bluuebunny/crossref_metadata_2025 huggingface dataset:
Ab initio investigation of the surface properties of dispenser B-type and scandate thermionic emission cathodes
Authors: Vlahos Vasilios , Lee Yueh-Lin , Booske John H. , Morgan Dane , Turek Ladislav , Kirshner Mark , Kowalczyk Richard , Wilsen Craig
Published: May 2009

Scandate cathodes (BaxScyOz on W) are important thermionic electron emission materials whose emission mechanism remains unclear. Ab initio modeling is used to investigate the surface properties of both scandate and traditional B-type (Ba–O on W) cathodes. We demonstrate that the Ba–O dipole surface structure believed to be present in active B-type cathodes is not thermodynamically stable, suggesting that a nonequilibrium steady state dominates the active cathode’s surface structure. We identify a stable, low work function BaxScyOz surface structure, which may be responsible for some scandate cathode properties and demonstrate that multicomponent surface coatings can lower cathode work functions.
Buckling beam micromechanical memory with on-chip readout
Authors: Roodenburg D. , Spronck J. W. , van der Zant H. S. J. , Venstra W. J.
Published: May 2009

We have used double clamped beams to implement a mechanical memory. Compressive stress is generated by resistive heating of the beams and beyond the buckling limit the bistable regime is accessed. Bits are written by applying lateral electrostatic forces. The state of the beam is read out by measuring the capacitance between beam and electrodes. Two ways to implement a mechanical memory are discussed: compensation of initial beam imperfections and snap through of the postbuckled beam. Although significant relaxation effects are observed, both methods prove reliable over thousands of write cycles.
Magnetocaloric effect in Ho2In over a wide temperature range
Authors: Zhang Q. , Cho J. H. , Li B. , Hu W. J. , Zhang Z. D.
Published: May 2009

The compound Ho2In exhibits two successive magnetic phase transitions: a spin-reorientation transition at TSR=32 K and a magnetic-ordering transition at TC=85 K. The maximum reversible −ΔSM values are 6.3 and 11.2 J/kg K at TSR and TC, respectively, for a field change of 5 T. These two −ΔSM peaks with the same sign are partly overlapping, which results in a wide temperature interval with appreciable magnetocaloric effect. The results on Ho2In indicate that materials with successive SR and magnetic-ordering transitions may constitute an important new class of magnetic refrigerants since they work in a wider temperature range than the conventional refrigerant materials.
Defect-induced negative differential resistance of GaN nanowires measured by conductive atomic force microscopy
Authors: Chu Wen-Huei , Chiang Hsin-Wei , Liu Chuan-Pu , Lai Yi-Feng , Hsu Kuang-Yuan , Chung Hung-Chin
Published: May 2009

We report on negative differential resistance (NDR) from individual GaN nanowires prepared without catalysts by thermal chemical vapor deposition. Conductive atomic force microscopy was used to characterize the electron transport behavior and transmission electron microscopy was employed to characterize the microstructure of the GaN nanowires. The current-voltage curve exhibits two clear NDR regions in the forward bias. The defect assisted inelastic tunneling process resulting in the NDR behavior and the related mechanism for energy band diagram is proposed and discussed.
New kind of ultralong dimers are observed
Authors: Day Charles
Published: May 2009

The dimeric bond joins the chemists’ familiar roster of ionic, covalent, hydrogen, and van der Waals.
The competition is gaining on platinum as a catalyst for hydrogen fuel cells
Authors: Levi Barbara Goss
Published: May 2009

A new iron-based catalyst is active enough to compete with its expensive rival, but more work is needed to make a viable fuel cell.
Hunkered down, academe waits for the full fallout of the economic crisis
Authors: Feder Toni
Published: May 2009

With academic jobs an early victim of the fiscal slump, many in the rising generation may have little choice but to leave science.
Science representatives seek to ease tensions in Middle East
Authors: Kramer David
Published: May 2009

US science delegation visits Syria with hope of improving bilateral relations. Similar overtures with Iran suffer a setback.
Photoacoustics for molecular imaging and therapy
Authors: Emelianov Stanislav Y. , Li Pai-Chi , O’Donnell Matthew
Published: May 2009

Sound waves generated by light are the basis of a sensitive medical imaging technique with applications to cancer diagnosis and treatment.
Heterogeneities in granular materials
Authors: Mehta Anita , Barker Gary C. , Luck Jean-Marc
Published: May 2009

Different parts of a sandpile can exhibit very different dynamical behaviors ranging from jammed to fluid. To understand them, one needs to look at the networks of contacts between individual grains.
Erk1/2 MAP kinases are required for epidermal G2/M progression
Authors: Dumesic Phillip A. , Scholl Florence A. , Barragan Deborah I. , Khavari Paul A.
Published: May 2009

