Tot Values Research Articles

Stratigraphy and geochemical characterization of the Oligocene–Miocene Maikop series: Implications for the paleogeography of Eastern Azerbaijan

The Oligocene–Miocene Maikop Series is a world-class source rock responsible for much of the oil and gas found in the South Caspian Basin. It is composed of up to 3 km of marine mudstone, and contains a nearly continuous record of deposition during progressive tectonic closure of the basin as the Arabian Peninsula converged northward into Eurasia. Historically, the stratigraphy of this interval has been difficult to define due to the homogenous nature of the fine-grained, clay-dominated strata. Outcrop exposures in eastern Azerbaijan allow direct observation and detailed sampling of the interval, yielding a more comprehensive stratigraphic context and a more advanced understanding of syndepositional conditions in the eastern Paratethys Sea. Specifically, the present investigation reveals that coupling field-based stratigraphic characterization with geochemical analyses (e.g., bulk elemental geochemistry, Rock-Eval pyrolysis, bulk stable isotope geochemistry) yields a more robust understanding of internal variations within the Maikop Series. Samples from seven sections located within the Shemakha–Gobustan oil province reveal consistent stratigraphic and spatial geochemical trends. It is proposed that the Maikop Series be divided into three members based on these data along with lithostratigraphic and biostratigraphic data reported herein. When comparing Rupelian (Early Oligocene) and Chattian (Late Oligocene) strata, the Rupelian-age strata commonly possess higher TOC values, more negative δ 15N tot values, more positive δ 13C org values, and higher radioactivity relative to Chattian-age rocks. The trace metals Mo and V (normalized to Al) are positively correlated with TOC, with maximum values occurring at the Rupelian–Chattian boundary and overall higher average values in the Rupelian. Across the Oligocene–Miocene boundary, a slight drop in V/Al, Mo/Al ratios is observed, along with drops in %S and TOC. These results indicate that geochemical signatures of the Maikop Series are regional in nature, and furthermore that analogous fine-grained sections may be better characterized and subdivided using similar techniques. In general, geochemical indicators suggest that the basin was in limited communication with the Tethys Sea throughout the Oligocene–Early Miocene, with suboxic to anoxic conditions present during the Oligocene and to a lesser extent in the Miocene. This increased isolation was likely due to tectonic uplift to both the south and north of the study area, and greatly enhanced by global sea-level fluctuations. These data serve as the basis for a more detailed understanding of the tectonic evolution of the region, and support a standardized chemostratigraphic division of the important petroleum source interval.

Dehydration experiments on natural omphacites: qualitative and quantitative characterization by various spectroscopic methods

A series of natural omphacites from a wide range of P, T occurrences were investigated by electron microprobe (EMP), infrared (IR)-, Mössbauer (MS)- and optical spectroscopy in the UV/VIS spectral range (UV/VIS), secondary ion mass spectrometry (SIMS) and single crystal structure refinement by X-ray diffraction (XRD) to study the influence of hydrogen loss on valence state and site occupancies of iron. In accordance with literature data we found Fe2+ at M1 as well as at M2, and in a first approach assigned Fe3+ to M1, as indicated by MS and XRD results. Hydrogen content of three of our omphacite samples were measured by SIMS. In combination with IR spectroscopy we determined an absorption coefficient: ε i,tot = 65,000 ± 3,000 lmolH2O −1 cm−2. Using this new ε i,tot value, we obtained water concentrations ranging from 60 to 700 ppm H2O (by weight). Hydrogen loss was simulated by stepwise heating the most water rich samples in air up to 800°C. After heat treatment the samples were analyzed again by IR, MS, UV/VIS, and XRD. Depending on the type of the OH defect, the grade of dehydration with increasing temperature is significantly different. In samples relatively poor in Fe3+ (<0.1 Fe3+ pfu), hydrogen associated with vacancies at M2 (OH bands around 3,450 cm−1) starts to leave the structure at about 550°C and is completely gone at 780°C. Hydrogen associated with Al3+ at the tetrahedral site (OH bands around 3,525 cm−1, Koch-Müller et al., Am Mineral, 89:921–931, 2004) remains completely unaffected by heat treatment up to 700°C. But all hydrogen vanished at about 775°C. However, this is different for a more Fe3+-rich sample (0.2 Fe3+ pfu). Its IR spectrum is characterized by a very intense OH band at 3,515 cm−1 plus shoulder at 3,450 cm−1. We assign this intense high-energy band to vibrations of an OH dipole associated with Fe3+ at M1 and a vacancy either at M1 or M2. OH release during heating is positively correlated with decrease in Fe2+ and combined with increase in Fe3+. That dehydration is correlated with oxidation of Fe2+ is indirectly confirmed by annealing of one sample in a gas mixing furnace at 700°C under reducing conditions keeping almost constant OH− content and giving no indication of Fe2+-oxidation. Obtained data indicate that in samples with a relatively high concentration of Fe2+ at M2 and low-water concentrations, i.e., at a ratio of Fe2+ M2/H > 10 dehydration occurs by iron oxidation of Fe2+ exclusively at the M2 site following the reaction: \( {\left[ {{\text{Fe}}^{{{\text{2 + [ M2]}}}}{\text{OH}}^{ - } } \right]} = {\left[ {{\text{Fe}}^{{{\text{3 + [ M2]}}}} {\text{O}}^{{{\text{2}} - }} } \right]} + {\text{1/2}}\;{\text{H}}_{{\text{2}}} \uparrow . \) In samples having relatively low concentration of Fe2+ at M2 but high-water concentrations, i.e., ratio of Fe2+ M2/H < 5.0 dehydration occurs through oxidation of Fe2+ at M1.

Valence of titanium and vanadium in pyroxene in refractory inclusion interiors and rims

The clinopyroxene in coarse-grained refractory inclusions contains significant amounts of Ti and V, two elements that are multivalent over the range of temperatures and oxygen fugacities under which the inclusions formed. The Ti 3+/Ti 4+ ratios and the valence of V of these pyroxenes are valuable recorders of nebular conditions. The former can be calculated stoichiometrically from electron probe analyses, but only for relatively Ti-rich grains (i.e., >∼4 wt% TiO 2 tot ). For Ti-poor pyroxene, and for measurement of V valence, another technique is needed. We have, for the first time, applied K-edge X-ray absorption near edge structure (XANES) spectroscopy to the measurement of Ti and V valence in meteoritic clinopyroxene in refractory inclusions. Use of MicroXANES, a microbeam technique with high (μm-scale) spatial resolution, allowed measurement of Ti and V valence along traverses across (a) Ti-, V-rich “spikes” in pyroxene in Type B1 inclusions; (b) typical grains in a Type B2 inclusion; and (c) the pyroxene layer of the Wark–Lovering rim sequence on the outsides of two inclusions. Measurements of Ti 3+/(Ti 3+ + Ti 4+), or Ti 3+/Ti tot, by XANES agree with values calculated from electron probe analyses to within ∼0.1, or ∼2 σ. The results show that Ti 3+/Ti tot increases sharply at the spikes, from 0.46 ± 0.03 to 0.86 ± 0.06, but the V valence, or V 2+/(V 2+ + V 3+), does not change, with V 2+ ≈ V 3+. We found that pyroxene in both Types B1 and B2 inclusions has Ti 3+/Ti tot and V 2+/V tot ratios between 0.4 and 0.7, except for the spikes. These values indicate, to first order, formation at similar, highly reducing oxygen fugacities that are consistent with a solar gas. The pyroxene in the rim on an Allende fluffy Type A coarse-grained refractory inclusion, TS24, has an average Ti 3+/Ti tot of 0.51 ± 0.08 and an average V 2+/V tot of 0.61 ± 0.06, determined by XANES. These values are within the range of those of pyroxene in the interiors of inclusions, indicating that the rims also formed under highly reducing conditions. Measurements of Ti 3+/Ti tot of pyroxene in the rim of a Leoville compact Type A inclusion, 144A, by both XANES and electron probe give a wide range of results. Of our 72 XANES analyses of this rim, 66% have Ti 3+/Ti tot of 0.40–0.71, and the remaining analyses range from 0 to 0.38. In data from Simon et al. [Simon J. I., Young E. D., Russell S. S., Tonui E. K., Dyl K. A., and Manning C. E. (2005) A short timescale for changing oxygen fugacity in the solar nebula revealed by high-resolution 26Al– 26Mg dating of CAI rims. Earth Planet. Sci. Lett. 238, 272–283.] for this sample, 7 electron probe analyses yield calculated Ti 3+/Ti tot values that are positive and 15 do not. In the probe analyses that have no calculated Ti 3+, Ca contents are anticorrelated and Al contents directly correlated with the total cations per 6 oxygens, and the data fall along trends calculated for addition of 1–7% spinel to pyroxene. It appears likely that electron probe analyses of pure pyroxene spots have Ti 3+/Ti tot values that are typical of refractory inclusions, in agreement with the majority of the XANES results. The average of the XANES data for 144A, 0.41 ± 0.14, is within error of that for TS24. The rim of 144A probably formed under reducing conditions like those expected for a solar gas, and was later heterogeneously altered, resulting in an uneven distribution of secondary, FeO-, Ti-bearing alteration products in the rim, and accounting for the measurements with low Ti 3+/Ti tot values.

Effect of prior heavy exercise on muscle deoxygenation kinetics at the onset of subsequent heavy exercise

This study examines the effect of prior heavy exercise on muscle deoxygenation kinetics at the onset of heavy-intensity cycling exercise. Ten young male adults (20 +/- 2 years) performed two repetitions of step transitions (6 min) from 35 W to heavy-intensity exercise preceded by either no warm-up or by a heavy-intensity exercise. VO2 was measured breath-by-breath, and muscle deoxygenation (HHb) and total hemoglobin (Hb(tot)) were monitored continuously by near-infrared spectroscopy. We used a two-exponential model to describe the VO2 kinetics and a mono-exponential model for the HHb kinetic. The parameters of the phase II VO2 kinetics (TD1 VO2, tau1 VO2 and A1 VO2) were unaffected by prior heavy exercise, while some parameters of local muscle deoxygenation kinetics were significantly faster (TD HHb: 7 +/- 2 vs. 5 +/- 2 s; P < 0.001, MRT HHb: 20 +/- 3 vs. 15+/- 4 s; P < 0.05). Blood lactate, heart rate and Hb(tot) values were significantly higher before the second bout of heavy exercise. These results collectively suggest that the prior heavy exercise probably increased muscle O2 availability and improved O2 utilization at the onset of a subsequent bout of heavy exercise.

Blood glucose on day of intensive care unit admission as a surrogate of subsequent glucose control in intensive care

Purpose The aim of the study was to test whether the mean of the highest and lowest glucose values on day 1 (Glu 1) is a useful surrogate marker of mean blood glucose during the totality of intensive care unit (ICU) stay (Glu tot). Materials and Methods Glu tot values were extracted from electronically stored biochemical databases (point-of-care laboratory) and Glu 1 values from electronically stored prospectively collected patient databases in ICUs of 4 hospitals from January 2000 to October 2004. Statistical assessment of relationship between Glu 1 and Glu tot was done. Results There were 197 227 blood glucose measurements for 8039 patients. The average of all blood glucose measurements was 8.22 ± 2.75 mmol/L. The difference between the average of all glucose values (N = 197 227) and average of Glu 1 (n = 8039) was 0.17 mmol/L. This difference in each hospital was also small (0.26, −0.13, 0.12, and 0.37 mmol/L, respectively). Conclusions Glu 1 was a good predictor of Glu tot across all study hospitals. This observation makes it possible to use Glu 1 as a surrogate of glucose control during ICU stay and opens the door to understanding ICU glucose control across the whole of Australia and New Zealand.

The X-ray emission properties and the dichotomy in the central stellar cusp shapes of early-type galaxies

The Hubble Space Telescope has revealed a dichotomy in the central surface brightness profiles of early-type galaxies, which have subsequently been grouped into two families: core, boxy, anisotropic systems; and cuspy (‘power-law’), discy, rotating ones. Here we investigate whether a dichotomy is also present in the X-ray properties of the two families. We consider both their total soft emission (LSX,tot), which is a measure of the galactic hot gas content, and their nuclear hard emission (LHX,nuc), mostly coming from Chandra observations, which is a measure of the nuclear activity. At any optical luminosity, the highest LSX,tot values are reached by core galaxies; this is explained by their being the central dominant galaxies of groups, subclusters or clusters, in many of the log LSX,tot (erg s−1) ≳ 41.5 cases. The highest LHX,nuc values, similar to those of classical active galactic nuclei (AGNs), in this sample are hosted only by core or intermediate galaxies; at low luminosity AGN levels, LHX,nuc is independent of the central stellar profile shape. The presence of optical nuclei (also found by HST) is unrelated to the level of LHX,nuc, even though the highest LHX,nuc are all associated with optical nuclei. The implications of these findings for galaxy evolution and accretion modalities at the present epoch are discussed.

