169,776 research outputs found
Effects of acute systemic administration of serotonin2A/C receptor ligands in a delay-based decision-making task in rats.
No full textSerotonin (5-hydoxytryptamine; 5-HT) has been implicated in the regulation of impulsivity, and high levels of impulsive behavior are associated with certain neuropsychiatric disorders. An important aspect of impulsive behavior is the inability to tolerate delays in reward. This study investigated the effects of the 5-HT2A/C receptor agonist DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride] and the 5-HT2A receptor antagonist ketanserin on impulsive behavior measured in a delay-based decision-making task. Male Wistar rats were trained in a T-maze to choose a large but 10-s delayed food reward instead of a small immediate reward. After stable baseline performance (70% choice of large reward), the effects of acute systemic administration of 5-HT2A/C receptor ligands on waiting capacity were tested. Systemic administration of DOI (0.1, 0.3, and 0.5 mg/kg) impaired waiting capacity in a dose-dependent manner, whereas ketanserin had no effect. When combined with ketanserin, DOI did not impair waiting capacity. The data indicate that DOI-induced impairment of the ability to discount a delay in reward in a T-maze is probably regulated by 5-HT2A receptors. Furthermore, this study extends the existing findings of 5-HT2 receptor involvement in different tasks of delay aversion in rodents
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
PCV112 - PATTERN OF USE OF ANTIHYPERTENSIVE DRUGS IN TWO EUROPEAN COUNTRIES: COMPARISON OF THE INDEX THERAPIES AND PERSISTENCE
No full textMitomycin 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
Energy Efficiency and Distributed Solar Energy Targeted to Underserved Communities: Perspectives on the Illinois Future Energy Jobs Act
No full textThis Article focuses on one of the most comprehensive state laws adopted to date, aimed at significantly advancing energy efficiency and distributed solar generation in underserved communities, the Illinois Future Energy Jobs Act (FEJA). It begins by examining what constitutes energy justice and then discusses the disproportionate burdens and benefits related to energy production and use that underserved communities must deal with on a day-to-day basis. The Article then turns to a review of FEJA with a particular emphasis on the critical role community organizations played in designing, negotiating, and implementing the law. These efforts represent important development in both substantive and procedural energy justice. It then looks at the role of one particular community organization, Elevate Energy, in implementing the law with an emphasis on multi-family housing. FEJA, the engagement of community groups in the development and passage of FEJA, and the role of Elevate Energy all play a role in addressing critical issues of energy justice. The Article concludes by looking at new Illinois legislation that would build on FEJA to create more energy-related job opportunities for underserved communities
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
Structural and functional characterization of the p62 complex, a subcomplex of the nuclear pore complex
No full textThe nuclear pore complex (NPC) is a highly conserved eukaryotic protein complex, which perforates
the nuclear envelope and regulates nucleocytoplasmic transport of cargos between the cytoplasm and nucleus. The structure and function of NPCs were examined in recent years by different molecular and structural biology techniques, such as immunoprecipitation, RNA interference, or electron- and fluorescence microscopy, allowing deeper insights into the molecular mechanisms underlying nucleocytoplasmic
transport. In this introduction, I will highlight recent developments in understanding the organization of four subcomplexes of the central region of the NPC, namely, the p62 complex, the Nup93 complex, the Nup107-160 complex, and the Nup155 complex as well as their impact on nucleocytoplasmic transport. In addition, I will discuss the role of these subcomplexes in cell cycle regulation and their impact
on human diseases. Furthermore, the molecular interactions between different transport receptors, cargos, and components of the NPC are described.
The nuclear pore complex (NPC) is the only known gateway for exchange of macromolecules between the cytoplasm and nucleus of eukaryotic cells. One key compound of the NPC is the p62 subcomplex,
which consists of the nucleoporins p62, p54, and p58/p45 and is supposed to be involved in nuclear protein import and export. In this study we show the localization of different domains of the p62 complex by immuno-electron microscopy using isolated nuclei from Xenopus oocytes. To determine the exact position of the p62 complex, we examined the localization of the C- and N-terminal domains of p62 by immunolabeling using domain-specific antibodies against p62. In addition, we expressed epitope-
tagged versions of p62, p54, and p58 in Xenopus oocytes and localized the domains with antibodies against the tags. This first systematic analysis of the domain topology of the p62 complex within the NPC revealed that the p62 complex is anchored to the cytoplasmic face of the NPC most likely by the coiled-coil domains of the three nucleoporins. Furthermore, we found the phenylalanine-glycine (FG)-repeat domain of p62, but not of p58 and p54, to be mobile and flexible nature.
