Predicting Spacecraft Trajectories by the WeavEncke Method

A combination of methods is proposed of predicting spacecraft trajectories that possibly include multiple maneuvers and/or perturbing accelerations, with greater speed, accuracy, and repeatability than were heretofore achievable. The combination is denoted the WeavEncke method because it is based on unpublished studies by Jonathan Weaver of the orbit-prediction formulation of the noted astronomer Johann Franz Encke. Weaver evaluated a number of alternatives that arise within that formulation, arriving at an orbit-predicting algorithm optimized for complex trajectory operations. In the WeavEncke method, Encke's method of prediction of perturbed orbits is enhanced by application of modern numerical methods. Among these methods are efficient Kepler s-equation time-of-flight solutions and self-starting numerical integration with time as the independent variable. Self-starting numerical integration satisfies the requirements for accuracy, reproducibility, and efficiency (and, hence, speed). Self-starting numerical integration also supports fully analytic regulation of integration step sizes, thereby further increasing speed while maintaining accuracy

Normalization of Gravitational Acceleration Models

Unlike the uniform density spherical shell approximations of Newton, the con- sequence of spaceflight in the real universe is that gravitational fields are sensitive to the nonsphericity of their generating central bodies. The gravitational potential of a nonspherical central body is typically resolved using spherical harmonic approximations. However, attempting to directly calculate the spherical harmonic approximations results in at least two singularities which must be removed in order to generalize the method and solve for any possible orbit, including polar orbits. Three unique algorithms have been developed to eliminate these singularities by Samuel Pines [1], Bill Lear [2], and Robert Gottlieb [3]. This paper documents the methodical normalization of two1 of the three known formulations for singularity-free gravitational acceleration (namely, the Lear [2] and Gottlieb [3] algorithms) and formulates a general method for defining normalization parameters used to generate normalized Legendre Polynomials and ALFs for any algorithm. A treatment of the conventional formulation of the gravitational potential and acceleration is also provided, in addition to a brief overview of the philosophical differences between the three known singularity-free algorithms

Methodology and Results of the Near-Earth Object (NEO) Human Space Flight (HSF) Accessible Targets Study (NHATS)

Near-Earth Asteroids (NEAs) have been identified by the Administration as potential destinations for human explorers during the mid-2020s. Planning such ambitious missions requires selecting potentially accessible targets from the growing known population of 8,008 NEAs. NASA is therefore conducting the Near-Earth Object (NEO) Human Space Flight (HSF) Accessible Targets Study (NHATS), in which the trajectory opportunities to all known NEAs are being systematically evaluated with respect to a set of defined constraints. While the NHATS algorithms have identified hundreds of NEAs which satisfy purposely inclusive trajectory constraints, only a handful of them offer truly attractive mission opportunities in the time frame of greatest interest. In this paper we will describe the structure of the NHATS algorithms and the constraints utilized in the study, present current study results, and discuss various mission design considerations for future human space flight missions to NEAs

The spatially resolved star formation history of the dwarf spiral galaxy NGC 5474

We study the resolved stellar populations and derive the star formation history of NGC 5474, a peculiar star-forming dwarf galaxy at a distance of $\sim 7$ Mpc, using Hubble Space Telescope Advanced Camera for Surveys data from the Legacy Extragalactic UV Survey (LEGUS) program. We apply an improved colour-magnitude diagram fitting technique based on the code SFERA and use the latest PARSEC-COLIBRI stellar models. Our results are the following. The off-centre bulge-like structure, suggested to constitute the bulge of the galaxy, is dominated by star formation (SF) activity initiated $14$ Gyr ago and lasted at least up to $1$ Gyr ago. Nevertheless, this component shows clear evidence of prolonged SF activity (lasting until $\sim 10$ Myr ago). We estimate the total stellar mass of the bulge-like structure to be $(5.0 \pm 0.3) \times 10^{8}$ \MSUN. Such a mass is consistent with published suggestions that this structure is in fact an independent system orbiting around and not within NGC 5474's disc. The stellar over-density located to the South-West of the bulge-like structure shows a significant SF event older than $1$ Gyr, while it is characterised by two recent peaks of SF, around $\sim10$ and $\sim100$ Myr ago. In the last Gyr, the behavior of the stellar disc is consistent with what is known in the literature as `gasping'. The synchronised burst at $10-35$ Myr in all components might hint to the recent gravitational interaction between the stellar bulge-like structure and the disc of NGC 5474.Comment: 18 pages, 12 figures, accepted for publication in Monthly Notices of the Royal Astronomical Societ

