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- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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- Deng, JN, et al.
(författare)
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Textures and local textures in severely cold-rolled and annealed ultra-fine-grained FeCo alloy
- 2005
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Ingår i: Materials Science Forum. - 0255-5476 .- 1662-9752. ; 495-497, s. 731-736
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Tidskriftsartikel (refereegranskat)abstract
- We find that a severely rolled FeCo alloy has anomalous enhancement of the rotated-cube {100}< 011 > texture component and a decrease of the {111} components after annealing, which is contrast to the recrystalliization behaviors reported in traditional BCC metals and alloys. The local texture measurements show that two kinds of grains with obviously different orientations, i.e. {100} and {111}, are heterogeneously distributed in the deformed specimen and the migration of high-angle grain boundaries is observed after annealing in the disordering temperature region.
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- Laukkanen, P, et al.
(författare)
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Electronic and structural properties of GaAs(100)(2x4) and InAs(100)(2x4) surfaces studied by core-level photoemission and scanning tunneling microscopy
- 2005
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Ingår i: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 72:4
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Tidskriftsartikel (refereegranskat)abstract
- Electronic and structural properties of GaAs(100)(2x4), InAs(100)(2x4), and Sb/InAs(100)(2x4) reconstructed surfaces have been studied by synchrotron-radiation photoelectron spectroscopy and scanning tunneling microscopy (STM). Based on the difference spectrum of As 3d core-level spectra of III-As(100)(2x4), measured in different surface-sensitivity conditions, as well as the line shape of the As 3d emission from the Sb-induced (2x4) surface, we give evidence that the As 3d spectra of GaAs(100)(2x4) and InAs(100)(2x4) consist of two surface-core-level-shifted components. One of them is shifted about 0.2 eV to the lower kinetic energy from the bulk component. On the basis of the relative component intensities, this surface-shifted As 3d component is assigned to the emission from the first-layer As dimers in the established model of the (2x4) surface. The other component, shifted about 0.3 eV to the higher kinetic energy, is connected to the third-layer As-dimer site. The comparison of the core-level results between GaAs(100)(2x4) and InAs(100)(2x4) suggests that the alpha 2 phase, which has one As dimer in both the first and third atomic layers per unit cell, exists on GaAs(100)(2x4), similarly to the case of InAs(100)(2x4), as predicted in theory but not observed to date. Furthermore, the STM observation of the GaAs(100)(2x4)alpha 2 phase is reported.
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- Peng, B, et al.
(författare)
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LipidCreator workbench to probe the lipidomic landscape
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 2057-
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Tidskriftsartikel (refereegranskat)abstract
- Mass spectrometry (MS)-based targeted lipidomics enables the robust quantification of selected lipids under various biological conditions but comprehensive software tools to support such analyses are lacking. Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.
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- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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- Zaborowski, AM, et al.
(författare)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Tidskriftsartikel (refereegranskat)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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