180,992 research outputs found

    Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in pancreatic cancer cells

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    Gli effetti anti-tumorali dei cannabinoidi sono noti da alcuni decenni e sono stati studiati in vari tipi di tumore. Nonostante il crescente interesse verso l’utilizzo di questi composti come potenziali farmaci anti-tumorali, il loro meccanismo d’azione resta ancora poco chiaro. L’obiettivo di questo progetto di dottorato è stato quello di analizzare i meccanismi molecolari attraverso i quali i cannabinoidi inducono morte cellulare autofagica in cellule di adenocarcinoma pancreatico. Analisi di metabolomica combinate con saggi di attività enzimatica, mostrano che il trattamento della linea cellulare Panc1 con due cannabinoidi sintetici, GW e ACPA, determina un significativo aumento dell’attivazione di AMPK, dovuto all’aumentato rapporto AMP:ATP dipendente da stress ossidativo. I risultati mostrano, inoltre, che le specie reattive dell’ossigeno (ROS) indotte dai cannabinoidi promuovono la traslocazione dell’enzima gliceraldeide-3 fosfato deidrogenasi (GAPDH) nel nucleo, fenomeno amplificato ulteriormente dall’attivazione della chinasi AMPK, con la conseguente attenuazione della via glicolitica. Il trattamento con i cannabinoidi determina anche un accumulo di NADH dipendente da ROS, suggerendo un blocco della catena respiratoria e, a sua volta, del ciclo di Krebs. I cannabinoidi, inoltre, inibiscono la via Akt/c-Myc, effetto che determina la diminuzione dell’attività dell’enzima piruvato chinasi isoforma M2 (PKM2), de-regolando ulteriormente la glicolisi e inibendo l’incorporazione di glutammina. In conclusione, questo studio mostra tramite quali vie i cannabinoidi regolano il metabolismo energetico, inducono autofagia e inibiscono la proliferazione di cellule di adenocarcinoma pancreatico.The anti-tumoral effects of cannabinoids have been described in different tumor systems, but their mechanism of action remains unclear. The aim of this thesis was to unravel key pathways mediating cannabinoid dependent inhibition of pancreatic cancer cell growth through the analysis of energetic metabolism. Panc1 cells treated with two synthetic cannabinoids, GW and ACPA, showed elevated AMPK activation induced by a ROS-dependent increase of AMP:ATP ratio. ROS promoted nuclear translocation of GAPDH, which was further amplified by AMPK, thereby attenuating glycolysis. Furthermore, ROS determined the accumulation of NADH, suggestive of a blockage in the respiratory chain, which in turn inhibited the Krebs cycle. Concomitantly, inhibition of Akt/c-Myc pathway led to a decreased activity of pyruvate kinase isoform M2 (PKM2), further down-regulating glycolysis, and glutamine uptake. Altogether, these alterations of cancer cell metabolism mediated by cannabinoids resulted in a strong induction of autophagy and inhibition of cell growth

    Regulation of catalase expression in chronic lymphocytic leukemia cells.

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    The aim of this study is to investigate the genetic, transcriptional and post-transcriptional processes that underlie the catalase expression in CLL subtypes

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    Ophthalmology. 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

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    We 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

    Raising teenagers’ awareness of musculoskeletal health through LifeLab: a collaboration between school students, teachers and clinical academic researchers

