In masked priming lexical decision tasks in alphabetic or syllabic script languages, latencies are longer when a word target is primed by a higher frequency neighbor (e.g., blue–BLUR) than when primed by an unrelated word of equivalent frequency (e.g., care–BLUR) – an “inhibitory neighbor priming effect.” In contrast, Zhou et al. (1999) demonstrated facilitatory orthographic neighbor priming for two-character Chinese words (e.g., 华丽–华贵). However, Zhou et al. did not control for relative prime-target frequency, which has been shown to be important in experiments when examining languages with other scripts. In the present Experiment 1 word neighbor primes (e.g., 容易-容貌) produced an inhibitory neighbor priming effect when the prime was higher frequency than the target, paralleling effects in other script languages. In further experiments, paralleling those in other script languages, two-character targets primed by nonword neighbors (容待-容貌) or single constituent characters matching the target in either position (容-容貌) showed significant facilitation. These results suggest that lexical activation/competition processes for two-character Chinese words are reasonably similar to those for words in alphabetic/syllabic script languages.

Children with fragile X syndrome (FXS) often avoid eye contact, a behavior that is potentially related to hyperarousal. Prior studies, however, have focused on between-person associations rather than coupling of within-person changes in gaze behaviors and arousal. In addition, there is debate about whether prompts to maintain eye contact are beneficial for individuals with FXS. In a study of young females (ages 6–16), we used eye tracking to assess gaze behavior and pupil dilation during social interactions in a group with FXS (n = 32) and a developmentally similar comparison group (n = 23). Participants engaged in semi-structured conversations with a female examiner during blocks with and without verbal prompts to maintain eye contact. We identified a social–behavioral and psychophysiological profile that is specific to females with FXS; this group exhibited lower mean levels of eye contact, significantly increased mean pupil dilation during conversations that included prompts to maintain eye contact, and showed stronger positive coupling between eye contact and pupil dilation. Our findings strengthen support for the perspective that gaze aversion in FXS reflects negative reinforcement of social avoidance behavior. We also found that behavioral skills training may improve eye contact, but maintaining eye contact appears to be physiologically taxing for females with FXS.

OBJECTIVES/GOALS: SGLT2i therapy is currently a cornerstone in heart failure with preserved ejection fraction (HFpEF) therapy. Similarly, H2S has been shown to be beneficial in preclinical models of heart failure. With this in mind, we sought to investigate the effects of the SGLT2i and H2S donor therapy alone or in combination in a rodent model of cardiometabolic HFpEF. METHODS/STUDY POPULATION: Male C57BL/6N mice (9 weeks of age) were fed a high fat, Western diet (HFD) and received L-NG-Nitro arginine methyl ester (L-NAME) in the drinking water (0.5 g/L) to induce HFpEF. At 5 weeks, animals were randomized to either control, H2S donor (SG-1002, 90 mg/kg/d, P.O), Empagliflozin (155 mg/L, P.O), or the combination of SG-1002 and Empagliflozin for an additional 5 weeks while being maintained on HFD and L-NAME. Echocardiography, left ventricular invasive LV and systemic hemodynamics, and exercise capacity testing were performed to assess cardiovascular disease severity. Fasted glucose, circulating triglyceride and cholesterol content were similarly measured to quantify key clinical metabolic parameters. H2S and its metabolite, sulfane sulfur, were quantified to assure adequate H2S donation. RESULTS/ANTICIPATED RESULTS: Administration of SG-1002 restored H2S and sulfane sulfur to normal circulating levels. All treatment groups exhibited similar improvements in LV diastolic dysfunction as measured by E/E’and LVEDP. Combination therapy significantly improved exercise capacity whereas the monotherapy groups did not. Treatment with SG-1002 decreased fasting glucose and circulating cholesterol while all treatment groups displayed decreased circulating triglycerides and body weight compared to HFpEF control. DISCUSSION/SIGNIFICANCE: These data indicate that restoring H2S or treatment with an SGLT2i in this preclinical HFpEF model attenuates pathology. Combination of both drugs exhibited greater benefit than either monotherapy in important HFpEF parameters such as exercise capacity. Further studies are underway to characterize the benefits observed from combination therapy.

