bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic Ambipolar Conjugated Molecules for Electronics: Synthesis and Structure–Property Relationships
Authors: Jiang Hongji
Published: July 2010

The field of organic electronics has been developed vastly in the past two decades, and the performance and lifetime of these devices are critically dependent on the materials development, device design, deposition processes, and modeling, among which the active materials of organic semiconductor play a crucial role. The unique properties of organic semiconductor are largely based on the versatility to synthesize multifunctional organic conjugated materials by judicious molecular design. To effectively adjust the optoelectronic properties, especially energy levels, of organic semiconductor, the scientists have presented a synthesis methodology of organic ambipolar conjugated molecules, in which typical p‐dope type and n‐dope type segments are incorporated into one molecule. The present review summarizes the progress on organic ambipolar conjugated molecules for electronics in the past few years. Some issues to be addressed are also highlighted and discussed.

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Simultaneous Surface and Bulk Imaging of Polymer Blends with X‐ray Spectromicroscopy
Authors: Watts Benjamin , McNeill Christopher R.
Published: July 2010

We demonstrate the utility of soft X‐ray spectromicroscopy to simultaneously image the surface and bulk composition of polymer blend thin films. In addition to conventional scanning transmission X‐ray microscopy that employs a scintillator and photomultiplier tube to measure the transmitted X‐ray flux, channeltron detection of near‐surface photoelectrons is employed to provide information of the composition of the first few nanometers of the film. Laterally phase‐separated blends of two polyfluorene co‐polymers are studied, with the structure of both wetting and capping layers clearly imaged. This new information provides insight into the connectivity of bulk and surface structures that is of particular relevance to the operation of such blends in optoelectronic devices.

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Conformational and Dynamical Properties of the Isolated, Three‐Dimensional Single‐ and Double‐Tethered Polymer Chain on an Infinite Surface
Authors: Fritsche Miriam , Heermann Dieter W. , Dutra Mariana , Cordeiro Claudette E.
Published: July 2010

By Monte Carlo simulations we provide insight into the isolated single‐ and double‐tethered (ST and DT) polymer chain attached to an impenetrable surface to elucidate open theoretical questions and guide future experiments investigating the impact of tethering on the genome packaging by concurrent visualisation of multiple loci along the chromosome(s). In the models, either one or both ends (at a grafting distance d) are fixed or the ST and DT chain are “annealed” by permitting the anchor(s) to diffuse laterally along the surface. We analyse chain self‐entanglement, intrachain segment correlations, the relationship between mean square physical distance and corresponding contour length and provide the first report on the diffusion behaviour.

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Univariate modelling of monthly maximum temperature time series over northeast India: neural network versus Yule–Walker equation based approach
Authors: Chattopadhyay Surajit , Jhajharia Deepak , Chattopadhyay Goutami
Published: July 2010

The present paper has adopted an autoregressive approach to inspect the time series of monthly maximum temperature (Tmax) over northeast India. Through autocorrelation analysis the Tmax time series of northeast India is identified as non‐stationary, with a seasonality of 12 months, and it is also found to show an increasing trend by using both parametric and non‐parametric methods. The autoregressive models of the reduced Tmax time series, which has become stationary on removal of the seasonal and the trend components from the original time series, were generated through Yule–Walker equations. The sixth order autoregressive model (AR(6)) is identified as a suitable representative of the Tmax time series based on the Akaike information criteria, and the prediction potential of AR(6) is also established statistically through Willmott's indices. Subsequently, autoregressive neural network models were generated as a multilayer perceptron, a generalized feed forward neural network and a modular neural network. An autoregressive neural network model of order four (AR‐NN(4)), in the form of a modular neural network (MNN), has performed comparably well with that of AR(6) based on the high values of Willmott's indices and the low values of the prediction error. Therefore, AR‐NN(4)‐MNN will be a better option than AR(6) to forecast a time series, i.e. the monthly Tmax time series of northeast India, because AR‐NN(4)‐MNN requires fewer predictors for a superior forecast of a time series. Copyright © 2010 Royal Meteorological Society
Bifurcation Analysis of a Tubular Reactor for Nitroxide‐Mediated Radical Polymerization of Styrene
Authors: Zitlalpopoca‐Soriano Angel Guillermo , Vivaldo‐Lima Eduardo , Flores‐Tlacuahuac Antonio
Published: July 2010

In this work, the nonlinear bifurcation behavior of a tubular reactor where nitroxide‐mediated radical polymerization of styrene takes place is analyzed. The effects of the cooling flow rate, feed stream temperature, cooling water temperature, feed stream monomer concentration, flow rate of monomer feed, diameter, and global heat transfer are addressed. The results showed that these changes have different impacts on the nonlinear operability characteristics of the polymerization reactor, and prompted for the development of a runaway boundary in the reactor. The mathematical model for this polymerization system is represented by a system of partial differential equations system (PDE) which is properly discretized by using the numerical method of lines. The resulting set of ordinary differential equations, representing heat and mass balances, as well as moment equations, are then used in the AUTO software to assess embedded nonlinear behavior patterns.