Erk1/2 mitogen-activated protein kinases (MAPKs) are often hyperactivated in human cancers, where they affect multiple processes, including proliferation. However, the effects of Erk1/2 loss in normal epithelial tissue, the setting of most extracellular signal-regulated kinase (Erk)–associated neoplasms, are unknown. In epidermis, loss of Erk1 or Erk2 individually has no effect, whereas simultaneous Erk1/2 depletion inhibits cell division, demonstrating that these MAPKs are necessary for normal tissue self-renewal. Growth inhibition caused by Erk1/2 loss is rescued by reintroducing Erk2, but not by activating Erk effectors that promote G1 cell cycle progression. Unlike fibroblasts, in which Erk1/2 loss decreases cyclin D1 expression and induces G1/S arrest, Erk1/2 loss in epithelial cells reduces cyclin B1 and c-Fos expression and induces G2/M arrest while disrupting a gene regulatory network centered on cyclin B1–Cdc2. Thus, the cell cycle stages at which Erk1/2 activity is required vary by cell type, with Erk1/2 functioning in epithelial cells to enable progression through G2/M.
Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion
Authors: Lapetina Stefanie , Mader Christopher C. , Machida Kazuya , Mayer Bruce J. , Koleske Anthony J.
Published: May 2009

The molecular mechanisms by which the Abelson (Abl) or Abl-related gene (Arg) kinases interface with the actin polymerization machinery to promote cell edge protrusions during cell–matrix adhesion are unclear. In this study, we show that interactions between Arg and the Arp2/3 complex regulator cortactin are essential to mediate actin-based cell edge protrusion during fibroblast adhesion to fibronectin. Arg-deficient and cortactin knockdown fibroblasts exhibit similar defects in adhesion-dependent cell edge protrusion, which can be restored via reexpression of Arg and cortactin. Arg interacts with cortactin via both binding and catalytic events. The cortactin Src homology (SH) 3 domain binds to a Pro-rich motif in the Arg C terminus. Arg mediates adhesion-dependent phosphorylation of cortactin, creating an additional binding site for the Arg SH2 domain. Mutation of residues that mediate Arg–cortactin interactions abrogate the abilities of both proteins to support protrusions, and the Nck adapter, which binds phosphocortactin, is also required. These results demonstrate that interactions between Arg, cortactin, and Nck1 are critical to promote adhesion-dependent cell edge protrusions.
Synaptic activity prompts γ-secretase–mediated cleavage of EphA4 and dendritic spine formation
Authors: Inoue Eiji , Deguchi-Tawarada Maki , Togawa Aki , Matsui Chiyuki , Arita Kohei , Katahira-Tayama Sayaka , Sato Toshitaka , Yamauchi Emiko , Oda Yoshiya , Takai Yoshimi
Published: May 2009

Alzheimer's disease is an age-dependent neurodegenerative disorder that is characterized by a progressive decline in cognitive function. γ-secretase dysfunction is evident in many cases of early onset familial Alzheimer's disease. However, the mechanism by which γ-secretase dysfunction results in memory loss and neurodegeneration is not fully understood. Here, we demonstrate that γ-secretase is localized at synapses and regulates spine formation. We identify EphA4, one of the Ephrin receptor family members, as a substrate of γ-secretase, and find that EphA4 processing is enhanced by synaptic activity. Moreover, overexpression of EphA4 intracellular domain increases the number of dendritic spines by activating the Rac signaling pathway. These findings reveal a function for EphA4-mediated intracellular signaling in the morphogenesis of dendritic spines and suggest that the processing of EphA4 by γ-secretase affects the pathogenesis of Alzheimer's disease.
Two structurally distinct domains of the nucleoporin Nup170 cooperate to tether a subset of nucleoporins to nuclear pores
Authors: Flemming Dirk , Sarges Phillip , Stelter Philipp , Hellwig Andrea , Böttcher Bettina , Hurt Ed
Published: May 2009

How individual nucleoporins (Nups) perform their role in nuclear pore structure and function is largely unknown. In this study, we examined the structure of purified Nup170 to obtain clues about its function. We show that Nup170 adopts a crescent moon shape with two structurally distinct and separable domains, a β-propeller N terminus and an α-solenoid C terminus. To address the individual roles of each domain, we expressed these domains separately in yeast. Notably, overexpression of the Nup170 C domain was toxic in nup170Δ cells and caused accumulation of several Nups in cytoplasmic foci. Further experiments indicated that the C-terminal domain anchors Nup170 to nuclear pores, whereas the N-terminal domain functions to recruit or retain a subset of Nups, including Nup159, Nup188, and Pom34, at nuclear pores. We conclude that Nup170 performs its role as a structural adapter between cytoplasmically oriented Nups and the nuclear pore membrane.
Role of the Ndc1 interaction network in yeast nuclear pore complex assembly and maintenance
Authors: Onischenko Evgeny , Stanton Leslie H. , Madrid Alexis S. , Kieselbach Thomas , Weis Karsten
Published: May 2009

The nuclear pore complex (NPC) mediates all nucleocytoplasmic transport, yet its structure and biogenesis remain poorly understood. In this study, we have functionally characterized interaction partners of the yeast transmembrane nucleoporin Ndc1. Ndc1 forms a distinct complex with the transmembrane proteins Pom152 and Pom34 and two alternative complexes with the soluble nucleoporins Nup53 and Nup59, which in turn bind to Nup170 and Nup157. The transmembrane and soluble Ndc1-binding partners have redundant functions at the NPC, and disruption of both groups of interactions causes defects in Ndc1 targeting and in NPC structure accompanied by significant pore dilation. Using photoconvertible fluorescent protein fusions, we further show that the depletion of Pom34 in cells that lack NUP53 and NUP59 blocks new NPC assembly and leads to the reversible accumulation of newly made nucleoporins in cytoplasmic foci. Therefore, Ndc1 together with its interaction partners are collectively essential for the biosynthesis and structural integrity of yeast NPCs.
Piecing together nuclear pore complex assembly during interphase
Authors: Rexach Michael
Published: May 2009

