No abstract

Immunization of BALB/c mice with peptide HVSGHRMAWDMMMNWA, encompassing residues 121-135 from hepatitis C virus E1 protein, induced CD4 ⍣ T h 1 cells as well as a long-lasting CD8 ⍣ cytotoxic T lymphocyte (CTL) response in vivo when the peptide was administered s.c. with or without incomplete Freund's adjuvant. Using truncated peptides from this sequence it was shown that the determinant recognized by cytotoxic T cells was encompassed by residues SGHRMAWDM. Deletion of residues from the N-terminus or the C-terminus of the wild-type peptide abrogated its helper character. When Val122 of the wild peptide was replaced by Ala, the ability to induce a cytotoxic response was lost concomitantly with the loss of the T h 1 pattern of cytokine production. Interestingly, the Ala-modified peptide, when co-immunized with a peptide encompassing residues 323-329 from ovalbumin (OVA), which is able to induce a T h 1 response in BALB/c mice, restored the capacity of the modified peptide to induce CTL. However, co-immunization of the Ala-modified peptide with a peptide encompassing residues 106-118 from sperm whale myoglobin, which induces a T h 0 cytokine profile in BALB/c mice, was much less efficient than the OVA peptide to restore CTL induction. These results demonstrate that CTL induction with a short synthetic peptide requires that this peptide contains domains recognized by T c cells as well as by T h 1 cells. For those peptides that do not contain this type of T h domain, competent T cell help can be provided by co-immunization with a distinct peptide that is able to stimulate a T h 1 response.

The societal costs of natural hazards are large and steadily increasing in Canada due to increased urban development, an aging infrastructure, and limited capacities to anticipate and plan for unexpected disasters. Lessons learned from recent disasters underscore the need for a comprehensive risk-based approach to land use planning and emergency management at all levels of government-one that utilizes available knowledge about the risk environment to inform actions that have a potential to minimize future disaster losses and increase the resilience of communities to the dynamic and uncertain forces of change. We cannot predict or prevent earthquakes from happening. However, we do have the knowledge and capabilities to change the outcome of earthquake disasters through a combination of risk assessment and disaster resilience planning. Risk assessment is the process through which knowledge about a community and its exposure to natural hazards is used to anticipate the likely impacts and consequences of an unexpected event at some point in the future. Disaster resilience planning is focused on actions that can be taken in advance to balance policy trade offs for growth and development (opportunities) with risk reduction investments that have a potential to minimize future losses (liabilities) while increasing capabilities of a community to withstand, respond to and recover from unexpected disaster events (resilience). This study provides a detailed assessment of earthquake risk for the District of North Vancouver - an urban municipality of approximately 83,000 people situated along the North Shore Mountains in southwestern British Columbia. It describes the probable impacts of a significant earthquake with greater clarity and detail than ever before, and develops both a methodology and target criteria to guide future risk reduction and disaster resilience planning activities through the lens of building performance, public safety, lifeline resilience and socioeconomic security. We examine cause-effect relationships and seismic risks for a plausible earthquake scenario in the Strait of Georgia (M7.3), and undertake a more general assessment of who and what are vulnerable to known earthquake hazards in the region using probabilistic ground motion models that are consistent with those used to establish seismic safety guidelines in the National Building Code of Canada (NBCC, 2010). Study outputs offer a capacity to explore thresholds of risk tolerance and opportunities for mitigation through ongoing emergency planning and land use decision-making activities in the community. Methodologies and insights gained through this study are transferrable to other communities who may face similar challenges of managing growth and development in areas exposed to earthquake hazards. Key findings and recommendations of the study contribute to broader efforts led by the Canadian Safety and Security Program to support disaster resilience planning at a community level in Canada.

Fresh peripheral blood mononuclear cells (PBM) isolated from healthy human donors and activated with concanavalin A (Con A) induced suppression of the proliferation response to Con A in an allogeneic mixed leukocyte culture reaction (MLC). When PBM were incubated in media alone for 24 hr prior to Con A activation of suppressor cells there was a significant decrease in the suppressive response. PBM incubated in the presence of thymosin for 24 hr prior to Con A activation of the suppressor cells promoted a further augmentation of mitogen-induced proliferation. When PBM were incubated with thymosin in the absence of Con A activation of suppressor cells, enhancement of proliferation was observed in the MLC. These experiments suggest that thymosintreated PBM from healthy donors promote a helper rather than suppressive effect on mitogen-induced proliferation of allogeneic responder lymphocytes.