We perform a direct numerical simulation (DNS) of interacting Kelvin–Helmholtz instabilities (KHI) that arise at a stratified shear layer where KH billow cores are misaligned or exhibit varying phases along their axes. Significant evidence of these dynamics in early laboratory shear-flow studies by Thorpe (Geophys. Astrophys. Fluid Dyn., vol. 34, 1985, pp. 175–199) and Thorpe (J. Geophys. Res., vol. 92, 1987, pp. 5231–5248), in observations of KH billow misalignments in tropospheric clouds (Thorpe, Q. J. R. Meteorol. Soc., vol. 128, 2002, pp. 1529–1542) and in recent direct observations of such events in airglow and polar mesospheric cloud imaging in the upper mesosphere reveals that these dynamics are common. More importantly, the laboratory and mesospheric observations suggest that these dynamics lead to more rapid and more intense instabilities and turbulence than secondary convective instabilities in billow cores and secondary KHI in stratified braids between and around adjacent billows. To date, however, no simulations exploring the dynamics and energetics of interacting KH billows (apart from pairing) have been performed. Our DNS performed for Richardson number $Ri=0.10$ and Reynolds number $Re=5000$ demonstrates that KHI tubes and knots (i) comprise strong and complex vortex interactions accompanying misaligned KH billows, (ii) accelerate the transition to turbulence relative to secondary instabilities of individual KH billows, (iii) yield significantly stronger turbulence than secondary KHI in billow braids and secondary convective instabilities in KHI billow cores and (iv) expand the suite of secondary instabilities previously recognized to contribute to KHI dynamics and breakdown to turbulence in realistic geophysical environments.

Boundary-layer transition is accompanied by a significant increase in skin friction whose origin is rigorously explained using the stochastic Lagrangian formulation of the Navier–Stokes equations. This formulation permits the exact analysis of vorticity dynamics in individual realizations of a viscous incompressible fluid flow. The Lagrangian reconstruction formula for vorticity is here extended for the first time to Neumann boundary conditions (Lighthill source). We can thus express the wall vorticity, and, therefore, the wall stress, as the expectation of a stochastic Cauchy invariant in backward time, with contributions from (a) wall vorticity flux (Lighthill source) and (b) interior vorticity that has been evolved by nonlinear advection, viscous diffusion, vortex stretching and tilting. We consider the origin of stress maxima in the transitional region, examining a sufficient number of events to represent the increased skin friction. The stochastic Cauchy analysis is applied to each event to trace the origin of the wall vorticity. We find that the Lighthill source, vortex tilting, diffusion and advection of the outer vorticity make minor contributions. They are less important than spanwise stretching of near-wall spanwise vorticity, which is the dominant source of skin-friction increase during laminar-to-turbulent transition. Our analysis should assist more generally in understanding drag generation and reduction strategies and flow separation in terms of near-wall vorticity dynamics.

Fritts et al. (J. Fluid Mech., vol. xx, 2022, xx) describe a direct numerical simulation of interacting Kelvin–Helmholtz instability (KHI) billows arising due to initial billow cores that exhibit variable phases along their axes. Such KHI exhibit strong ‘tube and knot’ dynamics identified in early laboratory studies by Thorpe (Geophys. Astrophys. Fluid Dyn., vol. 34, 1985, pp. 175–199). Thorpe (Q.J.R. Meteorol. Soc., vol. 128, 2002, pp. 1529–1542) noted that these dynamics may be prevalent in the atmosphere, and they were recently identified in atmospheric observations at high altitudes. Tube and knot dynamics were found by Fritts et al. (J. Fluid. Mech., 2022) to drive stronger and faster turbulence transitions than secondary instabilities of individual KH billows. Results presented here reveal that KHI tube and knot dynamics also yield energy dissipation rates $\sim$2–4 times larger as turbulence arises and that remain $\sim$2–3 times larger to later stages of the flow evolution, compared with those of secondary convective instabilities (CI) and secondary KHI accompanying KH billows without tube and knot influences. Elevated energy dissipation rates occur due to turbulence transitions by tube and knot dynamics arising on much larger scales than secondary CI and KHI where initial KH billows are misaligned. Tube and knot dynamics also excite large-scale Kelvin ‘twist waves’ that cause vortex tube and billow core fragmentation, more energetic cascades of similar interactions to smaller scales and account for the strongest energy dissipation events accompanying such KH billow evolutions.

The incidence of scarlet fever has increased dramatically in recent years in Chongqing, China, but there has no effective method to forecast it. This study aimed to develop a forecasting model of the incidence of scarlet fever using a seasonal autoregressive integrated moving average (SARIMA) model. Monthly scarlet fever data between 2011 and 2019 in Chongqing, China were retrieved from the Notifiable Infectious Disease Surveillance System. From 2011 to 2019, a total of 5073 scarlet fever cases were reported in Chongqing, the male-to-female ratio was 1.44:1, children aged 3–9 years old accounted for 81.86% of the cases, while 42.70 and 42.58% of the reported cases were students and kindergarten children, respectively. The data from 2011 to 2018 were used to fit a SARIMA model and data in 2019 were used to validate the model. The normalised Bayesian information criterion (BIC), the coefficient of determination (R2) and the root mean squared error (RMSE) were used to evaluate the goodness-of-fit of the fitted model. The optimal SARIMA model was identified as (3, 1, 3) (3, 1, 0)12. The RMSE and mean absolute per cent error (MAPE) were used to assess the accuracy of the model. The RMSE and MAPE of the predicted values were 19.40 and 0.25 respectively, indicating that the predicted values matched the observed values reasonably well. Taken together, the SARIMA model could be employed to forecast scarlet fever incidence trend, providing support for scarlet fever control and prevention.

OBJECTIVES/GOALS: The goal of this study is to evaluate the role of WNT5A and WNT5a-AS1 in sex-differences of GBM progression. In our preliminary studies, we found that a long non-coding RNA WNT5A-AS1 is overexpressed in male GBM patients. We also found that WNT5A-AS1s expression shows a negative correlation with overall survival within male patients. METHODS/STUDY POPULATION: We will define the mechanism by which WNT5A-AS1 regulates WNT5a-mediated glioma stem cell (GSC) maintenance by assessing the effects of inhibiting WNT5A-AS1 expression on transcriptional activity and stemness in GSCs. We will determine if there are distinct Wnt-signaling patterns in male and female isogenic murine astrocytes by examining the expression of downstream proteins in the Wnt signaling pathway and how inhibition of WNT5A-AS1 alters this expression. We will then examine the impact of WNT5A-AS1 on temozolomide (TMZ) resistance in-vitro and in-vivo. We will assess the cell viability and survival of GBM PDX cells upon treatment with TMZ in vitro. Next, we will assess the capacity of knockdown of WNT5A-AS1 to increase sensitivity to TMZ-induced cell death and prolong survival in vivo in intracranial models. RESULTS/ANTICIPATED RESULTS: We hypothesize that WNT5A-AS1 targets Wnt5a and regulates its expression. We anticipate that knockdown of WNT5A-AS1 will upregulate WNT5A expression. We also expect that inhibiting WNT5A-AS1 will alter GSC stem maintenance and functional effects. We expect to see an increase in downstream Wnt5a signaling proteins in males vs females when treated with exogenous Wnt5a. We hypothesize that knockdown of both, WNT5A-AS1 and WNT5A will alter the expression of downstream proteins. We hypothesize that knockdown of WNT5A-AS1 will decrease tumor growth and therapeutic resistance to TMZ while increasing survival in patient derived xenographs in vivo and in vitro. DISCUSSION/SIGNIFICANCE: This study will provide insight into the mechanisms underlying the difference in GBM onset and progression between male and female patients, which is clinically important. We will also characterize the biological role WNT5A-AS1 which is currently unknown to date and elucidate differential role of GSCs in GBM progression between male and female.

OBJECTIVES/GOALS: Biliary atresia (BA) is a progressive congenital disease that is characterized by periductular inflammation and fibrosis that leads to bile duct destruction and cholestasis in neonates. Galectin-3 (Gal3) plays a key role in inflammation and fibrosis. The aim of this study was to evaluate plasma Gal3 levels in early and late BA. METHODS/STUDY POPULATION: Samples from our institutional Pediatric Liver Biobank were used for this study. Patients were categorized as early BA (at diagnosis), late BA (at liver transplant), early other cholestatic liver disease (CLD), late other CLD, or controls without cholestasis or structural liver disease. Plasma Gal3 levels were measured by standard ELISA. Inflammatory cytokines were measured in a subset of samples using MSD Proinflammatory Panel 1 multiplex ELISA. Liver fibrosis was categorized as none (Ishak or METAVIR 0), mild (Ishak 1-2 or METAVIR 1), moderate (Ishak 3-4 or METAVIR 2-3), and severe (Ishak 5-6 or METAVIR 4) based on histology. Data are presented as median (IQR) and compared using Kruskal-Wallis test. Spearmans correlation was used to assess the relationship between Gal3 and clinical and inflammatory markers. RESULTS/ANTICIPATED RESULTS: Samples from 10 controls, 26 early BA, 24 late BA, 13 early other CLD, and 8 late other CLD patients were used for this study. Gal3 levels in late BA (20.8 [12.4-30.5] ng/mL) and late other CLD (21.8 [16.9 – 27.2] ng/mL) were significantly higher than in controls (10.2 [7.6 – 14.5] ng/mL, p < 0.02) and early BA (11.3 [8.7 – 16.8] ng/mL, p < 0.01), but not significantly different from early other CLD (15.7 [11.9 – 21.4] ng/mL, p > 0.05). Gal3 positively correlated with fibrosis score (rho 0.3, p = 0.01), total bilirubin (rho 0.3, p = 0.002), ALT (rho 0.3, p = 0.01), AST (rho 0.3, p = 0.005), and APRI score (rho 0.3, p = 0.009), and negatively correlated with albumin (rho -0.3, p = 0.01). Out of the 10 cytokine proinflammatory panel, Gal3 was significantly correlated with IL-6 (rho 0.3, p = 0.006). DISCUSSION/SIGNIFICANCE: Gal3 is elevated in late BA and other CLD at time of transplant and correlated with degree of fibrosis, suggesting it may play a role in disease progression to cirrhosis. If targeted in the early disease stage, blocking Gal3 in pediatric cholestatic liver diseases may help delay the progression to cirrhosis and need for transplant.

OBJECTIVES/GOALS: Pain Catastrophizing is a negative coping mechanism involving rumination, magnification, and helplessness and is associated with worse chronic pain. The neurobiological mechanisms underlying this relationship are poorly understood. We aim to examine the intrinsic activity of a functional pathway in patients with chronic orofacial pain. METHODS/STUDY POPULATION: This is the second phase of a parent study examining genetics, placebos, and the brain in temporomandibular disorders (TMD). We intend to recruit 120 of the original 398 TMD patients for this phase. Participants completed the Graded Chronic Pain Scale to assess TMD pain intensity and disability and the Pain Catastrophizing Scale. Behaviorally, pain catastrophizing scores and pain intensity and disability will be analyzed using structural equation modeling. Resting-state functional magnetic resonance imaging will be used to record intrinsic brain activity. The functional connectivity between the posterior cingulate, anterior insula, and periaqueductal grey will be assessed as a causal pathway relating pain catastrophizing to pain intensity and disability. Mediation analyses will be used to test causality. RESULTS/ANTICIPATED RESULTS: We anticipate that greater engagement in catastrophic thinking about pain increases the functional connectivity strength between the posterior cingulate, anterior insula, and periaqueductal grey, which ultimately leads to heightened perception of pain intensity and disability. Therefore, we expect to see increased functional connectivity in those with high pain catastrophizing levels as compared to those with low pain catastrophizing levels, and that this pathway will mediate the relationship between pain catastrophizing and pain intensity and disability. Further, we predict that helplessness will most strongly correlate with the change in functional connectivity as compared to rumination and magnification. Results will be presented in full at the conference. DISCUSSION/SIGNIFICANCE: Understanding how pain catastrophizing can influence chronic pain pathways will not only promote a more integrative approach to chronic pain management but will also help identify the mechanisms by which pain itself develops and persists in the particularly vulnerable pain population of TMD.

