bluuebunny/crossref_metadata_2025 huggingface dataset:
Object sequences: encoding categorical and spatial information for a yes/no visual question answering task
Authors: Garg Shivam , Srivastava Rajeev
Published: July 2018

The task of visual question answering (VQA) has gained wide popularity in recent times. Effectively solving the VQA task requires the understanding of both the visual content in the image and the language information associated with the text‐based question. In this study, the authors propose a novel method of encoding the visual information (categorical and spatial object information) of all the objects present in the image into a sequential format, which is called an object sequence. These object sequences can then be suitably processed by a neural network. They experiment with multiple techniques for obtaining a joint embedding from the visual features (in the form of object sequences) and language‐based features obtained from the question. They also provide a detailed analysis on the performance of a neural network architecture using object sequences, on the Oracle task of GuessWhat dataset (a Yes/No VQA task) and benchmark it against the baseline.
Characteristics analysis of electromagnetic force and noise of claw pole alternators with different pole and slot combinations and phase number
Authors: Wu Shuanglong , Zuo Shuguang
Published: July 2018

This study analysed the characteristics of electromagnetic force and noise of claw pole alternators with different pole and slot combinations and different phase number. The magnetic flux density in the airgap was first derived based on the magnetomotive force and permeance. Then the electromagnetic force was obtained using Maxwell stress tensor method. According to the analytical model, the spatial order and frequency of electromagnetic force can be expressed as the function of pole‐pairs number p, slot number s and phase number m. Afterwards, the electromagnetic noise of three different alternators was tested in a semi‐anechoic chamber. Combined with the 2D fast Fourier transform of electromagnetic force, the main force harmonics that caused the electromagnetic noise were distinguished. Finally, the relationship between the frequencies of electromagnetic force and noise and the number of pole‐pairs and phase were established. Analysis result shows that for m‐phase 2p‐pole/s‐slot integer slot claw pole alternators, the spatial order of electromagnetic force is kp (k = 0, 1, 2, 3,…) and the corresponding frequency of these force harmonic is [±2mpk′ + (±kp)]fr (k′ = 0, 1, 2, 3 …). The main order (frequency domain) of electromagnetic noise is 2mp which is independent of the slot number.
Constrained optimisation approach for parameter estimation of PV modules with single‐diode equivalent model
Authors: Moshksar Ehsan , Ghanbari Teymoor
Published: July 2018

This study deals with estimation of five unknown parameters in single‐diode equivalent model of photovoltaic (PV) modules. First, to simplify the problem, the unknown parameters are reduced to series resistance and diode thermal voltage. These two parameters have significant role for PV model identification. On the other hand, PV model has the least sensitivity to the choice of parallel resistance. Hence, an approximation is utilised for parallel resistance and large value is assigned to this electrical parameter. Thanks to the proposed approximation, a novel cost function is designed for the reduced model such that all of its optimum solutions remain in a small interval of the reduced model. A set of inequality constraints are defined to generate an almost convex optimisation problem with all solutions located in a very small set. The gradient update laws are developed to find the solutions in the tiny set forced by the constructed optimisation problem. The proposed estimation technique generates an accurate model for PV modules, especially at voltage values lower and equal to maximum voltage value.
Exergy analysis of a weir‐type cascade solar still connected to PV/T collectors
Authors: Sarhaddi Faramarz
Published: July 2018

In this study, the exergy analysis of a weir‐type cascade solar still connected to photovoltaic thermal (PV/T) collectors is provided. By formulating the energy balance for different components of solar still system, the governing equations were obtained as a set of non‐linear ordinary differential equations. A perfect exergy analysis is used to obtain irreversibility rates, exergy fractions and exergy efficiency. To find various temperatures and freshwater productivity, the governing equations are solved numerically. Moreover, through experimental data of previous studies, the numerical results were validated. In this study, the effect of the mass flow rate of brackish water and the number of PV/T collectors on the hourly variation of exergy efficiency, irreversibility rates and exergy fractions were investigated. Results showed that by connecting two PV/T collectors to the cascade solar still, the exergy efficiency can be improved twice. Moreover, the connection of two PV/T collectors and use of their output electrical power for heating brackish water can increment the fresh water production rate by 56.8%. The absorber plate and PV/T collectors include maximum 55.8 and 36.8% of system total irreversibility, respectively. The maximum exergy fraction is obtained in evaporating with a value of 0.85.
Multi‐time‐scale coordinated ramp‐rate control for photovoltaic plants and battery energy storage
Authors: Ai Xiaomeng , Li Jiaming , Fang Jiakun , Yao Wei , Xie Hailian , Cai Rong , Wen Jinyu
Published: July 2018

The variability of solar irradiance with a high ramp rate may lead to fluctuation in the output of photovoltaic (PV) plants and burdens the power system regulations. A novel control method coordinating the solar PV plants and the battery energy storages (BES) is proposed, aiming at minimising the gap between multi‐time‐scale ramp of solar PV station and the grid code requirement. The proposed control method combines the computationally efficient feedback control and the mathematical optimisation. Both the short‐term forecast and the historical samples are utilised to regulate the output of the PV plants and BES. The state‐of‐charge reference is adapted by the proposed control in real‐time operation for the better performances. The necessary solar power curtailment is investigated with limited BES capacity. The effectiveness of the proposed control method is comprehensively verified by simulations based on real‐world measurements of solar PV power under various BES capacity and ramp range requirements.
Consensus control strategy of an inverter air conditioning group for renewable energy integration based on the demand response
Authors: Wang Beibei , Zhang Tianwei , Hu Xiaoqing , Bao Yuqing , Su Huiling
Published: July 2018

In order to improve the degree of renewable energy integration, the demand response resource, especially on the air conditioning load side, has received attention. Currently, most of the control modes for air conditioners are centralised control, which is difficult to be applied to widely distributed air conditioning. The current studies focus on central air conditioning, but there are few studies on split‐type inverter air conditioning, even though inverter air conditioning has become the most common split air system on the market. With this background, this study designs a consensus control strategy on the basis of distributed control mode, which for inverter air conditioners. The strategy is used for renewable energy integration in the studied region. The test results of various cases reveal the following findings: (i) the strategy adapts to the widely distributed air conditioning, (ii) the strategy can guarantee a fair allocation of power imbalance and user comfort, (iii) the control strategy can adapt to the uncertainties of air conditioners and the urban microclimate while efficiently consuming renewable energy. Therefore, the proposed consensus control strategy has practical value.
Cold gas in a complete sample of group-dominant early-type galaxies
Authors: O’Sullivan E. , Combes F. , Salomé P. , David L.P. , Babul A. , Vrtilek J. M. , Lim J. , Olivares V. , Raychaudhury S. , Schellenberger G.
Published: July 2018

We present IRAM 30 m and APEX telescope observations of CO(1-0) and CO(2-1) lines in 36 group-dominant early-type galaxies, completing our molecular gas survey of dominant galaxies in the Complete Local-volume Groups Sample. We detect CO emission in 12 of the galaxies at > 4σ significance, with molecular gas masses in the range ∼ 0.01 − 6 × 108 M⊙, as well as CO in absorption in the non-dominant group member galaxy NGC 5354. In total 21 of the 53 CLoGS dominant galaxies are detected in CO and we confirm our previous findings that they have low star formation rates (0.01–1 M⊙yr−1) but short depletion times (>1 Gyr) implying rapid replenishment of their gas reservoirs. Comparing molecular gas mass with radio luminosity, we find that a much higher fraction of our group-dominant galaxies (60 ± 16%) are AGN-dominated than is the case for the general population of ellipticals, but that there is no clear connection between radio luminosity and the molecular gas mass. Using data from the literature, we find that at least 27 of the 53 CLoGS dominant galaxies contain H I, comparable to the fraction of nearby non-cluster early type galaxies detected in H I and significantly higher that the fraction in the Virgo cluster. We see no correlation between the presence of an X-ray detected intra-group medium and molecular gas in the dominant galaxy, but find that the H I-richest galaxies are located in X-ray faint groups. Morphological data from the literature suggests the cold gas component most commonly takes the form of a disk, but many systems show evidence of galaxy-galaxy interactions, indicating that they may have acquired their gas through stripping or mergers. We provide improved molecular gas mass estimates for two galaxies previously identified as being in the centres of cooling flows, NGC 4636 and NGC 5846, and find that they are relatively molecular gas poor compared to our other detected systems.
Towards an image-guided restricted drug release in friendly implanted therapeutics
Authors: Razek Adel
Published: July 2018

This review aims to expose a possible therapeutics scheme of using active implants for restricted drug release accounting for friendly wellbeing and security of patient. The review of embedded therapeutics, regulated drug administration, minimally-invasive issues and governing non-ionizing position detection suggested a possible MR image-guided approach. The magnetic resonance imaging is then investigated and its environmental compatibility is explored through electromagnetic compatibility analysis for embedded therapeutics.
Universal CubeSat Platform Design Technique
Authors: Chen Zhiyong
Published: July 2018

This article summarizes cubesat technology, provides examples of their scientific impact, and describes the design and the manufacturing of a Cubesat platform. As for the design of the overall frame structure of the CubeSat, we have searched a lot of literature and consulted many predecessors' designs, and collected many satellite structure images. After analyzing the data, we aimed at all kinds of different structures’ advantages and disadvantages, finally we got a best design. It is a satellite of cubic shape (10 cm per side), weighing approximately 1kg, based on the creation of a central body made of different material using the 3D-Printing techniques. The 3D-Printing technique has several advantages including fast implementation, accuracy in manufacturing small parts and low cost. Moreover, concerning the construction of a small satellite, this technique is very useful thanks to the accuracy achievable in details, which are sometimes difficult and expensive to realize with the use of tools machine. The structure must be able to withstand the launch loads. For this reason, several simulations using an FEM simulation and an intensive vibration test campaign will be performed in the system development and test phase.
Effects of the Wet Steam Non-Equilibrium Condensation on the Dynamics of the Excitation-Relying Bearing-Rotor system
Authors: Guo Bing , Tang Weixiao , Zhen Tianhui
Published: July 2018

This paper investigated the effects of the wet steam non-equilibrium condensation on the dynamic characteristics of the bearing as well as the bearing-rotor system by constructing and analyzing a non-linear coupled model of the bearing-rotor system. An excitation-relying dynamic model of bearing is established based on the finite difference method, in which the excitation is converted from the pressure pulsation on the surface of rotor blades generated from the non-equilibrium condensation process. The Raccia transfer matrix method is implemented to analyse the dynamic behavior of this coupled system. Results show that the wet steam non-equilibrium condensation process would greatly reduce the bearing stiffness and damping and result in more intense vibration of the system, besides, its induced pulsed displacement would drive the excitation-relying bearing-rotor system more unstable.
Dynamic Analysis of Shaft Structure Based on ANSYS/LS-DYNA
Authors: WANG Yu-ning , Zhao-gang Zhang , Yi-zhen Lin , Ming-ang Yin
Published: July 2018

