bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaborative configuration for distributed energy storages and cyber systems in low‐voltage distribution networks with high penetration of PV systems
Authors: Cai Yongxiang , Tang Wei , Zhang Bo , Wang Yue
Published: July 2018

Energy storage systems (ESSs) have recently been incorporated into low‐voltage distribution networks (DNs) for promoting hosting capacity of photovoltaic (PV) systems. On the other hand, applications of information communications technologies enhance the self‐regulation ability of LVDNs and are playing an important role to resolve integration problems of PV systems. Although the two aspects influence each other, they are generally configured separately in LVDNs. This study proposes a collaborative configuration scheme based on a bi‐level optimisation model for distributed ESSs and cyber systems in LVDNs with high penetration of PV systems. In the upper level, the ESSs and wireless control terminals are deployed to minimise investment and operation cost with consideration of specific control of ESSs. In the lower level, communication topology is further optimised according to the upper‐level results to promote control performance and balance communication topology complexity. The economy and effectiveness of the proposed configuration scheme are demonstrated by comparing with separated cyber and physical configuration schemes in case studies.
Internet of things: how the electrical grid can be controlled and managed in other dimensions
Authors: Cárdenas Jorge , Menéndez David
Published: July 2018

The ‘Internet of things’ is the ‘new revolution’. During the past decades, there were major changes in the energy industry: the increased implementation of renewable generation, together with a greater use of electronic power elements in the network such as high‐voltage DC links and the use of flexible AC transmission system and new market requirements, introduce new challenges and a need for more intelligent assets monitoring; and additional optimisation with a better balance in the combination of different energy sources and thus guaranteeing the reliability of supply and quality of energy; together with the identification of new business models that allow the integration of new technologies, neutralising cyber threats and ensure an adequate dissemination of knowledge to new generations. Companies are migrating to a more digital model based fundamentally on three pillars: communications, big data and artificial intelligence. The right combination of these three pillars will optimise the operation of the electrical system, reducing costs and polluting emissions, accelerating the adoption of non‐polluting energies and renewable energies, while maximising economic performance and a closer way of interacting with users. The industrial Internet of things (IIoT) has been identified as one of the technologies with most potential impact in the next years.
Observations of solar chromospheric heating at sub-arcsec spatial resolution
Authors: Smitha H. N. , Chitta L. P. , Wiegelmann T. , Solanki S. K.
Published: July 2018

A wide variety of phenomena such as gentle but persistent brightening, dynamic slender features (∼100 km), and compact (∼1″) ultraviolet (UV) bursts are associated with the heating of the solar chromosphere. High spatio-temporal resolution is required to capture the finer details of the likely magnetic reconnection-driven, rapidly evolving bursts. Such observations are also needed to reveal their similarities to large-scale flares, which are also thought to be reconnection driven, and more generally their role in chromospheric heating. Here we report observations of chromospheric heating in the form of a UV burst obtained with the balloon-borne observatory SUNRISE. The observed burst displayed a spatial morphology similar to that of a large-scale solar flare with a circular ribbon. While the co-temporal UV observations at 1.5″ spatial resolution and 24 s cadence from the Solar Dynamics Observatory showed a compact brightening, the SUNRISE observations at diffraction-limited spatial resolution of 0.1″ at 7 s cadence revealed a dynamic substructure of the burst that it is composed of an extended ribbon-like feature and a rapidly evolving arcade of thin (∼0.1″) magnetic loop-like features, similar to post-flare loops. Such a dynamic substructure reveals the small-scale nature of chromospheric heating in these bursts. Furthermore, based on magnetic field extrapolations, this heating event is associated with a complex fan-spine magnetic topology. Our observations strongly hint at a unified picture of magnetic heating in the solar atmosphere from some large-scale flares to small-scale bursts, all associated with such a magnetic topology.
Molecular characterization and new genotypes of Enterocytozoon bieneusi in minks (Neovison vison) in China
Authors: Cong Wei , Qin Si-Yuan , Meng Qing-Feng
Published: July 2018

Microsporidiosis is an emerging and opportunistic disease, and Enterocytozoon bieneusi is the main cause of this disease in humans. Little information is available on prevalence and genotyping of E. bieneusi in minks. We collected 559 feces samples of minks from Heilongjiang and Jilin provinces in 2017, and studied E. bieneusi prevalence by nested PCR. A total of 23 out of 559 minks (4.1%) were detected as E. bieneusi-positive, and were raised in five of the seven investigated farms. Age was the only risk factor associated with E. bieneusi prevalence in investigated minks through logistic regression analysis. Sequence analysis of the ITS gene revealed that five E. bieneusi ITS genotypes, including Peru11, EbpC, and three novel genotypes (HLJM-1, HLJM-2 and JLM-1) were present, suggesting minks may be a potential source of human microsporidiosis.
Nachbehandlung einer komplizierten Knieverletzung – ein Fallbeispiel
Authors: Bakodi René
Published: July 2018

Erik hat sich eine komplizierte Verletzung am Knie zugezogen. Drei verschiedene Strukturen sind betroffen, von denen jede für sich ein bestimmtes
Nachbehandlungsschema erfordert. Wie Erik dennoch eine gute Funktion innerhalb der ersten drei postoperativen Monate erreicht, erläutert René Bakodi.
Behandlung einer Patientin mit möglicher Frozen Shoulder auf sichere und einfache Weise (KISS)
Authors: Westerhuis Pieter
Published: July 2018

Die klassischen Symptome der Frozen Shoulder sind Steifigkeit und Schmerzen in der Schulter.

