169,782 research outputs found
Peripheral Interaction for Sports - Exploring Two Modalities for Real-Time Feedback
No full textWe believe that sports is a domain that would both provide valuable input to the area of peripheral interaction, as well as benefit from peripheral interaction itself. We present two pilot studies on peripheral interaction for cross-country skiing and golf using vibration feedback and audio feedback respectively. We believe the results of these initial studies are encouraging and aim to pursue the concept of peripheral interaction for the sports domain
Catalytic mechanisms and evolution of leukotriene A4 hydrolyse
No full textInflammation is the first response of the body to infection or physical irritation. This response can potentially trigger the whole immune system but in the initial stage mainly involves leukocytes of the innate immune system and a complex cascade of chemical mediators, which by different means control, maintain and resolve the process. One group of such mediators is the leukotrienes, among which LTB4 is found. LTB4 has several immunomodulating properties and mainly acts by recruiting leukocytes to the site of injury or infection. LTB4 is mainly formed by leukocytes of the innate immune system, but recruits cells of both the innate as well as the adaptive immune systems. Thus, it constitutes an important link between the two systems. Moreover, LTB4 is known to be involved in several pathological inflammatory conditions.Leukotriene A4 hydrolase (LTA4H) is a bifunctional zinc metalloenzyme that catalyzes the last step in the formation of LTB4. In addition, LTA4H catalyzes hydrolysis of oligo-peptides. Hence the enzyme is bifunctional and the two activities of LTA4H actually share a common active site. While LTB4 has a characterized biological functions in the inflammatory response, the physiological relevance of the peptidase activity of LTA4H is yet unknown.According to sequence homology, LTA4H sorts as a member of the M1 family of aminopeptidases, a vast enzyme family found in most organisms and with a variety of biological functions. Among these peptidases, a subset present in vertebrates has the intrinsic capacity to catalyze LTA4 ¨ LTB4 formation.The present investigations deal with the catalytic mechanism of both activities of LTA4H, as well as the divergent evolution of LTA4H from ancestral aminopeptidases. For the first part of the work, the recently determined crystal structure of LTA4H served as a guideline for the design of experiments. In these, an approach mainly including mutagenesis, enzyme kinetics, molecular modeling and crystallography led to determination of the basic requirements for catalysis by LTA4H as well as an insight into the molecular events underlying its evolution from ancestral aminopeptidases. To refine these findings, a novel assay for enzyme kinetics was developed, which allowed a faster and more adequate analysis of the peptidase activity. Finally, the novel assay in combination with crystal structure determinations of LTA4H in complex with different ligands, allowed a yet deeper understanding of the reaction mechanism for peptide hydrolysis catalyzed by LTA4H.For the peptidase activity it was specifically shown that the peptide substrate is anchored between Arg-563 and Glu-271 with its C- and N-terminal, respectively. Together, these two residues function as an effective filter which selectively favors peptide substrates consisting of three residues, i.e. tri-peptides. The specific preference of the enzyme for arginyl tripeptides is achieved by interaction between basic N-terminal groups of the substrate and Asp-375. During the course of peptide hydrolysis, Tyr-383 together with the zinc ion function as a site for oxyanion stabilization of the reaction intermediate. The general base Glu-296, not only facilitates the nucleophilic attack by the hydrolytic water, but also functions as a proton shuffle, which in the last step of peptide hydrolysis protonates the leaving arnine. Considering sequence homology, these findings to a large extent holds true also for other metallopeptidases of the MA clan and specifically for aminopeptidases of the M1 family.For the epoxide hydrolase activity, it was shown that the carboxylate group of LTA4 binds to Arg-563 to achieve proper positioning, with respect to catalytic residues, of the reacting moieties of the substrate. During LTA4 hydrolysis, Glu-271 and Asp-375 are required for epoxide ring opening and for catalyzing the stereospecific attack by the hydrolytic water at carbon 12 of LTA4.Notably, Arg-563 