Computation of a Theoretical Membrane Phase Diagram, and the Role of Phase in Lipid Raft-Mediated Protein Organization

Lipid phase heterogeneity in the plasma membrane is thought to be crucial for many aspects of cell signaling, but the physical basis of participating membrane domains such as "lipid rafts" remains controversial. Here we consider a lattice model yielding a phase diagram that includes several states proposed to be relevant for the cell membrane, including microemulsion - which can be related to membrane curvature - and Ising critical behavior. Using a neural network-based machine learning approach, we compute the full phase diagram of this lattice model. We analyze selected regions of this phase diagram in the context of a signaling initiation event in mast cells: recruitment of the membrane-anchored tyrosine kinase Lyn to a cluster of transmembrane of IgE-Fc{\epsilon}RI receptors. We find that model membrane systems in microemulsion and Ising critical states can mediate roughly equal levels of kinase recruitment (binding energy ~ -0.6 kBT), whereas a membrane near a tricritical point can mediate much stronger kinase recruitment (-1.7 kBT). By comparing several models for lipid heterogeneity within a single theoretical framework, this work points to testable differences between existing models. We also suggest the tricritical point as a new possibility for the basis of membrane domains that facilitate preferential partitioning of signaling components.Comment: 33 pages, 7 figures, 16 supplementary pages, 10 supplementary figure

Flux domes in superconducting films without edges

Domelike magnetic-flux-density distributions previously have been observed experimentally and analyzed theoretically in superconducting films with edges, such as in strips and thin plates. Such flux domes have been explained as arising from a combination of strong geometric barriers and weak bulk pinning. In this paper we predict that, even in films with bulk pinning, flux domes also occur when vortices and antivortices are produced far from the film edges underneath current-carrying wires, coils, or permanent magnets placed above the film. Vortex-antivortex pairs penetrating through the film are generated when the magnetic field parallel to the surface exceeds H_{c1}+K_c, where H_{c1} is the lower critical field and K_c = j_c d is the critical sheet-current density (the product of the bulk critical current density j_c and the film thickness d). The vortices and antivortices move in opposite directions to locations where they join others to create separated vortex and antivortex flux domes. We consider a simple arrangement of a pair of current-carrying wires carrying current I_0 in opposite directions and calculate the magnetic-field and current-density distributions as a function of I_0 both in the bulk-pinning-free case (K_c = 0) and in the presence of bulk pinning, characterized by a field-independent critical sheet-current density (K_c > 0).Comment: 15 pages, 23 figure

Roles for Ca2+ mobilization and its regulation in mast cell functions: recent progress

Ca(2+)mobilization in response to cross-linking of IgE bound to its high affinity receptor, FcεRI, on mast cells is central to immune allergic responses. Stimulated tyrosine phosphorylation caused by this cross-linking activates store-operated Ca(2+)entry that results in sustained Ca(2+)oscillations dependent on Rho family GTPases and phosphoinositide synthesis. Coupling of the endoplasmic reticulum (ER) Ca(2+)sensor, stromal interaction molecule 1 (STIM1), to the Ca(2+)-selective channel, Orai1, is regulated by these elements and depends on membrane organization, both at the plasma membrane and at the ER. Mitochondria also contribute to the regulation of Ca(2+)mobilization, and we describe recent evidence that the ER membrane protein vesicle-associated membrane protein-associated protein (VAP) plays a significant role in the coupling between ER and mitochondria in this process. In addition to granule exocytosis, Ca(2+)mobilization in these cells also contributes to stimulated outward trafficking of recycling endosomes and to antigen-stimulated chemotaxis, and it is pathologically regulated by protozoan parasitic invasion

Translation Regulation of the Glutamyl-prolyl-tRNA Synthetase Gene EPRS through Bypass of Upstream Open Reading Frames with Noncanonical Initiation Codons

In the integrated stress response, phosphorylation of eIF2α (eIF2α-P) reduces protein synthesis while concomitantly promoting preferential translation of specific transcripts associated with stress adaptation. Translation of the glutamyl-prolyl-tRNA synthetase gene EPRS is enhanced in response to eIF2α-P. To identify the underlying mechanism of translation control, we employed biochemical approaches to determine the regulatory features by which upstream ORFs (uORFs) direct downstream translation control and expression of the EPRS coding region. Our findings reveal that translation of two inhibitory uORFs encoded by noncanonical CUG and UUG initiation codons in the EPRS mRNA 5'-leader serve to dampen levels of translation initiation at the EPRS coding region. By a mechanism suggested to involve increased translation initiation stringency during stress-induced eIF2α-P, we observed facilitated ribosome bypass of these uORFs, allowing for increased translation of the EPRS coding region. Importantly, EPRS protein expression is enhanced through this preferential translation mechanism in response to multiple known activators of eIF2α-P and likely serves to facilitate stress adaptation in response to a variety of cellular stresses. The rules presented here for the regulated ribosome bypass of noncanonical initiation codons in the EPRS 5'-leader add complexity into the nature of uORF-mediated translation control mechanisms during eIF2α-P and additionally illustrate the roles that previously unexamined uORFs with noncanonical initiation codons can play in modulating gene expression

Morphology of the recently re-classified Tasman masked booby (Sula dactylatra tasmani) breeding on the Kermadec Islands

Once thought to be extinct, the Tasman Booby Sula tasmani has recently been re-classified as a subspecies of the Masked Booby S. dactylatra on the basis of genetic data. This re-classification raises the issue of whether this novel clade has a distinct morphology. Morphological differences in size, as well as coloration of integuments, bill and iris have been found in other subspecies of the Masked Booby but have not yet been reported for live Kermadec Islands breeding individuals. Museum specimens from this breeding location have been separated from other Pacific breeding subspecies by their longer wings. We sampled a total of 21 individuals from North Meyer Islet, Kermadec Group, New Zealand, and applied molecular sexing to obtain sex-specific morphometric measurements. We matched dimorphism in vocalization with genetic sexing results and photographic documentation of human-assessed bill, foot and eye coloration. While culmen measurements were consistent with reports from museum specimens, wing chords from living specimens of Tasman Masked Boobies were 3% and 4% larger in males and females, respectively. Females had larger culmens and wings than males, consistent with the low extent of sexual dimorphism reported from museum skins. Adult Tasman Masked Boobies had yellow to buff-yellow feet, while fledglings, as in most sulids, had grey to greyish-yellow feet. Our findings confirm the distinctively long wing and particular iris coloration previously reported for the taxon and provide the first description of integument coloration of live specimens. This study highlights the importance of including in situ assessment in taxon descriptions

Parametric vision simulation study, part 2 Final report

Effects of landing site redesignation on visibility during manned lunar landin

Syzygies in equivariant cohomology for non-abelian Lie groups

We extend the work of Allday-Franz-Puppe on syzygies in equivariant cohomology from tori to arbitrary compact connected Lie groups G. In particular, we show that for a compact orientable G-manifold X the analogue of the Chang-Skjelbred sequence is exact if and only if the equivariant cohomology of X is reflexive, if and only if the equivariant Poincare pairing for X is perfect. Along the way we establish that the equivariant cohomology modules arising from the orbit filtration of X are Cohen-Macaulay. We allow singular spaces and introduce a Cartan model for their equivariant cohomology. We also develop a criterion for the finiteness of the number of infinitesimal orbit types of a G-manifold.Comment: 28 pages; minor change

A characterization of Dirac morphisms

Relating the Dirac operators on the total space and on the base manifold of a horizontally conformal submersion, we characterize Dirac morphisms, i.e. maps which pull back (local) harmonic spinor fields onto (local) harmonic spinor fields.Comment: 18 pages; restricted to the even-dimensional cas

Perceptual lossless medical image coding

A novel perceptually lossless coder is presented for the compression of medical images. Built on the JPEG 2000 coding framework, the heart of the proposed coder is a visual pruning function, embedded with an advanced human vision model to identify and to remove visually insignificant/irrelevant information. The proposed coder offers the advantages of simplicity and modularity with bit-stream compliance. Current results have shown superior compression ratio gains over that of its information lossless counterparts without any visible distortion. In addition, a case study consisting of 31 medical experts has shown that no perceivable difference of statistical significance exists between the original images and the images compressed by the proposed coder