Bei der hier vorgestellten 60-jährigen Patientin manifestierten sich bei Schulterbewegungen hauptsächlich Bewegungseinschränkungen und kaum Schmerzempfindungen.

Dieser Fallbericht beschreibt einen pragmatischen und realistischen Behandlungsansatz sowie den Clinical-Reasoning-Prozess bei Frozen-Shoulder-Syndrom.
Assessment: Quality of Life Profile for Spinal Disorders (QLPSD) – Deutsche Version – Lebensqualität von Menschen mit Skoliose erheben
Authors: Kroggel Lena , Kraus Laurent
Published: July 2018

Viele Menschen mit einer Skoliose sind in ihrer Beweglichkeit eingeschränkt und haben Schmerzen. Meist leidet auch ihre Lebensqualität. Die subjektive Sicht der Patienten lässt sich mit dem QLPSD erfassen.
Stereodynamic Analysis of New Atropisomeric 4,7-Di(naphthalen-1-yl)-5,6-dinitro-1H-indoles
Authors: Petrillo Giovanni , Mancinelli Michele , Pagano Angela , Marotta Emanuela , Mazzanti Andrea , Tavani Cinzia
Published: July 2018

A series of atropisomeric molecules containing the indole ring and two stereogenic axes were prepared. The four atropisomers were resolved by enantioselective HPLC. The rotational barriers of the indole–naphthyl axes were evaluated by means of kinetic analysis either by NMR or enantioselective HPLC. The absolute configuration of the ­atropisomers was determined by a combination of X-ray spectroscopy and TD-DFT simulation of electronic circular dichroism spectra.
From Natural to Artificial Antitumor Lipidic Alkynylcarbinols: Asymmetric Synthesis, Enzymatic Resolution, and Refined SARs
Authors: Génisson Yves , Maraval Valérie , Chauvin Remi , Listunov Dymytrii , Joly Etienne , Rullière Pauline , Gaspard Hafida , Bernardes-Génisson Vania
Published: July 2018

Among acetylenic natural products, chiral lipidic alkynylcarbinol (LAC) metabolites, mostly extracted from marine sponges, have revealed a broad spectrum of biological activities, in particular, remarkable antitumor cytotoxicity. With reference to one of the simplest natural representatives, [(S)-eicos-(4E)-en-1-yn-3-ol], and a given cancer cell line (HCT116), combined extensive efforts in chemical synthesis (relying on the use of a large chemical toolbox) and biological analysis (in vitro tests), have provided systematic structure–activity relationships (SARs) where the initially selected four structural parameters appear as independent principal components: (i) and (ii) the sp/sp2 content and extent of the terminal and internal unsaturations adjacent to the carbinol center, (iii) the absolute configuration of the latter, (iv) the length of the n-aliphatic backbone. Two key criteria have also been established regarding the functional alkynylcarbinol pharmacophore: the alkynylcarbinol unit must be both secondary and terminal (i.e., substituted by a short ethynyl or ethenyl C2 group). This review is intended to provide a further illustration of the value of a simple rational approach for drug design, and to act as a benchmark for future optimization of LACs as antitumor agents.

1 Introduction

2 2C2-Unsaturated Pharmacophore Candidates

2.1 Alkenylalkynylcarbinols (AACs)

2.2 Dialkynylcarbinols (DACs or DACys)

2.3 Alkynylalkenylcarbinols (iso-AACs) and Dialkenylcarbinols (DACes)

2.4 Oxidation-Protected Dialkynylcarbinols and Dialkynylketones

2.5 Fluorophore-Labeled Lipidic Dialkynylcarbinols

3 C2/C3-Unsaturated Pharmacophore Candidates

3.1 Cyclopropylalkynylcarbinols (CACs)

3.2 Allenylalkynylcarbinols (AllACs)

4 C2/C4- and 3C2-Unsaturated Pharmacophore Candidates

4.1 Butadiynylalkynylcarbinols (BACs)

4.2 Trialkynylcarbinols (TACs)

5 Double-AC-Headed Pharmacophore Candidates

6 Screening on the Lipidic Chain Length

7 Conclusion
Synthesis of Functionalized 1,4-Dioxanes with an Additional (Hetero)Aliphatic Ring
Authors: Grygorenko Oleksandr , Bondarenko Andriy , Tolmachev Andrey , Vashchenko Bohdan
Published: July 2018

An approach to the preparation of 2-mono-, 2,2- and 2,3-disubstituted 1,4-dioxane derivatives is described. The reaction sequence commences from readily available epoxides, in most cases prepared via the Corey–Chaikovsky reaction of the corresponding aldehydes and ketones. The key step of the method is epoxide ring opening with ethylene glycol monosodium salt, followed by further cyclization of the diols obtained. The utility of the approach was demonstrated by multigram preparation of novel functionalized 1,4-dioxanes bearing additional cycloalkane, piperidine or pyrrolidine rings, mostly spirocyclic compounds, which are advanced building blocks for medicinal chemistry.
Electrical Aggregometry in Whole Blood from Human, Pig and Rabbit
Authors: Galvez Angel E , Badimon Lina , Badimon Juan-Jose , Fuster Valentin
Published: July 2018

