bluuebunny/crossref_metadata_2025 huggingface dataset:
Local tentative bonding method to maintain alignment accuracy in bonding process using resin as an adhesive material
Authors: Kondo Masahiro , Komiyama Ryohei , Miyashita Hidetoshi , Lee Sang‐Seok
Published: March 2018

The authors proposed a novel method to maintain the alignment accuracy in the wafer‐bonding process, which uses a resin as an adhesive material. Recently, the resin has received attention as an adhesive material for wafer bonding in microelectromechanical system device fabrication because of its multiple advantageous material properties. However, because of its inherent material viscosity, the alignment accuracy cannot be easily maintained, particularly when two wafers are bonded with a thick resin after alignment. To solve this problem, they proposed a local tentative bonding method. After aligning the two wafers, they irradiated the adhesive resin layer between the wafers using a near‐infrared (NIR) spotlight (wavelength = 1020 nm), which is transparent to Si wafers. Using several NIR irradiation spots aimed at the resin layer after aligning the wafers, the resin layer was bonded locally and tentatively, which was sufficiently secure to avoid wafer shifting in the subsequent process. The local tentative bonded areas acted as anchors, which held the wafers during the bonding process. They performed experiments to demonstrate the effectiveness of their method using resins, such as polyimide, benzocyclobutene and SU‐8. Consequently, they achieved an alignment accuracy <5 µm, which is a significant improvement compared with the typical bonding results.
The shape of convective core overshooting from gravity-mode period spacings
Authors: Pedersen M. G. , Aerts C. , Pápics P. I. , Rogers T. M.
Published: March 2018

Context.The evolution of stars born with a convective core is highly dependent on the efficiency and extent of near core mixing processes, which effectively increases both the core mass and main-sequence lifetime. These mixing processes remain poorly constrained and therefore result in large uncertainties in the stellar structure and evolution models of such stars.

Aims.We investigate to what extent gravity-mode period spacings in slowly pulsating B-type stars observed by theKeplermission can be used to constrain both the shape and extent of convective core overshoot and additional mixing in the radiative envelope.

Methods.We compute grids of 1D stellar structure and evolution models for two different shapes of convective core overshooting and three shapes of radiative envelope mixing. The models in these grids are compared to a set of benchmark models to evaluate their capability of mimicking the dipole progradeg-modes of the benchmark models.

Results.Through our model comparisons we find that at a central hydrogen content ofXc = 0.5, dipole progradeg-modes in the period range 0.8−3 d are capable of differentiating between step and exponential diffusive overshooting. This ability disappears towards the terminal age main sequence atXc = 0.1. Furthermore, theg-modes behave the same for the three different shapes of radiative envelope mixing considered. However, a constant envelope mixing requires a diffusion coefficient near the convective core five times higher than chemical mixing from internal gravity waves to obtain a surface nitrogen excess of ~ 0.5 dex within the main-sequence lifetime.

Conclusions.Within the estimated frequency errors of theKeplermission, the ability ofg-modes to distinguish between step and exponential diffusive overshooting depends on the evolutionary stage. Combining information from the average period spacing and observed surface abundances, notably nitrogen, could potentially be used to constrain the shape of mixing in the radiative envelope of massive stars.
Morphological and growth responses of two green algal strains to toxic Microcystis are dependent on the cultivation growth phase of filtrate and target strain
Authors: Dong Jing , Chang Mengyang , Li Chenlu , Li Jincan , Shang Xiangyang
Published: March 2018

Allelopathic interactions amongst phytoplankton are considered an important factor contributing to species competition and succession in aquatic ecosystems, but their mechanisms in plankton dynamics are poorly described. In this study, whether toxic Microcystis aeruginosa could affect the growth of Chlorella vulgaris and Kirchneriella sp. was examined according to filtrate experiments at different cultivation phases. Results indicated that M. aeruginosa filtrate significantly influenced the growth and morphological characteristics of the two target green algae, which were dependent on the cultivation growth phase of filtrate and target strain. At the beginning of the experiment, the formation of a large C. vulgaris colony was induced by M. aeruginosa filtrate. The effects of filtrate in the stationary phase (SP) was more significant than that of the exponential phase (EP). Subsequently, the colonies gradually broke into small colonies or single cells. The growth rate of C. vulgaris was finally promoted in the filtrate treatment. For Kirchneriella sp., the colonies formed and remained in M. aeruginosa filtrate under EP until the end of the experiment. Smaller colonies were observed in Kirchneriella sp. by M. aeruginosa filtrate under SP than those in the control, and larger colonies were not detected. The growth rate of Kirchneriella sp. was inhibited in the filtrate of EP but was promoted in SP. This study provided new insights into the interaction between the morphological responses and growth effects of algae and proposed a new theoretical basis for algal succession in aquatic ecosystems.
Determining the distribution of ion channels from experimental data
Authors: Bourgeron Thibault , Conca Carlos , Lecaros Rodrigo
Published: March 2018

The authors study an integral inverse problem arising in the biology of the olfactory system. The transduction of an odor into an electrical signal is accomplished by a depolarising influx of ions through cyclic-nucleotide-gated (CNG for short) channels on the cilium membrane. The inverse problem studied in this paper consists in finding the spatial distribution of the CNG channels from the measured transduce electrical signals. The Mellin transform allows us to write an explicit formula for its solution. Proving observability and continuity inequalities is then a question of estimating the Mellin transform of the kernel of this integral equation on vertical lines. New estimates using arguments in the spirit of the stationary phase method are proven and a numerical scheme is proposed to reconstruct the density of CNG channels from modeled current representing experimental data, for an approximated model. For the original model an identifiability and a non observability (in some weighted L2spaces) results are proven.
A Mach-sensitive splitting approach for Euler-like systems
Authors: Iampietro D. , Daude F. , Galon P. , Hérard J.-M.
Published: March 2018

