bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracing atmospheric transport of soil microorganisms and higher plant waxes in the East Asian outflow to the North Pacific Rim by using hydroxy fatty acids: Year‐round observations at Gosan, Jeju Island
Authors: Tyagi Poonam , Kawamura Kimitaka , Kariya Tadashi , Bikkina Srinivas , Fu Pingqing , Lee Meehye
Published: March 2017

Atmospheric transport of soil microorganisms and higher plant waxes in East Asia significantly influences the aerosol composition over the North Pacific. This study investigates the year‐round atmospheric abundances of hydroxy fatty acids (FAs), tracers of soil microorganisms (β‐isomers), and plant waxes (α‐ and ω‐isomers), in total suspended particles collected at Gosan, Jeju Island, during April 2001 to March 2002. These hydroxy FAs showed a pronounced seasonality, higher concentrations in winter/spring and lower concentrations in summer/autumn, which are consistent with other tracers of soil microbes (trehalose), resuspended dust (nss‐Ca2+), and stable carbon isotopic composition (δ13C) of total carbon. The molecular distributions of β‐hydroxy FAs (predominance of C12 and C16 in winter/spring and summer/autumn, respectively) are consistent with those from a remote island (Chichijima) in the North Pacific and Asian dust standards (CJ‐1 and CJ‐2). This observation together with back trajectories over Gosan reveal that desert sources in China during winter and arid regions of Mongolia and Russian Far East during spring are the major contributors of soil microbes over the North Pacific. Predominance of ω‐isomers (83%) over β‐hydroxy FAs (16%) revealed a major contribution of terrestrial lipids from higher plant waxes over soil microbes in the East Asian outflow.
Insights on the formation of longitudinal surface structures on ice sheets from analysis of their spacing, spatial distribution, and relationship to ice thickness and flow
Authors: Ely J. C. , Clark C. D. , Ng F. S. L. , Spagnolo M.
Published: March 2017

Longitudinal surface structures (LSSs) are prevalent upon the ice streams, ice shelves, and outlet glaciers of ice sheets. These features inform our understanding of past and present ice sheet behavior. However, consensus regarding their genesis has not been reached. Here we analyze 42,311 LSS segments mapped across Antarctica together with geophysical data to determine their morphological and glaciological properties. Most LSSs are spaced 450 to 1500 m apart, a distance positively correlated with the width of the ice flow unit on which they occur. The start points (upstream end locations) of LSSs have diverse ice thicknesses and velocities. The majority of LSSs occur where ice flow is converging or broadly parallel, and they are prominent at ice confluences. Some occur at slow‐flowing ice stream onsets. Occasionally, LSSs relate to sudden variations in basal shear stress due to basal perturbations. From these observations, we argue that LSSs are the consequence of increased strain which occurs during the lateral compression and longitudinal extension of ice: (i) converging/flowing into a channel (this scenario characterizes most LSSs), (ii) at the onset of ice streaming, (iii) at flow unit confluence, and (iv) as ice flows over and around a basal perturbation.
Pore network extraction from pore space images of various porous media systems
Authors: Yi Zhixing , Lin Mian , Jiang Wenbin , Zhang Zhaobin , Li Haishan , Gao Jian
Published: March 2017

Pore network extraction, which is defined as the transformation from irregular pore space to a simplified network in the form of pores connected by throats, is significant to microstructure analysis and network modeling. A physically realistic pore network is not only a representation of the pore space in the sense of topology and morphology, but also a good tool for predicting transport properties accurately. We present a method to extract pore network by employing the centrally located medial axis to guide the construction of maximal‐balls‐like skeleton where the pores and throats are defined and parameterized. To validate our method, various rock samples including sand pack, sandstones, and carbonates were used to extract pore networks. The pore structures were compared quantitatively with the structures extracted by medial axis method or maximal ball method. The predicted absolute permeability and formation factor were verified against the theoretical solutions obtained by lattice Boltzmann method and finite volume method, respectively. The two‐phase flow was simulated through the networks extracted from homogeneous sandstones, and the generated relative permeability curves were compared with the data obtained from experimental method and other numerical models. The results show that the accuracy of our network is higher than that of other networks for predicting transport properties, so the presented method is more reliable for extracting physically realistic pore network.
S
hannon Entropy Measures
Authors: Asadi Majid , Ebrahimi Nader , Soofi Ehsan S.
Published: March 2017

This article gives an overview of the basic properties of the Shannon entropy and the associated measures, namely the Kullback–Leibler information divergence between two distributions, the mutual information between two random variables, and the Jensen–Shannon divergence of the mixture distribution. We give outlines of the classic and some recent maximum entropy approaches for developing probability models based on moment information and the dynamic maximum entropy subject to the mean residual and hazard inequality constraints. We also introduce the notion of expected residual life entropy.
Fractional order model reference adaptive control for anesthesia
Authors: Navarro‐Guerrero Gerardo , Tang Yu
Published: March 2017

The design of a fractional order model reference adaptive control for anesthesia based on a fractional order model is proposed in the paper. This model gets around many difficulties in controller designs based on the pharmacokinetic/pharmacodynamic model, commonly used for anesthesia for theses purposes, and allows to design a simple adaptive controller with stability and positivity of the system ensured via Lyapunov analysis. Also, the convergence of the tracking error to zero is established by applying an extension of the Barbalat lemma, proven in the paper. Simulations illustrate the effectiveness and robustness of the proposed control.
Nanocrystalline Intermetallic Tungsten Carbide: Nanoscaled Solidoid Synthesis, Nonfaradaic Pseudocapacitive Property, and Electrode Material Application
Authors: Zhang Wei‐Bin , Ma Xue‐Jing , Kong Ling‐Bin
Published: March 2017

