The Potential of a Novel Class of EPAC-Selective Agonists to Combat Cardiovascular Inflammation

The cyclic 3′,5′-adenosine monophosphate (cAMP) sensor enzyme, EPAC1, is a candidate drug target in vascular endothelial cells (VECs) due to its ability to attenuate proinflammatory cytokine signalling normally associated with cardiovascular diseases (CVDs), including atherosclerosis. This is through the EPAC1-dependent induction of the suppressor of cytokine signalling gene, SOCS3, which targets inflammatory signalling proteins for ubiquitinylation and destruction by the proteosome. Given this important role for the EPAC1/SOCS3 signalling axis, we have used high throughput screening (HTS) to identify small molecule EPAC1 regulators and have recently isolated the first known non-cyclic nucleotide (NCN) EPAC1 agonist, I942. I942 therefore represents the first in class, isoform selective EPAC1 activator, with the potential to suppress pro-inflammatory cytokine signalling with a reduced risk of side effects associated with general cAMP-elevating agents that activate multiple response pathways. The development of augmented I942 analogues may therefore provide improved research tools to validate EPAC1 as a potential therapeutic target for the treatment of chronic inflammation associated with deadly CVDs

Small representations of finite classical groups

Finite group theorists have established many formulas that express interesting properties of a finite group in terms of sums of characters of the group. An obstacle to applying these formulas is lack of control over the dimensions of representations of the group. In particular, the representations of small dimensions tend to contribute the largest terms to these sums, so a systematic knowledge of these small representations could lead to proofs of important conjectures which are currently out of reach. Despite the classification by Lusztig of the irreducible representations of finite groups of Lie type, it seems that this aspect remains obscure. In this note we develop a language which seems to be adequate for the description of the "small" representations of finite classical groups and puts in the forefront the notion of rank of a representation. We describe a method, the "eta correspondence", to construct small representations, and we conjecture that our construction is exhaustive. We also give a strong estimate on the dimension of small representations in terms of their rank. For the sake of clarity, in this note we describe in detail only the case of the finite symplectic groups.Comment: 18 pages, 9 figures, accepted for publications in the proceedings of the conference on the occasion of Roger Howe's 70th birthday (1-5 June 2015, Yale University, New Haven, CT

Identification of Neural Circuits by Imaging Coherent Electrical Activity with FRET-Based Dyes

AbstractWe show that neurons that underlie rhythmic patterns of electrical output may be identified by optical imaging and frequency-domain analysis. Our contrast agent is a two-component dye system in which changes in membrane potential modulate the relative emission between a pair of fluorophores. We demonstrate our methods with the circuit responsible for fictive swimming in the isolated leech nerve cord. The output of a motor neuron provides a reference signal for the phase-sensitive detection of changes in fluorescence from individual neurons in a ganglion. We identify known and possibly novel neurons that participate in the swim rhythm and determine their phases within a cycle. A variant of this approach is used to identify the postsynaptic followers of intracellularly stimulated neurons

Wide-field dynamic astronomy in the near-infrared with Palomar Gattini-IR and DREAMS

There have been a dramatic increase in the number of optical and radio transient surveys due to astronomical transients such as gravitational waves and gamma ray bursts, however, there have been a limited number of wide-field infrared surveys due to narrow field-of-view and high cost of infrared cameras, we present two new wide-field near-infrared fully automated surveyors; Palomar Gattini-IR and the Dynamic REd All-sky Monitoring Survey (DREAMS). Palomar Gattini-IR, a 25 square degree J-band imager that begun science operations at Palomar Observatory, USA in October 2018; we report on survey strategy as well as telescope and observatory operations and will also providing initial science results. DREAMS is a 3.75 square degree wide-field imager that is planned for Siding Spring Observatory, Australia; we report on the current optical and mechanical design and plans to achieve on-sky results in 2020. DREAMS is on-track to be one of the first astronomical telescopes to use an Indium Galium Arsenide (InGaAs) detector and we report initial on-sky testing results for the selected detector package. DREAMS is also well placed to take advantage and provide near-infrared follow-up of the LSST

Origin of minor and trace element compositional diversity in anorthitic feldspar phenocrysts and melt inclusions from the Juan de Fuca Ridge

Melt inclusions trapped in phenocryst phases are important primarily due to their potential of preserving a significant proportion of the diversity of magma composition prior to modification of the parent magma array during transport through the crust. The goal of this investigation was to evaluate the impact of formational and post-entrapment processes on the composition of melt inclusions hosted in high anorthite plagioclase in MORB. Our observations from three plagioclase ultra-phyric lavas from the Endeavor Segment of the Juan de Fuca Ridge document a narrow range of major elements and a dramatically greater range of minor and trace elements within most host plagioclase crystals. Observed host/inclusion partition coefficients for Ti are consistent with experimental determinations. In addition, observed values of D[subscript]Ti are independent of inclusion size and inclusion TiO₂ content of the melt inclusion. These observations preclude significant effects from the re-homogenization process, entrapment of incompatible element boundary layers or dissolution/precipitation. The observed wide range of TiO₂ contents in the host feldspar, and between bands of melt inclusions within individual crystals rule out modification of TiO₂ contents by diffusion, either pre-eruption or due to re-homogenization. However, we do observe comparatively small ranges for values of K₂O and Sr compared to P₂O₅ and TiO₂ in both inclusions and crystals that can be attributed to diffusive processes that occurred prior to eruption.KEYWORDS: crustal processes, magma transport, plagioclas

