bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Bile Salt Export Pump (BSEP) Inhibition in Membrane Vesicles Using Radioactive and LC/MS‐Based Detection Methods
Authors: Marroquin Lisa D. , Bonin Paul D. , Keefer Julie , Schroeter Thomas
Published: February 2017

The bile salt export pump (BSEP, ABCB11) belongs to the ATP‐binding‐cassette superfamily of transporters and is predominately found in the liver. BSEP is an efflux transporter that plays a critical role in the secretion of bile salts into the bile. Inhibition of BSEP function by drugs can result in the buildup of bile salts in the liver and eventually leads to cholestasis and drug‐induced liver injury (DILI). DILI is a major cause of withdrawal of drugs from the pharmaceutical market and accounts for >50% of acute liver failures. Therefore, early detection of BSEP inhibition by drugs can help to mitigate the possibility of BSEP‐associated liver injury. This unit describes two assays that investigate the relationship between drug interference with BSEP function and liver injury using membrane vesicles prepared from Hi5 insect cells transfected with human BSEP. Comprehensive protocols for assessing BSEP inhibition in a 384‐well format using radiolabeled and liquid chromatography/mass spectrometry (LC/MS)–based detection methods are described. © 2017 by John Wiley & Sons, Inc.
Evaluating the consequences of salmon nutrients for riparian organisms: Linking condition metrics to stable isotopes
Authors: Vizza Carmella , Sanderson Beth L. , Coe Holly J. , Chaloner Dominic T.
Published: February 2017

Stable isotope ratios (δ13C and δ15N) have been used extensively to trace nutrients from Pacific salmon, but salmon transfer more than carbon and nitrogen to stream ecosystems, such as phosphorus, minerals, proteins, and lipids. To examine the importance of these nutrients, metrics other than isotopes need to be considered, particularly when so few studies have made direct links between these nutrients and how they affect riparian organisms. Our study specifically examined δ13C and δ15N of riparian organisms from salmon and non‐salmon streams in Idaho, USA, at different distances from the streams, and examined whether the quality of riparian plants and the body condition of invertebrates varied with access to these nutrients. Overall, quality and condition metrics did not mirror stable isotope patterns. Most notably, all riparian organisms exhibited elevated δ15N in salmon streams, but also with proximity to both stream types suggesting that both salmon and landscape factors may affect δ15N. The amount of nitrogen incorporated from Pacific salmon was low for all organisms (<20%) and did not correlate with measures of quality or condition, probably due to elevated δ15N at salmon streams reflecting historical salmon runs instead of current contributions. Salmon runs in these Idaho streams have been declining, and associated riparian ecosystems have probably seen about a 90% reduction in salmon‐derived nitrogen since the 1950s. In addition, our results support those of other studies that have cautioned that inferences from natural abundance isotope data, particularly in conjunction with mixing models for salmon‐derived nutrient percentage estimates, may be confounded by biogeochemical transformations of nitrogen, physiological processes, and even historical legacies of nitrogen sources. Critically, studies should move beyond simply describing isotopic patterns to focusing on the consequences of salmon‐derived nutrients by quantifying the condition and fitness of organisms putatively using those resources.
Duration of the parasitic phase determines subsequent performance in juvenile freshwater pearl mussels (Margaritifera margaritifera)
Authors: Marwaha Janhavi , Jensen Knut Helge , Jakobsen Per Johan , Geist Juergen
Published: February 2017

Host–parasite systems have been useful in understanding coevolutionary patterns in sympatric species. Based on the exceptional interaction of the long‐lived and highly host‐specific freshwater pearl mussel (FPM; Margaritifera margaritifera) with its much shorter‐lived host fish (Salmo trutta or Salmo salar), we tested the hypotheses that a longer duration of the parasitic phase increases fitness‐related performance of mussels in their subsequent post parasitic phase, and that temperature is the main factor governing the duration of the parasitic phase. We collected juvenile mussels from naturally and artificially infested fish from eight rivers in Norway. Excysted juvenile mussels were maintained separately for each collection day, under similar temperature and food regimes, for up to 56 days. We recorded size at excystment, post excystment growth, and survival as indicators of juvenile fitness in relation to the duration of the parasitic phase. We also recorded the daily average temperatures for the entire excystment period. We observed strong positive relationships between the length of the parasitic phase and the post parasitic growth rate, size at excystment and post parasitic survival. Temperature was identified as an important factor governing excystment, with higher temperatures decreasing the duration of the parasitic phase. Our results indicate that juvenile mussels with the longest parasitic phase have better resources (larger size and better growth rate) to start their benthic developmental phase and therefore to survive their first winter. Consequently, the parasitic phase is crucial in determining subsequent survival. The temperature dependence of this interaction suggests that climate change may affect the sensitive relationship between endangered FPMs and their fish hosts.
Plant interactions as biotic drivers of plasticity in leaf litter traits and decomposability of Quercus petraea
Authors: Henneron Ludovic , Chauvat Matthieu , Archaux Frédéric , Akpa‐Vinceslas Marthe , Bureau Fabrice , Dumas Yann , Mignot Laurent , Ningre François , Perret Sandrine , Richter Claudine , Balandier Philippe , Aubert Michaël
Published: February 2017

