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PubMed2003

High density lipoprotein can modulate the inhibitory effect of oxLDL on prostacyclin generation by rat aorta in vitro.

To examine the effect of oxidized low density lipoprotein (oxLDL) on prostacyclin (PGI2) generation by rat aorta in vitro and whether high density lipoprotein (HDL) has any protective effect against the inhibition of PGI2 generation induced by oxLDL is the objective of this study. Preincubation of aortas with oxLDL resulted in significant inhibition of PGI2 generation compared to preincubation with normal low density lipoprotein (nLDL) or buffer only. The inhibitory effect of oxLDL resided in its lipid moiety while the lipid fraction of nLDL showed no effect. Aortas preincubated with 10 microg/ml of lyso phosphatidycholine (lyso PC) also showed 30% inhibition of PGI2 generation, indicating that lyso PC was among the lipid components of oxLDL which inhibited PGI2 generation. Preincubation of aortas with a mixture of HDL and oxLDL at a ratio of 10:1 showed a significant recovery of PGI2 generation compared to aortas preincubated with only oxLDL, indicating a protective role for HDL. When HDL was incubated with oxLDL the transfer of lyso PC from oxLDL to HDL suggested that HDL trapped lyso PC from oxLDL thus preventing it from acting on the aorta. However, when a mixture of HDL and oxLDL at a ratio of 3:1 was preincubated with aortas, no protective effect of HDL was observed. Preincubation of aortas with a mixture of HDL plus oxLDL at a ratio of 8:1, which was incubated for 1 h at 37 degrees C, produced significantly less PGI2 than aortas preincubated only with oxLDL, indicating that HDL under these conditions was not protective but even enhanced the inhibitory effect of oxLDL. Similarly, aortas preincubated with HDL plus whole oxLDL (at a ratio of 10:1); containing all the small molecular weight oxidation products and characterized by high levels of thiobarbituric acid reactive substance (TBARS) and lipid hydroperoxides; produced significantly less PGI2 than aortas preincubated with whole oxLDL. These results were evaluated in light of possible modification of HDL by oxLDL and its lipid oxidation products such as aldehydes and lipid peroxides. The modified HDL can add more lipid peroxides and increase the effectiveness of lipid peroxides originally present in oxLDL.

Animals↗
PubMed1999

Parallel constraint-based generative theories of language.

A re-evaluation of the goals and techniques of generative grammar since the mid-1960s suggests that its mentalistic/biological program for describing language is still sound and has been borne out by subsequent developments. Likewise, the idea of a generative system of combinatorial rules has led to a tremendous expansion of our understanding of linguistic phenomena. However, certain fundamental features of the versions of generative grammar based on Chomsky's work prevent the theory from making deep liaisons with related fields such as language processing and neuroscience. Perhaps the most prominent of these is the assumption that all creative aspects of language stem from syntactic structure. In this article, I propose a model of generative grammar that generalizes features of several, alternative, non-Chomskyan generative frameworks. In this model, language is seen as composed of three independent generative components (phonological, syntactic, and semantic/conceptual structure), whose respective structures are placed in correspondence by 'interface components'. Besides being able to incorporate a host of purely linguistic facts, this view leads to a more direct relationship between the theory of grammar and the theory of lexical and grammatical processing.

Journal Article↗
PubMed2000

Effect of food reductones on the generation of the pyrazine cation radical and on the formation of the mutagens in the reaction of glucose, glycine and creatinine.

One of the possible pathways of the formation of mutagens in heated foods is through the pyrazine cation radical generated in the early stage of the Maillard reaction. The aim of the present study was to elucidate how food reductones contribute to the pyrazine cation radical generation in the reaction of glucose (Glc) and glycine (Gly), and to the formation of the mutagens in the reaction of Glc, Gly and creatinine. Electron spin resonance (ESR) studies showed that fragrant reductones, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) and 4-hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF), generated in the Maillard reactions, enhanced the generation of the pyrazine cation radical in the reaction of Glc and Gly, and the reaction of DMHF or HEMF with Gly generated a larger amount of the pyrazine cation radical than the reaction of Glc and Gly, indicating that the furanones were intermediates of the pyrazine cation radical. By contrast, food antioxidants, ascorbic acid and erythorbic acid, effectively scavenged the pyrazine cation radical generated in the reaction of Glc and Gly. DMHF and HEMF were not effective to modulate the mutagen formation in the reaction of Glc, Gly and creatinine, and the mutagenicity produced in the reaction of DMHF or HEMF, Gly and creatinine was lower than that produced in the reaction of Glc, Gly and creatinine. On the other hand, ascorbic acid and erythorbic acid were effective to decrease the mutagen formation in the reaction of Glc, Gly and creatinine.

Animals↗
PubMed2000

GALEN: a third generation terminology tool to support a multipurpose national coding system for surgical procedures.

Generalised architecture for languages, encyclopedia and nomenclatures in medicine (GALEN) has developed a new generation of terminology tools based on a language independent model describing the semantics and allowing computer processing and multiple reuses as well as natural language understanding systems applications to facilitate the sharing and maintaining of consistent medical knowledge. During the European Union 4 Th. framework program project GALEN-IN-USE and later on within two contracts with the national health authorities we applied the modelling and the tools to the development of a new multipurpose coding system for surgical procedures named CCAM in a minority language country, France. On one hand, we contributed to a language independent knowledge repository and multilingual semantic dictionaries for multicultural Europe. On the other hand, we support the traditional process for creating a new coding system in medicine which is very much labour consuming by artificial intelligence tools using a medically oriented recursive ontology and natural language processing. We used an integrated software named CLAW (for classification workbench) to process French professional medical language rubrics produced by the national colleges of surgeons domain experts into intermediate dissections and to the Grail reference ontology model representation. From this language independent concept model representation, on one hand, we generate with the LNAT natural language generator controlled French natural language to support the finalization of the linguistic labels (first generation) in relation with the meanings of the conceptual system structure. On the other hand, the Claw classification manager proves to be very powerful to retrieve the initial domain experts rubrics list with different categories of concepts (second generation) within a semantic structured representation (third generation) bridge to the electronic patient record detailed terminology.

Abstracting and Indexing↗
PubMedDate not supplied

Natural language generation of surgical procedures.

A number of compositional Medical Concept Representation systems are being developed. Although these provide for a detailed conceptual representation of the underlying information, they have to be translated back to natural language for used by end-users and applications. The GALEN programme has been developing one such representation and we report here on a tool developed to generate natural language phrases from the GALEN conceptual representations. This tool can be adapted to different source modelling schemes and to different destination languages or sublanguages of a domain. It is based on a multilingual approach to natural language generation, realised through a clean separation of the domain model from the linguistic model and their link by well defined structures. Specific knowledge structures and operations have been developed for bridging between the modelling 'style' of the conceptual representation and natural language. Using the example of the scheme developed for modelling surgical operative procedures within the GALEN-IN-USE project, we show how the generator is adapted to such a scheme. The basic characteristics of the surgical procedures scheme are presented together with the basic principles of the generation tool. Using worked examples, we discuss the transformation operations which change the initial source representation into a form which can more directly be translated to a given natural language. In particular, the linguistic knowledge which has to be introduced--such as definitions of concepts and relationships is described. We explain the overall generator strategy and how particular transformation operations are triggered by language-dependent and conceptual parameters. Results are shown for generated French phrases corresponding to surgical procedures from the urology domain.

Linguistics↗
PubMed2002

Scalp-recorded Bereitschaftspotential is the result of the activity of cortical and subcortical generators--a hypothesis.

