98 research outputs found
Foreign Is Not Unfamiliar. A Translation Impact Study Involving Taiwan Subjects
The research discussed in this paper is the last of a trilogy investigating the impact of foreignized and domesticated translations on sampled readers. The two precursors had been conducted in two Chinese Mainland cities (Beijing and Guangzhou) and this last one was conducted in the Taiwanese city of Douliou. Therefore, comparisons can be made with the two precursors in the discussion of the research procedure and findings of the Taiwan project. The paper begins with a brief introduction of the background in which the Taiwan project was conceived and a brief profile of the subjects sampled for the project. Then there is a description of the research design, including the hypotheses and field work methodology. Four hypotheses were tested: a) the subjects would have distinguishable ideas about the two renditions; b) they would have a more intense feeling of exoticism when reading the foreignized rendition; c) their degree of sensing the rendition to be exotic or not would be correlated with their other socio-linguistic perceptions of that text; d) the findings of the present investigation would corroborate those obtained from the two precursors. The description of the research design is followed by a presentation of the data analysis conducted for the project together with a statement of the conventions adopted for reading the statistics. Based on the data analysis, interpretations are made in relation to the hypotheses.Le présent article fait état des travaux issus du troisième volet d’une recherche portant sur les effets de traductions « étrangéisées » ou naturalisées, qui ont été observés chez un échantillon de lecteurs. Les deux premiers volets de cette recherche avaient été menés dans deux villes de Chine continentale (Beijing et Guangzhou), tandis que le troisième volet a été réalisé à Douliou, à Taiwan. Il est ainsi possible de comparer les résultats à ceux qui ont été obtenus antérieurement. L’article introduit brièvement le contexte du projet mené à Taiwan ainsi qu’un bref profil des sujets participants. Le plan de l’étude est ensuite présenté, y compris les hypothèses et la méthodologie de collecte des données. Quatre hypothèses ont été testées : a) les sujets distinguent clairement les deux modes de traduction ; b) ils éprouvent davantage un sentiment d’exotisme à la lecture de la version étrangéisée ; c) leur opinion quant au caractère exotique ou non de la traduction est corrélée aux autres caractéristiques sociolinguistiques perçues pour le texte ; d) les résultats de la présente étude corroborent ceux qui ont été obtenus dans le cadre des deux premiers volets. La description du plan de l’étude est suivie de la présentation de l’analyse des données, laquelle est accompagnée des conventions nécessaires à l’interprétation des calculs statistiques. L’interprétation des résultats au regard des hypothèses avancées se fonde sur cette analyse
Strategies to reinvigorate exhausted CD8+ T cells in tumor microenvironment
CD8+ T cell exhaustion is a stable dysfunctional state driven by chronic antigen stimulation in the tumor microenvironment (TME). Differentiation of exhausted CD8+ T cells (CD8+ TEXs) is accompanied by extensive transcriptional, epigenetic and metabolic reprogramming. CD8+ TEXs are mainly characterized by impaired proliferative and cytotoxic capacity as well as the increased expression of multiple co-inhibitory receptors. Preclinical tumor studies and clinical cohorts have demonstrated that T cell exhaustion is firmly associated with poor clinical outcomes in a variety of cancers. More importantly, CD8+ TEXs are regarded as the main responder to immune checkpoint blockade (ICB). However, to date, a large number of cancer patients have failed to achieve durable responses after ICB. Therefore, improving CD8+ TEXs may be a breakthrough point to reverse the current dilemma of cancer immunotherapy and eliminate cancers. Strategies to reinvigorate CD8+ TEXs in TME mainly include ICB, transcription factor-based therapy, epigenetic therapy, metabolism-based therapy and cytokine therapy, which target on different aspects of exhaustion progression. Each of them has its advantages and application scope. In this review, we mainly focus on the major advances of current strategies to reinvigorate CD8+ TEXs in TME. We summarize their efficacy and mechanisms, identify the promising monotherapy and combined therapy and propose suggestions to enhance the treatment efficacy to significantly boost anti-tumor immunity and achieve better clinical outcomes
Review and prospect of coal rock hydraulic fracturing physical experimental research
Physical simulation of hydraulic fracturing is an approximate representation of fracture evolution and its dynamic process, which represents an important direction of fracture evolution research. Similarity theory is the theoretical basis of the transformation between field prototype and experimental model. Test equipment and similar materials are the material premise of physical simulation experiment. Monitoring and detection technology is the key part to evaluate the fracturing effect of hydraulic fracturing. This paper summarizes the development of similarity theory of hydraulic fracturing physical experiments, the evolution of experimental materials and devices, and the characteristics and application scope of common monitoring and detection methods from the above three aspects. The analysis shows that: the similarity criterion of hydraulic fracturing has been preliminarily formed, but it needs to be further modified according to the physical and mechanical properties of coal and rock. Numerical simulation method can be used to explore the influence degree of minor factors ignored in the derivation of similarity criterion, so as to improve the reliability and applicability of the empirical equation. In view of various physical and mechanical properties of coal and rock, many empirical formula equations of similar materials have been obtained at present, but a set of detailed experimental specification and a large number of experimental attempts are still needed to improve the repeatability of the experiments, so as to establish a more universal database of empirical equations of similar material matching. Fracturing devices are developing towards the direction of multi-field coupling with more simulation conditions, larger simulation scale and wider simulation range, and fracturing methods are gradually diversified with engineering applications. However, the accuracy of triaxial loading of fracturing devices needs to be further improved to ensure effective fracturing experiments under high stress conditions, and reduce the impact of experimental operations on the final results. Monitoring methods and detection technologies have their own advantages in evaluating the fracturing effect of hydraulic fracturing, and similar materials also have a significant impact on the effectiveness and accuracy of monitoring methods and detection technologies. How to rationally select and combine monitoring methods and detection technologies based on experiments is the key to meet the research needs of micro-structures
T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells
Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62LhighCD44low Sca-1+ T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells. © 2013 Li et al
Population pharmacokinetics of tigecycline in critically ill patients with severe infections
We sought to describe the population pharmacokinetics of tigecycline in critically ill patients and to determine optimized dosing regimens of tigecycline for different bacterial infections. This prospective study included 10 critically ill patients given a standard dose of tigecycline. Blood samples were collected during one dosing interval and were analyzed using validated chromatography. Population pharmacokinetics and Monte Carlo dosing simulations were undertaken using Pmetrics. Three target exposures, expressed as ratios of the 24-h area under the curve to MICs (AUC(0-24)/MIC), were evaluated (>= 17.9 for skin infections, >= 6.96 for intraabdominal infections, >= 4.5 for hospital-acquired pneumonia). The median age, total body weight, and body mass index (BMI) were 67 years, 69.1 kg, and 24.7 kg/m(2), respectively. A two-compartment linear model best described the time course of tigecycline concentrations. The parameter estimates (expressed as means +/- standard deviations [SD]) from the final model were as follows: clearance (CL), 7.50 +/- 1.11 liters/h; volume in the central compartment, 72.50 +/- 21.18 liters; rate constant for tigecycline distribution from the central to the peripheral compartment, 0.31 +/- 0.16 h(-1); and rate constant for tigecycline distribution from the peripheral to the central compartment, 0.29 +/- 0.30 h(-1). A larger BMI was associated with increased CL of tigecycline. Licensed doses were found to be sufficient for Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus for an AUC(0- 24)/MIC target of 4.5 or 6.96. For a therapeutic target of 17.9, an increased tigecycline dose is required, especially for patients with higher BMI. The dosing requirements of tigecycline differ with the indication, with pathogen susceptibility, and potentially with patient BMI
TIM-3 Expression Characterizes Regulatory T Cells in Tumor Tissues and Is Associated with Lung Cancer Progression
