The 68,000-Dalton Neurofilament-Associated Polypeptide is a Component of Nonneuronal Cells and of Skeletal Myofibrils

Purified preparations of 10-nm neurofilaments from rat spinal cord and bovine or porcine brain contain a predominant 68,000-dalton polypeptide. This polypeptide is also a major component of the neurofilaments that copurify with brain tubulin isolated by cycles of polymerization and depolymerization. A protein that has the same isoelectric point and molecular weight as the neurofilament-associated polypeptide has also been identified as a cytoskeletal protein in a variety of avian and mammalian cell types, including baby hamster kidney (BHK-21) mouse 3T3, Novikoff rat hepatoma, chicken fibroblast, and chicken muscle cells. This protein is also a component of isolated chicken skeletal myofibrils. One-dimensional peptide maps of the 68,000-dalton proteins purified by two-dimensional isoelectric focusing/NaDodSO4/polyacrylamide gel electrophoresis from myofibrils, cycled tubulin, purified neurofilaments, and various cultured cell types were identical. In immunofluorescence this protein was associated with cytoplasmic intermediate filaments and myofibril Z discs. These results indicate that the neurofilament-associated polypeptide is a conserved protein that is present in many different cell types in addition to neuronal cells. Because some of these cells contain the major components of two other intermediate filament classes, desmin and vimentin, a given cell type may contain the subunits of at least three distinct intermediate filament types

On the chain length dependence of local correlations in polymer melts and a perturbation theory of symmetric polymer blends

The self-consistent field (SCF) theory of dense polymer liquids assumes that short-range correlations are almost independent of how monomers are connected into polymers. Some limits of this idea are explored in the context of a perturbation theory for mixtures of structurally identical polymer species, A and B, in which the AB pair interaction differs slightly from the AA and BB interaction, and the difference is controlled by a parameter alpha Expanding the free energy to O(\alpha) yields an excess free energy of the form alpha $z(N)\phi_{A}\phi_{B}$, in both lattice and continuum models, where z(N) is a measure of the number of inter-molecular near neighbors of each monomer in a one-component liquid. This quantity decreases slightly with increasing N because the self-concentration of monomers from the same chain is slightly higher for longer chains, creating a deeper correlation hole for longer chains. We analyze the resulting $N$-dependence, and predict that $z(N) = z^{\infty}[1 + \beta \bar{N}^{-1/2}]$, where $\bar{N}$ is an invariant degree of polymerization, and $\beta=(6/\pi)^{3/2}$. This and other predictions are confirmed by comparison to simulations. We also propose a way to estimate the effective interaction parameter appropriate for comparisons of simulation data to SCF theory and to coarse-grained theories of corrections to SCF theory, which is based on an extrapolation of coefficients in this perturbation theory to the limit $N \to \infty$. We show that a renormalized one-loop theory contains a quantitatively correct description of the $N$-dependence of local structure studied here.Comment: submitted to J. Chem. Phy

Parallel machine architecture and compiler design facilities

The objective is to provide an integrated simulation environment for studying and evaluating various issues in designing parallel systems, including machine architectures, parallelizing compiler techniques, and parallel algorithms. The status of Delta project (which objective is to provide a facility to allow rapid prototyping of parallelized compilers that can target toward different machine architectures) is summarized. Included are the surveys of the program manipulation tools developed, the environmental software supporting Delta, and the compiler research projects in which Delta has played a role

Increased hazard of myocardial infarction with insulin‐provision therapy in actively smoking patients with diabetes mellitus and stable ischemic heart disease: The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial

Background In the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial, randomization of diabetic patients with stable ischemic heart disease to insulin provision ( IP ) therapy, as opposed to insulin sensitization ( IS ) therapy, resulted in biochemical evidence of impaired fibrinolysis but no increase in adverse clinical outcomes. We hypothesized that the prothrombotic effect of IP therapy in combination with the hypercoagulable state induced by active smoking would result in an increased risk of myocardial infarction ( MI ). Methods and Results We analyzed BARI 2D patients who were active smokers randomized to IP or IS therapy. The primary end point was fatal or nonfatal MI . PAI ‐1 (plasminogen activator inhibitor 1) activity was analyzed at 1, 3, and 5 years. Of 295 active smokers, MI occurred in 15.4% randomized to IP and in 6.8% randomized to IS over the 5.3 years ( P =0.023). IP therapy was associated with a 3.2‐fold increase in the hazard of MI compared with IS therapy (hazard ratio: 3.23; 95% confidence interval, 1.43–7.28; P =0.005). Baseline PAI ‐1 activity (19.0 versus 17.5 Au/mL, P =0.70) was similar in actively smoking patients randomized to IP or IS therapy. However, IP therapy resulted in significantly increased PAI ‐1 activity at 1 year (23.0 versus 16.0 Au/mL, P =0.001), 3 years (24.0 versus 18.0 Au/mL, P =0.049), and 5 years (29.0 versus 15.0 Au/mL, P =0.004) compared with IS therapy. Conclusions Among diabetic patients with stable ischemic heart disease who were actively smoking, IP therapy was independently associated with a significantly increased hazard of MI . This finding may be explained by higher PAI ‐1 activity in active smokers treated with IP therapy. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00006305. </jats:sec

Constitutively active FOXO1 diminishes activin induction of Fshb transcription in immortalized gonadotropes.

In the present study, we investigate whether the FOXO1 transcription factor modulates activin signaling in pituitary gonadotropes. Our studies show that overexpression of constitutively active FOXO1 decreases activin induction of murine Fshb gene expression in immortalized LβT2 cells. We demonstrate that FOXO1 suppression of activin induction maps to the -304/-95 region of the Fshb promoter containing multiple activin response elements and that the suppression requires the FOXO1 DNA-binding domain (DBD). FOXO1 binds weakly to the -125/-91 region of the Fshb promoter in a gel-shift assay. Since this region of the promoter contains a composite SMAD/FOXL2 binding element necessary for activin induction of Fshb transcription, it is possible that FOXO1 DNA binding interferes with SMAD and/or FOXL2 function. In addition, our studies demonstrate that FOXO1 directly interacts with SMAD3/4 but not SMAD2 in a FOXO1 DBD-dependent manner. Moreover, we show that SMAD3/4 induction of Fshb-luc and activin induction of a multimerized SMAD-binding element-luc are suppressed by FOXO1 in a DBD-dependent manner. These results suggest that FOXO1 binding to the proximal Fshb promoter as well as FOXO1 interaction with SMAD3/4 proteins may result in decreased activin induction of Fshb in gonadotropes

Seismic Site Classifications for the St. Louis Urban Area

Regional National Earthquake Hazards Reduction Program (NEHRP) soil class maps have become important input parameters for seismic site characterization and hazard studies. The broad range of shallow shear-wave velocity (VS30, the average shear-wave velocity in the upper 30 m) measurements in the St. Louis area results in significant uncertainties between the actual spot values and the averaged values used to assign NEHRP soil classes for regional seismic hazard studies. In the preparation of an NEHRP site classification map of the St. Louis urban area, we analyzed 92 shear-wave velocity (VS) measurements, supplemented by 1400+ standard penetration test (SPT) profiles in areas bereft of VS measurements. SPT blow counts correlated to VS values based on the published correlations. The data were then compiled for respective surficial geologic units and bedrock type. These data suggest that the reciprocal of VS30 exhibits a fairly linear relationship with depth to bedrock, likely because VS30 is a function of the thickness of surficial materials exhibiting relatively low VS values. The VS30 values were interpolated by summing the regressed VS30 on the depth to bedrock and kriged values of the regression residuals. The resulting NEHRP site classification maps predict that upland areas of the St. Louis area are spatially classified as soil site classes SB to SD, while the low-lying floodplains are consistently classified as SD to SF

Seismic-Hazard Map of Southeast Missouri and Likely Magnitude of the February 1812 New Madrid Earthquake

The New Madrid seismic zone lies beneath the upper Mississippi Embayment, straddling the border between southeastern Missouri and northwestern Tennessee. In late 1811 and early 1812, it produced five earthquakes of magnitudes \u3e6.5, violently shaking the central and eastern United States (CEUS). Its magnitude and recurrence are of concern to today\u27s central United States regions. By considering the effects of local geology, deterministic scenario maps (Mw 7.3 and 7.7) were produced for ground motions intended to simulate the 7 February 1812 event (NM3), which was the largest felt. These maps include spatial estimates of peak ground acceleration and of 0.2 s and 1.0 s spectral acceleration (SA). Compared with the isoseismic map of modified Mercalli intensities (MMIs) in southeast Missouri, the MMIs converted from 0.2 s SA suggest that Mw 7.7 is a plausible scenario for NM3. To better constrain its magnitude, other CEUS sites shaken during NM3 were also examined. Local site conditions were studied and evaluated before calculating the threshold magnitude for the reported MMIs. These results indicate that the magnitude of NM3 was at least Mw 7.6, which validates our estimated size of Mw 7.7 for southeastern Missouri

Representing Structural Information of Helical Charge Distributions in Cylindrical Coordinates

Structural information in the local electric field produced by helical charge distributions, such as dissolved DNA, is revealed in a straightforward manner employing cylindrical coordinates. Comparison of structure factors derived in terms of cylindrical and helical coordinates is made. A simple coordinate transformation serves to relate the Green function in cylindrical and helical coordinates. We also compare the electric field on the central axis of a single helix as calculated in both systems.Comment: 11 pages in plain LaTex, no figures. Accepted for publication in PRE March, 199