Donor-Advised Funds: The Case for Consistent Principles

Each and every sponsoring organization maintaining donor-advised funds – as well as each donor – is subject to a host of requirements under existing law to ensure that charitable funds are used exclusively for charitable purposes. Beginning with the requirements of the “operational test” for tax exemption and continuing through focused penalty provisions (which are not yet fully implemented), the foundation is in place to enforce compliance and prevent abuses, with much room for additional regulatory guidance and enforcement. Ensuring that charitable funds are properly used depends on rigorous employment and enforcement of these rules of general application, and not on arbitrary classifications and labels imposed on sponsoring organizations

Gaining Understanding through Creativity: Comparison of the Understanding by Design Model and General Creativity Concepts

Results of the analysis presented here indicated that there are clusters of connections which suggest a moderate to strong link between the facets of Creativity and the facets of Understanding. Examining the facets of Perspective, Synthesis, Empathy, Application, Self-Knowledge, and Connect demonstrate the relationship appears to be a mutually supportive symbiosis between the Creativity and Understanding facets. This symbiosis from Creativity strengthens and supports the Understanding facets, and from Understanding strengthens and supports the Creativity facets

Modulating antibody-antigen binding by light

Antibodies are an important class of biomolecules that have contributed immensely to several fields including, medicine, diagnostics, and as an important biomolecule required for a plethora of scientific procedures. However, methods to control antibody-antigen binding using exogenous stimuli such as light remain limited. The use of antibodies in a therapeutic setting has become a dominant biological platform in the pharmaceutical market and has been successfully employed for the treatment of numerous diseases including autoimmune disorders, cancers, infections, and cardiovascular diseases. Cancer immunotherapeutics are often developed to target overexpressed antigens near tumour cells or on the surface of malignant cells. Often these disease targets are essential biological receptors that have developed mutations affecting expression levels or activity. Although highly expressed on targeted tumour cells, basal levels of targeted receptors can be present on healthy cells. Consequently, the reduced specificity of antigen targeting between healthy and diseased cells can cause severe side-effects of antibody therapeutics. By introducing methods to enable the spatiotemporal control of antibody-antigen binding affinities by light, an additional level of safety and improved targeting is achieved for these therapeutic molecules. The research performed in this thesis aimed to explore strategies and available technologies for the site-specific incorporation of designer amino acids with unique chemistries that could facilitate the spatiotemporal control over antibody-antigen binding with the use of external stimuli. A simple and robust method was designed for the genetic incorporation of photocaged tyrosine (pcY) into the structure of an anti-EGFR antibody fragment, 7D12. Subsequent techniques developed to evaluate light-mediated binding of 7D12 mutants to its target on the surface of cancer cells demonstrated binding inhibition with the presence of pcY in two positions, Y32pcY and Y113pcY and upon irradiation with 365 nm light and de-caging of pcY, binding was restored

The petrology and petrography of the igneous rocks of Riley County, Kansas

Call number: LD2668 .T4 1953 B7Master of Scienc

A New Global Regression Analysis Method for the Prediction of Wind Tunnel Model Weight Corrections

A new global regression analysis method is discussed that predicts wind tunnel model weight corrections for strain-gage balance loads during a wind tunnel test. The method determines corrections by combining "wind-on" model attitude measurements with least squares estimates of the model weight and center of gravity coordinates that are obtained from "wind-off" data points. The method treats the least squares fit of the model weight separate from the fit of the center of gravity coordinates. Therefore, it performs two fits of "wind- off" data points and uses the least squares estimator of the model weight as an input for the fit of the center of gravity coordinates. Explicit equations for the least squares estimators of the weight and center of gravity coordinates are derived that simplify the implementation of the method in the data system software of a wind tunnel. In addition, recommendations for sets of "wind-off" data points are made that take typical model support system constraints into account. Explicit equations of the confidence intervals on the model weight and center of gravity coordinates and two different error analyses of the model weight prediction are also discussed in the appendices of the paper

Site‐specific encoding of photoactivity in antibodies enables light‐mediated antibody‐antigen binding on live cells

Antibodies have found applications in several fields, including, medicine, diagnostics, and nanotechnology, yet methods to modulate antibody‐antigen binding using an external agent remain limited. Here, we have developed photoactive antibody fragments by genetic site‐specific replacement of single tyrosine residues with photocaged tyrosine, in an antibody fragment, 7D12. A simple and robust assay is adopted to evaluate the light‐mediated binding of 7D12 mutants to its target, epidermal growth factor receptor (EGFR), on the surface of cancer cells. Presence of photocaged tyrosine reduces 7D12‐EGFR binding affinity by over 20‐fold in two out of three 7D12 mutants studied, and binding is restored upon exposure to 365 nm light. Molecular dynamics simulations explain the difference in effect of photocaging on 7D12‐EGFR interaction among the mutants. Finally, we demonstrate the application of photoactive antibodies in delivering fluorophores to EGFR‐positive live cancer cells in a light‐dependent manner

Strength of Steel-to-Steel Screw Connections - Update to Provisions

The objective of this research was to review the existing provisions of the AISI S100-16 North American Specification for Cold-Formed Steel Structural Members [1], for screw connections loaded in shear and tension (but not combined actions). This study performed a comprehensive analysis of available steel-to-steel screw connection strength test data, totaling 702 shear tests, 143 pull-over tests, and 335 pull-out tests. The tested strength of these connections was compared to the predicted strength from the existing strength equations in the AISI S100-16 Standard. The validity of the existing equations was evaluated based on how well the predicted strengths matched the tested strengths. From this analysis, recommended adjustments to the equations, factors of safety, and/or resistance were determined and reported. This study found that the existing equations in AISI S100-16 for screw connections loaded in shear do not need to be revised, although the resistance factors for both LRFD and LSD could be increased. For the limit state of pull-over, the existing equations in AISI S100-16 do not need to be revised, while the resistance and safety factors for pull-over could be revised, with distinction between connections with ductile steel and connections with low-ductility steel. This study did not look at the effect of geometry on pull-over, and further investigation is recommended. For the limit state of pull-out, the analysis of available test data indicates that the current nominal strength prediction equation in AISI S100-16 should be revised by including an adjustment factor into the equation. The proposed adjustment factor results in increased usable strength in connections with sheet thickness greater than 0.04 inches. It was found that the pullout resistance factors could be increased slightly.This project was undertaken as an AISI Student Fellowship with funding provided by the American Iron and Steel Institute and the Steel Deck Institute

Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1. Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay. Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques