Spatio-temporal modeling of morphology and gene-expressions during C. elegans embryogenesis using a new imaging framework

Many aspects of ontogenesis, the process whereby an organism develops from the fertilized egg to a grown adult, are still poorly understood, despite having been studied since Aristotle's time. The advent of modern biology with the sequencing of entire genomes and mapping of all genes offers the promise that one day we will understand how genes function to regulate cell division and differentiation. These advances offer new possibilities to solve the question that humanity has been asking since the beginning of time, how is a new life created? The aim of this thesis is to establish methods to study when and where particular genes are expressed in the model organism Caenorhabditis elegans by means of microscopy. Ultimately, this will aid our understanding of embryology in more complex organisms and in human. The usefulness of the software is however not limited to embryology but is also useful for microscopy in general. In Paper I we present our open source software platform, Endrov (http://www.endrov.net), for image processing and microscopy. It is strongly modular and meant to allow tight integration with all kinds of infrastructure (microscopes, cameras, controllers, etc.) needed for modern biological and non-biological imaging. Endrov supports modern visualization, over 100 file formats, can connect to the OMERO image server and can control many modern light microscopes. We have also implemented 140 image processing algorithms and several types of annotations, e.g., for particle tracking, 3D surfaces, point-text annotation, neuron/vascular 4D annotation and more. A novel feature is the concept of laziness, which makes Endrov scale for large data sets and consequently makes it easier to prototype algorithms. The entire application is written in Java and consists of about 150 000 lines of code. In Paper II we have developed procedures to record wild-type C. elegans embryos in 3D over time (4D). Endrov was used to analyze the data and we generated a model of normal embryonic development complete up to the 150 cell-stage. The variance in cell positioning and division timing was calculated and the cell-cell contacts estimated. When compared to a previous model made from a squeezed embryo, our model has a higher time resolution and is more reproducible. In Paper III we have generated a revised list of all homeobox genes in C. elegans, showing that out of 103 homeobox genes, 70 are co-orthologous to human homeobox genes. A number of modules have been developed for analyzing and quantifying expression data. These are not only suitable for C. elegans but can also be used for other biological model systems. Special features include automatic adjustment of exposure time during recording resulting in an increased dynamic range beyond the limits of the microscope camera, and annotation of the cells in 3D rendered space. We have applied the new framework to examine homeobox gene expression patterns and provide an analysis of the patterns that we have recorded. In Paper IV we have extended the applicability of Endrov by using it to study the mitochondrial polymerase gamma (polg-1) in C. elegans. polg-1 deletion mutant alleles were analyzed for phenotypes using methods such as measuring lifespan and brood size, qPCR for mtDNA content and transcript levels, and light and TEM microscopy. The main findings were that homozygous polg-1 mutant animals develop normally, although later in the adult stage they exhibit compromised gonadal function, sterility, as well as reduced viability due to rupture at the vulva. 3D modeling of the gonad revealed structural abnormalities in the germline. Further, the few descendants that are generated are severely compromised and die during embryogenesis. We can deduce that while mtDNA copy number is a limiting factor for development, the maternally contributed mitochondria are enough to sustain development to adulthood. In summary, we have created the Endrov software framework that allows processing of large multidimensional microscopy image data sets and demonstrated that it can be applied to a wide range of problems

Vattnet stiger

Klimatförändringarna är en av vår tids stora utmaningar. Stigande havsnivåer, torrperioder och kraftiga skyfall, alla är de effekter av hur klimaten förändras. De här utmaningarna tillsammans med utmaningen om hur en hållbar stad byggs, en stad där vatten, natur och bebyggelse samspelar är bakgrunden till det här examensarbetet. Syftet med arbetet är dels att skapa en diskussion om ämnet och att uppnå en bättre förståelse och kunskap för hur det här samspelet kan se ut och vilka svårigheter och möjligheter som finns. Men även att utforska hur en gestaltning kan ses ut som både minimerar risker och som ger mervärden som biologiska värden. Föreliggande arbete har därför som mål att ta fram ett förslag för stadsdelen Tullkammarkajen i Halmstad som både kan hantera stigande vatten men som också ger biologiska mervärden. Arbetet har utgått från en designprocess. Till grund för designprocessen ligger en teoretisk bakgrundsstudie och en studie över ett antal exempelplatser. Det färdiga förslaget visar en gestaltning som tar fasta på arbetets huvudsakliga syfte och mål och visar på hur en alternativ utformning kan se ut som både kan hantera ökade vattenmängder i staden samt ger mervärde i form av biologiska värden. Förslaget har utvärderats gentemot två andra alternativ genom ett flertal aspekter, vilket visade på fördelar och nackdelar både med det egna förslaget samt alternativ förslagen. Efter utvärderingen kan ingen generell rekommendation göras för vilket alternativ som bör användas, men det här arbetet kan ses som inspiration och vägledande i den fortsatta utredningen om hur Tullkammarkajen i Halmstad ska utvecklas.Climate change is one of the great challenges of our time. Rising sea levels, dry periods and cloudburst, all are they effects of changing climate. These challenges, together with the challenge of how to build a sustainable city, a city where water, nature and buildings interact is the background to this master thesis. The purpose of this thesis is partly to create a discussion on the subject and to gain a better understanding and knowledge of what this interaction can look like and what difficulties and opportunities that exist. It is also to explore how a design can look like that both minimizing the risks and provide benefits as biological values. The present thesis therefore aims to produce a proposal for the district of Tullkammarkajen in Halmstad, which can both handle rising water and provide biological benefits. The thesis is based on a design process. The basis of the design process is a theoretical background study and a study of some example sites. The final proposal present a design that addresses the main purpose and goals of this thesis and shows how an alternative design can look like that can both handle increased water levels in the city as well as provide added value in the form of biological values. The proposal has been evaluated against two other alternatives through a number of aspects, which both shows the advantages and disadvantages of the own proposal and the alternative proposals. After the evaluation, no general recommendation can be made for which alternative should be used. But this work can be seen as inspiration and guidance in the continuing investigation of how the Tullkammarkajen in Halmstad should be developed

