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In this presentation I will describe our efforts at understanding how molecular properties of proteins determine fitness landscape of populations of carrier organisms. Recent multi-scale evolutionary models, which assume certain relationship between organismal fitness and stability of their proteins, have been successful in predicting such biological phenomena as lethal mutagenesis (six mutations per genome per generation), distributions of protein stabilities (“marginal” protein stability being a consequence of a mutation-selection balance), correlation between evolutionary rates and abundances. However, many of the underlying assumptions of these models have not been tested experimentally. Our recent efforts aim to close this gap. We explored fitness landscape of E.coli through controlled rational mutational genomic perturbations of expression level and stability of an essential protein Dihydrofolate Reductase (DHFR). To that end we created transgenic E.coli, which carry specified chromosomally incorporated mutations in the folA gene encoding DHFR and also placed the folA gene under an IPTG controllable promoter, making it possible to change the intracellular abundance of DHFR in a wide range. Using competition essays, we measured how biological fitness depends on biophysical properties of chromosomally incorporated mutant DHFR such as their abundance in the cytoplasm, stability of its native state and folding intermediate, and catalytic activity. Mutant DHFR proteins in a few strains aggregated rendering them nonviable but the majority exhibited fitness higher than wild type at a growth temperature of 42oC. We found that mutational destabilization of DHFR proteins in E. coli is counterbalanced by soluble oligomerization that restores their structural stability and protects from aggregation. Further, we found that protein homeostasis plays a defining role in sculpting fitness effect of mutations. In particular, overexpression of GroEL as well as deletion of one of the proteases, Lon, resulted in complete recovery of fitness of unviable strains. Further study, including in vitro essays of ANS binding showed that GroEL and Lon compete for folding intermediate of DHFR and their relative concentrations determines the outcome. We developed a computational model to analyze this competition, which lead us to the conclusion that our observations cannot be reconciled with GroEL role as just caging device to protect DHFR mutants from aggregation and proteolysis. Rather, it must play an active role in converting intermediate to folded molecules.

The study of nuclei with equal numbers of neutrons and protons (N = Z) is one of the declared objectives of radioactive-ion-beam facilities. Currently, N=Z experiments are approaching 100Sn, involving studies of nuclei where nucleons are dominantly confined to the 1g9/2 orbit. In this talk it is shown that the aligned neutron-proton pair with angular momentum J=9 and isospin T=0 plays a central role in the low-energy spectroscopy of the N~Z nuclei in this mass region. This observation is made by analyzing shell-model wave functions in terms
of a variety of two-nucleon pairs with different angular momentum J and isospin T. On the basis of these results one concludes that a simple model can be formulated in terms of b (i.e., aligned J=9) bosons. Due to its simplicity, such a model could be of use to elucidate the main structural features of N~Z nuclei in this mass region. Examples of simple predictions resulting from this approach are discussed.

Positron Annihilation Spectroscopy (PAS) includes well-established research methods used in the fields of solid state physics, chemistry, materials science and materials engineering. The sensitivity of PAS methods to point defects as small as mono-vacancies, in concentrations as low as 10-6 a-1, make them perfect tools to study radiation damage in its first stages of creation. Especially, Positron Annihilation Lifetime Spectroscopy (PALS) is sensitive to size and concentration of the point defects and Coincidence Doppler Broadening (CDB) can probe changes in defect characteristics as well as electron momenta in the lattice.

The basic measuring concepts of PAS methods will be presented, together with a detailed description of the PALS measuring system at NRCN. The data collection and analysis tools, adopted from nuclear experimental methods, lead to time resolution of ~140 ps, which is the state of the art in this field.

Research goals are motivated by the need to understand first stages of radiation damage in materials, in order to predict macroscopic characteristics of materials with accumulated damage.

Abstract:
The focus of this lecture is on how computational chemistry helps the understanding and design of organometallic reactions. Later exemplification of the underlying concept will be used to create new frameworks by Csp2-Csp2 coupling catalyzed by palladium and iron complexes. A particular attention will be devoted to the relationship between oxidation states and mechanistic possibilities. It will be shown that unusual oxidation state are perhaps more usable than usually thought.

I will describe the use of AdS/CFT methods to the study of the evolution of strongly coupled boost-invariant plasma starting from generic initial conditions at tau=0, through a phase of far-from equilibrium expansion and into the hydrodynamic regime.
I will describe the numerical relativity formulation as well as some surprising regularities in the observed characteristics of thermalization understood here as the transition to hydrodynamics.