Petrogenetic reconnaissance investigation of mafic sills associated with flood basalts, Mekelle basin, northern Ethiopia: implications for Ni–Cu exploration

Mafic sills of the Mekelle basin were explored on a reconnaissance level for their magmatic sulphide potential. The sills are related to Oligocene flood basalt magmatism in Ethiopia. They intrude Jurassic shales and limestones and crystallized from high-Ti tholeiitic basalt magmas. Three compositional groups were differentiated. Among them GD1 gabbrodolerites (11.6–4% MgO) show evidence of a fractionation controlled magmatic lineage, while GD2 (∼5.2% MgO) and GD3 gabbrodolerites (5.4–3% MgO) show element depletion and enrichment patterns which deviate from the magmatic fractionation trend. Compared to GD1 rocks with MgO values ∼5%, GD2 gabbrodolerites have higher SiO 2 and Na 2O but lower FeO tot, TiO 2, P 2O 5, Nb, Zr, Y, Cu, and Ni values, while GD3 gabbrodolerites show higher SiO 2, Na 2O, P 2O 5, Ba and Sr and lower FeO tot, TiO 2, Nb, Zr, Y, Cu, and Ni values. The distinct geochemical signatures of the latter two gabbrodolerite groups are likely caused by conjunct processes of crustal assimilation and fractional removal of silicate/oxide mineral phases. Depletion of chalcophile elements in the contaminated gabbrodolerites indicates also the segregation of Ni and Cu sulphides. However, settling of sulphide minerals occurred prior to sill emplacement probably in a deeper seated magma chamber. The indication of chalcophile element depleted mafic sills, genetically related to a major flood basalt province clearly warrants further exploration in the area.

Delivery levels and behavior of 1,3-butadiene, acrylonitrile, benzene, and other toxic volatile organic compounds in mainstream tobacco smoke from two brands of commercial cigarettes.

Mainstream tobacco smoke (MTS) was collected from Camel and Marlboro cigarettes for the determination of the delivery levels and equilibrium gas/particle partitioning constants K(p) (m(3) microg(-)(1)) of 26 volatile organic compounds (VOCs) of toxicological interest. K(p) values are important for understanding the fractional distribution of each compound of interest between the gas and the particle phases of MTS. The experimental method involved (i) drawing a smoke sample into a Teflon sampling bag at 20 degrees C, (ii) allowing the smoke particulate matter (PM) to collect on the walls of the bag, (iii) sampling the bag to determine the initial gas phase concentration of each VOC, (iv) removing the gas phase from the bag, (v) refilling the bag with humidified nitrogen gas, (vi) reestablishing the gas/PM equilibrium, and (vii) redetermining the gas phase concentrations. For each smoke sample, a comparison of the initial and redetermined gas phase concentrations allowed calculation of the total (i.e., gas + particle) delivery level (= m(tot), ng cig(-)(1)) and K(p) value (= c(p)/c(g)) at 20 degrees C for each compound, where c(p) (ng microg(-)(1)) = concentration in the PM phase and c(g) (ng m(-)(3)) = concentration in the gas phase. Significant deliveries were observed for a number of carcinogenic VOCs. For the Camel cigarettes tested, the average m(tot) values for 1,3-butadiene, acrylonitrile, and benzene were 10(4.6), 10(4.4), and 10(4.8) ng cig(-)(1), respectively; for Marlboro, the m(tot) values were 10(5.0), 10(4.6), and 10(4.7) ng cig(-)(1), respectively. For each of the 26 VOCs, the smoke PM from the two brands yielded very similar K(p) values at 20 degrees C. In addition, the vapor pressure-dependent K(p) values of the 26 VOCs were in close agreement with predictions made by the Pankow theory of absorptive gas/particle partitioning [Pankow, J. F. (1994) Atmos. Environ. 28, 185-188]. These results can be used in general predictions of chemical behavior in tobacco smoke, including deposition mechanisms and rates in the respiratory tract from inhaled MTS. Example calculations are provided to illustrate how the gas phase fraction at equilibrium (f(g,e)) increases strongly with increasing compound vapor pressure and temperature and with dilution of the inhaled tobacco smoke total PM concentration (microg m(-)(3)).

