bluuebunny/crossref_metadata_2025_split huggingface dataset:
Equatorial Disturbance Dynamo Vertical Plasma Drifts Over Jicamarca: Bimonthly and Solar Cycle Dependence
Authors: Navarro L. A. , Fejer B. G. , Scherliess L. 
Published: June 2019

AbstractWe use extensive incoherent scatter radar observations from the Jicamarca Radio Observatory to study the local time and bimonthly dependence of the equatorial disturbance dynamo vertical plasma drifts on solar flux and geomagnetic activity. We show that the daytime disturbance drifts have generally small magnitudes with largest values before noon and an apparent annual variation. Near dusk, they are downward throughout the year with largest values during the equinoxes and smallest during June solstice. These downward drifts increase strongly with solar flux and shift to later local times. They also increase with increasing geomagnetically active conditions with no apparent local time shift. The equinoctial evening downward disturbance drifts are larger during the autumnal equinox than during the vernal equinox. The nighttime disturbance drifts are upward and have small seasonal and solar cycle dependence but increase strongly with geomagnetic activity, particularly in the late night sector. Our results are in general agreement with those from previous theoretical and experimental studies, except near dusk where our results show much stronger seasonal and solar cycle dependence.
Programmable mutually exclusive alternative splicing for generating RNA and protein diversity
Authors: Mathur Melina , Kim Cameron M. , Munro Sarah A. , Rudina Shireen S. , Sawyer Eric M. , Smolke Christina D. 
Published: June 2019

AbstractAlternative splicing performs a central role in expanding genomic coding capacity and proteomic diversity. However, programming of splicing patterns in engineered biological systems remains underused. Synthetic approaches thus far have predominantly focused on controlling expression of a single protein through alternative splicing. Here, we describe a modular and extensible platform for regulating four programmable exons that undergo a mutually exclusive alternative splicing event to generate multiple functionally-distinct proteins. We present an intron framework that enforces the mutual exclusivity of two internal exons and demonstrate a graded series of consensus sequence elements of varying strengths that set the ratio of two mutually exclusive isoforms. We apply this framework to program the DNA-binding domains of modular transcription factors to differentially control downstream gene activation. This splicing platform advances an approach for generating diverse isoforms and can ultimately be applied to program modular proteins and increase coding capacity of synthetic biological systems.
RNA interference core components identified and characterised in Verticillium nonalfalfae, a vascular wilt pathogenic plant fungi of hops
Authors: Jeseničnik Taja , Štajner Nataša , Radišek Sebastjan , Jakše Jernej 
Published: June 2019

AbstractThe conserved RNA interference mechanism (RNAi) in the fungal kingdom has become a focus of intense scientific investigation. The three catalytic core components, Dicer-like (DCL), Argonaute (AGO), and RNA-dependent RNA polymerase (RdRP), and their associated small interfering RNA molecules (siRNAs) have been identified and characterised in several fungal species. Recent studies have proposed that RNAi is a major contributor to the virulence of fungal pathogens as a result of so-called trans-kingdom RNA silencing. In the present study, we report on the existence of three core RNAi proteins in the pathogenic plant fungus Verticillium nonalfalfae, which is a soilborne plant pathogen that causes severe wilting disease in hops (Humulus lupulus L.). Two DCL proteins, two AGO proteins, and two RdRP proteins were identified, and their conserved RNAi domains were characterised. Our phylogeny results confirm the existing taxonomic relationships in the Ascomycete fungal phylum and show that the fungi of the Hypocreomycetidae subclass of the Sordariomycetes class have high amino acid sequence similarity. The expression analysis revealed a potential role of RNAi in the pathogenicity of the fungi, since all the RNAi genes were highly upregulated in the highly virulent isolate T2 and were also differentially expressed in the V. nonalfalfae-susceptible Celeia and V. nonalfalfae-resistant Wye Target cultivars.
A landmark in drug discovery based on complex natural product synthesis
Authors: Kawano Satoshi , Ito Ken , Yahata Kenzo , Kira Kazunobu , Abe Takanori , Akagi Tsuyoshi , Asano Makoto , Iso Kentaro , Sato Yuki , Matsuura Fumiyoshi , Ohashi Isao , Matsumoto Yasunobu , Isomura Minetaka , Sasaki Takeo , Fukuyama Takashi , Miyashita Yusuke , Kaburagi Yosuke , Yokoi Akira , Asano Osamu , Owa Takashi , Kishi Yoshito 
Published: June 2019

