Biochemical and immunochemical analysis of the arrangement of connexin43 in rat heart gap junction membranes

A 43 × 10^3 M_r protein (designated connexin43 or Cx43) is a major constituent of heart gap junctions. The understanding of its arrangement in junctional membranes has been extended by means of site-directed antibodies raised against synthetic peptides of Cx43. These represent part of the first extracellular loop (EL-46), the cytoplasmic loop (CL-100), the second extracellular loop (EL-186) and carboxy-terminal sequences (CT-237 and CT-360). All of the antibodies raised reacted with their respective peptides and the Cx43 protein on Western blots. By immunoelectron microscopy two of the antibodies (CL-100 and CT-360) were shown to label the cytoplasmic surface of isolated gap junction membranes. Immunofluorescent labeling at locations of neonatal cardiac myocyte-myocyte apposition required an alkali/urea treatment when the EL-46 and EL-186 antibodies were used. Immunoblot analysis of endoproteinase Lys-C-digested gap junctions revealed that the Cx43 protein passed through the lipid bilayer four times. Alkaline phosphatase digestion of isolated junctions was used to show that the CT-360 antibody recognized many phosphorylated forms of Cx43. Our results unequivocally confirm models of the organization of Cx43 that were based on a more limited set of data and a priori considerations of the sequence

Weighted-density approximation for general nonuniform fluid mixtures

In order to construct a general density-functional theory for nonuniform fluid mixtures, we propose an extension to multicomponent systems of the weighted-density approximation (WDA) of Curtin and Ashcroft [Phys. Rev. A 32, 2909 (1985)]. This extension corrects a deficiency in a similar extension proposed earlier by Denton and Ashcroft [Phys. Rev. A 42, 7312 (1990)], in that that functional cannot be applied to the multi-component nonuniform fluid systems with spatially varying composition, such as solid-fluid interfaces. As a test of the accuracy of our new functional, we apply it to the calculation of the freezing phase diagram of a binary hard-sphere fluid, and compare the results to simulation and the Denton-Ashcroft extension.Comment: 4 pages, 4 figures, to appear in Phys. Rev. E as Brief Repor

A Xenon Ion Pumped Blue Dye Laser

A pulsed xenon ion laser with an output power of 5 kW at 364.5 nm has been used as a pump source for several blue dyes. Broadband conversion efficiencies exceed 20 percent. The use of a birefringent filter provides tunable output in the blue region of the spectrum with a bandwidth of 0.08 nm and a pulse width of 120 ns. © 1978 IEE

Non-specific filtering of beta-distributed data.

BackgroundNon-specific feature selection is a dimension reduction procedure performed prior to cluster analysis of high dimensional molecular data. Not all measured features are expected to show biological variation, so only the most varying are selected for analysis. In DNA methylation studies, DNA methylation is measured as a proportion, bounded between 0 and 1, with variance a function of the mean. Filtering on standard deviation biases the selection of probes to those with mean values near 0.5. We explore the effect this has on clustering, and develop alternate filter methods that utilize a variance stabilizing transformation for Beta distributed data and do not share this bias.ResultsWe compared results for 11 different non-specific filters on eight Infinium HumanMethylation data sets, selected to span a variety of biological conditions. We found that for data sets having a small fraction of samples showing abnormal methylation of a subset of normally unmethylated CpGs, a characteristic of the CpG island methylator phenotype in cancer, a novel filter statistic that utilized a variance-stabilizing transformation for Beta distributed data outperformed the common filter of using standard deviation of the DNA methylation proportion, or its log-transformed M-value, in its ability to detect the cancer subtype in a cluster analysis. However, the standard deviation filter always performed among the best for distinguishing subgroups of normal tissue. The novel filter and standard deviation filter tended to favour features in different genome contexts; for the same data set, the novel filter always selected more features from CpG island promoters and the standard deviation filter always selected more features from non-CpG island intergenic regions. Interestingly, despite selecting largely non-overlapping sets of features, the two filters did find sample subsets that overlapped for some real data sets.ConclusionsWe found two different filter statistics that tended to prioritize features with different characteristics, each performed well for identifying clusters of cancer and non-cancer tissue, and identifying a cancer CpG island hypermethylation phenotype. Since cluster analysis is for discovery, we would suggest trying both filters on any new data sets, evaluating the overlap of features selected and clusters discovered

