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Most studies investigating the influence of H2O2 on cells in culture apply nonphysiological concentrations over nonphysiological time periods (i.e., a one-time bolus that is metabolized in minutes). As an alternative, the glucose oxidase/catalase (GOX/CAT) system allows application of physiologically relevant H2O2 concentrations (300 nM–10 µM) over physiologically relevant time periods (up to 24 h). Recent findings suggest that bolus and GOX/CAT treatments can lead to opposing cellular responses, thus warranting a quantitative comparison between the two approaches. First, we established a reaction–diffusion model that can predict the behavior of the GOX/CAT system with spatiotemporal resolution, thus aiding selection of optimal experimental conditions for its application. Measurements of H2O2 concentration in the cellular supernatant with the luminol/hypochlorite system were consistent with the predictions of the model. Second, we compared the impact of bolus and GOX/CAT treatments on cytosolic H2O2 levels over time. Intracellular H2O2 was monitored by the response of the thiol peroxidase Prx2 and the H2O2 sensor roGFP2-Orp1. We found that Prx2 rapidly and reversibly responds to submicromolar H2O2 levels and accurately reflects kinetic competition with cellular catalase. Our measurements reveal fundamental differences in the dynamic response of cellular H2O2 concentrations following either bolus or GOX/CAT treatments. Thus, different, or even opposing, biological outcomes from differing means of H2O2 delivery may be expected. Cellular responses induced by bolus treatment may not occur under GOX/CAT conditions, and vice versa.

The efficient antimycotic agent aureobasidin A, isolated from the culture broth of Aureobasidium pullulans R 106, and the [(R)-Pro9]-aureobasidin A were prepared starting from benzyl N-Boc-N-methyl-(S)-β-triethylsiloxyvalinate, the synthesis of which is described here. The easy accessibility of the tripeptolide benzyl Boc-leucyl-N-methyl-β-hydroxyvalyl-(2R)-oxy-(3R)-methylpentanoate [Boc-Leu-HOMeVal-(R)-HMP-OBn] facilitates the construction of the cyclopeptolides 28, 34, 45 and 47. The peptide bonds of the N-methylamino acids were formed with the help of O-(7-azabenzotria-zol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophophate. The rings of [(R)-Pro9]-aureobasidin A and of cyclopeptolides 28, 34, 45 and 47 were closed by way of pentafluorophenyl esters. The ring of aureobasidin A could only be formed with bromo-tris-pyrrolidino-phosphonium hexafluorophosphate.

The exchange of carbonyl sulfide (OCS) and CS 2 between the atmosphere and the pedosphere was investigated in a temperate zone spruce forest in the Solling Mountains (51°N), Germany during three field campaigns in 1999. Dynamic (flow-through) chambers were used to measure the OCS and carbon disulfide ( CS 2 ) exchange fluxes between the soil and the atmosphere. All measurements showed a net OCS flux from the atmosphere into the soil. On average ( ± standard error of the mean), the OCS uptake rate of the soil was 0.81 ( ± 0.03 ) pmol m - 2 s - 1 and the total range was between 0.23 and 1.38 pmol m - 2 s - 1 . CS 2 fluxes varied between an uptake of 0.11 pmol m - 2 s - 1 and an emission of 0.23 pmol m - 2 s - 1 . Therefore, CS 2 is emitted by the soil in a nearly balanced mean flux of 0.01 ( ± 0.01 ) pmol m - 2 s - 1 . Slight dependencies of the OCS flux on soil temperature and soil water content were detected. The fluxes varied by about a factor of 2 over a distance of 10 m. A comparison of the OCS fluxes between soil and atmosphere with the fluxes observed simultaneously above the canopies revealed that only 1% of the OCS which was taken up by the whole forest ecosystem is deposited in the soil. The impact of the CS 2 exchange between soil and atmosphere for the whole ecosystem flux of CS 2 was even more negligible.

Recent functional imaging studies have reported evidence of alterations in the serotonergic system induced by 3,4-methylenedioxymethamphetamine (MDMA), or "Ecstasy." However, these studies have often been limited by small sample size, lack of tracer selectivity, unreliable assessment of MDMA doses, insufficiently matched comparison groups, or region-of-interest analysis.Positron emission tomography (PET) using the specific serotonin transporter ligand [(11)C](+)McN5652 was performed in 117 subjects: 30 current MDMA users, 29 former MDMA users, 29 drug-naive comparison subjects, and 29 users of drugs other than MDMA (polydrug comparison subjects). Self-assessment of drug history was checked by analyzing hair samples. Local serotonin transporter availability was computed by a regularized reference tissue approach. Voxel-based comparison of serotonin transporter availability was performed using statistical parametric mapping (SPM 99).Serotonin transporter availability in current MDMA users was significantly reduced in the mesencephalon, thalamus, left caudate, hippocampus, occipital cortex, temporal lobes, and posterior cingulate gyrus compared with all other groups. Reduction was more pronounced in female than in male subjects. There was no significant difference of serotonin transporter availability among former MDMA users and the drug-naive and polydrug comparison subjects. A negative correlation between serotonin transporter availability and mean MDMA dose was found in occipital visual areas and in the left precentral sulcus of current MDMA users. In addition, there was a significant positive correlation between the serotonin transporter availability and the MDMA abstention period in brainstem and in the basal forebrain in all MDMA users.These findings support the hypothesis of MDMA-induced protracted alterations of the serotonergic system and indicate that the reduced availability of serotonin transporter, as measured by PET, might be reversible. Women appear to be more susceptible than men to MDMA-induced alterations of the serotonergic system.

Groups of five male and five female Wistar rats were treated by gavage with 0, 1, 10, and 100 mg/kg body weight (b.w.) flutamide (FLU) or 0.01, 0.05, and 0.2 mg/kg b.w. of ethinylestradiol (EE2) for at least 28 days according to an enhanced Organization for Economic Cooperation and Development (OECD) test guideline (TG) 407 to investigate which of the current and/or additional parameters would detect effects on the endocrine system and to provide data on intralaboratory variability. Two identical studies were performed in parallel on each compound. Common enhancements were determination of thyroid hormones (T3, T4) and thyroid stimulating hormone (TSH), of the stage of the estric cycle to ensure necropsy of females in diestrus, of the number and morphology of epididymal sperm, and of additional organ weights (e.g., male accessory sex organs, MASO) and histopathology of additional organs (e.g., pituitary, vagina). Endocrine-mediated findings consistently observed in these studies were decreased relative weights of MASO at 100 mg/kg FLU and at 0.2 mg/kg EE2, histological changes in pituitary and testes at > or = 10 mg/kg and in MASO, epididymis and adrenals at 100 mg/kg in FLU-treated males, histological changes in the mammary gland at > or = 0.05 mg/kg and in testes, MASO and adrenals at 0.2 mg/kg in EE2-treated males, estrogenization of uterus and vagina (despite necropsy in diestrus) at > or = 0.01 mg/kg EE2, and changes in the ovary at 0.2 mg/kg EE2. Spermatology was insensitive (EE2) or revealed changes only at the maximum tolerated dose (MTD). Determination of T3, T4, and TSH did not contribute to the detection of the endocrine effects (FLU) or provided equivocal results. Doubling the group size to 10 animals by combining the studies run in parallel did not increase the sensitivity of detection of endocrine-mediated effects above the level obtained by histopathological examination of groups of five animals. Only some of the proposed enhancements evaluated were helpful in detecting the endocrine-mediated effects of FLU and EE2. Evaluation of studies according to an enhanced TG 407 on 10 compounds with different endocrine activities will identify the most appropriate enhancements.

