Progressive Mauve: Multiple alignment of genomes with gene flux and rearrangement

Multiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms. We describe a method to align two or more genomes that have undergone large-scale recombination, particularly genomes that have undergone substantial amounts of gene gain and loss (gene flux). The method utilizes a novel alignment objective score, referred to as a sum-of-pairs breakpoint score. We also apply a probabilistic alignment filtering method to remove erroneous alignments of unrelated sequences, which are commonly observed in other genome alignment methods. We describe new metrics for quantifying genome alignment accuracy which measure the quality of rearrangement breakpoint predictions and indel predictions. The progressive genome alignment algorithm demonstrates markedly improved accuracy over previous approaches in situations where genomes have undergone realistic amounts of genome rearrangement, gene gain, loss, and duplication. We apply the progressive genome alignment algorithm to a set of 23 completely sequenced genomes from the genera Escherichia, Shigella, and Salmonella. The 23 enterobacteria have an estimated 2.46Mbp of genomic content conserved among all taxa and total unique content of 15.2Mbp. We document substantial population-level variability among these organisms driven by homologous recombination, gene gain, and gene loss. Free, open-source software implementing the described genome alignment approach is available from http://gel.ahabs.wisc.edu/mauve .Comment: Revision dated June 19, 200

Hypertensive Acute Decompensated Heart Failure Presentations: On the Decline? : A Master\u27s Thesis

Background: The initial systolic blood pressure (SBP) in patients with acute heart failure (AHF) can be used as a guide when choosing specific pharmacologic treatments by helping identify the underlying type of HF (e.g., HF with preserved ejection fraction). Clinical experience and research data from our medical center suggests that AHF with elevated SBP may be presenting less frequently than in the past. This may call into question the utility of initial SBP as a clinical guide. The goal of this Master’s Thesis is to test the hypothesis that the frequency of AHF patients with a SBP\u3e160mmhg has declined over time. Methods: This observational study compares data from 4 cohorts of adult patients admitted with AHF in central MA. Data were obtained from a contemporary (2011-2013) study of patients with AHF as well as from the 1995, 2000, 2006 Worcester Heart Failure Study (WHFS) cohorts. The Framingham criteria the diagnostic criterion for AHF. The main outcome was the proportion of patients with AHF with a SBP \u3e 160 mmHg who presented in each of the 4 study cohorts and was examined by multivariate logistic regression. Results: 2,366 patients comprised the study population. The average age was 77 years, 55% were female, 94% white, and 75% had prior HF. In 1995 33.6% of AHF patients had a SBP \u3e160 mmHg compared to 19.5% in 2011-2013 (p160 mmHg in 2006 (0.64, (0.42-0.96)) and 2011-13 (0.46, (0.28-0.74)). Conclusion: The proportion of patients with AHF and an initial SBP \u3e160 mmHg has significantly declined over time. This may warrant a reexamination of the utility of SBP to inform diagnosis and treatment in patients with AHF

Surveilling Wolves, Reticent Rabbits, and Pecking Parties: Discourse as Power Mechanism for Policing Queerness in Ken Kesey’s One Flew Over the Cuckoo’s Nest

Ken Kesey’s One Flew Over the Cuckoo’s Nest (1962) presents a mental health institution, which, through narrator “Chief” Bromden’s eyes, is a factory for “the Combine,” the all-encompassing, normalizing power structure throughout society. Nurse Ratched, a caricature of the emasculating villainess, controls the men inside the ward through surveillance, forced confessional discourse, and discipline. Scholarship has primarily focused on the misogyny and hypermasculinity in the novel, wholly ignoring the queerness that undercurrents Bromden and fellow patient Dale Harding. Bromden—inherently queered as a Native man in a settler state— and Harding— symbolic of internalized heteronormative pressures— together represent how institutions and relationships alike function to forcibly “straighten” queer individuals. Evoking Foucault, Sedgwick, and queer Indigenous scholars, this thesis argues that Kesey’s novel, despite its dated and offensive depiction of women and people of color, nevertheless remains a relevant warning of power’s influence and shifting technologies of control over queer individuals