bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic linear response of a shock/turbulent-boundary-layer interaction using constrained perturbations
Authors: Adler Michael C. , Gaitonde Datta V. 
Published: February 2018

Comprehensive experimental and computational investigations have revealed possible mechanisms underlying low-frequency unsteadiness observed in spanwise homogeneous shock-wave/turbulent-boundary-layer interactions (STBLI). In the present work, we extend this understanding by examining the dynamic linear response of a moderately separated Mach 2.3 STBLI to small perturbations. The statistically stationary linear response is analysed to identify potential time-local and time-mean linear tendencies present in the unsteady base flow: these provide insight into the selective amplification properties of the flow at various points in the limit cycle, as well as asymmetry and restoring mechanisms in the dynamics of the separation bubble. The numerical technique uses the synchronized large-eddy simulation method, previously developed for free shear flows, significantly extended to include a linear constraint necessary for wall-bounded flows. The results demonstrate that the STBLI fosters a global absolute linear instability corresponding to a time-mean linear tendency for upstream shock motion. The absolute instability is maintained through constructive feedback of perturbations through the recirculation: it is self-sustaining and insensitive to external forcing. The dynamics are characterized for key frequency bands corresponding to high–mid-frequency Kelvin–Helmholtz shedding along the separated shear layer$(St_{L}\sim 0.5)$, low–mid-frequency oscillations of the separation bubble$(St_{L}\sim 0.1)$and low-frequency large-scale bubble breathing and shock motion$(St_{L}\sim 0.03)$, where the Strouhal number is based on the nominal length of the separation bubble,$L$:$St_{L}=fL/U_{\infty }$. A band-pass filtering decomposition isolates the dynamic flow features and linear responses associated with these mechanisms. For example, in the low-frequency band, extreme shock displacements are shown to correlate with time-local linear tendencies toward more moderate displacements, indicating a restoring mechanism in the linear dynamics. However, a disparity between the linearly stable shock position and the mean shock position leads to an observed asymmetry in the low-frequency shock motion cycle, in which upstream motion occurs more rapidly than downstream motion. This is explained through competing linear and nonlinear (mass depletion through shedding) mechanisms and discussed in the context of an oscillator model. The analysis successfully illustrates how time-local linear dynamics sustain several key unsteady broadband flow features in a causal manner.
Diverse single-amino-acid repeat profiles in the genusCryptosporidium
Authors: Widmer Giovanni 
Published: February 2018

AbstractGenome sequencing has greatly contributed to our understanding of parasitic protozoa. This is particularly the case forCryptosporidiumspecies (phylum Apicomplexa) which are difficult to propagate. Because of their polymorphic nature, simple sequence repeats have been used extensively as genotypic markers to differentiate between isolates, but no global analysis of amino acid repeats inCryptosporidiumgenomes has been reported. Taking advantage of several newly sequencedCryptosporidiumgenomes, a comparative analysis of single-amino-acid repeats (SAARs) in seven species was undertaken. This analysis revealed a striking difference between the SAAR profile of the gastric and intestinal species which infect mammals and one species which infects birds. In average, total SAAR length in gastric species is only 25% of the cumulative SAAR length in the genome ofCryptosporidium parvum,Cryptosporidium hominisandCryptosporidium meleagridis, species infectious to humans. The SAAR profile in the avian parasiteCryptosporidium baileyistands out due to the presence of long asparagine repeats.Cryptosporidium baileyiproteins with repeats ⩾20 residues are significantly enriched in regulatory functions. As postulated for the related apicomplexan speciesPlasmodium falciparum, these observations suggest thatCryptosporidiumSAARs evolve in response to selective pressure. The putative selective mechanisms driving SAAR evolution inCryptosporidiumspecies are unknown.
Trends in rotavirus from 2001 to 2015 in two paediatric hospitals in Atlanta, Georgia
Authors: Sederdahl B. K. , Yi J. , Jerris R. C. , Gillespie S. E. , Westblade L. F. , Kraft C. S. , Shane A. L. , Anderson E. J. 
Published: February 2018