Exploring the IMF of star clusters: a joint SLUG and LEGUS effort

We present the implementation of a Bayesian formalism within the Stochastically Lighting Up Galaxies (SLUG) stellar population synthesis code, which is designed to investigate variations in the initial mass function (IMF) of star clusters. By comparing observed cluster photometry to large libraries of clusters simulated with a continuously varying IMF, our formalism yields the posterior probability distribution function (PDF) of the cluster mass, age and extinction, jointly with the parameters describing the IMF. We apply this formalism to a sample of star clusters from the nearby galaxy NGC 628, for which broad-band photometry in five filters is available as part of the Legacy ExtraGalactic UV Survey (LEGUS). After allowing the upper-end slope of the IMF (α3) to vary, we recover PDFs for the mass, age and extinction that are broadly consistent with what is found when assuming an invariant Kroupa IMF. However, the posterior PDF for α3 is very broad due to a strong degeneracy with the cluster mass, and it is found to be sensitive to the choice of priors, particularly on the cluster mass. We find only a modest improvement in the constraining power of α3 when adding Hα photometry from the companion Hα-LEGUS survey. Conversely, Hα photometry significantly improves the age determination, reducing the frequency of multi-modal PDFs. With the aid of mock clusters, we quantify the degeneracy between physical parameters, showing how constraints on the cluster mass that are independent of photometry can be used to pin down the IMF properties of star clusters.GA acknowledges support from the Science and Technology Facilities Council (ST/L00075X/1 and ST/M503472/1). MF acknowledges support by the Science and Technology Facilities Council [grant number ST/L00075X/1]. DAG kindly acknowledges financial support by the German Research Foundation (DFG) through programme GO 1659/3-2

Space Science Opportunities Augmented by Exploration Telepresence

Since the end of the Apollo missions to the lunar surface in December 1972, humanity has exclusively conducted scientific studies on distant planetary surfaces using teleprogrammed robots. Operations and science return for all of these missions are constrained by two issues related to the great distances between terrestrial scientists and their exploration targets: high communication latencies and limited data bandwidth. Despite the proven successes of in-situ science being conducted using teleprogrammed robotic assets such as Spirit, Opportunity, and Curiosity rovers on the surface of Mars, future planetary field research may substantially overcome latency and bandwidth constraints by employing a variety of alternative strategies that could involve: 1) placing scientists/astronauts directly on planetary surfaces, as was done in the Apollo era; 2) developing fully autonomous robotic systems capable of conducting in-situ field science research; or 3) teleoperation of robotic assets by humans sufficiently proximal to the exploration targets to drastically reduce latencies and significantly increase bandwidth, thereby achieving effective human telepresence. This third strategy has been the focus of experts in telerobotics, telepresence, planetary science, and human spaceflight during two workshops held from October 3–7, 2016, and July 7–13, 2017, at the Keck Institute for Space Studies (KISS). Based on findings from these workshops, this document describes the conceptual and practical foundations of low-latency telepresence (LLT), opportunities for using derivative approaches for scientific exploration of planetary surfaces, and circumstances under which employing telepresence would be especially productive for planetary science. An important finding of these workshops is the conclusion that there has been limited study of the advantages of planetary science via LLT. A major recommendation from these workshops is that space agencies such as NASA should substantially increase science return with greater investments in this promising strategy for human conduct at distant exploration sites

Selective Induction of Cell Death in Melanoma Cell Lines through Targeting of Mcl-1 and A1

Melanoma is an often fatal form of skin cancer which is remarkably resistant against radio- and chemotherapy. Even new strategies that target RAS/RAF signaling and display unprecedented efficacy are characterized by resistance mechanisms. The targeting of survival pathways would be an attractive alternative strategy, if tumor-specific cell death can be achieved. Bcl-2 proteins play a central role in regulating survival of tumor cells. In this study, we systematically investigated the relevance of antiapoptotic Bcl-2 proteins, i.e., Bcl-2, Bcl-xL, Bcl-w, Mcl-1, and A1, in melanoma cell lines and non-malignant cells using RNAi. We found that melanoma cells required the presence of specific antiapoptotic Bcl-2 proteins: Inhibition of Mcl-1 and A1 strongly induced cell death in some melanoma cell lines, whereas non-malignant cells, i.e., primary human fibroblasts or keratinocytes were not affected. This specific sensitivity of melanoma cells was further enhanced by the combined inhibition of Mcl-1 and A1 and resulted in 60% to 80% cell death in all melanoma cell lines tested. This treatment was successfully combined with chemotherapy, which killed a substantial proportion of cells that survived Mcl-1 and A1 inhibition. Together, these results identify antiapoptotic proteins on which specifically melanoma cells rely on and, thus, provide a basis for the development of new Bcl-2 protein-targeting therapies