The importance of plant litter traits and decomposability for nutrient cycling processes and plant community dynamics through plant–litter–soil feedbacks has been largely emphasized. However, the role of biotic interactions as drivers of intraspecific variability in litter traits remains surprisingly little studied. In this study, we used a large‐scale, multi‐site network of long‐term tree removal experiments manipulating the abundance of a foundation tree species, i.e., Quercus petraea, to assess how plant interactions control intraspecific variation in oak leaf litter traits and decomposability. We studied 19 plots across eight experimental sites covering a large gradient of oak abundance, stand age, and local abiotic context. Oak leaf litter quality strongly declined with tree removal in early forest successional stage. Litter became poorer in nutrients such as N and Mg and richer in secondary metabolites such as lignin and condensed tannins. This in turn slowed its decomposition. Importantly, litter N loss switched from N release to N immobilization. Variance partitioning indicated that oak abundance explained as much variation in oak leaf litter traits as oak age and twice as much as soil inherent fertility. Confirmatory path analysis revealed that the decline of oak leaf litter quality induced by tree removal was most likely driven by a shift in understory plant species composition. Plasticity of oak leaf litter traits to the shortage of nutrient supply related to the development of understory plants competitors with higher nutrient capture and retention ability could potentially explain this response pattern. Our data also give consistent but weaker support that the decline of oak leaf litter quality could be driven by alleviated competition for light among canopy trees and subsequent enhanced crown exposure to light. Overall, our study provides evidence that biotic factors such as plant interactions are major drivers of plasticity in leaf litter traits and decomposability. This finding contributes to the emerging view that phenotypic plasticity is fundamentally related to biotic interactions for sessile organisms, especially for long‐lived and large plant species such as trees. Taking this source of functional diversity into account could help us to better understand plant community dynamics and ecological processes in terrestrial ecosystems.
Long‐term tree inventory data from mountain forest plots in France
Authors: Fuhr Marc , Cordonnier Thomas , Courbaud Benoît , Kunstler Georges , Mermin Eric , Riond Catherine , Tardif Pascal
Published: February 2017

We present repeated tree measurement data from 63 permanent plots in mountain forests in France. Plot elevations range from 800 (lower limit of the montane belt) to 1942 m above sea level (subalpine belt). Forests mainly consist of pure or mixed stands dominated by European beech (Fagus sylvatica), Silver fir (Abies alba), and Norway spruce (Picea abies), in association with various broadleaved species at low elevation and with Arolla pine (Pinus cembra) at high elevation. The plot network includes 23 plots in stands that have not been managed for the last 40 years (at least) and 40 plots in plots managed according to an uneven‐aged system with single‐tree or small‐group selection cutting. Plot sizes range from 0.2 to 1.9 ha. Plots were installed from 1994 to 2004 and remeasured two to five times during the 1994–2015 period. During the first census (installation), living trees more than 7.5 cm in dbh were identified, their diameter at breast height (dbh) was measured and their social status (strata) noted. Trees were spatially located, either with x, y, and z coordinates (40 plots) or within 0.25‐ha square subplots (23 plots). In addition, in a subset of plots (58 plots), tree heights and tree crown dimensions were measured on a subset of trees and dead standing trees and stumps were included in the census. Remeasurements after installation include live tree diameters (including recruited trees), tree status (living, damaged, dead, stump), and for a subset of trees, height. At the time of establishment of the plots, plot densities range from 181 to 1328 stems/ha and plot basal areas range from 13.6 to 81.3 m2/ha.
Synthesis of Water‐Soluble Triazinophanes and Evaluation of Their Molecular Recognition Properties
Authors: Kusano Shuhei , Konishi Sae , Ishikawa Ryuta , Sato Norihiro , Kawata Satoshi , Nagatsugi Fumi , Hayashida Osamu
Published: February 2017

Molecular recognition properties of water‐soluble triazinophane 1a–1c, derivatized through the straightforward SNAr reaction of common intermediate 5, were explored in aqueous media. Fluorescence titration of 1a–1c by using mono cationic aromatic hydrocarbon G1 and G2 as guests revealed that 1 prefers to form a host–guest complex with pyrene derivative G2 rather than anthracene derivative G1. Complex formation between the derivatives of 1 and G2 were in a 1:1 equimolar ratio with binding constants of ≈ 8 × 103 (m–1), regardless of the substitution groups on the triazine rings. In addition, we found that the molecular recognition of 1 was successfully fine‐tuned through post‐modification of the triazine rings. With dicationic anthracene G3 as a guest only 1b formed a host–guest complex (Ka = 5.5 × 103 m–1).
Brain changes associated with cognitive and emotional factors in chronic pain: A systematic review
Authors: Malfliet A. , Coppieters I. , Van Wilgen P. , Kregel J. , De Pauw R. , Dolphens M. , Ickmans K.
Published: February 2017

An emerging technique in chronic pain research is MRI, which has led to the understanding that chronic pain patients display brain structure and function alterations. Many of these altered brain regions and networks are not just involved in pain processing, but also in other sensory and particularly cognitive tasks. Therefore, the next step is to investigate the relation between brain alterations and pain related cognitive and emotional factors. This review aims at providing an overview of the existing literature on this subject. Pubmed, Web of Science and Embase were searched for original research reports. Twenty eight eligible papers were included, with information on the association of brain alterations with pain catastrophizing, fear‐avoidance, anxiety and depressive symptoms. Methodological quality of eligible papers was checked by two independent researchers. Evidence on the direction of these associations is inconclusive. Pain catastrophizing is related to brain areas involved in pain processing, attention to pain, emotion and motor activity, and to reduced top‐down pain inhibition. In contrast to pain catastrophizing, evidence on anxiety and depressive symptoms shows no clear association with brain characteristics. However, all included cognitive or emotional factors showed significant associations with resting state fMRI data, providing that even at rest the brain reserves a certain activity for these pain‐related factors. Brain changes associated with illness perceptions, pain attention, attitudes and beliefs seem to receive less attention in literature.

