bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery
Authors: Christiansen D. , Earnest-Silveira L. , Grubor-Bauk B. , Wijesundara D. K. , Boo I. , Ramsland P. A. , Vincan E. , Drummer H. E. , Gowans E. J. , Torresi J. 
Published: June 2019

AbstractThe introduction of directly acting antiviral agents (DAAs) has produced significant improvements in the ability to cure chronic hepatitis C infection. However, with over 2% of the world’s population infected with HCV, complications arising from the development of cirrhosis of the liver, chronic hepatitis C infection remains the leading indication for liver transplantation. Several modelling studies have indicated that DAAs alone will not be sufficient to eliminate HCV, but if combined with an effective vaccine this regimen would provide a significant advance towards achieving this critical World Health Organisation goal. We have previously generated a genotype 1a, 1b, 2a, 3a HCV virus like particle (VLP) quadrivalent vaccine. The HCV VLPs contain the core and envelope proteins (E1 and E2) of HCV and the vaccine has been shown to produce broad humoral and T cell immune responses following vaccination of mice. In this report we further advanced this work by investigating vaccine responses in a large animal model. We demonstrate that intradermal microneedle vaccination of pigs with our quadrivalent HCV VLP based vaccine produces long-lived multi-genotype specific and neutralizing antibody (NAb) responses together with strong T cell and granzyme B responses and normal Th1 and Th2 cytokine responses. These responses were achieved without the addition of adjuvant. Our study demonstrates that our vaccine is able to produce broad immune responses in a large animal that, next to primates, is the closest animal model to humans. Our results are important as they show that the vaccine can produce robust immune responses in a large animal model before progressing the vaccine to human trials.
The Functional Mammalian CRES (Cystatin-Related Epididymal Spermatogenic) Amyloid is Antiparallel β-Sheet Rich and Forms a Metastable Oligomer During Assembly
Authors: Do Hoa Quynh , Hewetson Aveline , Myers Caitlyn , Khan Nazmul H. , Hastert Mary Catherine , M. Harsini Faraz , Latham Michael P. , Wylie Benjamin J. , Sutton R. Bryan , Cornwall Gail A. 
Published: June 2019

AbstractAn amyloid matrix composed of several family 2 cystatins, including the reproductive cystatin CRES, is an integral structure in the mouse epididymal lumen and has proposed functions in sperm maturation and protection. Understanding how CRES amyloid assemblesin vitromay provide clues on how the epididymal amyloid matrix formsin vivo. We therefore purified full-length CRES under nondenaturing conditions and followed its aggregation from monomer to amyloid under conditions that may approximate those in the epididymal lumen. CRES transitioned into a metastable oligomer that was resistant to aggregation and only over extended time formed higher-ordered amyloids. High protein concentrations facilitated oligomer assembly and also were required to maintain the metastable state since following dilution the oligomer was no longer detected. Similar to other amyloid precursors, the formation of CRES amyloids correlated with a loss of α-helix and a gain of β-sheet content. However, CRES is unique in that its amyloids are rich in antiparallel β-sheets instead of the more common parallel β-sheets. Taken together, our studies suggest that early metastable oligomers may serve as building blocks for functional amyloid assembly and further reveal that antiparallel β-sheet-rich amyloids can be functional forms.
Differentiation between wild boar and domestic pig in food by targeting two gene loci by real-time PCR
Authors: Kaltenbrunner Maria , Mayer Walter , Kerkhoff Kirsten , Epp Rita , Rüggeberg Hermann , Hochegger Rupert , Cichna-Markl Margit 
Published: June 2019

