NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.

Glacier motion responds dynamically to changing meltwater inputs, but the multi-decadal response of basal sliding to climate remains poorly constrained due to its sensitivity across multiple timescales. Observational records of glacier motion provide critical benchmarks to decode processes influencing glacier dynamics, but multi-decadal records that precede satellite observation and modern warming are rare. Here we present a record of motion in the ablation zone of Saskatchewan Glacier that spans seven decades. We combine in situ and remote-sensing observations to inform a first-order glacier flow model used to estimate the relative contributions of sliding and internal deformation on dynamics. We find a significant increase in basal sliding rates between melt-seasons in the 1950s and those in the 1990s and 2010s and explore three process-based explanations for this anomalous behavior: (i) the glacier surface steepened over seven decades, maintaining flow-driving stresses despite sustained thinning; (ii) the formation of a proglacial lake after 1955 may support elevated basal water pressures; and (iii) subglacial topography may cause dynamic responses specific to Saskatchewan Glacier. Although further constraints are necessary to ascertain which processes are of greatest importance for Saskatchewan Glacier's dynamic evolution, this record provides a benchmark for studies of multi-decadal glacier dynamics.

OBJECTIVES/GOALS: Current approaches to drug development for the aggressive triple negative breast cancer rely on current 2D and 3D in vitro models which have limited capabilities. We have developed a translational microphysiological system that can maintain the human breast microenvironment to capture the complex interaction with the tumor microenvironment. METHODS/STUDY POPULATION: Three different TNBC cell lines were seeded in BC-MPS: MDA-MB-231 parental cell line, MDA-MB-231wiht the gene, LKB1 overexpressed, which is a tumor suppressor, and MDA-MB-231 with the enzyme, ERK5, an enzyme associated with increased metastasis and drug resistance, knocked out. These three TNBC cell lines were cultured in a standard 2D 96-well plate and in BC-MPS. Time-lapse videos were taken to track cellular mobility. RNA-sequencing was performed to compare different expression levels of various cancer related genes of the cell lines cultured in standard 2D and BC-MPS. RESULTS/ANTICIPATED RESULTS: The LKB1 overexpressed MDA-MB-231 and the ERK5-ko MDA-MB-231 cell lines are expected to have decreased mobility compared to the parental cells. The cell lines are expected to have increased expression of cancer related genes when cultured in BC-MPS than when cultured in standard 2D due to the presence of human breast tissue. DISCUSSION/SIGNIFICANCE: BC-MPS is a promising new translational MPS that facilitates studying long term interactions between real human breast tissue and cancer cells. The BC-MPS systems ability to support the growth of established cell lines has been demonstrated. Future studies will focus on developing the model for personalized medicine.

Exoskeletons that assist the hip, knee, and ankle joints have begun to improve human mobility, particularly by reducing the metabolic cost of walking. However, direct comparisons of optimal assistance of these joints, or their combinations, have not yet been possible. Assisting multiple joints may be more beneficial than the sum of individual effects, because muscles often span multiple joints, or less effective, because single-joint assistance can indirectly aid other joints. In this study, we used a hip–knee–ankle exoskeleton emulator paired with human-in-the-loop optimization to find single-joint, two-joint, and whole-leg assistance that maximally reduced the metabolic cost of walking. Hip-only and ankle-only assistance reduced the metabolic cost of walking by 26 and 30% relative to walking in the device unassisted, confirming that both joints are good targets for assistance (N = 3). Knee-only assistance reduced the metabolic cost of walking by 13%, demonstrating that effective knee assistance is possible (N = 3). Two-joint assistance reduced the metabolic cost of walking by between 33 and 42%, with the largest improvements coming from hip-ankle assistance (N = 3). Assisting all three joints reduced the metabolic cost of walking by 50%, showing that at least half of the metabolic energy expended during walking can be saved through exoskeleton assistance (N = 4). Changes in kinematics and muscle activity indicate that single-joint assistance indirectly assisted muscles at other joints, such that the improvement from whole-leg assistance was smaller than the sum of its single-joint parts. Exoskeletons can assist the entire limb for maximum effect, but a single well-chosen joint can be more efficient when considering additional factors such as weight and cost.