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The possibility of microarray‐based analysis using cell‐free placental mRNA in maternal plasma
Authors: Miura Kiyonori , Miura Shoko , Yamasaki Kentaro , Shimada Takako , Kinoshita Akira , Niikawa Norio , Yoshiura Koh‐ichiro , Masuzaki Hideaki
Published: July 2010

Objective

The purpose of this study is to investigate a possibility of overall assessment of cell‐free (CF) placental mRNAs in maternal plasma.

Methods

First, placenta‐predominantly expressed transcripts were selected by the analysis of GeneChip using three sets of placental tissues and corresponding maternal blood cells. Subsequently, a custom cDNA array panel of placenta‐predominantly expressed transcripts was designed and used to compare the RNA profiles of maternal plasma collected from 12 preeclamptic and 12 uncomplicated pregnancies. Scatter plots for the signal intensities of the comparative cDNA hybridization revealed either unchanged or aberrant patterns.

Results

We selected top 50 placenta‐predominantly expressed transcripts that were > 2500 times higher in placental tissues than in corresponding whole blood samples. A custom cDNA array analysis detected the aberrant pattern in five preeclamptic women with severe hypertension but not in seven preeclamptic women with mild hypertension (P < 0.05, Fisher's direct method). The aberrant pattern of above RNA transcripts in maternal plasma was validated by quantitative real‐time reverse transcription‐polymerase chain reaction. The mean (range) value of coefficient of variations in this custom array quantification was 9.4% (3.0–16.2%).

Conclusion

Our custom cDNA array is expected to be useful for overall assessment of CF placental mRNAs in maternal plasma in a single experiment. Copyright © 2010 John Wiley & Sons, Ltd.
On the optical, electronic, and structural properties of zinc sulfide nanoclusters
Authors: Mohajeri Afshan , Alipour Mojtaba
Published: July 2010

The optical, electronic, and structural properties of stoichiometric zinc sulfide clusters ((ZnS)n, n ≤ 10) have been systematically investigated using the density functional approach. The size evolution of several reactivity descriptors such as ionization potential, electron affinity, chemical hardness, and static dipole polarizability has been determined for ZnS clusters. Energetically, the relative stability of ZnS clusters at different sizes is studied by calculating their binding energy, the highest occupied molecular orbital‐lowest unoccupied molecular orbital energy gap, and the second‐order difference in total energy. In addition to energetic analysis, minimum polarizability principle and principle of maximum hardness are used to characterize the magic number clusters. Moreover, it is shown that the differential mean polarizability can also be a useful quantity to characterize the stability of the studied clusters. Also, it is found that there is a strong inverse correlation between the static dipole polarizability and the ionization potential of the ZnS clusters. Similarly, the softness has also been shown to mostly correlate with the dipole polarizability of these clusters. Thus, this work will have some important implications for the calculation of polarizability of ZnS clusters in terms of the corresponding ionization potentials directly. Finally, the similarity function has been also used to investigate the extent that the clusters are similar to the pure ZnS or to each other. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011
High‐Throughput Near‐Field Optical Nanoprocessing of Solution‐Deposited Nanoparticles
Authors: Pan Heng , Hwang David J. , Ko Seung H. , Clem Tabitha A. , Fréchet Jean M. J. , Bäuerle Dieter , Grigoropoulos Costas P.
Published: July 2010

The application of nanoscale electrical and biological devices will benefit from the development of nanomanufacturing technologies that are high‐throughput, low‐cost, and flexible. Utilizing nanomaterials as building blocks and organizing them in a rational way constitutes an attractive approach towards this goal and has been pursued for the past few years. The optical near‐field nanoprocessing of nanoparticles for high‐throughput nanomanufacturing is reported. The method utilizes fluidically assembled microspheres as a near‐field optical confinement structure array for laser‐assisted nanosintering and nanoablation of nanoparticles. By taking advantage of the low processing temperature and reduced thermal diffusion in the nanoparticle film, a minimum feature size down to ≈100 nm is realized. In addition, smaller features (50 nm) are obtained by furnace annealing of laser‐sintered nanodots at 400 °C. The electrical conductivity of sintered nanolines is also studied. Using nanoline electrodes separated by a submicrometer gap, organic field‐effect transistors are subsequently fabricated with oxygen‐stable semiconducting polymer.
Density Fluctuations and Phase Transitions of Ferroelectric Polymer Nanowires
Authors: Serghei Anatoli , Lutkenhaus Jodie L. , Miranda Daniel F. , McEnnis Kathleen , Kremer Friedrich , Russell Thomas P.
Published: July 2010

Phase transitions of polymeric materials are accompanied by changes in density as a function of temperature. Being able to measure these changes in polymeric systems in one, two or three dimensions on the nanoscopic length‐scale is a challenge, but it would provide a simple route to assess phase transitions in nanoscopically confined systems. It is shown that the measurement of the dielectric permittivity in the high frequency limit (in spectral regions not affected by dielectric dispersions) offers an effective and very sensitive means to assess density fluctuations, and hence phase transitions, in nanoscopic systems. The sensitivity of this approach is demonstrated by assessing the phase transition behavior of ferroelectric polymer nanowires confined within alumina membranes. No significant shifts in the Curie transition are observed down to pore diameters as small as 15 nm.
Histone deacetylase inhibitors: clinical implications for hematological malignancies
Authors: Tambaro Francesco Paolo , Dell’Aversana Carmela , Carafa Vincenzo , Nebbioso Angela , Radic Branka , Ferrara Felicetto , Altucci Lucia
Published: July 2010