AbstractDespite their outstanding antitumour activity in mice, the limited supply from the natural sources has prevented drug discovery/development based on intact halichondrins. We achieved a total synthesis of C52-halichondrin-B amine (E7130) on a >10 g scale with >99.8% purity under GMP conditions. Interestingly, E7130 not only is a novel microtubule dynamics inhibitor but can also increase intratumoural CD31-positive endothelial cells and reduce α-SMA-positive cancer-associated fibroblasts at pharmacologically relevant compound concentrations. According to these unique effects, E7130 significantly augment the effect of antitumour treatments in mouse models and is currently in a clinical trial. Overall, our work demonstrates that a total synthesis can address the issue of limited material supply in drug discovery/development even for the cases of complex natural products.
In-situ fabrication of a novel anisotropic PC-matrix light-scattering materials containing spindle-shaped core-shell particles
Authors: Ding Yitong , Li Xingwei , Zhao Ziru , Xiong Ying , Guo Shaoyun 
Published: June 2019

AbstractPolycarbonate (PC)/Poly(styrene-co-acrylonitrile) (SAN)-organic silica bead (OSB) anisotropic light-scattering materials containing novel spindle-shaped core-shell particles through simple, low-cost hot stretching methods are prepared in situ, which have excellent and easily tunable optical properties. The effects of OSB particle size, OSB mass fraction and stretching ratio on the morphology of the spindle-shaped core-shell particles and the scattering properties of PC/SAN-OSB composites were studied in detail. The results show that smaller particle size OSB and smaller draw ratio are more conducive to the production of spindle-shaped core-shell particles. And because of the multiple scattering effects of the spindle-shaped core-shell particles, they have a significant compensation effect on the pattern short-axis light-scattering range of the PC anisotropic materials while ensuring that the pattern long-axis direction light-scattering range is not impaired.
Effectiveness of augmentative biological control depends on landscape context
Authors: Perez-Alvarez Ricardo , Nault Brian A. , Poveda Katja 
Published: June 2019

AbstractBiological pest control by natural enemies is an important component of sustainable crop production. Among biological control approaches, natural enemy augmentation is an effective alternative when naturally occurring enemies are not sufficiently abundant or effective. However, it remains unknown whether the effectiveness of augmentative biocontrol varies along gradients of landscape composition, and how the interactions with resident enemies may modulate the collective impact on pest suppression. By combining field and lab experiments, we evaluated how landscape composition influenced the effectiveness of predator augmentation, and the consequences on pest abundance, plant damage, and crop biomass. We show for the first time that the effectiveness of predator augmentation is landscape-dependent. In complex landscapes, with less cropland area, predator augmentation increased predation rates, reduced pest abundance and plant damage, and increased crop biomass. By contrast, predator releases in simple landscapes had a negative effect on pest control, increasing plant damage and reducing crop biomass. Results from the lab experiment further suggested that landscape simplification can lead to greater interference among predators, causing a decrease in predator foraging efficiency. Our results indicate that landscape composition influence the effectiveness of augmentative biocontrol by modulating interactions between the introduced predators and the local enemy community.
Efficient visible light modulation based on electrically tunable all dielectric metasurfaces embedded in thin-layer nematic liquid crystals
Authors: Sun Mingyu , Xu Xuewu , Sun Xiao Wei , Liang Xin’an , Valuckas Vytautas , Zheng Yuanjin , Paniagua-Domínguez Ramón , Kuznetsov Arseniy I. 
Published: June 2019

AbstractAll-dielectric metasurfaces have attracted attention for highly efficient visible light manipulation. So far, however, they are mostly passive devices, while those allowing dynamic control remain a challenge. A highly efficient tuning mechanism is immersing the metasurface in a birefringent liquid crystal (LC), whose refractive index can be electrically controlled. Here, an all-dielectric tunable metasurface is demonstrated based on this concept, operating at visible frequencies and based on TiO2 nanodisks embedded in a thin LC layer. Small driving voltages from 3~5 V are sufficient to tune the metasurface resonances, with an associated transmission modulation of more than 65%. The metasurface optical responses, including the observed electric and magnetic dipole resonance shifts as well as the interfacial anchoring effect of the LC induced by the presence of the nanostructures, are systematically discussed. The dynamic tuning observed in the transmission spectra can pave the way to dynamically tunable metasurface devices for efficient visible light modulation applications.
Role of Hierarchical Protrusions in Water Repellent Superhydrophobic PTFE Surface Produced by Low Energy Ion Beam Irradiation
Authors: Pachchigar Vivek , Ranjan Mukesh , Mukherjee Subroto 
Published: June 2019

