170,657 research outputs found
Biosynthetic investigations of the v-type ATPase inhibitors bafilomycin A(1), B-1 and concanamycin A
No full textThe plecomacrolides bafilornycin A(1) and B-1 (1, 2) and concanamycin A (3), produced by different Streptomyces species, show a unique macrolactone structure with characteristic side chains and exhibit striking biological activities including distinct V-type ATPase inhibition. The biosynthesis of 1 and 2 has been established by feeding experiments with C-13-labelled precursors. Both, bafilomycin (1, 2) and concanamycin. (3) feature an "unusual C-2 chain extension unit" of as yet unknown origin which was addressed by feeding labelled 2-hydroxy- and 2-methoxymalonyl-derivatives
Biosynthetic origin of the methoxyl extender unit in bafilomycin and concanamycin using stereospecifically labeled precursors
No full textThe microbial macrolides bafilomycin A(1), B-1, and concanamycin A from Streptomyces spp. are potent and specific inhibitors of V-ATPases. The question of the biosynthetic origin of the two uncommon "glycolate units" of each of the macrolide structures was addressed by feeding experiments with stereo specifically C-13-labeled precursors. Our studies clearly indicate that glycerol is a source for the methoxylated C-2-units and determines the orientation of the incorporation. Products from the carboxylic acid pool or TCA cycle are ruled out as key precursors. The data suggest the action of a glycerol kinase and point to phosphoglycerate as an intermediate in their biosynthesis. However, glycerate itself is not accepted as a precursor. We present the likely biosynthetic pathway and show the value of stereospecifically labeled presursors as an important tool for biosynthetic investigations.NIBIB NIH HHS [EB002166
Enhancing Electrogenerated Chemiluminescence on Platinum Electrodes through Surface Modification
No full textIncreasing the light emission of electrogenerated chemiluminescence is an important goal for enhancing the sensitivity for potential practical applications. Electrogenerated chemiluminescence is primarily triggered by a heterogeneous electron transfer reaction, for which the electrode material plays a pivotal role. We investigated how a platinum electrode, one of the most used but poorly efficient noble metal electrode materials in electrogenerated chemiluminescence, can be modified to enhance light emission. A polypyrrole layer was deposited on the platinum electrode through electrochemically induced polymerization, and subsequently pyrolyzed with the formation of a carbonaceous film. Electrochemiluminescence of the [Ru(bpy)3]2+/tri-n-propylamine system on such carbon film electrodes showed an enhancement of up to a 4 times increase, as compared with the bare platinum electrode
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Biosynthetic origin of the methoxyl extender unit in bafilomycin and concanamycin using stereospecifically labeled precursors
No full textThe microbial macrolides bafilomycin A(1), B-1, and concanamycin A from Streptomyces spp. are potent and specific inhibitors of V-ATPases. The question of the biosynthetic origin of the two uncommon "glycolate units" of each of the macrolide structures was addressed by feeding experiments with stereo specifically C-13-labeled precursors. Our studies clearly indicate that glycerol is a source for the methoxylated C-2-units and determines the orientation of the incorporation. Products from the carboxylic acid pool or TCA cycle are ruled out as key precursors. The data suggest the action of a glycerol kinase and point to phosphoglycerate as an intermediate in their biosynthesis. However, glycerate itself is not accepted as a precursor. We present the likely biosynthetic pathway and show the value of stereospecifically labeled presursors as an important tool for biosynthetic investigations.NIBIB NIH HHS [EB002166
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
Improving classification in protein structure databases using text mining
Full text linkBackground: The classification of protein domains in the CATH resource is primarily based on structural comparisons, sequence similarity and manual analysis. One of the main bottlenecks in the processing of new entries is the evaluation of 'borderline' cases by human curators with reference to the literature, and better tools for helping both expert and non-expert users quickly identify relevant functional information from text are urgently needed. A text based method for protein classification is presented, which complements the existing sequence and structure-based approaches, especially in cases exhibiting low similarity to existing members and requiring manual intervention. The method is based on the assumption that textual similarity between sets of documents relating to proteins reflects biological function similarities and can be exploited to make classification decisions.Results: An optimal strategy for the text comparisons was identified by using an established gold standard enzyme dataset. Filtering of the abstracts using a machine learning approach to discriminate sentences containing functional, structural and classification information that are relevant to the protein classification task improved performance. Testing this classification scheme on a dataset of 'borderline' protein domains that lack significant sequence or structure similarity to classified proteins showed that although, as expected, the structural similarity classifiers perform better on average, there is a significant benefit in incorporating text similarity in logistic regression models, indicating significant orthogonality in this additional information. Coverage was significantly increased especially at low error rates, which is important for routine classification tasks: 15.3% for the combined structure and text classifier compared to 10% for the structural classifier alone, at 10(-3) error rate. Finally when only the highest scoring predictions were used to infer classification, an extra 4.2% of correct decisions were made by the combined classifier.Conclusion: We have described a simple text based method to classify protein domains that demonstrates an improvement over existing methods. The method is unique in incorporating structural and text based classifiers directly and is particularly useful in cases where inconclusive evidence from sequence or structure similarity requires laborious manual classification
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
ElKowmGIS : ein neues System zur Dokumentation archäologischer Fundstellen
Full text linkSeit dem Jahr 2005 beruht die Dokumentation der paläolithischen Grabung Hummal (El Kowm, Syrien) auf der Dokumentation mittels Computer. Hierfür wurde, speziell für die Vermessung, die Software AutoCAD mit den Applikationen TachyCAD und Photoplan angeschafft. Hierbei handelt es sich um eine kommerzielle Lösung, welche in vielen archäologischen Institutionen zum Einsatz kommt. Während der Arbeit mit diesem System fiel jedoch auf, dass nicht alle Belange, welche ein Archäologe haben kann, berücksichtigt werden (können). Eine Anpassung der Software auf die individuelle Grabung ist nicht ohne weiteres möglich, da es sich hierbei um Lösungen handelt, die nicht frei veränderbar sind. Aus der Notwendigkeit, eine anpassbare Lösung zu haben, entstand die Idee, eine eigene Softwarelösung zu produzieren, welche von Archäologen für Archäologen geschaffen wurde. Hierbei handelt es sich um ElKowmGIS, einem archäologischen Dokumentationssystem, welches im Wesentlichen die drei Bestandteile CAD, GIS und Datenbank in einem Paket vereint. Für die Entwicklung von ElKowmGIS wurden im Rahmen einer Doktorarbeit folgende Grundregeln definiert:
- Plattformunabhängigkeit: Der User soll die Software auf “seinem“ Computer nutzen können, egal welches Betriebssystem installiert ist.
- Modularer Aufbau: Das System soll so aufgebaut sein, dass für jede Aufgabenstellung Module zur Verfügung gestellt werden. Fehlt ein Modul, so kann es ohne weiteres nachträglich erstellt werden.
- Adaption der Software: Die Software soll auf die Dokumentationsstruktur anpassbar sein, nicht umgekehrt.
- “Künstliche Intelligenz“: Das Programm soll gewisse Aufgaben, z.B. Weiterführung der Laufnummer, Sortieren der Bilder, etc., selbstständig ausführen. Der Benutzer muss lediglich die Regeln hierfür vorgeben.
- Dokumentstruktur und Dateigrößen: Die verwendete Datenbank im Hintergrund soll es ermöglichen, mit kleinstmöglichem Platzbedarf und Zeitaufwand die erhobenen Daten zu sichern und auch zu verwenden.
- Anwenderfreundlichkeit: Das Programm soll selbsterklärend sein, d.h. der User soll sich alleine zurechtfinden, ohne tagelang ein Handbuch wälzen zu müssen.
Für die Implementierung wurde die Kombination aus JAVA, für die Programmierung der Benutzeroberfläche, und PostgreSQL als Datenbankserver gewählt. Zum einen bietet sich hier die Möglichkeit, die Plattformunabhängigkeit zu implementieren. Zum anderen lässt sich dadurch das ganze System modular aufbauen
Development and application of imaging techniques for the investigation of dentinal hypersensitivity
Full text linkThe overall aim of this thesis is to examine the underlying physical basis of
dentinal hypersensitivity and to assess methods of treating this cause using
imaging techniques. The scanned probe microscopy (SPM) techniques are then
extended to the study of carbon-based electrode surfaces, as described in the final
chapter.
The use of scanning electrochemical microscopy (SECM), combined with in situ
pressure-time measurements, is described as a means to investigate the flow of
fluid through human and bovine dentine, and the subsequent effect of occlusion
treatments on this flow. Scanning Ion Conductance Microscopy (SICM) is also
introduced as a technique for imaging dentine, with instrument design and
development described, and also calibration of the technique.
Laser scanning confocal microscopy (LSCM) coupled to a constant volume flowpressure
measuring system is introduced as a new technique for the quantitative
measurement of fluid flow across porous materials. The methodology described
herein firstly allows a ready assessment of the general efficacy of treatments via
hydraulic permeability measurements. Second, LSCM images allow the nature of
the flow process and the mode of action of the treatments to be revealed at high
spatial resolution. For the particular case of dentine, we demonstrate how the
method allows candidate treatments to be compared and assessed.
To complement the studies into dentinal hypersensitivity, microscopic
dissolution of bovine enamel is investigated. This chapter describes a novel
approach, based on SECM, to promote the localised dissolution of bovine
enamel, effected by the application of a proton flux to the enamel surface from a
UME positioned within 5 μm of the surface, in aqueous solution. The approach
results in a well-defined “acid challenge” yielding well-defined etch pits that
were characterised using light microscopy and white light interferometry. The
effect of etching in the presence of lactate is considered, as is the effect of
treating the enamel samples with sodium fluoride prior to etching. The approach
described is amenable to mass transport modelling, allowing quantitative
interpretation of etch features.
The techniques developed throughout the thesis are applied to the investigation
of two types of carbon electrodes: boron-doped diamond (BDD) and highly
ordered pyrolytic graphite (HOPG). Heterogeneities in the electroactivity of
these substrates are explored.A scanning micropipet contact method (SMCM) is
described which promises wide-ranging application in imaging and quantifying
electrode activity at high spatial resolution
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