Voluntary postural sway control and mobility in adults with low back pain

IntroductionLow back pain (LBP) is associated with altered somatosensory perception, which is involved in both involuntary and voluntary control of posture. Currently, there is a lack of methods and tools for assessing somatosensory acuity in patients with LBP. The purpose of this study was (1) to assess the reliability of the sway discrimination apparatus (SwayDA) (2) to evaluate the differences in somatosensory acuity between patients with LBP and pain-free individuals, and (3) to examine relationships between somatosensory acuity, severity of LBP, and mobility in patients with LBP.MethodsTwenty participants (10 patients with LBP and 10 matched asymptomatic controls) were recruited in a test–retest reliability test. Another 56 participants were recruited for this study with 28 individuals presenting with LBP and a further twenty-eight being asymptomatic. The SwayDA was custom-built to measure somatosensory perception during voluntary anterior–posterior (SwayDA-AP), medial-lateral to the dominant side (SwayDA-ML-D), and non-dominant side (SwayDA-ML-ND) postural sway control. Participants also completed mobility tests, including 10 times and 1-min sit-to-stand tests (10-STS, 1 m-STS). The area under the receiver operating characteristic curve (AUC) was calculated to quantify somatosensory acuity in discriminating different voluntary postural sway extents.ResultsThe ICC (2.1) for the SwayDA-AP, SwayDA-ML-D, and SwayDA-ML-ND were 0.741, 0.717, and 0.805 with MDC95 0.071, 0.043, and 0.050. Patients with LBP demonstrated significantly lower SwayDA scores (tSwayDA-AP = −2.142, p = 0.037; tSwayDA-ML-D = -2.266, p = 0.027) than asymptomatic controls. The AUC values of the SwayDA-AP test were significantly correlated with ODI (rSwayDA-AP-ODI = −0.391, p = 0.039). Performances on the 1 m-STS and the 10-STS were significantly correlated with the AUC scores from all the SwayDA tests (−0.513 ≤ r ≤ 0.441, all p < 0.05).DiscussionThe SwayDA tests evaluated showed acceptable reliability in assessing somatosensory acuity during voluntary postural sway. Somatosensory acuity was diminished in patients with LBP compared to asymptomatic controls. In patients with LBP, lower somatosensory acuity was associated with increased LBP-related disability. Future research could focus on investigating the factors contributing to the decreased somatosensory perception and mobility in individuals with LBP

Discovery of an intermediate-luminosity red transient in M51 and its likely dust-obscured, infrared-variable progenitor

We present the discovery of an optical transient (OT) in Messier 51, designated M51 OT2019-1 (also ZTF19aadyppr, AT 2019abn, ATLAS19bzl), by the Zwicky Transient Facility (ZTF). The OT rose over 15 days to an observed luminosity of $M_r=-13$ (${\nu}L_{\nu}=9\times10^6~L_{\odot}$), in the luminosity gap between novae and typical supernovae (SNe). Spectra during the outburst show a red continuum, Balmer emission with a velocity width of $\approx400$ km s$^{-1}$, Ca II and [Ca II] emission, and absorption features characteristic of an F-type supergiant. The spectra and multiband light curves are similar to the so-called "SN impostors" and intermediate-luminosity red transients (ILRTs). We directly identify the likely progenitor in archival Spitzer Space Telescope imaging with a $4.5~\mu$m luminosity of $M_{[4.5]}\approx-12.2$ and a $[3.6]-[4.5]$ color redder than 0.74 mag, similar to those of the prototype ILRTs SN 2008S and NGC 300 OT2008-1. Intensive monitoring of M51 with Spitzer further reveals evidence for variability of the progenitor candidate at [4.5] in the years before the OT. The progenitor is not detected in pre-outburst Hubble Space Telescope optical and near-IR images. The optical colors during outburst combined with spectroscopic temperature constraints imply a higher reddening of $E(B-V)\approx0.7$ mag and higher intrinsic luminosity of $M_r\approx-14.9$ (${\nu}L_{\nu}=5.3\times10^7~L_{\odot}$) near peak than seen in previous ILRT candidates. Moreover, the extinction estimate is higher on the rise than on the plateau, suggestive of an extended phase of circumstellar dust destruction. These results, enabled by the early discovery of M51 OT2019-1 and extensive pre-outburst archival coverage, offer new clues about the debated origins of ILRTs and may challenge the hypothesis that they arise from the electron-capture induced collapse of extreme asymptotic giant branch stars.Comment: 21 pages, 5 figures, published in ApJ

Wide-field dynamic astronomy in the near-infrared with Palomar Gattini-IR and DREAMS

There have been a dramatic increase in the number of optical and radio transient surveys due to astronomical transients such as gravitational waves and gamma ray bursts, however, there have been a limited number of wide-field infrared surveys due to narrow field-of-view and high cost of infrared cameras, we present two new wide-field near-infrared fully automated surveyors; Palomar Gattini-IR and the Dynamic REd All-sky Monitoring Survey (DREAMS). Palomar Gattini-IR, a 25 square degree J-band imager that begun science operations at Palomar Observatory, USA in October 2018; we report on survey strategy as well as telescope and observatory operations and will also providing initial science results. DREAMS is a 3.75 square degree wide-field imager that is planned for Siding Spring Observatory, Australia; we report on the current optical and mechanical design and plans to achieve on-sky results in 2020. DREAMS is on-track to be one of the first astronomical telescopes to use an Indium Galium Arsenide (InGaAs) detector and we report initial on-sky testing results for the selected detector package. DREAMS is also well placed to take advantage and provide near-infrared follow-up of the LSST