An actively controllable cascaded proton acceleration driven by a separate 0.8 picosecond (ps) laser is demonstrated in proof-of-principle experiments. MeV protons, initially driven by a femtosecond laser, are further accelerated and focused into a dot structure by an electromagnetic pulse (EMP) on the solenoid, which can be tuned into a ring structure by increasing the ps laser energy. An electrodynamics model is carried out to explain the experimental results and show that the dot-structured proton beam is formed when the outer part of the incident proton beam is optimally focused by the EMP force on the solenoid; otherwise, it is overfocused into a ring structure by a larger EMP. Such a separately controlled mechanism allows precise tuning of the proton beam structures for various applications, such as edge-enhanced proton radiography, proton therapy and pre-injection in traditional accelerators.

Objectives/Goals: Rare disease patients often face lengthy delays in receiving accurate diagnoses or experience misdiagnoses due to a lack of available information. The NCATS Rare Disease Alert System (RDAS) is a public, comprehensive rare disease resource to collect and share accurate, up-to-date, and standardized data on rare diseases. Methods/Study Population: RDAS is composed of a frontend UI, Application Programming Interfaces, and backend Neo4j graph database. Each component of data collection, data annotation, data standardization, and data representation as steps were implemented during the process of each graph database creation. The UI allows users to search, browse, and subscribe to RDAS to receive the latest information and findings about their rare disease(s) of interest. The back-end data include four knowledge graphs built by integrating information from the NCATS Genetic and Rare Disease program, PubMed articles, clinical trials, and NIH grant funding. Ultimately, the integrative information pertinent to rare diseases from RDAS would advance rare diseases research. Results/Anticipated Results: Of 5001 rare diseases belonging to 32 distinct disease categories, we identified 1294 diseases that are mapped to 45,647 distinct, NIH-funded projects obtained from the NIH ExPORTER by implementing semantic annotation of project titles. To capture semantic relationships presenting among mapped research funding data, we defined a data model comprised of seven primary classes and corresponding object and data properties. A Neo4j knowledge graph based on this predefined data model has been developed, and we performed multiple case studies over this knowledge graph to demonstrate its use in directing and promoting rare disease research. Discussion/Significance of Impact: We developed an integrative knowledge graph with rare disease data and demonstrated its use as a source to identify and generate scientific evidence to support rare disease research. With the success of this study, we plan to implement advanced computation to analyze more funding related data and link to other types of data to perform further research.

Broadband frequency-tripling pulses with high energy are attractive for scientific research, such as inertial confinement fusion, but are difficult to scale up. Third-harmonic generation via nonlinear frequency conversion, however, remains a trade-off between bandwidth and conversion efficiency. Based on gradient deuterium deuterated potassium dihydrogen phosphate (KDxH2-xPO4, DKDP) crystal, here we report the generation of frequency-tripling pulses by rapid adiabatic passage with a low-coherence laser driver facility. The efficiency dependence on the phase-matching angle in a Type-II configuration is studied. We attained an output at 352 nm with a bandwidth of 4.4 THz and an efficiency of 36%. These results, to the best of our knowledge, represent the first experimental demonstration of gradient deuterium DKDP crystal in obtaining frequency-tripling pulses. Our research paves a new way for developing high-efficiency, large-bandwidth frequency-tripling technology.

The presence of dispersed-phase droplets can result in a notable increase in a system's drag. However, our understanding of the mechanism underlying this phenomenon remains limited. In this study, we use three-dimensional direct numerical simulations with a modified multi-marker volume-of-fluid method to investigate liquid–liquid two-phase turbulence in a Taylor–Couette geometry. The dispersed phase has the same density and viscosity as the continuous phase. The Reynolds number $Re\equiv r_i\omega _i d/\nu$ is fixed at 5200, the volume fraction of the dispersed phase is up to $40\,\%$, and the Weber number $We\equiv \rho u^2_\tau d/\sigma$ is approximately 8. It is found that the increase in the system's drag originates from the contribution of interfacial tension. Specifically, droplets experience significant deformation and stretching in the streamwise direction due to shear near the inner cylinder. Consequently, the rear end of the droplets lags behind the fore head. This causes opposing interfacial tension effects on the fore head and rear end of the droplets. For the fore head of the droplets, the effect of interfacial tension appears to act against the flow direction. For the rear end, the effect appears to act in the flow direction. The increase in the system's drag is attributed primarily to the effect of interfacial tension on the fore head of the droplets which leads to the hindering effect of the droplets on the surrounding continuous phase. This hindering effect disrupts the formation of high-speed streaks, favouring the formation of low-speed ones, which are generally associated with higher viscous stress and drag of the system. This study provides new insights into the mechanism of drag enhancement reported in our previous experiments.

