Engineering Education and Research Using MATLAB

MATLAB is a software package used primarily in the field of engineering for signal processing, numerical data analysis, modeling, programming, simulation, and computer graphic visualization. In the last few years, it has become widely accepted as an efficient tool, and, therefore, its use has significantly increased in scientific communities and academic institutions. This book consists of 20 chapters presenting research works using MATLAB tools. Chapters include techniques for programming and developing Graphical User Interfaces (GUIs), dynamic systems, electric machines, signal and image processing, power electronics, mixed signal circuits, genetic programming, digital watermarking, control systems, time-series regression modeling, and artificial neural networks

Advanced photonic and electronic systems - WILGA 2017

WILGA annual symposium on advanced photonic and electronic systems has been organized by young scientist for young scientists since two decades. It traditionally gathers more than 350 young researchers and their tutors. Ph.D students and graduates present their recent achievements during well attended oral sessions. Wilga is a very good digest of Ph.D. works carried out at technical universities in electronics and photonics, as well as information sciences throughout Poland and some neighboring countries. Publishing patronage over Wilga keep Elektronika technical journal by SEP, IJET by PAN and Proceedings of SPIE. The latter world editorial series publishes annually more than 200 papers from Wilga. Wilga 2017 was the XL edition of this meeting. The following topical tracks were distinguished: photonics, electronics, information technologies and system research. The article is a digest of some chosen works presented during Wilga 2017 symposium. WILGA 2017 works were published in Proc. SPIE vol.10445

Lost in the archive: vision, artefact and loss in the evolution of hypertext

How does one write the history of a technical machine? Can we say that technical machines have their own genealogies, their own evolutionary dynamic? The technical artefact constitutes a series of objects, a lineage or a line. At a cursory level, we can see this in the fact that technical machines come in generations - they adapt and adopt characteristics over time, one suppressing the other as it becomes obsolete. It is argued that technics has its own evolutionary dynamic, and that this dynamic stems neither from biology nor from human societies. Yet 'it is impossible to deny the role of human thought in the creation of technical artefacts' (Guattari 1995, p. 37). Stones do not automatically rise up into a wall - humans 'invent' technical objects. This, then, raises the question of technical memory. Is it humans that remember previous generations of machines and transfer their characteristics to new machines? If so, how and where do they remember them? It is suggested that humans learn techniques from technical artefacts, and transfer these between machines. This theory of technical evolution is then used to understand the genealogy of hypertext. The historical differentiations of hypertext in different technical systems is traced. Hypertext is defined as both a technical artefact and also a set of techniques: both are a part of this third milieu, technics. The difference between technical artefact and technical vision is highlighted, and it is suggested that technique and vision change when they are externalised as material artefact. The primary technique traced is association, the organisational principle behind the hypertext systems explored in the manuscript. In conclusion, invention is shown to be an act of exhumation, the transfer and retroactiviation of techniques from the past. This thesis presents an argument for a new model of technical evolution, a model which claims that technics constitutes its own dynamic, and that this dynamic exceeds human evolution. It traces the genealogy of hypertext as a set of techniques and as series of material artefacts. To create this geneaology I draw on interviews conducted with Douglas Engelbart, Ted Nelson and Andries van Dam, as well as a wide variety of primary and secondary resources

Modelling and measurement in synthetic biology

Synthetic biology applies engineering principles to make progress in the study of complex biological phenomena. The aim is to develop understanding through the praxis of construction and design. The computational branch of this endeavour explicitly brings the tools of abstraction and modularity to bear. This thesis pursues two distinct lines of inquiry concerning the application of computational tools in the setting of synthetic biology. One thread traces a narrative through multi-paradigm computational simulations, interpretation of results, and quantification of biological order. The other develops computational infrastructure for describing, simulating and discovering, synthetic genetic circuits. The emergence of structure in biological organisms, morphogenesis, is critically important for understanding both normal and pathological development of tissues. Here, we focus on epithelial tissues because models of two dimensional cellular monolayers are computationally tractable. We use a vertex model that consists of a potential energy minimisation process interwoven with topological changes in the graph structure of the tissue. To make this interweaving precise, we define a language for propagators from which an unambiguous description of the simulation methodology can be constructed. The vertex model is then used to reproduce laboratory results of patterning in engineered mammalian cells. The assertion that the claim of reproduction is justified is based on a novel measure of structure on coloured graphs which we call path entropy. This measure is then extended to the setting of continuous regions and used to quantify the development of structure in house mouse (Mus musculus) embryos using three dimensional segmented anatomical models. While it is recognised that DNA can be considered a powerful computational environment, it is far from obvious how to program with nucleic acids. Using rule-based modelling of modular biological parts, we develop a method for discovering synthetic genetic programs that meet a specification provided by the user. This method rests on the concept of annotation as applied to rule-based programs. We begin with annotating rules and proceed to generating entire rule-based programs from annotations themselves. Building on those tools we describe an evolutionary algorithm for discovering genetic circuits from specifications provided in terms of probability distributions. This strategy provides a dual benefit: using stochastic simulation captures circuit behaviour at low copy numbers as well as complex properties such as oscillations, and using standard biological parts produces results that are implementable in the laboratory

Novel pharmacological strategies for antagonizing anti-apoptosis protein function in malignancy.

