36 research outputs found

    Knowledge Boundary and Persona Dynamic Shape A Better Social Media Agent

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    Constructing personalized and anthropomorphic agents holds significant importance in the simulation of social networks. However, there are still two key problems in existing works: the agent possesses world knowledge that does not belong to its personas, and it cannot eliminate the interference of diverse persona information on current actions, which reduces the personalization and anthropomorphism of the agent. To solve the above problems, we construct the social media agent based on personalized knowledge and dynamic persona information. For personalized knowledge, we add external knowledge sources and match them with the persona information of agents, thereby giving the agent personalized world knowledge. For dynamic persona information, we use current action information to internally retrieve the persona information of the agent, thereby reducing the interference of diverse persona information on the current action. To make the agent suitable for social media, we design five basic modules for it: persona, planning, action, memory and reflection. To provide an interaction and verification environment for the agent, we build a social media simulation sandbox. In the experimental verification, automatic and human evaluations demonstrated the effectiveness of the agent we constructed

    Massively Parallel Sequencing of a Chinese Family with DFNA9 Identified a Novel Missense Mutation in the LCCL Domain of COCH

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    DFNA9 is a late-onset, progressive, autosomal dominantly inherited sensorineural hearing loss with vestibular dysfunction, which is caused by mutations in the COCH (coagulation factor C homology) gene. In this study, we investigated a Chinese family segregating autosomal dominant nonsyndromic sensorineural hearing loss. We identified a missense mutation c.T275A p.V92D in the LCCL domain of COCH cosegregating with the disease and absent in 100 normal hearing controls. This mutation leads to substitution of the hydrophobic valine to an acidic amino acid aspartic acid. Our data enriched the mutation spectrum of DFNA9 and implied the importance for mutation screening of COCH in age related hearing loss with vestibular dysfunctions

    Transduction of Adeno-Associated Virus Vectors Targeting Hair Cells and Supporting Cells in the Neonatal Mouse Cochlea

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    Adeno-associated virus (AAV) is the preferred vector for gene therapy of hereditary deafness, and different viral serotypes, promoters and transduction pathways can influence the targeting of AAV to different types of cells and the expression levels of numerous exogenous genes. To determine the transduction and expression patterns of AAV with different serotypes or promoters in hair cells and supporting cells in the neonatal mouse cochlea, we examined the expression of enhanced green fluorescent protein (eGFP) for five different types of AAV vectors [serotypes 2, 9, and Anc80L65 with promoter cytomegalovirus (CMV)-beta-Globin and serotypes 2 and 9 with promoter chicken beta-actin (CBA)] in in vitro cochlear explant cultures and we tested the transduction of AAV2/2-CBA, AAV2/9-CBA, and AAV2/Anc80L65-CMV by in vivo microinjection into the scala media of the cochlea. We found that each AAV vector had its own transduction and expression characteristics in hair cells and supporting cells in different regions of the cochlea. There was a tonotopic gradient for the in vitro transduction of AAV2/2-CBA, AAV2/9-CBA, AAV2/2-CMV, and AAV2/9-CMV in outer hair cells (OHCs), with more OHCs expressing eGFP at the base of the cochlea than at the apex. AAV2/2-CBA in vitro and AAV2/Anc80L65-CMV in vivo induced more supporting cells expressing eGFP at the apex than in the base. We found that AAV vectors with different promoters had different expression efficacies in hair cells and supporting cells of the auditory epithelium. The CMV-beta-Globin promoter could drive the expression of the delivered construct more efficiently in hair cells, while the CBA promoter was more efficient in supporting cells. The in vitro and in vivo experiments both demonstrated that AAV2/Anc80L65-CMV was a very promising vector for gene therapy of deafness because of its high transduction rates in hair cells. These results might be useful for selecting the appropriate vectors for gene delivery into different types of inner ear cells and thus improving the effectiveness of gene therapy

    Temperature Management With Paracetamol in Acute Stroke Patients: Evidence From Randomized Controlled Trials

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    Whether or not paracetamol can improve functional outcomes in patients with acute stroke has been examined in several clinical trials. The inconsistent results of these trials have caused great controversy regarding the need for further studies. In the present meta-analysis, we have aimed to address this controversy. The main databases (Medline, Embase, and Cochrane Library) were searched for randomized controlled trials involving the use of paracetamol in acute stroke patients. Pooled relative risks (RRs) or mean differences (MDs) and 95% confidence intervals (CIs) were calculated using a random-effects model. A total of 1,836 patients were pooled from four phase II and two phase III trials. The use of paracetamol resulted in a significant reduction in body temperature after 24 h (MD, −0.21; 95% CI, −0.28 to −0.13; P < 0.001) and mortality rate after 7–14 days (RR, 0.62; 95% CI, 0.41–0.93; P = 0.02) when compared with the placebo group; however, no effect of paracetamol was observed in the modified Rankin Scale score (RR, 1.07; 95% CI, 0.91–1.27; P = 0.40) or Barthel Index score (RR, 0.98; 95% CI, 0.91–1.06; P = 0.63) at 30 or 90 days. No significant differences were observed with respect to serious adverse events between the paracetamol and the placebo groups (P > 0.05). Subgroup analyses were performed to detect the source of the heterogeneity, which showed that ischemic stroke, serious condition at baseline, and late time-to-treatment had adverse impacts on the effect of paracetamol post stroke. In conclusion, temperature management with paracetamol in acute stroke patients is safe. Although paracetamol reduced the mortality rate in the early stage of stroke, it did not appear to affect long-term mortality and functional recovery. It should be noted that this conclusion is based on the results from studies of poor quality. A large clinical trial with a focus on early treatment of patients with acute stroke is warranted

