Free Precursor Research Articles

The 5- exo- trig radical cyclization reaction under reductive and oxidative conditions in the synthesis of optically pure GABA derivatives

Free radical precursors 4a and 4b were synthesized and treated under reductive or oxidative conditions to obtain the corresponding optically pure pyrrolidinones 5– 8 , which were subsequently transformed into corresponding optically pure GABA derivatives 9– 11 . When reductive radical conditions ( 4a → 7 and 8 ) were used, a Ph 1–5 migration product 14 was obtained; presumably depending upon the specific conformation of the rotamer precursor and also 14 was found to be a kinetic product.

Chemistry of a novel family of tridentate alkoxy tin(II) clusters.

The chemical interconversions observed for a novel family of trihydroxymethyl ethane (THME-H(3)) ligated Sn(II) compounds have been determined using single-crystal X-ray and (119)Sn NMR experiments. (mu-THME)(2)Sn(3) (1) was isolated from the reaction of 3 equiv of [Sn(NR(2))(2)](2) (R = SiMe(3)) with 4 equiv of THME as a unique trinuclear species capped above and below the plane of Sn atoms by two THME ligands. Upon reaction with "Sn(NR(2))(2)", compound 1 rearranged to yield another novel molecule [(mu-THME)Sn(2)(NR(2))](2) (2). Compound 2 could also be formed directly from the stoichiometric mixture of THME-H(3) and [Sn(NR(2))(2)](2). Further studies revealed that 1 would also rearrange in the presence of Sn(OR)(2) to form [(mu-THME)Sn(2)(mu-OR)](2) [OR = OMe (3), OCH(2)Me (4), OCH(2)CH(Me)CH(2)CH(3) (5), OCH(2)CMe(3) (6, ONep), OC(6)H(5) (7, not structurally characterized), OC(6)H(4)Me-3 (8), OC(6)H(4)Me-2 (9), OC(6)H(3)(Me)(2)-2,6 (10), OC(6)H(3)(CHMe(2))(2)-2,6 (11). Additionally, 3-11 could by synthesized from the reaction of 2 and the appropriate H-OR. (119)Sn solution NMR studies of 2-11, in THF-d(8), indicate that an equilibrium between the parent complex and its disassociation products (1 and the free parent Sn alkoxy or amide precursor) exists at room temperature. This is a likely reason behind the ease of interconversion observed for 1. The generality of this exchange was further verified through the reaction of 1 with [Ti(mu-ONep)(ONep)(3)](2), which led to the isolation of (mu-ONep)(2)Sn(3)(mu-THME)(2)Ti(ONep)(2) (12). For 12, the solid-state structure was maintained in solution with no indication of an equilibrium.

Comparative study of structure-properties relationship for novel beta-halogenated lanthanide porphyrins and their nickel and free bases precursors, as a function of number and nature of halogens atoms.

The synthetic route of partially beta-halogenated via a "metal-assisted" reaction and perhalogenated terbium complexes is described. This protocol allows the facile insertion of the halogens (bromines or chlorides) to the porphyrin peripheral positions. The electronic absorption spectra and the redox potentials of the free porphyrins as well as the terbium complexes are dramatically affected as the number of halogen atoms increase. In fact, two antagonistic effects are responsible for that, the inductive and the distortion effects on the porphyrin ring. They result in a red shift for the Soret band and a stabilization/destabilization of the HOMOs/LUMOs which in turn is manifested by variations on the redox potentials. The novel crystal structure of the Ni(Cl(8)TPP) is discussed in great detail and compared with the previously reported structures of Tb(Cl(8)TPP) (OAc)(DMSO)(2) x 3PhCH(3) x MeOH and H(2)(Br(8)TPP), as well as with other perhalogenated nickel porphyrins available in the literature.

