bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of novel small-molecule histone deacetylase inhibitors by medium-throughput screening using a fluorigenic assay
Authors: Wegener Dennis , Hildmann Christian , Riester Daniel , Schober Andreas , Meyer-Almes Franz-Josef , Deubzer Hedwig E. , Oehme Ina , Witt Olaf , Lang Siegmund , Jaensch Martina , Makarov Vadim , Lange Corinna , Busse Benedikt , Schwienhorst Andreas
Published: June 2008

HDACs (histone deacetylases) are considered to be among the most important enzymes that regulate gene expression in eukaryotic cells. In general, increased levels of histone acetylation are associated with increased transcriptional activity, whereas decreased levels are linked to repression of gene expression. HDACs associate with a number of cellular oncogenes and tumour-suppressor genes, leading to an aberrant recruitment of HDAC activity, which results in changes of gene expression, impaired differentiation and excessive proliferation of tumour cells. Therefore HDAC inhibitors are efficient anti-proliferative agents in both in vitro and in vivo pre-clinical models of cancer, making them promising anticancer therapeutics. In the present paper, we present the results of a medium-throughput screening programme aiming at the identification of novel HDAC inhibitors using HDAH (HDAC-like amidohydrolase) from Bordetella or Alcaligenes strain FB188 as a model enzyme. Within a library of 3719 compounds, several new classes of HDAC inhibitor were identified. Among these hit compounds, there were also potent inhibitors of eukaryotic HDACs, as demonstrated by an increase in histone H4 acetylation, accompanied by a decrease in tumour cell metabolism in both SHEP neuroblastoma and T24 bladder carcinoma cells. In conclusion, screening of a compound library using FB188 HDAH as model enzyme identified several promising new lead structures for further development.
Working Class Women, Gambling and the Dream of Happiness
Authors: Casey Emma
Published: June 2008

This paper offers an account of the relationship between gender, class and notions of happiness. It draws on recent research conducted into the experiences of working class women who play the UK National Lottery. In particular, it explores the notion that gambling offers working class women the opportunity to dream of the ‘good life’ – of enhancing their lives and of making ‘improvements’ to their own and their families’ well-being. In this paper, the discourse of happiness will be examined, and the tacit assumption that working class women in particular are prone to turning to gambling as a last ditch attempt to personal and emotional fulfilment will be challenged. The paper argues that developing understandings of culture and consumption practices is imperative for producing a more complex understanding of the subjective realities of working class women's everyday lives. By engaging with feminist accounts of respectability, daydream and fantasy, the paper will present a thorough exploration of National Lottery play in working class women's everyday experiences of happiness.
Country Matters: Sexing the Reconciled Republic of Australia
Authors: Probyn-Rapsey Fiona
Published: June 2008

This essay analyses how Australian postcolonial discourses, influenced by both Republicanism and Reconciliation, deploy the trope of woman to signify political change in both feminist and cultural debates about belonging, national legitimacy and sovereignty. I point out that white feminist rejection of the Queen in favour of embracing indigeneity is itself complicit with a history of ‘incorporating’ and assimilating indigeneity – a complicity that is sublimated in favour of a triumphant rejection of Imperial white womanhood. The essay looks at a contemporary Australian novel, media depictions of Paul Keating's ‘embrace’ of Queen Elizabeth II (as a kind of captivity narrative), critical whiteness studies’ ‘rejection’ of the Queen and the misrecognition of Australia's distinct characteristics as a ‘settler culture’ (that incorporates indigeneity) within Australian feminist debates and claims of ‘transgression’ that are made for interracial relationships in Australia.
‘Period Problems’ at the Coalface
Authors: Lahiri-Dutt Kuntala , Robinson Kathryn
Published: June 2008

Menstruation leave for women workers brings into the public domain of mining ongoing debates around protective legislation for women. It brings into focus the presumed tensions between gender equity and gender difference with regard to women's economic citizenship. Large-scale mining in East Kalimantan in Indonesia has offered some opportunities to poor and unskilled rural women to find formal jobs in the mines as truck and heavy equipment operators. This paper presents a case study of women in mining occupations, considers the implications of current menstruation leave provisions on the employment of women in the mines and raises serious issues related to gender equity in the workplace. The involvement of women in a non-conventional workplace such as the mine pits, providing a novel site for contestation over the rights of women workers, illuminates a less-debated area in feminist studies, especially in view of the significant ongoing changes in the Indonesian framework for industrial relations.
Thermodynamics of apoplastocyanin folding: Comparison between experimental and theoretical results
Authors: Yoshidome Takashi , Kinoshita Masahiro , Hirota Shun , Baden Naoki , Terazima Masahide
Published: June 2008

