bluuebunny/crossref_metadata_2025 huggingface dataset:
Patch-distribution effect on diffusion-limited process in dilute suspension of partially active spheres
Authors: Wu Jui-Chuang , Lu Shih-Yuan
Published: January 2006

The normalized overall rate constant, kp∕kf for diffusion-limited processes in a dilute suspension of spheres, partially covered with active patches of varying distribution states, is studied with sped-up Brownian dynamic simulations. A dimensionless separation index Is is defined to quantify the characteristics of patch distribution on the sphere surfaces, with values of 0 and 1 corresponding to the states of the most compact and loosest patch distributions, respectively. Remarkably, the normalized overall rate constant is found to strongly correlate with the dimensionless separation index at fixed patch coverage fcover exhibiting a positive, linear relationship. In addition, the slope of the kp∕kfvsIs line, a measure of sensitivity of kp∕kf to variation in the separation state of the distributed patches, is found to depend on patch coverage and patch size. This sensitivity exhibits a maximum value with respect to an increase in patch coverage, and the magnitude of the maximum sensitivity decreases with increasing patch size. The patch coverage, at which the maximum sensitivity occurs, increases with increasing patch size.
Numerical simulation of kinetic Alfvén waves to study filament formation and their nonlinear dynamics in solar wind and corona
Authors: Singh H. D. , Sharma R. P.
Published: January 2006

This paper presents a numerical simulation leading to the formation of intense magnetic filaments of kinetic Alfvén waves (KAWs) in steady state when the nonlinearity arises due to ponderomotive effects and Joule heating. The nonlinear dynamical equation for the KAW satisfies the modified nonlinear Schrödinger equation. When the plain KAW is perturbed by a transverse perturbation, filamentary structures in solar wind and coronal holes are observed. By changing the parameters of the perturbation (such as the wave number and the phase factor), filamentary structures of KAW magnetic field have been observed. The effect of the change of the dimensionless transverse wave number Γ (normalized in terms of electron’s collisionless skin depth of the KAW) plays a very important role on filamentary dynamics. Besides the study of the magnetic-field intensity, we have done various diagnostics such as phase portraits and surface plots, and also studied the power spectrum. The effect of changing the value of Γ on power spectrum is significant. The motion is found to be quasiperiodic and appears to be chaotic for different parametric regimes. The relevance of these studies in coronal heating and solar wind acceleration/turbulence has also been pointed out.
Combinatorial investigation of the isolated nanoparticle to coalescent layer transition in a gradient sputtered gold nanoparticle layer on top of polystyrene
Authors: Roth S. V. , Walter H. , Burghammer M. , Riekel C. , Lengeler B. , Schroer C. , Kuhlmann M. , Walther T. , Sehrbrock A. , Domnick R. , Müller-Buschbaum P.
Published: January 2006

Within a combinatorial investigation, a gradient sputtered gold layer on top of polystyrene on silicon substrate is addressed. Results from a real-space inspection by transmission electron microscopy are compared with surface-sensitive microbeam grazing incidence small-angle x-ray scattering. The combinatorial approach allows distinguishing different morphologies prepared under exactly the same environmental conditions on one single substrate. The transition of a coalescent layer to an isolated nanoparticle layer is determined as a function of sputter rate. Though optical spectra show only slight differences, the morphology and structure are distinctly different from evaporated layers prepared with same mass thickness.
Suspended architecture formation process of single-walled carbon nanotubes
Authors: Homma Yoshikazu , Takagi Daisuke , Kobayashi Yoshihiro
Published: January 2006

The formation processes of suspended structures and bundles of single-walled carbon nanotubes (SWNTs) are directly observed by in situ scanning electron microscopy during chemical vapor deposition of SWNTs on a patterned specimen. SWNTs exhibit lively movements during extension from micropillar patterns, resulting in bridging, bundling, merging, and debundling. Fluctuation of the extension direction of a SWNT cantilever is observed. Swing of the SWNT cantilever is the reason for the enhanced-nearest-neighbor interconnection.
Polymeric conical structure formation by probe-induced electrohydrodynamical nanofluidic motion
Authors: Chung Hong Jing , Xie Xian Ning , Sow Chorng Haur , Bettiol Andrew Anthony , Wee Andrew Thye Shen
Published: January 2006

We report the creation of polymeric structures by atomic force microscopy (AFM) probe induced electrohydrodynamic (EHD) instability and nanofluidic flow. By biasing the AFM probe in a high field regime, single conical structure was produced on poly(methylmethacrylate) due to the initiation of strong EHD instability in the locally heated polymer melts. The pattern formation is dominated by the interplay of polymer EHD motion, polymer ablation, and AFM tip repulsion. The dependence of cone formation probability on the bending of AFM cantilevers with different stiffness was also discussed.
Effects of ferromagnetic nanowires on singlet and triplet exciton fractions in fluorescent and phosphorescent organic semiconductors
Authors: Hu Bin , Wu Yue , Zhang Zongtao , Dai Sheng , Shen Jian
Published: January 2006

We report a magnetic field-dependent electroluminescence (EL) induced by ferromagnetic Co53Pt47 nanowires in fluorescent conjugated polymer poly[2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylenevinylene] and phosphorescent iridium-complex Ir(ppy)3 molecules. The photoluminescence and EL studies indicate that the dispersed CoPt nanowires increase the singlet-to-triplet exciton ratio in organic semiconductors, suggesting that the spin-polarized holes were injected into the organic molecules from the CoPt nanowires under electrical excitation. Therefore, the use of ferromagnetic nanomaterials demonstrates a pathway to tune the optoelectronic properties that are related to singlet and triplet states in organic semiconducting materials.
Measurements of secondary electron emission effects in the Hall thruster discharge
Authors: Raitses Y. , Smirnov A. , Staack D. , Fisch N. J.
Published: January 2006

