A new sampling system tailored to experimentally-derived mechanical properties of icy analogs for evolved Enceladus surface plume deposits

Enceladus is unique amongst Ocean Worlds in our Solar System: the contents of its internal ocean are continuously emitted to space by its present-day activity, and some of these materials are redeposited on the surface. This tiny moon of Saturn thus presents an opportunity to directly measure the composition of the ocean and seek evidence for habitability (including past or extant life), either by collecting and analyzing plume particles as previously proposed by Discovery and New Frontiers mission concepts, or via more ambitious mission concepts that involve landing, surface sampling and analysis, and potential deployment of subsurface probes to reach the ocean itself (Hofgartner et al., this meeting). However, the low surface gravity (1% of Earth’s) and extreme cryogenic conditions in the South Pole regions (~ 50 K, away from the Tiger Stripes) raises questions: how to best sample the upper ~ 1 cm of the surface around a lander, made of most freshly deposited plume materials? What are the expected properties of these materials, i.e. how fast does sintering proceed and how strong would these materials be as function of their exposure age? We provide answers to these questions via a two-pronged approach. First, we surveyed experimentally the time evolution of mechanical strength of large samples of ice spherules at several temperatures. A custom sample preparation system has been developed to synthesize ice spheres with a grain size distribution of mean ~ 12 microns. The samples are subsequently held at temperatures of -30, -50, and -80 C, over extended periods of time (up to 9 months at time of writing), and their strength is tested at frequent intervals using cone penetration tests. The data obtained to date suggests that the observed temperature dependence of the strength evolution is commensurate with expectations from vapor diffusion. Second, we developed a new sampling system that enables rapid sampling and transfer of surface materials into receptacles. Those receptacles can then deposit the sampled materials into the inlet of an instrument dedicated to analyzing the chemical composition of these materials and seek tracers of past or extant life. The geometry of the system and principles of operation have been established and validated by experimental tests, as well as dynamical simulations

Relationship between a Weighted Multi-Gene Algorithm and Blood Pressure Control in Hypertension

Hypertension (HTN) is a complex disease with interactions among multiple organ systems, including the heart, vasculature, and kidney with a strong heritable component. Despite the multifactorial nature of HTN, no clinical guidelines utilize a multi-gene approach to guide blood pressure (BP) therapy. Non-smokers with a family history of HTN were included in the analysis (n = 384; age = 61.0 ± 0.9, 11% non-white). A total of 17 functional genotypes were weighted according to the previous effect size in the literature and entered into an algorithm. Pharmacotherapy was ranked from 1⁻4 as most to least likely to respond based on the algorithmic assessment of individual patient's genotypes. Three-years of data were assessed at six-month intervals for BP and medication history. There was no difference in BP at diagnosis between groups matching the top drug recommendation using the multi-gene weighted algorithm (n = 92) vs. those who did not match (n = 292). However, from diagnosis to nadir, patients who matched the primary recommendation had a significantly greater drop in BP when compared to patients who did not. Further, the difference between diagnosis to current 1-year average BP was lower in the group that matched the top recommendation. These data suggest an association between a weighted multi-gene algorithm on the BP response to pharmacotherapy.Geneticure Inc.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Radionuclide production and separation techniques for radiopharmaceutical development and nuclear waste processing

Dr. Silvia S. Jurisson, Dissertation Supervisor.Includes vita.Field of study: Chemistry."May 2018."[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] With increasing cancer incident rates and advancements in nuclear medicine, the demand for optimizing pathways to produce radionuclides or investigating new radionuclides that improve current diagnostic and therapeutic methods are crucial. In this research, the production pathways and separation of radionuclides for diagnostic imaging and/or therapeutic purposes were evaluated and developed. Diagnostic Single Photon Emission Computed Tomography (SPECT) imaging with 99mTc, a well-established radionuclide applied in over 80% of nuclear medicine, supports the need for a therapeutic rhenium analogue. Both 186,189Re radionuclides have favorable decay properties for therapy, but their current production routes with reactors or few facilities with high energy particles limits their routine applicability. This research evaluated the production of 186,189Re using low-mid energy protons, which are more accessible worldwide, from bombardment of W and Os targets. Developing suitable production of 186,189Re would provide a 99mTc/186,189Re diagnostic/therapeutic matched pair. In this research, the 72As/77As diagnostic/therapeutic matched pair are also of interest. A positron-emitting radionuclide with applications for Positron Emission Tomography (PET), 72As has a longer half-life than most PET radionuclides, which matches the biological half-life of slower localizing biomolecules, such as antibodies or proteins. The University of Missouri Research Reactor (MURR) has demonstrated the therapeutic analogue, 77As, can be produced routinely from 76Ge targets, but the diagnostic analogue, 72As, can be made available from the decay of 72Se in the form of a 72Se/72As generator. This research evaluated the production and separation of 72Se from Ge and As targets and evaluated the integrity of 72Se/72As generators. Developing the production of 72Se and optimizing a 72Se/72As generator-based system would provide transportation of 72Se and on demand availability of 72As for PET imaging. A theranostic radionuclide with suitable decay properties for both SPECT and therapy is 105Rh, which has a favorable electronic configuration and has demonstrated high in vivo stability. Sufficient quantities of 105Rh can be produced from enriched 104Ru metal targets at MURR; however, no recycling method to recover 104Ru metal has been evaluated. In this research, a scheme to recycle and reuse 104Ru was developed for further production of 105Rh. These diagnostic/therapeutic matched pair and dual imaging/therapy radionuclides are critical for expanding the pool of available radionuclides and advancing the field of the nuclear medicine.Includes bibliographical references (pages 134-142)

Detection of Microsatellite Instability in Colonoscopic Biopsies and Postal Urine Samples from Lynch Syndrome Cancer Patients Using a Multiplex PCR Assay

Identification of mismatch repair (MMR)-deficient colorectal cancers (CRCs) is recommended for Lynch syndrome (LS) screening, and supports targeting of immune checkpoint inhibitors. Microsatellite instability (MSI) analysis is commonly used to test for MMR deficiency. Testing biopsies prior to tumour resection can inform surgical and therapeutic decisions, but can be limited by DNA quantity. MSI analysis of voided urine could also provide much needed surveillance for genitourinary tract cancers in LS. Here, we reconfigure an existing molecular inversion probe-based MSI and BRAF c.1799T > A assay to a multiplex PCR (mPCR) format, and demonstrate that it can sample >140 unique molecules per marker from <1 ng of DNA and classify CRCs with 96–100% sensitivity and specificity. We also show that it can detect increased MSI within individual and composite CRC biopsies from LS patients, and within preoperative urine cell free DNA (cfDNA) from two LS patients, one with an upper tract urothelial cancer, the other an undiagnosed endometrial cancer. Approximately 60–70% of the urine cfDNAs were tumour-derived. Our results suggest that mPCR sequence-based analysis of MSI and mutation hotspots in CRC biopsies could facilitate presurgery decision making, and could enable postal-based screening for urinary tract and endometrial tumours in LS patients