Molecular basis for resistance of acanthamoeba tubulins to all major classes of antitubulin compounds

Tubulin is essential to eukaryotic cells and is targeted by several antineoplastics, herbicides, and antimicrobials. We demonstrate that Acanthamoeba spp. are resistant to five antimicrotubule compounds, unlike any other eukaryote studied so far. Resistance correlates with critical amino acid differences within the inhibitor binding sites of the tubulin heterodimers

Tricarbonylchlorido(6'7'-dihydro-5’H-spiro[cyclopentane-1,6'-dipyrido-[3,2-d:2',3'-f][1,3]diazepine]-κ2N1,N11)-rhenium(I)

In the title compound, [ReCl(C15H16N4)(CO)3], the ReI ion is coordinated in a distorted octahedral geometry by one Cl atom, two N atoms of the bidentate ligand and three carbonyl groups. The cyclopentane group is orientated in a transoid fashion with respect to the chloride ligand. The dihedral angle between the pryridine rings is 10.91 (12)°. In the crystal, N-H...Cl hydrogen bonds link complex molecules, forming a two-dimensional network parallel to (001)

Tricarbonylchlorido(6’,7’-dihydro-5’H-spiro[cyclohexane-1,6’-dipyrido[3,2-d :2’,3’-f][1,3]diazepine]-κ2N1,N11)rhenium(I)

In the title compound, [ReCl(C16H18N4)(CO)3], the ReI ion is coordinated in a distorted octahedral geometry by one Cl atom, two N atoms of the bidentate ligand and three carbonyl groups. The cyclohexane group is orientated in a transoid fashion with respect to the chloride ligand. In the crystal, N-H...Cl hydrogen bonds link complex molecules, forming a two-dimensional network parallel to (100)

The Impact of Motivation on Continued VFR into IMC: Another Perspective to an On-Going Problem

Continued flight under visual flight rules into instrument meteorological conditions remains the predominant cause for fatal accidents by percentage for general aviation aircraft operations. There are gaps in the research in determining how motivation might influence the decision-making process. Therefore, the purpose of this study was to determine how motivation and meteorological conditions might affect a pilot’s willingness to persist in flight into meteorological conditions. Four hundred and fifty-four general aviation pilots participated in a mixed factorial experiment to assess their willingness to persist in varying weather conditions. Participants were randomly assigned into one of three motivation groups (intrinsic, extrinsic, or no motivation) and were subjected to all three meteorological conditions (visual, marginal, and instrument) that were randomized in order of appearance. They were then asked to indicate their willingness to persist in each condition via a slider scale, scaled from 0 to 100. The results indicated the main effect of meteorological condition has a significant effect on willingness to persist, while the main effect of motivation did not. The interaction between meteorological condition and motivation resulted in a significant effect, particularly in the marginal meteorological condition

A rhenium(I) complex which reacts with aldehydes and ketones in aqueous media: a structural, spectroscopic and theoretical analysis

A Re(I) complex of 3,3′-diamino-2,2′-bipyridine reacts irreversibly with aldehydes and unhindered ketones in water to form bis-aminal cyclised derivatives with the solid-state structure of the reaction with benzaldehyde reported. This reaction produces a Re(I) complex which is significantly more emissive than the starting compound

Photochemistry of [Ru(pytz)(btz)2]2+and Characterization of a κ1-btz Ligand-Loss Intermediate

We report the synthesis, characterisation and photochemical reactivity of the triazole-containing complex [Ru(pytz)(btz)2]2+ (1, pytz = 1-benzyl-4-(pyrid-2-yl)-1,2,3-triazole, btz = 1,1’-dibenzyl-4,4’-bi-1,2,3-triazolyl). The UV-visible absorption spectrum of 1 exhibits pytz- and btz-centred 1MLCT bands at 365 and 300 nm respectively. Upon photo-excitation, acetonitrile solutions of 1 undergo conversion to the ligand loss intermediate, trans-[Ru(pytz)(2-btz)(1-btz)(NCMe)]2+ (2, 363 = 0.013) and ultimately to the ligand loss product trans-[Ru(pytz)(btz)(NCMe)2]2+ (3), both of which are observed and characterised by 1H NMR spectroscopy. Time-dependent density functional theory calculations reveal that the S1 state of the complex has primarily HOMOLUMO pytz-based 1MLCT character. Data show that the 3MLCT and 3MC states are in close energetic proximity ( 0.11 eV to 2 d.p.) and that the T1 state from a single point triplet state calculation at the S0 geometry suggests 3MC character. Optimisation of the T1 state of the complex starting from the ground state geometry leads to elongation of the two Ru-N(btz) bonds cis to the pytz ligand to 2.539 and 2.544 Å leading to a psuedo 4-coordinate 3MC state rather than the 3MLCT state. The work therefore provides additional insights into the photophysical and photochemical properties of ruthenium triazole-containing complexes and their excited state dynamics

