EdShare: towards sharing resources for learning and teaching at the University of Southampton

At the University of Southampton, in the UK, we have been developing the Research Repository (e-Prints Soton) since 2005, to showcase the research output and make it more accessible. As a significant next step, the University has taken the strategic decision to develop a repository for educational materials. In developing EdShare at Southampton, we are promoting a cultural shift to a more open and collaborative approach to scholarship as well as research.Successful implementation in such a context requires a lightweight and very simple approach to sharing content facilitated by web 2.0 functionality.<br/

Diffusion quantum Monte Carlo study of three-dimensional Wigner crystals

We report diffusion quantum Monte Carlo calculations of three-dimensional Wigner crystals in the density range r_s=100-150. We have tested different types of orbital for use in the approximate wave functions but none improve upon the simple Gaussian form. The Gaussian exponents are optimized by directly minimizing the diffusion quantum Monte Carlo energy. We have carefully investigated and sought to minimize the potential biases in our Monte Carlo results. We conclude that the uniform electron gas undergoes a transition from a ferromagnetic fluid to a body-centered-cubic Wigner crystal at r_s=106+/-1. The diffusion quantum Monte Carlo results are compared with those from Hartree-Fock and Hartree theory in order to understand the role played by exchange and correlation in Wigner crystals. We also study "floating" Wigner crystals and give results for their pair-correlation functions

Rapid and deep-scale ubiquitylation profiling for biology and translational research

Protein ubiquitylation is involved in a plethora of cellular processes. While antibodies directed at ubiquitin remnants (K-ɛ-GG) have improved the ability to monitor ubiquitylation using mass spectrometry, methods for highly multiplexed measurement of ubiquitylation in tissues and primary cells using sub-milligram amounts of sample remains a challenge. Here, we present a highly sensitive, rapid and multiplexed protocol termed UbiFast for quantifying ~10,000 ubiquitylation sites from as little as 500 μg peptide per sample from cells or tissue in a TMT10plex in ca. 5 h. High-field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) is used to improve quantitative accuracy for posttranslational modification analysis. We use the approach to rediscover substrates of the E3 ligase targeting drug lenalidomide and to identify proteins modulated by ubiquitylation in models of basal and luminal human breast cancer. The sensitivity and speed of the UbiFast method makes it suitable for large-scale studies in primary tissue samples

Mapping the unique and shared functions of oncogenic KRAS and RIT1 with proteome and transcriptome profiling

Aberrant activation of RAS oncogenes is prevalent in lung adenocarcinoma, with somatic mutation of KRAS occurring in ∼30% of tumors. Recently, we identified somatic mutation of the RAS-family GTPase RIT1 in lung adenocarcinoma, but relatively little is known about the biological pathways regulated by RIT1 and how these relate to the oncogenic KRAS network. Here we present quantitative proteomic and transcriptomic profiles from KRAS-mutant and RIT1-mutant isogenic lung epithelial cells and globally characterize the signaling networks regulated by each oncogene. We find that both mutant KRAS and mutant RIT1 promote S6 kinase, AKT, and RAF/MEK signaling, and promote epithelial-to-mesenchymal transition and immune evasion via HLA protein loss. However, KRAS and RIT1 diverge in regulation of phosphorylation sites on EGFR, USO1, and AHNAK proteins. The majority of the proteome changes are related to altered transcriptional regulation, but a small subset of proteins are differentially regulated by both oncoproteins at the post-transcriptional level, including intermediate filament proteins, metallothioneins, and MHC Class I proteins. These data provide the first global, unbiased characterization of oncogenic RIT1 network and identify the shared and divergent functions of oncogenic RIT1 and KRAS GTPases in lung cancer

Receptor tyrosine kinase activation of RhoA is mediated by AKT phosphorylation of DLC1