AbstractStudies indicate that many meat products are not authentic, most frequently because the meat species differ from those given on the food labels. At present, DNA based methods play the most important role in meat species authentication. Discrimination of wild boar and domestic pig meat in food is challenging because it is differentiation on the subspecies level. We developed and validated two singleplex real-time PCR assays targeting SNP rs81416363 on chromosome 9 and a duplex real-time PCR assay targeting SNP g.299084751 C > T in the NR6A1 gene located on chromosome 1. The singleplex real-time PCR assays led to some ambiguous results for Mangalica and Krškopolje pig breeds and wild boar individuals from Germany, the duplex real-time PCR assay particularly for the Turopolje pig breed. We demonstrate that the probability of misclassification can be substantially reduced if the results of both the singleplex real-time PCR assays and the duplex real-time PCR assay are taken into consideration. 86 (91.5%) of a total of 94 individuals, comprising 64 domestic pigs (14 different breeds and 6 cross-breeds) and 30 wild boars (from Austria, Germany, Romania, USA and Estonia), were classified correctly.
Winter storms accelerate the demise of sea ice in the Atlantic sector of the Arctic Ocean
Authors: Graham Robert M. , Itkin Polona , Meyer Amelie , Sundfjord Arild , Spreen Gunnar , Smedsrud Lars H. , Liston Glen E. , Cheng Bin , Cohen Lana , Divine Dmitry , Fer Ilker , Fransson Agneta , Gerland Sebastian , Haapala Jari , Hudson Stephen R. , Johansson A. Malin , King Jennifer , Merkouriadi Ioanna , Peterson Algot K. , Provost Christine , Randelhoff Achim , Rinke Annette , Rösel Anja , Sennéchael Nathalie , Walden Von P. , Duarte Pedro , Assmy Philipp , Steen Harald , Granskog Mats A. 
Published: June 2019

AbstractA large retreat of sea-ice in the ‘stormy’ Atlantic Sector of the Arctic Ocean has become evident through a series of record minima for the winter maximum sea-ice extent since 2015. Results from the Norwegian young sea ICE (N-ICE2015) expedition, a five-month-long (Jan-Jun) drifting ice station in first and second year pack-ice north of Svalbard, showcase how sea-ice in this region is frequently affected by passing winter storms. Here we synthesise the interdisciplinary N-ICE2015 dataset, including independent observations of the atmosphere, snow, sea-ice, ocean, and ecosystem. We build upon recent results and illustrate the different mechanisms through which winter storms impact the coupled Arctic sea-ice system. These short-lived and episodic synoptic-scale events transport pulses of heat and moisture into the Arctic, which temporarily reduce radiative cooling and henceforth ice growth. Cumulative snowfall from each sequential storm deepens the snow pack and insulates the sea-ice, further inhibiting ice growth throughout the remaining winter season. Strong winds fracture the ice cover, enhance ocean-ice-atmosphere heat fluxes, and make the ice more susceptible to lateral melt. In conclusion, the legacy of Arctic winter storms for sea-ice and the ice-associated ecosystem in the Atlantic Sector lasts far beyond their short lifespan.
Generalization of the small-world effect on a model approaching the Erdős–Rényi random graph
Authors: Maier Benjamin F. 
Published: June 2019

AbstractThe famous Watts–Strogatz (WS) small-world network model does not approach the Erdős–Rényi (ER) random graph model in the limit of total randomization which can lead to confusion and complicates certain analyses. In this paper we discuss a simple alternative which was first introduced by Song and Wang, where instead of rewiring, edges are drawn between pairs of nodes with a distance-based connection probability. We show that this model is simpler to analyze, approaches the true ER random graph model in the completely randomized limit, and demonstrate that the WS model and the alternative model may yield different quantitative results using the example of a random walk temporal observable. An efficient sampling algorithm for the alternative model is proposed. Analytic results regarding the degree distribution, degree variance, number of two-stars per node, number of triangles per node, clustering coefficient, and random walk mixing time are presented. Subsequently, the small-world effect is illustrated by showing that the clustering coefficient decreases much slower than an upper bound on the message delivery time with increasing long-range connection probability which generalizes the small-world effect from informed searches to random search strategies. Due to its accessibility for analytic evaluations, we propose that this modified model should be used as an alternative reference model for studying the influence of small-world topologies on dynamic systems as well as a simple model to introduce numerous topics when teaching network science.
Physical activity associates with subarachnoid hemorrhage risk– a population-based long-term cohort study
Authors: Lindbohm Joni V. , Rautalin Ilari , Jousilahti Pekka , Salomaa Veikko , Kaprio Jaakko , Korja Miikka 
Published: June 2019

