Objectives/Goals: This research aims to identify genetic alterations influencing congenital anomalies of the kidney and urinary tract (CAKUT) and bridge a fundamental gap in understanding the cellular mechanisms underlying kidney development, with the long-term goal of enhancing treatments for congenital renal anomalies. Methods/Study Population: We will use a loss-of-function approach in combination with immunofluorescent microscopy techniques to determine the influence of Dnmbp perturbation on Daam1 localization, actin assembly, and junctional turnover. Additionally, to establish a foundation for delineating the molecular mechanism of DNMBP during kidney development, we will utilize clinical whole exome sequencing data to identify human DNMBP mutations associated with urogenital anomalies. Furthermore, we will determine whether human DNMBP mutations linked to CAKUT lead to disruptions in nephron development through loss-of-function rescue experiments in Xenopus. Results/Anticipated Results: Here, we evaluate the dynamics of Dnmbp-mediated transport of Daam1 within the developing kidney and show preliminary data suggesting that Dnmbp and Daam1 directly interact to promote adhesive contact formation between nephron progenitor cells. Furthermore, we propose a model in which Dnmbp functions as a critical regulator of epithelial tissue morphogenesis and provides a functional link between the dynamic processes of actin cytoskeleton regulation, intracellular adhesion, and vesicular transport. Future studies will determine whether Dnmbp interaction with Daam1 facilitates junctional actin assembly by directing Daam1 to cell–cell contact sites via Dnmbp-associated vesicle targeting, enhancing our understanding of the cellular mechanisms influencing tubule morphogenesis. Discussion/Significance of Impact: This research will establish a previously unknown role for DNMBP in kidney development and provide a comprehensive understanding of the impacts of simultaneously regulating vesicular transport and actin dynamics in nephrogenesis.

Objectives/Goals: Ischemic stroke treatments assist in restoring blood flow, but do not guarantee good outcomes. Since extracellular vesicles (EVs) able to cross the blood brain barrier, total (nonspecific) and astrocyte enriched EVs (TEVs, AEVs, respectively) from plasma may emerge as plasma biomarkers for prognostication and targeted therapeutics. Methods/Study Population: “Blood and Clot Thrombectomy Registry and Collaboration” (BACTRAC; NCT03153683) is a human stroke biobank at the University of Kentucky that collects samples at the time of mechanical thrombectomy during emergent large vessel occlusions (ELVO; ischemic stroke). EVs were isolated, via size exclusion chromatography, from unbanked plasma and concentrated resulting in TEVs. AEVs were immunoprecipitated with anti-EAAT1 (GLAST), an astrocyte-specific transmembrane glycoprotein. Isolated protein was sent to Olink and ran on their metabolic panel. Demographics and medical histories of the subjects were exported from REDcap and investigators were blinded during EV analysis. Results/Anticipated Results: ELVO subjects (8 females/ 5 males) were an average age of 71.1 ± 11.7 years. Lower TEV enolase 2, a neuronal glycolysis enzyme, associated with increased stroke severity (NIHSS; rs =  -0.7819, p = 0.0476). Higher systemically TEV quinoid dihydropteridine reductase (QDPR), essential co-factor enzyme, was associated with more severe strokes (NIHSS; rs =  0.8486, p = 0.0123) and lower cognition (MoCA; r2 =  0.7515, p = 0.0254). Interestingly, higher intracranial AEVs QDPR was associated with lower infarct volumes (rs =  -0.7333, p = 0.0202), less severe strokes (NIHSS; rs =  -0.6095, p = 0.0388), and better cognition (MoCA; r2 =  0.6095, p = 0.0388). Increased AEV nicotinamide adenine dinucleotide kinase another essential co-factor enzyme, intracranially also correlated to higher cognition (MoCA; rs =  0.8356, p = 0.0298). Discussion/Significance of Impact: Plasma TEV and AEV metabolic proteins correlate with the progression of stroke outcomes and should be investigated as target therapies during MT to improve outcomes.

Ventilator-associated pneumonia (VAP) is a well-established cause of morbidity in critically ill patients. Current VAP criteria exclude patients on extracorporeal membrane oxygenation (ECMO). This retrospective analysis tests the validity of VAP in this population, as well as a new proposed diagnostic criterion for ECMO-associated pneumonia.