All nucleocytoplasmic traffic of macromolecules occurs through nuclear pore complexes (NPCs), which function as stents in the nuclear envelope to keep nuclear pores open but gated. Three studies in this issue (Flemming, D., P. Sarges, P. Stelter, A. Hellwig, B. Böttcher, and E. Hurt. 2009. J. Cell Biol. 185:387–395; Makio, T., L.H. Stanton, C.-C. Lin, D.S. Goldfarb, K. Weis, and R.W. Wozniak. 2009. J. Cell Biol. 185:459–491; Onishchenko, E., L.H. Stanton, A.S. Madrid, T. Kieselbach, and K. Weis. 2009. J. Cell Biol. 185:475–491) further our understanding of the NPC assembly process by reporting what happens when the supply lines of key proteins that provide a foundation for building these marvelous supramolecular structures are disrupted.
The response of sound scatterers to El Niño- and La Niña-like oceanographic regimes in the southeastern Atlantic
Authors: Ostrowski Marek , da Silva José C. B. , Bazik-Sangolay Bomba
Published: May 2009

Ostrowski, M., da Silva, J. C. B., and Bazik-Sangolay, B. 2009. The response of sound scatterers to El Niño- and La Niña-like oceanographic regimes in the southeastern Atlantic. – ICES Journal of Marine Science, 66: 1063–1072. Oceanographic conditions off Angola alternate seasonally between upwelling in the austral winter and El Niño-like intrusions and downwelling in summer. During winter in regions deeper than 30 m, the water column consists of a top layer of warm, tropical water overlying cold, nutrient-rich, and hypoxic South Atlantic Central Water (SACW). Closer inshore the water becomes well mixed. In the stratified region, acoustic backscatter at 38 kHz matches the oceanographic structure. It is strong in the top layer, but declines sharply in the SACW. During summer, the water column is continuously stratified, and the SACW is absent from the shelf. The backscatter reveals multiple thin layers extending across much of the shelf. The scattering layers are often perturbed by internal waves. The combined evidence from multiple acoustic surveys and the existing synthetic-aperture radar imagery suggests that tidal internal waves are a pervasive phenomenon in Angolan waters.
Mathematical models of the electrical action potential of Purkinje fibre cells
Authors: Stewart Philip , Aslanidi Oleg V. , Noble Denis , Noble Penelope J. , Boyett Mark R. , Zhang Henggui
Published: May 2009

Early development of ionic models for cardiac myocytes, from the pioneering modification of the Hodgkin–Huxley giant squid axon model by Noble to the iconic DiFrancesco–Noble model integrating voltage-gated ionic currents, ion pumps and exchangers, Ca
2+
sequestration and Ca
2+
-induced Ca
2+
release, provided a general description for a mammalian Purkinje fibre (PF) and the framework for modern cardiac models. In the past two decades, development has focused on tissue-specific models with an emphasis on the sino-atrial (SA) node, atria and ventricles, while the PFs have largely been neglected. However, achieving the ultimate goal of creating a virtual human heart will require detailed models of all distinctive regions of the cardiac conduction system, including the PFs, which play an important role in conducting cardiac excitation and ensuring the synchronized timing and sequencing of ventricular contraction. In this paper, we present details of our newly developed model for the human PF cell including validation against experimental data. Ionic mechanisms underlying the heterogeneity between the PF and ventricular action potentials in humans and other species are analysed. The newly developed PF cell model adds a new member to the family of human cardiac cell models developed previously for the SA node, atrial and ventricular cells, which can be incorporated into an anatomical model of the human heart with details of its electrophysiological heterogeneity and anatomical complexity.
A systems perspective on the effective connectivity of overt speech production
Authors: Eickhoff Simon B. , Heim Stefan , Zilles Karl , Amunts Katrin
Published: May 2009

The aim of this study was to provide a computational system model of effective connectivity in the human brain underlying overt speech production. Meta-analysis of neuroimaging studies and functional magnetic resonance imaging data acquired during a verbal fluency task revealed a core network consisting of Brodmann's area (BA) 44 in Broca's region, anterior insula, basal ganglia, cerebellum, premotor cortex (PMC, BA 6) and primary motor cortex (M1, areas 4a/4p). Dynamic causal modelling (DCM) indicated the highest evidence for a system architecture featuring the insula in a serial position between BA 44 and two parallel nodes (cerebellum/basal ganglia), from which information converges onto the PMC and finally M1. Parameter inference revealed that effective connectivity from the insular relay into the cerebellum/basal ganglia is primarily task driven (preparation) while the output into the cortical motor system strongly depends on the actual word production rate (execution). DCM hence allowed not only a quantitative characterization of the human speech production network, but also the distinction of a preparatory and an executive subsystem within it. The proposed model of physiological integration during speech production may now serve as a reference for investigations into the neurobiology of pathological states such as dysarthria and apraxia of speech.
Markov models for ion channels: versatility versus identifiability and speed
Authors: Fink Martin , Noble Denis
Published: May 2009

