Capturing Creative Program Management Best Practices

This research attempted to capture the creative aspects of government program management in three specific areas: efficiently navigating oversight, capturing the intent of regulations, and developing innovative risk management practices. Respected acquisition leaders with diverse backgrounds and experiences were interviewed with ranks ranging from 0-6 to 0-8 and GS-15 to SES. Several contractor interviews were conducted for specific purposes. The data were iteratively coded and analyzed using ATLAS.ti. The results were categorized into four themes, each with three sub-elements. Differences between respondents with program director experience and those with rapid acquisition experience are discussed. A survey was then distributed to the interviewees and junior acquisition professionals. The predominant research finding is that senior acquisition professionals believe that relationship-building is of paramount importance. This, along with creative practices regarding how to externally communicate program strategies, greatly increases the probability of successfully navigating oversight and obtaining waivers or tailoring regulations. Various risk management techniques and management reserve techniques are presented. In addition, knowledge gaps between the junior acquisition workforce and senior leaders were identified based on statistical significance and corrective actions recommended where applicable. Reports and outbriefs were developed, tailored to each class, to relay these creative practices to junior acquisition professionals

Using M&S to Maximize Space Satellite Data Collection with Multiple Ground Stations

With the continued operations of FalconSAT-3 well beyond its design life, an opportunity exists to utilize multiple ground stations beyond the original site at the US Air Force Academy (USAFA) to enhance individual training missions at the Air Force Institute of Technology (AFIT), United States Military Academy (USMA), and the Undergraduate Space Training (UST) course at Vandenberg Air Force Base. Using multiple ground stations can enhance FalconSAT-3 experiments beyond the original design. However, with multiple ground stations coordination needs to increase. The problem of distributed files becomes an issue, and all files need to be compiled to maximize experiment analysis. A discrete event simulation of the file distribution was calculated to show how the files are spread across the ground stations. The characteristics of each ground station and available crew rates at the respective stations contribute to the overall ability to download (or miss the opportunity to download) files. The simulation shows the capability of each site to download files and which sites’ missed opportunities for file download were caused by crew availability. Implications of downloaded files and missed opportunities can affect the design of the distributed network of ground stations to support FalconSAT-3

Understanding Enterprise Risk Across an Aquisition Portfolio: A Grounded Theory Approach

Every acquisition program contains risks. But what impact do these risks have on the entire portfolio of acquisition activities? What does risk at the Enterprise level really mean? For example, risk collectively could portend great danger to the acquisition manager’s overall portfolio which might be otherwise masked by traditional program performance and analysis. Alternatively, these risks also might represent opportunities to achieve greater results when analyzed from a portfolio perspective. Initial review of the literature suggests that most leaders are unable to articulate the risk carried by their portfolio of product development activities or what this means to them. However, the same literature suggests they strongly desire this capability. Beginning with a review of the applicable literature in the areas of risk, product development (acquisition) and product portfolio management, portfolio-level risk applications are found to be sparse and ill-conceived. Initial analysis of interviews with portfolio leaders involving military product development activities in portfolios of large, complex, system development will be presented with a discussion of the implications of enterprise risk for product portfolio management

Rapid Development: A Content Analysis Comparison of Literature and Purposive Sampling of Rapid Reaction Projects

In the current environment of military operations requesting short development timelines to counter insurgent tactics, the engineering team often searches for ways to deliver the “80% solution”, typically in 6-12 months. These are labeled rapid development projects. A content analysis of best practices in commercial product development literature, where time to market is often a driving factor, was accomplished showing varying emphasis of systems engineering (SE) technical and technical management processes. This analysis confirms a preconceived notion of “plan upfront and early” by emphasizing Stakeholder Requirements Definition, Architecture Design and Technical Planning. A purposive sampling of Air Force Research Laboratory rapid development project managers and engineers was conducted to identify important SE processes and then compared to the literature content analysis. The results of this sampling did not strongly emphasize one process over another, however Architecture Design and Implementation scored higher among Technical Processes. Decision Analysis, Technical Planning, Technical Assessment and Data Management scored slightly higher among Technical Management Processes. Anecdotal evidence also emphasized iterating prototype designs based on early customer feedback, focusing mostly on managing critical risks and holding frequent early reviews until trust is built in the team

Effects of enamel matrix derivative and transforming growth factor-β1 on human osteoblastic cells

<p>Abstract</p> <p>Background</p> <p>Extracellular matrix proteins are key factors that influence the regenerative capacity of tissues. The objective of the present study was to evaluate the effects of enamel matrix derivative (EMD), TGF-β1, and the combination of both factors (EMD+TGF-β1) on human osteoblastic cell cultures.</p> <p>Methods</p> <p>Cells were obtained from alveolar bone of three adult patients using enzymatic digestion. Effects of EMD, TGF-β1, or a combination of both were analyzed on cell proliferation, bone sialoprotein (BSP), osteopontin (OPN) and alkaline phosphatase (ALP) immunodetection, total protein synthesis, ALP activity and bone-like nodule formation.</p> <p>Results</p> <p>All treatments significantly increased cell proliferation compared to the control group at 24 h and 4 days. At day 7, EMD group showed higher cell proliferation compared to TGF-β1, EMD + TGF-β1 and the control group. OPN was detected in the majority of the cells for all groups, whereas fluorescence intensities for ALP labeling were greater in the control than in treated groups; BSP was not detected in all groups. All treatments decreased ALP levels at 7 and 14 days and bone-like nodule formation at 21 days compared to the control group.</p> <p>Conclusions</p> <p>The exposure of human osteoblastic cells to EMD, TGF-β1 and the combination of factors <it>in vitro </it>supports the development of a less differentiated phenotype, with enhanced proliferative activity and total cell number, and reduced ALP activity levels and matrix mineralization.</p

Relating enhancer genetic variation across mammals to complex phenotypes using machine learning

[INTRODUCTION] Diverse phenotypes, including large brains relative to body size, group living, and vocal learning ability, have evolved multiple times throughout mammalian history. These shared phenotypes may have arisen repeatedly by means of common mechanisms discernible through genome comparisons.[RATIONALE] Protein-coding sequence differences have failed to fully explain the evolution of multiple mammalian phenotypes. This suggests that these phenotypes have evolved at least in part through changes in gene expression, meaning that their differences across species may be caused by differences in genome sequence at enhancer regions that control gene expression in specific tissues and cell types. Yet the enhancers involved in phenotype evolution are largely unknown. Sequence conservation–based approaches for identifying such enhancers are limited because enhancer activity can be conserved even when the individual nucleotides within the sequence are poorly conserved. This is due to an overwhelming number of cases where nucleotides turn over at a high rate, but a similar combination of transcription factor binding sites and other sequence features can be maintained across millions of years of evolution, allowing the function of the enhancer to be conserved in a particular cell type or tissue. Experimentally measuring the function of orthologous enhancers across dozens of species is currently infeasible, but new machine learning methods make it possible to make reliable sequence-based predictions of enhancer function across species in specific tissues and cell types.[RESULTS] To overcome the limits of studying individual nucleotides, we developed the Tissue-Aware Conservation Inference Toolkit (TACIT). Rather than measuring the extent to which individual nucleotides are conserved across a region, TACIT uses machine learning to test whether the function of a given part of the genome is likely to be conserved. More specifically, convolutional neural networks learn the tissue- or cell type–specific regulatory code connecting genome sequence to enhancer activity using candidate enhancers identified from only a few species. This approach allows us to accurately associate differences between species in tissue or cell type–specific enhancer activity with genome sequence differences at enhancer orthologs. We then connect these predictions of enhancer function to phenotypes across hundreds of mammals in a way that accounts for species’ phylogenetic relatedness. We applied TACIT to identify candidate enhancers from motor cortex and parvalbumin neuron open chromatin data that are associated with brain size relative to body size, solitary living, and vocal learning across 222 mammals. Our results include the identification of multiple candidate enhancers associated with brain size relative to body size, several of which are located in linear or three-dimensional proximity to genes whose protein-coding mutations have been implicated in microcephaly or macrocephaly in humans. We also identified candidate enhancers associated with the evolution of solitary living near a gene implicated in separation anxiety and other enhancers associated with the evolution of vocal learning ability. We obtained distinct results for bulk motor cortex and parvalbumin neurons, demonstrating the value in applying TACIT to both bulk tissue and specific minority cell type populations. To facilitate future analyses of our results and applications of TACIT, we released predicted enhancer activity of >400,000 candidate enhancers in each of 222 mammals and their associations with the phenotypes we investigated.[CONCLUSION] TACIT leverages predicted enhancer activity conservation rather than nucleotide-level conservation to connect genetic sequence differences between species to phenotypes across large numbers of mammals. TACIT can be applied to any phenotype with enhancer activity data available from at least a few species in a relevant tissue or cell type and a whole-genome alignment available across dozens of species with substantial phenotypic variation. Although we developed TACIT for transcriptional enhancers, it could also be applied to genomic regions involved in other components of gene regulation, such as promoters and splicing enhancers and silencers. As the number of sequenced genomes grows, machine learning approaches such as TACIT have the potential to help make sense of how conservation of, or changes in, subtle genome patterns can help explain phenotype evolution.This work used the Extreme Science and Engineering Discovery Environment (XSEDE), through the Pittsburgh Supercomputing Center Bridges and Bridges-2 Compute Clusters, which was supported by National Science Foundation grants TG-BIO200055 and ACI-1548562 (131). Portions of this research were conducted on Lehigh University’s Research Computing infrastructure, which is partially supported by NSF award 2019035.Funding was provided by a Carnegie Mellon University Computational Biology Department Lane Fellowship (I.M.K.); NIH NIDA DP1DA046585 grant (D.E.S., M.E.W., X.Z., A.R.B., and A.R.P.); NSF grant 2046550 (I.M.K. and A.R.P.); an Alfred P. Sloan Foundation Research Fellowship (I.M.K., M.E.W., and A.R.P.); the Carnegie Mellon University Computational Biology Department (C.S.); NSF Graduate Research Fellowship Program grant DGE1252522 (A.J.L.); NSF Graduate Research Fellowship Program grant DGE1745016 (A.J.L.); a Carnegie Mellon University Summer Undergraduate Research Fellowship (D.E.S.); NIH NIDA Fellowship grant F30DA053020 (B.N.P.); NIH UG3-MH-120094 (K.P.); NSF grant 2022046 (D.P.G.); NIH NHGRI R01HG008742 grant (E.K.K.); and a Swedish Research Council Distinguished Professor Award (K.L.-T.).Peer reviewe

