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Full-Text Articles in Physical Sciences and Mathematics

A Causal Inference Approach For Spike Train Interactions, Zach Saccomano Feb 2024

A Causal Inference Approach For Spike Train Interactions, Zach Saccomano

Dissertations, Theses, and Capstone Projects

Since the 1960s, neuroscientists have worked on the problem of estimating synaptic properties, such as connectivity and strength, from simultaneously recorded spike trains. Recent years have seen renewed interest in the problem coinciding with rapid advances in experimental technologies, including an approximate exponential increase in the number of neurons that can be recorded in parallel and perturbation techniques such as optogenetics that can be used to calibrate and validate causal hypotheses about functional connectivity. This thesis presents a mathematical examination of synaptic inference from two perspectives: (1) using in vivo data and biophysical models, we ask in what cases the …


De Novo Design And Engineering Of Functional Metal And Porphyrin-Binding Protein Domains, Bernard Howard Everson Feb 2015

De Novo Design And Engineering Of Functional Metal And Porphyrin-Binding Protein Domains, Bernard Howard Everson

Dissertations, Theses, and Capstone Projects

In this work, I describe an approach to the rational, iterative design and characterization of two functional cofactor-binding protein domains. First, a hybrid computational/experimental method was developed with the aim of algorithmically generating a suite of porphyrin-binding protein sequences with minimal mutual sequence information. This method was explored by generating libraries of sequences, which were then expressed and evaluated for function. One successful sequence is shown to bind a variety of porphyrin-like cofactors, and exhibits light- activated electron transfer in mixed hemin:chlorin e6 and hemin:Zn(II)-protoporphyrin IX complexes. These results imply that many sophisticated functions such as cofactor binding and electron …