The Gravitational Lens Candidate FBQ 1633+3134

We present our ground-based optical imaging, spectral analysis, and high resolution radio mapping of the gravitational lens candidate FBQ 1633+3134. This z=1.52, B=17.7 quasar appears double on CCD images with an image separation of 0.66 arcseconds and a flux ratio of ~3:1 across BVRI filters. A single 0.27 mJy radio source is detected at 8.46 GHz, coincident to within an arcsecond of both optical components, but no companion at radio wavelengths is detected down to a flux level of 0.1 mJy (3 sigma). Spectral observations reveal a rich metal-line absorption system consisting of a strong Mg II doublet and associated Fe I and Fe II absorption features, all at an intervening redshift of z=0.684, suggestive of a lensing galaxy. Point spread function subtraction however shows no obvious signs of a third object between the two quasar images, and places a detection limit of I > 23.0 if such an object exists. Although the possibility that FBQ 1633+3134 is a binary quasar cannot be ruled out, the evidence is consistent with it being a single quasar lensed by a faint, metal-rich galaxy.Comment: 24 pages, 5 figures. Accepted by AJ. A calibration error affecting B and V band apparent magnitudes has been corrected. The conclusions of the paper are not change

The Gap to Fill: Rationale for Rapid Initiation and Optimal Titration of Comprehensive Disease-modifying Medical Therapy for Heart Failure with Reduced Ejection Fraction

There are gaps in the use of therapies that save lives and improve quality of life for patients with heart failure with reduced ejection fraction, both in the US and abroad. The evidence is clear that initiation and titration of guideline-directed medical therapy (GDMT) and comprehensive disease-modifying medical therapy (CDMMT) to maximally tolerated doses improves patient-focused outcomes, yet observational data suggest this does not happen. The purpose of this review is to describe the gap in the use of optimal treatment worldwide and discuss the benefits of newer heart failure therapies including angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors. It will also cover the efficacy and safety of such treatments and provide potential pathways for the initiation and rapid titration of GDMT/CDMMT

Modeling of Tunable Elastic Ultralight Aircraft

Aircraft weight is one of the most critical factors in the design and operation of modern vehicles. The ability to integrate ultra-light materials into the primary load bearing structures has the potential to reduce aircraft weight significantly. Ultralight materials tend to be lattice-based meta-materials that are difficult and computationally expensive to model. One of the advantages of meta-materials is to be able to tune or "program" their bulk material properties through the placement of heterogeneous components in the material. A large amount of time devoted to the simulation in the development time for the tuning of the material can be a barrier to the adoption of large scale lattice materials. In this paper, we present a workflow and analysis tool-set to provide first-order estimates for rapid development of engineered lattice materials for aerospace applications. We present results for estimating the displacement and maximum structural stresses

Fast Radio Burst Tomography of the Unseen Universe

The discovery of Fast Radio Bursts (FRBs) at cosmological distances has opened a powerful window on otherwise unseen matter in the Universe. In the 2020s, observations of $>10^{4}$ FRBs will assess the baryon contents and physical conditions in the hot/diffuse circumgalactic, intracluster, and intergalactic medium, and test extant compact-object dark matter models.Comment: Science white paper submitted to the Astro2020 Decadal Survey. 15 pages, 3 color figure

Using natural experimental studies to guide public health action: turning the evidence-based medicine paradigm on its head.

Despite smaller effect sizes, interventions delivered at population level to prevent non-communicable diseases generally have greater reach, impact and equity than those delivered to high-risk groups. Nevertheless, how to shift population behaviour patterns in this way remains one of the greatest uncertainties for research and policy. Evidence about behaviour change interventions that are easier to evaluate tends to overshadow that for population-wide and system-wide approaches that generate and sustain healthier behaviours. Population health interventions are often implemented as natural experiments, which makes their evaluation more complex and unpredictable than a typical randomised controlled trial (RCT). We discuss the growing importance of evaluating natural experiments and their distinctive contribution to the evidence for public health policy. We contrast the established evidence-based practice pathway, in which RCTs generate 'definitive' evidence for particular interventions, with a practice-based evidence pathway in which evaluation can help adjust the compass bearing of existing policy. We propose that intervention studies should focus on reducing critical uncertainties, that non-randomised study designs should be embraced rather than tolerated and that a more nuanced approach to appraising the utility of diverse types of evidence is required. The complex evidence needed to guide public health action is not necessarily the same as that which is needed to provide an unbiased effect size estimate. The practice-based evidence pathway is neither inferior nor merely the best available when all else fails. It is often the only way to generate meaningful evidence to address critical questions about investing in population health interventions.DO, JP and NW are supported by the Medical Research Council (Unit Programme numbers MC_UU_12015/6 and MC_UU_12015/1). The paper was initially developed in the course of a visiting appointment as Thought Leader in Residence at the School of Public Health at the University of Sydney, for which the intellectual environment and financial support provided by the Prevention Research Collaboration is gratefully acknowledged. It was further developed under the auspices of the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence at the University of Cambridge, for which funding from the British Heart Foundation, Economic and Social Research Council, Medical Research Council, National Institute for Health Research and the Wellcome Trust, under the auspices of the United Kingdom Clinical Research Collaboration, is gratefully acknowledge

VPRBP functions downstream of the androgen receptor and OGT to restrict p53 activation in prostate cancer

Androgen receptor (AR) is a major driver of prostate cancer initiation and progression. O-GlcNAc transferase (OGT), the enzyme that catalyzes the covalent addition of UDP-N-acetylglucosamine (UDP-GlcNAc) to serine and threonine residues of proteins, is often highly expressed in prostate cancer with its expression correlated with high Gleason score. In this study, we have identified an AR and OGT coregulated factor, Vpr (HIV-1) binding protein (VPRBP) also known as DDB1 and CUL4 Associated Factor 1 (DCAF1). We show that VPRBP is regulated by the AR at the transcript level, and stabilized by OGT at the protein level. VPRBP knockdown in prostate cancer cells led to a significant decrease in cell proliferation, p53 stabilization, nucleolar fragmentation, and increased p53 recruitment to the chromatin. In human prostate tumor samples, VPRBP protein overexpression correlated with AR amplification, OGT overexpression, a shorter time to postoperative biochemical progression and poor clinical outcome. In clinical transcriptomic data, VPRBP expression was positively correlated with the AR and also with AR activity gene signatures.ImplicationsIn conclusion, we have shown that VPRBP/DCAF1 promotes prostate cancer cell proliferation by restraining p53 activation under the influence of the AR and OGT

Brain Specificity of Diffuse Optical Imaging: Improvements from Superficial Signal Regression and Tomography

Functional near infrared spectroscopy (fNIRS) is a portable monitor of cerebral hemodynamics with wide clinical potential. However, in fNIRS, the vascular signal from the brain is often obscured by vascular signals present in the scalp and skull. In this paper, we evaluate two methods for improving in vivo data from adult human subjects through the use of high-density diffuse optical tomography (DOT). First, we test whether we can extend superficial regression methods (which utilize the multiple source–detector pair separations) from sparse optode arrays to application with DOT imaging arrays. In order to accomplish this goal, we modify the method to remove physiological artifacts from deeper sampling channels using an average of shallow measurements. Second, DOT provides three-dimensional image reconstructions and should explicitly separate different tissue layers. We test whether DOT's depth-sectioning can completely remove superficial physiological artifacts. Herein, we assess improvements in signal quality and reproducibility due to these methods using a well-characterized visual paradigm and our high-density DOT system. Both approaches remove noise from the data, resulting in cleaner imaging and more consistent hemodynamic responses. Additionally, the two methods act synergistically, with greater improvements when the approaches are used together