bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation of 4′‐Spirocyclobutyl Nucleoside Analogues as Novel and Versatile Adenosine Scaffolds
Authors: Verhoeven Jonas , De Vleeschouwer Freija , Kong Hanchu , Van Hecke Kristof , Pande Vineet , Sun Weimei , Vos Ann , Wu Tongfei , Meerpoel Lieven , Thuring Jan Willem , Verniest Guido 
Published: October 2019

AbstractDespite the large variety of modified nucleosides that have been reported, the preparation of constrained 4′‐spirocyclic adenosine analogues has received very little attention. We discovered that the [2+2]‐cycloaddition of dichloroketene on readily available 4′‐exo‐methylene furanose sugars efficiently results in the diastereoselective formation of novel 4′‐spirocyclobutanones. The reaction mechanism was investigated via density functional theory (DFT) and found to proceed either via a non‐synchronous or stepwise reaction sequence, controlled by the stereochemistry at the 3′‐position of the sugar substrate. The obtained dichlorocyclobutanones were converted into nucleoside analogues, providing access to a novel class of chiral 4′‐spirocyclobutyl adenosine mimetics in eight steps from commercially available sugars. Assessment of the biological activity of designed 4′‐spirocyclic adenosine analogues identified potent inhibitors for protein methyltransferase target PRMT5.
Integrin α11β1 is expressed in breast cancer stroma and associates with aggressive tumor phenotypes
Authors: Smeland Hilde Ytre‐Hauge , Askeland Cecilie , Wik Elisabeth , Knutsvik Gøril , Molven Anders , Edelmann Reidunn J , Reed Rolf K , Warren David J , Gullberg Donald , Stuhr Linda , Akslen Lars A 
Published: October 2019

AbstractCancer‐associated fibroblasts are essential modifiers of the tumor microenvironment. The collagen‐binding integrin α11β1 has been proposed to be upregulated in a pro‐tumorigenic subtype of cancer‐associated fibroblasts. Here, we analyzed the expression and clinical relevance of integrin α11β1 in a large breast cancer series using a novel antibody against the human integrin α11 chain. Several novel monoclonal antibodies against the integrin α11 subunit were tested for use on formalin‐fixed paraffin‐embedded tissues, and Ab 210F4B6A4 was eventually selected to investigate the immunohistochemical expression in 392 breast cancers using whole sections. mRNA data from METABRIC and co‐expression patterns of integrin α11 in relation to αSMA and cytokeratin‐14 were also investigated. Integrin α11 was expressed to varying degrees in spindle‐shaped cells in the stroma of 99% of invasive breast carcinomas. Integrin α11 co‐localized with αSMA in stromal cells, and with αSMA and cytokeratin‐14 in breast myoepithelium. High stromal integrin α11 expression (66% of cases) was associated with aggressive breast cancer features such as high histologic grade, increased tumor cell proliferation, ER negativity, HER2 positivity, and triple‐negative phenotype, but was not associated with breast cancer specific survival at protein or mRNA levels. In conclusion, high stromal integrin α11 expression was associated with aggressive breast cancer phenotypes.
Sensory cutaneous papillae in the sea lamprey (Petromyzon marinus L.): I. Neuroanatomy and physiology
Authors: Daghfous Gheylen , Auclair François , Blumenthal Felix , Suntres Tina , Lamarre‐Bourret Jessica , Mansouri Masoud , Zielinski Barbara , Dubuc Réjean 
Published: October 2019

AbstractMolecules present in an animal's environment can indicate the presence of predators, food, or sexual partners and consequently, induce migratory, reproductive, foraging, or escape behaviors. Three sensory systems, the olfactory, gustatory, and solitary chemosensory cell (SCC) systems detect chemical stimuli in vertebrates. While a great deal of research has focused on the olfactory and gustatory system over the years, it is only recently that significant attention has been devoted to the SCC system. The SCCs are microvillous cells that were first discovered on the skin of fish, and later in amphibians, reptiles, and mammals. Lampreys also possess SCCs that are particularly numerous on cutaneous papillae. However, little is known regarding their precise distribution, innervation, and function. Here, we show that sea lampreys (Petromyzon marinus L.) have cutaneous papillae located around the oral disk, nostril, gill pores, and on the dorsal fins and that SCCs are particularly numerous on these papillae. Tract‐tracing experiments demonstrated that the oral and nasal papillae are innervated by the trigeminal nerve, the gill pore papillae are innervated by branchial nerves, and the dorsal fin papillae are innervated by spinal nerves. We also characterized the response profile of gill pore papillae to some chemicals and showed that trout‐derived chemicals, amino acids, and a bile acid produced potent responses. Together with a companion study (Suntres et al., Journal of Comparative Neurology, this issue), our results provide new insights on the function and evolution of the SCC system in vertebrates.
Low‐Temperature Reverse Water–Gas Shift Process and Transformation of Renewable Carbon Resources to Value‐Added Chemicals
Authors: Shen Xiaojun , Meng Qinglei , Dong Minghua , Xiang Junfeng , Li Shaopeng , Liu Huizhen , Han Buxing 
Published: October 2019

AbstractThe use of CO2 instead of toxic CO in the production of important chemicals has attracted widespread interest, and the reverse water–gas shift reaction (RWGSR) is the key step for this kind of processes. Although the thermodynamic limitations are overcome by the reaction of CO with other compounds, the temperature of most reactions involving RWGSR is usually very high owing to the inertness of CO2. Herein, it was found that Ru3(CO)12 could catalyze the RWGSR in the ionic liquid HMimBF4 without ligand or promoter, and CO could be produced at 80 °C, which was much lower than the temperatures reported to date. Detailed studies showed that the BF4− in the ionic liquid played a crucial role in the low‐temperature RWGSR. Based on the low‐temperature RWGSR, three important routes to transform CO2 into valuable chemicals were developed, including synthesis of xanthone from CO2 and diaryl ethers, synthesis of phenol and acetic acid from CO2 and anisole, and production of acetic acid from CO2 and lignin. The reactions could occur at temperature as low as 80 °C, and low‐temperature RWGSR was essential for the reactions under mild conditions. The strategy opens the way to produce value‐added chemicals by using CO2 and H2 as feedstocks under low temperature.
Host tolerance and resistance to parasitic nest flies differs between two wild bird species
Authors: Grab Kirstine M. , Hiller Brian J. , Hurlbert John H. , Ingram McKenzie E. , Parker Alexandra B. , Pokutnaya Darya Y. , Knutie Sarah A. 
Published: October 2019

Abstract

Hosts have developed and evolved defense strategies to limit parasite damage. Hosts can reduce the damage that parasites cause by decreasing parasite fitness (resistance) or without affecting parasite fitness (tolerance). Because a parasite species can infect multiple host species, determining the effect of the parasite on these hosts and identifying host defense strategies can have important implications for multi‐host–parasite dynamics.

Over 2 years, we experimentally manipulated parasitic flies (Protocalliphora sialia) in the nests of tree swallows (Tachycineta bicolor) and eastern bluebirds (Sialia sialis). We then determined the effects of the parasites on the survival of nestlings and compared defense strategies between host species. We compared resistance between host species by quantifying parasite densities (number of parasites per gram of host) and measured nestling antibody levels as a mechanism of resistance. We quantified tolerance by determining the relationship between parasite density and nestling survival and blood loss by measuring hemoglobin levels (as a proxy of blood recovery) and nestling provisioning rates (as a proxy of parental compensation for resources lost to the parasite) as potential mechanisms of tolerance.

For bluebirds, parasite density was twice as high as for swallows. Both host species were tolerant to the effects of P. sialia on nestling survival at their respective parasite loads but neither species were tolerant to the blood loss to the parasite. However, swallows were more resistant to P. sialia compared to bluebirds, which was likely related to the higher antibody‐mediated immune response in swallow nestlings. Neither blood recovery nor parental compensation were mechanisms of tolerance.

