Early diagnosis remains the most reliable way to cure chidren with melanoma: Response

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48703/1/20398_ftp.pd

Yeast homotypic vacuole fusion requires the Ccz1–Mon1 complex during the tethering/docking stage

The function of the yeast lysosome/vacuole is critically linked with the morphology of the organelle. Accordingly, highly regulated processes control vacuolar fission and fusion events. Analysis of homotypic vacuole fusion demonstrated that vacuoles from strains defective in the CCZ1 and MON1 genes could not fuse. Morphological evidence suggested that these mutant vacuoles could not proceed to the tethering/docking stage. Ccz1 and Mon1 form a stable protein complex that binds the vacuole membrane. In the absence of the Ccz1–Mon1 complex, the integrity of vacuole SNARE pairing and the unpaired SNARE class C Vps/HOPS complex interaction were both impaired. The Ccz1–Mon1 complex colocalized with other fusion components on the vacuole as part of the cis-SNARE complex, and the association of the Ccz1–Mon1 complex with the vacuole appeared to be regulated by the class C Vps/HOPS complex proteins. Accordingly, we propose that the Ccz1–Mon1 complex is critical for the Ypt7-dependent tethering/docking stage leading to the formation of a trans-SNARE complex and subsequent vacuole fusion

Optimization of a parallel ocean general circulation model

Global climate modeling is one of the grand challenges of computational science, and ocean modeling plays an important role in both understanding the current climatic conditions and predicting the future climate change. Three-dimensional time-dependent ocean general circulation models (OGCMs) require a large amount of memory and processing time to run realistic simulations. Recent advances in computing hardware have dramatically affected the prospect of studying the global climate. The significant computational resources of massively parallel supercomputers promise to make such studies feasible. In addition to using advanced hardware, designing and implementing a well-optimized parallel ocean code will significantly improve the computational performance and reduce the total research time to complete these studies. In our present work, we chose the most widely used OGCM code as our base code. This OGCM is based on the Parallel Ocean Program (POP) developed in FORTRAN 90 on the Los Alamos CM-2 Connection Machine by the Los Alamos ocean modeling research group. During the first half of 1994, the code was ported to the Cray T3D by Cray Research using SHMEM-based message passing. Since the code on the T3D was still time-consuming when large problems were encountered, improving the code performance was considered essential. We have developed several general strategies to optimize the ocean general circulation model on the Cray T3D. These strategies include memory optimization, effective use of arithmetic pipelines, and usage of optimized libraries. The optimize

An efficient basis set representation for calculating electrons in molecules

The method of McCurdy, Baertschy, and Rescigno, J. Phys. B, 37, R137 (2004) is generalized to obtain a straightforward, surprisingly accurate, and scalable numerical representation for calculating the electronic wave functions of molecules. It uses a basis set of product sinc functions arrayed on a Cartesian grid, and yields 1 kcal/mol precision for valence transition energies with a grid resolution of approximately 0.1 bohr. The Coulomb matrix elements are replaced with matrix elements obtained from the kinetic energy operator. A resolution-of-the-identity approximation renders the primitive one- and two-electron matrix elements diagonal; in other words, the Coulomb operator is local with respect to the grid indices. The calculation of contracted two-electron matrix elements among orbitals requires only O(N log(N)) multiplication operations, not O(N^4), where N is the number of basis functions; N = n^3 on cubic grids. The representation not only is numerically expedient, but also produces energies and properties superior to those calculated variationally. Absolute energies, absorption cross sections, transition energies, and ionization potentials are reported for one- (He^+, H_2^+ ), two- (H_2, He), ten- (CH_4) and 56-electron (C_8H_8) systems.Comment: Submitted to JC

A Significant Population of Very Luminous Dust-Obscured Galaxies at Redshift z ~ 2

Observations with Spitzer Space Telescope have recently revealed a significant population of high-redshift z~2 dust-obscured galaxies (DOGs) with large mid-IR to UV luminosity ratios. These galaxies have been missed in traditional optical studies of the distant universe. We present a simple method for selecting this high-z population based solely on the ratio of the observed mid-IR 24um to optical R-band flux density. In the 8.6 sq.deg Bootes NDWFS Field, we uncover ~2,600 DOG candidates (= 0.089/sq.arcmin) with 24um flux densities F24>0.3mJy and (R-[24])>14 (i.e., F[24]/F[R] > 1000). These galaxies have no counterparts in the local universe, and become a larger fraction of the population at fainter F24, representing 13% of the sources at 0.3~mJy. DOGs exhibit evidence of both star-formation and AGN activity, with the brighter 24um sources being more AGN- dominated. We have measured spectroscopic redshifts for 86 DOGs, and find a broad z distribution centered at ~2.0. Their space density is 2.82E-5 per cubic Mpc, similar to that of bright sub-mm-selected galaxies at z~2. These redshifts imply very large luminosities LIR>~1E12-14 Lsun. DOGs contribute ~45-100% of the IR luminosity density contributed by all z~2 ULIRGs, suggesting that our simple selection criterion identifies the bulk of z~2 ULIRGs. DOGs may be the progenitors of ~4L* present-day galaxies seen undergoing a luminous,short- lived phase of bulge and black hole growth. They may represent a brief evolution phase between SMGs and less obscured quasars or galaxies. [Abridged]Comment: Accepted for publication in the Astrophysical Journa

Latent ice recrystallization inhibition activity in nonantifreeze proteins : Ca2+-activated plant lectins and cation-activated antimicrobial peptides

Organisms living in polar regions have evolved a series of antifreeze (glyco) proteins (AFGPs) to enable them to survive by modulating the structure of ice. These proteins have huge potential for use in cellular cryopreservation, ice-resistant surfaces, frozen food, and cryosurgery, but they are limited by their relatively low availability and questions regarding their mode of action. This has triggered the search for biomimetic materials capable of reproducing this function. The identification of new structures and sequences capable of inhibiting ice growth is crucial to aid our understanding of these proteins. Here, we show that plant c-type lectins, which have similar biological function to human c-type lectins (glycan recognition) but no sequence homology to AFPs, display calcium-dependent ice recrystallization inhibition (IRI) activity. This IRI activity can be switched on/off by changing the Ca2+ concentration. To show that more (nonantifreeze) proteins may exist with the potential to display IRI, a second motif was considered, amphipathicity. All known AFPs have defined hydrophobic/hydrophilic domains, rationalizing this choice. The cheap, and widely used, antimicrobial Nisin was found to have cation-dependent IRI activity, controlled by either acid or addition of histidine-binding ions such as zinc or nickel, which promote its amphipathic structure. These results demonstrate a new approach in the identification of antifreeze protein mimetic macromolecules and may help in the development of synthetic mimics of AFPs

Mid-infrared Selection of Active Galactic Nuclei with the Wide-Field Infrared Survey Explorer. I. Characterizing WISE-selected Active Galactic Nuclei in COSMOS

The Wide-field Infrared Survey Explorer (WISE) is an extremely capable and efficient black hole finder. We present a simple mid-infrared color criterion, W1 – W2 ≥ 0.8 (i.e., [3.4]–[4.6] ≥0.8, Vega), which identifies 61.9 ± 5.4 active galactic nucleus (AGN) candidates per deg^2 to a depth of W2 ~ 15.0. This implies a much larger census of luminous AGNs than found by typical wide-area surveys, attributable to the fact that mid-infrared selection identifies both unobscured (type 1) and obscured (type 2) AGNs. Optical and soft X-ray surveys alone are highly biased toward only unobscured AGNs, while this simple WISE selection likely identifies even heavily obscured, Compton-thick AGNs. Using deep, public data in the COSMOS field, we explore the properties of WISE-selected AGN candidates. At the mid-infrared depth considered, 160 μJy at 4.6 μm, this simple criterion identifies 78% of Spitzer mid-infrared AGN candidates according to the criteria of Stern et al. and the reliability is 95%. We explore the demographics, multiwavelength properties and redshift distribution of WISE-selected AGN candidates in the COSMOS field

Measurement of the branching fractions of the radiative leptonic τ decays τ→eγνν[bar] and τ→μγνν[bar] at BABAR

We perform a measurement of the τ→lγνν [bar] (l=e,μ) branching fractions for a minimum photon energy of 10 MeV in the τ rest frame, using 431  fb^(−1) of e^+ e^− collisions collected at the center-of-mass energy of the Υ(4S) resonance with the BABAR detector at the PEP-II storage rings. We find B(τ→μγνν [bar])=(3.69±0.03±0.10)×10^(−3) and B(τ→eγνν[bar]¯ )=(1.847±0.015±0.052)×10^(−2), where the first quoted error is statistical and the second is systematic. These results are substantially more precise than previous measurements

Sodium/Hydrogen Exchanger Gene Defect in Slow-Wave Epilepsy Mutant Mice

AbstractThe “housekeeping” sodium/hydrogen exchanger, NHE1, mediates the electroneutral 1:1 exchange of Na+ and H+ across the plasma membrane. NHE1 is ubiquitous and is studied extensively for regulation of pH i, cell volume, and response to growth factors. We describe a spontaneous mouse mutant, s low-w ave e pilepsy, (swe), with a neurological syndrome including ataxia and a unique epilepsy phenotype consisting of 3/sec absence and tonic-clonic seizures. swe was fine-mapped on Chromosome 4 and identified as a null allele of Nhe1. Mutants show selective neuronal death in the cerebellum and brainstem but otherwise are healthy. This first example of a disease-causing mutation in an Nhe gene provides a new tool for studying the delicate balance of neuroexcitability and cell survival within the CNS