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This thesis covers two topics. First, I attempt to generate stochastic resonance (SR) in a biological system. Synthetic bistable systems were chosen because the inducer range in which they exhibit bistability can satisfy one of the three requirements of SR: a weak periodic force is unable to make the transition between states happen. I synthesized several different bistable systems, including toggle switches and self-activators, to select systems matching another requirement: the system has a clear threshold between the two energy states. Their bistability was verified and characterized. At the same time, I attempted to figure out the third requirement for SR – an effective noise serving as the stochastic force – through one of the most widespread toggles, the mutual inhibition toggle, in both yeast and E. coli. A mathematic model for SR was written and adjusted.
Secondly, I began work on designing a new genetic system capable of responding to pulsed magnetic fields. The operators responding to pulsed magnetic stimuli in the rpoH promoter were extracted and reorganized. Different versions of the rpoH promoter were generated and tested, and their varying responsiveness to magnetic fields was recorded. In order to improve efficiency and produce better operators, a directed evolution method was applied with the help of a CRISPR-dCas9 nicking system. The best performing promoters thus far show a five-fold difference in gene expression between trials with and without the magnetic field.
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appears in a smaller region inside of the tumor. Simulations show that if the aggressive strain focuses its efforts on proliferating and does not contribute to angiogenesis signaling when in a hypoxic state, a hypertumor will form. More importantly, this resultant aggressive tumor is paradoxically prone to extinction and hypothesize is the cause of necrosis in many vascularized tumors.
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In this study, WRF-Chem is utilized at high resolution (1.333 km grid spacing for the innermost domain) to investigate impacts of southern California anthropogenic emissions (SoCal) on Phoenix ground-level ozone concentrations ([O3]) for a pair of recent exceedance episodes. First, WRF-Chem control simulations, based on the US Environmental Protection Agency (EPA) 2005 National Emissions Inventories (NEI05), are conducted to evaluate model performance. Compared with surface observations of hourly ozone, CO, NOX, and wind fields, the control simulations reproduce observed variability well. Simulated [O3] are comparable with the previous studies in this region. Next, the relative contribution of SoCal and Arizona local anthropogenic emissions (AZ) to ozone exceedances within the Phoenix metropolitan area is investigated via a trio of sensitivity simulations: (1) SoCal emissions are excluded, with all other emissions as in Control; (2) AZ emissions are excluded with all other emissions as in Control; and (3) SoCal and AZ emissions are excluded (i.e., all anthropogenic emissions are eliminated) to account only for Biogenic emissions and lateral boundary inflow (BILB). Based on the USEPA NEI05, results for the selected events indicate the impacts of AZ emissions are dominant on daily maximum 8 h average (DMA8) [O3] in Phoenix. SoCal contributions to DMA8 [O3] for the Phoenix metropolitan area range from a few ppbv to over 30 ppbv (10–30 % relative to Control experiments). [O3] from SoCal and AZ emissions exhibit the expected diurnal characteristics that are determined by physical and photochemical processes, while BILB contributions to DMA8 [O3] in Phoenix also play a key role.
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In the decade since Yamanaka and colleagues described methods to reprogram somatic cells into a pluripotent state, human induced pluripotent stem cells (hiPSCs) have demonstrated tremendous promise in numerous disease modeling, drug discovery, and regenerative medicine applications. More recently, the development and refinement of advanced gene transduction and editing technologies have further accelerated the potential of hiPSCs. In this review, we discuss the various gene editing technologies that are being implemented with hiPSCs. Specifically, we describe the emergence of technologies including zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 that can be used to edit the genome at precise locations, and discuss the strengths and weaknesses of each of these technologies. In addition, we present the current applications of these technologies in elucidating the mechanisms of human development and disease, developing novel and effective therapeutic molecules, and engineering cell-based therapies. Finally, we discuss the emerging technological advances in targeted gene editing methods.
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This paper studies the effect of targeted observations on state and parameter estimates determined with Kalman filter data assimilation (DA) techniques. We first provide an analytical result demonstrating that targeting observations within the Kalman filter for a linear model can significantly reduce state estimation error as opposed to fixed or randomly located observations. We next conduct observing system simulation experiments for a chaotic model of meteorological interest, where we demonstrate that the local ensemble transform Kalman filter (LETKF) with targeted observations based on largest ensemble variance is skillful in providing more accurate state estimates than the LETKF with randomly located observations. Additionally, we find that a hybrid ensemble Kalman filter parameter estimation method accurately updates model parameters within the targeted observation context to further improve state estimation.
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