It has been experimentally shown that the folding of apoplastocyanin (apoPC) accompanies a very large enthalpic loss [N. Baden et al., J. Chem. Phys. 127, 175103 (2007)]. This implies that an even larger entropic gain occurs in stabilizing the folded structure to overcome the enthalpic loss. Here, we calculate the water-entropy gain upon the folding of apoPC using the angle-dependent integral equation theory combined with the multipolar water model and the recently developed morphometric approach. It is demonstrated that the calculated value is in quantitatively good accord with the value estimated from the experimental data by accounting for the conformational-entropy loss. According to a prevailing view, the water adjacent to a hydrophobic group is unstable especially in terms of the rotational entropy and the folding is driven primarily by the release of such unfavorable water to the bulk through the burial of nonpolar side chains. We show, however, that the resultant entropic gain is too small to elucidate the experimental result. The great entropic gain observed is ascribed to the reduction in the restriction for the translational motion of water molecules in the whole system.
Coupled-cluster dynamic polarizabilities including triple excitations
Authors: Hammond Jeff R. , de Jong Wibe A. , Kowalski Karol
Published: June 2008

Dynamic polarizabilities for open- and closed-shell molecules were obtained by using coupled-cluster (CC) linear response theory with full treatment of singles, doubles, and triples (CCSDT-LR) with large basis sets utilizing the NWChem software suite. By using four approximate CC methods in conjunction with augmented cc-pVNZ basis sets, we are able to evaluate the convergence in both many-electron and one-electron spaces. For systems with primarily dynamic correlation, the results for CC3 and CCSDT are almost indistinguishable. For systems with significant static correlation, the CC3 tends to overestimate the triples contribution, while the PS(T) approximation [J. Chem. Phys. 127, 164105 (2007)] produces mixed results that are heavily dependent on the accuracies provided by noniterative approaches used to correct the equation-of-motion CCSD excitation energies. Our results for open-shell systems show that the choice of reference (restricted open-shell Hartree–Fock versus unrestricted Hartree–Fock) can have a significant impact on the accuracy of polarizabilities. A simple extrapolation based on pentuple-zeta CCSD calculations and triple-zeta CCSDT calculations reproduces experimental results with good precision in most cases.
How noise statistics impact models of enzyme cycles
Authors: Warmflash Aryeh , Adamson David N. , Dinner Aaron R.
Published: June 2008

Theoretical tools for adequately treating stochastic effects are important for understanding their role in biological processes. Although master equations provide rigorous means for investigating effects associated with fluctuations of discrete molecular copy numbers, they can be very challenging to treat analytically and numerically. Approaches based on the Langevin approximation are often more tractable, but care must be used to ensure that it is justified in each situation. Here, we examine a model of an enzyme cycle for which noise qualitatively alters the behavior of the system: fluctuations in the population of an enzyme can result in amplification and multistability in the distribution of its product. We compare master equation and Langevin treatments of this system and show that results derived previously with a white noise Langevin equation [M. Samoilov et al., Proc. Natl. Acad. Sci. U.S.A. 102, 2310 (2005)] are inconsistent with the master equation. A colored noise Langevin equation captures some, but not all, of the essential physics of the system. The advantages and disadvantages of the Langevin approximation for modeling biological processes are discussed.
Effects of impedance matching network on the discharge mode transitions in a radio-frequency inductively coupled plasma
Authors: Ding Z. F. , Yuan G. Y. , Gao W. , Sun J. C.
Published: June 2008

In inductively coupled plasma sources, discharge transitions from electrostatic mode (E mode) to electromagnetic mode (H mode) and from H mode to E mode occur. In previous studies, only a few works paid attention to the effects of the impedance matching network. Cunge et al. [Plasma Sources Sci. Technol. 8, 576 (1999)] investigated the E-H and H-E mode transitions under two different impedance matching situations, but no physical mechanism or interpretation was presented. This issue is remained to be systematically and quantitatively investigated, and the underlying mechanism to be unveiled. In this paper, the effects of the impedance matching network were experimentally studied in electropositive argon gas by varying the series capacitance in an inversely L-shaped matching network. The positive and negative feedback regions are established according to the effect of varying the series capacitance on the output power of the rf power supply. It was found that under the same experimental parameters, the discharge mode transitions are apt to be discontinuous and continuous in the positive and negative feedback regions, respectively. In addition, the critical coil rf current (or applied power) at the mode transition, the hysteretic loop width, and the difference in applied power during the discharge mode transition vary with the series capacitance. The critical coil rf current at the E-H mode transition is not always higher than that at the H-E mode transition.
Thermodynamic scaling and the characteristic relaxation time at the phase transition of liquid crystals
Authors: Roland C. M. , Bogoslovov R. B. , Casalini R. , Ellis A. R. , Bair S. , Rzoska S. J. , Czuprynski K. , Urban S.
Published: June 2008

The longitudinal relaxation time τ of a series of alkyl-isothiocyanato-biphenyls (nBT) liquid crystals in the smectic E phase was measured as a function of temperature T and pressure P using dielectric spectroscopy. This relaxation time was found to become essentially constant, independent of T and P, at both the clearing point and the lower temperature crystalline transition. τ(T,P) could also be superposed as a function of the product TVγ, where V is the specific volume and γ is a material constant. It then follows from the invariance of the relaxation time at the transition that the exponent γ superposing τ(T,V) can be identified with the thermodynamic ratio Γ=−∂log(Tc)∕∂log(Vc), where the subscript c denotes the value at the phase transition. Analysis of literature data on other liquid crystals shows that they likewise exhibit a constant τ at their phase transitions. Thus, there is a surprising relationship between the thermodynamic conditions defining the stability limits of a liquid crystalline phase and the dynamic properties reflected in the magnitude of the longitudinal relaxation time.
A viscosity self-oscillation of polymer solution induced by the Belousov–Zhabotinsky reaction under acid-free condition
Authors: Hara Yusuke , Yoshida Ryo
Published: June 2008

