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Mitochondria are epicentres of eukaryotic metabolism and bioenergetics. Pioneering efforts in recent decades have established the core protein componentry of these organelles 1 and have linked their dysfunction to more than 150 distinct disorders 2 , 3 . Still, hundreds of mitochondrial proteins lack clear functions 4 , and the underlying genetic basis for approximately 40% of mitochondrial disorders remains unresolved 5 . Here, to establish a more complete functional compendium of human mitochondrial proteins, we profiled more than 200 CRISPR-mediated HAP1 cell knockout lines using mass spectrometry-based multiomics analyses. This effort generated approximately 8.3 million distinct biomolecule measurements, providing a deep survey of the cellular responses to mitochondrial perturbations and laying a foundation for mechanistic investigations into protein function. Guided by these data, we discovered that PIGY upstream open reading frame (PYURF) is an S -adenosylmethionine-dependent methyltransferase chaperone that supports both complex I assembly and coenzyme Q biosynthesis and is disrupted in a previously unresolved multisystemic mitochondrial disorder. We further linked the putative zinc transporter SLC30A9 to mitochondrial ribosomes and OxPhos integrity and established RAB5IF as the second gene harbouring pathogenic variants that cause cerebrofaciothoracic dysplasia. Our data, which can be explored through the interactive online MITOMICS.app resource, suggest biological roles for many other orphan mitochondrial proteins that still lack robust functional characterization and define a rich cell signature of mitochondrial dysfunction that can support the genetic diagnosis of mitochondrial diseases. A multiomics resource characterizing human mitochondrial proteins enables identification of biological functions and supports genetic diagnosis of mitochondrial pathologies.

The objective of this research was to improve the forging outcome of peritectic solidifying cast titanium aluminide (TiAl) 4822 alloy (Ti-48Al-2Nb-2Cr at.%) in hot isostatic pressed and homogenised (HH) condition using cyclic induction heat treatment (CHT). This study adds to research around CHT for TiAl alloys by applying industrially relevant induction heating to conduct five heating cycles at the single αphase temperatures (1370 °C) necessary for grain refinement. Two cooling rates were explored in each cycle, air cooling (ACCHT) and controlled furnace-like cooling (FCCHT), without returning to room temperature. Samples were assessed at each stage in terms of their morphologies, lamellar grain size and content, as well as phase and dynamic recrystallised fraction, and subsequent primary and secondary compression behaviour with uniaxial isothermal compression. The FCCHT process resulted in a homogeneously refined fully lamellar microstructure, and ACCHT, in a heterogeneous microstructure consisting of lamellar and feathery γ (γf) at differing fractions across the piece, depending on the cooling rate compared with HH. The results show that CHT improved forging outcomes for both compression stages investigated, resulting in uniform compression samples with higher volumes of dynamic recrystallised material compared with the instability seen with the compression of HH material.

Current healthcare practices are reactive and based on limited physiological information collected months or years apart. By enabling patients and healthy consumers access to continuous measurements of health, wearable devices and digital medicine stand to realize highly personalized and preventative care. However, most current digital technologies provide information on a limited set of physiological traits, such as heart rate and step count, which alone offer little insight into the etiology of most diseases. Here we propose to integrate data from biohealth smartphone applications with continuous metabolic phenotypes derived from urine metabolites. This combination of molecular phenotypes with quantitative measurements of lifestyle reflect the biological consequences of human behavior in real time. We present data from an observational study involving two healthy subjects and discuss the challenges, opportunities, and implications of integrating this new layer of physiological information into digital medicine. Though our dataset is limited to two subjects, our analysis (also available through an interactive web-based visualization tool) provides an initial framework to monitor lifestyle factors, such as nutrition, drug metabolism, exercise, and sleep using urine metabolites.

Continental flood basalts (CFBs) are dominated by two characteristic lava morphologies. The first type, referred to as ‘compound’ or ‘hummocky pāhoehoe,’ exhibits pillow-like lava flow lobes with cross-sections of ~ 0.5–2 m and thin chilled margins. The second type, referred to as ‘simple’ or ‘sheet lobes’ preserves more massive, inflated flow interiors that are laterally continuous on scales of 100s of meters to kilometers. Previous hypotheses suggest that two factors may contribute to stratigraphic changes in morphology from ‘compound’ to ‘simple’: 1) increased eruption duration or 2) increased extrusion rate. We test the hypothesis that a large increase in extrusion rate would result in flow morphology transitioning from multiple small lobes to inflated sheet lobes due to a shift in flow propagation from intraflow resurfacing-dominated to marginal breakout-dominated. Using polyethylene glycol (PEG) wax extruded into a circular water-filled tank 130 cm in diameter, we produced larger, more complex experiments than previous studies. Our efforts simulated more complex lava fields which change flow morphology with distance from the eruptive vent, characteristic of CFBs. Whereas previous PEG studies linked extrusion rate to near-source surface morphologies, our experiments evaluated how flow propagation mechanisms change with variable extrusion rate and distance from the source. Two flow propagation styles were identified: 1) resurfacing, in which molten material breaks through the surface of a flow and covers the older crust and 2) marginal breakouts, in which molten material extends beyond the crust at the active distal margin of the flow. Flows that propagated via marginal breakouts were found to have lower proportions of resurfaced area and vice versa. We show that significant resurfacing is needed to preserve internal chilled boundaries within a flow and a low-extrusion-rate surface morphology, whereas marginal breakout-dominated flows tend to inflate the pillow-like surface morphology preserving a massive interior at great distances from the vent. Higher and more steady extrusion rates tend to decrease the extent of resurfacing and increase the distance between the source and preserved low-extrusion-rate surface morphologies. We find that an extrusion rate increase equivalent to a jump in the extrusion rate scaling factor, Ψ value, from < 1 to > 5 would be necessary to ensure a switch from resurfacing-dominated lobate morphologies to marginal breakout-dominated propagation style. This amounts to a factor of 125 increase in effusion rate for fissure eruptions and a factor of 625 for point source eruptions, assuming no change in vent geometry. This would be equivalent to an effusion rate of 0.2 m 3 /s, as documented in 1987–1990 Kīlauea eruptions, increasing to 125 m 3 /s, which was commonly measured during the 2014 Holuhraun eruption in Iceland and the 2018 eruption at Leilani Estates in Hawai‘i. Thus, we propose that continental flood basalts do not require unusually large effusion rates, but instead were active for a longer and more consistent time period than smaller-volume eruptions.

Throughout its approximately fifty-year history as a vehicle for punk cultural production, the cassette tape remains a powerful signifier of anti-commercialism for punks. This dissertation considers the legacy of the cassette tape as a companion to punk rock and as a recording and playback medium that democratized the means of documentation through its accessibility, portability, durability, and copiability. Drawing on archival research and interviews, I construct four case studies—1970s New York City (NYC), 1980s/1990s East Bay (California), 2000s/2010s Midwest emo revival, and 1980s Washington D.C. Hardcore —that demonstrate the evolving significance of the cassette tape, and illustrate how antiquated technologies continue to live on after their supposed obsolescence. Through my four case studies I examine the significance of the cassette tape as a type of sonic memoir, do-it-yourself history tool, object of nostalgia, and physical artifact in an increasingly digitized world. I also challenge popular imaginaries of both the cassette tape and punk that depict the medium and subculture as democratizing forces in the production and dissemination of art, asking how does the cassette tape’s use in punk also demonstrates a curatorial and gatekeeping function? In exploring the significance of the cassette tape to these punk scenes, I aim to illustrate the importance of recording and playback media as a means of shaping what is possible and how we recognize and imagine ourselves through technology.

Lava flow emplacement in the laboratory and on the surface of Mars was investigated. In the laboratory, the effects of unsteady effusion rates at the vent on four modes of emplacement common to lava flow propagation: resurfacing, marginal breakouts, inflation, and lava tubes was addressed. A total of 222 experiments were conducted using a programmable pump to inject dyed PEG wax into a chilled bath (~ 0° C) in tanks with a roughened base at slopes of 0, 7, 16, and 29°. The experiments were divided into four conditions, which featured increasing or decreasing eruption rates for either 10 or 50 s. The primary controls on modes of emplacement were crust formation, variability in the eruption rate, and duration of the pulsatory flow rate. Resurfacing – although a relatively minor process – is inhibited by an extensive, coherent crust. Inflation requires a competent, flexible crust. Tube formation requires a crust and intermediate to low effusion rates. On Mars, laboratory analogue experiments combined with models that use flow dimensions to estimate emplacement conditions and using high resolution image data and digital terrain models (e.g. THEMIS IR, CTX, HRSC), the eruption rates, viscosities, and yield strengths of 40 lava flows in the Tharsis Volcanic Province have been quantified. These lava flows have lengths, mean widths, and mean thicknesses of 15 – 314 km, 0.5 – 29 km, and 11 – 91 m, respectively. Flow volumes range from ~1 – 430 km3. Based on laboratory experiments, the 40 observed lava flows were erupted at 0.2 – 6.5x103 m3/s, while the Graetz number and Jeffrey’s equation when applied to 34 of 40 lava flows indicates eruption rates and viscosities of 300 – ~3.5 x 104 m3/s and ~105 – 108 Pa s, respectively. Another model which accounts for mass loss to levee formation was applied to a subset of flows, n = 13, and suggests eruption rates and viscosities of ~30 – ~1.2 x 103 m3/s and 4.5 x 106 – ~3 x 107 Pa s, respectively. Emplacement times range from days to centuries indicating the necessity for long-term subsurface conduits capable of delivering enormous volumes of lava to the surface.

