Single-electron transmetalation is recognized as an enabling technology for the mild transfer of alkyl groups to transition metal catalysts in cross-coupling reactions. Hypercoordinate silicates ...represent a new and improved class of radical precursors because of their low oxidation potentials and the innocuous byproducts generated upon oxidation. Herein, we report the cross-coupling of secondary and primary ammonium alkylsilicates with (hetero)aryl bromides in good to excellent yields. The base-free conditions have exceptional protic group tolerance on both partners, permitting the cross-coupling of unprotected primary and secondary amines.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Nucleophilic radical additions at innately electrophilic C(sp2) centers are perfectly suited for the direct functionalization of heterocycles. Using bench stable and commercially available alkyl ...oxamate and oxamic acid derivatives in combination with photoredox catalysis, a direct carbamoylation of heterocycles yielding amide functionalized pharmacophores in a single step is reported. The reaction conditions reported are compatible with structurally complex heterocyclic substrates of pharmaceutical interest. Notably, derivatives containing functional groups incompatible with standard amidation reactions, such as carboxylic acids and unprotected amines, were found to be amenable to this reaction paradigm.
Non‐obvious amide: Bench stable and commercially available alkyl oxamates are used for the direct C−H carbamoylation of heterocycles by using visible‐light photoredox mediated conditions. This method yields amide functionalized pharmacophores in a single step and is amenable with derivatives having functional groups incompatible with standard amidation reactions.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In plants, cytosine methylation, an epigenetic mark critical for transposon silencing, is maintained over generations by key enzymes that directly methylate DNA and is facilitated by chromatin ...remodelers, like DECREASE IN DNA METHYLATION1 (DDM1). Short-interfering RNAs (siRNAs) also mediate transposon DNA methylation through a process called RNA-directed DNA methylation (RdDM). In tomato (Solanum lycopersicum), siRNAs are primarily mapped to gene-rich chromosome arms, and not to pericentromeric regions as in Arabidopsis thaliana. Tomato encodes two DDM1 genes. To better understand their functions and interaction with the RdDM pathway, we targeted the corresponding genes via the CRISPR/Cas9 technology, resulting in the isolation of Slddm1a and Slddm1b knockout mutants. Unlike the single mutants, Slddm1a Slddm1b double mutant plants display pleiotropic vegetative and reproductive phenotypes, associated with severe hypomethylation of the heterochromatic transposons in both the CG and CHG methylation contexts. The methylation in the CHH context increased for some heterochromatic transposons and conversely decreased for others localized in euchromatin. We found that the number of heterochromatin-associated siRNAs, including RdDM-specific small RNAs, increased significantly, likely limiting the transcriptional reactivation of transposons in Slddm1a Slddm1b. Taken together, we propose that the global production of siRNAs and the CHH methylation mediated by the RdDM pathway are restricted to chromosome arms in tomato. Our data suggest that both pathways are greatly enhanced in heterochromatin when DDM1 functions are lost, at the expense of silencing mechanisms normally occurring in euchromatin.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Without a systematic SpO2i measurement, a normal breathing rate could mask profound hypoxia and make severity assessment in COVID-19 patients all the more difficult in an out-of-hospital setting. ......prehospital pulse oximetry might be used as a red flag for early detection of “silent hypoxemia” in COVID-19 patients. Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: the utility of the ROX index.
This paper presents a method for formation control of marine surface craft inspired by Lagrangian mechanics. The desired formation configuration and response of the marine surface craft are given as ...a set of constraint functions. The functions are treated according to constraints in analytical mechanics. Thus, constraint forces arise and feedback from the constraint functions keeps the formation assembled. Since the constraint functions are designed for a desired effect, the forces can be interpreted as control laws. Examples of constraint functions that maintain a formation are presented. Furthermore, the same approach has been applied with no major modification to position control purposes for a single vessel. An extension to underactuated vessels is given. Simulations with nonlinear models of tugboats illustrate the proposed method versatility and its robustness with respect to environmental disturbances and time delays
Plant genomes are populated by different types of repetitive elements including transposable elements (TEs) and simple sequence repeats (SSRs) that can have a strong impact on genome size and dynamic ...as well as on the regulation of gene transcription. At least two-thirds of the tomato genome is composed of repeats. While their bulk impact on genome organization has been recently revealed by whole genome assembly, their influence on tomato biology and phenotype remains largely unaddressed. More specifically, the effects and roles of DNA repeats on the maturation of fleshy fruits, which is a complex process of key agro-economic interest, still needs to be investigated comprehensively and tomato is arguably an excellent model for such study.
We have performed a comprehensive annotation of the tomato repeatome to explore its potential impact on tomato genome composition and gene transcription. Our results show that the tomato genome can be fractioned into three compartments with different gene and repeat density, each compartment presenting contrasting repeat and gene composition, repeat-gene associations and different gene transcriptional levels. In the context of fruit ripening, we found that repeats are present in the majority of differentially methylated regions (DMRs) and thousands of repeat-associated DMRs are found in gene proximity including hundreds that are differentially regulated. Furthermore, we found that repeats are also present in the proximity of binding sites of the key ripening protein RIN. We also observed that some repeat families are present at unexpected high frequency in the proximity of genes that are differentially expressed during tomato ripening.
Altogether, our study emphasizes the fractionation as defined by repeat content in the tomato genome and enables to further characterize the specificities of each genomic compartment. Additionally, our results present strong associations between differentially regulated genes, differentially methylated regions and repeats, suggesting a potential adaptive function of repeats in tomato ripening. Our work therefore provides significant perspectives for the understanding of the impact of repeats on the maturation of fleshy fruits.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
L’orthopédie, un choix Jouffroy, P.
Bulletin de l'Académie nationale de médecine,
October 2021, 2021-10-00, Volume:
205, Issue:
8
Journal Article
Peer reviewed
Open access
L’orthopédie n’est pas a priori une discipline attrayante pour une femme. Liée à la cancérologie, la rhumatologie, la pédiatrie et l’infectiologie ainsi que de très près à la radiologie, son histoire ...française est due à trois écoles parallèles, compétitrices et créatives. Le dynamisme de l’école Judet peut contaminer une femme pour son goût de l’innovation : la chirurgie du cotyle et du bassin représente une véritable aventure tant chirurgicale que radiologique en raison des progrès considérables de l’imagerie. Devenir chef de service est un autre choix, inspiré par les modèles que sont les patrons, pour mener de front l’enseignement, la transmission et la responsabilité.
At first glance, orthopedic surgery is not an attractive specialty for a woman. Linked to oncology, rheumatology, pediatrics and infectious diseases, and very closely associated with radiology. Its French history originates from three parallel, creative and competitive schools. The energy of Judet's school was very appealing for a woman with her taste for innovation: pelvic and acetabular surgery was a real adventure both surgical and radiological with the considerable progress of imaging. To become department head is another choice, inspired to me by my mentors who taught me responsibility, management and teaching at the same time.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Axially chiral biaryl fragments are recurrent scaffolds in drugs. These essential synthons are often built via metal catalyzed Csp2–Csp2 bond formation and subsequent separation of the atropisomers, ...resulting in low yields and excess waste. Asymmetric variants have been reported, unfortunately without reaching the optical purity desired for active pharmaceutical ingredients. Additional enantioenriching steps are therefore required, but even if efficient, these methods generate waste and are often problematic on scale. Herein, we report an unprecedented chiral Suzuki–Miyaura/enzymatic kinetic resolution sequence for the synthesis of JNJ-4355 and other atropisomeric biaryls yielding the targets in high enantiopurity without chiral separation.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
PDF