Herein, a Mach-sensitive fractional step approach is proposed for Euler-like systems. The key idea is to introduce a time-dependent splitting which dynamically decouples convection from acoustic phenomenon following the fluctuations of the flow Mach number. By doing so, one seeks to maintain the accuracy of the computed solution for all Mach number regimes. Indeed, when the Mach number takes high values, a time-explicit resolution of the overall Euler-like system is entirely performed in one of the present splitting step. On the contrary, in the low-Mach number case, convection is totally separated from the acoustic waves production. Then, by performing an appropriate correction on the acoustic step of the splitting, the numerical diffusion can be significantly reduced. A study made on both convective and acoustic subsystems of the present approach has revealed some key properties as hyperbolicity and positivity of the density and internal energy in the case of an ideal gas thermodynamics. The one-dimensional results made on a wide range of Mach numbers using an ideal and a stiffened gas thermodynamics show that the present approach is as accurate and CPU-consuming as a state of the art Lagrange-Projection-type method.
A uniformly accurate (UA) multiscale time integrator pseudospectral method for the nonlinear Dirac equation in the nonrelativistic limit regime
Authors: Cai Yongyong , Wang Yan
Published: March 2018

A multiscale time integrator Fourier pseudospectral (MTI-FP) method is proposed and rigorously analyzed for the nonlinear Dirac equation (NLDE), which involves a dimensionless parameter ε ∈ (0, 1] inversely proportional to the speed of light. The solution to the NLDE propagates waves with wavelength O (ε2) and O (1) in time and space, respectively. In the nonrelativistic regime,i.e., 0 < ε ≪ 1, the rapid temporal oscillation causes significantly numerical burdens, making it quite challenging for designing and analyzing numerical methods with uniform error bounds inε ∈ (0, 1]. The key idea for designing the MTI-FP method is based on adopting a proper multiscale decomposition of the solution to the NLDE and applying the exponential wave integrator with appropriate numerical quadratures. Two independent error estimates are established for the proposed MTI-FP method as hm0+τ2/ε2andhm0 + τ2 + ε2, where his the mesh size, τis the time step and m0depends on the regularity of the solution. These two error bounds immediately suggest that the MTI-FP method converges uniformly and optimally in space with exponential convergence rate if the solution is smooth, and uniformly in time with linear convergence rate at O (τ) for all ε ∈ (0, 1] and optimally with quadratic convergence rate at O (τ2) in the regimes when either ε = O (1) or 0 < ε ≲ τ. Numerical results are reported to demonstrate that our error estimates are optimal and sharp.
AATR an ionospheric activity indicator specifically based on GNSS measurements
Authors: Juan José Miguel , Sanz Jaume , Rovira-Garcia Adrià , González-Casado Guillermo , Ibáñez D. , Perez R. Orus
Published: March 2018

This work reviews an ionospheric activity indicator useful for identifying disturbed periods affecting the performance of Global Navigation Satellite System (GNSS). This index is based in the Along Arc TEC Rate (AATR) and can be easily computed from dual-frequency GNSS measurements. The AATR indicator has been assessed over more than one Solar Cycle (2002–2017) involving about 140 receivers distributed world-wide. Results show that it is well correlated with the ionospheric activity and, unlike other global indicators linked to the geomagnetic activity (i.e. DST or Ap), it is sensitive to the regional behaviour of the ionosphere and identifies specific effects on GNSS users. Moreover, from a devoted analysis of different Satellite Based Augmentation System (SBAS) performances in different ionospheric conditions, it follows that the AATR indicator is a very suitable mean to reveal whether SBAS service availability anomalies are linked to the ionosphere. On this account, the AATR indicator has been selected as the metric to characterise the ionosphere operational conditions in the frame of the European Space Agency activities on the European Geostationary Navigation Overlay System (EGNOS). The AATR index has been adopted as a standard tool by the International Civil Aviation Organization (ICAO) for joint ionospheric studies in SBAS. In this work we explain how the AATR is computed, paying special attention to the cycle-slip detection, which is one of the key issues in the AATR computation, not fully addressed in other indicators such as the Rate Of change of the TEC Index (ROTI). After this explanation we present some of the main conclusions about the ionospheric activity that can extracted from the AATR values during the above mentioned long-term study. These conclusions are: (a) the different spatial correlation related with the MOdified DIP (MODIP) which allows to clearly separate high, mid and low latitude regions, (b) the large spatial correlation in mid latitude regions which allows to define a planetary index, similar to the geomagnetic ones, (c) the seasonal dependency which is related with the longitude and (d) the variation of the AATR value at different time scales (hourly, daily, seasonal, among others) which confirms most of the well-known time dependences of the ionospheric events, and finally, (e) the relationship with the space weather events.
Überzeugendes Nutzen-Risiko-Profil mit Apixaban
Authors: Grübler Beate
Published: March 2018

