Paper Session III-B - Risk Management for Small Satellite Programs

During an era of shrinking federal budgets, the Space Test Program has developed a management philosophy for accepting greater risks in managing small satellite programs for technology demonstration. This innovative philosophy complies with the latest government initiatives to reduce cost by using contractors’ best practices, eliminating use of government specifications and standards, and minimizing the size of the program office. We achieve program cost goals by matching the contract type to the perceived program risk, reducing program documentation, using non-redundant subsystems where possible, relaxing test requirements, and using minimal staff during on-orbit operations. However, we mitigate these increased risks and successfully perform our mission by developing detailed payload requirements early in the program, building system redundancy in appropriate areas, and applying vigorous attention to the spacecraft interfaces to the payload, the launch vehicle, and the mission control center. While these practices may not be appropriate for all satellite programs, we feel they apply to a broad range of research and technology demonstration spacecraft

An aggregation-based approximate dynamic programming approach for the periodic review model with random yield

A manufacturer places orders periodically for products that are shipped from a supplier. During transit, orders get damaged with some probability, that is, the order is subject to random yield. The manufacturer has the option to track orders to receive information on damages and to potentially place additional orders. Without tracking, the manufacturer identifies potential damages after the order has arrived. With tracking, the manufacturer is informed about the damage when it occurs and can respond to this information. We model the problem as a dynamic program with stochastic demand, tracking cost, and random yield. For small problem sizes, we provide an adjusted value iteration algorithm that finds the optimal solution. For moderate problem sizes, we propose a novel aggregation-based approximate dynamic programming (ADP) algorithm and provide solutions for instances for which it is not possible to obtain optimal solutions. For large problem sizes, we develop a heuristic that takes tracking costs into account. In a computational study, we analyze the performance of our approaches. We observe that our ADP algorithm achieves savings of up to 16% compared to existing heuristics. Our heuristic outperforms existing ones by up to 8.1%. We show that dynamic tracking reduces costs compared to tracking always or never and identify savings of up to 3.2%

Chronic Allergic Inflammation Causes Vascular Remodeling and Pulmonary Hypertension in Bmpr2 Hypomorph and Wild-Type Mice

Loss-of-function mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene have been identified in patients with heritable pulmonary arterial hypertension (PAH); however, disease penetrance is low, suggesting additional factors play a role. Inflammation is associated with PAH and vascular remodeling, but whether allergic inflammation triggers vascular remodeling in individuals with BMPR2 mutations is unknown. Our goal was to determine if chronic allergic inflammation would induce more severe vascular remodeling and PAH in mice with reduced BMPR-II signaling. Groups of Bmpr2 hypomorph and wild-type (WT) Balb/c/Byj mice were exposed to house dust mite (HDM) allergen, intranasally for 7 or 20 weeks to generate a model of chronic inflammation. HDM exposure induced similar inflammatory cell counts in all groups compared to controls. Muscularization of pulmonary arterioles and arterial wall thickness were increased after 7 weeks HDM, more severe at 20 weeks, but similar in both groups. Right ventricular systolic pressure (RVSP) was measured by direct cardiac catheterization to assess PAH. RVSP was similarly increased in both HDM exposed groups after 20 weeks compared to controls, but not after 7 weeks. Airway hyperreactivity (AHR) to methacholine was also assessed and interestingly, at 20 weeks, was more severe in HDM exposed Bmpr2 hypomorph mice versus WT. We conclude that chronic allergic inflammation caused PAH and while the severity was mild and similar between WT and Bmpr2 hypomorph mice, AHR was enhanced with reduced BMPR-II signaling. These data suggest that vascular remodeling and PAH resulting from chronic allergic inflammation occurs independently of BMPR-II pathway alterations

The periodic review model with independent age‐dependent lifetimes

A retailer places orders periodically for items that are shipped by a wholesaler. Items that are not sold perish randomly and independently of one another, with the perish probability depending on the age class. We consider a first-in first-out policy for depleting items. We model this problem as a Markov Decision Process with stochastic demand, unit holding, outdating and ordering costs, plus unit penalty costs for lost sales. We prove convexity for the penultimate period, and show convexity may not hold any earlier. A dynamic program can be solved optimally for small instances. We introduce both a one-stage-lookahead heuristic and a heuristic which is a combination of two existing standard approaches, the newsvendor and periodic review models. For simulated data, we compare these heuristics to the optimal solution for small problem instances and to further lookahead policies for larger problem instances. We show that the two new heuristics achieve results close to optimal. Our numerical study, which includes real data from a large European retail chain, highlights that products perishing independently from each other strongly affects model behaviour compared to existing approaches from the literature

How to build up big team science: A practical guide for large-scale collaborations

The past decade has witnessed a proliferation of Big Team Science (BTS), endeavours where a comparatively large number of researchers pool their intellectual and/or material resources in pursuit of a common goal. Despite this burgeoning interest, there exists little guidance on how to create, manage, and participate in these collaborations. In this paper, we integrate insights from a multidisciplinary set of BTS initiatives to provide a how-to guide for BTS. We first discuss initial considerations for launching a BTS project, such as building the team, identifying leadership, governance, tools, and open science approaches. We then turn to issues related to running and completing a BTS project, such as study design, ethical approvals, and issues related to data collection, management, and analysis. Finally, we address topics that present special challenges for BTS, including authorship decisions, collaborative writing, and team decision making

The Cancer Paradigm of Severe Pulmonary Arterial Hypertension

The plexiform lesions of severe pulmonary arterial hypertension (PAH) are similar in histologic appearance, whether the disease is idiopathic or secondary. Both forms of the disease show actively proliferating endothelial cells without evidence of apoptosis. Here, we discuss the pathobiology of the atypical, angioproliferative endothelial cells in severe PAH. The concept of the endothelial cell as a “quasi-malignant” cell provides a new framework for antiproliferative, antiangiogenic therapy in severe PAH

GCN sensitive protein translation in yeast.

Levels of protein translation by ribosomes are governed both by features of the translation machinery as well as sequence properties of the mRNAs themselves. We focus here on a striking three-nucleotide periodicity, characterized by overrepresentation of GCN codons and underrepresentation of G at the second position of codons, that is observed in Open Reading Frames (ORFs) of mRNAs. Our examination of mRNA sequences in Saccharomyces cerevisiae revealed that this periodicity is particularly pronounced in the initial codons-the ramp region-of ORFs of genes with high protein expression. It is also found in mRNA sequences immediately following non-standard AUG start sites, located upstream or downstream of the standard annotated start sites of genes. To explore the possible influences of the ramp GCN periodicity on translation efficiency, we tested edited ramps with accentuated or depressed periodicity in two test genes, SKN7 and HMT1. Greater conformance to (GCN)n was found to significantly depress translation, whereas disrupting conformance had neutral or positive effects on translation. Our recent Molecular Dynamics analysis of a subsystem of translocating ribosomes in yeast revealed an interaction surface that H-bonds to the +1 codon that is about to enter the ribosome decoding center A site. The surface, comprised of 16S/18S rRNA C1054 and A1196 (E. coli numbering) and R146 of ribosomal protein Rps3, preferentially interacts with GCN codons, and we hypothesize that modulation of this mRNA-ribosome interaction may underlie GCN-mediated regulation of protein translation. Integration of our expression studies with large-scale reporter studies of ramp sequence variants suggests a model in which the C1054-A1196-R146 (CAR) interaction surface can act as both an accelerator and braking system for ribosome translation