OBJECTIVES/GOALS: Despite advances in precision medicine and understanding of the molecular pathways, melanoma remains the deadliest skin cancer, warranting identification of novel biomarkers. In this study, we performed bioinformatic analysis of melanoma patient tumors to identify novel dysregulated gene and micro-RNA (miRNA) targets responsible for survival. METHODS/STUDY POPULATION: Genetic sequencing data for 594 patient samples of melanoma and normal skin tissue from 10 databases were accessed using the NCBI Gene Expression Omnibus. Genes and miRNA that were significantly dysregulated (adjusted p-value < 0.05, log fold change > ± 2) in melanoma compared to normal skin were identified using the GEO2R program. Dataset expression profiles were cross-referenced to identify genetic elements dysregulated in at least 50% of datasets and filtered for association with poor survival using R2 Genomics Analysis and Visualization Platform. DAVID 6.8 provided pathway analysis of dysregulated genes. miRTarBase linked genes associated with poor survival and dysregulated miRNA from our database analysis. RESULTS/ANTICIPATED RESULTS: Bioinformatic analysis revealed consistent differential regulation of 205 genes (down=177 and up=28) and 38 miRNA across datasets with fold change >2 (bonf. p<0.05). Pathway analysis indicated that PPAR, phosphatidylinositol signaling, Rap1 signaling, and p53 signaling pathways were enriched by downregulated genes while the NF-kB pathway was enriched up regulated genes. Survival analysis of the differentially regulated genes identified 11 downregulated (ACSL1, CEBPA, CES4A, CRIP1, GATA3, HLADQB2, PTGS1, PYCARD, PPARG, PKP3, RSSF6) and 3 upregulated (DUXAP10, SLC2A3 and PRAME) hub genes to be associated with poor overall survival. Out of the 13 miRNA associated with hub genes, five miRNA (hsa-miR-125b-5p, hsa-miR-130b-3p, hsa-miR-26n-5p, hsa-miR-30b, hsa-miR-30c) were linked to multiple hub genes. DISCUSSION/SIGNIFICANCE: Our analysis identified 14 hub genes (regulators of PPARA, adipocyte differentiation, and transcriptional pathways) as well as miRNAs hsa-miR-30c (regulator of PTGS1 and SLC2A3) and hsa-let-7i-5p (regulator of ASCL1) as potential therapeutic targets. Further studies for validation of the targets are needed for clinical translation in melanoma.

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.

Knowledge of the effects of burial depth and burial duration on seed viability and, consequently, seedbank persistence of Palmer amaranth (Amaranthus palmeri S. Watson) and waterhemp [Amaranthus tuberculatus (Moq.) J. D. Sauer] ecotypes can be used for the development of efficient weed management programs. This is of particular interest, given the great fecundity of both species and, consequently, their high seedbank replenishment potential. Seeds of both species collected from five different locations across the United States were investigated in seven states (sites) with different soil and climatic conditions. Seeds were placed at two depths (0 and 15 cm) for 3 yr. Each year, seeds were retrieved, and seed damage (shrunken, malformed, or broken) plus losses (deteriorated and futile germination) and viability were evaluated. Greater seed damage plus loss averaged across seed origin, burial depth, and year was recorded for lots tested at Illinois (51.3% and 51.8%) followed by Tennessee (40.5% and 45.1%) and Missouri (39.2% and 42%) for A. palmeri and A. tuberculatus, respectively. The site differences for seed persistence were probably due to higher volumetric water content at these sites. Rates of seed demise were directly proportional to burial depth (α=0.001), whereas the percentage of viable seeds recovered after 36 mo on the soil surface ranged from 4.1% to 4.3% compared with 5% to 5.3% at the 15-cm depth for A. palmeri and A. tuberculatus, respectively. Seed viability loss was greater in the seeds placed on the soil surface compared with the buried seeds. The greatest influences on seed viability were burial conditions and time and site-specific soil conditions, more so than geographical location. Thus, management of these weed species should focus on reducing seed shattering, enhancing seed removal from the soil surface, or adjusting tillage systems.

The Megamaser Cosmology Project (MCP) measures the Hubble Constant by determining geometric distances to circumnuclear 22 GHz H2O megamasers in galaxies at low redshift (z < 0.05) but well into the Hubble flow. In combination with the recent, exquisite observations of the Cosmic Microwave Background by WMAP and Planck, these measurements provide a direct test of the standard cosmological model and constrain the equation of state of dark energy. The MCP is a multi-year project that has recently completed observations and is currently working on final analysis. Based on distance measurements to the first four published megamasers in the sample, the MCP currently determines H0 = 69.3 ± 4.2 km s−1 Mpc−1. The project is finalizing analysis for five additional galaxies. When complete, we expect to achieve a ~4% measurement. Given the tension between the Planck prediction of H0 in the context of the standard cosmological model and astrophysical measurements based on standard candles, the MCP provides a critical and independent geometric measurement that does not rely on external calibrations or a distance ladder.