Overall, these results suggest that bluebirds and swallows are both tolerant of their respective parasite loads but swallows are more resistant to the parasites. These results demonstrate that different host species have evolved similar and different defenses against the same species of parasite.
Modelling long‐distance floating seed dispersal in salt marsh tidal channels
Authors: Shi Wei , Shao Dongdong , Gualtieri Carlo , Purnama Anton , Cui Baoshan 
Published: October 2019

AbstractSeed dispersal is a primary factor influencing plant community development in salt‐marshes. However, studies on seed dispersal in marsh‐channel system are relatively scarce, and relevant mathematical modelling is particularly lacking. In this study, we developed a one‐dimensional advection–dispersion model to explore the patterns of long‐distance floating seed dispersal in tidal channels. Oscillatory tidal current velocity and water depth were assumed to represent the tidal effects. An exponential decay coefficient was introduced to account for the loss of floating seeds due to water‐logged deposition and retention by trapping agents along the channel banks. An analytical solution in integral form was derived using the method of Green's function. The developed model was applied to simulate floating Spartina densiflora seed dispersal in a real tidal channel. Seed floating duration and seed collection data reported in the literature were used for model calibration and validation. The leptokurtic seed dispersal kernel in the marsh‐channel system was quantified for the first time using the predicted spatio‐temporal distribution of deposited and retained seeds. The range of the long‐distance floating seed dispersal and its distribution concentration that have important implications for salt marsh protection and restoration activities were evaluated through statistical parameters such as the centroid displacement and the variance of the floating seed cloud and floating seed concentration contours. The developed model provides a useful tool for ecological management of tidal marshes, as data on the long‐distance floating seed dispersal are rarely available and hard to gather.
Correlative climatic niche models predict real and virtual species distributions equally well
Authors: Journé Valentin , Barnagaud Jean‐Yves , Bernard Cyril , Crochet Pierre‐André , Morin Xavier 
Published: October 2019

AbstractClimate is one of the main factors driving species distributions and global biodiversity patterns. Obtaining accurate predictions of species’ range shifts in response to ongoing climate change has thus become a key issue in ecology and conservation. Correlative species distribution models (cSDMs) have become a prominent tool to this aim in the last decade and have demonstrated good predictive abilities with current conditions, irrespective of the studied taxon. However,cSDMs rely on statistical association between species’ presence and environmental conditions and have rarely been challenged on their actual capacity to reflect causal relationships between species and climate. In this study, we question whethercSDMs can accurately identify if climate and species distributions are causally linked, a prerequisite for accurate prediction of range shift in relation to climate change. We compared the performance ofcSDMs in predicting the distributions of 132 European terrestrial species, chosen randomly within five taxonomic groups (three vertebrate groups and two plant groups), and of 1,320 virtual species whose distribution is causally fully independent from climate. We found that (1) for real species, the performance ofcSDMs varied principally with range size, rather than with taxonomic groups and (2)cSDMs did not predict the distributions of real species with a greater accuracy than the virtual ones. Our results unambiguously show that the high predictive power ofcSDMs can be driven by spatial autocorrelation in climatic and distributional data and does not necessarily reflect causal relationships between climate and species distributions. Thus, high predictive performance ofcSDMs does not ensure that they accurately depict the role of climate in shaping species distributions. Our findings therefore call for strong caution when usingcSDMs to provide predictions on future range shifts in response to climate change.
Familial implications of autoimmune disease: Recurrence risks of alopecia areata and associated conditions in first‐degree relatives
Authors: Agre Katherine , McCarthy Veach Patricia , Bemmels Heather , Wiens Katie , LeRoy Bonnie S. , Hordinsky Maria 
Published: October 2019