The observed behaviour of passive objects in simple flows can be surprisingly intricate, and is complicated further by object activity. Inspired by the motility of bacterial swimmers, in this two-part study we examine the three-dimensional motion of rigid active particles in shear Stokes flow, focusing on bodies that induce rapid rotation as part of their activity. In Part 1 we develop a multiscale framework to investigate these emergent dynamics and apply it to simple spheroidal objects. In Part 2 (Dalwadi et al., J. Fluid Mech., vol. 979, 2024, A2) we apply our framework to understand the emergent dynamics of more complex shapes; helicoidal objects with chirality. Via a multiple scales asymptotic analysis for nonlinear systems, we systematically derive emergent equations of motion for long-term trajectories that explicitly account for the strong (leading-order) effects of fast spinning. Supported by numerical examples, we constructively link these effective dynamics to the well-known Jeffery's orbits for passive spheroids, deriving an explicit closed-form expression for the effective shape of the active particle, broadening the scope of Jeffery's seminal study to spinning spheroids.

In this two-part study, we investigate the motion of rigid, active objects in shear Stokes flow, focusing on bodies that induce rapid rotation as part of their activity. In Part 2, we derive and analyse governing equations for rapidly spinning complex-shaped particles – general helicoidal objects with chirality. Using the multiscale framework that we develop in Part 1 (Dalwadi et al., J. Fluid Mech., vol. 979, 2024, A1), we systematically derive emergent equations of motion for the angular and translational dynamics of these chiral spinning objects. We show that the emergent dynamics due to rapid rotation can be described by effective generalised Jeffery's equations, which differ from the classic versions via the inclusion of additional terms that account for chirality and other asymmetries. Furthermore, we use our analytic results to characterise and quantify the explicit effect of rotation on the effective hydrodynamic shape of the chiral objects, expanding significantly the scope of Jeffery's seminal study.

Three kaolinite reference samples identified as KGa-1, KGa-1b, and KGa-2 from the Source Clays Repository of The Clay Mineral Society (CMS) are used widely in diverse fields, but the defect structures have still not been determined with certainty. To solve this problem, powder diffraction patterns of the KGa-1, KGa-1b, and KGa-2 samples were modeled. In a kaolinite layer among three symmetrically independent octahedral sites named as A, B, and C and separated from each other by b/3 along the b parameter, the A and B sites are occupied by Al cations, whereas, the C sites located along the long diagonal of the oblique kaolinite unit cell are vacant. The layer displacement vectors t1 and t2 are related by a pseudo-mirror plane from defect-free 1Tc kaolinite enantiomorphs, whereas, the random interstratification within individual kaolinite crystallites creates right-hand and left-hand layer sub-sequences producing structural disorder. A third layer displacement vector, t0, located along the long diagonal of the oblique layer unit cell that contains the vacant octahedral site and coincides with the layer pseudo-mirror plane may exist. Thus, a structural model should be defined by the probability of t1, t2, and t0 layer displacement translations Wt1, Wt2, and Wt0, respectively, determined by simulated experimental X-ray diffraction (XRD) patterns. X-ray diffraction patterns were calculated for structures with a given content of randomly interstratified displacement vectors, and other XRD patterns were calculated for a physical mixture of crystallites having contrasting structural order with only C-vacant layers. The samples differ from each other by the content of high- and low-ordered phases referred to as HOK and LOK. The HOK phase has an almost defect-free structure in which 97% of the layer pairs are related by just the layer displacement vector t1 and only 3% of the layer pairs form the enantiomorphic fragments. In contrast, the LOK phases in the KGa-1, KGa-1b, and KGa-2 samples differ from HOK phases by the occurrence probabilities for the t1, t2, and t0 layer displacements. In addition, the LOK phases contain stacking faults that displace adjacent layers in arbitrary lengths and directions. Low XRD profile factors (Rp = 8-11%) support the defect structure models. Additional structural defects and previously published models are discussed.

