Binding of active site directed ligands to phospholipase A2: Implications on the molecular constraints and catalytic mechanism

Molecular constraints for the localization of active site directed ligands (competitive inhibitors and substrates) in the active site of phospholipase A2 (PLA2) are characterized. Structure activity relationships with known inhibitors suggest that the head : group interactions dominate the selectivity as well as a substantial part of the affinity. The ab initio fitting of the amide ligands in the active site was carried out to characterize the head group interactions. Based on a systematic coordinate space search, formamide is docked with known experimental constraints such as coordination of the carbonyl group to Ca2+ and hydrogen bond between amide nitrogen and ND1 of His48. An optimal position for a bound water molecule is identified and its significance for the catalytic mechanism is postulated. Unlike the traditional ''pseudo-triad'' mechanism, the ''Ca-coordinatedoxyanion'' mechanism proposed here invokes activation of the catalytic water to form the oxyanion in the coordination sphere of calcium. As it attacks the carbonyl carbon of the ester, a near-tetrahedral intermediate is formed. As the second proton of the catalytic water is abstracted by the ester oxygen, its reorientation and simultaneous cleavage form hydrogen bond with ND1 of His48. In this mechanism of esterolysis, a catalytic role for the water co-ordinated to Ca2+ is recognised.

Authigenic carbonate of ODP SIte 104-643

Different generations of complex authigenic carbonates formed in siliceous muds (lithologic Unit IV) and hemipelagic clays (lithologic Unit V) of ODP Site 643, Leg 104 Norwegian Sea. The dominant phase in Unit IV is an early diagenetic Mn, Fe-calcite with a strong negative d13C ( -14 to -16 per mil) signature, and slightly negative d180 values. The strong negative d13C results from extensive incorporation of 12C-enriched CO2 derived from bacterial degradation of marine organic matter into early Mn, Fe - calcite cements. Concomitant framboidal pyrite precipitation and abundant SEM microtextures showing excellent preservation of delicate structures of fragile diatom valves by outpourings with early Mn-calcites strongly support their shallow burial formation before the onset of compaction. Later generations of authigenic mineralizations in lithologic Unit IV include minor amounts of a second generation of calcite with platy crystals, possibly precipitated along with opal-A dissolution, and finally opal-CT crystallization in deeper seated environments overgrowing earlier precipitates with films and lepispheres. The last mineralization is collophane (fluor apatite) forming amorphous aggregates and tiny hexagonal crystals. Authigenic mineral assemblages in lithologic Unit V consist of rhodochrosites, transitional rhodochrosite/manganosiderites, and apatite. A negative d13C ( -7.1 to -15.6 per mil) and a fluctuating d18O signal indicates that the micritic to sparitic rhodochrosites, transitional rhodochrosites/manganosiderites were formed at various burial depths. CO2 resulted from organic matter degradation in the lowermost sulfate reduction zone and from biogenic methane generation in the lowermost sediments, resulting in variable and negative d13C signals. The change in carbonate mineralogy reflects major compositional differences compared to sediments in Unit IV. Most prominent is an increase in altered ash as a primary sediment component and a sudden decrease of siliceous microfossils. Upward diffusion of cations, lowered salinities in pore waters, and elevated temperatures provide diagenetic environments favoring increased remobilization processes.

Fluorescent probe studies of biomembranes and model systems. The design and use of anionic site reporters

The fluorescence properties of a homologous series of fluorescent alkylamines are described. The binding of the probes to crythrocyte membranes increases with the length of the alkyl chain. The probes are shown to interact more strongly with membranes than with protein and lipid model systems. The binding of the probes to the membrane is sensitive to the cation concentration of the medium.

Robust dielectric properties of B-site size-disordered hexagonal Ln(2)CuTiO(6) (Ln = Y, Dy, Ho, Er, and Yb)

