Neutrophil Chemotaxis in Multiple Chemoattractant Gradients

Chemotaxis, the phenomenon in which cells move in response to extracellular chemical gradients, plays a prominent role in the mammalian immune response. During this process, a number of chemical signals, called chemoattractants, are produced at or proximal to sites of infection and diffuse into the surrounding tissue. Immune cells sense these chemoattractants and move in the direction where their concentration is greatest, thereby locating the source of attractants and their associated targets. Leading the assault against new infections is a specialized class of leukocytes (white blood cells) known as neutrophils, which normally circulate in the bloodstream. Upon activation, these cells emigrate out of the vasculature and navigate through interstitial tissues toward target sites. There they phagocytose bacteria and release a number of proteases and reactive oxygen intermediates with antimicrobial activity. Neutrophils recruited by infected tissue in vivo are likely confronted by complex chemical environments consisting of a number of different chemoattractant species. These signals may include end target chemicals produced in the vicinity of the infectious agents, and endogenous chemicals released by local host tissues during the inflammatory response. To successfully locate their pathogenic targets within these chemically diverse and heterogeneous settings, activated neutrophils must be capable of distinguishing between the different signals and employing some sort of logic to prioritize among them. This ability to simultaneously process and interpret mulitple signals is thought to be essential for efficient navigation of the cells to target areas. In particular, aberrant cell signaling and defects in this functionality are known to contribute to medical conditions such as chronic inflammation, asthma and rheumatoid arthritis. To elucidate the biomolecular mechanisms underlying the neutrophil response to different chemoattractants, a number of efforts have been made toward understanding how cells respond to different combinations of chemicals. Most notably, recent investigations have shown that in the presence of both end target and endogenous chemoattractant variants, the cells migrate preferentially toward the former type, even in very low relative concentrations of the latter. Interestingly, however, when the cells are exposed to two different endogenous chemical species, they exhibit a combinatorial response in which distant sources are favored over proximal sources. Some additional results also suggest that cells located between two endogenous chemoattractant sources will respond to the vectorial sum of the combined gradients. In the long run, this peculiar behavior could result in oscillatory cell trajectories between the two sources. To further explore the significance of these and other observations, particularly in the context of physiological conditions, we introduce in this work a simplified phenomenological model of neutrophil chemotaxis. In particular, this model incorporates a trait commonly known as directional persistence - the tendency for migrating neutrophils to continue moving in the same direction (much like momentum) - while also accounting for the dose-response characteristics of cells to different chemical species. Simulations based on this model suggest that the efficiency of cell migration in complex chemical environments depends significantly on the degree of directional persistence. In particular, with appropriate values for this parameter, cells can improve their odds of locating end targets by drifting through a network of attractant sources in a loosely-guided fashion. This corroborates the prediction that neutrophils randomly migrate from one chemoattractant source to the next while searching for their end targets. These cells may thus use persistence as a general mechanism to avoid being trapped near sources of endogenous chemoattractants - the mathematical analogue of local maxima in a global optimization problem. Moreover, this general foraging strategy may apply to other biological processes involving multiple signals and long-range navigation.

