bluuebunny/crossref_metadata_2025 huggingface dataset:
Arterial spin labeling and dynamic susceptibility contrast CBF MRI in postischemic hyperperfusion, hypercapnia, and after mannitol injection
Authors: Tanaka Yoji , Nagaoka Tsukasa , Nair Govind , Ohno Kikuo , Duong Timothy Q
Published: December 2010

Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) are widely used to image cerebral blood flow (CBF) in stroke. This study examined how changes in tissue spin-lattice relaxation-time constant ( T1), blood-brain barrier (BBB) permeability, and transit time affect CBF quantification by ASL and DSC in postischemic hyperperfusion in the same animals. In Group I ( n = 6), embolic stroke rats imaged 48hours after stroke showed regional hyperperfusion. In normal pixels, ASL- and DSC-CBF linearly correlated pixel-by-pixel. In hyperperfusion pixels, ASL-CBF was significantly higher than DSC-CBF pixel-by-pixel (by 25%). T1 increased from 1.76 ± 0.14 seconds in normal pixels to 1.93 ± 0.17 seconds in hyperperfusion pixels. Arterial transit time decreased from 300 milliseconds in normal pixels to 200 milliseconds in hyperperfusion pixels. Δ R2* profiles showed contrast-agent leakages in the hyperperfusion regions. In Group II ( n = 3) in which hypercapnic inhalation was used to increase CBF without BBB disruption, CBF increased overall but ASL- and DSC-CBF remained linearly correlated. In Group III ( n = 3) in which mannitol was used to break the BBB, ASL-CBF was significantly higher than DSC-CBF. We concluded that in normal tissue, ASL and DSC provide comparable quantitative CBF, whereas in postischemic hyperperfusion, ASL-CBF and DSC-CBF differed significantly because ischemia-induced changes in T1 and BBB permeability affected the two methods differently.
Emergence of tissue polarization from synergy of intracellular and extracellular auxin signaling
Authors: Wabnik Krzysztof , Kleine‐Vehn Jürgen , Balla Jozef , Sauer Michael , Naramoto Satoshi , Reinöhl Vilém , Merks Roeland M H , Govaerts Willy , Friml Jiří
Published: December 2010

Plant development is exceptionally flexible as manifested by its potential for organogenesis and regeneration, which are processes involving rearrangements of tissue polarities. Fundamental questions concern how individual cells can polarize in a coordinated manner to integrate into the multicellular context. In canalization models, the signaling molecule auxin acts as a polarizing cue, and feedback on the intercellular auxin flow is key for synchronized polarity rearrangements. We provide a novel mechanistic framework for canalization, based on up‐to‐date experimental data and minimal, biologically plausible assumptions. Our model combines the intracellular auxin signaling for expression of PINFORMED (PIN) auxin transporters and the theoretical postulation of extracellular auxin signaling for modulation of PIN subcellular dynamics. Computer simulations faithfully and robustly recapitulated the experimentally observed patterns of tissue polarity and asymmetric auxin distribution during formation and regeneration of vascular systems and during the competitive regulation of shoot branching by apical dominance. Additionally, our model generated new predictions that could be experimentally validated, highlighting a mechanistically conceivable explanation for the PIN polarization and canalization of the auxin flow in plants.
Defining the transcriptome and proteome in three functionally different human cell lines
Authors: Lundberg Emma , Fagerberg Linn , Klevebring Daniel , Matic Ivan , Geiger Tamar , Cox Juergen , Älgenäs Cajsa , Lundeberg Joakim , Mann Matthias , Uhlen Mathias
Published: December 2010

An essential question in human biology is how cells and tissues differ in gene and protein expression and how these differences delineate specific biological function. Here, we have performed a global analysis of both mRNA and protein levels based on sequence‐based transcriptome analysis (RNA‐seq), SILAC‐based mass spectrometry analysis and antibody‐based confocal microscopy. The study was performed in three functionally different human cell lines and based on the global analysis, we estimated the fractions of mRNA and protein that are cell specific or expressed at similar/different levels in the cell lines. A highly ubiquitous RNA expression was found with >60% of the gene products detected in all cells. The changes of mRNA and protein levels in the cell lines using SILAC and RNA ratios show high correlations, even though the genome‐wide dynamic range is substantially higher for the proteins as compared with the transcripts. Large general differences in abundance for proteins from various functional classes are observed and, in general, the cell‐type specific proteins are low abundant and highly enriched for cell‐surface proteins. Thus, this study shows a path to characterize the transcriptome and proteome in human cells from different origins.
Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action
Authors: Kapitzky Laura , Beltrao Pedro , Berens Theresa J , Gassner Nadine , Zhou Chunshui , Wüster Arthur , Wu Julie , Babu M Madan , Elledge Stephen J , Toczyski David , Lokey R Scott , Krogan Nevan J
Published: December 2010

We present a cross‐species chemogenomic screening platform using libraries of haploid deletion mutants from two yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. We screened a set of compounds of known and unknown mode of action (MoA) and derived quantitative drug scores (or D‐scores), identifying mutants that are either sensitive or resistant to particular compounds. We found that compound–functional module relationships are more conserved than individual compound–gene interactions between these two species. Furthermore, we observed that combining data from both species allows for more accurate prediction of MoA. Finally, using this platform, we identified a novel small molecule that acts as a DNA damaging agent and demonstrate that its MoA is conserved in human cells.
Drug Use During Antenatal Period at a Tertiary Care Hospital
Authors: Kureshee Nargis , Dhande Priti , Pandit Vijaya
Published: December 2010

Objective

- To assess current treatment practices and awareness of drug intake, in pregnant women, at a tertiary care hospital.Methodology- Observational, cross-sectional study, involving interview with 60 pregnant women, in outpatient clinic and ward of Obstetrics-Gynaecology department. Data from prescriptions & case-files also collected. Drugs were classified according to pharmacological class and teratogenic potential using U.S. FDA classification.