Tl 2Ba 2CaCu 2O 8 thin film high frequency filters on 3 inch sapphire substrates

Modern communication systems require densely packed frequency channels in the expensive frequency bands. Therefore high temperature superconducting (HTS) high frequency filters are of increasing importance, taking advantage of their outstanding properties namely steep filter skirts, low insertion loss, and furthermore reduced mass and volume compared to conventional cavity or dielectric resonator systems. Within the framework of a German BMBF pilot project a HTS equiped satellite repeater will be developed to demonstrate the performance advantage of HTS. For that purpose we prepare filters on double-sided Tl 2Ba 2CaCu 2O 8 thin films on CeO 2 buffered 3 inch sapphire substrates. The HTS films are prepared in the two-step process by sputtering an amorphous thallium free precursor and following oxythallination. The critical temperature and spatial distribution of critical current density at 77 K, both measured by inductive techniques, show values above 100 K or 1 MA/cm 2, respectively. We use a dielectric resonator technique at 3.9 GHz and power levels up to some mT to determine the films surface resistance. We present measurements of input filters made from our double-sided 3 inch films.

Managing Cutaneous Manifestations of Hyperandrogenic Disorders

Cutaneous manifestations of hyperandrogenic disorders (acne, seborrhea, hirsutism and androgenetic alopecia) can be caused by elevated levels of free testosterone or androgen precursors. In women with normal serum levels of testosterone or androgen precursors, enhanced local conversion to testosterone, or to the more potent androgen dihydrotestosterone, may lead to increased androgen activity in the pilosebaceous unit. Large individual variations in the response to normal or elevated androgens suggests considerable differences in local androgen metabolism and androgen receptor-mediated activities, which may partly be related to genetic disposition. Androgens cause opposite effects on hair follicles in the scalp compared with the face and body, and there are large differences in the length of anagen phase. Androgens enhance sebum production and keratinization, prolong the growth phase of face and body hair, stimulate the transformation of vellus to terminal hair, and shorten the anagen phase of scalp hair. Estrogens may antagonize the androgen-induced actions on sebaceous glands and hair follicles. Treatment with oral contraceptives (OCs) reduces the production of androgens and androgen precursors and increases sex hormone-binding globulin, resulting in a decrease of free testosterone levels. According to type and dose, the estrogen and progestogen components of OCs may directly reduce the effect of androgens within sebaceous glands and hair follicles. Therefore, OCs with a predominant estrogen effect may improve mild to moderate forms of acne and seborrhea, hirsutism and androgenetic alopecia, in a time-dependent manner. In women who do not respond satisfactorily, treatment with OCs containing a progestogen with antiandrogenic activity is recommended. In many women with severe acne or hirsutism, a considerable increase in the local concentration of the antiandrogenic progestogen is required to reduce the androgenic interaction with the androgen receptor. For this therapy, an OC containing cyproterone acetate can be used. If necessary, the dose of cyproterone acetate can be increased in a stepwise manner. While androgenetic alopecia is best treated with a low-dose OC containing cyproterone acetate (optimal effect occurs after at least 12 months of therapy), severe acne and hirsutism are significantly improved after 6-12 months of regimens containing high doses of cyproterone acetate (25-100 mg/day). After termination of treatment the disorders may reappear, therefore treatment with suitable low-dose formulations is recommended to maintain the therapeutic effect.

Thermal Chemical Vapor Deposition of Silicon Carbide Films as Protective Coatings for Microfluidic Structures

ABSTRACTAmorphous silicon carbide (SiC) films were deposited on silicon substrates by thermal chemical vapor deposition (TCVD) technique, at substrate temperatures ranging from 620 °C - 850 °C. A novel, single-source halide free precursor, SP-4000, belonging to the family of polysilenemethylenes (PSM) (nominal structure [-SiH2-CH2-]n, n = 2–8 including branched and cyclic isomers) was used as source. Argon was used, as both the precursor carrier gas and the dilution gas. Other reactants, such as hydrogen or hydrocarbons, were not used. The deposition yielded films with Si/C ratio of 1±0.2. The highest achieved growth rate was 83 nm/min.The modulus of elasticity and the nanohardness of the SiC films were measured with the aid of a nanoindenter at various depths, which did not exceed 25% of the film thickness. The average nanohardness at indentation depths of approximately 10% of the film thickness was measured up to 13 ± 4 GPa. The results of the nanoindentation will be discussed in conjunction with the microstructural analysis of the films.In addition, the development of a viable TCVD SiC process presents significant opportunities in the nano/micro systems field. In particular, the ability to custom tailor the surfaces of microfluidic structures allows for the development of valves, pumps and channels for use in corrosive or high temperature environments. Initial results from the deposition of SiC films on prototype microfluidic components will be presented.