OBJECTIVES/GOALS: Disparities in pediatric kidney transplantation (KT) result in reduced access and worse outcomes for minority children. We aimed to assess the impact of recent systemic changes on these disparities. METHODS/STUDY POPULATION: Retrospective cohort study of pediatric patients utilizing data from the United States Renal Data System (USRDS) and Scientific Registry of Transplant Recipients (SRTR). We compared access to transplantation, time to deceased donor kidney transplant (DDKT), and allograft failure (ACGF) using Cox proportional hazards in the 4 years preceding KAS to the 4 years post-KAS implementation. RESULTS/ANTICIPATED RESULTS: Compared to the pre-KAS era, patients post-KAS were more likely to be pre-emptively listed (26.8% vs 38.1%, p<0.001) and pre-emptively transplanted (23.8% vs 28.0%, p<0.001), however these benefits were not uniform across racial groups. Only 12.7% and 15.7% of Black and Hispanic children received a pre-emptive transplant compared to 29.6%, 49.8% and 54.4% of White, Asian and Other race children respectively. Compared to White children, Black and Hispanic children had a lower likelihood of transplant listing within 2 years of first dialysis service aHR 0.67 (0.59-0.76) and 0.82 (0.73-0.92), in the post-KAS era. Time to DDKT after listing was comparable across all racial groups in both eras. Black children have disproportionally worse 5-yr ACGF, aHR 1.50 (1.08-2.09), p=0.02. DISCUSSION/SIGNIFICANCE: After KAS implementation there remains equity in time to DDKT, however disparities persist in transplant listing and ACGF among Black children. Further studies are needed to identify granular SES factors impacting delayed referral and systemic barriers to transplant, as well as risk factors for poor allograft outcomes among minority children.

Parasitic nematodes devastate human and animal health. The limited number of anthelmintics available is concerning, especially because of increasing drug resistance. Anthelmintics are commonly derived from natural products, e.g. fungi and plants. This investigation aimed to develop a high-throughput whole organism screening method based on a motility assay using the wMicroTracker system. Anthelmintic activity of extracts from Hawaiian fungi was screened against third-stage larvae of the parasitic nematode Angiostrongylus cantonensis, categorized according to the degree of motility reduction. Of the 108 crude samples and fractionated products, 48 showed some level of activity, with 13 reducing motility to 0–25% of the maximum exhibited, including two pure compounds, emethacin B and epicoccin E, neither previously known to exhibit anthelmintic properties. The process of bioassay-guided fractionation is illustrated in detail based on analysis of one of the crude extracts, which led to isolation of lamellicolic anhydride, a compound with moderate activity. This study validates the wMicroTracker system as an economical and high-throughput option for testing large suites of natural products against A. cantonensis, adds to the short list of diverse parasites for which it has been validated and highlights the value of A. cantonensis and Hawaiian fungi for discovery of new anthelmintics.

Upon drop impact on a surface of comparable size to that of the drop, a sheet is produced that evolves freely in the air, bounded by a rim from which ligaments and droplets are continuously shed. This process is a canonical example of unsteady sheet fragmentation. The sheet dynamics is coupled with continuous ligament and drop shedding (Wang & Bourouiba, J. Fluid Mech., vol. 848, 2018b, 946–967; Wang & Bourouiba, J. Fluid Mech., vol. 910, 2021b, A39) and is governed by a nonlinear non-Galilean Taylor–Culick law (Wang & Bourouiba, 2022 (in press)). Here, we report the results of a combined theoretical and experimental study of the partition and temporal evolution of mass, momentum and energy in each part of the system composed of sheet, rim, ligaments and drops. We elucidate and derive analytical predictions, without fitting parameters, of the temporal evolution of the fractions of volume/mass, momentum and energy in each sub-part of the system: from sheet, to rim to fluid shed. We show that their temporal evolution and partitioning are independent of impact conditions. Interestingly this implies, for example, that the fraction of initial drop volume shed from an impacting drop is independent of the initial energy (or Weber number) of impact. We validate our predictions against precise measurements. Finally, we show that the partition laws for this unsteady fragmentation system are robust to changes of fluid properties (viscosity, surface tension and density). We provide the ranges of validity of our partition law on a Weber–Reynolds numbers regime map.

The long-distance stable transport of relativistic electron beams (REBs) in plasmas is studied by full three-dimensional particle-in-cell simulations. Theoretical analysis shows that the beam transport is mainly influenced by three transverse instabilities, where the excitation of self-modulation instability, and the suppression of the filamentation instability and the hosing instability are important to realize the beam stable transport. By modulating the transport parameters such as the electron density ratio, the relativistic Lorentz factor, the beam envelopes and the density profiles, the relativistic bunches having a smooth density profile and a length of several plasma wave periods can suppress the beam-plasma instabilities and propagate in plasmas for long distances with small energy losses. The results provide a reference for the research of long-distance and stable transport of REBs, and would be helpful for new particle beam diagnosis technology and space active experiments.

The epidemic of tuberculosis has posed a serious burden in Qinghai province, it is necessary to clarify the epidemiological characteristics and spatial-temporal distribution of TB for future prevention and control measures. We used descriptive epidemiological methods and spatial statistical analysis including spatial correlation and spatial-temporal analysis in this study. Furthermore, we applied an exponential smoothing model for TB epidemiological trend forecasting. Of 43 859 TB cases, the sex ratio was 1.27:1 (M:F), and the average annual TB registered incidence was 70.00/100 000 of 2009–2019. More cases were reported in March and April, and the worst TB stricken regions were the prefectures of Golog and Yushu. High TB registered incidences were seen in males, farmers and herdsmen, Tibetans, or elderly people. 7132 cases were intractable, which were recurrent, drug resistant, or co-infected with other infections. Three likely cases clusters with significant high risk were found by spatial-temporal scan on data of 2009–2019. The exponential smoothing winters' additive model was selected as the best-fitting model to forecast monthly TB cases in the future. This research indicated that TB in Qinghai is still a serious threaten to the local residents' health. Multi-departmental collaboration and funds special for TB treatments and control are still needed, and the exponential smoothing model is promising which could be applied for forecasting of TB epidemic trend in this high-altitude province.

