Synthesis of the S and C-linked diaccharide analogues related to hyaluronic acid

Hyaluronic acid is a ubiquitous glycosaminoglycan found in several mammalian tissues. It has been implicated in the development and progression of cancer by interacting with a cell\u27s CD 44 receptor. Our goal was to synthesize small molecules that are hyaluronic acid mimics, which contain CH2 and S groups strategically placed, as to render the molecules hydrolytically stable. Described in this dissertation are the synthetic efforts involved in assembling the disaccharide units related to hyaluronic acid that can potentially serve as building blocks for the synthesis of long-chain, enzymatically stable, oligosaccharide mimics. Both the S- and CH2- linked disaccharide analogues proved synthetically formidable. However, they were successfully synthesized. The C-disaccharide, after several methods were attempted, was obtained from the coupling of a glycosyl tin derivative with an aldehyde derived from methyl α-D-glucopyranoside. The S-disaccharide was successfully accomplished through an SN2 displacement of an axial triflate by a thiol

Fragmented Landscapes: An Archaeology of Transformations in The Pra River Basin, Southern Ghana

This doctoral archaeological research examines the Pra River Basin in southern Ghana through lenses of landscape, temporality, and transformation. Drawing on the Annales school and the writings of Tim Ingold, this study moves away from binary constructions of natural and cultural landscape features toward a more integrated view of the landscape\u27s long human history. The primary temporal focus of this research is the past three millennia but evidence recovered of even more ancient eras is also examined. The artifacts and features documented while surveying this landscape allow us to glimpse pre-Atlantic (pre-1450 CE) settlement patterns, subsistence, and technology, as well as more recent and ongoing transformations of the landscape. Artifacts including ceramics, quartz flakes, stone beads, ground stone tools, and iron slag were found on hilltop sites throughout the surveyed areas. Most of these sites represent a pre-Atlantic pattern of settlement that continues, to a lesser extent, into the early Atlantic era (1450-1700 CE). Long grinding slicks, possibly related to Nyame Akuma production, are present on numerous rock outcrops in the region. Test excavation at an iron smelting site near Adiembra (AD31) yielded a temporally extensive range of dates. The bulk of the slag was deposited in the early second century CE, but deeper ceramic bearing contexts stretched back through the first millennium BCE. A single early seventh millennium BCE date associated with stone flakes underlay the site, representing the oldest date recovered from an archaeological context in the region. The archaeological evidence this study presents suggests the entire landscape has undergone continual alteration for numerous millennia, but much of the landscape\u27s current form represents Atlantic influences and more recent historical dynamics and transformations of the colonial and post-colonial periods. I examine this fragmented landscape using satellite remote sensing, archaeological pedestrian survey, diagnostic artifact analyses, and limited test excavations to identify and assess features and transformative processes

The Hormonal Regulation of the Claudin Genes in the Ovary

The ovary is a dynamic organ that responds to many hormonal signals. When these hormonal signals are disrupted, ovarian dysfunction can occur. One such example is Polycystic Ovarian Syndrome (PCOS). PCOS patients suffer from high levels of testosterone. Excess testosterone may misregulate genes in the ovary and disrupt ovarian function. The Claudin (Cldn) 3 and Cldn11 genes have been shown to be regulated by androgens in the testis, while studies in ovarian cancer cells suggests a coregulatory mechanism for the expressions of Cldn3 and Cldn4 in the ovary. The objective of this study was to characterize the hormonal regulation of Claudin gene expression in the ovary. The ovaries of estrogen receptor alpha knockout (αERKO) mice have high serum testosterone concentrations, therefore Claudin expression was measured in these ovaries. Experiments were conducted using Quantitative Real Time PCR (QRT-PCR) to monitor the expression of Cldn3, 4, and 11 in wild-type (WT) and αERKO mouse ovaries. These experiments indicated that Cldn3, 4, and 11 were more highly expressed in αERKO mice than their wild-type counterparts (p \u3c 0.05, n = 5). Further experiments characterized Claudin expression in the ovaries of mice treated with Dihydrotestosterone (DHT) for 90 days which serve as a common mouse model of PCOS. DHT treated mice were found to express Cldn3 and Cldn11 significantly higher than control mice. Cldn4 expression decreased in DHT treated mice when compared to the controls (p \u3c 0.05, n = 4 for control and DHT groups). These findings indicated that Cldn3 and Cldn11 are upregulated by testosterone in the ovary. The data also indicates Cldn4 is regulated via different mechanisms than the other Claudin genes in the mouse ovary. DHT reduces expression of Cldn4, while increases are observed in the absence of ERα. Claudin expression was also evaluated in the ovaries of mice that were treated with testosterone propionate (TP) for three or six days. No expression of Cldn3 or Cldn11 was found, however Cldn4 steadily increased in conjunction with the duration of the testosterone propionate treatment. Western blot analysis for the presence of CLDN3 in the ovaries of control and TP treated mice yielded no detectable signal for either group. Studies done in cell lines found that CLDN4 expression decreased when BG-1 ovarian epithelial cells were treated with testosterone. These findings provide a first consider the regulation of the Claudin genes in the ovary, while providing a basis for future research to explore how they may contribute to PCOS

