Transient Plasma Ignition for Delay Reduction in Pulse Detonation Engines

45th AIAA Aerospace Sciences Meeting and Exhibit 8 - 11 January 2007, Reno, NevadaThis paper reviews the testing and evaluation of transient plasma for pulse detonation engine (PDE) ignition conducted at five laboratories. It also presents data showing significant reductions in times required for detonation. Critical to achieving functional levels of thrust are increased repetition rates, thus minimal delay to detonation times are an important parameter. Experiments have been conducted at the University of Southern California and in collaboration with researchers at the Naval Postgraduate School, Wright Patterson Air Force Research Laboratory, Stanford University, Ohio State University and the University of Cincinnati. In these studies it was observed that TPI significantly reduces delay times (factor of 2 to 9) in both static and flowing systems

Transient Plasma Ignition for Delay Reduction in Pulse Detonation Engines

This presentation reviews testing and evaluation at four laboratories of transient plasma for pulse detonation engine (PDE) ignition, and presents data showing significant reductions in times required for detonation. The aerospace community has ongoing interests in the development of propulsion technologies based on pulse detonating engines (PDE), and work is underway to determine whether this is a feasible technology. The PDE provides impulse through fuel detonation, and potential advantages include efficient operation at both subsonic and supersonic speeds. In theory a PDE can efficiently operate from Mach 0 to more than Mach 4 [1,2]. In order to achieve almost continuous thrust firing rates of 100 Hz or more are needed. Critical to achieving high repetition rates are minimal delay to detonation times. In work supported by the Office of Naval Research and the Air Force Office of Scientific Research, transient plasma ignition (TPI) has consistently shown substantial reductions in ignition delay time for various fuels [3,4,5]. Experiments have been conducted at the University of Southern California and in collaboration with researchers at the Naval Postgraduate School, Wright Patterson Air Force Research Laboratory, Stanford University, the University of Cincinnati, and California Institute of Technology [6]. In these studies it was observed that TPI significantly reduces delay times in both static and flowing systems. Transient plasma ignition is attractive as an ignition source for PDEs because it produces reductions in ignition delay times, can reduce Deflagration to Detonation Transition (DDT) times, and has been shown to provide the capability to ignite under leaner conditions. This allows for high repetition rates, high altitude operation, and reduced NO, emissions [7,8]. The geometry of the discharge area is such that ignition is achieved with a high degree of spatial uniformity over a large volume relative to traditional spark ignition. The short timescale of the pulse ( < 100 ns) prevents formation of an arc, and a voluminous array of streamers is used for ignition. It is possible that energetic electrons in the highly non-equilibrated electron energy distribution of the streamers cause dissociation of hydrocarbon chain molecules, producing active radicals throughout the ignition volume [9]. A further advantage of TPI is that a smaller fraction of the electrical energy goes into thermal heating of the mixture. These effects allow for large numbers of active species to be generated throughout the volume

Characterization of dynamic patterns of human fetal to neonatal brain asymmetry with deformation-based morphometry

IntroductionDespite established knowledge on the morphological and functional asymmetries in the human brain, the understanding of how brain asymmetry patterns change during late fetal to neonatal life remains incomplete. The goal of this study was to characterize the dynamic patterns of inter-hemispheric brain asymmetry over this critically important developmental stage using longitudinally acquired MRI scans.MethodsSuper-resolution reconstructed T2-weighted MRI of 20 neurotypically developing participants were used, and for each participant fetal and neonatal MRI was acquired. To quantify brain morphological changes, deformation-based morphometry (DBM) on the longitudinal MRI scans was utilized. Two registration frameworks were evaluated and used in our study: (A) fetal to neonatal image registration and (B) registration through a mid-time template. Developmental changes of cerebral asymmetry were characterized as (A) the inter-hemispheric differences of the Jacobian determinant (JD) of fetal to neonatal morphometry change and the (B) time-dependent change of the JD capturing left-right differences at fetal or neonatal time points. Left-right and fetal-neonatal differences were statistically tested using multivariate linear models, corrected for participants’ age and sex and using threshold-free cluster enhancement.ResultsFetal to neonatal morphometry changes demonstrated asymmetry in the temporal pole, and left-right asymmetry differences between fetal and neonatal timepoints revealed temporal changes in the temporal pole, likely to go from right dominant in fetal to a bilateral morphology in neonatal timepoint. Furthermore, the analysis revealed right-dominant subcortical gray matter in neonates and three clusters of increased JD values in the left hemisphere from fetal to neonatal timepoints.DiscussionWhile these findings provide evidence that morphological asymmetry gradually emerges during development, discrepancies between registration frameworks require careful considerations when using DBM for longitudinal data of early brain development