Markov models (MMs) represent a generalization of Hodgkin–Huxley models. They provide a versatile structure for modelling single channel data, gating currents, state-dependent drug interaction data, exchanger and pump dynamics, etc. This paper uses examples from cardiac electrophysiology to discuss aspects related to parameter estimation. (i) Parameter unidentifiability (found in 9 out of 13 of the considered models) results in an inability to determine the correct layout of a model, contradicting the idea that model structure and parameters provide insights into underlying molecular processes. (ii) The information content of experimental voltage step clamp data is discussed, and a short but sufficient protocol for parameter estimation is presented. (iii) MMs have been associated with high computational cost (owing to their large number of state variables), presenting an obstacle for multicellular whole organ simulations as well as parameter estimation. It is shown that the stiffness of models increases computation time more than the number of states. (iv) Algorithms and software programs are provided for steady-state analysis, analytical solutions for voltage steps and numerical derivation of parameter identifiability. The results provide a new standard for ion channel modelling to further the automation of model development, the validation process and the predictive power of these models.
Simulation of the human intracranial arterial tree
Authors: Grinberg Leopold , Anor Tomer , Cheever Elizabeth , Madsen Joseph R. , Karniadakis George Em
Published: May 2009

High-resolution unsteady three-dimensional flow simulations in large intracranial arterial networks of a healthy subject and a patient with hydrocephalus have been performed. The large size of the computational domains requires the use of thousands of computer processors and solution of the flow equations with approximately one billion degrees of freedom. We have developed and implemented a two-level domain decomposition method, and a new type of outflow boundary condition to control flow rates at tens of terminal vessels of the arterial network. In this paper, we demonstrate the flow patterns in the normal and abnormal intracranial arterial networks using patient-specific data.
Towards a virtual fly brain
Authors: Armstrong J. Douglas , van Hemert Jano I.
Published: May 2009

Models of the brain that simulate sensory input, behavioural output and information processing in a biologically plausible manner pose significant challenges to both computer science and biology. Here we investigated strategies that could be used to create a model of the insect brain, specifically that of
Drosophila melanogaster
that is very widely used in laboratory research. The scale of the problem is an order of magnitude above the most complex of the current simulation projects, and it is further constrained by the relative sparsity of available electrophysiological recordings from the fly nervous system. However, fly brain research at the anatomical and behavioural levels offers some interesting opportunities that could be exploited to create a functional simulation. We propose to exploit these strengths of
Drosophila
central nervous system research to focus on a functional model that maps biologically plausible network architecture onto phenotypic data from neuronal inhibition and stimulation studies, leaving aside biophysical modelling of individual neuronal activity for future models until more data are available.
Relationship between structural changes and hyperpolarized gas magnetic resonance imaging in chronic obstructive pulmonary disease using computational simulations with realistic alveolar geometry
Authors: Plotkowiak Michal , Burrowes Kelly , Wolber Jan , Buckley Christopher , Davies Robert , Gleeson Fergus , Gavaghan David , Grau Vicente
Published: May 2009

Both the development of accurate models of lung function and their quantitative validation can be significantly enhanced by the use of functional imaging techniques. The advent of hyperpolarized noble gas magnetic resonance imaging (MRI) technology has increased the amount of local, functional information we can obtain from the lung. In particular, application of
3
He to measure apparent diffusion coefficients has enabled some measure of lung microstructure and airspace size within the lung. Models mimicking image acquisition in hyperpolarized gas MRI can improve understanding of the relationship between image findings and lung structure, and can be used to improve the definition of imaging protocols. In this paper, we review the state of the art in hyperpolarized gas MRI modelling. We also present our own results, obtained using a Monte Carlo approach and a realistic alveolar sac geometry, which has previously been applied in functional lung studies. In this way, we demonstrate the potential for models combining lung function and image acquisition, which could provide valuable tools in both basic studies and clinical practice.
From
in vivo
plasma composition to
in vitro
cardiac electrophysiology and
in silico
virtual heart: the extracellular calcium enigma
Authors: Severi Stefano , Corsi Cristiana , Cerbai Elisabetta
Published: May 2009

In spite of its potential impact on simulation results, the problem of setting the appropriate Ca
2+
concentration ([Ca
2+
]
o
) in computational cardiac models has not yet been properly considered. Usually [Ca
2+
]
o
values are derived from
in vitro
electrophysiology. Unfortunately, [Ca
2+
]
o
in the experiments is set significantly far (1.8 or 2 mM) from the physiological [Ca
2+
] in blood (1.0–1.3 mM). We analysed the inconsistency of [Ca
2+
]
o
among
in vivo
,
in vitro
and
in silico
studies and the dependence of cardiac action potential (AP) duration (APD) on [Ca
2+
]
o
. Laboratory measurements confirmed the difference between standard extracellular solutions and normal blood [Ca
2+
]. Experimental data on human atrial cardiomyocytes confirmed literature data, demonstrating an inverse relationship between APD and [Ca
2+
]
o
. Sensitivity analysis of APD on [Ca
2+
]
o
for five of the most used cardiac cell models was performed. Most of the models responded with AP prolongation to increases in [Ca
2+
]
o
, i.e. opposite to the AP shortening observed
in vitro
and
in vivo.
Modifications to the Ten Tusscher–Panfilov model were implemented to demonstrate that qualitative consistency among
in vivo
,
in vitro
and
in silico
studies can be achieved. The Courtemanche atrial model was used to test the effect of changing [Ca
2+
]
o
on quantitative predictions about the effect of K
+
current blockade. The present analysis suggests that (i) [Ca
2+
]
o
in cardiac AP models should be changed from 1.8 to 2 mM to approximately 1.15 mM in order to reproduce
in vivo
conditions, (ii) the sensitivity to [Ca
2+
]
o
of ventricular AP models should be improved in order to simulate real conditions, (iii) modifications to the formulation of Ca
2+
-dependent
I
CaL
inactivation can make models more suitable to analyse AP when [Ca
2+
]
o
is set to lower physiological values, and (iv) it could be misleading to use non-physiological high [Ca
2+
]
o
when the quantitative analysis of
in vivo
pathophysiological mechanisms is the ultimate aim of simulation.
Characterizing the evolution of genetic variance using genetic covariance tensors
Authors: Hine Emma , Chenoweth Stephen F. , Rundle Howard D. , Blows Mark W.
Published: May 2009

Determining how genetic variance changes under selection in natural populations has proved to be a very resilient problem in evolutionary genetics. In the same way that understanding the availability of genetic variance within populations requires the simultaneous consideration of genetic variance in sets of functionally related traits, determining how genetic variance changes under selection in natural populations will require ascertaining how genetic variance–covariance (G) matrices evolve. Here, we develop a geometric framework using higher-order tensors, which enables the empirical characterization of howGmatrices have diverged among populations. We then show how divergence among populations in genetic covariance structure can then be associated with divergence in selection acting on those traits using key equations from evolutionary theory. Using estimates ofGmatrices of eight male sexually selected traits from nine geographical populations ofDrosophila serrata, we show that much of the divergence in genetic variance occurred in a single trait combination, a conclusion that could not have been reached by examining variation among the individual elements of the nineGmatrices. Divergence inGwas primarily in the direction of the major axes of genetic variance within populations, suggesting that genetic drift may be a major cause of divergence in genetic variance among these populations.
Evolution in plant populations as a driver of ecological changes in arthropod communities
Authors: Johnson Marc T.J. , Vellend Mark , Stinchcombe John R.
Published: May 2009

Heritable variation in traits can have wide-ranging impacts on species interactions, but the effects that ongoing evolution has on the temporal ecological dynamics of communities are not well understood. Here, we identify three conditions that, if experimentally satisfied, support the hypothesis that evolution by natural selection can drive ecological changes in communities. These conditions are: (i) a focal population exhibits genetic variation in a trait(s), (ii) there is measurable directional selection on the trait(s), and (iii) the trait(s) under selection affects variation in a community variable(s). When these conditions are met, we expect evolution by natural selection to cause ecological changes in the community. We tested these conditions in a field experiment examining the interactions between a native plant (Oenothera biennis) and its associated arthropod community (more than 90 spp.).Oenothera biennisexhibited genetic variation in several plant traits and there was directional selection on plant biomass, life-history strategy (annual versus biennial reproduction) and herbivore resistance. Genetically based variation in biomass and life-history strategy consistently affected the abundance of common arthropod species, total arthropod abundance and arthropod species richness. Using two modelling approaches, we show that evolution by natural selection in largeO. biennispopulations is predicted to cause changes in the abundance of individual arthropod species, increases in the total abundance of arthropods and a decline in the number of arthropod species. In smallO. biennispopulations, genetic drift is predicted to swamp out the effects of selection, making the evolution of plant populations unpredictable. In short, evolution by natural selection can play an important role in affecting the dynamics of communities, but these effects depend on several ecological factors. The framework presented here is general and can be applied to other systems to examine the community-level effects of ongoing evolution.
From genes to ecosystems: a synthesis of the effects of plant genetic factors across levels of organization
Authors: Bailey Joseph K. , Schweitzer Jennifer A. , Úbeda Francisco , Koricheva Julia , LeRoy Carri J. , Madritch Michael D. , Rehill Brian J. , Bangert Randy K. , Fischer Dylan G. , Allan Gerard J. , Whitham Thomas G.
Published: May 2009

Using two genetic approaches and seven different plant systems, we present findings from a meta-analysis examining the strength of the effects of plant genetic introgression and genotypic diversity across individual, community and ecosystem levels with the goal of synthesizing the patterns to date. We found that (i) the strength of plant genetic effects can be quite high; however, the overall strength of genetic effects on most response variables declined as the levels of organization increased. (ii) Plant genetic effects varied such that introgression had a greater impact on individual phenotypes than extended effects on arthropods or microbes/fungi. By contrast, the greatest effects of genotypic diversity were on arthropods. (iii) Plant genetic effects were greater on above-ground versus below-ground processes, but there was no difference between terrestrial and aquatic environments. (iv) The strength of the effects of intraspecific genotypic diversity tended to be weaker than interspecific genetic introgression. (v) Although genetic effects generally decline across levels of organization, in some cases they do not, suggesting that specific organisms and/or processes may respond more than others to underlying genetic variation. Because patterns in the overall impacts of introgression and genotypic diversity were generally consistent across diverse study systems and consistent with theoretical expectations, these results provide generality for understanding the extended consequences of plant genetic variation across levels of organization, with evolutionary implications.
Modelling single nucleotide effects inphosphoglucose isomeraseon dispersal in the Glanville fritillary butterfly: coupling of ecological and evolutionary dynamics
Authors: Zheng Chaozhi , Ovaskainen Otso , Hanski Ilkka
Published: May 2009

Dispersal comprises a complex life-history syndrome that influences the demographic dynamics of especially those species that live in fragmented landscapes, the structure of which may in turn be expected to impose selection on dispersal. We have constructed an individual-based evolutionary sexual model of dispersal for species occurring as metapopulations in habitat patch networks. The model assumes correlated random walk dispersal with edge-mediated behaviour (habitat selection) and spatially correlated stochastic local dynamics. The model is parametrized with extensive data for the Glanville fritillary butterfly. Based on empirical results for a single nucleotide polymorphism (SNP) in thephosphoglucose isomerase(Pgi) gene, we assume that dispersal rate in the landscape matrix, fecundity and survival are affected by a locus with two alleles, A and C, individuals with the C allele being more mobile. The model was successfully tested with two independent empirical datasets on spatial variation inPgiallele frequency. First, at the level of local populations, the frequency of the C allele is the highest in newly established isolated populations and the lowest in old isolated populations. Second, at the level of sub-networks with dissimilar numbers and connectivities of patches, the frequency of C increases with decreasing network size and hence with decreasing average metapopulation size. The frequency of C is the highest in landscapes where local extinction risk is high and where there are abundant opportunities to establish new populations. Our results indicate that the strength of the coupling of the ecological and evolutionary dynamics depends on the spatial scale and is asymmetric, demographic dynamics having a greater immediate impact on genetic dynamics than vice versa.
Non-random distribution of individual genetic diversity along an environmental gradient
Authors: Porlier Mélody , Bélisle Marc , Garant Dany
Published: May 2009

Improving our knowledge of the links between ecology and evolution is especially critical in the actual context of global rapid environmental changes. A critical step in that direction is to quantify how variation in ecological factors linked to habitat modifications might shape observed levels of genetic variability in wild populations. Still, little is known on the factors affecting levels and distribution of genetic diversity at the individual level, despite its vital underlying role in evolutionary processes. In this study, we assessed the effects of habitat quality on population structure and individual genetic diversity of tree swallows (Tachycineta bicolor) breeding along a gradient of agricultural intensification in southern Québec, Canada. Using a landscape genetics approach, we found that individual genetic diversity was greater in poorer quality habitats. This counter-intuitive result was partly explained by the settlement patterns of tree swallows across the landscape. Individuals of higher genetic diversity arrived earlier on their breeding grounds and settled in the first available habitats, which correspond to intensive cultures. Our results highlight the importance of investigating the effects of environmental variability on individual genetic diversity, and of integrating information on landscape structure when conducting such studies.
An evolutionary maximum principle for density-dependent population dynamics in a fluctuating environment
Authors: Lande Russell , Engen Steinar , Sæther Bernt-Erik
Published: May 2009

The evolution of population dynamics in a stochastic environment is analysed under a general form of density-dependence with genetic variation in
r
and
K
, the intrinsic rate of increase and carrying capacity in the average environment, and in
σ
e
2
, the environmental variance of population growth rate. The continuous-time model assumes a large population size and a stationary distribution of environments with no autocorrelation. For a given population density,
N
, and genotype frequency,
p
, the expected selection gradient is always towards an increased population growth rate, and the expected fitness of a genotype is its Malthusian fitness in the average environment minus the covariance of its growth rate with that of the population. Long-term evolution maximizes the expected value of the density-dependence function, averaged over the stationary distribution of
N
. In the
θ
-logistic model, where density dependence of population growth is a function of
N

θ

, long-term evolution maximizes E[
N

θ

]=[1−
σ
e
2
/(2
r
)]
K

θ

. While
σ
e
2
is always selected to decrease,
r
and
K
are always selected to increase, implying a genetic trade-off among them. By contrast, given the other parameters,
θ
has an intermediate optimum between 1.781 and 2 corresponding to the limits of high or low stochasticity.
From stochastic environments to life histories and back
Authors: Tuljapurkar Shripad , Gaillard Jean-Michel , Coulson Tim
Published: May 2009

Environmental stochasticity is known to play an important role in life-history evolution, but most general theory assumes a constant environment. In this paper, we examine life-history evolution in a variable environment, by decomposing average individual fitness (measured by the long-run stochastic growth rate) into contributions from average vital rates and their temporal variation. We examine how generation time, demographic dispersion (measured by the dispersion of reproductive events across the lifespan), demographic resilience (measured by damping time), within-year variances in vital rates, within-year correlations between vital rates and between-year correlations in vital rates combine to determine average individual fitness of stylized life histories. In a fluctuating environment, we show that there is often a range of cohort generation times at which the fitness is at a maximum. Thus, we expect ‘optimal’ phenotypes in fluctuating environments to differ from optimal phenotypes in constant environments. We show that stochastic growth rates are strongly affected by demographic dispersion, even when deterministic growth rates are not, and that demographic dispersion also determines the response of life-history-specific average fitness to within- and between-year correlations. Serial correlations can have a strong effect on fitness, and, depending on the structure of the life history, may act to increase or decrease fitness. The approach we outline takes a useful first step in developing general life-history theory for non-constant environments.
Solubility of Structurally Complicated Materials: 3. Hair
Authors: Horvath Ari L.
Published: May 2009

