Mathematical models of cellular decisions: investigating immune response and apoptosis

The main objective of this thesis is to develop and analyze mathematical models of cellular decisions. This work focuses on understanding the mechanisms involved in specific cellular processes such as immune response in the vascular system, and those involved in apoptosis, or programmed cellular death. A series of simple ordinary differential equation (ODE) models are constructed describing the macrophage response to hemoglobin:haptoglobin (Hb:Hp) complexes that may be present in vascular inflammation. The models proposed a positive feedback loop between the CD163 macrophage receptor and anti-inflammatory cytokine interleukin-10 (IL-10) and bifurcation analysis predicted the existence of a cellular phenotypic switch which was experimentally verified. Moreover, these models are extended to include the intracellular mediator heme oxygenase-1 (HO-1). Analysis of the proposed models find a positive feedback mechanism between IL-10 and HO-1. This model also predicts cellular response of heme and IL-10 stimuli. For the apoptotic (cell suicide) system, a modularized model is constructed encompassing the extrinsic and intrinsic signaling pathways. Model reduction is performed by abstracting the dynamics of complexes (oligomers) at a steady-state. This simplified model is analyzed, revealing different kinetic properties between type I and type II cells, and reduced models verify results. The second model of apoptosis proposes a novel mechanism of apoptosis activation through receptor-ligand clustering, yielding robust bistability and hysteresis. Using techniques from algebraic geometry, a model selection criterion is provided between the proposed and existing model as experimental data becomes available to verify the mechanism. The models developed throughout this thesis reveal important and relevant mechanisms specific to cellular response; specifically, interactions necessary for an organism to maintain homeostasis are identified. This work enables a deeper understanding of the biological interactions and dynamics of vascular inflammation and apoptosis. The results of these models provide predictions which may motivate further experimental work and theoretical study

B2B customer experience factors: understanding the relationship with SME customers – interim report

As part of the 2014 programme, our members asked us to extend the research done in 2013 (“Measuring Customer Satisfaction And Understanding Customer Effort In A B2B Context” - Tony Harrington and Andrew Bryan) to incorporate the SME customer sector. This project was set up to explore customer experience factors in the SME segment and to address a number of questions:- What are the most important factors that contribute to the customer experience from both the supplier’s and the SME customer’s perspectives? From the customer’s perspective, what about the relationship with the supplier requires the ‘most’ or ‘least’ effort and what changes do customers suggest? Where a customer has both a personal and a business relationship with the supplier, how does this impact their views? The approach was to develop an online survey for completion by SME customers and their supplier. Initially, seven companies and the Henley SME Forum volunteered to participate in the research. However, it proved to be extremely difficult to go from agreement to be involved to actually getting survey responses and, in the event, the survey achieved the following result:- A good response was achieved from 2 companies with around 40 SME responses for each company. A poor response was achieved from 1 company and from the SME Group so their data is currently of limited value. There were other companies that would still like to participate and there are 3 offers to participate at a later date. Analysis of the responses showed that useful conclusions could be made from the data collected so far but that it would be more valuable if more companies were persuaded to participate in the future. As a result, this report has been prepared as an interim statement of what has been learnt and to provide specific feedback to the participating companies. With member’s permission, further responses will be sought at a later date to refine the learning and provide feedback to more companies. This report presents the results of analysis from the survey on a company-by-company basis. Most of the data is only relevant at company level but consolidated results are shown where possible. The results from the analysis of responses lead to a number of initial conclusions. SME companies look to their suppliers to deliver against their promises in a responsive, consistent and proactive manner. Their priority is to have their problems solved in a timely manner. Relationship factors are more important in the B2B relationships between large companies than for SME’s. The SME customer is much more interested in just having the service performed with a minimum of fuss and doesn’t really want to develop a relationship. Questions about customer effort (or the ease of doing business) are as valuable in the SME segment as in any other in terms of identifying opportunities for improvement. Businesses should consider whether their SME customers might also be a customer in their personal home life. If so, they should be aware that this will have an effect on their satisfaction – and could be either positive or negative

Buddhist Brains: A Case Study in the Reenchantment of the Brain Sciences

History of Scienc

God and Health: What More Is There To Say?

History of Scienc

Teaching Critical and Creative Thinking Skills as Part of the Technical Communications Curriculum

I incorporated critical thinking instruction in the writing curriculum by using three writing projects: journal writing, a policy paper on AIDS, and an assignment to evaluate grammar checkers. In their journal writing students both generated and evaluated ideas. In the AIDS project, they reinforced these convergent and divergent thinking skills within the context of a real-world issue. For the software project, students practiced thinking skills in an arena that was more technical and objective, but in which they were evaluating fundamental writing criteria. These diverse assignments, based on a philosophically compatible approach to the teaching of writing, helped students develop critical and creative thinking skills along with content knowledge and effective written expression

Joining and decomposing reaction networks

In systems and synthetic biology, much research has focused on the behavior and design of single pathways, while, more recently, experimental efforts have focused on how cross-talk (coupling two or more pathways) or inhibiting molecular function (isolating one part of the pathway) affects systems-level behavior. However, the theory for tackling these larger systems in general has lagged behind. Here, we analyze how joining networks (e.g., cross-talk) or decomposing networks (e.g., inhibition or knock-outs) affects three properties that reaction networks may possess---identifiability (recoverability of parameter values from data), steady-state invariants (relationships among species concentrations at steady state, used in model selection), and multistationarity (capacity for multiple steady states, which correspond to multiple cell decisions). Specifically, we prove results that clarify, for a network obtained by joining two smaller networks, how properties of the smaller networks can be inferred from or can imply similar properties of the original network. Our proofs use techniques from computational algebraic geometry, including elimination theory and differential algebra.Comment: 44 pages; extensive revision in response to referee comment

Mindfulness Meditation: Frames and Choices

History of Scienc

Texas’s New Habeas Corpus Procedure For Death-Row Inmates: Kafkaesque-And Probably Unconstitutional

Texas courts should embrace their duty to protect the constitution and forbid the legislature from pursuing a politically popular agenda at the expense of the fundamental rights of certain citizens. Article 11.071 of the Texas Code of Criminal Procedure runs afoul of the language, intent, and purpose of Texas constitutional guarantees, and eliminates procedural protections designed to guard against the execution of innocent persons. The Texas Legislature should not be allowed to shorten the time period for seeking habeas relief. Article 11.071 violates the due course of law provisions of the Texas Constitution and violates the Texas equal rights provision. The principal purpose of the writ of habeas corpus is to provide prisoners with the means to challenge the legality of his or her confinement outside of the ordinary appellate process. By limiting access to the Great Writ, the Texas Legislature has engaged in the very governmental abuses that the framers and ratifiers of the Texas Bill of Rights sought to prevent

Zen, Suzuki, and the Art of Psychotherapy

History of Scienc