Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry

Background: Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry. Methods: We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category. Results: For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction. Conclusion: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry

MoS2 Decorated Carbon Nanofibers as Efficient and Durable Electrocatalyst for Hydrogen Evolution Reaction

Hydrogen is an efficient fuel which can be generated via water splitting, however hydrogen evolution occurs at high overpotential, and efficient hydrogen evolution catalysts are desired to replace state-of-the-art catalysts such as platinum. Here, we report an advanced electrocatalyst that has low overpotential, efficient charge transfers kinetics, low Tafel slope and durable. Carbon nanofibers (CNFs), obtained by carbonizing electrospun fibers, were decorated with MoS2 using a facile hydrothermal method. The imaging of catalyst reveals a flower like morphology that allows for exposure of edge sulfur sites to maximize the HER process. HER activity of MoS2 decorated over CNFs was compared with MoS2 without CNFs and with commercial MoS2. MoS2 grown over CNFs and MoS2-synthesized produced about 374 and 98 times higher current density at −0.30 V (vs. Reversible Hydrogen Electrode, RHE) compared with the MoS2-commercial sample, respectively. MoS2-commercial, MoS2-synthesized and MoS2 grown over CNFs showed a Tafel slope of 165, 79 and 60 mV/decade, capacitance of 0.99, 5.87 and 15.66 mF/cm2, and turnover frequency of 0.013, 0.025 and 0.54 s−1, respectively. The enhanced performance of MoS2-CNFs is due to large electroactive surface area, more exposure of edge sulfur to the electrolyte, and easy charge transfer from MoS2 to the electrode through conducting CNFs

Synthesis and characterization of platinum decorated iron oxide nanoparticles for biomedical applications

This dissertation focuses on the development of a bifunctional nanoparticle system that can potentially offer simultaneous imaging and therapy in the future. Recently, small platinum (Pt) nanoparticles (< 5 nm) have shown great potential in therapeutic applications, such as DNA dissociation, radiation therapy, and oxidative stress treatment. Therefore, the small Pt nanoparticles of size comparable to DNA grooves are chosen as potential therapeutic components in this research. However, such small sized Pt nanoparticles tends to aggregate, and are difficult to target. Therefore, this research reports the synthesis, characterization, and DNA interaction of small Pt decorated iron oxide nanoparticles. The iron oxide carriers provide stability to the small Pt nanoparticles, and can potentially serve as MRI contrast agents. The hypothesis of this research is that the Pt nanoparticles supported on iron oxide nanoparticle surfaces can effectively interact with DNA molecules similar to the free Pt nanoparticles. A reproducible synthetic technique was first developed to prepare iron oxide nanoparticles with excellent size control and narrow size distribution. Subsequently, two different approaches were utilized to produce multiple small Pt nanoparticle attached iron oxide nanoparticles. The first route involved attachment of Pt nanoparticles onto iron oxide seeds of various shapes in an organic solvent, followed by an aqueous phase transfer. Here, the shape of the nanoparticles was controlled to facilitate heterogeneous nucleation of Pt nanoparticles. The protective biocompatible polymer coating (polyacrylic acid) in this method could prevent interaction of the Pt nanoparticles with undesirable biomolecules. Several non-spherical iron oxide nanoparticles were explored, including whiskers, worms, plates, and flowers. In the second method, an aqueous phase ligand exchange process was performed first, prior to the deposition of multiple Pt nanoparticles. This facile method provided more accessibility of the Pt nanoparticles for DNA interactions. The DNA interaction of these nanoparticles was investigated using gel electrophoresis, electron microscopy, dynamic light scattering, and atomic absorption spectroscopy. By comparing with control DNA, we suggested that two possible interactions between DNA and Pt-iron oxide nanoparticles were present: (1) DNA molecules directly linked to the Pt-iron oxide nanoparticles, and (2) DNA molecules de-attached the Pt nanoparticles from the iron oxide support. This reported nanodrug system could potentially open up new possibilities in the design of therapeutic agents using multifunctional nanoparticles. Future efforts are to investigate the in vivo characteristics of this integrated nanostructure. (Published By University of Alabama Libraries