205 research outputs found

    UA3/3/1 Analysis of the Demand for Married Student Housing at WKU, 1966-1967

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    The purpose of this study is to bring forth relevant information needed to determine the feasibility of an investment project for a married student housing complex on the campus of Western Kentucky University. Only the demand side of the market is analyzed; a potential investor will have the construction and land costs for such an enterprise at his disposal. With the information presented in this study it is hoped that a decision to construct a housing complex will be forthcoming. The study group attempted to present information that will allow a potential investor to make an intelligent decision as to the profitability of the investment. It is hoped that the critical questions concerning the investment have been answered by this study. The time period in which the study was carried out was January, 1967 to June, 1967, i.e., the second semester of the 1966-67 school year. The information presented was obtained from a single sample of the married population. Seventy married family units (8.4 percent of the population) were stratified according to class standing (Freshman, Sophomore, Junior, Senior, and Graduate) and then picked randomly within the class stratifications. A more desirable method would have been a sequential sampling method, but the time and expense of the method did not allow its use. Future studies can be carried out in order to substantiate the data presented at this time. The estimated size of the investment would seem to warrant at least one more comprehensive examination of the market in order that a more exact market character can be determined. The study group contacted state institutions that have married housing units in order to see if any useful information could be obtained from their experience in the determination of market character and size of their married students. None of the schools contacted had conducted a market study prior to the construction of such a housing unit. Discovering this factor did not disturb the study group. It was assumed that the market character at the various educational institutions would be significantly different with reference to income, rent, family size, etc., that no useful comparison could be made. The reason for this assumption rests on the fact that the educational institutions differ in such things as type and size of the graduate program and community size and industrial development. These factors have a direct influence on the family unit\u27s income, numbers, and the rate of growth of the married student body. The purpose of contacting the various institutions was to examine the methodology used in the study of the market for married student housing

    Quantifying Intramolecular Binding in Multivalent Interactions: A Structure-Based Synergistic Study on Grb2-Sos1 Complex

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    Numerous signaling proteins use multivalent binding to increase the specificity and affinity of their interactions within the cell. Enhancement arises because the effective binding constant for multivalent binding is larger than the binding constants for each individual interaction. We seek to gain both qualitative and quantitative understanding of the multivalent interactions of an adaptor protein, growth factor receptor bound protein-2 (Grb2), containing two SH3 domains interacting with the nucleotide exchange factor son-of-sevenless 1 (Sos1) containing multiple polyproline motifs separated by flexible unstructured regions. Grb2 mediates the recruitment of Sos1 from the cytosol to the plasma membrane where it activates Ras by inducing the exchange of GDP for GTP. First, using a combination of evolutionary information and binding energy calculations, we predict an additional polyproline motif in Sos1 that binds to the SH3 domains of Grb2. This gives rise to a total of five polyproline motifs in Sos1 that are capable of binding to the two SH3 domains of Grb2. Then, using a hybrid method combining molecular dynamics simulations and polymer models, we estimate the enhancement in local concentration of a polyproline motif on Sos1 near an unbound SH3 domain of Grb2 when its other SH3 domain is bound to a different polyproline motif on Sos1. We show that the local concentration of the Sos1 motifs that a Grb2 SH3 domain experiences is approximately 1000 times greater than the cellular concentration of Sos1. Finally, we calculate the intramolecular equilibrium constants for the crosslinking of Grb2 on Sos1 and use thermodynamic modeling to calculate the stoichiometry. With these equilibrium constants, we are able to predict the distribution of complexes that form at physiological concentrations. We believe this is the first systematic analysis that combines sequence, structure, and thermodynamic analyses to determine the stoichiometry of the complexes that are dominant in the cellular environment

    14-3-3ζ Interacts with Stat3 and Regulates Its Constitutive Activation in Multiple Myeloma Cells

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    The 14-3-3 proteins are a family of regulatory signaling molecules that interact with other proteins in a phosphorylation-dependent manner and function as adapter or scaffold proteins in signal transduction pathways. One family member, 14-3-3ζ, is believed to function in cell signaling, cycle control, and apoptotic death. A systematic proteomic analysis done in our laboratory has identified signal transducers and activators of transcription 3 (Stat3) as a novel 14-3-3ζ interacting protein. Following our initial finding, in this study, we provide evidence that 14-3-3ζ interacts physically with Stat3. We further demonstrate that phosphorylation of Stat3 at Ser727 is vital for 14-3-3ζ interaction and mutation of Ser727 to Alanine abolished 14-3-3ζ/Stat3 association. Inhibition of 14-3-3ζ protein expression in U266 cells inhibited Stat3 Ser727 phosphorylation and nuclear translocation, and decreased both Stat3 DNA binding and transcriptional activity. Moreover, 14-3-3ζ is involved in the regulation of protein kinase C (PKC) activity and 14-3-3ζ binding to Stat3 protects Ser727 dephosphorylation from protein phosphatase 2A (PP2A). Taken together, our findings support the model that multiple signaling events impinge on Stat3 and that 14-3-3ζ serves as an essential coordinator for different pathways to regulate Stat3 activation and function in MM cells

    Factors That Drive Peptide Assembly and Fibril Formation: Experimental and Theoretical Analysis of Sup35 NNQQNY Mutants

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    Residue mutations have substantial effects on aggregation kinetics and propensities of amyloid peptides and their aggregate morphologies. Such effects are attributed to conformational transitions accessed by various types of oligomers such as steric zipper or single β-sheet. We have studied the aggregation propensities of six NNQQNY mutants: NVVVVY, NNVVNV, NNVVNY, VIQVVY, NVVQIY, and NVQVVY in water using a combination of ion-mobility mass spectrometry, transmission electron microscopy, atomic force microscopy, and all-atom molecular dynamics simulations. Our data show a strong correlation between the tendency to form early β-sheet oligomers and the subsequent aggregation propensity. Our molecular dynamics simulations indicate that the stability of a steric zipper structure can enhance the propensity for fibril formation. Such stability can be attained by either hydrophobic interactions in the mutant peptide or polar side-chain interdigitations in the wild-type peptide. The overall results display only modest agreement with the aggregation propensity prediction methods such as PASTA, Zyggregator, and RosettaProfile, suggesting the need for better parametrization and model peptides for these algorithms

    Technology and the Era of the Mass Army

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    Problems with using mechanisms to solve the problem of extrapolation

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    Mudança científica: modelos filosóficos e pesquisa histórica

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