Background: T cell immunoglobulin-3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in immune tolerance. TIM-3 is upregulated in exhausted CD8 + T cells in both chronic infection and tumor. However, the nature of TIM-3 +CD4 + T cells in the tumor microenvironment is unclear. This study is to characterize TIM-3 expressing lymphocytes within human lung cancer tissues and establish clinical significance of TIM-3 expression in lung cancer progression. Methodology: A total of 51 human lung cancer tissue specimens were obtained from pathologically confirmed and newly diagnosed non-small cell lung cancer (NSCLC) patients. Leukocytes from tumor tissues, distal normal lung tissues, and peripheral blood mononuclear cells (PBMC) were analyzed for TIM-3 surface expression by flow cytometry. TIM-3 expression on tumor-infiltrating lymphocytes (TILs) was correlated with clinicopathological parameters. Conclusions: TIM-3 is highly upregulated on both CD4 + and CD8 + TILs from human lung cancer tissues but negligibly expressed on T cells from patients' peripheral blood. Frequencies of IFN-γ + cells were reduced in TIM-3 +CD8 + TILs compared to TIM-3 -CD8 + TILs. However, the level of TIM-3 expression on CD8 + TILs failed to associate with any clinical pathological parameter. Interestingly, we found that approximately 70% of TIM-3 +CD4 + TILs expressed FOXP3 and about 60% of FOXP3 + TILs were TIM-3 +. Importantly, TIM-3 expression on CD4 + T cells correlated with poor clinicopathological parameters of NSCLC such as nodal metastasis and advanced cancer stages. Our study reveals a new role of TIM-3 as an important immune regulator in the tumor microenvironment via its predominant expression in regulatory T cells. © 2012 Gao et al
Increased Levels of BAFF and APRIL Related to Human Active Pulmonary Tuberculosis
BACKGROUND: Despite great efforts to improve diagnosis and treatment, tuberculosis (TB) remains a major health problem worldwide, especially in developing countries. Lack of concrete immune markers is still the obstacle to properly evaluate active TB. Therefore, identification of more validated biomarkers and phenotypic signatures is imperative. In particular, T cell-related biomarkers are more significant. METHODOLOGY: To understand the nature of CD4(+) T cell-derived signatures involved in infection and disease development, we examined and analyzed whole genome expression profiles of purified CD4(+) T cells from healthy individuals (HD), two distinct populations with latent infection (with low or high IFN-Îł levels, LTB(L)/LTB(H)) and untreated TB patients. Following, we validated the expression profiles of genes in the peripheral CD4(+) T cells from each group and examined secretion levels of distinct cytokines in serum and pleural effusion. PRINCIPAL FINDINGS: Our bio-informatic analyses indicate that the two latent populations and clinical TB patients possess distinct CD4(+) T cell gene expression profiles. Furthermore, The mRNA and protein expression levels of B cell activating factor (BAFF), which belongs to the TNF family, and a proliferation-inducing ligand (APRIL) were markedly up-regulated at the disease stage. In particular, the dramatic enhancement of BAFF and APRIL in the pleural effusion of patients with tuberculosis pleurisy suggests that these proteins may present disease status. In addition, we found that the BAFF/APRIL system was closely related to the Th1 immune response. Our study delineates previously unreported roles of BAFF and APRIL in the development of tuberculosis, and these findings have implications for the diagnosis of the disease. Our study also identifies a number of transcriptional signatures in CD4(+) T cells that have the potential to be utilized as diagnostic and prognostic tools to combat the tuberculosis epidemic
MicroRNA-21 regulates prostaglandin E2 signaling pathway by targeting 15-hydroxyprostaglandin dehydrogenase in tongue squamous cell carcinoma
Enhancement of Green Tires Performance through Ultrasound-Assisted Mixing
Combined with the traditional internal mixing process, a custom-built ultrasonic generator was introduced in this study. The effect of ultrasonic parameters on the comprehensive performance of tread rubber formulations was investigated. Compared to the traditional mixing process without ultrasonic wave loading, the introduction of ultrasonic enhanced the dispersion and distribution of composite particles in the rubber matrix and improved the overall performance of rubber products. The devil’s triangle relationship among the rolling resistance, wet skid resistance, and abrasion resistance of tires was improved. When the wet skid resistance was slightly lost, the rolling resistance and wear rate were effectively reduced. This study provides new insights into a strategy for optimizing the mixing process of the traditional internal mixer, reducing vehicle emissions, extending the service life of tires, and promoting the development of green tires
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