Mathematical Modeling of Perifusion Cell Culture Experiments

In perifusion cell cultures, the culture medium flows continuously through a chamber containing immobilized cells and the effluent is collected at the end. In our main applications, gonadotropin releasing hormone (GnRH) or oxytocin is introduced into the chamber as the input. They stimulate the cells to secrete luteinizing hormone (LH), which is collected in the effluent. To relate the effluent LH concentration to the cellular processes producing it, we develop and analyze a mathematical model consisting of coupled partial differential equations describing the intracellular signaling and the movement of substances in the cell chamber. We analyze three different data sets and give cellular mechanisms that explain the data. Our model indicates that two negative feedback loops, one fast and one slow, are needed to explain the data and we give their biological bases. We demonstrate that different LH outcomes in oxytocin and GnRH stimulations might originate from different receptor dynamics. We analyze the model to understand the influence of parameters, like the rate of the medium flow or the fraction collection time, on the experimental outcomes. We investigate how the rate of binding and dissociation of the input hormone to and from its receptor influence its movement down the chamber. Finally, we formulate and analyze simpler models that allow us to predict the distortion of a square pulse due to hormone-receptor interactions and to estimate parameters using perifusion data. We show that in the limit of high binding and dissociation the square pulse moves as a diffusing Gaussian and in this limit the biological parameters can be estimated.

Reckoning With Apartheid: The Conundrum of Working Through the Past, An Introduction

From April 26-29, 1994, South Africa held its first universal, democratic elections. Witnessed by the world, South Africans of all races waited patiently in line to cast their ballots, signaling the official and symbolic birth of the “new” South Africa. The subsequent years, marked initially with euphoric hopes for racial healing enabled by institutional processes such as the Truth and Reconciliation Commission (TRC), have instead, most recently, inspired deep concern about epidemic levels of HIV/AIDS, violent crime, state corruption, and unbridled market reforms directed at everything from property to bodies to babies. Now, seemingly beleaguered state officials deploy the mantra “TINA” (There Is No Alternative [to neoliberal development]) to fend off criticism of growing income and wealth disparities. To coincide, more or less, with the anniversary of 1994—less to commemorate than to signal something about the trajectory of the past twenty years—we are proposing an interdisciplinary, special theme section of Comparative Studies in South Asia, Africa, and the Middle East (CSSAAME) entitled “The Haunted Present: Reckoning After Apartheid” (tentative title). The special theme section is framed around questions of reckoning in the double sense of both a moral and practical accounting for historical injury alongside the challenges and failures of the no-longer “new” South Africa. Against accounts depicting the liberation era as non-violent and peaceable, more nuanced analysis we argue suggests not only that South Africa’s “revolution” was marked by both collective and individual violence—on the part of the state and the liberation movements—but that reckoning with the present demands of scholars, the media, and cultural commentators that they begin to grapple more fully with the dimensions and different figurations of South Africa’s violent colonial history. Indeed, violence and reckoning appear as two central forces in contemporary South African political, economic, and social life. In response, we are driven to pose the following questions: In the post-apartheid period, what forms of (individual, structural) violence have come to bear on South African life? How does this violence reckon with apartheid and its legacies? Does it in fact reckon with the past? How can we or should we think about violence as a response to the (failed?) reckoning of state initiatives like the TRC? What has enabled or enables aesthetic forms—literature, photography, plastic arts, and other modes of expressive culture—to respond to the difficulties of South Africa’s ongoing transition? What, in fact, would a practice or ethic of reckoning defined in the following way look like? ˈrekəniNG/ noun: • the action or process of calculating or estimating something: last year was not, by any reckoning, a particularly good one; the system of time reckoning in Babylon • a person’s view, opinion, or judgment: by ancient reckoning, bacteria are plants • archaic, a bill or account, or its settlement • the avenging or punishing of past mistakes or misdeeds: the fear of being brought to reckoning there will be a terrible reckoning (Oxford English Dictionary) Looking back on the period, just before 1994, is sobering indeed. At the time, many saw in the energies and courage of those fighting for liberation the possibilities of a post-racial, post-conflict society. Yet as much as the new was ushered in, old apartheid forms lingered. Recalling Nadine Gordimer’s invocation of Gramsci’s “morbid symptoms” more and more it seems “the old is dying and the new cannot be born” (Gramsci cited in Gordimer 1982). And even as the new began to emerge other forces—both internal and external to South Africa—redefined the conditions for transformation. The so-called “new” South Africa, as Jennifer Wenzel has argued, was really more than anything “the changing face of old oppressions” (Wenzel 2009:159). The implications for our special theme section of CSSAAME are many. We begin by exploring the gender, race, and class dimensions of contemporary South African life by way of its literatures, histories, and politics, its reversion to custom, the claims of ancestors on the living, in brief, the various cultural expressive modes in which contemporary South Africa reckons with its past and in so doing accounts, day by day, for the ways in which the present can be lived, pragmatically. This moves us some distance from the exercise in “truth and reconciliation” of the earlier post-transition years to consider more fully the nature of post-conflict, the suturing of old enmities in the present, and the ways of resolving those lingering suspicions both ordinary and the stuff of the dark night of the soul (Nelson 2009:xv).

Reckoning With Apartheid: The Conundrum of Working Through the Past

From April 26-29, 1994, South Africa held its first universal, democratic elections. Witnessed by the world, South Africans of all races waited patiently in line to cast their ballots, signaling the official and symbolic birth of the “new” South Africa. The subsequent years, marked initially with euphoric hopes for racial healing enabled by institutional processes such as the Truth and Reconciliation Commission (TRC), have instead, most recently, inspired deep concern about epidemic levels of HIV/AIDS, violent crime, state corruption, and unbridled market reforms directed at everything from property to bodies to babies. Now, seemingly beleaguered state officials deploy the mantra “TINA” (There Is No Alternative [to neoliberal development]) to fend off criticism of growing income and wealth disparities. To coincide, more or less, with the anniversary of 1994—less to commemorate than to signal something about the trajectory of the past twenty years—we are proposing an interdisciplinary, special theme section of Comparative Studies in South Asia, Africa, and the Middle East (CSSAAME) entitled “The Haunted Present: Reckoning After Apartheid” (tentative title). The special theme section is framed around questions of reckoning in the double sense of both a moral and practical accounting for historical injury alongside the challenges and failures of the no-longer “new” South Africa. Against accounts depicting the liberation era as non-violent and peaceable, more nuanced analysis we argue suggests not only that South Africa’s “revolution” was marked by both collective and individual violence—on the part of the state and the liberation movements—but that reckoning with the present demands of scholars, the media, and cultural commentators that they begin to grapple more fully with the dimensions and different figurations of South Africa’s violent colonial history. Indeed, violence and reckoning appear as two central forces in contemporary South African political, economic, and social life. In response, we are driven to pose the following questions: In the post-apartheid period, what forms of (individual, structural) violence have come to bear on South African life? How does this violence reckon with apartheid and its legacies? Does it in fact reckon with the past? How can we or should we think about violence as a response to the (failed?) reckoning of state initiatives like the TRC? What has enabled or enables aesthetic forms—literature, photography, plastic arts, and other modes of expressive culture—to respond to the difficulties of South Africa’s ongoing transition? What, in fact, would a practice or ethic of reckoning defined in the following way look like? ˈrekəniNG/ noun: • the action or process of calculating or estimating something: last year was not, by any reckoning, a particularly good one; the system of time reckoning in Babylon • a person’s view, opinion, or judgment: by ancient reckoning, bacteria are plants • archaic, a bill or account, or its settlement • the avenging or punishing of past mistakes or misdeeds: the fear of being brought to reckoning there will be a terrible reckoning (Oxford English Dictionary) Looking back on the period, just before 1994, is sobering indeed. At the time, many saw in the energies and courage of those fighting for liberation the possibilities of a post-racial, post-conflict society. Yet as much as the new was ushered in, old apartheid forms lingered. Recalling Nadine Gordimer’s invocation of Gramsci’s “morbid symptoms” more and more it seems “the old is dying and the new cannot be born” (Gramsci cited in Gordimer 1982). And even as the new began to emerge other forces—both internal and external to South Africa—redefined the conditions for transformation. The so-called “new” South Africa, as Jennifer Wenzel has argued, was really more than anything “the changing face of old oppressions” (Wenzel 2009:159). The implications for our special theme section of CSSAAME are many. We begin by exploring the gender, race, and class dimensions of contemporary South African life by way of its literatures, histories, and politics, its reversion to custom, the claims of ancestors on the living, in brief, the various cultural expressive modes in which contemporary South Africa reckons with its past and in so doing accounts, day by day, for the ways in which the present can be lived, pragmatically. This moves us some distance from the exercise in “truth and reconciliation” of the earlier post-transition years to consider more fully the nature of post-conflict, the suturing of old enmities in the present, and the ways of resolving those lingering suspicions both ordinary and the stuff of the dark night of the soul (Nelson 2009:xv).

Development of Plasmonic Nanoplatforms for Diagnostics, Therapy, and Sensing

Recent advances in nanotechnology have led to the application of nanoparticles in a wide variety of fields. In the field of nanomedicine, there is great emphasis on combining diagnostic and therapeutic modalities into a single nanoparticle construct (theranostics). In particular, anisotropic nanoparticles have shown great potential for surface-enhanced Raman scattering (SERS) detection due to their unique optical properties. Gold nanostars are a type of anisotropic nanoparticle with one of the highest SERS enhancement factors in a non-aggregated state. By utilizing the distinct characteristics of gold nanostars, new plasmonic materials for diagnostics, therapy, and sensing can be synthesized. The work described herein is divided into two main themes. The first half presents a novel, theranostic nanoplatform that can be used for both SERS detection and photodynamic therapy (PDT). The second half involves the rational design of silver-coated gold nanostars for increasing SERS signal intensity and improving reproducibility and quantification in SERS measurements.

The theranostic nanoplatforms consist of Raman-labeled gold nanostars coated with a silica shell. Photosensitizer molecules for PDT can be loaded into the silica matrix, while retaining the SERS signal of the gold nanostar core. SERS detection and PDT are performed at different wavelengths, so there is no interference between the diagnostic and therapeutic modalities. Singlet oxygen generation (a measure of PDT effectiveness) was demonstrated from the drug-loaded nanocomposites. In vitro testing with breast cancer cells showed that the nanoplatform could be successfully used for PDT. When further conjugating the nanoplatform with a cell-penetrating peptide (CPP), efficacy of both SERS detection and PDT is enhanced.

The rational design of plasmonic nanoparticles for SERS sensing involved the synthesis of silver-coated gold nanostars. Investigation of the silver coating process revealed that preservation of the gold nanostar tips was necessary to achieve the increased SERS intensity. At the optimal amount of silver coating, the SERS intensity is increased by over an order of magnitude. It was determined that a majority of the increased SERS signal can be attributed to reducing the inner filter effect, as the silver coating process moves the extinction of the particles far away from the laser excitation line. To improve reproducibility and quantitative SERS detection, an internal standard was incorporated into the particles. By embedding a small-molecule dye between the gold and silver surfaces, SERS signal was obtained both from the internal dye and external analyte on the particle surface. By normalizing the external analyte signal to the internal reference signal, reproducibility and quantitative analysis are improved in a variety of experimental conditions.