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- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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- Zaborowski, AM, et al.
(author)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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In: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Journal article (peer-reviewed)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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| 12. |
- Lissek, T, et al.
(author)
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Building Bridges through Science
- 2017
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In: Neuron. - : Elsevier BV. - 1097-4199 .- 0896-6273. ; 96:4, s. 730-735
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Journal article (peer-reviewed)
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| 13. |
- Rousseau-Nepton, L., et al.
(author)
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SIGNALS : I. Survey description
- 2019
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 489:4, s. 5530-5546
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Journal article (peer-reviewed)abstract
- SIGNALS, the Star formation, Ionized Gas, and Nebular Abundances Legacy Survey, is a large observing programme designed to investigate massive star formation and HII regions in a sample of local extended galaxies. The programme will use the imaging Fourier transform spectrograph SITELLE at the Canada-France-Hawaii Telescope. Over 355 h (54.7 nights) have been allocated beginning in fall 2018 for eight consecutive semesters. Once completed, SIGNALS will provide a statistically reliable laboratory to investigate massive star formation, including over 50 000 resolved HII regions: the largest, most complete, and homogeneous data base of spectroscopically and spatially resolved extragalactic HII regions ever assembled. For each field observed, three datacubes covering the spectral bands of the filters SN1 (363386 nm), SN2 (482-513 nm), and SN3 (647-685 nm) are gathered. The spectral resolution selected for each spectral band is 1000, 1000, and 5000, respectively. As defined, the project sample will facilitate the study of small-scale nebular physics and many other phenomena linked to star formation at a mean spatial resolution of similar to 20 pc. This survey also has considerable legacy value for additional topics, including planetary nebulae, diffuse ionized gas, and supernova remnants. The purpose of this paper is to present a general outlook of the survey, notably the observing strategy, galaxy sample, and science requirements.
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| 14. |
- Tobias, Deirdre K, et al.
(author)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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In: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Research review (peer-reviewed)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 15. |
- Falgas, N., et al.
(author)
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Contribution of CSF biomarkers to early-onset Alzheimer's disease and frontotemporal dementia neuroimaging signatures
- 2020
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 41:8, s. 2004-2013
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Journal article (peer-reviewed)abstract
- Prior studies have described distinct patterns of brain gray matter and white matter alterations in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), as well as differences in their cerebrospinal fluid (CSF) biomarkers profiles. We aim to investigate the relationship between early‐onset AD (EOAD) and FTLD structural alterations and CSF biomarker levels. We included 138 subjects (64 EOAD, 26 FTLD, and 48 controls), all of them with a 3T MRI brain scan and CSF biomarkers available (the 42 amino acid‐long form of the amyloid‐beta protein [Aβ42], total‐tau protein [T‐tau], neurofilament light chain [NfL], neurogranin [Ng], and 14‐3‐3 levels). We used FreeSurfer and FSL to obtain cortical thickness (CTh) and fraction anisotropy (FA) maps. We studied group differences in CTh and FA and described the “AD signature” and “FTLD signature.” We tested multiple regression models to find which CSF‐biomarkers better explained each disease neuroimaging signature. CTh and FA maps corresponding to the AD and FTLD signatures were in accordance with previous literature. Multiple regression analyses showed that the biomarkers that better explained CTh values within the AD signature were Aβ and 14‐3‐3; whereas NfL and 14‐3‐3 levels explained CTh values within the FTLD signature. Similarly, NfL levels explained FA values in the FTLD signature. Ng levels were not predictive in any of the models. Biochemical markers contribute differently to structural (CTh and FA) changes typical of AD and FTLD.
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| 20. |
- Perez-Tomas, A, et al.
(author)
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Schottky versus bipolar 3.3 kV SiC diodes
- 2008
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In: SEMICONDUCTOR SCIENCE AND TECHNOLOGY. - : IOP Publishing. - 0268-1242 .- 1361-6641. ; 23:12, s. 125004-
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Journal article (peer-reviewed)abstract
- A comparative study of the electrical characteristics of 3.3 kV SiC Schottky barrier (SBD), junction bipolar Schottky (JBS) and PiN diodes is presented. 3.3 kV class 4H-SiC SBD, JBS and PiN diodes have been fabricated with an analogous technology process on similar epi wafers. Diodes have been characterized in forward, reverse and switching mode in the 25 degrees C - 300 degrees C temperature range. The optimum performance of the diodes depends on the adequate use of the unipolar or bipolar advantages and is established by the final application specifications. In this respect, a reverse recovery charge versus on-resistance diagram for different current densities is also presented. DC stress tests have been performed to investigate the forward voltage drift, related to the formation of stacking faults, during the bipolar mode of operation.
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| 21. |
- Brosselard, P, et al.
