Objectives/Goals: This project will enrich our understanding of basal breast carcinogenesis, highlighting the distinct biological differences in breast cancer risk between non-Hispanic Black (NHB) or non-Hispanic White (NHW) women, but also has the potential to provide real-world solutions thereby contributing to reducing health disparities in breast cancer outcomes Methods/Study Population: In the biological investigation, I am utilizing a unique cohort of normal breast tissues from Mayo Clinic patients who underwent breast reduction surgery that have self-identified as NHB or NHW premenopausal women. From these tissues, we are able to subculture human mammary epithelial cells, which we will use for our consequent experiments. For the qualitative study, I aim to recruit up to 40–50 eligible NHB women identified at increased risk for breast cancer and conduct semi-structured qualitative interviews informed by the National Institute on Minority Health and Health Disparities Research Framework. Results/Anticipated Results: Gene expression profiling on our cohort of 15 NHB and 40 NHW premenopausal women identified a gene expression signature in NHB women indicative of elevated Hedgehog signaling, a key factor in triple-negative breast cancer (TNBC) development and progression. I hypothesize that persistent activation of Hedgehog signaling within NHB women instigates the proliferation and transformation of basal stem cells within the breast, thus fueling TNBC development. Understanding the perceptions and experiences of NHB women that are identified as being at an increased risk for BC will aid in the identification of barriers and facilitators to their risk reduction care and in turn provide implementation strategies that could contribute to alleviating the racial disparity seen in TNBC morbidity, mortality, and preventative care. Discussion/Significance of Impact: The significance of this project lies in its dual approach, uncovering basal breast cancer mechanisms in a high-risk group using normal breast tissue and evaluating the perspectives from NHB women to enhance the practical relevance of our findings.

This essay proposes a novel framework for conceptualising climate politics through the lens of maritime custom. Drawing on A. W. Brian Simpson’s study of Regina vs Dudley and Stephens (1884) and Cătălin Avramescu’s intellectual history of cannibalism, it critically examines ‘providential’ and ‘catastrophic’ lifeboat metaphors in political thought. Despite their apparent opposition, these metaphors share common assumptions rooted in natural law traditions. As an alternative, the essay introduces the concept of the ‘commonist lifeboat’, grounded in maritime custom, class consciousness and environmental encounters. Inspired by historical practices of survival and mutual aid at sea, this approach suggests principles for addressing climate adaptation through bottom-up customs rather than top-down theoretical solutions. Three brief illustrations address climate policy’s intersections with property law, criminal law and international human rights law. This approach ultimately offers a historically informed perspective on climate crisis challenges, reconciling consequentialist arguments with concerns for dignity and consent.

One of the earliest discoveries of Permo-Carboniferous terrestrial vertebrates in North America occurred in 1875 along Horseshoe Bend, a cutbank on the Salt Fork of the Vermilion River west of Danville, Vermilion County, east-central Illinois. The discovery was soon eclipsed by the description of similar but much more complete remains from the Lower Permian of Texas in 1878. The deposit itself was obliterated by slumping and erosion in the earliest 1900s and has not been collected since despite repeated efforts. Previously unreported outcrop records and subsurface data indicate that the deposit originated as a paleochannel fill in the Inglefield Sandstone Member of the Patoka Formation, which underlies the Macoupin Limestone Member (early Missourian Stage of the Midcontinent, early Kasimovian Stage of global Carboniferous time scale). In addition to aquatic to terrestrial tetrapods, teeth of lungfishes (Sagenodus Owen, 1867, Conchopoma Cope, 1877a, Gnathorhiza Cope, 1883a) and teeth, occipital spines, and coprolites of a xenacanth shark (Orthacanthus Agassiz, 1838) are known from Horseshoe Bend. The teeth of the marine petalodont shark Janassa Münster, 1839, also are present in the collection but presumed to have been derived from one of the beds on the cutbank that produced brackish to marine invertebrate fossils. Alhough not diverse, the tetrapod assemblage is significant in that it contains the oldest diplocaulid amphibian (Diplocaulus salamandroides Cope, 1877a), fragmentary remains of the oldest diadectid and limnoscelid stem reptiles, and possibly the oldest captorhinid eureptile, all of which have not been adequately described. The ophiacodontid synapsid Clepsydrops Cope, 1875, is the most common fossil at Danville, which could be an artifact of primitive collecting methods that did not promote the recovery of articulated material. An accurate stratigraphic placement of the Horseshoe Bend deposit and a review of other late Carboniferous tetrapod localities reveals that this important Illinois locality combines an overlooked vanguard of terrestrial taxa regarded as Permo-Carboniferous (Kasimovian-Asselian) and amphibious to aquatic forms known from older, Moscovian deposits.

We examined the effect of transition to electronic medical records on the antimicrobial stewardship service (AMS) in our healthcare service, finding significant increases (P < 0.001) in the number and type of prescribed restricted antimicrobials identified for review, number of patients seen, and AMS intervention significance post transition.

The notion of infrastructure has recently featured prominently in international legal scholarship. The ambition behind the turn to infrastructure in international legal theory is comparable to other large attempts to conceptualize the discipline. Yet, against the backdrop of work in the humanities and social sciences, theoretical engagement with infrastructure is still nascent in the legal discipline. In this Article, we build on another recent development in international legal scholarship—the turn to “materiality”—to articulate a systematic theory of infrastructure in international law. At the center of our study is the case study of the cruise ship. Studying cruise ships and their legal and political environment in detail, we introduce three conceptual building blocks through which we develop a more comprehensive theory of infrastructure: Platform, object and rupture. Although we focus on cruise ships, the theory of legal infrastructure that we offer is applicable to a wide array of industries and issues.

In Ray Cummings's loony 1922 novel The Girl in the Golden Atom, a man known only as the Chemist discovers a beautiful woman in a subatomic world in the gold of his mother's wedding ring. Smitten, he figures out how to shrink himself to join her. Upon his return to our world, he finds that although seven days passed for him while “in the ring,” he has arrived back only forty hours after leaving. Over drinks, the Banker asks him to explain how the difference is possible. The Chemist replies, “To get a conception of this change you must analyze definitely what time is. We measure and mark it by years, months, and so forth, down to minutes and seconds, all based upon the movements of our earth around its sun. But that is the measurement of time, not time itself.” He then turns to the Big Business Man and asks, “How would you describe time?” “The Big Business Man smiled. ‘Time,’ he said, ‘is what keeps everything from happening at once.’”

Shiga toxin-producing Escherichia coli (STEC) is a group of bacteria that causes gastrointestinal illness and occasionally causes large foodborne outbreaks. It represents a major public health concern due to its ability to cause severe illness which can sometimes be fatal. This study was undertaken as part of a rapid investigation into a national foodborne outbreak of STEC O145. On 22 May 2024, United Kingdom (UK) public health agencies and laboratories identified an increase in stool specimens submissions and patients testing positive for Shiga toxin-producing E. coli (STEC). Whole genome sequencing (WGS) identified serotype O145:H28 stx2a/eae belonging to the same five single nucleotide polymorphism (SNP) single linkage cluster as the causative agent. By 3 July 2024, 288 cases had been linked to the cluster. Most cases were adults (87%) and females (57%), 49% were hospitalized with a further 10% attending emergency care. Descriptive epidemiology and analytical studies were conducted which identified consumption of nationally distributed pre-packed sandwiches as a common food exposure. The implicated food business operators voluntarily recalled ready-to-eat sandwiches and wraps containing lettuce on 14 June 2024.

Oysters have unique life history strategies among molluscs and a long history in the fossil record. The Ostreid form, particularly species from the genus Crassostrea, facilitated the invasion into intertidal, estuarine habitats and reef formation. While there is general acknowledgement that oysters have highly variable growth, few studies have quantified variability in oyster allometry. This project aimed to (1) describe the proportional carbonate contributions from each valve and (2) examine length–weight relationships for shell and tissue across an estuarine gradient. We collected 1122 C. virginica from 48 reefs in eight tributaries and the main stem of the Virginia portion of the Chesapeake Bay. On average, the left valve was responsible for 56% of the total weight of the shell, which was relatively consistent across a size range (24.9–172 mm). Nonlinear mixed-effects models for oyster length–weight relationships suggest oysters exhibit allometric growth (b < 3) and substantial inter-reef variation, where upriver reefs in some tributaries appear to produce less shell and tissue biomass on average for a given size. We posit this variability may be due to differences in local conditions, particularly salinity, turbidity, and reef density. Allometric growth maximizes shell production and surface area for oyster settlement, both of which contribute to maintaining the underlying reef structure. Rapid growth and intraspecific plasticity in shell morphology enabled oysters to invade and establish reefs as estuaries moved in concert with changes in sea level over evolutionary time.

