miR-221 Mediates Chemoresistance of Esophageal Adenocarcinoma by Direct Targeting of DKK2 Expression

Background:Chemoresistance is a main obstacle to effective esophageal cancer (EC) therapy. We hypothesize that altered expression of microRNAs (miRNAs) play a role in EC cancer progression and resistance to 5-fluorouracil (5-FU) based chemotherapeutic strategies.Methods:Four pairs of esophageal adenocarcinoma (EAC) cell lines and corresponding 5-FU resistant variants were established. The expression levels of miRNAs previously shown to be involved in the general regulation of stem cell pathways were analyzed by qRT-PCR. The effects of selected miRNAs on proliferation, apoptosis, and chemosensitivity were evaluated both in vitro and in vivo. We identified a particular miRNA and analyzed its putative target genes in 14 pairs of human EC tumor specimens with surrounding normal tissue by qRT-PCR as well as Wnt pathway associated genes by immunohistochemistry in another 45 EAC tumor samples.Results:MiR-221 was overexpressed in 5-FU resistant EC cell lines as well as in human EAC tissue. DKK2 was identified as a target gene for miR-221. Knockdown of miR-221 in 5-FU resistant cells resulted in reduced cell proliferation, increased apoptosis, restored chemosensitivity, and led to inactivation of the Wnt/-catenin pathway mediated by alteration in DKK2 expression. Moreover, miR-221 reduction resulted in alteration of EMT-associated genes such as E-cadherin and vimentin as well as significantly slower xenograft tumor growth in nude mice. RT2 profiler analysis identified a substantial dysregulation of 4 Wnt/-catenin signaling and chemoresistance target genes as a result of miR-221 modulation: CDH1, CD44, MYC, and ABCG2.Conclusion:MiR-221 controls 5-FU resistance of EC partly via modulation of Wnt/-catenin-EMT pathways by direct targeting of DKK2 expression. MiR-221 may serve as a prognostic marker and therapeutic target for patients with 5-FU resistant EAC

Relationship between resident workload and self-perceived learning on inpatient medicine wards: a longitudinal study

BACKGROUND: Despite recent residency workload and hour limitations, little research on the relationship between workload and learning has been done. We sought to define residents' perceptions of the optimal patient workload for learning, and to determine how certain variables contribute to those perceptions. Our hypothesis was that the relationship between perceived workload and learning has a maximum point (forming a parabolic curve): that either too many or too few patients results in sub-optimal learning. METHODS: Residents on inpatient services at two academic teaching hospitals reported their team and individual patient censuses, and rated their perception of their learning; the patient acuity; case variety; and how challenged they felt. To estimate maximum learning scores, linear regression models with quadratic terms were fit on learning score. RESULTS: Resident self-perceived learning correlated with higher acuity and greater heterogeneity of case variety. The equation of census versus learning score, adjusted for perception of acuity and case mix scores, showed a parabolic curve in some cases but not in others. CONCLUSION: These data suggest that perceived resident workload is complex, and impacted by additional variables including patient acuity and heterogeneity of case variety. Parabolic curves exist for interns with regard to overall census and for senior residents with regard to new admissions on long call days

Design and validation of an EB-PVD shadowed TBC thickness prediction model

This MQP group set out to modify an existing model for predicting thermal-barrier coating thickness on a flat plate. Sponsored by Pratt & Whitney, a leading aircraft engine manufacturer in East Hartford, Conn., we combined onsite experimental design with on-campus scientific analysis. The short-term goal of this project is to design and analyze a predictive model for shadowed-coating profiles. This will contribute greatly to WPI's joint venture with Pratt & Whitney to create a rules-based software program that can predict the coating thickness on any modeled shape

Improving the Leviton absolute optical encoder

As technology advances, the need for faster and more accurate position encoding devices increases. Currently, although not publicly available, the Leviton Absolute Optical Pattern Recognition Encoder prototype is the most accurate encoder available. The purpose of this project was to improve the design of this encoder so as to reduce board size, maximize hardware efficiency, provide video output for image alignment calibrations, and package the encoder as a stand alone device with industry standard serial I/O. Through a rigorous evaluation of a Leviton Absolute Optical Pattern Recognition Encoder prototype, a faster, more efficient model was designed

Worcester: a search for synergy

This project's main goal is to identify potential synergies among the diverse economic development visions in the City of Worcester. To accomplish this goal, three objectives were met. First, organizations with economic development visions were identified. Second, their agendas and visions were determined using semi-structured interviews and questionnaires. Third, areas of potential synergy were drawn out from the data. This report can be used for parties to coordinate their actions and provide ideas for new Worcester Community Project Center IQPs