Many accretion disks surrounding supermassive black holes in nearby AGN are observed to host 22 GHz water maser activity. We have analyzed single-dish 22 GHz spectra taken with the GBT to identify 32 such “Keplerian disk systems,” which we used to investigate maser excitation and explore the possibility of disk reverberation. Our results do not support a spiral shock model for population inversion in these disks, and we find that any reverberating signal propagating radially outwards from the AGN must constitute <10% of the total observed maser variability. Additionally, we have used ALMA to begin exploring the variety of sub-mm water megamasers that are also predicted, and in the case of the 321 GHz transition found, to be present in these accretion disks. By observing multiple masing transitions within a single system, we can better constrain the physical conditions (e.g., gas temperature and density) in the accretion disk.

The exclusive association of Class II methanol masers with high mass star formation regions and in turn spiral arms, makes them ideal tracers of spiral structure. The bright and compact nature of masers also makes them good sources for Very Long Baseline Interferometry, with their fluxes visible on some of the longest terrestrial baselines. The success of the BeSSeL (Bar and Spiral Structure Legacy) project has demonstrated the use of masers in large scale high–precision trigonometric parallax surveys. This survey was then able to precisely map the spiral arms visible from the Northern Hemisphere and recalculate the fundamental Milky Way parameters R0 and θ0. The majority of the Milky Way is visible from the Southern Hemisphere and at the present time the Australian LBA (Long Baseline Array) is the only Southern Hemisphere array capable of taking high–precision trigonometric parallax data. We present the progress–to–date of the Southern Hemisphere experiment. We will also unveil a new broadband Southern Hemisphere array, capable of much faster parallax turnaround and atmospheric calibration.

Maser astrometry is now providing parallaxes with accuracies of ±10 micro-arcseconds, which corresponds to 10% accuracy at a distance of 10 kpc! The VLBA BeSSeL Survey and the Japanese VERA project have measured ≈200 parallaxes for masers associated with young, high-mass stars. Since these stars are found in spiral arms, we now are directly mapping the spiral structure of the Milky Way. Combining parallaxes, proper motions, and Doppler velocities, we have complete 6-dimensional phase-space information. Modeling these data yields the distance to the Galactic Center, the rotation speed of the Galaxy at the Sun, and the nature of the rotation curve.

Amaranthus species, commonly referred to as “pigweeds,” are among the most troublesome weeds in many crop production systems. Effective control of these species often begins with an understanding of their biological and reproductive characteristics. At two sites in Missouri, six pigweed species (redroot pigweed, common waterhemp, spiny amaranth, tumble pigweed, smooth pigweed, and Palmer amaranth) were established in 60-m rows spaced 1.5 m apart. At biweekly intervals, plant heights and dry weights were recorded for each species; seed numbers were estimated at the end of the growing season. Dry weight of Palmer amaranth was up to 65% greater than those of all other species 2 wk after planting (WAP). Palmer amaranth biomass accumulation remained greater than those of the other species throughout the season and at the end of the season was 1.2- and 2.7-fold greater than those of redroot and tumble pigweed, respectively. Palmer amaranth was approximately 10 cm tall 2 WAP (37% taller than the next tallest species, redroot pigweed) and approximately 24 cm tall 4 WAP (45% taller than redroot pigweed). In contrast, common waterhemp had not emerged 2 WAP, and plant dry weight 4 WAP was approximately 11 and 26% those of Palmer amaranth and redroot pigweed, respectively. Final plant height ranged from 58 (tumble pigweed) to 208 cm (Palmer amaranth). Redroot pigweed, smooth pigweed, common waterhemp, and Palmer amaranth plants each produced over 250,000 seeds plant−1. Spiny amaranth and tumble pigweed produced approximately 114,000 and 50,000 seeds plant−1, respectively. Common waterhemp produced 535 seeds g−1 of total plant dry weight; this seed production was 1.4-, 1.4-, 2.0-, 3.4-, and 3.4-fold greater than those of redroot pigweed, smooth pigweed, Palmer amaranth, tumble pigweed, and spiny amaranth, respectively. Because the timing for many postemergence herbicides depends on weed height, rapid growth shortly after emergence reduces the time frame for optimum control of species such as Palmer amaranth. Delayed emergence also could result in escaped common waterhemp. Escape of only a few plants could result in a rapid increase in seed populations in the soil seed bank and may select for late-emerging biotypes.

