Relative Contributions of Prenylation and Postprenylation Processing in Cryptococcus neoformans Pathogenesis.

Prenyltransferase enzymes promote the membrane localization of their target proteins by directing the attachment of a hydrophobic lipid group at a conserved C-terminal CAAX motif. Subsequently, the prenylated protein is further modified by postprenylation processing enzymes that cleave the terminal 3 amino acids and carboxymethylate the prenylated cysteine residue. Many prenylated proteins, including Ras1 and Ras-like proteins, require this multistep membrane localization process in order to function properly. In the human fungal pathogen Cryptococcus neoformans, previous studies have demonstrated that two distinct forms of protein prenylation, farnesylation and geranylgeranylation, are both required for cellular adaptation to stress, as well as full virulence in animal infection models. Here, we establish that the C. neoformans RAM1 gene encoding the farnesyltransferase β-subunit, though not strictly essential for growth under permissive in vitro conditions, is absolutely required for cryptococcal pathogenesis. We also identify and characterize postprenylation protease and carboxyl methyltransferase enzymes in C. neoformans. In contrast to the prenyltransferases, deletion of the genes encoding the Rce1 protease and Ste14 carboxyl methyltransferase results in subtle defects in stress response and only partial reductions in virulence. These postprenylation modifications, as well as the prenylation events themselves, do play important roles in mating and hyphal transitions, likely due to their regulation of peptide pheromones and other proteins involved in development. IMPORTANCE Cryptococcus neoformans is an important human fungal pathogen that causes disease and death in immunocompromised individuals. The growth and morphogenesis of this fungus are controlled by conserved Ras-like GTPases, which are also important for its pathogenicity. Many of these proteins require proper subcellular localization for full function, and they are directed to cellular membranes through a posttranslational modification process known as prenylation. These studies investigate the roles of one of the prenylation enzymes, farnesyltransferase, as well as the postprenylation processing enzymes in C. neoformans. We demonstrate that the postprenylation processing steps are dispensable for the localization of certain substrate proteins. However, both protein farnesylation and the subsequent postprenylation processing steps are required for full pathogenesis of this fungus.

Coding Strategies and Implementations of Compressive Sensing

This dissertation studies the coding strategies of computational imaging to overcome the limitation of conventional sensing techniques. The information capacity of conventional sensing is limited by the physical properties of optics, such as aperture size, detector pixels, quantum efficiency, and sampling rate. These parameters determine the spatial, depth, spectral, temporal, and polarization sensitivity of each imager. To increase sensitivity in any dimension can significantly compromise the others.

This research implements various coding strategies subject to optical multidimensional imaging and acoustic sensing in order to extend their sensing abilities. The proposed coding strategies combine hardware modification and signal processing to exploiting bandwidth and sensitivity from conventional sensors. We discuss the hardware architecture, compression strategies, sensing process modeling, and reconstruction algorithm of each sensing system.

Optical multidimensional imaging measures three or more dimensional information of the optical signal. Traditional multidimensional imagers acquire extra dimensional information at the cost of degrading temporal or spatial resolution. Compressive multidimensional imaging multiplexes the transverse spatial, spectral, temporal, and polarization information on a two-dimensional (2D) detector. The corresponding spectral, temporal and polarization coding strategies adapt optics, electronic devices, and designed modulation techniques for multiplex measurement. This computational imaging technique provides multispectral, temporal super-resolution, and polarization imaging abilities with minimal loss in spatial resolution and noise level while maintaining or gaining higher temporal resolution. The experimental results prove that the appropriate coding strategies may improve hundreds times more sensing capacity.

Human auditory system has the astonishing ability in localizing, tracking, and filtering the selected sound sources or information from a noisy environment. Using engineering efforts to accomplish the same task usually requires multiple detectors, advanced computational algorithms, or artificial intelligence systems. Compressive acoustic sensing incorporates acoustic metamaterials in compressive sensing theory to emulate the abilities of sound localization and selective attention. This research investigates and optimizes the sensing capacity and the spatial sensitivity of the acoustic sensor. The well-modeled acoustic sensor allows localizing multiple speakers in both stationary and dynamic auditory scene; and distinguishing mixed conversations from independent sources with high audio recognition rate.