We report a high-power ultra-narrow fiber-coupled diode laser using a Faraday anomalous dispersion optical filter (FADOF) as an external cavity element. An external cavity suitable for both the fiber-coupled package and FADOF configuration has been proposed. Using a 87Rb-based FADOF as the frequency-selective element, we realized a 103 W continuous laser output with a uniform circular beam. The center wavelength was precisely locked at the D2 line of the Rb resonance, and the bandwidth was narrowed from 1.8 nm (free-running, full width at half maximum (FWHM)) to 0.013 nm (6.9 GHz, FWHM). The side mode suppression ratio reached 31 dB. Such diode lasers with precise wavelength and high spectral brightness have critical applications in many fields, such as high-energy gas laser pumping, spin-exchange optical pumping, Raman spectroscopy and nonlinear optics.

We investigate the coupling effects of the two-phase interface, viscosity ratio and density ratio of the dispersed phase to the continuous phase on the flow statistics in two-phase Taylor–Couette turbulence at a system Reynolds number of $6\times 10^3$ and a system Weber number of 10 using interface-resolved three-dimensional direct numerical simulations with the volume-of-fluid method. Our study focuses on four different scenarios: neutral droplets, low-viscosity droplets, light droplets and low-viscosity light droplets. We find that neutral droplets and low-viscosity droplets primarily contribute to drag enhancement through the two-phase interface, whereas light droplets reduce the system's drag by explicitly reducing Reynolds stress due to the density dependence of Reynolds stress. In addition, low-viscosity light droplets contribute to greater drag reduction by further reducing momentum transport near the inner cylinder and implicitly reducing Reynolds stress. While interfacial tension enhances turbulent kinetic energy (TKE) transport, drag enhancement is not strongly correlated with TKE transport for both neutral droplets and low-viscosity droplets. Light droplets primarily reduce the production term by diminishing Reynolds stress, whereas the density contrast between the phases boosts TKE transport near the inner wall. Therefore, the reduction in the dissipation rate is predominantly attributed to decreased turbulence production, causing drag reduction. For low-viscosity light droplets, the production term diminishes further, primarily due to their greater reduction in Reynolds stress, while reduced viscosity weakens the density difference's contribution to TKE transport near the inner cylinder, resulting in a more pronounced reduction in the dissipation rate and consequently stronger drag reduction. Our findings provide new insights into the physics of turbulence modulation by the dispersed phase in two-phase turbulence systems.

Many real-world intertemporal decisions involve a group of two or more individuals making consensual decisions through group collaboration. Here, we ask how group collaboration affects intertemporal choices. In two experiments, participants completed intertemporal choices individually first (the precollaboration phase). Then, participants were placed into groups of two or three and completed a similar intertemporal task, with the group arriving at a consensual decision on each trial (the group collaboration phase). Finally, participants once again completed the intertemporal choices individually (the postcollaboration phase). Results showed that after group collaboration, the delay discounting significantly decreased compared to before collaboration both at group level and at individual level. The effect of group collaboration on individual intertemporal choices was no longer discernible by 1 week later. Therefore, the current research demonstrates the effectiveness of group collaboration and provides a way to nudge both groups and individuals to make farsighted choices.

Timing of food intake is an emerging aspect of nutrition; however, there is a lack of research accurately assessing food timing in the context of the circadian system. The study aimed to investigate the relation between food timing relative to clock time and endogenous circadian timing with adiposity and further explore sex differences in these associations among 151 young adults aged 18–25 years. Participants wore wrist actigraphy and documented sleep and food schedules in real time for 7 consecutive days. Circadian timing was determined by dim-light melatonin onset (DLMO). The duration between last eating occasion and DLMO (last EO-DLMO) was used to calculate the circadian timing of food intake. Adiposity was assessed using bioelectrical impedance analysis. Of the 151 participants, 133 were included in the statistical analysis finally. The results demonstrated that associations of adiposity with food timing relative to circadian timing rather than clock time among young adults living in real-world settings. Sex-stratified analyses revealed that associations between last EO-DLMO and adiposity were significant in females but not males. For females, each hour increase in last EO-DLMO was associated with higher BMI by 0·51 kg/m2 (P = 0·01), higher percent body fat by 1·05 % (P = 0·007), higher fat mass by 0·99 kg (P = 0·01) and higher visceral fat area by 4·75 cm2 (P = 0·02), whereas non-significant associations were present among males. The findings highlight the importance of considering the timing of food intake relative to endogenous circadian timing instead of only as clock time.

