Radiocarbon (14C) data for 2nd millennium BC urban sites in northern Mesopotamia have been lacking until recently. This article presents a preliminary dataset and Bayesian model addressing the Middle and early Late Bronze Age (Old Babylonian and pre/early Mittani) strata of Kurd Qaburstan—one of the largest archaeological sites on the Erbil plain of Iraqi Kurdistan. The results place the large, densely occupied and fortified Middle Bronze Age city in the first part of the 18th century BC, an outcome consistent with the site’s tentative identification as ancient Qabra. A long occupation gap (up to two centuries) probably ensued, before a smaller town confined to the high mound and part of the northeastern lower town resumed in the late 16th and early 15th centuries BC, possibly before this region became part of the Late Bronze Age kingdom of Mittani.

OBJECTIVES/GOALS: Determine if the Conserved Transcriptional Response to Adversity transcriptomic profile established in primary blood mononuclear cells (PBMC) of chronically stress caregivers, is present in individuals with early Alzheimer’s disease. Chronic stress is a risk factor for Alzheimer’s, and may be an untapped biomarker for disease risk and pathology. METHODS/STUDY POPULATION: To collect preliminary data on the Conserved Transcriptional Response to Adversity profile in individuals with Alzheimer’s disease, we were able to utilize primary blood mononuclear cell samples from a small open label pilot study called Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease, designed to clear stressed senescent cells. We hypothesized senolytics may beneficially reverse this stress profile. We developed a NanoString assay (measuring 19 inflammatory, 31 type-1 interferon, and 3 antibody synthesis genes) to compare these transcriptomic changes within 4 individuals measured at baseline, post-treatment with an intermittent 12-week senolytic therapy, and at an optional extended post-treatment follow-up time point > 3 months after their post treatment visit. RESULTS/ANTICIPATED RESULTS: There was relative downregulation of expression in transcription in 7 of 19 measured inflammatory genes (FOS, PTGS2, IL8, FOS, Il1b, JUNB, and JUN) in Alzheimer’s disease participants after receiving senolytic treatment (baseline vs. post-treatment). This is consistent with a decrease in the inflammatory arm of the Conserved Transcriptional Response to Adversity profile. These differences were not significant between baseline and the extended follow-up, indicative of a transient effect of senolytic. There were no changes in type 1 interferon or antibody synthesis genes. This data provides preliminary evidence for larger controlled studies to further establish this profile in Alzheimer’s disease, providing exciting evidence for transcript changes that may be reproducible with senolytic therapy. DISCUSSION/SIGNIFICANCE: Literature relevant to Alzheimer’s disease indicates global increases in inflammation paired with deficits in immune response, capturing some genes associated with the Conserved Transcriptional Response to Adversity. This profile may be a useful biomarker for prediction of disease severity or risk of dementia due to chronic stress.

Seismic Rayleigh wave ellipticity measurements are the horizontal-to-vertical ratio of the Rayleigh wave particle motion, and are sensitive to the subsurface structure beneath a seismic station. H/V ratios measured from the ambient vibrations of the Earth are being increasingly used in glaciological applications to determine glacier and ice sheet thickness, seismic velocities and firn properties. Using the newly developed degree-of-polarisation (DOP-E) method which exploits the polarisation properties of seismic noise, we identify and extract Rayleigh waves from seismic stations in Greenland, and relate them to sea ice processes and the geology of the upper crust. Finally, we provide some suggestions for future applications of DOP-E method to gain greater insight into seasonal and long-term variability of sea ice formation and breakup as well as the monitoring of ice sheet thickness, subglacial environment and firn layers in the poles.

The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimization of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimization. Here, an automated, HRR-compatible system produced high-fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimization of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimization of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources.

We present the development and characterization of a high-stability, multi-material, multi-thickness tape-drive target for laser-driven acceleration at repetition rates of up to 100 Hz. The tape surface position was measured to be stable on the sub-micrometre scale, compatible with the high-numerical aperture focusing geometries required to achieve relativistic intensity interactions with the pulse energy available in current multi-Hz and near-future higher repetition-rate lasers ( $>$ kHz). Long-term drift was characterized at 100 Hz demonstrating suitability for operation over extended periods. The target was continuously operated at up to 5 Hz in a recent experiment for 70,000 shots without intervention by the experimental team, with the exception of tape replacement, producing the largest data-set of relativistically intense laser–solid foil measurements to date. This tape drive provides robust targetry for the generation and study of high-repetition-rate ion beams using next-generation high-power laser systems, also enabling wider applications of laser-driven proton sources.

A 2016 study season and 2017 excavation season at the 95-hectare walled site of Kurd Qaburstan on the Erbil plain have generated a variety of new results. Geophysical survey on the lower town revealed details of the Middle Bronze occupation in the southeast part of the site, including the city wall, a large open area, streets, houses, and a monumental temple comparable to examples from Tell al Rimah, Aššur, and Larsa. Excavations confirmed the Middle Bronze date of the temple and explored further Middle Bronze contexts elsewhere on the lower town. On the High Mound North Slope, Middle Bronze occupation included a fortification wall and large-scale architecture inside it. On the High Mound East, Late Bronze architecture of apparent elite character was documented. Archaeobotanical analyses complementing the excavations reveal the existence of naan-style bread in both Middle and Late Bronze contexts. Given radiocarbon and ceramic results, the Middle Bronze occupation at Kurd Qaburstan is datable to c. 1800 B.C., while the Late Bronze phases on the High Mound East belong to an early LB horizon in the 16–15th centuries B.C., perhaps predating the imposition of Mittani political authority in the region.

OBJECTIVES/GOALS: The goal of this study was to understand the impact of a high sodium diet on gene networks in the kidney that correlate with blood pressure in female primates, and translating findings to women. METHODS/STUDY POPULATION: Sodium-naïve female baboons (n=7) were fed a low-sodium (LS) diet for 6 weeks followed by a high sodium (HS) diet for 6 weeks. Sodium intake, serum 17 beta-estradiol, and ultrasound-guided kidney biopsies for RNA-Seq were collected at the end of each diet. Blood pressure was continuously measured for 64-hour periods throughout the study by implantable telemetry devices. Weighted gene coexpression network analysis was performed on RNA-Seq data to identify transcripts correlated with blood pressure on each diet. Network analysis was performed on transcripts highly correlated with BP, and in silico findings were validated by immunohistochemistry of kidney tissues. RESULTS/ANTICIPATED RESULTS: On the LS diet, Na+ intake and serum 17 beta-estradiol concentration correlated with BP. Cell type composition of renal biopsies was consistent among all animals for both diets. Kidney transcriptomes differed by diet; analysis by unbiased weighted gene co-expression network analysis revealed modules of genes correlated with BP on the HS diet. Network analysis of module genes showed causal networks linking hormone receptors, proliferation and differentiation, methylation, hypoxia, insulin and lipid regulation, and inflammation as regulators underlying variation in BP on the HS diet. Our results show variation in BP correlated with novel kidney gene networks with master regulators PPARG and MYC in female baboons on a HS diet. DISCUSSION/SIGNIFICANCE: Previous studies in primates to identify molecular networks dysregulated by HS diet focused on males. Current clinical guidelines do not offer sex-specific treatment plans for sodium sensitive hypertension. This study leveraged variation in BP as a first step to identify correlated kidney regulatory gene networks in female primates after a HS diet.

Unresolved states of mind regarding experiences of loss/abuse (U/d) are identified through lapses in the monitoring of reasoning, discourse, and behavior surrounding loss/abuse in response to the Adult Attachment Interview. Although the coding system for U/d has been widely used for decades, the individual indicators of unresolved loss/abuse have not been validated independently of the development sample. This study examined the psychometric validity of U/d, using individual participant data from 1,009 parent–child dyads across 13 studies. A latent class analysis showed that subsets of commonly occurring U/d indicators could differentiate interviewees with or without unresolved loss/abuse. Predictive models suggested a psychometric model of U/d consisting of a combination of these common indicators, with disbelief and psychologically confused statements regarding loss being especially important indicators of U/d. This model weakly predicted infant disorganized attachment. Multilevel regression analysis showed no significant association between ratings of unresolved other trauma and infant disorganized attachment, over and above ratings of unresolved loss/abuse. Altogether, these findings suggest that the coding system of U/d may have been overfitted to the initial development sample. Directions for further articulation and optimization of U/d are provided.

