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A multitude of experiments over the past century have yielded deep insights into the cellular and synaptic organization of the microcircuitry of the neocortex and its possible role as a functional unit - a column of cells across 6 layers. The available data is, however, not standardized, is highly fragmented and often conflicting. More importantly, there are large gaps in our knowledge requiring an impractical number of experiments to fill. We therefore developed a strategy to accelerate a comprehensive analysis of the neocortical column by attempting to reconstruct it from partial information. We performed a spectrum of standardized biological experiments on strategic cellular and synaptic properties of the microcircuitry of the somatosensory cortex of a young rat and gathered further relevant data from previously published studies. We developed a generic supercomputer-based platform to build and simulate biologically-detailed brain models, and attempted to reconstruct a first draft of a unifying model at the cellular level of detail. The model integrates and unifies most of the current data, significantly predicts missing data, and provides a broad range of new insights into the structural and functional organization of neocortical microcircuitry. The model also serves as a virtual specimen for a new generation of simulation-based experimentation that can accelerate an integrated understanding of the cellular and synaptic basis of neocortical function.

Thousands of new neurons are generated daily during adult life but only a fraction of them survive, mature and incorporate into the neural circuits; the rest die, and their corpses are presumably cleared by other healthy cells. How the dying neurons are removed and how such clearance influences neurogenesis are not well understood. We identified an unexpected phagocytic role for the doublecortin (DCX)-positive neuronal progenitor cells during adult neurogenesis. Our in vivo and ex vivo studies demonstrate that DCX+ cells comprise of a significant phagocytic population within the neurogenic zones. Intracellular engulfment protein ELMO1, which promotes Rac activation downstream of phagocytic receptors, was required for phagocytosis by DCX+ cells. Disruption of engulfment in vivo genetically (in Elmo1-null mice) or pharmacologically (in wild type mice) led to reduced uptake by DCX+ cells, accumulation of apoptotic nuclei in the neurogenic niches, and impaired neurogenesis. Implication of this phenomenon could be relevant to clinical conditions associated with induced (stroke) or impaired (depression) neurogenesis.
We extended our studies of phagocytic activity to neurodevelopmental diseases, such as autistic spectrum disorders and Rett syndrome, in particular. We found that myeloid compartment of Rett mice is impaired in phagocytic activity. When myeloid compartment is replaced using bone marrow transplantation from wild-type bone marrow into Mecp2‒/y mice, the disease is arrested and life expectancy is increased by more than five-fold. Bone marrow transplantation results in engraftment of the brain parenchyma with wild type microglia-like cells, capable of clearing apoptotic debris load, which presumably allows more efficient neuronal function. Our data unexpectedly implicate myeloid cells in Rett pathology, and suggest that these immune cells might offer a feasible target for future therapeutic intervention for this devastating disease.

The accurate theoretical treatment and simulation of quantum dynamical processes in many-body systems is a central issue in chemical and condensed matter physics. In this talk, the multilayer multiconfiguration time-dependent Hartree (ML-MCTDH) method [1] is discussed as an example of an approach that allows an accurate description of quantum dynamics and transport in systems with many degrees of freedom. The ML-MCTDH method is a variational basis-set approach, which uses a multiconfiguration expansion of the wavefunction employing a multilayer representation and time-dependent basis functions. It extends the original MCTDH method [2] to significantly larger and more complex systems. Employing the second quantization representation of Fock space, the ML-MCTDH method has recently been extended to allow the treatment of indistinguishable particles [3,4]. Applications of the method to models for charge transport in molecular systems are discussed, in particular to photoinduced electron transfer at dye-semiconductor interfaces an electron transport in molecular junctions [4,5,6].

[1] H. Wang and M. Thoss, J. Chem. Phys. 119, 1289 (2003).
[2] H.-D. Meyer, U. Manthe, and L.S. Cederbaum, Chem. Phys. Lett. 165 , 73 (1990); H.-D. Meyer, F. Gatti, and G.A. Worth (Eds.), Multidimensional Quantum Dynamics: MCTDH Theory and Applications, Wiley-VCH, Weilheim, 2009.
[3] H. Wang and M. Thoss, J. Chem. Phys. 131, 024114 (2009).
[4] H. Wang, I. Pshenichnyuk, R. Härtle, M. Thoss, J. Chem. Phys. 135, 244506 (2011). [5] J. Li, I. Kondov, H. Wang, and M. Thoss, J. Phys. Chem. C 114, 18481 (2010).
[6] I. Craig, M. Thoss, and H. Wang, J. Chem. Phys. 135, 064504 (2011)

The radius of the proton, generally assumed to be a well measured and understood quantity has recently come under scrutiny due to highly precise, yet conflicting, experimental results. These new results have generated a host of interpretations, none of which are completely satisfactory. I will present a general overview to the topic, from the early measurements of the 1950s to the high precision experiments performed today. I will further discuss the various radii and measurements and present some of the attempted explanations for the discrepancies observed. Lastly, I will discuss a planned experiment at the Paul Scherrer Institute which may help shed new light on the issue.