The Multiscale Systems Immunology project: software for cell-based immunological simulation.

BACKGROUND: Computer simulations are of increasing importance in modeling biological phenomena. Their purpose is to predict behavior and guide future experiments. The aim of this project is to model the early immune response to vaccination by an agent based immune response simulation that incorporates realistic biophysics and intracellular dynamics, and which is sufficiently flexible to accurately model the multi-scale nature and complexity of the immune system, while maintaining the high performance critical to scientific computing. RESULTS: The Multiscale Systems Immunology (MSI) simulation framework is an object-oriented, modular simulation framework written in C++ and Python. The software implements a modular design that allows for flexible configuration of components and initialization of parameters, thus allowing simulations to be run that model processes occurring over different temporal and spatial scales. CONCLUSION: MSI addresses the need for a flexible and high-performing agent based model of the immune system.

Memory-Based Attentional Guidance: A Window to the Relationship between Working Memory and Attention

Attention, the cognitive means by which we prioritize the processing of a subset of information, is necessary for operating efficiently and effectively in the world. Thus, a critical theoretical question is how information is selected. In the visual domain, working memory (WM)—which refers to the short-term maintenance and manipulation of information that is no longer accessible by the senses—has been highlighted as an important determinant of what is selected by visual attention. Furthermore, although WM and attention have traditionally been conceived as separate cognitive constructs, an abundance of behavioral and neural evidence indicates that these two domains are in fact intertwined and overlapping. The aim of this dissertation is to better understand the nature of WM and attention, primarily through the phenomenon of memory-based attentional guidance, whereby the active maintenance of items in visual WM reliably biases the deployment of attention to memory-matching items in the visual environment. The research presented here employs a combination of behavioral, functional imaging, and computational modeling techniques that address: (1) WM guidance effects with respect to the traditional dichotomy of top-down versus bottom-up attentional control; (2) under what circumstances the contents of WM impact visual attention; and (3) the broader hypothesis of a predictive and competitive interaction between WM and attention. Collectively, these empirical findings reveal the importance of WM as a distinct factor in attentional control and support current models of multiple-state WM, which may have broader implications for how we select and maintain information.

Geographic Information Systems-Based Approaches to Study Congressional Redistricting in the United States

The ability for the citizens of a nation to determine their own representation has long been regarded as one of the most critical objectives of any electoral system. Without having the assurance of equality in representation, the fundamental nature and operation of the political system is severely undermined. Given the centuries of institutional reforms and population changes in the American system, Congressional Redistricting stands as an institution whereby this promise of effective representation can either be fulfilled or denied. The broad set of processes that encapsulate Congres- sional Redistricting have been discussed, experimented, and modified to achieve clear objectives and have long been understood to be important. Questions remain about how the dynamics which link all of these processes operate and what impact the real- ities of Congressional Redistricting hold for representation in the American system. This dissertation examines three aspects of how Congressional Redistricting in the Untied States operates in accordance with the principle of “One Person, One Vote.” By utilizing data and data analysis techniques of Geographic Information Systems (GIS), this dissertation seeks to address how Congressional Redistricting impacts the principle of one person, one vote from the standpoint of legislator accountability, redistricting institutions, and the promise of effective minority representation.

The Role of Home Practice Engagement in a Mindfulness-Based Intervention

Over the last three decades, there has been a precipitous rise in curiosity regarding the clinical use of mindfulness meditation for the self-management of a broad range of chronic health conditions. Despite the ever-growing body of evidence supporting the use of mindfulness-based therapies for both medical and psychological concerns, data on the active ingredients of these mind-body interventions are relatively scarce. Regular engagement in formal mindfulness practice is considered by many to be requisite for generating therapeutic change; however, previous investigations of at-home practice in MBIs have produced mixed results. The equivocal nature of these findings has been attributed to significant methodological limitations, including the lack of standardized, systematic practice monitoring tools, and a singular focus on practice time, with little attention paid to the nature and quality of one’s practice. The present study used a prospective, observational design to assess the effects of home-based practice on dispositional mindfulness, self-compassion, and psychological functioning in twenty-eight people enrolled in an MBSR or MBCT program. To address some of the aforementioned limitations, the present study collected detailed weekly accounts of participants’ home-based practice engagement, including information about practice time (i.e., frequency and duration), exercise type, perceived effort and barriers to participation, and practice quality. Hierarchical multiple regression was used to examine the relative contribution of practice time and practice quality on treatment outcomes, and to explore possible predictors of adherence to at-home practice recommendations. As anticipated, practice quality and perceived effort improved with time; however, rather unexpectedly, practice quality was not a significant predictor of treatment-related improvements in psychological health. Home practice engagement, however, was predictive of change in dispositional mindfulness, in the expected direction. Results of our secondary analyses demonstrated that employment status was predictive of home practice engagement, with those who were unemployed completing more at-home practice on average. Mindfulness self-efficacy at baseline and previous experience with meditation or other contemplative practices were independently predictive of mean practice quality. The results of this study suggest that home practice helps generate meaningful change in dispositional mindfulness, which is purportedly a key mechanism of action in mindfulness-based interventions.

US-Based Food and Agricultural Value Chains and Their Relevance to Healthy Diets.

This article examines the structure and health implications of two industries, chicken and tomatoes, that play prominent roles in US food and agricultural competitiveness. Both industries have become more concentrated over time, with powerful "lead firms" driving geographical, technological, and marketing changes. Overall, a processed food revolution has taken place in agricultural products that transforms the types of food and dietary options available to consumers. The nature of contemporary food and agricultural value chains affects the strategies and policies that can be effectively employed to address major health goals such as improved nutrition, food safety, and food security.

Resonance Energy Transfer-Based Molecular Switch Designed Using a Systematic Design Process Based on Monte Carlo Methods and Markov Chains

A RET network consists of a network of photo-active molecules called chromophores that can participate in inter-molecular energy transfer called resonance energy transfer (RET). RET networks are used in a variety of applications including cryptographic devices, storage systems, light harvesting complexes, biological sensors, and molecular rulers. In this dissertation, we focus on creating a RET device called closed-diffusive exciton valve (C-DEV) in which the input to output transfer function is controlled by an external energy source, similar to a semiconductor transistor like the MOSFET. Due to their biocompatibility, molecular devices like the C-DEVs can be used to introduce computing power in biological, organic, and aqueous environments such as living cells. Furthermore, the underlying physics in RET devices are stochastic in nature, making them suitable for stochastic computing in which true random distribution generation is critical.

In order to determine a valid configuration of chromophores for the C-DEV, we developed a systematic process based on user-guided design space pruning techniques and built-in simulation tools. We show that our C-DEV is 15x better than C-DEVs designed using ad hoc methods that rely on limited data from prior experiments. We also show ways in which the C-DEV can be improved further and how different varieties of C-DEVs can be combined to form more complex logic circuits. Moreover, the systematic design process can be used to search for valid chromophore network configurations for a variety of RET applications.

We also describe a feasibility study for a technique used to control the orientation of chromophores attached to DNA. Being able to control the orientation can expand the design space for RET networks because it provides another parameter to tune their collective behavior. While results showed limited control over orientation, the analysis required the development of a mathematical model that can be used to determine the distribution of dipoles in a given sample of chromophore constructs. The model can be used to evaluate the feasibility of other potential orientation control techniques.