A High Throughput Assay for the Detection of Stimulator of Interferon Genes (STING) Agonists

The innate immune system includes a menagerie of different cell types, each with a different role in the process of monitoring the body for invaders and presenting gathered debris (antigen) to the adaptive immune system. Somatic cells have intracellular receptors for the same purpose. Cancer cells, however, have avoided these methods of detection despite, in many cases, the tumor’s immunogenic traits. Immuno-oncology is a field dedicated to the immunological traits of tumors, more recently finding ways of instigating an immune response against tumors. In this regard, STING, a receptor of cyclic dinucleotides (CDN), has come to the forefront of immuno-oncology. Activation of STING has been shown to induce profound CD8 T cell-led immune reaction against immunologically suppressed tumors, as well as a memory response upon rechallenge and abscopal response. Most importantly, its simplistic method of activation (intratumoral administration of CDN, with current research formulations exploring the IV route) has scientists clamoring for a CDN mimetic or molecule that likewise activates STING. Currently, numerous pharmaceutical companies have synthesized STING agonists, with some deviating from the canonical CDN formulation. These non-CDN molecules represent the next generation of STING agonists. This thesis set out to develop an efficient screen to discover next generation STING agonists within a commercial compound deck

Testing and evaluation of nickel-cadmium spacecraft-type cells Final technical report, 6 May 1966 - 6 May 1967

Cycle life testing and evaluation of nickel- cadmium spacecraft batteries - voltage characteristic

SSBBR-X: Candidate Engine for Concorde

Advances in each component of a low bypass ratio turbofan were considered to improve the performance for Concorde’s mission. The bypass fan will feature a multi-stage design intended to increase pressure ratio and exit velocity of the bypass air to speeds exceeding cruising speed. The multi-stage fan will allow a variable bypass design to be utilized for optimization in different flight regimes. Preliminary research suggests that using a bypass ratio of around 1.0 will be feasible to implement in the design. The exit nozzle will be a variable converging-diverging nozzle to allow for necessary mass flow at different velocities, which is now an industry standard. Compressors of the past have been high in weight with limited pressure ratios, but by using new technologies currently available and new materials proposed to be available, compressors can be lighter and have higher-pressure ratios per stage. Using a bladed disk (or blisk) alone can lead to a weight savings up to 30% and new materials have been proven to have higher operating temperatures, allowing for higher efficiency and thrust for the entire system. New research has proposed a redesign of the burner-turbine system which would reduce the turbine inlet temperatures as well as increase efficiency and thrust. This new system is the Inter-Turbine Burner (ITB) which adds a second combustion chamber in between the high and low-pressure turbine stages. The effect of an ITB is to burn the fuel from the first burner and use all the remaining oxygen in the system. The ITB system eliminates the need for cooling channels in the turbine blades, which subsequently eliminates the need for a cooling system and bleed valves. This reduces the high complexity and weight of turbines while simultaneously reducing the cost of manufacturing traditional blades. Traditional blades are made of superalloys that are manufactured by casting a one direction crystal structure in the metal. New methods for manufacturing blades have been proposed, consisting of using additive manufacturing and advancements in composite materials. Using composites and additive manufacturing, turbine blades can be made with a high tolerance to temperature, which will decrease the TSFC as well as cost. These systems were tested using parametric cycle analysis implemented in MATLAB, VuCalc, GasTurb13, and AxSTREAM to effectively compare their impact on the entire engine and gauge whether any combination of the new component technologies will be ready for a 2028 entry-into-service date. This analysis is a precursor to a different AIAA design competition with the purpose of designing engines to replace those on the Concorde aircraft. The results of this engine will be compared to Concorde’s original Olympus 593 engines to determine if better performance was achieved

Opponent-process additivity--I: Red/green equilibria

A red/green equilibrium light is one which appears neither reddish nor greenish (i.e. either uniquely yellow, uniquely blue, or achromatic). A subset of spectral and nonspectral red/green equilibria was determined for several luminance levels, in order to test whether the set of all such equilibria is closed under linear color-mixture operations.The spectral loci of equilibrium yellow and blue showed either no variation or visually insignificant variation over a range of 1-2 log10 unit. There were no trends that were repeatable across observers. We concluded that spectral red/green equilibria are closed under scalar multiplication; consequently they are invariant hues relative to the Bezold-Brucke shift.The additive mixture of yellow and blue equilibrium wavelengths, in any luminance ratio, is also an equilibrium light. Small changes of the yellowish component of a mixture toward redness or greeness must be compensated by predictable changes of the bluish component of the mixture toward greenness or redness. We concluded that yellow and blue equilibria are complementary relative to an equilibrium white; that desaturation of a yellow or blue equilibrium light with such a white produces no Abney hue shift; and that the set of red/green equilibria is closed under general linear operations.One consequence is that the red/green chromatic-response function, measured by the Jameson-Hurvich technique of cancellation to equilibrium, is a linear function of the individual's color-matching coordinates. A second consequence of linear closure of equilibria is a strong constraint on the class of combination rules by which receptor outputs are recoded into the red/green opponent process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22247/1/0000683.pd

Spectral Tuning of Opponent Channels is Spatially Dependent

Psychophysical detection and appearance data suggest that the spectral tuning of opponent pathways varies with test size. The present study examines the effect on spectral sensitivity of the relative size of test and surround fields. Increment thresholds and flashed‐field sensitivities were obtained for 580 nm and 641 nm targets. Three spatial configurations were used. The pattern of sensitivity loss is shown to depend on the spatial relation between test and field; the effect of the spatial relation in turn depends on test wavelength. The findings are explained by the activity of a changing network of spatially and spectrally opponent cells