The dependence of the maximum electron temperature on the discharge voltage is studied for two Hall thruster configurations, in which a collisionless plasma is bounded by channel walls made of materials with different secondary electron emission (SEE) properties. The linear growth of the temperature with the discharge voltage, observed in the channel with a low SEE yield, suggests that SEE is responsible for the electron temperature saturation in the thruster configuration with the channel walls having a higher SEE yield. The fact that the values of the electron temperature at saturation are rather high may indirectly support the recently predicted kinetic regime of the space charge saturation of the near-wall sheath in the thruster discharge. A correlation between the effects of the channel wall material on the electron temperature and the electron cross-field current was also observed.
Control of coercivities in (Ga,Mn)As thin films by small concentrations of MnAs nanoclusters
Authors: Wang K. Y. , Sawicki M. , Edmonds K. W. , Campion R. P. , Rushforth A. W. , Freeman A. A. , Foxon C. T. , Gallagher B. L. , Dietl T.
Published: January 2006

We demonstrate that low concentrations of a secondary magnetic phase in (Ga,Mn)As thin films can enhance the coercivity by factors up to ∼100 without significantly degrading the Curie temperature or saturation magnetization. Magnetic measurements indicate that the secondary phase consists of MnAs nanoclusters, of average size ∼7nm. This approach to controlling the coercivity while maintaining a high Curie temperature may be important for realizing ferromagnetic semiconductor based devices.
Efficient spin injection into self-assembled quantum dots via LO-phonon-assisted resonant electron tunneling
Authors: Murayama A. , Asahina T. , Nishibayashi K. , Souma I. , Oka Y.
Published: January 2006

Spin injection from a diluted magnetic semiconductor quantum well (DMS-QW) into self-assembled quantum dots (QDs) of CdSe is demonstrated via LO-phonon-assisted resonant electron tunneling. The experimental evidence for the spin injection is clearly shown by time-resolved circularly polarized exciton photoluminescence (PL) with the polarization degree up to 40% in QDs. In addition, a type II transition with the lifetime of 3.5ns between electrons in the QDs and heavy holes in the DMS-QW is observed. These PL energies directly indicate that the electron tunneling is resonantly assisted by LO-phonon scattering, which realizes an efficient spin-injection process into QDs.
Generation of monodisperse gel emulsions in a microfluidic device
Authors: Priest Craig , Herminghaus Stephan , Seemann Ralf
Published: January 2006

We demonstrate that high dispersed phase volume fraction emulsions (i.e., gel emulsions) can be prepared in situ for microfluidic applications. Previously, the production of gel-like emulsions in microfluidic devices, where the droplet size is less than the length-scale of the channel, required multistep splitting of larger droplets in a branched microchannel network. Instead, we employ an abrupt change in the aspect ratio of a single microchannel to rapidly destabilize a confined coflowing stream, forming highly monodisperse droplets (coefficient of variance <1.5%). Using this emulsification mechanism, gel emulsions can be prepared in a single production step.
Improved elastic scattering model of electrons in limited media
Authors: Chaoui Zine-El-Abidine
Published: January 2006

An improved practical method to simulate elastic electron scattering is described. Single scattering events are simulated using simple analytical expressions derived from the Wentzel model. The present paper shows that simulating with the Wentzel model reduces to a pure problem of optimization. Indeed, a novel method of optimization, based on genetic algorithms, has been applied so as to reproduce the values of the total elastic cross sections and the first and second transport cross sections obtained from partial wave calculations. The resulting model yields a simple analytical formula for the random sampling of the angular deflection that overcomes the problem of the unfeasibility of the detailed simulation when the energy of the incident particles is larger than a hundred keV.
Dielectrophoretic manipulation of drops for high-speed microfluidic sorting devices
Authors: Ahn Keunho , Kerbage Charles , Hunt Tom P. , Westervelt R. M. , Link Darren R. , Weitz D. A.
Published: January 2006

We demonstrate a high-throughput drop sorter for microfluidic devices that uses dielectrophoretic forces. Microelectrodes underneath a polydimethylsiloxane channel produce forces of more than 10nN on a water drop in an inert oil, resulting in sorting rates greater than 1.6kHz. We investigate the dependence of such forces on drop size and flow. Alternate designs with electrodes on either side of a symmetric channel Y junction provide refined control over droplet selection.
Tunable high-power high-brightness linearly polarized vertical-external-cavity surface-emitting lasers
Authors: Fan Li , Fallahi Mahmoud , Murray James T. , Bedford Robert , Kaneda Yushi , Zakharian Aramis R. , Hader Jörg , Moloney Jerome V. , Stolz Wolfgang , Koch Stephan W.
Published: January 2006

We report on the development and the demonstration of tunable high-power high-brightness linearly polarized vertical-external-cavity surface-emitting lasers (VECSELs). A V-shaped cavity, in which the antireflection-coated VECSEL chip (active mirror) is located at the fold, and a birefringent filter are employed to achieve a large wavelength tuning range. Multiwatt cw linearly polarized TEM00 output with a 20nm tuning range and narrow linewidth is demonstrated at room temperature.
Micro-Brillouin scattering from a single isolated nanosphere
Authors: Li Y. , Lim H. S. , Ng S. C. , Wang Z. K. , Kuok M. H. , Vekris E. , Kitaev V. , Peiris F. C. , Ozin G. A.
Published: January 2006

Inelastic light scattering from a single isolated silica sphere, of diameter as small as 260nm, has been measured as a function of sphere size by micro-Brillouin spectroscopy. The feasibility of recording spectra of a sample as tiny as this, and for which only one particle is needed, further enhances the capabilities of Brillouin light scattering as a powerful investigative tool. Such measurements afford the evaluation of the elastic properties of single nanospheres and a determination of the size polydispersity of an aggregate of particles from the asymmetric broadening of its Brillouin spectrum. Unlike conventional Brillouin scattering from acoustic waves, what is observed here is the inelastic scattering from the eigenvibrations of a nanosphere.
Experiment and theory for heterogeneous nucleation of protein crystals in a porous medium
Authors: Chayen Naomi E. , Saridakis Emmanuel , Sear Richard P.
Published: January 2006

The determination of high-resolution structures of proteins requires crystals of suitable quality. Because of the new impetus given to structural biology by structural genomics/proteomics, the problem of crystallizing proteins is becoming increasingly acute. There is therefore an urgent requirement for the development of new efficient methods to aid crystal growth. Nucleation is the crucial step that determines the entire crystallization process. Hence, the holy grail is to design a “universal nucleant,” a substrate that induces the nucleation of crystals of any protein. We report a theory for nucleation on disordered porous media and its experimental testing and validation using a mesoporous bioactive gel-glass. This material induced the crystallization of the largest number of proteins ever crystallized using a single nucleant. The combination of the model and the experimental results opens up the scope for the rational design of nucleants, leading to alternative means of controlling crystallization.
Discovery of a reaction intermediate of aliphatic aldoxime dehydratase involving heme as an active center
Authors: Konishi Kazunobu , Ohta Takehiro , Oinuma Ken-Ichi , Hashimoto Yoshiteru , Kitagawa Teizo , Kobayashi Michihiko
Published: January 2006

Recently, we discovered an intriguing hemoprotein [aliphatic aldoxime dehydratase (OxdA)] that catalyzes the dehydration of aliphatic aldoximes [R–CH=N–OH] to the corresponding nitriles [R–C≡N] in the industrial
Pseudomonas chlororaphis
B23 strain. Unlike the utilization of H
2
O
2
or O
2
as a mediator of the catalysis by other heme-containing enzymes (e.g., P450), OxdA is notable for the direct binding of a substrate to the heme iron, experimental evidence of which was obtained here by means of resonance Raman (RR) analysis with an isotope technique. We found that the addition of a large amount of butyraldoxime (final concentration, 200 mM) to ferrous OxdA with a low enzyme concentration (final concentration, 5 μM) yields a long-lived OxdA–substrate complex (named OS-II), whose UV-vis spectrum is different from the corresponding spectra of the OxdA–substrate complex I and CO-bound, ferrous, and ferric forms of OxdA. Intriguingly, the RR analysis demonstrated that OS-II includes a highly oxidized heme with strong bonding between a substrate and the heme iron, as judged from the heme oxidation state marker ν
4
band at 1,379 cm
–1
and the
15
N-isotope-substituted butyraldoxime sensitive band at 857 cm
–1
in the RR spectra. It is noteworthy that OS-II has a highly oxidized heme like the ferryl-oxo heme species (e.g., compound II) formed by some general hemoproteins, although the function of OxdA is different from those (transport of electrons, transport of oxygen, sensing of oxygen or carbon monoxide, and catalysis of redox reactions) of general hemoproteins.
Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission
Authors: Greaves Laura C. , Preston Sean L. , Tadrous Paul J. , Taylor Robert W. , Barron Martin J. , Oukrif Dahmane , Leedham Simon J. , Deheragoda Maesha , Sasieni Peter , Novelli Marco R. , Jankowski Janusz A. Z. , Turnbull Douglass M. , Wright Nicholas A. , McDonald Stuart A. C.
Published: January 2006

The understanding of the fixation of mutations within human tissues and their subsequent clonal expansion is a considerable problem, of which little is known. We have previously shown that nononcogenic mutations in the mitochondrial genome occur in one of a number of morphologically normal colonic crypt stem cells, the progeny of which later occupy the whole crypt. We propose that these wholly mutated crypts then clonally expand by crypt fission, where each crypt divides into two mutated daughter crypts. Here we show that (
i
) mutated crypts in the process of fission share the same mutated mitochondrial genotype not present in neighboring cytochrome
c
oxidase-positive crypts (the odds of this being a random event are ≥2.48 × 10
9
:1); (
ii
) neighboring mutated crypts have the same genotype, which is different from adjacent cytochrome
c
oxidase-positive crypts; (
iii
) mutated crypts are clustered together throughout the colon; and (
iv
) patches of cytochrome
c
oxidase-deficient crypts increase in size with age. We thus demonstrate definitively that crypt fission is the mechanism by which mutations spread in the normal human colon. This has important implications for the biology of the normal adult human colon and possibly for the growth and spread of colorectal neoplasms.
Ras pathway signaling accelerates programmed cell death in the pathogenic fungus
Candida albicans
Authors: Phillips Andrew J. , Crowe Jonathan D. , Ramsdale Mark
Published: January 2006

