It is known that the water entry of a body with a recessed, cupped nose can suppress the splash and air cavity typically observed for solid body entry (Mathai, Govardhan & Arakeri, Appl. Phys. Lett., vol. 106, 2015, 064101). However, the interplay between the captive gas in the cup, the cavity and the splash is quite subtle and has not been thoroughly explored. Here we study the cavity and splash dynamics associated with the vertical water entry of cups and find a variety of regimes over a range of Weber numbers ($We_D$) and dimensionless cup depths. Our parameter space spans a transition between slow-developing cavities with long closure times (low $We_D$) to fast-sealing cavities (high $We_D$). An important dynamic event is the evacuation of trapped gas from within the cup, which drives the ensuing cavity and splash behaviour. Through modelling, we predict the conditions for which the evacuating gas inflates a cavity that opens to the atmosphere versus inflating a submerged cavity that suppresses air entrainment from above the surface. We also compare our cup water entry findings to the impact phenomena observed for flat disks, which entrap gas on the front surface similar to cups. In doing so, we reveal the sensitivity of disk splash and cavity behaviour to impact angle, and show that disks share a common regime with cups, in which a thin splash quickly seals on the body. We deduce the mechanisms by which increasing cup depth delays the cavity seal time in this regime. These findings reveal that cups may in fact promote or suppress cavity growth, depending on the cup depth and impact conditions.

The Swan Point site in interior Alaska contains a significant multi-component archaeological record dating back to 14,200 cal BP. The site’s radiocarbon (14C) chronology has been presented in scattered publications that mostly focus on specific archaeological periods in Alaska, in particular its terminal Pleistocene components associated with the East Beringian tradition. This paper synthesizes the site’s 14C data and provides sequential Bayesian models for its cultural zones and subzones. The 14C and archaeological record at Swan Point attests that the location was persistently used over the last 14,000 years, even though major changes are evident within regional vegetation and local faunal communities, reflecting long-term trends culminating in Dene-Athabascan history.

OBJECTIVES/GOALS: We aim to discover safer and more effective therapeutics for CNS disorders. Current therapeutic development is hindered by dosing out drugs for safe consumption. By identifying proteins with narrow functional roles in the brain (i.e., behavioral control), we can develop drugs targeting these proteins for improved treatment safety and efficacy. METHODS/STUDY POPULATION: We focused on an evolutionarily new, non-neuronal, non-synaptic glutamate signaling mechanism, system xc- (Sxc). Sxc activity was eliminated by mutating the gene Slc7a11 through pronuclear injection of zinc-finger nucleases into Sprague Dawley rat embryos to create a line of rats lacking Sxc (MSxc). To confirm Sxc mutation, we verified that tissue from MSxc rats had a complete lack of xCT, which is the regulatory subunit of Sxc that is encoded by Slc7a11. We also verified that astrocyte cultures generated from MSxc tissue lacked cystine-evoked glutamate release. Next, we measured development (body weight), CNS regulation of metabolism, and other indicators of generalized, non-specific brain function as well as behaviors that are reliant on behavioral control, such as impulse control and response inhibition. RESULTS/ANTICIPATED RESULTS: Eliminating Sxc was not lethal and did not impair development or produce widespread changes in brain function as is commonly observed when deleting other glutamate mechanisms. MSxc rats did not differ from wildtype in growth rate, central regulation of metabolism as reflected by absolute or diurnal changes in core body temperature, locomotor activity in a familiar or novel environment, or simple forms of cognition such as novel object recognition, or operant responding (food and cocaine-reinforced). In contrast, behaviors that rely on behavioral control were impaired. MSxc rats displayed deficits in impulse control and behavioral flexibility. We hypothesize that MSxc rats will also show deficits in response inhibition using the stop signal reaction time task, a common metric used in clinical populations. DISCUSSION/SIGNIFICANCE: Eliminating Sxc activity in rats produced deficits in behaviors reliant on impulse control, without impacting development or simple brain function. These results show the potential of targeting Sxc to restore behavioral control without generating therapeutically limiting adverse effects resulting from non-specific changes in brain function.

