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Osborne, M.

Publications and source records attributed to Osborne, M..

2 recordsLinked to original sources

Personalized Closed-Loop Brain Stimulation for Effective Neurointervention Across Participants

Accumulating evidence from human-based research has highlighted that the prevalent one-size-fits-all approach for neural and behavioral interventions is inefficient. This approach can benefit one individual, but be ineffective or even detrimental for another. Studying the efficacy of the large range of different parameters for different individuals is costly, time-consuming and requires a large sample size that makes such research impractical and hinders effective interventions. Here an active machine learning technique is presented across participants--personalized Bayesian optimization (pBO)--that searches available parameter combinations to optimize an intervention as a function of an individuals ability. This novel technique was utilized to identify transcranial alternating current stimulation frequency and current strength combinations most likely to improve arithmetic performance, based on a subjects baseline arithmetic abilities. The pBO was performed across all subjects tested, building a model of subject performance, capable of recommending parameters for future subjects based on their baseline arithmetic ability. pBO successfully searches, learns, and recommends parameters for an effective neurointervention as supported by behavioral, stimulation, and neural data. The application of pBO in human-based research opens up new avenues for personalized and more effective interventions, as well as discoveries of protocols for treatment and translation to other clinical and non-clinical domains.

neuroscience

Independence of HIF1a and androgen signaling pathways in prostate cancer

Androgen signaling drives prostate cancer progression and is a therapeutic target. Hypoxia/HIF1a signaling is associated with resistance to hormone therapy and a poor prognosis in patients treated with surgery or radiotherapy. It is not known whether the pathways operate in cooperation or independently. Using LNCaP cells with and without stable transfection of a HIF1a expression vector, we show that combined AR and HIF1a signaling promotes tumor growth in vitro and in vivo, and the capacity of HIF1a to promote tumor growth in the absence of endogenous androgen in vivo. Gene expression analysis identified 7 genes that were upregulated by both androgen and HIF1a. ChIP-Seq analysis showed that the AR and HIF/hypoxia signaling pathways function independently regulating the transcription of different genes with few shared targets. In clinical datasets elevated expression of 5 of the 7 genes was associated with a poor prognosis. Our findings suggest that simultaneous therapeutic inhibition of AR and HIF1a signaling pathways should be explored as a potential therapeutic strategy.

cancer biology