Histone modifications have widely been implicated in cancer development and progression and are potentially reversible by drug treatments. The N-terminal tails of each histone extend outward through the DNA strand containing amino acid residues modified by posttranslational acetylation, methylation, and phosphorylation. These modifications change the secondary structure of the histone protein tails in relation to the DNA strands, increasing the distance between DNA and histones, and thus allowing accessibility of transcription factors to gene promoter regions. A large number of HDAC inhibitors have been synthesized in the last few years, most being effective in vitro, inducing cancer cells differentiation or cell death. The majority of the inhibitors are in clinical trials, unlike the suberoylanilide hydroxamic acid, a pan-HDACi, and Romidepsin (FK 228), a class I-selective HDACi, which are only approved in the second line treatment of refractory, persistent or relapsed cutaneous T-cell lymphoma, and active in approximately 150 clinical trials, in monotherapy or in association. Preclinical studies investigated the use of these drugs in clinical practice, as single agents and in combination with chemotherapy, hypomethylating agents, proteasome inhibitors, and MTOR inhibitors, showing a significant effect mostly in hematological malignancies. The aim of this review is to focus on the biological features of these drugs, analyzing the possible mechanism(s) of action and outline an overview on the current use in the clinical practice.
Løvehovden fault and Billefjorden rift basin segmentation and development, Spitsbergen, Norway
Authors: MAHER H. D. , BRAATHEN A.
Published: July 2010

The Carboniferous Billefjorden rift basin is a well-known example of a suite of Carboniferous basins on the Barents Shelf and NE Greenland. The basin has a clastic, carbonate and evaporite fill with complex and disputed stratigraphic relationships, especially regarding the Ebbadalen and Minkinfjellet formations. Geometrically, the basin is considered a simple half-graben. A N–S-trending fault and monocline structure within the northern portion of the basin, the Løvehovden fault, has lithological and thickness differences across it within the Minkinfjellet and possibly Ebbadalen formations. The fault shows W-side-down movement, defining a sub-basin within the larger half-graben. Significant along-strike changes occur. Down-throw to the west is at least 150 metres and possibly 400 metres, as shown by across-fault thickness differences of Ebbadalen and/or Minkinfjellet formations. To the east of the fault, the contact between the Ebbadalen and Minkinfjellet formations is a disconformity with significant local relief, and is interpreted to represent exposure from footwall uplift, and associated near- or at-surface solution, producing basal stratiform breccias. A similar contact is not exposed west of the fault. Monoclinal deformation and thickening of the younger Wordiekammen Formation above and across the monocline constrain a later movement component. Kinematic data and the structural style clearly indicate the Løvehovden fault is a normal fault with associated tri-shear zone development, consistent with the regional Carboniferous rift setting. Earlier interpretations describe the Løvehovden fault and monocline as Tertiary contractional features. In contrast, our work advocates that they are an important architectural basin element, defining a sub-basin within the Billeforden Trough during Minkinfjellet Formation deposition, with insignificant, if any, Tertiary reactivation. The Løvehovden fault is aligned with and represents the southern termination of the Lemströmfjellet fault to the north. Thus, the Billefjorden basin changes from a narrow graben to a broader half-graben to the south. These along-strike changes have important implications for the stratigraphic architecture of the basin, and for palaeogeographic reconstructions. These results and application of 3-D models for extension related tri-shear zones may help inform interpretation of other Carboniferous basins on the Barents Shelf.
The evaporatively driven cloud-top mixing layer
Authors: MELLADO JUAN PEDRO
Published: July 2010

Direct numerical simulations of the turbulent temporally evolving cloud-top mixing layer are used to investigate the role of evaporative cooling by isobaric mixing locally at the stratocumulus top. It is shown that the system develops a horizontal layered structure whose evolution is determined by molecular transport. A relatively thin inversion with a constant thickness h = κ/we is formed on top and travels upwards at a mean velocity we ≃ 0.1(κ |bs|χc2)1/3, where κ is the mixture-fraction diffusivity, bs < 0 is the buoyancy anomaly at saturation conditions χs and χc is the cross-over mixture fraction defining the interval of buoyancy reversing mixtures. A turbulent convection layer develops below and continuously broadens into the cloud (the lower saturated fluid). This turbulent layer approaches a self-preserving state that is characterized by the convection scales constructed from a constant reference buoyancy flux Bs = |bs|we/χs. Right underneath the inversion base, a transition or buffer zone is defined based on a strong local conversion of vertical to horizontal motion that leads to a cellular pattern and sheet-like plumes, as observed in cloud measurements and reported in other free-convection problems. The fluctuating saturation surface (instantaneous cloud top) is contained inside this intermediate region. Results show that the inversion is not broken due to the turbulent convection generated by the evaporative cooling, and the upward mean entrainment velocity we is negligibly small compared to the convection velocity scale w* of the turbulent layer and the corresponding growth rate into the cloud.
Effect of gravity on the dynamics of non-isothermic ultra-thin two-layer films
Authors: NEPOMNYASHCHY ALEXANDER , SIMANOVSKII ILYA
Published: July 2010