AbstractThe surface wettability of polytetrafluoroethylene (PTFE) was investigated with low energy Ar+ ion beam irradiation varied from 300 eV to 800 eV both at normal and oblique angle of incidence (0°–70°) and at a low irradiation time of few 10 s of seconds. A remarkable change in surface wettability was observed, surface became hydrophobic to superhydrophobic just at 800 eV energy and in 30 s time. A systematic increase in the contact angle was observed with increase in beam energy and irradiation time. For a given ion energy and a threshold irradiation time, the hierarchical protrusions developed that leads to the rolling and bouncing of water droplet even on the horizontal PTFE surface. For the above energy range, the rolling speed was found to be in the range of ~19–31 mm/s. This induced wetting behaviour due to ion irradiation leads to the Cassie-Baxter state as confirmed by the calculation of sliding angle, contact angle hysteresis (CAH) and surface free energy (SE). The CAH values were found to be reduced from 18° for untreated surface (SE ~ 20 mN/m) to 2° for 800 eV, 180 s irradiated surface (SE ~ 0.35 mN/m) at normal incidence.
Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria
Authors: Santucci Pierre , Johansen Matt D. , Point Vanessa , Poncin Isabelle , Viljoen Albertus , Cavalier Jean-François , Kremer Laurent , Canaan Stéphane 
Published: June 2019

AbstractMycobacteria share with other actinomycetes the ability to produce large quantities of triacylglycerol (TAG), which accumulate as intracytoplasmic lipid inclusions (ILI) also known as lipid droplets (LD). Mycobacterium tuberculosis (M. tb), the etiologic agent of tuberculosis, acquires fatty acids from the human host which are utilized to synthesize TAG, subsequently stored in the form of ILI to meet the carbon and nutrient requirements of the bacterium during long periods of persistence. However, environmental factors governing mycobacterial ILI formation and degradation remain poorly understood. Herein, we demonstrated that in the absence of host cells, carbon excess and nitrogen starvation promote TAG accumulation in the form of ILI in M. smegmatis and M. abscessus, used as surrogate species of M. tb. Based on these findings, we developed a simple and reversible in vitro model to regulate ILI biosynthesis and hydrolysis in mycobacteria. We also showed that TAG formation is tgs1 dependent and that lipolytic enzymes mediate TAG breakdown. Moreover, we confirmed that the nitrogen-deprived and ILI-rich phenotype was associated with an increased tolerance towards several drugs used for treating mycobacterial infections. Importantly, we showed that the presence of ILI substantially enhanced the bacterial burden and granuloma abundance in zebrafish embryos infected with lipid-rich M. abscessus as compared to embryos infected with lipid-poor M. abscessus, suggesting that ILI are actively contributing to mycobacterial virulence and pathogenesis.
Structure of an engineered multidrug transporter MdfA reveals the molecular basis for substrate recognition
Authors: Wu Hsin-Hui , Symersky Jindrich , Lu Min 
Published: June 2019

AbstractMdfA is a prototypical H+-coupled multidrug transporter that is characterized by extraordinarily broad substrate specificity. The involvement of specific H-bonds in MdfA-drug interactions and the simplicity of altering the substrate specificity of MdfA contradict the promiscuous nature of multidrug recognition, presenting a baffling conundrum. Here we show the X-ray structures of MdfA variant I239T/G354E in complexes with three electrically different ligands, determined at resolutions up to 2.2 Å. Our structures reveal that I239T/G354E interacts with these compounds differently from MdfA and that I239T/G354E possesses two discrete, non-overlapping substrate-binding sites. Our results shed new light on the molecular design of multidrug-binding and protonation sites and highlight the importance of often-neglected, long-range charge-charge interactions in multidrug recognition. Beyond helping to solve the ostensible conundrum of multidrug recognition, our findings suggest the mechanistic difference between substrate and inhibitor for any H+-dependent multidrug transporter, which may open new vistas on curtailing efflux-mediated multidrug resistance.
Lewis base-catalyzed intermolecular triazene alkyne cycloaddition for late-stage functionalization and scaffold diversification
Authors: Lv Shuaipeng , Zhou Hui , Yu Xin , Xu Yue , Zhu Huijuan , Wang Min , Liu Haitao , Dai Ziru , Sun Guibo , Gong Xiaojie , Sun Xiaobo , Wang Lei 
Published: June 2019

Abstract3-Trifluoromethylpyrazole and its derivatives are of major interest to both the agrochemical and pharmaceutical industry for their diverse biological activities. Reported routes for the synthesis of 3-trifluoromethylpyrazoles are hindered by poor regioselectivity and limited scope of application. Here we report a directed Lewis base catalyzed intermolecular triazene-alkyne cycloaddition. It is featured that the combination of 1,8-diazabicyclo[5.4.0]undec-7-ene and 2,2,2-trifluorodiazoethane produces reactive triazene intermediates, which readily participate in cycloaddition reactions with terminal/internal alkynes, thus assembling densely substituted 3-trifluoromethylpyrazole scaffolds with environmental friendliness and operational simplicity. Synthetic utility of the protocol is highlighted by late-stage functionalization and scaffolds diversification. The practical value is also emphasized in potential platelet aggregation inhibitor synthesis.
A Practical Guide to Establishing an Online Speech Therapy Private Practice
Authors: Ben-Aharon Avivit 
Published: June 2019

Purpose
Telepractice, although not new, is an innovative, rapidly evolving field. Accessible, secure, interactive, and effective are the main benefits of this online method of providing speech therapy services. While a trained clinician is well versed in providing clinical services, the process of establishing a private telepractice can be a daunting task. From setting up the business model, marketing plan, and record-keeping systems to choosing a video conference platform and learning the rules and regulations, this article aims to provide an introductory overview of the logistics and lay the groundwork to facilitate the process of setting up a private telepractice.

Conclusion
While endorsed by the American Speech-Language-Hearing Association as an appropriate method of service delivery in 2005, public perception, lack of controlled, substantiated research proving the effectiveness of the telepractice model, and the general absence of insurance reimbursement for service are still obstacles in the growth of online speech therapy. Education and advocacy are needed to push this cause forward and fill in the gaps.
First grids of low-mass stellar models and isochrones with self-consistent treatment of rotation
Authors: Amard L. , Palacios A. , Charbonnel C. , Gallet F. , Georgy C. , Lagarde N. , Siess L. 
Published: June 2019

Aims.We present an extended grid of state-of-the art stellar models for low-mass stars including updated physics (nuclear reaction rates, surface boundary condition, mass-loss rate, angular momentum transport, rotation-induced mixing, and torque prescriptions). We evaluate the impact of wind braking, realistic atmospheric treatment, rotation, and rotation-induced mixing on the structural and rotational evolution from the pre-main sequence (PMS) to the turn-off.Methods.Using the STAREVOL code, we provide an updated PMS grid. We computed stellar models for seven different metallicities, from [Fe/H] = −1 dex to [Fe/H] = +0.3 dex with a solar composition corresponding toZ = 0.0134. The initial stellar mass ranges from 0.2 to 1.5M⊙with extra grid refinement around one solar mass. We also provide rotating models for three different initial rotation rates (slow, median, and fast) with prescriptions for the wind braking and disc-coupling timescale calibrated on observed properties of young open clusters. The rotational mixing includes the most recent description of the turbulence anisotropy in stably stratified regions.Results.The overall behaviour of our models at solar metallicity, and their constitutive physics, are validated through a detailed comparison with a variety of distributed evolutionary tracks. The main differences arise from the choice of surface boundary conditions and initial solar composition. The models including rotation with our prescription for angular momentum extraction and self-consistent formalism for angular momentum transport are able to reproduce the rotation period distribution observed in young open clusters over a wide range of mass values. These models are publicly available and can be used to analyse data coming from present and forthcoming asteroseismic and spectroscopic surveys such asGaia, TESS, and PLATO.
Recent results of the NA64 experiment at the CERN SPS
Authors: Kirsanov Mikhail 
Published: June 2019