A Fully Abstract Game Semantics for Countable Nondeterminism

The concept of fairness for a concurrent program means that the program must be able to exhibit an unbounded amount of nondeterminism without diverging. Game semantics models of nondeterminism show that this is hard to implement; for example, Harmer and McCusker\u27s model only admits infinite nondeterminism if there is also the possibility of divergence. We solve a long standing problem by giving a fully abstract game semantics for a simple stateful language with a countably infinite nondeterminism primitive. We see that doing so requires us to keep track of infinitary information about strategies, as well as their finite behaviours. The unbounded nondeterminism gives rise to further problems, which can be formalized as a lack of continuity in the language. In order to prove adequacy for our model (which usually requires continuity), we develop a new technique in which we simulate the nondeterminism using a deterministic stateful construction, and then use combinatorial techniques to transfer the result to the nondeterministic language. Lastly, we prove full abstraction for the model; because of the lack of continuity, we cannot deduce this from definability of compact elements in the usual way, and we have to use a stronger universality result instead. We discuss how our techniques yield proofs of adequacy for models of nondeterministic PCF, such as those given by Tsukada and Ong

Direct calculation of the hard-sphere crystal/melt interfacial free energy

We present a direct calculation by molecular-dynamics computer simulation of the crystal/melt interfacial free energy, $\gamma$, for a system of hard spheres of diameter $\sigma$. The calculation is performed by thermodynamic integration along a reversible path defined by cleaving, using specially constructed movable hard-sphere walls, separate bulk crystal and fluid systems, which are then merged to form an interface. We find the interfacial free energy to be slightly anisotropic with $\gamma$ = 0.62$\pm 0.01$, 0.64$\pm 0.01$ and 0.58$\pm 0.01 k_BT/\sigma^2$ for the (100), (110) and (111) fcc crystal/fluid interfaces, respectively. These values are consistent with earlier density functional calculations and recent experiments measuring the crystal nucleation rates from colloidal fluids of polystyrene spheres that have been interpreted [Marr and Gast, Langmuir {\bf 10}, 1348 (1994)] to give an estimate of $\gamma$ for the hard-sphere system of $0.55 \pm 0.02 k_BT/\sigma^2$, slightly lower than the directly determined value reported here.Comment: 4 pages, 4 figures, submitted to Physical Review Letter

Particle Dark Energy

We explore the physics of a gas of particles interacting with a condensate that spontaneously breaks Lorentz invariance. The equation of state of this gas varies from 1/3 to less than -1 and can lead to the observed cosmic acceleration. The particles are always stable. In our particular class of models these particles are fermions with a chiral coupling to the condensate. They may behave as relativistic matter at early times, produce a brief period where they dominate the expansion with w<0 today, and behave as matter at late time. There are no small parameters in our models, which generically lead to dark energy clustering and, depending on the choice of parameters, smoothing of small scale power.Comment: 8 pages, 5 figures; minor update with added refs; version appearing in Phys. Rev.

High Flux Beam Source Of Thermal Rare-gas Metastable Atoms

A high-flux beam source has been constructed for the production of helium, neon and argon metastable atoms. The source is a DC electric discharge maintained in an expanding gas. A metastable flux of 3.5*1014, and 7.2*1013 atoms s-1 sr-1 has been achieved with most probable energies of 66, 72 and 74 meV for the helium, neon and argon sources, respectively. Time-of-flight measurements showed the widths of the respective velocity distributions to be 45%, 27% and 27%