Apixaban (Eliquis®) ist seit 2014 zur Behandlung von tiefen Venenthrombosen (TVT) und Lungenembolien (LE) sowie zur Prophylaxe rezidivierender TVT und LE bei Erwachsenen zugelassen (1). Grundlage dafür waren die guten Wirksamkeitsund Verträglichkeitsergebnisse in den Studien AMPLIFY* und AMPLIFY-EXT+, in denen Apixaban vs. der bisherigen Standardtherapie (Heparin/VKA) bzw. Placebo untersucht wurden (2, 3). In einer Subanalyse der AMPLIFY-Studie war Apixaban bei der Behandlung von TVT und LE zu vordefinierten Zeitpunkten (7, 21 und 90 Tage) vergleichbar wirksam wie Enoxaparin/Warfarin bei einem niedrigeren Risiko für schwere Blutungen (4).
Quantitative Bildgebung für die Dosimetrie mit SPECT/CT
Authors: Tran-Gia Johannes , Lassmann Michael , Kuwert Torsten , Ritt Philipp
Published: March 2018

Die möglichst genaue Bestimmung von in Tumoren und kritischen Organen aufgenommenen Aktivitäten ist eine der Grundvoraussetzungen für die Planung und Überwachung der molekularen Radiotherapie mithilfe von interner Dosimetrie. Aufgrund zahlreicher Verbesserungen im Bereich der Hardware, v. a. aber auch im Bereich der Rekonstruktionssoftware, ist die SPECT/CT-Bildgebung zu einer der am besten geeigneten und am weitesten verbreiteten Bildgebungsmethoden für die Abschätzung von Organaktivitäten und Aktivitätsverteilungen geworden. Trotz ihres großen Potenzials hat die SPECT/CT-Bildgebung jedoch immer noch mit einer Reihe von Schwierigkeiten zu kämpfen, die eine volumenbasierte Bestimmung von Organaktivitäten erschweren. Insbesondere sind die Umrechnung von Impuls- in Aktivitätsverteilung, die Korrektur von Partialvolumeneffekten, sowie die Standardisierung von Aufnahme- und Rekonstruktionsprotokollen immer noch Gegenstand der Forschung.

In dieser Arbeit werden zunächst die wichtigsten Prinzipien der quantitativen SPECT/CT-Bildgebung vorgestellt, und anschließend einige Vorschläge und Hilfestellungen für die praktische Umsetzung gegeben.
Effective and less invasive diagnostic strategy for gastrointestinal GVHD
Authors: Endo Katsuya , Fujishima Fumiyoshi , Kuroha Masatake , Moroi Rintaro , Onodera Motoyuki , Naito Takeo , Kanazawa Yoshitake , Kimura Tomoya , Shiga Hisashi , Kakuta Yoichi , Kinouchi Yoshitaka , Shimosegawa Tooru
Published: March 2018

Background and study aims Rectosigmoidoscopy with biopsy has been regarded to be a useful procedure to diagnose gastrointestinal graft-versus-host disease (GVHD). However, little is known about the specific colonoscopic features of gastrointestinal GVHD. In this study, we focused on the 4 unique colonoscopic findings – orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect – which are possible specific findings of gastrointestinal GVHD. We aimed to estimate the usefulness of these four unique colonoscopic findings in the rectosigmoid portion to diagnose gastrointestinal GVHD.

Patients and methods Seventy patients who were histologically diagnosed with gastrointestinal GVHD at our institute were retrospectively enrolled. Colonoscopic findings were reviewed, focusing on the four characteristic findings. The percentage of the positive cases for the characteristic findings was calculated. The final scoping portion and the number of cases showing any of the four characteristic findings in the rectosigmoid portion were also evaluated. The relationships between biopsy sites and the histological findings were also evaluated.

Results Orange peel appearance was observed in 66 cases (94.3 %). Spotty redness was observed in 45 cases (64.3 %). Small mucosal sloughing was observed in 49 cases (70.0 %). Diffuse mucosal defect was observed in six cases (8.6 %). The number of cases that were concurrently positive for one, two, and three findings were 16 (20.8 %), 20 (26.0 %), and 34 (48.6 %), respectively. Fifty-eight cases (82.9 %) were investigated up to the rectosigmoid portion, and 12 (17.1 %) were investigated beyond the sigmoid colon. All of the cases showed at least 1 of the 4 characteristics in the rectosigmoid portion. The percentage of crypt apoptosis in the biopsy specimen from orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect were 87.5 %, 83.3 %, 87.2 %, and 88.9 %, respectively.

Conclusion Orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect are the characteristic colonoscopic findings useful for diagnosis of gastrointestinal GVHD. These findings are frequently observed in the rectosigmoid portion. The histological detection rates for crypt cell apoptosis from these findings are high. Identifying the four characteristic findings on rectosigmoidoscopy and taking biopsies from these areas could be essential for the diagnostic strategy for gastrointestinal GVHD.
How familiar are we with decision-making concerning the treatment of perforation after endoscopic mucosal resection (EMR) in the colon? A case report
Authors: Tribonias George , Daferera Niki , Manola Margarita-Eleni , Svernlöv Rikard , Ignatova Simone , Hjortswang Henrik
Published: March 2018

Background and study aims We describe a case of perforation after colonic endoscopic mucosal resection (EMR) that was treated conservatively. We would like to highlight the importance of decision-making mainly based on the endoscopist's point of view in combination with the surgical consultation. Although the radiological imaging is always needed, it cannot solely lead to a decision for operation. Intraperitoneal gas in computed tomography is not always associated with a hole in the endoscopic field and could be possibly explained from a “balloon” phenomenon. The amount of extraluminal air after an EMR does not correlate reciprocally with patient's pain after the procedure. Even though perforation is a radiological diagnosis and endoscopists should be aware of the common post-EMR radiological findings, the surgical examination is mandatory and should be coupled with the endoscopic opinion in order to guide appropriately the treatment in patients with acute pain.
Gastroösophageale Refluxkrankheit – was tun, wenn PPI nicht ausreichend wirksam,
verträglich oder erwünscht sind?
Authors: Labenz Joachim , Koop Herbert
Published: March 2018