Redox imbalance and immune functions: opposite effects of oxidized low-density lipoproteins and N-acetylcysteine.

This study investigates the in vitro effects of oxidized low-density lipoproteins (ox-LDL), 'physiological' pro-oxidants, N-acetylcysteine (NAC), a free radical scavenger and glutathione precursor, and their combination on human peripheral blood mononuclear cell functions. We found that treatment with ox-LDL induced a significant down-regulation of proliferative response to mitogens, antigens and interleukin-2. Lipid extracts from ox-LDL were able to reproduce the same effect as the lipoprotein. On the other hand, NAC exposure induced a significant up-regulation of proliferative responses to all the stimuli used. Moreover, we showed that natural killer (NK) cell-mediated cytotoxic activity was significantly down-regulated by ox-LDL while treatment with NAC induced a significant up-regulation of NK-cell activity. Finally, we found that ox-LDL and NAC exerted opposite effects on the cytokine network, interfering both at the protein secretion level and the messenger RNA synthesis level. More importantly, when NAC was used in combination with ox-LDL the proliferative responses, NK-cell-mediated cytotoxic activity and cytokine production were restored to values comparable to controls. These data indicate that ox-LDL and NAC modulate immune functions, exerting opposite effects reflecting their pro-oxidant and antioxidant behaviours. Our results add new insights to the key role played by redox imbalance as a modulator of immune system homeostasis and suggest that an antioxidant drug such as NAC could be useful against pathologies associated with an increase in lipid peroxidation.

Kinetics and mechanisms of dolomite dissolution in neutral to alkaline solutions revisited

