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.

Empowering K-12 STEM Teachers through a Bioscience Academy United States science education is in crisis. In spite of efforts to make school districts accountable through the 'No Child Left Behind' legislation, the top-down approaches employed failed to yield improved secondary educational outcomes.

The tumor suppressor BRCA1 plays an important role in the homologous recombination (HR) pathwayof DNA double strand break (DSB) repair. From a mechanistic perspective, BRCA1 facilitates recruitment ofnucleases required for end resection, the commitment step in HR repair, yet paradoxically, BRCA1 has beenshown to inhibit the nuclease activity in vitro. It is unclear how nuclease-recruiting and -inhibiting activities ofBRCA1 can be reconciled in HR repair.

Most BRCA1-asociated breast tumors are basal-like, yet they originate from luminal progenitor cells.BRCA1 plays important roles in double strand break (DSB) repair and response to DNA replication stress.However, it remains a conundrum as to whether these ubiquitously important functions of BRCA1 are sufficientto account for its cell lineage-specific breast tumor suppression. Filling this longstanding intellectual disconnectcould inform more effective risk assessment and disease prevention.