74 research outputs found

    Synchronous dynamic game on system observability considering one or two steps optimality

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    This paper studies a system security problem in the context of observability based on a two-party non-cooperative asynchronous dynamic game. A system is assumed to be secure if it is not observable. Both the defender and the attacker have means to modify dimension of the unobservable subspace, which is set as the value function. Utilizing tools from geometric control, we construct the best response set under one-step or two-step optimality to minimize or maximize the value function. We find that the best response sets under one-step optimality are not single-valued maps, resulting in a variety of game outcomes. In the dynamic game considering two-step optimality, definition and existence conditions of lock and oscillation game modes are given. Finally, the best response under two-step optimality and the Stackelberg game equilibrium are compared

    Linking ecosystem services and circuit theory to identify ecological security patterns

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    The rapid process of urbanization, accompanied by the sharp increase of urban population and expansion of artificial surface, has resulted in the loss of natural ecosystems and the degradation of ecosystem services. Identifying and protecting key places that have high importance for ecological sustainability are great challenges. Ecological security patterns are such an integrated approach to protecting regional ecological sustainability. In this study, taking Yunnan Province, China as a case study area, ecological sources were identified through ecosystem services, and circuit theory was used to model ecosystem processes in heterogeneous landscapes via calculating the ‘resistance’ or ‘current’, and thus to identify ecological corridors and key ecological nodes. The results showed that, ecological security patterns included 66 ecological sources, 186 ecological corridors, 24 pinch-points and 10 barriers. In details, the ecological sources were mainly distributed in the southwest and northwest of Yunnan Province, with the ecological corridors locating along the high mountains, and both ecological sources and corridors were mostly covered with forest land. Pinch-points covered by forest land and cultivated land, were distributed in the middle of Yunnan Province along the rivers. Approximately 75.9% nature reserves were located in the identified ecological sources, and the remainings were mainly distributed in eastern Yunnan Province with small area, showing the effectiveness in identifying ecological security patterns. Among 81 projects of low–slope hill development carried out in Yunnan Province, 46.9% showed potential human stress on regional ecological security. Based on ecosystem services and circuit theory, this study provides a new approach to identifying the spatial range of ecological corridors and the specific location of key nodes for effective ecological conservation and restoration

    Stratospheric PULSE–continental cold air outbreak coupling relationships: Interannual and interdecadal changes

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    Stratospheric processes and their role in weather and climate have attracted increasing interests. The correspondence between the occurrence of pulse-like, stronger stratospheric poleward warm airmass transport (PULSE) events and the continental-scale cold air outbreak (CAO) events in northern hemispheric winter is found to be unstable from year to year. This increases the difficulties in utilizing the more predictable stratospheric variability in the sub-seasonal forecasts of CAOs, which can cause cold hazards. Using the ERA5 reanalysis data covering 37 winters (November–March) in the period 1979–2015, this study categorizes the CAO events over mid-latitudes of Eurasia (CAO_EA) and those over North America (CAO_NA) into two groups: those coupled with and those decoupled with the PULSE events. The coupled CAOs are further categorized into events that are, respectively, lead-coupled and lag-coupled with PULSEs. The intensity and affected area of extremely cold temperatures tend to be larger during CAOs that are coupled with PULSEs, particularly during the CAO_NA events that are lag-coupled with PULSEs and the CAO_EA events that are lead-coupled with PULSEs. Remarkable interannual and interdecadal variations are observed in the percentage of CAOs that are coupled with PULSEs for each winter, which is an important reference for determining the window of opportunity for skillful sub-seasonal forecasts of CAO by using the stratospheric signals. At both interdecadal and interannual timescales, a warm phase of the El Niño–Southern Oscillation (ENSO) in winter is favorable for the higher lag-coupling rate of CAO_NA and the lead-coupling rate of CAO_EA, and vice versa. The ENSO signals related to the interdecadal changes of the CAO coupling rate in winter can be traced back to the previous winter, while an ENSO phase transition from the previous winter to the current winter is closely related to the interannual changes of the CAO coupling rate

    Observation study of using a small dose of rituximab treatment for thyroid-associated ophthalmopathy in seven Chinese patients: One pilot study