Significance

This review shows that maladaptive cognitive and emotional factors are associated with several brain regions involved in chronic pain. Targeting these factors in these patients might normalize specific brain alterations.
The effects of epoxiconazole and α-cypermethrin on Daphnia magna growth, reproduction, and offspring size
Authors: Gottardi Michele , Birch Michala Rosa , Dalhoff Kristoffer , Cedergreen Nina
Published: February 2017

Two of the main classes of pesticides commonly used in agriculture are azole fungicides and pyrethroid insecticides. Because azoles have been shown to synergize the effect of pyrethroids, the effect of their mixture is of concern. The aim of the present study was to investigate the effect of sublethal concentrations of epoxiconazole and α-cypermethrin and their mixture on growth, reproduction, and in vivo cytochrome P450 activity of the aquatic crustacean Daphnia magna over 42 d. Continuous exposure to nonlethal concentrations of α-cypermethrin at 20 ng/L negatively affected adult growth and number and size of neonates within the first 14 d of exposure. Exposure to epoxiconazole at 25 μg/L increased protein content of adults within 1 to 3 d after initiating exposure and increased cumulative number of offspring at exposure times >31 d. Epoxiconazole enhanced the negative effect of α-cypermethrin up to 3-fold leading to decreased growth, cytochrome P450 activity, and reproduction of D. magna within the first 14 d of exposure. After 14 d, the synergistic interactions disappeared. The reported effects, although lacking direct negative consequence in the long term, might have cumulative toxicity with other stressors such as food scarcity, predation, and pathogens, posing an additional hazard for the organisms at the beginning of their life cycle. Environ Toxicol Chem 2017;36:2155–2166. © 2017 SETAC
Assessing the Benefits of Andean Crop Diversity on Farmers' Livelihood: Insights from a Development Programme in Bolivia and Peru
Authors: Gotor Elisabetta , Bellon Alejandro , Polar Vivian , Caracciolo Francesco
Published: February 2017

This paper analyses the impact of a development programme designed at promoting the sustainable use of Andean Grain diversity. Results demonstrate that knowledge‐sharing on agronomic practices, on benefits derived from consumption, and improving Andean Grain quality had a positive impact on income generation and farmer livelihoods. These results demonstrate the effectiveness of programmes aimed at improving rural livelihoods through greater knowledge transfer and use of local agrobiodiversity, wherein private benefits may incentivise the public benefits of agrobiodiversity use and conservation. Findings warrant the need to further monitor and evaluate the potential of agrobiodiversity to improve the well‐being of rural communities. © 2017 The Authors Journal of International Development Published by John Wiley & Sons Ltd.
Placentation in watersnakes I: Placental histology and development in North American Nerodia (Colubridae: Natricinae)
Authors: Blackburn Daniel G. , Anderson Kristie E. , Aronson Kera W. , Burket Mary K. , Chin Jessica F. , San‐Francisco Susan K. , Callard Ian P.
Published: February 2017

As part of a broad survey of placental structure, function, and evolution in reptilian sauropsids paraffin‐section histology was used to study microscopic anatomy of the uterus and fetal membranes of three species of North American watersnakes (Nerodia: Colubridae). The pre‐ovulatory uterus is poorly vascularized with inactive shell glands. These shell glands are activated during vitellogenesis but regress during pregnancy. Two placentas develop through apposition of the uterine lining to the chorioallantois and the yolk sac omphalopleure. Fetal and maternal components of the chorioallantoic placenta are progressively vascularized during development. Their epithelia are attenuated, but (contrary to a previous report), epithelia of neither the uterus nor the chorion are eroded. The fetal portion of the yolk sac placenta is an omphalallantois, formed of avascular omphalopleure, isolated yolk mass, and allantois. This placenta is progressively replaced by chorioallantoic placenta during mid‐ to late‐development through depletion of the isolated yolk mass. The chorioallantoic placenta is anatomically specialized for maternal–fetal gas exchange, and its expansion during development reflects the growing needs of the fetus for gas exchange. The yolk sac placenta is morphologically unsuited for gas exchange, but may serve other functions in maternal‐fetal exchange.
Waveport modeling for the DGTD simulation of electromagnetic devices
Authors: Chang Chang‐Pao , Chen Geng , Yan Su , Jin Jianming
Published: February 2017

The issue of waveport modeling for the numerical simulation of electromagnetic devices using the discontinuous Galerkin time‐domain (DGTD) method is investigated. A new implementation of the waveport boundary condition (WPBC) is presented along with a fast evaluation of the required convolution. The performance of the WPBC for the DGTD simulation is then compared with that of the first‐order absorbing boundary condition and the uniaxial perfectly matched layer (UPML). Two numerical examples are presented to demonstrate the waveport modeling for the DGTD simulation of electromagnetic devices based on the WPBC and UPML.
Global solutions and self‐similar solutions for coupled nonlinear Schrödinger equations
Authors: Ye Yaojun
Published: February 2017

