Soo Xin , Kueh Jerome
Published: June 2019

This paper aims to examine the potential determinants of current account balance, which has been an interesting research topic in analysis over the decade. The relationship between current account balance and several different variables, such as fiscal balance, public debt, real GDP, and age dependency ratio for old and young, are examined. In this paper, the selected time period is from 1990 to 2016, in order to include the financial crisis period in six ASEAN countries (Indonesia, Malaysia, Philippines, Singapore, Thailand, and Vietnam). To this end, the research is based on the estimation of panel unit root, panel cointegration, panel Vector Error-Correction Model (VECM) and panel Granger causality. The findings show that all variables are cointegrated in the long-run and there are also unidirectional and bidirectional causal relationships in the short-run.
De informatieplicht voor de franchisegever naar Nederlands recht
Authors: Kruisinga S.A. , Nijenhof-Wolters M.I.
Published: June 2019

De informatieplicht voor de franchisegever naar Nederlands recht. Beschouwingen naar aanleiding van het Albert Heijn-arrest

In het Albert Heijn-arrest heeft de Hoge Raad opnieuw bevestigd dat naar huidig Nederlands recht geen algemene regel geldt dat een franchisegever een (toekomstige) franchisenemer moet inlichten omtrent de te verwachten omzet of omtrent de winstverwachting. De bijzondere omstandigheden van het geval kunnen echter wel een zodanige verplichting meebrengen. De vraag rijst of in het voorontwerp van de Wet Franchise dat op 12 december 2018 werd gepubliceerd een andere benadering is gekozen. In dit voorontwerp wordt voorgesteld een – vrij ruim geformuleerde – informatieplicht voor de franchisegever te introduceren. In deze bijdrage wordt ingegaan op het Albert Heijn–arrest en wordt de uitkomst van deze procedure afgezet tegen het Nederlandse conceptwetsvoorstel en de Belgische regelgeving voor franchiseovereenkomsten.
Linear Data-Model Based Adaptive ILC for Freeway Ramp Metering without Identical Conditions on Initial States and Reference Trajectory
Authors: Liang Hao , Lin Na , Chi Ronghu , Sun Yumei
Published: June 2019

Although freeway traffic system is conducted with a repeatable pattern day-to-day, the initial volume/or speed and the desired density of the traffic flow may vary with days due to the external disturbances. In this paper, a new linear data-model based adaptive ILC (LDM-AILC) is proposed to address ramp metering in a macroscopic level freeway environment. A linear data-model is developed for the nonlinear macroscopic traffic flow model by introducing an equivalent dynamical linearization approach in the time domain. Then the LDM-AILC is designed with a feedback control law and a parameter updating law. The proposed scheme is data-driven intrinsically, where only the I/O data is required for the controller design and analysis. The convergence is shown by rigorous analysis without any identical conditions exposed on both the initial state and the reference trajectory. Extensive simulation results are provided to verify the effectiveness of the proposed LDM-AILC.
Optimized RRT-A* Path Planning Method for Mobile Robots in Partially Known Environment
Authors: Ayawli Ben Beklisi Kwame , Mei Xue , Shen Moquan , Appiah Albert Yaw , Kyeremeh Frimpong
Published: June 2019

This paper presents optimized rapidly exploring random trees A* (ORRT-A*) method to improve the performance of RRT-A* method to compute safe and optimal path with low time complexity for autonomous mobile robots in partially known complex environments. ORRT-A* method combines morphological dilation, goal-biased RRT, A* and cubic spline algorithms. Goal-biased RRT is modified by introducing additional step-size to speed up the generation of the tree towards the goal after which A* is applied to obtain the shortest path. Morphological dilation technique is used to provide safety for the robots while cubic spline interpolation is used to smoothen the path for easy navigation. Results indicate that ORRT-A* method demonstrates improved path quality compared to goal-biased RRT and RRT-A* methods. ORRT-A* is therefore a promising method in achieving autonomous ground vehicle navigation in unknown environments
Classification of Motor Imagery Using Combination of Feature Extraction and Reduction Methods for Brain-Computer Interface
Authors: Jusas Vacius , Samuvel Sam Gilvine
Published: June 2019

The motor imagery (MI) based brain-computer interface systems (BCIs) can help with new communication ways. A typical electroencephalography (EEG)-based BCI system consists of several components including signal acquisition, signal pre-processing, feature extraction and feature classification. This paper focuses on the feature extraction step and proposes to use a combination of different feature extraction and feature reduction methods. The research presented in the paper explores the methods of band power, time domain parameters, fast Fourier transform and channel variance for feature extraction. These methods are investigated by combining them in pairs. The application of two feature extraction methods increases the number of selected features that can be redundant or irrelevant. The utilization of too many features can lead to wrong classification results. Therefore, the methods of feature reduction have to be applied. The following feature reduction methods are investigated: principal component analysis, sequential forward selection, sequential backward selection, locality preserving projections and local Fisher discriminant analysis. The combination of the methods of fast Fourier transform, channel variance and principal component analysis performed the best among the combinations of methods. The obtained classification accuracy of the above-mentioned combination of the methods is much higher than that of the individual feature extraction method. The novelty of the approach is based on consolidated sequence of methods for feature extraction and feature reduction.
Moisture Safety of Wooden Buildings – Design, Construction and Operation
Authors: Mjörnell Kristina , Olsson Lars
Published: June 2019

During the last decade, building in wood has increased, mainly due to environmental awareness andtargets to decrease the carbon footprint originated from the production of building materials. Newtechnologies such as CLT (cross laminated timber) have accelerated the construction of multi-storywooden buildings. The CLT structure has been used both for housing and offices. Due to the extensivesize of the buildings and relatively fast assembly of the buildings, weather protection has not alwaysbeen used. It is commonly known that building materials sensitive to moisture need to be protectedagainst high moisture conditions and water during construction. If this is not done, there is an increasedrisk of microbial growth which can result in health problems for future users of the building, extensivecosts for the remediation and exchange of materials, but also lack of trust in the construction industry.There are disagreements between the building industry and researchers how sensitive wooden buildingsare to exposure to high moisture levels and water during storage at sites and construction. Based onresults from several research projects studying moisture conditions both in the laboratory and in thefield, recommendations for procurement, storage and handling of wood during construction to assuremoisture safety are suggested in this paper.
The normative value of political entertainment: Deliberative antecedents and consequences of media users’ entertainment experiences
Authors: Weinmann Carina
Published: June 2019

Dieser Beitrag beschäftigt sich mit den normativen Bedingungen und Wirkungen des Unterhaltungserlebens von Mediennutzerinnen und -nutzern im Kontext politischer Medieninhalte. Auf Basis von Zwei-Prozess-Modellen der Unterhaltung sowie der deliberativen Demokratietheorie wird dabei zum einen ausgearbeitet, inwiefern sich spezifische normative Merkmale politischer Medienangebote auf das Unterhaltungserleben von Mediennutzer/-innen auswirken. Zum anderen wird untersucht, inwiefern dieses Unterhaltungserleben zu internen deliberativen Denkprozessen beitragen kann. Überprüft werden die theoretisch hergeleiteten Effekte und Zusammenhänge durch zwei Befragungsstudien, von denen eine experimentell, die andere korrelativ angelegt ist. Insgesamt ergeben sich aus den Studien gemischte Befunde im Hinblick auf die Auswirkung deliberativer inhaltlicher Merkmale auf das Unterhaltungserleben von Rezipient/-innen. Allerdings zeigen beide Studien, dass sich insbesondere das eudaimonische Unterhaltungserleben von Mediennutzer/-innen positiv auf deliberative Denkprozesse auswirkt.
A Argentina Inflamada de Vogue Paris
Authors:   Universidade do Estado de Santa Catarina, Novelli Daniela
Published: June 2019

A edição francesa do periódico Vogue publicada em fevereiro de 2006, inteiramente consagrada à Argentina, incluindo o editorial de moda Tango des Passions, revelou simbolicamente a aproximação dos laços de transmissão cultural entre a Europa e a Argentina, a partir de uma construção discursiva baseada na philia - uma das atitudes fundamentais que regem a representação do Outro no diálogo intercultural. Realizado por Carine Roitfeld e fotografado por Mario Testino, foi interpretado à luz da teoria de Daniel-Henri Pageaux, que colocou a valorização da “cultura olhada” no centro de uma tensão permanente, cujo espelho reflete um “Eu-narrador” explicitamente duplicado, como um duplo corpo [branco] da alta moda europeia. Seja pelo “temperamento borbulhante”, pelo “teatro da moda”, pelo “excesso latino” ou ainda pela “dor estonteante” atribuídos à imagem da Argentina e à sua própria imagem, Vogue Paris estabelece um diálogo intercultural ambíguo e inflamado.
tRNA ligase structure reveals kinetic competition between non-conventional mRNA splicing and mRNA decay
Authors: Peschek Jirka , Walter Peter
Published: June 2019

Yeast tRNA ligase (Trl1) is an essential trifunctional enzyme that catalyzes exon-exon ligation during tRNA biogenesis and the non-conventional splicing of HAC1 mRNA during the unfolded protein response (UPR). The UPR regulates the protein folding capacity of the endoplasmic reticulum (ER). ER stress activates Ire1, an ER-resident kinase/RNase, which excises an intron from HAC1 mRNA followed by exon-exon ligation by Trl1. The spliced product encodes for a potent transcription factor that drives the UPR. Here we report the crystal structure of Trl1 RNA ligase domain from Chaetomium thermophilum at 1.9 Å resolution. Structure-based mutational analyses uncovered kinetic competition between RNA ligation and degradation during HAC1 mRNA splicing. Incompletely processed HAC1 mRNA is degraded by Xrn1 and the Ski/exosome complex. We establish cleaved HAC1 mRNA as endogenous substrate for ribosome-associated quality control. We conclude that mRNA decay and surveillance mechanisms collaborate in achieving fidelity of non-conventional mRNA splicing during the UPR.
I kjønneste orden?
Authors: Blix Hilde Synnøve , Mittner Lilli , Gjærum Rikke Gürgens
Published: June 2019

Denne artikkelen har som mål å bidra til diskusjoner om begrepet kvalitet slik det framkommer i bedømmelsesprosesser ved professor- og dosentopprykk, gjennom å utforske hvorvidt og hvordan kjønn har betydning for måten kvalitet vurderes og kommer til uttrykk på i slike prosesser. Studien er en analyse av dybdeintervjuer med fem erfarne komitémedlemmer i kunstutdanningsfeltet i Norge. Vår analyse av datamaterialet ledet til tre sentrale diskurser: kvalitetsdiskursen, kjønnsdiskursen og elitediskursen. Studien viser at komitémedlemmene operasjonaliserer sin kvalitetsforståelse med utgangspunkt i markører som arena, publikumstype, nyskaping, samarbeidsrelasjoner og egenart. Samtidig framhever informantene at kvalitetskriteriene i forskriften er for uklare. Disse vage kriteriene for opprykk, sammen med et dominerende elitistisk kunstsyn i kunstutdanningsfeltet, fører ifølge informantene til at de som allerede har definisjonsmakt fortsetter å forvalte rådende definisjoner av kvalitet. Informantene forteller at det er de spesifikt kunstfaglige kriteriene som er vanskeligst å konkretisere. Komitémedlemmene mener at kjønn har en betydning både for måten en bedømmer kvalitet på og måten en fremskriver kvalitet på i egen søknad. Studien viser et eksplisitt behov for tydelig artikulerte kriterier i forskriften for hva som konstituerer kvalitet i utøvende kunst på professor-/dosentnivå i Norge.
Biochemistry and Molecular Biology of Mechanisms of Action of Fibrates – An Overview
Authors: Prasad A.S. V.
Published: June 2019