(author)
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Low loss, large area 4.5 kV 4H-SiC PIN diodes with reduced forward voltage drift
- 2009
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In: SEMICONDUCTOR SCIENCE AND TECHNOLOGY. - : IOP Publishing. - 0268-1242 .- 1361-6641. ; 24:9, s. 095004-
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Journal article (peer-reviewed)abstract
- 4H-SiC PIN diodes have been fabricated on a Norstel P+/N/N+ substrate with a combination of Mesa and JTE as edge termination. A breakdown voltage of 4.5 kV has been measured at 1 mu A for devices with an active area of 2.6 mm(2). The differential on-resistance at 15 A (600 A cm(-2)) was of only 1.7 m Omega cm(2) (25 degrees C) and 1.9 m Omega cm(2) at 300 degrees C. The reduced recovery charge was of 300 nC for a switched current of 15 A (500 V) at 300 degrees C. 20% of the diodes showed no degradation at all after 60 h of dc stress (25-225 degrees C). Other 30% of the diodes exhibit a reduced voltage shift below 1 V. For those diodes, the leakage current remains unaffected after the dc stress. Electroluminescence investigations reveal a very low density of stacking faults after the dc stress. The manufacturing yield evidences the efficiency of the substrate surface preparation and our technological process.
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| 22. |
- Gomez-Escudero, Jesus, et al.
(author)
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PKM2 regulates endothelial cell junction dynamics and angiogenesis via ATP production
- 2019
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In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Journal article (peer-reviewed)abstract
- Angiogenesis, the formation of new blood vessels from pre-existing ones, occurs in pathophysiological contexts such as wound healing, cancer, and chronic inflammatory disease. During sprouting angiogenesis, endothelial tip and stalk cells coordinately remodel their cell-cell junctions to allow collective migration and extension of the sprout while maintaining barrier integrity. All these processes require energy, and the predominant ATP generation route in endothelial cells is glycolysis. However, it remains unclear how ATP reaches the plasma membrane and intercellular junctions. In this study, we demonstrate that the glycolytic enzyme pyruvate kinase 2 (PKM2) is required for sprouting angiogenesis in vitro and in vivo through the regulation of endothelial cell-junction dynamics and collective migration. We show that PKM2-silencing decreases ATP required for proper VE-cadherin internalization/traffic at endothelial cell-cell junctions. Our study provides fresh insight into the role of ATP subcellular compartmentalization in endothelial cells during angiogenesis. Since manipulation of EC glycolysis constitutes a potential therapeutic intervention route, particularly in tumors and chronic inflammatory disease, these findings may help to refine the targeting of endothelial glycolytic activity in disease.
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| 23. |
- Gutiérrez, Gabriel, et al.
(author)
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Subtracting the sequence bias from partially digested MNase-seq data reveals a general contribution of TFIIS to nucleosome positioning
- 2017
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In: Epigenetics & Chromatin. - : Springer Science and Business Media LLC. - 1756-8935. ; 10
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Journal article (peer-reviewed)abstract
- Background: TFIIS stimulates RNA cleavage by RNA polymerase II and promotes the resolution of backtracking events. TFIIS acts in the chromatin context, but its contribution to the chromatin landscape has not yet been investigated. Co-transcriptional chromatin alterations include subtle changes in nucleosome positioning, like those expected to be elicited by TFIIS, which are elusive to detect. The most popular method to map nucleosomes involves intensive chromatin digestion by micrococcal nuclease (MNase). Maps based on these exhaustively digested samples miss any MNase-sensitive nucleosomes caused by transcription. In contrast, partial digestion approaches preserve such nucleosomes, but introduce noise due to MNase sequence preferences. A systematic way of correcting this bias for massively parallel sequencing experiments is still missing.Results: To investigate the contribution of TFIIS to the chromatin landscape, we developed a refined nucleosome-mapping method in Saccharomyces cerevisiae. Based on partial MNase digestion and a sequence-bias correction derived from naked DNA cleavage, the refined method efficiently mapped nucleosomes in promoter regions rich in MNase-sensitive structures. The naked DNA correction was also important for mapping gene body nucleosomes, particularly in those genes whose core promoters contain a canonical TATA element. With this improved method, we analyzed the global nucleosomal changes caused by lack of TFIIS. We detected a general increase in nucleosomal fuzziness and more restricted changes in nucleosome occupancy, which concentrated in some gene categories. The TATA-containing genes were preferentially associated with decreased occupancy in gene bodies, whereas the TATA-like genes did so with increased fuzziness. The detected chromatin alterations correlated with functional defects in nascent transcription, as revealed by genomic run-on experiments.Conclusions: The combination of partial MNase digestion and naked DNA correction of the sequence bias is a precise nucleosomal mapping method that does not exclude MNase-sensitive nucleosomes. This method is useful for detecting subtle alterations in nucleosome positioning produced by lack of TFIIS. Their analysis revealed that TFIIS generally contributed to nucleosome positioning in both gene promoters and bodies. The independent effect of lack of TFIIS on nucleosome occupancy and fuzziness supports the existence of alternative chromatin dynamics during transcription elongation.
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