Mid- and far-infrared (IR) photometric and spectroscopic observations are fundamental to a full understanding of the dust-obscured Universe and the evolution of both star formation and black hole accretion in galaxies. In this work, using the specifications of the SPace Infrared telescope for Cosmology and Astrophysics (SPICA) as a baseline, we investigate the capability to study the dust-obscured Universe of mid- and far-IR photometry at 34 and $70\, {\rm{\mu }}\mathrm{m}$ and low-resolution spectroscopy at $17{-}36\, {\rm{\mu }}\mathrm{m}$ using the state-of-the-art Spectro-Photometric Realisations of Infrared-selected Targets at all-z (Spritz) simulation. This investigation is also compared to the expected performance of the Origins Space Telescope and the Galaxy Evolution Probe. The photometric view of the Universe of a SPICA-like mission could cover not only bright objects (e.g. $L_{IR}>10^{12}\,{\rm L}_{\odot}$ ) up to ${z}=10$ , but also normal galaxies ( $L_{IR}<10^{11}\,{\rm L}_{\odot}$ ) up to $\textit{z}\sim4$ . At the same time, the spectroscopic observations of such mission could also allow us to estimate the redshifts and study the physical properties for thousands of star-forming galaxies and active galactic nuclei by observing the polycyclic aromatic hydrocarbons and a large set of IR nebular emission lines. In this way, a cold, 2.5-m size space telescope with spectro-photometric capability analogous to SPICA, could provide us with a complete three-dimensional (i.e. images and integrated spectra) view of the dust-obscured Universe and the physics governing galaxy evolution up to $\textit{z}\sim4$ .

The early identification and prediction of hand-foot-and-mouth disease (HFMD) play an important role in the disease prevention and control. However, suitable models are different in regions due to the differences in geography, social economy factors. We collected data associated with daily reported HFMD cases and weather factors of Zibo city in 2010~2019 and used the generalised additive model (GAM) to evaluate the effects of weather factors on HFMD cases. Then, GAM, support vectors regression (SVR) and random forest regression (RFR) models are used to compare predictive results. The annual average incidence was 129.72/100 000 from 2010 to 2019. Its distribution showed a unimodal trend, with incidence increasing from March, peaking from May to September. Our study revealed the nonlinear relationship between temperature, rainfall and relative humidity and HFMD cases and based on the predictive result, the performances of three models constructed ranked in descending order are: SVR > GAM> RFR, and SVR has the smallest prediction errors. These findings provide quantitative evidence for the prediction of HFMD for special high-risk regions and can help public health agencies implement prevention and control measures in advance.

The cosmic evolution of the chemical elements from the Big Bang to the present time is driven by nuclear fusion reactions inside stars and stellar explosions. A cycle of matter recurrently re-processes metal-enriched stellar ejecta into the next generation of stars. The study of cosmic nucleosynthesis and this matter cycle requires the understanding of the physics of nuclear reactions, of the conditions at which the nuclear reactions are activated inside the stars and stellar explosions, of the stellar ejection mechanisms through winds and explosions, and of the transport of the ejecta towards the next cycle, from hot plasma to cold, star-forming gas. Due to the long timescales of stellar evolution, and because of the infrequent occurrence of stellar explosions, observational studies are challenging, as they have biases in time and space as well as different sensitivities related to the various astronomical methods. Here, we describe in detail the astrophysical and nuclear-physical processes involved in creating two radioactive isotopes useful in such studies, $^{26}\mathrm{Al}$ and $^{60}\mathrm{Fe}$ . Due to their radioactive lifetime of the order of a million years, these isotopes are suitable to characterise simultaneously the processes of nuclear fusion reactions and of interstellar transport. We describe and discuss the nuclear reactions involved in the production and destruction of $^{26}\mathrm{Al}$ and $^{60}\mathrm{Fe}$ , the key characteristics of the stellar sites of their nucleosynthesis and their interstellar journey after ejection from the nucleosynthesis sites. This allows us to connect the theoretical astrophysical aspects to the variety of astronomical messengers presented here, from stardust and cosmic-ray composition measurements, through observation of $\gamma$ rays produced by radioactivity, to material deposited in deep-sea ocean crusts and to the inferred composition of the first solids that have formed in the Solar System. We show that considering measurements of the isotopic ratio of $^{26}\mathrm{Al}$ to $^{60}\mathrm{Fe}$ eliminate some of the unknowns when interpreting astronomical results, and discuss the lessons learned from these two isotopes on cosmic chemical evolution. This review paper has emerged from an ISSI-BJ Team project in 2017–2019, bringing together nuclear physicists, astronomers, and astrophysicists in this inter-disciplinary discussion.