The objective of this study was to characterize and standardize whole blood electrical aggregometry (WBEA) in the pig and rabbit, animal models extensively used in atherosclerosis research, and to compare their platelet response with that of man. Platelet aggregation was studied in blood (WBEA) and platelet rich plasma (optical aggregometry, OA). Dose response curves were obtained for ADP and collagen. The effect of hematocrit on WBEA was also evaluated. Aggregation with ADP and collagen using WBEA was more extensive with human than with pig or rabbit platelets. OA revealed similar differences among species but the time to reach maximal aggregation was markedly shorter. Using WBEA, the extent of aggregation was inversely related to the hematocrit. We conclude that WBEA is a useful technique that may be of particular importance in situations where hyper-lipidemic plasma prevents the use of OA, as occurs in some atherosclerosis research animal models.
Anticoagulant Activities of Pentosan Polysulphate (Hémoclar) Due to Release of Hepatic Triglyceride Lipase (HTGL)
Authors: Barrowcliffe T W , Gray E , Merton R E , Dawes J , Jennings C A , Hubbard A R , Thomas D P
Published: July 2018

Subcutaneous injections of 50 mg pentosan poly sulphate (Hemoclar) were given to normal volunteers and the effects on anti-Factor Xa activity, thrombin generation and lipase release measured. Concentrations of pentosan polysulphate were measured by a competitive binding assay and the mean peak level found to be 1.6 μg/ml. Anti-Xa clotting activity rose to 0.034 iu/ml and thrombin generation induced by lipid peroxides was inhibited by approximately 50%. Neither of these effects could be accounted for by the direct action of pentosan polysulphate at the concentrations measured. Pentosan poly sulphate was very effective in releasing lipase, approximately 70-80% of the total enzyme activity being due to hepatic triglyceride lipase (HTGL). In vitro addition of purified HTGL to plasma markedly enhanced anti-Xa clotting activity, and caused a 70% inhibition of lipid peroxide induced thrombin generation. Anti-Xa activity of postinjection plasma was increased rather than neutralised by addition of polybrene, and this effect could be mimicked by addition of polybrene to plasma containing pentosan polysulphate and purified HTGL. It is concluded that, when given in low doses subcutaneously, pentosan polysulphate acts as an indirect anticoagulant, its major effects being due to release of HTGL.
The Relation Between Platelet Reactivity and Coronary Angiographic Findings in Young Female Survivors of Acute Myocardial Infarction
Authors: Kutti Jack , Wadenvik Hans , Johansson Saga , Vilén Lars , Vedin Anders , Wilhelmsson Claes
Published: July 2018

In 31 women who had survived their first acute myocardial infarction (MI) studies of platelet reactivity were related to coronary angiographic findings. The results were compared to those obtained from 38 age-matched control women. According to the cardioangiographic findings the group of MI was subdivided into: 9 patients with 1-vessel disease (VD), 10 patients with 2-VD, and 5 patients with 3-VD; 7 subjects did not reveal significant coronary stenosis. When each of these 4 subgroups of MI-patients were compared with the control material significant difference with respect to PF4 was found only for subjects with 1-VD (20.0 ± 4.8 vs. 10.3 ± 0.6 ng/ml). As regards BTG the difference was significant for 1-VD and 2-VD patients (69 ± 12 and 59 ± 3, respectively vs. 40 ± 2 ng/ml). The cumulative frequency for secondary aggregation differed only as regards 1-VD patients (78 vs 40%).
Increased Procoagulant Response of Monocytes from Patients with Familial Mediterranean Fever
Authors: Courillon-Mallet Anne , Bevilacqua Michael , Wautier Jean-Luc , Dervichian Michel , Cattan Daniel , Caen Jacques
Published: July 2018

Familial Mediterranean Fever (FMF) is an inherited disease of unknown etiology characterized by recurrent inflammatory episodes. Circulating fibrin was found in patients with FMF in absence of clinical manifestation of thrombosis and was statistically less frequently observed in patients treated with colchicine. These results suggest a cellular dysfunction. Therefore, we examined the procoagulant activity (PCA) of isolated mononuclear leukocytes and purified monocytes from FMF patients (n = 20). No PCA was detectable on freshly-isolated monocytes. After several hours of culture, FMF monocytes contained more PCA than control cells and the difference was more marked after endotoxin stimulation. Data obtained with coagulation factor-deficient plasma and anti-human apoprotein III antiserum indicated that the enhanced PCA in FMF monocytes is thromboplastin-like. Lysozyme and interleukin 1 production by monocytes were similar in patients and controls. The increased monocyte PCA appears to be due to an intrinsic and selective higher responsiveness of monocytes.
Managing Adhesive Small Bowel Obstruction with Water-Soluble Contrast Should Be Protocolized: A Retrospective Analysis
Authors: Köstenbauer Jakob
Published: July 2018

Aim Current literature emphasizes the effectiveness of computed tomography (CT) and water-soluble contrast agent, Gastrografin, in the investigation of adhesive small bowel obstruction (ASBO). As there is no management protocol for ASBO at our institution, the aim of this study was to determine the effect of imaging methods—CT, Gastrografin challenge (GC), or plain-film X-ray—on patient outcomes in a clinical setting.

Methods All 163 emergency presentations of ASBO during the study period between December 2010 and September 2012 were collected retrospectively. Cases were divided into three groups: CT with oral contrast, GC, or plain-film X-ray only. The primary outcome was time to theater.

Results Patients investigated with X-ray only were significantly less likely to require surgery (6% in plain-film X-ray vs. 35% and 20% in CT and GC, respectively; p = 0.003). In cases requiring surgery, GC was associated with a 24-hour longer time to imaging than CT (p < 0.001). The time to theater was 71:25 hours for GC versus 46:39 for CT (p = 0.039). There was no significant difference in bowel resection or complication rates.

