Gathering preliminary data

Prior to any large-scale basic science or clinical research project being funded, it is important for researchers to gather preliminary data. This is essential for providing evidence for the feasibility of research projects and helping to design larger-scale studies. When gathering preliminary data one needs to consider how many data are required, how this work is to be funded and where and when the data will be generated. Most importantly researchers should ensure that the planned data collection will be meaningful, serve its intended purpose and follow the principles of good clinical practice

The JCMT Gould Belt Survey: properties of star-forming filaments in Orion A North

We develop and apply a Hessian-based filament detection algorithm to submillimetre continuum observations of Orion A North. The resultant filament radial density profiles are fitted with beam-convolved line-of-sight Plummer-profiles using Markov chain Monte Carlo techniques. The posterior distribution of the radial decay parameter demonstrates that the majority of filaments exhibit p = 1.5–3, with a mode at p = 2.2, suggesting deviation from the Ostriker p = 4 isothermal, equilibrium, self-gravitating cylinder. The spatial distribution of young stellar objects relative to the high column density filaments is investigated, yielding a lower limit on the star-forming age of the integral-shaped filament ∼1.4 Myr. Additionally, inferred lifetimes of filaments are examined which suggest long-term filament accretion, varying rates of star formation, or both. Theoretical filament stability measures are determined with the aid of HARP C18O J = 3–2 observations and indicate that the majority of filaments are gravitationally subcritical, despite the presence of young protostars. The results from this investigation are consistent with the one-dimensional accretion flow filament model recently observed in numerical simulations

Analysis of Nkx3.1:Cre-driven Erk5 deletion reveals a profound spinal deformity which is linked to increased osteoclast activity

Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate. While grossly normal at birth, we observed an unexpected phenotype of spinal protrusion in Nkx3.1:Cre;Erk5fl/fl (Erk5fl/fl) mice by ~6–8 weeks of age. X-ray, histological and micro CT (µCT) analyses showed that 100% of male and female Erk5fl/fl mice had a severely deformed curved thoracic spine, with an associated loss of trabecular bone volume. Although sex-specific differences were observed, histomorphometry measurements revealed that both bone resorption and bone formation parameters were increased in male Erk5fl/fl mice compared to wild type (WT) littermates. Osteopenia occurs where the rate of bone resorption exceeds that of bone formation, so we investigated the role of the osteoclast compartment. We found that treatment of RANKL-stimulated primary bone marrow-derived macrophage (BMDM) cultures with small molecule ERK5 pathway inhibitors increased osteoclast numbers. Furthermore, osteoclast numbers and expression of osteoclast marker genes were increased in parallel with reduced Erk5 expression in cultures generated from Erk5fl/fl mice compared to WT mice. Collectively, these results reveal a novel role for Erk5 during bone maturation and homeostasis in vivo

Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer

Prostate cancer (CaP) is the most common adult male cancer in the developed world. The paucity of biomarkers to predict prostate tumor biology makes it important to identify key pathways that confer poor prognosis and guide potential targeted therapy. Using a murine forward mutagenesis screen in a Pten-null background, we identified peroxisome proliferator-activated receptor gamma (Pparg), encoding a ligand-activated transcription factor, as a promoter of metastatic CaP through activation of lipid signaling pathways, including up-regulation of lipid synthesis enzymes [fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACLY)]. Importantly, inhibition of PPARG suppressed tumor growth in vivo, with down-regulation of the lipid synthesis program. We show that elevated levels of PPARG strongly correlate with elevation of FASN in human CaP and that high levels of PPARG/FASN and PI3K/pAKT pathway activation confer a poor prognosis. These data suggest that CaP patients could be stratified in terms of PPARG/FASN and PTEN levels to identify patients with aggressive CaP who may respond favorably to PPARG/FASN inhibition

The JCMT Gould Belt survey: Dense core clusters in Orion B

The James Clerk Maxwell Telescope Gould Belt Legacy Survey obtained SCUBA-2 observations of dense cores within three sub-regions of OrionB: LDN1622, NGC2023/2024, and NGC2068/2071, all of which contain clusters of cores. We present an analysis of the clustering properties of these cores, including the two-point correlation function and Cartwright’s Q parameter. We identify individual clusters of dense cores across all three regions using a minimal spanning tree technique, and find that in each cluster, the most massive cores tend to be centrally located. We also apply the independent M–Σ technique and find a strong correlation between core mass and the local surface density of cores. These two lines of evidence jointly suggest that some amount of mass segregation in clusters has happened already at the dense core stage

The JCMT Gould Belt Survey: a quantitative comparison between SCUBA-2 data reduction methods

Performing ground-based submillimetre observations is a difficult task as the measurements are subject to absorption and emission from water vapour in the Earth's atmosphere and time variation in weather and instrument stability. Removing these features and other artefacts from the data is a vital process which affects the characteristics of the recovered astronomical structure we seek to study. In this paper, we explore two data reduction methods for data taken with the Submillimetre Common-User Bolometer Array-2 (SCUBA-2) at the James Clerk Maxwell Telescope (JCMT). The JCMT Legacy Reduction 1 (JCMT LR1) and The Gould Belt Legacy Survey Legacy Release 1 (GBS LR1) reduction both use the same software (starlink) but differ in their choice of data reduction parameters. We find that the JCMT LR1 reduction is suitable for determining whether or not compact emission is present in a given region and the GBS LR1 reduction is tuned in a robust way to uncover more extended emission, which better serves more in-depth physical analyses of star-forming regions. Using the GBS LR1 method, we find that compact sources are recovered well, even at a peak brightness of only three times the noise, whereas the reconstruction of larger objects requires much care when drawing boundaries around the expected astronomical signal in the data reduction process. Incorrect boundaries can lead to false structure identification or it can cause structure to be missed. In the JCMT LR1 reduction, the extent of the true structure of objects larger than a point source is never fully recovered

Sprouty2 loss‐induced IL6 drives castration‐resistant prostate cancer through scavenger receptor B1

Metastatic castration‐resistant prostate cancer (mCRPC) is a lethal form of treatment‐resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre‐clinical human and murine mCRPC models, we show that SPRY2 deficiency leads to an androgen self‐sufficient form of CRPC. Mechanistically, HER2‐IL6 signalling axis enhances the expression of androgen biosynthetic enzyme HSD3B1 and increases SRB1‐mediated cholesterol uptake in SPRY2‐deficient tumours. Systemically, IL6 elevated the levels of circulating cholesterol by inducing host adipose lipolysis and hepatic cholesterol biosynthesis. SPRY2‐deficient CRPC is dependent on cholesterol bioavailability and SRB1‐mediated tumoral cholesterol uptake for androgen biosynthesis. Importantly, treatment with ITX5061, a clinically safe SRB1 antagonist, decreased treatment resistance. Our results indicate that cholesterol transport blockade may be effective against SPRY2‐deficient CRPC

Observing Extended Sources with the \Herschel SPIRE Fourier Transform Spectrometer

The Spectral and Photometric Imaging Receiver (SPIRE) on the European Space Agency's Herschel Space Observatory utilizes a pioneering design for its imaging spectrometer in the form of a Fourier Transform Spectrometer (FTS). The standard FTS data reduction and calibration schemes are aimed at objects with either a spatial extent much larger than the beam size or a source that can be approximated as a point source within the beam. However, when sources are of intermediate spatial extent, neither of these calibrations schemes is appropriate and both the spatial response of the instrument and the source's light profile must be taken into account and the coupling between them explicitly derived. To that end, we derive the necessary corrections using an observed spectrum of a fully extended source with the beam profile and the source's light profile taken into account. We apply the derived correction to several observations of planets and compare the corrected spectra with their spectral models to study the beam coupling efficiency of the instrument in the case of partially extended sources. We find that we can apply these correction factors for sources with angular sizes up to \theta_{D} ~ 17". We demonstrate how the angular size of an extended source can be estimated using the difference between the sub-spectra observed at the overlap bandwidth of the two frequency channels in the spectrometer, at 959<\nu<989 GHz. Using this technique on an observation of Saturn, we estimate a size of 17.2", which is 3% larger than its true size on the day of observation. Finally, we show the results of the correction applied on observations of a nearby galaxy, M82, and the compact core of a Galactic molecular cloud, Sgr B2.Comment: Accepted for publication by A&

Raman spectroscopy in prostate cancer : techniques, applications and advancements

Optical techniques are widely used tools in the visualisation of biological species within complex matrices, including biopsies, tissue resections and biofluids. Raman spectroscopy is an emerging analytical approach that probes the molecular signature of endogenous cellular biomolecules under biocompatible conditions with high spatial resolution. Applications of Raman spectroscopy in prostate cancer include biopsy analysis, assessment of surgical margins and monitoring of treatment efficacy. The advent of advanced Raman imaging techniques, such as stimulated Raman scattering, is creating opportunities for real-time in situ evaluation of prostate cancer. This review provides a focus on the recent preclinical and clinical achievements in implementing Raman-based techniques, highlighting remaining challenges for clinical applications. The research and clinical results achieved through in vivo and ex vivo Raman spectroscopy illustrate areas where these evolving technologies can be best translated into clinical practice