Demonstration of Active Combustion Control

The primary objective of this effort was to demonstrate active control of combustion instabilities in a direct-injection gas turbine combustor that accurately simulates engine operating conditions and reproduces an engine-type instability. This report documents the second phase of a two-phase effort. The first phase involved the analysis of an instability observed in a developmental aeroengine and the design of a single-nozzle test rig to replicate that phenomenon. This was successfully completed in 2001 and is documented in the Phase I report. This second phase was directed toward demonstration of active control strategies to mitigate this instability and thereby demonstrate the viability of active control for aircraft engine combustors. This involved development of high-speed actuator technology, testing and analysis of how the actuation system was integrated with the combustion system, control algorithm development, and demonstration testing in the single-nozzle test rig. A 30 percent reduction in the amplitude of the high-frequency (570 Hz) instability was achieved using actuation systems and control algorithms developed within this effort. Even larger reductions were shown with a low-frequency (270 Hz) instability. This represents a unique achievement in the development and practical demonstration of active combustion control systems for gas turbine applications

A quantitative metric of pioneer activity reveals that HNF4A has stronger in vivo pioneer activity than FOXA1

BACKGROUND: We and others have suggested that pioneer activity - a transcription factor\u27s (TF\u27s) ability to bind and open inaccessible loci - is not a qualitative trait limited to a select class of pioneer TFs. We hypothesize that most TFs display pioneering activity that depends on the TF concentration and the motif content at their target loci. RESULTS: Here, we present a quantitative in vivo measure of pioneer activity that captures the relative difference in a TF\u27s ability to bind accessible versus inaccessible DNA. The metric is based on experiments that use CUT&Tag to measure the binding of doxycycline-inducible TFs. For each location across the genome, we determine the concentration of doxycycline required for a TF to reach half-maximal occupancy; lower concentrations reflect higher affinity. We propose that the relative difference in a TF\u27s affinity between ATAC-seq labeled accessible and inaccessible binding sites is a measure of its pioneer activity. We estimate binding affinities at tens of thousands of genomic loci for the endodermal TFs FOXA1 and HNF4A and show that HNF4A has stronger pioneer activity than FOXA1. We show that both FOXA1 and HNF4A display higher binding affinity at inaccessible sites with more copies of their respective motifs. The quantitative analysis of binding suggests different modes of binding for FOXA1, including an anti-cooperative mode of binding at certain accessible loci. CONCLUSIONS: Our results suggest that relative binding affinities are reasonable measures of pioneer activity and support the model wherein most TFs have some degree of context-dependent pioneer activity

On Toroidal Horizons in Binary Black Hole Inspirals

We examine the structure of the event horizon for numerical simulations of two black holes that begin in a quasicircular orbit, inspiral, and finally merge. We find that the spatial cross section of the merged event horizon has spherical topology (to the limit of our resolution), despite the expectation that generic binary black hole mergers in the absence of symmetries should result in an event horizon that briefly has a toroidal cross section. Using insight gained from our numerical simulations, we investigate how the choice of time slicing affects both the spatial cross section of the event horizon and the locus of points at which generators of the event horizon cross. To ensure the robustness of our conclusions, our results are checked at multiple numerical resolutions. 3D visualization data for these resolutions are available for public access online. We find that the structure of the horizon generators in our simulations is consistent with expectations, and the lack of toroidal horizons in our simulations is due to our choice of time slicing.Comment: Submitted to Phys. Rev.

A test of the pioneer factor hypothesis using ectopic liver gene activation

The pioneer factor hypothesis (PFH) states that pioneer factors (PFs) are a subclass of transcription factors (TFs) that bind to and open inaccessible sites and then recruit non-pioneer factors (non-PFs) that activate batteries of silent genes. The PFH predicts that ectopic gene activation requires the sequential activity of qualitatively different TFs. We tested the PFH by expressing the endodermal PF FOXA1 and non-PF HNF4A in K562 lymphoblast cells. While co-expression of FOXA1 and HNF4A activated a burst of endoderm-specific gene expression, we found no evidence for a functional distinction between these two TFs. When expressed independently, both TFs bound and opened inaccessible sites, activated endodermal genes, and \u27pioneered\u27 for each other, although FOXA1 required fewer copies of its motif for binding. A subset of targets required both TFs, but the predominant mode of action at these targets did not conform to the sequential activity predicted by the PFH. From these results, we hypothesize an alternative to the PFH where \u27pioneer activity\u27 depends not on categorically different TFs but rather on the affinity of interaction between TF and DNA

