We present a 1000 km transect of phase-sensitive radar measurements of ice thickness, basal reflection strength, basal melting and ice-column deformation across the Ross Ice Shelf (RIS). Measurements were gathered at varying intervals in austral summer between 2015 and 2020, connecting the grounding line with the distant ice shelf front. We identified changing basal reflection strengths revealing a variety of basal conditions influenced by ice flow and by ice–ocean interaction at the ice base. Reflection strength is lower across the central RIS, while strong reflections in the near-front and near-grounding line regions correspond with higher basal melt rates, up to 0.47 ± 0.02 m a−1 in the north. Melting from atmospherically warmed surface water extends 150–170 km south of the RIS front. Melt rates up to 0.29 ± 0.03 m a−1 and 0.15 ± 0.03 m a−1 are observed near the grounding lines of the Whillans and Kamb Ice Stream, respectively. Although troublesome to compare directly, our surface-based observations generally agree with the basal melt pattern provided by satellite-based methods but provide a distinctly smoother pattern. Our work delivers a precise measurement of basal melt rates across the RIS, a rare insight that also provides an early 21st-century baseline.

This article serves as an introduction to this guest-edited special issue of American Antiquity entitled “Global Archaeologies of the Long Emancipation.” We begin by discussing Rinaldo Walcott's notion of the Long Emancipation, noting how the failed promises of the legal ending of slavery led to sensations of freedom and ongoing forms of anti-Blackness. In response, Black communities have employed various strategies in pursuit of freedom. We then apply this argument to archaeological thought and practice, suggesting that archaeology is well positioned to provide evidence of Black creativity, action, and struggle in a variety of global contexts. The article closes with an overview of this special issue, which includes a brief summary of individual contributions.

The 2022 bicentennial of the arrival of Black Americans to West African shores was a moment of reflection for many Liberians. In the wake of civil war, many questioned the celebratory tone of the occasion and challenged settler heritage narratives. At the same time, Providence Island featured prominently in official programming. Since 2019, our Back-to-Africa Heritage and Archaeology project has worked on the island to investigate the site's function beyond the mythic 1822 encounter between those seeking freedom from racial injustice in the Americas and Indigenous West Africans, instead offering a more inclusive and complex account of the public heritage space. We specifically focus on deposits that date to the decades prior to, during, and after 1822, demonstrating the tensions surrounding freedom-making and Black Republicanism from past to present, concluding that the binary of pre- and post-settlement fails to capture the complexities of Liberian pasts that unfolded on the island.

We present radio observations of the galaxy cluster Abell S1136 at 888 MHz, using the Australian Square Kilometre Array Pathfinder radio telescope, as part of the Evolutionary Map of the Universe Early Science program. We compare these findings with data from the Murchison Widefield Array, XMM-Newton, the Wide-field Infrared Survey Explorer, the Digitised Sky Survey, and the Australia Telescope Compact Array. Our analysis shows the X-ray and radio emission in Abell S1136 are closely aligned and centered on the Brightest Cluster Galaxy, while the X-ray temperature profile shows a relaxed cluster with no evidence of a cool core. We find that the diffuse radio emission in the centre of the cluster shows more structure than seen in previous low-resolution observations of this source, which appeared formerly as an amorphous radio blob, similar in appearance to a radio halo; our observations show the diffuse emission in the Abell S1136 galaxy cluster contains three narrow filamentary structures visible at 888 MHz, between $\sim$80 and 140 kpc in length; however, the properties of the diffuse emission do not fully match that of a radio (mini-)halo or (fossil) tailed radio source.

On 15 January 2022, 04h:15 UTC, the volcano Hunga Tonga-Hunga Ha'apai in the south-west Pacific Ocean (20°32'32.37''S, 175°23'38.67''W) erupted in what proved to be the most powerful such event since Krakatau in 1883. Among the many impacts of the eruption, a substantial tsunami propagated throughout the south-west Pacific Ocean. The signatures of the eruption were recorded at a wide range of recording stations globally, including the atmospheric pressure wave, the tsunami itself and, in addition, higher-order responses, such as a tsunami associated with the pressure wave (Carvajal et al. 2022).

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

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 commercialization of medical devices and biotechnology products is characterized by high failure rates and long development lead times particularly among start-up enterprises. To increase the success rate of these high-risk ventures, the University of Massachusetts Lowell (UML) and University of Massachusetts Medical School (UMMS) partnered to create key academic support centers with programs to accelerate entrepreneurship and innovation in this industry. In 2008, UML and UMMS founded the Massachusetts Medical Device Development Center (M2D2), which is a business and technology incubator that provides business planning, product prototyping, laboratory services, access to clinical testing, and ecosystem networking to medical device and biotech start-up firms. M2D2 has three physical locations that encompass approximately 40,000 square feet. Recently, M2D2 leveraged these resources to expand into new areas such as health security, point of care technologies for heart, lung, blood, and sleep disorders, and rapid diagnostics to detect SARS-CoV-2. Since its inception, M2D2 has vetted approximately 260 medical device and biotech start-up companies for inclusion in its programs and provided active support to more than 80 firms. This manuscript describes how two UMass campuses leveraged institutional, state, and Federal resources to create a thriving entrepreneurial environment for medical device and biotech companies.

Mass asymptomatic SARS-CoV-2 nucleic acid amplified testing of healthcare personnel (HCP) was performed at a large tertiary health system. A low period-prevalence of positive HCP was observed. Of those who tested positive, half had mild symptoms in retrospect. HCP with even mild symptoms should be isolated and tested.