The effect of gravity on the dynamics of non-isothermic ultra-thin two-layer films is studied in this paper. The joint action of disjoining pressure and thermocapillary forces is taken into account. The problem is considered in a long-wave approximation. The linear stability of a quiescent state and thermocapillary flows is investigated. It has been found that the influence of the upper fluid density is significantly stronger than that of the difference of fluid densities. Nonlinear flow regimes are studied by means of numerical simulations. The gravity can lead to the formation of stripes or holes instead of droplets. The two-dimensional wavy patterns are replaced by one-dimensional waves with the fronts inclined or transverse to the direction of the horizontal temperature gradient.
Relative velocity of inertial particles in turbulent flows
Authors: PAN LIUBIN , PADOAN PAOLO
Published: July 2010

We present a model for the relative velocity of inertial particles in turbulent flows that provides new physical insight into this problem. Our general formulation shows that the relative velocity has contributions from two terms, referred to as the ‘generalized acceleration’ and ‘generalized shear’, because they reduce to the well-known acceleration and shear terms in the Saffman–Turner limit. The generalized shear term represents particles' memory of the flow velocity difference along their trajectories and depends on the inertial particle pair dispersion backward in time. The importance of this backward dispersion in determining the particle relative velocity is emphasized. We find that our model with a two-phase separation behaviour, an early ballistic phase and a later tracer-like phase, as found by recent simulations for the forward (in time) dispersion of inertial particle pairs, gives good fits to the measured relative speeds from simulations at low Reynolds numbers. In the monodisperse case with identical particles, the generalized acceleration term vanishes and the relative velocity is determined by the generalized shear term. At large Reynolds numbers, our model gives a St1/2-dependence of the relative velocity on the Stokes number St in the inertial range for both the ballistic behaviour and the Richardson separation law. This leads to the same inertial-range scaling for the two-phase separation that well fits the simulation results. Our calculations for the bidisperse case show that, with the friction timescale of one particle fixed, the relative speed as a function of the other particle's friction time has a dip when the two timescales are similar. This indicates that similar-size particles tend to have stronger velocity correlation than different ones. We find that the primary contribution at the dip, i.e. for similar particles, is from the generalized shear term, while the generalized acceleration term is dominant for particles of very different sizes. Future numerical studies are motivated to check the accuracy of the assumptions made in our model and to investigate the backward-in-time dispersion of inertial particle pairs in turbulent flows.
On the instability of a free viscous rim
Authors: ROISMAN ILIA V.
Published: July 2010

This paper is devoted to the theoretical description of the dynamics of a rim formed by capillary forces at the edge of a free, thin liquid sheet. The rim dynamics are described using a quasi-one-dimensional approach accounting for the inertia of the liquid in the rim and for the liquid flow entering the rim from the sheet, surface tension and viscous stresses. The governing equations are derived from the mass, momentum and moment-of-momentum-balance equations of the rim. The theory provides a basis from which to analyse the linear stability of a straight line rim bounding a planar liquid sheet. The combined effect of the axisymmetric disturbances of the radius of the rim cross-section as well as of the transverse disturbances of the rim centreline is considered. The effect of the viscosity, relative film thickness and rim deceleration are investigated. The predicted wavelength of the most unstable mode is always very similar to the Rayleigh wavelength of the instability of an infinite cylindrical jet. This prediction is confirmed by various experimental data found in the literature. The maximum rate of growth of rim disturbances depends on all the parameters of the problem; however, the most pronounced effect can be attributed to the rim deceleration. This conclusion is confirmed by nonlinear simulations of rim deformation.
Population dynamics and spatial distribution of monogeneans on the gills ofOreochromis mossambicus(Peters, 1852) from two lakes of the Limpopo River System, South Africa
Authors: Madanire-Moyo G.N. , Matla M.M. , Olivier P.A.S. , Luus-Powell W.J.
Published: July 2010

An investigation was conducted into the parasitic infection of an indigenous cichlid,Oreochromis mossambicus, collected seasonally from the Nwanedi-Luphephe dams of the Limpopo River System from July 2007 to April 2009. Of 157 host specimens examined, 115 (73.25%) were infected by at least one gill parasite. In all, 1565 monogenean specimens were collected, belonging to five different species and two genera:Cichlidogyrus(C. halli,C. sclerosus,C. tilapiaeandC. dossoui) andScutogyrus(S. longicornis). Infracommunities were poor, with only 27 (17.20%) hosts harbouring four of the five species observed.Cichlidogyrus halliwas the dominant species, with a prevalence of 73.25%. Prevalence values for each of the other four species were less than 50%. The mean intensities for each of the five species were low ( < 8 parasites/host). The parasite abundance and intensity levels were not influenced by either the sex or the size of the host. The abundance of all parasite species except forS. longicornisexhibited seasonal fluctuations, reaching peaks in winter and summer. The spatial distribution of each parasite was studied on different regions of the gill, and positive associations among some species were revealed.
The joint velocity, torque, and power capability evaluation of a redundant parallel manipulator
Authors: Zhao Yongjie , Gao Feng
Published: July 2010

