Pegylated arginine deiminase synergistically increases the cytotoxicity of gemcitabine in human pancreatic cancer.

BackgroundPancreatic ductal adenocarcinoma has proven to be one of the most chemo-resistant among all solid organ malignancies. Several mechanisms of resistance have been described, though few reports of strategies to overcome this chemo-resistance have been successful in restoring sensitivity to the primary chemotherapy (gemcitabine) and enter the clinical treatment arena.MethodsWe examined the ability of cellular arginine depletion through treatment with PEG-ADI to alter in vitro and in vivo cytotoxicity of gemcitabine. The effect on levels of key regulators of gemcitabine efficacy (e.g. RRM2, hENT1, and dCK) were examined.ResultsCombination of PEG-ADI and gemcitabine substantially increases growth arrest, leading to increased tumor response in vivo. PEG-ADI is a strong inhibitor of the gemcitabine-induced overexpression of ribonucleotide reductase subunit M2 (RRM2) levels both in vivo and in vitro, which is associated with gemcitabine resistance. This mechanism is through the abrogation of the gemcitabine-mediated inhibitory effect on E2F-1 function, a transcriptional repressor of RRM2.ConclusionThe ability to alter gemcitabine resistance in a targeted manner by inducing metabolic stress holds great promise in the treatment of advanced pancreatic cancer

Resistance mechanisms of birch to bronze birch borer

Outbreaks of bronze birch borer, Agrilus anxius, a North American wood-boring beetle, have occurred periodically over the last 100 years, causing extensive tree mortality. Little is known about mechanisms underlying tree resistance to wood-boring insects, but previous studies have suggested that secondary metabolites and wound periderm (callus) tissue may play a role. North American birches (Betula spp.) are much more resistant to bronze birch borer than exotic species that lack a coevolutionary history. We compared patterns of constitutive phenolic chemistry and the rate of wound periderm formation in phloem tissues of North American paper birch (B. papyrifera) to exotic European white birch (B. pendula). Six phenolic compounds were in higher concentrations in phloem of paper birch than in European white birch and might be involved in resistance. There were no interspecific differences in rate of wound periderm formation

Professional Philosophy: Education is Dialogue

This paper reflects the author\u27s personal philoso- phy of education and is influenced extensively by the philosophies of Martin Buber and Paulo Freire. The author has chosen to use the lens of dialogue to focus on the nature of education and her role in it, her perspectives on her role as an educator, and her perspectives on student affairs educators as professionals

The Embassy of Everaard van Weede, Lord of Dykvelt, to England in 1687

The importance of the embassy of Everaard van Weede, Lord of Dykvelt, to England in 1687, has been variously estimated by the many historians of the Revolution of 1688. Bishop Burnet, who played an important role in all the counsels of William and acted as the spiritual minister to Mary, speaks intimately of the whole affair. He gives an account of the mission which purports to be as he had it from the envoy himself. In Burnet\u27s opinion the embassy may from one point of view be looked upon as a failure, for its ostensible objects were not attained. But Burnet believed that the real significance of the embassy was to be found in the management of instructions to the Parliamentary leaders and that from this point of view the embassy was more prosperous. A secret cabal, he says, fotmed under the direction of Dykvelt, concerted such advices and advertisements as might be fit for the prince to know, ... and upon these the prince governed all his motions. Burnet intimates that already at this time the Prince had in mind some change in the face of affairs as would amaze all the world. Avaux, the French ambassador at the Hague, suspicious, crafty, and vigilant, seems to have noted the whole project of William at this time. Yet, he confesses many months afterwards, when the enterprise was on the point of taking place, that he could never understand how Dykvelt and the others had been able to establish in England a sufficiently large commerce for fomenting an uprising of so many different people or how they had distributed money for this enterprise without the King of England discovering anything of it

Paradoxical Leadership: A Review of the Literature

This literature review examines a growing field of research on paradoxical leadership, the leadership style that stands against a pervasive culture of fear, aggression, and criticism and instead highlights other power- inducing characteristics. Specifically, the review summarizes material that supports the growing requirement for such fundamental characteristics as vulnerability, authenticity, heart, and love in today’s and tomorrow’s leaders

Interviewer Effects on Data Quality: Does Interviewer Experience Favor Completions Over Quality?