OBJECTIVES/GOALS: Smoking is a well-established risk factor for lung cancer, but never smokers account for up to 25% of lung cancer cases. There is mounting evidence that lung cancer in never smokers is biologically distinct. We aim to characterize the genomic and immunologic features of lung adenocarcinoma in never smokers versus smokers. METHODS/STUDY POPULATION: We examined clinical, genomic, and bulk-RNA sequencing data from 499 patients in the TCGA lung adenocarcinoma cohort. Tumor mutation burden was analyzed using maftools (R package). Tumor immune characterization was completed using CIBERSORTx, a digital cytometry tool that uses single cell reference profiles to determine immune cell type frequencies from bulk-RNA sequencing data. Single cell reference profiles for 19 different immune cell types were constructed from sequencing of freshly resected lung tumor tissue from UCSF patients. Partitioning Around Medoids (PAM; R package) was used to identify distinct immune phenotypes based on immune cell composition. Fisher’s exact test was used to evaluate for associations between immune phenotypes and smoking status. RESULTS/ANTICIPATED RESULTS: Of the 499 TCGA lung adenocarcinoma patients, 75 were never smokers, 269 were female, and 246 were over the age of 65. Never smokers had lower tumor mutation burden and lower predicted neoantigen burden compared to smokers (p < 0.001). There was no difference in total tumor immune cell infiltration between never smokers and smokers. PAM yielded 2 distinct clusters/immune phenotypes. The first was enriched in M1 Macrophages, cytotoxic T Cells, helper T Cells, regulatory T Cells, and Plasma Cells. The second was enriched in plasmacytoid Dendritic Cells, M2 Macrophages, and exhausted cytotoxic T Cells. Never smoking status was associated with an increased odds of having the first immune phenotype (OR 1.95, 95% CI: 1.15 - 3.35) and this association was statistically significant (p = 0.0086). DISCUSSION/SIGNIFICANCE: Our findings suggest that never smokers have an immune phenotype that is distinct from that observed in smokers. The distinct immune characteristics we observed could explain clinical trial data suggesting immune checkpoint inhibitors are less effective in never smokers and hold implications for tailoring therapy.

Until recently, the influence of basal liquid water on the evolution of buried glaciers in Mars' mid latitudes was assumed to be negligible because the latter stages of Mars' Amazonian period (3 Ga to present) have long been thought to have been similarly cold and dry to today. Recent identifications of several landforms interpreted as eskers associated with these young (100s Ma) glaciers calls this assumption into doubt. They indicate basal melting (at least locally and transiently) of their parent glaciers. Although rare, they demonstrate a more complex mid-to-late Amazonian environment than was previously understood. Here, we discuss several open questions posed by the existence of glacier-linked eskers on Mars, including on their global-scale abundance and distribution, the drivers and dynamics of melting and drainage, and the fate of meltwater upon reaching the ice margin. Such questions provide rich opportunities for collaboration between the Mars and Earth cryosphere research communities.

Understanding spatial variation in origination and extinction can help to unravel the mechanisms underlying macroevolutionary patterns. Although methods have been developed for estimating global origination and extinction rates from the fossil record, no framework exists for applying these methods to restricted spatial regions. Here, we test the efficacy of three metrics for regional analysis, using simulated fossil occurrences. These metrics are then applied to the marine invertebrate record of the Permian and Triassic to examine variation in extinction and origination rates across latitudes. Extinction and origination rates were generally uniform across latitudes for these time intervals, including during the Capitanian and Permian–Triassic mass extinctions. The small magnitude of this variation, combined with the possibility of its attribution to sampling bias, cautions against linking any observed differences to contrasting evolutionary dynamics. Our results indicate that origination and extinction levels were more variable across clades than across latitudes.

