Time-Lapse Active Source Seismic Characterization of a Leaky CO\u3csub\u3e2\u3c/sub\u3e Reservoir: Little Grand Wash Fault, Utah

A carbon capture and sequestration (CCS) approach requires economical methods to monitor reservoir CO2 flow paths through time. I explore the use of an inexpensive surface seismic approach to monitor the time-varying response of a leaky CO2 reservoir. My site is located in east central Utah, where the Little Grand Wash fault provides a natural analogue for a failed sequestration site. This fault and related anticlinal trap provides a conduit to collect and deliver CO2 from shallow reservoir depths to the atmosphere. Elevated soil CO2 flux measurements, outgassing at the Crystal Geyser, and travertine deposits provide the surface expression of CO2 seeps along and near the fault. Borehole and past geophysical data provide a structural and stratigraphic framework for the site. Through historic and new water temperature data, I identify and characterize eruption cycles at the Crystal Geyser. I show that the frequency and duration of eruptions changes through time, and I observe an overall increase in eruption duration. With a new seismic monitoring approach, I show that a surface-based accelerated weight drop source into a stationary geophone spread is repeatable and appropriate for time-lapse seismic studies to monitor reservoir changes. I show repeated surface and body wave measurements with a 30-hour time-lapse dataset. I model seismic velocity changes with changing CO2 saturation within the main Navajo Sandstone reservoir. My models show that during initial saturations, seismically resolvable reservoir changes are possible to monitor. However, I show that a critically saturated reservoir, like that along the Little Grand Wash fault, shows travel time or amplitude changes that are below the resolving capabilities of my surface-based seismic system. While my surface based seismic approach is not appropriate for monitoring CO2 changes at my field site, this same approach could be used to monitor CO2 changes during initial CCS injection where a larger seismic response would be expected

Data from: Impact of genetic reduction of NMNAT2 on chemotherapy-induced losses in cell viability in vitro and peripheral neuropathy in vivo

Nicotinamide mononucleotide adenylyl transferases (NMNATs) are essential neuronal maintenance factors postulated to preserve neuronal function and protect against axonal degeneration in various neurodegenerative disease states. We used in vitro and in vivo approaches to assess the impact of NMNAT2 reduction on cellular and physiological functions induced by treatment with a vinca alkaloid (vincristine) and a taxane-based (paclitaxel) chemotherapeutic agent. NMNAT2 null (NMNAT2-/-) mutant mice die at birth and cannot be used to probe functions of NMNAT2 in adult animals. Nonetheless, primary cortical cultures derived from NMNAT2-/- embryos showed reduced cell viability in response to either vincristine or paclitaxel treatment whereas those derived from NMNAT2 heterozygous (NMNAT2+/-) mice were preferentially sensitive to vincristine-induced degeneration. Adult NMNAT2+/- mice, which survive to adulthood, exhibited a 50% reduction of NMNAT2 protein levels in dorsal root ganglia relative to wildtype (WT) mice with no change in levels of other NMNAT isoforms (NMNAT1 or NMNAT3), NMNAT enzyme activity (i.e. NAD/NADH levels) or microtubule associated protein-2 (MAP2) or neurofilament protein levels. We therefore compared the impact of NMNAT2 knockdown on the development and maintenance of chemotherapy-induced peripheral neuropathy induced by vincristine and paclitaxel treatment using NMNAT2+/- and WT mice. NMNAT2+/- did not differ from WT mice in either the development or maintenance of either mechanical or cold allodynia induced by either vincristine or paclitaxel treatment. Intradermal injection of capsaicin, the pungent ingredient in hot chili peppers, produced equivalent hypersensitivity in NMNAT2+/- and WT mice receiving vehicle in lieu of paclitaxel. Capsaicin-evoked hypersensitivity was enhanced by prior paclitaxel treatment but did not differ in either NMNAT2+/- or WT mice. Thus, capsaicin failed to unmask differences in nociceptive behaviors in either paclitaxel-treated or paclitaxel-untreated NMNAT2+/- and WT mice. Moreover, no differences in motor behavior were detected between genotypes in the rotarod test. Our studies do not preclude the possibility that complete knockout of NMNAT2 in a conditional knockout animal could unmask a role for NMNAT2 in protection against detrimental effects of chemotherapeutic treatment

The chemotherapeutic agent paclitaxel selectively impairs learning while sparing source memory and spatial memory

