Multiscale, mechanistic model of Rheumatoid Arthritis to enable decision making in late stage drug development.

Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease that affects about 0.1% to 2% of the population worldwide. Despite the development of several novel therapies, there is only limited benefit for many patients.

A spiking Basal Ganglia model of synchrony, exploration and decision making.

To make an optimal decision we need to weigh all the available options, compare them with the current goal, and choose the most rewarding one. Depending on the situation an optimal decision could be to either "explore" or "exploit" or "not to take any action" for which the Basal Ganglia (BG) is considered to be a key neural substrate. In an attempt to expand this classical picture of BG function, we had earlier hypothesized that the Indirect Pathway (IP) of the BG could be the subcortical substrate for exploration.

Modeling the contributions of Basal ganglia and Hippocampus to spatial navigation using reinforcement learning.

A computational neural model that describes the competing roles of Basal Ganglia and Hippocampus in spatial navigation is presented. Model performance is evaluated on a simulated Morris water maze explored by a model rat. Cue-based and place-based navigational strategies, thought to be subserved by the Basal ganglia and Hippocampus respectively, are described.

On the neural substrates for exploratory dynamics in basal ganglia: a model.

We present a neural network model of basal ganglia that departs from the classical Go/NoGo picture of the function of its key pathways-the direct pathway (DP) and the indirect pathway (IP). In classical descriptions of basal ganglia function, the DP is known as the Go pathway since it facilitates movement and the IP is called the NoGo pathway since it inhibits movement. Between these two regimes, in the present model, we posit that there is a third Explore regime, which denotes random exploration of the space of actions.

Modelling of the regulation of the hilA promoter of type three secretion system of Salmonella enterica serovar Typhimurium.

One of the most common modes of secretion of toxins in gram-negative bacteria is via the type three secretion system (TTSS), which enables the toxins to be specifically exported into the host cell. The hilA gene product is a key regulator of the expression of the TTSS located on the pathogenicity island (SPI-1) of Salmonella enterica serovar Typhimurium. It has been proposed earlier that the regulation of HilA expression is via a complex feedforward loop involving the transactivators HilD, HilC and RtsA.