Der Cyclooctadien-Komplex [Rh(η4-C8H12)(κ2-tBu2AsCH2PiPr2)](PF6) (1a) reagiert mit CO und CNtBu zu den Substitutionsprodukten [Rh(L)2(κ2-tBu2AsCH2PiPr2)](PF6) (2, 3. Aus 1a und Na(acac) entsteht in Gegenwart von CO die Neutralverbindung [Rh(κ2-acac)(CO)(κ-P-tBu2AsCH2PiPr2)] (4). Durch Umsetzung von 1a, dem entsprechenden B(ArF)4-Salz 1b und [Rh(η4-C8H12)(κ2-iPr2AsCH2PiPr2)](PF6) (5) mit Acetonitril unter H2-Atmosphare erhalt man die Komplexe [Rh(CH3CN)2(κ2-R2AsCH2PiPr2)]X (6a, 6b, 7), von denen 6a (R = tBu; X = PF6) mit Na(acac-f6) zu der Bis(chelat)-Verbindung [Rh(κ2-acac-f6)(κ2-tBu2AsCH2PiPr2)] (8) reagiert. Aus 8 und CH3I bildet sich durch oxidative Addition ein Gemisch zweier Stereoisomere der Zusammensetzung [Rh(CH3)I(κ2-acac-f6)(κ2-tBu2AsCH2-PiPr2)] (9/10), von denen das Racemat 9 kristallographisch charakterisiert wurde. Die Reaktion von 1a und 5 mit CO in Gegenwart von NaCl fuhrt zu den “A-frame”-Komplexen [Rh2(CO)2(μ-Cl)(μ-R2AsCH2PiPr2)2](PF6) (11, 12), deren Strukturen bestimmt wurden. Aus 11 und 12 erhalt man durch Austausch des verbruckenden Chlorids gegen Bromid, Hydrid oder Hydroxid die Substitutionsprodukte [Rh2(CO)2(μ-X)(μ-R2AsCH2PiPr2)2](PF6) (13-16). Wahrend 12 (R = iPr) mit NaI zu dem entsprechenden “A-frame”-Komplex 18 reagiert, entsteht aus 11 (R = tBu) und NaI die einkernige Chelatverbindung [RhI(CO)(κ2-tBu2AsCH2PiPr2)] (20). Deren Reaktion mit CH3I liefert den Acetyl-Komplex [RhI2{C(O)CH3}(κ2-tBu2AsCH2PiPr2)] (21) mit funffach koordiniertem Rhodiumatom. Mono- and Dinuclear Rhodium Complexes with Arsino(phosphino)methanes in Different Coordination Modes The cyclooctadiene complex [Rh(η4-C8H12)(κ2-tBu2AsCH2PiPr2)](PF6) (1a) reacts with CO and CNtBu to give the substitution products [Rh(L)2(κ2-tBu2AsCH2PiPr2)](PF6) (2, 3). From 1a and Na(acac) in the presence of CO the neutral compound [Rh(κ2-acac)(CO)(κ-P-tBu2AsCH2PiPr2)] (4) is formed. The reactions of 1a, the corresponding B(ArF)4-salt 1b and [Rh(η4-C8H12)(κ2-iPr2AsCH2PiPr2)](PF6) (5) with acetonitrile under a H2 atmosphere affords the complexes [Rh(CH3CN)2(κ2-R2AsCH2PiPr2)]X (6a, 6b, 7), of which 6a (R = tBu; X = PF6) gives upon treatment with Na(acac-f6) the bis(chelate) compound [Rh(κ2-acac-f6)(κ2-tBu2AsCH2PiPr2)] (8). From 8 and CH3I a mixture of two stereoisomers of composition [Rh(CH3)I(κ2-acac-f6)(κ2-tBu2AsCH2PiPr2)] (9/10) is generated by oxidative addition, and the molecular structure of the racemate 9 has been determined. The reactions of 1a and 5 with CO in the presence of NaCl leads to the formation of the “A-frame” complexes [Rh2(CO)2(μ-Cl)(μ-R2AsCH2PiPr2)2](PF6) (11, 12), which have been characterized crystallographically. From 11 and 12 the dinuclear substitution products [Rh2(CO)2(μ-X)(μ-R2AsCH2PiPr2)2](PF6) (13-16) are obtained by replacing the bridging chloride for bromide, hydride or hydroxide, respectively. While 12 (R = iPr) reacts with NaI to give the related “A-frame” complex 18, treatment of 11 (R = tBu) with NaI yields the mononuclear chelate compound [RhI(CO)(κ2-tBu2AsCH2PiPr2)] (20). The reaction of 20 with CH3I affords the acetyl complex [RhI2{C(O)CH3}(κ2-tBu2AsCH2PiPr2)] (21) with five-coordinate rhodium atom.

The peralkylated arsino(phosphino)methanes R2AsCH2PiPr2 (R = tBu 2, iPr 3) react with trans-[PdCl2(NCPh)2] 1 to give the chelate compounds [PdCl2(κ2-R2AsCH2PiPr2)] 4, 5 which, via salt metathesis with KBr, KI (or NaI) and CF3CO2Ag, are converted to the dibromo-, diiodo-, and bis(trifluoracetato)-palladium(II) derivatives 6–11, respectively. Whereas from 2, 3 and [{Pd(μ-Cl)(η3-C3H5)}2] 12 the mono-cationic species [Pd(η3-C3H5)(κ2-R2AsCH2PiPr2)]PF613, 14 are obtained, treatment of 4, 5 with AgPF6 in acetonitrile affords the di-cationic complexes [Pd(NCCH3)2(κ2-R2AsCH2PiPr2)](PF6)215, 16. Compound 15 (R = tBu) reacts with Na(acac) to give [Pd(κ2-acac)(κ2-R2AsCH2PiPr2)]PF617. The reaction of 4, 5 with AgPF6 in acetone leads to the formation of the di-nuclear complexes [{Pd(μ-Cl)(κ2-R2AsCH2PiPr2)}2](PF6)218, 19, which in the presence of SbiPr3 or pyridine undergo bridge cleavage to yield the mono-nuclear chelate derivatives [PdCl(L)(κ2-R2AsCH2PiPr2)]PF6, mostly as a mixture of cis/trans isomers. The methylpalladium(II) compound [PdCl(CH3)(κ2-tBu2AsCH2PiPr2)] 25, prepared from [PdCl(CH3)(η4-C8H12)] 24 and 2, reacts with Na[B(ArF)4] to afford the A-frame type complex [Pd2(CH3)2(μ-Cl)(μ-tBu2AsCH2PiPr2)2][B(ArF)4] 27. In contrast, the related precursor [PdCl(CH3)(κ2-iPr2AsCH2PiPr2)], generated in situ from 24 and 3, gives, upon treatment with Na[B(ArF)4], a mixture of two products 28a,b being the corresponding head-to-tail and head-to-head isomers. The mono-nuclear compounds 4 and 13 as well as the A-frame type complex 27 have been characterized by X-ray crystallography.

Turbulent fluxes of carbonyl sulfide (COS) and carbon disulfide (CS2) were measured over a spruce forest in Central Germany using the relaxed eddy accumulation (REA) technique. A REA sampler was developed and validated using simultaneous measurements of CO2 fluxes by REA and by eddy correlation. REA measurements were conducted during six campaigns covering spring, summer, and fall between 1997 and 1999. Both uptake and emission of COS and CS2 by the forest were observed, with deposition occurring mainly during the sunlit period and emission mainly during the dark period. On the average, however, the forest acts as a sink for both gases. The average fluxes for COS and CS2 are -93 ± 11.7 pmol m-2 s-1 and -18 ± 7.6 pmol m-2 s-1, respectively. The fluxes of both gases appear to be correlated to photosynthetically active radiation and to the CO2 and chem{H_2O} fluxes, supporting the idea that the air-vegetation exchange of both gases is controlled by stomata. An uptake ratio COS/CO2 of 10 ± 1.7 pmol m mol-1 has been derived from the regression line for the correlation between the COS and CO2 fluxes. This uptake ratio, if representative for the global terrestrial net primary production, would correspond to a sink of 2.3 ± 0.5 Tg COS yr-1.

Background — In heart failure, sarcoplasmic reticulum (SR) Ca 2+ -ATPase (SERCA2a) activity is decreased, resulting in abnormal calcium handling and contractile dysfunction. We have previously shown that increasing SERCA2a expression by gene transfer improves ventricular function in a rat model of heart failure created by ascending aortic constriction. Methods and Results — In this study, we tested the effects of gene transfer of SERCA2a on survival, left ventricular (LV) volumes, and metabolism. By 26 to 27 weeks after aortic banding, all animals developed heart failure (as documented by >25% decrease in fractional shortening) and were randomized to receive either an adenovirus carrying the SERCA2a gene (Ad.SERCA2a) or control virus (Ad.βgal-GFP) by use of a catheter-based technique. Sham-operated rats, uninfected or infected with either Ad.βgal-GFP or Ad.SERCA2a, served as controls. Four weeks after gene transfer, survival in rats with heart failure treated with Ad.βgal-GFP was 9%, compared with 63% in rats receiving Ad.SERCA2a. LV volumes were significantly increased in heart failure (0.64±0.05 versus 0.35±0.03 mL, P 31 P NMR analysis showed a reduced ratio of phosphocreatine to ATP content in failing+Ad.βgal-GFP compared with sham+Ad.βgal-GFP (0.82±0.13 versus 1.38±0.14, P Conclusions — In this study, we show that unlike inotropic agents that improve contractile function at the expense of increased mortality and worsening metabolism, gene transfer of SERCA2a improves survival and the energy potential in failing hearts.

OBJECTIVESWe sought to evaluate the ability of type 5 phosphodiesterase (PDE5) inhibitors to augment the antithrombotic effects of inhaled nitric oxide (NO) in a canine model of platelet-mediated coronary thrombosis after thrombolysis.BACKGROUNDType 5 phosphodiesterase inhibitors potentiate the ability of NO to inhibit platelet aggregation in vitro by preventing platelet cyclic guanosine monophosphate catabolism. We previously reported that breathing low concentrations of NO gas attenuated, but did not prevent, cyclic flow reductions (CFRs) in a canine model of coronary thrombosis after thrombolysis.METHODSCyclic flow reductions were induced after creation of a left anterior descending coronary artery stenosis, endothelial injury, thrombus formation and thrombolysis. Dogs were either untreated or treated with inhaled NO (20 ppm by volume), intravenous zaprinast, intravenous dipyridamole or the combination of inhaled NO with either PDE5 inhibitor (n = 4 per group).RESULTSCyclic flow reductions ceased, and complete coronary patency was achieved in all dogs after they breathed NO combined with zaprinast (by 12.0 ± 4.7 min [mean ± SEM]) or dipyridamole (by 9.8 ± 4.7 min). The frequency of CFRs was unaffected by NO, dipyridamole or zaprinast alone. Systemic arterial blood pressure and bleeding time were unchanged with any treatment. Ex vivo thrombin-induced platelet aggregation in dogs breathing NO and receiving dipyridamole was reduced by 75 ± 7% (p < 0.05).CONCLUSIONSThe PDE5 inhibitors potentiated the antithrombotic properties of inhaled NO in a canine model of platelet-mediated coronary artery thrombosis after thrombolysis, without prolonging the bleeding time or causing systemic hypotension.

SUMMARY We analyse balloon-borne measurements of ozone (03) and nitrous oxide (N20) in the Arctic, obtained during the European Arctic Stratospheric Ozone Experiment campaign in winter and early spring 1991192. Using N20 as a long-lived tracer, we identify chemical ozone depletion in the Arctic vortex in the presence of ozone variations caused by dynamical effects. Substantial chemical ozone loss of about 25% locally over the height range of IS-21 km, corresponding to the potential-temperature range of 400-550 K, is deduced for late winter. Mixing processes can be ruled out as the major cause of the observed anomaly in the O3-N2O relation by considering the concurrently measured chloroflurocarbon- 1 I-N2 0 relation. The chemical ozone loss derived from the balloon-borne measurements is in agreement with the loss derived, following the same methodology, from satellite (Halogen Occultation Experiment) vortex observations. Consistent with the dynamical development of the polar vortex and with the observed chlorine activation, the major fraction of the ozone decline occurred before February 1992. The reduced ozone levels persisted over the lifetime of the polar vortex until late March

During two balloon flights in the Arctic winter in February 1994 two distinctly different vertical profiles of ClO were measured. On 1 February enhanced values of ClO were observed between about 420 and 620 K inside the polar vortex in an air mass that had experienced moderately cold temperatures about 10 h prior to our measurements. In contrast, on 9 February an unstructured vertical profile was observed outside of the vortex with lower mixing ratios of ClO. Based on calculations with a photochemical box trajectory model we show that the observed enhancement in ClO can be explained by heterogeneous processing of chlorine reservoir species on supercooled liquid aerosols. When NAT formation is forced in the model or when lee wave processing is assumed, the mixing ratios of ClO inside the vortex are overpredicted. Under conditions where air masses are only cooled to low temperatures for a short period of time this may be a very important chlorine activation mechanism.

