Unspoken Connections: How I Learned to Love Punctuation

There’s a secret about punctuation that most English teachers don’t tell you: beyond “rules” and correctness, there’s a power and beauty to those little symbols that we find ourselves placing between and around the words place on the page or computer screen. Rather than thinking about punctuation marks as necessary and therefore tedious— perhaps even unwelcome— we can learn to love their curves and points and use them with purpose, creativity, and yes, even affection. With the help of some of the best poets and prose readers, Professor Amy Nawrocki shows how various marks (parentheses, dashes, semicolons and commas) can inspire and delight, open us to the possibilities of a deep and enduring love of language and all its decorations

A Memoir of No Memory: Rethinking Self Analysis and Navigating Medical Narratives

Faculty Research Day 2018: Faculty Competitive Poster WinnerMy sabbatical project explores the themes of health, wellness, identity, and creative voice. In a series of essays, I am investigating and writing about life events—both traumatic and ordinary—and their effects on memory, personal psychology, and the choices I make as a writer. The first of these essays describes and analyzes an illness I endured in 1992. I spent over three months in a "prolonged coma," and an additional six months in rehabilitation. This research project brought me back into that world of hospitals, tests, diagnoses, and jargon. Having no concrete recollection of those summer months, I began with one central question: How can I write a memoir about something I can’t remember? My explorations became the focus of The Comet's Tail: A Memoir of No Memory (Homebound Publications, 2018). The challenges of subjectivity forced me to question my duty as a memoirist and whether impartiality is ever really possible. I had to piece together three threads—journal entries written before I got sick, medical notes transcribed at the time, and emerging memories after the event. Examining these various accounts forced me to confront new questions of perspective and documentation. How much was true record and how much was inaccurate recollection of witnesses or imaginative invention? How is memory formed, and what is the role of trauma in our ability to reconstruct and understand the past

UB Knightlines Summer/Fall 2012

The UB Knightlines newsletter for Summer/Fall 2012. This issue contains articles discussing UB's 102nd commencement, graduates of the class of 2012, SASD students helping revamp the Bridgeport Public Library, health professionals using UB's new anatomy lab, UB's naturopathic-university herbarium, UB faculty summer reading lists, industrial design students gaining on the job experience, UB engineering outreach to local students with bridge building, UB MBA students with the Connecticut Stock Market Challenge, UB professors encouraging girls interest in STEM, a SASD alum winning UB's Lifetime Achievement Award, UB's first student to be admitted to UConn's School of Pharmacy, two International College students winning U.S. State Department Critical Language Scholarships, Dr. Kraft's lobbying for the American Physical Society, Coordinator for the Division of Health Sciences Lena Minervino, professor Emily Larned's ideas for reopening Bridgeport's Pleasure Beach, Chuch Sadowski being presented a 25-year Award from the College Sports Information Directors of America, donors to the UB Gymnastics program, UB's Akil Pompey playing for Khoromkhon FC in Ulaanbaatar, Joe Tonelli taking over at UB's Basketball coach, UB alum Gaetano Giunta's experience playing for UB Baseball and the New Jersey Jackels, and other campus and sports news

Enterovirus D68 outbreak detection through a syndromic disease epidemiology network

BACKGROUND: In 2014, enterovirus D68 (EV-D68) was responsible for an outbreak of severe respiratory illness in children, with 1,153 EV-D68 cases reported across 49 states. Despite this, there is no commercial assay for its detection in routine clinical care. BioFire® Syndromic Trends (Trend) is an epidemiological network that collects, in near real-time, deidentified. BioFire test results worldwide, including data from the BioFire® Respiratory Panel (RP). OBJECTIVES: Using the RP version 1.7 (which was not explicitly designed to differentiate EV-D68 from other picornaviruses), we formulate a model, Pathogen Extended Resolution (PER), to distinguish EV-D68 from other human rhinoviruses/enteroviruses (RV/EV) tested for in the panel. Using PER in conjunction with Trend, we survey for historical evidence of EVD68 positivity and demonstrate a method for prospective real-time outbreak monitoring within the network. STUDY DESIGN: PER incorporates real-time polymerase chain reaction metrics from the RPRV/EV assays. Six institutions in the United States and Europe contributed to the model creation, providing data from 1,619 samples spanning two years, confirmed by EV-D68 gold-standard molecular methods. We estimate outbreak periods by applying PER to over 600,000 historical Trend RP tests since 2014. Additionally, we used PER as a prospective monitoring tool during the 2018 outbreak. RESULTS: The final PER algorithm demonstrated an overall sensitivity and specificity of 87.1% and 86.1%, respectively, among the gold-standard dataset. During the 2018 outbreak monitoring period, PER alerted the research network of EV-D68 emergence in July. One of the first sites to experience a significant increase, Nationwide Children's Hospital, confirmed the outbreak and implemented EV-D68 testing at the institution in response. Applying PER to the historical Trend dataset to determine rates among RP tests, we find three potential outbreaks with predicted regional EV-D68 rates as high as 37% in 2014, 16% in 2016, and 29% in 2018. CONCLUSIONS: Using PER within the Trend network was shown to both accurately predict outbreaks of EV-D68 and to provide timely notifications of its circulation to participating clinical laboratories