We succeeded in measuring a viscosity self-oscillation induced by the Belousov-Zhabotinsky (BZ) reaction for a polymer solution on the constant temperature condition under acid-free condition. The polymer chain is consisted of N-isopropylacrylamide, ruthenium complex as a catalyst of the BZ reaction, and an acrylamide-2-methylpropanesulfonic acid (AMPS) as a pH and the solubility control site. The viscosity self-oscillation for the AMPS-containing polymer solution was attributed to the difference between viscosities for the polymer solution in the reduced and oxidized states. The effects of the polymer concentration and the temperature of the polymer solution on the viscosity self-oscillation were investigated. As a result, the viscosity self-oscillating behavior significantly depended on the polymer concentration and the temperature of the polymer solution. The period of the viscosity self-oscillation decreased with increasing temperature in accordance with the Arrenius equation.
Parametric instabilities of Alfvén waves in a multispecies plasma: Kinetic effects
Authors: Kauffmann K. , Araneda J. A.
Published: June 2008

Parametric instabilities of a circularly polarized Alfvén wave in a multispecies magnetized plasma are considered. An analytic kinetic description and hybrid simulations for the linear behavior of the instabilities are given. It is found that, even for low-β regimes, both the kinetic effects and the presence of heavy ions substantially modify the characteristics of parametric instabilities as compared to the fluid model. The decay instability can be severely quenched in a plasma composed of massless electrons, protons, and alpha particles when the alphas are slightly hotter than the protons. These results could be important in describing the heating processes of heavy ions in the solar corona.
Electron paramagnetic resonance spectrum of the FCO2 radical isolated in noble gas matrices
Authors: Beckers H. , Willner H. , Grote D. , Sander W. , Geier J.
Published: June 2008

The EPR spectra of the fluoroformyloxyl radical FCO2 isolated in noble gas matrices at temperatures from 5to30K have been investigated. This study provides principal g values and F19 hyperfine coupling constants of FCO2 measured in Ar matrices at 5K, and yields isotropic values at 30K. A detailed analysis of the coupling parameters obtained from the EPR and a concomitant high resolution spectroscopic MMW study supported by quantum chemical calculations rationalized the fine and hyperfine interactions of this simple fluorooxyl radical.
Morphology of spinodal decompositions in liquid crystal–colloid mixtures
Authors: Matsuyama Akihiko
Published: June 2008

We study the morphology of spinodal decompositions (SDs) in mixtures of a liquid crystal and a colloidal particle by solving time-dependent Landau–Ginzburg equations for a conserved order parameter (concentration) and two nonconserved order parameters (orientation and crystallization). We numerically examine the coupling between concentration, nematic ordering, and crystalline ordering in two dimensional fluid mixtures, coexisting a nematic and a crystalline phase. On increasing the concentration of colloidal particles, we have three different SDs: a nematic order-induced SD, a phase-separation-induced SD (PSD), and a crystalline-order-induced SD (CSD). In NSD, the phase ordering can lead to fibrillar and cellular networks of the minority colloidal-particle-rich phase in early stages. In the PSD, we find a bicontinuous network structure consisting of a nematic phase rich in liquid crystal and a crystalline phase rich in colloidal particles. In the CSD, nematic droplets can be formed in a crystalline matrix. Asymmetric mixtures of a liquid crystal and a colloidal particle lead to rich varieties of morphologies.
Contact stiffness of finite size subsurface defects for atomic force microscopy: Three-dimensional finite element modeling and experimental verification
Authors: Parlak Zehra , Levent Degertekin F.
Published: June 2008

We describe a three-dimensional (3D) finite element analysis model of the contact between an atomic force microscopy (AFM) tip and a substrate with finite size subsurface structures. The model can simulate the contact stiffness measured by a scanning AFM tip on the surface of a sample with buried nanoscale structures. In addition to the analytical verification and convergence analysis, we present the results of an experimental verification study. For this purpose, we use an atomic force acoustic microscopy setup and special silicon samples with well defined subsurface cavities fabricated by focused ion beam techniques. The 3D model is also used for parametric analysis of subsurface defect detection, and imaging simulations are performed for practical applications such as AFM imaging of electromigration defects.
Waveguide evanescent field fluorescence microscopy: Thin film fluorescence intensities and its application in cell biology
Authors: Hassanzadeh Abdollah , Nitsche Michael , Mittler Silvia , Armstrong Souzan , Dixon Jeff , Langbein Uwe
Published: June 2008