Conclusion Patients undergoing water-soluble contrast studies were subjected to unnecessary delays in their clinical course. These delays are costly and avoidable. The development and implementation of an evidence-based protocol for the management of small bowel obstruction is strongly recommended. The lack of a protocol likely caused significant delays in Gastrografin administration, reducing its known benefits for clinical decision-making and length of stay.
Skull Base 3D Modeling of Rigid Buttress for Gasket-Seal Closure Using Operative Endoscopic Imaging: Cadaveric Feasibility
Authors: Shin James , Forbes Jonathan , Lehner Kurt , Tomasiewicz Hilarie , Schwartz Theodore H. , Phillips C.
Published: July 2018

Surgical defect closure following endonasal transsphenoidal tumor resection is a critical component of procedural success. Three-dimensional (3D) modeling of relevant skull base anatomy during resection can potentially facilitate design of a custom rigid buttress for gasket-seal closure; however, access to conventional cross-sectional imaging intraoperatively is limited and cumbersome. Endoscopic imaging, by contrast, is always available. This work demonstrates the feasibility of 3D modeling of the visible skull base through structure-from-motion photogrammetric postprocessing techniques, providing a suitable template to design a gasket-seal buttress. Additionally, endoscopic 3D reconstruction of skull base surface anatomy may represent a more robust depiction of the surgical defect than is available by conventional 3D modeling with computed tomography, which suboptimally recapitulates very thin bones and mucosal surfaces typical of this regional anatomy.
Laufen für Einsteiger
Authors: Haas Hans-Josef
Published: July 2018

Eine physiotherapeutische Behandlungsserie führt oft dazu, dass der Patient beschließt, wieder mehr „für sich“ zu tun – z.B. laufen zu gehen. Beachtet er dabei ein paar Regeln, stehen die Chancen gut, dass aus der anfänglichen Schwärmerei eine Leidenschaft wird, die am Ende sogar von sportlichen Erfolgen gekrönt ist.
Active damping and disturbance rejection control of a six-axis magnetic levitation stage
Authors: Sheng Xiaochao , Menq Chia-Hsiang , Tao Tao
Published: July 2018

This paper presents the design and application of a novel active damping and disturbance rejection controller for a magnetic levitation stage. Feedback linearization, based on the rigid-body dynamics of the levitated stage, and force distribution, based on a time-varying force distribution matrix that takes six-axis motion of a floater into account, are adopted to establish a decoupled and linearized dynamics between the six inputs and the six-axis motion. By integrating an augmented state estimator that provides full state and disturbance estimation, a linear controller that provides active damping for each axis is designed, providing the whole controller with active damping and disturbance rejection capability. In addition, the parameters of the designed controller can be easily selected based on the desired damping and natural frequency, while the parameters of the augmented estimator can be determined according to the desired estimator bandwidth and first system resonance, which make the parameter tuning have a clear physical meaning. Finally, the designed controller was implemented in a field programmable gate array-based control system. Experimental results of the proposed controller and comparison with the previously designed controller are provided to illustrate the feasibility and effectiveness of the designed control algorithm.
Towards a deeper understanding of nanoscratch-induced deformation in an optical glass
Authors: Fu Jiacheng , He Hongtu , Yuan Weifeng , Zhang Yafeng , Yu Jiaxin
Published: July 2018

In this work, the factors affecting the nanoscratch-induced deformation of oxide glass in the completely ductile range are classified into three independent aspects, including plastic damage, densification, and chemistry-enhanced material-removal. Through comparing the deformation volume of a phosphate laser glass subject to different conditions, viz., in dry or humid air and before or after annealing, the contributions of the three factors to the total deformation were quantified and their evolution mechanisms were clarified for sustained scratching. Analyses indicate that the combined action of plastic damage and densification dominates the glass deformation in fewer-pass scratching, while plastic damage and chemistry-enhanced material-removal together determine the final deformation volume for multi-pass scratching in humid air. The results presented in this study provide further insights into the physics of glass deformation.
In-plane and out-of-plane structural response of spiral interconnects for highly stretchable electronics
Authors: Qaiser N. , Khan S. M. , Hussain M. M.
Published: July 2018

Stretchable electronics are commonly used as a diverse class of interconnected architectures, which accommodate large strain during stretching. A systematic understanding of the underlying mechanism of these interconnects, i.e., stress/strain states is essential to optimize the spiral designs. Here, we demonstrate the in-depth structural response of the spiral-island system when subjected to in-plane and out-of-plane stretchings. We use numerical modeling to simulate the stresses and strains along the arm of the spiral when stretched at a prescribed displacement of 1000 μm. We show the strain contours for spirals connected in-series. Our results show that the additional spirals connected in-series share the prescribed displacement equally and thus lower the von Mises stresses and principal strains. We also compare the stress generated in arms for single spiral and triangular configurations, especially when we stretch out these configurations in-plane and out-of-plane. The evolved stress depends on the angular position of spirals for triangular configuration. For the out-of-plane case, we stretch the spirals vertically and diagonally outward, i.e., along the z direction and x-z directions, respectively. Our results show that spirals experience higher stress during stretching along the x-z direction. However, for the out-of-plane z direction stretching, the spiral's end, which is connected to the island, experiences higher stress as compared to that of x-z direction case. We use 3D printing to additively manufacture the replica for single spiral and triangular configuration and perform the tensile out-of-plane stretching. Our experimental results for elongations corroborate with numerical calculations.
Development of thermal image plate using ceramic luminescence materials for aligning and stabilizing beam axis of CO2 laser
Authors: Ohtani Y. , Sasao H. , Sakuma T.
Published: July 2018