A capacitive electrode material of nanocrystalline intermetallic W2C has been synthesized and studied for electrochemical capacitors. A specific capacitance of 158.2 F g−1 is found in 1 mol dm−3 H2SO4 (aq) at a specific current density of 1 A g−1, and 99.5% of capacitance remains after 5000 cycles of charging–discharging. 88.9% of the initial value remains at a current density of 10 A g−1. W2C exhibits a high electrochemical capacitance that may be attributed to the electrical conductivity, which can promote the electrochemical performance more observably and ensure a long life cycle and fast electrical charge transfer rate. Based on the specific surface areas and specific capacitances, the sub‐surface space nonfaradaic pseudocapacitive mechanism is proposed. In addition, the assembled asymmetrical electrochemical capacitor of W2C//activated carbon shows a high energy density and accompanying power density of 19.2 and 8976.6 W kg−1, facilitating high duty applications.
Early Pleistocene hominin deciduous teeth from the Homo antecessor Gran Dolina‐TD6 bearing level (Sierra de Atapuerca, Spain)
Authors: Bermúdez de Castro José María , Martinón‐Torres María , Martín‐Francés Laura , Martínez de Pinillos Marina , Modesto‐Mata Mario , García‐Campos Cecilia , Wu Xiujie , Xing Song , Liu Wu
Published: March 2017

Objectives

During the last 13 years, the late Early Pleistocene Gran Dolina‐TD6‐2 level (Sierra de Atapuerca, northern Spain) has yielded an additional sample of 26 dental specimens attributed to Homo antecessor. In this report, we present a descriptive and comparative study of the six deciduous teeth.

Methods

We provide external and internal morphological descriptions following classical terminology, as well as the mesiodistal and buccolingual measurements of the teeth. The internal morphology was described by means of micro‐CT technique.

Results

The TD6 deciduous teeth preserve primitive features regarding the Homo clade, such as the presence of styles in lower and upper canines and developed anterior and posterior foveae in the dm2. However, other features related to the complexity of the crown morphology (e.g., cingulum) are not present in this sample. Furthermore, the great reduction of the talonid of the dm1s is also noteworthy. Despite the limited comparative evidence, the presence of a remarkably well‐developed tuberculum molare in the dm1 and dm1s from TD6 can be also considered a derived feature in the genus Homo. The TD6 hominins exhibit dental dimensions similar to those of other Pleistocene hominins. The dm1s are buccolingually elongated and the buccolingual diameter of ATD6‐93 is the largest recorded so far in the Homo fossil record.

Conclusions

This study expands the list of plesiomorphic features of H. antecessor, and provides some information on the evolutionary status of this species. However, the identification of some advanced traits evinces a step towards the derived morphology of European Pleistocene teeth. The study of the deciduous dentition confirms the mosaic pattern of H. antecessor morphology revealed in previous studies of this hominin sample.
Synthesis and Identification of Key Biosynthetic Intermediates for the Formation of the Tricyclic Skeleton of Saxitoxin
Authors: Tsuchiya Shigeki , Cho Yuko , Yoshioka Renpei , Konoki Keiichi , Nagasawa Kazuo , Oshima Yasukatsu , Yotsu‐Yamashita Mari
Published: March 2017

Saxitoxin (STX) and its analogues are potent voltage‐gated sodium channel blockers biosynthesized by freshwater cyanobacteria and marine dinoflagellates. We previously identified genetically predicted biosynthetic intermediates of STX at early stages, Int‐A′ and Int‐C′2, in these microorganisms. However, the mechanism to form the tricyclic skeleton of STX was unknown. To solve this problem, we screened for unidentified intermediates by analyzing the results from previous incorporation experiments with 15N‐labeled Int‐C′2. The presence of monohydroxy‐Int‐C′2 and possibly Int‐E′ was suggested, and 11‐hydroxy‐Int‐C′2 and Int‐E′ were identified from synthesized standards and LC‐MS. Furthermore, we observed that the hydroxy group at C11 of 11‐hydroxy‐Int‐C′2 was slowly replaced by CD3O in CD3OD. Based on this characteristic reactivity, we propose a possible mechanism to form the tricyclic skeleton of STX via a bicyclic intermediate from 11‐hydroxy‐Int‐C′2.
Gold‐Catalyzed Oxidative [2+2+1] Annulations of Aryldiazo Nitriles with Imines To Yield Polyarylated Imidazolium Salts
Authors: Pawar Samir Kundlik , Yang Ming‐Chung , Su Ming‐Der , Liu Rai‐Shung
Published: March 2017

Gold‐catalyzed oxidative [2+2+1] annulations between two imines and one α‐cyano arylgold carbene afforded polyarylated imidazolium salts and molecular hydrogen efficiently. Control experiments suggest that the gold catalyst alone facilitates the main annulation, whereas Ag+ avoids the formation of inactive LAuCN. DFT calculations suggest that the success of this annulation relies on a 6 π‐electrocyclization of cyano‐free intermediates with cis‐configured imines as initial reagents.
Synthesis of Responsive Two‐Dimensional Polymers via Self‐Assembled DNA Networks
Authors: Yu Hao , Alexander Duncan T. L. , Aschauer Ulrich , Häner Robert
Published: March 2017