Hair is composed of proteins, lipids, water, and small amounts of trace elements. All proteins in animal and human bodies are built from permutations of amino acid molecules in a polypeptide string. The polypeptide chains of protein keratin are organized into filaments in hair cells. Hair is one of the most difficult proteins to digest or solubilize. Among the most common dissolving procedures for hair are acidic, alkaline, and enzymatic hydrolysis. For the analysis of hair, the solid samples are transferred by solubilization via digestion into a liquid phase. Small molecular solvents and molecules with hydrophobic groups appear to have higher affinity for hair. A good solvent attacks the disulfide bonds between cystine molecules and hydrates the hair shaft. Consequently, the hair becomes a jelly-like mass.
Gene expression profiling of advanced‐stage serous ovarian cancers distinguishes novel subclasses and implicates ZEB2 in tumor progression and prognosis
Authors: Yoshihara Kosuke , Tajima Atsushi , Komata Dai , Yamamoto Tadashi , Kodama Shoji , Fujiwara Hiroyuki , Suzuki Mitsuaki , Onishi Yoshitaka , Hatae Masayuki , Sueyoshi Kazunobu , Fujiwara Hisaya , Kudo Yoshiki , Inoue Ituro , Tanaka Kenichi
Published: May 2009

To elucidate the mechanisms of rapid progression of serous ovarian cancer, gene expression profiles from 43 ovarian cancer tissues comprising eight early stage and 35 advanced stage tissues were carried out using oligonucleotide microarrays of 18 716 genes. By non‐negative matrix factorization analysis using 178 genes, which were extracted as stage‐specific genes, 35 advanced stage cases were classified into two subclasses with superior (n = 17) and poor (n = 18) outcome evaluated by progression‐free survival (log rank test, P = 0.03). Of the 178 stage‐specific genes, 112 genes were identified as showing different expression between the two subclasses. Of the 48 genes selected for biological function by gene ontology analysis or Ingenuity Pathway Analysis, five genes (ZEB2, CDH1, LTBP2, COL16A1, and ACTA2) were extracted as candidates for prognostic factors associated with progression‐free survival. The relationship between high ZEB2 or low CDH1 expression and shorter progression‐free survival was validated by real‐time RT‐PCR experiments of 37 independent advanced stage cancer samples. ZEB2 expression was negatively correlated with CDH1 expression in advanced stage samples, whereas ZEB2 knockdown in ovarian adenocarcinoma SKOV3 cells resulted in an increase in CDH1 expression. Multivariate analysis showed that high ZEB2 expression was independently associated with poor prognosis. Furthermore, the prognostic effect of E‐cadherin encoded by CDH1 was verified using immunohistochemical analysis of an independent advanced stage cancer samples set (n = 74). These findings suggest that the expression of epithelial–mesenchymal transition‐related genes such as ZEB2 and CDH1 may play important roles in the invasion process of advanced stage serous ovarian cancer. (Cancer Sci 2009)
Glypican‐3 expression is correlated with poor prognosis in hepatocellular carcinoma
Authors: Shirakawa Hirofumi , Suzuki Hitomi , Shimomura Manami , Kojima Motohiro , Gotohda Naoto , Takahashi Shinichiro , Nakagohri Toshio , Konishi Masaru , Kobayashi Nobuaki , Kinoshita Taira , Nakatsura Tetsuya
Published: May 2009

The relationship between overexpression of glypican (GPC)‐3 that is specific for hepatocellular carcinoma (HCC) and the prognosis has not yet been clarified. We attempted to determine the expression profile of GPC3 in association with the clinicopathological factors by immunohistochemical analysis in HCC patients and investigated the potential prognostic value of GPC3 by comparing the survival rate between the GPC3‐positive and GPC3‐negative HCC patients. Primary HCC tissue samples (n = 107) obtained from patients who had undergone hepatectomy between 2000 and 2001 were analyzed. GPC3 expression was less frequently observed in well‐differentiated HCC than in moderately and poorly differentiated HCC, the difference in the frequency being statistically significant. GPC3‐positive HCC patients had a significantly lower 5‐year survival rate than the GPC3‐negative HCC patients (54.5 vs 87.7%, P = 0.031). Among 80 of the 107 (74.6%) patients with initial treatment who underwent hepatectomy, none of GPC3‐negative HCC patients (n = 16, 20.0%) died during the follow‐up period. No deaths were noted in the GPC3‐negative HCC patients among the 71 (88.7%) patients with moderately and poorly differentiated HCC. Multivariate analysis identified GPC3 expression (P = 0.034) as an independent prognostic factor for the overall survival. We showed that GPC3 expression is correlated with a poor prognosis in HCC patients. (Cancer Sci 2009)
‘I felt I have grown up as an adult’: caregiving experience of children affected by HIV/AIDS in China
Authors: Zhang L. , Li X. , Kaljee L. , Fang X. , Lin X. , Zhao G. , Zhao J. , Hong Y.
Published: May 2009

Background  The growing global epidemic of HIV/AIDS has a significant impact on the lives of both people living with HIV/AIDS and their family members including children. Children of parents with HIV/AIDS may experience an increased responsibility of caregiving in family. However, limited data are available regarding the caregiving experience and its impact on psychosocial well‐being among these children. This study was designed to address these issues by using qualitative data collected from children affected by HIV/AIDS in China.

Methods  The qualitative data were collected in 2006 in rural central China, where many residents were infected with HIV/AIDS through unhygienic blood collection procedures. In‐depth individual interviews were conducted by trained interviewers with 47 children between 8 and 17 years of age who had lost one or both parents to AIDS.