AbstractWe compared rotavirus detection patterns before (2001–2006) and after (2008–2015) rotavirus vaccine introduction. We also compared rotavirus detection patterns in odd (2009, 2011, 2013, 2015) and even (2008, 2010, 2012, 2014) years post-vaccine separately. Results of stool rotavirus antigen testing from inpatient, outpatient and emergency department encounters from July 2000 to July 2015 at two paediatric hospital laboratories in Atlanta, Georgia were reviewed. Post-vaccine, rotavirus detection declined (30.2% vs. 13.7% (overall 54.6% decline, P <0.001)), occurred more frequently outside the rotavirus season (19.8% vs. 3.5%; P < 0.001), and was more common among older children (26 vs. 13 median months of age; P < 0.001). During odd years post-vaccine, rotavirus detection was significantly higher than even years (20.2% vs. 6.4%; P < 0.001). Rotavirus detection declined substantially and developed a biennial pattern in the post-vaccine era. The intensity and temporality of rotavirus detection in odd years post-vaccine resembled that observed pre-vaccine, although considerably reduced in magnitude.
Association of cytosolic sialidase Neu2 with plasma membrane enhances Fas-mediated apoptosis by impairing PI3K-Akt/mTOR-mediated pathway in pancreatic cancer cells
Authors: Nath Shalini , Mandal Chhabinath , Chatterjee Uttara , Mandal Chitra 
Published: February 2018

AbstractModulation of sialylation by sialyltransferases and sialidases plays essential role in carcinogenesis. There are few reports on sialyltransferase, however, the contribution of cytosolic sialidase (Neu2) remains unexplored in pancreatic ductal adenocarcinoma (PDAC). We observed lower expression of Neu2 in different PDAC cells, patient tissues, and a significant strong association with clinicopathological characteristics. Neu2 overexpression guided drug-resistant MIAPaCa2 and AsPC1 cells toward apoptosis as evidenced by decreased Bcl2/Bax ratio, activation of caspase-3/caspase-6/caspase-8, PARP reduction, reduced CDK2/CDK4/CDK6, and cyclin-B1/cyclin-E with unaffected caspase-9. Neu2-overexpressed cells exhibited higher expression of Fas/CD95-death receptor, FasL, FADD, and Bid cleavage confirming extrinsic pathway-mediated apoptosis. α2,6-linked sialylation of Fas helps cancer cells to survive, which is a substrate for Neu2. Therefore, their removal should enhance Fas-mediated apoptosis. Neu2-overexpressed cells indeed showed increased enzyme activity even on membrane. Interestingly, this membrane-bound Neu2 exhibited enhanced association with Fas causing its desialylation and activation as corroborated by decreased association of Fas with α2,6-sialic acid-binding lectin. Additionally, enhanced cytosolic Neu2 inhibited the expression of several growth factor-mediated signaling molecules involved in PI3K/Akt–mTOR pathway probably through desialylation which in turn also causes Fas activation. Furthermore, Neu2-overexpressed cells exhibited reduced cell migration, invasion with decreased VEGF, VEGFR, and MMP9 levels. To the best of our knowledge, this is the first report of cytosolic Neu2 on membrane, its association with Fas, enhanced desialylation, activation, and Fas-mediated apoptosis. Taken together, our study ascertains a novel concept by which the function of Fas/CD95 could be modulated indicating a critical role of upstream Neu2 as a promising target for inducing apoptosis in pancreatic cancer.
RIPK1-dependent cell death: a novel target of the Aurora kinase inhibitor Tozasertib (VX-680)
Authors: Martens Sofie , Goossens Vera , Devisscher Lars , Hofmans Sam , Claeys Polien , Vuylsteke Marnik , Takahashi Nozomi , Augustyns Koen , Vandenabeele Peter 
Published: February 2018

AbstractThe Aurora kinase family (Aurora A, B and C) are crucial regulators of several mitotic events, including cytokinesis. Increased expression of these kinases is associated with tumorigenesis and several compounds targeting Aurora kinase are under evaluation in clinical trials (a.o. AT9283, AZD1152, Danusertib, MLN8054). Here, we demonstrate that the pan-Aurora kinase inhibitor Tozasertib (VX-680 and MK-0457) not only causes cytokinesis defects through Aurora kinase inhibition, but is also a potent inhibitor of necroptosis, a cell death process regulated and executed by the RIPK1, RIPK3 and MLKL signalling axis. Tozasertib’s potency to inhibit RIPK1-dependent necroptosis and to block cytokinesis in cells is in the same concentration range, with an IC50 of 1.06 µM and 0.554 µM, respectively. A structure activity relationship (SAR) analysis of 67 Tozasertib analogues, modified at 4 different positions, allowed the identification of analogues that showed increased specificity for either cytokinesis inhibition or for necroptosis inhibition, reflecting more specific inhibition of Aurora kinase or RIPK1, respectively. These results also suggested that RIPK1 and Aurora kinases are functionally non-interacting targets of Tozasertib and its analogues. Indeed, more specific Aurora kinase inhibitors did not show any effect in necroptosis and Necrostatin-1s treatment did not result in cytokinesis defects, demonstrating that both cellular processes are not interrelated. Finally, Tozasertib inhibited recombinant human RIPK1, human Aurora A and human Aurora B kinase activity, but not RIPK3. The potency ranking of the newly derived Tozasertib analogues and their specificity profile, as observed in cellular assays, coincide with ADP-Glo recombinant kinase activity assays. Overall, we show that Tozasertib not only targets Aurora kinases but also RIPK1 independently, and that we could generate analogues with increased selectivity to RIPK1 or Aurora kinases, respectively.
The gastrointestinal tract microbiota of northern white-cheeked gibbons (Nomascus leucogenys) varies with age and captive condition
Authors: Jia Ting , Zhao Sufen , Knott Katrina , Li Xiaoguang , Liu Yan , Li Ying , Chen Yuefei , Yang Minghai , Lu Yanping , Wu Junyi , Zhang Chenglin 
Published: February 2018

AbstractNutrition and health of northern white-cheeked gibbons (Nomascus leucogenys) are considered to be primarily influenced by the diversity of their gastrointestinal tract (GIT) microbiota. However, the precise composition, structure, and role of the gibbon GIT microbiota remain unclear. Microbial communities from the GITs of gibbons from Nanning (NN, n = 36) and Beijing (BJ, n = 20) Zoos were examined through 16S rRNA sequencing. Gibbon’s GITs microbiomes contained bacteria from 30 phyla, dominated by human-associated microbial signatures: Firmicutes, Bacteroidetes, and Proteobacteria. Microbial species richness was markedly different between adult gibbons (>8 years) under distinct captive conditions. The relative abundance of 14 phyla varied significantly in samples of adults in BJ versus NN. Among the age groups examined in NN, microbiota of adult gibbons had greater species variation and richer community diversity than microbiota of nursing young (<6 months) and juveniles (2–5 years). Age-dependent increases in the relative abundances of Firmicutes and Fibrobacteres were detected, along with simultaneous increases in dietary fiber intake. A few differences were detected between sex cohorts in NN, suggesting a very weak correlation between sex and GIT microbiota. This study is the first to taxonomically identify gibbon’s GITs microbiota confirming that microbiota composition varies with age and captive condition.
Role of intestinal trefoil factor in protecting intestinal epithelial cells from burn-induced injury
Authors: Hu Jianhong , Shi Yan , Wang Chao , Wan Hanxing , Wu Dan , Wang Hongyu , Peng Xi 
Published: February 2018

AbstractAlthough intestinal trefoil factor (ITF) can alleviate the burn-induced intestinal mucosa injury, the underlying mechanisms remains elusive. In this study, we investigated if ITF alters glutamine transport on the brush border membrane vesicles (BBMVs) of the intestines in Sprague-Dawley rats inflicted with 30% TBSA and the underlying mechanisms. We found that ITF significantly stimulated intestinal glutamine transport in burned rats. Mechanistically, ITF enhanced autophagy, reduces endoplasmic reticulum stress (ERS), and alleviates the impaired PDI, ASCT2, and B0AT1 in IECs and BBMVs after burn injury likely through AMPK activation. Therefore, ITF may protect intestinal epithelial cells from burn-induced injury through improving glutamine transport by alleviating ERS.
Transcriptomics reveals a cross-modulatory effect between riboflavin and iron and outlines responses to riboflavin biosynthesis and uptake in Vibrio cholerae
Authors: Sepúlveda-Cisternas Ignacio , Lozano Aguirre Luis , Fuentes Flores Andrés , Vásquez Solis de Ovando Ignacio , García-Angulo Víctor Antonio 
Published: February 2018

AbstractVibrio cholerae, a pandemic diarrheagenic bacterium, is able to synthesize the essential vitamin riboflavin through the riboflavin biosynthetic pathway (RBP) and also to internalize it through the RibN importer. In bacteria, the way riboflavin biosynthesis and uptake functions correlate is unclear. To gain insights into the role of the riboflavin provision pathways in the physiology of V. cholerae, we analyzed the transcriptomics response to extracellular riboflavin and to deletions of ribD (RBP-deficient strain) or ribN. Many riboflavin-responsive genes were previously reported to belong to the iron regulon, including various iron uptake genes. Real time PCR analysis confirmed this effect and further documented that reciprocally, iron regulates RBP and ribN genes in a riboflavin-dependent way. A subset of genes were responding to both ribD and ribN deletions. However, in the subset of genes specifically affected in the ∆ribD strain, the functional terms protein folding and oxidation reduction process were enriched, as determined by a Gene Ontology analysis. In the gene subset specifically affected in the ∆ribN strain, the cytochrome complex assembly functional term was enriched. Results suggest that iron and riboflavin interrelate to regulate its respective provision genes and that both common and specific effects of biosynthesized and internalized riboflavin exist.
Prevalence and impact of baseline resistance-associated substitutions on the efficacy of ledipasvir/sofosbuvir or simeprevir/sofosbuvir against GT1 HCV infection
Authors: Wang Gary P. , Terrault Norah , Reeves Jacqueline D. , Liu Lin , Li Eric , Zhao Lisa , Lim Joseph K. , Morelli Giuseppe , Kuo Alexander , Levitsky Josh , Sherman Kenneth E. , Frazier Lynn M. , Ramani Ananthakrishnan , Peter Joy , Akuskevich Lucy , Fried Michael W. , Nelson David R. 
Published: February 2018