Despite a growing interest in two‐dimensional polymers, their rational synthesis remains a challenge. The solution‐phase synthesis of a two‐dimensional polymer is reported. A DNA‐based monomer self‐assembles into a supramolecular network, which is further converted into the covalently linked two‐dimensional polymer by anthracene dimerization. The polymers appear as uniform monolayers, as shown by AFM and TEM imaging. Furthermore, they exhibit a pronounced solvent responsivity. The results demonstrate the value of DNA‐controlled self‐assembly for the formation of two‐dimensional polymers in solution.
Organocatalytic Redox Deracemization of Cyclic Benzylic Ethers Enabled by An Acetal Pool Strategy
Authors: Wan Miao , Sun Shutao , Li Yangshan , Liu Lei
Published: March 2017

The first redox deracemization of a series of cyclic benzylic ethers, including 6H‐benzo[c]chromenes, isochromans, and 1H‐isochromenes, is described. An “acetal pool” strategy was adopted to harmonize the complete oxidation of secondary ethers with imidodiphosphoric acid catalyzed asymmetric transfer hydrogenation. The synthetic utility of the process was demonstrated by the effective deracemization of biologically active molecules of interest that are difficult to prepare by other methods.
Early Childhood Development of Boys with Genital Anomalies
Authors: Schneuer Francisco J. , Bentley Jason P. , Holland Andrew J.A. , Lain Samantha J. , Jamieson Sarra E. , Badawi Nadia , Nassar Natasha
Published: March 2017

Background

Male genital anomalies often require surgery in early life to address functional and cosmetic consequences. However, there has been little assessment of developmental outcomes of affected boys.

Methods

We conducted a population‐based cohort study of all boys born in New South Wales, Australia, and undergoing school‐entry developmental assessment in 2009 or 2012. Health and developmental information was obtained by means of record‐linkage of birth, hospital and Australian Early Development Census data. Boys with hypospadias or undescended testis (UDT) were compared with those without. Developmental outcomes were assessed in five domains (physical health, emotional maturity, communication, cognitive skills, and social competence), and boys were categorized as vulnerable (<10th centile of national scores), developmentally high risk (DHR; vulnerable in 2+ domains), and special needs.

Results

We included 420 boys with hypospadias, 873 with UDT, and 77,176 unaffected boys. There was no difference in the proportion of boys developmentally vulnerable in any domain or DHR between boys with hypospadias (DHR: n = 49; 13.1%; p = 0.9), UDT (n = 116; 15.2%; p = 0.06), and unaffected boys (n = 9278; 12.9%). Compared with unaffected boys (n = 4826; 6.3%), boys with hypospadias (n = 43; 10.2%; p < 0.001) or UDT (n = 105; 12.0%; p < 0.001) were more likely to have special needs. Stratified analyses revealed that only boys with UDT and coexisting anomalies had increased risk of being DHR (odds ratio: 2.65; 95% confidence interval, 1.61–4.36) or special needs (odds ratio: 2.91; 95% confidence interval, 2.00–4.22).

Conclusion

We found no increased risk of poor development among boys with hypospadias or UDT. However, boys with UDT and coexisting anomalies were more likely to have poorer development and special needs. Birth Defects Research 109:535–542, 2017. © 2017 Wiley Periodicals, Inc.
Sensitive and specific LC‐ESI‐MS/MS method for determination of ZYDPLA1, a novel long‐acting dipeptidyl peptidase 4 inhibitor in rat plasma: An application for toxicokinetic study in rats
Authors: Giri Poonam , Patel Nirmal , Patel Bharat , Patel Harilal , Bahekar Rajesh , Srinivas Nuggehally R. , Patel Pankaj R. , Desai Ranjit
Published: March 2017

A rapid and highly specific assay was developed and validated for the estimation of ZYDPLA1 in rat plasma using liquid chromatography coupled to tandem mass spectrometry with positive electrospray ionization. Method validation comprised of parameters such as specificity, matrix effect, precision, accuracy, recovery, stability, etc. The assay procedure involved a simple protein precipitation of ZYDPLA1 and alprazolam (internal standard) from rat plasma using acetonitrile. Chromatographic separation was achieved with a gradient mobile phase comprising: (A) 0.2% ammonia in purified water; (B) 0.1% formic acid in isopropyl alcohol/methanol (1: 1 v/v); and (C) acetonitrile at a flow rate of 1 mL/min on an ACE‐5, C18 (4.6 × 50 mm) column with a run time of 5.5 min. The quantitation of ZYDPLA1 was achieved by the summation of four multiple reaction mode transitions (m/z 399.7 → 383.0, 399.7 → 276.10, 399.7 → 153.20 and 399.7 → 127.20), while that of the internal standard was by a single multiple reaction mode transition (m/z 309.10 → 281.00). The lower limit of quantitation achieved was 0.01 μg/mL and the method showed linearity from 0.01 to 25 μg/mL. The intra‐ and inter‐day precision (%CV) of the quality control samples was within 8.81% and accuracy was ±10% of nominal values. This novel method was applied for evaluation of toxicokinetics of ZYDLA1 in rats.
Contents variation analysis of free amino acids, nucleosides and nucleobases in semen sojae praeparatum fermentation using UFLC‐QTRAP MS
Authors: Chai Chuan , Cui Xiaobing , Shan Chenxiao , Yu Sheng , Wen Hongmei
Published: March 2017

