Palomar Gattini-IR: Survey overview, data processing system, on-sky performance and first results

Palomar Gattini-IR is a new wide-field, near-infrared (NIR) robotic time domain survey operating at Palomar Observatory. Using a 30 cm telescope mounted with a H2RG detector, Gattini-IR achieves a field of view (FOV) of 25 sq. deg. with a pixel scale of 8.”7 in J-band. Here, we describe the system design, survey operations, data processing system and on-sky performance of Palomar Gattini-IR. As a part of the nominal survey, Gattini-IR scans ≈7500 square degrees of the sky every night to a median 5σ depth of 15.7 AB mag outside the Galactic plane. The survey covers ≈15,000 square degrees of the sky visible from Palomar with a median cadence of 2 days. A real-time data processing system produces stacked science images from dithered raw images taken on sky, together with point-spread function (PSF)-fit source catalogs and transient candidates identified from subtractions within a median delay of ≈4 hr from the time of observation. The calibrated data products achieve an astrometric accuracy (rms) of ≈0.”7 with respect to Gaia DR2 for sources with signal-to-noise ratio > 10, and better than ≈0.”35 for sources brighter than ≈12 Vega mag. The photometric accuracy (rms) achieved in the PSF-fit source catalogs is better than ≈3% for sources brighter than ≈12 Vega mag and fainter than the saturation magnitude of ≈8.5 Vega mag, as calibrated against the Two Micron All Sky Survey catalog. The detection efficiency of transient candidates injected into the images is better than 90% for sources brighter than the 5σ limiting magnitude. The photometric recovery precision of injected sources is 3% for sources brighter than 13 mag, and the astrometric recovery rms is ≈0.”9. Reference images generated by stacking several field visits achieve depths of ≳16.5 AB mag over 60% of the sky, while it is limited by confusion in the Galactic plane. With a FOV ≈40× larger than any other existing NIR imaging instrument, Gattini-IR is probing the reddest and dustiest transients in the local universe such as dust obscured supernovae in nearby galaxies, novae behind large columns of extinction within the galaxy, reddened microlensing events in the Galactic plane and variability from cool and dust obscured stars. We present results from transients and variables identified since the start of the commissioning period

Valvular regurgitation and surgery associated with fenfluramine use: an analysis of 5743 individuals

<p>Abstract</p> <p>Background</p> <p>Use of fenfluramines for weight loss has been associated with the development of characteristic plaques on cardiac valves causing regurgitation. However, previously published studies of exposure to fenfluramines have been limited by relatively small sample size, short duration of follow-up, and the lack of any estimate of the frequency of subsequent valvular surgery. We performed an observational study of 5743 users of fenfluramines examined by echocardiography between July 1997 and February 2004 in a single large cardiology clinic.</p> <p>Results</p> <p>The prevalence of at least mild aortic regurgitation (AR) or moderate mitral regurgitation (MR) was 19.6% in women and 11.8% in men (<it>p </it>< 0.0001 for gender difference). Duration of use was strongly predictive of mild or greater AR (<it>p </it>< 0.0001 for trend), MR (<it>p </it>= 0.002), and tricuspid regurgitation (TR) (<it>p </it>< 0.0001), as was earlier scan date (<it>p </it>< 0.0001 for those scanned prior to 1 January 2000 versus later). Increasing age was also independently associated with increased risk of AR and MR (both <it>p </it>< 0.0001). With mean follow-up of 30.3 months, AR worsened in 15.2%, remained the same in 63.1%, and improved in 21.7%. Corresponding values for MR were 24.8%, 47.4% and 27.9%. Pulmonary hypertension was strongly associated with MR but not AR. Valve surgery was performed on 38 patients (0.66% of 5743), 25 (0.44%) with clear evidence of fenfluramine-related etiology.</p> <p>Conclusion</p> <p>Regurgitant valvulopathy was common in individuals exposed to fenfluramines, more frequent in females, and associated with duration of use in all valves assessed. Valve surgery was performed as frequently for aortic as mitral valves and some tricuspid valve surgeries were also performed. The incidence of surgery appeared to be substantially increased compared with limited general population data.</p

Engineering of cyclodextrin glucanotransferases and the impact for biotechnological applications

Cyclodextrin glucanotransferases (CGTases) are industrially important enzymes that produce cyclic α-(1,4)-linked oligosaccharides (cyclodextrins) from starch. Cyclodextrin glucanotransferases are also applied as catalysts in the synthesis of glycosylated molecules and can act as antistaling agents in the baking industry. To improve the performance of CGTases in these various applications, protein engineers are screening for CGTase variants with higher product yields, improved CD size specificity, etc. In this review, we focus on the strategies employed in obtaining CGTases with new or enhanced enzymatic capabilities by searching for new enzymes and improving existing enzymatic activities via protein engineering

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60&nbsp;years old