The cooperative guidance problem of multiple inferior missiles intercepting a hypersonic target with the specific impact angle constraint in the two-dimensional plane is addressed in this paper, taking into consideration variations in a missile’s speed. The guidance law is designed with two subsystems: the direction of line-of-sight (LOS) and the direction of normal to LOS. In the direction of LOS, by applying the algebraic graph theory and the consensus theory, the guidance command is designed to make the system convergent in a finite time to satisfy the goal of cooperative interception. In the direction of normal to LOS, the impact angle is constrained to transform into the LOS angle at the time of interception. In view of the difficulty of measuring unknown target acceleration information in real scenarios, the guidance command is designed by utilising a super-twisting algorithm based on a nonsingular fast-terminal sliding mode (NFTSM) surface. Numerical simulation results manifest that the proposed guidance law performs efficiently and the guidance commands are free of chattering. In addition, the overall performance of this guidance law is assessed with Monte Carlo runs in the presence of measurement errors. The simulation results demonstrate that the robustness can be guaranteed, and that overall efficiency and accuracy in intercepting the hypersonic target are achieved.

The settling velocity of porous particles in linear stratification is affected by the diffusive exchange between interstitial and ambient water. The extent to which buoyancy and interstitial mass adaptation alters the settling velocity depends on the ratio of the diffusive and viscous time scales. We conducted schlieren experiments and lattice Boltzmann simulations for highly porous (95 %) but impermeable spheres settling in linear stratification. For a parameter range that resembles marine porous particles, ‘marine aggregates’, i.e. low Reynolds numbers ($0.05\leq \textit {Re}\leq 10$), intermediate Froude numbers ($0.1\leq \textit {Fr}\leq 100$) and Schmidt number of salt ($\textit {Sc}=700$), we observe delayed mass adaptation of the interstitial fluid due to lower-density fluid being dragged by a particle that forms a density boundary layer around the particle. The boundary layer buffers the diffusive exchange of stratifying agent with the ambient fluid, leading to an enhanced density contrast of the interstitial pore fluid. Stratification-related drag enhancement by means of additional buoyancy of dragging lighter fluid and buoyancy-induced vorticity resembles earlier findings for solid spheres. However, the exchange between density boundary layer and pore fluid substantially increases stratification drag for small $\textit {Fr}$. To estimate the effect of stratification on marine aggregates settling in the ocean, we derived scaling laws and show that small particles ($\leq$0.5 mm) experience enhanced drag which increases retention times by 10 % while larger porous particle (>0.5 mm) settling is dominated by delayed mass adaptation that diminishes settling velocity by 10 % up to almost 100 %. The derived relationships facilitate the integration of stratification-dependent settling velocities into biogeochemical models.

International relations scholarship concerns dyads, yet standard modeling approaches fail to adequately capture the data generating process behind dyadic events and processes. As a result, they suffer from biased coefficients and poorly calibrated standard errors. We show how a regression-based approach, the Additive and Multiplicative Effects (AME) model, can be used to account for the inherent dependencies in dyadic data and glean substantive insights in the interrelations between actors. First, we conduct a simulation to highlight how the model captures dependencies and show that accounting for these processes improves our ability to conduct inference on dyadic data. Second, we compare the AME model to approaches used in three prominent studies from recent international relations scholarship. For each study, we find that compared to AME, the modeling approach used performs notably worse at capturing the data generating process. Further, conventional methods misstate the effect of key variables and the uncertainty in these effects. Finally, AME outperforms standard approaches in terms of out-of-sample fit. In sum, our work shows the consequences of failing to take the dependencies inherent to dyadic data seriously. Most importantly, by better modeling the data generating process underlying political phenomena, the AME framework improves scholars’ ability to conduct inferential analyses on dyadic data.

This paper highlights the intersection of gender, sexuality and class in shaping the ways in which ‘leftover’ women navigate legal and social discrimination. ‘Leftover women’ is a stigmatising term in China that refers to women who do not get married by the time they reach their late twenties. Based on my fieldwork in China with queer and heterosexual ‘leftover’ women, I introduce two strategies of stigma management: ‘buying a licence to be deviant’ and ‘identity-hopping’. The former is a strategy adopted by heterosexual women with financial resources and a desire frequently expressed by queer women. ‘Buying a licence to be deviant’ refers to the strategy of accumulating sufficient financial resources to justify one's choice to be deviant and deal with the legal consequences of the evasion of the population policies. ‘Identity-hopping’ is popular among those with a lower social and financial status, who use the law's labelling function to hop from one stigmatised identity to another as a way to deal with stigma. From an intersectional lens, this paper advances law and society's study of stigma and discrimination by emphasising the hierarchy of stigmatised identities and the strategy of using the law's power of labelling identities to hop from one identity to another. It also demonstrates how the intersection of gender, sexuality and class complicates the ways in which leftover women understand and engage with the law.

This study investigates the interactions between combustor and isolator and the role played by combustion on choking-induced unstart. Shock train unsteadiness and pressure fluctuations in non-reacting environments have been previously explained in terms of shock-boundary layer interaction and acoustic forcing but, when applied to scramjets, it is still unclear whether and how this picture is altered by combustion effects. The novel experimental set-up used in this study consists of a circular cross-section model scramjet, with optically accessible combustor and isolator, tested in a high-enthalpy hypersonic free stream at Mach 4.5. A comparison is made between cases in which flow choking is induced via thermal (combustion) and non-thermal (mass addition) mechanisms using time-resolved static wall pressure measurements, high-speed flow visualization and planar laser-induced fluorescence of the OH radical as diagnostic tools. Further details on the nature of the interactions observed were provided by experiments performed in a low-enthalpy $\textrm {CO}_2$ free stream at Mach 4 using planar laser scattering visualization. The results revealed remarkable qualitative similarities between unstart processes occurring at high and low enthalpy. At high enthalpy the similarities between thermal and non-thermal choking-induced unstart were both qualitative and quantitative, suggesting very limited effect of combustion on the dynamics of the isolator shock train. Isolator flow unsteadiness, on the other hand, drastically affected the propagation of the pseudo-normal shock in the combustor, but no significant feedback effect on the isolator behaviour was observed.

A12-week experiment was conducted to evaluate the influences of thiamine ongrowth performance, and intestinal mitochondrial biogenesis and function of Megalobramaamblycephala fed a high-carbohydrate (HC) diet. Fish (24·73 (sem 0·45) g) were randomly assigned to one of four diets: two carbohydrate (CHO) levels (30 and 45 %) and two thiamine levels (0 and 1·5 mg/kg). HC diets significantly decreased DGC, GRMBW, FIMBW, intestinal activities of amylase, lipase, Na+, K+-ATPase, CK, complexes I, III and IV, intestinal ML, number of mitochondrial per field, ΔΨm, the P-AMPK: T-AMPK ratio, PGC-1β protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1β, mitochondrial transcription factor A, Opa-1, ND-1 and COX-1 and 2, while the opposite was true for ATP, AMP and reactive oxygen species, and the transcriptions of dynamin-related protein-1, fission-1 and mitochondrial fission factor. Dietarythiamine concentrations significantly increased DGC, GRMBW, intestinal activities of amylase, Na+, K+-ATPase, CK, complexes I and IV, intestinal ML, number of mitochondrial per field, ΔΨm, the P-AMPK:T-AMPK ratio, PGC-1β protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1β, Opa-1, ND-1, COX-1 and 2, SGLT-1 and GLUT-2. Furthermore, a significant interaction between dietary CHO and thiamine was observed in DGC, GRMBW, intestinal activities of amylase, CK, complexes I and IV, ΔΨm, the AMP:ATP ratio, the P-AMPK:T-AMPK ratio, PGC-1β protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1β, Opa-1, COX-1 and 2, SGLT-1 and GLUT-2. Overall, thiamine supplementation improved growth performance, and intestinal mitochondrial biogenesis and function of M. amblycephala fed HC diets.

We report the results of an experimental investigation into the decay of turbulence in plane Couette–Poiseuille flow using ‘quench’ experiments where the flow laminarises after a sudden reduction in Reynolds number $Re$. Specifically, we study the velocity field in the streamwise–spanwise plane. We show that the spanwise velocity containing rolls decays faster than the streamwise velocity, which displays elongated regions of higher or lower velocity called streaks. At final Reynolds numbers above $425$, the decay of streaks displays two stages: first a slow decay when rolls are present and secondly a more rapid decay of streaks alone. The difference in behaviour results from the regeneration of streaks by rolls, called the lift-up effect. We define the turbulent fraction as the portion of the flow containing turbulence and this is estimated by thresholding the spanwise velocity component. It decreases linearly with time in the whole range of final $Re$. The corresponding decay slope increases linearly with final $Re$. The extrapolated value at which this decay slope vanishes is $Re_{a_z}\approx 656\pm 10$, close to $Re_g\approx 670$ at which turbulence is self-sustained. The decay of the energy computed from the spanwise velocity component is found to be exponential. The corresponding decay rate increases linearly with $Re$, with an extrapolated vanishing value at $Re_{A_z}\approx 688\pm 10$. This value is also close to the value at which the turbulence is self-sustained, showing that valuable information on the transition can be obtained over a wide range of $Re$.

