Sequences, sequence clusters and bacterial species

Whatever else they should share, strains of bacteria assigned to the same species should have house-keeping genes that are similar in sequence. Single gene sequences (or rRNA gene sequences) have very few informative sites to resolve the strains of closely related species, and relationships among similar species may be confounded by interspecies recombination. A more promising approach (multilocus sequence analysis, MLSA) is to concatenate the sequences of multiple house-keeping loci and to observe the patterns of clustering among large populations of strains of closely related named bacterial species. Recent studies have shown that large populations can be resolved into non-overlapping sequence clusters that agree well with species assigned by the standard microbiological methods. The use of clustering patterns to inform the division of closely related populations into species has many advantages for poorly studied bacteria (or to re-evaluate well-studied species), as it provides a way of recognizing natural discontinuities in the distribution of similar genotypes. Clustering patterns can be used by expert groups as the basis of a pragmatic approach to assigning species, taking into account whatever additional data are available (e.g. similarities in ecology, phenotype and gene content). The development of large MLSA Internet databases provides the ability to assign new strains to previously defined species clusters and an electronic taxonomy. The advantages and problems in using sequence clusters as the basis of species assignments are discussed

Microscopic Model of Charge Carrier Transfer in Complex Media

We present a microscopic model of a charge carrier transfer under an action of a constant electric field in a complex medium. Generalizing previous theoretical approaches, we model the dynamical environment hindering the carrier motion by dynamic percolation, i.e., as a medium comprising particles which move randomly on a simple cubic lattice, constrained by hard-core exclusion, and may spontaneously annihilate and re-appear at some prescribed rates. We determine analytically the density profiles of the "environment" particles, as seen from the stationary moving charge carrier, and calculate its terminal velocity as the function of the applied field and other system parameters. We realize that for sufficiently small external fields the force exerted on the carrier by the "environment" particles shows a viscous-like behavior and define an analog of the Stokes formula for such dynamic percolative environments. The corresponding friction coefficient is also derived.Comment: appearing in Chem. Phys. Special Issue on Molecular Charge Transfer in Condensed Media - from Physics and Chemistry to Biology and Nano-Engineering, edited by A.Kornyshev (Imperial College London), M.Newton (Brookhaven Natl Lab) and J.Ulstrup (Technical University of Denmark

High efficacy and low toxicity of weekly docetaxel given as first-line treatment for metastatic breast cancer

Background: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer. Patients and Methods: All patients received docetaxel, 35 mg/m(2) weekly for 6 weeks, followed by 2 weeks of rest. Subsequent cycles ( 3 weeks of treatment, 2 weeks of rest) were given until a maximum of 5 cycles or disease progression. Premedication consisted of 8 mg dexamethasone intravenously 30 min prior to the infusion of docetaxel. Results: Fifty-four patients at a median age of 58 years with previously untreated MBC were included in the study. A median of 10 doses ( median cumulative dose 339 mg/m(2)) was administered ( range: 2 - 18). The overall response rate was 48.1% ( 95% CI: 34 - 61%, intent-to-treat). Median survival was 15.8 months and median time to progression was 5.9 months ( intent-to-treat). Hematological toxicity was mild with absence of neutropenia-related complications. Grade 3 neutropenia was observed in 3.7% of patients and grade 3 and 4 anemia was observed in 5.6 and 1.9% of patients, respectively. Conclusion: The weekly administration of docetaxel is highly efficient and safe as first-line treatment for MBC and may serve as an important treatment option specifically in elderly patients and patients with a reduced performance status. Copyright (C) 2005 S. Karger AG, Basel

Micro internal combustion swing engine (MICSE) for portable power generation systems

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76989/1/AIAA-2002-722-277.pd

