Gene editing in yeast cells using the CRISPR/Cas9 system

https://scholarworks.moreheadstate.edu/student_scholarship_posters/1267/thumbnail.jp

Generalization and Equilibrium in Generative Adversarial Nets (GANs)

We show that training of generative adversarial network (GAN) may not have good generalization properties; e.g., training may appear successful but the trained distribution may be far from target distribution in standard metrics. However, generalization does occur for a weaker metric called neural net distance. It is also shown that an approximate pure equilibrium exists in the discriminator/generator game for a special class of generators with natural training objectives when generator capacity and training set sizes are moderate. This existence of equilibrium inspires MIX+GAN protocol, which can be combined with any existing GAN training, and empirically shown to improve some of them.Comment: This is an updated version of an ICML'17 paper with the same title. The main difference is that in the ICML'17 version the pure equilibrium result was only proved for Wasserstein GAN. In the current version the result applies to most reasonable training objectives. In particular, Theorem 4.3 now applies to both original GAN and Wasserstein GA

Wettability controlling effects on the fluid occurrence and flow in shale gas reservoirs: Present problems and new sights

The wettability of shale is critical for the development of shale oil and gas reservoirs. Due to its complex composition, which includes organic materials and a number of different inorganic minerals, shale’s wettability may show high heterogeneity. This could significantly affect fluid occurrence and flow processes in various kinds of pores. Organic and inorganic pores may have varying capillary pressures. The methodologies to describe the capillary forces in these two varieties of pores are still lacking, though. Additionally, due to the strong capillary pressure that may prevent liquid water from entering organic pores, the mechanisms by which water and methane accumulate in inorganic pores and organic pores may differ. Therefore, the two-phase occurrence mechanisms in the various types of pores in shale continue to be difficult problems. Furthermore, because organic and inorganic pores differ in their capillary pressure and fluid occurrence, wettability can have a significant effect on relative permeability. Thus, wettability is a significant factor that impacts the exploration and development of shale gas reservoirs. The development of shale gas reservoirs could benefit significantly from a thorough understanding of wettability heterogeneity, capillary pressure, water-methane occurrence, and relative permeability.Document Type: Current minireviewCited as: Zhang, S., Wang, T., Gao, Z., Zhang, Y. Wettability controlling effects on the fluid occurrence and flow in shale gas reservoirs: Present problems and new sights. Capillarity, 2023, 9(2): 25-31. https://doi.org/10.46690/capi.2023.11.0

Non-asymptotic Convergence of Adam-type Reinforcement Learning Algorithms under Markovian Sampling

Despite the wide applications of Adam in reinforcement learning (RL), the theoretical convergence of Adam-type RL algorithms has not been established. This paper provides the first such convergence analysis for two fundamental RL algorithms of policy gradient (PG) and temporal difference (TD) learning that incorporate AMSGrad updates (a standard alternative of Adam in theoretical analysis), referred to as PG-AMSGrad and TD-AMSGrad, respectively. Moreover, our analysis focuses on Markovian sampling for both algorithms. We show that under general nonlinear function approximation, PG-AMSGrad with a constant stepsize converges to a neighborhood of a stationary point at the rate of $\mathcal{O}(1/T)$ (where $T$ denotes the number of iterations), and with a diminishing stepsize converges exactly to a stationary point at the rate of $\mathcal{O}(\log^2 T/\sqrt{T})$. Furthermore, under linear function approximation, TD-AMSGrad with a constant stepsize converges to a neighborhood of the global optimum at the rate of $\mathcal{O}(1/T)$, and with a diminishing stepsize converges exactly to the global optimum at the rate of $\mathcal{O}(\log T/\sqrt{T})$. Our study develops new techniques for analyzing the Adam-type RL algorithms under Markovian sampling

CD40- and 41BB-specific antibody fusion proteins with PDL1 blockade-restricted agonism

Background: A strategy to broaden the applicability of checkpoint inhibitors is the combined use with antibodies targeting the immune stimulatory receptors CD40 and 41BB. However, the use of anti-CD40 and anti-41BB antibodies as agonists is problematic in two ways. First, anti-CD40 and anti-41BB antibodies need plasma membrane-associated presentation by FcγR binding to exert robust agonism but this obviously limits their immune stimulatory efficacy by triggering ADCC, CDC or anti-inflammatory FcγRIIb activities. Second, off tumor activation of CD40 and 41BB may cause dose limiting systemic inflammation. Methods: To overcome the FcγR-dependency of anti-41BB and anti-CD40 antibodies, we genetically fused such antibodies with a PDL1-specific blocking scFv as anchoring domain to enable FcγR-independent plasma membrane-associated presentation of anti-CD40- and anti-41BB antibodies. By help of GpL-tagged variants of the resulting bispecific antibodies, binding to their molecular targets was evaluated by help of cellular binding studies. Membrane PDL1-restricted engagement of CD40 and 41BB but also inhibition of PDL1-induced PD1 activation were evaluated in coculture assays with PDL1-expressing tumor cell lines and 41BB, CD40 and PD1 responsible cell lines or T-cells. Results: The binding properties of the bispecific antibody fusion proteins remained largely unchanged compared to their parental molecules. Upon anchoring to membrane PDL1, the bispecific antibody fusion proteins activated CD40/41BB signaling as efficient as the parental anti-CD40/anti-41BB antibodies when bound to FcγRs or cells expressing membrane-bound CD40L/41BBL. PD1 inhibition remained intact and the anti-41BB fusion protein thus showed PDL1-restricted costimulation of T-cells activated in vitro with anti-CD3 or a BiTe. Conclusions: Targeting of anti-CD40 and anti-41BB fusion proteins to membrane PDL1 with a blocking PDL1 scFv links PD1-PDL1 checkpoint blockade intrinsically with engagement of CD40 or 41BB