AbstractBenefit of physical activity in prevention of aneurysmal subarachnoid hemorrhage (SAH) is unclear. We aimed to clarify this by studying how different types of physical activity associate with SAH risk. By following 65 521 population-based FINRISK participants prospectively from medical and autopsy registries since 1972 until 2014, we detected 543 incident SAHs. At baseline, we measured leisure-time physical activity (LTPA), occupational physical activity (OPA), and commuting physical activity (CPA) levels. The Cox model adjusted for all well-known SAH risk factors and for socioeconomic status, provided hazard ratios (HRs) for physical activity variables. Every 30-minute increase in weekly LTPA decreased SAH risk linearly in men and women HR = 0.95 (95% CI = 0.90–1.00). CPA reduced SAH risk as well, but the association diminished as participants retired. In contrast, individuals with moderate (1.41, 1.04–1.92) and high OPA (1.34, 0.99–1.81) had elevated SAH risk. Protective association of LTPA persisted in all age and hypertension groups, and was even greater in current smokers 0.88 (0.81–0.96) than non-smokers (p = 0.04 for difference). Commuting and leisure time physical activity seem to reduce SAH risk in men and women and is most beneficial for smokers. Future intervention studies should investigate whether physical activity can reduce the rupture risk of intracranial aneurysms.
How typhoons trigger turbidity currents in submarine canyons
Authors: Sequeiros Octavio E. , Bolla Pittaluga Michele , Frascati Alessandro , Pirmez Carlos , Masson Douglas G. , Weaver Philip , Crosby Alexander R. , Lazzaro Gianluca , Botter Gianluca , Rimmer Jeffrey G. 
Published: June 2019

AbstractIntense turbidity currents occur in the Malaylay Submarine Canyon off the northern coast of Mindoro Island in the Philippines. They start in very shallow waters at the shelf break and reach deeper waters where a gas pipeline is located. The pipeline was displaced by a turbidity current in 2006 and its rock berm damaged by another 10 years later. Here we propose that they are triggered near the mouth of the Malaylay and Baco rivers by direct sediment resuspension in the shallow shelf and transport to the canyon heads by typhoon-induced waves and currents. We show these rivers are unlikely to generate hyperpycnal flows and trigger turbidity currents by themselves. Characteristic signatures of turbidity currents, in the form of bed shear stress obtained by numerical simulations, match observed erosion/deposition and rock berm damage patterns recorded by repeat bathymetric surveys before and after typhoon Nock-ten in December 2016. Our analysis predicts a larger turbidity current triggered by typhoon Durian in 2006; and reveals the reason for the lack of any significant turbidity current associated with typhoon Melor in December 2015. Key factors to assess turbidity current initiation are typhoon proximity, strength, and synchronicity of typhoon induced waves and currents. Using data from a 66-year hindcast we estimate a ~8-year return period of typhoons with capacity to trigger large turbidity currents.
Alpha-band oscillations reflect external spatial coding for tactile stimuli in sighted, but not in congenitally blind humans
Authors: Schubert Jonathan T. W. , Buchholz Verena N. , Föcker Julia , Engel Andreas K. , Röder Brigitte , Heed Tobias 
Published: June 2019

AbstractWe investigated the function of oscillatory alpha-band activity in the neural coding of spatial information during tactile processing. Sighted humans concurrently encode tactile location in skin-based and, after integration with posture, external spatial reference frames, whereas congenitally blind humans preferably use skin-based coding. Accordingly, lateralization of alpha-band activity in parietal regions during attentional orienting in expectance of tactile stimulation reflected external spatial coding in sighted, but skin-based coding in blind humans. Here, we asked whether alpha-band activity plays a similar role in spatial coding for tactile processing, that is, after the stimulus has been received. Sighted and congenitally blind participants were cued to attend to one hand in order to detect rare tactile deviant stimuli at this hand while ignoring tactile deviants at the other hand and tactile standard stimuli at both hands. The reference frames encoded by oscillatory activity during tactile processing were probed by adopting either an uncrossed or crossed hand posture. In sighted participants, attended relative to unattended standard stimuli suppressed the power in the alpha-band over ipsilateral centro-parietal and occipital cortex. Hand crossing attenuated this attentional modulation predominantly over ipsilateral posterior-parietal cortex. In contrast, although contralateral alpha-activity was enhanced for attended versus unattended stimuli in blind participants, no crossing effects were evident in the oscillatory activity of this group. These findings suggest that oscillatory alpha-band activity plays a pivotal role in the neural coding of external spatial information for touch.
Evidence of nitrite acting as a stable and robust inducer of non-cultivability in Mycobacterium tuberculosis with physiological relevance
Authors: Gample Suwarna P. , Agrawal Sonia , Sarkar Dhiman 
Published: June 2019