ABSTRACT IMPACT: Screening the effect of thousands of non-coding genetic variants will help identify variants important in the etiology of diseases OBJECTIVES/GOALS: Massively parallel reporter assays (MPRAs) can experimentally evaluate the impact of genetic variants on gene expression. In this study, our objective was to systematically evaluate the functional activity of 3’-UTR SNPs associated with neurological disorders and use those results to help understand their contributions to disease etiology. METHODS/STUDY POPULATION: To choose variants to evaluate with the MPRA, we first gathered SNPs from the GWAS Catalog that were associated with any neurological disorder trait with p-value < 10-5. For each SNP, we identified the region that was in linkage disequilibrium (r2 > 0.8) and retrieved all the common 3’-UTR SNPs (allele-frequency > 0.05) within that region. We used an MPRA to measure the impact of these 3’-UTR variants in SH-SY5Y neuroblastoma cells and a microglial cell line. These results were then used to train a deep-learning model to predict the impact of variants and identify features that contribute to the predictions. RESULTS/ANTICIPATED RESULTS: Of the 13,515 3’-UTR SNPs tested, 400 and 657 significantly impacted gene expression in SH-SY5Y and microglia, respectively. Of the 84 SNPs significantly impacted in both cells, the direction of impact was the same in 81. The direction of eQTL in GTEx tissues agreed with the assay SNP effect in SH-SY5Y cells but not microglial cells. The deep-learning model predicted sequence activity level correlated with the experimental activity level (Spearman’s corr = 0.45). The deep-learning model identified several predictive motifs similar to motifs of RNA-binding proteins. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study demonstrates that MPRAs can be used to evaluate the effect of non-coding variants, and the results can be used to train a machine learning model and interpret its predictions. Together, these can help identify causal variants and further understand the etiology of diseases.

The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at −15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (−15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.

Owing to their ultra-high accelerating gradients, combined with injection inside micrometer-scale accelerating wakefield buckets, plasma-based accelerators hold great potential to drive a new generation of free-electron lasers (FELs). Indeed, the first demonstration of plasma-driven FEL gain was reported recently, representing a major milestone for the field. Several groups around the world are pursuing these novel light sources, with methodology varying in the use of wakefield driver (laser-driven or beam-driven), plasma structure, phase-space manipulation, beamline design, and undulator technology, among others. This paper presents our best attempt to provide a comprehensive overview of the global community efforts towards plasma-based FEL research and development.

Previous studies have revealed associations of meteorological factors with tuberculosis (TB) cases. However, few studies have examined their lag effects on TB cases. This study was aimed to analyse nonlinear lag effects of meteorological factors on the number of TB notifications in Hong Kong. Using a 22-year consecutive surveillance data in Hong Kong, we examined the association of monthly average temperature and relative humidity with temporal dynamics of the monthly number of TB notifications using a distributed lag nonlinear models combined with a Poisson regression. The relative risks (RRs) of TB notifications were >1.15 as monthly average temperatures were between 16.3 and 17.3 °C at lagged 13–15 months, reaching the peak risk of 1.18 (95% confidence interval (CI) 1.02–1.35) when it was 16.8 °C at lagged 14 months. The RRs of TB notifications were >1.05 as relative humidities of 60.0–63.6% at lagged 9–11 months expanded to 68.0–71.0% at lagged 12–17 months, reaching the highest risk of 1.06 (95% CI 1.01–1.11) when it was 69.0% at lagged 13 months. The nonlinear and delayed effects of average temperature and relative humidity on TB epidemic were identified, which may provide a practical reference for improving the TB warning system.

The study of enclaves in granitic plutons provides fundamental information on the petrogenesis of their host rocks. Here we combine U–Pb zircon ages, petrography, geochemistry and Nd–Hf isotope composition to investigate the origin of dioritic–granodioritic enclaves and their host granodiorites and biotite granites in the Xuehuading–Panshanchong area, which is a pivotal site to study the Palaeozoic intracontinental orogenic processes of the South China Block. Obtained ages indicate that the host rocks were formed in early Silurian time (c. 432 Ma). The enclaves are fine grained, but with mineral assemblages similar to their hosts and contain amphibole, biotite and plagioclase. All rocks have fractionated rare earth element patterns ((La/Yb)N = 2.86–8.16), except for one biotite granite that has a concave rare earth element pattern ((La/Yb)N = 1.50). Most rocks are depleted in Ta–Nb–Ti, and have negative Eu anomalies and ϵNd(t) (–8.86 to –5.75) and zircon ϵHf(t) (–13.30 to –4.11, except for one, –39.08). We interpret that the enclaves were formed at the borders of magma-ascending conduits, where the mafic mineral crystallization was enhanced by rapid cooling. Conversely, the biotite granites were produced by fractional crystallization from a related granodiorite magma. The sample with a concave rare earth element pattern may have been influenced by hydrothermal fluid–melt interaction. Geochemical modelling suggests that the granodiorites were likely generated by disequilibrium melting of heterogeneous amphibolites in the middle–lower crust. Considering the geological data for the Palaeozoic magmatic rocks in the South China Block, we propose that the Xuehuading–Panshanchong magmatism was likely triggered by piecemeal removal of the thickened lithospheric root and subsequent thermal upwelling of mantle, without a mantle-derived magma contribution to the granites.