Bayesian Reinforcement Learning With Limited Cognitive Load.

All biological and artificial agents must act given limits on their ability to acquire and process information. As such, a general theory of adaptive behavior should be able to account for the complex interactions between an agent's learning history, decisions, and capacity constraints. Recent work in computer science has begun to clarify the principles that shape these dynamics by bridging ideas from reinforcement learning, Bayesian decision-making, and rate-distortion theory. This body of work provides an account of capacity-limited Bayesian reinforcement learning, a unifying normative framework for modeling the effect of processing constraints on learning and action selection. Here, we provide an accessible review of recent algorithms and theoretical results in this setting, paying special attention to how these ideas can be applied to studying questions in the cognitive and behavioral sciences.

Feasibility and safety of transfemoral transcatheter aortic valve implantation performed with a percutaneous coronary intervention-like approach.

BACKGROUND: Transfemoral percutaneous transcatheter aortic valve implantation (TF-TAVI) is a safe, reproducible and established procedure, mainly performed under local anaesthesia, which is mostly administered and monitored by a dedicated anaesthesia team (regular approach). Our centre has developed a standardized pathway of care, and eligible patients are selected for a minimalist TF-TAVI, entirely managed by operators without the presence of the anaesthesia team in the operating room, like most interventional coronary procedures ("percutaneous coronary intervention-like" approach [PCI approach]). AIM: To compare the safety and efficacy of TF-TAVI performed with the PCI approach versus the regular approach. METHODS: The analysis population comprised all patients who underwent TF-TAVI with the PCI or regular approach in our institution from November 2016 to July 2019. The two co-primary endpoints were early safety composite and early efficacy composite at 30days as defined by the Valve Academic Research Consortium-2. The PCI (n=137) and Regular (n=221) approaches were compared using the propensity score based method of inverse probability of treatment weighting. RESULTS: No differences were observed after comparison of TAVI performed with the PCI or regular approach regarding the composite safety endpoint (7.3% vs. 11.3%; odds ratio 0.63, 95% confidence interval 0.37 to 1.07; P=0.086) or the composite efficacy endpoint (4.4% vs. 6.3%; odds ratio 0.78, 95% confidence interval 0.41 to 1.49; P=0.45). CONCLUSIONS: This study suggests that the efficacy and safety of TF-TAVI entirely managed by a PCI approach for selected patients are not different to those when TF-TAVI is performed with the attendance of a full anaesthesia care team. The PCI approach appears to be a safe and efficient clinical pathway, providing an appropriate and rational utilization of anaesthesiology resources, and could be used for the majority of TF-TAVI procedures.

Flanking residues are central to DO11.10 T cell hybridoma stimulation by ovalbumin 323-339.

T cell activation requires formation of a tri-molecular interaction between a major histocompatibility complex (MHC), peptide, and T cell receptor. In a common model system, the ovalbumin epitope 323-339 binds the murine class II MHC, I-A(d), in at least three distinct registers. The DO11.10 T cell recognizes the least stable of these, as determined by peptide-MHC dissociation rates. Using exogenous peptides and peptide insertions into a carrier protein in combination with IL-2 secretion assays, we show that the alternate registers do not competitively inhibit display of the active register four. In contrast, this weakly binding register is stabilized by the presence of n-terminal flanking residues active in MHC binding. The DO11.10 hybridoma is sensitive to the presence of specific wild-type residues extending to at least the P-3 peptide position. Transfer of the P-4 to P-2 flanking residues to a hen egg lysozyme epitope also presented by I-A(d) increases the activity of that epitope substantially. These results illustrate the inherent complexity in delineating the interaction of multiple registers based on traditional thermodynamic measurements and demonstrate the potential of flanking residue modification for increasing the activity of weakly bound epitopes. The latter technique represents an alternative to substitution of anchor residues within a weakly bound register, which we show can significantly decrease the activity of the epitope to a responding T cell.

Microarrays in infection and immunity.

Over the past decade, microarrays have revolutionized the scientific world as dramatically as the internet has changed everyday life. From the initial applications of DNA microarrays to uncover gene expression patterns that are diagnostic and prognostic of cancer, understanding the interplay between immune responses and disease has been a prime application of this technology. More recent efforts have moved beyond genetic analysis to functional analysis of the molecules involved, including identification of immunodominant antigens and peptides as well as the role of post-translational glycosylation. Here, we focus on recent applications of microarray technology in understanding the detailed chemical biology of immune responses to disease in an effort to guide development of vaccines and other protective therapies.

Toxic concentrations of exogenously supplied methylglyoxal in hybridoma cell culture.

Concentrations at which methylglyoxal, a by-product of cellular metabolism, can be toxic to hybridoma cell cultures were determined using exogenously supplied doses. Trypan blue cell counts of 6-well cultures incubated for 24 h with various methylglyoxal concentrations revealed inhibition of cell growth at 300 muM and higher, with a median inhibitory concentration of 490+/-20 muM. The primary mode of death was apoptosis, as assessed by chromatin condensation, and the effects of methylglyoxal were observed to be complete by approximately eight hours. Yet, the impact of methylglyoxal was a function of the rate of dosing; stepwise addition of MG during the first 6 h of incubation inhibited growth but caused much less cell death than a comparable bolus dose. Inhibition of cellular metabolism by MG was found to coincide with inhibition of cell growth, with a comparable median inhibitory concentration of 360+/-20 muM. The effects on viable cell density and metabolism were both linear at doses approaching zero, with lowest observable effect levels of 54 and 77 muM, respectively. These results provide quantitative estimates for concentrations of methylglyoxal that may be inhibitory to biopharmaceutical-producing cell lines.