Experimental observation of the Aubry transition in two-dimensional colloidal monolayers

The possibility to achieve entirely frictionless, i.e. superlubric, sliding between solids, holds enormous potential for the operation of mechanical devices. At small length scales, where mechanical contacts are well-defined, Aubry predicted a transition from a superlubric to a pinned state when the mechanical load is increased. Evidence for this intriguing Aubry transition (AT), which should occur in one dimension (1D) and at zero temperature, was recently obtained in few-atom chains. Here, we experimentally and theoretically demonstrate the occurrence of the AT in an extended two-dimensional (2D) system at room temperature using a colloidal monolayer on an optical lattice. Unlike the continuous nature of the AT in 1D, we observe a first-order transition in 2D leading to a coexistence regime of pinned and unpinned areas. Our data demonstrate that the original concept of Aubry does not only survive in 2D but is relevant for the design of nanoscopic machines and devices at ambient temperature.Comment: 12 pages including 4 figures + 9 pages supplemental informatio

Effects of oxidation agents and metal ions on binding of p53 to supercoiled DNA

Wild type human full length (f.l.) tumor suppressor p53 protein binds preferentially to supercoiled (sc) DNA in vitro both in the presence and absence of the p53 consensus sequence (p53CON). This binding produces a ladder of retarded bands on the agarose gel. Bands revealed by immunoblotting with antibody DO-1 corresponded to the ethidium stained retarded bands. The intensity and the number of bands of p53-scDNA complex were decreased by physiological concentrations of unchelated zinc ions. Nickel and cobalt ions inhibited binding of p53 to scDNA and to p53CON in linear DNA fragments less efficiently than zinc. Compared to the intrinsic zinc strongly bound to Cys 176, Cys 238, Cys 242 and His 179 in the p53 core domain, binding of additional Zn2+ to p53 was much weaker as shown by an easy removal of the latter ions by low concentrations of EDTA. Oxidation of the protein with diamide resulted in a decrease of the number of the retarded bands. Under the same conditions, no binding of oxidized p53 to p53CON in a linear DNA fragment was observed. In agreement with the literature oxidation of f.l. p53 with diamide was irreversible and was not reverted by an excess of DTT. We showed that in the presence of 0.1 mM zinc ions, oxidation of p53 became reversible. Other divalent cations tested (cadmium, cobalt, nickel) exhibited no such effect. We suggested that the irreversibility of p53 oxidation was due, at least in part, to the removal of intrinsic zinc from its position in the DNA binding domain (after oxidation of the three cysteines to which the zinc ion is coordinated in the reduced protein) accompanied by a change in the p53 conformation. Binding of C-terminal anti-p53 antibody also protected bacterially expressed protein against irreversible loss of activity due to diamide oxidation. Binding the human p53 core domain (segment 94-312) to scDNA greatly differed from that observed with the full-length p53. The core domain did not posses the ability to bind strongly to many sites in scDNA regardless of the presence or absence of p53CON suggesting involvement of some other domain (probably C-terminal) in binding of the full-length p53 to scDNA. Supershift experiments using antibodies against p53 N- or C-terminus suggested that in oxidized p53, scDNA binding through the C-terminus gained importance

Biophysical and electrochemical studies of protein-nucleic acid interactions

This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

State Of the Art Report in the fields of numerical analysis and scientific computing. Final version as of 16/02/2020 deliverable D4.1 of the HORIZON 2020 project EURAD.: European Joint Programme on Radioactive Waste Management

Document information Project Acronym EURAD Project Title European Joint Programme on Radioactive Waste Management Project Type European Joint Programme (EJP) EC grant agreement No. 847593 Project starting / end date 1 st June 2019-30 May 2024 Work Package No. 4 Work Package Title Development and Improvement Of NUmerical methods and Tools for modelling coupled processes Work Package Acronym DONUT Deliverable No. 4.

Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes?:Systematic review

background: It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. methods: Systematic review of the literature and narrative synthesis. results: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. conclusions: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers