This renewal extends our work during the last award period and seeks to translate these findings to thecriminal justice system. Our accomplishments include: (a) developing methods for processing transdermalalcohol concentration data that yield clinically-meaningful quantification of drinking; (b) demonstratingcontingency management can be successfully implemented using transdermal alcohol monitors and thatcontingency management can produce sustained reductions in heavy drinking in non-treatment-seekingproblematic drinkers; and (c) establishing collaborations within the judicial system.

Lung pathology is a significant cause of the morbidity and mortality associated with acute respiratory virus infection. Respiratory viruses, such as influenza virus not only cause damage to the epithelium, but activate immune defense mechanisms. Although these immune mechanisms are employed to destroy and remove infected cells in an attempt to clear the virus, they can also promote lung pathology. However, the key cellular and molecular mechanisms that regulate the balance between protection and tissue damage during acute viral infection remain poorly understood.

The two subtypes of estrogen receptor, ERa and ERb, carry out non-overlapping functions inreproductive biology. ERb is capable of both interfering with ERa function and exerting its biological activityindependent of ERa. It remains unclear how the ERa-independent and ERa-competing functions of ERb areregulated. We recently made the pioneering discovery of an ERb-specific phosphotyrosine switch thatregulates ERb function in reproductive organs.

Saliva performs a number of extremely important biological functions that are instrumental in maintaining oral health. It has been estimated that more than 5 million people in the US suffers from salivary gland dysfunction. Secretion of saliva is driven by concerted activities of a number of ion channels and transporters. Although, it is believed that calcium is the primary intracellular factor that regulates fluid secretion, the molecular mechanism involved in the regulation of cytosolic calcium is not clearly understood.

Mitochondria in hepatocytes play a major role in maintaining whole-body energy metabolism and normalfunction of the liver. Impaired mitochondrial function is closely associated with various metabolic diseases suchas obesity, insulin resistance, and hepatosteatosis. However, the precise underlying mechanisms remain to befully elucidated.

The program is designed to provide short-term experience and training inbiomedical research for undergraduate students from racial/ethnic-underrepresented groups, and forstudents from disadvantaged backgrounds. For the renewal, Penn State is joining with the Universityof Texas Health Science Center at San Antonio (UTHSCSA) to enhance recruitment of URM studentsand increase the scope of student research experiences. W. Brian Reeves, M.D., Chair of Medicine atUTHSCSA and previously the PI of Penn State STEP-UP will serve as the contact PI. Dr.

Our long-term goal is to understand the mechanism and function of the ubiquitin- proteasome system in health and disease. This proposal focuses on the function of the XPC-Rad23 complex in DNA damage response and proteolysis. Mutations in XPC protein lead to a genetic disorder Xeroderma pigmentosum (XP) that exhibits extreme sunlight sensitivity and a strong propensity for skin cancer. XPC was known previously as a key DNA repair factor that cells employ to protect from sunlight-inflicted DNA injury.