R. v. Oakes 1986-1997: Back to the Drawing Board

The Supreme Court of Canada, in R. v. Oakes, identified two standards of justification in applying section 1. The first standard was normative. The second was methodological, called the Oakes test. The Court, until recently, applied the Oakes test mechanically and avoided the normative standard. More recently, in Egan v. Canada and RJR-MacDonald Inc. v. Canada (A.G.), it resorted to a normative analysis that is indeterminate and unpredictable. This article challenges both the mechanical application of the Oakes test and the Court\u27s new normative approach. It proposes, and illustrates, a preferable alternative that is both determinate and predictable. It is supported by appendices that analyze section 1 cases between 1986 and 1997

Experimental demonstration of ray-rotation sheets

We have built microstructured sheets that rotate, on transmission, the direction of light rays by an arbitrary, but fixed, angle around the sheet normal. These ray-rotation sheets comprise two pairs of confocal lenticular arrays. In addition to rotating the direction of transmitted light rays, our sheets also offset ray position sideways on the scale of the diameter of the lenticules. If this ray offset is sufficiently small so that it cannot be resolved, our ray-rotation sheets appear to perform generalized refraction

Towards Graph Representation Learning in Emergent Communication

Recent findings in neuroscience suggest that the human brain represents information in a geometric structure (for instance, through conceptual spaces). In order to communicate, we flatten the complex representation of entities and their attributes into a single word or a sentence. In this paper we use graph convolutional networks to support the evolution of language and cooperation in multi-agent systems. Motivated by an image-based referential game, we propose a graph referential game with varying degrees of complexity, and we provide strong baseline models that exhibit desirable properties in terms of language emergence and cooperation. We show that the emerged communication protocol is robust, that the agents uncover the true factors of variation in the game, and that they learn to generalize beyond the samples encountered during training

Association of functional variants of PTPN22 and tp53 in psoriatic arthritis: a case-control study

Recent studies have implicated PTPN22 and tp53 in susceptibility to several autoimmune diseases, including rheumatoid arthritis, suggesting that these genes are important in maintaining immune homeostasis. Because autoimmune diseases may share similar susceptibility loci, investigation of these genes in psoriatic arthritis (PsA) is of potential relevance. As a result we investigated known coding polymorphisms in PTPN22 and tp53 in a homogenous Caucasian PsA cohort from Newfoundland, Canada and an admixed Caucasian PsA cohort from Toronto, Canada. We observed a moderate association of the R620W variant of PTPN22 with PsA in the Toronto population only. Because of the conflicting findings reported regarding the association of PTPN22 with PsA, further studies in other PsA populations are warranted

Relaxation of Microwave Nonlinearity in a Cuprate Superconducting Resonator

The second- and third-order nonlinear microwave response of a superconducting YBa2Cu3O7 thin-film resonator was synchronously measured using three input tones. This technique permits the local measurement, and hence mapping, of intermodulation distortion inside the resonator. Second- and third-order IMD measured with a fixed probe relaxed in remarkably different ways after the removal of a static magnetic field. The second-order IMD relaxed by two different magnetic processes, a fast process that appears related to bulk remanent magnetization and a slow process that fits the description of Bean and Livingston. The third-order IMD relaxes by only one process that is distinct from the two processes controlling second order relaxation

Cap mesenchyme cell swarming during kidney development is influenced by attraction, repulsion, and adhesion to the ureteric tip

Morphogenesis of the mammalian kidney requires reciprocal interactions between two cellular domains at the periphery of the developing organ: the tips of the epithelial ureteric tree and adjacent regions of cap mesenchyme. While the presence of the cap mesenchyme is essential for ureteric branching, how it is specifically maintained at the tips is unclear. Using ex vivo timelapse imaging we show that cells of the cap mesenchyme are highly motile. Individual cap mesenchyme cells move within and between cap domains. They also attach and detach from the ureteric tip across time. Timelapse tracks collected for >800 cells showed evidence that this movement was largely stochastic, with cell autonomous migration influenced by opposing attractive, repulsive and cell adhesion cues. The resulting swarming behaviour maintains a distinct cap mesenchyme domain while facilitating dynamic remodelling in response to underlying changes in the tip

Structural Inductive Biases in Emergent Communication

In order to communicate, humans flatten a complex representation of ideas and their attributes into a single word or a sentence. We investigate the impact of representation learning in artificial agents by developing graph referential games. We empirically show that agents parametrized by graph neural networks develop a more compositional language compared to bag-of-words and sequence models, which allows them to systematically generalize to new combinations of familiar features.Comment: The first two authors contributed equally. Poster presented at CogSci 202