Under the extremely cold conditions in the polar winter stratosphere, heterogeneous reactions involving HCl and CIONO(sub 2) on the surfaces of polar stratospheric cloud particles can release large amounts of reactive chlorine from these reservoirs leading to rapid chemical loss of ozone in the Arctic lower stratosphere during late winter and early spring.

The highly cytostatic didemnins contain a 23-membered cyclopeptolide with a side chain attached to the backbone through the amine group of threonine. Thirty-six derivatives varying the side chain were prepared, but only compounds with D-MeLeu attached to threonine show remarkable biological activities. To protect the macrocycle from degradation by lipases the two ester bonds were replaced successively by amide bonds. Although these variations have a major effect on the conformation and rigidity of the ring, the compound which contains exclusively amide bonds is highly active, equivalent to acetyl-didemnin A.

Objective To assess the effect of a combined antithrombin III and C1-esterase inhibitor treatment on intravascular organ fibrin deposition and cardiorespiratory changes following intravenous Escherichia coli endotoxin (lipopolysaccharide [LPS] 80 [micro sign]g/kg iv) exposure. Design Prospective, randomized trial. Setting Research laboratory of a university medical center. Subjects Anesthetized, instrumented and mechanically ventilated rabbits ([Chbb:CH); n = 40). Interventions Endotoxin was given to 30 animals. Ten animals received no inhibitor (endotoxin control group). The other animals were either treated by high-dose (300 units/kg; n = 10) or low-dose (100 units/kg; n = 10) combined antithrombin III and C1-esterase inhibitor administration. Ten rabbits (time control group) were given placebo (sodium chloride 0.9%). Cardiorespiratory variables were assessed at baseline, 120 mins, and 240 mins after endotoxin or placebo administration. Four hours after endotoxin injection, liver, lung, and kidney tissue samples were examined for intravascular fibrin deposition by light microscopy. Measurements and Main Results Inhibitor treatment significantly decreased clot formation in lungs and livers without, however, demonstrating a clear dose-dependent effect. Combined antithrombin III/C1-esterase treatment attenuated the decrease of mean arterial pressure and cardiac output observed following endotoxin injection. Blood pressure improvement was significantly dependent on dosage administered. Conclusion Combination of antithrombin III and C1-esterase inhibitor treatment during early endotoxin shock decreased organ fibrin deposition and improved cardiovascular stability. (Crit Care Med 1999; 27:597-604)

Symmetrical and unsymmetrical bis(phosphino)methanes R2PCH2PR′2 (8–16) as well as the arsino(phosphino) analogues R′2AsCH2PR2 (21–25) with bulky alkyl, cycloalkyl or aryl groups R and R′ were prepared from the stannylated phosphines R2PCH2SnR″3 (3–5, 6, 7) via metalation with MeLi or PhLi in the presence of tetramethylethylenediamine and subsequent treatment with R′2PCl or R′2AsCl, respectively. Compound 25 [R′ = Cy, R = (R)-menthyl] is the first arsino(phosphino)methane which has been structurally characterized. The bis(phosphino)methanes R2PCH2PR2 (R = Pri 17, Cy 18) and R2PCH2PR′2 (12, 19, 20) were also obtained by thermal reaction of R2PCH2SnPh3 and the corresponding chlorophosphine R2PCl or R′2PCl in the absence of solvent. The bis(cyclooctene) derivative [RhCl(C8H14)2]2 26 reacted with excess Pri2PCH2PPri2 to give [Rh(κ2P,P′-Pri2PCH2PPri2)2]Cl 27, while treatment of 26 with Ph2PCH2PPri2 yielded the chloro-bridged dimer [RhCl(κ2P,P′-Ph2PCH2PPri2)]2 28. The reaction of the cationic species [Rh(C8H14)2(OCMe2)2]PF6 29 with Cy2PCH2PPri2 in benzene or toluene afforded the half-sandwich-type complexes [(η6-C6H6)Rh(κ2P,P′-Cy2PCH2PPri2)]PF6 30, [(η6-C6H5CH3)Rh(κ2P,P′-Cy2PCH2PPri2)]PF6 31, of which the latter was characterized by X-ray crystallography.

A new lightweight in situ instrument designed to measure ClO was flown on a balloon launched into the arctic vortex at dawn on February 3, 1995 at Kiruna, Sweden during the Second European Stratospheric Arctic and Mid-latitude Experiment (SESAME), together with instruments to measure ozone and long-lived tracers. Observations on ascent and descent at different solar zenith angles are compared to results from Lagrangian and box model calculations that assume the airmasses at similar potential temperatures had comparable photochemical histories. Between 20 and 22 km, in a region where ClO was significantly enhanced, a model constrained by currently recommended rate parameters significantly underestimates the abundances of ClO that were observed on ascent at high solar zenith angles, whereas the agreement is much better if a smaller ClO-Cl2O2 equilibrium constant, one inferred from previous ER-2 aircraft observations of ClO in the Arctic during nighttime, is assumed. On ascent, ClO is additionally enhanced in a narrow region between 20 and 21 km. We believe the most plausible explanation for this feature is rapid photolysis of OClO produced by the slow bimolecular reaction ClO + ClO over the 48 hours prior to the observations when the airmass was warmed to 225 K by adiabatic compression while in polar darkness. These results suggest that under special circumstances, OClO can be produced by a reaction other than one involving BrO, and, hence, OClO is not necessarily a universal proxy for BrO abundances in the perturbed polar vortex.

The long term temporal trend of CCl2F2 (CFC-12) in the lower stratosphere has been derived from a series of balloon-borne observations of long-lived trace gases made since 1978. In order to remove the effect of dynamical processes in the individual profile observations, nitrous oxide (N2O) is used as a vertical coordinate. The calculated trend in the lowermost stratosphere follows the observed tropospheric increase very closely, however, the observed mixing ratios in the lowermost stratosphere appear to lag the global mean tropospheric trend by about one year. The most recent observations indicate that the slowing down of the tropospheric increase has propagated into the lowermost stratosphere. While CFC-12 increased at an average rate of 18.5±1.8 ppt per year between 1978 and 1990, the growth rate decreased to 11.9±4.2 ppt per year between 1990 and 1997.

Vertical profiles of H2O and CH4 were measured using in situ techniques in the Arctic winter stratosphere during the European Arctic Stratospheric Ozone Experiment (EASOE) 1991/1992 in the pressure range between 12 and 80 hPa. The measurements were grouped according to the meteorological situation, i.e., their position relative to the polar vortex. The mixing ratio of the quantity 2·CH4 + H2O was determined in the altitude region between the hygropause and 30 km to be quasi constant at a mean mixing ratio of 6.91 ± 0.41 ppmv. No significant difference of 2·CH4 + H2O was observed inside and outside the vortex. From the correlation between CH4 and H2O ΔH2O/ΔCH4, i.e., the water vapor yield of the methane oxidation, was calculated to be −1.82 ± 0.21. The globally averaged H2O mixing ratio of air entering the stratosphere was found to be 3.61 ± 0.28 ppmv. The data are compared with studies on the total hydrogen budget over the past 20 years. Despite the variety of instrumental techniques used in these studies, an increase of total hydrogen is apparent over this period.