Chemotherapeutic agents are widely used to treat patients with systemic cancer. The efficacy of these therapies is undermined by their adverse side-effect profiles such as cognitive deficits that have a negative impact on the quality of life of cancer survivors. Cognitive side effects occur across a variety of domains, including memory, executive function, and processing speed. Such impairments are exacerbated under cognitive challenges and a subgroup of patients experience long-term impairments. Episodic memory in rats can be examined using a source memory task. In the current study, rats received paclitaxel, a taxane-derived chemotherapeutic agent, and learning and memory functioning was examined using the source memory task. Treatment with paclitaxel did not impair spatial and episodic memory, and paclitaxel treated rats were not more susceptible to cognitive challenges. Under conditions in which memory was not impaired, paclitaxel treatment impaired learning of new rules, documenting a decreased sensitivity to changes in experimental contingencies. These findings provide new information on the nature of cancer chemotherapy- induced cognitive impairments, particularly regarding the incongruent vulnerability of episodic memory and new learning following treatment with paclitaxel

NMNAT Vonfrey Acetone Vincristine 9 29 14

Contains raw data for the Vincristine graphs and experiments. Group A is the NMNAT2 +/- group and B is the wild-type group

Data from: Impact of genetic reduction of NMNAT2 on chemotherapy-induced losses in cell viability in vitro and peripheral neuropathy in vivo

Nicotinamide mononucleotide adenylyl transferases (NMNATs) are essential neuronal maintenance factors postulated to preserve neuronal function and protect against axonal degeneration in various neurodegenerative disease states. We used in vitro and in vivo approaches to assess the impact of NMNAT2 reduction on cellular and physiological functions induced by treatment with a vinca alkaloid (vincristine) and a taxane-based (paclitaxel) chemotherapeutic agent. NMNAT2 null (NMNAT2-/-) mutant mice die at birth and cannot be used to probe functions of NMNAT2 in adult animals. Nonetheless, primary cortical cultures derived from NMNAT2-/- embryos showed reduced cell viability in response to either vincristine or paclitaxel treatment whereas those derived from NMNAT2 heterozygous (NMNAT2+/-) mice were preferentially sensitive to vincristine-induced degeneration. Adult NMNAT2+/- mice, which survive to adulthood, exhibited a 50% reduction of NMNAT2 protein levels in dorsal root ganglia relative to wildtype (WT) mice with no change in levels of other NMNAT isoforms (NMNAT1 or NMNAT3), NMNAT enzyme activity (i.e. NAD/NADH levels) or microtubule associated protein-2 (MAP2) or neurofilament protein levels. We therefore compared the impact of NMNAT2 knockdown on the development and maintenance of chemotherapy-induced peripheral neuropathy induced by vincristine and paclitaxel treatment using NMNAT2+/- and WT mice. NMNAT2+/- did not differ from WT mice in either the development or maintenance of either mechanical or cold allodynia induced by either vincristine or paclitaxel treatment. Intradermal injection of capsaicin, the pungent ingredient in hot chili peppers, produced equivalent hypersensitivity in NMNAT2+/- and WT mice receiving vehicle in lieu of paclitaxel. Capsaicin-evoked hypersensitivity was enhanced by prior paclitaxel treatment but did not differ in either NMNAT2+/- or WT mice. Thus, capsaicin failed to unmask differences in nociceptive behaviors in either paclitaxel-treated or paclitaxel-untreated NMNAT2+/- and WT mice. Moreover, no differences in motor behavior were detected between genotypes in the rotarod test. Our studies do not preclude the possibility that complete knockout of NMNAT2 in a conditional knockout animal could unmask a role for NMNAT2 in protection against detrimental effects of chemotherapeutic treatment

DRGEXP

DRG quantification data from western blots and NAD/NADH activity

NMNATGraphPad

The primary graph file used to generate figures 2-5. Contains averages of each subject throughout the necessary timecourse (via the spreadsheets)

Capsascin

The capsaicin spreadsheet contains raw data for each timepoint following capsaicin administration, as well as a tab for nocifensive behavior. The animals are the same as the paclitaxel spreadsheet

Vonfrey Acetone and RotaRod Data Paclitaxel

Contains raw data for the paclitaxel graphs and expiriments as well as rotarod data averages. Group A is the NMNAT2 +/- group and B is the wild-type group

MTT data

Contains average output for three experiments for WT vs HET vs KO as well as the graph template for Figure 1