Die Standardtherapie der GERD mit PPI ist weniger wirksam als gedacht: Mindestens 30 % der Patienten haben
persistierende Symptome und Läsionen (Therapielücke). Bei persistierender Symptomatik oder Wunsch einer
alternativen Behandlung ist eine stratifizierte Diagnostik erforderlich. Alginate und neue Operationsverfahren
erweitern die Therapieoptionen
Durch das Cochlea-Implantat zum CODA?
Authors: Vogel Arno
Published: March 2018

Die Cochlea-Implantat-Versorgung gehörloser Kinder mit gehörlosen bzw. hochgradig hörgeschädigten Eltern ist
möglich. Bereits vor der Operation muss ein tragfähiges (Re-)Habilitationskonzept zur Entwicklung und
Förderung des Hör-Sprachprozesses erarbeitet werden. Der Erfolg der Kinder hängt von Vermittlern ab, die die
Eltern unterstützen. Die Kinder wachsen zweisprachig auf: Gebärdensprache und Lautsprache. Sie können Schulen
für Hörgeschädigte oder allgemeine Schulen für Hörende besuchen.
Kopf-Hals-MRT: Was HNO-Ärzte wissen sollten
Authors: Widmann Gerlig
Published: March 2018

Die Magnetresonanztomografie (MRT) hat sich für die HNO-Heilkunde zu einem wichtigen bildgebenden Verfahren
entwickelt. Ziel des vorliegenden CME-Beitrags für HNO-Ärzte ist es, einen Überblick über die Vor- und
Nachteile sowie die Möglichkeiten der Kopf-Hals-MRT zu bieten und die wichtigsten klinischen Anwendungsgebiete
der verschiedenen MRT-Sequenzen zusammenzufassen.
Recent advances in quartz enhanced photoacoustic sensing
Authors: Patimisco Pietro , Sampaolo Angelo , Dong Lei , Tittel Frank K. , Spagnolo Vincenzo
Published: March 2018

This review aims to discuss the latest advancements in quartz-enhanced photoacoustic spectroscopy (QEPAS) based trace-gas sensing. Starting from the QEPAS basic physical principles, the most used QEPAS configurations will be described. This is followed by a detailed theoretical analysis and experimental study regarding the influence of quartz tuning forks (QTFs) geometry on their optoacoustic transducer performance. Furthermore, an overview of the latest developments in QEPAS trace-gas sensor technology employing custom QTFs will be reported. Results obtained by exploiting novel micro-resonator configurations, capable of increasing the QEPAS signal-to-noise ratio by more than two orders of magnitude and the utilization of QTF overtone flexural modes for QEPAS based sensing will be presented. A comparison of the QEPAS performance of different spectrophone configurations is reported based upon signal-to-noise ratio. Finally, a novel QEPAS approach allowing simultaneous dual-gas detection will be described.
Darcy-Forchheimer flow of Maxwell nanofluid flow with nonlinear thermal radiation and activation energy
Authors: Sajid T. , Sagheer M. , Hussain S. , Bilal M.
Published: March 2018

The present article is about the study of Darcy-Forchheimer flow of Maxwell nanofluid over a linear stretching surface. Effects like variable thermal conductivity, activation energy, nonlinear thermal radiation is also incorporated for the analysis of heat and mass transfer. The governing nonlinear partial differential equations (PDEs) with convective boundary conditions are first converted into the nonlinear ordinary differential equations (ODEs) with the help of similarity transformation, and then the resulting nonlinear ODEs are solved with the help of shooting method and MATLAB built-in bvp4c solver. The impact of different physical parameters like Brownian motion, thermophoresis parameter, Reynolds number, magnetic parameter, nonlinear radiative heat flux, Prandtl number, Lewis number, reaction rate constant, activation energy and Biot number on Nusselt number, velocity, temperature and concentration profile has been discussed. It is viewed that both thermophoresis parameter and activation energy parameter has ascending effect on the concentration profile.
Optical haze of randomly arranged silver nanowire transparent conductive films with wide range of nanowire diameters
Authors: Marus M. , Hubarevich A. , Fan W. J. , Wang H. , Smirnov A. , Wang K. , Huang H. , Sun X. W.
Published: March 2018

The effect of the diameter of randomly arranged silver nanowires on the optical haze of silver nanowire transparent conductive films was studied. Proposed simulation model behaved similarly with the experimental results, and was used to theoretically study the optical haze of silver nanowires with diameters in the broad range from 30 nm and above. Our results show that a thickening of silver nanowires from 30 to 100 nm results in the increase of the optical haze up to 8 times, while from 100 to 500 nm the optical haze increases only up to 1.38. Moreover, silver nanowires with diameter of 500 nm possess up to 5% lower optical haze and 5% higher transmittance than 100 nm thick silver nanowires for the same 10-100 Ohm/sq sheet resistance range. Further thickening of AgNWs can match the low haze of 30 nm thick AgNWs, but at higher transmittance. The results obtained from this work allow deeper analysis of the silver nanowire transparent conductive films from the perspective of the diameter of nanowires for various optoelectronic devices.
Unsteady flow over a decelerating rotating sphere
Authors: Turkyilmazoglu M.
Published: March 2018