Historically, cytotoxic therapies have provided the greatest advances in the treatment of malignant disease. Although some cancers are curable, many are not. Chemotherapeutic drugs rely upon the induction of a phylogenically old, cell suicide programme termed apoptosis for their efficacy. Apoptotic sensitivity is associated with curability, whereas, intrinsic resistance plays a major role in limiting therapeutic effectiveness. Mitochondria, the centres for aerobic respiration in the cell also play a pivotal role in regulating apoptosis. The anti-death proteins Bcl-2 and Bc1-XL localize to the outer mitochondrial membrane, and are expressed at high levels in many resistant malignacies compared with normal tissues. These proteins contribute to resistance by blocking apoptosis, and therefore represent valid targets for the development of novel inhibitory strategies. This thesis presents two strategies with therapeutic potential for antagonizing the anti-death action of Bcl-2 and Bc1-XL in haematological and epithelial malignancies. The first, involves the suppression of Bcl-2 and Bc1-XL gene expression by antisense oligodeoxynucleotides in vitro and in vivo. Mathematical models of antisense pharmacology are presented. The second, targets the mitochondrial megachannel that is intimately involved in apoptosis, and is regulated by binding to Bcl-2 and Bc1-XL In order to quantitatively measure the putative apoptosis sensitizing efficacy of these approaches at single cell resolution, stochastic models are described, enabling robust estimation of the distribution of tolerances and latency preceding apoptosis. The peripheral benzodiazepine receptor interacts with the mitochondrial megachannel. Evidence is provided, that Bcl-2 resistant apoptosis sensitization is mediated in vitro, in vivo, and ex vivo, by the ligand PK11195, through a mechanism involving direct megachannel regulation. This occurs not via the peripheral benzodiazepine receptor as previously thought, but through de novo generation of reactive oxygen species. Investigations of PK11195 pharmacodynamics, and molecular structural studies using proton nuclear magnetic resonance spectroscopy support a novel mechanism of action

AutoGraff: towards a computational understanding of graffiti writing and related art forms.

The aim of this thesis is to develop a system that generates letters and pictures with a style that is immediately recognizable as graffiti art or calligraphy. The proposed system can be used similarly to, and in tight integration with, conventional computer-aided geometric design tools and can be used to generate synthetic graffiti content for urban environments in games and in movies, and to guide robotic or fabrication systems that can materialise the output of the system with physical drawing media. The thesis is divided into two main parts. The first part describes a set of stroke primitives, building blocks that can be combined to generate different designs that resemble graffiti or calligraphy. These primitives mimic the process typically used to design graffiti letters and exploit well known principles of motor control to model the way in which an artist moves when incrementally tracing stylised letter forms. The second part demonstrates how these stroke primitives can be automatically recovered from input geometry defined in vector form, such as the digitised traces of writing made by a user, or the glyph outlines in a font. This procedure converts the input geometry into a seed that can be transformed into a variety of calligraphic and graffiti stylisations, which depend on parametric variations of the strokes

Probing the lipid environment of the G-protein coupled receptor Metabotropic glutamate receptor 2

The Metabotropic glutamate receptor 2 (mGluR2) belongs to the family of G-protein coupled receptors, a specific class of transmembrane proteins involved in cellular signaling. The functionality of such transmembrane proteins has been identified to largely depend on their microenvironment, namely the lipid bilayer surrounding them. However, the regulation of the receptors by their lipid microenvironment remains poorly understood. In particular, it remains unclear how specific protein-lipid interactions may modulate the function of mGluR2. In the last years, general motifs for non-covalent cholesterol and sphingolipid interaction within helical domains of transmembrane proteins have been described. In these motifs, both tryptophan and tyrosine residues have been found to play a decisive role. For that reason, an alanine mutagenesis screening, targeting tryptophan and tyrosine residues at the transmembrane surface, was carried out in the search of specific sphingolipid or cholesterol interaction sites for mGluR2. For the different Y→A and W→A variants, surface biotinylation and co-immunoprecipitation showed that neither trafficking nor dimerization were disturbed by substitution of these aromatic residues. In contrast, cellular photo-crosslinking assays demonstrated that cholesterol binding was compromised if one tyrosine residue located at the helix five or another at the helix six was replaced. Thus, these experiments suggested these two helices to contain specific cholesterol binding sites. To get a better molecular insight into these specific protein-lipid interactions, lipid binding to the transmembrane domain of mGluR2 was investigated in molecular dynamics (MD) simulation. The molecular dynamics simulations in GROMACS were performed in collaboration with the Max Planck tandem group of Dr. Camilo Aponte-Santamaría. All-atom and coarse-grained MD simulations of the mGluR2 transmembrane domain confirmed the experimental observation, by revealing a highly-localized density of cholesterol near these residues in helices five and six, which smeared out when they were changed to alanine in silico. The simulations also revealed flexibility of the protein structure at the exoplasmic end of helix six which changed upon introduction of point mutations. Overall, the work combining functional assays and MD simulations demonstrated the existence of specific cholesterol binding sites in mGluR2. It will be highly interesting to investigate the functional implications of this newly-found specific protein–cholesterol interaction on the activity and conformation of the receptor

Photocaged amino acids for photoinducible protein-protein interactions in Caenorhabditis elegans

Natural proteins are polymers of the twenty canonical amino acids. The twenty canonical amino acids have a variety of structures, and while sufficient to build the observed versatility of protein functions, they represent a miniscule portion of the possible amino acid structural space. The rest of this space is occupied by noncanonical amino acids (ncAAs). ncAAs can be designed to impart novel chemistries to proteins for specific tasks and can be incorporated into proteins in vivo by the method of Genetic Code Expansion (GCE). Photocaged amino acids are a variety of ncAA that can install photocontrol over incorporated protein function. Photocaged amino acids consist of a canonical amino acid structure conjugated with a photosensitive aromatic moiety called a caging group that is removed by illumination with 365 nm light. The caging group can prevent protein function, but allows function to be regained upon its removal by 365 nm illumination. In the nematode worm Caenorhabditis elegans, photocaged amino acids have been used for single-cell activation of CRE recombinase in induce gene expression and caspase-8 to induce apoptosis. In this thesis, I explore the application of photocaged amino acids to control protein-protein interactions in C. elegans. Photocaged protein interactions could be used to install photocontrol over protein localisation, which is a viable strategy for controlling protein activity in the case that activity can’t be controlled by the photocaging of a catalytic residue. In Chapter 1, I give a general introduction to the thesis. I begin with a background on translation, that process which is central to GCE. I describe translation’s key components – aminoacyl-tRNA synthesases, tRNAs, ribosomes, and the degenerate genetic code – and how each has been adapted for the incorporation of ncAAs. Finally, the model organism C. elegans is detailed: its history, traits, and uses, particularly in the context of GCE with photocaged amino acids. In Chapter 2, photocaged amino acids are used to install photocontrol over nanobody/GFP interactions. Nanobodies are small, single domain antibodies that bind targets with high specificity and strength, and are efficiently expressed in eukaryotic cytoplasm. Two anti-GFP nanobodies have been identified to have tyrosine residues that appear integral to GFP binding. Substitution of these tyrosine residues with photocaged tyrosines does not break GFP binding, and therefore fails to achieve photoinducibility. I use computational alanine scanning to identify other nanobody residues that when mutated could attenuate GFP binding to achieve photoinducibility. These mutations in combination with photocaging were found to achieve photoinducible GFP binding. Chapter 3 describes an alternate approach for using photocaged amino acids to control protein interactions. When the SpyTag and SpyCatcher proteins interact, an isopeptide bond is formed between them. Replacing one of the catalytic lysine residues on SpyCatcher with a photocaged lysine could install photocontrol over the interaction between these proteins. Preliminary results suggest photoinducible binding is achieved by this photocaging, but substantial work is required to reduce background synthesis of non-photocaged SpyCatcher. In Chapter 4, a potential application of photocaged interactions for photoinducible protein degradation is investigated. Ubiquitin ligase proteins such as TIR-1 have been used to induce ubiquitination and subsequent degradation of proteins in C. elegans. Preliminary results suggest that an autoinhibited TIR-1 could be activated by TEV protease. A photocaged TEV protease has been reported in mammalian cells, and could provide a route to photoactivation of the autoinhibited TIR-1 for photoinducible protein degradation

A dynamic clamp protocol to artificially modify cell capacitance

Dynamics of excitable cells and networks depend on the membrane time constant, set by membrane resistance and capacitance. Whereas pharmacological and genetic manipulations of ionic conductances of excitable membranes are routine in electrophysiology, experimental control over capacitance remains a challenge. Here, we present capacitance clamp, an approach that allows electrophysiologists to mimic a modified capacitance in biological neurons via an unconventional application of the dynamic clamp technique. We first demonstrate the feasibility to quantitatively modulate capacitance in a mathematical neuron model and then confirm the functionality of capacitance clamp in in vitro experiments in granule cells of rodent dentate gyrus with up to threefold virtual capacitance changes. Clamping of capacitance thus constitutes a novel technique to probe and decipher mechanisms of neuronal signaling in ways that were so far inaccessible to experimental electrophysiology.Peer Reviewe

Making a stronger case for comparative research to investigate the behavioral and neurological bases of three-dimensional navigation

The rich diversity of avian natural history provides exciting possibilities for comparative research aimed at understanding three-dimensional navigation. We propose some hypotheses relating differences in natural history to potential behavioral and neurological adaptations possessed by contrasting bird species. This comparative approach may offer unique insights into some of the important questions raised by Jeffery et al