Future Exploration of the Outer Heliosphere and Very Local Interstellar Medium by Interstellar Probe.

A detailed overview of the knowledge gaps in our understanding of the heliospheric interaction with the largely unexplored Very Local Interstellar Medium (VLISM) are provided along with predictions of with the scientific discoveries that await. The new measurements required to make progress in this expanding frontier of space physics are discussed and include in-situ plasma and pick-up ion measurements throughout the heliosheath, direct sampling of the VLISM properties such as elemental and isotopic composition, densities, flows, and temperatures of neutral gas, dust and plasma, and remote energetic neutral atom (ENA) and Lyman-alpha (LYA) imaging from vantage points that can uniquely discern the heliospheric shape and bring new information on the interaction with interstellar hydrogen. The implementation of a pragmatic Interstellar Probe mission with a nominal design life to reach 375 Astronomical Units (au) with likely operation out to 550 au are reported as a result of a 4-year NASA funded mission study.

Impact Melt Facies in the Moon's Crisium Basin: Identifying, Characterizing, and Future Radiogenic Dating.

Both Earth and the Moon share a common history regarding the epoch of large basin formation, though only the lunar geologic record preserves any appreciable record of this Late Heavy Bombardment. The emergence of Earth's first life is approximately contemporaneous with the Late Heavy Bombardment; understanding the latter informs the environmental conditions of the former, which are likely necessary to constrain the mechanisms of abiogenesis. While the relative formation time of most of the Moon's large basins is known, the absolute timing is not. The timing of Crisium Basin's formation is one of many important events that must be constrained and would require identifying and dating impact melt formed in the Crisium event. To inform a future lunar sample dating mission, we thus characterized possible outcrops of impact melt. We determined that several mare lava-embayed kipukas could contain impact melt, though the rim and central peaks of the partially lava-flooded Yerkes Crater likely contain the most pure and intact Crisium impact melt. It is here where future robotic and/or human missions could confidently add a key missing piece to the puzzle of the combined issues of early Earth-Moon bombardment and the emergence of life.

Prebiotic Chemistry of Pluto.

We present the case for the presence of complex organic molecules, such as amino acids and nucleobases, formed by abiotic processes on the surface and in near-subsurface regions of Pluto. Pluto's surface is tinted with a range of non-ice substances with colors ranging from light yellow to red to dark brown; the colors match those of laboratory organic residues called tholins. Tholins are broadly characterized as complex, macromolecular organic solids consisting of a network of aromatic structures connected by aliphatic bridging units (e.g., Imanaka et al., 2004; Materese et al., 2014, 2015). The synthesis of tholins in planetary atmospheres and in surface ices has been explored in numerous laboratory experiments, and both gas- and solid-phase varieties are found on Pluto. A third variety of tholins, exposed at a site of tectonic surface fracturing called Virgil Fossae, appears to have come from a reservoir in the subsurface. Eruptions of tholin-laden liquid H2O from a subsurface aqueous repository appear to have covered portions of Virgil Fossae and its surroundings with a uniquely colored deposit (D.P. Cruikshank, personal communication) that is geographically correlated with an exposure of H2O ice that includes spectroscopically detected NH3 (C.M. Dalle Ore, personal communication). The subsurface organic material could have been derived from presolar or solar nebula processes, or might have formed in situ. Photolysis and radiolysis of a mixture of ices relevant to Pluto's surface composition (N2, CH4, CO) have produced strongly colored, complex organics with a significant aromatic content having a high degree of nitrogen substitution similar to the aromatic heterocycles pyrimidine and purine (Materese et al., 2014, 2015; Cruikshank et al., 2016). Experiments with pyrimidines and purines frozen in H2O-NH3 ice resulted in the formation of numerous nucleobases, including the biologically relevant guanine, cytosine, adenine, uracil, and thymine (Materese et al., 2017). The red material associated with the H2O ice may contain nucleobases resulting from energetic processing on Pluto's surface or in the interior. Some other Kuiper Belt objects also exhibit red colors similar to those found on Pluto and may therefore carry similar inventories of complex organic materials. The widespread and ubiquitous nature of similarly complex organic materials observed in a variety of astronomical settings drives the need for additional laboratory and modeling efforts to explain the origin and evolution of organic molecules. Pluto observations reveal complex organics on a small body that remains close to its place of origin in the outermost regions of the Solar System.

