467 research outputs found

    Comparative study of the power transferred from satellite-magnetosphere interactions to auroral emissions

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    Io's interaction with the Jovian magnetosphere generates a power of about 1012 W which propagates as Alfvn waves along the magnetic field lines and is partly transferred to electrons, resulting in intense auroral emissions. A recent study of the power transmission along the Io flux tube and of the electron acceleration at high latitudes showed that the power of the observed emissions is well explained by assuming filamentation of the Alfvn waves in the torus and the acceleration of the electrons at high latitude. At Jupiter, UV footprints related to Europa and Ganymede have also been observed. At Saturn recent observations revealed a weak UV footprint of Enceladus. We apply the Io interaction model to the Europa and Enceladus interactions. We show that the Alfvn wave filamentation leads to a precipitating electron power consistent with the power of the observed UV footprints

    C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins

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    An expanded GGGGCC repeat in C9orf72 is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. A fundamental question is whether toxicity is driven by the repeat RNA itself and/or by dipeptide repeat proteins generated by repeat-associated, non-ATG translation. To address this question we developed in vitro and in vivo models to dissect repeat RNA and dipeptide repeat protein toxicity. Expression of pure repeats in Drosophila caused adult-onset neurodegeneration attributable to poly-(glycine-arginine) proteins. Thus, expanded repeats promoted neurodegeneration through neurotoxic proteins. Expression of individual dipeptide repeat proteins with a non-GGGGCC RNA sequence showed both poly-(glycine-arginine) and poly-(proline-arginine) proteins caused neurodegeneration. These findings are consistent with a dual toxicity mechanism, whereby both arginine-rich proteins and repeat RNA contribute to C9orf72-mediated neurodegeneration

    Kolb in de klas: vijf docenten in het hoger onderwijs onderzoeken de waarde van Kolbs leerstijlen voor hun eigen onderwijspraktijk

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    Deze bundel bevat de resultaten van vijf kortlopende onderzoeken door deelnemers aan de masteropleiding Teaching in Higher Education, allen docenten in het hoger onderwijs, naar de waarde van de leerstijlen van Kolb voor hun eigen lespraktijk. Uit de onderzoeken komt naar voren dat het onderwijsaanbod niet geheel bepaald wordt door de leerstijl van de docent, maar dat het zou kunnen zijn dat het wel deels hierdoor beïnvloed wordt. Ook zijn vier manieren geïdentificeerd waarop docenten rekening houden met individuele verschillen tussen studenten. Ten aanzien van het verrichten van dit type onderzoek blijkt een noodzaak om het vóórkomen van en voorkeuren voor bepaalde leerstijlen op verschillende manieren te meten en om zowel met kwalitatieve als kwantitatieve methoden te werken; daarbij kan de Chi-square goodness-of-fit test voor één groep, goede diensten bewijzen. Ook lijkt het dat aangetroffen verschillen in leerstijlen wel eens veroorzaakt zouden kunnen zijn tussen verschillen in wat en hoe men meet, en geen reflectie zijn van feitelijke verschillen in leerstijlen

    Paper-based chromatic toxicity bioassay by analysis of bacterial ferricyanide reduction

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    Water quality assessment requires a continuous and strict analysis of samples to guarantee compliance with established standards. Nowadays, the increasing number of pollutants and their synergistic effects lead to the development general toxicity bioassays capable to analyse water pollution as a whole. Current general toxicity methods, e.g. Microtox®, rely on long operation protocols, the use of complex and expensive instrumentation and sample pre-treatment, which should be transported to the laboratory for analysis. These requirements delay sample analysis and hence, the response to avoid an environmental catastrophe. In an attempt to solve it, a fast (15 min) and low-cost toxicity bioassay based on the chromatic changes associated to bacterial ferricyanide reduction is here presented. E. coli cells (used as model bacteria) were stably trapped on low-cost paper matrices (cellulose-based paper discs, PDs) and remained viable for long times (1 month at -20 °C). Apart from bacterial carrier, paper matrices also acted as a fluidic element, allowing fluid management without the need of external pumps. Bioassay evaluation was performed using copper as model toxic agent. Chromatic changes associated to bacterial ferricyanide reduction were determined by three different transduction methods, i.e. (i) optical reflectometry (as reference method), (ii) image analysis and (iii) visual inspection. In all cases, bioassay results (in terms of half maximal effective concentrations, EC50) were in agreement with already reported data, confirming the good performance of the bioassay. The validation of the bioassay was performed by analysis of real samples from natural sources, which were analysed and compared with a reference method (i.e. Microtox). Obtained results showed agreement for about 70% of toxic samples and 80% of non-toxic samples, which may validate the use of this simple and quick protocol in the determination of general toxicity. The minimum instrumentation requirements and the simplicity of the bioassay open the possibility of in-situ water toxicity assessment with a fast and low-cost protocolPostprint (author's final draft