Results

- Most commonly prescribed drugs were iron, folic acid and calcium supplements. Out of the total 215 drugs prescribed, majority were from Category A(70.2%) followed by Category B(18.6%),Category C(8.8%),Category-X(1.3%) and Category-D(0.9%). 26.6% women believed that drugs used during pregnancy can be dangerous to both mother and fetus; 55% believed it is dangerous to fetus alone and 1.6% believed it is dangerous to mother alone. But 16.6% women believed that drugs are safe to both mother and fetus.

Conclusion

- Treatment practices are appropriate but there is a need to educate and counsel pregnant women.
Advances in Critical Fluid Processing
Authors: King Jerry W. , Srinivas Keerthi , Zhang Dongfang
Published: December 2010

Critical fluids have been historically applied as an extraction and/or reaction medium in the food, agricultural and nutraceutical industries. The solution thermodynamic properties of solvents such as water above its boiling point and under pressure, also known as “subcritical water”, is now being commonly employed as an option for the extraction of some polar components such as flavonoids and carbohydrates from natural products. This chapter discusses the application of subcritical fluids in extraction, reaction and/or hydrolysis of value-added products from food and agricultural matrices. Further, we discuss the option of coupling a relatively “polar” subcritical solvent such as water with a “non-polar” supercritical fluid such as carbon dioxide and utilize them in different unit processing modes. Carbonic acid is a “natural” catalyst which allows the pH to be controlled within certain limits and can aid in the extraction of natural products, a replacement for mineral acid catalysts in hydrolysis reactions and in microbial deactivation. Enhanced mass transfer of pressurized fluids through the feed matrix can also be achieved by tandem processing using expellers or extruders. Such processes are now being applied for the extraction of seed oil from matrices. Along with the documented success of SFE using SC-CO2, these additional processing options can accelerate an “all green” sustainable technology platform.
Quantitative Study of Vibrational Symmetry of Injured Vocal Folds Via Digital Kymography in Excised Canine Larynges
Authors: Krausert Christopher R. , Ying Di , Zhang Yu , Jiang Jack J.
Published: December 2010

Purpose

Digital kymography and vocal fold curve fitting are blended with detailed symmetry analysis of kymograms to provide a comprehensive characterization of the vibratory properties of injured vocal folds.

Method

Vocal fold vibration of 12 excised canine larynges was recorded under uninjured, unilaterally injured, and bilaterally injured conditions. Kymograms were created at 25%, 50%, and 75% of the vocal fold length, and vibratory parameters were compared quantitatively among conditions and were studied with respect to right–left and anterior–posterior symmetries.

Results

Anterior–posterior amplitude asymmetry was found in the bilateral condition. The unilateral condition showed significant right–left amplitude asymmetry, and it showed the lowest right–left phase symmetry among the conditions. In condition comparisons, vertical phase difference did not show significant differences among conditions, whereas amplitudes were significantly different among conditions at all line scan positions and most vocal fold lips. Significant differences in frequency were found among the conditions at all 4 vocal fold lips, with the bilateral condition exhibiting the greatest frequency.

Conclusion

Digital kymography and curve fitting provide detailed information about the vibratory behavior of injured vocal folds. Awareness of vibratory properties associated with vocal fold injury may aid in diagnosis, and the quantitative abilities of digital kymography may allow for objective treatment selection.
Treatment of Category Generation and Retrieval in Aphasia: Effect of Typicality of Category Items
Authors: Kiran Swathi , Sandberg Chaleece , Sebastian Rajani
Published: December 2010

Purpose

Kiran and colleagues (Kiran, 2007, 2008; Kiran & Johnson, 2008; Kiran & Thompson, 2003) previously suggested that training atypical examples within a semantic category is a more efficient treatment approach to facilitating generalization within the category than training typical examples. In the present study, the authors extended previous work examining the notion of semantic complexity within goal-derived (ad hoc) categories in individuals with aphasia.

Methods

Six individuals with fluent aphasia (age range = 39–84 years) and varying degrees of naming deficits and semantic impairments were involved. Thirty typical and atypical items, each from 2 categories, were selected after an extensive stimulus norming task. Generative naming for the 2 categories was tested during baseline and treatment.

Results

As predicted, training atypical examples in the category resulted in generalization to untrained typical examples in 5 of 5 patient–treatment conditions. In contrast, training typical examples (which was examined in 3 conditions) produced mixed results. One patient showed generalization to untrained atypical examples, whereas 2 patients did not show generalization to untrained atypical examples.

Conclusion

Results of the present study supplement existing data on the effect of a semantically based treatment for lexical retrieval by manipulating the typicality of category examples.
Perceptual Adaptation of Voice Gender Discrimination With Spectrally Shifted Vowels
Authors: Li Tianhao , Fu Qian-Jie
Published: December 2010

Purpose

To determine whether perceptual adaptation improves voice gender discrimination of spectrally shifted vowels and, if so, which acoustic cues contribute to the improvement.

