Paper Session III-C - Innovative Financing of a Large Space Project

This paper addresses the changes to the Space Frontier Operations, Inc. (SFO) Space Exploration Plan, (SEP) that was initially presented at the 37th. Space Congress in 1999. Progress since last year will be presented briefly and the progress made in finding the correct financing vehicles will be presented in detail. The SFO Space Exploration Project starts off as an international project that will present unique and difficult challenges to both the space and financial communities. The effects of these challenges will be discussed along with their impact to the process of raising capital for a project of this nature. The rationale behind establishing a separate but complimentary corporation will be discussed. The relationship between the commercial corporation and SFO will be delineated. It will be shown that complimentary roles are not only possible but also highly desirable. The way in which the SEP fits into the standard protocols used by the finance industry will be discussed. As the project proceeds to completion the issue of traditional financing with an Initial Public Offering will be addressed along with the possibility of bringing in one or more partners – either commercial or governmental. Finally, the work of the supporting commercial corporation will be presented and the current status of the two corporations will be discussed

Inferring the post-merger gravitational wave emission from binary neutron star coalescences

We present a robust method to characterize the gravitational wave emission from the remnant of a neutron star coalescence. Our approach makes only minimal assumptions about the morphology of the signal and provides a full posterior probability distribution of the underlying waveform. We apply our method on simulated data from a network of advanced ground-based detectors and demonstrate the gravitational wave signal reconstruction. We study the reconstruction quality for different binary configurations and equations of state for the colliding neutron stars. We show how our method can be used to constrain the yet-uncertain equation of state of neutron star matter. The constraints on the equation of state we derive are complimentary to measurements of the tidal deformation of the colliding neutron stars during the late inspiral phase. In the case of a non-detection of a post-merger signal following a binary neutron star inspiral we show that we can place upper limits on the energy emitted.Comment: 11 pages, 12 figures, final published versio

Pathway-extended gene expression signatures integrate novel biomarkers that improve predictions of patient responses to kinase inhibitors

Cancer chemotherapy responses have been related to multiple pharmacogenetic biomarkers, often for the same drug. This study utilizes machine learning to derive multi-gene expression signatures that predict individual patient responses to specific tyrosine kinase inhibitors, including erlotinib, gefitinib, sorafenib, sunitinib, lapatinib and imatinib. Support Vector Machine learning was used to train mathematical models that distinguished sensitivity from resistance to these drugs using a novel systems biology-based approach. This began with expression of genes previously implicated in specific drug responses, then expanded to evaluate genes whose products were related through biochemical pathways and interactions. Optimal pathway-extended support vector machines predicted responses in patients at accuracies of 70% (imatinib), 71% (lapatinib), 83% (sunitinib), 83% (erlotinib), 88% (sorafenib) and 91% (gefitinib). These best performing pathway-extended models demonstrated improved balance predicting both sensitive and resistant patient categories, with many of these genes having a known role in cancer etiology. Ensemble machine learning-based averaging of multiple pathway-extended models derived for an individual drug increased accuracy to \u3e70% for erlotinib, gefitinib, lapatinib, and sorafenib. Through incorporation of novel cancer biomarkers, machine learning-based pathway-extended signatures display strong efficacy predicting both sensitive and resistant patient responses to chemotherapy

Pathway‐extended gene expression signatures integrate novel biomarkers that improve predictions of patient responses to kinase inhibitors

Cancer chemotherapy responses have been related to multiple pharmacogenetic biomarkers, often for the same drug. This study utilizes machine learning to derive multi‐gene expression signatures that predict individual patient responses to specific tyrosine kinase inhibitors, including erlotinib, gefitinib, sorafenib, sunitinib, lapatinib and imatinib. Support vector machine (SVM) learning was used to train mathematical models that distinguished sensitivity from resistance to these drugs using a novel systems biology‐based approach. This began with expression of genes previously implicated in specific drug responses, then expanded to evaluate genes whose products were related through biochemical pathways and interactions. Optimal pathway‐extended SVMs predicted responses in patients at accuracies of 70% (imatinib), 71% (lapatinib), 83% (sunitinib), 83% (erlotinib), 88% (sorafenib) and 91% (gefitinib). These best performing pathway‐extended models demonstrated improved balance predicting both sensitive and resistant patient categories, with many of these genes having a known role in cancer aetiology. Ensemble machine learning‐based averaging of multiple pathway‐extended models derived for an individual drug increased accuracy to \u3e70% for erlotinib, gefitinib, lapatinib and sorafenib. Through incorporation of novel cancer biomarkers, machine learning‐based pathway‐extended signatures display strong efficacy predicting both sensitive and resistant patient responses to chemotherapy

