Human Apolipoprotein B Transgenic Mice Generated with 207- and 145-Kilobase Pair Bacterial Artificial Chromosomes. Evidence that a distant 5'-element confers appropriate transgene expression in the intestine

We reported previously that ~80-kilobase pair (kb) P1 bacteriophage clones spanning either the human or mouse apoB gene (clones p158 and p649, respectively) confer apoB expression in the liver of transgenic mice, but not in the intestine. We hypothesized that the absence of intestinal expression was due to the fact that these clones lacked a distant DNA element controlling intestinal expression. To test this possibility, transgenic mice were generated with 145- and 207-kb bacterial artificial chromosomes (BACs) that contained the human apoB gene and more extensive 5'- and 3'-flanking sequences. RNase protection, in situ hybridization, immunohistochemical, and genetic complementation studies revealed that the BAC transgenic mice manifested appropriate apoB gene expression in both the intestine and the liver, indicating that both BACs contained the distant intestinal element. To determine whether the regulatory element was located 5' or 3' to the apoB gene, transgenic mice were generated by co-microinjecting embryos with p158 and either the 5'- or 3'-sequences from the 145-kb BAC. Analysis of these mice indicated that the apoB gene's intestinal element is located 5' to the structural gene. Cumulatively, the transgenic mouse studies suggest that the intestinal element is located between -33 and -70 kb 5' to the apoB gene

LCDG4 and DigiSim - Simulation activities at NICADD/NIU

We present two software packages developed to support detector R&D studies for the International Linear Collider. LCDG4 is a full-detector simulator that provides energy deposits from particles traversing the sensitive volumes of the detector. It has been extensively used within the American ILC community, providing data for algorithm development and detector optimization studies. DigiSim models real-life digitization effects, converting the idealized response into simulated detector readout. It has many useful features to improve the realism in modeling detector response. The main characteristics of these two complementary packages are discussed.Comment: 8 pages, 7 figures, submitted to LCWS05 conference proceedings. Uses slac_one.rt

The replicative lifespan-extending deletion of SGF73 results in altered ribosomal gene expression in yeast.

Sgf73, a core component of SAGA, is the yeast orthologue of ataxin-7, which undergoes CAG-polyglutamine repeat expansion leading to the human neurodegenerative disease spinocerebellar ataxia type 7 (SCA7). Deletion of SGF73 dramatically extends replicative lifespan (RLS) in yeast. To further define the basis for Sgf73-mediated RLS extension, we performed ChIP-Seq, identified 388 unique genomic regions occupied by Sgf73, and noted enrichment in promoters of ribosomal protein (RP)-encoding genes. Of 388 Sgf73 binding sites, 33 correspond to 5' regions of genes implicated in RLS extension, including 20 genes encoding RPs. Furthermore, half of Sgf73-occupied, RLS-linked RP genes displayed significantly reduced expression in sgf73Δ mutants, and double null strains lacking SGF73 and a Sgf73-regulated, RLS-linked RP gene exhibited no further increase in replicative lifespan. We also found that sgf73Δ mutants display altered acetylation of Ifh1, an important regulator of RP gene transcription. These findings implicate altered ribosomal protein expression in sgf73Δ yeast RLS and highlight altered acetylation as a pathway of relevance for SCA7 neurodegeneration

Resolving singular forces in cavity flow: Multiscale modeling from atoms to millimeters

A multiscale approach for fluid flow is developed that retains an atomistic description in key regions. The method is applied to a classic problem where all scales contribute: The force on a moving wall bounding a fluid-filled cavity. Continuum equations predict an infinite force due to stress singularities. Following the stress over more than six decades in length in systems with characteristic scales of millimeters and milliseconds allows us to resolve the singularities and determine the force for the first time. The speedup over pure atomistic calculations is more than fourteen orders of magnitude. We find a universal dependence on the macroscopic Reynolds number, and large atomistic effects that depend on wall velocity and interactions.Comment: 4 pages,3 figure

Exploring the Dust Content of Galactic Winds with Herschel. I. NGC 4631

We present a detailed analysis of deep far-infrared observations of the nearby edge-on star-forming galaxy NGC 4631 obtained with the Herschel Space Observatory. Our PACS images at 70 and 160 um show a rich complex of filaments and chimney-like features that extends up to a projected distance of 6 kpc above the plane of the galaxy. The PACS features often match extraplanar Halpha, radio-continuum, and soft X-ray features observed in this galaxy, pointing to a tight disk-halo connection regulated by star formation. On the other hand, the morphology of the colder dust component detected on larger scale in the SPIRE 250, 350, and 500 um data matches the extraplanar H~I streams previously reported in NGC 4631 and suggests a tidal origin. The PACS 70/160 ratios are elevated in the central ~3.0 kpc region above the nucleus of this galaxy (the "superbubble"). A pixel-by-pixel analysis shows that dust in this region has a higher temperature and/or an emissivity with a steeper spectral index (beta > 2) than the dust in the disk, possibly the result of the harsher environment in the superbubble. Star formation in the disk seems energetically insufficient to lift the material out of the disk, unless it was more active in the past or the dust-to-gas ratio in the superbubble region is higher than the Galactic value. Some of the dust in the halo may also have been tidally stripped from nearby companions or lifted from the disk by galaxy interactions.Comment: Accepted for publication in The Astrophysical Journa

Probing the N=14N = 14 subshell closure: gg factor of the 26^{26}Mg(21+^+_1) state

The first-excited state $g$~factor of $^{26}$Mg has been measured relative to the $g$ factor of the $^{24}$Mg($2^+_1$) state using the high-velocity transient-field technique, giving $g=+0.86\pm0.10$. This new measurement is in strong disagreement with the currently adopted value, but in agreement with the $sd$-shell model using the USDB interaction. The newly measured $g$ factor, along with $E(2^+_1)$ and $B(E2)$ systematics, signal the closure of the $\nu d_{5/2}$ subshell at $N=14$. The possibility that precise $g$-factor measurements may indicate the onset of neutron $pf$ admixtures in first-excited state even-even magnesium isotopes below $^{32}$Mg is discussed and the importance of precise excited-state $g$-factor measurements on $sd$~shell nuclei with $N\neq Z$ to test shell-model wavefunctions is noted.Comment: 8 pages, 5 figure

Application of Market Models to Network Equilibrium Problems

We present a general two-side market model with divisible commodities and price functions of participants. A general existence result on unbounded sets is obtained from its variational inequality re-formulation. We describe an extension of the network flow equilibrium problem with elastic demands and a new equilibrium type model for resource allocation problems in wireless communication networks, which appear to be particular cases of the general market model. This enables us to obtain new existence results for these models as some adjustments of that for the market model. Under certain additional conditions the general market model can be reduced to a decomposable optimization problem where the goal function is the sum of two functions and one of them is convex separable, whereas the feasible set is the corresponding Cartesian product. We discuss some versions of the partial linearization method, which can be applied to these network equilibrium problems.Comment: 18 pages, 3 table

Breathing Spots in a Reaction-Diffusion System

A quasi-2-dimensional stationary spot in a disk-shaped chemical reactor is observed to bifurcate to an oscillating spot when a control parameter is increased beyond a critical value. Further increase of the control parameter leads to the collapse and disappearance of the spot. Analysis of a bistable activator-inhibitor model indicates that the observed behavior is a consequence of interaction of the front with the boundary near a parity breaking front bifurcation.Comment: 4 pages RevTeX, see also http://chaos.ph.utexas.edu/ and http://t7.lanl.gov/People/Aric

Optimizing end-labeled free-solution electrophoresis by increasing the hydrodynamic friction of the drag-tag

We study the electrophoretic separation of polyelectrolytes of varying lengths by means of end-labeled free-solution electrophoresis (ELFSE). A coarse-grained molecular dynamics simulation model, using full electrostatic interactions and a mesoscopic Lattice Boltzmann fluid to account for hydrodynamic interactions, is used to characterize the drag coefficients of different label types: linear and branched polymeric labels, as well as transiently bound micelles. It is specifically shown that the label's drag coefficient is determined by its hydrodynamic size, and that the drag per label monomer is largest for linear labels. However, the addition of side chains to a linear label offers the possibility to increase the hydrodynamic size, and therefore the label efficiency, without having to increase the linear length of the label, thereby simplifying synthesis. The third class of labels investigated, transiently bound micelles, seems very promising for the usage in ELFSE, as they provide a significant higher hydrodynamic drag than the other label types. The results are compared to theoretical predictions, and we investigate how the efficiency of the ELFSE method can be improved by using smartly designed drag-tags.Comment: 32 pages, 11 figures, submitted to Macromolecule

Place matters: but does local leadership?

The arrival of New Labour into Government witnessed the prominent re-emergence of place onto the policy agenda. This heralded a range of area-based-initiatives designed to both tackle neighbourhood forms of deprivation and to re-establish a sense of identity and connection between individuals and their local community. In terms of place-making, effective and inclusive participation, representation and leadership were all identified as prerequisites for the creation of sustainable communities . But how important is local leadership and strategic vision within local public service organisations in achieving the desired place-making outcomes? This paper examines the extent to which local leadership and strategic vision represents a significant factor in promoting higher levels of satisfaction, belonging, cohesion and participation across single tier councils in England. The ensuing empirical evidence raises significant questions not only about the importance of local leadership in place-making, but also the environmental and organizational factors that shape local places