UFLC–QTRAP MS was used to develop a sensitive and rapid method of evaluating content variation during Semen sojae praeparatum (SSP) fermentation. It did this through the simultaneous quantification of 22 free amino acids and 16 nucleosides and nucleobases in the raw materials and processed products of SSP. The method was shown to be reproducible and accurate. The limits of detection and quantity values were 0.09–168.75 and 0.31–562.50 ng/mL for the 38 analytes, respectively. The data were examined through principal components analysis to compare the content variations. The quantitative results showed that the ingredients were properly determined in most of the samples and were converted regularly throughout the SSP fermentation process. These results correspond to the morphologic changes and principal components analysis results.
The importance of functional tests to assess the effect of a new CFTR variant when genotype–phenotype correlation is not possible
Authors: Hinzpeter Alexandre , Reboul Marie‐Pierre , Callebaut Isabelle , Zordan Cécile , Costes Bruno , Guichoux Julie , Iron Albert , Lacombe Didier , Martin Natacha , Arveiler Benoit , Fanen Pascale , Fergelot Patricia , Girodon Emmanuelle
Published: March 2017

Key Clinical Message

In vitro functional tests aimed to investigate CFTR dysfunction appear critical to help elucidate the functional impact of new variants of uncertain clinical significance and solve inconclusive cases, especially in early deceased newborns.
A left atrial appendage thrombus that developed during prophylactic low‐dose dabigatran treatment resolved after switching to apixaban
Authors: Koyama Taku , Otsuka Yoritaka , Kawahara Masaaki , Imoto Yuki , Nakamura Keita , Kodama Sunao , Noguchi Hiroo
Published: March 2017

Key Clinical Message

We describe a case of atrial fibrillation in which an intracardiac thrombus that could not be prevented with “low‐dose” dabigatran treatment was resolved by switching to apixaban treatment. Thrombolysis using direct oral anticoagulants (DOACs) could be a therapeutic option for patients with intracardiac thrombi, although the efficacies of different DOACs seem to differ and need further examination.
Limited Diffusion and Cell Dimensions in a Micrometer Layer of Solution: An Electrochemical Impedance Spectroscopy Study
Authors: Botasini Santiago , Méndez Eduardo
Published: March 2017

The electrochemical impedance behavior observed for a newly proposed electrochemical system [Botasini et al., Analyst, 2016, 141, 5996–6001], in which the complete electrodic system is screen‐printed on the same plane and homogeneously covered by a thin layer of solution, was studied in a wide frequency domain (10 mHz to 100 kHz) involving 127 logarithmically spaced frequencies. Two distinctive frequency domain behaviors were considered, with the addition of a series‐connected capacitor, representing the physical limit of the electrochemical cell. Two diffusion regimes for the electroactive species were detected: i) semi‐infinite linear diffusion close to the electrode surface and limited by a reflecting boundary, followed by ii) distorted diffusion corresponding to the bulk solution enclosed within the thin‐layer cell. From the electric circuit parameters, the diffusion length of the semi‐infinite linear diffusion process, the heterogeneous rate constant for the charge transfer, and the width of the thin‐layer experimental cell can be calculated. For the first time, electrochemical impedance spectroscopy analysis provides a thorough means to study limited diffusion in micrometer‐sized layer that includes the physical limit of the electrochemical cell. All these data are fundamental in the design of novel micro‐ and nano‐fluidic systems.
Cytosine–Cytosine Base‐Pair Mismatch and Chirality in Nucleotide Supramolecular Coordination Complexes
Authors: Qiu Qi‐ming , Zhou Pei , Gu Leilei , Hao Liang , Liu Minghua , Li Hui
Published: March 2017

The base‐pair sequences are the foundation for the biological processes of DNA or RNA, and base‐pair mismatch is very important to reveal genetic diseases and DNA rearrangements. However, the lack of well‐defined structural information about base‐pair mismatch is obstructing the investigation of this issue. The challenge is to crystallize the materials containing the base‐pair mismatch. Engineering the small‐molecule mimics or model is an effective strategy to solve this issue. Here, six cytidine‐5′‐monophosphate (CMP) and 2′‐deoxycytidine‐5′‐monophosphate (dCMP) coordination polymers were reported containing cytosine–cytosine base‐pair mismatch (i‐motif), and their single‐crystal structures and chiralities were studied. The precise control over the formation of the i‐motif was demonstrated, in which the regulating of supramolecular interactions was achieved based on molecular design. In addition, the chiralities of these coordination polymers were investigated according to their crystal structures and solution‐ and solid‐state circular dichroism spectroscopy.
Rafoxanide and Closantel Inhibit SPAK and OSR1 Kinases by Binding to a Highly Conserved Allosteric Site on Their C‐terminal Domains
Authors: AlAmri Mubarak A. , Kadri Hachemi , Alderwick Luke J. , Simpkins Nigel S. , Mehellou Youcef
Published: March 2017

