Computer simulations play a profound and fundamental role inmodern theoretical physics, chemistry and materials science. Tounderstand the complex physics of metally liquids, metals,quasicrystals and metally glasses a working model imposing thelocal and global order is needed. Experiments and theory havepredicted the local order in liquid metals to beicosahedral. The current work has been done using molecular dynamicscomputer simulations of a monatomic system using a simplepair-potential for the interactions. Two new pair-potentialshas been developed, the Zetterling-1(Z1) and Zetterling-2(Z2)potentials. They are specifically modeled to impose icosahedralorder. The basis for the development of the potentials was theold Dzugutov potential which is known to freeze into adodecagonal quasicrystal. The new Zetterling potentials have alonger interaction range and a narrower first minimum. The morenarrow first minimum will enhance the local icosahedralordering and the longer interaction range was introduced toincorporate a second maximum in the potential mimicing theFriedel oscillations found in metallic systems. These Friedeloscillations are due to the singularity which arises at theFermi surface due to the screening of the positive charge bythe electron gas. Five papers are included in the study. The first two papersare studies of icosahedral clustering in the liquid andsupercooled liquid. The simulations in Paper I was done usingthe old Dzugutov potential while the new potentials were usedin Paper II using both molecular dynamics and the Basin Hoppingalgorithm presented in Chapter 5. Paper III considers theconcept of dynamical ergodicity in the context of thesuper-cooled liquid behaviour. The simulations were made usingthe old Dzugutov potential. Paper IVr eports a moleculardynamics simulation using the Dzugutov potential undersuper-cooling. A formation of icosahedrally structured domainswith distinctly slow diffusion which grows with cooling in alow-dimensional manner and percolate around Tc, the criticaltemperature of the mode-coupling theory. A sharp slowing downof the structural relaxation relative to diffusion is observed.It is concluded that this effect cannot be accounted for by thespatial variation in atomic mobility. The low-dimensionalclustering is discussed as a possible mechanism of fragility.Paper Vin vestigates the crystallization of a simple monatomicliquid model which utilizes the Zetterling-1 potential. Thesystem forms a thermodynamically stable solid phase exhibitingcubic symmetry. Its diffraction pattern is identified as thatof γ-brass, a tetrahedrally packed crystalline structurewith 52 atoms in the unit cell. <b>Keywords:</b>simple liquids, molecular dynamics, pairpotential, icosahedral cluster.

<p>Computer simulations play a profound and fundamental role inmodern theoretical physics, chemistry and materials science. Tounderstand the complex physics of metally liquids, metals,quasicrystals and metally glasses a working model imposing thelocal and global order is needed. Experiments and theory havepredicted the local order in liquid metals to beicosahedral.</p><p>The current work has been done using molecular dynamicscomputer simulations of a monatomic system using a simplepair-potential for the interactions. Two new pair-potentialshas been developed, the Zetterling-1(Z1) and Zetterling-2(Z2)potentials. They are specifically modeled to impose icosahedralorder. The basis for the development of the potentials was theold Dzugutov potential which is known to freeze into adodecagonal quasicrystal. The new Zetterling potentials have alonger interaction range and a narrower first minimum. The morenarrow first minimum will enhance the local icosahedralordering and the longer interaction range was introduced toincorporate a second maximum in the potential mimicing theFriedel oscillations found in metallic systems. These Friedeloscillations are due to the singularity which arises at theFermi surface due to the screening of the positive charge bythe electron gas.</p><p>Five papers are included in the study. The first two papersare studies of icosahedral clustering in the liquid andsupercooled liquid. The simulations in Paper I was done usingthe old Dzugutov potential while the new potentials were usedin Paper II using both molecular dynamics and the Basin Hoppingalgorithm presented in Chapter 5. Paper III considers theconcept of dynamical ergodicity in the context of thesuper-cooled liquid behaviour. The simulations were made usingthe old Dzugutov potential. Paper IVr eports a moleculardynamics simulation using the Dzugutov potential undersuper-cooling. A formation of icosahedrally structured domainswith distinctly slow diffusion which grows with cooling in alow-dimensional manner and percolate around Tc, the criticaltemperature of the mode-coupling theory. A sharp slowing downof the structural relaxation relative to diffusion is observed.It is concluded that this effect cannot be accounted for by thespatial variation in atomic mobility. The low-dimensionalclustering is discussed as a possible mechanism of fragility.Paper Vin vestigates the crystallization of a simple monatomicliquid model which utilizes the Zetterling-1 potential. Thesystem forms a thermodynamically stable solid phase exhibitingcubic symmetry. Its diffraction pattern is identified as thatof γ-brass, a tetrahedrally packed crystalline structurewith 52 atoms in the unit cell.</p><p><b>Keywords:</b>simple liquids, molecular dynamics, pairpotential, icosahedral cluster.</p>

Indiana University-Purdue University Indianapolis (IUPUI) / The innate and adaptive immune responses are critical for host survival. The TNFα/NF-κB signaling pathway is a major regulator of the immune response. The TNFα/NF-κB signaling pathway has also been proposed to play a role in the regulation of hematopoiesis. In the TNFα signaling pathway, full induction of NF-κB (specifically the p65 subunit) dependent transcription is regulated by a co-activator SIMPL. The biological significance of SIMPL in TNFα dependent responses is poorly understood. To study SIMPL in vitro and in vivo in mammalian cells, a knockdown system utilizing shRNA (short hairpin RNA) was used. Analysis of hematopoietic progenitor cells infected with a retrovirus encoding the SIMPL shRNA was used to study the role of SIMPL in hematopoiesis. The ability of progenitor cells lacking SIMPL to grow and differentiate was not compromised. In contrast in the progenitors cells lacking SIMPL, TNFα mediated inhibition of colony formation was significantly enhanced. These growth inhibitory effects of SIMPL were not due to an increase in apoptosis. The enhanced inhibitory affects were specific for TNFα and not found in other common hematopoietic inhibitors (TGF-β1 and IFNγ). Results of this work reveal that SIMPL is a component of the hematopoiesis that is required for TNFα dependent effects upon myeloid progenitors.

Indiana University-Purdue University Indianapolis (IUPUI) / SIMPL is a transcriptional co-activator that alters the activity of transcription factor, NF-κB. In response to pathogens, cytokines such as Interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF) signal through the IL-1 and TNF-α receptors, respectively, which are found on various cell types. Activation of these receptors can result in the nuclear localization of NF-κB where it enables the transcription of several different genes key in the innate immune response. Endogenous co-localization of the SIMPL protein with NF-κB in response to these same cytokine signals has yet to be demonstrated. Polyclonal antibody generated against a truncated version of the SIMPL protein was purified from the sera obtained from immunized rabbits using affinity chromatography. The antibody was found to have a high specificity for both the native and denatured form of the protein as demonstrated by the lack of nonspecific bands observed in immunoprecipitations and Western blotting. The antibody was utilized in immunofluorescence experiments on mouse endothelial cells that were either unstimulated or were stimulated (IL-1 or TNF-α). In the absence of cytokine, SIMPL was localized in both the cytoplasm and the nucleus as opposed to NF-κB which was almost exclusively localized in the cytoplasm. In the presence of IL-1, the concentration of SIMPL in the nucleus was increased, and in the presence of TNF-α, the concentration of SIMPL in the nucleus was even greater. Results of this study identified future routes for SIMPL antibody isolation as well as to demonstrate that endogenous SIMPL protein nuclear localization may not be solely dependent upon TNF-α signaling.