The Property of the Nation : Democracy and the Memory of George Washington, 1799-1865

This dissertation explores how Americans personally experienced George Washington’s legacy in the nineteenth century through visits to his estate and tomb at Mount Vernon. By the 1820s many Americans had conflicting memories of the American Revolution and its most iconic figure, George Washington. As America grew more divided, so too did the memory of Washington. On multiple occasions, government factions and organizations attempted to claim his remains for political reasons. At the same time, Americans and foreign travelers journeyed to Mount Vernon to experience his tomb and forge a deeper personal connection with the man. These visitors collected objects such as sticks, stones, and flowers from his gravesite, mementoes that not only represented their visits but also served as a reminder of a nostalgic American past. African slaves, free blacks, and European gardeners greeted these visitors as the first historical interpreters of Washington history. These individuals not only shared anecdotes but they also wove themselves into the narrative to profit from their affiliation with Washington. The history of Washington’s tomb therefore illuminates the origins of an American celebrity culture, one that elevated Washington in significance and also ultimately transformed him into a democratic figure

When to Best Apply Peer Response Activities to the Writing Process in the High School Classroom

Indiana University-Purdue University Indianapolis (IUPUI)This study explored how to best incorporate peer response activities into the high school classroom. Three honors 10th grade classes completed peer response activities at different places in the research paper writing process, modeling Elbow and Belanoff's "bones, muscles, and skin" analogy. Surveys and final draft grades were used to evaulate where and how peer response can have the most benefit

One-dimensional Chern-Simons theory and the A^\hat{A} genus

We construct a Chern-Simons gauge theory for dg Lie and L-infinity algebras on any one-dimensional manifold and quantize this theory using the Batalin-Vilkovisky formalism and Costello's renormalization techniques. Koszul duality and derived geometry allow us to encode topological quantum mechanics, a nonlinear sigma model of maps from a 1-manifold into a cotangent bundle T*X, as such a Chern-Simons theory. Our main result is that the partition function of this theory is naturally identified with the A-genus of X. From the perspective of derived geometry, our quantization construct a volume form on the derived loop space which can be identified with the A-class.Comment: 61 pages, figures, final versio

Carbon monoxide poisoning: novel magnetic resonance imaging pattern in the acute setting

The presentation of carbon monoxide (CO) poisoning is non-specific and highly variable. The diagnosis is made when a compatible history and examination occur in a patient with elevated carboxyhaemoglobin levels. The severity of intoxication is difficult to assess accurately based on laboratory markers alone. Magnetic resonance imaging (MRI) has been shown to have superior sensitivity to computed tomography for the detection of abnormalities post CO poisoning. We report a novel imaging pattern on MRI undertaken in the acute setting in a patient with CO intoxication. We also discuss the management and follow up of patients with CO poisoning

Carbon monoxide poisoning: Novel magnetic resonance imaging pattern in the acute setting

The presentation of carbon monoxide (CO) poisoning is non-specific and highly variable. The diagnosis is made when a compatible history and examination occur in a patient with elevated carboxyhaemoglobin levels. The severity of intoxication is difficult to assess accurately based on laboratory markers alone. Magnetic resonance imaging (MRI) has been shown to have superior sensitivity to computed tomography for the detection of abnormalities post CO poisoning. We report a novel imaging pattern on MRI undertaken in the acute setting in a patient with CO intoxication. We also discuss the management and follow up of patients with CO poisoning

Tissue engineering strategies to bioengineer the ageing skin phenotype in vitro

Human skin ageing is a complex and heterogeneous process, which is influenced by genetically determined intrinsic factors and accelerated by cumulative exposure to extrinsic stressors. In the current world ageing demographic, there is a requirement for a bioengineered ageing skin model, to further the understanding of the intricate molecular mechanisms of skin ageing, and provide a distinct and biologically relevant platform for testing actives and formulations. There have been many recent advances in the development of skin models that recapitulate aspects of the ageing phenotype in vitro. This review encompasses the features of skin ageing, the molecular mechanisms that drive the ageing phenotype, and tissue engineering strategies that have been utilised to bioengineer ageing skin in vitro

Defining Prostatic Vascular Pedicle Recurrence and the Anatomy of Local Recurrence of Prostate Cancer on Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography.

