Next-generation equipment and procedures for combined resonant column and torsional shear testing

In this dissertation, work aimed at developing next-generation equipment and procedures for combined resonant column and torsional shear (RCTS) testing are detailed. The work in this dissertation covers three key areas of RCTS testing that need improvement to reach the next level of RCTS testing. The first area involved improvement in measurement resolution with modern control and monitoring equipment. Concurrently, original software was written to enhance the efficiency, accuracy, and repeatability of the test. The second area involved advancing concepts for evaluating and modeling nonlinear behavior of soil, which was done in part by using raw RCTS test data collected and stored from 2013-2017. The third area involved evaluating and modifying the design of the existing RCTS device to accommodate higher levels of shearing strain and provide higher loading capacity. First, when testing at small shear strains (< 0.001%) within the linear-elastic range of soils, very small excitation voltages must be used and very small voltages are recorded from the RCTS sensors. Obtaining accurate measurements in the linear-elastic range is critically important when testing at low confining pressures (in the range of 0.1 to 1 atm). In traditional RCTS data acquisition systems, very small recorded voltages are lost due to limited resolution of the control and monitoring subsystems. Concurrently, the very small recorded voltages are generally heavily contaminated by environmental background noise that invalidates the automated process for reducing raw data into engineering results. Control and monitoring equipment and software were developed that can enhance the measurement and data reduction process when making low-strain measurements. Second, testing of soil in the nonlinear shear strain range (typically greater than 0.001%) is a complex process that departs from traditional dynamic models for single-degree-of-freedom (SDOF) systems. Traditionally, RCTS results from testing in the nonlinear shear strain range involve slight adaptation of traditional SDOF models to obtain nonlinear relationships. Nonlinear dynamics model concepts were taken from literature and adapted to better understand and model nonlinear behavior of soils in RCTS testing. Furthermore, development of nonlinear models at moderate strains help to bridge the spectrum of soil testing which tends to divide into evaluating soils at small to moderate strains (< 0.2%) or at large strains (≥ 0.2%). Third, when testing soils at large shearing strains (> 0.2%), traditional RCTS systems are physically or electronically limited. At higher confining pressures (> 2 atm) where soils become quite stiff, the traditional RCTS control equipment is electronically incapable of driving enough torque output to strain soils in shear above desired levels (> 0.1%). At low confining pressures ( 0.5%). An RCTS testing device was designed that has a torque-output capacity at least three times greater than a traditional RCTS device and an allowable degree of twist that can generate shearing strains above 1%.Civil, Architectural, and Environmental Engineerin

PROBING EARTH DEFORMATION IN RESPONSE TO LOCALIZED HYDROLOGIC MASS LOADING, SUSITNA RIVER BASIN, ALASKA

Surface mass loading contributes a ubiquitous signal to GPS time series that can be modeled and removed for individual sources. We utilize nine GPS stations in the Susitna River watershed, Alaska, to investigate surface displacements from surface mass loading. We find that modeling atmospheric surface pressure and regional hydrologic mass reduces root mean square (RMS) error by 27-39% for all GPS time series. We observe moderate correlation between residual time series pairs and distance, with elevation differences influencing the strength of this correlation. Seasonal horizontal and vertical displacements are observed after removal of all loading models; stations displace downward and northwest during winter months, and upward and southeast during summer months. The temporal displacements are generally correlated with precipitation and Susitna River discharge. Removing the common mode error (CME) from all stations highlights small variations in both spatial and temporal displacements, with time series reflecting local loading sources rather than being dominated by regional trends. The standard deviation of the post-CME measurements indicates that there is moderate uncertainty in both phase and amplitude information. GPS measurement uncertainties contribute to the standard deviation, as well as inter-annual variations in climate; stations also deform due to local variations in temperature and precipitation

Strontium Isotopic Variations of Neoproterozoic Seawater: Implications for Crustal Evolution