Interviewer experience has been identified as an important factor in achieving higher response rates for telephone interviews. The causal mechanisms underlying this relationship remain unclear (Couper and Groves 1992; Jackle, Lynn, Sinibaldi and Tipping 2013; West and Blom 2016), but extant research suggests a combination of experience and personality traits, skills and attitudes explain substantial variation in cooperation rates (Groves and Couper; Jackle et al 2013). West and Blom (2016) summarize the positive relationship between experience and response rates and call for work to identify additional mediators of these relationships. The relationship between experience and data quality is even less clear, with research results split between evidence of both positive and negative relationships (West and Blom 2016). While higher experience levels can lead to higher response rates, this investigation assesses the relationship between response rates and data quality; do more experienced interviewers gather higher numbers of unit responses but sacrifice higher data quality? This study examines interviewer experience in a computer-assisted telephone interview (CATI) setting. Specifically, we will examine the number of hours interviewers are actively engaged in dialing and speaking to respondents, interviewers’ response rates (the number of completed interviews divided by the hours worked) as well as data quality (item nonresponse in the form of number of refused responses or recorded responses of “Don’t Know” (DK) per completed interview). Initial exploratory analyses from 36 interviewers working on one statewide dual-frame telephone survey revealed a statistically significant correlation between the number of hours worked and our measurement of data quality. Interestingly, the direction of this correlation showed that as interviewer hours increase, so did the ratio of DK responses and refusals per completed survey (Pearson correlation = 0.38, p \u3c 0.05). Analysis of effects on data quality using a general linear model showed significant differences in data quality between five binned categories of interviewer hours (ranging from low to high). The adjusted R2 for the model was 0.531, indicating a high level of explanation for the variance seen in data quality. Similar analyses will be completed for 3 other dual-frame statewide telephone surveys to allow for replication of the findings across multiple interviewers and topics. Additional hierarchical multiple regression analyses will extend the scope of the study to include additional variables such as respondent demographic characteristics that could also influence data quality (the propensity for DKs and refusals) or interact with interviewer experience to impact data quality

Disability Support: Developing a Model of Empowerment

This paper seeks to identify current best practices in supporting students with disabilities at West Coast public institutions of higher education. The authors identify three exemplary models of best practice at a variety of institutions. The first examines disability identity development at the University of California, Berkeley, the second a recreational sports facility at Portland State Uni- versity, the third a clearinghouse model of adap- tive equipment for a group of Washington com- munity colleges. Using these three cases, a holistic model of best practices that supports students with disabilities is put forth for implementation at other institutions

Lessons Learned From a Research Data Management Pilot Course at an Academic Library

Setting and Objective: From January-March 2014, three librarians from the University of Washington (UW) taught a course in research data management as a pilot for the New England Collaborative Data Management Curriculum (NECDMC). The goals of the workshops were to a) pilot the NECDMC curriculum to see how effective it was as an out-of-the box solution for teaching research data management (RDM), and b) to gauge interest in an RDM class among certain UW student populations, and c) to teach UW’s first RDM workshop offered to non-librarians. Design and Methods: The NECDMC consists of 7 modules that can be taught independently or as a series. UW decided to teach all seven modules consecutively, as one-hour long weekly workshops. Each module included a lecture and activity or discussion. We taught at one location on upper campus, and live-streamed the lecture to another location in the Health Sciences Library. Each module was assessed at the end of the class. Results: Interest in a research data management class is high; however, retention for a non-credit, 7-week class is low. Individual assessments show that students thought the content was important and well-delivered. Conclusions: Based on registration, graduate students at UW in many disciplines are interested in learning research data management skills. A non-credit, 7-week class had low retention; another type of class structure might increase retention. The NECDMC curriculum is an excellent framework, but modification to individual modules are necessary to provide a thorough and localized curriculum specific to one institution