Method

Voice gender discrimination was measured for 10 normal-hearing subjects, during 5 days of adaptation to spectrally shifted vowels, produced by processing the speech of 5 male and 5 female talkers with 16-channel sine-wave vocoders. The subjects were randomly divided into 2 groups; one subjected to 50-Hz, and the other to 200-Hz, temporal envelope cutoff frequencies. No preview or feedback was provided.

Results

There was significant adaptation in voice gender discrimination with the 200-Hz cutoff frequency, but significant improvement was observed only for 3 female talkers with F
0
> 180 Hz and 3 male talkers with F
0
< 170 Hz. There was no significant adaptation with the 50-Hz cutoff frequency.

Conclusions

Temporal envelope cues are important for voice gender discrimination under spectral shift conditions with perceptual adaptation, but spectral shift may limit the exclusive use of spectral information and/or the use of formant structure on voice gender discrimination. The results have implications for cochlear implant users and for understanding voice gender discrimination.
Adhesion and cyclic stretching of Au thin film on poly(dimethyl-siloxane) for stretchable electronics
Authors: Akogwu Onobu , Kwabi David , Munhutu Auxillia , Tong Tiffany , Soboyejo W. O.
Published: December 2010

This paper presents the results of an experimental study of the effects of cyclic damage and adhesion on nanoscale Au thin films deposited on a flexible poly(dimethyl-siloxane) substrate. The deformation and cracking mechanisms are elucidated as functions of film thickness. The implications of the results are also discussed for the design of stretchable electronic structures.
Asymptotics of Selberg-like integrals: The unitary case and Newton's interpolation formula
Authors: Carré Christophe , Deneufchatel Matthieu , Luque Jean-Gabriel , Vivo Pierpaolo
Published: December 2010

We investigate the asymptotic behavior of the Selberg-like integral \documentclass[12pt]{minimal}\begin{document}$\frac{1}{N!}\int _{[0,1]^N}x_1^p$\break $\prod _{i<j}(x_i-x_j)^2\prod _ix_i^{a-1}(1-x_i)^{b-1}dx_i,$\end{document}1N!∫[0,1]Nx1p∏i<j(xi−xj)2∏ixia−1(1−xi)b−1dxi, as N → ∞ for different scalings of the parameters a and b with N. Integrals of this type arise in the random matrix theory of electronic scattering in chaotic cavities supporting N channels in the two attached leads. Making use of Newton's interpolation formula, we show that an asymptotic limit exists and we compute it explicitly.
On the phase behavior of hard aspherical particles
Authors: Miller William L. , Cacciuto Angelo
Published: December 2010

We use numerical simulations to understand how random deviations from the ideal spherical shape affect the ability of hard particles to form fcc crystalline structures. Using a system of hard spheres as a reference, we determine the fluid-solid coexistence pressures of both shape-polydisperse and monodisperse systems of aspherical hard particles. We find that when particles are sufficiently isotropic, the coexistence pressure can be predicted from a linear relation involving the product of two simple geometric parameters characterizing the asphericity of the particles. Finally, our results allow us to gain direct insight into the crystallizability limits of these systems by rationalizing empirical data obtained for analogous monodisperse systems.
Three-dimensional Brownian diffusion of rod-like macromolecules in the presence of randomly distributed spherical obstacles: Molecular dynamics simulation
Authors: Sakha Farzaneh , Fazli Hossein
Published: December 2010

Brownian diffusion of rod-like polymers in the presence of randomly distributed spherical obstacles is studied using molecular dynamics simulations. It is observed that dependence of the reduced diffusion coefficient of these macromolecules on the available volume fraction can be described reasonably by a power law function. Despite the case of obstructed diffusion of flexible polymers in which reduced diffusion coefficient has a weak dependence on the polymer length, this dependence is noticeably strong in the case of rod-like polymers. Diffusion of these macromolecules in the presence of obstacles is observed that is anomalous at short time scales and normal at long times. Duration time of the anomalous diffusion regime is found that increases very rapidly with increasing both the polymer length and the obstructed volume fraction. Dynamics of diffusion of these polymers is observed that crosses over from Rouse to reptation type with increasing the density of obstacles.
Shell structures of assemblies of equicharged particles subject to radial power-law confining potentials
Authors: Cioslowski Jerzy
Published: December 2010

Constituting the simplest generalization of spherical Coulomb crystals, assemblies of N equicharged particles confined by radial potentials proportional to the λth power of distance are amenable to rigorous analysis within the recently introduced shell model. Thanks to the power scaling of the confining potential and the resulting pruning property of the shell configurations (i.e., the lists of shell occupancies), the shell-model estimates of the energies and the mean radii of such assemblies at equilibrium geometries follow simple recursive formulas. The formulas greatly facilitate derivations of the first two leading terms in the large-N asymptotics of these estimates, which are given by power series in \documentclass[12pt]{minimal}\begin{document}$\xi ^{4/3}\:N^{-2/3}$\end{document}ξ4/3N−2/3, where \documentclass[12pt]{minimal}\begin{document}$-(\xi /2)\; n^{3/2}$\end{document}−(ξ/2)n3/2 is the leading angular-correlation correction to the minimum energy of n electrons on the surface of a sphere with a unit radius (the solution of the Thomson problem). Although the scaled occupancies of the outermost shells conform to a universal scaling law, the actual filling of the shells tends to follow rather irregular patterns that vary strongly with λ. However, the number of shells K(N) for a given N decreases in general upon an increase in the power-law exponent, which is due to the \documentclass[12pt]{minimal}\begin{document}$(\lambda +1)^2\:\xi ^2$\end{document}(λ+1)2ξ2 dependence of shell capacities that roughly measure the maximum numbers of particles sustainable within individual shells. Several types of configuration transitions (i.e., the changes in the number of shells upon addition of one particle) are observed in the crystals with up to 10 000 particles and integer values of λ between 1 and 10, but the rule |K(N + 1) − K(N)| ⩽ 1 is found to be strictly obeyed.
Equations of state for energetic materials from density functional theory with van der Waals, thermal, and zero-point energy corrections
Authors: Landerville A. C. , Conroy M. W. , Budzevich M. M. , Lin Y. , White C. T. , Oleynik I. I.
Published: December 2010