Rapid infant growth increases the risk for adult obesity. The gut microbiome is associated with early weight status; however, no study has examined how interactions between microbial and host ribonucleic acid (RNA) expression influence infant growth. We hypothesized that dynamics in infant stool micro-ribonucleic acids (miRNAs) would be associated with both microbial activity and infant growth via putative metabolic targets. Stool was collected twice from 30 full-term infants, at 1 month and again between 6 and 12 months. Stool RNA were measured with high-throughput sequencing and aligned to human and microbial databases. Infant growth was measured by weight-for-length z-score at birth and 12 months. Increased RNA transcriptional activity of Clostridia (R = 0.55; Adj p = 3.7E-2) and Burkholderia (R = −0.820, Adj p = 2.62E-3) were associated with infant growth. Of the 25 human RNAs associated with growth, 16 were miRNAs. The miRNAs demonstrated significant target enrichment (Adj p < 0.05) for four metabolic pathways. There were four associations between growth-related miRNAs and growth-related phyla. We have shown that longitudinal trends in gut microbiota activity and human miRNA levels are associated with infant growth and the metabolic targets of miRNAs suggest these molecules may regulate the biosynthetic landscape of the gut and influence microbial activity.

We develop a deep autoencoder architecture that can be used to find a coordinate transformation which turns a non-linear partial differential equation (PDE) into a linear PDE. Our architecture is motivated by the linearising transformations provided by the Cole–Hopf transform for Burgers’ equation and the inverse scattering transform for completely integrable PDEs. By leveraging a residual network architecture, a near-identity transformation can be exploited to encode intrinsic coordinates in which the dynamics are linear. The resulting dynamics are given by a Koopman operator matrix K. The decoder allows us to transform back to the original coordinates as well. Multiple time step prediction can be performed by repeated multiplication by the matrix K in the intrinsic coordinates. We demonstrate our method on a number of examples, including the heat equation and Burgers’ equation, as well as the substantially more challenging Kuramoto–Sivashinsky equation, showing that our method provides a robust architecture for discovering linearising transforms for non-linear PDEs.

OBJECTIVES/GOALS: The objective of this study is to define the molecular mechanisms that control survival of malignant stem cells in acute myeloid leukemia (AML). Leukemia stem cells (LSCs) are not effectively eradicated by standard treatment and lead to resistance and relapse, which contribute to poor survival rates. METHODS/STUDY POPULATION: The recently FDA approved venetoclax, a BCL2 inhibitor, with azacitidine, a hypomethylating agent leads to a 70% response rate in AML patients. Analysis of patients treated with this regimen showed direct targeting of LSCs. BCL2 has a non-canonical function in regulation of intracellular calcium. To determine how BCL2 mediated calcium signaling plays a role in LSC biology, we used LSCs isolated from venetoclax/azacitidine (ven/aza) sensitive and resistant patient samples to measure expression of calcium channels via RNA seq. BIO-ID, siRNA, flow cytometry, seahorse assays, calcium measurements and colony assays were used to determine the effects of calcium channel perturbation on LSC biology. RESULTS/ANTICIPATED RESULTS: BCL2 inhibition leads to decreased OXPHOS activity in primary AML specimens. BIO-ID studies revealed cation/metal ion transporters, ER membrane proteins and ER membrane organization as top enriched pathways interacting with BCL2. RNA-seq data showed increased expression of genes involved in calcium influx into the ER in ven/aza sensitive LSCs and increased expression of genes involved in calcium efflux from the ER in ven/aza resistant samples. Ven/Aza resistant LSCs have increased mitochondrial calcium content, consistent with their increased OXPHOS activity as calcium is required for OXPHOS. Perturbation of these channels leads to decreased OXPHOS activity and decreased viability in LSCs. DISCUSSION/SIGNIFICANCE OF IMPACT: We postulate that a deeper understanding of the mechanisms behind ven/aza targeting of LSCs will lead to the development of novel therapies for patients who do not respond to ven/aza. Our data show targeting intracellular calcium signaling could be a viable therapeutic strategy for AML patients.

Art may be made as a guide to understanding sense of place, and also as a pathway to understanding and valuing scientific ideas. Here we consider this connection in the context of a selected history of artists working in Antarctica, from early explorers to the modern era. This provides a parallel trajectory for the nature, realisation and purpose of the art. We then consider the interaction between art and science and the nature of interdisciplinary work by looking at work produced in a sea ice-based science field camp by an artist collecting data – both scientific and art focused. The artist participated in two field campaigns a year apart, allowing comparison of the evolution of both the artistic practice and the science data collection. Furthermore, the collection of data that served both needs provides a unique point of connection between two fields of endeavour, which are typically considered as separate.

Several application modes and methods (schemes) of using herbicides are available to control undesirable vegetation on electric transmission line rights-of-way (ROW). Preferential use of a management scheme can be based on its cost effectiveness, i.e., degree of vegetation control and treatment cost. A treatment that increases/maintains desirable plants, decreases/maintains undesirable plants, and has relatively low cost, can be considered cost effective. Three common herbicides, 2,4-D, picloram and triclopyr, were applied in the field to test treatment mode (selective and nonselective) and method (cut stump, basal, and stem-foliar) effects on cost effectiveness during initial clearing and first and second conversion cycles on one electric transmission line ROW in Upstate New York. Clear or selective cutting with no herbicide was most cost effective during initial clearing. Nonselective and selective stem-foliar schemes were most cost effective during the first and second conversion cycles, respectively.