Aviation spirit - past, present, and future

The volatile fuel of the high-speed internal combustion engine has, in the past, consisted almost exclusively of the lighter distillates from crude petroleum. Alternative and supplementary fuels are discussed such as: tetraline, dekalin, alcohol, cyclo-hexenes

Disordered proteins mitigate the temperature dependence of site-specific binding free energies

Biophysical characterization of protein-protein interactions involving disordered proteins is challenging. A common simplification is to measure the thermodynamics and kinetics of disordered site binding using peptides containing only the minimum residues necessary. We should not assume, however, that these few residues tell the whole story. Son of sevenless (Sos), a multidomain signaling protein from Drosophila melanogaster, is critical to the mitogen-activated protein kinase pathway, passing an external signal to Ras, which leads to cellular responses. The disordered 55 kDa C-terminal domain of Sos is an auto-inhibitor that blocks guanidine exchange factor activity. Activation requires another protein, Downstream of receptor kinase (Drk), which contains two Src homology 3 (SH3) domains. Here, we utilize nuclear magnetic resonance spectroscopy and isothermal titration calorimetry to quantify the thermodynamics and kinetics of the N-terminal SH3 domain binding to the strongest sites incorporated into the flanking disordered sequences. Comparing these results to those for isolated peptides provides information about how the larger domain affects binding. The affinities of sites on the disordered domain are like those of the peptides at low temperatures but less sensitive to temperature. Our results, combined with observations showing that IDPs become more compact with increasing temperature, suggest a mechanism for this effect

DISORDERED PROTEINS IN VITRO AND IN CELLS

One requirement for the survival and reproduction of living organisms is the ability to receive external stimuli and then respond appropriately. It is increasingly understood that intrinsically disordered proteins are key to many of these biological processes, providing a flexible foundation that allow cells to coordinate and tune signal transduction cascades. To understand how these proteins behave and function, researchers from diverse intellectual backgrounds have examined their biological functions, physical properties, and interactions with other species. My dissertation is an attempt to build on prior research and integrate knowledge of intrinsically disordered proteins within the field of macromolecular crowding—i.e., how the packing of many biological molecules inside of a single cell impact protein and protein-complex stability. I first discuss intrinsically disordered proteins and their properties and predict what types of disordered protein properties might be affected by macromolecular crowding. I then examine mitogen-activated protein kinase pathway signaling through the lens of Epidermal Growth Factor signaling to highlight some of the biological roles that disordered proteins perform. I quantify the binding between the C-terminal tail of Son of sevenless and its native SH3-binding domain partner and demonstrate that precise quantification is possible even when the disordered domain is extended. I then demonstrate an improved method for eukaryotic in-cell NMR for quantifying the effects of the cytoplasm on protein and protein-complexes in living cells. Finally, I provide comments regarding questions and experiments that I attempted thought my PhD training that will hopefully provide assistance for researchers who come after me. Overall, the perspectives and results in this document provide a roadmap for those who want to study disordered proteins in complex and crowded environments. Our understanding of disordered protein properties will continue to evolve, and I attempt to highlight relevant questions and areas researchers interested in developing macromolecular crowding theories must address and provide a foundation for the actual biological processes that underlie disordered protein function.Doctor of Philosoph

Magnetic circular dichroism of x-ray absorption spectroscopy at rare-earth L2,3 edges in RE2Fe14B compounds (RE = La, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu)

Magnetic circular dichroism (MCD) in the x-ray absorption spectroscopy (XAS) at the L2,3 edges for almost entire series of rare-earth (RE) elements in RE2Fe14B, is studied experimentally and theoretically. By a quantitative comparison of the complicated MCD spectral shapes, we find that (i) the 4f-5d intra-atomic exchange interaction not only induces the spin and orbital polarization of the 5d states, which is vital for the MCD spectra of the electric dipole transition from the 2p core states to the empty 5d conduction band, but also it accompanies a contraction of the radial part of the 5d wave function depending on its spin and orbital state, which results in the enhancement of the 2p-5d dipole matrix element, (ii) there are cases where the spin polarization of the 5d states due to the hybridization with the spin polarized 3d states of surrounding irons plays important roles, and (iii) the electric quadrupole transition from the 2p core states to the magnetic vale! nce 4f states is appreciable at the pre-edge region of the dipole spectrum. Especially, our results evidence that it is important to include the enhancement effect of the dipole matrix element in the correct interpretation of the MCD spectra at the RE L2,3 edges.Comment: 9 pages, 5 figures, 1 table, REVTe

Improving Male Partner Involvement in HIV-Positive Women's Care Through Behavioral Change Interventions in Malawi (WeMen Study): A Prospective, Controlled Before-and-After Study

Several strategies and interventions have been implemented to improve male partner involvement (MI) in Sub-Saharan Africa, but evidence on successful interventions is scarce. This controlled before-and-after intervention study aims to evaluate the impact of three interventions on male partners' involvement in HIV+ women's care in Malawi. We piloted these three interventions: the organization of a special day for men, the deployment of male champions in communities to increase awareness on MI, and the delivery of an incentive (food package) for couples attending the facility. We observed a significant increase in the number of women accompanied by their partners (from 48.5 to 81.4%) and the number of women feeling safe at home (from 63.5 to 95.2%) after the special day intervention. This outcome increased after the deployment of male champions in communities (from 44.0 to 75.0%). No significant improvement was observed in the site where we delivered the incentive to couples. Our findings showed that the special day for men and the use of male champions might effectively increase the male involvement in the health of their female partners

Band-theoretical prediction of magnetic anisotropy in uranium monochalcogenides

Magnetic anisotropy of uranium monochalcogenides, US, USe and UTe, is studied by means of fully-relativistic spin-polarized band structure calculations within the local spin-density approximation. It is found that the size of the magnetic anisotropy is fairly large (about 10 meV/unit formula), which is comparable with experiment. This strong anisotropy is discussed in view of a pseudo-gap formation, of which crucial ingredients are the exchange splitting of U 5f states and their hybridization with chalcogen p states (f-p hybridization). An anomalous trend in the anisotropy is found in the series (US>>USe<UTe) and interpreted in terms of competition between localization of the U 5f states and the f-p hybridization. It is the spin-orbit interaction on the chalcogen p states that plays an essential role in enlarging the strength of the f-p hybridization in UTe, leading to an anomalous systematic trend in the magnetic anisotropy.Comment: 4 pages, 5 figure

Estrogen-Receptor Expression and Function in Thymocytes in Relation to Gender and Age

The expression of estrogen receptor (ER) in thymocytes was studied in young, middle-aged, and old (2, 12, and 24 months, respectively) female and male C57BL/6J mice. Western immunoblots prepared from the thymocytes of females of all age groups showed the presence of a 67-kD protein band, which has been associated with the apparent MW of denatured ER. Flow cytometry analysis o,f cells stained with a monoclonal anti-ER antibody (clone 13H2) disclosed ER expression in both females and males of all age groups. In vivo treatment with estradiol (E2) led to an increase in the specific activity of thymic creatine kinase (CK) in the female mice, whereas the male thymocytes responded with an increase in CK activity only on treatment with dihydrotestosterone (DHT). The data show no differences in ER expression between male and females, but the receptor appears not to be functional in males. Interestingly, when estradiol was applied to co-cultures of lymphoid-depleted fetal thymus (FT) explants and bone-marrow cells, or thymocytes, from young and old females, it resulted in increased cellularity of cultures containing cells of the young, and not those of the old. The proportion of CD4/CD8 phenotypes of the developing cells in these cultures was not affected by E2 treatment. These observations provide a new insight into ER expression and function in T-cell development in relation to gender and age

Observation of magnetic circular dichroism in Fe L_{2,3} x-ray-fluorescence spectra

We report experiments demonstrating circular dichroism in the x-ray-fluorescence spectra of magnetic systems, as predicted by a recent theory. The data, on the L_{2,3} edges of ferromagnetic iron, are compared with fully relativistic local spin density functional calculations, and the relationship between the dichroic spectra and the spin-resolved local density of occupied states is discussed

On-site correlation in valence and core states of ferromagnetic nickel

We present a method which allows to include narrow-band correlation effects into the description of both valence and core states and we apply it to the prototypical case of nickel. The results of an ab-initio band calculation are used as input mean-field eigenstates for the calculation of self-energy corrections and spectral functions according to a three-body scattering solution of a multi-orbital Hubbard hamiltonian. The calculated quasi-particle spectra show a remarkable agreement with photoemission data in terms of band width, exchange splitting, satellite energy position of valence states, spin polarization of both the main line and the satellite of the 3p core level.Comment: 14 pages, 10 PostScript figures, RevTeX, submitted to PR

Direct observation of electron doping in La0.7Ce0.3MnO3 using x-ray absorption spectroscopy

We report on a X-ray absorption spectroscopic (XAS) study on a thin film of La0.7Ce0.3MnO3, a manganite which was previously only speculated to be an electron doped system. The measurements clearly show that the cerium is in the Ce(IV) valence state and that the manganese is present in a mixture of Mn2+ and Mn3+ valence states. These data unambiguously demonstrate that La0.7Ce0.3MnO3 is an electron doped colossal magnetoresistive manganite, a finding that may open up new opportunities both for device applications as well as for further basic research towards a better modelling of the colossal magnetoresistance phenomenon in these materials.Comment: 4 pages, 3 figures, revised versio