Interaction enthalpies of solid human serum albumin with water–dioxane mixtures: comparison with water and organic solvent vapor sorption

Enthalpy changes (Δ H tot) on the immersion of dehydrated human serum albumin (HSA) into water–dioxane mixtures have been measured using a Setaram BT-2.15 calorimeter at 298 K. Thermodynamic activity of water was varied from 0 to 1. Calorimetric results are discussed together with the FTIR-spectroscopic data on water and organic solvent vapor adsorption/desorption isotherms on solid HSA. Dioxane sorption exhibits a pronounced hysteresis. Calorimetric and dioxane desorption dependencies consist of two parts. No dioxane sorption was observed in low water activity region ( a w<0.5). At low water activities, the Δ H tot values are close to zero. At water activity about 0.5 the sharp exothermic drop of the interaction enthalpy values was observed. This exothermic drop is accompanied by the sharp increase in the amount of sorbed dioxane and additional water sorption (compared with that for pure water). Dioxane adsorption branch resembles a smooth curve. In this case, solid HSA binds more than 300 mol dioxane/mol HSA at low water activities. By using a water activity-based comparison we distinguished between dioxane-assisted and dioxane-competitive effect on water sorption. The obtained results demonstrate that the hydration “history” of solid protein is an important factor that controls as the state of protein macromolecule as well as the sorption of low-molecular organic molecules.

Serum aminotransferase activity as a predictor of clearance of drugs metabolized by CYP isoforms in rats with acute hepatic failure induced by carbon tetrachloride

The values of serum aminotransferase activity (AST) in untreated rats and rats with acute hepatic failure at 24 h after an oral administration of CCl 4 (0.5 ml/kg) were 85±9 IU/l and 4260±620 IU/l (mean±S.D., n=6), respectively. The values of total clearance (CL tot) after intravenous administration of caffeine, tolbutamide, chlorzoxazone or lidocaine (as probe drugs for various CYP isoforms) to CCl 4-treated rats were decreased to about 1/8, 1/3, 1/3 or 1/2 compared with those in untreated rats. Good correlations were observed between mRNA expression and enzyme activity of CYP2C11, CYP2E1, CYP3A2 and CYP1A2 in livers of rats given various doses of CCl 4. There was also a good negative correlation between serum AST activity and hepatic enzyme activity of each CYP. The serum AST activities corresponding to a 50% decrease of CYP2C 11, CYP2E1, CYP3A2 and CYP1A2 activities were about 710, 780, 1030 and 1300 IU/l, respectively. In conclusion, when the serum AST value in CCl 4-treated rats reached about 4000 IU/l, the hepatic CYP activities were one-tenth or less of the control, although the degree of decrease of the CL tot values varied markedly. Nevertheless, the AST value appears to be a promising candidate for an indicator to predict appropriate dose modification of drugs for patients with acute hepatic failure.

Microbial surface thermodynamics and interactions in aqueous media

Microbial surface thermodynamics and interactions in aqueous media were investigated for seven typical rod-shaped bacterial strains of Enterobacteriaceae, Pseudomonadaceas, and Bacillaceae, which included Echerichia coli HB101, Echerichia coli JM109, Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas aeruginosa, Pseudomonas sp., and Bacillus subtilis. All the microorganisms studied exhibited a monopolar and predominant hydrophilic surface and a negative ΔG 132 tot , total free energy of interactions between microbes (1) and silica gel or Canadian River Alluvium (CRA) (2) immersed in water (3) at the equilibrium distance, which accounted for their attachment on the medium surface. The microbial attachment was proportional to the corresponding ΔG 132 tot values. Among the microorganisms studied, B. subtilis had the most attachment on both silica gel and CRA because it had the smallest ΔG 132 tot values ( −17.14kT for silica gel and −21.84kT for CRA). The origins of Lifshitz–van der Waals, Lewis acid/base, and electrostatic interactions were discussed and related to experimental observations.

Quantitative kinetic analysis of hydrogen transfer reactions from dietary polyphenols to the DPPH radical.

Diphenylpicrylhydrazyl (DPPH) is widely used for quickly assessing the ability of polyphenols to transfer labile H atoms to radicals, a likely mechanism of antioxidant protection. This popular test generally pays no attention to the kinetics of H atom transfer, which however could be even more important than the total H-atom-donating capacities (stoichiometry, EC50) typically evaluated. In the present work, a series of dietary polyphenols belonging to the most representative families (flavonols from onion, flavanol monomers and oligomers from barley, and caffeic acid and caffeoyl esters from artichoke and endive) are characterized not only by their total stoichiometries (n(tot)) but also by their rate constants of first H atom abstraction by DPPH (k(1)), deduced from the kinetic analysis of the decay of the DPPH visible band following addition of the antioxidant. The mildly reactive DPPH radical allows a good discrimation between polyphenols, as demonstrated by the relatively large ranges of k(1) (ca. 400-5000 M(-)(1) s(-)(1)) and n(tot) (ca. 1-5) values typically measured with antioxidants having a single polyphenolic nucleus. With antioxidants displaying more than one polyphenolic nucleus (procyanidin oligomers, dicaffeoyl esters), the kinetic analysis makes it possible to demonstrate significant differences in reactivity between the subunits (two distinct k(1) values whose ratio lies in the range 3-10) and nonadditive stoichiometries.