SPAK and OSR1 are two protein kinases that have emerged as attractive targets in the discovery of novel antihypertensive agents due to their role in regulating electrolyte balance in vivo. Herein we report the identification of an allosteric pocket on the highly conserved C‐terminal domains of these two kinases, which influences their activity. We also show that some known WNK signaling inhibitors bind to this allosteric site. Using in silico screening, we identified the antiparasitic agent rafoxanide as a novel allosteric inhibitor of SPAK and OSR1. Collectively, this work will facilitate the rational design of novel SPAK and OSR1 kinase inhibitors that could be useful antihypertensive agents.
A Study of Electrocyclic Reactions in a Molecular Junction: Mechanistic and Energetic Requirements for Switching in the Coulomb Blockade Regime
Authors: Olsen Stine T. , Brøndsted Nielsen Mogens , Hansen Thorsten , Ratner Mark A. , Mikkelsen Kurt V.
Published: March 2017

Molecular photoswitches incorporated in molecular junctions yield the possibility of light‐controlled switching of conductance due to the electronic difference of the photoisomers. Another isomerization mechanism, dark photoswitching, promoted by a voltage stimulus rather than by light, can be operative in the Coulomb blockade regime for a specific charge state of the molecule. Here we elucidate theoretically the mechanistic and thermodynamic restrictions for this dark photoswitching for donor–acceptor substituted 4n and 4n+2 π‐electron open‐chain oligoenes (1,3‐butadiene and 1,3,5‐hexatriene) by considering the molecular energies and orbitals of the molecules placed in a junction. For an electrocyclic ring closure reaction to occur for these compounds, we put forward two requirements: a) the closed stereoisomer (cis or trans form) must be of lower energy than the open form, and b) the reaction pathway must be in accordance to the orbital symmetry rules expressed by the Woodward–Hoffmann rules (when the electrodes do not significantly alter the molecular orbital appearances). We find these two requirements to be valid for the dianion of (1E,3Z,5E)‐hexa‐1,3,5‐triene‐1,6‐diamine, and the Coulomb blockade diamonds were therefore modeled for this compound to elucidate how a dark photoswitching event would manifest itself in the stability plot. From this modeling of conductance as a function of gate and bias potentials, we predict a collapse in Coulomb diamond size, that is, a decrease in the height of the island of zero conductance.
A rapid method for quantifying cytoplasmic versus nuclear localization in endogenous peripheral blood leukocytes by conventional flow cytometry
Authors: Brittain George C. , Gulnik Sergei
Published: March 2017

A biochemical system and method have been developed to enable the quantitative measurement of cytoplasmic versus nuclear localization within cells in whole blood. Compared with the analyses of nuclear localization by western blot or fluorescence microscopy, this system saves a lot of time and resources by eliminating the necessity of purification and culturing steps, and generates data that are free from the errors and artifacts associated with using tumor cell lines or calculating nuclear signals from 2D images. This user‐friendly system enables the analysis of cell signaling within peripheral blood cells in their endogenous environment, including measuring the kinetics of nuclear translocation for transcription factors without requiring protein modifications. We first demonstrated the efficiency and specificity of this system for targeting nuclear epitopes, and verified the results by fluorescence microscopy. Next, the power of the technique to analyze LPS‐induced signaling in peripheral blood monocytes was demonstrated. Finally, both FoxP3 localization and IL‐2‐induced STAT5 signaling in regulatory T cells were analyzed. We conclude that this system can be a useful tool for enabling multidimensional molecular‐biological analyses of cell signaling within endogenous peripheral blood cells by conventional flow cytometry. © 2017 The Authors. Cytometry Part A Published by Wiley Periodicals, Inc. on behalf of ISAC.
Plasticity results in delayed breeding in a long‐distant migrant seabird
Authors: Dobson F. Stephen , Becker Peter H. , Arnaud Coline M. , Bouwhuis Sandra , Charmantier Anne
Published: March 2017

A major question for conservationists and evolutionary biologists is whether natural populations can adapt to rapid environmental change through micro‐evolution or phenotypic plasticity. Making use of 17 years of data from a colony of a long‐distant migratory seabird, the common tern (Sterna hirundo), we examined phenotypic plasticity and the evolutionary potential of breeding phenology, a key reproductive trait. We found that laying date was strongly heritable (0.27 ± 0.09) and under significant fecundity selection for earlier laying. Paradoxically, and in contrast to patterns observed in most songbird populations, laying date became delayed over the study period, by about 5 days. The discrepancy between the observed changes and those predicted from selection on laying date was explained by substantial phenotypic plasticity. The plastic response in laying date did not vary significantly among individuals. Exploration of climatic factors showed individual responses to the mean sea surface temperature in Senegal in December prior to breeding: Common terns laid later following warmer winters in Senegal. For each 1°C of warming of the sea surface in Senegal, common terns delayed their laying date in northern Germany by 6.7 days. This suggests that warmer waters provide poorer wintering resources. We therefore found that substantial plastic response to wintering conditions can oppose natural selection, perhaps constraining adaptation.
Testing the role of ancient and contemporary landscapes on structuring genetic variation in a specialist grasshopper
Authors: Noguerales Víctor , Cordero Pedro J. , Ortego Joaquín
Published: March 2017