Dynamic Analysis of Vascular Morphogenesis Using Transgenic Quail Embryos

Background: One of the least understood and most central questions confronting biologists is how initially simple clusters or sheet-like cell collectives can assemble into highly complex three-dimensional functional tissues and organs. Due to the limits of oxygen diffusion, blood vessels are an essential and ubiquitous presence in all amniote tissues and organs. Vasculogenesis, the de novo self-assembly of endothelial cell (EC) precursors into endothelial tubes, is the first step in blood vessel formation [1]. Static imaging and in vitro models are wholly inadequate to capture many aspects of vascular pattern formation in vivo, because vasculogenesis involves dynamic changes of the endothelial cells and of the forming blood vessels, in an embryo that is changing size and shape. Methodology/Principal Findings: We have generated Tie1 transgenic quail lines Tg(tie1:H2B-eYFP) that express H2B-eYFP in all of their endothelial cells which permit investigations into early embryonic vascular morphogenesis with unprecedented clarity and insight. By combining the power of molecular genetics with the elegance of dynamic imaging, we follow the precise patterning of endothelial cells in space and time. We show that during vasculogenesis within the vascular plexus, ECs move independently to form the rudiments of blood vessels, all while collectively moving with gastrulating tissues that flow toward the embryo midline. The aortae are a composite of somatic derived ECs forming its dorsal regions and the splanchnic derived ECs forming its ventral region. The ECs in the dorsal regions of the forming aortae exhibit variable mediolateral motions as they move rostrally; those in more ventral regions show significant lateral-to-medial movement as they course rostrally. Conclusions/Significance: The present results offer a powerful approach to the major challenge of studying the relative role(s) of the mechanical, molecular, and cellular mechanisms of vascular development. In past studies, the advantages of the molecular genetic tools available in mouse were counterbalanced by the limited experimental accessibility needed for imaging and perturbation studies. Avian embryos provide the needed accessibility, but few genetic resources. The creation of transgenic quail with labeled endothelia builds upon the important roles that avian embryos have played in previous studies of vascular development

Searching for Planets Orbiting Fomalhaut with JWST/NIRCam

We report observations with the JWST/NIRCam coronagraph of the Fomalhaut system. This nearby A star hosts a complex debris disk system discovered by the IRAS satellite. Observations in F444W and F356W filters using the round 430R mask achieve a contrast ratio of ~ 4 x 10-7 at 1'' and ~ 4 x 10-8 outside of 3''. These observations reach a sensitivity limit <1 MJup across most of the disk region. Consistent with the hypothesis that Fomalhaut b is not a massive planet but is a dust cloud from a planetesimal collision, we do not detect it in either F356W or F444W (the latter band where a Jovian-sized planet should be bright). We have reliably detected 10 sources in and around Fomalhaut and its debris disk, all but one of which are coincident with Keck or HST sources seen in earlier coronagraphic imaging; we show them to be background objects, including the "Great Dust Cloud" identified in MIRI data. However, one of the objects, located at the edge of the inner dust disk seen in the MIRI images, has no obvious counterpart in imaging at earlier epochs and has a relatively red [F356W]-[F444W]>0.7 mag (Vega) color. Whether this object is a background galaxy, brown dwarf, or a Jovian mass planet in the Fomalhaut system will be determined by an approved Cycle 2 follow-up program. Finally, we set upper limits to any scattered light from the outer ring, placing a weak limit on the dust albedo at F356W and F444W.Comment: 24 pages, 17 figure

Disconnection Mechanism and Regional Cortical Atrophy Contribute to Impaired Processing of Facial Expressions and Theory of Mind in Multiple Sclerosis: A Structural MRI Study

Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients

Small RNA changes en route to distinct cellular states of induced pluripotency

MicroRNAs (miRNAs) are critical to somatic cell reprogramming into induced pluripotent stem cells (iPSCs), however, exactly how miRNA expression changes support the transition to pluripotency requires further investigation. Here we use a murine secondary reprogramming system to sample cellular trajectories towards iPSCs or a novel pluripotent ‘F-class’ state and perform small RNA sequencing. We detect sweeping changes in an early and a late wave, revealing that distinct miRNA milieus characterize alternate states of pluripotency. miRNA isoform expression is common but surprisingly varies little between cell states. Referencing other omic data sets generated in parallel, we find that miRNA expression is changed through transcriptional and post-transcriptional mechanisms. miRNA transcription is commonly regulated by dynamic histone modification, while DNA methylation/demethylation consolidates these changes at multiple loci. Importantly, our results suggest that a novel subset of distinctly expressed miRNAs supports pluripotency in the F-class state, substituting for miRNAs that serve such roles in iPSCs

