bluuebunny/crossref_metadata_2025 huggingface dataset:
Low temperature below 200 °C solution processed tunable flash memory device without tunneling and blocking layer
Authors: Mondal Sandip , Venkataraman V.
Published: May 2019

Intrinsic charge trap capacitive non-volatile flash memories take a significant share of the semiconductor electronics market today. It is challenging to create intrinsic traps in the dielectric layer without high temperature processing steps. The main issue is to optimize the leakage current and intrinsic trap density simultaneously. Moreover, conventional memory devices need the support of tunneling and blocking layers since the charge trapping dielectric layer is incapable of preventing the memory leakage. Here we report a tunable flash memory device without tunneling and blocking layer by combining the discovery of high intrinsic charge traps of more than 1012 cm−2, together with low leakage current of less than 10−7 A cm−2 in solution derived, inorganic, spin-coated dielectric films which were heated at 200 °C or below. In addition, the memory storage capacity is tuned systematically upto 96% by controlling the trap density with increasing heating temperature.
Elevated cytokine levels in tears and saliva of patients with primary Sjögren’s syndrome correlate with clinical ocular and oral manifestations
Authors: Chen Xiangjun , Aqrawi Lara A. , Utheim Tor Paaske , Tashbayev Behzod , Utheim Øygunn Aass , Reppe Sjur , Hove Lene Hystad , Herlofson Bente Brokstad , Singh Preet Bano , Palm Øyvind , Galtung Hilde Kanli , Jensen Janicke Cecilie Liaaen
Published: May 2019

Investigating cytokines in tear fluid and saliva may offer valuable information for understanding the pathogenesis of primary Sjögren’s syndrome (pSS). Cytokine profiles in both tear fluid and saliva of pSS patients, non-Sjögren’s syndrome (non-SS) subjects with sicca symptoms, and healthy controls without sicca complaints were analysed. Furthermore, relationships associating the severity of clinical ocular and oral manifestations with the upregulated cytokines were assessed. In tear fluid, pSS patients showed elevated levels of IL-1ra, IL-2, IL-4, IL-8, IL-12p70, IL-17A, IFN-γ, IP-10, MIP-1b, and Rantes compared to non-SS subjects and healthy controls. The increased cytokine levels (except IP-10) correlated significantly with reduced tear production, less stable tear film, and greater ocular surface damage. In saliva, pSS patients had a higher IP-10 level, which correlated with higher candida score; and an elevated MIP-1a level, which correlated significantly with lower unstimulated and stimulated whole saliva secretion rates. The upregulated cytokines identified in tear fluid and saliva of pSS patients show a clear interplay between innate and adaptive immune responses that may contribute to disease pathogenesis. The increase of IP-10 and MIP in both tears and saliva further emphasises the essential role of macrophages and innate immunity in pSS.
Soluble adenylyl cyclase links Ca2+ entry to Ca2+/cAMP-response element binding protein (CREB) activation in vascular smooth muscle
Authors: Parker Tony , Wang Kai-Wen , Manning Declan , Dart Caroline
Published: May 2019

Ca2+-transcription coupling controls gene expression patterns that define vascular smooth muscle cell (VSMC) phenotype. Although not well understood this allows normally contractile VSMCs to become proliferative following vessel injury, a process essential for repair but which also contributes to vascular remodelling, atherogenesis and restenosis. Here we show that the Ca2+/HCO3−-sensitive enzyme, soluble adenylyl cyclase (sAC), links Ca2+ influx in human coronary artery smooth muscle cells (hCASMCs) to 3′,5′-cyclic adenosine monophosphate (cAMP) generation and phosphorylation of the transcription factor Ca2+/cAMP response element binding protein (CREB). Store-operated Ca2+ entry (SOCE) into hCASMCs expressing the FRET-based cAMP biosensor H187 induced a rise in cAMP that mirrored cytosolic [Ca2+]. SOCE also activated the cAMP effector, protein kinase A (PKA), as determined by the PKA reporter, AKAR4-NES, and induced phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and CREB. Transmembrane adenylyl cyclase inhibition had no effect on the SOCE-induced rise in cAMP, while sAC inhibition abolished SOCE-generated cAMP and significantly reduced SOCE-induced VASP and CREB phosphorylation. This suggests that SOCE in hCASMCs activates sAC which in turn activates the cAMP/PKA/CREB axis. sAC, which is insensitive to G-protein modulation but responsive to Ca2+, pH and ATP, may therefore act as an overlooked regulatory node in vascular Ca2+-transcription coupling.
Apicoplast phylogeny reveals the position of Plasmodium vivax basal to the Asian primate malaria parasite clade
Authors: Arisue Nobuko , Hashimoto Tetsuo , Kawai Satoru , Honma Hajime , Kume Keitaro , Horii Toshihiro
Published: May 2019

The malaria parasite species, Plasmodium vivax infects not only humans, but also African apes. Human specific P. vivax has evolved from a single ancestor that originated from a parasite of African apes. Although previous studies have proposed phylogenetic trees positioning P. vivax (the common ancestor of human and African ape P. vivax) within the assemblages of Asian primate parasites, its position has not yet been robustly confirmed. We determined nearly complete apicoplast genome sequences from seven Asian primate parasites, Plasmodium cynomolgi (strains Ceylonensis and Berok), P. knowlesi P. fragile, P. fieldi, P. simiovale, P. hylobati, P. inui, and an African primate parasite, P. gonderi, that infects African guenon. Phylogenetic relationships of the Plasmodium species were analyzed using newly and previously determined apicoplast genome sequences. Multigene maximum likelihood analysis of 30 protein coding genes did not position P. vivax within the Asian primate parasite clade but positioned it basal to the clade, after the branching of an African guenon parasite, P. gonderi. The result does not contradict with the emerging notion that P. vivax phylogenetically originated from Africa. The result is also supported by phylogenetic analyses performed using massive nuclear genome data of seven primate Plasmodium species.
Conformational analysis of enantiomerization coupled to internal rotation in triptycyl-n-helicenes
Authors: Carreras Abel , Fuligni Luca , Alemany Pere , Llunell Miquel , Bofill Josep Maria , Quapp Wolfgang
Published: May 2019

