SEMIPARAMETRIC AND NONPARAMETRIC ANALYSIS FOR LONGITUDINAL DATA ON THE RELATIONSHIP BETWEEN CHILDHOOD EXTERNALIZING BEHAVIOR AND BODY MASS INDEX

This thesis is an extension of the longitudinal data analysis of the association between externalizing behavior in early childhood and body mass index (BMI) from age 2 to 12 years conducted in Anderson et al. (2010). Externalizing behaviors problems are characterized by aggressive, oppositional, disruptive, or inattentive behaviors beyond those that would be expected given a child's age and development. The aim of the thesis is to estimate the children's BMI trajectory and to evaluate to what extent the externalizing behavior is related to BMI using semiparametric and nonparametric time-varying coefficient models. Some valuable insights into how the externalizing behavior and BMI are associated will be provided. </italic

Systemic chemotherapy promotes HIF‐1α‐mediated glycolysis and IL‐17F pathways in cutaneous T‐cell lymphoma

BackgroundSystemic chemotherapy is often the last resort of advanced cutaneous T‐cell lymphoma (CTCL). Tumor recurrence and adverse effects of systemic chemotherapy are the main limitations.ObjectiveWe aim to investigate the metabolic alterations in tumor cells after CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) chemotherapy.Methods and ResultsIn advanced CTCL, CHOP chemotherapy has no survival benefit and the duration of response is significantly inferior to other canonical treatments. HIF‐1α is significantly elevated in lesions of advanced MF patients as well as tumor cell line Hut78 and tumor xenograft mice model. CHOP therapy also increased glycolytic activities in a HIF‐1α‐dependent manner. In CTCL xenograft tumor mice model, lesional cells showed a significant increase in IL‐17F after chemotherapy, shifting toward a Th17 phenotype, which process is also regulated by HIF‐1α. Echinomycin, HIF‐1α inhibitor, was co‐administered in xenograft tumor mouse models with CHOP and showed a significant reduction in tumor growth.ConclusionCHOP chemotherapy promotes glycolysis and IL‐17 pathways in a HIF‐1α‐dependent fashion. Furthermore, HIF‐1α blockade is promising as an accompanying agent in systemic chemotherapy for patients with advanced CTCL.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163433/2/exd14133.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163433/1/exd14133_am.pd

Prognostic implication of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma: a tissue microarray study

<p>Abstract</p> <p>Background</p> <p>p27^Kip1plays a major role as a negative regulator of the cell cycle. The regulation of p27^Kip1degradation is mediated by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. However, little is known regarding the prognostic utility of p27^Kip1, Skp2 and Cks1 expression in renal cell carcinoma.</p> <p>Methods</p> <p>Immunohistochemistry was performed for p27^Kip1, Skp2 and Cks1 in tissue microarrays of 482 renal cell carcinomas with follow-up. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance.</p> <p>Results</p> <p>Immunoreactivity of p27^Kip1, Skp2 and Cks1 was noted in 357, 71 and 82 patients, respectively. Skp2 and Cks1 expression were not noted in chromophobe cancers. A strong correlation was found between Skp2 and Cks1 expression (P < 0.001), both of which were inversely related to p27^Kip1levels (P = 0.006 and P < 0.001), especially in primary and clear-cell cancers. Low p27^Kip1expression and Skp2 expression were correlated with larger tumor size and higher stage, as well as tumor necrosis. Cks1 expression was only correlated with tumor size. In univariate analysis, low p27^Kip1expression, Skp2 and Cks1 expression were all associated with a poor prognosis, while in multivariate analysis, only low p27^Kip1expression were independent prognostic factors for both cancer specific survival and recurrence-free survival in patients with RCC.</p> <p>Conclusion</p> <p>Our results suggest that immunohistochemical expression levels of p27^Kip1, Skp2 and Cks1 may serve as markers with prognostic value in renal cell carcinoma.</p

Technology Review System of Water-Temperature Prediction for Reservoir Construction Project

AbstractIt is the important technical support for technology appraisal to establish technology review system of water-temperature prediction for reservoir construction project. In this study, the technical route, implementation method and process, the required basic data, and key issues were proposed for the water-temperature technology review. The realization of water-temperature technology review can provide technical guarantee for regulating the technical requirements on water temperature prediction in environment impact assessment (EIA) report. Technology review can also prevent arbitrariness in some EIA reports. Moreover technology review could resolve some experts doubts on the prediction result during the process of technology appraisal

Suppressing the MLK3 promotes glutamine metabolism: mechanism and implications in progression of colon cancer

This study was designed to explore the potential role of mixed-lineage protein kinase 3 (MLK3) in colorectal cancer (CRC) progression and its relationship with glutamine metabolism. The immunohistochemical staining results of MLK3 were primarily collected through 100 CRC patients. Wound healing and transwell assays were used to detect migration ability of CRC cells by transfecting cells with siMlk3. Gene set variation analysis (GSVA) and Spearman’s rank correlation coefficient were used as bioinformatics tools to explore the signaling pathways related to MLK3. Western blotting was performed to analyze the downstream of glutamine metabolism. The results suggested an increased expression of MLK3 in CRC tissues, which was related to adverse clinicopathological characteristics in those CRC patients. Knockdown of MLK3 inhibited the proliferative and migratory potential of CRCs. Bioinformatics analysis confirmed the relationship between MLK3 expression and cancer malignancy related signaling pathways. CRC cell lines transfected with siMlk3 suppressed glutamine metabolism by downregulating the glutamine transporter alanine-serine-cysteine transporter 2 (ASCT2). These results suggested the vital role of MLK3 in CRC progression, which may be related to the suppression of glutamine transporter, namely alanine, serine, cysteine transporter 2 (ASCT2)