A better understanding of the molecular basis of programmed cell death (PCD) in fungi could provide information that is useful in the design of antifungal drugs that combat life-threatening fungal infections. Harsh environmental stresses, such as acetic acid or hydrogen peroxide, have been shown to induce PCD in the pathogenic fungus
Candida albicans
. In this study, we show that dying cells progress from an apoptotic state to a secondary necrotic state and that the rate at which this change occurs is proportional to the intensity of the stimulus. Also, we found that the temporal response is modulated by Ras–cAMP–PKA signals. Mutations that block Ras–cAMP–PKA signaling (
ras1
Δ,
cdc35
Δ,
tpk1
Δ, and
tpk2
Δ) suppress or delay the apoptotic response, whereas mutations that stimulate signaling (

RAS1
val13

and
pde2
Δ) accelerate the rate of entry of cells into apoptosis. Pharmacological stimulation or inhibition of Ras signaling reinforces these findings. Transient increases in endogenous cAMP occur under conditions that stimulate apoptosis but not growth arrest. Death-specific changes in the abundance of different isoforms of the PKA regulatory subunit, Bcy1p, are also observed. Activation of Ras signals may regulate PCD of
C. albicans
, either by inhibiting antiapoptotic functions (such as stress responses) or by activating proapoptotic functions.
Herbicide-binding sites revealed in the structure of plant acetohydroxyacid synthase
Authors: McCourt Jennifer A. , Pang Siew Siew , King-Scott Jack , Guddat Luke W. , Duggleby Ronald G.
Published: January 2006

The sulfonylureas and imidazolinones are potent commercial herbicide families. They are among the most popular choices for farmers worldwide, because they are nontoxic to animals and highly selective. These herbicides inhibit branched-chain amino acid biosynthesis in plants by targeting acetohydroxyacid synthase (AHAS, EC 2.2.1.6). This report describes the 3D structure of
Arabidopsis thaliana
AHAS in complex with five sulfonylureas (to 2.5 Å resolution) and with the imidazolinone, imazaquin (IQ; 2.8 Å). Neither class of molecule has a structure that mimics the substrates for the enzyme, but both inhibit by blocking a channel through which access to the active site is gained. The sulfonylureas approach within 5 Å of the catalytic center, which is the C2 atom of the cofactor thiamin diphosphate, whereas IQ is at least 7 Å from this atom. Ten of the amino acid residues that bind the sulfonylureas also bind IQ. Six additional residues interact only with the sulfonylureas, whereas there are two residues that bind IQ but not the sulfonylureas. Thus, the two classes of inhibitor occupy partially overlapping sites but adopt different modes of binding. The increasing emergence of resistant weeds due to the appearance of mutations that interfere with the inhibition of AHAS is now a worldwide problem. The structures described here provide a rational molecular basis for understanding these mutations, thus allowing more sophisticated AHAS inhibitors to be developed. There is no previously described structure for any plant protein in complex with a commercial herbicide.
Ryanodine receptor/calcium release channel PKA phosphorylation: A critical mediator of heart failure progression
Authors: Wehrens Xander H. T. , Lehnart Stephan E. , Reiken Steven , Vest John A. , Wronska Anetta , Marks Andrew R.
Published: January 2006

Defective regulation of the cardiac ryanodine receptor (RyR2)/calcium release channel, required for excitation-contraction coupling in the heart, has been linked to cardiac arrhythmias and heart failure. For example, diastolic calcium “leak” via RyR2 channels in the sarcoplasmic reticulum has been identified as an important factor contributing to impaired contractility in heart failure and ventricular arrhythmias that cause sudden cardiac death. In patients with heart failure, chronic activation of the “fight or flight” stress response leads to protein kinase A (PKA) hyperphosphorylation of RyR2 at Ser-2808. PKA phosphorylation of RyR2 Ser-2808 reduces the binding affinity of the channel-stabilizing subunit calstabin2, resulting in leaky RyR2 channels. We developed RyR2-S2808A mice to determine whether Ser-2808 is the functional PKA phosphorylation site on RyR2. Furthermore, mice in which the RyR2 channel cannot be PKA phosphorylated were relatively protected against the development of heart failure after myocardial infarction. Taken together, these data show that PKA phosphorylation of Ser-2808 on the RyR2 channel appears to be a critical mediator of progressive cardiac dysfunction after myocardial infarction.
Inferring global levels of alternative splicing isoforms using a generative model of microarray data
Authors: Shai Ofer , Morris Quaid D. , Blencowe Benjamin J. , Frey Brendan J.
Published: January 2006

Motivation: Alternative splicing (AS) is a frequent step in metozoan gene expression whereby the exons of genes are spliced in different combinations to generate multiple isoforms of mature mRNA. AS functions to enrich an organism's proteomic complexity and regulates gene expression. Despite its importance, the mechanisms underlying AS and its regulation are not well understood, especially in the context of global gene expression patterns. We present here an algorithm referred to as the Generative model for the Alternative Splicing Array Platform (GenASAP) that can predict the levels of AS for thousands of exon skipping events using data generated from custom microarrays. GenASAP uses Bayesian learning in an unsupervised probability model to accurately predict AS levels from the microarray data. GenASAP is capable of learning the hybridization profiles of microarray data, while modeling noise processes and missing or aberrant data. GenASAP has been successfully applied to the global discovery and analysis of AS in mammalian cells and tissues.

Results: GenASAP was applied to data obtained from a custom microarray designed for the monitoring of 3126 AS events in mouse cells and tissues. The microarray design included probes specific for exon body and junction sequences formed by the splicing of exons. Our results show that GenASAP provides accurate predictions for over one-third of the total events, as verified by independent RT–PCR assays.

Contact:  ofer@psi.toronto.edu

Supplementary information:
Copying nodes versus editing links: the source of the difference between genetic regulatory networks and the WWW
Authors: Louzoun Yoram , Muchnik Lev , Solomon Sorin
Published: January 2006

We study two kinds of networks: genetic regulatory networks and the World Wide Web. We systematically test microscopic mechanisms to find the set of such mechanisms that optimally explain each networks' specific properties. In the first case we formulate a model including mainly random unbiased gene duplications and mutations. In the second case, the basic moves are website generation and rapid surf-induced link creation (/destruction). The different types of mechanisms reproduce the appropriate observed network properties. We use those to show that different kinds of networks have strongly system-dependent macroscopic experimental features. The diverging properties result from dissimilar node and link basic dynamics. The main non-uniform properties include the clustering coefficient, small-scale motifs frequency, time correlations, centrality and the connectivity of outgoing links. Some other features are generic such as the large-scale connectivity distribution of incoming links (scale-free) and the network diameter (small-worlds). The common properties are just the general hallmark of autocatalysis (self-enhancing processes), while the specific properties hinge on the specific elementary mechanisms.

Contact:  louzouy@math.biu.ac.il

Supplementary information: Supplementary data are available at Bioinformatics Online.
Short fuzzy tandem repeats in genomic sequences, identification, and possible role in regulation of gene expression
Authors: Boeva Valentina , Regnier Mireille , Papatsenko Dmitri , Makeev Vsevolod
Published: January 2006

Motivation: Genomic sequences are highly redundant and contain many types of repetitive DNA. Fuzzy tandem repeats (FTRs) are of particular interest. They are found in regulatory regions of eukaryotic genes and are reported to interact with transcription factors. However, accurate assessment of FTR occurrences in different genome segments requires specific algorithm for efficient FTR identification and classification.

Results: We have obtained formulas for P-values of FTR occurrence and developed an FTR identification algorithm implemented in TandemSWAN software. Using TandemSWAN we compared the structure and the occurrence of FTRs with short period length (up to 24 bp) in coding and non-coding regions including UTRs, heterochromatic, intergenic and enhancer sequences of Drosophila melanogaster and Drosophila pseudoobscura. Tandems with period three and its multiples were found in coding segments, whereas FTRs with periods multiple of six are overrepresented in all non-coding segment. Periods equal to 5–7 and 11–14 were characteristic of the enhancer regions and other non-coding regions close to genes.

Availability: TandemSWAN web page, stand-alone version and documentation can be found at

Contacts: valeyo@imb.ac.ru

Supplementary information: Supplementary data are available at Bioinformatics online.
Using a state-space model with hidden variables to infer transcription factor activities
Authors: Li Zheng , Shaw Stephen M. , Yedwabnick Matthew J. , Chan Christina
Published: January 2006

Motivation: In a gene regulatory network, genes are typically regulated by transcription factors (TFs). Transcription factor activity (TFA) is more difficult to measure than gene expression levels are. Other models have extracted information about TFA from gene expression data, but without explicitly modeling feedback from the genes. We present a state-space model (SSM) with hidden variables. The hidden variables include regulatory motifs in the gene network, such as feedback loops and auto-regulation, making SSM a useful complement to existing models.

Results: A gene regulatory network incorporating, for example, feed-forward loops, auto-regulation and multiple-inputs was constructed with an SSM model. First, the gene expression data were simulated by SSM and used to infer the TFAs. The ability of SSM to infer TFAs was evaluated by comparing the profiles of the inferred and simulated TFAs. Second, SSM was applied to gene expression data obtained from Escherichia coli K12 undergoing a carbon source transition and from the Saccharomyces cerevisiae cell cycle. The inferred activity profile for each TF was validated either by measurement or by activity information from the literature. The SSM model provides a probabilistic framework to simulate gene regulatory networks and to infer activity profiles of hidden variables.

Availability: Supplementary data and Matlab code will be made available at the URL below.

Contact:  krischan@egr.msu.edu

Supplementary information:
Optimized multilayer perceptrons for molecular classification and diagnosis using genomic data
Authors: Wang Zuyi , Wang Yue , Xuan Jianhua , Dong Yibin , Bakay Marina , Feng Yuanjian , Clarke Robert , Hoffman Eric P.
Published: January 2006

Motivation: Multilayer perceptrons (MLP) represent one of the widely used and effective machine learning methods currently applied to diagnostic classification based on high-dimensional genomic data. Since the dimensionalities of the existing genomic data often exceed the available sample sizes by orders of magnitude, the MLP performance may degrade owing to the curse of dimensionality and over-fitting, and may not provide acceptable prediction accuracy.

Results: Based on Fisher linear discriminant analysis, we designed and implemented an MLP optimization scheme for a two-layer MLP that effectively optimizes the initialization of MLP parameters and MLP architecture. The optimized MLP consistently demonstrated its ability in easing the curse of dimensionality in large microarray datasets. In comparison with a conventional MLP using random initialization, we obtained significant improvements in major performance measures including Bayes classification accuracy, convergence properties and area under the receiver operating characteristic curve (Az).

Supplementary information: The Supplementary information is available on

Contact:  yuewang@vt.edu
Permanent female mimics in a lekking shorebird
Authors: Jukema Joop , Piersma Theunis
Published: January 2006

Female mimics are known from many species, but permanent, non-conditional, alternative mating strategies are only known from an isopod, a fish, a lizard and a bird. The single bird example refers to lek-breeding ruffs
Philomachus pugnax
, a shorebird for which two strategies (independent and satellite) have been known for over 50 years. Ruffs also provided the single case of an animal with two, rather than three, permanent alternative mating strategies. Here, we describe a rare female-like morph of ruffs: the ‘missing’ third alternative mating strategy, which we have called ‘faeder’. Faeders are slightly larger than females and in late April have testes 2.5 time the size of testes of normal males. On leks in aviaries and in the wild they appear to combine feminine and masculine behaviours. Faeders may represent the ancestral, care-giving, male strategy, but their relatively large testes suggest that currently they behave as sneakers.
Toxicity of diclofenac to
Gyps
vultures
Authors: Swan Gerry E , Cuthbert Richard , Quevedo Miguel , Green Rhys E , Pain Deborah J , Bartels Paul , Cunningham Andrew A , Duncan Neil , Meharg Andrew A , Lindsay Oaks J , Parry-Jones Jemima , Shultz Susanne , Taggart Mark A , Verdoorn Gerhard , Wolter Kerri
Published: January 2006

Three endemic vulture species
Gyps bengalensis
,
Gyps indicus
and
Gyps tenuirostris
are critically endangered following dramatic declines in South Asia resulting from exposure to diclofenac, a veterinary drug present in the livestock carcasses that they scavenge. Diclofenac is widely used globally and could present a risk to
Gyps
species from other regions. In this study, we test the toxicity of diclofenac to a Eurasian (
Gyps fulvus
) and an African (
Gyps africanus
) species, neither of which is threatened. A dose of 0.8 mg kg
−1
of diclofenac was highly toxic to both species, indicating that they are at least as sensitive to diclofenac as
G. bengalensis
, for which we estimate an LD
50
of 0.1–0.2 mg kg
−1
. We suggest that diclofenac is likely to be toxic to all eight
Gyps
species, and that
G. africanus
, which is phylogenetically close to
G. bengalensis
, would be a suitable surrogate for the safety testing of alternative drugs to diclofenac.
Global climate drives southern right whale (
Eubalaena australis
) population dynamics
Authors: Leaper Russell , Cooke Justin , Trathan Phil , Reid Keith , Rowntree Victoria , Payne Roger
Published: January 2006

Sea surface temperature (SST) time-series from the southwest Atlantic and the El Niño 4 region in the western Pacific were compared to an index of annual calving success of the southern right whale (
Eubalaena australis
) breeding in Argentina. There was a strong relationship between right whale calving output and SST anomalies at South Georgia in the autumn of the previous year and also with mean El Niño 4 SST anomalies delayed by 6 years. These results extend similar observations from other krill predators and show clear linkages between global climate signals and the biological processes affecting whale population dynamics.
Longitudinally inhomogeneous deformation patterns in isotropic tubes under pure bending
Authors: Wadee M. Khurram , Wadee M. Ahmer , Bassom Andrew P , Aigner Andreas A
Published: January 2006

A variational model is formulated that accounts for the localization of deformation due to buckling under pure bending of thin-walled elastic tubes with circular cross-sections. Previous studies have successfully modelled the gradual process of ovalization of the cross-section with an accompanying progressive reduction in stiffness but these theories have had insufficient freedom to incorporate any longitudinal variation in the tube. Here, energy methods and small-strain nonlinear elastic theory are used to model the combined effects of cross-section deformation and localized longitudinal buckling. Results are compared with a number of case studies, including a nanotube, and it is found that the model gives rise to behaviours that correlate well with some published physical experiments and numerical studies.
Analytical models for bistable cylindrical shells
Authors: Guest S.D , Pellegrino S
Published: January 2006

Thin cylindrical shell structures can show interesting bistable behaviour. If made unstressed from isotropic materials they are only stable in the initial configuration, but if made from fibre-reinforced composites they may also have a second, stable configuration. If the layup of the composite is antisymmetric, this alternative stable configuration forms a tight coil; if the layup is symmetric the alternative stable configuration is helical. A simple two-parameter model for these structure is presented that is able to distinguish between these different behaviours.
On localization of pseudo-relativistic energy
Authors: Balinsky Alexander A , Tyukov Alexey E
Published: January 2006

We present a Kato-type inequality for bounded domains

,
n
≥2.
Three-dimensional flow due to a microcantilever oscillating near a wall: an unsteady slender-body analysis
Authors: Clarke R.J , Jensen O.E , Billingham J , Williams P.M
Published: January 2006

We compute the drag on a slender rigid cylinder, of uniform circular cross-section, oscillating in a viscous fluid at small amplitude near a horizontal wall. The cylinder's axis lies at an angleαto the horizontal and the cylinder oscillates in a vertical plane normal to either the wall or its own axis. The flow is described using an unsteady slender-body approximation, which we treat both numerically and using an iterative scheme that extends resistive-force theory to account for the leading-order effects of unsteady inertia and the wall. Whenαis small, two independent screening mechanisms are identified which suppress end-effects and produce approximately two-dimensional flow along the majority of the cylinder; however, three-dimensional effects influence the drag at larger tilt angles.
Optimization with missing data
Authors: Forrester Alexander I.J , Sóbester András , Keane Andy J
Published: January 2006

Engineering optimization relies routinely on deterministic computer based design evaluations, typically comprising geometry creation, mesh generation and numerical simulation. Simple optimization routines tend to stall and require user intervention if a failure occurs at any of these stages. This motivated us to develop an optimization strategy based on surrogate modelling, which penalizes the likely failure regions of the design space without prior knowledge of their locations. A Gaussian process based design improvement expectation measure guides the search towards the feasible global optimum.
Host-Mediated Phosphorylation of Type III Effector AvrPto PromotesPseudomonasVirulence and Avirulence in Tomato
Authors: Anderson Jeffrey C. , Pascuzzi Pete E. , Xiao Fangming , Sessa Guido , Martin Gregory B.
Published: January 2006

The AvrPto protein from Pseudomonas syringae pv tomato is delivered into plant cells by the bacterial type III secretion system, where it either promotes host susceptibility or, in tomato plants expressing the Pto kinase, elicits disease resistance. Using two-dimensional gel electrophoresis, we obtained evidence that AvrPto is phosphorylated when expressed in plant leaves. In vitro phosphorylation of AvrPto by plant extracts occurs independently of Pto and is due to a kinase activity that is conserved in tomato (Solanum lycopersicum), tobacco (Nicotiana tabacum), and Arabidopsis  thaliana. Three Ser residues clustered in the C-terminal 18 amino acids of AvrPto were identified in vitro as putative phosphorylation sites, and one site at S149 was directly confirmed as an in vivo phosphorylation site by mass spectrometry. Substitution of Ala for S149 significantly decreased the ability of AvrPto to enhance disease symptoms and promote growth of P. s. tomato in susceptible tomato leaves. In addition, S149A significantly decreased the avirulence activity of AvrPto in resistant tomato plants. Our observations support a model in which AvrPto has evolved to mimic a substrate of a highly conserved plant kinase to enhance its virulence activity. Furthermore, residues of AvrPto that promote virulence are also monitored by plant defenses.
ArabidopsisRibonucleotide Reductases Are Critical for Cell Cycle Progression, DNA Damage Repair, and Plant Development
Authors: Wang Chunxin , Liu Zhongchi
Published: January 2006

Ribonucleotide reductase (RNR), comprising two large (R1) and two small (R2) subunits, catalyzes a rate-limiting step in the production of deoxyribonucleotides needed for DNA replication and repair. Previous studies in yeast and mammals indicated that defective RNR often led to cell cycle arrest, growth retardation, and p53-dependent apoptosis, whereas abnormally increased RNR activities led to higher mutation rates. Because plants are constantly exposed to environmental mutagens and plant cells are totipotent, an understanding of RNR function in plants is important. We isolated and characterized mutations in all three R2 genes (TSO2, RNR2A, and RNR2B) in Arabidopsis thaliana. tso2 mutants had reduced deoxyribonucleoside triphosphate (dNTP) levels and exhibited developmental defects, including callus-like floral organs and fasciated shoot apical meristems. tso2 single and tso2 rnr2a double mutants were more sensitive to UV-C light, and tso2 rnr2a seedlings exhibited increased DNA damage, massive programmed cell death, and release of transcriptional gene silencing. Analyses of single and double r2 mutants demonstrated that a normal dNTP pool and RNR function are critical for the plant response to mutagens and proper plant development. The correlation between DNA damage accumulation and the subsequent occurrence of apoptotic nuclei in tso2 rnr2a double mutants suggests that perhaps plants, like animals, can initiate programmed cell death upon sensing DNA damage.
Caught Red-Handed:RcEncodes a Basic Helix-Loop-Helix Protein Conditioning Red Pericarp in Rice
Authors: Sweeney Megan T. , Thomson Michael J. , Pfeil Bernard E. , McCouch Susan
Published: January 2006

Rc is a domestication-related gene required for red pericarp in rice (Oryza sativa). The red grain color is ubiquitous among the wild ancestors of O. sativa, in which it is closely associated with seed shattering and dormancy. Rc encodes a basic helix-loop-helix (bHLH) protein that was fine-mapped to an 18.5-kb region on rice chromosome 7 using a cross between Oryza rufipogon (red pericarp) and O. sativa cv Jefferson (white pericarp). Sequencing of the alleles from both mapping parents as well as from two independent genetic stocks of Rc revealed that the dominant red allele differed from the recessive white allele by a 14-bp deletion within exon 6 that knocked out the bHLH domain of the protein. A premature stop codon was identified in the second mutant stock that had a light red pericarp. RT-PCR experiments confirmed that the Rc gene was expressed in both red- and white-grained rice but that a shortened transcript was present in white varieties. Phylogenetic analysis, supported by comparative mapping in rice and maize (Zea mays), showed that Rc, a positive regulator of proanthocyanidin, is orthologous with INTENSIFIER1, a negative regulator of anthocyanin production in maize, and is not in the same clade as rice bHLH anthocyanin regulators.
Rapid Neural Fos Responses to Oestradiol in Oestrogen Receptor αβ Double Knockout Mice
Authors: Dominguez‐Salazar E. , Shetty S. , Rissman E. F.
Published: January 2006

