169,955 research outputs found
Endotoxin-, glutamate- and drug-induced inflammation and cytotoxicity with emphasis on signal transduction mechanisms
No full textInflammatory cells such as monocytes and glial cells play an important role in the pathogenesis of ischemic- or drug-induced brain or liver injury. Excessive concentrations of glutamate is toxic to neural cells, and triggers a series of transcriptional events beginning with the expression of the immediate early genes like c-fos and c-jun, which in turn affect the expression of other genes necessary for the development of brain injury. Glial cells are important mediators in such response as they are responsible for the secretion of proinflammatory cytokines and chemokines which in turn will cause recruitment of immune cells into the brain. Using primary rat glial cell cultures we found that lipopolysaccharide (LPS)- induced c-fos expression was p38 MAPK-dependent and occurred via the activation of the SRE or the CRE elements in the promoter. In contrast to what has been shown in neurons, we found that glutamate-induced c-fos expression in glial cells involves a novel calciumdependent pathway. This mechanism requires the participation of mGluR5, mobilization of ER-calcium and de-repression of DREAM at the DRE element in the c-fos promoter.Similar mechanisms of inflammation as seen in the brain also occur in the liver, where Kupffer cells play a similar role functioning as the hepatic macrophages in their ability to release pro-inflammatory cytokines. Drug-induced hepatotoxicity is a major problem in drug development since preclinical in vitro as well as in vivo animal models usually are of little value for prediction of hepatotoxicity in humans. Pure hepatocyte cultures are generally not a sensitive enough model system to predict drug-induced cytotoxicity. We therefore developed a novel in vitro system containing both monocytes and hepatocytes. Ximelagatran (thrombin inhibitor) as well as the PPAR-gamma agonists troglitazone (hepatotoxic) and rosiglitazone (not hepatotoxic) were used as model compounds.Studies in single cultures of monocytes (THP-1) showed a ximelagatran dependent release of pro-inflammatory chemokines and decreased cell viability, which was shown by inhibitors to involve the JNK- and ERK-signal transduction pathways.A novel human in vitro co-culture model system containing THP-1 and hepatocytes (Huh-7) was established where the cells were separated by a permeable membrane. In such cocultures troglitazone-induced cytotoxicity was more apparent and observed earlier than using single cultures of either Huh-7 or THP-1 cells, whereas rosiglitazone showed no cytotoxicity in either system. The troglitazone effect was accompanied by a much greater expression of genes encoding pro-inflammatory cytokines, chemokines and several other stress-related genes using the co-culture system as compared to single cell type cultures. Conditioned medium from troglitazone-treated THP-1 cells decreased the viability of Huh-7 cells indicate the release of monocyte-derived mediators. It is concluded that such co-culture system might constitute a valuable tool for predictions of drug-induced hepatotoxicity.List of scientific papersI. Simi A, Edling Y, Ingelman-Sundberg M, Tindberg N (2005). Activation of c-fos by lipopolysaccharide in glial cells via p38 mitogen-activated protein kinase-dependent activation of serum or cyclic AMP/calcium response element. J Neurochem. 92(4): 915-24. https://pubmed.ncbi.nlm.nih.gov/15686494II. Edling Y, Ingelman-Sundberg M, Simi A (2007). Glutamate activates c-fos in glial cells via a novel mechanism involving the glutamate receptor subtype mGlu5 and the transcriptional repressor DREAM. Glia. 55(3): 328-40. https://pubmed.ncbi.nlm.nih.gov/17120244III. Edling Y, Andersson T. B., Porsmyr-Palmertz M, Ingelman-Sundberg M (2007). Pro-inflammatory response and adverse drug reactions: mechanisms of action of ximelagatran on chemokine and cytokine activation in a monocyte in vitro model. [Submitted]IV. Edling Y, Sivertsson L, Butura A, Ingelman-Sundberg M, Ek M (2008). Increased sensitivity for drug-induced hepatotoxicity using a novel human in vitro coculture model. [Submitted]</p
The Phenomenology of Specialization of Criminal Suspects
No full textA criminal career can be either general, with the criminal committing different types of crimes, or specialized, with the criminal committing a specific type of crime. A central problem in the study of crime specialization is to determine, from the perspective of the criminal, which crimes should be considered similar and which crimes should be considered distinct. We study a large set of Swedish suspects to empirically investigate generalist and specialist behavior in crime. We show that there is a large group of suspects who can be described as generalists. At the same time, we observe a non-trivial pattern of
specialization across age and gender of suspects. Women are less prone to commit crimes of certain types, and, for instance, are more prone to specialize in crimes related to fraud. We also find evidence of temporal specialization of suspects. Older persons are more specialized than younger ones, and some crime types are preferentially committed by suspects of different ages
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
PI3K class 1B controls the cell cycle checkpoint promoting cell proliferation in hepatocellular carcinoma
No full textA 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
The Role of Substrate Temperature and Magnetic Filtering for DLC by Cathodic Arc Evaporation
No full textDiamond-like carbon (DLC) films were deposited using two different types of high current arc evaporation. The first process used a magnetic particle filter to remove droplets from the plasma. For the second process, the samples were put into a metallic cage which was placed directly above the plasma source. For both processes, we varied the substrate temperature from 21 to 350 °C in order to investigate the temperature effect. The samples were characterized using SEM, AFM, XPS, Raman Spectroscopy, Ellipsometry, Photometry, and Nano Indentation in order to compare both methods of deposition and provide a careful characterization of such DLC films. We found that the sp3 content and the hardness can be precisely adjusted by changing the substrate temperature. Furthermore, in the case of unfiltered deposition, the optical constants can be shifted in the direction of higher absorbance in order to produce black and hard carbon coatings
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