Research Notes : Selection and inheritance of nitrate reductase mutants in soybeans

Our primary objective in looking for nitrate reductase (NR) mutants in soybeans is to attempt to overcome the inhibition of nitrogen fixation by soil nitrate. The rationale depends upon blocking normal nitrate metabolism by finding defective NR mutants, thus liberating additional carbon and ener-gy for use by nodules in nitrogen fixation. Additional benefits likely to result from the isolation of NR mutants in soybeans are a) a better under-standing of normal nitrate metabolism and b) provision of easily selectable genetic markers

Documenting and harnessing the biological potential of molecules in Distributed Drug Discovery (D3) virtual catalogs

Virtual molecular catalogs have limited utility if member compounds are (i) difficult to synthesize or (ii) unlikely to have biological activity. The Distributed Drug Discovery (D3) program addresses the synthesis challenge by providing scientists with a free virtual D3 catalog of 73,024 easy-to-synthesize N-acyl unnatural α-amino acids, their methyl esters, and primary amides. The remaining challenge is to document and exploit the bioactivity potential of these compounds. In the current work, a search process is described that retrospectively identifies all virtual D3 compounds classified as bioactive hits in PubChem-cataloged experimental assays. The results provide insight into the broad range of drug-target classes amenable to inhibition and/or agonism by D3-accessible molecules. To encourage computer-aided drug discovery centered on these compounds, a publicly available virtual database of D3 molecules prepared for use with popular computer docking programs is also presented

The depression in visual impairment trial (DEPVIT): trial design and protocol

<b>Background</b> The prevalence of depression in people with a visual disability is high but screening for depression and referral for treatment is not yet an integral part of visual rehabilitation service provision. One reason for this may be that there is no good evidence about the effectiveness of treatments in this patient group. This study is the first to evaluate the effect of depression treatments on people with a visual impairment and co morbid depression.<p></p> <b>Methods/design</b> The study is an exploratory, multicentre, individually randomised waiting list controlled trial. Participants will be randomised to receive Problem Solving Therapy (PST), a ‘referral to the GP’ requesting treatment according to the NICE’s ‘stepped care’ recommendations or the waiting list arm of the trial. The primary outcome measure is change (from randomisation) in depressive symptoms as measured by the Beck’s Depression Inventory (BDI-II) at 6 months. Secondary outcomes include change in depressive symptoms at 3 months, change in visual function as measured with the near vision subscale of the VFQ-48 and 7 item NEI-VFQ at 3 and 6 months, change in generic health related quality of life (EQ5D), the costs associated with PST, estimates of incremental cost effectiveness, and recruitment rate estimation.<p></p> <b>Discussion</b> Depression is prevalent in people with disabling visual impairment. This exploratory study will establish depression screening and referral for treatment in visual rehabilitation clinics in the UK. It will be the first to explore the efficacy of PST and the effectiveness of NICE’s ‘stepped care’ approach to the treatment of depression in people with a visual impairment.<p></p&gt

First-in-human clinical trial of ultrasonic propulsion of kidney stones

PURPOSE: Ultrasonic propulsion is a new technology using focused ultrasound energy applied transcutaneously to reposition kidney stones. We report what are to our knowledge the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones. MATERIALS AND METHODS: Subjects underwent ultrasonic propulsion while awake without sedation in clinic, or during ureteroscopy while anesthetized. Ultrasound and a pain questionnaire were completed before, during and after propulsion. The primary outcome was to reposition stones in the collecting system. Secondary outcomes included safety, controllable movement of stones and movement of stones less than 5 mm and 5 mm or greater. Adverse events were assessed weekly for 3 weeks. RESULTS: Kidney stones were repositioned in 14 of 15 subjects. Of the 43 targets 28 (65%) showed some level of movement while 13 (30%) were displaced greater than 3 mm to a new location. Discomfort during the procedure was rare, mild, brief and self-limited. Stones were moved in a controlled direction with more than 30 fragments passed by 4 of the 6 subjects who had previously undergone a lithotripsy procedure. The largest stone moved was 10 mm. One patient experienced pain relief during treatment of a large stone at the ureteropelvic junction. In 4 subjects a seemingly large stone was determined to be a cluster of small passable stones after they were moved. CONCLUSIONS: Ultrasonic propulsion was able to successfully reposition stones and facilitate the passage of fragments in humans. No adverse events were associated with the investigational procedure