AbstractTuberculosis (TB) is the ninth leading cause of death worldwide, ranking above human immunodeficiency virus. Latency is the major obstacle in the eradication of this disease. How the physiology of the pathogen changes in transition to the latent stage needs to be understood. The latent bacteria extracted from animal hosts exist in a nonculturable (NC) phase, whereas bacteria extracted from most in vitro models are culture-positive. In the present study, we observed that nitrite, up to a concentration of 5 mM, shows the growth of Mycobacterium tuberculosis (MTB) in liquid media, but this effect starts reversing at higher concentrations. At a concentration of 10 mM, nitrite induces rapid nonculturability of MTB at the aerobic stage. This noncultivable dormancy was confirmed by analyzing the characteristics of NC bacteria. Further differential gene expression analyses clearly supported the formation of a dormancy phenotype. This study will be helpful for the use of this bacillus as a dormancy model in future studies on TB latency.
Silver content dependent thermal conductivity and thermoelectric properties of electrodeposited antimony telluride thin films
Authors: Ferrer-Argemi Laia , Yu Ziqi , Kim Jiwon , Myung Nosang V. , Lim Jae-Hong , Lee Jaeho 
Published: June 2019

AbstractWhile electrodeposited antimony telluride thin films with silver contents demonstrated promising thermoelectric properties, their thermal conductivity and the silver content dependence remain unknown. Here, we report the thermal conductivities of Ag3.9Sb33.6Te62.5 and AgSbTe2 thin films with controlled annealing and temperature conditions and demonstrate the impact of silver content on thermal transport. After annealing at 160 °C, the room-temperature thermal conductivity of Ag3.9Sb33.6Te62.5 and AgSbTe2 thin films increases from 0.24 to 1.59 Wm−1 K−1 and from 0.17 to 0.56 Wm−1 K−1, respectively. Using phonon transport models and X-ray diffraction measurements, we attribute the thermal conductivity increases to the crystal growth and explain the thermal conductivity variations with the degree of crystallization. Unlike electrical properties reported in previous studies, the presence of silver contents has little impact on the thermal conductivity of Ag3.9Sb33.6Te62.5 and leads to a strong reduction in the thermal conductivity of AgSbTe2 thin films. By performing transient thermal conductivity measurements at 94 °C, we find the crystallization activation energy of Ag3.9Sb33.6Te62.5 and AgSbTe2 films as 1.14 eV and 1.16 eV, respectively. Their differences reveal the role of silver in inhibiting the nucleation and growth of Sb2Te3 crystals and impeding thermal transport. These findings provide guidance for optimizing doping and annealing conditions of antimony tellurides for near-room-temperature thermoelectric applications.
Unusual Flavones from Primula macrocalyx as Inhibitors of OAT1 and OAT3 and as Antifungal Agents against Candida rugosa
Authors: Li Xue , Wang Xue , Li Caiyu , Khutsishvili Manana , Fayvush George , Atha Daniel , Zhang Youcai , Borris Robert P. 
Published: June 2019

