A critical edition of John Pickering's Horestes

Thesis (M.A.)--Boston University, 1947The play under discussion has been classed by Tucker Brooke as a moral interlude which developed from the Morality Play of the fifteenth and sixteenth centuries. Although comic interludes were popular in the middle of the sixteenth century, tragedies and historical plays had also begun to make their appearance, and the Horestes was the first historical play with a classical source to appear on the English Stage. It was also the first play in England to use the revenge of a father theme which Kyd and Shakespeare used so successfully at the turn of the century. Other historical plays like Bishop Bayle's King John and Sackville and Norton's Gorboduc chose rather to us the native history of England as a basis for their drama

LSF small molecule inhibitors phenocopy LSF-targeted siRNAs causing mitotic defects and senescence in cancer cells

The oncogene LSF has been proposed as a novel target with therapeutic potential for multiple cancers. LSF overexpression correlates with poor prognosis for both liver and colorectal cancers, for which there are currently limited therapeutic treatment options. In particular, molecularly targeted therapies for hepatocellular carcinoma targeting cellular receptors and kinases have yielded disappointing clinical results, providing an urgency for targeting distinct mechanisms. LSF small molecule inhibitors, Factor Quinolinone Inhibitors (FQIs), have exhibited robust anti-tumor activity in multiple pre-clinical models of hepatocellular carcinoma, with no observable toxicity. To understand how the inhibitors impact cancer cell proliferation, we characterized the cellular phenotypes that result from loss of LSF activity. Phenotypically, inhibition of LSF activity induced a mitotic delay with condensed, but unaligned, chromosomes. This mitotic disruption resulted in improper cellular division leading to multiple outcomes: multi-nucleation, apoptosis, and cellular senescence. The cellular phenotypes observed upon FQI1 treatment were due specifically to the loss of LSF activity, as siRNA specifically targeting LSF produced nearly identical phenotypes. Taken together, these findings confirm that LSF is a promising therapeutic target for cancer treatment.First author draf

Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): evaluation using an endogenous HCC model

Hepatocellular carcinoma (HCC) is a lethal malignancy with high mortality and poor prognosis. Oncogenic transcription factor Late SV40 Factor (LSF) plays an important role in promoting HCC. A small molecule inhibitor of LSF, Factor Quinolinone Inhibitor 1 (FQI1), significantly inhibited human HCC xenografts in nude mice without harming normal cells. Here we evaluated the efficacy of FQI1 and another inhibitor, FQI2, in inhibiting endogenous hepatocarcinogenesis. HCC was induced in a transgenic mouse with hepatocyte-specific overexpression of c-myc (Alb/c-myc) by injecting N-nitrosodiethylamine (DEN) followed by FQI1 or FQI2 treatment after tumor development. LSF inhibitors markedly decreased tumor burden in Alb/c-myc mice with a corresponding decrease in proliferation and angiogenesis. Interestingly, in vitro treatment of human HCC cells with LSF inhibitors resulted in mitotic arrest with an accompanying increase in CyclinB1. Inhibition of CyclinB1 induction by Cycloheximide or CDK1 activity by Roscovitine significantly prevented FQI-induced mitotic arrest. A significant induction of apoptosis was also observed upon treatment with FQI. These effects of LSF inhibition, mitotic arrest and induction of apoptosis by FQI1s provide multiple avenues by which these inhibitors eliminate HCC cells. LSF inhibitors might be highly potent and effective therapeutics for HCC either alone or in combination with currently existing therapies.The present study was supported in part by grants from The James S. McDonnell Foundation, National Cancer Institute Grant R01 CA138540-01A1 (DS), National Institutes of Health Grant R01 CA134721 (PBF), the Samuel Waxman Cancer Research Foundation (SWCRF) (DS and PBF), National Institutes of Health Grants R01 GM078240 and P50 GM67041 (SES), the Johnson and Johnson Clinical Innovation Award (UH), and the Boston University Ignition Award (UH). JLSW was supported by Alnylam Pharmaceuticals, Inc. DS is the Harrison Endowed Scholar in Cancer Research and Blick scholar. PBF holds the Thelma Newmeyer Corman Chair in Cancer Research. The authors acknowledge Dr. Lauren E. Brown (Dept. Chemistry, Boston University) for the synthesis of FQI1 and FQI2, and Lucy Flynn (Dept. Biology, Boston University) for initially identifying G2/M effects caused by FQI1. (James S. McDonnell Foundation; R01 CA138540-01A1 - National Cancer Institute; R01 CA134721 - National Institutes of Health; R01 GM078240 - National Institutes of Health; P50 GM67041 - National Institutes of Health; Samuel Waxman Cancer Research Foundation (SWCRF); Johnson and Johnson Clinical Innovation Award; Boston University Ignition Award; Alnylam Pharmaceuticals, Inc.)Published versio

First record of epizootic ulcerative syndrome from the Upper Congo catchment: an outbreak in the Bangweulu swamps, Zambia

We report on the first outbreak of epizootic ulcerative syndrome (EUS) amongst wild fish populations in the Bangweulu swamps, an inland delta, in the north of Zambia during 2014. The area supports a large and diverse fish fauna related to, but distinct from, that of the Zambezi River system where EUS outbreaks have occurred since 2006. A sizeable artisanal fishery, based on extensive fish weirs, is sustained by the annual flooding of the swamps, and observations of the disease outbreak by fishermen were recorded. Signs typical of infection with Aphanomyces invadans were observed in a number of species. Clinical observations, histology and molecular diagnostic methods were used to confirm infection with A. invadans in two of the most commonly and severely affected species. Several features of the wetland may have contributed to the outbreak and the annual recurrence of the disease. Modes by which the disease may have been introduced into the swamps are discussed. The outbreak is of great significance as the Bangweulu swamps drain into the Congo River in neighbouring Democratic Republic of Congo, Africa's largest drainage system with an extensive and diverse fish fauna previously unaffected by EUS

Students Studying Students and Reasoning about Reasoning: A Qualitative Analysis

In this work, a faculty member takes a journey along with students as they enhance their understanding of how people solve mathematical problems through a mainly qualitative statistical project. Student authors of this paper registered for a problem solving seminar led by the faculty author, and then created and analyzed self-built assessment tools to explore problem solving techniques. Here we share our findings and recommendations, which we hope will inspire others to explore novel pedagogical techniques in the teaching of mathematical problem solving. We incorporate into our presentation ur voices, reflecting on how we and others solve problems

The importance of 1,5-oxygen-chalcogen interactions in enantioselective isochalcogenourea catalysis

Syngenta (Case Award to DJP) and a Philip Leverhulme Prize for funding (SLC, AE). RKM and PHW are grateful to the American Chemical Society Petroleum Research Fund and National Science Foundation (NSF-MRI: CHE-1429616).The importance of 1,5-O···chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch = O, S, Se) is investigated. Conformational analyses of N-acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5-O···Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram-scale synthesis of the most active selenium analogue was developed using a previously unreported seleno-Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density Functional Theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N-acylated intermediates.PostprintPeer reviewe

Prostate Intrafraction Translation Margins for Real-Time Monitoring and Correction Strategies

The purpose of this work is to determine appropriate radiation therapy beam margins to account for intrafraction prostate translations for use with real-time electromagnetic position monitoring and correction strategies. Motion was measured continuously in 35 patients over 1157 fractions at 5 institutions. This data was studied using van Herk's formula of (αΣ + γσ') for situations ranging from no electromagnetic guidance to automated real-time corrections. Without electromagnetic guidance, margins of over 10 mm are necessary to ensure 95% dosimetric coverage while automated electromagnetic guidance allows the margins necessary for intrafraction translations to be reduced to submillimeter levels. Factors such as prostate deformation and rotation, which are not included in this analysis, will become the dominant concerns as margins are reduced. Continuous electromagnetic monitoring and automated correction have the potential to reduce prostate margins to 2-3 mm, while ensuring that a higher percentage of patients (99% versus 90%) receive a greater percentage (99% versus 95%) of the prescription dose