Contribution of human hematopoietic stem cells to liver repair

Immune-deficient mouse models of liver damage allow examination of human stem cell migration to sites of damage and subsequent contribution to repair and survival. In our studies, in the absence of a selective advantage, transplanted human stem cells from adult sources did not robustly become hepatocytes, although some level of fusion or hepatic differentiation was documented. However, injected stem cells did home to the injured liver tissue and release paracrine factors that hastened endogenous repair and enhanced survival. There were significantly higher levels of survival in mice with a toxic liver insult that had been transplanted with human stem cells but not in those transplanted with committed progenitors. Transplantation of autologous adult stem cells without conditioning is a relatively safe therapy. Adult stem cells are known to secrete bioactive factors that suppress the local immune system, inhibit fibrosis (scar formation) and apoptosis, enhance angiogenesis, and stimulate recruitment, retention, mitosis, and differentiation of tissue-residing stem cells. These paracrine effects are distinct from the direct differentiation of stem cells to repair tissue. In patients at high risk while waiting for a liver transplant, autologous stem cell therapy could be considered, as it could delay the decline in liver function

Dense sampling of bird diversity increases power of comparative genomics (vol 587, pg 252, 2020)

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Challenges Using Modeling and Simulation in Architecture Development

A discrete event simulation was developed combining the Optical Tracking Network (TeleTrak) and Satellite Position Attained by RF-Keyed Tracking (SPARK) system into one system to track, image, and identify space objects as they pass through the space fence to increase space situational awareness for the United States Air Force. The objectives for this study are threefold: model a “to-be” architecture for a combined TeleTrak and SPARK system to develop system requirements, determine if an optimal position for the telescope exists to return to while waiting for the next collect, and demonstrate knowledge and understanding of DOE and simulation principles and techniques. The paper explores the uses and pitfalls of modeling and simulation with this case study. While a working model remained elusive, several important observations emerged. Six recommendations are given to help others become more successful in a modeling and simulation environment along with ideas to pursue in additional research