Hexagonal Ln(2)CuTiO(6) (Ln = Y, Dy, Ho, Er, and Yb) exhibits a rare combination of interesting dielectric properties, in the form of relatively large dielectric constants (epsilon' > 30), low losses, and extremely small temperature and frequency dependencies, over large ranges of temperature and frequency Choudhury et al., Appl. Phys. Lett. 96, 162903 (2010) and Choudhury et al., Phys. Rev. B 82, 134203 (2010)], making these compounds promising as high-k dielectric materials. The authors present a brief review of the existing literature on this interesting class of oxides, complimenting it with spectroscopic data in conjunction with first-principles calculation results, revealing a novel mechanism underlying these robust dielectric properties. These show that the large size differences in Cu2+ and Ti4+ at the B-site, aided by an inherent random distribution of CuO5 and TiO5 polyhedral units, frustrates the ferroelectric instability, inherent to the noncentrosymmetric P6(3) cm space group of this system, and gives rise to the observed relatively large dielectric constant values. Additionally, the phononic contributions to the dielectric constant are dominated primarily by mid-frequency (>100 cm(-1)) polar modes, involving mainly Ti4+ 3d(0) ions. In contrast, the soft polar phonon modes with frequencies typically less than 100 cm(-1), usually responsible for dielectric properties of materials, are found to be associated with non-d(0) Cu2+ ions and to contribute very little, giving rise to the remarkable temperature stability of dielectric properties of these compounds. (C) 2014 American Vacuum Society.

Effect of partial site occupation on the magnetic properties of Nd2Fe17-xSix by supercell calculation

The magnetic properties of the Nd2Fe17-xSix intermetallic compounds are studied by means of spin-polarized supercell calculations in which the selected sites of substitution are close to the situations in real samples. It is shown that the average Fe moment increases with x and saturates near x = 3. This correlates quite well with the experimental dependence of Te on x. The difference between supercell and unit cell calculations are pointed out and the influence of Si atoms on the density of states of the nearby Fe atoms is emphasized. (C) 1997 American Institute of Physics.

Delineation of within-site terroir effects using soil and vine water measurement. Investigation of Cabernet Franc

. The influence of vine water status was studied in commercial vineyard blocks of Vilis vinifera L. cv. Cabernet Franc in Niagara Peninsula, Ontario from 2005 to 2007. Vine performance, fruit composition and vine size of non-irrigated grapevines were compared within ten vineyard blocks containing different soil and vine water status. Results showed that within each vineyard block water status zones could be identified on GIS-generated maps using leaf water potential and soil moisture measurements. Some yield and fruit composition variables correlated with the intensity of vine water status. Chemical and descriptive sensory analysis was performed on nine (2005) and eight (2006) pairs of experimental wines to illustrate differences between wines made from high and low water status winegrapes at each vineyard block. Twelve trained judges evaluated six aroma and flavor (red fruit, black cherry, black current, black pepper, bell pepper, and green bean), thr~e mouthfeel (astringency, bitterness and acidity) sensory attributes as well as color intensity. Each pair of high and low water status wine was compared using t-test. In 2005, low water status (L WS) wines from Buis, Harbour Estate, Henry of Pelham (HOP), and Vieni had higher color intensity; those form Chateau des Charmes (CDC) had high black cherry flavor; those at RiefEstates were high in red fruit flavor and at those from George site was high in red fruit aroma. In 2006, low water status (L WS) wines from George, Cave Spring and Morrison sites were high in color intensity. L WS wines from CDC, George and Morrison were more intense in black cherry aroma; LWS wines from Hernder site were high in red fruit aroma and flavor. No significant differences were found from one year to the next between the wines produced from the same vineyard, indicating that the attributes of these wines were maintained almost constant despite markedly different conditions in 2005 and 2006 vintages. Partial ii Least Square (PLS) analysis showed that leaf \}' was associated with red fruit aroma and flavor, berry and wine color intensity, total phenols, Brix and anthocyanins while soil moisture was explained with acidity, green bean aroma and flavor as well as bell pepper aroma and flavor. In another study chemical and descriptive sensory analysis was conducted on nine (2005) and eight (2006) medium water status (MWS) experimental wines to illustrate differences that might support the sub-appellation system in Niagara. The judges evaluated the same aroma, flavor, and mouthfeel sensory attributes as well as color intensity. Data were analyzed using analysis of variance (ANOVA), principal component analysis (PCA) and discriminate analysis (DA). ANOV A of sensory data showed regional differences for all sensory attributes. In 2005, wines from CDC, HOP, and Hemder sites showed highest. r ed fruit aroma and flavor. Lakeshore and Niagara River sites (Harbour, Reif, George, and Buis) wines showed higher bell pepper and green bean aroma and flavor due to proximity to the large bodies of water and less heat unit accumulation. In 2006, all sensory attributes except black pepper aroma were different. PCA revealed that wines from HOP and CDC sites were higher in red fruit, black currant and black cherry aroma and flavor as well as black pepper flavor, while wines from Hemder, Morrison and George sites were high in green bean aroma and flavor. ANOV A of chemical data in 2005 indicated that hue, color intensity, and titratable acidity (TA) were different across the sites, while in 2006, hue, color intensity and ethanol were different across the sites. These data indicate that there is the likelihood of substantial chemical and sensory differences between clusters of sub-appellations within the Niagara Peninsula iii