OBJECTIVE: The source of scalp-recorded Bereitschaftspotential (BP) remains a subject of ongoing discussion. This paper presents arguments in favour of the hypothesis that explains scalp-recorded BP as the result of the activity of both cortical and subcortical BP generators. METHODS: Intracranial recordings of BP were performed, mostly with depth electrodes in epilepsy surgery candidates. In some patients undergoing intracranial exploration, an electrode may have had contacts in the subcortical structures. RESULTS: BP is generated in several cortical and subcortical structures that are known to be directly or indirectly linked with motor control. Cortical sources of BP were displayed contralaterally to the movement in the primary motor cortex and somatosensory cortex, and bilaterally in the supplementary motor area (SMA), in the preSMA, and in the cingulate. A few other generators may be revealed in structures that have not yet been sufficiently explored. Subcortical generators of BP were found in the putamen, pallidum, caudate, and in the thalamus. In earlier recordings, BP was described rostrally to the thalamic region and in the brainstem, i.e. in the pes peripedunculi, nucleus peripeduncularis, pulvinar, and medial geniculate. CONCLUSIONS: Our observations do not explain the generation of scalp-recorded BP by the contribution of either cortical or subcortical sources alone. Intracranial cortical recordings contradict a wide distribution of scalp-recorded BP. Widely synchronised cerebral electromagnetic activity can be recorded on the scalp. We presume that in the case of BP, the weak deep dipoles might reach the scalp, as they are produced by a relatively huge mass of subcortical neuronal tissue. We strongly suspect that scalp-recorded BP represents a summation of potentials that are generated simultaneously in several cortical as well as in several subcortical structures.

Cerebral Cortex↗
PubMed2003

The generation of free radicals by nitric oxide synthase.

Nitric oxide synthase (NOS) is an example of a family of heme-containing monooxygenases that, under the restricted control of a specific substrate, can generate free radicals. While the generation of nitric oxide (NO*) depends solely on the binding of L-arginine, NOS produces superoxide (O(2)*(-)) and hydrogen peroxide (H(2)O(2)) when the concentration of the substrate is low. Not surprisingly, effort has been put forth to understand the pathway by which NOS generates NO*, O(2)*(-) and H(2)O(2), including the role of substrate binding in determining the pathways by which free radicals are generated. By binding within the distal heme pocket near the sixth coordination position of the NOS heme iron, L-arginine alters the coordination properties of the heme iron that promotes formation of the perferryl complex NOS-[Fe(5+)=O](3+). This reactive iron intermediate has been shown to abstract a hydrogen atom from a carbon alpha to a heteroatom and generate carbon-centered free radicals. The ability of NOS to produce free radicals during enzymic cycling demonstrates that NOS-[Fe(5+)=O](3+) behaves like an analogous iron-oxo complex of cytochrome P-450 during aliphatic hydroxylation. The present review discusses the mechanism(s) by which NOS generates secondary free radicals that may initiate pathological events, along with the cell signaling properties of NO*, O(2)*(-) and H(2)O(2).

Animals↗
PubMed2005

Physicochemical and sensory characteristics of whey protein hydrolysates generated at different total solids levels.

Whey protein hydrolysates were generated at different total solids (TS) levels (50-300 g/l) using the commercially available proteolytic preparation Debitrase HYW20, while enzyme to substrate ratio, pH and temperature were maintained constant. Hydrolysis proceeded at a faster rate at lower TS reaching a degree of hydrolysis (DH) of 16.6% at 300 g TS/l, compared with a DH of 22.7% at 50 g TS/l after 6 h hydrolysis. The slower breakdown of intact whey proteins at high TS was quantified by gel-permeation HPLC. Reversed-phase (RP) HPLC of hydrolysate samples of equivalent DH (approximately 15%) generated at different TS levels indicated that certain hydrophobic peptide peaks were present at higher levels in hydrolysates generated at low TS. Sensory evaluation showed that hydrolysates with equivalent DH values were significantly (P < 0.0005) less bitter when generated at 300 g TS/l (mean bitterness score = 25.4%) than hydrolysates generated at 50 g TS/l (mean bitterness score = 39.9%). A specific hydrophobic peptide peak present at higher concentrations in hydrolysates generated at low TS was isolated and identified as beta-lactoglobulin f(43-57), a fragment having the physical and chemical characteristics of a bitter peptide.

Chemical Phenomena↗
PubMed1992

Effect of concurrent infection with Muellerius capillaris on the development of redial generations of Fasciola hepatica in Lymnaea truncatula.