Unsteady flow analysis induced by a decelerating rotating sphere is the main concern of this paper. A revolving sphere in a still fluid is supposed to slow down at an angular velocity rate that is inversely proportional to time. The governing partial differential equations of motion are scaled in accordance with the literature, reducing to the well-documented von Kármán equations in the special circumstance near the pole. Both numerical and perturbation approaches are pursued to identify the velocity fields, shear stresses, and suction velocity far above the sphere. It is detected that an induced flow surrounding the sphere acts accordingly to adapt to the motion of the sphere up to some critical unsteadiness parameters at certain latitudes. Afterward, the decay rate of rotation ceases such that the flow at the remaining azimuths starts revolving freely. At a critical unsteadiness parameter corresponding to s = −0.681, the decelerating sphere rotates freely and requires no more torque. At a value of s exactly matching the rotating disk flow at the pole identified in the literature, the entire flow field around the sphere starts revolving faster than the disk itself. Increasing values of -s almost diminish the radial outflow. This results in jet flows in both the latitudinal and meridional directions, concentrated near the wall region. The presented mean flow results will be useful for analyzing the instability features of the flow, whether of a convective or absolute nature.
Imaging aerosols with digital holography
Authors: Berg Matthew J. , Heinson Yuli W. , Kemppinen Osku
Published: March 2018

The shape and size of aerosol particles influence whether they heat or cool Earth and its atmosphere.
Mere formalities: fictional normativity and normative authority
Authors: Wodak Daniel
Published: March 2018

It is commonly said that some standards, such as morality, are ‘normatively authoritative’ in a way that other standards, such as etiquette, are not; standards like etiquette are said to be ‘not really normative’. Skeptics deny the very possibility of normative authority, and take claims like ‘etiquette is not really normative’ to be either empty or confused. I offer a different route to defeat skeptics about authority: instead of focusing on what makes standards like morality special, we should focus on what makes standards like etiquette ‘not really normative’. I defend a fictionalist theory on which etiquette is ‘not really normative’ in roughly the same way that Sherlock is ‘not really a detective’, and show that fictionalism about some normative standards helps us explain the possibility of normative authority.
Is international junior success a reliable predictor for international senior success in elite combat sports?
Authors: Li Pingwei , De Bosscher Veerle , Pion Johan , Weissensteiner Juanita R. , Vertonghen Jikkemien
Published: March 2018

Currently in the literature, there is a dearth of empirical research that confirms whether international junior success is a reliable predictor for future international senior success. Despite the uncertainty of the junior–senior relationship, federations and coaches still tend to use junior success as a predictor for long‐term senior success. A range of former investigations utilising a retrospective lens has merely focused on success that athletes attained at junior level competitions. Success that was achieved at senior‐level competitions but at a junior age was relatively ignored. This study explored to what extent international senior success can be predicted based on success that athletes achieved in either international junior level competitions (i.e. junior medalists) or senior competitions at a junior age (i.e. early achievers). The sample contains 4011 international male and female athletes from three combat sports (taekwondo, wrestling and boxing), who were born between 1974 and 1990 and participated in both international junior and senior‐level competitions between 1990 and 2016. Gender and sport differences were compared. The results revealed that 61.4% of the junior medalists and 90.4% of the early achievers went on to win international medals at a senior age. Among the early achievers, 92.2% of the taekwondo athletes, 68.4% of the wrestling athletes and 37.9% of the boxing athletes could be reliably “predicted” to win international senior medals. The findings demonstrate that specific to the three combat sports examined, international junior success appears to be an important predictor to long‐term international senior success.
Extracellular vesicles as a platform for membrane‐associated therapeutic protein delivery
Authors: Yang Yoosoo , Hong Yeonsun , Cho Eunji , Kim Gi Beom , Kim In‐San
Published: March 2018

Membrane proteins are of great research interest, particularly because they are rich in targets for therapeutic application. The suitability of various membrane proteins as targets for therapeutic formulations, such as drugs or antibodies, has been studied in preclinical and clinical studies. For therapeutic application, however, a protein must be expressed and purified in as close to its native conformation as possible. This has proven difficult for membrane proteins, as their native conformation requires the association with an appropriate cellular membrane. One solution to this problem is to use extracellular vesicles as a display platform. Exosomes and microvesicles are membranous extracellular vesicles that are released from most cells. Their membranes may provide a favourable microenvironment for membrane proteins to take on their proper conformation, activity, and membrane distribution; moreover, membrane proteins can cluster into microdomains on the surface of extracellular vesicles following their biogenesis. In this review, we survey the state‐of‐the‐art of extracellular vesicle (exosome and small‐sized microvesicle)‐based therapeutics, evaluate the current biological understanding of these formulations, and forecast the technical advances that will be needed to continue driving the development of membrane protein therapeutics.
Kindlin-2 regulates mesenchymal stem cell differentiation through control of YAP1/TAZ
Authors: Guo Ling , Cai Ting , Chen Keng , Wang Rong , Wang Jiaxin , Cui Chunhong , Yuan Jifan , Zhang Kuo , Liu Zhongzhen , Deng Yi , Xiao Guozhi , Wu Chuanyue
Published: March 2018

Precise control of mesenchymal stem cell (MSC) differentiation is critical for tissue development and regeneration. We show here that kindlin-2 is a key determinant of MSC fate decision. Depletion of kindlin-2 in MSCs is sufficient to induce adipogenesis and inhibit osteogenesis in vitro and in vivo. Mechanistically, kindlin-2 regulates MSC differentiation through controlling YAP1/TAZ at both the transcript and protein levels. Kindlin-2 physically associates with myosin light-chain kinase in response to mechanical cues of cell microenvironment and intracellular signaling events and promotes myosin light-chain phosphorylation. Loss of kindlin-2 inhibits RhoA activation and reduces myosin light-chain phosphorylation, stress fiber formation, and focal adhesion assembly, resulting in increased Ser127 phosphorylation, nuclear exclusion, and ubiquitin ligase atrophin-1 interacting protein 4–mediated degradation of YAP1/TAZ. Our findings reveal a novel kindlin-2 signaling axis that senses the mechanical cues of cell microenvironment and controls MSC fate decision, and they suggest a new strategy to regulate MSC differentiation, tissue repair, and regeneration.
SIRFing the replication fork: Assessing protein interactions with nascent DNA
Authors: Branzei Dana , Giannattasio Michele
Published: March 2018

Roy et al. (2018. J. Cell. Biol. https://doi.org/10.1083/jcb.201709121) describe an ingenious single-cell assay system, in situ analysis of protein interactions at DNA replication forks (SIRF), for the quantitative analysis of protein interactions with nascent DNA at active and stalled replication forks. The sensitive and accurate SIRF methodology is suitable for multiparameter measurements in cell populations.
Numerical Simulation of the Effect about Groundwater Level Fluctuation on the Concentration of BTEX Dissolved into Source Zone
Authors: Sun Liqun , Chen Yudao , Jiang Lingzhi , Cheng Yaping
Published: March 2018

The water level fluctuation of groundwater will affect the BTEX dissolution in the fuel leakage source zone. In order to study the effect, a leakage test of gasoline was performed in the sand-tank model in the laboratory, and the concentrations of BTEX along with water level were monitored over a long period. Combined with VISUAL MODFLOW software, RT3D module was used to simulate the concentrations of BTEX, and mass flux method was used to evaluate the effects of water level fluctuation on the BTEX dissolution. The results indicate that water level fluctuation can significantly increase the concentration of BTEX dissolved in the leakage source zone. The dissolved amount of BTEX can reach up to 2.4 times under the water level fluctuation condition. The method of numerical simulation combined with mass flux calculation can be used to evaluate the effect of water level fluctuation on BTEX dissolution.
Study of Goat Herdering System in Sawohan Village, Buduran District, Sidoarjo
Authors: Nasich M. , Suyadi  , Ciptadi G. , Budiarto A.
Published: March 2018

The aim of this research was to evaluate and analyze goat herdering system in group of goat “Oro-oro” in Sawohan Village, Buduran District, Sidoarjo. This research was conducted by case study method, using 5 members of goat farmers “Oro-oro” with 298 goats. The results of this study indicate that the average number of goat ownership was more than 50 head/farmer. The goat breed that raising by the farmers was Kacang goats. Average daily gains was 53.32 + 36.01 gram, litter size 1.34 + 0.51 head, mean of kidding interval 7,41 + 0,99 month and mortality of kid prenatal period was 20,4%. From this research can be concluded that productivity of goat in Sawohan village was good with herdering system, so it can be used as one of alternative in developing goat farming system in other area.
Composting of empty fruit bunches in the tower composter – effect of air intake holes
Authors: Irvan  , Husaini T , Trisakti B , Batubara F , Daimon H
Published: March 2018

The process of composting empty fruit bunches (EFB) by mixing with activated liquid organic fertilizer (ALOF) is an alternative utilization of solid waste generated from palm oil mill. This study aims to find composting techniques of EFB and to obtain degradation data of composting EFB by varying the air intake holes to produce good quality compost. Composting process was carried out by tearing the EFB into four shreds, then put into the tower composter while adding ALOF until it reached the optimum moisture content of 55 -65%. During the composting process, we maintained moisture content at optimum conditions by adding ALOF. Variations of air intake holes area to the outer surface area of the composter are 0/44.314; 72.39/44.314 and 144.78/44.314 (cm2/cm2). Composting is carried out for forty days, however, based on the result, compost began to mature on the 10th day. The results revealed that there was an influence of air intake holes to the composting process. The best degradation of EFB was obtained on the variation of air intake holes 72.39/44.314 (cm2/cm2), pH 8.1, moisture content 79.14%, water holding capacity 60%, electrical conductivity 4.725 dS/m and C/N ratio 20.97.
Involvement in surface antigen expression by a moonlighting FG-repeat nucleoporin in trypanosomes
Authors: Holden Jennifer M. , Koreny Ludek , Obado Samson , Ratushny Alexander V. , Chen Wei-Ming , Bart Jean-Mathieu , Navarro Miguel , Chait Brian T. , Aitchison John D. , Rout Michael P. , Field Mark C.
Published: March 2018

Components of the nuclear periphery coordinate a multitude of activities, including macromolecular transport, cell-cycle progression, and chromatin organization. Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport, mRNA processing, and transcriptional regulation, and NPC components can define regions of high transcriptional activity in some organisms at the nuclear periphery and nucleoplasm. Lineage-specific features underpin several core nuclear functions and in trypanosomatids, which branched very early from other eukaryotes, unique protein components constitute the lamina, kinetochores, and parts of the NPCs. Here we describe a phenylalanine-glycine (FG)-repeat nucleoporin, TbNup53b, that has dual localizations within the nucleoplasm and NPC. In addition to association with nucleoporins, TbNup53b interacts with a known trans-splicing component, TSR1, and has a role in controlling expression of surface proteins including the nucleolar periphery-located, procyclin genes. Significantly, while several nucleoporins are implicated in intranuclear transcriptional regulation in metazoa, TbNup53b appears orthologous to components of the yeast/human Nup49/Nup58 complex, for which no transcriptional functions are known. These data suggest that FG-Nups are frequently co-opted to transcriptional functions during evolution and extend the presence of FG-repeat nucleoporin control of gene expression to trypanosomes, suggesting that this is a widespread and ancient eukaryotic feature, as well as underscoring once more flexibility within nucleoporin function.
C3G dynamically associates with nuclear speckles and regulates mRNA splicing
Authors: Shakyawar Dhruv Kumar , Muralikrishna Bhattiprolu , Radha Vegesna
Published: March 2018

C3G (Crk SH3 domain binding guanine nucleotide releasing factor) (Rap guanine nucleotide exchange factor 1), essential for mammalian embryonic development, is ubiquitously expressed and undergoes regulated nucleocytoplasmic exchange. Here we show that C3G localizes to SC35-positive nuclear speckles and regulates splicing activity. Reversible association of C3G with speckles was seen on inhibition of transcription and splicing. C3G shows partial colocalization with SC35 and is recruited to a chromatin and RNase-sensitive fraction of speckles. Its presence in speckles is dependent on intact cellular actin cytoskeleton and is lost on expression of the kinase Clk1. Rap1, a substrate of C3G, is also present in nuclear speckles, and inactivation of Rap signaling by expression of GFP-Rap1GAP alters speckle morphology and number. Enhanced association of C3G with speckles is seen on glycogen synthase kinase 3 beta inhibition or differentiation of C2C12 cells to myotubes. CRISPR/Cas9-mediated knockdown of C3G resulted in altered splicing activity of an artificial gene as well as endogenous CD44. C3G knockout clones of C2C12 as well as MDA-MB-231 cells showed reduced protein levels of several splicing factors compared with control cells. Our results identify C3G and Rap1 as novel components of nuclear speckles and a role for C3G in regulating cellular RNA splicing activity.
CarbonylDB: a curated data-resource of protein carbonylation sites
Authors: Rao R Shyama Prasad , Zhang Ning , Xu Dong , Møller Ian Max
Published: March 2018

Motivation

Oxidative stress and protein damage have been associated with over 200 human ailments including cancer, stroke, neuro-degenerative diseases and aging. Protein carbonylation, a chemically diverse oxidative post-translational modification, is widely considered as the biomarker for oxidative stress and protein damage. Despite their importance and extensive studies, no database/resource on carbonylated proteins/sites exists. As such information is very useful to research in biology/medicine, we have manually curated a data-resource (CarbonylDB) of experimentally-confirmed carbonylated proteins/sites.

Results

The CarbonylDB currently contains 1495 carbonylated proteins and 3781 sites from 21 species, with human, rat and yeast as the top three species. We have made further analyses of these carbonylated proteins/sites and presented their occurrence and occupancy patterns. Carbonylation site data on serum albumin, in particular, provides a fine model system to understand the dynamics of oxidative protein modifications/damage.

Availability and implementation

The CarbonylDB is available as a web-resource and for download at http://digbio.missouri.edu/CarbonylDB/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Clinical Response and Complications are not Associated with Drug Levels in Patients with Severe Ulcerative Colitis on IV Cyclosporine Induction Therapy
Authors: Patel Parita , Yarur Andres , Dalal Sushila , Sakuraba Atsuhi , Rubin David T , Hanauer Stephen B , Hanan Ira , Raffals Laura H , Cohen Russell D , Pekow Joel
Published: March 2018

Background

IV ciclosporin therapy is effective in steroid-refractory ulcerative colitis. The optimal drug level to achieve response and minimize complications during induction therapy is not known.

Aim

The primary aim was to evaluate if serum ciclosporin drug levels are associated with increased risk of colectomy within 90 days of hospitalization. Secondary aims were to determine if ciclosporin levels are associated with avoidance of colectomy at 7 and 30 days, if ciclosporin levels are associated with drug-related and postoperative complications, and if patient-specific factors are associated with response to ciclosporin.

Methods

We conducted a retrospective analysis of 81 hospitalized patients with steroid-refractory ulcerative colitis treated with ciclosporin. Risk factors for colectomy within 7, 30, and 90 days, medication-specific and postoperative complications were compared by first, mean, and peak ciclosporin level during IV induction therapy.

Results

There were 47 patients (58%) who underwent surgery. There were no differences between initial, mean, and peak ciclosporin levels among responders and nonresponders and treatment-related or postoperative complications. Responders within 90 days had lower C-reactive-protein levels (20mg/L vs. 38mg/L, P = 0.01), lower serum albumin concentrations (3.4g/dL vs. 3.7g/dL, P = 0.03), and higher rates of kidney injury (50% vs 17%, P = 0.002).

Conclusion

Initial, mean, and peak serum levels of ciclosporin did not correlate with response or toxicity. However, C-reactive-protein levels levels and kidney injury may be helpful in predicting clinical response to ciclosporin.
A201 PREVALENCE OF NONALCOHOLIC FATTY LIVER DISEASE IN A COHORT OF HEALTHY CHILDREN IN ONTARIO
Authors: Dhaliwal J , Chavhan G , Wales P , Mouzaki M
Published: March 2018

Aims

To determine the prevalence of hepatic steatosis in a cohort of previously healthy children and adolescents, with the use of abdominal computer tomography (CT).

