Air-sea transfer of gas phase controlled compounds

Gases in the atmosphere/ocean have solubility that spans several orders of magnitude. Resistance in the molecular sublayer on the waterside limits the air-sea exchange of sparingly soluble gases such as SF6 and CO2. In contrast, both aerodynamic and molecular diffusive resistances on the airside limit the exchange of highly soluble gases (as well as heat). Here we present direct measurements of air-sea methanol and acetone transfer from two open cruises: the Atlantic Meridional Transect in 2012 and the High Wind Gas Exchange Study in 2013. The transfer of the highly soluble methanol is essentially completely airside controlled, while the less soluble acetone is subject to both airside and waterside resistances. Both compounds were measured concurrently using a proton-transfer-reaction mass spectrometer, with their fluxes quantified by the eddy covariance method. Up to a wind speed of 15 m s-1, observed air-sea transfer velocities of these two gases are largely consistent with the expected near linear wind speed dependence. Measured acetone transfer velocity is ~30% lower than that of methanol, which is primarily due to the lower solubility of acetone. From this difference we estimate the "zero bubble" waterside transfer velocity, which agrees fairly well with interfacial gas transfer velocities predicted by the COARE model. At wind speeds above 15 m s-1, the transfer velocities of both compounds are lower than expected in the mean. Air-sea transfer of sensible heat (also airside controlled) also appears to be reduced at wind speeds over 20 m s-1. During these conditions, large waves and abundant whitecaps generate large amounts of sea spray, which is predicted to alter heat transfer and could also affect the air-sea exchange of soluble trace gases. We make an order of magnitude estimate for the impacts of sea spray on air-sea methanol transfer.

iNOS-producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL/6 resistant mice.

Leishmania major parasites reside and multiply in late endosomal compartments of host phagocytic cells. Immune control of Leishmania growth absolutely requires expression of inducible Nitric Oxide Synthase (iNOS/NOS2) and subsequent production of NO. Here, we show that CD11b+ CD11c+ Ly-6C+ MHC-II+ cells are the main iNOS-producing cells in the footpad lesion and in the draining lymph node of Leishmania major-infected C57BL/6 mice. These cells are phenotypically similar to iNOS-producing inflammatory DC (iNOS-DC) observed in the mouse models of Listeria monocytogenes and Brucella melitensis infection. The use of DsRed-expressing parasites demonstrated that these iNOS-producing cells are the major infected population in the lesions and the draining lymph nodes. Analysis of various genetically deficient mouse strains revealed the requirement of CCR2 expression for the recruitment of iNOS-DC in the draining lymph nodes, whereas their activation is strongly dependent on CD40, IL-12, IFN-gamma and MyD88 molecules with a partial contribution of TNF-alpha and TLR9. In contrast, STAT-6 deficiency enhanced iNOS-DC recruitment and activation in susceptible BALB/c mice, demonstrating a key role for IL-4 and IL-13 as negative regulators. Taken together, our results suggest that iNOS-DC represent a major class of Th1-regulated effector cell population and constitute the most frequent infected cell type during chronic Leishmania major infection phase of C57BL/6 resistant mice.

Intrinsic gas-phase electrophilic reactivity of Ccclic N-alkyl- and N-acyliminium ions

he intrinsic gas-phase reactivity of cyclic N-alkyl- and N-acyliminium ions toward addition of allyltrimethylsilane (ATMS) has been compared using MS2 and MS3 pentaquadrupole mass spectrometric experiments. An order of electrophilic reactivity has been derived and found to agree with orders of overall reactivity in solution. The prototype five-membered ring N-alkyliminium ion 1a and its N-CH3 analogue 1b, as well as their six-membered ring analogues 1c and 1d, lack N-acyl activation and they are, accordingly, inert toward ATMS addition. The five- and six-membered ring N-acyliminium ions with N-COCH3 exocycclic groups, 3a and 3b, respectively, are also not very reactive. The N-acyliminium ions 2a and 2c, with s-trans locked endocyclic N-carbonyl groups, are the most reactive followed closely by 3c and 3d with exocyclic (and unlocked) N-CO2CH3 groups. The five-membered ring N-acyliminium ions are more reactive than their six-membered ring analogues, that is:  2a > 2c and 3c > 3d. In contrast with the high reactivity of 2a, its N-CH3 analogue 2b is inert toward ATMS addition. For the first time, the transient intermediates of a Mannich-type condensation reaction were isolatedthe β-silyl cations formed by ATMS addition to N-acyliminium ionsand their intrinsic gas-phase behavior toward dissociation and reaction with a nucleophile investigated. When collisionally activated, the β-silyl cations dissociate preferentially by Grob fragmentation, that is, by retro-addition. With pyridine, they react competitively and to variable extents by proton transfer and by trimethylsilylium ion abstractionthe final and key step postulated for α-amidoalkylation. Becke3LYP/6-311G(d,p) reaction energetics, charge densities on the electrophilic C-2 site, and AM1 LUMO energies have been used to rationalize the order of intrinsic gas-phase electrophilic reactivity of cyclic iminium and N-acyliminium ions.

Grain coarsening in contact metamorphic carbonates: effects of second-phase particles, fluid flow and thermal perturbations

Under contact metamorphic conditions, carbonate rocks in the direct vicinity of the Adamello pluton reflect a temperature-induced grain coarsening. Despite this large-scale trend, a considerable grain size scatter occurs on the outcrop-scale indicating local influence of second-order effects such as thermal perturbations, fluid flow and second-phase particles. Second-phase particles, whose sizes range from nano- to the micron-scale, induce the most pronounced data scatter resulting in grain sizes too small by up to a factor of 10, compared with theoretical grain growth in a pure system. Such values are restricted to relatively impure samples consisting of up to 10 vol.% micron-scale second-phase particles, or to samples containing a large number of nano-scale particles. The obtained data set suggests that the second phases induce a temperature-controlled reduction on calcite grain growth. The mean calcite grain size can therefore be expressed in the form D 1⁄4 C2 eQ*/RT(dp/fp)m*, where C2 is a constant, Q* is an activation energy, T the temperature and m* the exponent of the ratio dp/fp, i.e. of the average size of the second phases divided by their volume fraction. However, more data are needed to obtain reliable values for C2 and Q*. Besides variations in the average grain size, the presence of second-phase particles generates crystal size distribution (CSD) shapes characterized by lognormal distributions, which differ from the Gaussian-type distributions of the pure samples. In contrast, fluid-enhanced grain growth does not change the shape of the CSDs, but due to enhanced transport properties, the average grain sizes increase by a factor of 2 and the variance of the distribution increases. Stable d18O and d13C isotope ratios in fluid-affected zones only deviate slightly from the host rock values, suggesting low fluid/rock ratios. Grain growth modelling indicates that the fluid-induced grain size variations can develop within several ka. As inferred from a combination of thermal and grain growth modelling, dykes with widths of up to 1 m have only a restricted influence on grain size deviations smaller than a factor of 1.1.To summarize, considerable grain size variations of up to one order of magnitude can locally result from second-order effects. Such effects require special attention when comparing experimentally derived grain growth kinetics with field studies.

Deformation mechanisms in second-phase affected microstructures and their energy balance

Based on the relationship Zener parameter (Z=second-phase size/second-phase volume fraction) vs. calcite grain size (dg), second-phase controlled aggregates and microstructures that are weakly affected by second-phases are discriminated. The latter are characterized by large but constant grain sizes, high calcite grain boundary fractions and crystallographic preferred orientations (CPO), while calcite grain size and calcite grain boundary fraction decrease continuously and CPO weakens with decreasing Z in second-phase controlled microstructures. These observations suggest that second-phase controlled microstructures predominantly deform via granular flow because pinning of calcite grain boundaries reduces the efficiency of dynamic recrystallization favoring mass transfer processes and grain boundary sliding. In contrast, the balance of grain size reduction and growth by dynamic recrystallization maintains a steady state grain size in microstructures that are only weakly affected by second-phases promoting a predominance of dislocation creep. With increasing temperature, the relationship between Z and dg persists but the calcite grain size increases continuously. Based on microstructures, the energy of each modifying process is calculated and its relative contribution is compared with energies of the competing processes (surface energy, dragging energy, dynamic recrystallization energy). The steady state microstructures result from a temperature-dependent energy minimization procedure of the system.

Toxicological impact of JWH-018 and its phase I metabolite N-(3-hydroxypentyl) on human cell lines

"The emergence and abuse of synthetic cannabinoids has been increasing as an alternative to cannabis, mainly among youth. As their appearance on the drug market has been recent, the pharmacological and toxicological profiles of these psychoactive substances are poorly understood. Current studies suggest that they have stronger effects compared to their natural alternatives and their metabolites retain affinity towards CB1 receptors in CNS. Since studies on its toxicological properties are scarce, the effects of the drug in human derived cell lines were investigated. The present study was designed to explore the toxicological impact of parent drug versus phase I metabolites of synthetic cannabinoids on human cells with and without CB1 receptor. The human cell line of neuroblastoma SH-SY5Y and human kidney cell line HEK-293T were exposed to JWH-018 and to its N-(3-hydroxypentyl) metabolite. Cell toxicity was evaluated using the MTT and LDH assay. Additionally, a dual staining methodology with fluorescent Annexin V-FITC and propidium iodide was performed to address the question of whether JWH-018 N-(3-hydroxypentyl) metabolite is inducing cell death through apoptosis or necrosis, in HEK293T and SH-SY5Y cell lines. The obtained results show that JWH-018 does not cause a statistically significant decrease in cell viability, in contrast to its N-(3-hydroxypentyl) metabolite, which at ≥25μM causes a significant decrease in cell viability. Both cell lines are affected by JWH-018 metabolite. Our results point to higher toxicity of JWH-018 metabolite when compared to its parent drug, suggesting a non-CB1 receptor mediated toxicological mechanism. Comparing the results from Annexin V/PI with MTT and LDH assays of SH-SY5Y and HEK293T in the presence of the synthetic cannabinoid metabolite, emerges the picture that cellular viability decreases and associated death is occurring through necrosis."

Binocular functional architecture for detection of contrast-modulated gratings

Combination of signals from the two eyes is the gateway to stereo vision. To gain insight into binocular signal processing, we studied binocular summation for luminance-modulated gratings (L or LM) and contrast-modulated gratings (CM). We measured 2AFC detection thresholds for a signal grating (0.75 c/deg, 216msec) shown to one eye, both eyes, or both eyes out-of-phase. For LM and CM, the carrier noise was in both eyes, even when the signal was monocular. Mean binocular thresholds for luminance gratings (L) were 5.4dB better than monocular thresholds - close to perfect linear summation (6dB). For LM and CM the binocular advantage was again 5-6dB, even when the carrier noise was uncorrelated, anti-correlated, or at orthogonal orientations in the two eyes. Binocular combination for CM probably arises from summation of envelope responses, and not from summation of these conflicting carrier patterns. Antiphase signals produced no binocular advantage, but thresholds were about 1-3dB higher than monocular ones. This is not consistent with simple linear summation, which should give complete cancellation and unmeasurably high thresholds. We propose a three-channel model in which noisy monocular responses to the envelope are binocularly combined in a contrast-weighted sum, but also remain separately available to perception via a max operator. Vision selects the largest of the three responses. With in-phase gratings the binocular channel dominates, but antiphase gratings cancel in the binocular channel and the monocular channels mediate detection. The small antiphase disadvantage might be explained by a subtle influence of background responses on binocular and monocular detection.

Contrast and lustre:a model that accounts for eleven different forms of contrast discrimination in binocular vision

Our goal here is a more complete understanding of how information about luminance contrast is encoded and used by the binocular visual system. In two-interval forced-choice experiments we assessed observers' ability to discriminate changes in contrast that could be an increase or decrease of contrast in one or both eyes, or an increase in one eye coupled with a decrease in the other (termed IncDec). The base or pedestal contrasts were either in-phase or out-of-phase in the two eyes. The opposed changes in the IncDec condition did not cancel each other out, implying that along with binocular summation, information is also available from mechanisms that do not sum the two eyes' inputs. These might be monocular mechanisms. With a binocular pedestal, monocular increments of contrast were much easier to see than monocular decrements. These findings suggest that there are separate binocular (B) and monocular (L,R) channels, but only the largest of the three responses, max(L,B,R), is available to perception and decision. Results from contrast discrimination and contrast matching tasks were described very accurately by this model. Stimuli, data, and model responses can all be visualized in a common binocular contrast space, allowing a more direct comparison between models and data. Some results with out-of-phase pedestals were not accounted for by the max model of contrast coding, but were well explained by an extended model in which gratings of opposite polarity create the sensation of lustre. Observers can discriminate changes in lustre alongside changes in contrast.