Factors to drive clinical practice improvement in a Malaysian intensive care unit : assessment of organisational readiness using a mixed method approach

This study assessed organisational readiness and factors to drive clinical practice improvement for VAP, CRBSI and PU in a Malaysian intensive care unit (ICU). A mixed method study approach was undertaken in a 16-bed ICU in regional Malaysia using an environmental scan, key informant interviews, staff surveys, and patient audit to elucidate factors contributing to planning for clinical practice improvement. Measurements of sustainability of practice and regard for the practice environment were assessed using validated measures. An environmental scan demonstrated high patient occupancy and case load. Nineteen percent of ICU patients developed complications according to validated measures. Survey results indicated that the majority of nurses had a good knowledge of strategies to prevent ICU complications and a positive attitude toward change processes. Engaging executive leadership was identified as crucial in priming the clinical site for practice change. Providing nurses with tools to monitor their clinical practice and empowering them to change practices are important in improving clinical outcomes.

Potassium and argon concentrations and age determination of ODP Site 125-782 and 125-786

K-Ar whole-rock ages have been obtained for 30 samples from Sites 782 and 786, Ocean Drilling Program Leg 125 in the Izu-Bonin (Ogasawara) forearc region. They form a trimodal spread of ages between 9 Ma and 44 Ma and are, with a few exceptions, consistent with the inferred lithostratigraphy. The ages have been interpreted in terms of at least two distinct episodes of magmatic and/or hydrothermal activity. A group of ten samples, including the lava flows, gave an isochron age of 41.3 ± 0.5 Ma (middle-late Eocene). This is thought to represent the age of the principal magmatic development of the volcanic forearc basement, and is comparable to published ages on equivalent rocks from other parts of the forearc basement high (e.g., the Ogasawara Islands). It may be significant that this age is slightly younger than the timing of major plate reorganization in the Western Pacific at about 43 Ma. This was followed by a minor episode of intrusive magmatism at 34.6 ± 0.7 Ma (early Oligocene) which appears to have reset the ages of some of the earlier units. This event probably corresponds to the initiation of rifting of the "proto-arc" to form the Parece Vela Basin. Boninitic samples were erupted during both episodes of magmatism, the earlier being of low-Ca boninite type and the later being of medium- and high-Ca types. It is also possible that a third episode of intrusive magmatism affected the Izu-Bonin forearc region at both Sites 782 and 786 at about 17 Ma. This would be consistent with magmatic activity elsewhere in the region during the Miocene, associated with the end of active spreading in the Parece Vela Basin and the start of arc activity in the West Mariana Ridge.

Petrology and geochemistry of sedimentary Unit III of ODP Hole 135-840B

The sedimentary sequence recovered at Site 840, on the Tonga frontal-arc platform, is 597.3 m thick and is subdivided into three lithostratigraphic units. The lowermost, late Miocene Unit III is 336.8 m thick and consists of a sequence of volcaniclastic mass-flow deposits (predominantly turbidites) interbedded with pelagic/hemipelagic deposits. Unit III was deposited in the forearc basin of the Lau volcanic arc, probably on a slope dominated by mass flows that built eastward from the ridge front and across the forearc. Upward through the unit a thinning and fining of individual turbidites takes place, interpreted to reflect a reduced sediment supply and a change from large to smaller flows. Decreasing volcanic activity with time is inferred from a decrease in coarse-grained volcaniclastic content in the upper part of the unit. The majority of the turbidites show the typical Bouma-type divisions, although both high- and low-density turbidity currents are inferred. High-density turbidity currents were especially common in the lower part of the unit. Geochemical analyses of detrital glass lie mainly in the low-K tholeiite field with a compositional range from basalt to rhyolite. A coherent igneous trend indicates derivation from a single volcanic source. This source was probably situated on the rifted part of the Lau-Tonga Ridge, within the present Lau backarc basin. The initial opening of the Lau Basin may have been around 6.0 m.y. ago. The onset of more extensive rifting, approximately 5.6 m.y. ago, is reflected in an increase in the silica content of volcanic glass. At the boundary toward Unit II, at approximately 5.25 Ma, an influx of thicker bedded and coarser grained volcaniclastic material is interpreted to reflect increasing volcanism and tectonism during the final breakup of the Lau-Tonga Ridge.