In this study, a part of the shafting structure of the accessory transmission system consisting of shaft-gear-bearing is studied. ANSYS/LS-DYNA explicit dynamics simulation software is used to simulate the dynamics of the shaft structure. It compares and analyzes the overall shaft structure, gears and bearings. The simulation results show that: The place where the equivalent stress of the shaft structure is relatively large is mainly concentrated at the tooth root and the tooth surface, where the stress is mainly in the vicinity of two or three teeth. With the change of time, the maximum equivalent stress value and position of the rolling elements are also correspondingly changed, it provides a reference for the design and optimization of gear and bearing in the actual assembly process for transmission system.
Computer-aided Design for the Route of the Test Waveguides
Authors: Runze Wang , Yabin Jian , Xiaofang Yin , YaQin Hou , XinMing Su
Published: July 2018

With the rapid development of China's space industry, digitization and intelligent is the tendency of the future. The applications of the waveguide are gradually widespread. During the thermal test phase, the routes of the test waveguides are similar for each spacecraft. Although the waveguides are highly standardized, so far it needs engineers to design the particular route of the test waveguidess, then map the engineering drawing for every test. In order to efficiently design the route of waveguide, it needs to design an application to help the engineers. With the help of the MFC(Microsoft Foundation Classes) and the pro/toolkit, it is easily to do the modeling and simulation. After automatic design the particular the route of the waveguide, the API of AutoCAD type library is used to help to modify the engineer drawing. Engineers can supervise every step of this application, and easily to modify the key parameters.
Charge transport mechanism of polyaniline/ZnO nanocomposites based on inorganic/organic heterojunctions
Authors: Han Lei , Li Wen , Meng Chao , Chen Yan , Fan Shan
Published: July 2018

The key to improve the photocurrent is how to promote the generation rate and reduce the recombination rate of the photo-hole pair. In this paper, a p-n heterjunction structure in Polyaniline (PANI)/ZnO nanocomposites was formed via mechanical mixing process. Compared with ZnO, PANI doped ZnO nanocomposites exhibit obviously enhanced response. It might be attributed to the p-n heterojunctions formed between p-type and n-type enhanced response, enhancing the charge separation and in turn promoting the photoconductivity of the film. The 5at-%PANI doped ZnO nanocomposites demonstrates the highest response.
Unmanned Aircraft System Pilot/Operator Qualification Requirements and Training Study
Authors: Qi Shengjun , Wang Feng , Jing Li
Published: July 2018

With the rapid development of Unmanned Aircraft System (UAS) technology, UAS has become indispensable in military and civilian field. Growth in number of UAS and activity has required soaring demand for UAS pilot/operator who has become a hot profession in aviation. In this paper, the UAS classification and unique characteristics of operation are stated firstly. Then, considering current requirements about UAS Pilot/Operator qualification issued by aviation authorities in U.S, UK and China, the general and special qualification requirements are analyzed, which includes professional quality, medical requirements, psychological evaluation, training requirements, operating experience and cooperation. Furthermore, based on differences between UAS and manned aircraft pilot training, the training contents and methods, especially human factor and physiological health, are discussed, which is meaningful and helpful to selection and training of UAS pilot/operator.
Configurations and Key Issues of Low Thrust Measurement for Microspacecrafts
Authors: Zhou Wei-jing , Ye Ji-fei , Li Nan-lei , Chang Hao
Published: July 2018

Microthrusters on microspacecrafts are of interest and its output thrust must be characterized for a particular applicaton. The technology of micro thrust measurement can evaluate the performance of microthrusters. The measurement principles of steady-state thrust, pulse impulse, average thrust and instantaneous thrust are introduced. The classical thrust stands at home and broad are summarized and they are classified into torsional arm type, balance type, hanging pendulum type and flexure vibration type according to their dynamics configurations. The characters, purpose, advantages and disadvantages are analyzed. The key problems, such as error influence factors and its countermeasure, calibration, and measurement automatization, are pointed out.
Rotordynamic Characteristics Analysis for an aero-engine Low Pressure Rotor Rig Test Model
Authors: Song Huiying , Wang Shaohui , Sun Kai
Published: July 2018

3D whole engine finite element model of a low pressure rotor rig test model is established in this paper. Rotorynamic characteristics are mainly analysed with three models, which include rotor model with static stiffness, rotor model with dynamic stiffness, and whole engine model. The calculation results were compared and discussed deeply. Rotordynamic characteristics of rotor model with static stiffness are similar with the rotor model with dynamic stiffness, but the latter may have additional resonance peaks caused by dynamic stiffness. Whole engine model, which can capture the modes of casing and coupling vibration between stator and rotor, may have more critical speeds than rotor model only. The unbalance response amplitude and phase angle of the whole engine model are different with the only rotor model, in the values and distributions of the peaks. The result of rotor model with dynamic stiffness is closed to the whole engine model than the rotor model with static stiffness. The peak values of the whole engine model are smaller than the only rotor model. Rotordynamic characteristics with whole engine model are more accurate than rotor model only, so it necessary to analyse rotordynamic characteristics with whole engine model in detail design stage.
Research on Performance Seeking Control of Turbofan Engine at Cruise Status Based on Sequential Quadratic Programming Algorithm
Authors: Shufan Zhao , Heng Wu , Liming Shi , Cheng Huang , xinyi Yang
Published: July 2018

