596 research outputs found
The Dark Kinase Knowledgebase: An online compendium of knowledge and experimental results of understudied kinases
Kinases form the backbone of numerous cell signaling pathways, with their dysfunction similarly implicated in multiple pathologies. Further facilitated by their druggability, kinases are a major focus of therapeutic development efforts in diseases such as cancer, infectious disease and autoimmune disorders. While their importance is clear, the role or biological function of nearly one-third of kinases is largely unknown. Here, we describe a data resource, the Dark Kinase Knowledgebase (DKK; https://darkkinome.org), that is specifically focused on providing data and reagents for these understudied kinases to the broader research community. Supported through NIH\u27s Illuminating the Druggable Genome (IDG) Program, the DKK is focused on data and knowledge generation for 162 poorly studied or \u27dark\u27 kinases. Types of data provided through the DKK include parallel reaction monitoring (PRM) peptides for quantitative proteomics, protein interactions, NanoBRET reagents, and kinase-specific compounds. Higher-level data is similarly being generated and consolidated such as tissue gene expression profiles and, longer-term, functional relationships derived through perturbation studies. Associated web tools that help investigators interrogate both internal and external data are also provided through the site. As an evolving resource, the DKK seeks to continually support and enhance knowledge on these potentially high-impact druggable targets
Terahertz response of patterned epitaxial graphene
We study the interaction between polarized terahertz (THz) radiation and
micro-structured large-area graphene in transmission geometry. In order to efficiently
couple the radiation into the two-dimensional material, a lateral periodic patterning
of a closed graphene sheet by intercalation doping into stripes is chosen. We observe
unequal transmittance of the radiation polarized parallel and perpendicular to the
stripes. The relative contrast, partly enhanced by Fabry-Perot oscillations reaches
20 %. The effect even increases up to 50 % when removing graphene stripes in analogy
to a wire grid polarizer. The polarization dependence is analyzed in a large frequency
range from < 80 GHz to 3 THz, including the plasmon-polariton resonance. The results
are in excellent agreement with theoretical calculations based on the electronic energy
spectrum of graphene and the electrodynamics of the patterned structureThe authors thank J. Jobst for fruitful discussions. The research was performed in the
framework of the Sonderforschungsbereich 953 "Synthetic carbon allotropes", funded
by Deutsche Forschungsgemeinschaft. We acknowledge support from the EC under
Graphene Flagship (contract no. CNECT-ICT-604391)
Twenty-five years of two-dimensional rational conformal field theory
In this article we try to give a condensed panoramic view of the development
of two-dimensional rational conformal field theory in the last twenty-five
years.Comment: A review for the 50th anniversary of the Journal of Mathematical
Physics. Some references added, typos correcte
Virus shapes and buckling transitions in spherical shells
We show that the icosahedral packings of protein capsomeres proposed by
Caspar and Klug for spherical viruses become unstable to faceting for
sufficiently large virus size, in analogy with the buckling instability of
disclinations in two-dimensional crystals. Our model, based on the nonlinear
physics of thin elastic shells, produces excellent one parameter fits in real
space to the full three-dimensional shape of large spherical viruses. The
faceted shape depends only on the dimensionless Foppl-von Karman number
\gamma=YR^2/\kappa, where Y is the two-dimensional Young's modulus of the
protein shell, \kappa is its bending rigidity and R is the mean virus radius.
The shape can be parameterized more quantitatively in terms of a spherical
harmonic expansion. We also investigate elastic shell theory for extremely
large \gamma, 10^3 < \gamma < 10^8, and find results applicable to icosahedral
shapes of large vesicles studied with freeze fracture and electron microscopy.Comment: 11 pages, 12 figure
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Autofluorescence lifetime augmented reality as a means for real-time robotic surgery guidance in human patients
Due to loss of tactile feedback the assessment of tumor margins during robotic surgery is based only on visual inspection, which is neither significantly sensitive nor specific. Here we demonstrate time-resolved fluorescence spectroscopy (TRFS) as a novel technique to complement the visual inspection of oral cancers during transoral robotic surgery (TORS) in real-time and without the need for exogenous contrast agents. TRFS enables identification of cancerous tissue by its distinct autofluorescence signature that is associated with the alteration of tissue structure and biochemical profile. A prototype TRFS instrument was integrated synergistically with the da Vinci Surgical robot and the combined system was validated in swine and human patients. Label-free and real-time assessment and visualization of tissue biochemical features during robotic surgery procedure, as demonstrated here, not only has the potential to improve the intraoperative decision making during TORS but also other robotic procedures without modification of conventional clinical protocols
Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast
Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD
Discrete logic modelling as a means to link protein signalling networks with functional analysis of mammalian signal transduction
Large-scale protein signalling networks are useful for exploring complex biochemical pathways but do not reveal how pathways respond to specific stimuli. Such specificity is critical for understanding disease and designing drugs. Here we describe a computational approach—implemented in the free CNO software—for turning signalling networks into logical models and calibrating the models against experimental data. When a literature-derived network of 82 proteins covering the immediate-early responses of human cells to seven cytokines was modelled, we found that training against experimental data dramatically increased predictive power, despite the crudeness of Boolean approximations, while significantly reducing the number of interactions. Thus, many interactions in literature-derived networks do not appear to be functional in the liver cells from which we collected our data. At the same time, CNO identified several new interactions that improved the match of model to data. Although missing from the starting network, these interactions have literature support. Our approach, therefore, represents a means to generate predictive, cell-type-specific models of mammalian signalling from generic protein signalling networks
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