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Active fluids encompass a wide range of non-equilibrium fluids, in which the self-propulsion or rotation of their units can give rise to large-scale spontaneous flows. Despite the diversity of active fluids, they are commonly viscoelastic. Therefore, we develop a hydrodynamic model of isotropic active liquids by accounting for their viscoelasticity. Specifically, we incorporate an active stress term into a general viscoelastic liquid model to study the spontaneous flow states and their transitions in two-dimensional channel, annulus and disk geometries. We have discovered rich spontaneous flow states in a channel as a function of activity and Weissenberg number, including unidirectional flow, travelling-wave and vortex-roll states. The Weissenberg number acts against activity by suppressing the spontaneous flow. In an annulus confinement, we find that a net flow can be generated only if the aspect ratio of the annulus is not too large nor too small, akin to some three-dimensional active-flow phenomena. In a disk geometry, we observe a periodic chirality switching of a single vortex flow, resembling the bacteria-based active fluid experiments. The two phenomena reproduced in our model differ in Weissenberg number and frictional coefficient. As such, our active viscoelastic model offers a unified framework to elucidate diverse active liquids, uncover their connections and highlight the universality of dynamic active-flow patterns.
An optical spectrometer system based on 60 channels of fibers has been designed and employed to diagnose light emissions from laser–plasma interactions. The 60 fiber collectors cover an integrated solid angle of $\pi$, enabling the measurement of global energy losses in a symmetrical configuration. A detecting spectral range from ultraviolet to near-infrared, with angular distribution, allows for the understanding of the physical mechanisms involving various plasma modes. Experimental measurements of scattered lights from a conical implosion driven by high-energy nanosecond laser beams at the Shenguang-II Upgrade facility have been demonstrated, serving as reliable diagnostics to characterize laser absorption and energy losses from laser–plasma instabilities. This compact diagnostic system can provide comprehensive insights into laser energy coupling in direct-drive inertial confinement fusion research, which are essential for studying the driving asymmetry and improving the implosion efficiencies.
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.
This study analyses the current literature to evaluate the effectiveness of dabrafenib and trametinib in the multi-modal treatment of anaplastic thyroid cancer (ATC).
Method
A systematic review and meta-analysis of the literature were undertaken. The primary endpoint measured was overall response rate (ORR) defined by the RECIST v1.1 guidelines. Secondary endpoints were 12-month overall survival (OS), median OS and progression-free survival (PFS).
Results
Of 656 identified reports, 8 studies were included which featured 95 patients (median age 68.5 years, 46 per cent male). Median follow-up period was 11.8 months with a 12-month OS of 51 per cent. Median OS was 10.4 months. Progression-free survival (PFS) was 6.5 months. The ORR was 71 per cent. A total of 65 patients exhibited a partial or complete response in radiological tumour size. Side effects compared favourably to other kinase inhibitors.
Conclusion
Dabrafenib and trametinib exhibit a promising tumour response with a tolerable side profile. BRAF/MEK inhibitors continue to provide robust responses in BRAF-mutated ATC. The heterogeneity and lack of controls in included studies limits the confidence in the conclusions drawn.
Prior research on status has focused primarily on the cognitive perspective, exploring the effects of status and offering a limited understanding of the impact of positive status change and its emotional mechanisms. This study draws upon the two-facet model of pride to examine how positive status change influences the behaviors of new status holders. Specifically, we propose that when status differentiation is low, positive status change enhances new status holders' prosocial behavior through their authentic pride, while in cases of high status differentiation, it increases their self-interested behavior through their hubristic pride. To test our hypotheses, we conducted a series of studies, including a laboratory experiment, a scenario experiment, and a time-lagged multilevel and multisource field study. Our multilevel analyses of the data provided strong support for our hypotheses. Our findings shed light on when and why positive status change triggers different behaviors among new status holders, offering important insights into the emotional mechanisms that underlie the effects of status change.
Understanding the genetic basis of porcine mental health (PMH)-related traits in intensive pig farming systems may promote genetic improvement animal welfare enhancement. However, investigations on this topic have been limited to a retrospective focus, and phenotypes have been difficult to elucidate due to an unknown genetic basis. Intensively farmed pigs, such as those of the Duroc, Landrace, and Yorkshire breeds, have undergone prolonged selection pressure in intensive farming systems. This has potentially subjected genes related to mental health in these pigs to positive selection. To identify genes undergoing positive selection under intensive farming conditions, we employed multiple selection signature detection approaches. Specifically, we integrated disease gene annotations from three human gene–disease association databases (Disease, DisGeNET, and MalaCards) to pinpoint genes potentially associated with pig mental health, revealing a total of 254 candidate genes related to PMH. In-depth functional analyses revealed that candidate PMH genes were significantly overrepresented in signaling-related pathways (e.g., the dopaminergic synapse, neuroactive ligand‒receptor interaction, and calcium signaling pathways) or Gene Ontology terms (e.g., dendritic tree and synapse). These candidate PMH genes were expressed at high levels in the porcine brain regions such as the hippocampus, amygdala, and hypothalamus, and the cell type in which they were significantly enriched was neurons in the hippocampus. Moreover, they potentially affect pork meat quality traits. Our findings make a significant contribution to elucidating the genetic basis of PMH, facilitating genetic improvements for the welfare of pigs and establishing pigs as valuable animal models for gaining insights into human psychiatric disorders.
In the double-cone ignition scheme of inertial confinement fusion, the head-on collision of two compressed fuel jets from the cone-tips forms an isochoric plasma, which is then heated suddenly by a MeV relativistic electron beam produced by ultra-intense picosecond laser pulses. This fast-heating process was studied experimentally at the Shenguang II upgrade laser facility. By observing temporal-resolved X-ray emission and the spatial-resolved X-ray spectrum, the colliding process and heating process are carefully studied. The colliding plasma was imaged to have dimensions of approximately 86 μm in the implosion direction and approximately 120 μm in the heating direction. By comparing the simulated plasma X-ray spectrum with experimental data, the electron temperature of the heated plasma was found to rapidly increase to 600 ± 50 eV, almost doubling the temperature achieved before the heating laser incidence.
The measurement of X-ray continuous emission from laser-driven plasma was achieved through multiple monochromatic imaging utilizing a multilayer mirror array. This methodology was exemplified by the development of an eight-channel X-ray imaging system, capable of operating in the energy range of several keV with a spatial resolution of approximately 3 μm. By integrating this system with a streak camera, the temperature and trajectory of imploding capsules were successfully measured at the kJ-class Shenguang III prototype laser facility. This approach provides a synchronous diagnostic method for the spatial, temporal and spectral analysis of laser-driven plasma, characterized by its high efficiency and resolution.
Double-cone ignition [Zhang et al., Phil. Trans. R. Soc. A 378, 20200015 (2020)] was proposed recently as a novel path for direct-drive inertial confinement fusion using high-power lasers. In this scheme, plasma jets with both high density and high velocity are required for collisions. Here we report preliminary experimental results obtained at the Shenguang-II upgrade laser facility, employing a CHCl shell in a gold cone irradiated with a two-ramp laser pulse. The CHCl shell was pre-compressed by the first laser ramp to a density of 3.75 g/cm3 along the isentropic path. Subsequently, the target was further compressed and accelerated by the second laser ramp in the cone. According to the simulations, the plasma jet reached a density of up to 15 g/cm3, while measurements indicated a velocity of 126.8 ± 17.1 km/s. The good agreements between experimental data and simulations are documented.
Convergent evidence has suggested atypical relationships between brain structure and function in major psychiatric disorders, yet how the abnormal patterns coincide and/or differ across different disorders remains largely unknown. Here, we aim to investigate the common and/or unique dynamic structure–function coupling patterns across major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ).
Methods
We quantified the dynamic structure–function coupling in 452 patients with psychiatric disorders (MDD/BD/SZ = 166/168/118) and 205 unaffected controls at three distinct brain network levels, such as global, meso-, and local levels. We also correlated dynamic structure–function coupling with the topological features of functional networks to examine how the structure–function relationship facilitates brain information communication over time.
Results
The dynamic structure–function coupling is preserved for the three disorders at the global network level. Similar abnormalities in the rich-club organization are found in two distinct functional configuration states at the meso-level and are associated with the disease severity of MDD, BD, and SZ. At the local level, shared and unique alterations are observed in the brain regions involving the visual, cognitive control, and default mode networks. In addition, the relationships between structure–function coupling and the topological features of functional networks are altered in a manner indicative of state specificity.
Conclusions
These findings suggest both transdiagnostic and illness-specific alterations in the dynamic structure–function relationship of large-scale brain networks across MDD, BD, and SZ, providing new insights and potential biomarkers into the neurodevelopmental basis underlying the behavioral and cognitive deficits observed in these disorders.
Although studies pay increasing attention to how organizational citizenship behavior (OCB) affects work–family conflict, most research ignores the boundary conditions and underlying mechanisms of this relationship. Drawing on goal interdependence theory and conservation of resources theory, this research sees two types of goal interdependence as important boundary conditions of how helping behavior affects work–family conflict. We use a combination of quantitative and qualitative methods to test our theoretical model. Specifically, using two-wave survey data collected from 386 employees and 90 supervisors in a manufacturing company, our quantitative study shows that the interaction of helping behavior with cooperative goal interdependence is positively associated with work–goal progress, whereas its interaction with competitive goal interdependence is negatively associated with work–goal progress. In turn, work–goal progress is negatively associated with work–family conflict. The results further reveal that the indirect effect of helping behavior on work–family conflict via work–goal progress is positive and significant only when the level of competitive (cooperative) goal interdependence is high (low). We use 196 employees from the same organization to conduct our qualitative study, the results of which further substantiate and extend the findings from our quantitative study. Finally, we discuss the theoretical and practical implications of our findings.
Toll-interacting protein (Tollip) participates in multiple biological processes. However, the biological functions of Tollip proteins in insects remain to be further explored. Here, the genomic sequence of tollip gene from Antheraea pernyi (named Ap-Tollip) was identified with a length of 15,060 bp, including eight exons and seven introns. The predicted Ap-Tollip protein contained conserved C2 and CUE domains and was highly homologous to those tollips from invertebrates. Ap-Tollip was highly expressed in fat body compared with other determined tissues. As far as the developmental stages were concerned, the highest expression level was found at the 14th day in eggs or the 3rd day of the 1st instar. Ap-Tollip was also obviously regulated by lipopolysaccharide, polycytidylic acid or 20E in different tissues. In addition, the interaction between Ap-Tollip and ubiquitin was confirmed by western blotting and pull-down assay. RNAi of Ap-Tollip significantly affected the expression levels of apoptosis and autophagy-related genes. These results indicated that Ap-Tollip was involved in immunity and development of A. pernyi.
Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.
Research on corporate social responsibility (CSR) disclosure recognizes the importance of the government and examines how firms respond to government CSR regulations. However, little attention is given to how government regulations affect firms’ disclosure strategy in multiple fields of CSR. Based on institutional theory, this study proposes that mandatory CSR disclosure increases the legitimacy management cost for firms, and thus firms disclose more CSR scope to gain legitimacy and less CSR emphasis to reduce costs. Using data from Chinese A-share listed firms in 2008–2018, this study finds that mandatory CSR disclosure is positively related to CSR scope but negatively related to CSR emphasis. In addition, firm visibility strengthens the aforementioned positive and negative relations, whereas market competition weakens the relation between mandatory CSR disclosure and CSR emphasis. This study contributes to the literature on CSR disclosure and studies on organizational responses to the government mandate.
In the treatment of infertile patients with non-obstructive azoospermia (NOA) caused by the deletion of the azoospermia factor c region (AZFc) on the Y chromosome, synchronous and asynchronous surgical strategies are discussed. Clinical data from NOA patients with the AZFc deletion who underwent micro-TESE were analyzed retrospectively. The sperm retrieval rate (SRR) and sperm utilization rate of synchronous and asynchronous operation groups were followed up and compared. The fertilization rate, high-quality embryo rate, clinical pregnancy rate, abortion rate, and cumulative live birth rate of ICSI in patients with successful sperm retrieval were compared between the two groups. The two groups had sperm utilization rates of 98.9% (93/94) and 50.0% (14/28), respectively. The asynchronous group’s sperm consumption rates were much lower than those of the synchronous operation group. Fertilization rate, high-quality embryo rate, clinical pregnancy rate of fresh transfer cycle, abortion rate, and cumulative live birth rate of patients in the synchronous operation group with fresh sperm, and the asynchronous operation group with thawed sperm, respectively, were 30.6% vs 33.8%, 33.8% vs 40.7%, 40.0% vs 12.5%, 30.4% vs 7.1%. Between the two groups, there was no significant difference. This suggests that individuals with NOA caused by the AZFc deletion have a high possibility of successfully acquiring sperm using micro-TESE and ICSI to conceive their own offspring. Synchronous micro-TESE is recommended to improve sperm utilization rate and the cumulative live birth rate.
Do US Circuit Courts' decisions on criminal appeals influence sentence lengths imposed by US District Courts? This Element explores the use of high-dimensional instrumental variables to estimate this causal relationship. Using judge characteristics as instruments, this Element implements two-stage models on court sentencing data for the years 1991 through 2013. This Element finds that Democratic, Jewish judges tend to favor criminal defendants, while Catholic judges tend to rule against them. This Element also finds from experiments that prosecutors backlash to Circuit Court rulings while District Court judges comply. Methodologically, this Element demonstrates the applicability of deep instrumental variables to legal data.
Several amino acids can stimulate milk synthesis in mammary epithelial cells (MEC); however, the regulatory role of isoleucine (Ile) and underlying molecular mechanism remain poorly understood. In this study, we aimed to evaluate the regulatory effects of Ile on milk protein and fat synthesis in MEC and reveal the mediation mechanism of Brahma-related gene 1 (BRG1) on this regulation. Ile dose dependently affected milk protein and fat synthesis, mechanistic target of rapamycin (mTOR) phosphorylation, sterol regulatory element binding protein 1c (SREBP-1c) expression and maturation, and BRG1 protein expression in bovine MEC. Phosphatidylinositol 3 kinase (PI3K) inhibition by LY294002 treatment blocked the stimulation of Ile on BRG1 expression. BRG1 knockdown and gene activation experiments showed that it mediated the stimulation of Ile on milk protein and fat synthesis, mTOR phosphorylation, and SREBP-1c expression and maturation in MEC. ChIP-PCR analysis detected that BRG1 bound to the promoters of mTOR and SREBP-1c, and ChIP-qPCR further detected that these bindings were increased by Ile stimulation. In addition, BRG1 positively regulated the binding of H3K27ac to these two promoters, while it negatively affected the binding of H3K27me3 to these promoters. BRG1 knockdown blocked the stimulation of Ile on these two gene expressions. The expression of BRG1 was higher in mouse mammary gland in the lactating period, compared with that in the puberty or dry period. Taken together, these experimental data reveal that Ile stimulates milk protein and fat synthesis in MEC via the PI3K-BRG1-mTOR/SREBP-1c pathway.
The optimization of laser pulse shapes is of great importance and a major challenge for laser direct-drive implosions. In this paper, we propose an efficient intelligent method to perform laser pulse optimization via hydrodynamic simulations guided by the genetic algorithm and random forest algorithm. Compared to manual optimizations, the machine-learning guided method is able to efficiently improve the areal density by a factor of 63% and reduce the in-flight-aspect ratio by a factor of 30% at the same time. A relationship between the maximum areal density and ion temperature is also achieved by the analysis of the big simulation dataset. This design method has been successfully demonstrated by the 2021 summer double-cone ignition experiments conducted at the SG-II upgrade laser facility and has great prospects for the design of other inertial fusion experiments.