Eyesafe, Multi-function Coherent Doppler Lidar for Stand-Off Bioaerosol Discrimination

Chemical warfare agents such as bis-(b-chloroethyl) sulfide (HD) pose a significant threat to U.S. military and civilian populations. Exposure of skin to HD causes burn-like symptoms such as erythema, edema and severe incapacitating vesication(blistering). To combat this threat, prophylactic and/or therapeutic interventions to HD exposure are needed. Development of such interventions requires an understanding of the mechanism of action of HD. However, a major impediment to understanding ofHD-induced pathogenesis is lack of an adequate experimental model system of human skin. Since current models do not possess the appropriate attributes for HD research such as a complete basement membrane with dermal/epidermal adhesion structures, an invitro human skin model for HD-related studies is needed. The purpose of the current proposal is to develop an in vitro human skin model suitable for HD research. The model will contain human keratinocytes and/or fibroblasts and will possess allmorphological and ultrastructural features required for HD research. The model's response to HD or HD analogues will be investigated in terms of biochemical effects leading to blister formation. The model will also be utilized to gain a mechanisticunderstanding of HD-induced vesication and to investigate prophylactic and/or therapeutic interventions to HD exposure. In addition to providing a model which will greatly facilitate sulfur mustard vesication studies, this work will lead to a fullthickness skin model which will allow the study of numerous dermis-based skin phenomena such as photoaging, photodamage, wound healing and cancer progression. This improved tissue model will be useful to the cosmetic and pharmaceutical industry inirritancy and efficacy testing of their new products.