K2: Background Survey - The search for undiscovered transients in Kepler/K2 data

The K2 mission of the Kepler Space Telescope offers a unique possibility to examine sources of both Galactic and extragalactic origin with high-cadence photometry. Alongside the multitude of supernovae and quasars detected within targeted galaxies, it is likely that Kepler has serendipitously observed many transients throughout K2. Such events will likely have occurred in background pixels, coincidentally surrounding science targets. Analysing the background pixels presents the possibility to conduct a high-cadence survey with areas of a few square degrees per campaign. We demonstrate the capacity to independently recover key K2 transients such as KSN 2015K and SN 2018oh. With this survey, we expect to detect numerous transients and determine the first comprehensive rates for transients with lifetimes of <1 d.This research was supported by an Australian Government Research Training Program (RTP) Scholarship and utilizes data collected by the K2 missio

Comparison of Tissue Injury from Focused Ultrasonic Propulsion of Kidney Stones Versus Extracorporeal Shock Wave Lithotripsy

Purpose Focused ultrasonic propulsion is a new non-invasive technique designed to move kidney stones and stone fragments out of the urinary collecting system. However, the extent of tissue injury associated with this technique is not known. As such, we quantitated the amount of tissue injury produced by focused ultrasonic propulsion under simulated clinical treatment conditions, and under conditions of higher power or continuous duty cycles, and compared those results to SWL injury. Materials and Methods A human calcium oxalate monohydrate stone and/or nickel beads were implanted (with ureteroscopy) into 3 kidneys of live pigs (45–55 kg) and repositioned using focused ultrasonic propulsion. Additional pig kidneys were exposed to SWL level pulse intensities or continuous ultrasound exposure of 10 minutes duration (ultrasound probe either transcutaneous or on the kidney). These kidneys were compared to 6 kidneys treated with an unmodified Dornier HM3 Lithotripter (2400 shocks, 120 SWs/min and 24 kV). Histological analysis was performed to assess the volume of hemorrhagic tissue injury created by each technique (% functional renal volume, FRV). Results SWL produced a lesion of 1.56±0.45% FRV. Ultrasonic propulsion produced no detectable lesion with the simulated clinical treatment. A lesion of 0.46±0.37% FRV or 1.15±0.49% FRV could be produced if excessive treatment parameters were used while the ultrasound probe was placed on the kidney. Conclusions Focused ultrasonic propulsion produced no detectable morphological injury to the renal parenchyma when using clinical treatment parameters and produced injury comparable in size to SWL when using excessive treatment parameters

Revealing the progenitor of SN 2021zby through analysis of the TESSTESS shock-cooling light curve

We present early observations and analysis of the double-peaked Type IIb supernova (SN IIb) 2021zby. $TESS$ captured the prominent early shock cooling peak of SN 2021zby within the first $\sim$10 days after explosion with a 30-minute cadence. We present optical and near-infrared spectral series of SN 2021zby, including three spectra during the shock cooling phase. Using a multi-band model fit, we find that the inferred properties of its progenitor are consistent with a red supergiant or yellow supergiant, with an envelope mass of $\sim$0.3-3.0 M$_\odot$ and an envelope radius of $\sim$50-350$R_\odot$. These inferred progenitor properties are similar to those of other SNe IIb with double-peak feature, such as SNe 1993J, 2011dh, 2016gkg and 2017jgh. This study further validates the importance of the high cadence and early coverage in resolving the shape of the shock cooling light curve, while the multi-band observations, especially UV, is also necessary to fully constrain the progenitor properties.Comment: 12 pages, 5 figures, 2 tables, submitted to ApJ

SN 2021zny: an early flux excess combined with late-time oxygen emission suggests a double white dwarf merger event

We present a photometric and spectroscopic analysis of the ultra-luminous and slowly evolving 03fg-like Type Ia SN 2021zny. Our observational campaign starts from $\sim5.3$ hours after explosion (making SN 2021zny one of the earliest observed members of its class), with dense multi-wavelength coverage from a variety of ground- and space-based telescopes, and is concluded with a nebular spectrum $\sim10$ months after peak brightness. SN 2021zny displayed several characteristics of its class, such as the peak brightness ($M_{B}=-19.95$ mag), the slow decline ($\Delta m_{15}(B) = 0.62$ mag), the blue early-time colours, the low ejecta velocities and the presence of significant unburned material above the photosphere. However, a flux excess for the first $\sim1.5$ days after explosion is observed in four photometric bands, making SN 2021zny the third 03fg-like event with this distinct behavior, while its $+313$ d spectrum shows prominent [O I] lines, a very unusual characteristic of thermonuclear SNe. The early flux excess can be explained as the outcome of the interaction of the ejecta with $\sim0.04\:\mathrm{M_{\odot}}$ of H/He-poor circumstellar material at a distance of $\sim10^{12}$ cm, while the low ionization state of the late-time spectrum reveals low abundances of stable iron-peak elements. All our observations are in accordance with a progenitor system of two carbon/oxygen white dwarfs that undergo a merger event, with the disrupted white dwarf ejecting carbon-rich circumstellar material prior to the primary white dwarf detonation.Comment: 19 pages, 16 figures, accepted for publication in MNRA