Investigating the Tumor Suppressor Role of RUNX1 in Human Breast Cancer

Breast cancer (BrCa) remains the leading cause of cancer-related deaths in women worldwide. Current research suggests that the transcription factor RUNX1 functions as a regulator and potentially as a tumor suppressor in breast cancer progression. RUNX1 is the most dominant RUNX family member expressed in normal mammary epithelial cells and it has been demonstrated that RUNX1 activity decreases as breast cancer aggression increases. Yet, the mechanism of this regulation remains unclear. The significance of this project is to further the in-depth investigation of the relationship between RUNX1 and differentially expressed genes that influence human breast cancer progression. This study addresses the hypothesis that RUNX1 controls a myriad of genes that play roles in the suppression of the breast cancer stem cell (BCSC) population, a subpopulation of cancer cells that are capable of self-renewal and demonstrate an ability to resist common chemotherapies and treatments. BCSCs are therefore the most dangerous and most essential to eradicate if the cancer is to be cured. To test this hypothesis, RUNX1 was downregulated in the MCF10A breast cancer cell line using both the inducible CRISPRi and the shRNA-mediated gene knockdown approaches. Fluorescence-activated cell sorting (FACS) and quantitative polymerase chain reaction (qPCR) confirmed successful knockdown of RUNX1 and further genetic and proteomic expression analyses of known breast cancer driver genes was performed to determine how RUNX1 depletion exerts control over the progression of BrCa. It was found that RUNX1 may aid in maintaining the epithelial phenotype in BrCa while also suppressing the expression of key BrCa driver genes such as phosphatidylinositol-3-kinases (PI3K) PIK3CA and PIK3R1. Investigating the role of RUNX1 as a suppressor of the BCSC population adds a new level of knowledge to the field of breast cancer research, and may allow development of a safer, more targeted, and more effective plan of action to eradicate one of the deadliest diseases that exists today

Exact relativistic beta decay endpoint spectrum

The exact relativistic form for the beta decay endpoint spectrum is derived and presented in a simple factorized form. We show that our exact formula can be well approximated to yield the endpoint form used in the fit method of the KATRIN collaboration. We also discuss the three neutrino case and how information from neutrino oscillation experiments may be useful in analyzing future beta decay endpoint experiments.Comment: 12 pages, 3 figure

Improved treatment of the T2T_2 molecular final-states uncertainties for the KATRIN neutrino-mass measurement

The KArlsruhe TRItium Neutrino experiment (KATRIN) aims to determine the effective mass of the electron antineutrino via a high-precision measurement of the tritium beta-decay spectrum in its end-point region. The target neutrino-mass sensitivity of 0.2 eV / c^2 at 90% C.L. can only be achieved in the case of high statistics and a good control of the systematic uncertainties. One key systematic effect originates from the calculation of the molecular final states of T_2 beta decay. In the first neutrino-mass analyses of KATRIN the contribution of the uncertainty of the molecular final-states distribution (FSD) was estimated via a conservative phenomenological approach to be 0.02 eV^2 / c^4. In this paper a new procedure is presented for estimating the FSD-related uncertainties by considering the details of the final-states calculation, i.e. the uncertainties of constants, parameters, and functions used in the calculation as well as its convergence itself as a function of the basis-set size used in expanding the molecular wave functions. The calculated uncertainties are directly propagated into the experimental observable, the squared neutrino mass m_nu^2. With the new procedure the FSD-related uncertainty is constrained to 0.0013 eV^2 / c^4, for the experimental conditions of the first KATRIN measurement campaign

Wideband precision stabilization of the -18.6kV retarding voltage for the KATRIN spectrometer

The Karlsruhe Tritium Neutrino Experiment (KATRIN) measures the effective electron anti-neutrino mass with an unprecedented design sensitivity of 0.2 eV (90 % C.L.). In this experiment, the energy spectrum of beta electrons near the tritium decay endpoint is analyzed with a highly accurate spectrometer. To reach the KATRIN sensitivity target, the retarding voltage of this spectrometer must be stable to the ppm level and well known on various time scales ($\mu s$ up to months), for values around -18.6 kV. A custom-designed high-voltage regulation system mitigates the impact of interference sources in the absence of a closed electric shield around the large spectrometer vessel. In this article, we describe the regulation system and its integration into the KATRIN setup. Independent monitoring methods demonstrate a stability within 2 ppm, exceeding KATRIN's specifications.Comment: 28 pages, 17 figures, minor improvement

β\beta-Decay Spectrum, Response Function and Statistical Model for Neutrino Mass Measurements with the KATRIN Experiment

The objective of the Karlsruhe Tritium Neutrino (KATRIN) experiment is to determine the effective electron neutrino mass $m(\nu_\text{e})$ with an unprecedented sensitivity of $0.2\,\text{eV}$ (90\% C.L.) by precision electron spectroscopy close to the endpoint of the $\beta$ decay of tritium. We present a consistent theoretical description of the $\beta$ electron energy spectrum in the endpoint region, an accurate model of the apparatus response function, and the statistical approaches suited to interpret and analyze tritium $\beta$ decay data observed with KATRIN with the envisaged precision. In addition to providing detailed analytical expressions for all formulae used in the presented model framework with the necessary detail of derivation, we discuss and quantify the impact of theoretical and experimental corrections on the measured $m(\nu_\text{e})$. Finally, we outline the statistical methods for parameter inference and the construction of confidence intervals that are appropriate for a neutrino mass measurement with KATRIN. In this context, we briefly discuss the choice of the $\beta$ energy analysis interval and the distribution of measuring time within that range.Comment: 27 pages, 22 figures, 2 table