Understanding the processes underlying spatial patterns of genetic diversity and structure of natural populations is a central topic in evolutionary biogeography. In this study, we combine data on ancient and contemporary landscape composition to get a comprehensive view of the factors shaping genetic variation across the populations of the scrub‐legume grasshopper (Chorthippus binotatus binotatus) from the biogeographically complex region of southeast Iberia. First, we examined geographical patterns of genetic structure and employed an approximate Bayesian computation (ABC) approach to compare different plausible scenarios of population divergence. Second, we used a landscape genetic framework to test for the effects of (1) Late Miocene paleogeography, (2) Pleistocene climate fluctuations, and (3) contemporary topographic complexity on the spatial patterns of population genetic differentiation. Genetic structure and ABC analyses supported the presence of three genetic clusters and a sequential west‐to‐east splitting model that predated the last glacial maximum (LGM, c. 21 Kya). Landscape genetic analyses revealed that population genetic differentiation was primarily shaped by contemporary topographic complexity, but was not explained by any paleogeographic scenario or resistance distances based on climate suitability in the present or during the LGM. Overall, this study emphasizes the need of integrating information on ancient and contemporary landscape composition to get a comprehensive view of their relative importance to explain spatial patterns of genetic variation in organisms inhabiting regions with complex biogeographical histories.
Median floor acceleration spectra of linear structures with uncertain properties
Authors: Lucchini Andrea , Franchin Paolo , Mollaioli Fabrizio
Published: March 2017

Response parameters used to estimate nonstructural damage differ depending on whether deformation‐sensitive or acceleration‐sensitive components are considered. In the latter case, seismic demand is usually represented through floor spectra, that is response spectra in terms of pseudo‐acceleration, which are calculated at the floor levels of the structure where the nonstructural components are attached to. Objective of this paper is to present a new spectrum‐to‐spectrum method for calculating floor acceleration spectra, which is able to explicitly account for epistemic uncertainties in the modal properties of the supporting structure. By using this method, effects on the spectra of possible variations from nominal values of the periods of vibration of the structure can be estimated. The method derives from the extension of closed‐form equations recently proposed by the authors to predict uniform hazard floor acceleration spectra. These equations are built to rigorously account for the input ground motion uncertainty, that is the record‐to‐record variability of the nonstructural response. In order to evaluate the proposed method, comparisons with exact spectra obtained from a standard probabilistic seismic demand analysis, as well as spectra calculated using the Eurocode 8 equation, are finally shown. Copyright © 2017 John Wiley & Sons, Ltd.
Conceptualizing the Use of Translanguaging in Initial Content Assessments for Newly Arrived Emergent Bilingual Students
Authors: Lopez Alexis A. , Turkan Sultan , Guzman‐Orth Danielle
Published: March 2017

Translanguaging refers to the flexible use of the bilingual repertoire. In this report, we provide a theoretical framework to support the use of translanguaging to assess the academic content knowledge of newly arrived emergent bilingual students. In this report, we argue that translanguaging offers newly arrived emergent bilingual students the opportunity to demonstrate what they know and can do even if their English language and literacy skills are not fully developed. We propose two principles for incorporating translanguaging into initial content assessments for late‐arriving emergent bilingual students, and we theorize how translanguaging can be used within an assessment context by discussing test design applications and considerations. We also discuss some challenges when incorporating translanguaging within an assessment context.
Higher serum cholesterol is associated with intensified age‐related neural network decoupling and cognitive decline in early‐ to mid‐life
Authors: Spielberg Jeffrey M. , Sadeh Naomi , Leritz Elizabeth C. , McGlinchey Regina E. , Milberg William P. , Hayes Jasmeet P. , Salat David H.
Published: March 2017

Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age‐related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting‐state fMRI in a large sample of early‐ to mid‐life Veterans (N = 206, Meanage = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age‐related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically‐elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day‐to‐day disability and mediated age‐related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age‐related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within‐module communication (indexed by Within‐Module Degree Z‐Score) and increasing between‐module communication (indexed by Participation Coefficient), but only in participants with clinically‐elevated cholesterol. Follow‐up analyses indicated that all findings were driven by low‐density lipoprotein (LDL) levels, rather than high‐density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. Hum Brain Mapp 38:3249–3261, 2017. © 2017 Wiley Periodicals, Inc.
Potential epidemiologic, economic, and budgetary impacts of current rates of hepatitis C treatment in medicare and non‐medicare populations
Authors: Wittenborn John , Brady Joanne , Dougherty Michelle , Rein David
Published: March 2017

