Ongoing astrometric microlensing events from VVV and Gaia

6 pages, 2 figures, accepted MNRAS LettersWe extend predictive microlensing event searches using the Vista Variables in the Via Lactea survey and the second Gaia data release. We identify two events with maxima in 2019 that require urgent follow-up. First, we predict that the nearby M2 dwarf L 338-152 will align with a background source with a closest approach of $35^{+35}_{-23}$ mas on 2019 November $16^{+28}_{-27}$ d. This will cause a peak astrometric shift and photometric amplification of the background source of $2.7^{+3.5}_{-1.5}$ mas and $5.6^{+143.2}_{-5.2}$ mmag respectively. This event should be astrometrically detectable by both the Hubble Space Telescope (HST) and the Spectro-Polarimetric High-contrast Exoplanet Research instrument on the Very Large Telescope. Secondly, we predict the likely K dwarf NLTT 45128 will lens a background source with a closest approach of $105.3^{+12.2}_{-11.7}$ mas on 2019 September $26^{+15}_{-15}$ d. This will produce a peak astrometric shift of $0.329^{+0.065}_{-0.059}$ mas. NLTT 45128 is only 3.6 magnitudes brighter than the background source which makes it an excellent candidate for follow-up with HST. Characterisation of these signals will allow direct gravitational masses to be inferred for both L 338-152 and NLTT 45128 with an estimated precision of $\sim9$ and $\sim13$ per cent respectively.Peer reviewedFinal Published versio

HI intensity mapping with FAST

We discuss the detectability of large-scale HI intensity fluctuations using the FAST telescope. We present forecasts for the accuracy of measuring the Baryonic Acoustic Oscillations and constraining the properties of dark energy. The FAST $19$-beam L-band receivers ($1.05$--$1.45$ GHz) can provide constraints on the matter power spectrum and dark energy equation of state parameters ($w_{0},w_{a}$) that are comparable to the BINGO and CHIME experiments. For one year of integration time we find that the optimal survey area is $6000\,{\rm deg}^2$. However, observing with larger frequency coverage at higher redshift ($0.95$--$1.35$ GHz) improves the projected errorbars on the HI power spectrum by more than $2~\sigma$ confidence level. The combined constraints from FAST, CHIME, BINGO and Planck CMB observations can provide reliable, stringent constraints on the dark energy equation of state.Comment: 7 pages, 3 figures, submitted to "Frontiers in Radio Astronomy and FAST Early Sciences Symposium 2015" conference proceedin

Canonical and Non-Canonical Roles of GRK2 in Lymphocytes

G protein-coupled receptor kinase 2 (GRK2) is emerging as a key integrative signaling node in a variety of biological processes ranging from cell growth and proliferation to migration and chemotaxis. As such, GRK2 is now implicated as playing a role in the molecular pathogenesis of a broad group of diseases including heart failure, cancer, depression, neurodegenerative disease, and others. In addition to its long-known canonical role in the phosphorylation and desensitization of G protein-coupled receptors (GPCRs), recent studies have shown that GRK2 also modulates a diverse array of other molecular processes via newly identified GRK2 kinase substrates and via a growing number of protein-protein interaction binding partners. GRK2 belongs to the 7-member GRK family. It is a multidomain protein containing a specific N-terminal region (referred to as αN), followed by a regulator of G protein signaling homology (RH) domain, an AGC (Protein kinase A, G, C serine/threonine kinase family) kinase domain, and a C-terminal pleckstrin homology (PH) domain. GPCRs mediate the activity of many regulators of the immune system such as chemokines and leukotrienes, and thus GRK proteins may play key roles in modulating the lymphocyte response to these factors. As one of the predominant GRK family members expressed in immune cells, GRK2′s canonical and noncanonical actions play an especially significant role in normal immune cell function as well as in the development and progression of disorders of the immune system. This review summarizes our current state of knowledge of the roles of GRK2 in lymphocytes. We highlight the diverse functions of GRK2 and discuss how ongoing investigation of GRK2 in lymphocytes may inform the development of new therapies for diseases associated with lymphocyte dysregulation

A General Algorithm for Reusing Krylov Subspace Information. I. Unsteady Navier-Stokes

A general algorithm is developed that reuses available information to accelerate the iterative convergence of linear systems with multiple right-hand sides A x = b (sup i), which are commonly encountered in steady or unsteady simulations of nonlinear equations. The algorithm is based on the classical GMRES algorithm with eigenvector enrichment but also includes a Galerkin projection preprocessing step and several novel Krylov subspace reuse strategies. The new approach is applied to a set of test problems, including an unsteady turbulent airfoil, and is shown in some cases to provide significant improvement in computational efficiency relative to baseline approaches

disaggregation: An R Package for Bayesian Spatial Disaggregation Modeling

Disaggregation modeling, or downscaling, has become an important discipline in epidemiology. Surveillance data, aggregated over large regions, is becoming more common, leading to an increasing demand for modeling frameworks that can deal with this data to understand spatial patterns. Disaggregation regression models use response data aggregated over large heterogeneous regions to make predictions at fine-scale over the region by using fine-scale covariates to inform the heterogeneity. This paper presents the R package disaggregation, which provides functionality to streamline the process of running a disaggregation model for fine-scale predictions

CARMA3 Is a Critical Mediator of G Protein-Coupled Receptor and Receptor Tyrosine Kinase-Driven Solid Tumor Pathogenesis

The CARMA–Bcl10–MALT1 (CBM) signalosome is an intracellular protein complex composed of a CARMA scaffolding protein, the Bcl10 linker protein, and the MALT1 protease. This complex was first recognized because the genes encoding its components are targeted by mutation and chromosomal translocation in lymphoid malignancy. We now know that the CBM signalosome plays a critical role in normal lymphocyte function by mediating antigen receptor-dependent activation of the pro-inflammatory, pro-survival NF-κB transcription factor, and that deregulation of this signaling complex promotes B-cell lymphomagenesis. More recently, we and others have demonstrated that a CBM signalosome also operates in cells outside of the immune system, including in several solid tumors. While CARMA1 (also referred to as CARD11) is expressed primarily within lymphoid tissues, the related scaffolding protein, CARMA3 (CARD10), is more widely expressed and participates in a CARMA3-containing CBM complex in a variety of cell types. The CARMA3-containing CBM complex operates downstream of specific G protein-coupled receptors (GPCRs) and/or growth factor receptor tyrosine kinases (RTKs). Since inappropriate expression and activation of GPCRs and/or RTKs underlies the pathogenesis of several solid tumors, there is now great interest in elucidating the contribution of CARMA3-mediated cellular signaling in these malignancies. Here, we summarize the key discoveries leading to our current understanding of the role of CARMA3 in solid tumor biology and highlight the current gaps in our knowledge