We present a computational study of a reduced potential energy surface (PES) to describe enantiomerization and internal rotation in three triptycyl-n-helicene molecules, centering the discussion on the issue of a proper reaction coordinate choice.
Direct observation of pore collapse and tensile stress generation on pore walls due to salt crystallization in a PDMS channel
Authors: Naillon Antoine , Joseph Pierre , Prat Marc
Published: May 2019

In contrast with the classical picture where the generation of stress on pore walls due to salt crystallisation is analysed by a compressive stress using the concept of crystallization pressure, we report a mechanism leading to the generation of a local tensile stress.
Ab initio exploration and prediction of AE-containing nitrido(litho/magneso)tetrelates (AE = Ca, Sr; Tt = Si, Ge) with [Si2N6]10− or [Ge2N6]10− units
Authors: Niklaus Robin , Minár Ján , Strobel Philipp , Schmidt Peter J. , Schnick Wolfgang
Published: May 2019

First principles prediction of nitridogermanates and their properties with respect to optoelectronic applications.
Real-time optical fiber sensors based on light diffusing microlens arrays
Authors: Elsherif Mohamed , Moreddu Rosalia , Hassan Muhammad Umair , Yetisen Ali K. , Butt Haider
Published: May 2019

The applications of optical fibers are impeded in implantable medical diagnostics due to incompatibility with biological tissues, and immune reaction in vivo.
Solvent-tuned discriminant sensing of Al3+, Mg2+and HF2−by vanilinyl-picolinyl hydrazide Schiff base
Authors: Purkait Rakesh , Sinha Chittaranjan
Published: May 2019

X-ray structurally characterized solid-state emissive vanilinyl organic entity shows fluorescence sensitivity towards multi-analytes.
Excited-state intramolecular proton transfer (ESIPT) emitters based on a 2-(2′-hydroxybenzofuranyl)benzoxazole (HBBO) scaffold functionalised with oligo(ethylene glycol) (OEG) chains
Authors: Felouat Abdellah , Curtil Mathieu , Massue Julien , Ulrich Gilles
Published: May 2019

This article describes the multi-step synthesis of 2-(2′-hydroxybenzofuran)benzoxazole (HBBO) derivatives functionalised with one to three oligo(ethylene glycol) (OEG) chains with the goal to allow a good vectorization in aqueous media.
Transparent microparticles in water/sucrose solution
Authors: Payamyar Payam
Published: May 2019

Dispersion polymerization produces microparticles with a refractive index of 1.3770 that can be made transparent in water/sucrose solution.
Knockdown of Tcf3 enhances the wound healing effect of bone marrow mesenchymal stem cells in rats
Authors: He Bin , Chen Jia , Liu Liang , Wang Hao , Wang Shaohua , Li Ping , Zhou Jianda
Published: May 2019

The aim of the present study was to explore the wound healing effect of Tcf3 in rat bone marrow mesenchymal stem cells (BMSCs) and their effects on wound healing. Epidermal growth factor (EGF) and fibroblast growth factors (FGFs) were used to induce BMSCs differentiation into epithelial-like cells. Western Blotting analysis and RT-qPCR were performed to assess the expression levels of Tcf3 and the markers of epithelial-like cells, such as Cytokeratin-18 (CK-18), CK-19 and P63. Cell counting kit-8 (CCK-8) and clone formation assay were carried out to detect cell viability. Immunohistochemistry and HE staining were used to assess the level of Tcf3 protein and skin repair degree, respectively. Rat wound healing model was built to evaluate the effects of BMSCs with altered expression of Tcf3 on wound healing. Results showed that EGF and FGFs stimulation increased the expression of CK-18, CK-19 and P63, improved BMSCs viability, but decreased the expression of Tcf3. Knockdown of Tcf3 in BMSCs increased CK-18, CK-19 and P63 expression and improved cell proliferation, as well as accelerated wound healing process. Moreover, inhibition of Wnt/β-catenin signaling weakened the effect of Tcf3 down-regulation on BMSCs proliferation enhancement. And inhibition of Notch1 signaling impeded the epithelial-like cell differentiation of BMSCs induced by Tcf3 down-regulation. Our study reveals that knockdown of Tcf3 enhances the wound healing process of BMSCs in rat, which provides new approach for accelerating skin regeneration.
Long non-coding RNA MEG3 serves as a ceRNA for microRNA-145 to induce apoptosis of AC16 cardiomyocytes under high glucose condition
Authors: Chen Yiwei , Zhang Zhifang , Zhu Diqi , Zhao Wenchuo , Li Fen
Published: May 2019

Diabetic cardiomyopathy (DCM) is one of the most serious complications of diabetes, but its pathogenesis remains largely unclear. In the present study, we aimed to explore the potential role of long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) and to investigate the underlying mechanisms in human AC16 cardiomyocytes under high glucose (HG) condition. The results demonstrated that MEG3 was overexpressed in HG-treated AC16 cells, and MEG3 knockdown suppressed the HG-induced apoptosis in AC16 cells. Mechanistically, MEG3 directly binds to miR-145 in AC16 cells, thereby up-regulating the expression of PDCD4. Rescue experiments showed that the role of MEG3 in HG-treated AC16 cells was partly dependent on its suppression on miR-145. In summary, our findings suggested that the role of MEG3 in HG-treated human cardiomyocytes is to serve as a competing endogenous RNA (ceRNA), which negatively regulates miR-145. These findings may provide a valuable and promising therapeutic target for the treatment of DCM in the future.
Electron acceleration at comet 67P/Churyumov-Gerasimenko
Authors: Goldstein R. , Burch J. L. , Llera K. , Mokashi P. , Nilsson H. , Dokgo K. , Eriksson A. , Odelstad E. , Richter I.
Published: May 2019

We report the observation by the Ion and Electron Sensor (IES) of energetic (>1 keV) electrons in the plasma environment of comet 67P Churyumov-Gerasimenko (67P). Most of the electrons in the cometary coma are expected to be of solar wind, photoionization, or electron impact origin and are therefore not expected to exceed some hundreds of eV in energy. During the Vega flybys of comet Halley, 1 keV electrons were also observed, and these are explained as having been accelerated by lower hybrid (LH) waves resulting from the two-stream instability involving the solar wind and pickup-ion flows. These waves resonate with the cyclotron motion of the ions and the longitudinal motion of electrons and are on the order of several Hz, at least in the case of 67P. We postulate that the energetic electrons we have observed intermittently during December 2015 through January 2016 are also the result of such a process and that Landau damping causes the acceleration and subsequent abrupt decrease in this energy (also seen at Halley). We show from this study an event on 19 January 2016 when IES simultaneously observed accelerated electrons, solar wind protons, water ions, and LH waves. A dispersion analysis shows that the ion–ion two-stream instability has positive growth rates for such waves during the observation period.
Signatures of the resonances of a large Galactic bar in local velocity space
Authors: Monari G. , Famaey B. , Siebert A. , Wegg C. , Gerhard O.
Published: May 2019

The second data release of the Gaia mission has revealed a very rich structure in local velocity space. In terms of in-plane motions, this rich structure is also seen as multiple ridges in the actions of the axisymmetric background potential of the Galaxy. These ridges are probably related to a combination of effects from ongoing phase-mixing and resonances from the spiral arms and the bar. We have recently developed a method for capturing the behaviour of the stellar phase-space distribution function at a resonance by re-expressing it in terms of a new set of canonical actions and angles variables valid in the resonant region. Here, by properly treating the distribution function at resonances, and by using a realistic model for a slowly rotating large Galactic bar with pattern speed Ωb = 39 km s−1 kpc−1, we show that no fewer than six ridges in local action space can be related to resonances with the bar. Two of these ridges at low angular momentum correspond to the corotation resonance, and can be associated with the Hercules moving group in local velocity space. Another ridge at high angular momentum corresponds to the outer Lindblad resonance, and can tentatively be associated with the velocity structure seen as an arch at high azimuthal velocities in Gaia data. The other ridges are associated with the 3:1, 4:1, and 6:1 resonances. The last can be associated with the so-called “horn” of the local velocity distribution. While it is clear that effects from spiral arms and incomplete phase-mixing related to external perturbations also play a role in shaping the complex kinematics revealed by Gaia data, the present work demonstrates that, contrary to common misconceptions, the bar alone can create multiple prominent ridges in velocity and action space.
Status recognition for fused deposition modeling manufactured parts based on acoustic emission
Authors: Li Feng , Yu Zhonghua , Shen Xuanwei , Zhang Hao
Published: May 2019

Fused deposition modelling (FDM), as one technology of additive manufacturing, fabricates parts always with curl and looseness defects which restrict its development to a great extent. In this paper, a method based on acoustic emission (AE) was proposed to recognise the status of the manufactured part in FDM process. Experiments were carried out to acquire the AE signal when the printing part was respectively in normal, looseness and curl state. The ensemble empirical mode decomposition (EEMD) was employed to the process of feature extraction and both the methods of Hidden-semi Markov model (HSMM) and support vector machine(SVM) were applied to recognise the three states of the normal, looseness and curl. The results reveal that the combination of EEMD and HSMM makes it more accurate to recognize these three states.
Crane Cabins Development - Are there Innovations Needed?
Authors: Spasojevic Brkić Vesna , Veljković Zorica , Brkić Aleksandar
Published: May 2019

The use of load lifting/handling equipment makes workplaces dangerous given the high potential for injury, loss of life and material damage. Cranes are extremely important component in many different industrial operations today. Previous researches have highlighted the need of such equipment to be safely operated and easily maintained, while associated human errors should be considerably reduced. Hence, human centered issues have to be analyzed first and according to those conclusions certain innovations are necessary. This survey offers new crane cabin design based on univariate and multivariate approaches applied on operators’ anthropometric data in aim to enable their ergonomic convenience. Later, design issues are solved, through static and dynamic calculations using finite method elements in that context. Finally, crane cabin design in the light of Industry 4.0 concept is further analyzed together with inventions that are helpful there. Accordingly, we can conclude that in crane cabins development process proposed innovations are needed and very beneficial.
Improving Accuracy of Wind Analysis with Multiple Sampling Rates of Wind Measurement
Authors: Korprasertsak Natapol , Leephakpreeda Thananchai
Published: May 2019

The sampling rate in wind measurement has influences on accuracy of wind analysis. Missing wind data problem can be prevented with high sampling rates. However, a lot of data are unnecessarily required in wind analysis. In this work, optimal sampling rates are determined in real time by the Nyquist sampling theorem according to varying wind conditions. It is found that all statistical results in wind analysis are obtained with percentage errors of less than 1% while the amount of wind data is decreased significantly from the benchmark at fixed sampling rate of 10 Hz.
Research of lightning transient potential on the jacket foundation offshore wind turbines
Authors: Tao Shiqi , Yao Ximei , Liu Bojing , Zhang Xiaoqing , Wang Yaowu
Published: May 2019

Offshore wind turbines are often struck by lightning due to their tall structures and the harsh marine environment. The high transient potential from lightning strike can cause serious damage for the devices of offshore turbines. For analysing the effect of transient potential, a complete transient circuit model is established and an efficient algorithm is also presented to evaluate the circuit parameters of blade, tower, and jacket foundation. On the basis of the circuit model, the transient potential at the different locations of the offshore wind turbine can be carried out during direct lightning strike by PSCAD. Finally, the circuit model is used by a numerical example of an actual Chinese-built offshore wind turbine.
Cylinder liner deformation orders and efficiency of a piston ring-pack
Authors: Selmani Erjon , Delprete Cristiana , Bisha Arian
Published: May 2019

One of the several losses of a combustion chamber is the gas leakage toward the crankcase due to imperfect sealing of the rings. It is commonly known as blow by and it affects efficiency and emissions. The paper initially describes a bibliographic review of the phenomenon, together with the equations of the system. A typical piston ring pack for internal combustion engine is proposed to be analysed and solved using ©Ricardo RINGPAK Solver. A specific issue such as Bore distortion orders were used to investigate the sealing capacity of the ring-pack in terms of ring dynamics, inter-ring pressures and mass flows. Bore distortion orders and their magnitude showed to affect the ring pack behavior. Order zero distortion resulted to be the most important order due to the highest amount of gas lost in the crankcase, while orders three and four resulted to generate high blow-by values, even if their magnitude of distortion is lower in comparison to other orders.
Results from the Pierre Auger Observatory
Authors: Roulet Esteban
Published: May 2019

I describe some of the results on ultrahigh-energy cosmic rays that have been obtained with the Pierre Auger Observatory. These include measurements of the spectrum, composition and anisotropies. Possible astrophysical scenarios that account for these results are discussed.
Upgrading Plan Towards Multi-messenger Observation with LHAASO
Authors: Cao Z. , Chen M.J. , Li H.C. , Yao Z.G.
Published: May 2019

LHAASO is planning to enhance its sensitivity at energies around 100 GeV by utilize MCP staffed 20” PMT in the Water Cherekove Detector Array. The effective area for gamma ray detection will reach to 1800 m2 and differential sensitivity to 0.2 CU at 50 GeV. It will be the very useful survey detection for transient phenomena at 50 GeV in the northern sky. LHAASO is expected to play an important role in the multimessenger observation with the upgrading.
The AMS-02 detector on the ISS - Status and highlights, after the first 7 years on orbit
Authors: Duranti Matteo
Published: May 2019

The Alpha Magnetic Spectrometer, AMS-02, detector is operating on the International Space Station (ISS) since May the 19th, 2011. More than 120 billion events have been collected by the instrument in the first 7 years of data taking, providing detailed insight on the features of different species of cosmic rays. This contribution reviews the recent AMS-02 results based on 7 years of operations in space and their contribution to the advances in the understanding of cosmic ray origin, acceleration and propagation physics.
The Large Magellanic Cloud with the Cherenkov Telescope Array
Authors: Isabel Bernardos María , Benito María , Iocco Fabio , Mangano Salvatore , Sergijenko Olga , Karukes Ekaterina , Yang Lili
Published: May 2019

The Large Magellanic Cloud (LMC) is a spiral galaxy, satellite of the Milky way with a high star formation activity. It represents a unique laboratory for studying an extended and spatially resolved star-forming galaxy through gamma-ray observatories. Therefore, the LMC survey is one of the key science projects for the Cherenkov Telescope Array (CTA), the next-generation ground-based gamma-ray observatory. In this document we present the work performed over the last year by the CTA working group dedicated to the LMC, in order to offer a first characterization of the LMC at TeV energies. We have performed detectability forecasts based on the expected CTA performance for all sources in the region of interest of the LMC with known emission at GeV energies and above. Based on previous observations made by Fermi-LAT and H.E.S.S. we have characterized all point sources, extended sources and diffuse emission produced by cosmic-ray propagation, extrapolating their spectra to CTA energies. Finally, we have characterized the signal expected by different annihilation mechanisms of dark matter (DM) particles within the LMC, computing the detection sensitivity curve for this target in the cross-section-to-mass plane.
Latest results on dark matter searches with H.E.S.S
Authors: Rinchiuso Lucia
Published: May 2019

The nature of Dark Matter (DM) is one of the most debated questions of contemporary physics. Ground-based arrays of Cherenkov telescopes such as the High Energy Spectroscopic System (H.E.S.S.) search for DM signatures through the detection of Very-High-Energy (VHE, E > 100 GeV) gamma-rays. DM particles could selfannihilate in dense environments producing VHE γ-rays in the final states that could be eventually detected by H.E.S.S.. The H.E.S.S. observation strategy for DM search focuses towards the Galactic Centre (GC) region and nearby dwarf galaxy satellites of the Milky Way. The GC dataset provides the most stringent constraints on the DM annihilation cross section in the mass range 300 GeV - 70 TeV. Searches have been carried out towards classical and ultra-faint dwarf galaxies to test specific heavy DM models. The latest results towards the GC and dwarf galaxies are shown.
Highlights from H.E.S.S.
Authors: de Naurois Mathieu
Published: May 2019

In the 15 years since its construction, the H.E.S.S. gamma-ray observatory has allowed the study of the Very High Energy gamma-ray sky at resolutions and sensitivities which were never before possible. During this period H.E.S.S. has discovered a rich zoo of both galactic and extra galactic source classes, made measurements of the galactic cosmic ray spectrum and placed limits on fundamental physical processes. A summary of the latest H.E.S.S. results for these source classes has been presented at the conference, describing the most interesting new observations and their physical interpretation. Additionally the latest upgrades and improvements to the H.E.S.S. hardware and data analyses, and the future science prospects for the experiment have been described.
VERITAS: Status and Recent Results
Authors: Quinn John
Published: May 2019

VERITAS has just completed its 11th year of full four-telescope scientific operations and continues to function with excellent efficiency. Its science program, encompassing galactic, extragalactic, and fundamental physics, entails dedicated observations of specific targets as well as multi-messenger target-of-opportunity observations. The current operational status of VERITAS is presented, as well as recent science highlights, and the future plans for the observatory are discussed.
Recoil Directionality Experiment
Authors: Sanfilippo S. , Agnes P. , Arba M. , Ave M. , Baracchini E. , Boiano A. , Bonivento W. M. , Bottino B. , Cadeddu M. , Caminata A. , Caravati M. , Cariello M. , Carpinelli M. , Catalanotti S. , Cataudella V. , Cereseto R. , Cicalò C. , Covone G. , de Candia A. , De Filippis G. , De Rosa G. , Davini S. , Devoto A. , Dionisi C. , D’Urso D. , Fiorillo G. , Franco D. , Giovannetti G. K. , Giganti C. , Galbiati C. , Gulino M. , Korga G. , Kuss M. , La Commara M. , La Delfa L. , Lissia M. , Mariani A. , Mari S. M. , Martoff C. J. , Masone V. , Oleynikov V. , Pallavicini M. , Pandola L. , Razeto A. , Rescigno M. , Rossi N. , Sablone D. , Scapparone E. , Suvorov Y. , Testera G. , Tuveri M. , Wang H. , Wang Y.
Published: May 2019

Directional sensitivity to nuclear recoils could provide a smoking gun for a possible discovery of dark matter in the form of WIMPs. A hint of directional dependence of the response of a dual-phase liquid argon Time Projection Chamber was found in the SCENE experiment. Given the potential importance of such a capability in the frame work of dark matter searches, a new dedicated experiment, ReD (Recoil Directionality), was designed in the framework of the DarkSide Collaboration, in order to scrutinize this hint. This contribution will describe the performance of the detectors achieved during the first test-beam, the current status of ReD and the perspectives for physics measurements during the forthcoming beam-time.
Particle propagation in clumpy supernova remnants
Authors: Celli Silvia
Published: May 2019

The presence of dense clumps in the environment where a supernova remnant expands might have a strong impact in shaping the observed hadronic gamma-ray spectrum. A detailed numerical study about the penetration of relativistic protons into clumps which are engulfed by a supernova remnant shock is here presented, taking into account the magneto-hydrodynamical properties of the background plasma. This has strong implications for the formation of the spectrum of hadronic gamma rays, which does not reflect anymore the acceleration spectrum of protons, resulting substantially modified by propagation effects. A hadronic scenario including dense clumps inside the remnant shell is shown to adequately reproduce the broadband gamma-ray spectrum of the Galactic supernova remnant RX J1713-3946.7 from GeV to TeV energies.
The Cherenkov Telescope Array Science Goals and Current Status
Authors: The CTA Consortium  , Ong Rene A.
Published: May 2019

The Cherenkov Telescope Array (CTA) is the major ground-based gamma-ray observatory planned for the next decade and beyond. Consisting of two large atmospheric Cherenkov telescope arrays (one in the southern hemisphere and one in the northern hemisphere), CTA will have superior angular resolution, a much wider energy range, and approximately an order of magnitude improvement in sensitivity, as compared to existing instruments. The CTA science programme will be rich and diverse, covering cosmic particle acceleration, the astrophysics of extreme environments, and physics frontiers beyond the Standard Model. This paper outlines the science goals for CTA and covers the current status of the project.
Main scientific results of the DAMPE mission
Authors: Bernardini Paolo
Published: May 2019

DAMPE (DArk Matter Particle Explorer) is a satellite-born experiment, resulting from the collaboration of Chinese, Italian, and Swiss institutions. Since December 2015, DAMPE flights at the altitude of 500 km and collects data smoothly. The detector is made of four sub-detectors: top layers of plastic scintillators, a silicon-tungsten tracker, a BGO calorimeter (32 radiation lengths), and a bottom boron-doped scintillator to detect delayed neutrons. The main goal of the experiment is the search for indirect signals of Dark Matter in the electron and photon spectra with energies up to 10 TeV. Furthermore DAMPE studies cosmic charged and gamma radiation. The calorimeter depth and the large acceptance allow to measure cosmic ray fluxes in the range from 20 GeV up to hundreds of TeV. An overview of the latest results about light component (p+He) of charged cosmic rays, gamma astronomy and electron and positron spectrum will be presented.
Pulmonale Hypertonie: Diagnostik, Klassifikation und Therapie
Authors: Lücke Eva , Schmeißer Alexander , Schreiber Jens
Published: May 2019