We demonstrate an inexpensive alternative to total internal reflection fluorescence microscopy. A method for imaging ultrathin films and living cells located on waveguides—illuminated with their evanescent fields—is introduced. An extensive analysis of ion-exchanged waveguides focusing on their application as microscopy substrates for studying interfacial phenomena is presented. Experimental results are in excellent agreement with the simulations. As an application osteoblasts (bone matrix forming cells) and ultrathin Langmuir–Blodgett films were imaged. The fluorescence intensity has been used to determine the cell attachment.
Phonon-plasmon coupled-mode lifetime in semiconductors
Authors: Dyson A. , Ridley B. K.
Published: June 2008

Raman scattering measurements of the lifetime of hot phonons in GaN show a decrease with increasing electron concentration. Density-dependent lifetimes have also been deduced from noise measurements of AlGaN/GaN channels. We suggest that the results from Raman scattering can be understood by the frequency dependence of the anharmonic interaction for coupled modes and that the results from noise measurements can be understood qualitatively by the anharmonic interaction plus the migration of coupled modes.
Phononic band-gap crystals for radio frequency communications
Authors: El-Kady I. , Olsson R. H. , Fleming J. G.
Published: June 2008

We report on the experimental and theoretical observation of a phononic band-gap crystal operating in the megahertz regime. Our experimental data show over 25dB suppression of bulk acoustic waves, and our theoretical models predict almost linear scaling to the gigahertz frequencies, thus laying the foundation for the implementation of such devices in radio frequency communications. We further argue that cavities in such systems offer a unique opportunity to couple acoustic energy into a resonator utilizing piezoelectric materials, while at the same time allowing the realization of a resonance cavity in high-Q materials such as silicon oxide, silicon, and tungsten.
Sharp thresholds of blow-up and global existence for the coupled nonlinear Schrödinger system
Authors: Ma Li , Zhao Lin
Published: June 2008

In this paper, we establish two new types of invariant sets for the coupled nonlinear Schrödinger system in the Euclidean n-space Rn and derive two sharp thresholds of blow-up and global existence for its solutions. Some analogous results for the nonlinear Schrödinger system posed on the hyperbolic space Hn and on the standard 2-sphere S2 are also presented. Our arguments and constructions are improvements of some previous works on this direction. At the end, we give some heuristic analysis about the strong instability of the solitary waves. The relation between the two types of thresholds is a very interesting problem, and we leave it as an open problem for further study.
Exact closed-form electromagnetic Green’s functions for graded uniaxial multiferroic materials
Authors: Wang X. , Pan E. , Albrecht J. D.
Published: June 2008

Functionally graded multiferroic composites are being investingated in order to tailor the electromagnetic properties of synthetic surfaces and material interfaces. Theoretical representations of multiferroic materials simultaneously account for magnetization and ferroelectric polarization in a strongly coupled system. In this paper, exact closed-form electromagnetic Green’s functions due to electric and magnetic point sources are derived for the general class of uniaxial multiferroics with functionally graded compositions where the material property varies exponentially in an arbitrary direction. After the introduction of two new functions, the set of coupled governing partial differential equations is separated into two independent inhomogeneous partial differential equations. These resultant equations are further cast in Helmholtz form so that solutions can be derived expediently. We observed that the derived Green’s functions in the graded case possess symmetric properties in their indices, but not in their spatial variables. Numerical results show that the amplitudes of the field response along the direction of the compositional gradient can be either matched to a uniform material or systematically reduced, as necessary. Finally, Green’s functions are applied to study the electric dipole-induced electric and magnetic potentials in the functionally graded multiferroics.
Fluctuations of correlations and Green’s function reconstruction: Role of scattering
Authors: Larose Eric , Roux Philippe , Campillo Michel , Derode Arnaud
Published: June 2008

Correlations of ambient seismic or acoustic vibrations are now widely used to reconstruct the impulse response between two passive receivers as if a source was placed at one of them. This provides the opportunity to do imaging without a source, or passive imaging. Applications include terrestrial and solar seismology, underwater acoustics, and structural health monitoring, to cite only a few. Nevertheless, for a given set of data, correlations do not only yield Green’s function between the sensors. They also contain residual fluctuations that result from an imperfect time or source averaging that might eventually blur the images. In this article, we propose a heuristic model to describe the level of fluctuations of the correlations in the case of nonstationary wavefields, and more particularly in the case of scattering media. The work includes theoretical derivations and numerical simulations. The role of multiple scattering is quantitatively evaluated. The level of fluctuations decreases when the duration and intensity of the diffuse waves increase. The role of absorption is also discussed: absorption is properly retrieved by correlation, but the level of fluctuations is greater, thus degrading Green’s function reconstruction. Discrepancies of our simple model in the case of strong multiple scattering (kℓ*⩽18) are discussed.
Three-dimensional imaging of a complex concaved cuboctahedron copper sulfide crystal by x-ray nanotomography
Authors: Chen Jie , Wu Chunyan , Tian Jinping , Li Wenjie , Yu Shuhong , Tian Yangchao
Published: June 2008