Space Science Opportunities Augmented by Exploration Telepresence

Since the end of the Apollo missions to the lunar surface in December 1972, humanity has exclusively conducted scientific studies on distant planetary surfaces using teleprogrammed robots. Operations and science return for all of these missions are constrained by two issues related to the great distances between terrestrial scientists and their exploration targets: high communication latencies and limited data bandwidth. Despite the proven successes of in-situ science being conducted using teleprogrammed robotic assets such as Spirit, Opportunity, and Curiosity rovers on the surface of Mars, future planetary field research may substantially overcome latency and bandwidth constraints by employing a variety of alternative strategies that could involve: 1) placing scientists/astronauts directly on planetary surfaces, as was done in the Apollo era; 2) developing fully autonomous robotic systems capable of conducting in-situ field science research; or 3) teleoperation of robotic assets by humans sufficiently proximal to the exploration targets to drastically reduce latencies and significantly increase bandwidth, thereby achieving effective human telepresence. This third strategy has been the focus of experts in telerobotics, telepresence, planetary science, and human spaceflight during two workshops held from October 3–7, 2016, and July 7–13, 2017, at the Keck Institute for Space Studies (KISS). Based on findings from these workshops, this document describes the conceptual and practical foundations of low-latency telepresence (LLT), opportunities for using derivative approaches for scientific exploration of planetary surfaces, and circumstances under which employing telepresence would be especially productive for planetary science. An important finding of these workshops is the conclusion that there has been limited study of the advantages of planetary science via LLT. A major recommendation from these workshops is that space agencies such as NASA should substantially increase science return with greater investments in this promising strategy for human conduct at distant exploration sites

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Individual participant data meta-analysis of LR-5 in LI-RADS version 2018 versus revised LI-RADS for hepatocellular carcinoma diagnosis

Background A simplification of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 (v2018), revised LI-RADS (rLI-RADS), has been proposed for imaging-based diagnosis of hepatocellular carcinoma (HCC). Single-site data suggest that rLI-RADS category 5 (rLR-5) improves sensitivity while maintaining positive predictive value (PPV) of the LI-RADS v2018 category 5 (LR-5), which indicates definite HCC. Purpose To compare the diagnostic performance of LI-RADS v2018 and rLI-RADS in a multicenter data set of patients at risk for HCC by performing an individual patient data meta-analysis. Materials and Methods Multiple databases were searched for studies published from January 2014 to January 2022 that evaluated the diagnostic performance of any version of LI-RADS at CT or MRI for diagnosing HCC. An individual patient data meta-analysis method was applied to observations from the identified studies. Quality Assessment of Diagnostic Accuracy Studies version 2 was applied to determine study risk of bias. Observations were categorized according to major features and either LI-RADS v2018 or rLI-RADS assignments. Diagnostic accuracies of category 5 for each system were calculated using generalized linear mixed models and compared using the likelihood ratio test for sensitivity and the Wald test for PPV. Results Twenty-four studies, including 3840 patients and 4727 observations, were analyzed. The median observation size was 19 mm (IQR, 11–30 mm). rLR-5 showed higher sensitivity compared with LR-5 (70.6% [95% CI: 60.7, 78.9] vs 61.3% [95% CI: 45.9, 74.7]; P < .001), with similar PPV (90.7% vs 92.3%; P = .55). In studies with low risk of bias (n = 4; 1031 observations), rLR-5 also achieved a higher sensitivity than LR-5 (72.3% [95% CI: 63.9, 80.1] vs 66.9% [95% CI: 58.2, 74.5]; P = .02), with similar PPV (83.1% vs 88.7%; P = .47). Conclusion rLR-5 achieved a higher sensitivity for identifying HCC than LR-5 while maintaining a comparable PPV at 90% or more, matching the results presented in the original rLI-RADS study