The Effects of Concussion on the Determinants of Gait Velocity in Community-Dwelling Men and Women

Concussions affect the complex act of walking. While factors like sex influence the effects of concussion, cognitive and motor challenges performed during gait evoke further deficits. The purpose of this thesis is to characterize factors that may affect gait velocity in people with concussion. Chapter 1 addresses the current literature on gait and concussion as they relate to sex, identifies gaps in the literature, and consolidates this information as a conceptual model. Chapters 2 and 3 focus on the studies that were conducted in this thesis. The findings of Chapter 2 highlight the different strategies that men and women use to achieve gait velocity, as well as sex-dependent differences in Step Length Variability. In Chapter 3, a lack of consistency is reported in the factors that predict concussion-induced alterations in gait over time. Finally, Chapter 4 discusses the overall findings of this thesis and presents an updated conceptual model

Asymmetric Transfer Hydrogenation of Aryl Heteroaryl Ketones and o-Hydroxyphenyl Ketones Using Noyori-Ikariya Catalysts

In 1995, Noyori and co-workers made a breakthrough with their design of practical ruthenium-based catalysts, which combined the homochiral TsDPEN ligand with a Ru(II) arene [...

Broad and potent neutralizing antibodies are elicited in vaccinated individuals following Delta/BA.1 breakthrough infection

Despite the success of COVID-19 vaccines in preventing infection and/or severe disease, there has been an increase in SARS-CoV-2 infections in vaccinated individuals owing to the waning vaccine-derived immunity, and the emergence of new variants which encode escape mutations in Spike. Following breakthrough infection in vaccinated individuals, an increase in neutralization breadth has been observed in sera/plasma. However, how exposure to a heterologous Spike broadens the neutralizing response at the monoclonal antibody (mAb) level is not fully understood. Through isolation of 119 mAbs from three individuals receiving two doses of BNT162b2 vaccine before becoming Delta or Omicron/BA.1 infected, we show that serum breadth occurs due to the presence of somatically mutated mAbs with broad neutralization activity indicative of re-activation and maturation of B cells generated through previous COVID-19 vaccination. Isolated mAbs frequently show reduced neutralization of current circulating variants including BA.2.75.2, XBB, XBB.1.5, and BQ.1.1 confirming continuous selective pressure on Spike to evolve and evade neutralization. However, isolation of mAbs that display effective cross-neutralization against all variants indicates the presence of conserved epitopes on the receptor binding domain and a lesser extent the N-terminal domain. These findings have implications for the selection of Spike antigens for next-generation COVID-19 vaccines. IMPORTANCE With the emergence of SARS-CoV-2 viral variants, there has been an increase in infections in vaccinated individuals. Here, we isolated monoclonal antibodies (mAbs) from individuals experiencing a breakthrough infection (Delta or BA.1) to determine how exposure to a heterologous Spike broadens the neutralizing antibody response at the monoclonal level. All mAbs isolated had reactivity to the Spike of the vaccine and infection variant. While many mAbs showed reduced neutralization of current circulating variants, we identified mAbs with broad and potent neutralization of BA.2.75.2, XBB, XBB.1.5, and BQ.1.1 indicating the presence of conserved epitopes on Spike. These results indicate that variant-based vaccine boosters have the potential to broaden the vaccine response.</p