Nuclear pore complexes (NPCs) are large protein complexes, which are embedded in the nuclear envelope (NE) and control the traffic of proteins and RNAs between the nucleus and the cytoplasm in a signal-dependent manner. Transport receptors bind cargos and interact particularly with certain nucleoporins.
Phenylalanine-glycine (FG) repeat motifs were found in about a third of the nucleoporins, functioning as a major docking site for soluble transport receptors. The p62 complex, which contains several FG repeat domains, was previously described to be involved in protein import and to interact directly with soluble transport receptors. To examine the localization of this docking site and to find out how antibodies against single components of the p62 complex influence nucleocytoplasmic transport, we performed in vitro transport assays using nucleoplasmin-GFP as cargo. This cargo was used in transport assays with digitonin-permeabilized HeLa cells, which were treated with antibodies against the p62 complex components, or was directly conjugated to colloidal gold in ultrastructural transport assays, using isolated nuclei from Xenopus oocytes. Our data suggest that antibodies against the components of the p62 complex inhibit or reduce transport of cargos through the NPC. The ultratructural transport studies revealed that the second docking site for cargo/receptor complexes is masked when p62 complex antibodies are used in the transport assay.
During the past few years, evidence accumulated that distinct nuclear pore complex proteins do not only function in the nucleocytoplasmic transport, but also in the regulation of other cellular processes, such as mitosis. To study the function of the p62-complex (i.e. p62, p54, and p58) in a cellular context, we depleted its components from HeLa cells by RNA interference, which led to an arrest in cell growth and an increase of apoptotic cells as analyzed by fluorescence activated cell sorting. In vitro transport studies of p62- and p54-depleted HeLa cells further showed that the depletion of these p62 complex components had a significant inhibitory effect on nuclear protein import. Taken together, these results indicate that the p62 complex is not only critical for mediating nuclear protein import, but also for cell growth and cell division.
To determine the location of different domains of the p62 complex within the 3D structure of the NPC, we localized the different FG-repeat and coiled-coil domains of this subcomplex with immuno-EM. Previous immuno-EM showed controversial results concerning the anchoring sites and the localization of the p62 complex within the 3D structure of the NPC. Our new data revealed that the p62 complex is anchored with its coiled-coil domains to the cytoplasmic side of the NPC and that its FG-repeat domains show differences in their flexibility and their distribution within the 3D architecture of the NPC. Thus, the FG-repeat domain of the nucleoporin p62 could be found at the cytoplasmic as well as at the nuclear
side of the NPC, whereas the FG-repeat domains of p54 and p58 were restricted to the cytoplasmic side. This might be due to different anchoring sites of the distint FG-repeat domains, the varied length of the FG-repeat domains of the complex, and differences in the biophysical behavior of the FG-repeat domains.
Recently, a complementary technique to immuno-EM was established to observe FG-repeat domains
in vitro by AFM. Lim et al. examined the biophysical behavior of the FG-repeat domain of Nup153, immobilized to a gold dot, by AFM simulating nuclear import by adding importin β.and RanGTP (Lim, Fahrenkrog et al. 2007). The immobilized FG-repeat domains formed a polymer brush with a certain height, which collapsed after addition of importin β. This collapse could be reversed after addition of RanGTP, demonstrating a new biophysical principle for nucleocytoplasmic transport. The AFM-studies were attended by immuno-EM-studies with isolated nuclei of Xenopus oocytes, which showed that, after addition of importin β, the FG-repeat domains of Nup153 collapse to their anchoring sites at the nuclear basket.
It would be interesting to use the same experimental approach equally for the different FG-repeat domains of the p62 complex in order to examine if the FG-repeat domains can form polymer brushes similar to the ones formed by the FG-repeat domains of Nup153. Beyond that, it would be worth to uncover
the anchoring sites of the FG-repeat domains of the p62 complex by immuno-EM after addition of importin β (Lim, Fahrenkrog et al. 2007). In the near future, progress in EM tomography will facilitate the localization of antibodies against certain nucleoporins without the use of gold particles, which would reveal the exact binding sites of the antibodies to structural elements of the NPC
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