Pancreatectomy for metastasis to the pancreas from colorectal cancer and reconstruction of superior mesenteric vein: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tumors of the pancreatic head can infiltrate the superior mesenteric vein. In such cases, the deep veins of the lower limbs can serve as suitable autologous conduits for superior mesenteric vein reconstruction after its resection. Few data exist, however, describing the technique and the immediate patency of such reconstruction.</p> <p>Case report</p> <p>We present the case of a 70-year-old Caucasian man with a metachronous metastasis of colon cancer and infiltration of the uncinate pancreatic process, on the anterior surface of which the tumor was located. <it>En bloc </it>resection of the tumor was performed with resection of the superior mesenteric vein and reconstruction. A 10 cm segment of the superficial femoral vein was harvested for the reconstruction. The superficial femoral vein segment was inter-positioned in an end-to-end fashion. The post-operative conduit patency was documented ultrasonographically immediately post-operatively and after a six-month period. The vein donor limb presented subtle signs of post-operative venous hypertension with edema, which was managed with compression stockings and led to significant improvement after six months.</p> <p>Conclusion</p> <p>In cases of exploratory laparotomies with high clinical suspicion of pancreatic involvement, the potential need for vascular reconstruction dictates the preparation for leg vein harvest in advance. The superficial femoral vein provides a suitable conduit for the reconstruction of the superior mesenteric vein. This report supports the uncomplicated nature of this technique, since few data exist about this type of reconstruction.</p

Generalized model for dynamic percolation

We study the dynamics of a carrier, which performs a biased motion under the influence of an external field E, in an environment which is modeled by dynamic percolation and created by hard-core particles. The particles move randomly on a simple cubic lattice, constrained by hard-core exclusion, and they spontaneously annihilate and re-appear at some prescribed rates. Using decoupling of the third-order correlation functions into the product of the pairwise carrier-particle correlations we determine the density profiles of the "environment" particles, as seen from the stationary moving carrier, and calculate its terminal velocity, V_c, as the function of the applied field and other system parameters. We find that for sufficiently small driving forces the force exerted on the carrier by the "environment" particles shows a viscous-like behavior. An analog Stokes formula for such dynamic percolative environments and the corresponding friction coefficient are derived. We show that the density profile of the environment particles is strongly inhomogeneous: In front of the stationary moving carrier the density is higher than the average density, $\rho_s$, and approaches the average value as an exponential function of the distance from the carrier. Past the carrier the local density is lower than $\rho_s$ and the relaxation towards $\rho_s$ may proceed differently depending on whether the particles number is or is not explicitly conserved.Comment: Latex, 32 pages, 4 ps-figures, submitted to PR

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

In Vivo Characterization of the Homing Endonuclease within the polB Gene in the Halophilic Archaeon Haloferax volcanii

Inteins are parasitic genetic elements, analogous to introns that excise themselves at the protein level by self-splicing, allowing the formation of functional non-disrupted proteins. Many inteins contain a homing endonuclease (HEN) gene, and rely on its activity for horizontal propagation. In the halophilic archaeon, Haloferax volcanii, the gene encoding DNA polymerase B (polB) contains an intein with an annotated but uncharacterized HEN. Here we examine the activity of the polB HEN in vivo, within its natural archaeal host. We show that this HEN is highly active, and able to insert the intein into both a chromosomal target and an extra-chromosomal plasmid target, by gene conversion. We also demonstrate that the frequency of its incorporation depends on the length of the flanking homologous sequences around the target site, reflecting its dependence on the homologous recombination machinery. Although several evolutionary models predict that the presence of an intein involves a change in the fitness of the host organism, our results show that a strain deleted for the intein sequence shows no significant changes in growth rate compared to the wild type

High body burdens of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in California women.

Following our first report on elevated polybrominated diphenyl ether (PBDE) concentrations in California women, we expanded our investigation to include diverse groups of local women. We analyzed additional adipose and serum samples collected in the late 1990s from San Francisco Bay Area women participating in a breast cancer study and in a reproductive study, respectively. Adipose samples (n = 32) were analyzed by low-resolution mass spectrometry in negative-ion chemical ionization mode, whereas serum samples (n = 50) were analyzed by dual-column gas chromatography with electron capture detection. The results confirmed our earlier findings. Concentrations of 2,2,4,4 -tetrabromodiphenyl ether (BDE-47) in contemporary California women ranged between 5 and 510 ng/g lipid, with a median (16.5 ng/g lipid) 3-10 times higher than those reported from Europe. In contrast, PBDEs were not measurable in any of 420 archived serum samples collected in the 1960s from San Francisco Bay Area women participating in a study of child development. BDE-47 concentrations did not increase with age or with concentrations of a polychlorinated biphenyl (PCB-153), suggesting other routes of exposure in addition to diet. Rising body burdens of endocrine-disrupting chemicals such as PBDEs may pose a potential public health threat