A thermal image plate (TIP) using ceramic luminescence materials has been developed in order to visualize a beam spot of a CO2 laser which is used as a light source of an interferometer developed in JT-60SA. By using CaAlSiN3:Eu2+ (CASN), the TIP was developed, and its property was assessed. A CASN TIP was able to visualize the invisible CO2 laser beam as a negative image. The beam diameter and the stability of the beam axis measurement obtained with the CASN TIP were approximately the same as that obtained with a commercial TIP. Furthermore, the time response of the CASN TIP at the best was approximately the same as that of the commercial TIP. The CASN TIP which had the highest time response was applied to the beam axis stabilizer, and then the beam axis stabilization was successfully performed in 2 h.
Structural, magnetic and magnetocaloric effect studies of Ni42.5(Fe, Co, Ni, Cu)0.5Mn46Sn11 Heusler alloys
Authors: Ezekiel Itegbeyogene P. , Moyo Thomas
Published: July 2018

We investigated the structural and magnetic properties of Ni42.5(Fe, Co, Ni, Cu)0.5Mn46Sn11 alloys fabricated by arc melting. Substitution of Ni by Fe, Co and Cu causes lattice expansions consistent with increasing atomic sizes. The zero-field cooled and field cooled results show second-order magnetic transition at the high-temperature austenite phase to a first-order magnetic transition in the low-temperature martensite phase. The substitution of Ni by Fe and Co increases the austenite Curie temperature TCA from 282 K to 289 K and 294 K respectively while Cu reduces it to 278 K. The martensitic transition temperature TM increased from 221 K to 241 K for Fe substitution and decreased to 210 K and 209 K for Co and Cu respectively. The coercive field HC increased significantly from 457 Oe for Ni at 100 K to 729 Oe for Co at 80 K. The increase to 763 Oe for Fe and 769 Oe for Cu occurred at the same temperature of 40 K. We attribute such increases to domain wall pinning effects due to the inclusions of Fe, Co and Cu. The HC exhibited an anomalous temperature dependence in all the samples. The exchange bias field HEX also showed a significant enhancement below 40 K from 196 Oe for Ni to 476 Oe, 430 Oe and 434 Oe for Fe, Co, and Cu substitutions respectively. The fits to the temperature dependence of the HC reveal significant changes in the competition between ferromagnetic and antiferromagnetic interactions. The peak magnetic entropy change ΔSMpk has a linear dependence on the magnetic field H2/3. The highest value of 28.8 J kg-1 K−1 for ΔSM is obtained in the first order magnetic transition compared to 3.0 J kg-1 K−1 in the second order transition. We report an effective cooling power of 155 J kg-1 in the second order magnetic transition.
Even-numbered hydrogen ion generated for the first time, defying theoretical structure predictions
Authors: Liebendorfer Adam
Published: July 2018

Infrared spectroscopy findings from a recently generated H 6 + cation point to a highly anharmonic, strongly coupled system with unique isomer structures.
From object nominalization to object focus
Authors: Galucio Ana Vilacy , de Souza Nogueira Antônia Fernanda
Published: July 2018

This article proposes that the divergent pattern of verb argument marking found in object focus clauses in the Tuparian branch of the Tupian family comes from the reanalysis of an object nominalization in a cleft construction. Based on the distribution of free and bound person markers, the major alignment pattern can be characterized as nominative-absolutive in simple clauses, with free pronouns expressing the nominative, whereas bound person markers express the absolutive. However, object focus clauses show a distinct alignment pattern: the ergative, and not the absolutive, is indexed by the bound markers on the verb. We present arguments for identifying the object nominalization as the source of this grammar in the object focus clause, showing also how this reanalysis resulted in the nominalizer morpheme and the person markers gaining new functions.
Expletive negation is not expletive
Authors: Cépeda Paola
Published: July 2018

Spanish punctual hasta-clauses (‘until’) have been described as identical in meaning when containing or not an expletive negation, that is, a negative marker that apparently does not contribute to the sentence meaning. I show that the negation in the hasta-clause does in fact play a role in the meaning calculation. My proposal is that the semantic contribution of the so-called “expletive” negation is to negate that the eventuality in the main clause holds during the interval denoted in the hasta-clause; as a result, such eventuality is expected to hold after the eventuality in the hasta-clause is finished. The novelty of my analysis is the comparison of the aspect (specifically, the durativity component) of the eventualities expressed in the hasta-clause.
Prunasin production using engineered Escherichia coli expressing UGT85A47 from Japanese apricot and UDP-glucose biosynthetic enzyme genes
Authors: Yamaguchi Takuya , Asano Yasuhisa
Published: July 2018

Japanese apricot, Prunus mume Sieb. et Zucc., biosynthesizes the l-phenylalanine-derived cyanogenic glucosides prunasin and amygdalin. Prunasin has biological properties such as anti-inflammation, but plant extraction and chemical synthesis are impractical. In this study, we identified and characterized UGT85A47 from Japanese apricot. Further, UGT85A47 was utilized for prunasin microbial production. Full-length cDNA encoding UGT85A47 was isolated from Japanese apricot after 5ʹ- and 3ʹ-RACE. Recombinant UGT85A47 stoichiometrically catalyzed UDP-glucose consumption and synthesis of prunasin and UDP from mandelonitrile. Escherichia coli C41(DE3) cells expressing UGT85A47 produced prunasin (0.64 g/L) from racemic mandelonitrile and glucose. In addition, co-expression of genes encoding UDP-glucose biosynthetic enzymes (phosphoglucomutase and UTP-glucose 1-phosphate uridiltransferase) and polyphosphate kinase clearly improved prunasin production up to 2.3 g/L. These results showed that our whole-cell biocatalytic system is significantly more efficient than the existing prunasin production systems, such as chemical synthesis.
Carriers, exchangers, and cotransporters in the first 100 years of the Journal of General Physiology
Authors: Jennings Michael L.
Published: July 2018