and Glu-271 are essential for both reaction mechanisms. While Arg-563 serves the same purpose in both reaction mechanisms, i.e. binding of substrate carboxylates, Glu-271 has distinct roles in each reaction. The latter observation, with a single residue serving in two different catalytic mechanisms, is unique to LTA4H.Often, assaying peptidase activity either involves complex assays, when utilizing natural substrates, or relies on chrornogenic model substrates of limited physiological relevance. The novel assay developed circumvents these problems and allows simple and fast screening of natural peptide substrates and determination of kinetic constants for their hydrolysis.For the evolutionary studies, the yeast homologue of human LTA4H, an aminopeptidase with substrate specificities distinct ftom, human LTA4H, was used. This enzyme is activated by LTA4 but also to some extent hydrolyzes it. For peptide hydrolysis, it was shown that the yeast enzyme uses the corresponding residues as, human LTA4H. Additionally, it was shown that the active site pocket of the yeast enzyme allows LTA4 to bind in two conformations: one peptidase-activating and one compatible with LTA4 hydrolysis. A few point mutations of the yeast enzyme, which made it more similar to human LTA4H, sufficed to reengineer the pocket to more resemble the corresponding human one with LTA4-inhibition replacing the LTA4-activating effect. Thus, it appears as LTA4H through evolution has fine-tuned an existing lipid binding site to optimize it for LTA4-binding and turnover.List of scientific papersI. Rudberg PC, Tholander F, Thunnissen MM, Haeggstrom JZ (2002). Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms. J Biol Chem. 277(2): 1398-404. https://pubmed.ncbi.nlm.nih.gov/11675384II. Rudberg PC, Tholander F, Thunnissen MM, Samuelsson B, Haeggstrom JZ (2002). Leukotriene A4 hydrolase: selective abrogation of leukotriene B4 formation by mutation of aspartic acid 375. Proc Natl Acad Sci U S A. 99(7): 4215-20. https://pubmed.ncbi.nlm.nih.gov/11917124III. Rudberg PC, Tholander F, Andberg M, Thunnissen MM, Haeggstrom JZ (2004). Leukotriene A4 hydrolase: identification of a common carboxylate recognition site for the epoxide hydrolase and aminopeptidase substrates. J Biol Chem. 279(26): 27376-82. https://pubmed.ncbi.nlm.nih.gov/15078870IV. Tholander F, Kull F, Ohlson E, Shafqat J, Thunnissen MM, Haeggstrom JZ (2005). Leukotriene A4 hydrolase, insights into the molecular evolution by homology modeling and mutational analysis of enzyme from Saccharomyces cerevisiae. J Biol Chem. 280(39): 33477-86. https://pubmed.ncbi.nlm.nih.gov/16024909V. Tholander F, Haeggstrom JZ (2006). Assay for rapid analysis of the tri-peptidase activity of LTA4 hydrolase. [Manuscript]VI. Tholander F, Thunnissen MM, Haeggstrom JZ (2006). Structural basis for peptide hydrolysis by M1 aminopeptidases. [Manuscript]</p
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
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
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
Transcriptome Analyses of the Nematode-trapping Fungus Monacrosporium haptotylum
No full textNematode-trapping fungi are soil living organisms with the ability to infect and kill nematodes. These fungi have developed specialized infection structures, traps for the capture of nematodes. To be able to identify genes in nematode-trapping fungi that are involved in the infection of nematodes cDNA microarrays were constructed. The cDNA microarrays were printed with cDNA reporers obtained from expressed sequence tag (EST sequencing of four different cDNA libraries representing the mycelium and traps of the nematode-trapping fungus Monacrosporium haptotylum, as well as the fungus infecting the nematode Caenorhabditis elegans for 4 h and 24 h, respectively. In total, 8,466 EST seqences were generated from these libraries. Following an assembly of these sequences, 3,518 clones were amplified and printed on the array, 2,822 of fungal, 540 of worm, and 156 of unknown origin. In order to identify genes that are expressed and regulated during the development of traps, total RNA was isolated from knobs and mycelium and hybridized to the cDNA array. In spite of the fact that knobs and mycelium were grown in the same medium a total of 23.3% (657 of 2,822 of the gene representatives were differentially expressed in knobs as compared to mycelium. Several of the genes that were regulated in knobs showed sequence similarities to genes involved in development of plant pathogenic infection structures (appressoria). Typical for trap cells in nematodetrapping fungi is the presence of numerous dense bodies which are organelles related to peroxisomes. The transcriptional profiling of M. haptotylum traps identified one gene representative with homology to the peroxisomal membrane protein Pex11p from S. cerevisiae. This homolog was significantly upregulated in traps (knobs) as compared to mycelium. The Pex11p protein is known to have a role in peroxisome proliferation in yeast. In order to further characterize the M. haptotylum PEX11 homolog, th e full length cDNA was cloned and expressed in the yeast Hansenula polymorpha. The result showed that the M. haptotylum Pex11p could not functionally complement the pex11 mutant of H. polymorpha. In the third study, the changes in the transcripome of M. haptotylum were followed during the various stages of the infection. Isolated knobs from M. haptotylum were used in the infection of the nematode C. elegans. RNA was extracted from the infection samples at four different time-points corresponding to the varoius stages of of the infection (adhesion, penetration and digestion) and was subsequently used for hybridization to the cDNA array. RNA isolated from axenic knobs and noninfected nematodes were used as a reference sample in the hybridization of the cDNA array. In total, 58% (1,562) of the fungal genes represented on the array, were regulated in at least one of the stages of the infection. The most dramatic shift in the fungal transcriptome occurred after 4 h, a time-point associated with the penetration of the nematode
A Multi-Language Comparison of Influences on Author Verification using Character N-Grams
No full textWe create a new multi-language corpus for author verification based on Wikipedia talkpages, and evaluate the influence that differences in topic and time have on character n-gram author profiles. Topic alignment between two texts is found to increase author verification precision, and an authors writing style is found to change over time, but not more significantly after 3 years than after 1 year.Information ArchitectureWISElectrical Engineering, Mathematics and Computer Scienc
A 0.12mm<sup>2</sup> Wien-Bridge Temperature Sensor with 0.1°C (3σ) Inaccuracy from -40°C to 180°C
No full text Resistor-based temperature sensors can achieve much higher resolution and energy efficiency than conventional BJT-based sensors [1], but they typically occupy more area (> 0.25 mm 2 ) and have lower operating temperatures (le 125 {circ} {C}) [2]-[4]. This work describes a 0.12mm 2 resistor-based sensor that uses a Wien-bridge (WB) filter to achieve 0.1 {circ} {C} (3 sigma) inaccuracy from - 40 {circ} {C} to 180 {circ} {C}. Compared to a state-of-the-art WB sensor [4], it occupies 6 × less area and achieves comparable relative accuracy over a 76% wider operating range. Session 10.3 Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic InstrumentationMicroelectronic
A ±25A Versatile Shunt-Based Current Sensor with 10kHz Bandwidth and ±0.25% Gain Error from -40°C to 85°C Using 2-Current Calibration
No full textAccurate current sensing is critical in many industrial applications, such as battery management and motor control. Precise shunt-based current sensors have been reported with gain errors of less than 1% over the industrial temperature range (-40°C to 85°C) [1]–[4]. However, since they are intended for coulomb counting, their bandwidth is limited to a few tens of Hz, making them unsuitable for battery impedance or motor-current sensing. This paper presents a current sensor with a wide (10kHz) bandwidth and a tunable temperature compensation scheme (TCS), which allows it to be flexibly used with different types of shunts while maintaining high accuracy. A low-cost room-temperature calibration scheme is proposed to optimize gain flatness over temperature by exploiting the shunt's self-heating at large currents. Over the industrial temperature range and a ±25A current range, it achieves state-of-the-art gain error (±0.25%) with both low-cost PCB and stable metal-alloy shunts.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic InstrumentationMicroelectronic
An Article About Albertus C. Van Raalte, Author Unknown, Except for Parts Taken from an Article by Anna C. Post
No full textAn article about Albertus C. Van Raalte, author unknown, except for parts taken from an article by Anna C. Post. The author knew first generation persons in the Holland settlement and therefore, the article has some value.https://digitalcommons.hope.edu/vrp_1890s/1012/thumbnail.jp
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