Purpose: Plasma coenzyme Q10 (CoQ10) levels are lower in patients with septic shock (SS) than in healthy controls (HCs). However, CoQ10 status in critically ill patients without SS is unknown. Here, we investigated CoQ10 concentrations in patients with SS and without SS as compared with HCs. Materials and Methods: We enrolled 36 critically ill patients and 18 HCs. Plasma CoQ10 concentrations were measured, and patients' clinical and demographical data were collected. Results: Plasma CoQ10 concentrations were lower in critically ill patients (0.50 ± 0.36 μg/mL, P < .001), both in patients with SS (0.37 ± 0.25 μg/mL, P = .002) and patients without SS (0.56 ± 0.39, P = .04), as compared with HCs (0.79 ± 0.19). Coenzyme Q10 levels did not differ between patients with SS and patients without SS (P = .13). In critically ill patients, CoQ10 levels inversely correlated with age (r = -0.40, P = .015) and did not correlate with partial pressure of oxygen in the arterial blood/fraction of inspired oxygen, Simplified Acute Physiology Score II, Systemic Organ Failure Assessment score, or mortality. Lower CoQ10 levels were associated with lower activities of daily living score after discharge (P = .005), independent of age. Conclusions: Decreased plasma CoQ10 levels are not specific to patients with SS, but rather observed in a broad range of critically ill patients. In critically ill patients, CoQ10 insufficiency may be associated with various conditions; age may be a risk factor. © 2013 Elsevier Inc.

The purpose of this study is to investigate Coenzyme Q10 (Q10) levels in critically ill patients as compared to healthy volunteers. Q10 is an essential cofactor for the electron transport chain reactions necessary for the aerobic cellular respiration. Q10 insufficiency, therefore, leads to mitochondrial dysfunction. It also acts as an antioxidant. Oxidative state is prominent in critically ill patients, favoring the production of oxygen-free radicals. A recent study showed reduced Q10 levels in septic shock patients [1].

We present an analysis of chlorine chemistry in the Arctic stratosphere during the winter of 1991/92 and assess its potential implications for ozone depletion. In accordance with observations of total organic chlorine, ClONO2 and HCl, box model results indicate the following: (1) An almost complete activation of chlorine during the cold winter period. (2) A possible contribution from the heterogeneous reaction HOCl + HCl and the gas-phase reaction CH3O2 + ClO to the complete conversion of HCl to active chlorine. (3) A strong buildup of ClONO2 following PSC disappearance which remains the main chlorine reservoir for about a month, after which HCl becomes dominant. (4) Appreciable chemical ozone loss in the lower stratosphere inside the polar vortex is conceivable for the winter of 1991/92.

Eponemycin, an antibiotic with a highly potent and specific antitumor activity against B16 melanoma cells in vivo, has been synthesized. The framework of the western half of the molecule was built up from N-trityl-δ,γ-didehydroleucinal and the dilithium derivative LiO-CH 2 -C(Li)=CH 2 . In the final step, a vinyl ketone was oxidized nonstereoselectively to give a mixture of three isomers from which eponemycin was isolated in 40% yield

Transmembrane proteins frequently form (transient) oligomers on biomembranes, e.g., while participating in protein sorting and signaling events. Using coarse-grained membrane simulations we show here that transmembrane proteins show a subdiffusive motion on short time scales when being part of a linear oligomer, i.e., a flexible polymer, embedded in a two-dimensional membrane. Our results are in agreement with previous experimental observations. They further indicate that polymers of transmembrane proteins are well described by predictions from Rouse theory in two dimensions even in the presence of hydrodynamic interactions.

Appropriately protected di- and tripeptides containing (R,S)-tetrahydropyridazine-3-carboxylic acids were synthesized via protected γ-formyl-α-hydrazinobutyric acids. The latter compounds are obtained from acetals of either ethyl γ-formylbutyrate or ethyl γ-formyl-α-oxobutyrate

Enantiomerically pure pyrrolidine-2,4-diones (tetramic acids) which can be diastereoselectively hydrogenated to syn-statines (4-amino-3-hydroxy-6-methylheptanoic acids) have been prepared by catalytic hydrogenation of 4-(benzyloxycarbonylamino)-3-oxocarboxylic acid esters

Enantiomerically pure (2S,3R)- and (2S,3S)-2,3-diaminobutyric acids with Fmoc protected α-amino groups and compatibly protected β-amino groups [(2S,3R)- and (2S,3S)-3-(tert-butoxycarbonylamino)-2-(fluoren-9-ylmethoxycarbonylamino)butyric acid] can be prepared in decagram amounts starting from L-threonine and L-allothreonine via the corresponding hydrazides by the Mitsunobu reaction

A mixture of trifluoroacetylthiopyridine, the sodium salt of 1-hydroxybenzotriazole, and an acylamino acid is able to acylate amino acid esters in high yields with minimal racemization and should, therefore, be useful for fragment condensation reactions in the liquid phase.

At the ultracold neutron (UCN) source of the TRIGA research reactor in Mainz, we have measured for the first time the material optical wall-potential of cubic boron nitride. The measurements were performed with a time-of-flight (TOF) spectrometer. The samples investigated had a wall-potential of ( 305 ± 15 ) neV . This value is in good agreement with the result extracted from neutron reflectometry data and theoretical expectations. Because of its high critical velocity for UCN and its good dielectric characteristics, cubic boron nitride coatings (isotopically enriched) will be useful for a number of applications in UCN experiments.

The rearrangement of (E)-didehydroamino acid derivatives to the corresponding Z-derivatives under acid or basic catalysis as well as under the influence of radicals has been investigated. The condensation of N-benzyloxycarbonyl or N-tert-butoxycarbonyl protected alkyl 2-amino-2-(dimethoxyphosphoryl)acetates with aldehydes or ketones in dichloromethane in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene furnishes (Z)-didehydroamino acid ester derivatives diastereoselectively in excellent yields and with high purity