Beyond hope: Rhetorics of mobility, possibility, and literacy

When writing teachers enter the classroom, they often bring with them a deep faith in the power of literacy to rectify social inequalities and improve their students’ social and economic standing. It is this faith—this hope for change—that draws some writing teachers to locations of social and economic hardship. I am interested in how teachers and theorists construct their own narratives of social mobility, possibility, and literacy. My dissertation analyzes the production and expression of beliefs about literacy in the narratives of a diverse group of writing teachers and theorists, from those beginning their careers to those who are published and widely read. The central questions guiding this study are: How do teachers’ and theorists’ narratives of becoming literate intersect with literacy theories? and How do such literacy narratives intersect with beliefs in the power of literacy to improve individuals’ lives socially, economically, and personally? I contend that the professional literature needs to address more fully how teachers’ and theorists’ personal histories with literacy shape what they see as possible (and desirable) for students, especially those from marginalized communities. A central focus of the dissertation is on how teachers and theorists attempt to resolve a paradox they are likely to encounter in narratives about literacy. On one hand, they are immersed in a popular culture that cherishes narrative links between literacy and economic advancement (and, further, between such advancement and a “good life”). On the other hand, in professional discourse and in teacher preparation courses, they are likely to encounter narratives that complicate an assumed causal relationship between literacy and economic progress. Understanding, through literacy narratives, how teachers and theorists chart a practical path through or around this paradox can be beneficial to literacy education in three ways. First, it can offer direction in professional development and teacher education, addressing how teachers negotiate the boundaries between personal experience, theory, and pedagogy. Second, it can help teachers create spaces wherein students can explore the impact of paradoxical views about the role of literacy on their own lives. Finally, it can offer direction in public policy discourse, extending awareness of what we want—and need—from English language arts education in the twenty-first century. To explore these issues, I draw on case studies and ethnographic observation as well as narrative inquiry into teachers’ and theorists’ published literacy narratives. I situate my findings within three interrelated frames: 1) the narratives of new teachers, 2) the published works of literacy educators and theorists, and 3) my own literacy narrative. My first chapter, “Beyond Hope,” explores the tenuous connections between hope and critique in literacy studies and provides a methodological overview of the study. I argue that scholarship must move beyond a singular focus on either hope or critique in order to identify the transformative potential of literacy in particular circumstances. Analyzing literacy narratives provides a way of locating a critically informed sense of possibility. My second chapter, “Making Teachers, Making Literacy,” explores the intersection between teachers’ lives and the theories they study, based on qualitative analysis of a preservice course for secondary education English teachers. I examine how these preservice English teachers understood literacy, how their narratives of becoming literate and teaching English connected—and did not connect—with theoretical and pedagogical positions, and how these stories might inform their future work as practitioners. Centering primarily on preservice teachers who resisted Nancie Atwell’s pedagogy of possibility because they found it too good to be true, this research concentrates on moments of disjuncture, as expressed in class discussion and in one-on-one interviews, when literacy theories failed to align with aspiring teachers’ understandings of their own experiences and also with what they imagined as possible in disadvantaged educational settings. In my third and fourth chapters, I analyze the narratives of celebrated teachers and theorists who put forth an agenda that emphasizes possibilities through literacy, examining how they negotiate the relationship between their own literacy stories and literacy theories. Specifically, I investigate the narratives of three proponents of critical literacy: Mike Rose, Paulo Freire, and Myles Horton, all highly respected literacy teachers whose working-class backgrounds influenced their commitment to teaching in disenfranchised communities. In chapter 3, “Reading Lives on the Boundary,” I demonstrate how Mike Rose’s 1989 autobiographical text, Lives on the Boundary, juxtaposes rhetorics of mobility with critiques of such possibility. Through an analysis of work published in professional journals, I offer a reception history of Rose’s narrative, focusing specifically on how teachers have negotiated the tension between hope and critique. I follow this analysis with three case studies, drawn from a larger sampling, that inquire into the personal connections that writing teachers make with Lives on the Boundary. The teachers in this study, who provided written responses and participated in audio-recorded follow-up interviews, were asked to compare Rose’s story to their own stories, considering how their personal literacy histories influenced their teaching. My findings illustrate how a group of teachers and theorists have projected their own assessments of what literacy and higher education can and cannot accomplish onto this influential text. In my fourth chapter, “Horton and Freire’s Road as Literacy Narrative,” I concentrate on Myles Horton and Paulo Freire’s 1990 collaborative spoken book, We Make the Road by Walking. Central to my analysis are the educators’ stories about their formative years, including their own primary and secondary education experiences. I argue that We Make the Road by Walking demonstrates how theories of literacy cannot be divorced from personal histories. I begin by examining the spoken book as a literacy narrative that fuses personal and theoretical knowledge, focusing specifically on its authors’ ideas on theory. Drawing on Bakhtin’s notion of the chronotope—the intersection of time and space within narrative—I then explore the literacy narratives emerging from the production process of the book, in a video production about Horton and Freire’s meeting, and ultimately in the two men’s reflections on their childhood years (Dialogic). Interspersed with these accounts is archival material on the book’s editorial production that illustrates the value of increased dialogue between personal history and theories of literacy. My fifth chapter is both a reflective analysis and a qualitative study of my work at a men’s medium-high security prison in Illinois, where I conducted research and served as the instructor of an upper-level writing course, “Writing for a Change,” in the spring of 2009. Entitled “Doing Time with Literacy Narratives,” this chapter explores the complex ways in which literacy and incarceration are configured in students’ narratives as well as my own. With and against students’ stories, I juxtapose my own experiences with literacy, particularly in relation to being the son of an imprisoned father. In exploring the intersections between such stories, I demonstrate how literacy narratives can function as a heuristic for exploring beliefs about literacy between teachers and students both inside and outside of the prison-industrial complex. My conclusion pulls together the various themes that emerged in the three frames, from the making of new teachers to the published literacy narratives of teachers and theorists to my own literacy narrative. Writing teachers encounter considerable pressure to align their curricula with one or another theory of literacy, which has the effect of negating the authority of knowledge about literacy gleaned from experience as readers and writers. My dissertation contends that there is much to be gained by finding ways of articulating theories of literacy that encompass teachers’ knowledge of reading and writing as expressed in personal narratives of literacy. While powerful cultural rhetorics of upward social mobility often neutralize the critical potential of teachers’ own narratives of literacy—potential that has been documented by scholars in writing studies and allied disciplines—this is not always the case. The chapters in this dissertation offer evidence that hopeful and critical positions on the transformational possibilities of literacy are not mutually exclusive.