AbstractBaseline resistance-associated substitutions (RASs) have variable impacts in clinical trials but their prevalence and impact in real-world patients remains unclear. We performed baseline resistance testing using a commercial assay (10% cutoff) for 486 patients treated with LDV/SOF or SMV/SOF, with or without ribavirin, in the multi-center, observational HCV-TARGET cohort. Linkage of RASs was evaluated in selected samples using a novel quantitative single variant sequencing assay. Our results showed that the prevalence of NS3, NS5A, NS5B RASs was 45%, 13%, and 8%, respectively, and 10% of patients harbored RASs in 2 or more drug classes. Baseline LDV RASs in GT1a, TE, and cirrhosis LDV/SOF subgroup was associated with 2–4% lower SVR12 rates. SMV RASs was associated with lower SVR12 rates in GT1a, treatment-experienced, cirrhotics SMV/SOF subgroup. Pooled analysis of all patients with baseline RASs revealed that SVR12 was 100% (19/19) in patients treated for longer than 98 days but was 87% (81/93) in patients treated for shorter than 98 days. These results demonstrate that RASs prevalence and their impact in real world practice are in general agreement with registration trials, and suggest that longer treatment duration may overcome the negative impact of baseline RASs on SVR12 rates in clinical practice.
Nest substrate reflects incubation style in extant archosaurs with implications for dinosaur nesting habits
Authors: Tanaka Kohei , Zelenitsky Darla K. , Therrien François , Kobayashi Yoshitsugu 
Published: February 2018

AbstractDinosaurs thrived and reproduced in various regions worldwide, including the Arctic. In order to understand their nesting in diverse or extreme environments, the relationships between nests, nesting environments, and incubation methods in extant archosaurs were investigated. Statistical analyses reveal that species of extant covered nesters (i.e., crocodylians and megapodes) preferentially select specific sediments/substrates as a function of their nesting style and incubation heat sources. Relationships between dinosaur eggs and the sediments in which they occur reveal that hadrosaurs and some sauropods (i.e., megaloolithid eggs) built organic-rich mound nests that relied on microbial decay for incubation, whereas other sauropods (i.e., faveoloolithid eggs) built sandy in-filled hole nests that relied on solar or potentially geothermal heat for incubation. Paleogeographic distribution of mound nests and sandy in-filled hole nests in dinosaurs reveals these nest types produced sufficient incubation heat to be successful up to mid latitudes (≤47°), 10° higher than covered nesters today. However, only mound nesting and likely brooding could have produced sufficient incubation heat for nesting above the polar circle (>66°). As a result, differences in nesting styles may have placed restrictions on the reproduction of dinosaurs and their dispersal at high latitudes.
High quality self-separated GaN crystal grown on a novel nanoporous template by HVPE
Authors: Huo Qin , Shao Yongliang , Wu Yongzhong , Zhang Baoguo , Hu Haixiao , Hao Xiaopeng 
Published: February 2018

AbstractIn this study, a novel nanoporous template was obtained by a two-step etching process from MOCVD-GaN/Al2O3 (MGA) with electrochemical etching sequentially followed by chemical wet etching. The twice-etched MOCVD-GaN/Al2O3 (TEMGA) templates were utilized to grow GaN crystals by hydride vapor phase epitaxy (HVPE) method. The GaN crystals were separated spontaneously from the TEMGA template with the assistance of voids formed by the etched nanopores. Several techniques were utilized to characterize the quality of the free-standing GaN crystals obtained from the TEMGA template. Results showed that the quality of the as-obtained GaN crystals was improved obviously compared with those grown on the MGA. This convenient technique can be applied to grow high-quality free-standing GaN crystals.
Nitrogen isotope fractionation in protoplanetary disks
Authors: Visser Ruud , Bruderer Simon , Cazzoletti Paolo , Facchini Stefano , Heays Alan N. , van Dishoeck Ewine F. 
Published: February 2018

Aims. The two stable isotopes of nitrogen, 14N and 15N, exhibit a range of abundance ratios both inside and outside the solar system. The elemental ratio in the solar neighborhood is 440. Recent ALMA observations showed HCN/HC15N ratios from 83 to 156 in six T Tauri and Herbig disks and a CN/C15N ratio of 323 ± 30 in one T Tauri star. We aim to determine the dominant mechanism responsible for these enhancements of 15N: low-temperature exchange reactions or isotope-selective photodissociation of N2.
Methods. Using the thermochemical code DALI, we model the nitrogen isotope chemistry in circumstellar disks with a 2D axisymmetric geometry. Our chemical network is the first to include both fractionation mechanisms for nitrogen. The model produces abundance profiles and isotope ratios for several key N-bearing species. We study how these isotope ratios depend on various disk parameters.
Results. The formation of CN and HCN is closely coupled to the vibrational excitation of H2 in the UV-irradiated surface layers of the disk. Isotope fractionation is completely dominated by isotope-selective photodissociation of N2. The column density ratio of HCN over HC15N in the disk’s inner 100 au does not depend strongly on the disk mass, the flaring angle or the stellar spectrum, but it is sensitive to the grain size distribution. For larger grains, self-shielding of N2 becomes more important relative to dust extinction, leading to stronger isotope fractionation. Between disk radii of ~50 and 200 au, the models predict HCN/HC15N and CN/C15N abundance ratios consistent with observations of disks and comets. The HCN/HC15N and CN/C15N column density ratios in the models are a factor of 2–3 higher than those inferred from the ALMA observations.
High-resolution observations of IRAS 08544−4431
Authors: Bujarrabal V. , Castro-Carrizo A. , Van Winckel H. , Alcolea J. , Sánchez Contreras C. , Santander-García M. , Hillen M. 
Published: February 2018

Context. Aims. In order to study the effects of rotating disks in the post-asymptotic giant branch (post-AGB) evolution, we observe a class of binary post-AGB stars that seem to be systematically surrounded by equatorial disks and slow outflows. Although the rotating dynamics had only been well identified in three cases, the study of such structures is thought to be fundamental to the understanding of the formation of disks in various phases of the late evolution of binary stars and the ejection of planetary nebulae from evolved stars.
Methods. We present ALMA maps of 12CO and 13CO J = 3−2 lines in the source IRAS 08544−4431, which belongs to the above mentioned class of objects. We analyzed the data by means of nebula models, which account for the expectedly composite source and can reproduce the data. From our modeling, we estimated the main nebula parameters, including the structure and dynamics and the density and temperature distributions. We discuss the uncertainties of the derived values and, in particular, their dependence on the distance.
Results. Our observations reveal the presence of an equatorial disk in rotation; a low-velocity outflow is also found, probably formed of gas expelled from the disk. The main characteristics of our observations and modeling of IRAS 08544−4431 are similar to those of better studied objects, confirming our interpretation. The disk rotation indicates a total central mass of about 1.8 M⊙, for a distance of 1100 pc. The disk is found to be relatively extended and has a typical diameter of ~4 × 1016 cm. The total nebular mass is ~2 × 10−2 M⊙, of which ~90% corresponds to the disk. Assuming that the outflow is due to mass loss from the disk, we derive a disk lifetime of ~10 000 yr. The disk angular momentum is found to be comparable to that of the binary system at present. Assuming that the disk angular momentum was transferred from the binary system, as expected, the high values of the disk angular momentum in this and other similar disks suggest that the size of the stellar orbits has significantly decreased as a consequence of disk formation.
Product Divergence in Coinage-Metal-Catalyzed Reactions of π-Rich Compounds
Authors: Chan Philip , Boyle Joshua , Zhao Yichao 
Published: February 2018

This short review aims to summarize how the product outcome of reactions of a common starting material can sometimes be controlled by the judicious choice of copper, silver or gold as the catalyst. It highlights the different reactivities observed in the functional group transformations of π-rich substrates mediated by the three group 11 metal salts.1	Introduction2	Reactions of Propargyl Amines, Esters and Their Derivatives3	Reactions of Phenylacetylene Derivatives4	Reactions of π-Rich Alcohols and Ethers5	Indolyl Cyclopropene and Alkynone Rearrangements6	Reactions Involving Metal-Carbene and Metal-Carbenoid Intermediates7	Conclusion