Induced Pluripotent Stem Cell Lines Derived from Equine Fibroblasts

The domesticated horse represents substantial value for the related sports and recreational fields, and holds enormous potential as a model for a range of medical conditions commonly found in humans. Most notable of these are injuries to muscles, tendons, ligaments and joints. Induced pluripotent stem (iPS) cells have sparked tremendous hopes for future regenerative therapies of conditions that today are not possible to cure. Equine iPS (EiPS) cells, in addition to bringing promises to the veterinary field, open up the opportunity to utilize horses for the validation of stem cell based therapies before moving into the human clinical setting. In this study, we report the generation of iPS cells from equine fibroblasts using a piggyBac (PB) transposon-based method to deliver transgenes containing the reprogramming factors Oct4, Sox2, Klf4 and c-Myc, expressed in a temporally regulated fashion. The established iPS cell lines express hallmark pluripotency markers, display a stable karyotype even during long-term culture, and readily form complex teratomas containing all three embryonic germ layer derived tissues upon in vivo grafting into immunocompromised mice. Our EiPS cell lines hold the promise to enable the development of a whole new range of stem cell-based regenerative therapies in veterinary medicine, as well as aid the development of preclinical models for human applications. EiPS cell could also potentially be used to revive recently extinct or currently threatened equine species

Discrimination, Reliability, Sensitivity, and Specificity of Robotic Surgical Proficiency Assessment With Global Evaluative Assessment of Robotic Skills and Binary Scoring Metrics: Results From a Randomized Controlled Trial

Objective: To compare binary metrics and Global Evaluative Assessment of Robotic Skills (GEARS) evaluations of training outcome assessments for reliability, sensitivity, and specificity. Background: GEARS–Likert-scale skills assessment are a widely accepted tool for robotic surgical training outcome evaluations. Proficiency-based progression (PBP) training is another methodology but uses binary performance metrics for evaluations. Methods: In a prospective, randomized, and blinded study, we compared conventional with PBP training for a robotic suturing, knot-tying anastomosis task. Thirty-six surgical residents from 16 Belgium residency programs were randomized. In the skills laboratory, the PBP group trained until they demonstrated a quantitatively defined proficiency benchmark. The conventional group were yoked to the same training time but without the proficiency requirement. The final trial was video recorded and assessed with binary metrics and GEARS by robotic surgeons blinded to individual, group, and residency program. Sensitivity and specificity of the two assessment methods were evaluated with area under the curve (AUC) and receiver operating characteristics (ROC) curves. Results: The PBP group made 42% fewer objectively assessed performance errors than the conventional group (P &lt; 0.001) and scored 15% better on the GEARS assessment (P = 0.033). The mean interrater reliability for binary metrics and GEARS was 0.87 and 0.38, respectively. Binary total error metrics AUC was 97% and for GEARS 85%. With a sensitivity threshold of 0.8, false positives rates were 3% and 25% for, respectively, the binary and GEARS assessments. Conclusions: Binary metrics for scoring a robotic VUA task demonstrated better psychometric properties than the GEARS assessment. </jats:sec

Ophthalmology

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2/vascular endothelial growth factor (VEGF)-A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend-based regimen (T&E) with up to every-16-week (Q16W) dosing in the YOSEMITE/RHINE (NCT03622580/NCT03622593) phase 3 trials of diabetic macular edema (DME). DESIGN: Randomized, double-masked, noninferiority phase 3 trials. PARTICIPANTS: Adults with visual acuity loss due to center-involving DME. METHODS: Patients were randomized 1:1:1 to faricimab 6.0 mg Q8W, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg Q8W. The T&E up to Q16W dosing regimen was based on central subfield thickness (CST) and best-corrected visual acuity (BCVA) change. MAIN OUTCOME MEASURES: Included changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. RESULTS: In YOSEMITE/RHINE (N=940/951), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92/96/100 average) with faricimab Q8W (YOSEMITE/RHINE, +10.7/+10.9 letters) or T&E (+10.7/+10.1 letters) were comparable with aflibercept Q8W (+11.4/+9.4 letters). The median number of study drug injections was lower with faricimab T&E (YOSEMITE/RHINE, 10/11 injections) versus faricimab Q8W (15 injections) and aflibercept Q8W (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was further improved during year 2, with >60% of patients on Q16W dosing and ∼80% on ≥Q12W dosing at week 96. Almost 80% of patients who achieved Q16W dosing at week 52 maintained Q16W dosing without an interval reduction through week 96. Mean CST reductions were greater, and more patients achieved absence of DME (CST <325μm) and absence of intraretinal fluid with faricimab Q8W or T&E versus aflibercept Q8W through year 2. Overall, faricimab was well tolerated, with a safety profile comparable to aflibercept. CONCLUSIONS: Clinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to Q16W were maintained through year 2. Faricimab given as a personalized T&E-based dosing regimen supports the role of dual angiopoietin-2/VEGF-A inhibition to promote vascular stability and provide durable efficacy for patients with DME