The combination of chemotherapy and systemic immunotherapy with soluble B7-immunoglobulin G leads to cure of murine leukemia and lymphoma and demonstration of tumor-specific memory responses.

Major mechanisms underlying poor immune responses to autologous tumor-associated antigens are overwhelming tumor kinetics and the absence of effective T-cell costimulation by antigen-presenting cells. To address these issues, leukemia and lymphoma mice were treated with the combination of chemotherapy and systemic immunotherapy with recombinant soluble murine B7-immunoglobulin G (IgG) molecules. In this report, 3 murine models were used, a radiation-induced SJL acute myeloid leukemia, a transplantable spontaneous SJL lymphoma, and the C57BL/6 EL-4 thymic lymphoma. Various treatment modalities were evaluated: single treatments with either B7-IgG or chemotherapy as well as combination therapies. The results demonstrate the following: (1) in all tumor models, the combination of chemotherapy and soluble B7-IgGs is more potent than either therapy alone, leading to cure of tumor-bearing animals; (2) the therapeutic responses are T-cell-dependent, because combined therapy is not efficacious in severe combined immunodeficient mice; (3) the rejection of tumor cells leads to the development of tumor-specific immunity, because cured mice are immune to the rejected tumor but not to a different syngeneic tumor; and (4) (51)Cr release assays show that rejection of tumor cells leads to the development of very potent tumor-specific cytotoxic T-lymphocyte activity. On the basis of these results, it is proposed that chemotherapy-mediated tumor reduction, together with consequent augmented tumor-antigen presentation to activated T cells, are primary mechanisms leading to curative responses. The safety profile of the B7-IgG fusion proteins and their synergy with chemotherapy strongly suggest that the combination regimen is a promising strategy in cancer treatment.

Vaccines with interleukin-12-transduced acute myeloid leukemia cells elicit very potent therapeutic and long-lasting protective immunity.

Interleukin-12 (IL-12) is a heterodimeric cytokine mediating a dynamic interplay between T cells and antigen-presenting cells (APCs). Preclinical studies have demonstrated that recombinant murine IL-12 (rmIL-12) promotes specific antitumor immunity mediated by T cells in several types of tumors. However, the in vivo antitumor properties of IL-12 in acute myeloid leukemia (AML) have not been previously reported. We show here in a murine AML model that systemic administration of rmIL-12 significantly delays tumor growth but is incapable of rescuing mice from lethal leukemia. In contrast, AML cells genetically modified to express IL-12 (IL12-AML) using murine stem cell virus (MSCV) p40 + p35 elicit very potent antileukemic activity. Vaccines with lethally irradiated IL12-AML cells protect naive mice against challenge with wild-type AML cells and, more importantly, can cure mice bearing a considerable leukemic burden. Immunized mice show no signs of systemic IL-12 toxicity and their spleen histology is comparable with naive mice spleen. In vivo depletion of IL-12, interferon-gamma (IFN-gamma), or CD8(+) T cells after injections with live IL12-AML cells abrogates completely the antileukemia immune responses. Studies on the in vitro effects of IFN-gamma on AML cells demonstrate enhanced expression of major histocompatibility complex (MHC) and accessory molecules and induction of the costimulatory molecules B7.1 and B7.2, but no significant direct antiproliferative effect. (51)Cr release assays show that rejection of live IL12-AML cells supports the development of long-lasting leukemia-specific cytotoxic T lymphocyte (CTL) activity. In conclusion, our results demonstrate that IL12-AML vaccination is a safe and potent immunotherapeutic approach that has a great potential to eliminate minimal residual disease in patients with AML.