Measurement of associated Z plus charm production in proton-proton collisions at root s=8TeV

A study of the associated production of a Z boson and a charm quark jet (Z + c), and a comparison to production with a b quark jet (Z + b), in pp collisions at a centre-of-mass energy of 8 TeV are presented. The analysis uses a data sample corresponding to an integrated luminosity of 19.7 fb(-1), collected with the CMS detector at the CERN LHC. The Z boson candidates are identified through their decays into pairs of electrons or muons. Jets originating from heavy flavour quarks are identified using semileptonic decays of c or b flavoured hadrons and hadronic decays of charm hadrons. The measurements are performed in the kinematic region with two leptons with pT(l) > 20 GeV, vertical bar eta(l)vertical bar 25 GeV and vertical bar eta(jet)vertical bar Z + c + X) B(Z -> l(+)l(-)) = 8.8 +/- 0.5 (stat)+/- 0.6 (syst) pb. The ratio of the Z+c and Z+b production cross sections is measured to be sigma(pp -> Z+c+X)/sigma (pp -> Z+b+X) = 2.0 +/- 0.2 (stat)+/- 0.2 (syst). The Z+c production cross section and the cross section ratio are also measured as a function of the transverse momentum of theZ boson and of the heavy flavour jet. The measurements are compared with theoretical predictions.Peer reviewe

Measurement of the underlying event activity in inclusive Z boson production in proton-proton collisions at root s=13 TeV

This paper presents a measurement of the underlying event activity in proton-proton collisions at a center-of-mass energy of 13TeV, performed using inclusive Z boson production events collected with the CMS experiment at the LHC. The analyzed data correspond to an integrated luminosity of 2.1 fb(-1). The underlying event activity is quantified in terms of the charged particle multiplicity, as well as of the scalar sum of the charged particles' transverse momenta in different topological regions defined with respect to the Z boson direction. The distributions are unfolded to the stable particle level and compared with predictions from various Monte Carlo event generators, as well as with similar CDF and CMS measurements at center-of-mass energies of 1.96 and 7TeV respectively.Peer reviewe

Unspoken Connections: How I Learned to Love Punctuation

There’s a secret about punctuation that most English teachers don’t tell you: beyond “rules” and correctness, there’s a power and beauty to those little symbols that we find ourselves placing between and around the words place on the page or computer screen. Rather than thinking about punctuation marks as necessary and therefore tedious— perhaps even unwelcome— we can learn to love their curves and points and use them with purpose, creativity, and yes, even affection. With the help of some of the best poets and prose readers, Professor Amy Nawrocki shows how various marks (parentheses, dashes, semicolons and commas) can inspire and delight, open us to the possibilities of a deep and enduring love of language and all its decorations

UB Knightlines Summer/Fall 2012

The UB Knightlines newsletter for Summer/Fall 2012. This issue contains articles discussing UB's 102nd commencement, graduates of the class of 2012, SASD students helping revamp the Bridgeport Public Library, health professionals using UB's new anatomy lab, UB's naturopathic-university herbarium, UB faculty summer reading lists, industrial design students gaining on the job experience, UB engineering outreach to local students with bridge building, UB MBA students with the Connecticut Stock Market Challenge, UB professors encouraging girls interest in STEM, a SASD alum winning UB's Lifetime Achievement Award, UB's first student to be admitted to UConn's School of Pharmacy, two International College students winning U.S. State Department Critical Language Scholarships, Dr. Kraft's lobbying for the American Physical Society, Coordinator for the Division of Health Sciences Lena Minervino, professor Emily Larned's ideas for reopening Bridgeport's Pleasure Beach, Chuch Sadowski being presented a 25-year Award from the College Sports Information Directors of America, donors to the UB Gymnastics program, UB's Akil Pompey playing for Khoromkhon FC in Ulaanbaatar, Joe Tonelli taking over at UB's Basketball coach, UB alum Gaetano Giunta's experience playing for UB Baseball and the New Jersey Jackels, and other campus and sports news