By combining Fresnel zone-plate based transmission x-ray microscopy with computed tomography, the nanoscale features in materials with complex shapes can be imaged using synchrotron radiation. The tomographic data sets of a complex copper sulfide crystal were acquired in the angle range ±70° at photon energy of 8.0keV and then were reconstructed by a standard filtered-back-projection algorithm. This experiment shows the quantifiable three-dimensional information of the copper sulfide crystal, which offers a complete understanding of the concaved cuboctahedron structure with 14 faces comprising of six squares and eight triangles.
Carrier multiplication in carbon nanotubes studied by femtosecond pump-probe spectroscopy
Authors: Ueda Akihiro , Matsuda Kazunari , Tayagaki Takeshi , Kanemitsu Yoshihiko
Published: June 2008

Carbon nanotubes are one of the excellent materials for studying the many-body effects of excitons because of their unique band structures and large exciton binding energies. We studied exciton population dynamics in single-walled carbon nanotubes using pump-probe transient absorption measurements. The temporal profiles of the transient absorption signals depend on the excitation intensity and excitation photon energy. We observe carrier multiplication in carbon nanotubes at room temperature, when the excitation photon energy exceeds the third subband exciton energy.
Tuning of emission colors in zinc oxide quantum dots
Authors: Haranath D. , Sahai Sonal , Joshi Prachi
Published: June 2008

High brightness zinc oxide quantum dots were made with intentional alkali metal doping using quantum-confined atom model. The tuning of emission spectrum in the range of 480–562nm was achieved by dispersing them in solvents with varying index of refraction. The observed emission bands are quite distinct from the nonstructured green emission of zinc oxide at 2.4eV (515nm) but are attributed to donor-acceptor recombination involving the zinc vacancy and Li+∕Na+, or the modifications assigned to the surface states by the surrounding medium. The photoluminescence shifts are found to be sensitive to refractive index term n2−1∕2n2+1 useful for practical applications.
The effects of priming on frontal-temporal communication
Authors: Ghuman Avniel S. , Bar Moshe , Dobbins Ian G. , Schnyer David M.
Published: June 2008

Repeated exposure to a stimulus facilitates its processing. This is reflected in faster and more accurate identification, reduced perceptual identification thresholds, and more efficient classifications for repeated compared with novel items. Here, we test a hypothesis that this experience-based behavioral facilitation is a result of enhanced communication between distinct cortical regions, which reduces local processing demands. A magnetoencephalographic investigation revealed that repeated object classification led to decreased neural responses in the prefrontal cortex and temporal cortex. Critically, this decrease in absolute activity was accompanied by greater neural synchrony (a measure of functional connectivity) between these regions with repetition. Additionally, the onset of the enhanced interregional synchrony predicted the degree of behavioral facilitation. These findings suggest that object repetition results in enhanced interactions between brain regions, which facilitates performance and reduces processing demands on the regions involved.
Specific DNA-binding by Apicomplexan AP2 transcription factors
Authors: De Silva Erandi K. , Gehrke Andrew R. , Olszewski Kellen , León Ilsa , Chahal Jasdave S. , Bulyk Martha L. , Llinás Manuel
Published: June 2008

Malaria remains one of the most prevalent infectious diseases worldwide, affecting more than half a billion people annually. Despite many years of research, the mechanisms underlying transcriptional regulation in the malaria-causing
Plasmodium
spp., and in Apicomplexan parasites generally, remain poorly understood. In
Plasmodium
, few regulatory elements sufficient to drive gene expression have been characterized, and their cognate DNA-binding proteins remain unknown. This study characterizes the DNA-binding specificities of two members of the recently identified Apicomplexan AP2 (ApiAP2) family of putative transcriptional regulators from
Plasmodium falciparum
. The ApiAP2 proteins contain AP2 domains homologous to the well characterized plant AP2 family of transcriptional regulators, which play key roles in development and environmental stress response pathways. We assayed ApiAP2 protein–DNA interactions using protein-binding microarrays and combined these results with computational predictions of coexpressed target genes to couple these putative
trans
factors to corresponding
cis
-regulatory motifs in
Plasmodium
. Furthermore, we show that protein–DNA sequence specificity is conserved in orthologous proteins between phylogenetically distant Apicomplexan species. The identification of the DNA-binding specificities for ApiAP2 proteins lays the foundation for the exploration of their role as transcriptional regulators during all stages of parasite development. Because of their origin in the plant lineage, ApiAP2 proteins have no homologues in the human host and may prove to be ideal antimalarial targets.
Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity
Authors: Smith T. K. , Hager H. A. , Francis R. , Kilkenny D. M. , Lo C. W. , Bader D. M.
Published: June 2008