Inbound Medical Tourism to Barbados: A Qualitative Examination of Local Lawyers’ Prospective Legal and Regulatory Concerns

Background Enabled by globalizing processes such as trade liberalization, medical tourism is a practice that involves patients’ intentional travel to privately obtain medical care in another country. Empirical legal research on this issue is limited and seldom based on the perspectives of destination countries receiving medical tourists. We consulted with diverse lawyers from across Barbados to explore their views on the prospective legal and regulatory implications of the developing medical tourism industry in the country. Methods We held a focus group in February 2014 in Barbados with lawyers from across the country. Nine lawyers with diverse legal backgrounds participated. Focus group moderators summarized the study objective and engaged participants in identifying the local implications of medical tourism and the anticipated legal and regulatory concerns. The focus group was transcribed verbatim and analyzed thematically. Results Five dominant legal and regulatory themes were identified through analysis: (1) liability; (2) immigration law; (3) physician licensing; (4) corporate ownership; and (5) reputational protection. Conclusions Two predominant legal and ethical concerns associated with medical tourism in Barbados were raised by participants and are reflected in the literature: the ability of medical tourists to recover medical malpractice for adverse events; and the effects of medical tourism on access to health care in the destination country. However, the participants also identified several topics that have received much less attention in the legal and ethical literature. Overall this analysis reveals that lawyers, at least in Barbados, have an important role to play in the medical tourism sector beyond litigation – particularly in transactional and gatekeeper capacities. It remains to be seen whether these findings are specific to the ecology of Barbados or can be extrapolated to the legal climate of other medical tourism destination countries

The economic implications of HLA matching in cadaveric renal transplantation.

Abstract Background: The potential economic effects of the allocation of cadaveric kidneys on the basis of tissue-matching criteria are controversial. We analyzed the economic costs associated with the transplantation of cadaveric kidneys with various numbers of HLA mismatches and examined the potential economic benefits of a local, as compared with a national, system designed to minimize HLA mismatches between donor and recipient in first cadaveric renal transplantations. Methods: All data were supplied by the U.S. Renal Data System. Data on all payments made by Medicare from 1991 through 1997 for the care of recipients of a first cadaveric renal transplant were analyzed according to the number of HLA-A, B, and DR mismatches between donor and recipient and the duration of cold ischemia before transplantation. Results: Average Medicare payments for renal-transplant recipients in the three years after transplantation increased from $60,436 per patient for fully HLA-matched kidneys (those with no HLA-A, B, or DR mismatches) to$80,807 for kidneys with six HLA mismatches between donor and recipient, a difference of 34 percent (P\u3c0.001). By three years after transplantation, the average Medicare payments were $64,119 for transplantations of kidneys with less than 12 hours of cold-ischemia time and$74,997 for those with more than 36 hours (P\u3c0.001). In simulations, the assignment of cadaveric kidneys to recipients by a method that minimized HLA mismatching within a local geographic area (i.e., within one of the approximately 50 organ-procurement organizations, which cover widely varying geographic areas) produced the largest cost savings ($4,290 per patient over a period of three years) and the largest improvements in the graft-survival rate (2.3 percent) when the potential costs of longer cold-ischemia time were considered. Conclusions: Transplantation of better-matched cadaveric kidneys could have substantial economic advantages. In our simulations, HLA-based allocation of kidneys at the local level produced the largest estimated cost savings, when the duration of cold ischemia was taken into account. No additional savings were estimated to result from a national allocation program, because the additional costs of longer cold-ischemia time were greater than the advantages of optimizing HLA matching