302 research outputs found
The adoption intention of travel-related app: a framework integrating perceived characteristics of innovation and software quality
This thesis aims to analyze the views of customers who have great appetite for tourism
on the tourism application. According to the perception characteristics of technology
acceptance model, innovation diffusion theory and software quality model, the thesis sets up
the research model and puts forward the corresponding research hypothesis on the
combination of current research results.
In the manner of questionnaire design and collection and data processing, data analysis
and hypothesis verification will be conducted by the use of structural equation model. The
research result implies that application design attributes and application performance features
are key to promote the adoption of mobile travel application.
In addition, this research broadens our horizons on the accidental impact of application
attributes on adoption behavior through adding user gender as a variable to the model, and
increases an awesome theoretical basis for future research in this field.Esta tese tem como objetivo analisar as visões de potenciais turistas com grande interesse
por aplicações turÃsticas. De acordo com as caracterÃsticas de percepção do modelo de
aceitação de tecnologia, teoria da difusão da inovação e modelo de qualidade de software, a
tese estabelece o modelo de investigação e propõe hipóteses de investigação correspondentes,
sobre a combinação de resultados da pesquisa atual.
Uma vez realizado o desenho do questionário e feita a recolha e processamento de dados,
a análise de dados e a verificação de hipóteses foram conduzidas pelo uso do modelo de
equações estruturais. O resultado da pesquisa implica que os atributos de design do aplicativo
e os recursos de desempenho do aplicativo são fundamentais para promover a adoção do
aplicativo móvel de viagem.
Além disso, esta pesquisa amplia os horizontes sobre o impacto acidental de atributos de
aplicação no comportamento de adoção, adicionando o gênero do usuário como uma variável
ao modelo, e aumenta uma importante base teórica para pesquisas futuras neste campo
Ethanol inhibits LPS-induced signaling and modulates cytokine production in peritoneal macrophages in vivo in a model for binge drinking
<p>Abstract</p> <p>Background</p> <p>Previous reports indicate that ethanol, in a binge drinking model in mice, inhibits the production of pro-inflammatory cytokines in vivo. However, the inhibition of signaling through TLR4 has not been investigated in this experimental model in vivo. Considering evidence that signaling can be very different in vitro and in vivo, the present study was conducted to determine if effects of ethanol on TLR4 signaling reported for cells in culture or cells removed from ethanol treated mice and stimulated in culture also occur when ethanol treatment and TLR4 activation occur in vivo.</p> <p>Results</p> <p>Phosphorylated p38, ERK, and c-Jun (nuclear) were quantified with kits or by western blot using samples taken 15, 30, and 60 min after stimulation of peritoneal macrophages with lipopolysaccharide in vivo. Effects of ethanol were assessed by administering ethanol by gavage at 6 g/kg 30 min before administration of lipopolysaccharide (LPS). Cytokine concentrations in the samples of peritoneal lavage fluid and in serum were determined at 1, 2, and 6 hr after lipopolysaccharide administration. All of these data were used to measure the area under the concentration vs time curve, which provided an indication of the overall effects of ethanol in this system. Ethanol suppressed production of most pro-inflammatory cytokines to a similar degree as it inhibited key TLR4 signaling events. However, NF-κB (p65) translocation to the nucleus was not inhibited by ethanol. To determine if NF-κB composed of other subunits was inhibited, transgenic mice with a luciferase reporter were used. This revealed a reproducible inhibition of NF-κB activity, which is consistent with the observed inhibition of cytokines whose expression is known to be NF-κB dependent.</p> <p>Conclusion</p> <p>Overall, the effects of ethanol on signalling in vivo were similar to those reported for in vitro exposure to ethanol and/or lipopolysaccharide. However, inhibition of the activation of NF-κB was not detected as translocation of p65 to the nucleus but was detected using transgenic reporter mice. The observation that ethanol given 24 hr before dosing with LPS modulated production of some cytokines indicates a persistent effect which does not require continued presence of ethanol.</p
Global gene expression analysis reveals reduced abundance of putative microRNA targets in human prostate tumours
<p>Abstract</p> <p>Background</p> <p>Recently, microRNAs (miRNAs) have taken centre stage in the field of human molecular oncology. Several studies have shown that miRNA profiling analyses offer new possibilities in cancer classification, diagnosis and prognosis. However, the function of miRNAs that are dysregulated in tumours remains largely a mystery. Global analysis of miRNA-target gene expression has helped illuminate the role of miRNAs in developmental gene expression programs, but such an approach has not been reported in cancer transcriptomics.</p> <p>Results</p> <p>In this study, we globally analysed the expression patterns of miRNA target genes in prostate cancer by using several public microarray datasets. Intriguingly, we found that, in contrast to global mRNA transcript levels, putative miRNA targets showed a reduced abundance in prostate tumours relative to benign prostate tissue. Additionally, the down-regulation of these miRNA targets positively correlated with the number of types of miRNA target-sites in the 3' untranslated regions of these targets. Further investigation revealed that the globally low expression was mainly driven by the targets of 36 specific miRNAs that were reported to be up-regulated in prostate cancer by a miRNA expression profiling study. We also found that the transcript levels of miRNA targets were lower in androgen-independent prostate cancer than in androgen-dependent prostate cancer. Moreover, when the global analysis was extended to four other cancers, significant differences in transcript levels between miRNA targets and total mRNA backgrounds were found.</p> <p>Conclusion</p> <p>Global gene expression analysis, along with further investigation, suggests that miRNA targets have a significantly reduced transcript abundance in prostate cancer, when compared with the combined pool of all mRNAs. The abnormal expression pattern of miRNA targets in human cancer could be a common feature of the human cancer transcriptome. Our study may help to shed new light on the functional roles of miRNAs in cancer transcriptomics.</p
Transcriptomic Analysis of Peritoneal Cells in a Mouse Model of Sepsis: Confirmatory and Novel Results in Early and Late Sepsis.