Unified analysis of terminal-time control in classical and quantum systems

Many phenomena in physics, chemistry, and biology involve seeking an optimal control to maximize an objective for a classical or quantum system which is open and interacting with its environment. The complexity of finding an optimal control for maximizing an objective is strongly affected by the possible existence of sub-optimal maxima. Within a unified framework under specified conditions, control objectives for maximizing at a terminal time physical observables of open classical and quantum systems are shown to be inherently free of sub-optimal maxima. This attractive feature is of central importance for enabling the discovery of controls in a seamless fashion in a wide range of phenomena transcending the quantum and classical regimes.Comment: 10 page

Dentine Oxygn Isotopes (δ18O) as a Proxy for Odontocete Distributions and Movements.

Spatial variation in marine oxygen isotope ratios ( δ18O) resulting from differential evaporation rates and precipitation inputs is potentially useful for characterizing marine mammal distributions and tracking movements across δ18O gradients. Dentine hydroxyapatite contains carbonate and phosphate that precipitate in oxygen isotopic equilibrium with body water, which in odontocetes closely tracks the isotopic composition of ambient water. To test whether dentine oxygen isotope composition reliably records that of ambient water and can therefore serve as a proxy for odontocete distribution and movement patterns, we measured δ18O values of dentine structural carbonate (δ18OSC) and phosphate (δ18OP) of seven odontocete species (n = 55 individuals) from regional marine water bodies spanning a surface water δ18O range of several per mil. Mean dentine δ18OSC (range +21.2 to +25.5‰ VSMOW) and δ18OP (+16.7 to +20.3‰) values were strongly correlated with marine surface water δ18O values, with lower dentine δ18OSC and δ18OP values in high-latitude regions (Arctic and Eastern North Pacific) and higher values in the Gulf of California, Gulf of Mexico, and Mediterranean Sea. Correlations between dentine δ18OSC and δ18OP values with marine surface water δ18O values indicate that sequential δ18O measurements along dentine, which grows incrementally and archives intra- and interannual isotopic composition over the lifetime of the animal, would be useful for characterizing residency within and movements among water bodies with strong δ18O gradients, particularly between polar and lower latitudes, or between oceans and marginal basins

Comprehensive linkage and linkage heterogeneity analysis of 4344 sibling pairs affected with hypertension from the Family Blood Pressure Program

Linkage analyses of complex, multifactorial traits and diseases, such as essential hypertension, have been difficult to interpret and reconcile. Many published studies provide evidence suggesting that different genes and genomic regions influence hypertension, but knowing which of these studies reflect true positive results is challenging. The reasons for this include the diversity of analytical methods used across these studies, the different samples and sample sizes in each study, and the complicated biological underpinnings of hypertension. We have undertaken a comprehensive linkage analysis of 371 autosomal microsatellite markers genotyped on 4,334 sibling pairs affected with hypertension from five ethnic groups sampled from 13 different field centers associated with the Family Blood Pressure Program (FBPP). We used a single analytical technique known to be robust to interpretive problems associated with a lack of completely informative markers to assess evidence for linkage to hypertension both within and across the ethnic groups and field centers. We find evidence for linkage to a number of genomic regions, with the most compelling evidence from analyses that combine data across field center and ethnic groups (e.g., chromosomes 2 and 9). We also pursued linkage analyses that accommodate locus heterogeneity, which is known to plague the identification of disease susceptibility loci in linkage studies of complex diseases. We find evidence for linkage heterogeneity on chromosomes 2 and 17. Ultimately our results suggest that evidence for linkage heterogeneity can only be detected with large sample sizes, such as the FBPP, which is consistent with theoretical sample size calculations. Genet. Epidemiol . 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56011/1/20202_ftp.pd