The evaluation of joint velocity, torque, and power capability of the 8-PSS redundant parallel manipulator is investigated in this paper. A series of new joint capability indices with obvious physical meanings are presented. The torque index used to evaluate the respective joint dynamic capability of the redundant parallel manipulator is decoupled into the acceleration, velocity, and gravity term. With these velocity, torque, and power indices, it is possible to control the respective joint capability of the redundant parallel manipulator in different directions. The indices have been applied to evaluate the joint capability of the redundant parallel manipulator by simulation. They are general and can be used for other types of parallel manipulators.
Curriculum Development for Advancing Heritage Language Competence: Recent Research, Current Practices, and a Future Agenda
Authors: Kondo-Brown Kimi
Published: July 2010

In the last few decades, research on teaching heritage language (HL) learners has expanded enormously and encouraged language professionals to work toward responsible curriculum development for this specific type of learners. This article suggests ways to expand current curriculum research and practices with the goal of advancing the HL competence of learners. To this end, this article examines the scope, trends, and issues in recent theoretical and practical studies concerning curriculum development for HL learners from various language backgrounds, especially those in the United States. A definition of HL learners is presented first, which is followed by a discussion of general second language curriculum development frameworks with specific reference to HL instruction. Then, the article examines the contexts, challenges, and possibilities for teaching HLs to school-age children in precollegiate programs. Next, it turns to a discussion of issues and recommendations for teaching postsecondary HL students. The article concludes by discussing curricular and pedagogical recommendations for HL professionals as well as a future research agenda that could promote the advancement of HL competence in all educational institutions.
Semantic Theory and Second Language Acquisition
Authors: Slabakova Roumyana
Published: July 2010

The article identifies four different types of meaning situated in different modules of language. Such a modular view of language architecture suggests that there may be differential difficulties of acquisition for the different modules. It is argued that second language (L2) acquisition of meaning involves acquiring interpretive mismatches at the first and second language (L1-L2) syntax-semantics interfaces. In acquiring meaning, learners face two types of learning situations. One situation where the sentence syntax presents less difficulty but different pieces of functional morphology subsume different primitives of meaning is dubbed simple syntax–complex semantics. Another type of learning situation is exemplified in less frequent, dispreferred, or syntactically complex sentences where the sentential semantics offers no mismatch; these are labeled complex syntax–simple semantics. Studies representative of these learning situations are reviewed. The issues of importance of explicit instruction with respect to interpretive properties and the effect of the native language are addressed. Studies looking at acquisition of language-specific discourse properties and universal pragmatics are also reviewed. These representative studies and numerous other studies on the L2 acquisition of meaning point to no visible barrier to ultimate success in the acquisition of semantics and pragmatics.
Intensity-dependent facial emotion recognition and cognitive functions in Parkinson’s disease
Authors: ASSOGNA FRANCESCA , PONTIERI FRANCESCO E. , CRAVELLO LUCA , PEPPE ANTONELLA , PIERANTOZZI MARIANGELA , STEFANI ALESSANDRO , STANZIONE PAOLO , PELLICANO CLELIA , CALTAGIRONE CARLO , SPALLETTA GIANFRANCO
Published: July 2010

Patients with Parkinson’s disease (PD) frequently display non-motor symptoms. In this study, we investigated intensity-dependent facial emotion recognition in patients with PD and healthy controls (HC), matched for age, gender, and education, and its relationship to individual cognitive domains. Seventy patients with PD and 70 HC were submitted to a clinical, neuropsychological, and psychopathological evaluation. Facial emotion recognition performance was assessed using the Penn Emotion Recognition Test (PERT). The patients with PD recognized fewer low- and high-intensity facial expressions of disgust than HC. This effect was selective, because their global ability to recognize emotions was intact. Both patients with PD and HC recognized high-intensity better than low-intensity emotions, except for disgust, which was recognized better at low intensity. In the patients with PD, overall facial emotion recognition and selective disgust recognition performances were related to deficits in many neuropsychological domains (verbal and visuo-spatial memory, attention, praxis, and verbal fluency). The ability to recognize emotions is a complex cognitive process requiring the integrity of several functions. Therefore, it is likely that structural or functional derangement of the discrete neural pathways involved in these cognitive functions in patients with PD makes it difficult for them to recognize emotions expressed by others. (JINS, 2010, 16, 867–876.)
Extracellular proteomes of M‐CSF (CSF‐1) and GM‐CSF‐dependent macrophages
Authors: Bailey Mark J , Lacey Derek C , de Kok Bernard VA , Veith Paul D , Reynolds Eric C , Hamilton John A
Published: July 2010

Macrophage colony‐stimulating factor (M‐CSF) (also known as CSF‐1) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) have distinct effects on macrophage lineage populations, which are likely to be contributing to their functional heterogeneity. A comparative proteomic analysis of proteins released into culture media from such populations after M‐CSF and GM‐CSF exposure was carried out. Adherent macrophage populations, termed bone marrow‐derived macrophage (BMM) and GM‐BMM, were generated after treatment of murine bone marrow precursors with M‐CSF and GM‐CSF, respectively. Proteins in 16‐h serum‐free conditioned media (CM) were identified by two‐dimensional gel electrophoresis and mass spectrometry. Respective protein profiles from BMM and GM‐BMM CM were distinct and there was the suggestion of a switch from primarily signal peptide‐driven secretion to non‐classical secretion pathways from BMM to GM‐BMM. Extracellular expression of cathepsins (lysosomal proteases) and their inhibitors seems to be a characteristic difference between these macrophage cell types with higher levels usually observed in BMM‐CM. Furthermore, we have identified a number of proteins in BMM‐CM and GM‐BMM‐CM that could be involved in various tissue regeneration and inflammatory (immune) processes, respectively. The uncharacterized protein C19orf10, a protein found at high levels in the synovial fluid of arthritis patients, was also differentially regulated; its extracellular levels were upregulated in the presence of GM‐CSF.
Protein–protein interactions
Authors: Williamson Mike P. , Sutcliffe Michael J.
Published: July 2010

In the present article, we describe the two standard high-throughput methods for identification of protein complexes: two-hybrid screens and TAP (tandem affinity purification) tagging. These methods have been used to characterize the interactome of Saccharomyces cerevisiae, showing that the majority of proteins are part of complexes, and that complexes typically consist of a core to which are bound ‘party’ and ‘dater’ proteins. Complexes typically are merely the sum of their parts. A particularly interesting type of complex is the metabolon, containing enzymes within the same metabolic pathway. There is reasonably good evidence that metabolons exist, but they have not been detected using high-thoughput assays, possibly because of their fragility.
High-throughput identification of transient extracellular protein interactions
Authors: Wright Gavin J. , Martin Stephen , Bushell K. Mark , Söllner Christian
Published: July 2010

Protein interactions are highly diverse in their biochemical nature, varying in affinity and are often dependent on the surrounding biochemical environment. Given this heterogeneity, it seems unlikely that any one method, and particularly those capable of screening for many protein interactions in parallel, will be able to detect all functionally relevant interactions that occur within a living cell. One major class of interactions that are not detected by current popular high-throughput methods are those that occur in the extracellular environment, especially those made by membrane-embedded receptor proteins. In the present article, we discuss some of our recent research in the development of a scalable assay to identify this class of protein interaction and some of the findings from its application in the construction of extracellular protein interaction networks.
The stressosome: molecular architecture of a signalling hub
Authors: Marles-Wright Jon , Lewis Richard J.
Published: July 2010

The stressosome co-ordinates the response of Bacillus subtilis to the imposition of a variety of physical and environmental insults. These stresses include fluctuations in salt concentration, the presence of ethanol, changes in pH and even the level of UV light. Despite the obvious and significant differences between these quite different physicochemical stimuli, the result is the same: the stressosome is phosphorylated by a key kinase to initiate the σB cascade. The phosphorylation of the stressosome initiates a signal transduction system that up-regulates the expression of stress-responsive genes so that the Bacillus can survive the imposition of stress. Hence the stressosome acts as a hub, receiving manifold different stimuli to effect a single outcome. Using single-particle analysis of cryo-electron micrographs, we have been able to reconstruct a series of molecular envelopes of the stressosome. These maps have been interpreted at near-atomic resolution with crystal structures of the individual components of the stressosome to provide the first visualization of this unique signalling hub. The macromolecular structure adopted by the stressosome provides the signalling cascade with the potential for co-operative behaviour, which we have also measured in live bacteria. These experiments are consistent with the tuning of the response of B. subtilis to stress relative to the magnitude of the insult.
Can infrared spectroscopy provide information on protein–protein interactions?
Authors: Haris Parvez I.
Published: July 2010

For most biophysical techniques, characterization of protein–protein interactions is challenging; this is especially true with methods that rely on a physical phenomenon that is common to both of the interacting proteins. Thus, for example, in IR spectroscopy, the carbonyl vibration (1600–1700 cm−1) associated with the amide bonds from both of the interacting proteins will overlap extensively, making the interpretation of spectral changes very complicated. Isotope-edited infrared spectroscopy, where one of the interacting proteins is uniformly labelled with 13C or 13C,15N has been introduced as a solution to this problem, enabling the study of protein–protein interactions using IR spectroscopy. The large shift of the amide I band (approx. 45 cm−1 towards lower frequency) upon 13C labelling of one of the proteins reveals the amide I band of the unlabelled protein, enabling it to be used as a probe for monitoring conformational changes. With site-specific isotopic labelling, structural resolution at the level of individual amino acid residues can be achieved. Furthermore, the ability to record IR spectra of proteins in diverse environments means that isotope-edited IR spectroscopy can be used to structurally characterize difficult systems such as protein–protein complexes bound to membranes or large insoluble peptide/protein aggregates. In the present article, examples of application of isotope-edited IR spectroscopy for studying protein–protein interactions are provided.
Tau phosphorylation in hippocampus results in toxic gain-of-function
Authors: Avila Jesús , Gómez de Barreda Elena , Engel Tobias , Lucas Jose J. , Hernández Félix
Published: July 2010

