Although the existence of neutrino mass is firmly established, the precise neutrino mass scale remains unknown.  To directly probe this property, measurements of the endpoint of the tritium beta spectrum have achieved the greatest sensitivity, recently reaching the sub-eV scale.  In this talk, I will present Project 8, an experimental concept based on the novel Cyclotron Radiation Emission Spectroscopy (CRES) technique.  Project 8 has recently released its first measurements of the tritium beta spectral endpoint and demonstrated its high precision spectroscopy using krypton calibration.  An R&D campaign is now underway to demonstrate scalability of the CRES technique and to develop the atomic tritium source required.  Building on these successes, a next-generation experiment is envisioned with neutrino mass sensitivity down to 40 meV.

All undergraduate and graduate College of Arts & Sciences Students of Color in Mathematics and Science (SCiMS) are invited for an evening of fellowship, food, and fun!

Please join UK’s College of Arts & Sciences faculty authors for readings and inspirations featuring their newest book releases

Reception to follow in the Alumni Gallery

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Abstract: The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this resistance phenotype. Thus, an approved CYP1B1 inhibitor may be of immense benefit to cancer patients struggling against chemotherapy-resistant disease.

However, developing selective inhibitors of CYP1B1 is challenging due to the existence of approximately fifty related cytochromes P450 found in humans which share similar structural features. Confounding this fact, CYP1B1 preferentially binds substrates of low three-dimensional complexity and with high lipophilicity, which from a synthetic viewpoint are relatively nondescript, making rational inhibitor design difficult.

This work offers new synthetic approaches toward the solution to the challenge of developing selective CYP1B1 inhibitors. The first part of the work describes the discovery and mode of action of a previously unknown inhibitor of CYP1B1 active at sub-nanomolar concentrations, and with unprecedented selectivity compared to existing inhibitors. Next, the pharmacokinetic optimization of this lead compound was undertaken resulting in an improved lead with excellent metabolic stability for future applications in disease models, and with the long-term goal of translation into the clinic for use in human patients. Together, the development of a series of new molecular entities is described which enable the exquisite control of the activity of this medically relevant enzyme and is an important step toward the development of drug candidates.