Bves is an integral membrane protein with no determined function and no homology to proteins outside of the Popdc family. It is widely expressed throughout development in myriad organisms. Here, we demonstrate an interaction between Bves and guanine nucleotide exchange factor T (GEFT), a GEF for Rho-family GTPases. This interaction represents the first identification of any protein that has a direct physical interaction with any member of the Popdc family. Bves and GEFT are shown to colocalize in adult skeletal muscle. We also demonstrate that exogenous expression of Bves reduces Rac1 and Cdc42 activity levels while not affecting levels of active RhoA. Consistent with a repression of Rac1 and Cdc42 activity, we show changes in speed of cell locomotion and cell roundness also result from exogenous expression of Bves. Modulation of Rho-family GTPase signaling by Bves would be highly consistent with previously described phenotypes occurring upon disruption of Bves function in a wide variety of model systems. Therefore, we propose Bves as a novel regulator of the Rac1 and Cdc42 signaling cascades.
p190RhoGAP is the convergence point of adhesion signals from α5β1 integrin and syndecan-4
Authors: Bass Mark D. , Morgan Mark R. , Roach Kirsty A. , Settleman Jeffrey , Goryachev Andrew B. , Humphries Martin J.
Published: June 2008

The fibronectin receptors α5β1 integrin and syndecan-4 cocluster in focal adhesions and coordinate cell migration by making individual contributions to the suppression of RhoA activity during matrix engagement. p190Rho–guanosine triphosphatase–activating protein (GAP) is known to inhibit RhoA during the early stages of cell spreading in an Src-dependent manner. This paper dissects the mechanisms of p190RhoGAP regulation and distinguishes the contributions of α5β1 integrin and syndecan-4. Matrix-induced tyrosine phosphorylation of p190RhoGAP is stimulated solely by engagement of α5β1 integrin and is independent of syndecan-4. Parallel engagement of syndecan-4 causes redistribution of the tyrosine-phosphorylated pool of p190RhoGAP between membrane and cytosolic fractions by a mechanism that requires direct activation of protein kinase C α by syndecan-4. Activation of both pathways is necessary for the efficient regulation of RhoA and, as a consequence, focal adhesion formation. Accordingly, we identify p190RhoGAP as the convergence point for adhesive signals mediated by α5β1 integrin and syndecan-4. This molecular mechanism explains the cooperation between extracellular matrix receptors during cell adhesion.
Can There Be Stochastic Evolutionary Causes?
Authors: Forber Patrick , Reisman Kenneth
Published: June 2008

Do evolutionary processes such as selection and random driftcauseevolutionary change, or are they merely convenient ways of describing or summarizing it? Philosophers have lined up on both sides of this question. One recent defense (Reisman and Forber 2005) of the causal status of selection and drift appeals to a manipulability theory of causation. Yet, even if one accepts manipulability, there are still reasons to doubt that genetic drift, in particular, is genuinely causal. We will address two challenges to treating drift as causal within a manipulation framework. We will argue that both challenges ultimately fail, but that they raise interesting and subtle issues about the nature of causation and the differences between selection and drift.
Optimality Modeling and Explanatory Generality
Authors: Potochnik Angela
Published: June 2008

The optimality approach to modeling natural selection has been criticized by many biologists and philosophers of biology. For instance, Lewontin (1979) argues that the optimality approach is a shortcut that will be replaced by models incorporating genetic information, if and when such models become available. In contrast, I think that optimality models have a permanent role in evolutionary study. I base my argument for this claim on what I think it takes to best explain an event. In certain contexts, optimality and game-theoretic models best explain some central types of evolutionary phenomena.
The Singular Nature of Spacetime
Authors: Lam Vincent
Published: June 2008

We consider to what extent the fundamental question of spacetime singularities is relevant for the philosophical debate about the nature of spacetime. After reviewing some basic aspects of the spacetime singularities within general relativity, we argue that the well known difficulty to localize them in a meaningful way may challenge the received metaphysical view of spacetime as a set of points possessing some intrinsic properties together with some spatiotemporal relations. Considering the algebraic formulation of general relativity, we argue that the spacetime singularities highlight the philosophically misleading dependence on the standard geometric representation of spacetime.
Constraints on Data in Worlds with Closed Timelike Curves
Authors: Dowe Phil
Published: June 2008

It is claimed that unacceptable constraints on initial data are imposed by certain responses to paradoxes that threaten time travel, closed timelike curves (CTCs) and other backwards causation hypotheses. In this paper I argue against the following claims: to say “contradictions are impossible so something must prevent the paradox” commits in general to constraints on initial data, that for fixed point dynamics so-called grey state solutions explain why contradictions do not arise, and the latter have been proved to avoid constraints on initial data.
Niels Bohr's Interpretation and the Copenhagen Interpretation—Are the Two Incompatible?
Authors: Gomatam Ravi
Published: June 2008

The Copenhagen interpretation, which informs the textbook presentation of quantum mechanics, depends fundamentally on the notion of ontological wave-particle duality and a viewpoint called “complementarity.” In this paper, Bohr's own interpretation is traced in detail and is shown to be fundamentally different from and even opposed to the Copenhagen interpretation in virtually all its particulars. In particular, Bohr's interpretation avoids the ad hoc postulate of wave function ‘collapse’ that is central to the Copenhagen interpretation. The strengths and weakness of both interpretations are summarized.
Reconstructing Instead of Interpreting Quantum Theory
Authors: Grinbaum Alexei
Published: June 2008