Transporters, pumps, and channels are proteins that catalyze the movement of solutes across membranes. The single-solute carriers, coupled exchangers, and coupled cotransporters that are collectively known as transporters are distinct from conductive ion channels, water channels, and ATP-hydrolyzing pumps. The main conceptual framework for studying transporter mechanisms is the alternating access model, which comprises substrate binding and release events on each side of the permeability barrier and translocation events involving conformational changes between inward-facing and outward-facing conformational states. In 1948, the Journal of General Physiology began to publish work that focused on the erythrocyte glucose transporter—the first transporter to be characterized kinetically—followed by articles on the rates, stoichiometries, asymmetries, voltage dependences, and regulation of coupled exchangers and cotransporters beginning in the 1960s. After the dawn of cDNA cloning and sequencing in the 1980s, heterologous expression systems and site-directed mutagenesis allowed identification of the functional roles of specific amino acid residues. In the past two decades, structures of transport proteins have made it possible to propose specific models for transporter function at the molecular level. Here, we review the contribution of JGP articles to our current understanding of solute transporter mechanisms. Whether the topic has been kinetics, energetics, regulation, mutagenesis, or structure-based modeling, a common feature of these articles has been a quantitative, mechanistic approach, leading to lasting insights into the functions of transporters.
Influences: Sodium channel excitement
Authors: Mandel Gail
Published: July 2018

Mandel reflects on the influence that a very broad training had on her scientific career.
The Functional Role of Large-scale Brain Network Coordination in Placebo-induced Anxiolysis
Authors: Meyer Benjamin , Yuen Kenneth S L , Saase Victor , Kalisch Raffael
Published: July 2018

Anxiety reduction through mere expectation of anxiolytic treatment effects (placebo anxiolysis) has enormous clinical importance. Recent behavioral and electrophysiological data suggest that placebo anxiolysis involves reduced vigilance and enhanced internalization of attention; however, the underlying neurobiological mechanisms are not yet clear. Given the fundamental function of intrinsic connectivity networks (ICNs) in basic cognitive processes, we investigated ICN activity patterns associated with externally and internally directed mental states under the influence of an anxiolytic placebo medication. Based on recent findings, we specifically analyzed the functional role of the rostral anterior cingulate cortex (rACC) in coordinating placebo-dependent cue-related (phasic) and cue-unrelated (sustained) network activity. Under placebo, we observed a down-regulation of the entire salience network (SN), particularly in response to threatening cues. The rACC exhibited enhanced cue-unrelated functional connectivity (FC) with the SN, which correlated with reductions in tonic arousal and anxiety. Hence, apart from the frequently reported modulation of aversive cue responses, the rACC appears to be crucially involved in exerting a tonically dampening control over salience-responsive structures. In line with a more internally directed mental state, we also found enhanced FC within the default mode network (DMN), again predicting reductions in anxiety under placebo.
Involvement of Phosphodiesterase 2A Activity in the Pathophysiology of Fragile X Syndrome
Authors: Maurin Thomas , Melancia Francesca , Jarjat Marielle , Castro Liliana , Costa Lara , Delhaye Sébastien , Khayachi Anouar , Castagnola Sara , Mota Elia , Di Giorgio Audrey , Servadio Michela , Drozd Malgorzata , Poupon Gwénola , Schiavi Sara , Sardone Lara , Azoulay Stéphane , Ciranna Lucia , Martin Stéphane , Vincent Pierre , Trezza Viviana , Bardoni Barbara
Published: July 2018

The fragile X mental retardation protein (FMRP) is an RNA-binding protein involved in translational regulation of mRNAs that play key roles in synaptic morphology and plasticity. The functional absence of FMRP causes the fragile X syndrome (FXS), the most common form of inherited intellectual disability and the most common monogenic cause of autism. No effective treatment is available for FXS. We recently identified the Phosphodiesterase 2A (Pde2a) mRNA as a prominent target of FMRP. PDE2A enzymatic activity is increased in the brain of Fmr1-KO mice, a recognized model of FXS, leading to decreased levels of cAMP and cGMP. Here, we pharmacologically inhibited PDE2A in Fmr1-KO mice and observed a rescue both of the maturity of dendritic spines and of the exaggerated hippocampal mGluR-dependent long-term depression. Remarkably, PDE2A blockade rescued the social and communicative deficits of both mouse and rat Fmr1-KO animals. Importantly, chronic inhibition of PDE2A in newborn Fmr1-KO mice followed by a washout interval, resulted in the rescue of the altered social behavior observed in adolescent mice. Altogether, these results reveal the key role of PDE2A in the physiopathology of FXS and suggest that its pharmacological inhibition represents a novel therapeutic approach for FXS.
Adenosine Receptor-Mediated Developmental Loss of Spike Timing-Dependent Depression in the Hippocampus
Authors: Pérez-Rodríguez Mikel , Arroyo-García Luis E , Prius-Mengual José , Andrade-Talavera Yuniesky , Armengol José A , Pérez-Villegas Eva M , Duque-Feria Paloma , Flores Gonzalo , Rodríguez-Moreno Antonio
Published: July 2018

