Functional imaging of numerical processing in adults and 4-y-old children.

Adult humans, infants, pre-school children, and non-human animals appear to share a system of approximate numerical processing for non-symbolic stimuli such as arrays of dots or sequences of tones. Behavioral studies of adult humans implicate a link between these non-symbolic numerical abilities and symbolic numerical processing (e.g., similar distance effects in accuracy and reaction-time for arrays of dots and Arabic numerals). However, neuroimaging studies have remained inconclusive on the neural basis of this link. The intraparietal sulcus (IPS) is known to respond selectively to symbolic numerical stimuli such as Arabic numerals. Recent studies, however, have arrived at conflicting conclusions regarding the role of the IPS in processing non-symbolic, numerosity arrays in adulthood, and very little is known about the brain basis of numerical processing early in development. Addressing the question of whether there is an early-developing neural basis for abstract numerical processing is essential for understanding the cognitive origins of our uniquely human capacity for math and science. Using functional magnetic resonance imaging (fMRI) at 4-Tesla and an event-related fMRI adaptation paradigm, we found that adults showed a greater IPS response to visual arrays that deviated from standard stimuli in their number of elements, than to stimuli that deviated in local element shape. These results support previous claims that there is a neurophysiological link between non-symbolic and symbolic numerical processing in adulthood. In parallel, we tested 4-y-old children with the same fMRI adaptation paradigm as adults to determine whether the neural locus of non-symbolic numerical activity in adults shows continuity in function over development. We found that the IPS responded to numerical deviants similarly in 4-y-old children and adults. To our knowledge, this is the first evidence that the neural locus of adult numerical cognition takes form early in development, prior to sophisticated symbolic numerical experience. More broadly, this is also, to our knowledge, the first cognitive fMRI study to test healthy children as young as 4 y, providing new insights into the neurophysiology of human cognitive development.

"Double Rainbow," "Appalachiana," and "'The Invisible Mass': Exploring Compositional Technique in Alfred Schnittke's Second Symphony"

This dissertation consists of three distinct components: (1) “Double Rainbow,” a notated composition for an acoustic ensemble of 10 instruments, ca. 36 minutes. (2) “Appalachiana”, a fixed-media composition for electro-acoustic music and video, ca. 30 minutes, and (3) “'The Invisible Mass': Exploring Compositional Technique in Alfred Schnittke’s Second Symphony”, an analytical article.

(1) Double Rainbow is a ca. 36 minute composition in four movements scored for 10 instruments: flute, Bb clarinet (doubling on bass clarinet), tenor saxophone (doubling on alto saxophone), french horn, percussion (glockenspiel, vibraphone, wood block, 3 toms, snare drum, bass drum, suspended cymbal), piano, violin, viola, cello, and double bass. Each of the four movements of the piece explore their own distinct character and set of compositional goals. The piece is presented as a musical score and as a recording, which was extensively treated in post-production.

(2) Appalachiana, is a ca. 30 minute fixed-media composition for music and video. The musical component was created as a vehicle to showcase several approaches to electro-acoustic music composition –fft re-synthesis for time manipulation effects, the use of a custom-built software instrument which implements generative approaches to creating rhythm and pitch patterns, using a recording of rain to create rhythmic triggers for software instruments, and recording additional components with acoustic instruments. The video component transforms footage of natural landscapes filmed at several locations in North Carolina, Virginia, and West Virginia into a surreal narrative using a variety of color, lighting, distortion, and time-manipulation video effects.

(3) “‘The Invisible Mass:’ Exploring Compositional Technique in Alfred Schnittke’s Second Symphony” is an analytical article that focuses on Alfred Schnittke’s compositional technique as evidenced in the construction of his Second Symphony and discussed by the composer in a number of previously untranslated articles and interviews. Though this symphony is pivotal in the composer’s oeuvre, there are currently no scholarly articles that offer in-depth analyses of the piece. The article combines analyses of the harmony, form, and orchestration in the Second Symphony with relevant quotations from the composer, some from published and translated sources and others newly translated by the author from research at the Russian State Library in St. Petersburg. These offer a perspective on how Schnittke’s compositional technique combines systematic geometric design with keen musical intuition.

You and I: The Effects of Intra- and Inter-Species Interactions on Microbial Biofilms, Growth, and Morphology

Humanity is shaped by its relationships with microbes. From bacterial infections to the production of biofuels, industry and health often hinge on our control of microbial populations. Understanding the physiological and genetic basis of their behaviors is therefore of the highest importance. To this end I have investigated the genetic basis of plastic adhesion in Saccharomyces cerevisiae, the mechanistic and evolutionary dynamics of mixed species biofilms with Escherichia coli and S. cerevisiae, and the induction of filamentation in E. coli. Using a bulk segregant analysis on experimentally evolved populations, I detected 28 genes that are likely to mediate plastic adhesion in S. cerevisiae. With a variety of imaging and culture manipulation techniques, I found that particular strains of E. coli are capable of inducing flocculation and macroscopic biofilm formation via coaggregation with yeast. I also employed experimental evolution and microbial demography techniques to find that selection for mixed species biofilm association leads to lower fecundity in S. cerevisiae. Using culture manipulation and imaging techniques, I also found that E. coli are capable of inducing a filamentous phenotype with a secreted signal that has many of the qualities of a quorum sensing molecule.

Direct In Vivo Manipulation and Imaging of Calcium Transients in Neutrophils Identify a Critical Role for Leading-Edge Calcium Flux.

Calcium signaling has long been associated with key events of immunity, including chemotaxis, phagocytosis, and activation. However, imaging and manipulation of calcium flux in motile immune cells in live animals remain challenging. Using light-sheet microscopy for in vivo calcium imaging in zebrafish, we observe characteristic patterns of calcium flux triggered by distinct events, including phagocytosis of pathogenic bacteria and migration of neutrophils toward inflammatory stimuli. In contrast to findings from ex vivo studies, we observe enriched calcium influx at the leading edge of migrating neutrophils. To directly manipulate calcium dynamics in vivo, we have developed transgenic lines with cell-specific expression of the mammalian TRPV1 channel, enabling ligand-gated, reversible, and spatiotemporal control of calcium influx. We find that controlled calcium influx can function to help define the neutrophil's leading edge. Cell-specific TRPV1 expression may have broad utility for precise control of calcium dynamics in other immune cell types and organisms.