Steady-state dissolution rates of dolomite were measured at 25°C in a mixed-flow reactor as a function of pH (from 5–12), ionic strength (0.002 < I < 0.1 M), total dissolved carbonate (10⁻⁵ < ∑CO₂ < 0.1 M), calcium (10⁻⁶ −0.003 M), magnesium (3 · 10⁻⁷ −0.005 M), and inorganic (sulfate) and organic (acetate, ascorbate, formiate, tartrate, oxalate, citrate, and EDTA) ligands concentration. Dissolution rates were found to be pH-independent at 6 ≤ pH ≤ 8 and to decrease with increasing pH at pH > 8 and ∑CO₂ > 10⁻³ M. In the alkaline pH region, carbonate and bicarbonate ions significantly inhibit dissolution rates at far from equilibrium conditions. Dissolved Ca was found to be a strong inhibitor of dolomite dissolution at pH above 7, whereas dissolved Mg has no effect on the dissolution rate. The surface complexation model developed by Pokrovsky, Schott, and Thomas (1999b) was used to correlate dolomite dissolution kinetics with its surface speciation. At the conditions of this study (5 < pH ≤ 12), dissolution is controlled by the hydration of Mg surface sites and formation of >MgOH₂⁺ species. This Ca and CO₃-free surface precursor complex allows us to account for the inhibiting effect of aqueous calcium and carbonate ions on dolomite dissolution. Based on these results and those of Pokrovsky, Schott, and Thomas (1999b), the following rate equation, consistent with transition state theory, was used to describe dolomite dissolution kinetics over the full range of solution composition: \[\mathrm{R}{=}{[}\mathrm{k}_{\mathrm{CO}3}{\cdot}{\{}{>}\mathrm{CO}_{3}\mathrm{H}{^\circ}{\}}^{2.0}{+}\mathrm{k}_{\mathrm{Mg}}{\cdot}{\{}{>}\mathrm{MgOH}_{2}^{{+}}{\}}^{1.9}{]}{\cdot}(1{-}\mathrm{exp}({-}1.9\mathrm{A}/\mathrm{RT}))\] or, alternatively, at pH above 6 and I = 0.1 M, \[\mathrm{R}{=}\mathrm{k}_{\mathrm{Mg}}{\ast}{\cdot}{\{}\frac{\mathrm{K}_{\mathrm{CO}3}{\ast}{\cdot}\mathrm{K}_{\mathrm{Ca}}{\ast}}{\mathrm{K}_{\mathrm{CO}3}{\ast}{\cdot}\mathrm{K}_{\mathrm{Ca}}{\ast}{+}\mathrm{K}_{\mathrm{Ca}}{\ast}{\cdot}\mathrm{a}_{\mathrm{CO}_{3}^{2{-}}}{+}\mathrm{a}_{\mathrm{CO}_{3}^{2{-}}}{\cdot}\mathrm{a}_{\mathrm{Ca}^{2{+}}}}{\}}^{1.9}{\cdot}{[}1{-}(\frac{\mathrm{Q}}{\mathrm{K}_{\mathrm{sp}}^{0}})^{1.9}{]}\] where {>i} stands for surface species concentration (mol/m²), A refers to the chemical affinity of the overall reaction, k_CO₃, k_Mg, k_Mg*, K_CO₃*, K_Ca* are constants, and (Q/K_sp⁰) stands for dolomite saturation index. This equation reflects the formation of two different precursor complexes that contain two protonated >CO₃H° and two hydrated >MgOH₂⁺ groups in acid and in neutral and alkaline solutions, respectively. Crystallization of dolomite was found to occur in highly supersaturated solutions as confirmed by outlet solutions analysis and SEM observation of reacted grains. Very low dolomite crystallization rates (that is, ∼10⁻¹⁶ mol/cm²/s) are consistent with those observed in natural conditions and predicted by the empirical model of Arvidson and Mackenzie (1997). Dolomite dissolution rate is promoted by the addition of inorganic and organic ligands with the following effectiveness: sulfate ≈ formiate ≈ tartrate < acetate < ascorbate ≤ oxalate < citrate ≪ EDTA. The effect of these ligands can be modeled within the framework of the surface coordination theory.

Two glycoforms are present in the GPI-membrane anchor of the surface antigen 1 (P30) of Toxoplasma gondii

SAG1 (P30) is the major surface protein of the Toxoplasma gondii tachyzoite, the life cycle stage associated with the acute phase of infection. The protein is inserted into the parasite's plasma membrane by a glycosyl-phosphatidylinositol anchor, a modification that is present on all T. gondii surface proteins characterized so far. Here we describe a detailed structural analysis of this anchor. GPI anchor peptides were isolated from [ 3H]glucosamine labeled purified P30 by protease digestion and phase partitioning. Neutral glycans were prepared from this material by dephosphorylation and deamination. Two glycoforms were characterized by gel filtration and high performance ion exchange chromatography in combination with exoglycosidase treatment. Both forms were shown to carry an N-acetylgalactosamine bound to the first mannose of the conserved three-mannosyl core. Glycan B carries an additional terminal hexose linked to GalNAc. To identify the nature of this hexose, bulk anchor peptide was prepared and glycans were purified by aminopropyl-HPLC. Highly purified glycans were subjected to MALDI-TOF-MS and, after derivatization, to FAB-MS and methylation linkage analysis. The structures of the two anchors found on SAG1 were determined to be: Man-α1,2-Man-α1,6-Man-[GalNAc-β1,4-]-α1,4-GlcN-PI and Man-α1,2-Man-α1,6-Man [Glc-α1,4-GalNAc-β1,4-]-α1,4-GlcN-PI. Comparison of these structures with free GPI glycolipid precursors characterized in T. gondii suggests that core modification of the anchor takes place prior to transfer to the protein.

Of flux and flooding: the advantages and problems of different isotopic methods for quantifying protein turnover in vivo : II. Methods based on the incorporation of a tracer.

The most common methods for measuring the incorporation of tracer amino acids into tissue protein are the constant tracer infusion and the flooding dose. The flooding dose is an attractive method for measuring tissue protein synthesis because of its convenience and precision. A primary assumption of the method, that the free amino acid precursor pools are equilibrated with the true precursor pool, aminoacyl-transfer RNA, has recently been validated. When short labelling periods are involved, the large dose of amino acid does not appear to alter protein synthesis. The constant tracer infusion is a satisfactory method from a theoretical point of view, but its use requires the measurement of the protein synthetic precursor pool. The best estimate of the aminoacyl-tRNA precursor pool for the constant infusion method appears to be the acid-soluble tissue pool in muscle and VLDL apolipoprotein B-100 in the liver. The experimental approach chosen for measuring tissue protein synthesis should be dictated by the question being addressed.

In vivo effect of pancreatic phospholipase A2 on the arachidonic acid cascade.

In acute pancreatitis, pancreatic phospholipase A2 increases in systemic circulation. Yet the pathophysiological significance is controversial, because previous in vitro studies have shown that the enzyme has little cytotoxicity or ability to activate the arachidonic acid cascade by itself in contrast to other isozymes. The aims of this study are to examine the effect of pancreatic phospholipase A2 on the arachidonic acid cascade in vivo; to explain the discrepancy, if present, between in vitro and in vivo findings; and to reassess the pathophysiological significance of circulating pancreatic phospholipase A2. Pancreatic phospholipase A2 was infused intravenously in guinea pigs, and changes in the arachidonic acid cascade, plasma lipoprotein, and cardiopulmonary function were investigated. Plasma concentrations of 6-keto-prostaglandin F1alpha, prostaglandin E2, and thromboxane B2 increased after intravenous (iv) infusion of pancreatic phospholipase A2. Some of the plasma phospholipids such as phosphatidylcholine and phosphatidylethanolamine decreased, and free dihomo-gamma-linolenic acid, arachidonic acid, and eicosapentaenoic acid were detected in plasma. These changes were accompanied with decreases in blood pressure, heart rate, and base excess. Circulating pancreatic phospholipase A2 activates the arachidonic acid cascade, probably by supplying free eicosanoid precursors from plasma lipoprotein to eicosanoid-producing cells. It is supposed to be a cause of systemic complications in acute pancreatitis.

TRNA Recognition of tRNA-guanine Transglycosylase from a Hyperthermophilic Archaeon, Pyrococcus horikoshii

In the biosynthesis of archaeosine, archaeal tRNA-guanine transglycosylase (TGT) catalyzes the replacement of guanine at position 15 in the D loop of most tRNAs by a free precursor base. We examined the tRNA recognition of TGT from a hyperthermophilic archaeon, Pyrococcus horikoshii. Mutational studies using variant tRNA(Val) transcripts revealed that both guanine and its location (position 15) were strictly recognized by TGT without any other sequence-specific requirements. It appeared that neither the global L-shaped structure of a tRNA nor the local conformation of the D loop contributed to recognition by TGT. A minihelix composed of the acceptor stem and D arm of tRNA(Val), designed as a potential minimal substrate, failed to serve as a substrate for TGT. Only a minihelix with mismatched nucleotides at the junction between the two domains served as a good substrate, suggesting that mismatched nucleotides in the helix provide the specific information that allows TGT to recognize the guanine in the D loop. Our findings indicate that the tRNA recognition requirements of P. horikoshii TGT are sufficiently limited and specific to allow the enzyme to recognize efficiently any tRNA species whose structure is not fully stabilized in an extremely high temperature environment.

Dissemination of Peroxidative Stress via Intermembrane Transfer of Lipid Hydroperoxides: Model Studies with Cholesterol Hydroperoxides

Lipid hydroperoxides (LOOHs) can be generated in cells when cholesterol (Ch) and other unsaturated lipids in cell membranes are degraded under conditions of oxidative stress. If LOOHs escape reductive detoxification by glutathione-dependent selenoperoxidases, they may undergo iron-catalyzed one-electron reduction to free radical species, thus triggering peroxidative chain reactions which exacerbate oxidative membrane damage. LOOHs are more polar than parent lipids and much longer-lived than free radical precursors or products. Accordingly, intermembrane transfer of LOOHs (analogous to that of unoxidized precursors) might be possible, and this could jeopardize acceptor membranes. We have investigated this possibility, using photoperoxidized [14C]Ch-labeled erythrocyte ghosts as cholesterol hydroperoxide (ChOOH) donors and unilamellar liposomes [e.g., dimyristoyl-phosphatidylcholine/Ch, 9:1 mol/mol] as acceptors. ChOOH material consisted mainly of 5α-hydroperoxide, a singlet oxygen adduct. Time-dependent transfer of ChOOH versus Ch at 37°C was determined, using high-performance liquid and thin-layer chromatographic methods to analyze liposomal extracts for these species. A typical experiment in which the starting ChOOH/Ch mol ratio in ghosts was ∼0.05 showed that the initial transfer rate of ChOOH was ∼16 times greater than that of parent Ch. Using [14C]Ch as a reporter in liposome acceptors, we found that transfer-acquired ChOOHs, when exposed to a lipophilic iron chelate and ascorbate, could trigger strong peroxidative chain reactions, as detected by accumulation of [14C]Ch oxidation products. These findings support the hypothesis that intermembrane transfer of ChOOHs can contribute to their prooxidant membrane damaging and cytotoxic potential.

The formation of the trace gases NO and N2O in soils by the coupled processes of nitrification and denitrification: results of kinetic 15N tracer investigations

Biogenic production in soils, especially when fertilized with high levels of nitrogen, is one of the main sources of nitrous oxide (N2O) and may be a significant source of nitric oxide (NO). NO and N2O are formed by the microbial processes of nitrification and denitrification but in soils these processes are not fully understood in detail. The kinetic 15N isotope method, is very useful for investigating the mechanism of such complex N transformation processes in soils. We used this method with 15NH4+, 15NO2−, and 15NO3− as tracers to study the processes of NO and N2O formation in black earth soil (Haplic Phaeozem). The experiments were conducted using a special analytical set-up in which the incubation vessels were directly connected to a gas chromatograph quadrupole mass spectrometer system. This system allows simultaneous determination of the concentration of N2O, NO and N2 along with their 15N abundance in the gas phase. The results of these investigations are discussed and combined in a diagram, termed the model of coupled nitrification and denitrification, illustrating the formation of NO and N2O. Nitrification and denitrification proceed under both water-unsaturated (nearly aerobic) and water-saturated (nearly anaerobic) conditions. The two processes are linked by a “common” nitrate pool. In contrast the nitrite, an important intermediate of the two processes, evidently exists within two separate pools. NO is mainly produced by nitrification as a by-product of the oxidation of ammonium to nitrite or directly by nitrite decomposition. If NH4+ contents are high under aerobic conditions NO emission can markedly exceed that of N2O. Nitrous oxide is mainly formed by denitrification of nitrate. Therefore increasing water saturation promotes N2O emission. NO could not be confirmed as a free precursor of N2O formation via denitrification.

Active site determination of Gpi8p, a caspase-related enzyme required for glycosylphosphatidylinositol anchor addition to proteins.

Glycosylphosphatidylinositol (GPI) anchors are attached to newly synthesized proteins in the ER by a transamidation reaction during which a C-terminal GPI attachment signal is replaced by a preformed GPI precursor lipid. This reaction depends on GAA1 and GPI8, the latter belonging to a novel cysteine protease family. Homologies between this family and other Cys proteinases, such as caspases, pointed to Cys199 and His157 as potential active site residues. Indeed, gpi8 alleles mutated at Cys199 or His157 are nonfunctional, i.e., they are unable to suppress the lethality of Deltagpi8 mutants. The overexpression of these nonfunctional alleles in wild-type cells leads to the accumulation of the free GPI precursor lipid CP2, delays the maturation of the GPI protein Gas1p, and arrests cell growth. The dominant negative effect of the Cys199 mutant cannot be overcome by the simultaneous overexpression of Gaa1p. Most GPI8 alleles mutated in other conserved regions of the protein can complement the growth defect of Deltagpi8, but nevertheless accumulate CP2. CP2 accumulation, a delay in Gas1p maturation and a slowing of cell growth can also be observed when Gpi8p is depleted to 50% of its normal level in wild-type cells. The dominant negative effect of nonfunctional and partially functional mutant alleles can best be explained by assuming that Gpi8p works as part of a homo- or heteropolymeric complex.

PAF-induced synthesis of tetraenoic and pentaenoic leukotrienes in the isolated rabbit lung.

In an isolated rabbit lung model, we tested the hypothesis that platelet-activating factor (PAF)-induced leukotriene (LT) synthesis is critically dependent on the free precursor fatty acid supply and the possible substitution of arachidonic acid (AA) by eicosapentaenoic acid (EPA). To augment the intravascular polymorphonuclear neutrophils (PMNs) in the isolated lung, human PMNs were infused into the pulmonary artery. LTs and hydroxyeicosatetra(penta)enoic acids were quantified with HPLC techniques. Application of PAF (5 microM) or AA (10 microM) provoked the generation of limited quantities of 4-series LTs and 5-hydroxyeicosatetraenoic acid (total sum of 5-lipoxygenase products approximately 7 and approximately 27 pmol/ml in lungs both with and without infused PMNs, respectively). Combined administration amplified 5-lipoxygenase product formation, with a predominance of cysteinyl-LT synthesis in lungs both without (total sum approximately 67 pmol/ml) and, much more strikingly, with (total sum approximately 308 pmol/ml) an infusion of neutrophils. EPA (10 microM) elicited exclusive generation of 5-series LTs and 5-hydroxyeicosapentaenoic acid (total sum approximately 82 pmol/ml). Dual stimulation with PAF and EPA provoked amplification of EPA-derived 5-lipoxygenase product formation, again with predominance of cysteinyl-LTs in lungs without (total sum approximately 224 pmol/ml) and, in particular, with (total sum approximately 545 pmol/ml) preceding microvascular PMN entrapment. Combined application of PAF, AA, and EPA resulted in the synthesis of LTs derived from both fatty acids, with a predominance of 5-series products. We conclude that the PAF-evoked 5-lipoxygenase product formation in the neutrophil-harboring lung capillary bed is critically dependent on intravascular precursor fatty acid supply, with EPA representing the preferred substrate compared with AA. PMN-related transcellular eicosanoid synthesis is suggested to underlie the predominant generation of cysteinyl-LTs. The supply of n-3 versus n-6 precursor fatty acid may thus have a major impact on inflammatory mediator generation.

Further Evidence for Double-Strand Breaks Originating from a Paired Radical Precursor from Studies of Oxygen Fixation Processes

By using a fast reaction technique which employs H2S gas as a fast-reacting chemical repair agent, it is possible to measure the competition kinetics between chemical repair reactions and oxygen fixation reactions in model DNA and cellular systems. In plasmid pBR322 DNA irradiated with electrons, we have compared the oxygen fixation reactions of the free radical precursors that lead to the production of single-strand (SSBs) and double-strand breaks (DSBs). For the oxygen-dependent fixation of radical damage leading to SSBs, a second-order rate constant of 2.3 x 10(8) dm3 mol(-1) s(-1) was obtained compared to 8.9 x 10(7) dm3 mol(-1) s(-1) for DSBs. The difference is in general agreement with predictions from a multiple-radical model where the precursor of a DSB originates from two radicals. The fixation of this precursor by oxygen will require both radicals to be fixed for the DSB to be formed, which will have slower kinetics than that of single free-radical precursors of SSBs.

