Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

Background: Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results: Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion: The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in this response.

Generalised Dirichelt-to-Neumann map in time dependent domains

We study the heat, linear Schrodinger and linear KdV equations in the domain l(t) < x < ∞, 0 < t < T, with prescribed initial and boundary conditions and with l(t) a given differentiable function. For the first two equations, we show that the unknown Neumann or Dirichlet boundary value can be computed as the solution of a linear Volterra integral equation with an explicit weakly singular kernel. This integral equation can be derived from the formal Fourier integral representation of the solution. For the linear KdV equation we show that the two unknown boundary values can be computed as the solution of a system of linear Volterra integral equations with explicit weakly singular kernels. The derivation in this case makes crucial use of analyticity and certain invariance properties in the complex spectral plane. The above Volterra equations are shown to admit a unique solution.

Fully automated software solution for protein quantitation by global metabolic labeling with stable isotopes

Metabolic stable isotope labeling is increasingly employed for accurate protein (and metabolite) quantitation using mass spectrometry (MS). It provides sample-specific isotopologues that can be used to facilitate comparative analysis of two or more samples. Stable Isotope Labeling by Amino acids in Cell culture (SILAC) has been used for almost a decade in proteomic research and analytical software solutions have been established that provide an easy and integrated workflow for elucidating sample abundance ratios for most MS data formats. While SILAC is a discrete labeling method using specific amino acids, global metabolic stable isotope labeling using isotopes such as (15)N labels the entire element content of the sample, i.e. for (15)N the entire peptide backbone in addition to all nitrogen-containing side chains. Although global metabolic labeling can deliver advantages with regard to isotope incorporation and costs, the requirements for data analysis are more demanding because, for instance for polypeptides, the mass difference introduced by the label depends on the amino acid composition. Consequently, there has been less progress on the automation of the data processing and mining steps for this type of protein quantitation. Here, we present a new integrated software solution for the quantitative analysis of protein expression in differential samples and show the benefits of high-resolution MS data in quantitative proteomic analyses.

Heaney and the neighbour: poetry between politics and ethics

In this essay I argue that Heaney uses the figure of the neighbour to examine questions of otherness and cultural difference and their relationship to history and politics. The neighbour is of course a figure that has played a central role in Western philosophy and theology for centuries, from the Gospels and Kant to Freud and Lacan. It is also a concept to which Western poetry often returns, particularly in the work of Herbert, Clare, Eliot and Auden. Heaney too belongs to this tradition, in that his oeuvre contains many poems which consider the relationship between neighbours, and do so in ways profoundly suggestive for consideration of the relationship between historical events, social structures, cultural difference and psychic affect. In my essay I argue that Heaney sketches a profoundly materialist conception of subjectivity in its relationship with the Other. In doing so I contrast Heaney’s treatment of the neighbour, with its emphasis on questions of politics and locality, to the treatment of the neighbour in the ethical philosophy of Emmanuel Levinas.

Minimum norm regularization of descriptor systems by mixed output feedback

We study the regularization problem for linear, constant coefficient descriptor systems Ex' = Ax+Bu, y1 = Cx, y2 = Γx' by proportional and derivative mixed output feedback. Necessary and sufficient conditions are given, which guarantee that there exist output feedbacks such that the closed-loop system is regular, has index at most one and E+BGΓ has a desired rank, i.e., there is a desired number of differential and algebraic equations. To resolve the freedom in the choice of the feedback matrices we then discuss how to obtain the desired regularizing feedback of minimum norm and show that this approach leads to useful results in the sense of robustness only if the rank of E is decreased. Numerical procedures are derived to construct the desired feedback gains. These numerical procedures are based on orthogonal matrix transformations which can be implemented in a numerically stable way.

A time-domain probe method for three-dimensional rough surface reconstructions

The task of this paper is to develop a Time-Domain Probe Method for the reconstruction of impenetrable scatterers. The basic idea of the method is to use pulses in the time domain and the time-dependent response of the scatterer to reconstruct its location and shape. The method is based on the basic causality principle of timedependent scattering. The method is independent of the boundary condition and is applicable for limited aperture scattering data. In particular, we discuss the reconstruction of the shape of a rough surface in three dimensions from time-domain measurements of the scattered field. In practise, measurement data is collected where the incident field is given by a pulse. We formulate the time-domain fieeld reconstruction problem equivalently via frequency-domain integral equations or via a retarded boundary integral equation based on results of Bamberger, Ha-Duong, Lubich. In contrast to pure frequency domain methods here we use a time-domain characterization of the unknown shape for its reconstruction. Our paper will describe the Time-Domain Probe Method and relate it to previous frequency-domain approaches on sampling and probe methods by Colton, Kirsch, Ikehata, Potthast, Luke, Sylvester et al. The approach significantly extends recent work of Chandler-Wilde and Lines (2005) and Luke and Potthast (2006) on the timedomain point source method. We provide a complete convergence analysis for the method for the rough surface scattering case and provide numerical simulations and examples.