Development of a Novel Class of Agents Targeting the RNA-Splicing Machinery in Myeloid Malignancies

Abstract SF3B1 is a splicing factor gene whose mutations are pathognomonic of MDS with ring sideroblasts. Because of the ubiquitous importance of splicing, a major barrier in targeting cells with spliceosomal mutations is the discovery of agents decreasing the competitiveness of mutant cells while preserving the integrity of wild type cells. To date no specific therapies are FDA approved for SF3B1 mutant (SF3B1MT) MDS and few agents are in early clinical testing. We describe a novel targeted approach to drug development for SF3B1MT malignancies. Our investigative strategy started with a high throughput drug screen. We introduced K700E mutation into myeloid cells using CRISPR/Cas9. We then subjected K562+/K700E and matched-parental K562 cells to high throughput drug screen of a library of 3,000 mechanistically annotated, non-redundant, bioactive compounds. Top hits were validated by dose response testing (8 concentrations in half-log dilutions). Our interest focused on compounds with cytostatic activity towards K562+/K700E cells. Among these, a 4-pyridyl-2-anilinothiazole (PAT) showed preferential inhibition of growth in K562+/K700E cells with an IC50 of 3uM. Dose response showed that K562+/K700E cells were significantly sensitive to PAT with a growth inhibition of 20%, 32%, 51%, 65%, 95% at .3uM (P=.01), 1uM (P=.002), 3uM (P<.0001), 10uM (P<.0001), and 20uM (P=.01). High doses (10, 20uM) were toxic to parental cells. PAT treatment did not induce growth arrest in other myeloid cells (THP1, MOLM13FLT3, OCI-AML3DNMT3A, SIG-M5TET2/DNMT3A, K562PHF6) including cells with mutations in other splicing factors (K562U2AF1, K562LUC7L2). PAT induced similar effects in primary SF3B1MT MDS cells at 3uM while it did not induce significant growth inhibition in primary MDS cells with other mutations, including other spliceosomal mutations (e.g.,U2AF1) (N=6). In normal bone marrow cells (N=6), complete growth arrest of erythroid and myeloid cells was observed at high doses (20uM). Using PAT as our lead, we employed a fragment based reiterative medicinal chemistry approach to synthesize selective compounds and improve therapeutic index. Libraries were constructed following Lipinski rules with ease of synthetic construction in mind. Pilot libraries were constructed via the classic Hantsch thiazole synthesis which involves condensation of α-halo ketones with substituted thioureas. This enterprise investigated SAR modifications of PAT by considering features such as regiochemistry and basicity of the nitrogen of the pyridine ring in the head region; replacement of the spacer 2,4-disubstituted thiazole ring with heteroatom containing rings (5,6,7 membered aromatic or aliphatic ring structures); alternatives for the aniline of the tail region e.g., sulfonamide, amide, and substituted amine linkers and substituted aromatic and aliphatic ring structures for the phenyl substituent. A major challenge in drug development of agents targeting spliceosomal mutations is the identification of key clusters of aberrantly spliced genes restored by drug treatment, e.g., identification of a pharmacodynamic endpoint that could be used to prove that that the drug reached its target. SF3B1 mutations induce aberrant 3′-ss selection by promoting use of alternative branch points. To identify biomarkers of splicing changes to screen our libraries, K562+/K700E and parental cells were treated with PAT (3uM) and RNA libraries were subjected to RNA Seq. The splicing pattern of parental cells was used as reference. We identified 328 cassette exons (±25% splicing inclusion difference, pFDR<.05) in K562+/K700E cells of whom the splicing of 22 exons was partially or completely restored upon treatment. Among these, PAT treatment restored the splicing of exons in sensitive 3′-ss sequences (ENOSF1), RNA binding SR-related factors (ACIN1), zing fingers (ZC3H7A) already associated with SF3B1 downregulation, histone modifiers (HMGN3), mitochondrial genes (TMEM126B), proto-oncogenes (CREB1) and heat shock proteins (DNAJC24). Ongoing experiments include tests of the ability of PATs to restore the splicing of misspliced exons and its efficacy in reducing the percentage of SF3B1MT cells in xenografts of K562+/K700E and primary SF3B1MT cells and Sf3b1+/K700E mice. In sum, we described novel classes of compounds that inhibit the expansion of SF3B1MT cells by restoring the splicing defects intrinsically associated with SF3B1. Disclosures Carraway: Novartis: Speakers Bureau; Jazz: Speakers Bureau; FibroGen: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy; Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ra Pharmaceuticals, Inc: Consultancy