AbstractAlopecia areata (AA), a complex autoimmune hair loss condition, affects approximately 2.1% of the population. Individuals with AA have increased susceptibility to diseases such as atopy and autoimmune disorders, but little is known about first‐degree relatives' risk to develop AA and associated conditions. Genetic counseling for multifactorial conditions, including autoimmune disease is complex, but potentially valuable. Anecdotally we know patients with AA ask medical providers about recurrence risk for family members as well as question whether they and their relatives are at risk for other conditions. Data on AA recurrence risks and comorbid conditions among relatives of affected individuals comprise valuable information that may guide clinical management by genetic counselors. This study investigated the recurrence risk of AA and compared the prevalence of associated conditions among first‐degree relatives to the general population. The study also assessed the validity of self‐reported conditions for a subset of participants. Relatives of individuals with AA (N = 155), recruited from the National Alopecia Areata Foundation Registry, completed telephone surveys about their personal medical history for 70 medical conditions associated with AA. Medical records for 60 participants were compared to self‐reported responses. One‐sided proportional tests, in which it is assumed the disease prevalence in first‐degree relatives is higher than for those in the general population, yielded a 7.8% estimated risk of AA versus the general population prevalence of 2.1%. Furthermore, there are increased risks of 33 associated conditions, including atopy and other autoimmune conditions. Comparison of medical reports to self‐reported conditions indicated only 12% was incongruent. The findings may help genetic counselors better serve patients and their families by informing them of lifetime risk estimates of developing AA and comorbid conditions, resulting in early diagnosis of autoimmune diseases in AA families. Findings also provide evidence supporting the validity of self‐report data in AA families.
MRI cine‐tagging of cardiac‐induced motion for noninvasive staging of liver fibrosis
Authors: Lefebvre Thierry , Petitclerc Léonie , Hébert Mélanie , Bilodeau Laurent , Sebastiani Giada , Olivié Damien , Gao Zu‐Hua , Sylvestre Marie‐Pierre , Cloutier Guy , Nguyen Bich N. , Gilbert Guillaume , Tang An 
Published: October 2019

BackgroundMR elastography is a noninvasive technique that provides high diagnostic accuracy for the staging of liver fibrosis; however, it requires external hardware and mainly assesses the right lobe.PurposeTo evaluate the diagnostic performance of MRI cine‐tagging for staging fibrosis in the left liver lobe, using biopsy as the reference standard.Study TypeInstitutional Review Board (IRB)‐approved two‐center prospective study.PopulationSeventy‐six patients with chronic liver disease who underwent an MRI cine‐tagging examination and a liver biopsy within a 6‐week interval.Field Strength/Sequence2D‐GRE multislice sequence at 3.0T with spatial modulation of the magnetization preparation sequence and peripheral pulse‐wave triggering on two coronal slices chosen underneath the heart apex to capture maximal deformation with consecutive breath‐holds adapted to patient cardiac frequency.AssessmentA region of interest was selected in the liver close to the heart apex. Maximal strain was evaluated with the harmonic phase (HARP) technique.Statistical TestsSpearman's correlation, Kruskal–Wallis test, Mann–Whitney U‐test, and receiver operating characteristic (ROC) analysis were performed.ResultsLiver strain measured on tagged images decreased with higher histological fibrosis stage (ρ = –0.68, P < 0.0001). Strain values were significantly different between all fibrosis stages (P < 0.0001), and between groups of fibrosis stages ≤F3 vs. F4 (P < 0.05). Areas under the ROC curves were 0.95 (95% confidence interval: 0.89–1.00) to distinguish fibrosis stages F0 vs. F4, 0.81 (0.70–0.92) for stages F0 vs. ≥F1, 0.84 (0.76–0.93) for stages ≤F1 vs. ≥F2, 0.86 (0.78–0.94) for stages ≤F2 vs. ≥F3, and 0.87 (0.77–0.96) for stages ≤F3 vs. F4.Data ConclusionMRI cine‐tagging is a promising technique for measuring liver strain without additional elastography hardware. It could be used to assess the left liver lobe as a complement to current techniques assessing the right lobe.Level of Evidence: 1Technical Efficacy: 3J. Magn. Reson. Imaging 2020;51:1570–1580.
Sensory properties of aqueous dispersions of protein‐rich extracts from Chlorella protothecoides at neutral and acidic pH
Authors: Grossmann Lutz , Wörner Vera , Hinrichs Jörg , Weiss Jochen 
Published: October 2019