It is shown that the introduction of zero-point energy and thermal effects to density functional theory with an empirical van der Waals correction results in a significant improvement in the prediction of equilibrium volumes and isothermal equations of state for hydrostatic compressions of energetic materials at nonzero temperatures. This method can be used to predict the thermophysical properties of these materials for a wide range of pressures and temperatures.
Room temperature multiferroic effects in superlattice nanocapacitors
Authors: Dussan S. , Kumar A. , Scott J. F. , Priya S. , Katiyar R. S.
Published: December 2010

A composite nanocapacitor was fabricated based on ferroelectric PbZr0.52Ti0.48O3(PZT) and half-metallic oxide La0.67Sr0.33MnO3(LSMO) with 5 nm/1 nm periodicity, respectively. X-ray θ-2θ scan and Φ-scan revealed epitaxial growth of nanocapacitors. At room temperature, a microscopic polarization of 11 μC/cm2 and magnetization of 50 emu/cm3 were measured for superlattice nanocapacitors. Local piezo force microscopy measurements revealed switching of polarization under external bias field confirming ferroelectric behavior. Zero field cooling measurements showed the existence of cusp in magnetization at low temperatures indicating spin-glass-like behavior contrary to Pb(ZrxTi1−x)O3/LaxSr1−xMnO3 bilayer structure. Frequency dependent dielectric anomaly was observed near room temperature suggesting dynamic magneto (resistance)-dielectric coupling.
Reduction in reset current of unipolar NiO-based resistive switching through nickel interfacial layer
Authors: Lee Hyung Dong , Nishi Yoshio
Published: December 2010

The role of interface between electrode and NiO on switching characteristics has been investigated for unipolar NiO-based resistive switching. The ten time reduction of reset current could be achieved relative to a few milliamperes in many literatures by inserting a thin nickel interfacial layer between cathodic electrode and NiO. A model describing the reduction of reset current mechanism was derived from the combination effect of oxygen vacancy formation/migration and the interfacial oxide layer at cathodic electrode.
Time-resolved amplified spontaneous emission in quantum dots
Authors: Gomis-Bresco J. , Dommers-Völkel S. , Schöps O. , Kaptan Y. , Dyatlova O. , Bimberg D. , Woggon U.
Published: December 2010

In time-resolved experiments at InGaAs/GaAs quantum-dots-in-a-well (DWELL) semiconductor optical amplifiers, pump-probe of the ground state (GS) population, and complementary measurement of the amplified spontaneous emission of the excited state (ES) population, we are able to separate the early subpicosecond dephasing dynamics from the later picosecond population relaxation dynamics. We observe a 10 ps delay between the nonlinear GS pulse amplification and the subsequent ES population drop-off that supports the dominance of a direct two dimensional reservoir-GS capture relaxation path in electrically pumped quantum-dot-DWELL structures.
Exploitation of a self-limiting process for reproducible formation of ultrathin Ni1−xPtx silicide films
Authors: Zhang Zhen , Yang Bin , Zhu Yu , Gaudet Simon , Rossnagel Steve , Kellock Andrew J. , Ozcan Ahmet , Murray Conal , Desjardins Patrick , Zhang Shi-Li , Jordan-Sweet Jean , Lavoie Christian
Published: December 2010

This letter reports on a process scheme to obtain highly reproducible Ni1−xPtx silicide films of 3–6 nm thickness formed on a Si(100) substrate. Such ultrathin silicide films are readily attained by sputter deposition of metal films, metal stripping in wet chemicals, and final silicidation by rapid thermal processing. This process sequence warrants an invariant amount of metal intermixed with Si in the substrate surface region independent of the initial metal thickness, thereby leading to a self-limiting formation of ultrathin silicide films. The crystallographic structure, thickness, uniformity, and morphological stability of the final silicide films depend sensitively on the initial Pt fraction.
Contamination of Antarctic snow by polycyclic aromatic hydrocarbons dominated by combustion sources in the polar region
Authors: Kukučka Petr , Lammel Gerhard , Dvorská Alice , Klánová Jana , Möller Andrea , Fries Elke
Published: December 2010