Lipopeptides, carrying the N-terminal lipoamino acid 2-(palmitoylamino)-6,7-bis(palmitoyloxy) heptanoic acid (Pam3Adh-OH, 1), were obtained by solid-phase synthesis and by synthesis in solution. 2-Amino-6,7-dihydroxyheptanoic acid (Adh) can be regarded as a methylene analogue of S-glycerylcysteine, the N-terminal amino acid of lipoprotein from the outer cell membrane of Escherichia coli (a methylene group substitutes for the sulfur atom). The lipopeptides Pam3Adh-Ser-Ser-Asn-Ala 2a-d, in which the four possible stereoisomers of Pam3Adh-OH (2S,6S)-1 (1a), (2S,6R)-1 (1b), (2R,6S)-1 (1c), and (2R,6R)-1 (1d) are linked to the naturally occurring sequence Ser-Ser-Asn-Ala of the N-terminus of lipoprotein, and also Pam3Adh-Ser-(Lys)4 [2S,6S)-3), with a peptide part rendering the molecule water soluble, were capable of stimulating murine splenocytes polyclonally in vitro, as determined in a proliferation assay and in a hemolytic plaque assay against trinitrophenylated sheep erythrocytes. The diastereomers (2S,6S)-2 and (2R,6S)-2 with S-configurated C-6 were more active than the diastereomers (2S,6R)-2 and (2R,6R)-2 with R-configurated C-6; a change of the configuration at C-2 had less effect on the stimulatory activity. (2S,6S)-2 and (2S,6S)-3 are potent immunoadjuvants. A significantly enhanced primary immune response against trinitrophenylated sheep erythrocytes was obtained in vitro at lipopeptide concentrations of about 5 micrograms/mL and an immunization dose of 10(7) sheep erythrocytes/mL. Balb/c mice, which were immunized with a mixture of ovalbumin and (2S,6S)-2 or (2S,6S)-3, respectively, had a substantially higher antiovalbumin titer 28 days after immunization than mice which had received ovalbumin, (2S,6S)-2 or (2S,6S)-3 alone. Finally, the novel lipopeptides constitute potent macrophage activators: (2S,6S)-3 was able to induce tumor cytotoxicity against the tumor cell line L929 in bone marrow derived macrophages.

A total synthesis of didemnins A, B, and C(1−3) which enables these highly cytotoxic cyclopeptides to be prepared in decigram amounts is described. The β-keto acid unit (hydroxyisovaleryl)propionic acid derivative (Hip, 6) was prepared by acylation of dibenzyl methylmalonate and subsequent cleavage of the benzyl groups by the action of boron trichloride. The free β-keto acid 6 was activated by the DCC method and allowed to react with the leucine ester 7 to furnish the amide 8. Activation, deprotectionn, and ring closure of the linear peptide 19 by means of the means of the pentafluorophenyl ester method in a two-phase system gave rise to the didemnin ring skeleton in 75% yield within a few minutes

Suitable protected derivatives of trihydroxynorleucines-[(2S,4S,5S')- and (2R,4S,5S')-2-amino-4,5,6-trihydroxyhexanoic acid,] of all isomeric dihydroxynorvalines [2-amino-4,5-dihydroxypentanoic acids), of all isomeric 2-amino-6,7-dihydroxyheptanoic acids and of (2S)-2-amino-6-hydroxymethyl-7-hydroxyheptanoic acid are synthesized via the corresponding α,β-didehydro compounds, which are hydrogenated with the optically active homogeneous catalyst [Rh(COD)(DIPAMP)] + BF − 4

Chemical ozone loss in winter 1991–1992 is recalculated based on observations of the HALOE satellite instrument, Version 19, ER-2 aircraft measurements and balloon data. HALOE satellite observations are shown to be reliable in the lower stratosphere below 400 K, at altitudes where the measurements are most likely disturbed by the enhanced sulfate aerosol loading, as a result of the Mt.~Pinatubo eruption in June 1991. Significant chemical ozone loss (13–17 DU) is observed below 380 K from Kiruna balloon observations and HALOE satellite data between December 1991 and March 1992. For the two winters after the Mt. Pinatubo eruption, HALOE satellite observations show a stronger extent of chemical ozone loss towards lower altitudes compared to other Arctic winters between 1991 and 2003. In spite of already occurring deactivation of chlorine in March 1992, MIPAS-B and LPMA balloon observations indicate that chlorine was still activated at lower altitudes, consistent with observed chemical ozone loss occurring between February and March and April. Large chemical ozone loss of more than 70 DU in the Arctic winter 1991–1992 as calculated in earlier studies is corroborated here.

Human platelet soluble guanylate cyclase activity was studied with respect to the function of its heme-containing regulatory subunit. As an enzyme source, the 10,000 x g supernatant was used and, since its specific activity proved to be too low for inhibition studies, also a partially purified preparation was employed. The partially purified enzyme was stimulated about 2.5-fold by carbon monoxide and this effect was abolished by illumination with visible light. Sodium nitroprusside also increased the basal activity about fourfold, which, however, is much less than the greater than 100-fold stimulation seen with the supernatant. Superoxide anions generated by the xanthine/xanthine-oxidase system were strongly inhibitory in the enriched preparation as well as in the CO-stimulated platelet supernatant (median effector concentration = 0.1 mU/ml). Unlike CO and NO, the effect of superoxide cannot be mediated through the heme-containing regulatory subunit, since heme-free enzyme, which could not be activated by NO or CO, was inhibited to the same extent as the heme-containing enzyme. Superoxide dismutase did not influence the basal activity, but resulted in a synergistic stimulation in the presence of CO. When Mn2+ replaced Mg2+ as a cofactor, the basal activity was higher but superoxide could not inhibit the enzyme, possibly due to the superoxide-dismutase-like activity of Mn2+. Superoxide turned out to be a potent and reversible inhibitor of soluble guanylate cyclase which, together with endothelium-derived relaxing factor, recently identified as NO, could form a physiologically relevant regulatory effector system.

Two aircraft instruments for the measurement of total odd nitrogen (NOy) were compared side by side aboard a Learjet A35 in April 2003 during a campaign of the AFO2000 project SPURT (Spurengastransport in der Tropopausenregion). The instruments albeit employing the same measurement principle (gold converter and chemiluminescence) had different inlet configurations. The ECO-Physics instrument operated by ETH-Zürich in SPURT had the gold converter mounted outside the aircraft, whereas the instrument operated by FZ-Jülich in the European project MOZAIC III (Measurements of ozone, water vapour, carbon monoxide and nitrogen oxides aboard Airbus A340 in-service aircraft) employed a Rosemount probe with 80 cm of FEP-tubing connecting the inlet to the gold converter. The NOy concentrations during the flight ranged between 0.3 and 3 ppb. The two data sets were compared in a blind fashion and each team followed its normal operating procedures. On average, the measurements agreed within 6%, i.e. within the combined uncertainty of the two instruments. This puts an upper limit on potential losses of HNO3 in the Rosemount inlet of the MOZAIC instrument. Larger transient deviations were observed during periods after calibrations and when the aircraft entered the stratosphere. The time lag of the MOZAIC instrument observed in these instances is in accordance with the time constant of the MOZAIC inlet line determined in the laboratory for HNO3.

The long-term changes of the stratospheric mixing ratio of CH4 over the period of 1978-2003 are derived from balloon-borne data of H-2, CH4 and N2O. The data were obtained by collecting whole air samples and subsequent gas chromatographic analyses. To eliminate the short-term variability attributed to dynamical processes, the N2O mixing ratio is used as a proxy for altitude. A correlation analysis for the individual years is applied and the CH4 mixing ratios are interpolated to four different levels of N2O, corresponding to altitudes of approximately 17, 23, 26 and 30 km at midlatitudes. For the investigated period of 1978 to 2003 we find increases at the four levels of 207 +/- 32 ppb, 159 +/- 21 ppb, 140 +/- 34 ppb and 111 +/- 60 ppb, respectively. The CH4 trend has slowed down in recent years and is best fitted by a second-order polynomial. The increase of CH4 can account for only 25-34% of the increase in stratospheric H2O of 1%/yr over the last decades as derived from previous studies. The simultaneously measured time series of stratospheric H-2 mixing ratios shows that the contribution of stratospheric H-2 to the H2O trend in the period 1988-2003 is minor.

