A recent study from Central Europe has changed our perception of the cat's domestication history. The authors discuss how this has led to the development of an interdisciplinary project combining palaeogenetics, zooarchaeology and radiocarbon dating, with the aim of providing insight into the domestic cat's expansion beyond the Mediterranean.

OBJECTIVES/GOALS: Immunomodulatory drugs (IMiDs) are critical to multiple myeloma (MM) disease control. IMiDs act by inducing Cereblon-dependent degradation of IKZF1 and IKZF3, which leads to IRF4 and MYC downregulation (collectively termed the “Ikaros axis”). We therefore hypothesized that IMiD treatment fails to downregulate the Ikaros axis in IMiD resistant MM. METHODS/STUDY POPULATION: To measure IMiD-induced Ikaros axis downregulation, we designed an intracellular flow cytometry assay that measured relative protein levels of IKZF1, IKZF3, IRF4 and MYC in MM cells following ex vivo treatment with the IMiD Pomalidomide (Pom). We established this assay using Pom-sensitive parental and dose-escalated Pom-resistant MM cell lines before assessing Ikaros axis downregulation in CD38+CD138+ MM cells in patient samples (bone marrow aspirates). To assess the Ikaros axis in the context of MM intratumoral heterogeneity, we used a 35-marker mass cytometry panel to simultaneously characterize MM subpopulations in patient samples. Lastly, we determined ex vivo drug sensitivity in patient samples via flow cytometry. RESULTS/ANTICIPATED RESULTS: Our hypothesis was supported in MM cell lines, as resistant lines showed no IMiD-induced decrease in any Ikaros axis proteins. However, when assessed in patient samples, Pom treatment caused a significant decrease in IKZF1, IKZF3 and IRF4 regardless of IMiD sensitivity. Mass cytometry in patient samples revealed that individual Ikaros axis proteins were differentially expressed between subpopulations. When correlating this with ex vivo Pom sensitivity of MM subpopulations, we observed that low IKZF1 and IKZF3 corresponded to Pom resistance. Interestingly, most of these resistant populations still expressed MYC. We therefore assessed whether IMiD resistant MM was MYC dependent by treating with MYCi975. In 88% (7/8) of patient samples tested, IMiD resistant MM cells were sensitive to MYC inhibition. DISCUSSION/SIGNIFICANCE: While our findings did not support our initial hypothesis, our data suggest a mechanism where MYC expression becomes Ikaros axis independent to drive IMiD resistance, and resistant MM is still dependent on MYC. This suggests targeting MYC directly or indirectly via a mechanism to be determined may be an effective strategy to eradicate IMiD resistant MM.

The plant availability of manure nitrogen (N) is influenced by manure composition in the year of application whereas some studies indicate that the legacy effect in following years is independent of the composition. The plant availability of N in pig and cattle slurries with variable contents of particulate matter was determined in a 3-year field study. We separated cattle and a pig slurry into liquid and solid fractions by centrifugation. Slurry mixtures with varying proportions of solid and liquid fraction were applied to a loamy sand soil at similar NH4+-N rates in the first year. Yields and N offtake of spring barley and undersown perennial ryegrass were compared to plots receiving mineral N fertilizer. The first year N fertilizer replacement value (NFRV) of total N in slurry mixtures decreased with increasing proportion of solid fraction. The second and third season NFRV averaged 6.5% and 3.8% of total N, respectively, for cattle slurries, and 18% and 7.5% for pig slurries and was not related to the proportion of solid fraction. The estimated net N mineralization of residual organic N increased nearly linearly with growing degree days (GDD) with a rate of 0.0058%/GDD for cattle and 0.0116%/GDD for pig slurries at 2000–5000 GDD after application. In conclusion NFRV of slurry decreased with increasing proportion of solid fraction in the first year. In the second year, NFRV of pig slurry N was significantly higher than that of cattle slurry N and unaffected by proportion between solid and liquid fraction.

Hydrogen lithography has been used to template phosphine-based surface chemistry to fabricate atomic-scale devices, a process we abbreviate as atomic precision advanced manufacturing (APAM). Here, we use mid-infrared variable angle spectroscopic ellipsometry (IR-VASE) to characterize single-nanometer thickness phosphorus dopant layers (δ-layers) in silicon made using APAM compatible processes. A large Drude response is directly attributable to the δ-layer and can be used for nondestructive monitoring of the condition of the APAM layer when integrating additional processing steps. The carrier density and mobility extracted from our room temperature IR-VASE measurements are consistent with cryogenic magneto-transport measurements, showing that APAM δ-layers function at room temperature. Finally, the permittivity extracted from these measurements shows that the doping in the APAM δ-layers is so large that their low-frequency in-plane response is reminiscent of a silicide. However, there is no indication of a plasma resonance, likely due to reduced dimensionality and/or low scattering lifetime.

OBJECTIVES/SPECIFIC AIMS: This study aims to understand the factors influencing engagement with out-patient services from pregnancy to 1 year postpartum among women in recovery from opioid use disorders (OUD). METHODS/STUDY POPULATION: We conducted semi-structured qualitative interviews and a brief survey with 20 mothers in OUD recovery recruited from health care and community organizations in Western MA. Transcripts were coded by two independent coders and analyzed using a qualitative descriptive approach. RESULTS/ANTICIPATED RESULTS: The average duration of any addiction treatment among the 20 participants was 5.6 years with 80% receiving medication-assisted treatment during a pregnancy. Approximately two-thirds experienced relapse during pregnancy or the first year postpartum. We identified 3 themes elucidating women’s experiences around service engagement: “How I see myself” (personal development), “How services see me” (service delivery quality), and “Are you with me?” Personal development included response to past trauma, coping strategies and self-advocacy, and adjusting to parenthood. Service delivery quality was influenced by service design, efficacy of individual providers, and cultural norms (organizational and societal). In the final theme, intersection of individual and service-level factors influenced the degree and quality of the women’s experience engaging with services. DISCUSSION/SIGNIFICANCE OF IMPACT: Women describe successful engagement when they experience service providers as being emotionally supportive, delivering relevant services, and advocating on their behalf. To best support and engage families affected by OUD, relevant and timely services should be linked with compassionate delivery.

We describe the design and performance of the Engineering Development Array, which is a low-frequency radio telescope comprising 256 dual-polarisation dipole antennas working as a phased array. The Engineering Development Array was conceived of, developed, and deployed in just 18 months via re-use of Square Kilometre Array precursor technology and expertise, specifically from the Murchison Widefield Array radio telescope. Using drift scans and a model for the sky brightness temperature at low frequencies, we have derived the Engineering Development Array’s receiver temperature as a function of frequency. The Engineering Development Array is shown to be sky-noise limited over most of the frequency range measured between 60 and 240 MHz. By using the Engineering Development Array in interferometric mode with the Murchison Widefield Array, we used calibrated visibilities to measure the absolute sensitivity of the array. The measured array sensitivity matches very well with a model based on the array layout and measured receiver temperature. The results demonstrate the practicality and feasibility of using Murchison Widefield Array-style precursor technology for Square Kilometre Array-scale stations. The modular architecture of the Engineering Development Array allows upgrades to the array to be rolled out in a staged approach. Future improvements to the Engineering Development Array include replacing the second stage beamformer with a fully digital system, and to transition to using RF-over-fibre for the signal output from first stage beamformers.

The Numeniini is a tribe of 13 wader species (Scolopacidae, Charadriiformes) of which seven are Near Threatened or globally threatened, including two Critically Endangered. To help inform conservation management and policy responses, we present the results of an expert assessment of the threats that members of this taxonomic group face across migratory flyways. Most threats are increasing in intensity, particularly in non-breeding areas, where habitat loss resulting from residential and commercial development, aquaculture, mining, transport, disturbance, problematic invasive species, pollution and climate change were regarded as having the greatest detrimental impact. Fewer threats (mining, disturbance, problematic native species and climate change) were identified as widely affecting breeding areas. Numeniini populations face the greatest number of non-breeding threats in the East Asian-Australasian Flyway, especially those associated with coastal reclamation; related threats were also identified across the Central and Atlantic Americas, and East Atlantic flyways. Threats on the breeding grounds were greatest in Central and Atlantic Americas, East Atlantic and West Asian flyways. Three priority actions were associated with monitoring and research: to monitor breeding population trends (which for species breeding in remote areas may best be achieved through surveys at key non-breeding sites), to deploy tracking technologies to identify migratory connectivity, and to monitor land-cover change across breeding and non-breeding areas. Two priority actions were focused on conservation and policy responses: to identify and effectively protect key non-breeding sites across all flyways (particularly in the East Asian- Australasian Flyway), and to implement successful conservation interventions at a sufficient scale across human-dominated landscapes for species’ recovery to be achieved. If implemented urgently, these measures in combination have the potential to alter the current population declines of many Numeniini species and provide a template for the conservation of other groups of threatened species.

In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.

The fragmented ecosystems along the Niagara Escarpment World Biosphere Reserve provide important habitats for biota including lichens. Nonetheless, the Reserve is disturbed by dense human populations and associated air pollution. Here we investigated patterns of lichen diversity within urban and rural sites at three different locations (Niagara, Hamilton, and Owen Sound) along the Niagara Escarpment in Ontario, Canada. Our results indicate that both lichen species richness and community composition are negatively correlated with increasing human population density and air pollution. However, our quantitative analysis of community composition using canonical correspondence analysis (CCA) indicates that human population density and air pollution is more independent than might be assumed. The CCA analysis suggests that the strongest environmental gradient (CCA1) associated with lichen community composition includes regional pollution load and climatic variables; the second gradient (CCA2) is associated with local pollution load and human population density factors. These results increase the knowledge of lichen biodiversity for the Niagara Escarpment and urban and rural fragmented ecosystems as well as along gradients of human population density and air pollution; they suggest a differential influence of regional and local pollution loads and population density factors. This study provides baseline knowledge for further research and conservation initiatives along the Niagara Escarpment World Biosphere Reserve.