Predictive Value Of Phase I Trials For Safety In Later Trials And Final Approved Dose: Analysis Of 61 Approved Cancer Drugs.

Phase I trials use a small number of patients to define a maximum tolerated dose (MTD) and the safety of new agents. We compared data from phase I and registration trials to determine whether early trials predicted later safety and final dose. We searched the U.S. Food and Drug Administration (FDA) website for drugs approved in nonpediatric cancers (January 1990-October 2012). The recommended phase II dose (R2PD) and toxicities from phase I were compared with doses and safety in later trials. In 62 of 85 (73%) matched trials, the dose from the later trial was within 20% of the RP2D. In a multivariable analysis, phase I trials of targeted agents were less predictive of the final approved dose (OR, 0.2 for adopting ± 20% of the RP2D for targeted vs. other classes; P = 0.025). Of the 530 clinically relevant toxicities in later trials, 70% (n = 374) were described in phase I. A significant relationship (P = 0.0032) between increasing the number of patients in phase I (up to 60) and the ability to describe future clinically relevant toxicities was observed. Among 28,505 patients in later trials, the death rate that was related to drug was 1.41%. In conclusion, dosing based on phase I trials was associated with a low toxicity-related death rate in later trials. The ability to predict relevant toxicities correlates with the number of patients on the initial phase I trial. The final dose approved was within 20% of the RP2D in 73% of assessed trials.

Assessment Of Robustness On Analysis Using Headspace Solid-phase Microextraction And Comprehensive Two-dimensional Gas Chromatography Through Experimental Designs.

Plackett-Burman experimental design was applied for the robustness assessment of GC×GC-qMS (Comprehensive Two-Dimensional Gas Chromatography with Fast Quadrupolar Mass Spectrometric Detection) in quantitative and qualitative analysis of volatiles compounds from chocolate samples isolated by headspace solid-phase microextraction (HS-SPME). The influence of small changes around the nominal level of six factors deemed as important on peak areas (carrier gas flow rate, modulation period, temperature of ionic source, MS photomultiplier power, injector temperature and interface temperature) and of four factors considered as potentially influential on spectral quality (minimum and maximum limits of the scanned mass ranges, ions source temperature and photomultiplier power). The analytes selected for the study were 2,3,5-trimethylpyrazine, 2-octanone, octanal, 2-pentyl-furan, 2,3,5,6-tetramethylpyrazine, and 2-nonanone e nonanal. The factors pointed out as important on the robustness of the system were photomultiplier power for quantitative analysis and lower limit of mass scanning range for qualitative analysis.

Chemical Immobilization Of Crosslinked Polymeric Ionic Liquids On Nitinol Wires Produces Highly Robust Sorbent Coatings For Solid-phase Microextraction.

Super elastic nitinol (NiTi) wires were exploited as highly robust supports for three distinct crosslinked polymeric ionic liquid (PIL)-based coatings in solid-phase microextraction (SPME). The oxidation of NiTi wires in a boiling (30%w/w) H2O2 solution and subsequent derivatization in vinyltrimethoxysilane (VTMS) allowed for vinyl moieties to be appended to the surface of the support. UV-initiated on-fiber copolymerization of the vinyl-substituted NiTi support with monocationic ionic liquid (IL) monomers and dicationic IL crosslinkers produced a crosslinked PIL-based network that was covalently attached to the NiTi wire. This alteration alleviated receding of the coating from the support, which was observed for an analogous crosslinked PIL applied on unmodified NiTi wires. A series of demanding extraction conditions, including extreme pH, pre-exposure to pure organic solvents, and high temperatures, were applied to investigate the versatility and robustness of the fibers. Acceptable precision of the model analytes was obtained for all fibers under these conditions. Method validation by examining the relative recovery of a homologous group of phthalate esters (PAEs) was performed in drip-brewed coffee (maintained at 60 °C) by direct immersion SPME. Acceptable recoveries were obtained for most PAEs in the part-per-billion level, even in this exceedingly harsh and complex matrix.

Elevated Cetp Activity During Acute Phase Of Myocardial Infarction Is Independently Associated With Endothelial Dysfunction And Adverse Clinical Outcome.