ABSTRACT IMPACT: Identifying an important pathway in treatment resistant TNBC will allow for the future development of clinical therapeutics specific for this disease. OBJECTIVES/GOALS: Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer characterized by negative expression of estrogen receptor, progesterone receptor, and HER2/neu amplification. It resists therapies and has a high recurrence rate after resection. The goal of my research is to identify & characterize a TNBC pathway for future development of therapies. METHODS/STUDY POPULATION: The project uses a combination of cell lines, patient derived xenograft (PDX) models, as well as patient databases. Standard cellular and molecular biology techniques will be used including: Cell culture, qPCR, western blotting, and flow cytometry. RESULTS/ANTICIPATED RESULTS: LKB1 is a master kinase that activates 14 possible downstream kinases. The signaling pathway has been demonstrated to play a role in energy homeostasis and metabolism. Mutation of LKB1 signaling results in Peutz-Jeghers Syndrome and is associated with neoplasias of the lung, pancreas, and breast. Based on preliminary analysis, overexpression of LKB1 by shRNA in TNBC cell lines results in suppression of EMT and reduction of the cancer stem cell population. Additional studies show that LKB1 overexpression has no effect on growth rate in 2D culture while significant reduction in 3D mammosphere formations can be seen. Downstream studies using commercially available SIK1 inhibitor HG-9-91-01 is able to induce a larger fraction of CSC from reduced LKB1 overexpression as well as from baseline levels. DISCUSSION/SIGNIFICANCE OF FINDINGS: Overall, our results suggest that LKB1 acts through SIK1 to suppress EMT and the generation of cancer stem cells. This results in reduced cancer functionality, as evidenced by inhibition of mammosphere formation. These results establishes a foundation for future mechanistic studies on the LKB1 axis and its mechanisms in TNBC.

Recently, a laboratory-scale method for measuring the rapid energy release from milligram quantities of energetic material has been developed based on the high-temperature plasma chemistry induced by a focused, nanosecond laser pulse. The ensuing exothermic chemical reactions result in an increase in the laser-induced shock wave velocity compared to inert materials. Laser-induced air shock from energetic materials (LASEM) provides a method for estimating the detonation performance of novel organic-based energetic materials prior to scale-up and full detonation testing. Here, the extension of LASEM to non-organic energetic materials is discussed. The laser-induced shock velocities from reactive materials such as Al/PTFE, Al/CuO, Al/Zr alloys, Al/aluminum iodate hexahydrate, and porous silicon composites have been measured; in many cases, the high sensitivity of the samples resulted in propagation of the reaction to the surrounding material, producing significantly higher shock velocities than conventional energetic materials. Methods for compensating for this effect will be discussed. Despite this limitation, the relative comparison of the shock velocities, emission spectra, and combustion behavior of each type of material provides some insight into the mechanisms for increasing the energy release of the material on a fast (μs) and/or slow (ms) timescale.

Annual grass weed control and switchgrass cultivar response to PRE-applied pendimethalin and POST-applied mesotrione and quinclorac was evaluated in 2005 and 2006 near Paterson, WA, in both newly seeded and 1-yr-old established switchgrass. Pendimethalin applied to newly planted switchgrass at 1.1 kg ai ha−1 at the one-leaf stage in 2005 or at 0.67 kg ha−1 PRE in 2006 severely injured and greatly reduced switchgrass stands. Mesotrione applied POST at 0.07 kg ai ha−1 injured newly planted switchgrass, reduced switchgrass height for several weeks after treatment, and reduced final switchgrass biomass by 54% both years. ‘Kanlow’ and ‘Cave-in-Rock’ cultivars were injured less by mesotrione than ‘Shawnee’ in 2005, whereas in 2006, Kanlow was injured less than Shawnee and Cave-in-Rock. Quinclorac applied POST at 0.56 kg ai ha−1 injured newly planted switchgrass less than mesotrione and pendimethalin but reduced final switchgrass biomass by 33% both years compared with treatment with atrazine alone. All three herbicide treatments controlled large crabgrass in the year of establishment. Green foxtail counts were reduced 93% or more by pendimethalin and quinclorac compared with nontreated controls, but mesotrione failed to control green foxtail. Pendimethalin applied PRE at 1.1 kg ha−1 did not injure 1-yr-old established switchgrass or reduce switchgrass biomass. Quinclorac applied POST at 0.56 kg ha−1 to established switchgrass reduced switchgrass biomass of the first harvest by 16% in 1 of 2 yr. Mesotrione applied POST at 0.07 kg ha−1 injured established switchgrass and reduced biomass of the first harvest by 33 and 17% in 2005 and 2006, respectively. Kanlow was injured the least by mesotrione in both years. Established switchgrass suppressed late-emerging annual grass weeds sufficiently to avoid the need for a grass-specific herbicide application.