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    ObjectiveTo report the efficacy, long-term safety, and tolerability of using a small dose (125 mg/m2 weekly for 4 weeks) of rituximab to treat Chinese patients with thyroid-associated ophthalmopathy (TAO).MethodsSeven patients with active moderate-to-severe TAO were prospectively recruited in this study. A small dose of rituximab (125mg/m2 body surface area) was given weekly with a duration of four weeks. Thyroid function, thyrotropin receptor antibody (TRAb), B cell and T cell subsets, ophthalmological examination, magnetic resonance imaging derived parameters, and adverse reactions were recorded at each visit.ResultsSeven patients were followed for an average of 224 weeks. B-cell depletion was observed in all patients following rituximab infusion. The clinical activity score (CAS) decreased from 4.86 ± 0.69 to 3.00 ± 0.82 at 5 weeks after treatment (P = 0.033) and remained significantly lower than baseline values at the end of follow-up (P = 0.001). Compared to baseline values, significant decreases in exophthalmos of the right eye, the thickness of extraocular muscles with maximum signal intensity, and the highest signal intensity ratio (SIR) of extraocular muscle to ipsilateral temporal muscle values were observed at the last follow-up (all P < 0.05). Disease progressions or recurrences were not observed during follow-up. Only mild fatigue was observed after the first infusion as a side effect (n = 1).ConclusionSmall dose of rituximab may be a promising option with adequate safety, tolerability, and long-term efficacy for patients with active moderate-to-severe TAO

    Effects of Octenyl-Succinylated Chitosan—Whey Protein Isolated on Emulsion Properties, Astaxanthin Solubility, Stability, and Bioaccessibility

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    The synthesis of octenyl-succinylated chitosan with different degrees of substitution resulting from chemical modification of chitosan and controlled addition of octenyl succinic acid was investigated. The modified products were characterized using 1H NMR, FTIR, and XRD, and the degree of substitution was also determined. The properties of the modified chitosan oligosaccharide in solution were evaluated by surface tension and dye solubilization, finding that the molecules self-assembled when they are above the critical aggregation concentration. The two methods yielded consistent results, showing that the self-assembly was reduced with higher levels of substitution. The antimicrobial activity of the octanyl-succinylated chitosan oligosaccharide (OSA-COS) derivatives against Staphylococcus aureus, Escherichia coli, and Fusarium oxysporum f.sp cucumerinum was investigated by the Oxford cup method. While the acetylated COS derivatives were not significantly effective against either E coli or S. aureus, they showed significant antifungal activity toward F. oxysporum that was superior to that of COS. The modified product was found to form a stable emulsion when mixed with whey protein isolate. The emulsion formed by the highly substituted derivatives have a certain stability and loading efficiency, which can be used for the encapsulation and delivery of astaxanthin

    Safety and immunogenicity of a modified Omicron-adapted inactivated vaccine in healthy adults: a randomized, double-blind, active-controlled Phase III clinical trial

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    BackgroundUpdated vaccine strategies are needed to protect against new SARS-CoV-2 variants with increased immune escape. Here, information on the safety and immunogenicity of an inactivated Omicron-adapted vaccine is presented, as compared with CoronaVac.MethodsA randomized, double-blind, active-controlled, phase III clinical trial was conducted to compare a modified Omicron-adapted vaccine (Omicron vaccine) with the authorized prototype vaccine (CoronaVac®) as a booster dose. Healthy adults aged ≥18 years, who have previously received 2 or 3 doses of CoronaVac (2C or 3C cohort) at least 6 months before, were enrolled to get a booster dose of Omicron vaccine or CoronaVac in a ratio of 2:1 (2C/3C+1O/1C). Back-up serums after two initial doses of CoronaVac (2C+0) for adults aged 26-45 years were collected from a previous study. Immunogenicity and safety data at 28 days after vaccination were collected and analyzed. One of the primary objectives was to evaluate the superiority of immunogenicity of Omicron vaccine booster against Omicron BA.1, compared with CoronaVac booster against BA.1. Another objective was to evaluate the non-inferiority of immunogenicity of Omicron vaccine booster against BA.1, compared with two initial doses of CoronaVac against ancestral strain.ResultsBetween June 1st and July 21st, 2022, a total of 1,500 healthy adults were enrolled. Results show that all pre-specified superiority criteria for BA.1 neutralizing antibody were met. Specifically, within the 3C cohort (3C+1O vs. 3C+1C), the geometric mean titers’ (GMT) ratio and 95% confidence interval (CI) was 1.64 (1.42, 1.89), with the lower 95%CI ≥1; a GMT ratio of 1.84 (1.57, 2.16) was observed for 2C+1O versus 3C+1C. For seroconversion rate, the lower 95%CIs of differences between immuno-comparative groups (2/3C+1O vs. 3C+1C) were all above the superiority criterion 0%. However, the non-inferiority criterion of the lower 95%CI of GMT ratio ≥2/3 was unfulfilled for 2C/3C+1O against BA.1 versus 2C+0 against ancestral strain. Safety profiles were similar between groups, with no safety concerns identified.ConclusionThe Omicron-adapted vaccine was well-tolerated and could elicit superior immune responses as compared with CoronaVac against Omicron, while it appeared inferior to CoronaVac against ancestral strain.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT05381350?term=NCT05381350&draw=2&rank=1, identifier NCT05381350