This study uses isotope and microbotanical data from the analysis of teeth and dental calculus to investigate camelid diet and foddering practices at Quilcapampa (AD 835–900). By providing taxonomically specific evidence of foods consumed, botanical data from dental calculus complement the more general impressions of photosynthetic pathways obtained through isotopic analysis. Results suggest that the camelid diet incorporated maize (Zea mays), algarrobo (Prosopis sp.), potato chuño (Solanum sp.), and other resources. The life-history profile of one camelid (Individual 3) reveals dietary change from mainly C3 plants to more C4 plant contributions as the animal aged. This pattern is supported by carbonate isotope results indicating that this individual spent its youth in the mid-valley ecozone before becoming more mobile later in life. As this life-history example shows, isotopic and microbotanical analyses are complementary approaches, clarifying a pattern of seasonal transhumance that linked the lives of humans and animals along the Middle Horizon (AD 600–1000) caravan networks that crisscrossed the central Andes.

This study compares cortisol concentrations in plasma and milk over a time-span of 1-4h following injection of an adrenocorticotropic hormone (ACTH) or a physiological stressor. Its aim was to characterize the usefulness of milk cortisol concentrations as short-term measures of acute stress.

Experiment 1: three groups of lactating cows (Groups B - D; n = 5, each) were injected with ACTH1-24 at 4, 2 and 1h before milking, respectively, so that each experienced a similar period of elevated adrenocortical activity, but presented at milking with varying plasma cortisol concentrations. Another group (Group A; n = 5) was a saline-treated control. Mean plasma cortisol concentrations at milking were 7, 8, 24 and 56ng ml−1 for Groups A, B, C and D, respectively. Mean cortisol concentrations in milk were similar for Groups A and B (1.2 and 0.5 ng ml−1, respectively), higher in Group C (2.4ng ml−1), and greatest in Group D (11.7 ng ml−1; p <0.001).

Experiment 2: lactating dairy cows (n = 15) were injected with ACTH, transported by truck, or blood-sampled only (control) during the 2h before milking. Mean plasma cortisol concentrations at milking were 6, 20 and 72 ng ml−1 following control, ACTH and transport treatments, respectively; mean concentrations of cortisol in milk displayed a similar pattern (1.1, 2.4 and 12.0 ng ml−1, respectively; p <0.001).

Milk cortisol concentrations were highly correlated with plasma levels at milking, but did not reflect those situations where, following a period of elevation within the previous 4h, plasma cortisol concentrations had returned to basal levels. Concentrations of cortisol in foremilk and composite milk were highly correlated, but the mechanisms of cortisol flux may differ between these two compartments. Milk cortisol concentration can be a useful indicator of responses of lactating cows to acute stressors which act up to 2h before collection of samples.

Dietary honey bee royal jelly increases insect growth rates and adult body size. Royal jelly as a dietary supplement could enhance mass insect production by increasing the body size of mass-reared model species. To determine the effect of royal jelly on a cricket species, Gryllodes sigillatus Walker (Orthoptera: Gryllidae), farmed for human consumption, we ran two experiments. We tested the dose-dependent response of G. sigillatus to royal jelly using a range of diets across 0–30% w/w royal jelly. We also measured the individual-level life history responses to royal jelly over time by individually rearing G. sigillatus nymphs on two separate diets: half were fed a commercial cricket diet, and half were fed the same diet mixed with 15% w/w fresh royal jelly. We found sex-dependent effects: females fed the royal jelly diet were 30% heavier, and this effect was driven by significantly longer abdomens containing 67% more eggs compared to those fed the standard diet. Female mass was optimised at approximately 17% w/w royal jelly. Our results reveal that although a royal jelly dietary supplement can increase the yield of mass-reared insects, the life history responses are species and sex specific.

The purpose of this investigation was to expand upon the limited existing research examining the test–retest reliability, cross-sectional validity and longitudinal validity of a sample of bioelectrical impedance analysis (BIA) devices as compared with a laboratory four-compartment (4C) model. Seventy-three healthy participants aged 19–50 years were assessed by each of fifteen BIA devices, with resulting body fat percentage estimates compared with a 4C model utilising air displacement plethysmography, dual-energy X-ray absorptiometry and bioimpedance spectroscopy. A subset of thirty-seven participants returned for a second visit 12–16 weeks later and were included in an analysis of longitudinal validity. The sample of devices included fourteen consumer-grade and one research-grade model in a variety of configurations: hand-to-hand, foot-to-foot and bilateral hand-to-foot (octapolar). BIA devices demonstrated high reliability, with precision error ranging from 0·0 to 0·49 %. Cross-sectional validity varied, with constant error relative to the 4C model ranging from −3·5 (sd 4·1) % to 11·7 (sd 4·7) %, standard error of the estimate values of 3·1–7·5 % and Lin’s concordance correlation coefficients (CCC) of 0·48–0·94. For longitudinal validity, constant error ranged from −0·4 (sd 2·1) % to 1·3 (sd 2·7) %, with standard error of the estimate values of 1·7–2·6 % and Lin’s CCC of 0·37–0·78. While performance varied widely across the sample investigated, select models of BIA devices (particularly octapolar and select foot-to-foot devices) may hold potential utility for the tracking of body composition over time, particularly in contexts in which the purchase or use of a research-grade device is infeasible.

Food insecurity on college campuses is a major public health problem and has been documented for the last decade. Sufficient food access is a crucial social determinant of health, thus campuses across the country have implemented various programmes, systems and policies to enhance access to food which have included food pantries, campus gardens, farmers’ markets, meal share or voucher programmes, mobile food applications, campus food gleaning, food recovery efforts, meal deliveries and task force/working groups. However, little is understood about how to best address food insecurity and support students who are struggling with basic needs. The impact of food insecurity on students’ academic and social success, in addition to their overall well-being, should be investigated and prioritised at each higher education institution. This is especially true for marginalised students, such as minority or first-generation students, who are at heightened risk for food insecurity. In order to create a culture of health equity, in which most at-risk students are provided resources and opportunities to achieve optimal well-being, higher education institutions must prioritise mitigating food insecurity on the college campus. Higher education institutions could benefit from adopting comprehensive and individualised approaches to promoting food security for marginalised students in order to facilitate equal opportunity for optimal scholastic achievement among students of all socio-demographic backgrounds.

The legal brief is a primary vehicle by which lawyers seek to persuade appellate judges. Despite wide acceptance that briefs are important, empirical scholarship has yet to establish their influence on the Supreme Court or fully explore justices’ preferences regarding them. We argue that emotional language conveys a lack of credibility to justices and thereby diminishes the party’s likelihood of garnering justices’ votes. The data concur. Using an automated textual analysis program, we find that parties who employ less emotional language in their briefs are more likely to win a justice’s vote, a result that holds even after controlling for other features correlated with success, such as case quality. These findings suggest that advocates seeking to influence judges can enhance their credibility and attract justices’ votes by employing measured, objective language.

Alternative plant-based meats have grown in popularity with consumers recently and researchers are examining the potential health effects, or risks, from consuming these products. Because there have been no studies to date that have specifically assessed the health effects of plant-based meats on biomarkers of inflammation, the purpose of this work was to conduct a secondary analysis of the Study With Appetizing Plantfood – Meat Eating Alternatives Trial (SWAP-MEAT). SWAP-MEAT was a randomised crossover trial that involved generally healthy adults eating 2 or more servings of plant-based meats per day for 8 weeks (i.e. Plant phase) followed by 2 or more servings of animal meats per day for 8 weeks (i.e. Animal phase). Results of linear mixed-effects models indicated only 4 out of 92 biomarkers reached statistical significance. The results were contrary to our hypothesis, since we expected relative improvements in biomarkers of inflammation from the plant-based meats.