Balloon-borne measurements of CFC11 (from the DIRAC in situ gas chromatograph and the DESCARTES grab sampler), ClO and O3 were made during the 1999/2000 Arctic winter as part of the SOLVE-THESEO 2000 campaign, based in Kiruna (Sweden). Here we present the CFC11 data from nine flights and compare them first with data from other instruments which flew during the campaign and then with the vertical distributions calculated by the SLIMCAT 3D CTM. We calculate ozone loss inside the Arctic vortex between late January and early March using the relation between CFC11 and O3 measured on the flights. The peak ozone loss (~1200ppbv) occurs in the 440-470K region in early March in reasonable agreement with other published empirical estimates. There is also a good agreement between ozone losses derived from three balloon tracer data sets used here. The magnitude and vertical distribution of the loss derived from the measurements is in good agreement with the loss calculated from SLIMCAT over Kiruna for the same days.

Toll-like receptor-4 (TLR4) and its signaling molecule interleukin-1 receptor-associated kinase (IRAK-1) play an important role in host defense and tissue inflammation. Intriguingly, systemic administration of lipopolysaccharide (LPS), the agonist for TLR4, confers a cardio-protective effect against ischemic injury. However, the mechanisms leading to the cardiac protection remain largely unknown. The present study was designed to investigate the role of TLR4 activation by LPS in protecting cardiomyocytes (CM) against apoptosis in an in vitro model of ischemia and to explore the downstream mechanisms leading to the protective effect. Incubation with LPS led to activation of IRAK-1 and protected CMs against serum deprivation (SD)-induced apoptosis as demonstrated by DNA laddering, histone-DNA fragment enzyme-linked immunosorbent assay, and activation of caspase-3. Phosphatidylinositol 3-kinase/Akt, extracellular signal-regulated kinase 1/2, and IkappaB kinase beta appear to contribute to the anti-apoptotic effect of LPS since the specific inhibitors, wortmannin, PD98059, and dominant negative IKKbeta transgene expression reversed the LPS effect. To assess whether LPS improves CM function, we examined intracellular Ca(2+) transients and cell shortening in single adult rat CMs. SD for 6 h dramatically inhibited Ca(2+) transients and CM contractility. LPS at 500 ng/ml significantly improved the [Ca(2+)](i) transients and enhanced contractility in control CMs as well as in CMs subjected to SD. Importantly, transient ischemia led to rapid activation of IRAK-1 in cultured CMs and in adult rat myocardium. Adenovirus-mediated transgene expression of IRAK-1 but not its kinase-deficient mutant IRAK-1(K239S) protected CMs against SD-induced apoptosis. Taken together, these data suggest an important role of TLR4 signaling via IRAK-1 in protecting against SD-induced apoptosis.

International audience; Balloon-borne measurements of CFC-11 (on flights of the DIRAC in situ gas chromatograph and the DESCARTES grab sampler), ClO and O3 were made during the 1999/2000 winter as part of the SOLVE-THESEO 2000 campaign. Here we present the CFC-11 data from nine flights and compare them first with data from other instruments which flew during the campaign and then with the vertical distributions calculated by the SLIMCAT 3-D CTM. We calculate ozone loss inside the Arctic vortex between late January and early March using the relation between CFC-11 and O3 measured on the flights, the peak ozone loss (1200 ppbv) occurs in the 440–470 K region in early March in reasonable agreement with other published empirical estimates. There is also a good agreement between ozone losses derived from three independent balloon tracer data sets used here. The magnitude and vertical distribution of the loss derived from the measurements is in good agreement with the loss calculated from SLIMCAT over Kiruna for the same days.

[1] Vertical profiles of nitrous oxide and methane at high latitudes (57–72°N; 64–89°S) were observed by the Improved Limb Atmospheric Spectrometer (ILAS) solar occultation sensor aboard Advanced Earth Observing Satellite. These measurements were made continuously from November 1996 through June 1997 with some additional periods in September–October 1996. A validation study of the nitrous oxide and methane data processed with the Version 5.20 ILAS retrieval algorithm is presented in this paper. Comparisons are made with (1) nitrous oxide and methane obtained by the ILAS validation balloon campaigns at Kiruna, Sweden, and at Fairbanks, Alaska, in the Arctic; (2) nitrous oxide and methane by the Photochemistry of Ozone Loss in the Arctic Region in Summer aircraft campaign in the Arctic; (3) nitrous oxide by the ground-based spectroscopic measurements and by the aircraft-based remote sensing measurements in the Arctic; and (4) methane by satellite measurements of the Version 19 Halogen Occultation Experiment in the Arctic and Antarctic. Comparisons of ILAS nitrous oxide and methane with Upper Atmosphere Research Satellite Reference Atmosphere data are also made. The results of the comparisons and additional ILAS internal consistency analyses are as follows: (1) the uncertainty of ILAS nitrous oxide is better than 10% over 10–30 km in altitude, and is larger than 50% over 30–40 km, which is comparable to the expected total errors of the ILAS measurements; (2) the uncertainty of ILAS methane is better than 10% over 10–50 km, except for 15–30 km in winter with positive biases exceeding 20%, which is smaller than or comparable to the expected total errors of the ILAS measurements (the quality of ILAS methane in the polar lower stratosphere is better in summer than in winter). In summary, the characteristics of ILAS measurements, i.e., high sampling frequency in polar latitudes with high vertical resolution, along with the good quality of ILAS Version 5.20 nitrous oxide for 10–40 km and the good quality of ILAS Version 5.20 methane for 10–50 km except for 15–30 km in winter, make the ILAS nitrous oxide and methane data set valuable for scientific study of various polar stratospheric phenomena.

Single-molecule counting using STORM/PALMDuring the last decade, several super-resolution microscopy techniques have been developed that enable the circumvention or even the breaking of Abbe's diffraction limit. One approach of achieving super-resolution is to control the emission state of individual fluorophores in time and the concomitant ability to localize active emitters with up to nanometer accuracy. Two of the most commonly implemented super-resolution techniques are stochastic optical reconstruction microscopy (STORM) and photo-activated localization microscopy (PALM). Each technique uses the localization of individual emitters to improve resolution as has been demonstrated with numerous intracellular structures. Beyond that, these techniques open the possibility of counting on a single molecule level. However, the ability to count is fundamentally limited by the fluorophores used for these techniques which blink many times before photobleaching. A typical STORM dye like Cy5 can cycle between tens and hundreds of times between a dark and a fluorescent state before photobleaching, thus leading to a set of localizations scattered around the true position. Whereas this property does not affect the reconstruction of images of extended objects like intracellular filaments or compartments, it severely influences the interpretation and quantification of objects for which the exact stoichiometry can be important like for membrane protein aggregates. To resolve this issue, we have implemented an algorithm that uses the spatial and temporal information of fluorophore localizations from STORM/PALM experiments to obtain a quantitative picture of the underlying molecule distribution. Our algorithm reliably operates on artificial data as well as on experimental data from biological constructs with a well-defined number of attached fluorophores.