We report several receptor tyrosine kinase (RTK) ligands increase RhoA-guanosine triphosphate (GTP) in untransformed and transformed cell lines and determine this phenomenon depends on the RTKs activating the AKT serine/threonine kinase. The increased RhoA-GTP results from AKT phosphorylating three serines (S298, S329, and S567) in the DLC1 tumor suppressor, a Rho GTPase-activating protein (RhoGAP) associated with focal adhesions. Phosphorylation of the serines, located N-terminal to the DLC1 RhoGAP domain, induces strong binding of that N-terminal region to the RhoGAP domain, converting DLC1 from an open, active dimer to a closed, inactive monomer. That binding, which interferes with the interaction of RhoA-GTP with the RhoGAP domain, reduces the hydrolysis of RhoA-GTP, the binding of other DLC1 ligands, and the colocalization of DLC1 with focal adhesions and attenuates tumor suppressor activity. DLC1 is a critical AKT target in DLC1-positive cancer because AKT inhibition has potent antitumor activity in the DLC1-positive transgenic cancer model and in a DLC1-positive cancer cell line but not in an isogenic DLC1-negative cell line

Stationary solutions of the one-dimensional nonlinear Schroedinger equation: I. Case of repulsive nonlinearity

All stationary solutions to the one-dimensional nonlinear Schroedinger equation under box and periodic boundary conditions are presented in analytic form. We consider the case of repulsive nonlinearity; in a companion paper we treat the attractive case. Our solutions take the form of stationary trains of dark or grey density-notch solitons. Real stationary states are in one-to-one correspondence with those of the linear Schr\"odinger equation. Complex stationary states are uniquely nonlinear, nodeless, and symmetry-breaking. Our solutions apply to many physical contexts, including the Bose-Einstein condensate and optical pulses in fibers.Comment: 11 pages, 7 figures -- revised versio

Deceleration and trapping of heavy diatomic molecules using a ring-decelerator

We present an analysis of the deceleration and trapping of heavy diatomic molecules in low-field seeking states by a moving electric potential. This moving potential is created by a 'ring-decelerator', which consists of a series of ring-shaped electrodes to which oscillating high voltages are applied. Particle trajectory simulations have been used to analyze the deceleration and trapping efficiency for a group of molecules that is of special interest for precision measurements of fundamental discrete symmetries. For the typical case of the SrF molecule in the (N,M) = (2, 0) state, the ring-decelerator is shown to outperform traditional and alternate-gradient Stark decelerators by at least an order of magnitude. If further cooled by a stage of laser cooling, the decelerated molecules allow for a sensitivity gain in a parity violation measurement, compared to a cryogenic molecular beam experiment, of almost two orders of magnitude

Radial asymptotics of Lemaitre-Tolman-Bondi dust models

We examine the radial asymptotic behavior of spherically symmetric Lemaitre-Tolman-Bondi dust models by looking at their covariant scalars along radial rays, which are spacelike geodesics parametrized by proper length $\ell$, orthogonal to the 4-velocity and to the orbits of SO(3). By introducing quasi-local scalars defined as integral functions along the rays, we obtain a complete and covariant representation of the models, leading to an initial value parametrization in which all scalars can be given by scaling laws depending on two metric scale factors and two basic initial value functions. Considering regular "open" LTB models whose space slices allow for a diverging $\ell$, we provide the conditions on the radial coordinate so that its asymptotic limit corresponds to the limit as $\ell\to\infty$. The "asymptotic state" is then defined as this limit, together with asymptotic series expansion around it, evaluated for all metric functions, covariant scalars (local and quasi-local) and their fluctuations. By looking at different sets of initial conditions, we examine and classify the asymptotic states of parabolic, hyperbolic and open elliptic models admitting a symmetry center. We show that in the radial direction the models can be asymptotic to any one of the following spacetimes: FLRW dust cosmologies with zero or negative spatial curvature, sections of Minkowski flat space (including Milne's space), sections of the Schwarzschild--Kruskal manifold or self--similar dust solutions.Comment: 44 pages (including a long appendix), 3 figures, IOP LaTeX style. Typos corrected and an important reference added. Accepted for publication in General Relativity and Gravitatio

Proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction

Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this "guilt-by-association" (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies