An Overview of High Bandwidth Liquid Fuel Flow Modulators Developed for Active Combustion Control Research

This paper presents a description of the general construction of three high bandwidth liquid fuel modulators along with data corresponding to their respective modulation performance. These devices are a critical element of the National Aeronautics and Space Administration Glenn Research Center's (NASA GRC) Active Combustion Control (ACC) task. These devices are not commercially-off-the-shelf available, primarily due to a one kHz bandwidth requirement. Given their special nature, NASA GRC developed specifications for the modulation devices and then, through Small Business Innovative Research (SBIR) contracts, had vendors with expertise in valve design manufacture them. The modulators described in this paper are the Active Signal Modulator (ASM), the Jansen's Aircraft System Controls (JASC) modulator, and the WASK Engineering (WASK) modulator. These modulators utilize magnetostrictive, electric motor, or piezoelectric actuation, respectively. The specifications for these devices evolved over time to meet the needs of changing objectives in the ACC research task. This is primarily true with respect to flow number as their designs accommodate a range from one to eight (lbm./hr-psi0.5). These designs also exhibit relatively small volume, weight, and power consumption with an ability to modulate approximately +/- 30% from the mean on a pressure basis. The modulators have been characterized and have undergone laboratory performance tests by the vendors. Their data indicated suitability for continued use in ACC research testing

Combustion Dynamics Characteristics and Fuel Pressure Modulation Responses of a Three-Cup Third-Generation Swirl-Venturi Lean Direct Injection Combustion Concept

This paper presents the combustion dynamic data and fuel modulation response of a three-cup Lean Direct Injection combustor developed by Woodward, FST. The test was conducted at the NASA Glenn Research Center CE-5 flame tube test facility. The facility provided inlet air up to 922 K and pressure up to 19.0 bar. At the low-power configuration, the combustion noise was quiet. Large combustion pressure oscillations were observed with the High-power configuration at an off design condition, with low inlet air temperature and pressure conditions and a high equivalence ratio (about T3=600 K, P3 = 800 kPa, and ER =0.46). The noise amplitude was as high as 1.5 psi at around 220 Hz. As inlet air pressure and temperature increased, this combustion instability decreased. Fuel modulated signals were produced with the WASK fuel modulator located in the fuel line upstream of the center cup pilot fuel-air mixer. The amplitudes of the modulated signals detected in the combustor were low. Only less than 0.13% (0.06 psi) of the input energy was detected, and the signal amplitudes decreased as the modulated frequencies increased. Interaction between the modulated signals and the combustion noise varied with operating conditions. At a condition with low combustion noise around 150 hz, modulating a signal at around the same frequency would increase the combustion noise from 0.2 psi to as high as 0.6 psi, whereas at a condition with a high combustion instability around 250 hz, the modulated signal did not seem to have much effect on the combustion noise

Design and Implementation of a Characterization Test Rig for Evaluating High Bandwidth Liquid Fuel Flow Modulators

A test rig was designed and developed at the NASA Glenn Research Center (GRC) for the purpose of characterizing high bandwidth liquid fuel flow modulator candidates to determine their suitability for combustion instability control research. The test rig is capable of testing flow modulators at up to 600 psia supply pressure and flows of up to 2 gpm. The rig is designed to provide a quiescent flow into the test section in order to isolate the dynamic flow modulations produced by the test article. Both the fuel injector orifice downstream of the test article and the combustor are emulated. The effect of fuel delivery line lengths on modulator dynamic performance can be observed and modified to replicate actual fuel delivery systems. For simplicity, water is currently used as the working fluid, although future plans are to use jet fuel. The rig is instrumented for dynamic pressures and flows and a high-speed data system is used for dynamic data acquisition. Preliminary results have been obtained for one candidate flow modulator

Active Combustion Control for Aircraft Gas-Turbine Engines-Experimental Results for an Advanced, Low-Emissions Combustor Prototype

Lean combustion concepts for aircraft engine combustors are prone to combustion instabilities. Mitigation of instabilities is an enabling technology for these low-emissions combustors. NASA Glenn Research Center s prior activity has demonstrated active control to suppress a high-frequency combustion instability in a combustor rig designed to emulate an actual aircraft engine instability experience with a conventional, rich-front-end combustor. The current effort is developing further understanding of the problem specifically as applied to future lean-burning, very low-emissions combustors. A prototype advanced, low-emissions aircraft engine combustor with a combustion instability has been identified and previous work has characterized the dynamic behavior of that combustor prototype. The combustor exhibits thermoacoustic instabilities that are related to increasing fuel flow and that potentially prevent full-power operation. A simplified, non-linear oscillator model and a more physics-based sectored 1-D dynamic model have been developed to capture the combustor prototype s instability behavior. Utilizing these models, the NASA Adaptive Sliding Phasor Average Control (ASPAC) instability control method has been updated for the low-emissions combustor prototype. Active combustion instability suppression using the ASPAC control method has been demonstrated experimentally with this combustor prototype in a NASA combustion test cell operating at engine pressures, temperatures, and flows. A high-frequency fuel valve was utilized to perturb the combustor fuel flow. Successful instability suppression was shown using a dynamic pressure sensor in the combustor for controller feedback. Instability control was also shown with a pressure feedback sensor in the lower temperature region upstream of the combustor. It was also demonstrated that the controller can prevent the instability from occurring while combustor operation was transitioning from a stable, low-power condition to a normally unstable high-power condition, thus enabling the high-power condition

Reprogramming human T cell function and specificity with non-viral genome targeting.

Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells

User empowerment and the reform of community care A study of early implementation in four localities

SIGLEGBUnited Kingdo

Reprogramming human T cell function and specificity with non-viral genome targeting.

Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells

Key Parameters of Tumor Epitope Immunogenicity Revealed Through a Consortium Approach Improve Neoantigen Prediction

Many approaches to identify therapeutically relevant neoantigens couple tumor sequencing with bioinformatic algorithms and inferred rules of tumor epitope immunogenicity. However, there are no reference data to compare these approaches, and the parameters governing tumor epitope immunogenicity remain unclear. Here, we assembled a global consortium wherein each participant predicted immunogenic epitopes from shared tumor sequencing data. 608 epitopes were subsequently assessed for T cell binding in patient-matched samples. By integrating peptide features associated with presentation and recognition, we developed a model of tumor epitope immunogenicity that filtered out 98% of non-immunogenic peptides with a precision above 0.70. Pipelines prioritizing model features had superior performance, and pipeline alterations leveraging them improved prediction performance. These findings were validated in an independent cohort of 310 epitopes prioritized from tumor sequencing data and assessed for T cell binding. This data resource enables identification of parameters underlying effective anti-tumor immunity and is available to the research community