Environmental context Is long-range transport from populated and industrialised areas to blame for pollution of remote regions? We report that, for the world's most remote region, Antarctica, and one prominent class of global pollutants, polycyclic aromatic hydrocarbons, long-range transport from other continents has not contributed significantly to recent snow contamination. Rather, the major sources are regional scientific stations and ocean transport, mostly tourism. Abstract Firn samples attributed to the period between 2002 and 2005 were collected from a snow pit on the Ekström Shelf Ice in the Weddell Sea (70°43.8′S, 8°25.1′W). Low-volume meltwater samples (5 mL) were extracted by solid-phase microextraction (SPME) and analysed for polycyclic aromatic hydrocarbons (PAHs) by gas chromatography-mass spectrometry. The recovery of the analytical method for the 4–6 ring PAHs was low. PAH concentrations in snow were found within the range of 26–197 ng L–1. The most prevailing substances were determined to be naphthalene, 1- and 2-methylnaphthalene, acenaphthylene, acenaphthene and phenanthrene, with naphthalene accounting for an overall mean of 82% of total PAH. Potential emission sources of PAHs in snow were studied using back-trajectory statistics and available emission data of combustion sources in and around Antarctica. The distance to the sources (ships and research stations) in this region was found to control the snow PAH concentrations. There was no indication for intercontinental transport or marine sources.
Photochlorination of bisphenol A by UV-Vis light irradiation in saline solution: effects of iron, nitrate and citric acid
Authors: Liu Hui , Zhao Huimin , Chen Shuo , Quan Xie , Zhang Yaobin
Published: December 2010

Environmental context Chlorinated organic compounds are ubiquitous in the environment, and cause concern owing to their persistence and toxicity to organisms. In addition to anthropogenic sources, photochemical processes in saline waters could also yield chlorinated organic compounds. The present paper investigates the effects of iron, pH, nitrate and dissolved organic matter on the photochlorination of bisphenol A, a widely distributed endocrine disrupting chemical. Abstract Effects of several key influencing factors of environmental photochemistry, including iron, nitrate and dissolved organic matter (DOM), on the photochlorination of bisphenol A (BPA) were investigated. Iron promoted the formation of chlorinated BPA, but the rate decreased with increasing pH. This result was consistent with the results of laser flash photolysis, which showed that high pH decreased the formation of reactive chlorine species (chlorine radical, Cl•/Cl2•–). Nitrate ion and citric acid, which was selected as an analogue of DOM, inhibited the chlorination of BPA separately. The results presented in this paper are helpful to get some idea of the degree of photochemical chlorination in aqueous environment.
The use of immunocontraception to improve rabies eradication in urban dog populations
Authors: Carroll Matthew J. , Singer Alexander , Smith Graham C. , Cowan Dave P. , Massei Giovanna
Published: December 2010

ContextRabies causes ~55 000 human deaths each year, primarily as a result of bites from dogs, which are the major rabies reservoir in the developing world. Current rabies control strategies include vaccination, culling and surgical sterilisation of dogs. However, recently developed immunocontraceptives could be used alongside vaccination to apply fertility control to more animals. AimsWe used a modelling approach to explore (1) whether adding single-dose contraceptives to rabies vaccination would improve effectiveness of rabies eradication, (2) how sensitive control methods are to variation in population parameters and (3) the effects of applying control continuously or in pulses on rabies eradication. MethodsA continuous time, compartmental model was created to describe canine rabies epidemiology. Parameters were derived from the literature. The following three control methods were applied at varying rates and durations: vaccination, vaccination plus fertility control (v + fc) and culling. Outcomes were classified into the following three categories: rabies persistence, rabies eradication and population extinction. Key resultsWhen control was applied continuously for up to 24 months, vaccination was least effective; the effort required to eradicate rabies was about twice that required with culling or v + fc. At realistic control rates, only v + fc consistently resulted in rabies eradication. Increasing population growth rate and city size made rabies eradication harder; for vaccination, considerably greater control rates and durations were required, whereas culling and v + fc showed only minor decreases in effectiveness. When control was applied for 1 or 2 months (for one month every 12 months or every 6 months) per year for up to 20 years, vaccination became less effective because of population turnover between control periods; v + fc lost little effectiveness, as decreased birth rates reduced the input of susceptible animals. ConclusionsUsing immunocontraception alongside vaccination could improve rabies control campaigns by reducing the proportion of the population that must be treated, or reducing the necessary duration of the campaign. It could also make control effective under larger population growths, in larger cities and when control is pulsed. ImplicationsImmunocontraceptives could become a useful tool in canine rabies control by allowing fertility control to be applied on a large scale. Further work is required to improve understanding of dog ecology and parameterise location-specific models, which could be used to inform management plans.
Support for agriculture during economic transformation: Impacts on poverty and undernutrition
Authors: Webb Patrick , Block Steven
Published: December 2010

This paper explores trends in poverty and nutrition during economic transformation and especially the impacts linked to government support for agriculture during the process. Analysis of multiyear data for 29 developing countries confirms that structural transformation raises total income and that poverty falls faster with strong support for agriculture. In turn, poverty reduction supports improved nutrition, especially in rural areas. However, transformation brings problems through health risks associated with rising obesity in rural as well as urban areas. Thus, the transition process must be managed better, through targeted support for smallholder agriculture and health interventions, if the negative consequences of obesity and chronic disease are to be mitigated.
Lamin A variants that cause striated muscle disease are defective in anchoring transmembrane actin-associated nuclear lines for nuclear movement
Authors: Folker Eric S. , Östlund Cecilia , Luxton G. W. Gant , Worman Howard J. , Gundersen Gregg G.
Published: December 2010