We forecast the health and budgetary impact of hepatitis C (HCV) treatment on the Medicare program based on currently observed rates of treatment among Medicare and non‐Medicare patients and identify the impact of higher rates of treatment among non‐Medicare populations. We developed a computer microsimulation model to conduct an epidemiologic forecast, a budgetary impact analysis, and a cost‐effectiveness analysis of the treatment of HCV based on three scenarios: 1) no treatment, 2) continuation of current‐treatment rates, and 3) treatment rates among non‐Medicare patients increased to match that of Medicare patients. The simulated population is based on National Health and Nutrition Examination Survey data. HCV progression rates and costs were calculated in Surveillance, Epidemiology, and End Results Program Medicare 5% claims data from the Chronic Hepatitis Cohort Study and published literature. We estimate that 13.6% of patients with HCV in the United States are enrolled in Medicare, but 75% will enter Medicare in the next 20 years. Medicare patients were over 5 times as likely to be treated in 2014‐2015 as other patients. Medicare paid over $9 billion in treatment costs in both 2015 and 2016 and will total $28.4 billion from 2017‐2026. Increasing treatment rates among non‐Medicare patients would lead to 234,000 more patients being treated, reduce HCV mortality by 19%, and decrease Medicare costs by $18.6 billion from 2017‐2026. We find that treatment remains cost‐effective under most assumptions, costing $31,718 per quality adjusted life year gained. Conclusion: Medicare treats a disproportionately large share of HCV patients. Continued low rates of treatment among non‐Medicare HCV patients will result in both reduced and deferred treatment, shifting future treatment costs to Medicare while increasing overall medical management costs, morbidity, and mortality. (Hepatology Communications 2017;1:99‐109)
Comparative genetic variability in HIV‐1 subtype C nef gene in early age groups of infants
Authors: Sharma Uma , Gupta Poonam , Singhal Megha , Singh Supriya , Gupta Sunil , Venkatesh Srinivas , Rai Arvind , Husain Mohammad
Published: March 2017

Targeting properties of vertically transmitted viruses in early infancy is important to understand disease progression. To investigate genotypic characteristics of transmitted viruses, blood samples were obtained from infants aged 6 weeks‐18 months, categorized in two age groups, acute (<6 months) and early (>6‐18 months). Nef having an important role in pathogenesis was selected to explore the viral characteristics. A total of 57 PCR positive samples, amplified by nef gene were sequenced. Analysis showed that 50 sequences belonged to subtype C. In one sequence of acute age group, a long insertion of 10 residues (AAERMRRAEP) in variable region and a 13 residues deletion (ATNNADCAWLEAQ) around proteolytic cleavage region of gene in another sequence was observed. Insertions were also observed in sequences of early age group, however, they ranged from two to eight residues only. In one sequence of early age group, 3/4 arginines at positions 19, 21, 22 of arginine cluster were mutated to glutamine, alanine, and glutamine, respectively. Entropy analysis of two age groups revealed presence of several residues with statistically significant differences in their variability. Among these, 15 (R18,R23,R24; A66,L68,Q71; E74,E77,E78; V87,M92; R119, P144, E167, and C176) belonged to functional motifs, out of which, 12 were in acute age group, suggesting that variability was greater in this group. Prediction of HLA binding peptide motif revealed that epitope LTFGWCFKL was present in >80% study sequences. This epitope was also present in maximum number of HLA types circulating in India and vaccine candidate sequences, suggesting that it may be helpful in designing an epitope‐based vaccine.
European hydroclimate response to volcanic eruptions over the past nine centuries
Authors: Gao Yujuan , Gao Chaochao
Published: March 2017

ABSTRACT

The climatic aftermath of the 1815 Tambora eruption in Europe suggests that large volcanic eruptions can introduce environmental and societal consequences in this region. Here, we analyse the European summer hydrological response to 31 tropical and 44 Northern Hemisphere mid‐to‐high latitude eruptions over the past nine centuries, using a newly published reconstruction of global volcanism and a proxy record of hydrological conditions (Old World Drought Atlas) together with a superposed epoch analysis. Our results show a significant wetting response (at the 95% confidence level) for year 0 and year +1 after tropical eruptions, followed by a significant drying in year +2. Spatially, wetting occurs in northeast and southern Europe, while a drying response develops in central and northwest Europe. Both the wetting and drying responses are more significant for the group of eruptions with higher sulphate injection magnitudes than the eruptions with low magnitudes. Large high latitude eruptions tend to cause a drying response in western‐central Europe in year +2, which shifts south‐eastwards in years +3 and +4. Correcting for the effects of El Nino does not noticeably change the response patterns. The response to eruptions counteracts the hydroclimate response to global warming in some regions, e.g. the Mediterranean, but exaggerates is in others, such as central Europe. Our results verify previous modelling studies from a longer term proxy perspective, and illuminate potential effects of stratospheric geoengineering in Europe.
Prediction of viral loads for diagnosis of Hepatitis C infection in human plasma samples using Raman spectroscopy coupled with partial least squares regression analysis
Authors: Nawaz H. , Rashid N. , Saleem M. , Asif Hanif M. , Irfan Majeed M. , Amin I. , Iqbal M. , Rahman M. , Ibrahim Ola , Baig S. M. , Ahmed M. , Bonnier F. , Byrne H. J.
Published: March 2017

Raman spectroscopy has been used to identify the biochemical changes associated with the presence of the Hepatitis C virus (HCV) in infected human blood plasma samples as compared with healthy samples, as control. The aim of the study was to establish the Raman spectral markers of hepatitis infection, which could be used for diagnostic purposes. Moreover, multivariate data analysis techniques, including Principal Component Analysis (PCA), coupled with Linear Discriminant Analysis (LDA), and Partial Least Square Regression (PLSR) are employed to further demonstrate the diagnostic capability of the technique. The PLSR model is developed to predict the viral loads of the HCV infected plasma on the basis of the biochemical changes caused by the viral infection.