When applied in the health sector, AI-based applications raise not only ethical but legal and safety concerns, where algorithms trained on data from majority populations can generate less accurate or reliable results for minorities and other disadvantaged groups.

Mixed flora in urine cultures usually occur due to preanalytic contamination. In our outpatient urology clinic, we detected a high prevalence of mixed flora (46.2%), which was associated with female sex and older age. Patient education did not influence the rate of mixed flora. Future efforts should target high-risk patients.

Suicidal thoughts and behaviors (STBs) are major public health concerns among adolescents, and research is needed to identify how risk is conferred over the short term (hours and days). Sleep problems may be associated with elevated risk for STBs, but less is known about this link in youth over short time periods. The current study utilized a multimodal real-time monitoring approach to examine the association between sleep problems (via daily sleep diary and actigraphy) and next-day suicidal thinking in 48 adolescents with a history of STBs during the month following discharge from acute psychiatric care. Results indicated that specific indices of sleep problems assessed via sleep diary (i.e., greater sleep onset latency, nightmares, ruminative thoughts before sleep) predicted next-day suicidal thinking. These effects were significant even when daily sadness and baseline depression were included in the models. Moreover, several associations between daily-level sleep problems and next-day suicidal thinking were moderated by person-level measures of the construct. In contrast, sleep indices assessed objectively (via actigraphy) were either not related to suicidal thinking or were related in the opposite direction from hypothesized. Together, these findings provide some support for sleep problems as a short-term risk factor for suicidal thinking in high-risk adolescents.

Whiteite-(MnMnMn), Mn2+Mn2+Mn2+2Al2(PO4)4(OH)2⋅8H2O, is a new whiteite-subgroup member of the jahnsite group from the Foote Lithium Company mine, Kings Mountain district, Cleveland County, North Carolina, USA. It was found in small vugs of partially oxidised pegmatite minerals on the East dump of the mine, in association with eosphorite, hureaulite, fairfieldite, mangangordonite, whiteite-(CaMnMn) and jasonsmithite. It occurs as sugary aggregates of blade-like crystals up to 0.1 mm long and as epitaxial overgrowths on whiteite-(CaMnMn). The crystals are colourless to very pale brown, with a vitreous lustre and a white streak. The blades are flattened on {001} and elongated along [010], with poor cleavage on {001}. The calculated density is 2.82 g⋅cm–3. Optically it is biaxial (–) with α = 1.599(2), β = 1.605(2), γ = 1.609(2) (white light); 2V (calc.) = 78.2°, having no observable dispersion or pleochroism, and with orientation X = b. Electron microprobe analyses and structure refinement gave the empirical formula (Mn2+0.59Ca0.38Na0.03)Σ1.00Mn1.00(Mn2+1.04Fe3+0.58Fe2+0.23Zn0.16Mg0.08)Σ2.09Al2.04(PO4)3.89(OH)3.18(H2O)7.26. Whiteite-(MnMnMn) is monoclinic, P2/a, a = 15.024(3) Å, b = 6.9470(14) Å, c = 9.999(2) Å, β = 110.71(3)°, V = 976.2(4) Å3 and Z = 2. The crystal structure was refined using synchrotron single-crystal data to wRobs = 0.057 for 2014 reflections with I > 3σ(I). Site occupancy refinements confirm the ordering of dominant Mn in the X, M1 and M2 sites of the general jahnsite-group formula XM1(M2)2(M3)2(H2O)8(OH)2(PO4)4. A review of published crystallochemical data for jahnsite-group minerals shows a consistent chemical pressure effect in these minerals, manifested as a contraction of the unit-cell parameter, a, as the mean size of the X and M1 site cations increases. This is analogous to negative thermal expansion, but with increasing cation size, rather than heating, inducing octahedral rotations that result in an anisotropic contraction of the unit cell.