180 research outputs found

    TB104: An Analysis of Moisture Content Variation in Eastern Spruce and Balsam Fir in Maine

    Get PDF
    This study was undertaken as an attempt to develop some estimate of the characteristic moisture content of green eastern spruce (Picea spp.) and balsam fir (Abies balsame a (L. ) Mill.), employing the methods prescribed under the Maine Weights and Measures Law. Certain procedural factors and conditions of growth were also considered, to evaluate their effect on the moisture content of the wood at the time of harvesting or shortly after cutting.https://digitalcommons.library.umaine.edu/aes_techbulletin/1088/thumbnail.jp

    Facilitated Diffusion on Mobile DNA:Configurational Traps and Sequence Heterogeneity

    Get PDF
    We present Brownian dynamics simulations of the facilitated diffusion of a protein, modelled as a sphere with a binding site on its surface, along DNA, modelled as a semi-flexible polymer. We consider both the effect of DNA organisation in 3D, and of sequence heterogeneity. We find that in a network of DNA loops, as are thought to be present in bacterial DNA, the search process is very sensitive to the spatial location of the target within such loops. Therefore, specific genes might be repressed or promoted by changing the local topology of the genome. On the other hand, sequence heterogeneity creates traps which normally slow down facilitated diffusion. When suitably positioned, though, these traps can, surprisingly, render the search process much more efficient

    Intracellular Facilitated Diffusion:Searchers, Crowders, and Blockers

    Get PDF
    In bacteria, regulatory proteins search for a specific DNA binding target via "facilitated diffusion": a series of rounds of 3D diffusion in the cytoplasm, and 1D linear diffusion along the DNA contour. Using large scale Brownian dynamics simulations we find that each of these steps is affected differently by crowding proteins, which can either be bound to the DNA acting as a road block to the 1D diffusion, or freely diffusing in the cytoplasm. Macromolecular crowding can strongly affect mechanistic features such as the balance between 3D and 1D diffusion, but leads to surprising robustness of the total search time

    Patients' internet use in New Zealand for information about medicines: Implications for policy and practice

    Get PDF
    BACKGROUND: The ubiquitous use of the internet sees patients increasingly look online for information about their medicines. OBJECTIVE: This study aimed to understand the use of internet to meet medicine information needs of a sample of New Zealand patients. METHOD: Using a descriptive exploratory approach 60 mental health and general medical adult patients at one large urban were interviewed. These semi-structured interviews were audio recorded, transcribed and coded for inductive thematic analysis. FINDINGS: This study found that the internet is frequently used to meet the medicines information needs of patients. Despite the ease of access to information on the internet patients need guidance to locate credible and trustworthy online resources. CONCLUSIONS: Implications from this study relate to both practice and policy, and include the need for health professionals to have enhanced communication skills as they become information brokers who provide supplementary, reliable sources of patient-centric medicines information. Having a New Zealand specific website that includes an extensive section on medicines is a policy recommendation of this study, as is identifying tools to readily identify patients’ needs and preferences for medicines information

    Integrating transposable elements in the 3D genome

    Get PDF
    Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

    High-resolution simulations of chromatin folding at genomic rearrangements in malignant B cells provide mechanistic insights into proto-oncogene deregulation

    Get PDF
    Genomic rearrangements are known to result in proto-oncogene deregulation in many cancers, but the link to 3D genome structure remains poorly understood. Here, we used the highly predictive heteromorphic polymer (HiP-HoP) model to predict chromatin conformations at the proto-oncogene CCND1 in healthy and malignant B cells. After confirming that the model gives good predictions of Hi-C data for the nonmalignant human B cell–derived cell line GM12878, we generated predictions for two cancer cell lines, U266 and Z-138. These possess genome rearrangements involving CCND1 and the immunoglobulin heavy locus (IGH), which we mapped using targeted genome sequencing. Our simulations showed that a rearrangement in U266 cells where a single IGH super-enhancer is inserted next to CCND1 leaves the local topologically associated domain (TAD) structure intact. We also observed extensive changes in enhancer-promoter interactions within the TAD, suggesting that it is the downstream chromatin remodeling which gives rise to the oncogene activation, rather than the presence of the inserted super-enhancer DNA sequence per se. Simulations of the IGH-CCND1 reciprocal translocation in Z-138 cells revealed that an oncogenic fusion TAD is created, encompassing CCND1 and the IGH super-enhancers. We predicted how the structure and expression of CCND1 changes in these different cell lines, validating this using qPCR and fluorescence in situ hybridization microscopy. Our work demonstrates the power of polymer simulations to predict differences in chromatin interactions and gene expression for different translocation breakpoints

    Computation of the Transient in Max-Plus Linear Systems via SMT-Solving

    Full text link
    This paper proposes a new approach, grounded in Satisfiability Modulo Theories (SMT), to study the transient of a Max-Plus Linear (MPL) system, that is the number of steps leading to its periodic regime. Differently from state-of-the-art techniques, our approach allows the analysis of periodic behaviors for subsets of initial states, as well as the characterization of sets of initial states exhibiting the same specific periodic behavior and transient. Our experiments show that the proposed technique dramatically outperforms state-of-the-art methods based on max-plus algebra computations for systems of large dimensions.Comment: The paper consists of 22 pages (including references and Appendix). It is accepted in FORMATS 2020 First revisio
    corecore