Low temperature evolution of crystalline BaTiO3 from alkali-metal free precursor using sol-gel process

Bulk structure and surface texture of BaTiO3 materials synthesized at low temperature using sol-gel technique have been investigated. The materials were produced by the pyrolysis of an xerogel precursor of the tentative formula BaTiO3-x(CH3COO)2x, which was prepared using 1: 1 molar ratio of barium acetate and titanium oxyacetate solution. The present method avoids using alkali-metal hydroxides (as a hydrolyzing agent), and thus produces an alkali-metal free precursor. The decomposition course of the xerogel at the onset of formation of crystalline BaTiO3 was probed applying thermogravimetry (TG), differential scanning calorimetery (DSC), Fourier-transform infrared spectroscopy (FTIR), and Xray diffraction (XRD) techniques. Results indicated that most of the precursor weight loss occurs below 400°C, with the formation of titania rich intermediates. However, it was not until the temperature reached ≥600°C that well crystallized BaTiO3 was produced. The specific surface area and porosity were assessed for BaTiO3 produced at 600–1000°C using N2 adsorption at liquid N2 temperature.

Molecular and crystal structures of two N α -protected α-aminoacyl fluorides and their free carboxylic acid synthetic precursors 1

Abstract The molecular and crystal structures of N-para-toluenesulphonyl-α-aminoisobutyric acid fluoride (1), N-para-toluenesulphonyl-N-methyl-α-aminoisobutyric acid fluoride (2), N-para-toluenesulphonyl-α-aminoisobutyric acid (3), and N-para-toluenesulphonyl-N-methyl-α-amino-isobutyric acid (4) have been determined by X-ray diffraction. Crystal parameters: (1) monoclinic, space group P21/a, a = 24.264(3) Å, b = 8.386(2) Å, c = 6.245(1) Å, β = 96.5(2)°, and Z = 4; (2) monoclinic, space group P21/n, a = 7.606(1) Å, b = 14.954(2) Å, c = 11.969(2) Å, β = 92.3(2)°, and Z = 4; (3) monoclinic, space group P21/n, a = 11.151(2) Å, b = 6.168(1) Å, c = 18.669(2) Å, β = 91.3(2)°, and Z = 4; (4) monoclinic, space group P21/c, a = 11.993(2) Å, b = 10.322(2) Å, c = 12.123(2) Å, β = 115.9(2)°, and Z = 4. The structures were solved by direct methods. The least-squares refinements led to conventional R factors of 0.044, 0.059, 0.045, and 0.056 for (1)–(4), respectively. This is the first geometrical and conformational characterization at atomic resolution of two N α -protected α-aminoacids containing the elusive acyl fluoride C-activating group.[unk]

Group IVB Oxides as High Permittivity Gate Insulators

AbstractIncreasing MOSFET performance requires scaling, the systematic reduction in device dimensions. Tunneling leakage, however, provides an absolute scaling limit for SiO2of about 1.5 nm. Power limitations and device reliability are likely to pose softer limits slightly above 2 nm. We have investigated the use of high permittivity materials such as TiO2, ZrO2, and their silicates as potential replacements for SiO2. We have synthesized titanium nitrate (Ti(NO3)4or TN), zirconium nitrate (Zr(NO3)4or ZrN), and hafnium nitrate (Hf(NO3)4or HfN) as hydrogen and carbon free deposition precursors. Several problems arise in the use of these films including the formation of an amorphous low permittivity interfacial layer. For TiO2this layer is formed by silicon up diffusion. Surface nitridation retards the formation of the interfacial layer. We discuss the effects of both thermal and remote plasma surface nitridation treatments on the properties of the film stack. ZrO2and HfO2appear to form a thermal layer of silicon oxide between the high permittivity film and the silicon and have excess oxygen in the bulk of the film.