Recent data suggests that cholesteryl ester transfer protein (CETP) activity may interact with acute stress conditions via inflammatory-oxidative response and thrombogenesis. We investigated this assumption in patients with ST-elevation myocardial infarction (STEMI). Consecutive patients with STEMI (n = 116) were enrolled <24-h of symptoms onset and were followed for 180 days. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), tumor necrosis factor (TNFα), 8-isoprostane, nitric oxide (NOx) and CETP activity were measured at enrollment (D1) and at fifth day (D5). Flow-mediated dilation (FMD) was assessed by ultrasound and coronary thrombus burden (CTB) was evaluated by angiography. Neither baseline nor the change of CETP activity from D1 to D5 was associated with CRP, IL-2, TNFα, 8-isoprostane levels or CTB. The rise in NOx from D1 to D5 was inferior [3.5(-1; 10) vs. 5.5(-1; 12); p < 0.001] and FMD was lower [5.9(5.5) vs. 9.6(6.6); p = 0.047] in patients with baseline CETP activity above the median value than in their counterparts. Oxidized HDL was measured by thiobarbituric acid reactive substances (TBARS) in isolated HDL particles and increased from D1 to D5, and remaining elevated at D30. The change in TBARS content in HDL was associated with CETP activity (r = 0.72; p = 0.014) and FMD (r = -0.61; p = 0.046). High CETP activity at admission was associated with the incidence of sudden death and recurrent MI at 30 days (OR 12.8; 95% CI 1.25-132; p = 0.032) and 180 days (OR 3.3; 95% CI 1.03-10.7; p = 0.044). An enhanced CETP activity during acute phase of STEMI is independently associated with endothelial dysfunction and adverse clinical outcome.

Evaluation Of The Location Of Capsules Swallowed With Food During The Pharyngeal Phase Triggering In Asymptomatic Adults.

To assess the location of hard gelatin capsules in the pharyngeal phase triggering among asymptomatic adults. The location of the bolus during the pharyngeal phase triggering provides information about the sensorimotor model of the beginning of deglutition onset. To evaluate the location of hard gelatin capsules in the pharyngeal phase triggering among asymptomatic adults. A videofluoroscopy swallowing study was carried out in 60 subjects (14 male and 46 female participants) aged between 27 and 55 years, who were evaluated with hard gelatin capsules #00 and #3 containing barium sulfate, swallowed with liquid food and pudding, in free volume. The first laryngeal elevation movement was the criterion to locate the pharyngeal phase triggering. Statistical analysis was based on the McNemar test. Capsule #3 presented higher percentage of location in the tongue dorsum compared to capsule #00, and capsule #00 presented higher percentage of location in the tongue base and vallecula compared to capsule #3. There was a difference between different capsules swallowed with liquid (p=0.016) and pudding (p=0.037). The capsule size influenced the location of the pharyngeal phase triggering. Smaller capsules started pharyngeal phase in the most anterior region (tongue dorsum) compared to larger capsules.

Molecularly Imprinted Solid Phase Extraction Of Fluconazole From Pharmaceutical Formulations.

This work encompasses a direct and coherent strategy to synthesise a molecularly imprinted polymer (MIP) capable of extracting fluconazole from its sample. The MIP was successfully prepared from methacrylic acid (functional monomer), ethyleneglycoldimethacrylate (crosslinker) and acetonitrile (porogenic solvent) in the presence of fluconazole as the template molecule through a non-covalent approach. The non-imprinted polymer (NIP) was prepared following the same synthetic scheme, but in the absence of the template. The data obtained from scanning electronic microscopy, infrared spectroscopy, thermogravimetric and nitrogen Brunauer-Emmett-Teller plot helped to elucidate the structural as well as the morphological characteristics of the MIP and NIP. The application of MIP as a sorbent was demonstrated by packing it in solid phase extraction cartridges to extract fluconazole from commercial capsule samples through an offline analytical procedure. The quantification of fluconazole was accomplished through UPLC-MS, which resulted in LOD≤1.63×10(-10) mM. Furthermore, a high percentage recovery of 91±10% (n=9) was obtained. The ability of the MIP for selective recognition of fluconazole was evaluated by comparison with the structural analogues, miconazole, tioconazole and secnidazole, resulting in percentage recoveries of 51, 35 and 32%, respectively.

Modelo para análise do ataque no futebol = : A model to analyze soccer offensive phase

Universidade Estadual de Campinas . Faculdade de Educação Física