Cis–trans isomerism in diphenoxido bridged dicopper complexes: role of crystallized water to stabilize the cis isomer, variation in magnetic properties and conversion of both into a trinuclear species

The trans-[Cu2L2Cl2] (1), and cis-[Cu2L2Cl2]·H2O (2) isomers of a diphenoxido bridged Cu2O2 core have been synthesized using a tridentate reduced Schiff base ligand 2-[(2-dimethylamino-ethylamino)-methyl]-phenol. The geometry around Cu(II) is intermediate between square pyramid and trigonal bipyramid (Addison parameter, tau = 0.463) in 1 but nearly square pyramidal (tau = 0.049) in 2. The chloride ions are coordinated to Cu(II) and are trans oriented in 1 but cis oriented in 2. Both isomers have been optimized using density functional theory (DFT) calculations and it is found that the trans isomer is 7.2 kcal mol(-1) more favorable than the cis isomer. However, the hydrogen bonding interaction of crystallized water molecule with chloride ions compensates for the energy difference and stabilizes the cis isomer. Both complexes have been converted to a very rare phenoxido-azido bridged trinuclear species, [Cu3L2(mu(1,1)-N-3)(2)(H2O)(2)(ClO4)(2)] (3) which has also been characterized structurally. All the complexes are antiferromagnetically coupled but the magnitude of the coupling constants are significantly different (J = -156.60, -652.31, and -31.54 cm(-1) for 1, 2, and 3 respectively). Density functional theory (DFT) calculations have also been performed to gain further insight into the qualitative theoretical interpretation on the overall magnetic behavior of the complexes.

Recognition of "difference" in Shari'a: a feminist scrutiny through the lens of substantive equality

The paper looks at the works of notable Islamic feminists to examine whether Islam can be reconciled with a substantive approach to gender equality. Located within contemporary feminist debates related to gender equality, it considers the Qur’anic verses related to two controversial areas of Shari’a law, namely, duty of obedience and polygamy, to explore how Islamic scriptures perceive ‘difference’ and its implications for substantive equality-based legal reforms in a Muslim society.

Introduction and the problems of weather interpretation

Numerical forecasts of the atmosphere based on the fundamental dynamical and thermodynamical equations have now been carried for almost 30 years. The very first models which were used were drastic simplifications of the governing equations and permitting only the prediction of the geostrophic wind in the middle of the troposphere based on the conservation of absolute vorticity. Since then we have seen a remarkable development in models predicting the large-scale synoptic flow. Verification carried out at NMC Washington indicates an improvement of about 40% in 24h forecasts for the 500mb geopotential since the end of the 1950’s. The most advanced models of today use the equations of motion in their more original form (i.e. primitive equations) which are better suited to predicting the atmosphere at low latitudes as well as small scale systems. The model which we have developed at the Centre, for instance, will be able to predict weather systems from a scale of 500-1000 km and a vertical extension of a few hundred millibars up to global weather systems extending through the whole depth of the atmosphere. With a grid resolution of 1.5 and 15 vertical levels and covering the whole globe it is possible to describe rather accurately the thermodynamical processes associated with cyclone development. It is further possible to incorporate sub-grid-scale processes such as radiation, exchange of sensible heat, release of latent heat etc. in order to predict the development of new weather systems and the decay of old ones. Later in this introduction I will exemplify this by showing some results of forecasts by the Centre’s model.

Acoustic scattering by an inhomogeneous layer on a rigid plate

The problem of scattering of time-harmonic acoustic waves by an inhomogeneous fluid layer on a rigid plate in R2 is considered. The density is assumed to be unity in the media: within the layer the sound speed is assumed to be an arbitrary bounded measurable function. The problem is modelled by the reduced wave equation with variable wavenumber in the layer and a Neumann condition on the plate. To formulate the problem and prove uniqueness of solution a radiation condition appropriate for scattering by infinite rough surfaces is introduced, a generalization of the Rayleigh expansion condition for diffraction gratings. With the help of the radiation condition the problem is reformulated as a system of two second kind integral equations over the layer and the plate. Under additional assumptions on the wavenumber in the layer, uniqueness of solution is proved and the nonexistence of guided wave solutions of the homogeneous problem established. General results on the solvability of systems of integral equations on unbounded domains are used to establish existence and continuous dependence in a weighted norm of the solution on the given data.