Keck Absorption‐Line Spectroscopy of Galactic Winds in Ultraluminous Infrared Galaxies

In this paper, we present moderately high resolution (~65 km s-1) spectroscopy, acquired with the Echellette Spectrograph and Imager on Keck II, of 11 ultraluminous infrared galaxies at z < 0.3 from the IRAS 1 Jy sample. The targets were chosen as good candidates to host galaxy-scale outflows, and most have infrared luminosities dominated by star formation. We use a χ2 minimization to fit one- to three-component profiles to the Na I D interstellar absorption doublet in each object. Assuming that gas blueshifted by more than 70 km s-1 relative to the systemic velocity of the host is outflowing, we detect outflows in 73% of these objects. We adopt a simple model of a mass-conserving free wind to infer mass outflow rates in the range tot(H) = 13-133 M☉ yr-1 for galaxies hosting a wind. These values of tot, normalized to the corresponding global star formation rates inferred from infrared luminosities, are in the range η ≡ tot/SFR = 0.1-0.7. This is on average a factor of only 10 less than η from recent measurements of nearby dwarfs, edge-on spirals, and lower luminosity infrared galaxies. Within our sample, we conclude that η has no dependence on the mass of the host (parameterized by host galaxy kinematics and absolute R- and K'-band magnitudes). We also attempt to estimate the average escape fraction fesc ≡ ∑ / ∑ and ejection efficiency δ ≡ ∑ / ∑ SFRi for our sample, which we find to be ~0.4-0.5 and ~0.1, respectively. The complex absorption-line properties of Mrk 231, an ultraluminous infrared galaxy that is optically classified as a Seyfert 1, are discussed separately in an appendix.

On the evaluation of quasi-thermodynamic magnitudes from rate constant values. Influence of the variational and tunnelling contributions

Quasi-thermodynamic magnitudes obtained from three different analytical fits to the experimental rate constants of the CH 4+OH reaction are compared to the values obtained from theoretical rate constants calculated using canonical variational transition state theory plus multidimensional tunnelling contributions. A right decomposition of ΔG tot,0 into its enthalpic and entropic contributions is not experimentally feasible because it depends on the particular analytical expression used for the rate constants. Then, theoretical calculation of the rate constants at all the required temperatures becomes the only way to get reliable values of ΔH tot,0 (and E a) and ΔS tot,0. Our results show that both variational and tunnelling nonsubstantial contributions to the quasi-thermodynamic magnitudes are significant for the CH 4+OH reaction and, probably, for a wide range of gas-phase chemical reactions.

Effect of multiple dosing of ketoconazole on pharmacokinetics of midazolam, a cytochrome P-450 3A substrate in beagle dogs.

To evaluate effects of multiple dosing of ketoconazole (KTZ) on hepatic CYP3A, the pharmacokinetics of intravenous midazolam (MDZ, 0.5 mg/kg) before and during multiple dosing of KTZ were investigated in beagle dogs. KTZ tablets were given orally to dogs (n = 4) for 30 days (200 mg b.i.d.). With coadministration of KTZ, t(1/2beta) of MDZ were significantly increased both on day 1 (2-fold) and on day 30 (3-fold). Total body clearance (CL(tot)) of MDZ declined gradually during the first 5 days after the start of KTZ treatment, and thereafter CL(tot) appeared to reach a plateau phase (one-fourth), depending on plasma KTZ concentrations. The effects of KTZ on the biotransformation of MDZ were also investigated using dog liver microsomes (n = 5). The K(i) values of KTZ for MDZ 1'-hydroxylation and 4-hydroxylation were 0.0237 and 0.111 microM, respectively, indicating that KTZ extensively inhibits hepatic CYP3A activity in dogs. CL(tot) values estimated from in vitro K(i) values corrected by unbound fraction of KTZ and unbound concentrations of the drug in plasma were consistent with in vivo CL(tot) of MDZ. The results in this study suggest that KTZ treatment is necessary until plasma concentrations of the drug reach a steady state to evaluate the effect of multiple dosing of the drug on hepatic CYP3A in vivo. In addition, it is suggested that K(i) values corrected by unbound fraction of KTZ and unbound concentrations of the drug in plasma enable precise in vitro-in vivo scaling.