Background The term local recurrence in prostate cancer is considered to mean persistent local disease in the prostatic bed, most commonly at the site of the vesicourethral anastomosis (VUA). Since the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging for assessment of early biochemical recurrence (BCR), we have found histologically confirmed prostate cancer in the prostatic vascular pedicle (PVP). If a significant proportion of local recurrences are distant to the VUA, it may be possible to alter adjuvant and salvage radiation fields in order to reduce the potential morbidity of radiation in selected patients. Objective To describe PVP local recurrence and to map the anatomic pattern of prostate bed recurrence on PSMA PET/CT. Design setting and participants This was a retrospective multicentre study of 185 patients imaged with PSMA PET/CT following radical prostatectomy (RP) between January 2016 and November 2018. All patient data and clinical outcomes were prospectively collected. Recurrences were documented according to anatomic location. For patients presenting with local recurrence, the precise location of the recurrence within the prostate bed was documented. Intervention PSMA PET/CT for BCR following RP. Results and limitations A total of 43 local recurrences in 41/185 patients (22%) were identified. Tumour recurrence at the PVP was found in 26 (63%), VUA in 15 (37%), and within a retained seminal vesicle and along the anterior rectal wall in the region of the neurovascular bundle in one (2.4%) each. Histological and surgical evidence of PVP recurrence was acquired in two patients. The study is limited by its retrospective nature with inherent selection bias. This is an observational study reporting on the anatomy of local recurrence and does not include follow-up for patient outcomes. Conclusions Our study showed that prostate cancer can recur in the PVP and is distant to the VUA more commonly than previously thought. This may have implications for RP technique and for the treatment of selected patients in the local recurrence setting. Patient summary We investigated more precise identification of the location of tumour recurrence after removal of the prostate for prostate cancer. We describe a new definition of local recurrence in an area called the prostatic vascular pedicle. This new concept may alter the treatment recommended for recurrent disease

<i>C9orf72 </i>Repeat Expansion Discordance in 6 Multigenerational Kindreds

Background and Objectives:A hexanucleotide repeat expansion in the noncoding region of the C9orf72 gene is the most common genetically identifiable cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in populations of European ancestry. Pedigrees associated with this expansion exhibit phenotypic heterogeneity and incomplete disease penetrance, the basis of which is poorly understood. Relatives of those carrying the C9orf72 repeat expansion exhibit a characteristic cognitive endophenotype independent of carrier status. To examine whether additional shared genetic or environmental risks within kindreds could compel this observation, we have conducted a detailed cross-sectional study of the inheritance within multigenerational Irish kindreds carrying the C9orf72 repeat expansion.Methods:One hundred thirty-one familial ALS pedigrees, 59 of which carried the C9orf72 repeat expansion (45.0% [95% CI 36.7–53.5]), were identified through the Irish population-based ALS register. C9orf72 genotyping was performed using repeat-primed PCR with amplicon fragment length analysis. Pedigrees were further investigated using SNP, targeted sequencing data, whole-exome sequencing, and whole-genome sequencing.Results:We identified 21 kindreds where at least 1 family member with ALS carried the C9orf72 repeat expansion and from whom DNA was available from multiple affected family members. Of these, 6 kindreds (28.6% [95% CI 11.8–48.3]) exhibited discordant segregation. The C9orf72 haplotype was studied in 2 families and was found to segregate with the C9orf72-positive affected relative but not the C9orf72-negative affected relative. No other ALS pathogenic variants were identified within these discordant kindreds.Discussion:Family members of kindreds associated with the C9orf72 repeat expansion may carry an increased risk of developing ALS independent of their observed carrier status. This has implications for assessment and counseling of asymptomatic individuals regarding their genetic risk

Cell Senescence-Independent Changes of Human Skin Fibroblasts with Age

Skin ageing is defined, in part, by collagen depletion and fragmentation that leads to a loss of mechanical tension. This is currently believed to reflect, in part, the accumulation of senescent cells. We compared the expression of genes and proteins for components of the extracellular matrix (ECM) as well as their regulators and found that in vitro senescent cells produced more matrix metalloproteinases (MMPs) than proliferating cells from adult and neonatal donors. This was consistent with previous reports of senescent cells contributing to increased matrix degradation with age; however, cells from adult donors proved significantly less capable of producing new collagen than neonatal or senescent cells, and they showed significantly lower myofibroblast activation as determined by the marker α-SMA. Functionally, adult cells also showed slower migration than neonatal cells. We concluded that the increased collagen degradation of aged fibroblasts might reflect senescence, the reduced collagen production likely reflects senescence-independent processes

The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complex

In vitro delivery of the diphtheria toxin catalytic (C) domain from the lumen of purified early endosomes to the external milieu requires the addition of both ATP and a cytosolic translocation factor (CTF) complex. Using the translocation of C-domain ADP-ribosyltransferase activity across the endosomal membrane as an assay, the CTF complex activity was 650–800-fold purified from human T cell and yeast extracts, respectively. The chaperonin heat shock protein (Hsp) 90 and thioredoxin reductase were identified by mass spectrometry sequencing in CTF complexes purified from both human T cell and yeast. Further analysis of the role played by these two proteins with specific inhibitors, both in the in vitro translocation assay and in intact cell toxicity assays, has demonstrated their essential role in the productive delivery of the C-domain from the lumen of early endosomes to the external milieu. These results confirm and extend earlier observations of diphtheria toxin C-domain unfolding and refolding that must occur before and after vesicle membrane translocation. In addition, results presented here demonstrate that thioredoxin reductase activity plays an essential role in the cytosolic release of the C-domain. Because analogous CTF complexes have been partially purified from mammalian and yeast cell extracts, results presented here suggest a common and fundamental mechanism for C-domain translocation across early endosomal membranes