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A solar sail propelled small satellite mission concept to intercept and potentially rendezvous with newly discovered transient interstellar objects (ISOs) is described. The mission concept derives from the proposal for a technology demonstration mission for exiting the solar system at high velocity, eventually to reach the focal region of the solar gravitational lens. The ISO mission concept is to fly a solar sail toward a holding orbit around the Sun and when the ISO orbit is confirmed, target the sailcraft to reach an escape velocity of over 6 AU/year. This would permit rapid response to a new ISO discovery and an intercept within 10 AU from the Sun. Two new proven interplanetary technologies are utilized to enable such a mission: i) interplanetary smallsats, such as those demonstrated by the MarCO mission, and ii) solar sails, such as demonstrated by LightSail and IKAROS missions and developed for NEA Scout and Solar Cruiser missions. Current technology work suggests that already within this decade such a mission could fly and reach an ISO moving through the solar system. It might enable the first encounter with an ISO to allow for imaging and spectroscopy, measurements of size and mass, potentially giving a unique information about the object’s origin and composition. A similar approach may be used to allow for a sample return.

The pathogenic significance of nucleotide variants commonly relies on nucleotide position within the gene, with exonic changes generally attributed to quantitative or qualitative alteration of protein biosynthesis, secretion, activity, or clearance. However, these changes may exert pleiotropic effects on both protein biology and mRNA splicing due to the overlapping of the amino acid and splicing codes, thus shaping the disease phenotypes. Here, we focused on hemophilia A, in which the definition of F8 variants’ causative role and association to bleeding phenotypes is crucial for proper classification, genetic counseling, and management of affected individuals. We extensively characterized a large panel of hemophilia A-causing variants (n = 30) within F8 exon 19 by combining and comparing in silico and recombinant expression analyses. We identified exonic variants with pleiotropic effects and dissected the altered protein features of all missense changes. Importantly, results from multiple prediction algorithms provided qualitative results, while recombinant assays allowed us to correctly infer the likely phenotype severity for 90% of variants. Molecular characterization of pathogenic variants was also instrumental for the development of tailored correction approaches to rescue splicing affecting variants or missense changes impairing protein folding. A single engineered U1snRNA rescued mRNA splicing of nine different variants and the use of a chaperone-like drug resulted in improved factor VIII protein secretion for four missense variants. Overall, dissection of the molecular mechanisms of a large panel of HA variants allowed precise classification of HA-affected individuals and favored the development of personalized therapeutic approaches.

Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha-fetoprotein, Model for End-Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n = 1,021) and validated in the remainder (n = 3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest-risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest-risk patients (HALTHCC > 35) (VI, 7.7%[ 1.2-14.2] vs. 70.6% [48.3-92.9] and PDC:4.6% [0.1%-9.8%] vs. 47.1% [22.6-71.5]; P < 0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C-index = 0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index = 0.71) and OS (C-index = 0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk among candidates with HCC worldwide. Prospective trials introducing HA

In recent tests the plume current density profile, plume ion energy, and radiated EMI were characterized for Pratt & Whitney's T-220HT Hall Effect thruster. The T-220HT is a high power (6-20 kW) thruster designed for maximum peak thrust. Tests covered a power range from 8-10 kW and discharge voltages of 300 and 600 V. Plume measurements at Air Force Research Laboratory (AFRL) facilities demonstrated plume widths narrower than typical Hall thrusters. Half- angles containing 90% of the integrated plume flux were in the range of 27-29. Radiated electromagnetic emissions were measured over a frequency range from 200 MHz to 60 GHz at The Aerospace Corporation. For discharge voltages at or below 300 V, EMI was below MIL-STD 461E limits except at a single peak below 1.4 GHz, where the limit was exceeded by only about 5 dB. Increasing the discharge voltage to 600 V noticeably increased emissions in this frequency range, but these were still generally below MIL-STD 461E. Plume ion energy spectra were also characterized at The Aerospace Corporation's facility. An RPA (Retarding Potential Analyzer) was mounted at a downstream distance of 1 meter and was varied in position from 20 deg. to 100 deg. from the thruster centerline. Measurements generally confirmed the plume profile data taken at AFRL. Energy spectra confirm that the flux at high angles is dominated by low energy charge- exchange ions., Prepared cooperation with AIAA Joint Propulsion Conference, 20-23 Jul 2003, Huntsville, Al.

This work continued to investigate thermionic energy conversion in the Knudsen (collisionless) operating mode. A SAVTEC-type converter with an interelectrode spacing of 18-22 microns was tested over a range of emitter temperatures up to about 1700 K. Maximum performance followed the predictions of vacuum-mode analysis for emitter temperatures below 1580 K. Above that temperature the converter operated in the unignited mode, with partial space-charge neutralization by surface ionization of cesium. It was found that collisionless and diffusion mode theories could be extended into the regime of maximum output power for the unignited mode (spacing and electron mean-free path about equal) to give good agreement with the experimental data. The Knudsen-mode thermionic converter with a structured emitter was also investigated. Analysis has shown that associative ionization between barium and cesium is unlikely to be the cause of the current enhancement observed in previously published work. An analysis which considered the trapping of positive ions in the emitter slots has given good qualitative agreement with published data. Work is continuing on this analysis. Parts for a structured emitter variable spacing converter have been constructed and are being assembled. Keywords: Thermionic energy conversion; Knudsen operating mode; Structured emitter; SAVTEC diodes.

This work is a study of discharge processes in Knudsen mode (collisionless), thermionic energy converters. Areas of research involve mechanisms for reducing the effects of electron space charge in such devices. Such mechanisms are essential for thermionic converters to produce useful current and power densities. The mechanisms we have chosen to study are: reduction of space-charge through a very close interelectrode gap (less than 10 microns); transport and retention of positive cesium ions generated by surface ionization; transport of positive cesium ions generated in an arc external to the electrodes; and the mechanism for enhanced current output due to a structured emitter in a mixed barium-cesium vapor. This last process may involve the production of barium-cesium dimer ions. The experimental work used SAVTEC (Self-Adjusting, Versatile Thermionic Energy Converter) diode structures, which were tested in a chamber containing 0.1-1.0 torr of cesium vapor. Comparison of measured volt-ampere curves with theory gave excellent agreement and indicated an interelectrode gap of 6.5 microns at an emitter temperature of 1250 K. A theoretical model of the collisionless thermionic diode was developed which included surface ionization, auxiliary ions from an external source, and trapping of charged particles in potential wells due to infrequent collisions. Studies show that trapping of positive ions leads to a large, beneficial increase in current density.