Two-Dimensional Numerical Study of Micronozzle Geometry

Supersonic micronozzles operate in the unique viscosupersonic flow regime, characterized by large Mach numbers (M\u3e1) and low Reynolds numbers (Re\u3c1000). Past research has primarily focused on the design and analysis of converging-diverging de Laval nozzles; however, plug (i.e. centerbody) designs also have some promising characteristics that might make them amenable to microscale operation. In this study, the effects of plug geometry on plug micronozzle performance are examined for the Reynolds number range Re = 80-640 using 2D Navier-Stokes-based simulations. Nozzle plugs are shortened to reduce viscous losses via three techniques: one - truncation, two - the use of parabolic contours, and three - a geometric process involving scaling. Shortened nozzle are derived from a full length geometry designed for optimal isentropic performance. Expansion ratio (ε = 3.19 and 6.22) and shortened plug length (%L = 10-100%) are varied for the full Reynolds number range. The performance of plug nozzles is then compared to that of linear-walled nozzles for equal pressure ratios, Reynolds numbers, and expansion ratios. Linear-walled nozzle half-angle is optimized to to ensure plug nozzles are compared against the best-case linear-walled design. Results indicate that the full length plug nozzle delivers poor performance on the microscale, incurring excessive viscous losses. Plug performance is increased by shortening the nozzle plug, with the scaling technique providing the best performance. The benefit derived from reducing plug length depends upon the Reynolds number, with a 1-2% increase for high Reynolds numbers an up to 14% increase at the lowest Reynolds number examined. In comparison to Linear-walled nozzle, plug nozzles deliver superior performance when under-expanded, however, this trend reverses at low pressure ratios when the nozzles become over-expanded

USM3D Simulations for Second Sonic Boom Workshop

The NASA Tetrahedral Unstructured Software System with the USM3D flow solver was used to compute test cases for the Second AIAA Sonic Boom Prediction Workshop. The intent of this report is to document the USM3D results for SBPW2 test cases. The test cases included an axisymmetric equivalent area body, a JAXA wing body, a NASA low boom supersonic configuration modeled with flow through nacelles and engine boundary conditions. All simulations were conducted for a free stream Mach number of 1.6, zero degrees angle of attack, and a Reynolds number of 5.7 million per meter. Simulations were conducted on tetrahedral grids provided by the workshop committee, as well as a family of grids generated by an in-house approach for sonic boom analyses known as BoomGrid using current best practices. The near-field pressure signatures were extracted and propagated to the ground with the atmospheric propagation code, sBOOM. The USM3D near-field pressure signatures, corresponding sBOOM ground signatures, and loudness levels on the ground are compared with mean values from other workshop participants

Preliminary Computational Study for Future Tests in the NASA Ames 9 foot' x 7 foot Wind Tunnel

The NASA Advanced Air Vehicles Program, Commercial Supersonics Technology Project seeks to advance tools and techniques to make over-land supersonic flight feasible. In this study, preliminary computational results are presented for future tests in the NASA Ames 9 foot x 7 foot supersonic wind tunnel to be conducted in early 2016. Shock-plume interactions and their effect on pressure signature are examined for six model geometries. Near- field pressure signatures are assessed using the CFD code USM3D to model the proposed test geometries in free-air. Additionally, results obtained using the commercial grid generation software Pointwise Reigistered Trademark are compared to results using VGRID, the NASA Langley Research Center in-house mesh generation program

Computational and Experimental Study of Plume and Shock Interaction Effects on Sonic Boom in the NASA Ames 9x7 Supersonic Wind Tunnel

A wind tunnel test was performed in the NASA Ames 9x7 Supersonic Wind Tunnel focusing on the shock waves traveling through and interacting with an exhaust nozzle plume. This experimental study was conducted to develop and validate the CFD capability required to accurately include nozzle flow with impinging shock effects on near field and groundpropagated sonic boom signatures. The model was made to be generic, and included a simple nozzle shape, two different aft decks, and a few generic horizontal tails. High pressure air was pumped through a nozzle at various nozzle pressure ratios (NPR) to represent the engine plume in flight. The three different aft body representations each created a different shock wave signature that passed through the plume. An aft deck configuration, where part of the aircraft shields the nozzle plume, was also tested. Retroreflective Background-Oriented Schlieren (RBOS) was used to obtain schlieren images of the flow field around the model and behind the model. This study compares wind tunnel data and numerical simulations conducted by the NASA Tetrahedral Unstructured Software System CFD code, USM3D

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

Regulation of activation-induced deaminase stability and antibody gene diversification by Hsp90

Hsp90 stabilizes and prevents degradation of cytoplasmic activation-induced deaminase

Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.

Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.Whole-genome sequencing of esophageal adenocarcinoma samples was performed as part of the International Cancer Genome Consortium (ICGC) through the oEsophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium and was funded by Cancer Research UK. We thank the ICGC members for their input on verification standards as part of the benchmarking exercise. We thank the Human Research Tissue Bank, which is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, from Addenbrooke’s Hospital and UCL. Also the University Hospital of Southampton Trust and the Southampton, Birmingham, Edinburgh and UCL Experimental Cancer Medicine Centres and the QEHB charities. This study was partly funded by a project grant from Cancer Research UK. R.C.F. is funded by an NIHR Professorship and receives core funding from the Medical Research Council and infrastructure support from the Biomedical Research Centre and the Experimental Cancer Medicine Centre. We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited. We would like to thank Dr. Peter Van Loo for providing the NGS version of ASCAT for copy number calling. We are grateful to all the patients who provided written consent for participation in this study and the staff at all participating centres. Some of the work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. The work at UCLH/UCL was also supported by the CRUK UCL Early Cancer Medicine Centre.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.365

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

Achievement of the planetary defense investigations of the Double Asteroid Redirection Test (DART) mission

NASA's Double Asteroid Redirection Test (DART) mission was the first to demonstrate asteroid deflection, and the mission's Level 1 requirements guided its planetary defense investigations. Here, we summarize DART's achievement of those requirements. On 2022 September 26, the DART spacecraft impacted Dimorphos, the secondary member of the Didymos near-Earth asteroid binary system, demonstrating an autonomously navigated kinetic impact into an asteroid with limited prior knowledge for planetary defense. Months of subsequent Earth-based observations showed that the binary orbital period was changed by –33.24 minutes, with two independent analysis methods each reporting a 1σ uncertainty of 1.4 s. Dynamical models determined that the momentum enhancement factor, β, resulting from DART's kinetic impact test is between 2.4 and 4.9, depending on the mass of Dimorphos, which remains the largest source of uncertainty. Over five dozen telescopes across the globe and in space, along with the Light Italian CubeSat for Imaging of Asteroids, have contributed to DART's investigations. These combined investigations have addressed topics related to the ejecta, dynamics, impact event, and properties of both asteroids in the binary system. A year following DART's successful impact into Dimorphos, the mission has achieved its planetary defense requirements, although work to further understand DART's kinetic impact test and the Didymos system will continue. In particular, ESA's Hera mission is planned to perform extensive measurements in 2027 during its rendezvous with the Didymos–Dimorphos system, building on DART to advance our knowledge and continue the ongoing international collaboration for planetary defense

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations