Objectives/Goals: Triple-negative breast cancer (TNBC) is a highly aggressive and prevalent breast cancer subtype that lacks targeted therapies. This study aims to investigate whether the niclosamide derivative HJC0152 can modulate tumor-derived PD-L1 expression and enhance the effectiveness of anti-PD-1 immunotherapy in treating TNBC. Methods/Study Population: Niclosamide derivative HJC0152 was developed as a novel cancer therapeutic and immunomodulating agent. Human TNBC cell line (MDA-MB-231) was treated with HJC0152, and activation of the STAT3 signaling pathway was evaluated using Western blotting. RNA-Seq was employed to analyze the expression of protein-coding genes, particularly those related to immune response. To study therapeutic potential in vivo, TNBC mouse models will be treated with single agent treatments as well as a combination therapy of HJC0152 and anti-PD-1. Tumor volume and mass will be measured over time to determine growth inhibition. Results/Anticipated Results: Preliminary studies indicate that HJC0152 exhibits enhanced solubility compared to Niclosamide, along with high anticancer potency both in vitro and in vivo. HJC0152 was found to effectively inhibit the activation of phosphorylated STAT3 (p-STAT3) in MDA-MB-231 cells, a key signaling pathway associated with cancer progression and immune evasion. RNA-Seq analysis of HJC0152-treated MDA-MB-231 cells revealed a decrease in PD-L1 expression, an essential immune checkpoint protein involved in tumor immune suppression. These findings suggest that HJC0152 is a promising immune modulator that may enhance the efficacy of immune checkpoint blockade therapy for TNBC. Discussion/Significance of Impact: This study explores an innovative immunotherapy for TNBC using the Niclosamide derivative HJC0152, which inhibits STAT3 signaling and downregulates PD-L1. Results from this study will provide a foundation for HJC0152’s inclusion in clinical trials and potentially offer a new and promising therapeutic option for TNBC treatment.

We introduce a general class of transport distances $\mathrm {WB}_{\Lambda }$ over the space of positive semi-definite matrix-valued Radon measures $\mathcal {M}(\Omega, \mathbb {S}_+^n)$, called the weighted Wasserstein–Bures distance. Such a distance is defined via a generalised Benamou–Brenier formulation with a weighted action functional and an abstract matricial continuity equation, which leads to a convex optimisation problem. Some recently proposed models, including the Kantorovich–Bures distance and the Wasserstein–Fisher–Rao distance, can naturally fit into ours. We give a complete characterisation of the minimiser and explore the topological and geometrical properties of the space $(\mathcal {M}(\Omega, \mathbb {S}_+^n),\mathrm {WB}_{\Lambda })$. In particular, we show that $(\mathcal {M}(\Omega, \mathbb {S}_+^n),\mathrm {WB}_{\Lambda })$ is a complete geodesic space and exhibits a conic structure.

The whitefly, Bemisia tabaci is a cryptic species complex in which one member, Middle East-Asia Minor 1 (MEAM1) has invaded globally. After invading large countries like Australia, China, and the USA, MEAM1 spread rapidly across each country. In contrast, our analysis of MEAM1 in India showed a very different pattern. Despite the detection of MEAM1 being contemporaneous with invasions in Australia, the USA, and China, MEAM1 has not spread widely and instead remains restricted to the southern regions. An assessment of Indian MEAM1 genetic diversity showed a level of diversity equivalent to that found in its presumed home range and significantly higher than that expected across the invaded range. The high level of diversity and restricted distribution raises the prospect that its home range extends into India. Similarly, while the levels of diversity in Australia and the USA conformed to that expected for the invaded range, China did not. It suggests that China may also be part of its home range. We also observed that diversity across the invaded range was primarily accounted for by a single haplotype, Hap1, which accounted for 79.8% of all records. It was only the invasion of Hap1 that enabled outbreaks to occur and MEAM1’s discovery.

The safety of human-collaborative operations with robots depends on monitoring the external torque of the robot, in which there are toque sensor-based and torque sensor-free methods. Economically, the classic method for estimating joint external torque is the first-order momentum observer (MOB) based on a physic model without torque sensors. However, uncertainties in the dynamic model, which encompasses parameters identification error and joint friction, affect the torque estimation accuracy. To address this issue, this paper proposes using the backpropagation neural network (BPNN) method to estimate joint external torque without the delicate physical model by utilizing the powerful machine learning ability to handle the uncertainties of the MOB method and improve the accuracy of torque estimation. Using data obtained from the torque sensor to train the BPNN to build up a digital torque model, the trained BPNN can perceive force in practical applications without relying on the torque sensor. In the end, by contrast to the classic first-order MOB, the result demonstrates that BPNN achieves higher estimation accuracy compared to the MOB.

Laser-driven inertial confinement fusion (ICF) diagnostics play a crucial role in understanding the complex physical processes governing ICF and enabling ignition. During the ICF process, the interaction between the high-power laser and ablation material leads to the formation of a plasma critical surface, which reflects a significant portion of the driving laser, reducing the efficiency of laser energy conversion into implosive kinetic energy. Effective diagnostic methods for the critical surface remain elusive. In this work, we propose a novel optical diagnostic approach to investigate the plasma critical surface. This method has been experimentally validated, providing new insights into the critical surface morphology and dynamics. This advancement represents a significant step forward in ICF diagnostic capabilities, with the potential to inform strategies for enhancing the uniformity of the driving laser and target surface, ultimately improving the efficiency of converting laser energy into implosion kinetic energy and enabling ignition.

Significant differences in life-history traits between the southern population (S) and northern (N) population of the cabbage beetle Colaphellus bowringi make it an excellent model for studying inheritance in this insect. In the present study, we observed the life-history traits of pure strains, F1, reciprocal backcross and reciprocal F2 progeny under a photoperiod of L:D 15:9 h at 22 °C. The S population had shorter larval development time, longer pupal time, higher body weight, growth rate and weight loss compared with the N population. In the F1 testing, the larval development time and body weight in hybrid populations were intermediate between the parents, and the paternal parents played a greater role in determining the larval development time, while the maternal parents exhibited a greater role in determining the body weight. The pupal time of hybrid populations was significantly shorter than that of the parents. In the reciprocal backcross testing, both father and grandfather affected the larval development time, while both mother and grandmother affected the body weight. Consistently, in the reciprocal F2 cross testing, the grandfather was more influential in determining the larval development time, and grandmother was more important in determining the body weight. In all tested populations, females had greater body weight, higher growth rate and weight loss than males. Hybridization pattern did not affect sex dimorphism and sex ratio. Overall, these findings suggest that different pathways (maternal or paternal effects) were involved in the inheritance of various life-history traits in C. bowringi.

The Northwest Tibet region is defined by several terranes, magmatic belts, basins and sutures, which were primarily shaped by the tectonic activities associated with Proto-, Palaeo- and Neo-Tethys Oceans. However, the basement nature and Precambrian tectonic evolution of the Northwest Tibet region, particularly within the Tashikuergan-Tianshuihai terrane, remain largely unknown. The Hongliutan area, located in the northeastern part of the Tashikuergan-Tianshuihai terrane, contains a critical sequence of Precambrian metamorphic rock strata. Detailed petrological, geochronological, and geochemical analyses of these metamorphic rocks – including plagioclase schist, quartz schist, amphibolite and nearby leucogranite – reveal the intricate processes of tectonic evolution within the Tianshuihai unit. Combining these findings with previous geochronological results is crucial for re-evaluating the nature of the Tashikuergan-Tianshuihai basement and its Precambrian tectonic evolution of the Tashikuergan-Tianshuihai basement. Our results reveal the following: (1) the leucogranite and amphibolite, identified as Cambrian igneous rocks, display distinct geochemical signatures indicative of a continental arc origin. These include calc-alkaline characteristics, enrichment in Th, U, Pb, Zr and Hf and depletion in Ba, Nb, Sr and Ti. Their εNd(t) values, close to zero, further support this tectonic setting, with the leucogranite and amphibolite formed at 506 and 522 Ma, respectively. (2) The plagioclase schist and quartz schist are interpreted to be Neoproterozoic volcaniclastic rocks that formed in a rifted (passive) continental margin setting. The quartz schist is particularly rich in detrital zircons, displaying a broad spectrum of 207Pb/206Pb ages, ranging from 901 to 3364 Ma. (3) A significant subset of detrital zircons within the quartz schist exhibits oscillatory zoning, high Th/U ratios and sharp-edged, anhedral-to-subhedral crystal forms, suggesting a derivation from proximal or deep-seated terranes. The concordant U–Pb zircon ages of 2468 and 974 Ma from the quartz schist, along with the 978 Ma age from the inherited zircons in the amphibolite, and the 1.2–2.1 Ga T2DM(Nd) from leucogranite and metamorphic rocks, collectively suggest that the Tianshuihai unit is likely underpinned by a Palaeoproterozoic basement that indicates Neoproterozoic reworking.

Therefore, our findings suggest the presence of a continuous, northwest-southeast trending Palaeoproterozoic basement underlying the entire Tashikuergan-Tianshuihai terrane. An alternative scenario posits that the ancient basement, currently beneath the Tashikuergan terrane, could extend into the Tianshuihai region, potentially indicating a Cambrian continental margin arc interspersed with remnants of older terranes.

Change-point analysis (CPA) is a well-established statistical method to detect abrupt changes, if any, in a sequence of data. In this paper, we propose a procedure based on CPA to detect test speededness. This procedure is not only able to classify examinees into speeded and non-speeded groups, but also identify the point at which an examinee starts to speed. Identification of the change point can be very useful. First, it informs decision makers of the appropriate length of a test. Second, by removing the speeded responses, instead of the entire response sequence of an examinee suspected of speededness, ability estimation can be improved. Simulation studies show that this procedure is efficient in detecting both speeded examinees and the speeding point. Ability estimation is dramatically improved by removing speeded responses identified by our procedure. The procedure is then applied to a real dataset for illustration purpose.

Missing data occur in many real world studies. Knowing the type of missing mechanisms is important for adopting appropriate statistical analysis procedure. Many statistical methods assume missing completely at random (MCAR) due to its simplicity. Therefore, it is necessary to test whether this assumption is satisfied before applying those procedures. In the literature, most of the procedures for testing MCAR were developed under normality assumption which is sometimes difficult to justify in practice. In this paper, we propose a nonparametric test of MCAR for incomplete multivariate data which does not require distributional assumptions. The proposed test is carried out by comparing the distributions of the observed data across different missing-pattern groups. We prove that the proposed test is consistent against any distributional differences in the observed data. Simulation shows that the proposed procedure has the Type I error well controlled at the nominal level for testing MCAR and also has good power against a variety of non-MCAR alternatives.

A multifunctional optical diagnostic system, which includes an interferometer, a refractometer and a multi-frame shadowgraph, has been developed at the Shenguang-II upgrade laser facility to characterize underdense plasmas in experiments of the double-cone ignition scheme of inertial confinement fusion. The system employs a 266 nm laser as the probe to minimize the refraction effect and allows for flexible switching among three modes of the interferometer, refractometer and multi-frame shadowgraph. The multifunctional module comprises a pair of beam splitters that attenuate the laser, shield stray light and configure the multi-frame and interferometric modules. By adjusting the distance and angle between the beam splitters, the system can be easily adjusted and switched between the modes. Diagnostic results demonstrate that the interferometer can reconstruct electron density below 1019 cm–3, while the refractometer can diagnose density approximately up to 1020 cm–3. The multi-frame shadowgraph is used to qualitatively characterize the temporal evolution of plasmas in the cases in which the interferometer and refractometer become ineffective.

A high-energy pulsed vacuum ultraviolet (VUV) solid-state laser at 177 nm with high peak power by the sixth harmonic of a neodymium-doped yttrium aluminum garnet (Nd:YAG) amplifier in a KBe2BO3F2 prism-coupled device was demonstrated. The ultraviolet (UV) pump laser is a 352 ps pulsed, spatial top-hat super-Gaussian beam at 355 nm. A high energy of a 7.12 mJ VUV laser at 177 nm is obtained with a pulse width of 255 ps, indicating a peak power of 28 MW, and the conversion efficiency is 9.42% from 355 to 177 nm. The measured results fitted well with the theoretical prediction. It is the highest pulse energy and highest peak power ever reported in the VUV range for any solid-state lasers. The high-energy, high-peak-power, and high-spatial-uniformity VUV laser is of great interest for ultra-fine machining and particle-size measurements using UV in-line Fraunhofer holography diagnostics.

The trace fossil record provides important insights into the evolution of early animals during the Ediacaran/Cambrian transition, with changes in ichnodiversity through time and between environments informing on the diversification of major body plans, behaviors, and niches. To quantify variation in the diversity of trace fossils across this critical interval, we propose a measure of trace fossil dissimilarity (ichnodissimilarity) based on vector calculation. Furthermore, by comparing discrepancies between the angular bisector and mean vector of two sets of vectorized fossil data, we are able to weigh the relative contribution of increases and decreases in the variation of occurrences of taxa. We used this metric to analyze an expansive dataset of Ediacaran/Cambrian trace fossils. The results allowed us to quantify the diversification of traces across this transition, informing on the timing of first appearance of different behaviors (e.g., foraging, grazing, and resting) and functional groups. By interpreting the results in the context of environmental changes and advancements in motility and sensory capabilities, we were able to pinpoint the onset and sequence of the Fortunian diversification event, Cambrian information revolution, and agronomic revolution, shedding light on the evolution of organismal body plans, behaviors, and locomotion during the Ediacaran/Cambrian transition. We identified two phases of origination and expansion during the divergence of early animal traces. Furthermore, by analyzing shallow- and deep-marine trace fossils, we were able to uncover evidence for a more rapid diversification of traces in shallow-marine environments, with progressive niche partitioning through the Ediacaran to Cambrian.

Pro-environmental behavior, including waste sorting and recycling, involves a combination of future-oriented (futureness) and other-oriented (otherness) attributes. Inspired by the perspective of intergenerational choice, this work explores whether eliciting concerns for future others could increase public support for recycling policy and recycling behavior. Study 1 consisted of an online random controlled trial and a laboratory experiment. In Study 1A (N = 400), future other-concern was primed using a static text manipulation, whereas in Study 1B (N = 192), a dynamic virtual manipulation was employed. The results showed that people in the conditions that elicited future other-concern reported greater household recycling intentions and more actual recycling behavior than those in the control conditions. Study 2A (N = 467) and Study 2B (N = 600) generalized this effect on the acceptance of the ‘Certain Time Certain Place’ waste sorting policy in China. Consistent with the intergenerational choice model, envisioning the future of subsequent generations is more impactful in gaining policy approval than merely envisioning a future time. These findings provide a new method for promoting public policy approval and recycling behavior, suggesting that people could become environmentally friendly when they are guided to consider future others.

The self-generated magnetic field in three-dimensional (3-D) single-mode ablative Rayleigh–Taylor instability (ARTI) relevant to the acceleration phase of a direct-drive inertial confinement fusion (ICF) implosion is investigated. It is found that stronger magnetic fields up to a few thousand teslas can be generated by 3-D ARTI rather than by its two-dimensional (2-D) counterpart. The Nernst effects significantly alter the magnetic field convection and amplify the magnetic fields. The magnetic field of thousands of teslas yields the Hall parameter of the order of unity, leading to profound magnetized heat flux modification. While the magnetic field significantly accelerates the bubble growth in the short-wavelength 2-D modes through modifying the heat fluxes, the magnetic field mostly accelerates the spike growth but has little influence on the bubble growth in 3-D ARTI. The accelerated growth of spikes in 3-D ARTI is expected to enhance material mixing and degrade ICF implosion performance. This work is focused on a regime relevant to direct-drive ICF parameters at the National Ignition Facility, and it also covers a range of key parameters that are relevant to other ICF designs and hydrodynamic/astrophysical scenarios.

The gas dynamics of shock-induced gas filtration through densely packed granular columns with vastly varying shock intensity and the structural parameters are numerically investigated using a coupled Eulerian–Lagrangian approach. The results shed fundamental light on the thermal effects of the shock-induced gas filtration manifested by a distinctive self-heating hot gas layer traversing the medium. The characteristics of the thermal effects in terms of the thermal intensity and uniformity are found to vary with the shock Mach number, Ms, and the filtration coefficient of the granular media, Π. As the incident shock transitions from weak to strong, and (or) the filtration coefficient increases from O(10−5) to O(104), the heating mechanisms transition between three distinct heating modes. A phase diagram of heating modes is established on the parameter space (Ms, Π), which enables us to predict the characteristics of the thermal effect in different shock-induced gas filtrations. The thermal effects markedly accelerate the pressure diffusion due to the additional heat influx when the time scale of the former is smaller than or comparable to the latter. Based on the contour map displaying the coupling degree of the thermal effects and the pressure diffusion, we identify a decoupling criterion whereby the isothermal assumption holds if only the pressure diffusion is concerned. The thermal effects may well bring about considerable thermal shocks which pose a great threat to the integrity of the solid skeleton and further reduce the overall shock resistance performance of the porous media.

Accurately converting satellite instantaneous evapotranspiration (λETi) over time to daily evapotranspiration (λETd) is crucial for estimating regional evapotranspiration from remote sensing satellites, which plays an important role in effective water resource management. In this study, four upscaling methods based on the principle of energy balance, including the evaporative fraction method (Eva-f method), revised evaporative fraction method (R-Eva-f method), crop coefficient method (Kc-ET0 method) and direct canopy resistance method (Direct-rc method), were validated based on the measured data of the Bowen ratio energy balance system (BREB) in maize fields in northwestern (NW) and northeastern (NE) China (semi-arid and semi-humid continental climate regions) from 2021 to 2023. Results indicated that Eva-f and R-Eva-f methods were superior to Kc-ET0 and Direct-rc methods in both climatic regions and performed better between 10:00 and 11:00, with mean absolute errors (MAE) and coefficient of efficiency (ɛ) reaching <10 W/m2 and > 0.91, respectively. Comprehensive evaluation of the optimal upscaling time using global performance indicators (GPI) showed that the Eva-f method had the highest GPI of 0.59 at 12:00 for the NW, while the R-Eva-f method had the highest GPI of 1.18 at 11:00 for the NE. As a result, the Eva-f approach is recommended as the best way for upscaling evapotranspiration in NW, with 12:00 being the ideal upscaling time. The R-Eva-f method is the optimum upscaling method for the Northeast area, with an ideal upscaling time of 11:00. The comprehensive results of this study could be useful for converting λETi to λETd.