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    Background: Musculoskeletal (MSK) disease is the major cause of years lived with disability in the UK. The UK is behind other comparable countries in confronting consequences of long-term diseases. One potentially effective approach is by educating people to become more health literate. Early life interventions relating to exercise and good MSK health practices may be an effective addition to traditional approaches.LifeLab is a science-based approach to improving teenagers’ health-related attitudes and behaviour. The LifeLab approach was developed at the University of Southampton and combines educationalists, scientists, clinical researchers and school children and has been effective in improving young peoples’ understanding of the nature of diseases and reasoning about health issues. However, no specific MSK health education components have previously been included in LifeLab.Methods: In 2014 the first MSK LifeLab workshop was designed with educationalists and researchers in biomechanics, occupational therapy, podiatry, and physiotherapy from the MSK Research Cluster at Southampton for year 8 (age 12-13) school students. The workshops aimed to promote young peoples’ health literacy in musculoskeletal health and integrated experiential learning using 3D motion analysis, real-time ultrasound scanning of muscles contracting; radiographs of normal and osteoarthritis foot joints; anatomy models and hand and hip joint implants. The workshops covered a) the impact of osteoarthritis joint disease on daily life b) capturing and illustrating joint movement using state of the art 3D motion analysis technology and c) an in-depth look at muscles using ultrasound imaging. Learning objectives included students being able to:1. Identify key components of active healthy living for bones, muscles and joints 2. Observe patterns in how healthy joints can move and contrast patterns with injured joint movement3. Discover what role muscles play in healthy joints 4. Compare healthy joint structures with arthritic joint structures Results: 58 students from 3 state secondary schools, attended a university widening participation outreach day within which the MSK LifeLab workshop was run. On the same day the students also attended workshops in Humanities and Oceanography. When asked which workshop of the outreach day was their favourite 43 % of the students identified the MSK workshops. Feedback on why the workshops were enjoyable included; “I enjoyed biomechanics because I like looking at how things work and move”; “Ostioarphritus. I'm into sports &amp; find the body interesting”; “The bones because you got to find out about the body”. The interactive nature of the workshop with teenagers having hands on learning was also well received “My favourite was bones because they made it fun”; “The bones experiments because the technology involved was awesome.”Conclusions: Using interactive MSK workshops as part of LifeLab presents an exciting health literacy approach to encourage young people to start to engage in understanding their MSK health. Acknowledgements: These are not included in the abstract but will appear if we get a paper accepted. LifeLab, has been developed as a joint initiative, involving, in addition to the University of Southampton and the University Hospital Southampton NHS Foundation Trust; the MRC Lifecourse Epidemiology Unit, the University of Southampton (UoS) Faculty of Medicine and Southampton Education School, the Mathematics and Science Learning Centre (MSLC), the NIHR Southampton Biomedical Research Centre and the Garfield Weston Foundation. KWT is supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre Some facilities and personnel in the MSK Research Cluster are funded by Arthritis Research UK.<br/

    Chthamalus alani Chan, Chen, Dando, Southward & Southward, 2016, nom. nov.

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    Chthamalus alani nom. nov. urn:lsid:zoobank.org:act:4C460612-D362-49BA-9A20-F2895C4CE1F5 the authority for this species name change rests with BKK Chan Figs 2A and 2B and 3–5 Chthamalus southwardorum Pitombo & Burton, 2007: 9, figs 9–14 [12] Chthamalus southwardorum A.—Wares et al., 2009: Table 1. [14] Etymology. Pitombo & Burton [12] stated explicitly that Chthamalus southwardorum is named “in honor of Dr A.J. Southward, for his extensive contribution to the knowledge of chthamalids and his careful collecting during the Tropical eastern Pacific Expedition”. Unfortunately, the suffix -orum indicates “for men or for man (men) and woman (women) together” (ICZN, 4th edition, 1999 Article 31.1.2). Since there is clear evidence of a lapsus calami in the original publication (ICZN ART 32.5.1) the name C. southwardorum is not admissible under ICZN Art. 21.13 and has to be treated as an incorrect original spelling that should be corrected to southwardi, taking the authorship and date of Pitombo & Burton [12]. However, Chthamalus southwardi Pitombo & Burton, 2007 is a junior primary homonym of Chthamalus southwardi Poltaruka, 2000 and therefore an invalid name (ICZN Art 57.2) and so a new replacement name is required for C. southwardorum. In the present study, I (BKKC) rename C. southwardorum as Chthamlaus alani, again in honour of Prof. Alan Southward, but using his first name, for his contributions to barnacle distribution, ecology and taxonomy. Specimens examined. AJS-2, 10 specimens, high intertidal shores, La Paz Bay, 24° 13' N, 110° 18.6' W, 3 Nov 1978; AJS-3, 7 specimens, intertidal shores, Point Lobos, Todos Santos, Baja California Sur, Mexico, 23° 24.8' N, 110° 57' W, 4 Nov 1978; TEPE78-36, 10 specimens, Ocean Front, Mazatlan, Sinaloa, Mexico, exposed rocky shores with large boulders, 23° 11.7' N, 106° 25.5' W, 19 April 1978. Diagnosis. Chthamalus with cirrus I having bidenticulate setae with or without basal guards on the distalmost segment of the posterior ramus and cirrus II having bidenticulate setae with basal guards on the two distalmost segments of the posterior ramus and the distalmost segment of the anterior ramus. Tergoscutal flaps orange-brown in colour when alive. COI sequence (Gene Bank Number KU356723). Description. Shell depressed, sutures between plates visible (Fig 2A and 2B). External surface white and smooth, sheath white, with ribs at the basal region, not extending to the apex (Fig 2A and 2B). Internal colour of shell white. Orifice oval, scutum and tergum articulated with a marked angle (Figs 2A and 2B and 3D). Tergoscutal flaps orange-brown when alive (Fig 2A and 2B), colour fades out when preserved in ethanol or formalin. Scutum triangular, basal margin about twice as long as tergal margin (Fig 3). Tergal margin with a wide and elevated articular ridge, ridge extending beyond the tergal margin, articular furrow wide. Occludent margin straight, without teeth. Adductor muscle pit oval and deep, not extending to the basal margin. Lateral depressor muscle scar deep and smooth (Fig 3). Tergum trapezoid, external surface smooth near the apex, basal region with growth lines or striations, spur wide and not obvious, basal margin with 4 rostral depressor muscle crests (Fig 3). Segment counts on cirri I-III were based on five specimens collected from Mazatlan, Mexico (TEPE-78-36). Segment counts on cirri IV-VI were based on a single specimen from Mazatlan, Mexico (Table 4). Cirrus I: posterior ramus 5 to 6-segmented (Fig 4A), the distalmost segment bears bidenticulate setae with or without basal guards (Fig 4B), serrulate type setae common on all segments of the rami, anterior ramus 6 to 8, serrulate type, setae common on all segments (Fig 4A, Table 4). Cirrus II: posterior ramus 4 to 7-segmented, the two distalmost segments bear bidenticulate setae with basal guards, anterior ramus 5- or 6-segmented, one or two of the distalmost segments have bidenticulate setae with basal guards, serrulate type setae common on both rami (Fig 4C and 4D, Table 4). Cirrus III: anterior and posterior rami similar in length (anterior and posterior rami length ratio = 0.9 ± 0.06), posterior ramus 11 to 16-segmented, anterior ramus 11 to 16-segmented (Fig 4E, Table 4). Cirrus IV: both anterior and posterior rami 16-segmented (Fig 4F). Cirrus V: posterior ramus 18-segmented, anterior ramus 19-segmented (Fig 4G). Cirrus VI: posterior ramus 18-segmented, anterior ramus 19-segmented (Fig 4H). Intermediate segments of both rami on cirri III-VI bear two pairs of long serrulate setae and three pairs of shorter simple setae (Fig 4E–4H). Note: cirrus I of C. anisopoma has bidenticulate setae without basal guards, whilst cirrus I of C. alani nom. nov. and C. newmani sp. nov. has bidenticulate setae with or without basal guards. doi:10.1371/journal.pone.0149556.t004 Maxilla bilobed, serrulate setae on apex of both lobes and on superior margin (Fig 5A). Maxillule notched, two large setae above notch, notch small, 8 setae on cutting margin below notch, inferior angle protuberant with bundles of simple setae (Fig 5B and 5C). Mandible has 4 major teeth, fourth tooth bidenticulate, pecten with 16 small teeth, inferior angle tipped with two pointed teeth (Fig 5D and 5E). Mandibular palp rectangular, serrulate setae on all margins (Fig 5F). Labrum concave, with 6–7 small teeth on both sides of the cutting edge (Fig 5G and 5H). Penis without basi-dorsal point. Distribution. Northern limit probably at about 29° N inside the Gulf of California and 24° 40' N on the Pacific coast; southern limit unknown, but probably north of 15° N. The holotype and paratypes of C. southwardorum Pitombo & Burton, 2007 were collected in the San Cristovan river estuary, San Blas, Nayarit, Mexico (21° 30' 54'' N, 105° 15' 53'' W), attached to an oyster shell, low midlittoral zone. Pitombo and Burton stated that the distribution of C. southwardorum was from Bahía Magdalena, Baja California Sur, Mexico to Puerto Chicama, Peru, but they did not distinguish it from the new species C. newmani described below.Published as part of Benny K. K. Chan, H. - N. Chen, P. R. Dando, A. J. Southward & E. C. Southward, 2016, Biodiversity and Biogeography of Chthamalid Barnacles from the North-Eastern Pacific (Crustacea Cirripedia), pp. 1-51 in PLoS ONE 11 (3) on pages 8-13, DOI: 10.1371/journal.pone.0149556, http://zenodo.org/record/116158

    A Multi-Language Comparison of Influences on Author Verification using Character N-Grams

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    We 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

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    Resistor-based temperature sensors can achieve much higher resolution and energy efficiency than conventional BJT-based sensors [1], but they typically occupy more area (&gt; 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

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    Accurate 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
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