The MAP (microtubule-associated protein) tau binds to tubulin, the main component of MTs (microtubules), which results in the stabilization of MT polymers. Tau binds to the C-terminal of tubulin, like other MAPs (including motor proteins such as kinesin) and it therefore may compete with these proteins for the same binding site in the tubulin molecule. In pathological conditions, tau is the main component of aberrant protein aggregates found in neurodegenerative disorders known as tauopathies where tau is present in its hyperphosphorylated form. GSK3 (glycogen synthase kinase 3, also known as tau kinase I) has been described as one of the main kinases involved in tau modifications. We have analysed the role of phospho-tau as a neurotoxic agent. We have analysed a transgenic mouse model which overexpresses GSK3β. In this transgenic mouse, a clear degeneration of the dentate gyrus, which increases with age, was found. In a double transgenic mouse, which overexpresses GSK3 and tau at the same time, dentate gyrus degeneration was dramatically increased. This result may suggest that phospho-tau may be toxic inside neurons of the dentate gyrus. Once neuronal degeneration takes place, intracellular tau is secreted to the extracellular space. The present review discusses the toxicity of this extracellular tau for surrounding neurons.
Phosphorylation differentiates tau-dependent neuronal toxicity and dysfunction
Authors: Papanikolopoulou Katerina , Kosmidis Stylianos , Grammenoudi Sofia , Skoulakis Efthimios M.C.
Published: July 2010

The heterogeneous pathology of tauopathies and the differential susceptibility of different neuronal types to WT (wild-type) and mutant tau suggest that phosphorylation at particular sites rather than hyperphosphorylation mediates toxicity or dysfunction in a cell-type-specific manner. Pan-neuronal accumulation of tau in the Drosophila CNS (central nervous system) specifically affected the MBs (mushroom body neurons), consistent with neuronal type-specific effects. The MB aberrations depended, at least in part, on occupation of two novel phosphorylation sites: Ser238 and Thr245. The degree of isoform-specific MB aberrations was paralleled by defects in associative learning, as blocking putative Ser238 and Thr245 phosphorylation yielded structurally normal, but profoundly dysfunctional, MBs, as animals accumulating the mutant protein exhibited strongly impaired associative learning. Similarly dysfunctional MBs were obtained by temporally restricting tau accumulation to the adult CNS, which also altered the tau phosphorylation pattern. Our data clearly distinguish tau-dependent neuronal degeneration and dysfunction and suggest that temporal differences in occupation of the same phosphorylation sites are likely to mediate these distinct effects of tau.
Insights from Drosophila models of Alzheimer's disease
Authors: Cowan Catherine M. , Shepherd David , Mudher Amritpal
Published: July 2010

AD (Alzheimer's disease) is a neurodegenerative disorder characterized by the abnormal hyperphosphorylation and aggregation of the microtubule-associated protein tau and the misfolding and deposition of Aβ peptide. The mechanisms by which tau and Aβ become abnormal is not clearly understood, neither is it known what role either protein plays in the neurodegenerative process underlying AD. We have modelled aspects of AD in Drosophila melanogaster to shed light on these processes and to further our understanding of the relationship between tau and amyloid in this disease.
Links between ApoE, brain cholesterol metabolism, tau and amyloid β-peptide in patients with cognitive impairment
Authors: Leoni Valerio , Solomon Alina , Kivipelto Miia
Published: July 2010

Brain neurons remove the excess of cholesterol via conversion into the more polar 24OHC [(24S)-hydroxycholesterol]. 24OHC acts as a signalling molecule inducing ApoE (apolipoprotein E)-mediated cholesterol efflux from astrocytes, by a direct effect on ApoE transcription, protein synthesis and secretion. In CSF (cerebrospinal fluid) collected form from patients with cognitive impairment (Alzheimer's disease and patients with mild cognitive impairment) the levels of ApoE, tau, p-tau (hyperphosphorylated tau) were significantly increased, together with 24OHC, compared with controls. We also found that the levels of tau and p-tau were significantly correlated with ApoE and 24OHC in the same samples. Such a correlation was not found in control patients. Increased levels of cholesterol in membranes and impairment in brain cholesterol metabolism were found to be involved both in APP (amyloid precursor protein) processing and amyloid β-peptide deposition and, recently, in tau pathology. The CSF tau levels are considered to be related to the neurodegenerative process in Alzheimer's disease. During neurodegeneration, the cholesterol accumulated in neurons is converted into 24OHC. The release of 24OHC from neurons induces ApoE secretion by astrocytes, and both are related to the intensity of the neurodegenerative process and neuronal injury. ApoE can also be involved in the scavenging of tau from neurons. The direct correlations between ApoE, 24OHC and tau suggest that cholesterol metabolism may be involved in generation of both tau and amyloid β-peptide and that the ApoE is released by astrocytes in order to counteract this ongoing process.
High-content screening of small compounds on human embryonic stem cells
Authors: Barbaric Ivana , Gokhale Paul J. , Andrews Peter W.
Published: July 2010