The sequential quadratic programming algorithm was applied to the performance seeking control of multi-variable turbofan engine. According to the actual condition of aircraft cruise status, the constant thrust condition is added in the constraint functions of nonlinear programming. Based on the mathematical modes of turbofan engine, the SQP algorithm is adopted to the minimum fuel consumption mode of cruise condition. The simulation results show that after the optimization process, the engine fuel consumption rate decreased by nearly 2%, and the turbine temperature dropped by about 1.2%, the dual optimization benefits have been achieved. There are great potentials in engineering applications.
Fangchinoline Protects Against Renal Injury in Diabetic Nephropathy
by Modulating the MAPK Signaling Pathway
Authors: Jiang Yingsong , Liu Jiguo , Zhou Zemei , Liu Ke , Liu Chun
Published: July 2018

In this study, we evaluated the nephroprotective effects of fangchinoline in rats
with diabetic nephropathy (DN). DN was induced by feeding a high-fat diet for 4
weeks and administering a single dose of streptozotocin (STZ)
(30 mg/kg) intraperitoneally. The rats were split into groups;
one group received oral fangchinoline (3 mg/kg) per day for 8
weeks. After completion of the 8-week study period, biomedical and inflammatory
markers were evaluated in serum and urine, and oxidative stress was estimated in
kidney tissues. In addition, Western blot assays, reverse
transcription-polymerase chain reaction, and immunohistochemical analyses were
performed in the kidney tissues of DN rats. The results suggest that treatment
with fangchinoline attenuated the biochemical marker changes induced by DN in
blood and urine. Moreover, a significant (p<0.01) reduction in
inflammatory markers in serum was found in the fangchinoline group compared to
the controls. Immunohistochemical analyses also revealed that treatment with
fangchinoline significantly reduced the expression of collagen IV and CD31 in
the kidneys compared to the control group. The expression of p38 MAPK,
TNF-α, COX-2, and MMP-9 was also attenuated by fangchinoline treatment
in the kidney tissues of DN rats. Together, the results of this study suggest
that fangchinoline protects against nephron damage by attenuating alterations in
the p38 MAPK pathway, thereby reducing oxidative stress and inflammation in DN
rats.
Multiresistente Erreger in der onkologischen und kardiologischen Rehabilitation – Ergebnisse einer Surveillancestudie in Brandenburg
Authors: Kiefer Thomas , Völler Heinz , Nothroff Jörg , Schikora Martin , von Podewils Sebastian , Sicher Claudia , Bartels-Reinisch Birgit , Heyne Karolin , Haase Hermann , Jünger Michael , Daeschlein Georg
Published: July 2018

In der vorliegenden Studie wurde die Prävalenz der Besiedlung mit multiresistenten Keimen an 155 Patienten aus der onkologischen und 157 Patienten aus der kardiologischen Rehabilitation mittels mikrobiologischen Screenings untersucht. Dabei zeigten 4,5% der onkologischen und 4,5% der kardiologischen Rehabilitationspatienten eine Besiedlung mit multiresistenten Erregern. Am häufigsten wurden 2-MRGN und ESBL (2,9%) nachgewiesen. Onkologische Rehapatienten zeigten doppelt so hohe Prävalenzraten für 3-MRGN im Vergleich zu kardiologischen (2,6 und 1,3%). Insgesamt zeigen onkologische und kardiologische Rehabilitationspatienten vergleichsweise niedrige Prävalenzraten für multiresistente Krankenhauskeime.
Gründe für die Nichtinanspruchnahme einer onkologischen Rehabilitation. Ergebnisse einer schriftlichen Befragung von Patienten aus onkologischen Versorgungszentren
Authors: Deck Ruth , Babaev Valentin , Katalinic Alexander
Published: July 2018

Hintergrund Inzidenz und Überlebensraten onkologischer Erkrankungen steigen und damit auch der potentielle Reha-Bedarf bei den Betroffenen. Invers zu den Krebserkrankungen gehen die Leistungen zur medizinischen Rehabilitation nach einer onkologischen Erkrankung zurück. Die Gründe für diesen Rückgang sind bislang nicht vollständig geklärt.

Methodik Schriftliche Befragung von Krebspatienten der Indikationen Brust-, Darm- und Prostatakrebs nach Akutbehandlung. Es beteiligten sich 376 Personen; erfasst wurden Inanspruchnahme einer Rehabilitation, die Gründe für die Nichtinanspruchnahme einer Rehabilitation sowie gesundheitsbezogene Merkmale. Die Auswertungen erfolgten überwiegend deskriptiv.

Ergebnisse Die Hälfte der Befragten hat eine medizinische Rehabilitation in Anspruch genommen. Patienten, die sich für eine Rehabilitation entscheiden, fühlen sich gesundheitlich stärker belastet und weisen einen höheren Schwergrad der Erkrankung auf. Als Gründe für die Nichtinanspruchnahme einer Rehabilitation werden familiäre, persönliche und private Motive genannt.

