Class II HMG-CoA Reductase Inhibitors targeting Methicillin-Resistant Staphylococcus pseudintermedius

Staphylococcus pseudintermedius is a component of the normal flora of companion animals that contributes to opportunistic infections in dogs. Clinical isolates of S. pseudintermedius (chiefly methicillin-resistant S. pseudintermedius (MRSP)) have been identified that exhibit resistance to nearly all antibiotic classes. There is a need for new antibiotics that target novel pathways within resistant pathogens such as MRSP. A possible novel antibacterial target in Gram-positive cocci is class II HMG-CoA reductase (HMGR), a key enzyme present in the mevalonate pathway that is essential for bacterial survival. In this study we examined novel synthetic compounds that are potent inhibitors of bacterial HMGRs. The compounds inhibited growth, in low micromolar concentration, of clinical isolates of methicillin-sensitive S. pseudintermedius (MSSP) and MRSP via the broth microdilution assay. The MTS assay confirmed the most potent compound (6) wasnot toxic to different mammalian cell lines (up to 128 µM). A time-kill assay revealed this compound rapidly eradicates a high inoculum of MRSP within two hours. This study provides evidence that compound 6 is a promising agent that warrants further investigation as a novel treatment option for MRSP infections

Enhancing Production of Bio-Isoprene Using Hybrid MVA Pathway and Isoprene Synthase in E. coli

The depleting petroleum reserve, increasingly severe energy crisis, and global climate change are reigniting enthusiasm for seeking sustainable technologies to replace petroleum as a source of fuel and chemicals. In this paper, the efficiency of the MVA pathway on isoprene production has been improved as follows: firstly, in order to increase MVA production, the source of the “upper pathway” which contains HMG-CoA synthase, acetyl-CoA acetyltransferase and HMG-CoA reductase to covert acetyl-CoA into MVA has been changed from Saccharomyces cerevisiae to Enterococcus faecalis; secondly, to further enhance the production of MVA and isoprene, a alanine 110 of the mvaS gene has been mutated to a glycine. The final genetic strain YJM25 containing the optimized MVA pathway and isoprene synthase from Populus alba can accumulate isoprene up to 6.3 g/L after 40 h of fed-batch cultivation

Searching for gravitational waves from known pulsars

We present upper limits on the amplitude of gravitational waves from 28 isolated pulsars using data from the second science run of LIGO. The results are also expressed as a constraint on the pulsars' equatorial ellipticities. We discuss a new way of presenting such ellipticity upper limits that takes account of the uncertainties of the pulsar moment of inertia. We also extend our previous method to search for known pulsars in binary systems, of which there are about 80 in the sensitive frequency range of LIGO and GEO 600.Comment: Accepted by CQG for the proceeding of GWDAW9, 7 pages, 2 figure

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

Solid-state conversion of a tube-type communications receiver

A Hammarlund SUPER-PRO SP-210 communications receiver of approximately 1940 design was rebuilt using modern solid-state components and associated circuitry in replacement of the original eighteen vacuum tubes. Replacement was effected in a stage- for-stage manner so as to utilize, wherever practicable, the original system of operation and particularly the existing tuned circuits for which the receiver was famous. The project goals were to gain experience in the applications of classroom theory to practical electronics, to observe the problems associated with both vacuum tube and solid-state circuitry, and to provide a starting point for continued research in electronics.http://archive.org/details/solidstateconver00steuLieutenant, United States Nav