AbstractA bioactivity guided program exploring the interaction of phytochemicals in the entire plant Primula macrocalyx with the organic anion transporters (OAT1 and OAT3) and microorganisms led to the elucidation of ten known flavones (1–4, 6–10, 12) and two previously undescribed flavones (5, 11). The structures of the compounds were determined by extensive analysis of spectroscopic data, as well as by comparison with data from previous reports. Two known flavones (9, 12) are reported for the first time from the family Primulaceae. All compounds were evaluated for inhibition of OAT1 and OAT3. Six flavones (2, 3, 6–8, 12) showed potent inhibitory activity on OAT1, while seven flavones (2, 3, 6–9, 12) showed marked inhibitory activity on OAT3, with IC50 ≤ 10.0 µM. Antimicrobial activities of crude fractions against sixteen microorganisms were tested to give a target yeast strain Candida rugosa for further evaluation of MICs on the isolates. Three flavones (7, 8, 12) showed marked antifungal activity with MIC < 2.0 µM. To our knowledge, this study is the first to evaluate these flavones as inhibitors of the OAT1 and OAT3, and as antifungal agents.
Antibody-driven capture of synaptic vesicle proteins on the plasma membrane enables the analysis of their interactions with other synaptic proteins
Authors: Richter Katharina N. , Patzelt Christina , Phan Nhu T. N. , Rizzoli Silvio O. 
Published: June 2019

AbstractMany organelles from the secretory pathway fuse to the plasma membrane, to exocytose different cargoes. Their proteins are then retrieved from the plasma membrane by endocytosis, and the organelles are re-formed. It is generally unclear whether the organelle proteins colocalize when they are on the plasma membrane, or whether they disperse. To address this, we generated here a new approach, which we tested on synaptic vesicles, organelles that are known to exo- and endocytose frequently. We tagged the synaptotagmin molecules of newly exocytosed vesicles using clusters of primary and secondary antibodies targeted against the luminal domains of these molecules. The antibody clusters are too large for endocytosis, and thus sequestered the synaptotagmin molecules on the plasma membrane. Immunostainings for other synaptic molecules then revealed whether they colocalized with the sequestered synaptotagmin molecules. We suggest that such assays may be in the future extended to other cell types and other organelles.
Insights into the water status in hydrous minerals using terahertz time-domain spectroscopy
Authors: Ma Yuanyuan , Huang Haochong , Hao Sibo , Qiu Kunfeng , Gao Hua , Gao Lu , Tang Weichong , Zhang Zili , Zheng Zhiyuan 
Published: June 2019

AbstractThe determinations of water status incorporated in hydrous minerals are of considerable significances in geoscience fields. Coincidentally, the aqueous sensitivity of terahertz radiation has motivated numerous explorations in several cross-domain applications. Terahertz time-domain spectroscopy is employed as a major probing technique coupling of traditional detecting methods to uncover the mask of water status in copper sulfate pentahydrate as well as mineral quartz in this article. Based on the quantitative identification of water status in copper sulfate pentahydrate, the water incorporated in mineral quartz is verified qualitatively. Notable differences of optical constants originating from the water content are obtained for copper sulfate pentahydrate and mineral quartz. These present works indicate that terahertz technology can be considered as a promising method to satisfy the ever-increasing requirements in hydrous mineral analyses.
Quantifying Uncertainty Due to Stochastic Weather Generators in Climate Change Impact Studies
Authors: Vesely Fosco M. , Paleari Livia , Movedi Ermes , Bellocchi Gianni , Confalonieri Roberto 
Published: June 2019

AbstractClimate change studies involve complex processes translating coarse climate change projections in locally meaningful terms. We analysed the behaviour of weather generators while downscaling precipitation and air temperature data. With multiple climate indices and alternative weather generators, we directly quantified the uncertainty associated with using weather generators when site specific downscaling is performed. We extracted the influence of weather generators on climate variability at local scale and the uncertainty that could affect impact assessment. For that, we first designed the downscaling experiments with three weather generators (CLIMAK, LARS-WG, WeaGETS) to interpret future projections. Then we assessed the impacts of estimated changes of precipitation and air temperature for a sample of 15 sites worldwide using a rice yield model and an extended set of climate metrics. We demonstrated that the choice of a weather generator in the downscaling process may have a higher impact on crop yield estimates than the climate scenario adopted. Should they be confirmed, these results would indicate that widely accepted outcomes of climate change studies using this downscaling technique need reconsideration.