In Paper I, we presented an overview of the Southern-sky MWA Rapid Two-metre (SMART) survey, including the survey design and search pipeline. While the combination of MWA’s large field-of-view and the voltage capture system brings a survey speed of ${\sim} 450\, {\textrm{deg}}^{2}\,\textrm{h}^{-1}$, the progression of the survey relies on the availability of compact configuration of the Phase II array. Over the past few years, by taking advantage of multiple windows of opportunity when the compact configuration was available, we have advanced the survey to 75% of the planned sky coverage. To date, about 10% of the data collected thus far have been processed for a first-pass search, where 10 min of observation is processed for dispersion measures out to 250 ${\textrm{pc cm}}^{-3}$, to realise a shallow survey that is largely sensitive to long-period pulsars. The ongoing analysis has led to two new pulsar discoveries, as well as an independent discovery and a rediscovery of a previously incorrectly characterised pulsar, all from ${\sim} 3\% $ of the data for which candidate scrutiny is completed. In this sequel to Paper I, we describe the strategies for further detailed follow-up including improved sky localisation and convergence to timing solution, and illustrate them using example pulsar discoveries. The processing has also led to re-detection of 120 pulsars in the SMART observing band, bringing the total number of pulsars detected to date with the MWA to 180, and these are used to assess the search sensitivity of current processing pipelines. The planned second-pass (deep survey) processing is expected to yield a three-fold increase in sensitivity for long-period pulsars, and a substantial improvement to millisecond pulsars by adopting optimal de-dispersion plans. The SMART survey will complement the highly successful Parkes High Time Resolution Universe survey at 1.2–1.5 GHz, and inform future large survey efforts such as those planned with the low-frequency Square Kilometre Array (SKA-Low).

We present an overview of the Southern-sky MWA Rapid Two-metre (SMART) pulsar survey that exploits the Murchison Widefield Array’s large field of view and voltage-capture system to survey the sky south of 30$^{\circ}$ in declination for pulsars and fast transients in the 140–170 MHz band. The survey is enabled by the advent of the Phase II MWA’s compact configuration, which offers an enormous efficiency in beam-forming and processing costs, thereby making an all-sky survey of this magnitude tractable with the MWA. Even with the long dwell times employed for the survey (4800 s), data collection can be completed in $<$100 h of telescope time, while still retaining the ability to reach a limiting sensitivity of $\sim$2–3 mJy (at 150 MHz, near zenith), which is effectively 3–5 times deeper than the previous-generation low-frequency southern-sky pulsar survey, completed in the 1990s. Each observation is processed to generate $\sim$5000–8000 tied-array beams that tessellate the full $\sim 610\, {\textrm{deg}^{2}}$ field of view (at 155 MHz), which are then processed to search for pulsars. The voltage-capture recording of the survey also allows a multitude of post hoc processing options including the reprocessing of data for higher time resolution and even exploring image-based techniques for pulsar candidate identification. Due to the substantial computational cost in pulsar searches at low frequencies, the survey data processing is undertaken in multiple passes: in the first pass, a shallow survey is performed, where 10 min of each observation is processed, reaching about one-third of the full-search sensitivity. Here we present the system overview including details of ongoing processing and initial results. Further details including first pulsar discoveries and a census of low-frequency detections are presented in a companion paper. Future plans include deeper searches to reach the full sensitivity and acceleration searches to target binary and millisecond pulsars. Our simulation analysis forecasts $\sim$300 new pulsars upon the completion of full processing. The SMART survey will also generate a complete digital record of the low-frequency sky, which will serve as a valuable reference for future pulsar searches planned with the low-frequency Square Kilometre Array.

Spectral variability offers a new technique to identify small scale structures from scintillation, as well as determining the absorption mechanism for peaked-spectrum (PS) radio sources. In this paper, we present very long baseline interferometry (VLBI) imaging using the long baseline array (LBA) of two PS sources, MRC 0225–065 and PMN J0322–4820, identified as spectrally variable from observations with the Murchison Widefield Array (MWA). We compare expected milliarcsecond structures based on the detected spectral variability with direct LBA imaging. We find MRC 0225–065 is resolved into three components, a bright core and two fainter lobes, roughly 430 pc projected separation. A comprehensive analysis of the magnetic field, host galaxy properties, and spectral analysis implies that MRC 0225–065 is a young radio source with recent jet activity over the last $10^2$–$10^3$ yr. We find PMN J0322–4820 is unresolved on milliarcsecond scales. We conclude PMN J0322–4820 is a blazar with flaring activity detected in 2014 with the MWA. We use spectral variability to predict morphology and find these predictions consistent with the structures revealed by our LBA images.