Reducing drag under high turbulence is a critical but challenging issue that has engendered great concern. This study utilizes hydrophilic tips in superhydrophobic (SHP) grooves to enhance the stability of plastron, which results in a considerable drag reduction ($DR$) up to 62 %, at Reynolds number ($Re$) reaching $2.79 \times 10^{4}$. The effect of the spacing width $w$ of the microgrooves on both $DR$ and flow structures is investigated. Experimental results demonstrate that $DR$ increases as either microgroove spacing $w$ or $Re$ increases. The velocity fields obtained using particle image velocimetry indicate that the air-filled SHP grooves induce a considerable wall slip. This slip significantly weakens the intensity of Taylor rolls, reduces local momentum transport, and consequently lowers drag. This phenomenon becomes more pronounced with increasing $w$. Furthermore, to quantify the multiscale relationship between global response and geometrical as well as driving parameters, $DR\sim (w, \phi _s, Re)$, a theoretical model is established based on angular momentum defect theory and magnitude estimate. It is demonstrated that a decrease in the surface solid fraction can reduce wall shear, and an increase in the groove width can weaken turbulence kinetic energy production, rendering enhanced slip and drag reduction. This research has implications for designing and optimizing turbulent-drag-reducing surfaces in various engineering applications, such as transportation and marine engineering.

Growing evidence indicates a link between diet and depression risk. We aimed to examine the association between an inflammatory diet index and depression utilising extensive data from UK biobank cohort. The energy-adjusted dietary inflammation index (E-DII) was calculated to quantify the potential of daily diet, with twenty-seven food parameters utilised. The E-DII scores were classified into two categories (low v. high) based on median value. To mitigate bias and ensure comparability of participant characteristics, propensity score matching was employed. To ascertain the robustness of these associations, sensitivity analyses were conducted. Subgroup analyses were performed to evaluate the consistency of these associations within different subpopulations. Totally, 152 853 participants entered the primary analyses with a mean age of 56·11 (sd 7·98) years. Employing both univariate and multivariate logistic regression models, adjustments were made for varying degrees of confounding factors (socio-demographics, lifestyle factors, common chronic medical conditions including type 2 diabetes and hypertension). Results consistently revealed a noteworthy positive correlation between E-DII and depression. In the context of propensity score matching, participants displaying higher E-DII scores exhibited an increased likelihood of experiencing incident depression (OR = 1·12, 95 % CI: 1·05, 1·19; P = 0·000316). Subgroup analysis results demonstrated variations in these associations across diverse subpopulations. The E-value for the point-estimate OR calculated from the propensity score matching dataset was 1·48. Excluding individuals diagnosed with type 2 diabetes or hypertension, the findings consistently aligned with the positive association in the primary analysis. These findings suggested that consumption of a diet with higher pro-inflammatory potential might associated with an increase of future depression risk.

Studies on obesity and risk factors from a life-course perspective among residents in the Tibet Plateau with recent economic growth and increasing obesity are important and urgently needed. The birth cohort in this area provides a unique opportunity to examine the association between maternal dietary practice and neonatal obesity. The study aims to detect the prevalence of obesity among neonates, associated with maternal diet and other factors, supporting life-course strategies for obesity control. A cohort of pregnant women was enrolled in Tibet Plateau and followed till childbirth. Dietary practice during pregnancy was assessed using the Chinese FFQ – Tibet Plateau version, food items and other variables were associated with the risk for obesity of neonates followed by logistic regression, classification and regression trees (CART) and random forest. Of the total 1226 mother–neonate pairs, 40·5 % were Tibetan and 5·4 % of neonates with obesity. Consuming fruits as a protective factor for obesity of neonates with OR (95 % CI) = 0·61 (0·43, 0·87) from logistic regression; as well as OR = 0·20 (0·12, 0·35) for consuming fruits (≥ weekly) from CART. Removing fruit consumption to avoid overshadowing effects of other factors, the following were influential from CART: maternal education (more than middle school, OR = 0·22 (0·13, 0·37)) and consumption of Tibetan food (daily, OR = 3·44 (2·08, 5·69). Obesity among neonates is prevalent in the study population. Promoting healthy diets during pregnancy and strengthening maternal education should be part of the life-course strategies for obesity control.

Obesity is associated with osteoarthritis (OA), but few studies have used fetal origin to explore the association. Our study aims to disentangle the causality between birth weight, childhood obesity, and adult OA using Mendelian randomization (MR). We identified single nucleotide polymorphisms (SNPs) related to birth weight (n = 298,142) and childhood obesity (n = 24,160) from two genome-wide association studies contributed by the Early Growth Genetics Consortium. Summary statistics of OA and its phenotypes (knee, hip, spine, hand, thumb, and finger OA) from the Genetics of Osteoarthritis Consortium (n = 826,690) were used to estimate the effects of SNPs on OA. Multivariable MR (MVMR) was conducted to investigate the independent effects of exposures. It turned out that genetically predicted standard deviation increase in birth weight was not associated with OA. In contrast, there was a marginally positive effect of childhood obesity on total [odds ratio (OR) = 1.07, 95% confidence interval (CI) = 1.00, 1.15 using IVW], knee (OR = 1.13, 95% CI = 1.05, 1.22 using weighted median), hip (OR = 1.13, 95% CI = 1.04, 1.24 using IVW), and spine OA (OR = 1.12, 95% CI = 1.03, 1.22 using IVW), but not hand, thumb, or finger OA. MVMR indicated a potential adulthood body mass index-dependent causal pathway between childhood obesity and OA. In conclusion, no association of birth weight with OA was suggested. Childhood obesity, however, showed a causality with OA in weight-bearing joints, which seems to be a general association of obesity with OA.

This paper presents a comprehensive technical overview of the Linac Coherent Light Source II (LCLS-II) photoinjector laser system, its first and foremost component. The LCLS-II photoinjector laser system serves as an upgrade to the original LCLS at SLAC National Accelerator Laboratory. This advanced laser system generates high-quality laser beams for the LCLS-II, contributing to the instrument’s unprecedented brightness, precision and flexibility. Our discussion extends to the various subsystems that comprise the photoinjector, including the photocathode laser, laser heater and beam transport systems. Lastly, we draw attention to the ongoing research and development infrastructure underway to enhance the functionality and efficiency of the LCLS-II, and similar X-ray free-electron laser facilities around the world, thereby contributing to the future of laser technology and its applications.

Pi-d2, which encodes a potential serine-threonine receptor-like kinase (RLK) membrane-spanning protein consisting of 825 amino acids, confers resistance to Magnaporthe oryzae strain ZB15 via an unidentified recognition mechanism. In this study, the Pid2 alleles of 303 rice (O. sativa) varieties from China's Yunnan region were amplified and sequenced in order to produce 24 haplotypes and 16 translation variants. Six of twenty-four alleles possessing the resistant site at the 441st amino acid were chosen for evaluating blast resistance by transforming into the blast-vulnerable rice variety Nipponbare. After being infected with 11 strains of M. oryzae, all transgenic lines exhibited resistance to ZB-15, whereas resistance to other strains varied. Notably, Pi-d2_H23 and Pi-d2_H24 exhibited resistance to all M. oryzae strains tested, indicating that these two alleles may have a broader resistance spectrum to M. oryzae. Alignment of these alleles’ amino acid sequences revealed that the differences in blast resistance spectra were primarily related to the amino acids present in the PAN domain at position 363 (valine/alanine). These findings suggested that the two extracellular signal recognition domains of PI-D2, B-lectin and PAN, may play a role in the identification of M. oryzae effectors. The present results provide insight into the mechanism of interaction between RLKs and M. oryzae.

During the existence of Proto-Tethys Ocean (550–430 Ma), microcontinents in northern East Gondwana merged with the northern margin of India-Australia, completing the assembly of Gondwana. Ongoing controversy surrounds the disappearance of the Proto-Tethys Ocean, the dynamic mechanisms of suturing and the palaeogeographic relationships among microcontinents in northern East Gondwana, contributing to the uncertainty about the tectonic evolution of the region. This paper concerns the lower Silurian Zusailing Formation in the Hainan Island and focuses on the affinity between Hainan Island and various microcontinents in northern East Gondwana during the early Silurian. We use detrital zircon geochronology to reconstruct the closure process of the Proto-Tethys Ocean and show that the detrital zircon U–Pb age groups of the lower Silurian Zusailing Formation are 2800–2200, 2100–1350, 1250–950, 600–480 and 480–430 Ma, with a significant age peak of ca. 449 Ma. Furthermore, the analysis of detrital zircon geochemistry and europium anomalies shows that the Hainan Island crust continued to thicken during 600–434 Ma. Comparing the age spectrum of early Palaeozoic detrital zircons from Hainan Island and various microcontinents in northern East Gondwana, as well as the affinity among them during the Silurian, we conclude that the closure of the eastern Proto-Tethys Ocean evolved from unidirectional subduction (600–480 Ma) to bidirectional subduction (480–430 Ma).