Red Rock: An Original Dramatic TV Series

The concept of my Capstone Project is a screenplay for an original, dramatic television series. The idea was conceived during the summer going into my senior year, as I examined the script I had just written for TRF 400: Dramatic Writing for Television, a class I took in spring 2009 with Tom Seeley. I had labored over the script for the second half of that semester, and Professor Seeley really liked the idea from the start, but ultimately I did not fare as well I wanted to in terms of the final grade. Thus, I decided that I would redraft the script and use further, more advanced copies of the script as my project. The one-hour drama I have created is about a construction company that operates around the greater Boston area. I have knowledge of that industry because it is what my father does for a living, and having worked with him on occasion, I can personally attest to the drama (and occasional comedy) that takes place in the office, on the job site, and everywhere in between. The major context of the work was to develop interesting characters, set a few story lines that would compel audiences to tune in, and write the dialogue in a way that kept the show engrossing. The timetable of creating the show was about eight weeks. The first few weeks involved setting characters and exact story lines, with the final five weeks or so concerned with actually writing the script, in weekly increments of about 10-20 pages, depending on the week. In terms of the processes used in creating the work, the bulk of the screenplay came from ideas I had about the construction business, what I thought would make a good story, and how I could translate those stories to the television medium. I spoke with my father about certain technicalities that needed to be addressed for my script, and I ran the stories by him to make sure they all made sense in terms of the business. I then talked to Professor Seeley about those stories, and he told me to go ahead with them. Once that was accomplished, I turned to a specialized software called Celtx, which is for writing screenplays and other dramatic works. I used Celtx to outline the story using an index card feature, and I also made character pages. I then used the software to write the script itself. As the script evolved over the course of the year with multiple rewrites, some characters had to be altered, dialogue changed drastically, and small parts of the story were either rearranged or cut out completely. It was a long process, but I am comfortable with the script I have at this juncture. I am proud of the work, and it has improved with each draft. My teachers in Newhouse have always told me that “writing is rewriting.” It sounds simple, but was difficult to grasp at first. I was proud of my initial draft, but taking a step back and examining the flaws, it was clear that my professors had always been correct. Having completed the Capstone process with this script, I can safely conclude that, yes indeed, writing is rewriting

Games and Activities Based on Grammatical Areas Which are Problems for the Intermediate ESL Student

This project consists of games and activities based on grammatical areas which are problems for the intermediate-level ESL student After polling ESL teachers, we selected three specific problem areas: (1) irregular past tense verbs (2) modal auxiliaries (3) verbs in the perfective For each grammatical area we have created a minimum of six games/activities, including at least one card game, one board game, one individualized activity, and one jazz chant. Every game and activity has been tested through actual use in at least one ESL classroom. Revisions have been made based on the results of this testing

Single-cell profiling of tuberculosis lung granulomas reveals functional lymphocyte signatures of bacterial control [preprint]

In humans and nonhuman primates, Mycobacterium tuberculosis lung infection yields a complex multicellular structure—the tuberculosis granuloma. All granulomas are not equivalent, however, even within the same host: in some, local immune activity promotes bacterial clearance, while in others, it allows persistence or outgrowth. Here, we used single-cell RNA-sequencing to define holistically cellular responses associated with control in cynomolgus macaques. Granulomas that facilitated bacterial killing contained significantly higher proportions of CD4+ and CD8+ T cells expressing hybrid Type1-Type17 immune responses or stem-like features and CD8-enriched T cells with specific cytotoxic functions; failure to control correlated with mast cell, plasma cell and fibroblast abundance. Co-registering these data with serial PET-CT imaging suggests that a degree of early immune control can be achieved through cytotoxic activity, but that more robust restriction only arises after the priming of specific adaptive immune responses, defining new targets for vaccination and treatment

Preparation of Single-Cell RNA-Seq Libraries for Next Generation Sequencing

For the past several decades, due to technical limitations, the field of transcriptomics has focused on population-level measurements that can mask significant differences between individual cells. With the advent of single-cell RNA-Seq, it is now possible to profile the responses of individual cells at unprecedented depth and thereby uncover, transcriptome-wide, the heterogeneity that exists within these populations. This unit describes a method that merges several important technologies to produce, in high-throughput, single-cell RNA-Seq libraries. Complementary DNA (cDNA) is made from full-length mRNA transcripts using a reverse transcriptase that has terminal transferase activity. This, when combined with a second “template-switch” primer, allows for cDNAs to be constructed that have two universal priming sequences. Following preamplification from these common sequences, Nextera XT is used to prepare a pool of 96 uniquely indexed samples ready for Illumina sequencing.National Institutes of Health (U.S.) (Centers of Excellence in Genomic Science 1P50HG006193-01)National Institutes of Health (U.S.) (Pioneer Award DP1OD003958-01)Broad Institute of MIT and HarvardHoward Hughes Medical InstituteKlarman Cell Observator

The Pine Needle, Winter 1948

Libraries and archives collect materials from different cultures and time periods to preserve and make available the historical record. As a result, materials such as those presented here may reflect sexist, misogynistic, abusive, racist, or discriminatory attitudes or actions that some may find disturbing, harmful, or difficult to view. Both a humor and literary magazine, The Pine Needle was a University of Maine student-produced periodical that began publication in the fall of 1946, the first post-World War II semester that saw GIs returning to campus. The Needle reflected an edginess and rebellion not found in previous UMaine student publications. While past student publications relied on euphemisms for alcohol and dating on campus, The Needle openly promoted the sexualization of co-eds and the use of drugs, tobacco, and alcohol by students who experienced war. The issue includes photographs of eight female UMaine students as pin-up girls wearing one and two-piece bathing suits. The women\u27s faces are obscured by round compositional shapes, and male readers are invited by the editorial staff to attempt to identify all eight. The contest winner was announced in the Easter 1949 issue as a fellow who: ...had a wealth of similar material to compare with what we had printed, for he is no mean picture taker himself. He has known the girls well through the last few years for he is the janitor at the Elms and at Balentine Hall. The unsigned cover illustration of this issue is an invisible woman, hands on hips, wearing bikini or French Bathing Suit, glasses, heels, and lipstick. The headline reads: Le numéro de la baigneus Française. The illustration sets the tone of the winter issue which lampoons bikinis, introduced in July 1946, and the women who wear them

Meniscus confined fabrication of multidimensional conducting polymer nanostructures with scanning electrochemical cell microscopy (SECCM)

Scanning electrochemical cell microscopy (SECCM) is demonstrated as a new approach for the construction of extended multi-dimensional conducting polymer (polyaniline) nanostructures, making use of a mobile dual-channel theta pipette cell to control and monitor the location, rate and extent of electropolymerisation

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli

Individual genetic variation affects gene expression in response to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness QTLs; reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant acts as an activator of the antiviral response; using RNAi, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli

The Pine Needle, March 1947

Libraries and archives collect materials from different cultures and time periods to preserve and make available the historical record. As a result, materials such as those presented here may reflect sexist, misogynistic, abusive, racist, or discriminatory attitudes or actions that some may find disturbing, harmful, or difficult to view. Both a humor and literary magazine, The Pine Needle was a University of Maine student-produced periodical that began publication in the fall of 1946, the first post-World War II semester that saw GIs returning to campus. The Needle reflected an edginess and rebellion not found in previous UMaine student publications. While past student publications relied on euphemisms for alcohol and dating on campus, The Needle overtly sexualized co-eds and discussed the use of drugs, tobacco, and alcohol by students who experienced war. Cover art for this issue depicts a pen-and-ink illustration by Lloyd Shapleigh (1924-2008), of barefoot man lounging under a tree, reading an issue of New Yorker magazine with a corked jug beside his right elbow. Lloyd P. Shapleigh, Jr. was born in Bangor, Maine, graduating from high school in 1942 before joining the Army Air Corps during World War II where he qualified as MOE 867-Pathfinder technician and served as a ground crew chief with the 458 Bomb Group (H), 2nd Air Division, 8th Air Force. After the war, Shapleigh used the G.I. Bill to earn Bachelor\u27s Degrees at the University of Maine and Rhode Island School of Design. Shapleigh eventually joined the industrial design team at Whirlpool where, in 1966, he conducted research testing the feasibility of household trash compaction. The trash compactor became the first new, major household appliance released by the Whirlpool corporation since before the war

Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response

Mycobacterium tuberculosis (Mtb) bacilli readily aggregate. We previously reported that Mtb aggregates lead to phagocyte death and subsequent efficient replication in the dead infected cells. Here, we examined the transcriptional response of human monocyte derived macrophages to phagocytosis of aggregated Mtb relative to phagocytosis of non-aggregated single or multiple bacilli. Infection with aggregated Mtb led to an early upregulation of pro-inflammatory associated genes and enhanced TNFα signaling via the NFκB pathway. These pathways were significantly more upregulated relative to infection with single or multiple non-aggregated bacilli per cell. Phagocytosis of aggregates led to a decreased phagosome acidification on a per bacillus basis and increased phagocyte cell death, which was not observed when Mtb aggregates were heat killed prior to phagocytosis. Mtb aggregates, observed in a granuloma from a patient, were found surrounding a lesion cavity. These observations suggest that TB aggregation may be a mechanism for pathogenesis. They raise the possibility that aggregated Mtb, if spread from individual to individual, could facilitate increased inflammation, Mtb growth, and macrophage cell death, potentially leading to active disease, cell necrosis, and additional cycles of transmission

Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

Mice engrafted with components of a human immune system have become widely-used models for studying aspects of human immunity and disease. However, a defined methodology to objectively measure and compare the quality of the human immune response in different models is lacking. Here, by taking advantage of the highly immunogenic live-attenuated yellow fever virus vaccine YFV-17D, we provide an in-depth comparison of immune responses in human vaccinees, conventional humanized mice, and second generation humanized mice. We demonstrate that selective expansion of human myeloid and natural killer cells promotes transcriptomic responses akin to those of human vaccinees. These enhanced transcriptomic profiles correlate with the development of an antigen-specific cellular and humoral response to YFV-17D. Altogether, our approach provides a robust scoring of the quality of the human immune response in humanized mice and highlights a rational path towards developing better pre-clinical models for studying the human immune response and disease.National Institute of General Medical Sciences (U.S.) (Award T32GM007753)Searle Scholars ProgramArnold and Mabel Beckman Foundation (Young Investigator Program)National Institutes of Health (U.S.) (1DP2OD020839)National Institutes of Health (U.S.) (5U24AI118672)National Institutes of Health (U.S.) (1U54CA217377)National Institutes of Health (U.S.) (1R33CA202820)National Institutes of Health (U.S.) (2U19AI089992)National Institutes of Health (U.S.) (21R01HL134539)National Institutes of Health (U.S.) (2RM1HG006193)National Institutes of Health (U.S.) (2R01HL095791)National Institutes of Health (U.S.) (P01AI039671)Bill & Melinda Gates Foundation (OPP1139972