Background
The events leading to sepsis start with an invasive infection of a primary organ of the body followed by an overwhelming systemic response. Intra-abdominal infections are the second most common cause of sepsis. Peritoneal fluid is the primary site of infection in these cases. A microarray-based approach was used to study the temporal changes in cells from the peritoneal cavity of septic mice and to identify potential biomarkers and therapeutic targets for this subset of sepsis patients. Results
We conducted microarray analysis of the peritoneal cells of mice infected with a non-pathogenic strain of Escherichia coli. Differentially expressed genes were identified at two early (1 h, 2 h) and one late time point (18 h). A multiplexed bead array analysis was used to confirm protein expression for several cytokines which showed differential expression at different time points based on the microarray data. Gene Ontology based hypothesis testing identified a positive bias of differentially expressed genes associated with cellular development and cell death at 2 h and 18 h respectively. Most differentially expressed genes common to all 3 time points had an immune response related function, consistent with the observation that a few bacteria are still present at 18 h. Conclusions
Transcriptional regulators like PLAGL2, EBF1, TCF7, KLF10 and SBNO2, previously not described in sepsis, are differentially expressed at early and late time points. Expression pattern for key biomarkers in this study is similar to that reported in human sepsis, indicating the suitability of this model for future studies of sepsis, and the observed differences in gene expression suggest species differences or differences in the response of blood leukocytes and peritoneal leukocytes
Lowering of Blood Lipid Levels with a Combination of Pitavastatin and Ezetimibe in Patients with Coronary Heart Disease: A Meta-Analysis
Objectives: According to the findings of randomized controlled trials, blood lipid levels in patients with coronary heart disease (CHD) can be significantly decreased through a combination of pitavastatin and ezetimibe; however, the effects and clinical applications of this treatment remain controversial. This meta-analysis was aimed at objectively assessing the efficacy and safety of pitavastatin and ezetimibe in lowering blood lipid levels.Design: Relevant studies were retrieved from electronic databases, including PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP, and WanFang Data, from database inception to June 8, 2022. The levels of low-density lipoprotein cholesterol, total cholesterol, triglycerides, and high-density lipoprotein cholesterol in patients’ serum after treatment were the primary endpoint.Results: Nine randomized controlled trials (2586 patients) met the inclusion criteria. The meta-analysis indicated that pitavastatin plus ezetimibe resulted in significantly lower levels of LDL-C [standardized mean difference (SMD)=−0.86, 95% confidence interval (CI) (−1.15 to −0.58), P<0.01], TC [SMD=−0.84, 95% CI (−1.10 to −0.59), P<0.01], and TG [SMD=−0.59, 95% CI (−0.89 to −0.28), P<0.01] than pitavastatin alone.Conclusions: Pitavastatin plus ezetimibe significantly decreased serum LDL-C, TC, and TG levels in patients with CHD
A TonB-dependent receptor regulates antifungal HSAF biosynthesis in \u3ci\u3eLysobacter\u3c/i\u3e
Lysobacter species are Gram-negative bacteria that are emerging as new sources of antibiotics, including HSAF (Heat Stable Antifungal Factor), which was identified from L. enzymogenes with a new mode of action. LesR, a LuxR solo, was recently shown to regulate the HSAF biosynthesis via an unidentified mechanism in L. enzymogenes OH11. Here, we used a comparative proteomic approach to identify the LesR targets and found that LesR influenced the expression of 33 proteins belonging to 10 functional groups, with 9 proteins belonging to the TBDR (TonB-Dependent Receptor) family. The fundamental role of bacterial TBDR in nutrient uptake motivates us to explore their potential regulation on HSAF biosynthesis which is also modulated by nutrient condition. Six out of 9 TBDR coding genes were individually in-frame deleted. Phenotypic and gene-expression assays showed that TBDR7, whose level was lower in a strain overexpressing lesR, was involved in regulating HSAF yield. TBDR7 was not involved in the growth, but played a vital role in transcribing the key HSAF biosynthetic gene. Taken together, the current lesR-based proteomic study provides the first report that TBDR7 plays a key role in regulating antibiotic (HSAF) biosynthesis, a function which has never been found for TBDRs in bacteria.