Mitochondria are epicenters of eukaryotic metabolism and bioenergetics. Pioneering efforts in recent decades have established the core protein componentry of these organelles1 and have linked their dysfunction to over 150 distinct disorders2,3. Still, hundreds of mitochondrial proteins lack clear functions4, and 40% of mitochondrial disorders remain unresolved5. To establish a more complete functional compendium of human mitochondrial proteins, we profiled over 200 CRISPR-mediated HAP1 cell knockout lines using mass spectrometry-based multi-omics analyses. This effort generated 8.3 million distinct biomolecule measurements, providing a deep survey of the cellular responses to mitochondrial perturbations, and laying a foundation for mechanistic investigations into protein function. Guided by these data, we discovered that PYURF is a SAM-dependent methyltransferase chaperone that supports both complex I assembly and coenzyme Q biosynthesis, and that is disrupted in a previously unresolved multisystemic mitochondrial disorder. We further linked the putative zinc transporter SLC30A9 to mitoribosome and OxPhos integrity and established RAB5IF as the second gene harboring pathogenic variants causing cerebrofaciothoracic dysplasia. Our data—which can be explored through an interactive online MITOMICS.app resource—suggest biological roles for many other orphan mitochondrial proteins still lacking robust functional characterization, and define a rich cell signature of mitochondrial dysfunction that can support the genetic diagnosis of mitochondrial diseases.

The use of 2-hydroxypropyl-β-cyclodextrin (2-HPCD) for the tandem extraction and proximity-induced energy transfer based detection of carcinogenic polycyclic aromatic hydrocarbons (PAHs) is described herein. Previous work investigated γ-cyclodextrin for this purpose, but the lower cost and reduced toxicity of 2-HPCD made it an attractive target for investigation. 2-HPCD was found to be highly efficient in the extraction of PAHs from oil samples, but was equally or slightly less efficient in promoting intra-cavity energy transfer to a high quantum yield fluorophore. The detection of PAHs via this system results in a new fluorescent signal that can be used to identify different PAHs in aqueous solution. This dual-function system can be very beneficial for oil spill remediation efforts.

Can ambient radio signals, such as the Sun, be used to monitor the thickness of glaciers? Traditional ice-penetrating radars transmit a powerful electromagnetic pulse and record the echo's delay time and power to measure ice sheet thickness and subsurface conditions. While active radar sounding is the principle remote sensing technique used to observe the subsurface of Greenland and Antarctica, existing radar systems are resource-intensive in terms of cost, power, and logistics when simultaneously monitoring ice sheets at both their evolving temporal (daily to multiannual) and spatial (tributary to continental) scales. However, these observations are critical as ice sheet contribution to sea level rise presents one of the greatest challenges our society faces in the next century. In this dissertation, we address this challenge by developing a novel, low-resource, passive radar sounding technique that uses ambient radio signals from the Sun to observe the subsurface of ice sheets at these spatiotemporal scales, instead of transmitting its own powerful radio signal for echo detection.In this work, we demonstrate for the first time that one can use the Sun as a signal of opportunity to measure ice sheet thickness. Starting from theory, simulation, and lab testing, we first show how one can extract the amplitude and delay time of a received white noise Sun echo. We then describe how this passive radar technique was used to measure ice thickness at Store Glacier, Greenland. We then evaluate the passive radar's performance and ability to provide valuable glaciological observations, such as melt rates, bed reflectivity changes, and englacial water storage-all scientific measurements that have traditionally been obtained using active radar systems but never passively.We then extend this technique to develop a novel passive synthetic aperture radar (SAR) approach that uses astronomical white noise, such as the Sun and Jupiter's radio emissions, as a source for echo detection, ranging, and imaging. We conclude with an analysis of how a passive HF radar could use Jupiter's radio emissions alongside an active VHF radar to correct for the dispersive effects of the ionosphere, estimate Europa's total electron content, and characterize Europa's ionosphere during a flyby mission.