    The prognostic value of high expression of FKBP1A in gastric cancer and the regulatory effect of targeted PI3K/AKT on glucose metabolism

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    Background and purpose: Gastric cancer is one of the common gastrointestinal malignancies. FKBP1A has been reported to be involved in the occurrence and development of various tumors, but the biological role and mechanism of it in gastric cancer remain unclear. This study aimed to investigate the expression level and prognostic value of FKBP1A in gastric cancer tissues, and to analyze the possible pathways and mechanisms of its regulation of gastric cancer progression. Methods: The expression of FKBP1A in gastric cancer was observed by immunohistochemistry, and its correlation with poor prognosis was analyzed by combining bioinformatics and clinicopathological parameters. Kaplan-Meier survival curve was used to analyze the effect of FKBP1A on the 5-year survival rate of patients with gastric cancer after surgery, and COX multivariate regression analysis was used to explore the independent prognostic factors affecting the 5-year survival rate of patients with gastric cancer after surgery. The diagnostic value of FKBP1A expression in patients with gastric cancer was analyzed using receiver operating characteristic (ROC) curve. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to enrich and analyze the biological function of FKBP1A and the possible signal pathways involved. We constructed the MGC803 cell model transfected with lentivirus in vitro, explored the influence of FKBP1A on the glucose metabolism and malignant biological behavior of MGC803 cells, and the possible molecular mechanism involved, and established a nude mouse transplantation tumor model in vitro to verify it. Results: Immunohistochemical results showed that FKBP1A was highly expressed in gastric cancer (P<0.01), and bioinformatics and clinical parameter analysis showed that FKBP1A was associated with poor prognosis. Kaplan-Meier survival analysis and COX regression analysis showed that the expression level of FKBP1A was negatively correlated with 5-year survival. And carcinoembryonic antigen (CEA)≥5 μg/L, carbohydrate antigen (CA) 19-9≥37 kU/L, T stage (T3-T4) and N stage (N2-N3) were independent prognostic factors affecting the 5-year survival rate of gastric cancer patients after surgery (P<0.05). ROC analysis showed that high expression of FKBP1A had good prognostic value (P<0.01). Enrichment of GO and KEGG suggested that FKBP1A was involved in regulating glucose metabolism in gastric cancer cells. In vitro experiments showed that overexpression of FKBP1A promoted glucose metabolism and proliferation, invasion and migration of MGC803 cells, while silencing of FKBP1A did the opposite (P<0.05). In vivo experiments showed that overexpression of FKBP1A in gastric cancer cells promoted the growth of transplanted tumor in nude mice, while silencing FKBP1A inhibited it (P<0.05). Mechanism analysis showed that overexpression of FKBP1A upregulated the expressions of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in gastric cancer cells, while silencing FKBP1A downregulated the expressions (P<0.05). Conclusion: FKBP1A is highly expressed in gastric cancer tissues, and is associated with poor prognosis, which may be due to the promotion of glucose metabolism and malignant biological behavior of gastric cancer cells by activating PI3K/AKT
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