Peptide Corrination for the Mitigation of Nausea and Emesis in the Treatment of Type 2 Diabetes

This thesis addresses several questions focused on the activation of receptors expressed withinthe area postrema (AP) and the nucleus tractus solitarius (NTS), regions known to influence nausea and emesis. Prevention of such effects were achieved via corrination, covalent attachment to vitamin B12 (B12) or other corrin constructs, of GLP glucagon-like peptide-one (GLP-1) receptor (GLP-1R) agonists or via the use of GRASP a growth differentiation factor 15 (GDF15) glial derived neurotropic family receptor α-like (GFRAL) complex antagonist

Design, synthesis, and characterization of monomeric peptide multiagonists for the mitigation of CNS-associated side effects in the treatment of Type II diabetes and Obesity

Current treatments for type 2 diabetes mellitus (T2DM) and obesity do not reliably achieve long-termweight-loss and up to 50% of patients experience nausea and vomiting. Thus, there is a critical need for obesity medications that provide glycemic control with enhanced weight loss and without sideeffects. We recently reported on the development of EP45, a first in class monomeric peptide drug, which displayed glucoregulation and profound weight loss in rats, and an absence of visceral malaise in shrews, a mammalian model capable of vomiting (unlike rats). By targeting multiple weight-loss and glucoregulatory pathways simultaneously with a single drug, GEP44, we can address multiple coexisting conditions to more efficaciously reduce body weight and blood glucose levels, all devoid of side-effects to improve patient tolerance and quality of life

Maritime expressions:a corpus based exploration of maritime metaphors

This study uses a purpose-built corpus to explore the linguistic legacy of Britain’s maritime history found in the form of hundreds of specialised ‘Maritime Expressions’ (MEs), such as TAKEN ABACK, ANCHOR and ALOOF, that permeate modern English. Selecting just those expressions commencing with ’A’, it analyses 61 MEs in detail and describes the processes by which these technical expressions, from a highly specialised occupational discourse community, have made their way into modern English. The Maritime Text Corpus (MTC) comprises 8.8 million words, encompassing a range of text types and registers, selected to provide a cross-section of ‘maritime’ writing. It is analysed using WordSmith analytical software (Scott, 2010), with the 100 million-word British National Corpus (BNC) as a reference corpus. Using the MTC, a list of keywords of specific salience within the maritime discourse has been compiled and, using frequency data, concordances and collocations, these MEs are described in detail and their use and form in the MTC and the BNC is compared. The study examines the transformation from ME to figurative use in the general discourse, in terms of form and metaphoricity. MEs are classified according to their metaphorical strength and their transference from maritime usage into new registers and domains such as those of business, politics, sports and reportage etc. A revised model of metaphoricity is developed and a new category of figurative expression, the ‘resonator’, is proposed. Additionally, developing the work of Lakov and Johnson, Kovesces and others on Conceptual Metaphor Theory (CMT), a number of Maritime Conceptual Metaphors are identified and their cultural significance is discussed