Mutations in
LMNA
, which encodes A-type lamins, result in disparate diseases, known collectively as laminopathies, that affect distinct tissues, including striated muscle and adipose tissue. Lamins provide structural support for the nucleus and sites of attachment for chromatin, and defects in these functions may contribute to disease pathogenesis. Recent studies suggest that A-type lamins may facilitate connections between the nucleus and the cytoskeleton mediated by nuclear envelope nesprin and SUN proteins. In mammalian cells, however, interfering with A-type lamins does not affect the localization of these proteins. Here, we used centrosome orientation in fibroblasts, which requires separate nuclear and centrosome positioning pathways, as a model system to understand how
LMNA
mutations affect nucleus-cytoskeletal connections. We find that
LMNA
mutations causing striated muscle diseases block actin-dependent nuclear movement, whereas most that affect adipose tissue inhibit microtubule-dependent centrosome positioning. Genetic deletion or transient depletion of A-type lamins also blocked nuclear movement, showing that mutations affecting muscle exhibit the null phenotype. Lack of A-type lamins, or expression of variants that cause striated muscle disease, did not affect assembly of nesprin-2G and SUN2 into transmembrane actin-associated nuclear (TAN) lines that attach the nucleus to retrogradely moving actin cables. Nesprin-2G TAN lines were less stable, however, and slipped over the nucleus rather than moving with it, indicating that they were not anchored. Nesprin-2G TAN lines also slipped in SUN2-depleted cells. Our results establish A-type lamins as anchors for nesprin-2G–SUN2 TAN lines to allow productive movement and proper positioning of the nucleus by actin.
Global declines in oceanic nitrification rates as a consequence of ocean acidification
Authors: Beman J. Michael , Chow Cheryl-Emiliane , King Andrew L. , Feng Yuanyuan , Fuhrman Jed A. , Andersson Andreas , Bates Nicholas R. , Popp Brian N. , Hutchins David A.
Published: December 2010

Ocean acidification produced by dissolution of anthropogenic carbon dioxide (CO
2
) emissions in seawater has profound consequences for marine ecology and biogeochemistry. The oceans have absorbed one-third of CO
2
emissions over the past two centuries, altering ocean chemistry, reducing seawater pH, and affecting marine animals and phytoplankton in multiple ways. Microbially mediated ocean biogeochemical processes will be pivotal in determining how the earth system responds to global environmental change; however, how they may be altered by ocean acidification is largely unknown. We show here that microbial nitrification rates decreased in every instance when pH was experimentally reduced (by 0.05–0.14) at multiple locations in the Atlantic and Pacific Oceans. Nitrification is a central process in the nitrogen cycle that produces both the greenhouse gas nitrous oxide and oxidized forms of nitrogen used by phytoplankton and other microorganisms in the sea; at the Bermuda Atlantic Time Series and Hawaii Ocean Time-series sites, experimental acidification decreased ammonia oxidation rates by 38% and 36%. Ammonia oxidation rates were also strongly and inversely correlated with pH along a gradient produced in the oligotrophic Sargasso Sea (
r
2
= 0.87,
P
< 0.05). Across all experiments, rates declined by 8–38% in low pH treatments, and the greatest absolute decrease occurred where rates were highest off the California coast. Collectively our results suggest that ocean acidification could reduce nitrification rates by 3–44% within the next few decades, affecting oceanic nitrous oxide production, reducing supplies of oxidized nitrogen in the upper layers of the ocean, and fundamentally altering nitrogen cycling in the sea.
Ferromagnetism in the upper branch of the Feshbach resonance and the hard-sphere Fermi gas
Authors: Chang Soon-Yong , Randeria Mohit , Trivedi Nandini
Published: December 2010

We address the question of ferromagnetism in repulsive Fermi gas, a problem of fundamental interest, using quantum Monte Carlo simulations that include backflow corrections. We investigate a two-component Fermi gas on the upper branch of a Feshbach resonance and contrast it with the hard-sphere gas. We find that, in both cases, the Fermi liquid becomes unstable to ferromagnetism at a
k

F

a
smaller than the mean field result, where
k

F

is the Fermi wavevector and
a
is the scattering length. Even though the total energies
E
(
k

F

a
) are similar in the two cases, their pair correlations and kinetic energies are completely different, reflecting the underlying potentials. We discuss the extent to which our calculations shed light on recent experiments.
Role for topoisomerase 1 in transcription-associated mutagenesis in yeast
Authors: Lippert Malcolm J. , Kim Nayun , Cho Jang-Eun , Larson Ryan P. , Schoenly Nathan E. , O'Shea Shannon H. , Jinks-Robertson Sue
Published: December 2010

High levels of transcription in
Saccharomyces cerevisiae
are associated with increased genetic instability, which has been linked to DNA damage. Here, we describe a
pGAL-CAN1
forward mutation assay for studying transcription-associated mutagenesis (TAM) in yeast. In a wild-type background with no alterations in DNA repair capacity, ≈50% of forward mutations that arise in the
CAN1
gene under high-transcription conditions are deletions of 2–5 bp. Furthermore, the deletions characteristic of TAM localize to discrete hotspots that coincide with 2–4 copies of a tandem repeat. Although the signature deletions of TAM are not affected by the loss of error-free or error-prone lesion bypass pathways, they are completely eliminated by deletion of the
TOP1
gene, which encodes the yeast type IB topoisomerase. Hotspots can be transposed into the context of a frameshift reversion assay, which is sensitive enough to detect Top1-dependent deletions even in the absence of high transcription. We suggest that the accumulation of Top1 cleavage complexes is related to the level of transcription and that their removal leads to the signature deletions. Given the high degree of conservation between DNA metabolic processes, the links established here among transcription, Top1, and mutagenesis are likely to extend beyond the yeast system.
Pressure-induced superconductivity in topological parent compound Bi
2
Te
3
Authors: Zhang J. L. , Zhang S. J. , Weng H. M. , Zhang W. , Yang L. X. , Liu Q. Q. , Feng S. M. , Wang X. C. , Yu R. C. , Cao L. Z. , Wang L. , Yang W. G. , Liu H. Z. , Zhao W. Y. , Zhang S. C. , Dai X. , Fang Z. , Jin C. Q.
Published: December 2010

We report a successful observation of pressure-induced superconductivity in a topological compound Bi
2
Te
3
with
T

c

of ∼3 K between 3 to 6 GPa. The combined high-pressure structure investigations with synchrotron radiation indicated that the superconductivity occurred at the ambient phase without crystal structure phase transition. The Hall effects measurements indicated the hole-type carrier in the pressure-induced superconducting Bi
2
Te
3
single crystal. Consequently, the first-principles calculations based on the structural data obtained by the Rietveld refinement of X-ray diffraction patterns at high pressure showed that the electronic structure under pressure remained topologically nontrivial. The results suggested that topological superconductivity can be realized in Bi
2
Te
3
due to the proximity effect between superconducting bulk states and Dirac-type surface states. We also discuss the possibility that the bulk state could be a topological superconductor.
Evolution in a family of chelatases facilitated by the introduction of active site asymmetry and protein oligomerization
Authors: Romão Célia V. , Ladakis Dimitrios , Lobo Susana A. L. , Carrondo Maria A. , Brindley Amanda A. , Deery Evelyne , Matias Pedro M. , Pickersgill Richard W. , Saraiva Lígia M. , Warren Martin J.
Published: December 2010

The class II chelatases associated with heme, siroheme, and cobalamin biosynthesis are structurally related enzymes that insert a specific metal ion (Fe
2+
or Co
2+
) into the center of a modified tetrapyrrole (protoporphyrin or sirohydrochlorin). The structures of two related class II enzymes, CbiX
S
from
Archaeoglobus fulgidus
and CbiK from
Salmonella enterica
, that are responsible for the insertion of cobalt along the cobalamin biosynthesis pathway are presented in complex with their metallated product. A further structure of a CbiK from
Desulfovibrio vulgaris
Hildenborough reveals how cobalt is bound at the active site. The crystal structures show that the binding of sirohydrochlorin is distinctly different to porphyrin binding in the protoporphyrin ferrochelatases and provide a molecular overview of the mechanism of chelation. The structures also give insights into the evolution of chelatase form and function. Finally, the structure of a periplasmic form of
Desulfovibrio vulgaris
Hildenborough CbiK reveals a novel tetrameric arrangement of its subunits that are stabilized by the presence of a heme
b
cofactor. Whereas retaining colbaltochelatase activity, this protein has acquired a central cavity with the potential to chaperone or transport metals across the periplasmic space, thereby evolving a new use for an ancient protein subunit.
How instructed knowledge modulates the neural systems of reward learning
Authors: Li Jian , Delgado Mauricio R. , Phelps Elizabeth A.
Published: December 2010

Recent research in neuroeconomics has demonstrated that the reinforcement learning model of reward learning captures the patterns of both behavioral performance and neural responses during a range of economic decision-making tasks. However, this powerful theoretical model has its limits. Trial-and-error is only one of the means by which individuals can learn the value associated with different decision options. Humans have also developed efficient, symbolic means of communication for learning without the necessity for committing multiple errors across trials. In the present study, we observed that instructed knowledge of cue-reward probabilities improves behavioral performance and diminishes reinforcement learning-related blood-oxygen level-dependent (BOLD) responses to feedback in the nucleus accumbens, ventromedial prefrontal cortex, and hippocampal complex. The decrease in BOLD responses in these brain regions to reward-feedback signals was functionally correlated with activation of the dorsolateral prefrontal cortex (DLPFC). These results suggest that when learning action values, participants use the DLPFC to dynamically adjust outcome responses in valuation regions depending on the usefulness of action-outcome information.
Experimental support for the evolution of symmetric protein architecture from a simple peptide motif
Authors: Lee Jihun , Blaber Michael
Published: December 2010

The majority of protein architectures exhibit elements of structural symmetry, and “gene duplication and fusion” is the evolutionary mechanism generally hypothesized to be responsible for their emergence from simple peptide motifs. Despite the central importance of the gene duplication and fusion hypothesis, experimental support for a plausible evolutionary pathway for a specific protein architecture has yet to be effectively demonstrated. To address this question, a unique “top-down symmetric deconstruction” strategy was utilized to successfully identify a simple peptide motif capable of recapitulating, via gene duplication and fusion processes, a symmetric protein architecture (the threefold symmetric β-trefoil fold). The folding properties of intermediary forms in this deconstruction agree precisely with a previously proposed “conserved architecture” model for symmetric protein evolution. Furthermore, a route through foldable sequence-space between the simple peptide motif and extant protein fold is demonstrated. These results provide compelling experimental support for a plausible evolutionary pathway of symmetric protein architecture via gene duplication and fusion processes.
Resistance to discodermolide, a microtubule-stabilizing agent and senescence inducer, is 4E-BP1–dependent
Authors: Chao Suzan K. , Lin Juan , Brouwer-Visser Jurriaan , Smith Amos B. , Horwitz Susan Band , McDaid Hayley M.
Published: December 2010