We report on the results of the search for a new sub-GeV vector boson (A’) mediated production of Dark Matter (χ) in the fixed-target experiment, NA64, at the CERN SPS. The A’, called dark photon, could be generated in the reaction e-Z → e-ZA’ of 100 GeV electrons dumped against an active target which is followed by the prompt invisible decay A’ $ \to \chi \bar{\chi } $. The experimental signature of this process would be an event with an isolated electron and large missing energy in the detector. From the analysis of the data sample collected in 2016 corresponding to 4.3 × 1010 electrons on target no evidence of such a process has been found. The constraints on the A’ mixing strength with photons, 10−5 ≤ ɛ ≤ 10−2, for the A’ mass range mA’ ≤ 1GeV are derived. Significantly more data were taken in 2017 and 2018. The analysis of these data is not yet finished, although the sensitivity is already estimated as about 3 times better than in the previously published result on the 2016 data.
For models considering scalar and fermionic thermal Dark Matter interacting with the visible sector through the vector portal the experiment starts to be sensitive to the regions of the dark-matter parameter $ y = \in^{2} \alpha_{D} (\frac{{m_{\chi } }}{{m_{{A^{\prime}}} }})^{4} $ predicted from the cosmological observations of Dark Matter.
We also report the improved results on a direct search for a new 16.7 MeV boson (X) which could explain the anomalous excess of e+e- pairs observed in the excited 8Be* nucleus decays. Due to its coupling to electrons, the X could be produced in the bremsstrahlung reaction e-Z → e-ZX by a beam of electrons incident on an active target in the NA64 experiment at the CERN SPS and observed through the subsequent decay into a e+e- pair. With 8.4 × 1010 electrons on target no evidence for such decays was found, allowing to set limits on the X - e- coupling in the range 1 × 10−4 ≤ ɛe ≤ 6 × 10−4 excluding part of the allowed parameter space. We also set new bounds on the mixing strength of photons with dark photons (A’) from non-observation of the decay A’ → e+e- of the bremsstrahlung A’ with a mass ≤ 23MeV.
Future plans of the NA64 experiment are presented.
Endlich läuft’s!
Authors: Jürgens Ute 
Published: June 2019

ZusammenfassungOft genug bleiben Vorhaben in der Planung stecken. Denn innere Barrieren hindern
uns, überhaupt anzufangen. Wenn Sie weder Luftschlösser bauen noch pessimistisch
verzagen, ergeben sich gangbare Wege zur Umsetzung der Wünsche. Vieles, was
früher liegenblieb, gedeiht jetzt besser.
Betriebliches Gesundheitsmanagement in der Fortbildungsakademie der Wirtschaft (FAW) gGmbH, Akademie Jena
Authors: Baumgärtel Saskia , Hamacher Vivian 
Published: June 2019

ZusammenfassungDie erfolgreiche Einführung von Prozessen sowie Umsetzung von Maßnahmen des Betrieblichen Gesundheitsmanagements (BGM) stellen insbesondere Unternehmen mit dezentraler Organisation vor große Herausforderungen. Die FAW gGmbH, Akademie Jena, versucht, sich dieser Problematik über verschiedene Wege und Akteure zu nähern. Tägliche Herausforderungen bleiben dabei die Allokationsproblematik, das grundsätzliche BGM-Verständnis jedes Mitarbeitenden sowie das Sichtbarmachen von Aktivitäten rund um die Mitarbeitergesundheit.
Crohn's Disease of the Esophagus, Duodenum, and Stomach
Authors: Schwartzberg David M. , Brandstetter Stephen , Grucela Alexis L. 
Published: June 2019

AbstractUpper gastrointestinal Crohn's is an under-reported, under-recognized phenotype of Crohn's disease. Routine screening in the pediatric population has shown a higher prevalence compared with adults; however, most adult patients remain asymptomatic with respect to upper gastrointestinal Crohn's disease. For the patients who are symptomatic, medical treatment is the first line of management, except for cases of obstruction, perforation, or bleeding. Though most patients respond to medical therapy, mainly steroids, with the addition of immunomodulators and more recently biologics agents, surgical intervention is usually required only for obstructing gastroduodenal disease secondary to strictures. Strictureplasty and bypass are safe operations with comparable morbidity, although bypass has higher rates of dumping syndrome and marginal ulceration in the long term. Rare cases of gastroduodenal fistulous disease from active distal disease may involve the stomach or duodenum, and esophageal Crohn's disease can fistulize to surrounding structures in the mediastinum which may require the highly morbid esophagectomy.