The standard mode of action for oestradiol is via activation of nuclear oestrogen receptors (ERs), which initiate DNA transcription leading to protein formation. In the present study, we examined the rapid and potentially ER‐independent action of oestradiol using Fos as a marker of neural activity. We assessed Fos immunoreactivity (ir) in brains of mice with functional versus nonfunctional ERs. Fos‐ir was compared in brains of control mice that did and did not receive oestradiol treatment prior to sacrifice, and cell numbers in the preoptic area (POA), ventromedial nucleus of the hypothalamus (VMH), area 2 of cingulate cortex (CG2), granular layer of accessory olfactory bulb (Gr‐AOB), olivary pretectal nucleus (OPT) and pyramidal layer of field CA3 of hippocampus (Py‐CA3) were increased 90 min after oestradiol treatment. By contrast, in brains of double oestrogen receptor αβ knockout (ERαβKO) female mice, no change in Fos‐ir was noted after oestradiol treatment in the POA, VMH, Gr‐AOB or Py‐CA3, suggesting that these responses to oestradiol depend on ERα and/or ERβ. However, Fos‐ir was induced by oestradiol in the OPT and CG2 in ERαβKO mice. These regions do not contain ERα‐ir in control brains. In ERαβKO brains as well, ERα‐ir was absent, suggesting that the mutant ERα (E1) present in ERαKO brain is also absent in these regions. We speculate that oestradiol has rapid effects in the OPT and CG2 via a novel mechanism that does not require either classic oestrogen receptor.
In vitroeffects of meloxicam with or without doxorubicin on canine osteosarcoma cells
Authors: WOLFESBERGER B. , HOELZL C. , WALTER I. , REIDER G. A. , FERTL G. , THALHAMMER J. G. , SKALICKY M. , EGERBACHER M.
Published: January 2006

Cyclooxygenase (COX) inhibitors, already widely used to reduce fever, inflammation and pain, are under increasing consideration as potential agents for the prevention and treatment of neoplasia. As COX‐2 was detected in human and canine osteosarcomas, we have evaluated the effect of the preferential COX‐2 inhibitor meloxicam on an established D‐17 canine osteosarcoma cell line, which expressed, as well as COX‐1 and COX‐2 also COX‐3 (as demonstrated by Western blot). An XTT proliferation kit was used to assess surviving cells after drug treatment. At low concentrations (1, 2, 4 and 10 μm) meloxicam caused an increase in cell numbers while a marked anti‐proliferative effect was observed at higher concentrations (100, 200 μm) after 3 days and also 3 weeks of incubation. The chemotherapeutic drug doxorubicin showed a cytotoxic effect at all concentrations (60–1920 nm). Exposure of tumour cells to combinations of meloxicam and doxorubicin revealed synergistic effects (with 240 nmdoxorubicin), as well as sub‐additive and antagonistic results, especially if combined with concentrations of meloxicam typically found in serum.

Care should be taken in concluding, on the basis of onein vitrostudy, that meloxicam does not have a role in the treatment of canine osteosarcomas given that the results fromin vivostudies may differ.
Clomipramine and selegiline: do they influence impulse control?
Authors: BERT B. , HARMS S. , LANGEN B. , FINK H.
Published: January 2006

Anxiety disorders in dogs are often accompanied by loss of impulse control and can result in inappropriate behaviour such as destructiveness, excessive barking and aggression. The reduction of these undesirable actions is the focus of behaviour therapy. Clomipramine and selegiline have been approved for the treatment of separation anxiety in dogs, but there are anecdotal reports that they produce inconsistent therapeutic effect. Hence, the aim of this study was to verify the efficacy of clomipramine and selegiline for regulating impulse control by using a rat model based on the delay of reward procedure. The principle is that the animal has to decide between an immediate small food reward, normally preferred by impulsive animals, and a delayed large food reward. In this study, acute effects of clomipramine (0.3–10.0 mg/kg), selegiline (0.3–3.0 mg/kg), and diazepam (1.0–3.0 mg/kg) on the impulsive behaviour of two breeding lines of rats with different anxiety‐related behaviour were investigated. Neither clomipramine nor selegiline had an effect on impulse control in either breeding line. However, motor activity was decreased by clomipramine and increased by selegiline. Diazepam led to an increase in impulsive behaviour of one rat line concomitant with an increase in motor activity. The results of this rat model for studying impulsive behaviour suggest that a single administration of selegiline and clomipramine has no influence on impulsive behaviour.
Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in the Korean catfish (Silurus asotus)
Authors: PARK B.‐K. , LIM J.‐H. , KIM M.‐S. , YUN H.‐I.
Published: January 2006

The pharmacokinetics of florfenicol and its metabolite, florfenicol amine, was investigated after its intravenous (i.v.) and oral (p.o.) administration of 20 mg/kg of body weight in Korean catfish (Silurus asotus). After i.v. florfenicol injection (as a bolus), the terminal half‐life (t1/2), the volume of distribution at steady state (Vdss), and total body clearance were 11.12 ± 1.06 h, 1.09 ± 0.09 L/kg and 0.07 ± 0.01 L·kg/h respectively. After p.o. administration of florfenicol, the t1/2, Cmax, tmax and oral bioavailability (F) were 15.69 ± 2.59 h, 9.59 ± 0.36 μg/mL, 8 h and 92.61 ± 10.1% respectively. Florfenicol amine, an active metabolite of florfenicol, was detected in all fish. After i.v. and p.o. administration of florfenicol, the observed Cmax values of florfenicol amine (3.91 ± 0.69 and 3.57 ± 0.65 mg/L) were reached at 0.5 and 7.33 ± 1.15 h. The mean metabolic rate of florfenicol amine after i.v. and p.o. administration was 0.4 and 0.5 respectively.