In this paper, we prove the existence and uniqueness for the global solutions of Cauchy problem for coupled nonlinear Schrödinger equations and obtain the continuous dependence result on the initial data and the stronger decay estimate of global solutions. In particular, we show the existence and uniqueness of self‐similar solutions. Also, we build some asymptotically self‐similar solutions. Copyright © 2017 John Wiley & Sons, Ltd.
Adaptive Modeling: An Approach for Incorporating Nonlinearity in Regression Analyses
Authors: Knafl George J. , Barakat Lamia P. , Hanlon Alexandra L. , Hardie Thomas , Knafl Kathleen A. , Li Yimei , Deatrick Janet A.
Published: February 2017

Although regression relationships commonly are treated as linear, this often is not the case. An adaptive approach is described for identifying nonlinear relationships based on power transforms of predictor (or independent) variables and for assessing whether or not relationships are distinctly nonlinear. It is also possible to model adaptively both means and variances of continuous outcome (or dependent) variables and to adaptively power transform positive‐valued continuous outcomes, along with their predictors. Example analyses are provided of data from parents in a nursing study on emotional‐health‐related quality of life for childhood brain tumor survivors as a function of the effort to manage the survivors' condition. These analyses demonstrate that relationships, including moderation relationships, can be distinctly nonlinear, that conclusions about means can be affected by accounting for non‐constant variances, and that outcome transformation along with predictor transformation can provide distinct improvements and can resolve skewness problems.© 2017 Wiley Periodicals, Inc.
Viscoelastic and thermally stable PDMS–SiO2 filled epoxy adhesive joint on steel substrate
Authors: Kumar Kaushal , Kumar Sudhir , Kumar Arun , Anant Ramkishor , Kumar Ravindra
Published: February 2017

The epoxy based composite adhesives have been prepared by reinforcing polydimethylsiloxane (PDMS) treated SiO2 nanoparticle with varying content of 2, 4, and 6 wt% in comparison of neat epoxy. PDMS treated SiO2/epoxy composites are fabricated using an ultrasonic mixing process. Dynamic mechanical analysis has been carried out to evaluate the viscoelastic properties on every group of the epoxy composite. The effect of PDMS treated SiO2 nanoparticles reinforcement on viscoelastic properties of epoxy resin have been studied in the terms of storage modulus and tanδ values with respect to temperature. The dispersion conditions of the PDMS–SiO2 nanoparticles in epoxy adhesive have been identified by field emission scanning electron microscopy (FESEM). Thermal gravimetric analysis has been used to identify the thermal stability of each group of PDMS–SiO2/epoxy composite. The effect of PDMS–SiO2/epoxy composite adhesive on the lap joints of mechanically treated mild steel substrate has also been investigated. POLYM. COMPOS., 39:2889–2896, 2018. © 2017 Society of Plastics Engineers
The impact of seasonalities on direct radiative effects and radiative heating rates of absorbing aerosols above clouds
Authors: Chang Ian , Christopher Sundar A.
Published: February 2017

The impact of seasonalities on direct radiative effects (DREs) and radiative heating rates (RHRs) of absorbing aerosols above clouds in the southeast Atlantic is examined using radiative transfer calculations. For an aerosol optical thickness of 0.6 located between 0 and 4 km, a cloud optical thickness of 9.0 and a cloud effective radius of 12.8 µm at 0.55 µm located between 1 and 2 km, the diurnally averaged RHR at noon in the aerosol layer increases from ∼6.6 K day−1 in June to ∼8.9 K day−1 in October. In June (October), the RHR in the cloud layer at noon is 1.3 (1.7) K day−1 higher than the case of pristine clouds. However, an elevated aerosol layer (2–4 km) reduces the RHR by ∼0.2 K day−1 in the cloud layer relative to a pristine cloudy case. The DRE at top‐of‐atmosphere (TOA) reaches its peak when the solar zenith angle (SZA) is 54°. The DRE increases (decreases) with SZA for SZA less (greater) than 54°. The primary peak DRE is ∼29.5 W m−2 at 5.0°S 5.0°E, occurring at 0800 UTC. At noon, the DRE at TOA is ∼18.9, ∼20.5 and ∼23.1 W m−2 at 5.0°S, 15.0°S and 25.0°S along 5.0°E, respectively. This study provides data and theoretical understanding to help positioning science flights that target measurements of above‐cloud aerosol radiative effects.
Selecting the Best Wild Card Entries in a Covering Array
Authors: Kim Youngil , Jang Dae‐Heung , Anderson‐Cook Christine M.
Published: February 2017

For some covering arrays, there are some wild card positions in the array where there is flexibility about what factor levels can be chosen with no impact on the basic properties of covering array, because all of the required pairs have been covered. The choice of how to fill these wild card positions can influence other properties, such as the degrees of orthogonality or three‐way coverage of the array. In this paper, some criteria are proposed for identifying the best choices for the wild card positions to create covering arrays with highly desirable properties. Accompanying graphical summaries are also described to highlight differing performance for several examples. Copyright © 2017 John Wiley & Sons, Ltd.
Treatment period and medical care costs to achieve the first live birth by assisted reproductive technology are lower in the single embryo transfer period than in the double embryo transfer period: a retrospective analysis of women younger than 40 years of age
Authors: Kawahara Shunsuke , Ueda Akane , Nakahori Takashi , Honda Tetsuro
Published: February 2017

Aim

It was examined whether the single embryo transfer policy makes the treatment period longer for couples to achieve their first live birth by assisted reproductive technology.