Fibrates are a class of medication that mainly lowers the blood triglyceride levels. They reduce the LDL and increase the levels of HDL C, in the blood. Clofibrate, the first member to be discovered  in 1962 , and introduced in USA in 1967, is withdrawn in 2002, due to unexplained hepatomegaly, hepato-toxicity and possible risk of hepatic cancer. Other fibrates are introduced in the late 1970s and early 1980s, such as gemfibrozil in the United States and bezafibrate and ciprofibrate in Europe. Their lipid lowering effects are found to decrease CVS risk , progression of atherosclerosis and metabolic syndrome,  macrovascular and microvascular diabetic complications  like stroke, myocardial infarction, peripheral vascular disease  and  diabetic  retinopathy .Various clinical trials like VA-HIT trial (Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial) ,  FIELD trail.  (the Fenofibrate Intervention and Event Lowering in Diabetes) Helsinki Heart Study,   ACCORD -Lipid trial  (The lipid component of the Action to Control Cardiovascular Risk in Diabetes trial ) and  BIP (Bezafibrate Infarction Prevention Study)  trial and angiography trials, like LOCAT (Lopid Coronary Angiography Trial)  and BECLAIT (Bezafibrate Coronary Atherosclerosis Intervention Trial) demonstrated the  beneficial effects of gemfibrozil and fenofibrate.  Their mechanism of action remained obscure for three decades, ie till 1990s, when their mode of action was found. The Mechanism of action of fibrates include limitation of substrate availability for triglyceride synthesis in the liver, promotion of the action of lipoprotein lipase, (LPL)  modulation of low density lipoprotein receptor/ligand interaction and stimulation of reverse cholesterol transport The biochemical and molecular mechanisms involving  the various  enzymes like LCAT (Lecithin-cholesterol acyl transferase)  and CYP7A1 etc.  (cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) ) ,  transporters like ABC , CETP (ATP-binding cassette transporter, Cholesterol ester binding protein) and NTCP, OATP (Na+-dependent taurocholate transporter / organic anion transporters) . These are the.) and nuclear factors like LXR, PPAR alfa etc. (liver orphan receptor α , and peroxisome proliferative nuclear factor) , in relation to the mechanisms  of action of fibrates are discussed . Areas of current interests in literature are briefed.
Antibiotic Susceptibility Profile of Bacteria Isolated from Kenyan Bank Notes Circulating in Nyeri Town
Authors: Muguongo S. G. , Nyamache A. K. , Maingi J. M.
Published: June 2019

Aims: The aim of this study was to characterize bacteria isolated from circulating Kenyan banknotes and also antibiotic susceptibility profiles within Nyeri County.

Study Design:  This was a cross-sectional study and simple random sampling was used to collect 25 of each paper currency denomination.

Place and Duration of Study: Samples analyses were done at Outspan Teaching and Referral Hospital (OTRH) laboratory, between March, 2019 and April, 2019.

Methodology: Total of 125 currencies of five different denominations were collected from different marketing sources such as Butcheries, Restaurants, Health facilities, Mpesa outlets and Transport Saccos and dropped in sterile bags. The bacterial isolates were characterized on the basis of their morphology, staining and biochemical tests. Antibiotic sensitivity tests were done by Kirby Bauer disc diffusion technique.

Results: Total of 19 different bacterial species were isolated from five Kenyan Bank note currencies. Of these, 37 (52.2%) was Staphylococcus aureus followed by Staphylococcus sciuri ssp.lentus 7 (9.9%), Staphylococcus gallinarum 2 (2.8%), Staphylococcus intermedius 6 (8.5%), Micrococcus sp. 1 (1.4%), Staphylococcus schleiferi ssp.coagulans 2 (2.8%), Staphylococcus sciuri ssp.rodentium 1 (1.4%), Kluyvera ascorbata 1 (1.4%), Proteus penneri 1 (1.4%), Aeromonas media 3 (4.2%), Burkholderia cepacia ssp.komplex (1.4%), Aeromonas enteropelogenes 1 (1.4%), Enterobacter cloacae 1 (1.4%), Klebsiella oxytoca 2 (2.8%), Leclercia adecarboxylata 1 (1.4%), Raoultella ornithinolytica 1 (1.4%), Vibrio metschnikovii  1 (1.4%), Myroides odoratus 1 (1.4%) and Yersinia pestis 1 (1.4%). Overall gram positive and gram negative bacterial isolates exhibited resistance to vancomycin, clindamycin and amoxycilin with percentages 40 (71%), 28 (50%), and 37 (66%) and 9 (64%), 8 (57%) and 6 (43%)  respectively.