Direct Detection and Sequencing of Damaged DNA Bases

Products of various forms of DNA damage have been implicated in a variety of important biological processes, such as aging, neurodegenerative diseases, and cancer. Therefore, there exists great interest to develop methods for interrogating damaged DNA in the context of sequencing. Here, we demonstrate that single-molecule, real-time (SMRT®) DNA sequencing can directly detect damaged DNA bases in the DNA template - as a by-product of the sequencing method - through an analysis of the DNA polymerase kinetics that are altered by the presence of a modified base. We demonstrate the sequencing of several DNA templates containing products of DNA damage, including 8-oxoguanine, 8-oxoadenine, O6-methylguanine, 1-methyladenine, O4-methylthymine, 5-hydroxycytosine, 5-hydroxyuracil, 5-hydroxymethyluracil, or thymine dimers, and show that these base modifications can be readily detected with single-modification resolution and DNA strand specificity. We characterize the distinct kinetic signatures generated by these DNA base modifications

RNAmotifs: prediction of multivalent RNA motifs that control alternative splicing

RNA-binding proteins (RBPs) regulate splicing according to position-dependent principles, which can be exploited for analysis of regulatory motifs. Here we present RNAmotifs, a method that evaluates the sequence around differentially regulated alternative exons to identify clusters of short and degenerate sequences, referred to as multivalent RNA motifs. We show that diverse RBPs share basic positional principles, but differ in their propensity to enhance or repress exon inclusion. We assess exons differentially spliced between brain and heart, identifying known and new regulatory motifs, and predict the expression pattern of RBPs that bind these motifs. RNAmotifs is available at https://bitbucket.org/rogrro/rna_motifs

Reconstructing gravitational wave signals from binary black hole mergers with minimal assumptions

We present a systematic comparison of the binary black hole (BBH) signal waveform reconstructed by two independent and complementary approaches used in LIGO and Virgo source inference: a template-based analysis, and a morphology-independent analysis. We apply the two approaches to real events and to two sets of simulated observations made by adding simulated BBH signals to LIGO and Virgo detector noise. The first set is representative of the 10 BBH events in the first Gravitational Wave Transient Catalog (GWTC-1). The second set is constructed from a population of BBH systems with total mass and signal strength in the ranges that ground based detectors are typically sensitive. We find that the reconstruction quality of the GWTC-1 events is consistent with the results of both sets of simulated signals. We also demonstrate a simulated case where the presence of a mismodelled effect in the observed signal, namely higher order modes, can be identified through the morphology-independent analysis. This study is relevant for currently progressing and future observational runs by LIGO and Virgo

Inferring the Post-Merger Gravitational Wave Emission from Binary Neutron Star Coalscences

We present a robust method to characterize the gravitational wave emission from the remnant of a neutron star coalescence. Our approach makes only minimal assumptions about the morphology of the signal and provides a full posterior probability distribution of the underlying waveform. We apply our method on simulated data from a network of advanced ground-based detectors and demonstrate the gravitational wave signal reconstruction. We study the reconstruction quality for different binary configurations and equations of state for the colliding neutron stars. We show how our method can be used to constrain the yet-uncertain equation of state of neutron star matter. The constraints on the equation of state we derive are complimentary to measurements of the tidal deformation of the colliding neutron stars during the late inspiral phase. In the case of a nondetection of a post-merger signal following a binary neutron star inspiral we show that we can place upper limits on the energy emitted

Behavioral implications of shortlisting procedures

We consider two-stage “shortlisting procedures” in which the menu of alternatives is first pruned by some process or criterion and then a binary relation is maximized. Given a particular first-stage process, our main result supplies a necessary and sufficient condition for choice data to be consistent with a procedure in the designated class. This result applies to any class of procedures with a certain lattice structure, including the cases of “consideration filters,” “satisficing with salience effects,” and “rational shortlist methods.” The theory avoids background assumptions made for mathematical convenience; in this and other respects following Richter’s classical analysis of preference-maximizing choice in the absence of shortlisting

A Comparative Analysis of Methylome Profiles of Campylobacter jejuni Sheep Abortion Isolate and Gastroenteric Strains Using PacBio Data

Campylobacter jejuni is a leading cause of human gastrointestinal disease and small ruminant abortions in the United States. The recent emergence of a highly virulent, tetracycline-resistant C. jejuni subsp. jejunisheep abortion clone (clone SA) in the United States, and that strain\u27s association with human disease, has resulted in a heightened awareness of the zoonotic potential of this organism. Pacific Biosciences\u27 Single Molecule, Real-Time sequencing technology was used to explore the variation in the genome-wide methylation patterns of the abortifacient clone SA (IA3902) and phenotypically distinct gastrointestinal-specific C. jejuni strains (NCTC 11168 and 81-176). Several notable differences were discovered that distinguished the methylome of IA3902 from that of 11168 and 81-176: identification of motifs novel to IA3902, genome-specific hypo- and hypermethylated regions, strain level variability in genes methylated, and differences in the types of methylation motifs present in each strain. These observations suggest a possible role of methylation in the contrasting disease presentations of these three C. jejuni strains. In addition, the methylation profiles between IA3902 and a luxS mutant were explored to determine if variations in methylation patterns could be identified that might explain the role of LuxS-dependent methyl recycling in IA3902 abortifacient potential