Discodermolide is a microtubule-stabilizing agent that induces accelerated cell senescence. A discodermolide-resistant cell line, AD32, was generated from the human lung cancer cell line A549. We hypothesize that the major resistance mechanism in these cells is escape from accelerated senescence. AD32 cells have decreased levels of 4E-BP1 mRNA and protein, relative to the parental discodermolide-sensitive A549 cells. Lentiviral-mediated re-expression of wild-type 4E-BP1 in AD32 cells increased the proliferation rate and reverted resistance to discodermolide via restoration of discodermolide-induced accelerated senescence. Consistent with this, cell growth and response to discodermolide was confirmed in vivo using tumor xenograft models. Furthermore, reintroduction of a nonphosphorylatable mutant (Thr-37/46 Ala) of 4E-BP1 was able to partially restore sensitivity and enhance proliferation in AD32 cells, suggesting that these effects are independent of phosphorylation by mTORC1. Microarray profiling of AD32-resistant cells versus sensitive A549 cells, and subsequent unbiased gene ontology analysis, identified molecular pathways and functional groupings of differentially expressed mRNAs implicated in overcoming discodermolide-induced senescence. The most statistically significant classes of differentially expressed genes included p53 signaling, G2/M checkpoint regulation, and genes involved in the role of BRCA1 in the DNA damage response. Consistent with this, p53 protein expression was up-regulated and had increased nuclear localization in AD32 cells relative to parental A549 cells. Furthermore, the stability of p53 was enhanced in AD32 cells. Our studies propose a role for 4E-BP1 as a regulator of discodermolide-induced accelerated senescence.
Epstein–Barr virus nuclear antigen 3C regulated genes in lymphoblastoid cell lines
Authors: Zhao Bo , Mar Jessica C. , Maruo Seiji , Lee Sungwook , Gewurz Benjamin E. , Johannsen Eric , Holton Kristina , Rubio Renee , Takada Kenzo , Quackenbush John , Kieff Elliott
Published: December 2010

EBV nuclear antigen 3C (EBNA3C) is an essential transcription factor for EBV transformed lymphoblast cell line (LCL) growth. To identify EBNA3C-regulated genes in LCLs, microarrays were used to measure RNA abundances in each of three different LCLs that conditionally express EBNA3C fused to a 4-OH-Tamoxifen–dependent estrogen receptor hormone binding domain (EBNA3CHT). At least three RNAs were assayed for each EBNA3CHT LCL under nonpermissive conditions, permissive conditions, and nonpermissive conditions with wild-type EBNA3C transcomplementation. Using a two-way ANOVA model of EBNA3C levels, we identified 550 regulated genes that were at least 1.5-fold up- or down-regulated with false discovery rates < 0.01. EBNA3C-regulated genes overlapped significantly with genes regulated by EBNA2 and EBNA3A consistent with coordinated effects on cell gene transcription. Of the 550 EBNA3C-regulated genes, 106 could be placed in protein networks. A seeded Bayesian network analysis of the 80 most significant EBNA3C-regulated genes suggests that RAC1, LYN, and TNF are upstream of other EBNA3C-regulated genes. Gene set enrichment analysis found enrichment for MAP kinase signaling, cytokine–cytokine receptor interactions, JAK-STAT signaling, and cell adhesion molecules, implicating these pathways in EBNA3C effects on LCL growth or survival. EBNA3C significantly up-regulated the CXCL12 ligand and its CXCR4 receptor and increased LCL migration. CXCL12 up-regulation depended on EBNA3C's interaction with the cell transcription factor, RBPJ, which is essential for LCL growth. EBNA3C also up-regulated MYC 1.3-fold and down-regulated CDKN2A exons 2 and 3, shared by p16 and p14, 1.4-fold, with false discovery rates < 5 × 10
−4
.
Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver
Authors: Österreicher Christoph H. , Penz-Österreicher Melitta , Grivennikov Sergei I. , Guma Monica , Koltsova Ekaterina K. , Datz Christian , Sasik Roman , Hardiman Gary , Karin Michael , Brenner David A.
Published: December 2010

Cirrhosis is the end result of chronic liver disease. Hepatic stellate cells (HSC) are believed to be the major source of collagen-producing myofibroblasts in cirrhotic livers. Portal fibroblasts, bone marrow-derived cells, and epithelial to mesenchymal transition (EMT) might also contribute to the myofibroblast population in damaged livers. Fibroblast-specific protein 1 (FSP1, also called S100A4) is considered a marker of fibroblasts in different organs undergoing tissue remodeling and is used to identify fibroblasts derived from EMT in several organs including the liver. The aim of this study was to characterize FSP1-positive cells in human and experimental liver disease. FSP1-positive cells were increased in human and mouse experimental liver injury including liver cancer. However, FSP1 was not expressed by HSC or type I collagen-producing fibroblasts. Likewise, FSP1-positive cells did not express classical myofibroblast markers, including αSMA and desmin, and were not myofibroblast precursors in injured livers as evaluated by genetic lineage tracing experiments. Surprisingly, FSP1-positive cells expressed F4/80 and other markers of the myeloid-monocytic lineage as evaluated by double immunofluorescence staining, cell fate tracking, flow cytometry, and transcriptional profiling. Similar results were obtained for bone marrow-derived and peritoneal macrophages. FSP1-positive cells were characterized by increased expression of COX2, osteopontin, inflammatory cytokines, and chemokines but reduced expression of MMP3 and TIMP3 compared with Kupffer cells/macrophages. These findings suggest that FSP1 is a marker of a specific subset of inflammatory macrophages in liver injury, fibrosis, and cancer.