    The translator’s disquiet or daring to make Bernardo Soares speak catalan

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    La relació entre traducció literària i edició, entesa com a fixació de l’original, afegeix complexitat a un procés que generalment només s’estudia com a generador de diversitat a l’extrem dels resultats, a l’output de la traducció. La història editorial del Llibre del desassossec, de Fernando Pessoa, esdevé un exemple de com pot afegir-se a aquesta complexitat ja coneguda el que suposa l’edició diferida del text. Tot plegat es tracta d’una oportunitat per posar en relleu les relacions entre els moments diversos del fet literari: la creació, l’edició, la publicació, la traducció i les reedicions diverses. S’estudia en aquest article la traducció com a procés de presa de decisions, multiplicadora de les opcions possibles, i també des del concepte de traductibilitat, entès com a atractiu que implica el text a traduir.The relationship between literary translation and editing, understood as the stabilisation of the original, increases the complexity of a process that is generally only studied in the diversification of the final product, in the output of the translation. An editorial history of the Book of Disquiet, by Fernando Pessoa, becomes an example of how we can add the differed edition of the text to this already understood complex process. In its entirety, this is an opportunity to demonstrate the relationships that exist between diverse literary moments: creation, edition, publishing, translating, and various re-editions. This article studies translation as a process of decision-making which multiplies possible options, as well as through the concept of translatability, understood as the attraction factor implicating the text in translation

    Aβ43 is neurotoxic and primes aggregation of Aβ40 in vivo

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    The involvement of Amyloid-β (Aβ) in the pathogenesis of Alzheimer’s disease (AD) is well established. However, it is becoming clear that the amyloid load in AD brains consists of a heterogeneous mixture of Aβ peptides, implying that a thorough understanding of their respective role and toxicity is crucial for the development of efficient treatments. Besides the well-studied Aβ and Aβ species, recent data have raised the possibility that Aβ peptides might be instrumental in AD pathogenesis, because they are frequently observed in both dense and diffuse amyloid plaques from human AD brains and are highly amyloidogenic in vitro. However, whether Aβ is toxic in vivo is currently unclear. Using Drosophila transgenic models of amyloid pathology, we show that Aβ peptides are mainly insoluble and highly toxic in vivo, leading to the progressive loss of photoreceptor neurons, altered locomotion and decreased lifespan when expressed in the adult fly nervous system. In addition, we demonstrate that Aβ species are able to trigger the aggregation of the typically soluble and non-toxic Aβ, leading to synergistic toxic effects on fly lifespan and climbing ability, further suggesting that Aβ peptides could act as a nucleating factor in AD brains. Altogether, our study demonstrates high pathogenicity of Aβ species in vivo and supports the idea that Aβ contributes to the pathological events leading to neurodegeneration in AD

    Arabidopsis KCBP interacts with AIR9 but stays in the cortical division zone throughout mitosis via its MyTH4-FERM domain

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    The preprophase band of microtubules performs the crucial function of marking the plane of cell division. Although the preprophase band depolymerises at the onset of mitosis, the division plane is 'memorized' by a cortical division zone to which the phragmoplast is attracted during cytokinesis. Proteins have been discovered that are part of the molecular memory but little is known about how they contribute to phragmoplast guidance. Previously, we found that the microtubule-associated protein AIR9 is found in the cortical division zone at preprophase and returns during cell plate insertion but is absent from the cortex during the intervening mitosis. To identify new components of the preprophase memory, we searched for proteins that interact with AIR9. We detected the kinesin-like calmodulin-binding protein, KCBP, which can be visualized at the predicted cortical site throughout division. A truncation study of KCBP indicates that its MyTH4-FERM domain is required for linking the motor domain to the cortex. These results suggest a mechanism by which minus-end-directed KCBP helps guide the centrifugally expanding phragmoplast to the cortical division site.Instituto de Biotecnologia y Biologia Molecula

    Hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: HARP-trial

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    Contains fulltext : 88436.pdf (publisher's version ) (Open Access)BACKGROUND: Transplantation is the only treatment offering long-term benefit to patients with chronic kidney failure. Live donor nephrectomy is performed on healthy individuals who do not receive direct therapeutic benefit of the procedure themselves. In order to guarantee the donor's safety, it is important to optimise the surgical approach. Recently we demonstrated the benefit of laparoscopic nephrectomy experienced by the donor. However, this method is characterised by higher in hospital costs, longer operating times and it requires a well-trained surgeon. The hand-assisted retroperitoneoscopic technique may be an alternative to a complete laparoscopic, transperitoneal approach. The peritoneum remains intact and the risk of visceral injuries is reduced. Hand-assistance results in a faster procedure and a significantly reduced operating time. The feasibility of this method has been demonstrated recently, but as to date there are no data available advocating the use of one technique above the other. METHODS/DESIGN: The HARP-trial is a multi-centre randomised controlled, single-blind trial. The study compares the hand-assisted retroperitoneoscopic approach with standard laparoscopic donor nephrectomy. The objective is to determine the best approach for live donor nephrectomy to optimise donor's safety and comfort while reducing donation related costs. DISCUSSION: This study will contribute to the evidence on any benefits of hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy. TRIAL REGISTRATION: Dutch Trial Register NTR1433

    1281O Atezolizumab (atezo) vs platinum-based chemo in blood-based tumour mutational burden-positive (bTMB+) patients (pts) with first-line (1L) advanced/metastatic (m)NSCLC: Results of the Blood First Assay Screening Trial (BFAST) phase III cohort C

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    Background: TMB is a promising biomarker for immunotherapy in NSCLC, but current data are mostly retrospective. As not all pts may have sufficient tissue for comprehensive biomarker testing, bTMB was prospectively tested as a novel biomarker using targeted next-generation sequencing. BFAST (NCT03178552), a global, open-label, multi-cohort trial, evaluated safety and efficacy of targeted therapies or immunotherapy in biomarker-selected pts with unresectable mNSCLC. Here we present results from Cohort C of 1L atezo vs platinum-based chemo in pts with bTMB+ mNSCLC. Methods: We planned to randomise ≈440 pts with 1L mNSCLC with measurable disease per RECIST 1.1 and bTMB ≥10 (9.1 mut/Mb; FMI bTMB assay) 1:1 to atezo 1200 mg IV every 3 weeks or chemo and stratified by tissue availability, ECOG PS, bTMB and histology. The primary endpoint was INV-PFS per RECIST 1.1 in bTMB ≥16 (14.5 mut/Mb) pts. Key secondary endpoints included OS in bTMB ≥10 (intent to treat, ITT) and bTMB ≥16 pts, and INV-PFS in ITT pts. Results: 471 pts were assigned to atezo (n=234) or chemo (n=237). At baseline, 72% had non-squamous histology, 2% never smoked and median SLD was 103 mm. 145 pts with bTMB ≥16 were assigned to atezo and 146 to chemo. At data cutoff (21 May 2020) minimum follow up was 6 mo. INV-PFS difference in bTMB ≥16 pts for atezo vs chemo was not significant (P=0.053; Table). Grade 3-4 TRAEs occurred in 18% (atezo) vs 46% (chemo) of pts. Serious TRAEs occurred in 12% (atezo) vs 14% (chemo). Results at other bTMB thresholds and by F1L CDx will also be presented as an exploratory analysis. Conclusions: The primary PFS endpoint in bTMB ≥16 pts was not met. OS was numerically better with atezo vs chemo but the difference was not statistically significant. The safety profile of atezo vs chemo was favourable and consistent with atezo monotherapy across indications
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