The rediae of Fasciola hepatica were counted according to generation in adult and juvenile Lymnaea truncatula following single infection with Fasciola hepatica, double infection with F. hepatica and then Muellerius capillaris, or double infection with M. capillaris and F. hepatica. The rediae found in double infections were essentially first generation and an early cohort from the second generation. The following differences were observed in adult snails which underwent double infection when compared to corresponding single infections: i) dependent rediae were almost completely absent; ii) degenerating independent rediae were found in identical or decreased numbers; iii) living independent rediae of the first generation were decreased in number, while those of the second generation had variable decreased numbers. The results were similar in juvenile snails with double infections, except that the numbers of degenerating independent rediae were higher than those found in corresponding single infections and the numbers of rediae of the second generation were increased. The order of exposure in double infections had no influence on the number and maturation of fasciolid rediae.

Animals↗
PubMed2006

Self-generated learning in people with multiple sclerosis.

Memory impairment is among the most common cognitive deficits in people with multiple sclerosis (MS). To remediate this problem, recent research has evaluated the benefits of self-generated encoding. These nascent investigations reveal that people with MS who have mild memory impairment demonstrate a significant memory benefit from self-generated encoding compared with didactic learning. To extend prior research, the present experiment included MS patients with moderate-severe, rather than just mild, memory impairment. Additionally, the experiment evaluated whether self-generated encoding improves memory for activities of daily living instead of abstract words. Specifically, the experiment determined whether self-generated encoding enhanced memory for names, appointments, and object locations. In agreement with and extending prior research, MS patients remembered more information if it was self-generated rather than didactically presented, and this finding occurred despite moderate-severe memory impairment. Furthermore, compared with didactic encoding, self-generation enhanced recall of activities of daily living. Implications of these findings for cognitive rehabilitation and the nature of memory impairment in MS are discussed.

Activities of Daily Living↗
PubMed2004

Nanoflow gradient generator for capillary high-performance liquid chromatography.

A novel method of generating a nanoflow gradient elution for a capillary high-performance liquid chromatography (HPLC) system has been developed. An important feature of this system is that any gradient (GR) profile generated by a conventional microflow GR pump can be asymptotically traced and converted as a corresponding nanoflow GR profile simply by using a 10-port switching valve with two injection loops installed. Consequently, it has been called an "asymptotic trace 10-port valve" (AT10PV) nanoflow GR generator. Performance of the AT10PV nanoflow GR generator was tested in the range of flow rates from 50 to 500 nL/min. The test demonstrated that the AT10PV nanoflow GR generator can asymptotically trace the original gradient profile with good reproducibility. A capillary HPLC system using the AT10PV nanoflow GR generator provides reasonably good repeatability of peak retention times on the chromatogram of the tryptic digest of a BSA sample, RSD of less than 0.3% at a flow rate of 200 nL/min. It also enables sequential running of a series of sample injections in the same manner as conventional analysis at microflow rates.

Acetone↗
PubMed1986

D-lactate oxidation and generation of the proton electrochemical gradient in membrane vesicles from Escherichia coli GR19N and in proteoliposomes reconstituted with purified D-lactate dehydrogenase and cytochrome o oxidase.

The respiratory chain in the cytochrome d deficient mutant Escherichia coli GR19N is a relatively simple, linear system consisting of primary dehydrogenases, ubiquinone 8, cytochrome b-556, and cytochrome o oxidase. By use of right-side-out and inside-out membrane vesicles from this strain, various oxidase activities and the generation of the H+ electrochemical gradient were studied. Oxidation of ubiquinol 1 or N,N,-N',N'-tetramethyl-p-phenylenediamine, which donate electrons directly to the terminal oxidase, generates a H+ electrochemical gradient comparable to that observed during D-lactate oxidation. In contrast, D-lactate/ubiquinone 1 or D-lactate/ferricyanide oxidoreductase activity does not appear to generate a membrane potential, suggesting that electron flow from D-lactate dehydrogenase to ubiquinone is not electrogenic. Moreover, proteoliposomes reconstituted with purified D-lactate dehydrogenase, ubiquinone 8, and purified cytochrome o catalyze D-lactate and ubiquinol 1 oxidation and generate a H+ electrochemical gradient similar to that observed in membrane vesicles. Strikingly, in inside-out vesicles, NADH oxidation generates a H+ electrochemical gradient that is very significantly greater than that produced by either D-lactate or ubiquinol 1; furthermore, NADH/ubiquinone 1 and NADH/ferricyanide oxidoreductase activities are electrogenic. It is suggested that the only component between D-lactate dehydrogenase or ubiquinol and oxygen in GR19N membranes that is directly involved in the generation of the H+ electrochemical gradient is cytochrome o, which functions as a "half-loop" (i.e., the oxidase catalyzes the scalar release of 2 H+ from ubiquinol on the outer surface of the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Membrane↗
PubMed1999

8-Nitro-2'-deoxyguanosine, a specific marker of oxidation by reactive nitrogen species, is generated by the myeloperoxidase-hydrogen peroxide-nitrite system of activated human phagocytes.

Reactive intermediates generated by phagocytes damage DNA and may contribute to the link between chronic inflammation and cancer. Myeloperoxidase, a heme protein secreted by activated phagocytes, is a potential catalyst for such reactions. Recent studies demonstrate that this enzyme uses hydrogen peroxide (H2O2) and nitrite (NO2-) to generate reactive nitrogen species which convert tyrosine to 3-nitrotyrosine. We now report that activated human neutrophils use myeloperoxidase, H2O2, and NO2- to nitrate 2'-deoxyguanosine, one of the nucleosides of DNA. Through HPLC, UV/vis spectroscopy, and mass spectrometry, the two major products of this reaction were identified as 8-nitroguanine and 8-nitro-2'-deoxyguanosine. Nitration required each component of the complete enzymatic system and was inhibited by catalase and heme poisons. However, it was independent of chloride ion and little affected by scavengers of hypochlorous acid, suggesting that the reactive agent is a nitrogen dioxide-like species that results from the one-electron oxidation of NO2- by myeloperoxidase. Alternatively, 2'-deoxyguanosine might be oxidized directly by the enzyme to yield a radical species which subsequently reacts with NO2- or NO2* to generate the observed products. Human neutrophils stimulated with phorbol ester also generated 8-nitroguanine and 8-nitro-2'-deoxyguanosine. The reaction required NO2- and was inhibited by catalase and heme poisons, implicating myeloperoxidase in the cell-mediated pathway. These results indicate that human neutrophils use the myeloperoxidase-H2O2-NO2- system to generate reactive species that can nitrate the C-8 position of 2'-deoxyguanosine. Our observations raise the possibility that reactive nitrogen species generated by myeloperoxidase and other peroxidases contribute to nucleobase oxidation and tissue injury at sites of inflammation.

Biomarkers↗
PubMed2006

Phenols and amine induced HO* generation during the initial phase of natural water ozonation.

The initial phase of ozone decomposition in natural water (t < 20 s) is poorly understood. It has recently been shown to result in very high transient HO* concentrations and, thereby, plays an essential role during processes such as bromate formation or contaminants oxidation. Phenols and amines are ubiquitous moieties of natural organic matter. Naturally occurring concentrations of primary, secondary, and tertiary amines, amino acids, and phenol were added to surface water, and ozone decomposition as well as HO* generation were measured starting 350 milliseconds after ozone addition. Six seconds into the process, 5 microM of dimethylamine and phenol had generated integral of HO* dt = 1 x 10(-10) M*s and 1.8 x 10(-10) M*s, respectively. With 10 microM dimethylamine and 1.5 mg O3/L, R(ct), (integral of HO*dt/ integral of O3dt) reached 10(-6), which is larger than in advanced oxidation processes (AOP) such as O3/H2O2. Experiments in the presence of HO*-scavengers indicated that a significant fraction of phenol-induced ozone decomposition and HO* generation results from a direct electron transfer to ozone. For dimethylamine, the main mechanism of HO* generation is direct formation of O2*- which reacts selectively with O3 to form O3*-. Pretreatment of phenol-containing water with HOCl or HOBr did not decrease HO* generation, while the same treatment of dimethylamine-containing water considerably reduced HO* generation.

Dimethylamines↗
PubMed2005

Spin dynamic study on the electric field dependence of carrier generation.

Using an acceptor-doped poly(N-vinylcarbazole) film, the magnetic field effect (MFE) on the generation efficiency of photoinduced charge was measured under various electric fields in order to clarify how the applied electric field affects the elementary processes in the photocarrier generation in photoconductive polymeric molecular solids. The external magnetic field influenced the electron spin dynamics among the geminate electron-hole pairs within a scale of a few nanometers and decreased the photocarrier generation efficiency. The observed MFE due to a hyperfine mechanism was almost independent of the electric field. By employing the stochastic Liouville equations based on a one-dimensional lattice model, we performed some model calculations for the dissociation, hopping, and recombination rate dependence of MFE on the generation efficiency. From a comparison between the observed and calculated MFE, it was concluded that the electric field affects the dissociation more than the hopping and the recombination. This coincides with the concepts in the Onsager model that is used to analyze the electric field dependence of carrier generation efficiency so far. The one-dimensional lattice model is a proper model for the carrier generation in polymeric molecular solids, which is qualitatively consistent with the Onsager model except for the long-range hole jump.

Journal Article↗
PubMed2005

Electrostatic layer-by-layer deposition of photoactive dendrimers with triviologen-like cores on their surfaces. Synthesis and electrochemical and photocurrent generation measurements.

The stepwise assembly of Fréchet-type dendrimers with naphthalene peripheral groups and positively charged viologen-like cores on quartz and ITO surfaces utilizing the layer-by-layer approach was investigated. We were able to deposit only the (+6) charged dendrimers series on ITO. The number of assembled dendrimers was found to increase as we go to higher-generation dendrimers. This dendrimer generation effect was evident from the UV-vis and electrochemical measurements of the assembled dendrimers. The half-wave potentials (E1/2) of the dendrimers shift to less negative values as the dendrimer generation increases in acetonitrile and to more negative values when assembled on ITO. Anodic photocurrent generation was seen upon light irradiation of the second- and third-generation dendrimers, NB1V3+6 and NB2V3+6, assembled on ITO but not for the zero-generation one, NV3+6. This observation was attributed to a fast charge recombination process in NV3+6 when compared to that of NB1V3+6 and NB2V3+6 dendrimers.

Journal Article↗
PubMed2001

Construction of gene-targeting vectors: a rapid Mu in vitro DNA transposition-based strategy generating null, potentially hypomorphic, and conditional alleles.

Gene targeting into mammalian genomes by means of homologous recombination is a powerful technique for analyzing gene function through generation of transgenic animals. Hundreds of mouse strains carrying targeted alleles have already been created and recent modifications of the technology, in particular generation of conditional alleles, have extended the usefulness of the methodology for a variety of special purposes. Even though the standard protocols, including the construction of gene-targeting vector plasmids, are relatively straightforward, they typically involve time-consuming and laborious gene mapping and/or sequencing steps. To produce various types of gene-targeting constructions rapidly and with minimum effort, we developed a strategy, that utilizes a highly efficient in vitro transposition reaction of phage Mu, and tested it in a targeting of the mouse Kcc2 gene locus. A vast number and different types of targeting constructions can be generated simultaneously with little or no prior sequence knowledge of the gene locus of interest. This quick and efficient general strategy will facilitate easy generation of null, potentially hypomorphic, and conditional alleles. Especially useful it will be in the cases when effects of several exons within a given gene are to be studied, a task that necessarily will involve generation of multiple constructions. The strategy extends the use of diverse recombination reactions for advanced genome engineering and complements existing recombination-based approaches for generation of gene-targeting constructions.

Alleles↗
PubMed1994

Incongruous item generation effects: a multiple-cue perspective.

In a series of studies, generation effects were obtained under encoding conditions designed to induce incongruous, unrelated item generation. Experiments 1 and 2, using free- and cued-recall measures, respectively, provided evidence that this unrelated generation effect was due to response-specific processing. Experiment 3 demonstrated a lack of relation between free recall and indices of clustering. A preliminary protocol study suggested that Ss generate multiple items in their search for appropriate unrelated responses. In Experiments 4 and 5, conditions designed to produce more extensive multiple generations demonstrated enhanced free recall. These results supported a multiple-cue account of facilitated recall for incongruous item generation. The multiple-cue perspective is consistent with traditional conceptualizations of memory, such as the principle of congruity, and contemporary distinctions between cue-target relational and item-specific processing.

Adult↗