Globalizing the Sculptural Landscapes of the Sarapis and Isis Cults in Hellenistic and Roman Greece

“Globalizing the Sculptural Landscape of Isis and Sarapis Cults in Roman Greece,” asks questions of cross-cultural exchange and viewership of sculptural assemblages set up in sanctuaries to the Egyptian gods. Focusing on cognitive dissonance, cultural imagining, and manipulations of time and space, I theorize ancient globalization as a set of loosely related processes that shifted a community's connections with place. My case studies range from the 3rd century BCE to the 2nd century CE, including sanctuaries at Rhodes, Thessaloniki, Dion, Marathon, Gortyna, and Delos. At these sites, devotees combined mainstream Greco-Roman sculptures, Egyptian imports, and locally produced imitations of Egyptian artifacts. In the last case, local sculptors represented Egyptian subjects with Greco-Roman naturalistic styles, creating an exoticized visual ideal that had both local and global resonance. My dissertation argues that the sculptural assemblages set up in Egyptian sanctuaries allowed each community to construct complex narratives about the nature of the Egyptian gods. Further, these images participated in a form of globalization that motivated local communities to adopt foreign gods and reinterpret them to suit local needs.

I begin my dissertation by examining how Isis and Sarapis were represented in Greece. My first chapter focuses on single statues of Egyptian gods, describing their iconographies and stylistic tendencies through examples from Corinth and Gortyna. By comparing Greek examples with images of Sarapis, Isis, and Harpokrates from around the Mediterranean, I demonstrate that Greek communities relied on globally available visual tropes rather than creating site or region-specific interpretations. In the next section, I examine what other sources viewers drew upon to inform their experiences of Egyptian sculpture. In Chapter 3, I survey the textual evidence for Isiac cult practice in Greece as a way to reconstruct devotees’ expectations of sculptures in sanctuary contexts. At the core of this analysis are Apuleius’ Metamorphoses and Plutarch’s De Iside et Osiride, which offer a Greek perspective on the cult’s theology. These literary works rely on a tradition of aretalogical inscriptions—long hymns produced from roughly the late 4th century B.C.E. into the 4th century C.E. that describe the expansive syncretistic powers of Isis, Sarapis, and Harpokrates. This chapter argues that the textual evidence suggests that devotees may have expected their images to be especially miraculous and likely to intervene on their behalf, particularly when involved in ritual activity inside the sanctuary.

In the final two chapters, I consider sculptural programs and ritual activity in concert with sanctuary architecture. My fourth chapter focuses on sanctuaries where large amounts of sculpture were found in underground water crypts: Thessaloniki and Rhodes. These groups of statues can be connected to a particular sanctuary space, but their precise display contexts are not known. By reading these images together, I argue that local communities used these globally available images to construct new interpretations of these gods, ones that explored the complex intersections of Egyptian, Greek, and Roman identities in a globalized Mediterranean. My final chapter explores the Egyptian sanctuary at Marathon, a site where exceptional preservation allows us to study how viewers would have experienced images in architectural space. Using the Isiac visuality established in Chapter 3, I reconstruct the viewer's experience, arguing that the patron, Herodes Atticus, intended his viewer to inform his experience with the complex theology of Middle Platonism and prevailing elite attitudes about Roman imperialism.

Throughout my dissertation, I diverge from traditional approaches to culture change that center on the concepts of Romanization and identity. In order to access local experiences of globalization, I examine viewership on a micro-scale. I argue that viewers brought their concerns about culture change into dialogue with elements of cult, social status, art, and text to create new interpretations of Roman sculpture sensitive to the challenges of a highly connected Mediterranean world. In turn, these transcultural perspectives motivated Isiac devotees to create assemblages that combined elements from multiple cultures. These expansive attitudes also inspired Isiac devotees to commission exoticized images that brought together disparate cultures and styles in an eclectic manner that mirrored the haphazard way that travel brought change to the Mediterranean world. My dissertation thus offers a more theoretically rigorous way of modeling culture change in antiquity that recognizes local communities’ agency in producing their cultural landscapes, reconciling some of the problems of scale that have plagued earlier approaches to provincial Roman art.

These case studies demonstrate that cultural anxieties played a key role in how viewers experienced artistic imagery in the Hellenistic and Roman Mediterranean. This dissertation thus offers a new component in our understanding of ancient visuality, and, in turn, a better way to analyze how local communities dealt with the rise of connectivity and globalization.