Structure, stability, and reorganization of 0.5 L0 topography in block copolymer thin films

The structure, stability, and reorganization of lamella-forming block copolymer thin film surface topography (“islands” and “holes”) were studied under boundary conditions driving the formation of 0.5 L0 thick structures at short thermal annealing times. Self-consistent field theory predicts that the presence of one perfectly neutral surface renders 0.5 L0 topography thermodynamically stable relative to 1 L0 thick features, in agreement with previous experimental observations. The calculated through-film structures match cross-sectional scanning electron micrographs, collectively demonstrating the pinning of edge dislocations at the neutral surface. Remarkably, near-neutral surface compositions exhibit 0.5 L0 topography metastability upon extended thermal treatment, slowly transitioning to 1 L0 islands or holes as evidenced by optical and atomic force microscopy. Surface restructuring is rationalized by invoking commensurability effects imposed by slightly preferential surfaces. The results described herein clarify the impact of interfacial interactions on block copolymer self-assembly and solidify an understanding of 0.5 L0 topography, which is frequently used to determine neutral surface compositions of considerable importance to contemporary technological applications

Experimental and Theoretical Design Methodology of Hemispherical Shells under Extreme Static Loading

We present mathematical dependences describing the research results for metal half-sperical shells subjected to static loading by external pressure. We studied the behavior and conditions of static buckling of empty, styrofoam- filled and geometrically imperfect shells. Regression equations in the form of incomplete cubic polinomials are derived. In planes of governing parameters we plot isolines, analysis of which makes it possible to draw qualitative and quantitative conclusions on the externally pressurized shell behavior.Представлены математические зависимости, описывающие результаты исследований металлических полусферических оболочек при статическом нагружении внешним давлением. При этом исследовались поведение и условия потери устойчивости как пустотелых, так и заполненных пенопластом оболочек с геометрическими несовершенствами. Получены уравнения регрессии в виде неполных кубических полиномов. В плоскостях определяющих параметров построены изолинии, анализ которых позволяет сделать качественные и количественные выводы о поведении оболочек в условиях нагружения внешним давлением.Представлено математичні залежності, що описують результати досліджень металевих напівсферичних оболонок при статичному навантаженні зовнішнім тиском. При цьому досліджувалися поведінка й умови втрати стійкості як пустотілих, так і заповнених пенопластом оболонок із геометричною недосконалістю. Отримано рівняння регресії у вигляді неповних кубічних поліномів. У плоскостях визначальних параметрів побудовано ізолінії, аналіз яких дозволяє зробити якісні і кількісні висновки щодо поведінки оболонок в умовах навантаження зовнішнім тиском

Pattern Transfer of Sub-10 nm Features via Tin-Containing Block Copolymers

Tin-containing block copolymers were investigated as materials for nanolithographic applications. Poly(4-trimethylstannylstyrene-block-styrene) (PSnS-PS) and poly(4-trimethylstannylstyrene-block-4-methoxystyrene) (PSnS-PMOST) synthesized by reversible addition–fragmentation chain transfer polymerization form lamellar domains with periodicities ranging from 18 to 34 nm. Thin film orientation control was achieved by thermal annealing between a neutral surface treatment and a top coat. Incorporation of tin into one block facilitates pattern transfer into SiO_2 via a two-step etch process utilizing oxidative and fluorine-based etch chemistries

Integrative analysis of macrophage ribo-Seq and RNA-Seq data define glucocorticoid receptor regulated inflammatory response genes into distinct regulatory classes

Glucocorticoids such as dexamethasone (Dex) are widely used to treat both acute and chronic inflammatory conditions. They regulate immune responses by dampening cell-mediated immunity in a glucocorticoid receptor (GR)-dependent manner, by suppressing the expression of pro-inflammatory cytokines and chemokines and by stimulating the expression of anti-inflammatory mediators. Despite its evident clinical benefit, the mechanistic underpinnings of the gene regulatory networks transcriptionally controlled by GR in a context-specific manner remain mysterious. Next generation sequencing methods such mRNA sequencing (RNA-seq) and Ribosome profiling (ribo-seq) provide tools to investigate the transcriptional and post-transcriptional mechanisms that govern gene expression. Here, we integrate matched RNA-seq data with ribo-seq data from human acute monocytic leukemia (THP-1) cells treated with the TLR4 ligand lipopolysaccharide (LPS) and with Dex, to investigate the global transcriptional and translational regulation (translational efficiency, ΔTE) of Dex-responsive genes. We find that the expression of most of the Dex-responsive genes are regulated at both the transcriptional and the post-transcriptional level, with the transcriptional changes intensified on the translational level. Overrepresentation pathway analysis combined with STRING protein network analysis and manual functional exploration, identified these genes to encode immune effectors and immunomodulators that contribute to macrophage-mediated immunity and to the maintenance of macrophage-mediated immune homeostasis. Further research into the translational regulatory network underlying the GR anti-inflammatory response could pave the way for the development of novel immunomodulatory therapeutic regimens with fewer undesirable side effects

Widespread translational control of fibrosis in the human heart by RNA-binding proteins

BACKGROUND: Fibrosis is a common pathology in many cardiac disorders and is driven by the activation of resident fibroblasts. The global post-transcriptional mechanisms underlying fibroblast-to-myofibroblast conversion in the heart have not been explored. METHODS: Genome-wide changes of RNA transcription and translation during human cardiac fibroblast activation were monitored with RNA sequencing and ribosome profiling. We then used an RNA-binding protein-based analyses to identify translational regulators of fibrogenic genes. The integration with cardiac ribosome occupancy levels of 30 dilated cardiomyopathy patients demonstrates that these post-transcriptional mechanisms are also active in the diseased fibrotic human heart. RESULTS: We generated nucleotide-resolution translatome data during the TGFβ1-driven cellular transition of human cardiac fibroblasts to myofibroblasts. This identified dynamic changes of RNA transcription and translation at several time points during the fibrotic response, revealing transient and early-responder genes. Remarkably, about one-third of all changes in gene expression in activated fibroblasts are subject to translational regulation and dynamic variation in ribosome occupancy affects protein abundance independent of RNA levels. Targets of RNA-binding proteins were strongly enriched in post-transcriptionally regulated genes, suggesting genes such as MBNL2 can act as translational activators or repressors. Ribosome occupancy in the hearts of patients with dilated cardiomyopathy suggested the same post-transcriptional regulatory network was underlying cardiac fibrosis. Key network hubs include RNA-binding proteins such as PUM2 and QKI that work in concert to regulate the translation of target transcripts in human diseased hearts. Furthermore, silencing of both PUM2 and QKI inhibits the transition of fibroblasts toward pro-fibrotic myofibroblasts in response to TGFβ1. CONCLUSIONS: We reveal widespread translational effects of TGFβ1 and define novel post-transcriptional regulatory networks that control the fibroblast-to-myofibroblast transition. These networks are active in human heart disease and silencing of hub genes limits fibroblast activation. Our findings show the central importance of translational control in fibrosis and highlight novel pathogenic mechanisms in heart failure