Bei der pulmonalen Hypertonie handelt es sich um eine Druckerhöhung in der Lungenstrombahn, dem sog. kleinen Kreislauf: Der pulmonalarterielle Mitteldruck (Messung im Rechtsherzkatheter) ist auf über 25 mmHg erhöht. Für die Prognose der meist stark beeinträchtigten Patienten ist eine frühe Diagnosestellung extrem wichtig. Der Beitrag widmet sich der Diagnostik, der klinischen Klassifikation und der gruppenspezifischen Therapie der pulmonalen Hypertonie.
Akute Brustschmerzen in der Hausarztpraxis – Unsicherheit zwischen abwartendem Offenhalten und Notarzteinsatz
Authors: Schmiemann Guido , Frantz Stefan
Published: May 2019

Acute chest pain is a frequent reason for encounter in primary care. In contrast to hospital/emergency departments serious diseases like acute coronary syndrome or a pulmonary embolism are relative rare in primary care. This overview presents the diagnostic work up and decisions for transfer to the hospital setting in patients with acute chest pain.
Herpes zoster – bewährte Indikationen
Authors: Bleul Gerhard
Published: May 2019

Homöopathische Differenzialdiagnose des Herpes zoster. Schnelle Mittelwahl aufgrund besonderer Charakteristika und Modalitäten sowie Auffälligkeiten in Stimmung und Verhalten.
Pharmacokinetic Study of SKL-18287, a Novel Long-Acting Glucagon-Like Peptide-1 Receptor Agonist, in Rats, Monkeys and Mini-Pigs
Authors: Takeuchi Mitsuaki , Okamoto Masayuki , Tamura Miyuki , Murase Takayo , Watanabe Nobuhide
Published: May 2019

Background Long-acting glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for treatment of type 2 diabetes (T2DM) in the United States, the European Union, and Japan. In our previous work, we designed and characterized a novel GLP-1 RA, SKL-18287. This RA consists of only natural L-amino acids, and is believed to exist in an oligomer form in systemic circulation. This unique feature may allow high biological stability and a long-lasting glucose lowering effect in T2DM treatment. In the present study, we investigated the pharmacokinetic properties of SKL-18287 in rats, monkeys, and mini-pigs. Tissue distributions of radioactivity were also studied in rats after subcutaneous administration of [3H]-SKL-18287.

Methods Plasma concentrations of SKL-18287 were measured by LC-MS/MS after intravenous and subcutaneous administration of SKL-18287 in rats, monkeys, and mini-pigs. Pharmacokinetic parameters were then calculated and compared among these animal species. Tissue concentrations of radioactivity were determined by liquid scintillation counting following sample combustion, after subcutaneous administration of [3H]-SKL-18287 to rats.

Results SKL-18287 showed an extended half-life of over 5 h, with good subcutaneous bioavailability, in all animal species. Prediction of the pharmacokinetic profiles of SKL-18287 in humans using an animal scale-up approach revealed an SKL-18287 half-life of 14.8 h. The radioactivity concentration in the pancreas, a target tissue of GLP-1RA, was relatively higher than in other tissues, until 12 h after [3H]-SKL-18287 administration.

Conclusion SKL-18287 might be sufficient to maintain an effective concentration for a once-daily treatment for T2DM, and is a unique GLP-1 RA with a pancreas-selective feature.
Simulation-Based Training of Ultrasound-Guided Procedures in Radiology – A Systematic Review
Authors: Kahr Rasmussen Niklas , Andersen Tobias Thostrup , Carlsen Jonathan , Østergaard Mia Louise , Konge Lars , Albrecht-Beste Elisabeth , Nielsen Michael Bachmann
Published: May 2019

Purpose To perform a systematic review of the effect of simulation-based training (SBT) of percutaneous abdominal and thoracic ultrasound-guided procedures and to assess the transfer of procedural competence to a clinical context.

Materials and Methods This systematic review was conducted in accordance with the PRISMA statement. Pubmed, Embase, Web of Science, and the Cochrane Library were searched for studies assessing procedural competence after SBT. Two authors independently reviewed all studies and extracted data. Risk of bias was assessed using the Cochrane tool for randomized studies (RoB) and non-randomized studies (ROBINS-I). Quality of evidence was assessed using the GRADE approach.

Results 42 studies were included. 6 were randomized controlled, 3 non-randomized controlled, and 33 non-randomized non-controlled. 26 studies examined US-guided abdominal procedures, 13 examined thoracic procedures, and 3 examined both. The results favored SBT compared to other educational interventions and found that training was superior to no training. Only two studies examined the transfer of procedural skills to a clinical context. All studies had a high or critical risk of bias. Thus, the quality of evidence for the effect of SBT on procedural competence was low, and evidence for its transfer to a clinical context was very low.

Conclusion The evidence supporting SBT of percutaneous abdominal and thoracic US-guided procedures remains insufficient due to methodological problems and a high risk of bias. Future studies should be randomized and single-blinded, use assessment tools supported by validity evidence, compare different educational strategies, and examine the transfer of skills to a clinical setting.
Microwave-Assisted CuCl-Catalyzed Three-Component Reactions of Alkynes, Aldehydes, and Amino Alcohols
Authors: Li Xiang , Chen Ning , Xu Jiaxi
Published: May 2019

A microwave (MW)-assisted three-component coupling of amino alcohols, aldehydes, and alkynes is developed under catalysis by CuCl. Compared with thermal conditions, MW irradiation greatly increases the reaction efficiency. The reactions of various primary N-alkyl/arylamino alcohols, aliphatic/aromatic aldehydes, and alkynes are systematically investigated, affording the desired products in moderate to good yields. Notably, acetylene is also an effective reactant under the current MW-assisted conditions.
Human Platelet-Secreted Proteins (LA-PF4, βTG) Do Not Modify Prostacyclin (PGI2) Production By Bovine Aortic Endothelial Cells
Authors: Poggi A , Niewiarowski S , Holt J C , Dall’Olio A , Stewart G J , Smith J B
Published: May 2019

It has been proposed that platelets may counteract the antithrombotic activity of the vessel wall by releasing proteins with inhibitory activity on vascular PGI2. The aim of our study has been to evaluate the effect of LA-PF4 and βTG, two human platelet-secreted proteins which may be increased in conditions associated with thrombosis, on the production of PGI2 by bovine endothelial cells (EC). Cells obtained by mild collagenase digestion of calf aortas, were plated in plastic dishes and cultured for 5-6 days in minimum essential medium. Only primary cultures were used. Confluent cells (6-10x105)5/dish) were washed twice with PBS and incubated in the same buffer at 37°C for 5-10 minutes in the presence or absence of the platelet-secreted proteins. LA-PF4 was prepared from washed human platelets aggregated with thrombin after chromatography on CM-sephadex and heparin- sepharose. βTG was obtained by partial trypsinization of LA-PF4. LA-PF4 or βTG at the doses of 5-50 ug/ml did not modify the production by EC of 6-keto PGF1α(measured by a radioimmunoassay). EC indeed released 8.9 ± 3.8 pmoles/ml of 6-keto PGF1α, when incubated with buffer, and 13.6 ± 2.3 or 4.1 ± 0.9 when incubated with LA-PF4 or βTG (10 ug/ml). A dose-dependent release of 6-keto-PGF1α was found after stimulation of EC with arachidonic acid (AA, 1-50 um). After addition of AA (2 uM) the generation of 6-keto-PGF1α was 153.5 ± 45.0 pmoles/ml in control samples, 86.7 ± 15.2 and 163.3 ± 15.2 in samples incubated with LA-PF4 or βTG, respectively. Similarly, no effect was found when PGI2 production by EC was measured by bioassay of its antiaggregatory activity. The tested proteins did not modify either the production of TXB2 (2-10 pmoles per ml of incubation medium) by the same EC. These data indicate that, in our experimental conditions, LA-PF4 and βTG did not show potentially thrombogenic effects on prostaglandin production by EC.
Factor VIII/Von Willibrand Factor Is An Integral Component Of The Platelet Surface
Authors: Ruggeri Z M , Bader R , Pareti F I , Mannucci L , Mannucci P M
Published: May 2019

Platelets contain Factor VIII/von Willebrand. Factor (FVIIl/vWF) but its localization on the platelet surface is still controversial. We now demonstrate that anti-FVIIl/vWF antibodies induce serotonin release and aggregation when added to suspensions of washed intact platelets from normal individuals (n=8) and patients with autosomal dominant von Willebrand’s disease (VWD) (n=6), but not from patients with severe, homozygous-like VWD (ns=4). One monospecific rabbit anti-human FVIIl/vWF antiserum, adsorbed with severe VWD plasma, and four unadsorbed homologous antisera,obtained from multitransfused patients with severe VWD, gave identical results. Serotonin release and aggregation were dependent on the anti-FVIIl/vWF titer and were completely blocked when purified human FVIII/vWF was added to the platelet suspension, Pre-incubation with 6-deoxy-glucose and antimycin rendered the platelet suspension unresponsive, suggesting that aggregation rather than agglutination was occurring. There was no evidence of cell lysis as shown by lack of release of the cytoplasmic marker adenylate kinase. Fab fragments prepared from anti-FVIII/vWF IgG failed to induce aggregation but completely blocked that by whole IgG, Radiolabeled Fab fragments bound to normal (n=6) and autosomal dominant VwD (n=4) platelets to a similar extent (mean binding 20±0.3 pg/107 platelets)but no binding was observed with severe VWD platelets (ns=2). In one patient with severe VWD platelets remained unreactive during and after prophylactic replacement therapy with FVIII/vKF concentrates for one month. Our studies suggest that FVIII/vWF is accessible on the surface of washed platelets except in severe VWD.
Conformational Flexibility In Fibrinogen
Authors: Hantgan Roy R
Published: May 2019

The structure of fibrinogen in solution has been investigated by the technique of steady state fluorescence polarization. Factor XIII a has been employed to catalyze the incorporation of approximately 3 moles dansylcadaverine per mole fibrinogen without disruption of its structure or function. Two γ-chain and one α-chain crosslink acceptor sites have been labelled, according to SDS-polyacrylamide gel electrophoresis. Light scattering and electron microscopy verify that this derivative forms normal fibrin upon thrombin activation; the modified protein is 93% clottable. The fluorescence emission maxiumum is shifted to 500 nm (vs. 540 nm for dansylcadaverine) and a substantial increase in fluorescence intensity is noted. Measurements of the fluorescent lifetime, by a phase shift technique, show an average lifetime of 14.5 ±2.5 nanoseconds (vs. 3 ns for dansylcadaverine). The rotational relaxation time, determined from a Perrin plot of polarization vs. temperature, is 165 ±13 ns. No change in rotational relaxation time was found in 0.005 M CaCl2 or at high ionic strength. The limiting polarization (extrapolated to infinite viscosity) agrees with that determined with dansylcadaverine fibrin (coarse gel conditions) as well as with the vlaue measured in 75% glycerol at 0°C. These controls confirm that overall macromolecular motion, not probe rotation,is being measured.

The measured rotational relaxation time for dansylcadaverine fibrinogen is substantially shorter than values calculated for an anhydrous rigid sphere (300 ns) or a prolate ellipsoid (1000 ns), as well as other models based on hydrodynamic data. These results indicate that the rotating unit is smaller than the entire fibrinogen molecule, i.e. that the structure of fibrinogen in solution is flexible. This observation is consistent with earlier polarization data reported for dansylchloride labelled fibrinogen, as well as structural data indicating fibrinogen to be a multidomain protein, whose globular portions are connected by helical chains.
Expression Of The Fc Receptor On Human Platelets Is Regulated By Cyclic Amp Changes
Authors: Timmons S , Timmons J , Graber S , Hawiger J
Published: May 2019

The Fc receptor of human platelets is involved in their injury by immune complexes composed of drugs, viruses, or bacteria and corresponding IgG antibody. Using Protein A- bearing staphylococci coated with isolated human IgG Fc fragment as a functional probe for the Fc receptor, we measured factors regulating its expression on human platelets. Isolated Fc fragment in the fluid phase and not bound to Protein A-bearing staphylococci remained without a measurable effect on human platelets isolated from plasma proteins. Fc fragment bound to Protein A-bearing staphylococci caused their aggregation and release of 3H-serotonin. Prostaglandin I2 (PGI2, prostacyclin) known as the most potent activator of platelet adenylate cyclase blocked the interaction between Fc fragment-coated staphylococci and human platelets. This effect was dose- and time-dependent. A corresponding rise in platelet cAMP levels was observed in parallel experiments. Refractoriness of PGI2-treated platelets was persistent up to 2 hr and was paralleled by a sustained increase in platelet cAMP level. Thus, a rise in platelet cAMP level induced by PGI2 is associated with a reduced expression of the Fc receptor on human platelets.
Plateiet-Activating Factor (1-0-Alkyl-2-Acetyl-sn-Glyceryl-3-Phosphorycholine) Stimulates Prostacyclin Synihesis By Cultured Human Endothelial Cells
Authors: Test S T , Bang N U
Published: May 2019

l-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (Ac-GEPC) has recently been established to possess biological properties identical to those of platelet-activating factor (PAF) released from stimulated mast cells and leucocytes (Demopoulos et al, J. Biol. Chem. 254:9355, 1979). Shaw et al (J. Imuunol. 121:1939, 1978) reported that PAF is capable of stimulating platelet thranbaxane A2 synthesis. We examine here whether synthetic Ac-GEPC stimulates PGI2 synthesis in human endothelial cell cultures. Human umbilical vein endothelial cells during the third passage were grown to confluency in 35 x 10 ran dishes and challenged with Na arachidonate(NaA), 8 x 10-5M or Ac-GEPC, 5 x 10-% (a concentration which produced optimal platelet aggregation in human platelet-rich plasma). PGI2 production was monitored through radioimmunoassays of its metabolite, 6-keto-PGF1α. After washing endothelial cell layers twice, the agonists were added in tris-Tyrodes buffer, pH 7.2 containing 2.5 g/L bovine serum albumin. Representative timed experiments produced the following results expressed in pM 6-keto-PGF1α/105 cells for NaA and Ac-GEPC respectively after the noted times of incubation: 10s: 274/467, 20s: 630/1136, 30s: 1111/1005, 60s: 1757/1217, 90s: 1842/1272, 120s: 1115/698, 180s: 1188/453. These data indicate that Ac-GEPC stimulates the production of PGI2 at a rate roughly comparable to that achieved by stimulation with NaA, reaching a maximum at 60 and 90s in these experiments. The decrease, compared to peak levels, in iranunoreactive 6-keto-PGF1α at 120 and 180s of 23% and 36% for NaA stimulated cells and 45% and 65% for Ac-GEPC stimulated cells suggests that enzymes are activated during the experiment which cause conversion of PGI2 into metabolites other than 6-keto-PGF1α (e.g. 6-keto-PGE1). These results suggest another theoretically important negative feedback mechanism for a potent platelet proaggregatorv substance.
Urokinase Treatment In Acute And Subacute Deep Vein Thrombosis
Authors: Trübestein G , Brecht Th , Ludwig M , Brecht G , Etzel F
Published: May 2019

So far 74 patients with acute and subacute Deep Vein Thrombosis (DVT) were treated with a standardized Urokinase (UK) heparin scheme. From these patients 19 patients had a 1-6 day and 55 patients a 1-6 week old thrombosis of the iliac, femoral, popliteal or subclavian veins. The initial dose of the UK regimen was mostly 250.000 IU UK/10 min; the maintenance dose was 1.000.000 IU UK/24h in 40 patients, 1.500.000 IU UK/24h in 12 patients and 2.000.000 IU UK/24h in 22 patients. Heparin was given from the very beginning, starting with a dose of 1.000 IU/h. In the further course of therapy heparin was adjusted so that the thrombin time was 2 to 4 times of the normal. The duration of fibrinolytic therapy was mostly between 3 and 6 days in acute and between 7 and 14 days in subacute DVT. Severe side effects were seen in 2 patients, who had a strong bleeding. One patient died of pulmonary embolism.

Results: The 1-6 day old thromboses of the 19 patients could be dissolved completely in 7 patients (37%) and partially in 4 patients (21%); no amelioration in the phlebo- grams was found in 8 patients (42%). The 1-6 week old thromboses of the 55 patients could be dissolved completely in 9 patients (16%) and partially in 30 patients (55%); no amelioration in the phlebograms was found in 16 patients (29%).

Conclusion: The standardized UK-heparin scheme with a medium dose 80.000 IU UK/h used by us proved to be effective in most patients with DVT.