Methods

This study retrospectively analyzed women who started assisted reproductive technology at younger than 40 years of age in the authors’ organization. The treatment periods for couples to achieve the first live birth by assisted reproductive technology, between the women who started assisted reproductive technology from 2004 to 2009 (the double embryo transfer period group, n=250), in which the double embryo transfer was predominant, and the women who started assisted reproductive technology from 2010 to 2015 (the single embryo transfer period group, n=298), in which the single embryo transfer was predominant, were compared.

Results

The age at the start of assisted reproductive technology, pregnancy rate per embryo transfer, and rate of women who achieved a live birth by assisted reproductive technology per number of women who tried assisted reproductive technology were all significantly higher in the single embryo transfer period group. Among the women who achieved a live birth by assisted reproductive technology, the incidence of multiple births and severe ovarian hyperstimulation syndrome, the treatment period, and medical care costs needed to achieve the first live birth were all significantly lower in the single embryo transfer period group.

Conclusion

In the single embryo transfer period group, those women who were younger than 40 years of age achieved their first live birth by assisted reproductive technology more safely, quickly, and reasonably.
Patient subgroup identification for clinical drug development
Authors: Huang Xin , Sun Yan , Trow Paul , Chatterjee Saptarshi , Chakravartty Arunava , Tian Lu , Devanarayan Viswanath
Published: February 2017

Causal mechanism of relationship between the clinical outcome (efficacy or safety endpoints) and putative biomarkers, clinical baseline, and related predictors is usually unknown and must be deduced empirically from experimental data. Such relationships enable the development of tailored therapeutics and implementation of a precision medicine strategy in clinical trials to help stratify patients in terms of disease progression, clinical response, treatment differentiation, and so on. These relationships often require complex modeling to develop the prognostic and predictive signatures. For the purpose of easier interpretation and implementation in clinical practice, defining a multivariate biomarker signature in terms of thresholds (cutoffs/cut points) on individual biomarkers is preferable. In this paper, we propose some methods for developing such signatures in the context of continuous, binary and time‐to‐event endpoints. Results from simulations and case study illustration are also provided. Copyright © 2017 John Wiley & Sons, Ltd.
The Reinvention of Magna Carta 1216–1616
Authors: Baker John
Published: February 2017

Magna Carta was largely ineffective for practical purposes between the fourteenth century and the sixteenth, late-medieval law lectures giving no hint of its later importance. A treatise by William Fleetwood (c.1558) was still in the traditional mould, but the lectures of the 'Puritan' barrister and MP Robert Snagge in 1581, and the speeches and tracts of his colleagues, advocated new uses for it. After centuries of oblivion, in 1587 there were eight reported cases in which chapter 29 was cited. Sir Edward Coke made extensive claims for chapter 29, linking it with habeas corpus, and then as a judge (1606–16) he deployed it with effect in challenging encroachments on the common law and the liberty of the subject. This book ends in 1616 with the lectures of Francis Ashley, summarising the effects of the new learning, and then Coke's dismissal for pushing his case too hard. A challenging new account.
Conservative Chick? Conservative Culture Warriors at War
Authors: SAUNDERS NATHAN
Published: February 2017

The American New Right that grew to prominence during the second half of the twentieth century consists of three major ideological strands – traditionalism, libertarianism, and anticommunism. The New Christian Right (NCR) that rose to prominence in the 1970s fell within the traditionalist camp. At the same time, not all theological conservatives or social traditionalists joined the NCR. The work of comic book artist Jack Chick demonstrates the phenomenon of opposition to the NCR among some theological and social conservatives. Beginning in the early 1960s, Chick published tracts and comic books that espoused extreme social conservatism while at the same time opposing government enforcement of social norms. He frequently criticized politically active or well-connected preachers such as Jerry Falwell and Billy Graham and opposed prayer in schools. Chick, along with many other fundamentalists, opposed the NCR because it involved cooperation with Roman Catholics. For Chick, doctrinal purity is more important than having a “Christian” nation. This essay concludes by noting how, as evangelicals lose ground in key battles of the culture wars, there are signs that Chick's antipolitics is gaining ground among conservative Protestants.
Automatic Biological Cell Counting Using a Modified Gradient Hough Transform
Authors: Denimal Emmanuel , Marin Ambroise , Guyot Stéphane , Journaux Ludovic , Molin Paul
Published: February 2017

We present a computational method for pseudo-circular object detection and quantitative characterization in digital images, using the gradient accumulation matrix as a basic tool. This Gradient Accumulation Transform (GAT) was first introduced in 1992 by Kierkegaard and recently used by Kaytanli & Valentine. In the present article, we modify the approach by using the phase coding studied by Cicconet, and by adding a “local contributor list” (LCL) as well as a “used contributor matrix” (UCM), which allow for accurate peak detection and exploitation. These changes help make the GAT algorithm a robust and precise method to automatically detect pseudo-circular objects in a microscopic image. We then present an application of the method to cell counting in microbiological images.
A cocktail of three virulent bacteriophages prevents Vibrio cholerae infection in animal models
Authors: Yen Minmin , Cairns Lynne S. , Camilli Andrew
Published: February 2017

Effective prevention strategies will be essential in reducing disease burden due to bacterial infections. Here we harness the specificity and rapid-acting properties of bacteriophages as a potential prophylaxis therapy for cholera, a severely dehydrating disease caused by Vibrio cholerae. To this end, we test a cocktail of three virulent phages in two animal models of cholera pathogenesis (infant mouse and rabbit models). Oral administration of the phages up to 24 h before V. cholerae challenge reduces colonization of the intestinal tract and prevents cholera-like diarrhea. None of the surviving V. cholerae colonies are resistant to all three phages. Genome sequencing and variant analysis of the surviving colonies indicate that resistance to the phages is largely conferred by mutations in genes required for the production of the phage receptors. For acute infections, such as cholera, phage prophylaxis could provide a strategy to limit the impact of bacterial disease on human health.
Complexion-mediated martensitic phase transformation in Titanium
Authors: Zhang J. , Tasan C. C. , Lai M. J. , Dippel A. -C. , Raabe D.
Published: February 2017

The most efficient way to tune microstructures and mechanical properties of metallic alloys lies in designing and using athermal phase transformations. Examples are shape memory alloys and high strength steels, which together stand for 1,500 million tons annual production. In these materials, martensite formation and mechanical twinning are tuned via composition adjustment for realizing complex microstructures and beneficial mechanical properties. Here we report a new phase transformation that has the potential to widen the application window of Ti alloys, the most important structural material in aerospace design, by nanostructuring them via complexion-mediated transformation. This is a reversible martensitic transformation mechanism that leads to a final nanolaminate structure ofα″ (orthorhombic) martensite bounded with planar complexions of athermalω(a–ω, hexagonal). Both phases are crystallographically related to the parentβ(BCC) matrix. As expected from a planar complexion, thea–ωis stable only at the hetero-interface.
Self-surface charge exfoliation and electrostatically coordinated 2D hetero-layered hybrids
Authors: Yang Min-Quan , Xu Yi-Jun , Lu Wanheng , Zeng Kaiyang , Zhu Hai , Xu Qing-Hua , Ho Ghim Wei
Published: February 2017

At present, the technological groundwork of atomically thin two-dimensional (2D) hetero-layered structures realized by successive thin film epitaxial growth is in principle constrained by lattice matching prerequisite as well as low yield and expensive production. Here, we artificially coordinate ultrathin 2D hetero-layered metal chalcogenides via a highly scalable self-surface charge exfoliation and electrostatic coupling approach. Specifically, bulk metal chalcogenides are spontaneously exfoliated into ultrathin layers in a surfactant/intercalator-free medium, followed by unconstrained electrostatic coupling with a dissimilar transition metal dichalcogenide, MoSe2, into scalable hetero-layered hybrids. Accordingly, surface and interfacial-dominated photocatalysis reactivity is used as an ideal testbed to verify the reliability of diverse 2D ultrathin hetero-layered materials that reveal high visible-light photoreactivity, efficient charge transfer and intimate contact interface for stable cycling and storage purposes. Such a synthetic approach renders independent thickness and composition control anticipated to advance the development of ‘design-and-build’ 2D layered heterojunctions for large-scale exploration and applications.
Processable high internal phase Pickering emulsions using depletion attraction
Authors: Kim KyuHan , Kim Subeen , Ryu Jiheun , Jeon Jiyoon , Jang Se Gyu , Kim Hyunjun , Gweon Dae-Gab , Im Won Bin , Han Yosep , Kim Hyunjung , Choi Siyoung Q.
Published: February 2017

High internal phase emulsions have been widely used as templates for various porous materials, but special strategies are required to form, in particular, particle-covered ones that have been more difficult to obtain. Here, we report a versatile strategy to produce a stable high internal phase Pickering emulsion by exploiting a depletion interaction between an emulsion droplet and a particle using water-soluble polymers as a depletant. This attractive interaction facilitating the adsorption of particles onto the droplet interface and simultaneously suppressing desorption once adsorbed. This technique can be universally applied to nearly any kind of particle to stabilize an interface with the help of various non- or weakly adsorbing polymers as a depletant, which can be solidified to provide porous materials for many applications.
Anisotropically organized three-dimensional culture platform for reconstruction of a hippocampal neural network
Authors: Kim So Hyun , Im Sun-Kyoung , Oh Soo-Jin , Jeong Sohyeon , Yoon Eui-Sung , Lee C. Justin , Choi Nakwon , Hur Eun-Mi
Published: February 2017

In native tissues, cellular and acellular components are anisotropically organized and often aligned in specific directions, providing structural and mechanical properties for actuating biological functions. Thus, engineering alignment not only allows for emulation of native tissue structures but might also enable implementation of specific functionalities. However, achieving desired alignment is challenging, especially in three-dimensional constructs. By exploiting the elastomeric property of polydimethylsiloxane and fibrillogenesis kinetics of collagen, here we introduce a simple yet effective method to assemble and align fibrous structures in a multi-modular three-dimensional conglomerate. Applying this method, we have reconstructed the CA3–CA1 hippocampal neural circuit three-dimensionally in a monolithic gel, in which CA3 neurons extend parallel axons to and synapse with CA1 neurons. Furthermore, we show that alignment of the fibrous scaffold facilitates the establishment of functional connectivity. This method can be applied for reconstructing other neural circuits or tissue units where anisotropic organization in a multi-modular structure is desired.
miR-34a inhibits pancreatic cancer progression through Snail1-mediated epithelial–mesenchymal transition and the Notch signaling pathway
Authors: Tang Yan , Tang Yong , Cheng Ying-sheng
Published: February 2017