Methods

Retrospective review of the Sickkids trauma database from (year 2004 to 2015). Inclusion criteria: previously healthy children ages 1-17yr having undergone an abdominal CT scan as a part of routine trauma assessment. Exclusion criteria: Involvement of spleen and/or liver in the injury, known metabolic condition, concurrent use of medications that could predispose to hepatic steatosis. Steatosis was defined as a liver spleen attenuation index (L/S AI) of <0.8. Anthropometrics and baseline demographics were collected. Statistical analyses were performed using Graphpad Prism 7.

Results

A total of 143 children were included in the analyses with a mean (SD) age of 7.12(4.26) years. 88 children were male (7.10(4.24) years old). The mean (SD) weight z score was 0.48 (0.97). Fifteen percent of the 137 children with a weight z-score between -2 to 2 had evidence of hepatic steatosis on imaging (using liver/spleen index <0.8). Twenty seven percent (6/22) of children with weight z-scores less than the 33rd percentile had L/S AI <0.8. An inverse correlation between weight z-scores and L/S AI was found in children >10 years (P<0.016) (Fig 1); however there was no correlation in pre-pubertal children (P<0.374).

Conclusions

Hepatic steatosis is highly prevalent in this cohort of healthy children in Ontario. Larger population based studies are needed to investigate the prevalence of hepatic steatosis in children across Canada.

Funding Agencies

None
E-cigarettes: A new hazard for children and adolescents
Authors: Richmond Sarah A , Pike Ian , Maguire Jonathon L , Macpherson Alison
Published: March 2018

Objectives

Electronic cigarettes and fluid (e-cigarettes, e-fluid) are hazardous materials that when inhaled or ingested may pose significant health risks to children and adolescents. The objective of this work was to explore the spectrum of injury related to e-cigarette exposure among Canadian children and adolescents.

Methods

A one-time survey was sent to all paediatricians in Canada. Information was collected on children and adolescents who presented with e-cigarette exposure (inhalation and ingestion cases) in the previous 12 months. Questions included the number of injuries and symptoms, in addition to age, sex, treatment setting, intentional e-cigarette use and how the products were accessed.

Results

A total of 520 surveys were completed and returned, identifying 220 cases. Symptoms related to inhalation were present in 135 cases (43 unintentional, 92 intentional) and in 85 ingestion cases (35 unintentional, 50 intentional). For inhalation cases, most were male, aged 15 to 19 years, who sought treatment for nausea/vomiting, cough, throat irritation or acute nicotine toxicity in an outpatient clinic/office. Most inhalation cases reported e-cigarette use 2 to 3 days/week, and e-cigarettes purchases from a mall kiosk/store. For ingestion cases, most were male, aged 1 to 4 years presenting to an emergency department with nausea/vomiting, cough or respiratory irritation. Younger cases accessed e-fluid at home, older cases purchased in a mall kiosk/store. E-fluid flavours reported consumed were fruit, candy, and tobacco.

Conclusions

E-cigarettes, recently introduced into the North American market are hazardous to children and adolescents. Further investigation into the risks that e-cigarettes pose and ways to reduce exposure is needed to minimize injury.
Resistance to Fluopicolide and Propamocarb and Baseline Sensitivity to Ethaboxam Among Isolates of Pseudoperonospora cubensis From the Eastern United States
Authors: Thomas A. , Neufeld K. N. , Seebold K. W. , Braun C. A. , Schwarz M. R. , Ojiambo P. S.
Published: March 2018

Chemical control is currently the most effective method for controlling cucurbit downy mildew (CDM) caused by Pseudoperonospora cubensis. Most commercial cucurbit cultivars, with the exception of a few new cucumber cultivars, lack adequate disease resistance. Fluopicolide and propamocarb were among the most effective fungicides against CDM in the United States between 2006 and 2009. Since then, reduced efficacy of these two fungicides under field conditions was reported starting around 2013 but occurrence of resistance to fluopicolide and propamocarb in field isolates of P. cubensis had not been established. Thirty-one isolates collected from cucurbits in the eastern United States were tested for their sensitivity to fluopicolide and propamocarb using a leaf disc assay. This same set of isolates and four additional isolates (i.e., 35 isolates) were also used to establish the baseline sensitivity of P. cubensis to ethaboxam, an ethylamino-thiazole-carboxamide fungicide, which was recently granted registration to control CDM in the United States. About 65% of the isolates tested were resistant to fluopicolide with at least one resistant isolate being present in samples collected from 12 of the 13 states in the eastern United States. About 74% of the isolates tested were sensitive to propamocarb with at least one resistant isolate being among samples collected from 8 of the 12 states in the study. The frequency of resistance to fluopicolide and propamocarb was high among isolates collected from cucumber, while the frequency was low among isolates collected from other cucurbit host types. All isolates tested were found to be sensitive to ethaboxam and EC50 values ranged from 0.18 to 3.08 mg a.i./liter with a median of 1.55 mg a.i./liter. The ratio of EC50 values for the least sensitive and the most sensitive isolate was 17.1, indicating that P. cubensis isolates were highly sensitive to ethaboxam. The most sensitive isolates to ethaboxam were collected from New York, North Carolina, and Ohio, while the least sensitive isolates were collected from Georgia, Michigan, and New Jersey. These results show that ethaboxam could be a viable addition to fungicide programs used to control CDM in the United States.