We report high precision Sr isotopic data on carbonates from the Neoproterozoic Shaler Group, Victoria Island, Northwest Territories, Canada. Lithostratigraphic correlations with the relatively well-dated Mackenzie Mountains Supergroup constrain Shaler deposition to approximately 770-880 Ma, a range corroborated by 723 +/- 3 Ma lavas that disconformably overlie Shaler carbonates and by Late Riphean microfossils within the section. Samples with low Rb-87/Sr-86 ratios (< 0.01) were selected for Sr isotopic analysis. delta-O-18, Mn, Ca, Mg, and Sr data were used to recognize altered samples. The altered samples are characterized by high Mn/Sr (greater-than-or-equal-to 2) and variable delta-O-18; most are dolomites. The data indicate that between ca. 790-850 Ma the Sr-87/Sr-86 ratio of seawater varued between 0.70676 and 0.70561. The samples show smooth and systematic variation, with the lowest Sr-87/Sr-86 value of 0.70561 at ca. 830 Ma. The low Sr-87/Sr-86 ratio of carbonates from the lower parts of our section is similar to a value reported for one sample from the Adrar of Mauritania (almost-equal-to 900 Ma), West African Craton. Isotopic ratios from the upper part of the Shaler section are identical to values from the lower part of the Neoproterozoic Akademikerbreen Group, Spitsbergen. Although a paucity of absolute age determinations hinders attempts at the precise correlation of Neoproterozoic successions, it is possible to draw a broad outline of the Sr isotopic composition of seawater for this period. Indeed, the Sr isotope data themselves provide a stratigraphic tool of considerable potential. Data from this study and the literature are used to construct a curve of the Sr-87/Sr-86 ratio of Neoproterozoic seawater. The new data reported in this study substantially improve the isotopic record of Sr in seawater for the period 790-850 Ma. The Sr isotope composition of seawater reflects primarily the balance between continental Sr input through river input and mantle input via hydrothermal circulation of seawater through mid-ocean ridges. Coupling of Nd and Sr isotopic systems allows us to model changes in seafloor spreading rates (or hydrothermal flux) and continental erosion. The Sr hydrothermal flux and the erosion rate (relative to present-day value) are modeled for the period 500-900 Ma. The results indicate that the hydrothermal flux reached a maximum value at ca. 830 Ma. In contrast, a large peak in erosion rate is indicated at ca. 570 Ma. The peaks in hydrothermal flux and erosion rate are most likely related to developments in the Pan-African and related orogenic events, whose initial development is characterized by production of juvenile crust during supercontinental break up and rifting. The time ca. 570 Ma is characterized by continent-continent collision and production of recycled crust. Sr isotope data from Proterozoic carbonates offer a valuable resource for understanding large-scale crust dynamics.Earth and Planetary SciencesOrganismic and Evolutionary Biolog

Diversity in rest-activity patterns among Lake Malawi cichlid fishes suggests a novel axis of habitat partitioning

Animals display remarkable diversity in rest and activity patterns that are regulated by endogenous foraging strategies, social behaviors and predator avoidance. Alteration in the circadian timing of activity or the duration of rest–wake cycles provide a central mechanism for animals to exploit novel niches. The diversity of the \u3e3000 cichlid species throughout the world provides a unique opportunity to examine variation in locomotor activity and rest. Lake Malawi alone is home to over 500 species of cichlids that display divergent behaviors and inhabit well-defined niches throughout the lake. These species are presumed to be diurnal, though this has never been tested systematically. Here, we measured locomotor activity across the circadian cycle in 11 Lake Malawi cichlid species. We documented surprising variability in the circadian time of locomotor activity and the duration of rest. In particular, we identified a single species, Tropheops sp. ‘red cheek’, that is nocturnal. Nocturnal behavior was maintained when fish were provided shelter, but not under constant darkness, suggesting that it results from acute response to light rather than an endogenous circadian rhythm. Finally, we showed that nocturnality is associated with increased eye size after correcting for evolutionary history, suggesting a link between visual processing and nighttime activity. Together, these findings identify diversity of locomotor behavior in Lake Malawi cichlids and provide a system for investigating the molecular and neural basis underlying variation in nocturnal activity