The impedance boundary value problem for the Helmholtz equation in a half-plane

We prove unique existence of solution for the impedance (or third) boundary value problem for the Helmholtz equation in a half-plane with arbitrary L∞ boundary data. This problem is of interest as a model of outdoor sound propagation over inhomogeneous flat terrain and as a model of rough surface scattering. To formulate the problem and prove uniqueness of solution we introduce a novel radiation condition, a generalization of that used in plane wave scattering by one-dimensional diffraction gratings. To prove existence of solution and a limiting absorption principle we first reformulate the problem as an equivalent second kind boundary integral equation to which we apply a form of Fredholm alternative, utilizing recent results on the solvability of integral equations on the real line in [5].

Input quality matters: some comments on input type and age-effects in adult SLA.

In accord with the general program of researching factors relating to ultimate attainment and maturational constraints in adult language acquisition, this commentary highlights the importance of input differences in amount, type, and setting between naturalistic and classroom learners of an L2. It is suggested that these variables are often confounded with age factors. Herein, we wish to call attention to the possible deterministic role that the differences in the grammatical quality of classroom input have on development and on competence outcomes. Framing what we see as greater formal complexity of the learning task for classroom learners, we suggest that one might benefit from focusing less on difference and more on how classroom L2 learners, at least some of them, come to acquire all that they do despite crucial qualitative differences in their input.

A SEPALLATA gene is involved in the development and ripening of strawberry (Fragaria X ananassa Duch.) fruit, a non-climacteric tissue

Climacteric and non-climacteric fruits have traditionally been viewed as representing two distinct programmes of ripening associated with differential respiration and ethylene hormone effects. In climacteric fruits, such as tomato and banana, the ripening process is marked by increased respiration and is induced and co-ordinated by ethylene, while in non-climacteric fruits, such as strawberry and grape, it is controlled by an ethylene-independent process with little change in respiration rate. The two contrasting mechanisms, however, both lead to texture, colour, and flavour changes that probably reflect some common programmes of regulatory control. It has been shown that a SEPALLATA(SEP)4-like gene is necessary for normal ripening in tomato. It has been demonstrated here that silencing a fruit-related SEP1/2-like (FaMADS9) gene in strawberry leads to the inhibition of normal development and ripening in the petal, achene, and receptacle tissues. In addition, analysis of transcriptome profiles reveals pleiotropic effects of FaMADS9 on fruit development and ripening-related gene expression. It is concluded that SEP genes play a central role in the developmental regulation of ripening in both climacteric and non-climacteric fruits. These findings provide important information to extend the molecular control of ripening in a non-climacteric fruit beyond the limited genetic and cultural options currently available.

Restrictive feeding practices and adiposity are differentially related to P3b cortical responses to food stimuli in children

Across two studies, we examined the association between adiposity, restrictive feeding practices and cortical processing bias to food stimuli in children. We assessed P3b event-related potential (ERP) during visual oddball tasks in which the frequently presented stimulus was non-food and the infrequently presented stimulus was either a food (Study 1) or non-food (Study 2) item. Children responded to the infrequently presented stimulus and accuracy and speed responses were collected. Restrictive feeding practices, children's height and weight were also measured. In Study 1, the difference in P3b amplitude for infrequently presented food stimuli, relative to frequently presented non-food stimuli, was negatively associated with adiposity and positively associated with restrictive feeding practices after controlling for adiposity. There was no association between P3b amplitude difference and adiposity or restriction in Study 2, suggesting that the effects seen in Study 1 were not due to general attentional processes. Taken together, our results suggest that attentional salience, as indexed by the P3b amplitude, may be important for understanding the neural correlates of adiposity and restrictive feeding practices in children.

Field-perpendicular and field-aligned plasma flows observed by EISCAT during a prolonged period of northward IMF

The effect of a prolonged period of strongly northward Interplanetary Magnetic Field (IMF) on the high-latitude F-region is studied using data from the EISCAT Common Programme Zero mode of operation on 11–12 August 1982. The analysis of the raw autocorrelation functions is kept to the directly derived parameters Ne, Te, Ti and velocity, and limits are defined for the errors introduced by assumptions about ion composition and by changes in the transmitted power and system constant. Simple data-cleaning criteria are employed to eliminate problems due to coherent signals and large background noise levels. The observed variations in plasma densities, temperatures and velocities are interpreted in terms of supporting data from ISEE-3 and local riometers and magnetometers. Both field-aligned and field-perpendicular plasma flows at Tromsø showed effects of the northward IMF: convection was slow and irregular and field-aligned flow profiles were characteristic of steady-state polar wind outflow with flux of order 1012 m−2 s−1. This period followed a strongly southward IMF which had triggered a substorm. The substorm gave enhanced convection, with a swing to equatorward flow and large (5 × 1012 m−2 s−1), steady-state field-aligned fluxes, leading to the possibility of O+ escape into the magnetosphere. The apparent influence of the IMF over both field-perpendicular and field-aligned flows is explained in terms of the cross-cap potential difference and the location of the auroral oval.