Results  Findings of this study suggest that many children affected by AIDS had experienced increased responsibilities in housework and caregiving for family members. Such caregiving included caring for self and younger siblings, caring for parents with illness and caring for elderly grandparents. Positive impacts from children's participation in family caregiving included personal growth and emotional maturity. Negative consequences included physical fatigue, psychological fear and anxiety and suboptimal schooling (dropping out from school, repeated absence from school and unable to concentrate in class).

Conclusion  While the increased caregiving responsibilities among children reflected some cultural beliefs and had some positive effect on personal growth, the caregiving experience generally negatively effected the children's physical and mental health and schooling. The findings in the current study suggest that community‐based caregiving support is necessary in areas with high prevalence of HIV and limited resources, especially for the families lacking adult caregivers. In addition, social and psychological support should be made available for children participating in family caregiving.
Human airway smooth muscle promotes eosinophil differentiation
Authors: Fanat A. I. , Thomson J. V. , Radford K. , Nair P. , Sehmi R.
Published: May 2009

Introduction
Human airway smooth muscle (HASM) cells in culture synthesize cytokines and chemokines that may orchestrate the tissue homing and in situ differentiation of haemopoietic progenitor cells from the peripheral circulation.

Objective
To study the effect of a supernatant from cultured HASM cells on the differentiative and transmigrational responses of haemopoietic progenitor cells.

Methods
HASM cells were grown to confluence and stimulated with a cytomix of TNF‐α, IL‐1β and IFN‐γ. Peripheral blood‐derived progenitors from atopic asthmatics (n=12) and non‐atopic controls (n=11) were grown in a methylcellulose culture with a supernatant from stimulated HASM cells to assess clonogenic potential. The ability of HASM cells to stimulate directional migration and adhesion to fibronectin of blood progenitors was also investigated.

Results
HASM cells stimulated significant growth of eosinophil/basophil colony forming units (Eo/B CFUs) from blood progenitor cells from both groups of subjects. This activity was significantly attenuated in the presence of anti‐IL‐5 and anti‐granulocyte macrophage‐colony forming factor blocking antibodies and by pre‐treatment with SB202190 [p38 mitogen‐activated protein kinase (MAPK) inhibitor]. An src kinase (srcK) inhibitor (Pyrazolopyrimidine 1) was less effective at attenuating IL‐5‐ and HASM‐stimulated Eo/B CFU growth from both groups of subjects. Examination of the phosphorylation of these kinases in CD34+ cells following co‐incubation with the major constituents of HASM showed activation of p38 MAPK but not that of the srcK pathway. The HASM supernatant had no significant effect on the migrational and adhesive responses of haemopoietic progenitor cells in vitro.

Conclusion
We have shown that HASM cell‐derived cytokines promote eosinophil differentiation that is dependent on p38 MAPK but not on the srcK pathway. This study shows that a major structural cell of the lungs, airway smooth muscle, has the capability to direct eosinophil differentiation and maturation from progenitor cells, which in turn may perpetuate an eosinophilic inflammation and consequently tissue remodelling in patients with chronic asthma.
Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo for the symptomatic treatment of seasonal allergic rhinitis: a randomized, double‐blind, parallel‐group study
Authors: Kuna P. , Bachert C. , Nowacki Z. , Van Cauwenberge P. , Agache I. , Fouquert L. , Roger A. , Sologuren A. , Valiente R. ,   The Bilastine International Working Group
Published: May 2009

Background
Bilastine is a new non‐sedative H1 receptor antagonist, indicated for the treatment of allergic rhinitis (AR) (seasonal and perennial).

Objective
To assess and compare the efficacy and safety of bilastine 20 mg vs. cetirizine 10 mg and placebo in relieving the symptoms of seasonal allergic rhinitis (SAR).

Methods
Overall, 683 SAR patients, aged 12–70 years, were randomized to a double‐blind treatment with bilastine 20 mg, cetirizine 10 mg or placebo, once daily for 14 days, in 61 centres across Europe. Patients recorded reflective (over the past 12 h) and instantaneous nasal (obstruction, rhinorrhoea, itching and sneezing) and non‐nasal (ocular tearing, redness and itching) symptom scores (NSS and NNSS, respectively) twice daily, according to a pre‐determined severity scale to provide reflective and instantaneous total symptom scores (TSS). The primary efficacy measure was the area under curve (AUC) of reflective TSS over 14 days of treatment (TSS‐AUC0−14 days). Secondary efficacy measures included mean change from baseline in TSS, NSS and NNSS; discomfort caused by AR; and investigator's clinical global impression of the treatment. Safety was assessed according to adverse events (AEs), laboratory tests and electrocardiograms.

Results
The mean TSS‐AUC0−14 days (score × day) was reduced in bilastine‐ and cetirizine‐treated groups to a similar and significantly greater extent, compared with placebo (76.5, 72.3 and 100.6, respectively; P<0.001). Similarly, bilastine and cetirizine were comparable and significantly superior to placebo for all secondary outcomes. While all treatments were well tolerated and the AE profiles of bilastine and placebo were similar, significantly fewer patients in the bilastine‐treated group experienced somnolence (1.8%; P<0.001) and fatigue (0.4%; P=0.02) than patients in the cetirizine‐treated group (7.5% and 4.8%, respectively).

Conclusions
Bilastine 20 mg once daily was significantly superior to placebo and comparable to cetirizine 10 mg in relieving symptoms of SAR, although it demonstrated a significantly better AE profile than cetirizine.