Critical periods of synaptic plasticity facilitate the reordering and refining of neural connections during development, allowing the definitive synaptic circuits responsible for correct adult physiology to be established. Presynaptic spike timing-dependent long-term depression (t-LTD) exists in the hippocampus, which depends on the activation of NMDARs and that probably fulfills a role in synaptic refinement. This t-LTD is present until the third postnatal week in mice, disappearing in the fourth week of postnatal development. We were interested in the mechanisms underlying this maturation related loss of t-LTD and we found that at CA3–CA1 synapses, presynaptic NMDA receptors (pre-NMDARs) are tonically active between P13 and P21, mediating an increase in glutamate release during this critical period of plasticity. Conversely, at the end of this critical period (P22–P30) and coinciding with the loss of t-LTD, these pre-NMDARs are no longer tonically active. Using immunogold electron microscopy, we demonstrated the existence of pre-NMDARs at Schaffer collateral synaptic boutons, where a decrease in the number of pre-NMDARs during development coincides with the loss of both tonic pre-NMDAR activation and t-LTD. Interestingly, this t-LTD can be completely recovered by antagonizing adenosine type 1 receptors (A1R), which also recovers the tonic activation of pre-NMDARs at P22–P30. By contrast, the induction of t-LTD was prevented at P13–P21 by an agonist of A1R, as was tonic pre-NMDAR activation. Furthermore, we found that the adenosine that mediated the loss of t-LTD during the fourth week of development is supplied by astrocytes. These results provide direct evidence for the mechanism that closes the window of plasticity associated with t-LTD, revealing novel events probably involved in synaptic remodeling during development.
Acute kidney injury after transcatheter aortic valve implantation and mortality risk—long-term follow-up
Authors: Kliuk-Ben Bassat Orit , Finkelstein Ariel , Bazan Samuel , Halkin Amir , Herz Itzhak , Salzer Gotler Dalit , Ravid Dor , Hakakian Odelia , Keren Gad , Banai Shmuel , Arbel Yaron
Published: July 2018

Background

Acute kidney injury (AKI) complicating transcatheter aortic valve implantation (TAVI) is relatively frequent and associated with significant morbidity. Previous studies have shown a higher 30-day and 1-year mortality risk in patients with periprocedural AKI. Our aim was to identify the prognostic impact of periprocedural AKI on long-term follow-up.

Methods

This is a single-center prospective study evaluating patients undergoing TAVI for severe aortic stenosis. AKI was defined according to the Valve Academic Research Consortium 2 definition, as an absolute increase in serum creatinine ≥0.3 mg/dL or an increase >50% within the first week following TAVI. Mortality data were compared between patients who developed AKI and those who did not. Logistic and Cox regressions were used for survival analysis.

Results

The final analysis included 1086 consecutive TAVI patients. AKI occurred in 201 patients (18.5%). During the follow-up period, 289 patients died. AKI was associated with an increased risk of 30-day mortality {4.5 versus 1.9% in the non-AKI group; hazard ratio [HR] 3.70 [95% confidence interval (CI) 1.35–10.13]}. Although 1-year mortality was higher in the AKI group in univariate analysis, it was not significant after a multivariate regression. AKI was a strong predictor of longer-term mortality [42.3 versus 22.7% for 7-year mortality; HR 1.71 (95% CI 1.30–2.25)]. In 189 of 201 patients we had data regarding recovery from AKI up to 30 days after discharge. In patients with recovery from AKI, the mortality rate was lower (38.2 versus 56.6% in the nonrecovery group; P = 0.022).

Conclusions

Periprocedural AKI following TAVI is a strong risk factor for short-term as well as long-term mortality (up to 7 years). Therefore more effort is needed to reduce this complication.
Increasing Rates of Invasive Group A Streptococcal Disease in Alberta, Canada; 2003–2017
Authors: Tyrrell Gregory J , Fathima Sumana , Kakulphimp Jocelyne , Bell Christopher
Published: July 2018

Background

We present an analysis of increasing rates of invasive group A streptococci (iGAS) over a 15-year period in Alberta, Canada.

Methods

From 2003 to 2017, the emm type of iGAS isolates was identified from patients with iGAS disease in Alberta. Demographic, clinical, and risk factor data were collected.

Results

A total of 3551 cases of iGAS were identified in Alberta by isolation of a GAS isolate from a sterile site. The age-standardized incidence rates of iGAS increased from 4.24/100 000 in 2003 to 10.24 in 2017. Rates (SD) were highest in those age <1 (9.69) years and 60+ (11.15) years; 57.79% of the cases were male. Commonly identified risk factors included diabetes, hepatitis C, nonsurgical wounds, addiction, alcohol abuse, drug use, and homelessness. The overall age-standardized case fatality rate was 5.11%. The most common clinical presentation was septicemia/bacteremia (41.84%), followed by cellulitis (17.25%). The top 4 emm types from 2003–2017 were emm1, 28, 59, and 12. In 2017, the top 4 emm types (emm1, 74, 101, and 59) accounted for 46.60% of cases.

Conclusions

The incidence of iGAS disease in Alberta, Canada, has increased from 2003 to 2017. This increase has been driven not by a single emm type, but rather what has been observed is a collection of common and emerging emm types associated with disease. In addition, it is also likely that societal factors are playing important roles in this increase as risk factors associated with marginalized populations (addiction, alcohol abuse, and drug use) were found to have increased during the survey period.
Oral Feeding Success
Authors: Griffith Thao T. , Bell Aleeca F. , Vincent Catherine , White-Traut Rosemary , Medoff-Cooper Barbara , Rankin Kristin
Published: July 2018

Background:

The term “oral feeding success” (OFS) is frequently used in clinical practice and research. However, OFS is inconsistently defined, which impacts the ability to adequately evaluate OFS, identify risk factors, and implement interventions in clinical practice and research.