SatCat5: A Low-Power, Mixed-Media Ethernet Network for Smallsats

In any satellite, internal bus and payload systems must exchange a variety of command, control, telemetry, and mission-data. In too many cases, the resulting network is an ad-hoc proliferation of complex, dissimilar protocols with incomplete system-to-system connectivity. While standards like CAN, MIL-STD-1553, and SpaceWire mitigate this problem, none can simultaneously solve the need for high throughput and low power consumption. We present a new solution that uses Ethernet framing and addressing to unify a mixed-media network. Low-speed nodes (0.1-10 Mbps) use simple interfaces such as SPI and UART to communicate with extremely low power and minimal complexity. High-speed nodes use so-called “media-independent” interfaces such as RMII, RGMII, and SGMII to communicate at rates up to 1000 Mbps and enable connection to traditional COTS network equipment. All are interconnected into a single smallsat-area-network using a Layer-2 network switch, with mixed-media support for all these interfaces on a single network. The result is fast, easy, and flexible communication between any two subsystems. SatCat5 is presented as a free and open-source reference implementation of this mixed-media network switch, with power consumption of 0.2-0.7W depending on network activity. Further discussion includes example protocols that can be used on such networks, leveraging IPv4 when suitable but also enabling full-featured communication without the need for a complex protocol stack

Metabolic requirements for cancer cell proliferation

Background: The study of cancer metabolism has been largely dedicated to exploring the hypothesis that oncogenic transformation rewires cellular metabolism to sustain elevated rates of growth and division. Intense examination of tumors and cancer cell lines has confirmed that many cancer-associated metabolic phenotypes allow robust growth and survival; however, little attention has been given to explicitly identifying the biochemical requirements for cell proliferation in a rigorous manner in the context of cancer metabolism. Results: Using a well-studied hybridoma line as a model, we comprehensively and quantitatively enumerate the metabolic requirements for generating new biomass in mammalian cells; this indicated a large biosynthetic requirement for ATP, NADPH, NAD+, acetyl-CoA, and amino acids. Extension of this approach to serine/glycine and glutamine metabolic pathways suggested lower limits on serine and glycine catabolism to supply one-carbon unit synthesis and significant availability of glutamine-derived carbon for biosynthesis resulting from nitrogen demands alone, respectively. We integrated our biomass composition results into a flux balance analysis model, placing upper bounds on mitochondrial NADH oxidation to simulate metformin treatment; these simulations reproduced several empirically observed metabolic phenotypes, including increased reductive isocitrate dehydrogenase flux. Conclusions: Our analysis clarifies the differential needs for central carbon metabolism precursors, glutamine-derived nitrogen, and cofactors such as ATP, NADPH, and NAD+, while also providing justification for various extracellular nutrient uptake behaviors observed in tumors. Collectively, these results demonstrate how stoichiometric considerations alone can successfully predict empirically observed phenotypes and provide insight into biochemical dynamics that underlie responses to metabolic perturbations.National Institutes of Health (U.S.) (Grant 1R01DK075850-01)National Institutes of Health (U.S.) (Grant 1R01CA160458-01A1

Why Do We Fall? Using Experiences of Failure to Design Case Libraries

Instructional designers can support ill-structured problem solving through case libraries that detail domain-specific principles. In this design project, case libraries were employed in an undergraduate sales management course to contextualize knowledge and describe the ill-structured nature of how solutions are derived to solve authentic problems. Whereas many learning environments employ examples of model behavior (Jonassen, 2011), this instructional design was innovative in that the case libraries consisted of sales management failure experiences as the means to facilitate learning. The failure cases embedded within the learning environment engendered design tensions on multiple levels throughout the instructional design. Specifically, this article discusses the issues of engaging the subject matter expert (SME) to talk about failure cases and subsequent challenges to translate the experiences into meaningful learning resources for ill-structured problem solving. Other challenges included how to strategically design the learning environment so that the case library was available at the optimal time for the learners. The design case concludes with a reflection upon the process

Initial supplementary dose of Dolutegravir in second-line antiretroviral therapy: a noncomparative, double-blind, randomized placebo-controlled trial

