972 research outputs found
A Sparse Graph-Structured Lasso Mixed Model for Genetic Association with Confounding Correction
While linear mixed model (LMM) has shown a competitive performance in
correcting spurious associations raised by population stratification, family
structures, and cryptic relatedness, more challenges are still to be addressed
regarding the complex structure of genotypic and phenotypic data. For example,
geneticists have discovered that some clusters of phenotypes are more
co-expressed than others. Hence, a joint analysis that can utilize such
relatedness information in a heterogeneous data set is crucial for genetic
modeling.
We proposed the sparse graph-structured linear mixed model (sGLMM) that can
incorporate the relatedness information from traits in a dataset with
confounding correction. Our method is capable of uncovering the genetic
associations of a large number of phenotypes together while considering the
relatedness of these phenotypes. Through extensive simulation experiments, we
show that the proposed model outperforms other existing approaches and can
model correlation from both population structure and shared signals. Further,
we validate the effectiveness of sGLMM in the real-world genomic dataset on two
different species from plants and humans. In Arabidopsis thaliana data, sGLMM
behaves better than all other baseline models for 63.4% traits. We also discuss
the potential causal genetic variation of Human Alzheimer's disease discovered
by our model and justify some of the most important genetic loci.Comment: Code available at https://github.com/YeWenting/sGLM
Study on “Chinese Cultural Aphasia” of Non-English Majors
Learning language is, as a matter of fact, a process of learning its culture. However, current college English language teaching focusses on Western culture, while Chinese culture is being neglected. Therefore, many college students cannot accurately express words or sentences about Chinese culture in English. The study found that more than half of the non-English majors have difficulty in expressing some words or sentences which connect with Chinese culture in English. The author presents some of the causes of this phenomenon and puts forward some relevant strategies to solve the “Chinese Cultural Aphasia”
Marketing strategy of organic agricultural products on e-commerce platforms
With the strong growth of China economy in the dozens of years, there has been increasing demand of products and services of high quality from Chinese consumers with rising salary and disposable income. Despite recent concerns of economy slowdown and softening currency, Chinese consumer confidence still keep upbeat and resilient with strong interest of shifting spending to premium segment. This trend is especially phenomenal when it comes to spending on agricultural products. Chinese consumers tend to choose products with clear and credible indication of Non-GMO and organic label. However, despite of strong demand, it has been a long existing challenge of insufficient supply of organic products in China agricultural market without a well-guarded and reliable system of quality assurance. With E-Commerce platform, a new advent of technology that bridges supply and demand of niche and emerging segment, more opportunities are exposed to both consumers and suppliers in increasing the outreach of organic agricultural products and consumers willing to pay extra. This study analyses pricing, branding and distribution strategy for organic agricultural products and devises a portfolio of integrative marketing strategies and tactics that is applicable in the new era of digital marketing, built from the case of JD.com, one of the largest B2C E-commerce platform in China
Impacts of Peer Response on the Cultivation of English Writing Ability
There are some common problems existing in the cultivation of university students’ English writing ability, such as college students’ low writing ability, the strong dependence of English writing, the lack of communication between teachers and students, the shortage of English teachers, and the longtime of teachers’ essay scoring. The effective reforms must be adopted in order to change the present cultivation situation of university students’ English writing ability. Peer response has several advantages in improving the cultivation models of English writing ability and can produce important impacts on the cultivation of university students’ English writing ability. The study explores the impacts from the assessment of English writing, improving students’ cognitive development, cultivating students’ critical thinking and stimulating students’ writing activity
Knowledge Sharing Mechanisms: Characteristics and Roles in Knowledge Sharing
Ph.DDOCTOR OF PHILOSOPH
AKT Inhibition Overcomes Rapamycin Resistance by Enhancing the Repressive Function of PRAS40 on mTORC1/4E-BP1 Axis
The mTORC1 inhibitors, rapamycin and its analogs, are known to show only modest antitumor activity in clinic, but the underlying mechanisms remain largely elusive. Here, we found that activated AKT signaling is associated with rapamycin resistance in breast and colon cancers by sustained phosphorylation of the translational repressor 4E-BP1. Treatment of tumor cells with rapamycin or the AKT inhibitor MK2206 showed a limited activity in inhibiting 4E-BP1 phosphorylation, cap-dependent translation, cell growth and motility. However, treatment with both drugs resulted in profound effects in vitro and in vivo. Mechanistic investigation demonstrated that the combination treatment was required to effectively inhibit PRAS40 phosphorylation on both Ser183 and Thr246 mediated by mTORC1 and AKT respectively, and with the combined treatment, dephosphorylated PRAS40 binding to the raptor/mTOR complex was enhanced, leading to dramatic repression of mTORC1-regulated 4E-BP1 phosphorylation and translation. Knockdown of PRAS40 or 4E-BP1 expression markedly reduced the dependence of tumor cells on AKT/mTORC1 signaling for translation and survival. Together, these findings reveal a critical role of PRAS40 as an integrator of mTORC1 and AKT signaling for 4E-BP1-mediated translational regulation of tumor cell growth and motility, and highlight PRAS40 phosphorylation as a potential biomarker to evaluate the therapeutic response to mTOR/AKT inhibitors
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