A10 – Human Factors Considerations of UAS Procedures and Control Stations: Tasks PC-1 through PC-3 Pilot and Crew (PC) Subtask, Recommended Requirements and Operational Procedures

The Alliance for System Safety of UAS through Research Excellence (ASSURE) conducted research focused on minimum pilot procedures and operational practices used by unmanned aircraft systems (UAS) operators today for the purpose of developing recommendations. This research recommends four pilot and 46 operational minimum procedures to operate a civil single-engine, fixed-wing, single-pilot-configured UAS flying in beyond visual line-of-sight (BVLOS) conditions. These recommendations are anticipated to support potential future aircrew procedure requirements for UAS larger than 55 lbs. operating in the National Airspace System (NAS). These procedures were validated using representative Control Stations in simulated environments

Uveal Melanoma Cell Line Proliferation Is Inhibited by Ricolinostat, a Histone Deacetylase Inhibitor

Uveal melanoma (UM) is the most common adult eye cancer. UM originates in the iris, ciliary body or choroid (collectively known as the uvea), in the middle layer of the eye. This first or primary UM is treated by targeting cancer cells using ocular radiation implants or by surgical removal of the eye. However, when UM spreads to the liver and other parts of the body, patients have a poor survival prognosis. Unfortunately, there are no effective treatment options for UM that has spread. Our aim is to help identify effective treatments for UM. In our study, we identified that the drug ACY-1215 prevents the growth of cells derived from UM in the eye and a UM that spread to the liver. Our pre-clinical study uncovered a potential treatment approach for advanced UM. Metastatic uveal melanoma (MUM) is characterized by poor patient survival. Unfortunately, current treatment options demonstrate limited benefits. In this study, we evaluate the efficacy of ACY-1215, a histone deacetylase inhibitor (HDACi), to attenuate growth of primary ocular UM cell lines and, in particular, a liver MUM cell line in vitro and in vivo, and elucidate the underlying molecular mechanisms. A significant (p = 0.0001) dose-dependent reduction in surviving clones of the primary ocular UM cells, Mel270, was observed upon treatment with increasing doses of ACY-1215. Treatment of OMM2.5 MUM cells with ACY-1215 resulted in a significant (p = 0.0001), dose-dependent reduction in cell survival and proliferation in vitro, and in vivo attenuation of primary OMM2.5 xenografts in zebrafish larvae. Furthermore, flow cytometry revealed that ACY-1215 significantly arrested the OMM2.5 cell cycle in S phase (p = 0.0001) following 24 h of treatment, and significant apoptosis was triggered in a time- and dose-dependent manner (p < 0.0001). Additionally, ACY-1215 treatment resulted in a significant reduction in OMM2.5 p-ERK expression levels. Through proteome profiling, the attenuation of the microphthalmia-associated transcription factor (MITF) signaling pathway was linked to the observed anti-cancer effects of ACY-1215. In agreement, pharmacological inhibition of MITF signaling with ML329 significantly reduced OMM2.5 cell survival and viability in vitro (p = 0.0001) and reduced OMM2.5 cells in vivo (p = 0.0006). Our findings provide evidence that ACY-1215 and ML329 are efficacious against growth and survival of OMM2.5 MUM cells

Spitzer observations of hydrogen deuteride

We report the detection of interstellar hydrogen deuteride (HD) toward the supernova remnant IC443, and the tentative detection of HD toward the Herbig Haro objects HH54 and HH7 and the star forming region GGD37 (Cepheus A West). Our detections are based upon spectral line mapping observations of the R(3) and R(4) rotational lines of HD, at rest wavelengths of 28.502 and 23.034 micron respectively, obtained using the Infrared Spectrograph onboard the Spitzer Space Telescope. The HD R(4)/R(3) line intensity ratio promises to be a valuable probe of the gas pressure in regions where it can be observed. The derived HD/H2 abundance ratios are 1.19(+0.35/-0.24)E-5, 1.80(+0.54/-0.32)E-5, and 1.41(+0.46/-0.33)E-5 respectively (68.3% confidence limits, based upon statistical errors alone) for IC443 (clump C), HH54, and HH7. If HD is the only significant reservoir of gas-phase deuterium in these sources, the inferred HD/H2 ratios are all consistent with a gas-phase elemental abundance [n(D)/n(H)](gas) ~ 7.5E-6, a factor 2 - 3 below the values obtained previously from observations of atomic deuterium in the local bubble and the Galactic halo. However, similarly low gas-phase deuterium abundances have been inferred previously for molecular gas clouds in the Orion region, and in atomic clouds along sight-lines within the Galactic disk to stars more distant than 500 pc from the Sun.Comment: 12 pages, including 5 figures. Accepted for publication in ApJ Letter

The Campbells: lordship, literature and liminality

The Campbells have the potential to offer much to the theme of literature and borders, given that the kindred’s astonishing political success in the late medieval and early modern period depended heavily upon the ability to negotiate multiple frontiers: between Highlands and Lowlands; between Gaelic Scotland and Ireland, and, especially after the Reformation, with England and the matter of Britain. This paper will explore the literary dimension to Campbell expansionism, from the Book of the Dean of Lismore in the earlier sixteenth century, to poetry addressed to dukes of Argyll in the earlier eighteenth century. Particular attention will be paid to the literary proclivities of the household of the Campbells of Glenorchy on either side of what appears to be a major watershed in 1550; and to the agenda of the Campbell protégé John Carswell, first post-Reformation bishop of the Isles, and author of the first printed book in Gaelic in either Scotland or Ireland, Foirm na n-Urrnuidheadh (‘The Form of Prayers’), published at Edinburgh in 1567

The Empirical Foundations of Telemedicine Interventions for Chronic Disease Management

The telemedicine intervention in chronic disease management promises to involve patients in their own care, provides continuous monitoring by their healthcare providers, identifies early symptoms, and responds promptly to exacerbations in their illnesses. This review set out to establish the evidence from the available literature on the impact of telemedicine for the management of three chronic diseases: congestive heart failure, stroke, and chronic obstructive pulmonary disease. By design, the review focuses on a limited set of representative chronic diseases because of their current and increasing importance relative to their prevalence, associated morbidity, mortality, and cost. Furthermore, these three diseases are amenable to timely interventions and secondary prevention through telemonitoring. The preponderance of evidence from studies using rigorous research methods points to beneficial results from telemonitoring in its various manifestations, albeit with a few exceptions. Generally, the benefits include reductions in use of service: hospital admissions/re-admissions, length of hospital stay, and emergency department visits typically declined. It is important that there often were reductions in mortality. Few studies reported neutral or mixed findings.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140284/1/tmj.2014.9981.pd

Monitoring Vibration and Other Critical Machine Conditions

Discussion Grou

Monitoring Vibration and Other Critical Machine Conditions

Discussion Grou

Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program

Background-We assessed whether 234 established dyslipidemia-associated loci modify the effects of metformin treatment and lifestyle intervention (versus placebo control) on lipid and lipid subfraction levels in the Diabetes Prevention Program randomized controlled trial. Methods and Results-We tested gene treatment interactions in relation to baseline-adjusted follow-up blood lipid concentrations (high-density lipoprotein [HDL] and low-density lipoprotein-cholesterol, total cholesterol, and triglycerides) and lipoprotein subfraction particle concentrations and size in 2993 participants with pre-diabetes. Of the previously reported single-nucleotide polymorphism associations, 32.5% replicated at PP>1.1×10-16) with their respective baseline traits for all but 2 traits. Lifestyle modified the effect of the genetic risk score for large HDL particle numbers, such that each risk allele of the genetic risk scores was associated with lower concentrations of large HDL particles at follow-up in the lifestyle arm (β=-0.11 μmol/L per genetic risk scores risk allele; 95% confidence interval,-0.188 to-0.033; P=5×10-3; Pinteraction=1×10-3 for lifestyle versus placebo), but not in the metformin or placebo arms (P>0.05). In the lifestyle arm, participants with high genetic risk had more favorable or similar trait levels at 1-year compared with participants at lower genetic risk at baseline for 17 of the 20 traits. Conclusions-Improvements in large HDL particle concentrations conferred by lifestyle may be diminished by genetic factors. Lifestyle intervention, however, was successful in offsetting unfavorable genetic loading for most lipid traits. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique Identifier: NCT00004992

DMAPT inhibits NF-κB activity and increases sensitivity of prostate cancer cells to X-rays in vitro and in tumor xenografts in vivo

Constitutive activation of the pro-survival transcription factor NF-κB has been associated with resistance to both chemotherapy and radiation therapy in many human cancers, including prostate cancer. Our lab and others have demonstrated that the natural product parthenolide can inhibit NF-κB activity and sensitize PC-3 prostate cancers cells to X-rays in vitro; however, parthenolide has poor bioavailability in vivo and therefore has little clinical utility in this regard. We show here that treatment of PC-3 and DU145 human prostate cancer cells with dimethylaminoparthenolide (DMAPT), a parthenolide derivative with increased bioavailability, inhibits constitutive and radiation-induced NF-κB binding activity and slows prostate cancer cell growth. We also show that DMAPT increases single and fractionated X-ray-induced killing of prostate cancer cells through inhibition of DNA double strand break repair and also that DMAPT-induced radiosensitization is, at least partially, dependent upon the alteration of intracellular thiol reduction-oxidation chemistry. Finally, we demonstrate that the treatment of PC-3 prostate tumor xenografts with oral DMAPT in addition to radiation therapy significantly decreases tumor growth and results in significantly smaller tumor volumes compared to xenografts treated with either DMAPT or radiation therapy alone, suggesting that DMAPT might have a potential clinical role as a radiosensitizing agent in the treatment of prostate cancer