Includes Supplementary materials
Uncovering the Genetic Link between Acute Myocardial Infarction and Ulcerative Colitis Co-Morbidity through a Systems Biology Approach
Background: Cardiovascular diseases, particularly acute myocardial infarction, are the leading cause of disability and death. Atherosclerosis, the pathological basis of AMI, can be accelerated by chronic inflammation. Ulcerative colitis (UC), a chronic inflammatory disease associated with immunity, contributes to the risk of AMI development. However, controversy continues to surround the relationship between these two diseases. The present study unravels the pathogenesis of AMI and UC, to provide a new perspective on the clinical management of patients with these comorbidities. Methods: Microarray datasets GSE66360 and GSE87473 were downloaded from the Gene Expression Omnibus database. Common differentially expressed genes (co-DEGs) between AMI and UC were identified, and the following analyses were performed: enrichment analysis, protein-protein interaction network construction, hub gene identification and co-expression analysis. Results: A total of 267 co-DEGs (233 upregulated and 34 downregulated) were screened for further analysis. GO enrichment analysis suggested important roles of chemokines and cytokines in AMI and UC. In addition, the lipopolysaccharide-mediated signaling pathway was found to be closely associated with both diseases. KEGG enrichment analysis revealed that lipid and atherosclerosis, NF-κB, TNF and IL-17 signaling pathways are the core mechanisms involved in the progression of both diseases. Finally, 11 hub genes were identified with cytoHubba: TNF, IL1B, TLR2, CXCL8, STAT3, MMP9, ITGAX, CCL4, CSF1R, ICAM1 and CXCL1. Conclusion: This study reveals a co-pathogenesis mechanism of AMI and UC regulated by specific hub genes, thus providing ideas for further mechanistic studies, and new perspectives on the clinical management of patients with these comorbidities
Research on blank optimization design based on low-carbon and low-cost blank process route optimization model
The optimization of blank design is the key to the implementation of a green innovation strategy. The process of blank design determines more than 80% of resource consumption and environmental emissions during the blank processing. Unfortunately, the traditional blank design method based on function and quality is not suitable for today’s sustainable development concept. In order to solve this problem, a research method of blank design optimization based on a low-carbon and low-cost process route optimization is proposed. Aiming at the processing characteristics of complex box type blank parts, the concept of the workstep element is proposed to represent the characteristics of machining parts, a low-carbon and low-cost multi-objective optimization model is established, and relevant constraints are set up. In addition, an intelligent generation algorithm of a working step chain is proposed, and combined with a particle swarm optimization algorithm to solve the optimization model. Finally, the feasibility and practicability of the method are verified by taking the processing of the blank of an emulsion box as an example. The data comparison shows that the comprehensive performance of the low-carbon and low-cost multi-objective optimization is the best, which meets the requirements of low-carbon processing, low-cost, and sustainable production
ACGT: advancing clinico-genomic trials on cancer - four years of experience.
The challenges regarding seamless integration of distributed, heterogeneous and multilevel data arising in the context of contemporary, post-genomic clinical trials cannot be effectively addressed with current methodologies. An urgent need exists to access data in a uniform manner, to share information among different clinical and research centers, and to store data in secure repositories assuring the privacy of patients. Advancing Clinico-Genomic Trials (ACGT) was a European Commission funded Integrated Project that aimed at providing tools and methods to enhance the efficiency of clinical trials in the -omics era. The project, now completed after four years of work, involved the development of both a set of methodological approaches as well as tools and services and its testing in the context of real-world clinico-genomic scenarios. This paper describes the main experiences using the ACGT platform and its tools within one such scenario and highlights the very promising results obtained
A Case Study of Processes Impacting Precipitation Phase and Intensity during the Vancouver 2010 Winter Olympics
Accurate forecasting of precipitation phase and intensity was critical information for many of the Olympic venue managers during the Vancouver 2010 Olympic and Paralympic Winter Games. Precipitation forecasting was complicated because of the complex terrain and warm coastal weather conditions in the Whistler area of British Columbia, Canada. The goal of this study is to analyze the processes impacting precipitation phase and intensity during a winter weather storm associated with rain and snow over complex terrain. The storm occurred during the second day of the Olympics when the downhill ski event was scheduled. At 0000 UTC 14 February, 2 h after the onset of precipitation, a rapid cooling was observed at the surface instrumentation sites. Precipitation was reported for 8 h, which coincided with the creation of a nearly 0°C isothermal layer, as well as a shift of the valley flow from up valley to down valley. Widespread snow was reported on Whistler Mountain with periods of rain at the mountain base despite the expectation derived from synoptic-scale models (15-km grid spacing) that the strong warm advection would maintain temperatures above freezing. Various model predictions are compared with observations, and the processes influencing the temperature, wind, and precipitation types are discussed. Overall, this case study provided a well-observed scenario of winter storms associated with rain and snow over complex terrain
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