The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Approaches, Derivatives and Applications Vasilios Georgakilas,† Michal Otyepka,‡ Athanasios B. Bourlinos,‡ Vimlesh Chandra, Namdong Kim, K. Christian Kemp, Pavel Hobza,‡,§,⊥ Radek Zboril,*,‡ and Kwang S. Kim* †Institute of Materials Science, NCSR “Demokritos”, Ag. Paraskevi Attikis, 15310 Athens, Greece ‡Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University Olomouc, 17. listopadu 12, 771 46 Olomouc, Czech Republic Center for Superfunctional Materials, Department of Chemistry, Pohang University of Science and Technology, San 31, Hyojadong, Namgu, Pohang 790-784, Korea Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo naḿ. 2, 166 10 Prague 6, Czech Republic

Functionalization of Graphene: Covalent and Non-Covalent Approaches, Derivatives and Applications

A theoretical perspective is provided on the glass transition in molecular liquids at thermal equilibrium, on the spatially heterogeneous and aging dynamics of disordered materials, and on the rheology of soft glassy materials. We start with a broad introduction to the field and emphasize its connections with other subjects and its relevance. The important role played by computer simulations in studying and understanding the dynamics of systems close to the glass transition at the molecular level is given. The recent progress on the subject of the spatially heterogeneous dynamics that characterizes structural relaxation in materials with slow dynamics is reviewed. The main theoretical approaches are presented describing the glass transition in supercooled liquids, focusing on theories that have a microscopic, statistical mechanics basis. We describe both successes and failures and critically assess the current status of each of these approaches. The physics of aging dynamics in disordered materials and the rheology of soft glassy materials are then discussed, and recent theoretical progress is described. For each section, an extensive overview is given of the most recent advances, but we also describe in some detail the important open problems that will occupy a central place in this field in the coming years.

Theoretical perspective on the glass transition and amorphous materials

Tissues can be soft like fat, which bears little stress, or stiff like bone, which sustains high stress, but whether there is a systematic relationship between tissue mechanics and differentiation is unknown. Here, proteomics analyses revealed that levels of the nucleoskeletal protein lamin-A scaled with tissue elasticity, E, as did levels of collagens in the extracellular matrix that determine E. Stem cell differentiation into fat on soft matrix was enhanced by low lamin-A levels, whereas differentiation into bone on stiff matrix was enhanced by high lamin-A levels. Matrix stiffness directly influenced lamin-A protein levels, and, although lamin-A transcription was regulated by the vitamin A/retinoic acid (RA) pathway with broad roles in development, nuclear entry of RA receptors was modulated by lamin-A protein. Tissue stiffness and stress thus increase lamin-A levels, which stabilize the nucleus while also contributing to lineage determination.

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Nuclear lamin-A Scales With Tissue Stiffness and Enhances Matrix-Directed Differentiation

eMedicine创建于1996年，由近万名临床医师作为作者或编辑参与此临床医学知识库的建设，其中编辑均是来自美国哈佛、耶鲁、斯坦福、芝加哥、德克萨斯、加州大学等各分校医学院的教授或副教授。

eMedicine

The performance of a light microscope is intrinsically constrained by the Abbe diffraction limit. No matter how close to optical perfection it is, an imaging system cannot resolve two objects that are beyond this natural limit, which is dependent on the wavelength of the observed light and its angular distribution. Several methods have been devised to beat the diffraction limit, but these have generally required esoteric excitation schemes, so remain impractical. Lee et al. are working on a new way of beating the limit, using nanoscale spherical lenses that self-assemble by bottom-up integration of cup-shaped organic molecules called calixarenes. Lenses produced in this way have very short focal lengths that can generate near-field magnification beyond the diffraction limit, enabling the resolution of features of the order of 200 nm. The lenses can be placed at will on a surface and, among other things, can be used to reduce the size of deep-ultraviolet lithography features. Cup-shaped molecules of calix[4]hydroquinone self-assemble on a surface into a lens shape; these lenses are shown to generate near-field magnification beyond the diffraction limit, enabling the resolution of features of the order of 200 nanometres. Such spherical nanolenses provide new pathways for lens-based near-field focusing and high-resolution optical imaging at very low intensities, which are useful for, among other things, bio-imaging and near-field lithography. It is well known that a lens-based far-field optical microscope cannot resolve two objects beyond Abbe’s diffraction limit. Recently, it has been demonstrated that this limit can be overcome by lensing effects driven by surface-plasmon excitation1,2,3, and by fluorescence microscopy driven by molecular excitation4. However, the resolution obtained using geometrical lens-based optics without such excitation schemes remains limited by Abbe’s law even when using the immersion technique5, which enhances the resolution by increasing the refractive indices of immersion liquids. As for submicrometre-scale or nanoscale objects, standard geometrical optics fails for visible light because the interactions of such objects with light waves are described inevitably by near-field optics6. Here we report near-field high resolution by nanoscale spherical lenses that are self-assembled by bottom-up integration7 of organic molecules. These nanolenses, in contrast to geometrical optics lenses, exhibit curvilinear trajectories of light, resulting in remarkably short near-field focal lengths. This in turn results in near-field magnification that is able to resolve features beyond the diffraction limit. Such spherical nanolenses provide new pathways for lens-based near-field focusing and high-resolution optical imaging at very low intensities, which are useful for bio-imaging, near-field lithography, optical memory storage, light harvesting, spectral signal enhancing, and optical nano-sensing.

Near-field focusing and magnification through self-assembled nanoscale spherical lenses

http://www.columbia.edu/cu/chemistry/groups/kaufman/publication%20pdfs/paperbiophysj.pdf

Glioma Expansion in Collagen I Matrices: Analyzing Collagen Concentration-Dependent Growth and Motility Patterns

Flow and magnetic field induced collagen alignment.

http://www.columbia.edu/cu/chemistry/groups/kaufman/publication%20pdfs/yangleonefinal.pdf

Elastic Moduli of Collagen Gels Can Be Predicted from Two-Dimensional Confocal Microscopy

We have demonstrated that fifth-order stimulated Raman spectra of the intermolecular modes in CS2 are dominated by cascading third-order processes. Previous studies have successfully discriminated against a sequential cascading process, but did not account for parallel third-order cascades. All of our measured spectra were successfully simulated considering only cascades built directly from our measured third-order spectra. Using an appropriately chosen phase matching geometry we also measured the sequential cascade, which should exist with equal probability to the parallel cascade. When employing a phase matching geometry that provided substantial discrimination against all of the third-order cascades we were not able to measure any signal. We assign an upper limit for the true fifth-order signal of 2% of the cascaded signal.

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Laura J. Kaufman

Papers

Near-field focusing and magnification through self-assembled nanoscale spherical lenses

Glioma Expansion in Collagen I Matrices: Analyzing Collagen Concentration-Dependent Growth and Motility Patterns

Flow and magnetic field induced collagen alignment.

Elastic Moduli of Collagen Gels Can Be Predicted from Two-Dimensional Confocal Microscopy

Fifth-order two-dimensional Raman spectra of CS2 are dominated by third-order cascades