A paradigmatic shift in the foundations of quantum mechanics is recorded, from interpreting to reconstructing quantum theory. Examples of reconstruction are analyzed, and conceptual foundations of the information-theoretic reconstruction developed. A concept of intentionally incomplete reconstruction is introduced to mark the novel content of research in the foundation of quantum theory.
Hierarchy Maintenance, Coalition Formation, and the Origins of Altruistic Punishment
Authors: Rohwer Yasha
Published: June 2008

Game theory has played a critical role in elucidating the evolutionary origins of social behavior. Sober and Wilson (1999) model altruism as a prisoner's dilemma and claim that this model indicates that altruism arose from group selection pressures. Sober and Wilson also suggest that the prisoner's dilemma model can be used to characterize punishment; hence, punishment too originated from group selection pressures. However, empirical evidence suggests that a group selection model of the origins of altruistic punishment may be insufficient. I argue that examining dominance hierarchies and coalition formation in chimpanzee societies suggests that the origins of altruistic punishment may be best captured by individual selection models. I suggest that this shows the necessity of coupling of game-theoretic models with a conception of what our actual social structure may have been like to best model the origins of our own behavior.
Mathematical Idealization
Authors: Pincock Christopher
Published: June 2008

Mathematical idealizations are scientific representations that result from assumptions that are believed to be false, and where mathematics plays a crucial role. I propose a two stage account of how to rank mathematical idealizations that is largely inspired by the semantic view of scientific theories. The paper concludes by considering how this approach to idealization allows for a limited form of scientific realism.
The Many-Worlds Interpretation and Quantum Computation
Authors: Duwell Armond
Published: June 2008

David Deutsch and others have suggested that the Many-Worlds Interpretation of quantum mechanics is the only interpretation capable of explaining the special efficiency quantum computers seem to enjoy over classical ones. I argue that this view is not tenable. Using a toy algorithm I show that the Many-Worlds Interpretation must crucially use the ontological status of the universal state vector to explain quantum computational efficiency, as opposed to the particular ontology of the MWI, that is, the computational histories of worlds. As such, any other interpretation that treats the state vector as representing real ontological features of a system can explain quantum speedup too.
Curve Fitting, the Reliability of Inductive Inference, and the Error-Statistical Approach
Authors: Spanos Aris
Published: June 2008

The main aim of this paper is to revisit the curve fitting problem using the reliability of inductive inference as a primary criterion for the ‘fittest’ curve. Viewed from this perspective, it is argued that a crucial concern with the current framework for addressing the curve fitting problem is, on the one hand, the undue influence of the mathematical approximation perspective, and on the other, the insufficient attention paid to the statistical modeling aspects of the problem. Using goodness-of-fit as the primary criterion for ‘best’, the mathematical approximation perspective undermines the reliability of inference objective by giving rise to selection rules which pay insufficient attention to ‘accounting for the regularities in the data’. A more appropriate framework is offered by the error-statistical approach, where (i) statistical adequacy provides the criterion for assessing when a curve captures the regularities in the data adequately, and (ii) the relevant error probabilities can be used to assess the reliability of inductive inference. Broadly speaking, the fittest curve (statistically adequate) is not determined by the smallness if its residuals, tempered by simplicity or other pragmatic criteria, but by the nonsystematic (e.g. white noise) nature of its residuals. The advocated error-statistical arguments are illustrated by comparing the Kepler and Ptolemaic models on empirical grounds.
Genetic structure in alpine brown trout Salmo trutta L. shows that indirect stocking affects native lake populations
Authors: Sønstebø J. H. , Borgstrøm R. , Heun M.
Published: June 2008

Genetic variation of brown trout inhabiting six connected lakes (Krokavatn, Skavatn, Kollsvatn, Litlosvatn, Kvennsjøen and Øvre Krokavatn) of the Hardangervidda mountain plateau was analysed by 11 microsatellites covering a period of 24–35 years. Temporal changes were found and are deemed to be mostly related to stocking in the headwater lakes Krokavatn and Skavatn. A pronounced change was evident in one population (Kollsvatn) and was the result of downstream migration of stocked fish from these headwater lakes. This indirect stocking accounted for up to 50% in the STRUCTURE analysis of Kollsvatn fish and was less pronounced in the other downstream populations of Litlosvatn (c. 28%), Kvennsjøen (c. 17%) and Øvre Krokavatn (c. 13%). Since significant downstream migration of stocked fish affecting native populations occurs, nature management efforts must respond accordingly.
Liver cyp1A protein expression and pigmented macrophage aggregates as indicators of polychlorinated biphenyl exposure in carp Cyprinus carpio L. from the Kalamazoo River Superfund site, Michigan
Authors: Fisher M. A. , Eversole R. , Mehne C. , Means J. C. , Delong C. , Mihalko D. , Ide C. F.
Published: June 2008

