Numerical Research on The Nozzle Damping Effect by A Wave Attenuation Method

AbstractNozzle damping is one of the most important factors in the suppression of combustion instability in solid rocket motors. For an engineering solid rocket motor that experiences combustion instability at the end of burning, a wave attenuation method is proposed to assess the nozzle damping characteristics numerically. In this method, a periodic pressure oscillation signal which frequency equals to the first acoustic mode is superimposed on a steady flow at the head end of the chamber. When the pressure oscillation is turned off, the decay rate of the pressure can be used to determine the nozzle attenuation constant. The damping characteristics of three other nozzle geometries are numerically studied with this method under the same operating condition. The results show that the convex nozzle provides more damping than the conical nozzle which in turn provides more damping than the concave nozzle. All the three nozzles have better damping effect than that of basic nozzle geometry. At last, the phase difference in the chamber is analyzed, and the numerical pressure distribution satisfies well with theoretical distribution

TaxAI: A Dynamic Economic Simulator and Benchmark for Multi-Agent Reinforcement Learning

Taxation and government spending are crucial tools for governments to promote economic growth and maintain social equity. However, the difficulty in accurately predicting the dynamic strategies of diverse self-interested households presents a challenge for governments to implement effective tax policies. Given its proficiency in modeling other agents in partially observable environments and adaptively learning to find optimal policies, Multi-Agent Reinforcement Learning (MARL) is highly suitable for solving dynamic games between the government and numerous households. Although MARL shows more potential than traditional methods such as the genetic algorithm and dynamic programming, there is a lack of large-scale multi-agent reinforcement learning economic simulators. Therefore, we propose a MARL environment, named \textbf{TaxAI}, for dynamic games involving $N$ households, government, firms, and financial intermediaries based on the Bewley-Aiyagari economic model. Our study benchmarks 2 traditional economic methods with 7 MARL methods on TaxAI, demonstrating the effectiveness and superiority of MARL algorithms. Moreover, TaxAI's scalability in simulating dynamic interactions between the government and 10,000 households, coupled with real-data calibration, grants it a substantial improvement in scale and reality over existing simulators. Therefore, TaxAI is the most realistic economic simulator, which aims to generate feasible recommendations for governments and individuals.Comment: 26 pages, 8 figures, 12 table

Timing Is Critical for an Effective Anti-Metastatic Immunotherapy: The Decisive Role of IFNγ/STAT1-Mediated Activation of Autophagy

BACKGROUND: Immunotherapy is often recommended as an adjuvant treatment to reduce the chance of cancer recurrence or metastasis. Interestingly, timing is very important for a successful immunotherapy against metastasis, although the precise mechanism is still unknown. METHODS AND FINDINGS: Using a mouse model of melanoma metastasis induced by intravenous injection of B16-F10 cells, we investigated the mechanism responsible for the diverse efficacy of the prophylactic or therapeutic TLR4 and TLR9 agonist complex against metastasis. We found that the activation of TLR4 and TLR9 prevented, but did not reverse, metastasis because the potency of this combination was neither sufficient to overcome the tumor cell-educated immune tolerance nor to induce efficacious autophagy in tumor cells. The prophylactic application of the complex promoted antimetastatic immunity, leading to the autophagy-associated death of melanoma cells via IFNγ/STAT1 activation and attenuated tumor metastasis. IFNγ neutralization reversed the prophylactic benefit induced by the complex by suppressing STAT1 activation and attenuating autophagy in mice. However, the therapeutic application of the complex did not suppress metastasis because the complex could not reverse tumor cell-induced STAT3 activation and neither activate IFNγ/STAT1 signaling and autophagy. Suppressing STAT3 activation with the JAK/STAT antagonist AG490 restored the antimetastatic effect of the TLR4/9 agonist complex. Activation of autophagy after tumor inoculation by using rapamycin, with or without the TLR4/9 agonist complex, could suppress metastasis. CONCLUSION AND SIGNIFICANCE: Our studies suggest that activation of IFNγ/STAT1 signaling and induction of autophagy are critical for an efficacious anti-metastatic immunotherapy and that autophagy activators may overcome the timing barrier for immunotherapy against metastasis

Adjustment of the GRACE score by HemoglobinA1c enables a more accurate prediction of long-term major adverse cardiac events in acute coronary syndrome without diabetes undergoing percutaneous coronary intervention

Background: The Global Registry of Acute Coronary Events (GRACE) risk score is widely recommended for risk assessment in patients with acute coronary syndrome (ACS). Chronic hyperglycemia [hemoglobinA1c (HbA1c)] can independently predict major adverse cardiac events (MACEs) in patients with ACS. We investigated whether the prediction of MACEs with the GRACE score could be improved with the addition of HbA1c content in ACS patients without diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI). Methods: We enrolled 549 ACS patients without DM who underwent PCI. The GRACE score and HbA1c content were determined on admission. Correlation was analyzed by Spearman's rank correlation. Cumulative MACE curve was calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of MACEs. Additionally, the predictive value of HbA1c content alone and combined with GRACE score was estimated by the area under the receiver-operating characteristic curve (AUC), continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results: During a median of 42.3 months (interquartile range 39.3-44.2 months), 16 (2.9 %) were lost to follow-up, and patients experienced 69 (12.9 %) MACEs: 51 (9.6 %) all-cause deaths and 18 (3.4 %) nonfatal myocardial infarction cases. The GRACE score was positively associated with HbA1c content. Multivariate Cox analysis showed that both GRACE score and HbA1c content were independent predictors of MACEs (hazard ratio 1.030; 95 % CI 1.020-1.040; p < 0.001; 3.530; 95 % CI 1.927-6.466; p < 0.001, respectively). Furthermore, Kaplan-Meier analysis demonstrated increased risk of MACEs with increasing HbA1c content (log-rank 33.906, p < 0.001). Adjustment of the GRACE risk estimate by HbA1c improved the predictive value of the GRACE score [increase in AUC from 0.75 for the GRACE score to 0.80 for the GRACE score plus HbA1c, p = 0.012; IDI = 0.055, p < 0.001; NRI (> 0) = 0.70, p < 0.001]. Conclusions: HbA1c content is positively associated with GRACE risk score and their combination further improved the risk stratification for ACS patients without DM undergoing PCI.National Natural Science Foundation of China [91339116, 81400181]; National Natural Science Fund for Distinguished Young Scholars of China [81025002]; National Basic Research Program of China ("973 Project") [2012CB517804]SCI(E)[email protected]

Observations on Copy Number Variations in a Kidney-yang Deficiency Syndrome Family

We have performed an analysis of a family with kidney-yang deficiency syndrome (KDS) in order to determine the structural genomic variations through a novel approach designated as “copy number variants” (CNVs). Twelve KDS subjects and three healthy spouses from this family were included in this study. Genomic DNA samples were genotyped utilizing an Affymetrix 100 K single nucleotide polymorphism array, and CNVs were identified by Copy Number Algorithm (CNAT4.0, Affymetrix). Our results demonstrate that 447 deleted and 476 duplicated CNVs are shared among KDS subjects within the family. The homologus ratio of deleted CNVs was as high as 99.78%. One-copy-duplicated CNVs display mid-range homology. For two copies of duplicated CNVs (CNV4), a markedly heterologous ratio was observed. Therefore, with the important exception of CNV4, our data shows that CNVs shared among KDS subjects display typical Mendelian inheritance. A total of 113 genes with established functions were identified from the CNV flanks; significantly enriched genes surrounding CNVs may contribute to certain adaptive benefit. These genes could be classified into categories including: binding and transporter, cell cycle, signal transduction, biogenesis, nerve development, metabolism regulation and immune response. They can also be included into three pathways, that is, signal transduction, metabolic processes and immunological networks. Particularly, the results reported here are consistent with the extensive impairments observed in KDS patients, involving the mass-energy-information-carrying network. In conclusion, this article provides the first set of CNVs from KDS patients that will facilitate our further understanding of the genetic basis of KDS and will allow novel strategies for a rational therapy of this disease