Conclusion: This study revealed that Kenyan banknote currencies circulating in Nyeri County were contaminated with different pathogenic and potential pathogenic bacteria including multi drug resistant strains. Hence, great care must be taken while handling money during the preparation and handling of food to avoid cross contamination.
New insights into structural and functional relationships between LonA proteases and ClpB chaperones
Authors: Rotanova Tatyana V. , Andrianova Anna G. , Kudzhaev Arsen M. , Li Mi , Botos Istvan , Wlodawer Alexander , Gustchina Alla
Published: June 2019

LonA proteases and ClpB chaperones are key components of the protein quality control system in bacterial cells. LonA proteases form a unique family of ATPases associated with diverse cellular activities (AAA+) proteins due to the presence of an unusual N‐terminal region comprised of two domains: a β‐structured N domain and an α‐helical domain, including the coiled‐coil fragment, which is referred to as HI(CC). The arrangement of helices in the HI(CC) domain is reminiscent of the structure of the H1 domain of the first AAA+ module of ClpB chaperones. It has been hypothesized that LonA proteases with a single AAA+ module may also contain a part of another AAA+ module, the full version of which is present in ClpB. Here, we established and tested the structural basis of this hypothesis using the known crystal structures of various fragments of LonA proteases and ClpB chaperones, as well as the newly determined structure of the Escherichia coli LonA fragment (235–584). The similarities and differences in the corresponding domains of LonA proteases and ClpB chaperones were examined in structural terms. The results of our analysis, complemented by the finding of a singular match in the location of the most conserved axial pore‐1 loop between the LonA NB domain and the NB2 domain of ClpB, support our hypothesis that there is a structural and functional relationship between two coiled–coil fragments and implies a similar mechanism of engagement of the pore‐1 loops in the AAA+ modules of LonAs and ClpBs.
Development and Reproducibility of a First Metatarsophalangeal Joint Osteoarthritis Magnetic Resonance Imaging Scoring System
Authors: Munteanu Shannon E. , Auhl Maria , Tan Jade M. , Landorf Karl B. , Elzarka Ayman , Tan Beng , Menz Hylton B.
Published: June 2019

Objective

To develop a magnetic resonance imaging (MRI) atlas for the assessment of osteoarthritis (OA) of the first metatarsophalangeal (MTP) joint, and to assess its intra‐ and interexaminer reproducibility.

Methods

MRI (proton density with and without fat suppression) was performed on the first MTP joint of 60 participants (30 participants with first MTP joint OA and 30 participants without first MTP joint OA). Characteristic MRI features of OA were then used to develop an MRI atlas of first MTP joint OA. The atlas assessed osteophytes (dorsal metatarsal head, plantar metatarsal head, dorsal proximal phalanx), bone marrow lesions (metatarsal head, proximal phalanx, sesamoids), cysts (metatarsal head, proximal phalanx), effusion‐synovitis (dorsal, plantar), joint space narrowing (metatarsal‐proximal phalanx, metatarsal sesamoids), and cartilage loss. To assess the reproducibility of the atlas, 2 examiners independently rated the MRIs of 30 participants on 2 occasions. Intra‐ and interexaminer reproducibility were determined using percentage agreement and Gwet's AC1.

Results

Observations using the atlas demonstrated fair‐to‐perfect intraexaminer reproducibility (percentage agreement from 67% to 100%, and Gwet's AC1 from 0.38 to 1.00) and fair‐to‐almost‐perfect interexaminer reproducibility (percentage agreement from 67% to 98%, and Gwet's AC1 from 0.40 to 0.96).

Conclusion

An MRI scoring system for the assessment of OA of the first MTP joint has been developed. The atlas demonstrates excellent intra‐ and interexaminer reproducibility. The atlas has the potential to allow for a better understanding of the cause(s) of pain in first MTP joint OA.
Enhanced adaptive control for a benchmark piezoelectric‐actuated system via fuzzy approximation
Authors: Yousef Hassan A , Hamdy Mohamed , Saleem Ashraf , Nashed Kyrillos , Mesbah Mustafa , Shafiq Muhammad
Published: June 2019

This paper investigates the problem of the high precision tracking control of piezoelectric actuators (PEAs) without using the inverse of the uncertain hysteresis. Based on fuzzy system approximator and particle swarm optimization (PSO) algorithm, a proposed enhanced
adaptive controller is developed. The proposed controller provides fast and robust adaptation simultaneously with guaranteed desired transient performance. Moreover, it has a simple form and requires fewer adaptation parameters. The adaptation gain is determined via PSO algorithm. The proposed controller is tested on a lab‐scale PEA system. Experimental results with comparative studies with different techniques have been developed. The simulation results reveal that the proposed controller outperforms the other controllers in terms of normalized root‐mean‐square and maximum tracking errors for different frequencies.
Pyridyl Disulfide Functionalized Polymers as Nanotherapeutic Platforms
Authors: Sui Binglin , Cheng Chen , Xu Peisheng
Published: June 2019

With the development of modern polymer synthesis techniques, polymer therapeutics have emerged and rapidly grown into a research hotspot and a promising tool for biomedical applications owing to their outstanding advantages in comparison to conventional drug therapy. Among an enormous number of polymers developed for therapeutic purposes, pyridyl disulfide (PD) group functionalized polymers have attracted increasing attention over the past decades. The highly reactive PD group could be replaced by almost any thiol‐containing groups, leading to the production of a disulfide bond. More importantly, the redox‐sensitive disulfide bond generated from the replacement can be exploited to develop stimuli‐responsive polymer therapeutics which will protect the loaded cargoes from premature leakage, while programmably releasing them in response to endogenous redox stimuli such as glutathione. Herein, the development of PD‐incorporated polymers and summarized PD‐based monomers that have been synthesized to prepare various functional polymeric architectures are reviewed. Moreover, this review also discusses the difference between polymers with PD as repeating pendants or terminal groups and emphasizes on the diverse promising applications of these polymers as nanotherapeutic platforms in the biomedical field.
A Generalized Crystallization Protocol for Scalable Deposition of High‐Quality Perovskite Thin Films for Photovoltaic Applications
Authors: Guo Fei , Qiu Shudi , Hu Jinlong , Wang Huahua , Cai Boyuan , Li Jianjun , Yuan Xiaocong , Liu Xianhu , Forberich Karen , Brabec Christoph J. , Mai Yaohua
Published: June 2019

Metal halide perovskite solar cells (PSCs) have raised considerable scientific interest due to their high cost‐efficiency potential for photovoltaic solar energy conversion. As PSCs already are meeting the efficiency requirements for renewable power generation, more attention is given to further technological barriers as environmental stability and reliability. However, the most major obstacle limiting commercialization of PSCs is the lack of a reliable and scalable process for thin film production. Here, a generic crystallization strategy that allows the controlled growth of highly qualitative perovskite films via a one‐step blade coating is reported. Through rational ink formulation in combination with a facile vacuum‐assisted precrystallization strategy, it is possible to produce dense and uniform perovskite films with high crystallinity on large areas. The universal application of the method is demonstrated at the hand of three typical perovskite compositions with different band gaps. P‐i‐n perovskite solar cells show fill factors up to 80%, underpinning the statement of the importance of controlling crystallization dynamics. The methodology provides important progress toward the realization of cost‐effective large‐area perovskite solar cells for practical applications.
Dihydrosulfenylation of Alkynes with Thiols Using a Nickel Catalyst through a Radical Process
Authors: Taniguchi Nobukazu , Kitayama Kenji
Published: June 2019

The dihydrosulfenylation of alkynes by thiols was achieved in the presence of a nickel catalyst under aerobic conditions. The reaction proceeded by employing a radical process, and anti‐Markovnikov type dithioacetals were regioselectively synthesized. The nickel catalyst efficiently promoted the procedure using alkyl alkynes or alkyl thiols.
Smoking and stroke: A mendelian randomization study
Authors: Larsson Susanna C. , Burgess Stephen , Michaëlsson Karl
Published: June 2019

We used the Mendelian randomization design to explore the potential causal association of smoking with ischemic stroke and intracerebral hemorrhage using summary statistics data for 34,217 ischemic stroke cases and 404,630 noncases, and 1,545 cases of intracerebral hemorrhage and 1,481 noncases. Genetic predisposition to smoking initiation (ever smoking regularly), based on up to 372 single‐nucleotide polymorphisms, was statistically significantly positively associated with any ischemic stroke, large artery stroke, and small vessel stroke but not cardioembolic stroke or intracerebral hemorrhage. This study provides genetic support for a causal association of smoking with ischemic stroke, particularly large artery and small vessel stroke. ANN NEUROL 2019;86:468–471
Ultrasensitive Detection of Salmonella and Listeria monocytogenes by Small‐Molecule Chemiluminescence Probes
Authors: Roth‐Konforti Michal , Green Ori , Hupfeld Mario , Fieseler Lars , Heinrich Nadine , Ihssen Julian , Vorberg Raffael , Wick Lukas , Spitz Urs , Shabat Doron
Published: June 2019

Detection of Salmonella and L. monocytogenes in food samples by current diagnostic methods requires relatively long time to results (2–6 days). Furthermore, the ability to perform environmental monitoring at the factory site for these pathogens is limited due to the need for laboratory facilities. Herein, we report new chemiluminescence probes for the ultrasensitive direct detection of viable pathogenic bacteria. The probes are composed of a bright phenoxy‐dioxetane luminophore masked by triggering group, which is activated by a specific bacterial enzyme, and could detect their corresponding bacteria with an LOD value of about 600‐fold lower than that of fluorescent probes. Moreover, we were able to detect a minimum of 10 Salmonella cells within 6 h incubation. The assay allows for bacterial enrichment and detection in one test tube without further sample preparation. We anticipate that this design strategy will be used to prepare analogous chemiluminescence probes for other enzymes relevant to specific bacteria detection and point‐of‐care diagnostics.
Guiding Drugs to Target‐Harboring Organelles: Stretching Drug‐Delivery to a Higher Level of Resolution
Authors: Louzoun‐Zada Sivan , Jaber Qais Z. , Fridman Micha
Published: June 2019

The ratio between the dose of drug required for optimal efficacy and the dose that causes toxicity is referred to as the therapeutic window. This ratio can be increased by directing the drug to the diseased tissue or pathogenic cell. For drugs targeting fungi and malignant cells, the therapeutic window can be further improved by increasing the resolution of drug delivery to the specific organelle that harbors the drug's target. Organelle targeting is challenging and is, therefore, an under‐exploited strategy. Here we provide an overview of recent advances in control of the subcellular distribution of small molecules with the focus on chemical modifications. Highlighted are recent examples of active and passive organelle‐specific targeting by incorporation of organelle‐directing molecular determinants or by chemical modifications of the pharmacophore. The outstanding potential that lies in the development of organelle‐specific drugs is becoming increasingly apparent.
Phosphorus Analogues of Methyl Nitrite and Nitromethane: CH3OPO and CH3PO2
Authors: Zhao Xiaofang , Chu Xianxu , Rauhut Guntram , Chen Changyun , Song Chao , Lu Bo , Zeng Xiaoqing
Published: June 2019

Methoxyphosphinidene oxide (CH3OPO) and isomeric methyldioxophosphorane (CH3PO2) are key intermediates in the degradation of organophosphorus compounds (OPCs). Unlike the nitrogen analogues CH3ONO and CH3NO2, the experimental data for these two prototypical OPCs are scarce. By high‐vacuum flash pyrolysis (HVFP) of the diazide CH3OP(O)(N3)2 at 1000 K, the cis and trans conformers of CH3OPO have been generated in the gas phase and subsequently isolated in cryogenic Ar and N2 matrices for IR spectroscopic characterization. Upon 266 nm laser irradiation of CH3OPO, cis→trans conformational conversion occurs with concurrent isomerization to CH3PO2. The spectroscopic identification of CH3OPO and CH3PO2 is supported by D‐, 13C‐, and 18O‐isotope labeling and quantum chemical calculations at the CCSD(T)‐F12a/cc‐pVTZ‐F12 level using configuration‐selective vibrational configuration interaction (VCI).
Hydrogen Bond Directed ortho‐Selective C−H Borylation of Secondary Aromatic Amides
Authors: Bai Shao‐Tao , Bheeter Charles B. , Reek Joost N. H.
Published: June 2019

Reported is an iridium catalyst for ortho‐selective C−H borylation of challenging secondary aromatic amide substrates, and the regioselectivity is controlled by hydrogen‐bond interactions. The BAIPy‐Ir catalyst forms three hydrogen bonds with the substrate during the crucial activation step, and allows ortho‐C−H borylation with high selectivity. The catalyst displays unprecedented ortho selectivities for a wide variety of substrates that differ in electronic and steric properties, and the catalyst tolerates various functional groups. The regioselective C−H borylation catalyst is readily accessible and converts substrates on gram scale with high selectivity and conversion.
Metal‐Free Oxidative B−N Coupling of nido‐Carborane with N‐Heterocycles
Authors: Yang Zhongming , Zhao Weijia , Liu Wei , Wei Xing , Chen Meng , Zhang Xiao , Zhang Xiaolei , Liang Yong , Lu Changsheng , Yan Hong
Published: June 2019

A general method for the oxidative substitution of nido‐carborane (7,8‐C2B9H12−) with N‐heterocycles has been developed by using 2,3‐dichloro‐5,6‐dicyanobenzoquinone (DDQ) as an oxidant. This metal‐free B−N coupling strategy, in both inter‐ and intramolecular fashions, gave rise to a wide array of charge‐compensated, boron‐substituted nido‐carboranes in high yields (up to 97 %) with excellent functional‐group tolerance under mild reaction conditions. The reaction mechanism was investigated by density‐functional theory (DFT) calculations. A successive single‐electron transfer (SET), B−H hydrogen‐atom transfer (HAT), and nucleophilic attack pathway is proposed. This method provides a new approach to nitrogen‐containing carboranes with potential applications in medicine and materials.
Asymmetric Catalytic Formal 1,4‐Allylation of β,γ‐Unsaturated α‐Ketoesters: Allylboration/Oxy‐Cope Rearrangement
Authors: Tang Qiong , Fu Kai , Ruan Peiran , Dong Shunxi , Su Zhishan , Liu Xiaohua , Feng Xiaoming
Published: June 2019

A highly enantioselective formal conjugate allyl addition of allylboronic acids to β,γ‐unsaturated α‐ketoesters has been realized by employing a chiral NiII/N,N′‐dioxide complex as the catalyst. This transformation proceeds by an allylboration/oxy‐Cope rearrangement sequence, providing a facile and rapid route to γ‐allyl‐α‐ketoesters with moderate to good yields (65–92 %) and excellent ee values (90–99 % ee). The isolation of 1,2‐allylboration products provided insight into the mechanism of the subsequent oxy‐Cope rearrangement reaction: substrate‐induced chiral transfer and a chiral Lewis acid accelerated process. Based on the experimental investigations and DFT calculations, a rare boatlike transition‐state model is proposed as the origin of high chirality transfer during the oxy‐Cope rearrangement.
Fibrocytes in Chronic Periaortitis: A Novel Mechanism Linking Inflammation and Fibrosis
Authors: Nicastro Maria , Vescovini Rosanna , Maritati Federica , Palmisano Alessandra , Urban Maria L. , Incerti Monia , Fenaroli Paride , Peyronel Francesco , Benigno Giuseppe D. , Mangieri Domenica , Volpi Riccardo , Becchi Gabriella , Romagnani Paola , Corradi Domenico , Vaglio Augusto
Published: June 2019

Objective

Chronic periaortitis (CP) is a rare disease characterized by periaortic and periiliac fibroinflammatory tissue. The pathogenic mechanisms leading to tissue accumulation and activation of fibroblasts are unclear. This study was undertaken to explore the role of fibrocytes, circulating precursors of tissue fibroblasts, in patients with CP.

Methods

We studied 44 patients with newly diagnosed CP and 30 healthy controls. Circulating fibrocytes were identified as Col1+CD45+ cells using flow cytometry. Retroperitoneal tissue biopsy samples from 9 CP patients were stained with anti–type I procollagen, anti‐CXCR4, and anti‐CD45 antibodies and analyzed by confocal microscopy to detect tissue‐infiltrating fibrocytes. Circulating levels and tissue expression of CXCL12, a CXCR4 ligand that promotes fibrocyte homing, were investigated using enzyme‐linked immunosorbent assay and immunohistochemistry, respectively. We also characterized T helper polarization in biopsy samples from CP patients and measured serum levels of a panel of cytokines that are hallmarks of T helper responses and capable of influencing fibrocyte differentiation.

Results

The frequency of circulating Col1+CD45+ fibrocytes was higher in patients than in controls (P = 0.0371). CD45+proCol1+ and CXCR4+proCol1+ cells were detected in all examined biopsy samples from CP patients. Serum levels of CXCL12 were also higher in CP patients than controls (P = 0.0056), and tissue‐infiltrating inflammatory cells intensely expressed CXCL12. Increased serum levels of Th2 cytokines (e.g., interleukin‐13 [IL‐13] and IL‐10) were found in patients, and immunohistochemistry revealed a dominant infiltration of GATA‐3+ cells, also indicating Th2 polarization; Th2‐skewed responses are known to promote fibrocyte differentiation.

Conclusion

Our findings indicate that fibrocytes are enriched in the peripheral blood of CP patients and infiltrate target lesions. The accumulation of fibrocytes in the pathologic tissue might be driven by CXCL12, and Th2‐skewed immune responses are likely to facilitate their differentiation.
Initiated by CREB: Resolving Gene Regulatory Programs in Learning and Memory
Authors: Kaldun Jenifer C. , Sprecher Simon G.
Published: June 2019

Consolidation of long‐term memory is a highly and precisely regulated multistep process. The transcription regulator cAMP response element‐binding protein (CREB) plays a key role in initiating memory consolidation. With time processing, first the cofactors are changed and, secondly, CREB gets dispensable. This ultimately changes the expressed gene program to genes required to maintain the memory. Regulation of memory consolidation also requires epigenetic mechanisms and control at the RNA level. At the neuronal circuit level, oscillation in the activity of CREB and downstream factor define engram cells. Together the combination of all regulation mechanisms allows correct memory processing while keeping the process dynamic and flexible to adjust to different contexts. Also see the video abstract here https://youtu.be/BhSCSmorpEc.
Engineering of alcohol dehydrogenase 2 hybrid‐promoter architectures in Pichia pastoris to enhance recombinant protein expression on ethanol
Authors: Ergün Burcu Gündüz , Gasser Brigitte , Mattanovich Diethard , Çalık Pınar
Published: June 2019

The aim of this work is to increase recombinant protein expression in Pichia pastoris over the ethanol utilization pathway under novel‐engineered promoter variants (NEPVs) of alcohol dehydrogenase 2 promoter (PADH2) through the generation of novel regulatory circuits. The NEPVs were designed by engineering of transcription factor binding sites (TFBSs) determined by in silico analyses and manual curation systematically, by (a) single‐handedly replacement of specified TFBSs with synthetic motifs for Mxr1, Cat8, and Aca1 binding, and synthetic TATA‐box integration; and, (b) nucleosome optimization. PADH2‐Cat8‐L2 and PADH2‐Cat8‐L1 designed by the integration of synthetic Cat8 binding sites were superior, and then PADH2‐NucOpt. Compared to that with PADH2 at t = 20 hr of the fermentations, PADH2‐Cat8‐L2 allowed the highest increase in enhanced green fluorescent protein expression as 4.8‐fold on ethanol and 3.8‐fold on methanol; and, PADH2‐NucOpt upregulated the expression 1.5‐fold on ethanol and enhanced 3.2‐fold on methanol. Using the superior two tools, Cat8‐L2 and NucOpt, we designed PADH2‐NucOpt‐Cat8‐L2. With PADH2‐NucOpt‐Cat8‐L2, the expression in the fermentation of ethanol was upregulated 3.7‐fold that is distinctly higher than that with PADH2‐NucOpt but lower than that with PADH2‐Cat8‐L2; while on methanol compared to that with PADH2, the expression was enhanced 8.8‐fold. Extracellular recombinant human serum albumin production was also studied with PADH2‐Cat8‐L2 and PADH2‐NucOpt, and average recombinant human serum albumin yield (YP/X) on ethanol was 1.13 and 0.38 mg/gWCW, respectively; whereas with PADH2, YP/X was 0.26 mg/gWCW. We conclude that as upregulation of transcription and enhanced expression correlate with the sequence of synthetic motifs and their location in the hybrid‐promoter architectures of NEPVs in coordination with trans‐acting factors, which are the design parameters in the engineering of binding sites; the NEPVs generated promising recombinant protein production platforms with a high impact on industrial scale production processes, as well as would open up new avenues for research in P. pastoris.
Facile synthesis of (−)‐vibo‐quercitol from maltodextrin via an in vitro synthetic enzymatic biosystem
Authors: Bai Xue , Meng Dongdong , Wei Xinlei , Zhou Xigui , Lu Fuping , You Chun
Published: June 2019

(−)‐vibo‐Quercitol (VQ: 1L‐1,2,4/3,5‐cyclohexanepentol), a form of deoxyinositol, is an alternative chiral building block in the synthesis of bioactive compounds to control diabetes. In this study, an adenosine triphosphate‐free in vitro synthetic enzymatic biosystem composed of five enzymes (including one enzyme for NADH regeneration) was constructed to produce VQ from maltodextrin in one‐pot. After optimization of reaction conditions, 7.6 g/L VQ was produced from 10 g/L maltodextrin with a product yield (mol/mol) of 77%, and 25.3 g/L VQ with a purity of 87% was produced from 50 g/L maltodextrin through simple scaling up of this nonfermentative enzymatic biosystem. Therefore, this study provides an economical and environmentally friendly method for the envisioned quercitol biosynthesis.
Morphology of Osteogenesis Imperfecta Collagen Mimetic Peptide Assemblies Correlates with the Identity of Glycine‐Substituting Residue
Authors: Yao Linyan , Liu Zhao , Yu Jingyuan , Luo Liting , Wang Jie , Xiao Jianxi
Published: June 2019

Osteogenesis imperfecta (OI) is a hereditary bone disorder with various phenotypes ranging from mild multiple fractures to perinatal lethal cases, and it mainly results from the substitution of Gly by a bulkier residue in type I collagen. Triple‐helical peptide models of Gly mutations have been widely utilized to decipher the etiology of OI, although these studies are mainly limited to characterizing the peptide features, such as stability and conformation in the solution state. Herein, we have constructed a new series of triple‐helical peptides DD(GPO)5ZPO(GPO)4DD (Z=Ala, Arg, Asp, Cys, Glu, Ser, and Val) mimicking the most common types of observed OI cases. The inclusion of special terminal aspartic acids enables these collagen mimetic peptides to self‐assemble to form nanomaterials upon the trigger of lanthanide ions. We have for the first time systematically evaluated the effect of different OI mutations on the aggregated state of collagen mimetic peptides. We have revealed that the identity of the Gly‐substituting residue plays a determinant role in the morphology and secondary structure of the collagen peptide assemblies, showing that bulkier residues tend to result in a disruptive secondary structure and defective morphology, which lead to more severe OI phenotypes. These findings of osteogenesis imperfecta collagen mimetic peptides in the aggregation state provide novel perspectives on the molecular mechanism of osteogenesis imperfecta, and may aid the development of new therapeutic strategies.
Tying the knot: An uncommon complication
Authors: Boumpoulis Konstantinos , Chatzis Andrew C. , Balanika Marina , Milonakis Michael , Khoury Mazen
Published: June 2019

Cardiothoracic procedures require continuous hemodynamic monitoring and a fair proportion of these require the insertion of a pulmonary artery catheter, known also as Swan‐Ganz catheter. Given, however, the invasive nature of these procedures, unforeseen complications may ensue. Early recognition and appropriate handling are essential to minimize adverse outcomes.
Indolent Propionibacterium acnes infection associated with orthopedic hardware in the ankle: A case report and literature review
Authors: Arain Abdul R. , Sullivan Connor W. , Angelicola‐Richardson Kyle , Haddad Stefanos , Rosenbaum Andrew
Published: June 2019

Propionibacterium acnes (P. acnes) infections of the foot and ankle are very rare and require a unique approach to prevention, diagnosis, and treatment. Clinicians should consider P. acnes as a cause for all late and indolent orthopedic infections, as appropriate surgical and medical management can result in a good outcome.
Insight into the Role of Water on the Methylation of Hexamethylbenzene in H‐SAPO‐34 from First Principle Molecular Dynamics Simulations
Authors: Bailleul Simon , Rogge Sven M. J. , Vanduyfhuys Louis , Van Speybroeck Veronique
Published: June 2019

The methylation of hexamethylbenzene with methanol is one of the key reactions in the methanol‐to‐olefins hydrocarbon pool reaction cycle taking place over the industrially relevant H‐SAPO‐34 zeolite. This methylation reaction can occur either via a concerted or via a stepwise mechanism, the latter being the preferred pathway at higher temperatures. Herein, we systematically investigate how a complex reaction environment with additional water molecules and higher concentrations of Brønsted acid sites in the zeolite impacts the reaction mechanism. To this end, first principle molecular dynamics simulations are performed using enhanced sampling methods to characterize the reactants and products in the catalyst pores and to construct the free energy profiles. The most prominent effect of the dynamic sampling of the reaction path is the stabilization of the product region where water is formed, which can either move freely in the pores of the zeolite or be stabilized through hydrogen bonding with the other protic molecules. These protic molecules also stabilize the deprotonated Brønsted acid site, created due to the formation of the heptamethylbenzenium cation, via a Grotthuss‐type mechanism. Our results provide fundamental insight in the experimental parameters that impact the methylation of hexamethylbenzene in H‐SAPO‐34, especially highlighting and rationalizing the crucial role of water in one of the main reactions of the aromatics‐based reaction cycle.
Recent Progress in Ruthenium Oxide‐Based Composites for Supercapacitor Applications
Authors: Majumdar Dipanwita , Maiyalagan Thandavarayan , Jiang Zhongqing
Published: June 2019

Electrochemical energy storage has emerged as one of the principal topics of present‐day research to deal with the high energy demands of modern society. Accordingly, besides fuel cells and battery technologies, interesting and challenging results have been observed in the recent past, during the materialization of “supercapacitors” or “ultracapacitors”, which have provoked a sharp increase in research inclination to revisit this aspect of renewable and sustainable energy storage. Supercapacitor performances are largely dependent on electrode materials, the nature of the electrolyte used, and the range of voltage windows employed. Carbon‐based electrode materials have tunable properties such as electrical conductivity, extensive surface area, and faster electron transfer kinetics with low fabrication costs. But their specific capacitances are found to be too low for commercialization. Ruthenium dioxide (RuO2), owing to its high theoretical specific capacitance value (1400–2000 F g−1), has been extensively recognized as a favorable material for supercapacitor devices, but high production cost and agglomeration effects stand as high barriers preventing marketable usage. Consequently, RuO2‐based nanocomposites have been widely studied to optimize the material cost, with simultaneous improvement in the electrochemical performances. This Review describes comprehensively the recent progress in terms of the fabrication and design, electrochemical performance, and achievements of RuO2 and its nanocomposites as electrode materials for supercapacitors, which will be beneficial for further research designing high‐performance supercapacitor devices.
Physicochemical and Electrochemical Properties of 1,1,2,2‐Tetrafluoroethyl‐2,2,3,3‐Tetrafluoropropyl Ether as a Co‐Solvent for High‐Voltage Lithium‐Ion Electrolytes
Authors: Xia Lan , Lee Saixi , Jiang Yabei , Li Shiqi , Liu Zhaoping , Yu Linpo , Hu Di , Wang Shuhan , Liu Yitong , Chen George Z.
Published: June 2019

Although high‐voltage positive electrode materials for high energy density lithium‐ion batteries have gained a great attention, the lack of compatible electrolytes with sufficiently high oxidative stability to deliver an excellent cycling ability restricts their practical application. Fluorinated solvents are considered as promising candidates for high‐voltage electrolyte solvents. In this study, we select 1,1,2,2‐tetrafluoroethyl‐2,2,3,3‐tetrafluoropropyl ether (TTE) with a high boiling point, low cost, and good SEI‐filming ability as a co‐solvent of fluoroethylene carbonate‐based electrolytes and extensively investigate its physicochemical and electrochemical properties for applications in high‐voltage lithium‐ion batteries. Our experimental results show that the TTE‐containing electrolyte exhibits not only a high oxidative stability up to 5.5 V (vs. Li/Li+), but also excellent wettability with the separator. In addition to high discharge capacity and increased coulombic efficiency of the Li/LiNi0.5Mn1.5O4 half‐cell assembled with the TTE‐containing electrolyte cycled between 3.0 and 4.9 V, the cell also displays a high rate capability. This work shows that partially fluorinated ethers, e. g., TTE, are promising co‐solvents for high‐voltage electrolytes that can enable commercial development of high energy density lithium‐ion batteries.