Stereotypic behaviours (SBs) are linked with behavioural inflexibility and resemble symptoms of autism, suggesting that stereotypic animals could have autistic-like social impairments. SBs are also common in caged mice. We therefore hypothesised relationships between stereotypic and social behaviours, predicting that highly stereotypic mice would give/receive more agonism and be less effective in social learning tasks. Experiment One used C57BL/6 and DBA/2 mice in non-enriched or enriched housing (15 cages each); Experiment Two, more cages (six non-enriched, 44 enriched) plus a third strain (BALB/c). Across both experiments, enrichment reduced SB and agonism (aggression, plus ‘displacements’ where one mouse supplants another at a resource). These effects appeared related: housing effects on agonism became negligible when SB was statistically controlled for, and, at least in enriched cages, SB covaried with receiving aggression. In Experiment Three, 20 DBAs varying in SB from Experiment Two acted as demonstrators in a ‘social transmission of food preferences’ task. They were fed a novel flavour (shatavari powder), then each mingled with a familiar but flavour-naïve C57 observer. Observers were subsequently offered two novel flavours: shatavari or marjoram. Those spontaneously choosing more shatavari (n = 10) tended to have had less stereotypic demonstrators than the other ten observer mice. Overall, highly stereotypic mice thus received more agonism — an effect with obvious welfare implications that can be reduced with enrichment — and seemed potentially less effective at inducing flavour preferences in conspecifics. Such effects are consistent with social impairment, suggesting that reducing SB may perhaps enhance interactions between conspecifics.

We describe a new low-frequency wideband radio survey of the southern sky. Observations covering 72–231 MHz and Declinations south of $+30^\circ$ have been performed with the Murchison Widefield Array “extended” Phase II configuration over 2018–2020 and will be processed to form data products including continuum and polarisation images and mosaics, multi-frequency catalogues, transient search data, and ionospheric measurements. From a pilot field described in this work, we publish an initial data release covering 1,447 $\mathrm{deg}^2$ over $4\,\mathrm{h}\leq \mathrm{RA}\leq 13\,\mathrm{h}$ , $-32.7^\circ \leq \mathrm{Dec} \leq -20.7^\circ$ . We process twenty frequency bands sampling 72–231 MHz, with a resolution of 2′–45′′, and produce a wideband source-finding image across 170–231 MHz with a root mean square noise of $1.27\pm0.15\,\mathrm{mJy\,beam}^{-1}$ . Source-finding yields 78,967 components, of which 71,320 are fitted spectrally. The catalogue has a completeness of 98% at ${{\sim}}50\,\mathrm{mJy}$ , and a reliability of 98.2% at $5\sigma$ rising to 99.7% at $7\sigma$ . A catalogue is available from Vizier; images are made available via the PASA datastore, AAO Data Central, and SkyView. This is the first in a series of data releases from the GLEAM-X survey.

A simple model for the motion of shape-changing swimmers in Poiseuille flow was recently proposed and numerically explored by Omori et al. (J. Fluid Mech., vol. 930, 2022, A30). These explorations hinted that a small number of interacting mechanics can drive long-time behaviours in this model, cast in the context of the well-studied alga Chlamydomonas and its rheotactic behaviours in such flows. Here, we explore this model analytically via a multiple-scale asymptotic analysis, seeking to formally identify the causal factors that shape the behaviour of these swimmers in Poiseuille flow. By capturing the evolution of a Hamiltonian-like quantity, we reveal the origins of the long-term drift in a single swimmer-dependent constant, whose sign determines the eventual behaviour of the swimmer. This constant captures the nonlinear interaction between the oscillatory speed and effective hydrodynamic shape of deforming swimmers, driving drift either towards or away from rheotaxis.