Phage display mediated immuno-PCR

Immuno-PCR (IPCR) is a powerful detection technology in immunological study and clinical diagnosis due to its ultrasensitivity. Here we introduce a new strategy termed phage display mediated immuno-PCR (PD-IPCR). Instead of utilization of monoclonal antibody (mAb) and chemically bond DNA that required in the conventional IPCR, a recombinant phage particle is applied as a ready reagent for IPCR experiment. The surface displayed single chain variable fragment (scFv) and phage DNA themselves can directly serve as detection antibody and PCR template, respectively. The aim of the design is to overcome shortcoming of low detection sensitivity of scFv so as to largely facilitate the real application of scFv in immunoassay. The idea has been demonstrated by applying hantaan virus nucleocapsid protein (NP) and prion protein (PrP) as detection targets in three experimental protocols (indirect, sandwich and real-time PD-IPCR assays). The detection sensitivity was increased 1000- to 10 000-folds compared with conventional enzyme-linked immunosorbent assays (ELISAs). This proof-of-concept study may serve as a new model to develop an easy to operate, low cost and ultrasensitive immunoassay method for broad applications

Fuzheng Huayu recipe prevents nutritional fibrosing steatohepatitis in mice

<p>Abstract</p> <p>Background</p> <p>Fuzheng Huayu recipe (FZHY), a compound of Chinese herbal medicine, was reported to improve liver function and fibrosis in patients with hepatitis B virus infection. However, its effect on nutritional fibrosing steatohepatitis is unclear. We aimed to elucidate the role and molecular mechanism of FZHY on this disorder in mice.</p> <p>Methods</p> <p>C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 8 weeks to induce fibrosing steatohepatitis. FZHY and/or heme oxygenase-1 (HO-1) chemical inducer (hemin) were administered to mice, respectively. The effect of FZHY was assessed by comparing the severity of hepatic injury, levels of hepatic lipid peroxides, activation of hepatic stellate cells (HSCs) and the expression of oxidative stress, inflammatory and fibrogenic related genes.</p> <p>Results</p> <p>Mice fed with MCD diet for 8 weeks showed severe hepatic injury including hepatic steatosis, necro-inflammation and fibrosis. Administration of FZHY or hemin significantly lowered serum levels of alanine aminotransferase, aspartate aminotransferase, reduced hepatic oxidative stress and ameliorated hepatic inflammation and fibrosis. An additive effect was observed in mice fed MCD supplemented with FZHY or/and hemin. These effects were associated with down-regulation of pro-oxidative stress gene cytochrome P450 2E1, up-regulation of anti-oxidative gene HO-1; suppression of pro-inflammation genes tumor necrosis factor alpha and interleukin-6; and inhibition of pro-fibrotic genes including α-smooth muscle actin, transforming growth factor beta 1, collagen type I (Col-1) and Col-3.</p> <p>Conclusions</p> <p>Our study demonstrated the protective role of FZHY in ameliorating nutritional fibrosing steatohepatitis. The effect was mediated through regulating key genes related to oxidative stress, inflammation and fibrogenesis.</p

Anthracenedione Derivatives as Anticancer Agents Isolated from Secondary Metabolites of the Mangrove Endophytic Fungi

In this article, we report anticancer activity of 14 anthracenedione derivatives separated from the secondary metabolites of the mangrove endophytic fungi Halorosellinia sp. (No. 1403) and Guignardia sp. (No. 4382). Some of them inhibited potently the growth of KB and KBv200 cells, among which compound 6 displayed strong cytotoxicity with IC50 values of 3.17 and 3.21 μM to KB and KBv200 cells, respectively. Furthermore, we demonstrate that the mechanism involved in the apoptosis induced by compound 6 is probably related to mitochondrial dysfunction. Additionally, the structure-activity relationships of these compounds are discussed