Schlussfolgerungen Die schriftliche Befragung lieferte eine Vielzahl von Gründen, warum eine medizinische Rehabilitation nach einer Krebserkrankung nicht in Anspruch genommen wird. Daraus lassen sich Vorschläge zur Optimierung der Rehabilitation und ihrer Ausgestaltung ableiten.
Einfluss der Atmungstherapie auf die Inzidenz von nosokomialen Pneumonien in der neurologisch-neurochirurgischen Frührehabilitation: Ergebnisse einer Fall-Kontroll-Analyse
Authors: Schmidt Simone Bianca , Boltzmann Melanie , Rollnik Jens Dieter
Published: July 2018

Hintergrund In der neurologisch-neurochirurgischen Frührehabilitation (NNFR) gehen viele Krankheitsbilder mit einem erhöhten Risiko von Pneumonien einher. Vor einigen Jahren wurde die Disziplin der Atmungstherapie etabliert, um respiratorische Komplikationen abzuwenden. Derzeit gibt es allerdings keine Studien, die die Effektivität der Atmungstherapie im Hinblick auf die Inzidenz von Pneumonien in der NNFR belegen könnten.

Methode In die Studie wurden 81 Phase-B-Patienten, die während ihres Aufenthaltes eine Atmungstherapie erhalten haben, und 81 Kontrollpatienten eingeschlossen. Routinemäßig erhobene Daten wie Alter, Geschlecht, Diagnosen, Komorbiditäten, Behandlungsdauer sowie Informationen zum Beatmungsstatus und der Entstehung von Pneumonien wurden retrospektiv analysiert.

Ergebnisse Die Entstehung einer Pneumonie war mit einer längeren Behandlungsdauer, einer höheren Anzahl an Beatmungsstunden, dem Vorhandensein einer Trachealkanüle und einem tendenziell niedrigerem Frühreha-Barthel-Index bei Aufnahme assoziiert. Die Inzidenzrate nosokomialer Pneumonien lag in beiden Studiengruppen bei 20%. Die Gruppen unterschieden sich signifikant in der Krankheitsschwere bei Aufnahme, der Behandlungsdauer, der Anzahl an Dysphagie-Patienten sowie in den Therapieintensitäten der Physio-und Sprachtherapie.

Schlussfolgerung Ein direkter Zusammenhang zwischen der Atmungstherapieintensität und der Pneumonieinzidenz in der NNFR konnte aufgrund der unzureichenden Vergleichbarkeit beider Studiengruppen nicht abschließend nachgewiesen werden. Die Intensität der Dysphagie-Therapie war neben der Beatmungsdauer der stärkste die Pneumonieinzidenz beeinflussende Faktor.
Application of Metathesis Reactions in the Synthesis and Transformations of Functionalized β-Amino Acid Derivatives
Authors: Kiss Loránd , Kardos Márton , Vass Csaba , Fülöp Ferenc
Published: July 2018

Because of their biological relevance, cyclic β-amino acids have generated increasing interest and had significant impact in drug research over the past two decades. Their preparation and further functionalization towards new types of molecular entities have received large interest in synthetic and medicinal chemistry. Various types of metathesis reactions, such as ring-opening (ROM), ring-closing (RCM), or cross metathesis (CM) are used widely for access to either alicyclic β-amino acids or other densely functionalized derivatives of this group of compounds. This account intends to provide an insight into the most relevant synthetic routes to this class of derivatives with the application of metathesis reactions. The review focuses on the presentation of selective and stereocontrolled methodologies in view of versatility, robustness, limitations and efficiency.

1 Introduction

2 Synthesis and Transformation of Cyclic β-Amino Acids through
Metathesis Reactions

2.1 Synthesis of Five- and Six-Membered Cyclic β-Amino Acids by
Ring-Closing Metathesis

2.2 Synthesis of Five- and Six-Membered Cyclic β-Amino Acids by
Cross Metathesis

2.3 Synthesis of β-Amino Acids with Larger Ring Systems by Ring-
Closing Metathesis

2.4 Synthesis of β-Amino Acids with Condensed Ring Systems by
Ring-Rearrangement Metathesis

2.5 Stereocontrolled One-Step Synthesis of Functionalized Cispentacin
and Transpentacin Derivatives

2.5.1 Stereocontrolled Synthesis of Functionalized Cispentacin and
Transpentacin Derivatives through Ring-Opening Metathesis of
Norbornene β-Amino Acid Derivatives

2.5.2 Stereocontrolled Synthesis of Functionalized Azetidinones and
β-Amino Acid Derivatives from Condensed Ring β-Lactams by
Ring-Opening Metathesis

2.5.3 Carbon–Carbon Double Bond Functionalization of β-Amino Acid
Derivatives and β-Lactams with α,β-Unsaturated Carbonyl Compounds through Cross Metathesis

2.5.4 Synthesis of Functionalized β-Amino Acid Derivatives and β-Lactams through Chemoselective Cross Metathesis

3 Conclusions and Outlook
An Efficient One-Step Synthesis of Dihydroquinoline and Its Application as a Fluorescence Sensor for Selective Detection of Copper (II)
Authors: Ajavakom Anawat , Hassan Kamrul , Jonsai Lamduan , Sittapairoj Pawitporn , Ajavakom Vachiraporn , Sukwattanasinitt Mongkol
Published: July 2018

An efficient one-step synthetic pathway to dihydroquinoline (DHQ) and benzodihydroquinoline (BDHQ) derivatives involving 1,2-Michael addition reaction between amino phenol/naphthol and two molecules of methyl propiolate followed by intramolecular cyclization and aromatization using cuprous iodide as a catalyst was successfully developed. The synthesized DHQ derivatives displayed highly selective fluorescence quenching in the presence of copper(II) with a very low detection limit (LOD for DHQ is 0.20 μM). Moreover, the mechanisms of both formation of the corresponding DHQ and the fluorescence quenching by copper(II) are proposed along with the evidence of X-ray diffraction data.
Development of Novel C–H Bond Transformations and Their Application to the Synthesis of Organic Functional Molecules
Authors: Kuninobu Yoichiro
Published: July 2018

This personal account summarizes our recent progress in the development of C–H transformations. We achieved ortho-selective C–H borylations and silylations by using Lewis acid–base interaction between two substrates and we achieved meta- and ortho-selective C–H borylations by using hydrogen bonding or Lewis acid–base interaction between a hydrogen donor or Lewis acid unit of a ligand and a functional group of a substrate. Regioselective C–H trifluoromethylations and related reactions of six-membered heteroaromatic compounds were realized at their 2- and 4-positions and at their benzylic positions. In addition, we developed C–H transformations directed towards the synthesis of organic functional materials, such as highly soluble polyimides or π-conjugated molecules containing either heteroatom(s) or a Lewis acid–base interaction.

1 Introduction

2 Regioselective C–H Transformations Controlled by Noncovalent Bond Interactions

2.1 Regioselective C–H Transformations Controlled by Lewis Acid–Base Interaction between Two Substrates

2.2 Regioselective C–H Transformation Controlled by Hydrogen Bonding between Ligand and Substrate

2.3 Regioselective C–H Transformations Controlled by Lewis Acid–Base Interactions between Ligands and Substrates

3 Trifluoromethylation and Related Transformations of Six-Membered Heteroaromatic Compounds

3.1 2-Position-Selective C–H Trifluoromethylation of Six-Membered Heteroaromatic Compounds

3.2 4-Position-Selective C–H Trifluoromethylation of Six-Membered Heteroaromatic Compounds

3.3 Benzyl Position-Selective C–H Trifluoromethylation of Six-Membered Heteroaromatic Compounds

4 C–H Transformations Leading to the Synthesis of Organic Functional Materials

4.1 Heteroatom-Containing π-Conjugated Molecules

4.2 π-Conjugated Molecules Containing a Lewis Acid–Base Interaction

4.3 Soluble Polyimide Derivatives

5 Conclusions
Thrombotic Risk of Women with Hereditary Antithrombin III-, Protein C- and Protein S-Deficiency Taking Oral Contraceptive Medication
Authors: Pabinger Ingrid , Schneider Barbara , Scharrer I , Hach-Wunderle V , Lechner K , Eichinger S , Kyrle P A , Vinazzer H , Lämmle B , Demarmels-Biasiutti F , Tilsner V , Marx G , Scifricd E , Gabelmann A , Aspöck G , Fischer M , Halbmaycr W M ,   The GTH Study Group on Natural Inhibitors,   GTH (Gesellschaft für Thrombose- und Hämostaseforschung) Study Group on Natural Inhibitors:
Published: July 2018

The thrombotic risk of women with a heterozygous natural clotting inhibitor deficiency taking oral contraceptives (OC) has not been evaluated. Therefore, a retrospective collaborative controlled cohort-study was carried out in 8 coagulation laboratories and thrombosis units in Austria, Germany and Switzerland.

The incidence of thromboembolism in 48 females heterozygous for hereditary type I deficiency of antithrombin ITT (n = 1.5), protein C. (n = 16) or protein S (n = 17), who had taken OC at least once in their life were compared with that of 48 deficient women, who had never taken OC (controls). Diagnosis of the deficiency state was made in the participating centers. Data on the onset and duration of OC intake and the date and site of thrombotic events were obtained from a questionnaire filled in by the patient or a physician during a visit at a participating center. The observation period in the OC patients was started with onset of OC intake and was terminated when a thromboembolic event had occurred or when OC medication were discontinued. In the patients without OC, the observation period began at an age matched to that of the OC patient and ended when a thromboembolic event had occurred or was continued as long as the corresponding OC patient was on treatment.

In AT Ill-deficient females the probability for thrombosis was significantly higher for patients taking OC compared to the non-OC-patients (Wilcoxon test p = 0.004, Log Rank test p = 0.005). In patients with protein C- ((3-error 0.8) and protein S-deficiency ((3-error 0.05) there was no significant difference between the OC- and non-OC-group. The incidence of thrombosis/patient year in AT III-, PC- and PS-deficient females on OC was 27.5%, 12% and 6.5%, respectively and 3.4%, 6.9% and 8.6%, respectively, in the control patients.

We conclude that females with hereditary antithrombin Ill-deficiency are at high risk for venous thromboembolism when taking OC. Therefore, OC should be strictly avoided in these females and AT III measurement is mandatory in female relatives of AT Ill-deficient patients at young age before starting OC. There is no evidence for an excess thrombotic risk by OC intake in PS-deficient females. In protein C-deficient women OC medication was not associated with a significant increase of thrombosis, but an increased risk cannot be excluded.
Heparin-Associated Thrombocytopenia: The Effects of Various Intravenous lgG Preparations on Antibody Mediated Platelet Activation - A Possible New Indication for High Dose i.v. IgG
Authors: Greinacher A , Liebenhoff U , Kiefel V , Presek P , Mueller-Eckhardt C
Published: July 2018

The immunologic type of heparin-associated thrombocytopenia (HAT) is caused by antibodies which activate platelets via the Fc-re- ceptor in the presence of polysulfated oligosaccharides. The antigen is formed by a releasable platelet protein (in many cases PF4) complexed to heparin. Since the role of GP Ilb/IIIa in platelet activation by HAT antibodies is controversial, we investigated platelet activation by antibodies related to HAT. We used normal platelets and platelets from a patient with Glanzmann’s thrombasthenia (GT) lacking GP Ilb/IIIa. Heparin and sera from patients with HAT stimulated GT platelets in the same manner as determined by 14C-serotonin release and the changes in phosphorylation of p20 and p47. Platelet activation could be inhibited by an anti FcRII monoclonal antibody (IV. 3, Fab-fragments), and by Fc-fragments, but not by F(ab’)2-fragments of human IgG. The effect of four different, commercially available preparations of intact i.v. IgG on the platelet activation by six HAT sera was investigated by 14C-seroto- nin release. The inhibitory effect was strongly dependent upon the manufacturing process. At a concentration of 20 mg/ml only IgG that had been subjected to low pH and traces of pepsin sufficiently inhibited platelet activation. IgG treated with polyethylenglycol or sulfitolysis was less effective, whereas beta-propiolactone-treated IgG almost completely lost the ability to inhibit platelet activation by antibodies related to HAT. We conclude that inhibition of GP Ilb/IIIa-fibrinogen interaction is insufficient for preventing platelet activation in HAT. This is, however, possible by high dose i.v. IgG, whereby inhibition of FcRII on platelets strongly depends upon the process by which the i.v. IgG preparation was manufactured.
A Collaborative Study to Establish the 2nd International Standard for Tissue Plasminogen Activator (t-PA)
Authors: Gaffney P J , Curtis A D
Published: July 2018

An international collaborative study involving ten laboratories located in eight different countries was undertaken in order to replace the current International Standard (I.S.) for tissue plasminogen activator (t-PA). Two lyophilised candidate preparations of high purity were assessed in comparison with the current I.S. for t-PA using only a clot lysis assay. One preparation (coded 861670) was purified from a cultured melanoma cell supernatant and was about 98% single chain t-PA while the other preparation (coded 861624) was derived from Chinese hamster ovary (CHO) cells following DNA recombinant procedures and was 75% single chain t-PA.

Both candidate preparations of t-PA compared in quite a satisfactory manner with the current I.S. from the viewpoint of the biometrics of parallel line bioassays and both preparations were quite stable for long periods at low temperatures and stable from up to 1 month at temperatures of 20° and 38° C. Both fultil the criteria to serve as a satisfactory Znd International Standard for t-PA. The Fibrinolysis Subcommittee of the International Committee for Thrombosis and Haemostasis recommended the melanoma source t-PA (861670) as the next I.S. in order to maintain continuity with the 1st I.S. which was also a melanomatype preparation. The data from the ten laboratories indicated that each ampoule of the new proposed standard contains 850 international units of t-PA activity by the clot lysis assay. It is planned to present the results of this study to the Expert Committee on Biological Standardization of the World Health Organization at its next meeting and to request that the preparation of t-PA, coded 861670, be established as the 2ndlnternational Standard for t-PA.
Hemostasis in Patients Undergoing Extracorporeal Circulation: The Effect of Aprotinin (Trasylol)
Authors: Lu He , Soria Claudine , Commin Pierre-Louis , Soria Jeannette , Piwnica Armand , Schumann Friedrich , Regnier Odile , Legrand Yves , Caen Jacques Philippe
Published: July 2018

The administration of aprotinin during extracorporeal circulation (ECC) reduces blood loss. To explore the mechanism of this effect, a placebo-controlled double-blind study was performed in 20 patients (10 were administered with a high dose of aprotinin, 10 with placebo) undergoing a primary, elective operation of coronary artery bypass grafting (CABG) with ECC. Biological tests were performed at 4 different time points during the operation.

A marked reduction in the placebo group of ristocetin-induced platelet agglutination (binding of von Willebrand factor [vWF] to platelet glycoprotein [GP] Ib) was shown during ECC and at the end of surgery, but not in the aprotinin group. This abnormality is not related to the hydrolysis of vWF or GP Ib, since washed platelets were resuspended in pooled normal plasma which provided a constant amount of vWF in this test and since the plasma concentration of the fragment of GP Ib (glycocalicin) did not correlate with this abnormality.

Despite a high concentration of heparin (5-7 IU/ml) in patient's plasma during bypass, activation of blood coagulation in both groups was evidenced by an increase in ATm (thrombin-modified antithrombin III) level. The level of ATm in the placebo group reached a maximum at the end of ECC during rewarming, while in the aprotinin group, ATm level at this time point was significantly lower than in the control group. In comparison to the placebo group, the generation of the fibrin degradation products (DDE complexes) was inhibited by aprotinin during ECC, but the level of DDE complexes in the aprotinin group was slightly elevated after ECC, although much less than in the placebo group. Other parameters measured did not show significant differences between the two groups.

These results indicate that the hemostatic defect in patients during and after ECC may result, at least in part, from the impairment of GP Ib-dependent platelet adhesion. Therefore, the administration of aprotinin in ECC may improve hemostasis by abrogating this impairment, in addition to the protective effect of aprotinin on hemostatic plug. Activation of blood coagulation occurs during cardiopulmonary bypass despite heparin therapy and this activation seems to be partially inhibited by aprotinin administration.
Treatment of Uremic Anemia with Recombinant Erythropoietin also Reduces the Defects in Platelet Adhesion and Aggregation Caused by Uremic Plasma
Authors: Zwaginga Jaap J , IJsseldijk Martin J W , de Groot Philip G , Kooistra Menno , Vos Jaap , van Es A , Koomans Hein A , Struyvenberg A , Sixma Jan J
Published: July 2018

In the present study, uremic patients on chronic maintenance hemodialysis were treated with recombinant erythropoietin. Before and after 20 weeks of treatment, platelet adhesion and aggregation were studied with perfusions over a sprayed collagen surface and over matrix of cultured endothelial cells with high tissue factor activity. The influence of the erythropoietin induced raise in hematocrit on platelet transport and adhesion was excluded by performing the perfusions at a standard red blood cell concentration. The present study clearly demonstrates that erythropoietin treatment improves platelet adhesion and aggregation in addition to and independent of its effect on the hematocrit.

Studies with control platelets resuspended in plasma of untreated patients showed that a uremic plasma factor reduced adhesion and thrombin- and collagen-dependent aggregation. Patient platelets resuspended in control plasma showed no defects. After erythropoietin treatment, the plasma-induced inhibition of adhesion and aggregation had almost completely disappeared from patient plasma.

The beneficial effect of the erythropoietin treatment on uremic hemostasis is therefore twofold. The increase of the red blood cell mass improves transport of platelets, and thus adhesion to the vessel wall. The intrinsic defect due to the presence of an inhibitory toxin in uremic plasma is, in large part, corrected. Improved neutralization of uremic toxins by red blood cells or less production of toxins by better oxygenated tissue might play a role in the observed phenomena.
Effects on Coagulation and Fibrinolysis of Desmopressin in Patients Undergoing Total Hip Replacement
Authors: Flordal Per Anders , Ljungström Karl-Gösta , Svensson Jan , Ekman Brenda , Neander Gustaf
Published: July 2018

Twelve patients undergoing total hip replacement, with regional anaesthesia and with dextran infusion for plasma expansion and thromboprophylaxis, were given the vasopressin analogue desmopressin (DDAVP) or placebo in a randomized, double-blind prospective study. In controls (n = 6) we found a prolongation of the bleeding time, low factor VIII (FVIII) and von Willebrand factor (vWF) and a decrease in antithrombin III to levels known to be at risk for venous thrombosis. Desmopressin shortened postoperative bleeding time, gave an early FVIII/vWF complex increase, prevented antithrombin III from falling to critically low values and appeared to activate the fibrinolytic system, both by tPA increase and PAI-1 decrease.

Thus in the controls we found changes in both coagulation and fibrinolysis indicating a haemorrhagic diathesis as well as a risk for thromboembolism. Desmopressin induced factor changes that possibly reduce both risks.
Inhibitory Effect of Retinoids on the Generation of Procoagulant Activity by Blood Mononuclear Phagocytes
Authors: Conese M , Montemurro P , Fumarulo R , Giordano D , Riccardi S , Colucci M , Semeraro N
Published: July 2018

Retinoids are known to modulate several functions of mononuclear phagocytes. We have studied the effect of retinyl acetate (RAc) and retinoic acid (RA) on the production of procoagulant activity (PCA) by human peripheral blood mononuclear cells stimulated with endotoxin (1 εg/ml, 4 or 20 h at 37°C). Both compounds caused a dose-dependent reduction in the expression of cell-associated PCA (from 86 to <10% of control in the range of concentration comprised between 0.1 and 100 εM). This effect was also observed when the cells were exposed to retinoids for 10 min and washed before challenge with endotoxin, indicating that it is rapid and irreversible. In contrast, incubation of RAc or RA for 3 h at 37° C with cells that have been already stimulated with endotoxin (20 h at 37° C) remained without influence on cell PCA. The inhibitory action of retinoids was also observed when monocyte-enriched (>85%) preparations or highly purified monocyte-derived macrophages (>99%) were used instead of whole mononuclear cells. BW755C, an inhibitor of cyclo-oxygenase and lipoxygenase, reversed the inhibitory effect of retinoids, whereas acetylsalycilic acid, an inhibitor of cyclo-oxygenase, was inactive, suggesting the involvement of a lipoxygenase product. The inhibition of monocyte/macrophage PCA production and the subsequent reduction of cell potential for fibrin deposition might represent one of the mechanisms whereby retinoids exert their antiinflammatory and immunomodulatory activities.
In Vitro Studies of Antiphospholipid Antibodies and Its Cofactor, β2-Glycoprotein I, Show Negligible Effects on Endothelial Cell Mediated Protein C Activation
Authors: Oosting Janine D , Derksen Ronald H W M , Hackeng Tilman M , van Vliet Marja , Preissner Klaus T , Bouma Bonno N , de Groot Philip G
Published: July 2018

The effect of sera and purified IgG isolated from plasma of 46 patients with systemic lupus erythematosus (SLE) and 9 healthy donors on the endothelial cell (EC) mediated protein C activation was investigated. Out of the 46 SLE sera used, 19 were antiphospholipid antibodies (aPL) positive. From 12 patients IgG was isolated, of which 6 contained aPL. EC were first incubated with IgG (7 mg/ml) or serum (1: 1 diluted) for 1 h and then tested for their ability to promote protein C activation by thrombin, with the cells either in a monolayer or in a suspension. The normal range (mean of control values ± 2 SD) of protein C activation was 80-120%. In contrast to others, we could not detect an inhibition of protein C activation by any of the patient IgG's or sera.

The recently described cofactor for binding of antiphospholipid antibodies to phospholipids, β2-glycoprotein I, was purified and added to the purified IgG's. A combination of these two components did not inhibit the EC mediated protein C activation by thrombin.

This study suggests that the inhibition of the protein C activation, mediated by EC, is not a general mechanism by which aPL related thrombosis can be explained.