Cytochrome p450 1A (cyp1A), pigmented macrophage aggregate (PMA) variables and fish descriptive characteristics were measured in field‐caught adult carp Cyprinus carpio from two upstream reference sites and two downstream Superfund sites contaminated with polychlorinated biphenyls (PCBs) in the Kalamazoo River, MI, U.S.A. Liver PCB content in fish differed among sites, and immunocytochemical cyp1A protein expression was significantly elevated in fish liver at contaminated sites and with liver PCBs. PMA number (number per mm2), mean size [mean size (area) per mm2] and percentage area occupied (total area of PMAs per total field area evaluated) were significantly greater in fish livers from the contaminated sites. PMA number was significantly greater at one contaminated site, Lake Allegan, than at the Trowbridge Dam impoundment, the other contaminated site. The level of cyp1A protein was significantly correlated with PMA mean size and PMA per cent area but not with PMA number. These results suggest that carp are responding to PCB contamination and point to complex site dynamics related to fish condition in the Kalamazoo River.
Kryptolebias marmoratus(Poey, 1880): a potential model species for molecular carcinogenesis and ecotoxicogenomics
Authors: Lee J.‐S. , Raisuddin S. , Schlenk D.
Published: June 2008

Kryptolebias marmoratus(Rivulus marmoratustill 2004, order Cyprinodontoformes; family Rivulidae) is the only known self‐fertilizing hermaphrodite vertebrate. Because of this uniqueness, there has been great interest in its biology, physiology, developmental biology and genomics along with other basic and applied areas of environmental genomics and molecular carcinogenesis. In laboratory studies,K. marmoratushas shown susceptibility to a number of xenobiotics including carcinogens. Toxicologists are interested in the mechanisms of action of environmental chemicals of contemporary interest such as endocrine disruptors and may consider this as a suitable fish model for the study of chemically induced carcinogenesis. Single short‐term exposure to model chemical carcinogens is sufficient to induce tumourigenesis inK. marmoratusin a relatively short time span. In recent years, considerable data have been generated about gene sequences ofK. marmoratus. Laboratory maintenance ofK. marmoratusis relatively easy. Gene bank data are readily available, though not as extensive as for zebrafishDanio rerioor Japanese madakaOryzias latipes. The expressed sequence tag (EST) data, differential display real‐time reverse‐transcriptase polymerase chain reaction and Gene Sequencer 20™ sequencing data have recently been helpful in understanding the genomics and proteomics of this species. Recently, sequences of the oncogene,ras, and tumour suppressor gene,p53, have been reported inK. marmoratus. The expression of these important genes that play significant roles not only in carcinogenesis but also in other signal transduction pathways was observed to be modulated by environmental endocrine‐disrupting chemicals. Having a large sequence database (cDNA sequences and ESTs), it is expected that the use of a microarray in the near future will open new vistas for this fish with applications in cancer research, aquatic toxicology, endocrinology and genomics. This review discusses potential uses ofK. marmoratusin new biotechnological approaches of aquatic toxicology.
Development of a 37 k high‐density oligonucleotide microarray: a new tool for functional genome research in rainbow trout
Authors: Salem M. , Kenney P. B. , Rexroad C. E. , Yao J.
Published: June 2008

A rainbow trout high‐density oligonucleotide microarray was constructed using all tentative consensus (TC) sequences that are publicly available from all international rainbow trout Oncorhynchus mykiss genomic research projects through the Rainbow Trout Gene Index database. The new array contains 60‐mer oligonucleotide probes representing 37 394 unique TC sequences and 1417 control spots. The array (4 × 44 format) was manufactured according to the design by Agilent Technologies using the inkjet‐based SurePrint technology (design number 016320). The performance of the new microarray platform was evaluated by analysing gene expression associated with rainbow trout, vitellogenesis‐induced muscle atrophy. This microarray will open new avenues of research that will aid in the development of novel strategies for genetic improvement for economically important traits benefiting the salmonid aquaculture industries.
Genomic resources and microarrays for the common carp Cyprinus carpio L.
Authors: Williams D. R. , Li W. , Hughes M. A. , Gonzalez S. F. , Vernon C. , Vidal M. C. , Jeney Z. , Jeney G. , Dixon P. , McAndrew B. , Bartfai R. , Orban L. , Trudeau V. , Rogers J. , Matthews L. , Fraser E. J. , Gracey A. Y. , Cossins A. R.
Published: June 2008

The common carp is an important fish species satisfying ornamental, food and recreational fisheries’ needs worldwide, but in common with other cyprinid fishes, it is particularly renowned for its environmental tolerance. Investigating the mechanistic basis of growth, disease and environmental tolerance is greatly enhanced by access to a comprehensive list of gene sequences and post‐genomic technologies. The current status of genomic resources is described for this species including 40 k cDNA clone collections, their associated expressed sequence tags (ESTs) and a developing series of 13 k–26 k cDNA microarrays fabricated from amplicons. The arrays have been directed at questions of response to environmental stress (cold and hypoxia), viral and bacterial disease and ectoparasite infection. Consequently, clones from a wide range of tissues were prepared. The authors discuss how these resources were generated and their application. Evidence is presented supporting that the carp microarray may also be useful as a heterologous set of probes in studies of other fish species.