Wavelength dependence of laser beam scintillation

Laser beam scintillation and log-amplitude variance evaluation for wavelengths on digital compute

SAO/NASA joint investigation of astronomical viewing quality at Mount Hopkins Observatory: 1969-1971

Quantitative measurements of the astronomical seeing conditions have been made with a stellar-image monitor system at the Mt. Hopkins Observatory in Arizona. The results of this joint SAO-NASA experiment indicate that for a 15-cm-diameter telescope, image motion is typically 1 arcsec or less and that intensity fluctuations due to scintillation have a coefficient of irradiance variance of less than 0.12 on the average. Correlations between seeing quality and local meteorological conditions were investigated. Local temperature fluctuations and temperature gradients were found to be indicators of image-motion conditions, while high-altitude-wind conditions were shown to be somewhat correlated with scintillation-spectrum bandwidth. The theoretical basis for the relationship of atmospheric turbulence to optical effects is discussed in some detail, along with a description of the equipment used in the experiment. General site-testing comments and applications of the seeing-test results are also included

The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms

Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A to FAM83H) interacted with the α and α-like isoforms of CK1; FAM83A, FAM83B, FAM83E, and FAM83H also interacted with the δ and ε isoforms of CK1. We detected no interaction between any FAM83 member and the related CK1γ1, CK1γ2, and CK1γ3 isoforms. Each FAM83 protein exhibited a distinct pattern of subcellular distribution and colocalized with the CK1 isoform(s) to which it bound. The interaction of FAM83 proteins with CK1 isoforms was mediated by the conserved domain of unknown function 1669 (DUF1669) that characterizes the FAM83 family. Mutations in FAM83 proteins that prevented them from binding to CK1 interfered with the proper subcellular localization and cellular functions of both the FAM83 proteins and their CK1 binding partners. On the basis of its function, we propose that DUF1669 be renamed the polypeptide anchor of CK1 domain

Activation loop targeting strategy for design of receptor-interacting protein kinase 2 (RIPK2) inhibitors

Development of selective kinase inhibitors remains a challenge due to considerable amino acid sequence similarity among family members particularly in the ATP binding site. Targeting the activation loop might offer improved inhibitor selectivity since this region of kinases is less conserved. However, the strategy presents difficulties due to activation loop flexibility. Herein, we report the design of receptor-interacting protein kinase 2 (RIPK2) inhibitors based on pankinase inhibitor regorafenib that aim to engage basic activation loop residues Lys169 or Arg171. We report development of CSR35 that displayed > 10-fold selective inhibition of RIPK2 versus VEGFR2, the target of regorafenib. A co-crystal structure of CSR35 with RIPK2 revealed a resolved activation loop with an ionic interaction between the carboxylic acid installed in the inhibitor and the side-chain of Lys169. Our data provides principle feasibility of developing activation loop targeting type II inhibitors as a complementary strategy for achieving improved selectivity

Proposed SLR Optical Bench Required to Track Debris Using 1550 nm Lasers

A previous study has indicated that by using approx.1550 nm wavelengths a laser ranging system can track debris objects in an "eye safe" manner, while increasing the expected return rate by a factor of approx. 2/unit area of the telescope. In this presentation we develop the optical bench required to use approx.1550nm lasers, and integration with a 532nm system. We will use the optical bench configuration for NGSLR as the baseline, and indicate a possible injection point for the 1550 nm laser. The presentation will include what elements may need to be changed for transmitting the required power on the approx.1550nm wavelength, supporting the alignment of the laser to the telescope, and possible concerns for the telescope optics

Small molecule inhibitors reveal an indispensable scaffolding role of RIPK2 in NOD2 signaling

RIPK2 mediates inflammatory signaling by the bacteria-sensing receptors NOD1 and NOD2. Kinase inhibitors targeting RIPK2 are a proposed strategy to ameliorate NOD-mediated pathologies. Here, we reveal that RIPK2 kinase activity is dispensable for NOD2 inflammatory signaling and show that RIPK2 inhibitors function instead by antagonizing XIAP-binding and XIAP-mediated ubiquitination of RIPK2. We map the XIAP binding site on RIPK2 to the loop between b2 and b3 of the N-lobe of the kinase, which is in close proximity to the ATP-binding pocket. Through characterization of a new series of ATP pocket-binding RIPK2 inhibitors, we identify the molecular features that determine their inhibition of both the RIPK2-XIAP interaction, and of cellular and in vivo NOD2 signaling. Our study exemplifies how targeting of the ATP-binding pocket in RIPK2 can be exploited to interfere with the RIPK2-XIAP interaction for modulation of NOD signaling

Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial.

AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791

Target highlights in CASP13: experimental target structures through the eyes of their authors

The functional and biological significance of selected CASP13 targets are described by the authors of the structures. The structural biologists discuss the most interesting structural features of the target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP13 experiment