Human ES (embryonic stem) cells and iPS (induced pluripotent stem) cells have been heralded as a source of differentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson's disease or diabetes. Despite the great potential for their use in regenerative therapy, the challenge remains to understand the basic biology of these remarkable cells, in order to differentiate them into any functional cell type. Given the scale of the task, high-throughput screening of agents and culture conditions offers one way to accelerate these studies. The screening of small-compound libraries is particularly amenable to such high-throughput methods. Coupled with high-content screening technology that enables simultaneous assessment of multiple cellular features in an automated and quantitative way, this approach is proving powerful in identifying both small molecules as tools for manipulating stem cell fates and novel mechanisms of differentiation not previously associated with stem cell biology. Such screens performed on human ES cells also demonstrate the usefulness of human ES/iPS cells as cellular models for pharmacological testing of drug efficacy and toxicity, possibly a more imminent use of these cells than in regenerative medicine.
snRNA 3′ end formation: the dawn of the Integrator complex
Authors: Chen Jiandong , Wagner Eric J.
Published: July 2010

The ubiquitously expressed uridine-rich snRNAs (small nuclear RNAs) are essential for the removal of introns, proper expression of histone mRNA and biosynthesis of ribosomal RNA. Much is known about their assembly into snRNP (small nuclear ribonucleoprotein) particles and their ultimate function in the expression of other genes; however, in comparison, less is known about the biosynthesis of these critical non-coding RNAs. The sequence elements necessary for 3′ end formation of snRNAs have been identified and, intriguingly, the processing of snRNAs is uniquely dependent on the snRNA promoter, indicating that co-transcriptional processing is important. However, the trans-acting RNA-processing factors that mediate snRNA processing remained elusive, hindering overall progress. Recently, the factors involved in this process were biochemically purified, and designated the Integrator complex. Since their initial discovery, Integrator proteins have been implicated not only in the production of snRNA, but also in other cellular processes that may be independent of snRNA biogenesis. In the present study, we discuss snRNA biosynthesis and the roles of Integrator proteins. We compare models of 3′ end formation for different classes of RNA polymerase II transcripts and formulate/propose a model of Integrator function in snRNA biogenesis.
Noise Reduction: The Postpolitical Quandary of Night Flights at Brussels Airport
Authors: Oosterlynck Stijn , Swyngedouw Erik
Published: July 2010

The emergence of the controversy over airport-generated noise at Brussels Airport as an environmental issue on the national political agenda coincided with the inauguration of Belgium's first ‘purple–green’ government in 1999. The new government announced explicitly the dawning of a new political age in which old controversies and adversarial left–right politics were relegated to the dustbin of history. From now onwards, the interests of market actors, environmental concerns, and social objectives would be negotiated and reconciled in the interest of all within the framework of a common and consensually agreed objective of achieving environmentally sustainable, socially inclusive, and market-based development. The controversy over DHL's night flights at Brussels Airport would prove to be one of the first real test cases of this ‘Third Way’ postpolitical approach to policing socioenvironmental affairs. However, after several years of acrimonious argument, successive attempts to negotiate a compromise with all relevant partners, and increasingly more entrenched antagonistic dispute, DHL abandoned Brussels Airport as its main European hub. This sequence belied the initial optimism of the government's postpolitical approach and, we argue in this paper, stands emblematically for the failure of such postpolitical modes of policing socioenvironmental affairs. The objective of this paper is to explore, both theoretically and empirically, the contradictions and tensions associated with the postpolitical model. First, we situate theoretically the emergence and consolidation of postpolitical modes of governing and the colonisation of the space of the political by forms of consensual depoliticised governance. Second, we shall analyse how urban socioenvironmental governance procedures associated with the problem of noise at Brussels Airport express the attempts to institute postdemocratic modes of governance, while exploring the contradictions of this model. In addition, the failure of postdemocratic and postpolitical arrangements is discussed, and an urgent need to repoliticise urban socioecological relations is argued.
Environmental Governance in Russia: The ‘Closed’ Pathway to Ecological Modernization
Authors: Tokunaga Masahiro
Published: July 2010

This paper examines the development of environmental governance in Russia, using the concept of ecological modernization as an analytical framework for an empirical study. From an investigation into both the relationship between economic growth and environmental stress on the basis of the revised model of decoupling and the development of institutional capacity for environmental policy in recent years, this paper reveals that Russia's pathway to ecological modernization is now ‘closed’ in most spheres owing to the economic crisis that followed the collapse of the Soviet Union; this is in contrast to China's experience, wherein ecological modernization has been ‘forced’ as a national policy. Russia is considered to be a typical case of failure of realization of industrial restructuring leading to a relative reduction in environmental stress in a centrally planned economy. Moreover, the country's hyperdepression since the introduction of a market economy has hindered the search for a pathway to medium-term and long-term ecological modernization, which has been exchanged for short-term ‘ecological improvement without environmental policy’.