    Strength and Micromechanism Analysis of Microbial Solidified Sand with Carbon Fiber

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    Microbially induced calcite precipitation (MICP) is an effective and ecofriendly technology that utilizes the microbes-induced mineralization to improve foundation soils of the transportation infrastructure. The carbon fiber can be used along with the MICP in order to reduce the brittleness of microbial solidified soil. This paper investigated the strength of carbon fiber-reinforced sand with different mass fractions through a series of unconfined compression tests. The effect of fiber content on the solidification of carbon fiber-reinforced sand was quantitatively analyzed using calcium carbonate content test and penetration test. The microsolidification mechanism was investigated by micrographs from the optical and scanning electron microscope (SEM). The test results showed that unconfined compressive strength generally increased first and then decreased with the increase of the fiber content. The optimal fiber content in the silica and calcareous sand was 0.2% and 0.1%, respectively. The bulging deformation of the fiber-reinforced sand sample was gradually developed along with the fiber breakage during loading

    Permeability Prediction Model Modified on Kozeny-Carman for Building Foundation of Clay Soil

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    Clay soil is a common building foundation material, and its permeability is very important for the safety of foundation pits and the later settlement of buildings. However, the traditional Kozeny-Carman (K-C) equation shows serious discrepancies when predicting the permeability of clay in building foundation treatment. Therefore, solving the application of K-C equation in clay is a problem faced by the engineers and scholars. In this paper, the influence of clay mineralogy on pore structure and permeability is analyzed, and then the effective e (eeff) and effective SSA (Seff) are proposed. Based on the eeff and Seff, the permeability prediction model modified on Kozeny-Carman is built. Then, seepage experiments are conducted on two types of clay samples to test this prediction model; at the same time, the MIP combining freeze-drying methods are used to obtain the Seff and eeff. Through the discussion of the test results, three main conclusions are obtained: (1) there are invalid pores in clay due to the influence of clay mineral, this is the reason for which K-C equation is unsuitable for clay; (2) the eeff and Seff can reflect the structural state of clay during seepage; (3) the results of the permeability prediction model in this paper agree well with the test results, which indicates that this prediction model is applicable to clay. The research results of this paper are significant to solve the academic problem that K-C equation is not applicable to clay and significant to ensure the safety of building foundation pits in clay areas

    Massively Parallel Sequencing of a Chinese Family with DFNA9 Identified a Novel Missense Mutation in the LCCL Domain of COCH

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    DFNA9 is a late-onset, progressive, autosomal dominantly inherited sensorineural hearing loss with vestibular dysfunction, which is caused by mutations in the COCH (coagulation factor C homology) gene. In this study, we investigated a Chinese family segregating autosomal dominant nonsyndromic sensorineural hearing loss. We identified a missense mutation c.T275A p.V92D in the LCCL domain of COCH cosegregating with the disease and absent in 100 normal hearing controls. This mutation leads to substitution of the hydrophobic valine to an acidic amino acid aspartic acid. Our data enriched the mutation spectrum of DFNA9 and implied the importance for mutation screening of COCH in age related hearing loss with vestibular dysfunctions

    Evaluate the value of prolonging the duration of tiopronin for injection administration in preventing hepatotoxicity

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    Abstract As part of supportive therapy, prophylaxis with tiopronin for injection (TI) against common hepatotoxicity complications has often been used. However, methods to prevent hepatotoxicity have not been established. Therefore, our study was aimed to find out the relationship between the periods of TI prophylaxis and post-treatment hepatotoxicity, and evaluated the value of prolonging the duration of TI administration in preventing hepatotoxicity. Hepatotoxicity was detected through liver transaminases, bilirubin, alkaline phosphatase, and clinical features of liver insufficiency. Multivariable logistic regressions were conducted to examine the association of the periods of TI prophylaxis and post-treatment hepatotoxicity. Between January 2022 and March 2023, a total of 452 patients with gynecological cancer were enrolled in the study, of which 93 (20.58%) participants were post-treatment hepatotoxicity positive. TI with different prevention days were no significant difference among participants with or without post-treatment hepatotoxicity in crude model (P > 0.05). The P-value, the odds ratios (OR) and 95% confidence intervals (CI) of participants with TI prophylaxis for 1 day for post-treatment hepatotoxicity were 0.040, 3.534 (1.061–11.765) in fully adjusted model. Past history of hepatotoxicity is a confounding variable, and there was no significant difference for post-treatment hepatotoxicity when stratified by past history of hepatotoxicity (P > 0.05). The study indicate that the periods of TI prophylaxis is not associated with post-treatment hepatotoxicity, suggesting that prolonged the periods of TI prophylaxis might be an invalid method for the prevention of post-treatment hepatotoxicity
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