Specific Raman spectral features are observed in the mean spectra of HCV plasma samples which are not observed in the control mean spectra. PCA differentiated the ‘normal’ and ‘HCV’ groups of the Raman spectra and PCA‐LDA was employed to increase the efficiency of prediction of the presence of HCV infection, resulting in a sensitivity and specificity 98.8% and 98.6%, with corresponding Positive Predictive Value of 99.2%, and Negative Predictive Value of 98%. PLSR modelling was found to be 99% accurate in predicting the actual viral loads of the HCV samples, as determined clinically using the Polymerase Chain Reaction (PCR) technique, on the basis of the Raman spectral changes caused by the virus during the process of the development of Hepatitis C. Copyright © 2017 John Wiley & Sons, Ltd.
Sequence‐Defined Oligoamide Drug Conjugates of Pretubulysin and Methotrexate for Folate Receptor Targeted Cancer Therapy
Authors: Truebenbach Ines , Gorges Jan , Kuhn Jasmin , Kern Sarah , Baratti Emanuele , Kazmaier Uli , Wagner Ernst , Lächelt Ulrich
Published: March 2017

The conjugation of small molecule drugs to ligand containing carrier systems facilitates receptor targeted delivery. The folate receptor (FR) constitutes an ideal target for tumor selective therapy, being overexpressed on several tumor types. It can be targeted using the vitamin folic acid (FolA) or the structurally related drug methotrexate (MTX). Several sequence‐defined oligoamides with mono‐ and multivalent FolA or MTX ligands and an additional thiol conjugation site are synthesized via solid‐phase assisted synthesis. Their structure activity relationships are assessed in respect to dihydrofolate reductase inhibition, receptor mediated endocytosis, and cytotoxicity. Then, the tubulin‐binding agent pretubulysin (PT), a highly potent drug exhibiting antitumoral, antiangiogenic, and antimetastatic properties, is conjugated via an activated mercaptane derivative to the set of FR‐targeting oligoamides. In a combined PT/MTX cytotoxicity study in FR‐overexpressing KB and L1210 cells, a 2‐arm MTX‐PT construct or the 4‐arm analog displays the highest potency in the respective cell lines.

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Vitamin C at high concentrations induces cytotoxicity in malignant melanoma but promotes tumor growth at low concentrations
Authors: Yang Guang , Yan Yao , Ma Younan , Yang Yixin
Published: March 2017

Vitamin C has been used in complementary and alternative medicine for cancers regardless of its ineffectiveness in clinical trials and the paradoxical effects antioxidants have on cancer. Vitamin C was found to induce cytotoxicity against cancers. However, the mechanisms of action have not been fully elucidated, and the effects of vitamin C on human malignant melanoma have not been examined. This study revealed that vitamin C at millimolar concentrations significantly reduced the cell viability as well as invasiveness, and induced apoptosis in human malignant melanoma cells. Vitamin C displayed stronger cytotoxicity against the Vemurafenib‐resistance cell line A2058 compared with SK‐MEL‐28. In contrast, vitamin C at micromolar concentrations promoted cell growth, migration and cell cycle progression, and protected against mitochondrial stress. Vemurafenib paradoxically activated the RAS‐RAF‐MEK‐ERK signaling pathway in the Vemurafenib‐resistant A2058, however, vitamin C abolished the activations. Vitamin C displayed synergistic cytotoxicity with Vemurafenib against the Vemurafenib‐resistant A2058. In vivo assay suggested that lower dosage (equivalent to 0.5 g/70 kg) of vitamin C administered orally increased the melanoma growth. Therefore, vitamin C may exert pro‐ or anti‐melanoma effect depending on concentration. The combination of vitamin C at high dosage and Vemurafenib is promising in overcoming the action of drug resistance.
GABA editing with macromolecule suppression using an improved MEGA‐SPECIAL sequence
Authors: Gu Meng , Hurd Ralph , Noeske Ralph , Baltusis Laima , Hancock Roeland , Sacchet Matthew D. , Gotlib Ian H. , Chin Frederick T. , Spielman Daniel M.
Published: March 2017

Purpose

The most common γ‐aminobutyric‐acid (GABA) editing approach, MEGA‐PRESS, uses J‐editing to measure GABA distinct from larger overlapping metabolites, but suffers contamination from coedited macromolecules (MMs) comprising 40 to 60% of the observed signal. MEGA‐SPECIAL is an alternative method with better MM suppression, but is not widely used primarily because of its relatively poor spatial localization. Our goal was to develop an improved MM‐suppressed GABA editing sequence at 3 Tesla.

Methods

We modified a single‐voxel MEGA‐SPECIAL sequence with an oscillating readout gradient for improved spatial localization, and used very selective 30‐ms editing pulses for improved suppression of coedited MMs.

Results

Simulation and in vivo experiments confirmed excellent MM suppression, insensitive to the range of B0 frequency drifts typically encountered in vivo. Both intersubject and intrasubject studies showed that MMs, when suppressed by the improved MEGA‐SPECIAL method, contributed approximately 40% to the corresponding MEGA‐PRESS measurements. From the intersubject study, the coefficient of variation for GABA+/Cre (MEGA‐PRESS) was 11.2% versus 7% for GABA/Cre (improved MEGA‐SPECIAL), demonstrating significantly reduced variance (P = 0.005), likely coming from coedited MMs.

Conclusions

This improved MEGA‐SPECIAL sequence provides unbiased GABA measurements with reduced variance as compared with conventional MEGA‐PRESS. This approach is also relatively insensitive to the range of B0 drifts typically observed in in vivo human studies. Magn Reson Med 79:41–47, 2018. © 2017 International Society for Magnetic Resonance in Medicine.