Three Essays on Dynamic Production and Pricing Decisions for New Products.

This dissertation focuses on dynamic production and pricing issues related to new products. The first essay is focused on the dynamic pricing issue for new product diffusion process when capacity is limited, the second essay is focused on the production lot sizing decisions for a pharmaceutical firm that manufactures new medicines for clinical trial, and the third essay deals with outsourcing decisions when firms manufacture a new product and production costs can be reduced through "learning-by-doing" effect. The first essay studies the dynamic production, pricing and sales decisions for new products with capacity constraint using control-theory framework. I show that in most of the cases, the optimal trajectory of demand is unimodal, as in the Bass model, but the optimal price trajectory can have multiple local maxima when capacity is limited. I also explore when pricing flexibility is most valuable using a numerical study. I find that benefits are highest when capacity is not unlimited nor very little, and when imitation effect dominates innovation effect. I also find that the capability to adjust prices is significantly more effective than the option of producing in advance and holding inventory. The second essay is focused on the lot sizing decisions with random yield, rigid demand and significant delay costs in pharmaceutical industry. I model this problem as a lot sizing decision with random yield and rigid demand in an M/G/1 queue environment. I show that the optimal production quantities are increasing in the number of waiting orders and the remaining quantity to be produced for the current lot. The third essay deals with an outsourcing problem where both Manufacturer and his Supplier may improve their operations and decrease production costs. Such cost reductions, however, require costly effort and are only possible when experimenting with actual production methods. While various reasons have been provided for dual sourcing, I provide a new explanation, which is driven by the fact that in-house production may facilitate learning about potential process improvements leading to eventual cost reductions.Ph.D.Business AdministrationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/61744/1/wenjings_1.pd

Yi-Zhi-Fang-Dai Formula Protects against A β

Yi-Zhi-Fang-Dai formula (YZFDF) is an experiential prescription used to cure dementia cases like Alzheimer’s disease (AD). In this study, the main effective compounds of YZFDF have been identified from this formula, and the neuroprotective effect against Aβ1–42 oligomer of YZFDF has been tested in SH-SY5Y cells. Our results showed that YZFDF could increase cell viability and could attenuate endothelial reticula- (ER-) mediated apoptosis. Evidence indicated that protein folding and endothelial reticula stress (ERS) played an important role in the AD pathological mechanism. We further explored the expression of Hsp70, an important molecular chaperon facilitating the folding of other proteins, and Grp78, the marker protein of ERS in SH-SY5Y cells. Data told us that YZFDF pretreatment could influence the mRNA and protein expression of these two proteins. At last, we also found that YZFDF pretreatment could activate Akt in SH-SY5Y cells. All these above indicate that YZFDF could be a potent therapeutic candidate for AD treatment

Consensus of Fractional-Order Multiagent Systems with Double Integrator under Switching Topologies

Due to the complexity of the practical environments, many systems can only be described with the fractional-order dynamics. In this paper, the consensus of fractional-order multiagent systems with double integrator under switching topologies is investigated. By applying Mittag-Leffler function, Laplace transform, and dwell time technique, a sufficient condition on consensus is obtained. Finally, a numerical simulation is presented to illustrate the effectiveness of the theoretical result

Novel PAX9 compound heterozygous variants in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9 variants

Studies have reported that >91.9% of non-syndromic tooth agenesis cases are caused by seven pathogenic genes. Objective: To report novel heterozygous PAX9 variants in a Chinese family with non-syndromic oligodontia and summarize the reported genotype-phenotype relationship of PAX9 variants. Methodology: We recruited 28 patients with non-syndromic oligodontia who were admitted to the Hospital of Stomatology Hebei Medical University (China) from 2018 to 2021. Peripheral blood was collected from the probands and their core family members for whole-exome sequencing (WES) and variants were verified by Sanger sequencing. Bioinformatics tools were used to predict the pathogenicity of the variants. SWISS-MODEL homology modeling was used to analyze the three-dimensional structural changes of variant proteins. We also analyzed the genotype-phenotype relationships of PAX9 variants. Results: We identified novel compound heterozygous PAX9 variants (reference sequence NM_001372076.1) in a Chinese family with non-syndromic oligodontia: a new missense variant c.1010C>A (p.T337K) in exon 4 and a new frameshift variant c.330_331insGT (p.D113Afs*9) in exon 2, which was identified as the pathogenic variant in this family. This discovery expands the known variant spectrum of PAX9; then, we summarized the phenotypes of non-syndromic oligodontia with PAX9 variants. Conclusion: We found that PAX9 variants commonly lead to loss of the second molars