Employing a participatory arts-based research approach, we examined an innovative program from rural Ontario, Canada, designed to address social isolation among older people. Older socially isolated adults were matched to trained volunteers, where in dyads, the eight pairs created expressive art in their home setting over the course of 10 home visits. With thematic and narrative inquiry, we analysed the experiences and perceptions of the program leader, older participants, and older volunteers via their artistic creations, weekly logs, evaluations, and field notes. The findings reveal a successful intervention that positively influenced the well-being of older adult participants and older volunteers, especially in regards to relationships, personal development, and creating meaning as well as extending the intervention’s impact beyond the program’s duration. We also discuss opportunities for similar programs to inform policy and enable positive community-based health and social service responses to rural social isolation.

The present study is the first record of twinning in Lagenorhynchus acutus and indeed any Lagenorhynchus sp. Both foetuses were male and located in the left uterine horn, had distinct grossly normal placentas and amniotic sacs, and were therefore likely dizygotic twins. The twins were an incidental finding in an animal that died of a systemic Brucella ceti infection.

Can concerns for one’s reputation cause non-governmental organizations (NGOs) to alter their behavior to the detriment of achieving their policy goals? To answer this question, we explore the relationship between NGOs and their donors. Our theoretical model reveals that reputation can be a key piece of information in the decision to fund an NGO’s activities. Reputation can become so important to the NGO’s survival that it interferes with the long-term policy goals of the organization. As such, reputations can become a double-edged sword, simultaneously providing the information donors seek while constraining NGOs from realizing policy goals. We apply this logic to the problem of NGO accountability, which has received increasing attention in recent years, and demonstrate that the tools used by donors to improve accountability can trigger unintended consequences. We illustrate this strategic dynamic with two types of NGO activity: water improvement and international crisis mediation.

We made dynamical black hole mass measurements from nineteen Seyfert 2 galaxies which host sub-parsec H2O maser disks using the H2O megamaser technique. The nearly perfect Keplerian rotation curves in many of these maser systems guarantee the high accuracy and precision of the black hole mass measurements. With the stellar velocity dispersion (σ∗) of the galaxy bulges measured with the Dupont 2.5 m telescope at Las Campanas Observatory in the South and the Apache Point Observatory (APO) 3.5m telescope in the North, we found that H2O maser galaxies, most of which host pseudo bulges rather than classical bulges, do not all follow the MBH–σ∗ relation shown in the literature. This result is well consistent with the latest findings by Kormendy & Ho (2013) that only early type galaxies and galaxies with classical bulges follow a tight MBH–σ∗ relation. Such a tight correlation may not exist in pseudo bulge galaxies.

Some evidence suggests that Ca and vitamin D supplements affect cancer risk; however, it is uncertain whether the effects are due to Ca, vitamin D or the combination. We investigated the effect of Ca supplements without co-administered vitamin D on cancer risk. Medline, Embase and the Cochrane Central Register of Controlled Trials, reference lists of meta-analyses and two clinical trial registries were searched for randomised, placebo-controlled trials of Ca supplements ( ≥ 500 mg/d), with ≥ 100 participants and duration >1 year. The lead authors of eligible trials supplied data on cancer outcomes. Trial-level data were analysed using random-effects meta-analyses and patient-level data using Cox proportional hazards models. A total of sixteen trials were eligible, six had no data available, ten provided trial-level data (n 10 496, mean duration 3·9 years), and of these, four provided patient-level data (n 7221, median duration 3·5 years). In the meta-analysis of trial-level data, allocation to Ca did not alter the risk of total cancer (relative risk 0·95, 95 % CI 0·76, 1·18, P= 0·63), colorectal cancer (relative risk 1·38, 95 % CI 0·89, 2·15, P= 0·15), breast cancer (relative risk 1·01, 95 % CI 0·64, 1·59, P= 0·97) or cancer-related mortality (relative risk 0·96, 95 % CI 0·74, 1·24, P= 0·75), but reduced the risk of prostate cancer (relative risk 0·54, 95 % CI 0·30, 0·96, P= 0·03), although there were few events. The meta-analysis of patient-level data showed similar results, with no effect of Ca on the risk of total cancer (hazard ratio 1·07, 95 % CI 0·89, 1·28, P= 0·50). Ca supplements without co-administered vitamin D did not alter total cancer risk over 4 years, although the meta-analysis lacked power to detect very small effects, or those with a longer latency.