Geochemical evidence for variations in delivery and deposition of sediment in Pleistocene light–dark color cycles under the Benguela Current Upwelling System

Distinctive light–dark color cycles in sediment beneath the Benguela Current Upwelling System indicate repetitive alternations in sediment delivery and deposition. Geochemical proxies for paleoproductivity and for depositional conditions were employed to investigate the paleoceanographic processes involved in creating these cycles in three mid-Pleistocene intervals from ODP Sites 1082 and 1084. Concentrations of total organic carbon (TOC) vary between 3.5 and 17.1%. Concentrations of CaCO 3 vary inversely to TOC and Al, which suggests that both carbonate dissolution and terrigenous dilution contribute to the light–dark cycles. Opal concentrations are independent of both TOC and CaCO 3, therefore eliminating diatom production and lateral transport of shelf material as causes of the light–dark cycles. δ 13C org and δ 15N tot values do not vary across light–dark sediment intervals, implying that the extent of relative nutrient utilization did not change. The stable δ 15N tot values represent a balanced change in nitrate supply and export production and therefore indicate that productivity was elevated during deposition of the TOC-rich layers. Parallel changes in concentrations of indicator trace elements and TOC imply that changes in organic matter delivery influenced geochemical processes on the seafloor by controlling consumption of pore water oxygen. Cu, Ni, and Zn are enriched in the darker sediment as a consequence of greater organic matter delivery. Redox-sensitive metals vary due to loss (Mn and Ba) or enrichment (Mo) under reducing conditions created by TOC oxidation. Organic matter delivery impacts subsequent geochemical changes such as carbonate dissolution, sulfate reduction and the concentration of metals. Thus, export production is considered ultimately responsible for the generation of the color cycles.

Implicit Solvent Model Studies of the Interactions of the Influenza Hemagglutinin Fusion Peptide with Lipid Bilayers

The “fusion peptide”, a segment of ∼20 residues of the influenza hemagglutinin (HA), is necessary and sufficient for HA-induced membrane fusion. We used mean-field calculations of the free energy of peptide-membrane association (Δ G tot) to deduce the most probable orientation of the fusion peptide in the membrane. The main contributions to Δ G tot are probably from the electrostatic (Δ G el) and nonpolar (Δ G np) components of the solvation free energy; these were calculated using continuum solvent models. The peptide was described in atomic detail and was modeled as an α-helix based on spectroscopic data. The membrane’s hydrocarbon region was described as a structureless slab of nonpolar medium embedded in water. All the helix-membrane configurations, which were lower in Δ G tot than the isolated helix in the aqueous phase, were in the same (wide) basin in configurational space. In each, the helix was horizontally adsorbed at the water-bilayer interface with its principal axis parallel to the membrane plane, its hydrophobic face dissolved in the bilayer, and its polar face in the water. The associated Δ G tot value was ∼−8 to −10 kcal/mol (depending on the rotameric state of one of the phenylalanine residues). In contrast, the Δ G tot values associated with experimentally observed oblique orientations were found to be near zero, suggesting they are marginally stable at best. The theoretical model did not take into account the interactions of the polar headgroups with the peptide and peptide-induced membrane deformation effects. Either or both may overcompensate for the Δ G tot difference between the horizontal and oblique orientations.

Operational correlates of prostanoid TP receptor expression in human non-pregnant myometrium are unaffected by excision site or menstrual cycle status of the donor.

1. Cumulative concentration-effect curves for the selective prostanoid TP receptor agonist, U46619, were constructed in strips of human non-pregnant myometrium grouped according to tissue excision site (top, lateral wall, lower uterine segment, sub-serosal or sub-endometrial), tissue orientation (strips cut either parallel or perpendicular to the serosa) and donor menstrual status (proliferative or secretory phase). 2. U46619 was excitatory in all tissues. There was no significant difference in either pEC50 or maximum response between groups (P<0.05). The range of pEC50 values was 6.8+/-0.1 (lateral wall, proliferative phase, n=5) to 7.1+/-0.3 (lateral wall, secretory phase, n=5). The range of maximum response values was 0.9+/-0.8 N cm-2 (lateral wall, proliferative phase, n=5) to 3.1+/-1.0 N cm-2 (lateral wall, secretory phase, n=5). 3. Saturation binding analyses were conducted using the radiolabelled TP receptor agonist, [125I]-BOP. Binding parameters were estimated for membranes prepared from human non-pregnant myometrium excised from the lateral wall and grouped according to donor menstrual status. 4. There were no significant differences in the mean pKd and [R]tot values for [125I]-BOP binding between the two groups (proliferative phase: pKd=8.3+/-0.3, [R]tot=412+/-319 fmol mg protein-1, n=5; secretory phase: pKd=8.5+/-0.4, [R]tot=369+/-192 fmol mg protein-1, n=6; P<0.05). 5. These data indicate that U46619-mediated responses in human non-pregnant myometrium are not influenced by tissue excision site, tissue orientation or donor menstrual status and that [125I]-BOP binding is not influenced by donor menstrual status. This suggests that the TP receptor population is homogeneous throughout the human non-pregnant myometrium, and not subject to hormonal regulation.