White sweetclover and narrowleaf hawksbeard are nonindigenous invasive plant species in Alaska that are rapidly spreading, including into areas that are otherwise free of nonindigenous plants. There has been concern that native moose could be dispersing germinable seed from these plants after ingestion. To address this concern, a study was conducted involving tame moose at the University of Alaska Fairbanks Agriculture and Forestry Experiment Station, Matanuska Experiment Farm, Palmer, AK. Objectives were to determine if seeds from these two plant species could survive mastication and digestive passage through moose, whether this passage impacted seed germination, and whether seed passage rates were the same as similar sized Cr-mordanted fiber. In this study, narrowleaf hawksbeard seed rarely survived mastication and digestion with only five seedlings recovered from 42,000 germinable seed fed to the moose. About 16% of germinable white sweetclover seed (3,595 of 22,000) fed to the moose produced seedlings. Most of the sweetclover seedlings came from feces produced 2 and 3 d after feeding. In two moose, sweetclover seedlings were grown from fecal material that was passed 11 d after feeding, raising the possibility that seeds could be transported long distances after ingestion. Cr-mordanted fiber passage did not closely follow seedling producing seed, possibly because time in the rumen might reduce seed germination. Once roadsides in Alaska become infested with white sweetclover, moose can then serve as a transport vector of these weeds into river channels and floodplains, which are distant from roads. This information will impact white sweetclover management programs and alert land managers to the potential for other instances of wildlife-mediated seed dispersal.

In the United States alone, ∼14,000 children are hospitalised annually with acute heart failure. The science and art of caring for these patients continues to evolve. The International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was held on February 4 and 5, 2015. The 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute was funded through the Andrews/Daicoff Cardiovascular Program Endowment, a philanthropic collaboration between All Children’s Hospital and the Morsani College of Medicine at the University of South Florida (USF). Sponsored by All Children’s Hospital Andrews/Daicoff Cardiovascular Program, the International Pediatric Heart Failure Summit assembled leaders in clinical and scientific disciplines related to paediatric heart failure and created a multi-disciplinary “think-tank”. The purpose of this manuscript is to summarise the lessons from the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children’s Heart Institute, to describe the “state of the art” of the treatment of paediatric cardiac failure, and to discuss future directions for research in the domain of paediatric cardiac failure.

We present an unconditionally energy stable and uniquely solvable finite difference scheme for the Cahn-Hilliard-Brinkman (CHB) system, which is comprised of a Cahn-Hilliard-type diffusion equation and a generalized Brinkman equation mod-eling fluid flow. The CHB system is a generalization of the Cahn-Hilliard-Stokes model and describes two phase very viscous flows in porous media. The scheme is based on a convex splitting of the discrete CH energy and is semi-implicit. The equations at the implicit time level are nonlinear, but we prove that they represent the gradient of a strictly convex functional and are therefore uniquely solvable, regardless of time step size. Owing to energy stability, we show that the scheme is stable in the time and space discrete and norms. We also present an efficient, practical nonlinear multigrid method . comprised of a standard FAS method for the Cahn-Hilliard part, and a method based on the Vanka smoothing strategy for the Brinkman part . for solving these equations. In particular, we provide evidence that the solver has nearly optimal complexity in typical situations. The solver is applied to simulate spinodal decomposition of a viscous fluid in a porous medium, as well as to the more general problems of buoyancy- and boundary-driven flows.