[1] We present balloon-borne observations of CO2 and SF6 and derived vertical profiles of mean age for polar winter (inside vortex) and for midlatitude (nonwinter) conditions. For SF6-derived mean ages above 5 years a mesospheric SF6 sink may lead to an overestimation of mean age, while for younger mean ages (below 2 years) the seasonal cycle of CO2 may influence the mean age determination based on CO2. We suggest that SF6 be used as an age tracer in the lower part of the stratosphere (i.e., for low mean age), whereas CO2 will be the better age tracer for older air. The mean age distributions together with an estimate of the width of the age spectrum are used to estimate the stratospheric chlorine loading. On the basis of an emission scenario and the lifetimes of chlorine-containing compounds we estimate the future stratospheric chlorine loading. Inside the polar vortex, at an altitude of 20 km, we expect total chlorine to return to the values present in this region in 1980, when the ozone hole first appeared, around the year 2060. This estimate is based on the assumption that the general transport characteristics will not change over the period of the analysis and can thus be regarded as a best estimate based on stationary transport, the assumed set of lifetimes and emissions, and the mean age distribution derived from our measurements. As other factors influencing ozone may undergo temporal changes, this does not mean that ozone will necessarily recover at this time. While total chlorine is probably a good proxy for inorganic chlorine at altitudes above 20 km inside the polar vortex, the changing halocarbon mix may actually lead to an earlier return of inorganic chlorine to pre-ozone-hole values at lower altitudes.

The configuration of the diastereoisomers of 6-(4-methylthiophenyl)-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline 1 (McN-5652) is determined and unequivocally assigned by NMR spectroscopy (NOE measurements) and an X-ray structural analysis of the trans diastereoisomer. The enantiomers of cis-1 are separated by preparative HPLC on a chiral phase. One of the enantiomers of cis-1 represents the precursor for imaging the serotonin 5-HT transporter with positron emission tomography (PET).

Messungen des Carbonylsulfid-(COS)-Gehaltes im Oberflächenwasser und in angrenzender Luftschicht des Meeres wurden auf zwei Fahrten mit dem Forschungsschiff RV Polarstern zwischen Bremerhaven, Deutschland und Kapstadt, Südafrika im Herbst 1997 und im Sommer 1998 vorgenommen. Sowohl die COS-Konzentrationen als auch das Sättigungsverhältnis zeigen einen deutlichen Tagesgang, jahreszeitliche Variation und Abhängigkeit von der geografischen Breite. Im Mittel betrugen die Konzentrationen des gelösten COS 14.7 pmol/L im Herbst und 18.1 pmol/L im Sommer. An den meisten Tagen war das Seewasser mit COS während der Nacht bis in die frühen Morgenstunden untersättigt und während der übrigen Tageszeit übersättigt, sodaß der Ozean im Tagesverlauf sowohl als Quelle als auch als Senke des COS wirken kann. Der COS Gehalt im Seewasser korrelierte signifikant mit der Globalstrahlung, der CH3SH-Konzentration und der Seewassertemperatur. Die Abschätzung des COS-Flusses vom Meer in die Atmosphäre mit Hilfe von Austauschkoeffizienten, die aus dem stabilitätsabhängigen Modell von Erickson für den Meer-Luft-Gasaustausch berechnet wurden, ergaben, daß der größte COS Fluß in die Atmosphäre in den Gebieten mit COS-Produktion (Benguela-Strom, Westafrikanisches Aufquellgebiet und Nordöstlicher Atlantik) während der wärmeren Jahreszeiten auftrat. Eine geringe Nettoaufnahme von COS durch den Ozean wurde im Bereich des Benguela-Stroms während des Winters auf der Südhalbkugel gefunden. Die durchschnittliche COS-Flußdichte des offenen Ozeans betrug jeweils 13.5 nmol COS/(m^2 d) und 28.6 nmol COS/(m^2 d) auf den beiden Fahrten. Aus den gemessenen Daten kann eine Quellstärke des offenen Ozeans von 0.10 Tg COS/Jahr extrapoliert werden. Das durchschnittliche atmosphärische Mischungsverhältnis betrug 474+/-33 pptv während der Herbstfahrt und 502+/-38 pptv während der Sommerfahrt und wies keinen signifikanten interhemisphärischen Gradienten auf.

1,2-Ethanediylbis[(o-methoxyphenyl)phenylphosphine] the ligand of the enantioselective catalyst [Rh(1,5-COD)(DIPAMP)] + BF 4 - is prepared from (1S)-bornyl (R) p -methyl(phenyl)phosphinate, which is diastereoselectively formed

The structures reported for the three cancerostatic all-l-cyclotetrapeptides cyclo(Pro-Leu)2, cyclo(Pro-Val)2 and cyclo(Pro-Phe)2 isolated from a tunicate seem questionable. The synthetic compounds claimed to be identical to the naturally occurring cyclotetrapeptides are in fact not cyclotetrapeptides but rather cyclooctapeptides. We have not been able to prepare the tyrosinase inhibitor cyclo(Pro-Val-Pro-Tyr). Ring closure of H-Pro-Val-Pro-Tyr-OC6F5 gave rise to 31% of cyclo(Pro-Val-Pro-d-Tyr). The same product was obtained in 53% yield from H-Pro-Val-Pro-d-Tyr-oc6F5. For the ring closure to the all-l-cyclopentapeptide cyclo(Pro-Ala-Ala-Phe-Leu), all ring closure positions have been investigated. The reaction at the nitrogen atom of leucine leads to 21% of the all-l-cyclopentapeptide. Dimers or mixtures of monomers and dimers result from reaction at all other positions. © Munksgaard 1997.

Endotoxin infusion (lipopolysaccharide from Escherichia coli 120 μg kg–1 i.v.) was titrated to produce hypercoagulability in rabbits and the effects of prostacyclin (PGI2) treatment (continuous infusion of 6 ng kg–1 min–1 i.v.) on coagulation variables, cardiorespiratory variables, and fibrin deposition in the microcirculation of vital organs were studied. PGI2 infusion did not influence the concentration of soluble fibrin, throm-belastographic variables, or systemic platelet aggregability. Fibrin deposition in the microcirculation of the liver and the lungs was reduced to 50% of that observed in untreated animals (p < 0.01). The antiplatelet properties of PGI2 were unable to reduce experimental endotoxin-induced systemic procoagulant turnover but improved organ perfusion during the initial phase of disseminated intravascular coagulation.