Lie detection research comparing manual and automated coding of linguistic cues is limited. In Experiment 1, we attempted to extend this line of research by directly comparing the veracity differences in manual coding and two coding software programs (Text Inspector and Linguistic Inquiry and Word Count [LIWC]) on the linguistic cue “total details” across eight published datasets. Mixed model analyses revealed that LIWC showed larger veracity differences in total details than Text Inspector and manual coding. Follow-up classification analyses showed that both automated coding and manual coding could accurately classify honest and false accounts. In Experiment 2, we examined if LIWC’s sensitivity to veracity differences was the result of honest accounts including more redundant (repeated) words than false accounts as LIWC—but not Text Inspector or manual coding—accounts for redundancy. Our prediction was supported, and the most redundant words were function words. The results implicated that automated coding can detect veracity differences in total details and redundancy, but it is not necessarily better than manual coding at accurately classifying honest and false accounts.

Plasma levels of branched-chain amino acids (BCAA) and their metabolites, branched-chain ketoacids (BCKA), are increased in insulin resistance. We previously showed that ketoisocaproic acid (KIC) suppressed insulin-stimulated glucose transport in L6 myotubes, especially in myotubes depleted of branched-chain ketoacid dehydrogenase (BCKD), the enzyme that decarboxylates BCKA. This suggests that upregulating BCKD activity might improve insulin sensitivity. We hypothesised that increasing BCAA catabolism would upregulate insulin-stimulated glucose transport and attenuate insulin resistance induced by BCKA. L6 myotubes were either depleted of BCKD kinase (BDK), the enzyme that inhibits BCKD activity, or treated with BT2, a BDK inhibitor. Myotubes were then treated with KIC (200 μM), leucine (150 μM), BCKA (200 μM), or BCAA (400 μM) and then treated with or without insulin (100 nM). BDK depletion/inhibition rescued the suppression of insulin-stimulated glucose transport by KIC/BCKA. This was consistent with the attenuation of IRS-1 (Ser612) and S6K1 (Thr389) phosphorylation but there was no effect on Akt (Ser473) phosphorylation. The effect of leucine or BCAA on these measures was not as pronounced and BT2 did not influence the effect. Induction of the mTORC1/IRS-1 (Ser612) axis abolished the attenuating effect of BT2 treatment on glucose transport in cells treated with KIC. Surprisingly, rapamycin co-treatment with BT2 and KIC further reduced glucose transport. Our data suggests that the suppression of insulin-stimulated glucose transport by KIC/BCKA in muscle is mediated by mTORC1/S6K1 signalling. This was attenuated by upregulating BCAA catabolic flux. Thus, interventions targeting BCAA metabolism may provide benefits against insulin resistance and its sequelae.

In order to study exoplanets, a comprehensive characterisation of the fundamental properties of the host stars – such as angular diameter, temperature, luminosity, and age, is essential, as the formation and evolution of exoplanets are directly influenced by the host stars at various points in time. In this paper, we present interferometric observations taken of directly imaged planet host 51 Eridani at the CHARA Array. We measure the limb-darkened angular diameter of 51 Eridani to be $\theta_\mathrm{LD} = 0.450\pm 0.006$ mas and combining with the Gaia zero-point corrected parallax, we get a stellar radius of $1.45 \pm 0.02$ R$_{\odot}$. We use the PARSEC isochrones to estimate an age of $23.2^{+1.7}_{-2.0}$ Myr and a mass of $1.550^{+0.006}_{-0.005}$ M$_{\odot}$. The age and mass agree well with values in the literature, determined through a variety of methods ranging from dynamical age trace-backs to lithium depletion boundary methods. We derive a mass of $4.1\pm0.4$ M$_\mathrm{Jup}$ for 51 Eri b using the Sonora Bobcat models, which further supports the possibility of 51 Eri b forming under either the hot-start formation model or the warm-start formation model.

We establish two-term spectral asymptotics for the operator of linear elasticity with mixed boundary conditions on a smooth compact Riemannian manifold of arbitrary dimension. We illustrate our results by explicit examples in dimension two and three, thus verifying our general formulae both analytically and numerically.