OBJECTIVES/GOALS: Childhood psychiatric symptoms are highly comorbid. Their co-occurrence and association with negative life outcomes is partially explained by deficits in executive control, or processes enabling self-regulation. Here, we test a novel executive neural target in three fMRI tasks and its relevance to shared psychopathology. METHODS/STUDY POPULATION: We studied 60 children [15 F/45 M; mean age (SD)=11.6 years (1.62)] with diverse diagnoses including attention deficit disorder (n=26) and autism spectrum disorder (n=22). We extracted a latent general factor of psychopathology using principal component analyses applied to parent-report Child Behavior Checklist syndrome scores. Subjects completed 3 executive control fMRI probes, tapping adaptive control, working memory, and inhibition. Correlational psychophysiological interaction (cPPI) analysis measured correlations between executive control-related modulations of activity in 414 network-affiliated parcels. We selected parcels exhibiting control-related cross-network correlations as well as control-related activity across all tasks and tested them for association with psychopathology. RESULTS/ANTICIPATED RESULTS: cPPI connectivity matrices were thresholded and graphs were identified using the Network-Based Statistic toolbox (p90th percentile PC) as well as control-related activation (>10% activated voxels; p DISCUSSION/SIGNIFICANCE: Our results examine cross-network interactions between brain regions during 3 fMRI tasks and their role in explaining individual variation in psychopathology. As executive control links to both comorbidity and life outcomes, identifying the clinically-relevant neural correlates of controlled behavior may lead to transdiagnostic treatments.

OBJECTIVES/GOALS: Smoking is a well-established risk factor for lung cancer, but never smokers account for up to 25% of lung cancer cases. There is mounting evidence that lung cancer in never smokers is biologically distinct. We aim to characterize the genomic and immunologic features of lung adenocarcinoma in never smokers versus smokers. METHODS/STUDY POPULATION: We examined clinical, genomic, and bulk-RNA sequencing data from 499 patients in the TCGA lung adenocarcinoma cohort. Tumor mutation burden was analyzed using maftools (R package). Tumor immune characterization was completed using CIBERSORTx, a digital cytometry tool that uses single cell reference profiles to determine immune cell type frequencies from bulk-RNA sequencing data. Single cell reference profiles for 19 different immune cell types were constructed from sequencing of freshly resected lung tumor tissue from UCSF patients. Partitioning Around Medoids (PAM; R package) was used to identify distinct immune phenotypes based on immune cell composition. Fisher’s exact test was used to evaluate for associations between immune phenotypes and smoking status. RESULTS/ANTICIPATED RESULTS: Of the 499 TCGA lung adenocarcinoma patients, 75 were never smokers, 269 were female, and 246 were over the age of 65. Never smokers had lower tumor mutation burden and lower predicted neoantigen burden compared to smokers (p < 0.001). There was no difference in total tumor immune cell infiltration between never smokers and smokers. PAM yielded 2 distinct clusters/immune phenotypes. The first was enriched in M1 Macrophages, cytotoxic T Cells, helper T Cells, regulatory T Cells, and Plasma Cells. The second was enriched in plasmacytoid Dendritic Cells, M2 Macrophages, and exhausted cytotoxic T Cells. Never smoking status was associated with an increased odds of having the first immune phenotype (OR 1.95, 95% CI: 1.15 - 3.35) and this association was statistically significant (p = 0.0086). DISCUSSION/SIGNIFICANCE: Our findings suggest that never smokers have an immune phenotype that is distinct from that observed in smokers. The distinct immune characteristics we observed could explain clinical trial data suggesting immune checkpoint inhibitors are less effective in never smokers and hold implications for tailoring therapy.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately impacted Black, indigenous, and people of color (BIPOC). Equitable access to therapeutics is key to addressing health disparities. We established a monoclonal infusion program in the emergency department of a safety-net hospital. Our program successfully reached underserved BIPOC communities and was sustained throughout the pandemic.

As a typical plasma-based optical element that can sustain ultra-high light intensity, plasma density gratings driven by intense laser pulses have been extensively studied for wide applications. Here, we show that the plasma density grating driven by two intersecting driver laser pulses is not only nonuniform in space but also varies over time. Consequently, the probe laser pulse that passes through such a dynamic plasma density grating will be depolarized, that is, its polarization becomes spatially and temporally variable. More importantly, the laser depolarization may spontaneously take place for crossed laser beams if their polarization angles are arranged properly. The laser depolarization by a dynamic plasma density grating may find application in mitigating parametric instabilities in laser-driven inertial confinement fusion.

The majority of children with maltreatment histories do not go on to develop depression in their adolescent and adult years. These individuals are often identified as being “resilient”, but this characterization may conceal difficulties that individuals with maltreatment histories might face in their interpersonal relationships, substance use, physical health, and/or socioeconomic outcomes in their later lives. This study examined how adolescents with maltreatment histories who exhibit low levels of depression function in other domains during their adult years. Longitudinal trajectories of depression (across ages 13–32) in individuals with (n = 3,809) and without (n = 8,249) maltreatment histories were modeled in the National Longitudinal Study of Adolescent to Adult Health. The same “Low,” “increasing,” and “declining” depression trajectories in both individuals with and without maltreatment histories were identified. Youths with maltreatment histories in the “low” depression trajectory reported lower romantic relationship satisfaction, more exposure to intimate partner and sexual violence, more alcohol abuse/dependency, and poorer general physical health compared to individuals without maltreatment histories in the same “low” depression trajectory in adulthood. Findings add further caution against labeling individuals as “resilient” based on a just single domain of functioning (low depression), as childhood maltreatment has harmful effects on a broad spectrum of functional domains.

This study aimed to assess human papillomavirus (HPV) vaccine effectiveness (VE) against both vaccine-type and nonvaccine-type high-risk HPV (hrHPV) infection, and duration of protection in United States. The study population was female participants aged 18–35 years with an HPV vaccination history and genital testing for HPV from the National Health and Nutrition Examination Survey, 2007–2016. Participants vaccinated before sexual debut were assessed against 13 nonvaccine-type hrHPV infection including 31/33/35/39/45/51/52/56/58/59/68/73/82. Multivariable logistic regression was used to estimate VE overall, by age at diagnosis, time since vaccination and lifetime sexual partners. A total of 3866 women were included in the analysis, with 23.3% (95% CI 21.3%–25.4%) having been vaccinated (≥1 dose). VE against vaccine-type HPV18/16/11/6 infection was 58% overall, which was mainly driven by those aged 18–22 years (VE = 64%) and 23–27 years (65%). Among participants aged 18–22 years vaccinated before sexual debut, the VE was 47% (23%–64%) against 13 nonvaccine-type hrHPV and 61% (95% CI 36%–77%) against 5 selected nonvaccine-type hrHPV35/39/52/58/59. Both direct effectiveness and cross-protection maintained effective for 5–10 years post vaccination. We also found the prevalence of ever diagnosed cervical cancer among vaccinated was significantly lower (0.46%, 4/874) than that among unvaccinated participants (1.27%, 38/2992). These findings highlight the potential of significant reduction of cervical cancer following the universal HPV vaccination programme.

A multiple-vehicles time-coordination guidance technique based on deep learning is suggested to address the cooperative guiding problem of hypersonic gliding vehicle entry phase. A dual-parameter bank angle profile is used in longitudinal guiding to meet the requirements of time coordination. A vehicle trajectory database is constructed along with a deep neural network (DNN) structure devised to fulfill the error criteria, and a trained network is used to replace the conventional prediction approach. Moreover, an extended Kalman filter is constructed to detect changes in aerodynamic parameters in real time, and the aerodynamic parameters are fed into a DNN. The lateral guiding employs a logic for reversing the sign of bank angle, which is based on the segmented heading angle error corridor. The final simulation results demonstrate that the built DNN is capable of addressing the cooperative guiding requirements. The algorithm is highly accurate in terms of guiding, has a fast response time, and does not need inter-munition communication, and it is capable of solving guidance orders that satisfy flight requirements even when aerodynamic parameter disruptions occur.

We assessed the efficacy of a culturally competent outreach model with promotoras in raising the coronavirus disease 2019 (COVID-19) first-dose vaccination rates in Chicago’s at-risk ZIP codes from February through May 2021. Utilizing community members from within target communities may reduce barriers, increase vaccination rates, and enhance COVID-19 prevention.

Direct numerical simulations were performed to characterize fully developed supersonic turbulent channel flows over isothermal rough walls. The effect of roughness was incorporated using a level-set/volume-of-fluid immersed boundary method. Turbulence statistics of five channel flows are compared, including one reference case with both walls smooth and four cases with smooth top walls and bottom walls with two-dimensional (2-D) and three-dimensional (3-D) sinusoidal roughnesses. Results reveal a strong dependence of the turbulence on the roughness topography and the associated shock patterns. Specifically, the 2-D geometries generate strong oblique shock waves that propagate across the channel and are reflected back to the rough-wall side. These strong shocks are absent in the smooth-wall channel and are significantly weaker in cases with 3-D roughness geometries, replaced by weak shocklets. At the impingement locations of the shocks on the top wall in the 2-D roughness cases, localized augmentations of turbulence shear production are observed. Such regions of augmented production also exist for the 3-D cases, at a much weaker level. The oblique shock waves are thought to be responsible for a more significant entropy generation for cases with 2-D surfaces than those with 3-D ones, leading to a higher irreversible heat generation and consequently higher temperature values in 2-D roughness cases. In the present supersonic channels, the effects of roughness extend beyond the near-wall layer due to the shocks. This suggests that outer layer similarity may not fully apply to a rough-wall supersonic turbulent flow.

Contemporary proof assistants such as Coq require that recursive functions be terminating and corecursive functions be productive to maintain logical consistency of their type theories, and some ensure these properties using syntactic checks. However, being syntactic, they are inherently delicate and restrictive, preventing users from easily writing obviously terminating or productive functions at their whim.

Meanwhile, there exist many sized type theories that perform type-based termination and productivity checking, including theories based on the Calculus of (Co)Inductive Constructions (CIC), the core calculus underlying Coq. These theories are more robust and compositional in comparison. So why haven’t they been adapted to Coq?

In this paper, we venture to answer this question with CIC $\widehat{\ast}$ , a sized type theory based on CIC. It extends past work on sized types in CIC with additional Coq features such as global and local definitions. We also present a corresponding size inference algorithm and implement it within Coq’s kernel; for maximal backward compatibility with existing Coq developments, it requires no additional annotations from the user.

In our evaluation of the implementation, we find a severe performance degradation when compiling parts of the Coq standard library, inherent to the algorithm itself. We conclude that if we wish to maintain backward compatibility, using size inference as a replacement for syntactic checking is impractical in terms of performance.

Biogeochemical analyses of organisms’ tissues provide direct proxies for diets, behaviors, and environmental interactions that have proven invaluable for studies of extant and extinct species. Applying these to Cretaceous ecosystems has at times produced anomalous results, however, as dinosaurs preserve unusually positive stable carbon isotope compositions relative to extant C3-feeding vertebrates. This has been hypothesized to be a unique property of dinosaur dietary physiology, with potential significance for our interpretations of their paleobiology. We test that hypothesis through multi-taxic stable carbon isotope analyses of a spatiotemporally constrained locality in the Late Cretaceous of Canada, and compare the results to a modern near-analogue environment in Louisiana. The stable carbon isotope anomaly is present in all sampled fossil vertebrates, dinosaur or not. This suggests another more widespread factor is responsible. Examinations of diagenetic effects suggest that, where present, they are insufficient to explain the isotope anomaly. The isotope anomaly is therefore not primarily the result of a unique dietary physiology of dinosaurs, but rather a mix of factors impacting all taxa, such as environmental and/or source-diet differences. Our study underscores the importance of multi-taxic samples from spatiotemporally constrained localities in testing hypotheses of extinct organisms and ecosystems, and in the use of modern data to “ground truth” when evaluating analogue versus non-analogue conditions in greenhouse paleoecosystems.

For a hypersonic-speed aircraft with a flat fuselage structure that has narrow space for a traditional wheel-type landing gear retraction, a novel type of wheel-ski landing gear is designed, which is different from traditional landing gears in force distribution and actuation methods. In order to capture the direction control performance of an aircraft with the wheel-ski landing gear, the aircraft ground taxiing nonlinear dynamic mathematical model is built based on a certain type of aircraft data. The experiment of the wheel-ski landing gear actuator and the differential brake control system is carried out to verify that the electric wheel-ski actuator model with the pressure sensor is in good agreement with the test results, indicating the model validity and the speediness of the differential brake response. Then a new fuzzy combined direction rectifying control law is designed based on the optimisation method and the fuzzy control theory. Comparing with the PD wheel-ski differential brake control, the direction rectifying efficiencies increase higher than 140% during the whole taxiing process. In addition, the combined control law can also decrease the overshoots of the yaw angle responses effectively. Finally, the stability and robustness of the designed combined direction control law are verified under various working conditions.