Epithelial–mesenchymal transition (EMT) and Notch signaling are important for the growth and invasion of pancreatic cancer, which is a leading cause of cancer-related deaths worldwide. miR-34a has been shown to play pivotal roles in the progression of several types of cancer. However, little is known about the regulatory mechanisms of miR-34a in pancreatic cancer processes. The aim of this study was to determine whether miR-34a has negative effects on pancreatic cancer and whether these effects are related to EMT and Notch signaling. In vitro, we demonstrated that miR-34a inhibited, while miR-34a inhibitors enhanced, migration and invasion of pancreatic cancer cell lines (PANC-1 and SW-1990).These effects were reversed by Snail1 overexpression or Snail1 shRNA. Furthermore, the anti-apoptotic effects of the miR-34a inhibitors in pancreatic cancer cells were abrogated by Notch1 shRNA. Luciferase reporter assays revealed that the Snail1 and Notch1 genes were direct targets of miR-34a. In vivo, we also demonstrated that miR-34a inhibited pancreatic cancer growth by decreasing Snail1 and Notch1 expression. Therefore, our results indicate that miR-34a inhibits pancreatic cancer progression by post-transcriptionally regulating Snail1 and Notch1 expression.
Caffeic Acid Cyclohexylamide Rescues Lethal Inflammation in Septic Mice through Inhibition of IκB Kinase in Innate Immune Process
Authors: Choi Jun Hyeon , Park Sun Hong , Jung Jae-Kyung , Cho Won-Jea , Ahn Byeongwoo , Yun Cheong-Yong , Choi Yong Pyo , Yeo Jong Hun , Lee Heesoon , Hong Jin Tae , Han Sang-Bae , Kim Youngsoo
Published: February 2017

Targeting myeloid differentiation protein 2 (MD-2) or Toll-like receptor 4 (TLR4) with small molecule inhibitor rescues the systemic inflammatory response syndrome (SIRS) in sepsis due to infection with Gram-negative bacteria but not other microbes. Herein, we provided IκB kinase β (IKKβ) in innate immune process as a molecular target of caffeic acid cyclohexylamide (CGA-JK3) in the treatment of polymicrobial TLR agonists-induced lethal inflammation. CGA-JK3 ameliorated E. coli lipopolysaccharide (LPS, MD-2/TLR4 agonist)-induced endotoxic shock, cecal ligation and puncture (CLP)-challenged septic shock or LPS plus D-galactosamine (GalN)-induced acute liver failure (ALF) in C57BL/6J mice. As a molecular basis, CGA-JK3 inhibited IKKβ-catalyzed kinase activity in a competitive mechanism with respect to ATP, displaced fluorescent ATP probe from the complex with IKKβ, and docked at the ATP-binding active site on the crystal structure of human IKKβ. Furthermore, CGA-JK3 inhibited IKKβ-catalyzed IκB phosphorylation, which is an axis leading to IκB degradation in the activating pathway of nuclear factor-κB (NF-κB), in macrophages stimulated with TLR (1/2, 2/6, 4, 5, 7, 9) agonists from Gram-positive/negative bacteria and viruses. CGA-JK3 consequently interrupted IKKβ-inducible NF-κB activation and NF-κB-regulated expression of TNF-α, IL-1α or HMGB-1 gene, thereby improving TLRs-associated redundant inflammatory responses in endotoxemia, polymicrobial sepsis and ALF.
Computational imaging reveals shape differences between normal and malignant prostates on MRI
Authors: Rusu Mirabela , Purysko Andrei S. , Verma Sadhna , Kiechle Jonathan , Gollamudi Jay , Ghose Soumya , Herrmann Karin , Gulani Vikas , Paspulati Raj , Ponsky Lee , Böhm Maret , Haynes Anne-Maree , Moses Daniel , Shnier Ron , Delprado Warick , Thompson James , Stricker Phillip , Madabhushi Anant
Published: February 2017

We seek to characterize differences in the shape of the prostate and the central gland (combined central and transitional zones) between men with biopsy confirmed prostate cancer and men who were identified as not having prostate cancer either on account of a negative biopsy or had pelvic imaging done for a non-prostate malignancy. T2w MRI from 70 men were acquired at three institutions. The cancer positive group (PCa+) comprised 35 biopsy positive (Bx+) subjects from three institutions (Gleason scores: 6–9, Stage: T1–T3). The negative group (PCa−) combined 24 biopsy negative (Bx−) from two institutions and 11 subjects diagnosed with rectal cancer but with no clinical or MRI indications of prostate cancer (Cl−). The boundaries of the prostate and central gland were delineated on T2w MRI by two expert raters and were used to construct statistical shape atlases for the PCa+, Bx− and Cl− prostates. An atlas comparison was performed via per-voxel statistical tests to localize shape differences (significance assessed at p < 0.05). The atlas comparison revealed central gland hypertrophy in the Bx− subpopulation, resulting in significant volume and posterior side shape differences relative to PCa+ group. Significant differences in the corresponding prostate shapes were noted at the apex when comparing the Cl− and PCa+ prostates.
ZP3 is Required for Germinal Vesicle Breakdown in Mouse Oocyte Meiosis
Authors: Gao Lei-Lei , Zhou Chun-Xiang , Zhang Xiao-Lan , Liu Peng , Jin Zhen , Zhu Gang-Yi , Ma Yang , Li Jing , Yang Zhi-Xia , Zhang Dong
Published: February 2017

ZP3 is a principal component of the zona pellucida (ZP) of mammalian oocytes and is essential for normal fertility, and knockout of ZP3 causes complete infertility. ZP3 promotes fertilization by recognizing sperm binding and activating the acrosome reaction; however, additional cellular roles for ZP3 in mammalian oocytes have not been yet reported. In the current study, we found that ZP3 was strongly expressed in the nucleus during prophase and gradually translocated to the ZP. Knockdown of ZP3 by a specific siRNA dramatically inhibited germinal vesicle breakdown (GVBD) (marking the beginning of meiosis), significantly reducing the percentage of MII oocytes. To investigate the ZP3-mediated mechanisms governing GVBD, we identified potential ZP3-interacting proteins by immunoprecipitation and mass spectrometry. We identified Protein tyrosine phosphatase, receptor type K (Ptprk), Aryl hydrocarbon receptor-interacting protein-like 1 (Aipl1), and Diaphanous related formin 2 (Diaph2) as potential candidates, and established a working model to explain how ZP3 affects GVBD. Finally, we provided preliminary evidence that ZP3 regulates Akt phosphorylation, lamin binding to the nuclear membrane via Aipl1, and organization of the actin cytoskeleton via Diaph2. These findings contribute to our understanding of a novel role played by ZP3 in GVBD.
Whole Genome Sequencing Identifies Novel Compound Heterozygous Lysosomal Trafficking Regulator Gene Mutations Associated with Autosomal Recessive Chediak-Higashi Syndrome
Authors: Jin Yaqiong , Zhang Li , Wang Senfen , Chen Feng , Gu Yang , Hong Enyu , Yu Yongbo , Ni Xin , Guo Yongli , Shi Tieliu , Xu Zigang
Published: February 2017

Chediak–Higashi syndrome (CHS) is a rare autosomal recessive disease characterized by varying degrees of oculocutaneous albinism, recurrent infections, and a mild bleeding tendency, with late neurologic dysfunction. This syndrome is molecularly characterized by pathognomonic mutations in the LYST (lysosomal trafficking regulator). Using whole genome sequencing (WGS) we attempted to identify novel mutations of CHS based on a family of CHS with atypical symptoms. The two patients demonstrated a phenotypic constellation including partial oculocutaneous albinism, frequency upper respiratory infection or a marginal intelligence, without bleeding tendency and severe immunodeficiency. WGS revealed two compound LYST mutations including a maternally inherited chr1:235969126G > A (rs80338652) and a novel paternally inherited chr1: 235915327A > AT, associated with autosomal recessive CHS. These two variants fall in the coding regions of LYST, resulting in premature truncation of LYST due to R1104X/N2535KfsX2 induced incomplete translation. Notably, the heterozygous carriers (i.e. parents) were unaffected. Our finding also reveals decreased plasma serotonin levels in patients with CHS compared with unaffected individuals for the first time. The present study contributes to improved understanding of the causes of this disease and provides new ideas for possible treatments.
Serum prealbumin and its changes over time are associated with mortality in acute kidney injury
Authors: Wang Wenji , Pan Yu , Tang Xiao , Hao Guihua , Xie Yingxin , Ma Shuai , Luo Jianfeng , Guo Daqiao , Ding Feng
Published: February 2017

Serum prealbumin is a clinically relevant indicator of nutritional status and inflammation in patients with acute kidney injury (AKI). This study aimed to determine whether serum prealbumin and its longitudinal changes over a week could improve the prediction of 90-day mortality in AKI patients. This prospective cohort study included 340 adults with AKI between 2014 and 2015. There were 94 (27.6%) patient deaths within 90 days. Serum prealbumin level <10 mg/dL at the time of AKI diagnosis was associated with a 155% increased death risk ratio (adjusted hazard ratio [HR], 2.55; 95% confidence interval [CI], 1.18 to 5.49; P = 0.02). Serum prealbumin fall >4 mg/dL was also associated with 90-day mortality in adjusted Cox regression models (HR, 1.79; 95% CI, 1.06 to 3.03; P = 0.03). Compared to serum albumin, mortality-predictability of serum prealbumin (P = 0.01) and its changes (P = 0.01) were both increased. Adding prealbumin and its changes on the conventional covariates improved the prediction of progression to 90-day mortality (NRI 0.29, P = 0.04; aIDI 0.08; P = 0.03). In conclusion, serum prealbumin, and its changes were independent predictors of worse prognosis in AKI, and could be potential surrogates to better predict 90-day mortality.
Identification of genomic regions for grain yield and yield stability and their epistatic interactions
Authors: Sehgal Deepmala , Autrique Enrique , Singh Ravi , Ellis Marc , Singh Sukhwinder , Dreisigacker Susanne
Published: February 2017

The task of identifying genomic regions conferring yield stability is challenging in any crop and requires large experimental data sets in conjunction with complex analytical approaches. We report findings of a first attempt to identify genomic regions with stable expression and their individual epistatic interactions for grain yield and yield stability in a large elite panel of wheat under multiple environments via a genome wide association mapping (GWAM) approach. Seven hundred and twenty lines were genotyped using genotyping-by-sequencing technology and phenotyped for grain yield and phenological traits. High gene diversity (0.250) and a moderate genetic structure (five groups) in the panel provided an excellent base for GWAM. The mixed linear model and multi-locus mixed model analyses identified key genomic regions on chromosomes 2B, 3A, 4A, 5B, 7A and 7B. Further, significant epistatic interactions were observed among loci with and without main effects that contributed to additional variation of up to 10%. Simple stepwise regression provided the most significant main effect and epistatic markers resulting in up to 20% variation for yield stability and up to 17% gain in yield with the best allelic combination.