Model-based analysis uncovers mutations altering autophagy selectivity in human cancer

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis

Robust supply chain design mechanisms: Applications to risk management, coordination, and multiple-modular design.

This thesis investigates three mechanisms to meet three challenges in designing a robust global supply chain. The first mechanism is using risk management tools to manage the challenge of the exchange rate risk brought by the accelerated integration of global economy. A dynamic finite-capacity model is suggested to study operational hedging and financial hedging of a Multi-national Risk-averse Newsvendor, who may produce and sell the product both at home and overseas. The optimal production and transshipment decisions and the optimal financial hedging decisions are fully characterized. Operational hedging is shown to be a more effective tool than financial hedging in most situations. The second mechanism is a restrictive strategy designed to improve coordination in a decentralized supply chain. The supply chain consists of one retailer and one supplier. The strategy enables the supplier to make significant cost reduction in inventory holding and backlogging and can bring significant savings to the cost of the whole supply chain in most situations. The third mechanism is use of a multiple-modular design to meet the challenge of achieving the product customization without sacrificing the economy of scale. A more reliable and fast algorithm is developed for some multiple-modular design problems.Ph.D.Applied SciencesIndustrial engineeringManagementSocial SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/125559/2/3192833.pd

Optimal Operational Versus Financial Hedging for a Risk-Averse Firm

revision for resubmission</p

Managing Capacitated Multiechelon Systems with Domain-Optimal Policies

under the 2nd review at Operations Research</p

A real-time parallel data acquisition and big data processing method for four-in-one optical fiber sensor network

We propose a real-time parallel data acquisition and big data processing method. This method can multiplex different types of fiber sensors and quickly complete the simultaneous sampling of thousands of sensors on hundreds of channels in four-parameter heterogeneous fiber sensor network, its sampling frequency is up to 6.4MHz, and the data throughput is up to 13.8MB/s. This method is three times faster than the usual method

Value of screening in procurement mechanism: An experimental study

Procurement mechanisms are widely employed and recommended for use in supply chain management practices. This study examines a retailer’s decision to design a separating mechanism (as opposed to pooling mechanism) which is applied when buying from a supplier whose production cost information is private. The retailer’s decision is based on the value of screening of the separating mechanism, as it allows the retailer to screen the supplier’s private cost information, whereas the pooling mechanism does not. We conducted a laboratory experiment to investigate the retailer’s decision-making behaviors, the supplier’s decision behaviors, and the value of screening. We found that the observed value of screening is negligible and significantly lower than predicted given a large market size; however, it is substantially higher than predicted given a medium market size. According to the behavioral model analysis, this effect is mainly caused by the supplier’s fairness concerns; the screening increases the supplier’s fairness concern when operating in a large market, but decreases it when operating in a medium sized market. The results imply that a retailer should use a separating mechanism if the screening reduces the supplier’s fairness concern; otherwise, a pooling mechanism suffices