AbstractBACKGROUNDWater‐soluble proteins extracted from the heterotrophically cultivated microalga Chlorella protothecoides have been shown to have a good solubility over a broad pH range, which makes them a promising candidate for beverage formulations. This study investigated the sensory properties of dispersions of a protein‐rich extract from C. protothecoides at neutral and pH 3.RESULTSSensory acceptance tests of the pure extract revealed an overall low acceptance at pH 7 without sucrose addition. Sensory acceptance was significantly (P ≤ 0.05) increased by lowering the pH to 3 with citric acid, and the addition of 50 g kg−1 sucrose. Here, overall positive sensory acceptance ratings were achieved up to a protein extract concentration of 40 g kg−1. Basic taste evaluations showed only low bitterness scores and no significant (P > 0.05) increase in bitterness with decreasing pH.CONCLUSIONIt is suggested that protein‐rich extracts from C. protothecoides have promising sensory properties in beverage formulations. © 2019 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
An exact method for a class of robust shortest path problems with scenarios
Authors: Duque Daniel , Medaglia Andrés L. 
Published: October 2019

AbstractIn this variant of the robust shortest path problem, the cost of traversing an arc is given by a discrete set of scenarios. The problem is then to find a (robust) path that takes into account the information arising from the multiple cost realizations of the possible scenarios. To account for a robust path, we adopt the bw‐robustness criterion, which ameliorates the dramatic role played by worst‐case approaches. Under this criterion, the parameter b represents a desirable upper bound for the cost that the decision maker wants for most of the scenarios; while parameter w strictly bounds the cost and represents a value that the decision maker is not willing to exceed in any scenario. To solve the problem, we extend the pulse algorithm, a general‐purpose solution strategy that has been used on shortest path problems with side constraints. The proposed algorithm compares favorably against an integer programming approach both in terms of speed and scalability on networks with up to 39 377 nodes and 192 094 arcs.
Permeability estimation from induced polarization: an evaluation of geophysical length scales using an effective hydraulic radius concept
Authors: Weller Andreas , Slater Lee 
Published: October 2019

ABSTRACTGeophysical length scales defined from induced‐polarization measurements can be used in models of permeability (k) prediction. We explore the relative merit of different induced‐polarization parameters as proxies of an effective hydraulic radius (reff) that can be used to predict permeability from a modified Hagen–Poiseuille equation. Whereas geometrical measures of the hydraulic radius are good proxies of reff, the induced‐polarization measures are not well correlated with reff. However, a new proxy of reff that considers both imaginary conductivity and formation factor shows an improved correlation with reff. The resulting model enables a better quality of permeability prediction compared with the other geophysical length scales, but does not reach the predictive quality of the models based on geometrical length scales. The specific polarizability defined when incorporating the effect of the formation factor on imaginary conductivity appears to be independent of pore geometry, indicating that it is the correct parameter representing the role of the surface electrochemistry on the induced‐polarization effect. However, the joint dependence of induced‐polarization measurements on both the pore radius and the tortuosity and porosity of the interconnected pore network is a limitation to the widely explored use of induced‐polarization measurements to isolate surface properties from volumetric properties of the interconnected pore network.
Puberty in the Bronze Age: First application of a puberty estimation method to a prehistoric population
Authors: Doe Danielle M. , Molina Moreno María , Rascón Pérez Josefina , Candelas González Nieves , Cambra‐Moo Oscar , Campo Martín Manuel , González Martín Armando 
Published: October 2019

AbstractPuberty and adolescence represent a significant period of physical growth and maturation and a critical life stage in which children transition into adults within their societies. Numerous studies have observed a secular trend and have determined that puberty is now occurring earlier than in the past. This investigation represents the first application of a methodology for assessing the pubertal status of osteological remains to a prehistoric skeletal sample. Six Bronze Age adolescent skeletons from the Cerro de La Encantada archaeological site (Ciudad Real, Spain) were analysed. Prepubescence was observed at age 9 and the transition phase of the pubertal growth spurt at 15 years of age. These results were similar to those obtained from medieval, Industrial Revolution, and modern populations, both within and outside of the Iberian Peninsula. The similarity in the development of the Bronze Age adolescents to that of other past and contemporary populations suggests that the pubertal process has remained essentially unchanged across millennia until recent times. However, other interpretations, including the influence of a subpar developmental environment and potential methodological artefacts, are possible. Nevertheless, studies of this type provide important information about a crucial transitory period in human development.