Purpose:

To develop the defining attributes, antecedents, and consequences for the concept of OFS in preterm infants during their initial hospitalization.

Methods:

PubMed, CINAHL, and PsycINFO databases were searched for English articles containing the key words “oral feeding success” and “preterm infants.” The Walker and Avant method for concept analysis was employed.

Results:

Sixteen articles revealed the defining attributes, antecedents, and consequences. Defining attributes included (1) physiologic stability; (2) full oral feeding; and (3) combined criteria of feeding proficiency (≥30% of the prescribed volume during the first 5 minutes), feeding efficiency (≥1.5 mL/min over the entire feeding), and intake quantity (≥80% of the prescribed volume).

Implications for Practice:

The 3 defining attributes may be used in clinical practice to consistently evaluate OFS. The antecedents of OFS provide clinicians with a frame of reference to assess oral feeding readiness, identify risk factors, and implement effective interventions. The consequences of OFS allow clinicians to anticipate challenges when OFS is not achieved and create a care plan to support the infants.

Implications for Research:

The empirical referents of OFS provide consistent and clear operational definitions of OFS for use in research. The antecedents and consequences may guide researchers to select specific measures or covariates to evaluate valid measures of OFS.
Female genitourinary tract melanoma: mutation analysis with clinicopathologic correlation: a single-institution experience
Authors: Saglam Ozlen , Naqvi Syeda M.H. , Zhang Yonghong , Mesa Tania , Teer Jamie K. , Yoder Sean , Lee Jae , Messina Jane
Published: July 2018

Female genitourinary tract melanoma (FGTM) is a rare and often-fatal form of mucosal melanoma. We describe our institutional experience with 55 cases of FGTM, 16 of which were evaluated with next-generation sequencing targeting 151 cancer-associated genes. Tumors tended to be thicker than conventional melanoma at presentation (median: 3.2 mm), were frequently ulcerated (50%), and characterized by incomplete initial resections. Regional lymph nodes showed tumor involvement at presentation in 28% of cases. With a median follow-up of 23.6 months, the median recurrence free survival was 14.5 months and the median overall survival was 29.6 months. Genomic analysis revealed mutually exclusive mutations in TP53 and KIT in 25%, while 19% of cases showed BRAF mutation. NRAS mutation was found in 13% of cases. Mutation in ATRX, previously undescribed in mucosal melanoma, was seen in three (10%) of 16 patients. Only invasive melanoma cases were included in statistical analyses. Patients with three or more mutations had marginally worse overall survival rates than those with two or less (P=0.07). Further studies are required for potential adjuvant treatment modalities to improve survival outcomes of FGTM.
High-Fidelity Simulation in an Entry-Level Physical Therapy Program: A Format for Debriefing
Authors: Bednarek Melissa , Williamson Ann , Downey Patricia
Published: July 2018

Purpose:

The importance of debriefing after high-fidelity simulation (HFS) is well accepted; however, no recommendations exist in physical therapy literature for how best to do this. The primary purpose of this study was to describe a format for debriefing and a secondary purpose was to report student responses to the educational benefit of that process.

Methods:

Based on a review of the literature and the HFS case objectives, a semi-structured debriefing format using open-ended questions was developed. Students were surveyed regarding the educational benefit of the debriefing process and the effectiveness of the debriefer using open-ended and Likert-scale questions. These responses were analyzed.

Results:

After each of the 3 HFS experiences, an experienced faculty member facilitated the debriefing process by moving students through a reaction, analysis, and summary phase. Based on student feedback, the debriefing format used seemed to be effective in providing an opportunity for student reflection. A statistically significant positive correlation was found between the perceived educational benefit of debriefing and the effectiveness of the debriefer.

Conclusions:

A semi-structured debriefing session after HFS, modeled on best practices in the literature, resulted in high student satisfaction. Future research should focus on standardization of the debriefing session and validating a debriefing tool.
Further Defining the 2012 Multi-Society Task Force Guidelines for Surveillance of High-risk Adenomas
Authors: Grunwald Douglas , Landau Alex , Jiang Zhenghui G. , Liu Joy J. , Najarian Robert , Sheth Sunil G.
Published: July 2018

Goals:

We set out to determine whether variation from this 3-year follow-up interval was associated with the finding of subsequent high-risk adenoma (HRA).

Background:

HRAs include the following: (1) an adenoma measuring ≥10 mm, (2) ≥3 adenomas found during a single procedure, and (3) an adenoma with high-grade dysplasia or villous architecture. The current Multi-Society Task Force guideline for timing of surveillance colonoscopy after removal of a HRA is 3 years.

Study:

In 2016, we analyzed 495 patients who had a HRA removed during a 2008 colonoscopy. We compared the frequency of finding another HRA at follow-up intervals. We used the current guidelines as our referent group and performed logistical regression to identify whether any patient characteristics, procedural factors, or type of HRA predicted the development of HRAs on follow-up colonoscopy.

Results:

Individuals who followed-up at a median of 4.5 years did not have more HRA on follow-up compared with those who followed-up at 3 years (25.2% vs. 21.0%, P=0.062). These groups had similar baseline characteristics. Older individuals, male gender, having a history of polyps, and piecemeal resection of an HRA predicted future HRAs. The removal of ≥3 adenomas in 2008 as well as a combination of multiple, large, and advanced polyps showed a higher risk of future HRAs.

Conclusions:

The 2012 Multi-Society Task Force recommendation of 3-year follow-up after removal of HRAs may not apply to all patients. We showed that a combination of patient demographics, procedural factors, and pathology best determines the surveillance colonoscopy interval.