BACKGROUND: Dolutegravir concentrations are reduced by efavirenz induction effect necessitating twice-daily dolutegravir dosing when coadministered. Efavirenz induction persists for several weeks after stopping, which could potentially select for dolutegravir resistance if switching occurred with unsuppressed human immunodeficiency virus type 1 (HIV-1) RNA levels and standard dolutegravir dosing. We evaluated the need for a lead-in supplementary dolutegravir dose in adults failing first-line tenofovir-emtricitabine-efavirenz (TEE). METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2 trial in Khayelitsha, South Africa. Eligible patients had virologic failure (2 consecutive HIV-1 RNA ≥1000 copies/mL) on first-line TEE. Participants were randomly assigned (1:1) to switch to tenofovir-lamivudine-dolutegravir (TLD) with a supplementary 50 mg dolutegravir dose or placebo taken 12 hours later for 14 days. Primary outcome was proportion with HIV-1 RNA <50 copies/mL at week 24. This study was not powered to compare arms. RESULTS: One hundred thirty participants were randomized (65 to each arm). Median baseline HIV-1 RNA was 4.0 log10 copies/mL and 76% had baseline resistance to both tenofovir and lamivudine. One participant died and 2 were lost to follow-up. At week 24, 55 of 64 (86% [95% confidence interval {CI}: 75%-93%]) in the supplementary dolutegravir arm and 53 of 65 (82% [95% CI: 70%-90%]) in the placebo arm had HIV-1 RNA <50 copies/mL. Grade 3 or 4 adverse events were similar in frequency between arms. None of 6 participants (3 in each arm) eligible for resistance testing by 24 weeks developed dolutegravir resistance. CONCLUSIONS: Our findings do not support the need for initial dolutegravir dose adjustment in patients switching to TLD who failed first-line TEE. CLINICAL TRIALS REGISTRATION: NCT03991013

Standard-dose versus double-dose dolutegravir in HIV-associated tuberculosis in South Africa (RADIANT-TB): a phase 2, non-comparative, randomised controlled trial

Background: The drug–drug interaction between rifampicin and dolutegravir can be overcome by supplemental dolutegravir dosing, which is difficult to implement in high-burden settings. We aimed to test whether virological outcomes with standard-dose dolutegravir-based antiretroviral therapy (ART) are acceptable in people with HIV on rifampicin-based antituberculosis therapy. Methods: RADIANT-TB was a phase 2b, randomised, double-blind, non-comparative, placebo-controlled trial at a single site in Khayelitsha, Cape Town, South Africa. Participants were older than 18 years of age, with plasma HIV-1 RNA greater than 1000 copies per mL, CD4 count greater than 100 cells per μL, ART-naive or first-line ART interrupted, and on rifampicin-based antituberculosis therapy for less than 3 months. By use of permuted block (block size of 6) randomisation, participants were assigned (1:1) to receive either tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus supplemental 50 mg dolutegravir 12 h later or tenofovir disoproxil fumarate, lamivudine, and dolutegravir plus matched placebo 12 h later. Participants received standard antituberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol for the first 2 months followed by isoniazid and rifampicin for 4 months). The primary outcome was the proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL) at week 24 analysed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03851588. Findings: Between Nov 28, 2019, and July 23, 2021, 108 participants (38 female, median age 35 years [IQR 31–40]) were randomly assigned to supplemental dolutegravir (n=53) or placebo (n=55). Median baseline CD4 count was 188 cells per μL (IQR 145–316) and median HIV-1 RNA was 5·2 log10 copies per mL (4·6–5·7). At week 24, 43 (83%, 95% CI 70–92) of 52 participants in the supplemental dolutegravir arm and 44 (83%, 95% CI 70–92) of 53 participants in the placebo arm had virological suppression. No treatment-emergent dolutegravir resistance mutations were detected up to week 48 in the 19 participants with study-defined virological failure. Grade 3 and 4 adverse events were similarly distributed between the study arms. The most frequent grade 3 and 4 adverse events were weight loss (4/108 [4%]), insomnia (3/108 [3%]), and pneumonia (3/108 [3%]). Interpretation: Our findings suggest that twice-daily dolutegravir might be unnecessary in people with HIV-associated tuberculosis. Funding: Wellcome Trust