Respiratory mechanics after chronic diethylcarbamazine

This study was performed to evaluate the role of diethylcarbamazine (DEC), the drug of choice for treating Lymphatic Filariasis and Tropical Pulmonary Eosinophilia, on respiratory mechanics of higid rats. Thus, during 30 days two groups of six rats each received intraperitoneally either isotonic saline solution, or 12 mg/kg per day of DEC. Thereafter, they were sedated, anesthetized, paralysed and mechanical ventilation followed. After airway occlusion at end inspiration, respiratory system, pulmonary and chest wall resistive pressures (ΔP 1,rs, ΔP 1,L, and ΔP 1,w, respectively) and viscoelastic/inhomogeneous pressures (ΔP 2,rs, ΔP 2,L and ΔP 2,w, respectively) were determined in each group. Total Δ pressures (ΔPtot) were calculated as the sum of ΔP 1 and ΔP 2, yielding the values of ΔP tot,rs, ΔP tot,L, and ΔP tot,w, respectively. Respiratory system, lung and chest wall static (E st,rs, E st,L, and E st,w, respectively) and dynamic elastances (E dyn,rs, E dyn,L, and E dyn,w, respectively), and the corresponding Δ elastances (calculated as E dyn−E st) were also obtained. DEC therapy significantly decreased ΔP tot,rs, ΔP tot,L, ΔP 2,rs, ΔP 2,L, E st,rs, E st,L, ΔE rs and ΔE L in relation to the respective control values. It can be concluded that DEC decreases respiratory system impedance, being potentially useful for allowing airway dilation at the lung periphery.

Solubility of cinnabar (red HgS) and implications for mercury speciation in sulfidic waters

New experiments have been conducted to determine the speciation of dissolved mercury (Hg) over wide pH (1–12) and sulfide concentration ranges (0.5–30 mM) and in the presence of elemental sulfur (S°) or Hg°, conditions that encompass those of near-bottom and pore waters of sediments. Samples containing synthetic red mercuric sulfide (HgS, cinnabar), buffer solution, aliquots of bisulfide (HS−) solution, and, in special cases, S° or Hg° were prepared anaerobically and allowed to equilibrate for several months. Filtered samples were analyzed for pH, total sulfide (ΣS2−), and total mercury [Hg]tot. Plots of [Hg]tot values vs. pH at varying ΣS2− verified the formation of three previously known mercury-sulfide complexes (HgS2H n n−2 ) and revealed that a new Hg2SOH+ complex is important at low pH and low ΣS2−. Our constants for ionic strength (I) 0.7 and 25° C are as follows: K1=10−5.76(+0.71, −102) for HgScinn + H2S ↔ HgS2H2° K2=10−4.82(+0.72, −1.10) for HgScinn + HS− ↔ HgS2H−; K3 =10−13.41(+O.76, −0.93) for HgScinn + HS−. ↔ HgS 2 2− . + H+; K4=10−8.36(+0.71, −0.93) for 2HgScinn + H+ + H2O ↔ Hg2SOH+ + H2S. With decreasing pH, below 1, Hg solubility decreased sharply, indicating the formation of a new solid phase, inferred to be corderoite (Hg3S2Cl2). From our solubility data, we calculated the free energy of formation (ΔGf°) of Hg3S2Cl2 to be −396 (+3, −11) kJ/mol. In experiments where excess S°(s) was present, a new mercury-polysulfide dimer was identified; its formation constant is K3=10−1.99(+0 69,−1.27) for 2HgScinn + 2HS− + nS° ↔ Hg2SΠ 4S°nH2 −. Data from experiments where Hg°(aq) was added confirmed the reversibility of HgS dissolution. An application of our mercury-sulfide speciation model to a natural anoxic basin, Saanich Inlet, British Columbia, is discussed.