Analytic Bootstrap for Perturbative Conformal Field Theories

Conformal field theories play a central role in theoretical physics with many applications ranging from condensed matter to string theory. The conformal bootstrap studies conformal field theories using mathematical consistency conditions and has seen great progress over the last decade. In this thesis we present an implementation of analytic bootstrap methods for perturbative conformal field theories in dimensions greater than two, which we achieve by combining large spin perturbation theory with the Lorentzian inversion formula. In the presence of a small expansion parameter, not necessarily the coupling constant, we develop this into a systematic framework, applicable to a wide range of theories. The first two chapters provide the necessary background and a review of the analytic bootstrap. This is followed by a chapter which describes the method in detail, taking the form of a practical guide to large spin perturbation theory by means of a step-by-step implementation. The second part of the thesis presents several explicit implementations of the framework, taking examples from a number of well-studied conformal field theories. We show how many literature results can be reproduced from a purely bootstrap perspective and how a variety of new results can be derived.Comment: DPhil thesis. 221 pages, 11 figures. Sections 6.3 and 6.4 contain some previously unpublished results. v2: typos correcte

Taming the ϵ\epsilon-expansion with Large Spin Perturbation Theory

We apply analytic bootstrap techniques to the four-point correlator of fundamental fields in the Wilson-Fisher model. In an $\epsilon$-expansion crossing symmetry fixes the double discontinuity of the correlator in terms of CFT data at lower orders. Large spin perturbation theory, or equivalently the recently proposed Froissart-Gribov inversion integral, then allows one to reconstruct the CFT data of intermediate operators of any spin. We use this method to compute the anomalous dimensions and OPE coefficients of leading twist operators. To cubic order in $\epsilon$ the double discontinuity arises solely from the identity operator and the scalar bilinear operator, making the computation straightforward. At higher orders the double discontinuity receives contributions from infinite towers of higher spin operators. At fourth order, the structure of perturbation theory leads to a proposal in terms of functions of certain degree of transcendentality, which can then be fixed by symmetries. This leads to the full determination of the CFT data for leading twist operators to fourth order.Comment: 16 pages. v2: Added discussion on low spin spectru

Flexible Implementation of Model Predictive Control Using Sub-Optimal Solutions

The on-line computational demands of model predictive control (MPC) often prevents its application to processes where fast sampling is necessary. This report presents a strategy for reducing the computational delay resulting from the on-line optimization inherent in many MPC formulations. Recent results have shown that feasibility, rather than optimality, is a prerequisite for stabilizing MPC algorithms, implying that premature termination of the optimization procedure may be valid, without compromising stability. The main result included in the report is a termination criterion for the on-line optimization algorithm giving rise to a sub-optimal, yet stabilizing, MPC algorithm. The termination criterion, based on an associated delay-dependent cost index, quantifies the trade-off between successively improved control profiles resulting form the optimization algorithm and the potential performance degradation due to increasing computational delay. It is also shown how the cost index may be used in a dynamic scheduling application, where the processor time is shared between two MPC tasks executing on the same CPU

Quadratic response functions in the relativistic four-component Kohn-Sham approximation.

International audienceA formulation and implementation of the quadratic response function in the adiabatic four-component Kohn-Sham approximation is presented. The noninteracting reference state is time-reversal symmetric and formed from Kramers pair spinors, and the energy density is gradient corrected. Example calculations are presented for the optical properties of disubstituted halobenzenes in their meta and ortho conformations. It is demonstrated that correlation and relativistic effects are not additive, and it is shown that relativity alone reduces the mubeta-response signal by 62% and 75% for meta- and ortho-bromobenzene, respectively, and enhances the same response by 17% and 21% for meta- and ortho-iodobenzene, respectively. Of the employed functionals, CAM-B3LYP shows the best performance and gives hyperpolarizabilities beta distinctly different from B3LYP

Classical Codes and Chiral CFTs at Higher Genus

Higher genus modular invariance of two-dimensional conformal field theories (CFTs) is a largely unexplored area. In this paper, we derive explicit expressions for the higher genus partition functions of a specific class of CFTs: code CFTs, which are constructed using classical error-correcting codes. In this setting, the $\mathrm{Sp}(2g,\mathbb Z)$ modular transformations of genus $g$ Riemann surfaces can be recast as a simple set of linear maps acting on $2^g$ polynomial variables, which comprise an object called the code enumerator polynomial. The CFT partition function is directly related to the enumerator polynomial, meaning that solutions of the linear constraints from modular invariance immediately give a set of seemingly consistent partition functions at a given genus. We then find that higher genus constraints, plus consistency under degeneration limits of the Riemann surface, greatly reduces the number of possible code CFTs. This work provides a step towards a full understanding of the constraints from higher genus modular invariance on 2d CFTs.Comment: 48p