@phdthesis{6291,
abstract = {Bacteria and their pathogens – phages – are the most abundant living entities on Earth. Throughout their coevolution, bacteria have evolved multiple immune systems to overcome the ubiquitous threat from the phages. Although the molecu- lar details of these immune systems’ functions are relatively well understood, their epidemiological consequences for the phage-bacterial communities have been largely neglected. In this thesis we employed both experimental and theoretical methods to explore whether herd and social immunity may arise in bacterial popu- lations. Using our experimental system consisting of Escherichia coli strains with a CRISPR based immunity to the T7 phage we show that herd immunity arises in phage-bacterial communities and that it is accentuated when the populations are spatially structured. By fitting a mathematical model, we inferred expressions for the herd immunity threshold and the velocity of spread of a phage epidemic in partially resistant bacterial populations, which both depend on the bacterial growth rate, phage burst size and phage latent period. We also investigated the poten- tial for social immunity in Streptococcus thermophilus and its phage 2972 using a bioinformatic analysis of potentially coding short open reading frames with a signalling signature, encoded within the CRISPR associated genes. Subsequently, we tested one identified potentially signalling peptide and found that its addition to a phage-challenged culture increases probability of survival of bacteria two fold, although the results were only marginally significant. Together, these results demonstrate that the ubiquitous arms races between bacteria and phages have further consequences at the level of the population.},
author = {Payne, Pavel},
pages = {83},
publisher = {IST Austria},
title = {{Bacterial herd and social immunity to phages}},
year = {2017},
}
@phdthesis{820,
abstract = {The lac operon is a classic model system for bacterial gene regulation, and has been studied extensively in E. coli, a classic model organism. However, not much is known about E. coli’s ecology and life outside the laboratory, in particular in soil and water environments. The natural diversity of the lac operon outside the laboratory, its role in the ecology of E. coli and the selection pressures it is exposed to, are similarly unknown.
In Chapter Two of this thesis, I explore the genetic diversity, phylogenetic history and signatures of selection of the lac operon across 20 natural isolates of E. coli and divergent clades of Escherichia. I found that complete lac operons were present in all isolates examined, which in all but one case were functional. The lac operon phylogeny conformed to the whole-genome phylogeny of the divergent Escherichia clades, which excludes horizontal gene transfer as an explanation for the presence of functional lac operons in these clades. All lac operon genes showed a signature of purifying selection; this signature was strongest for the lacY gene. Lac operon genes of human and environmental isolates showed similar signatures of selection, except the lacZ gene, which showed a stronger signature of selection in environmental isolates.
In Chapter Three, I try to identify the natural genetic variation relevant for phenotype and fitness in the lac operon, comparing growth rate on lactose and LacZ activity of the lac operons of these wild isolates in a common genetic background. Sequence variation in the lac promoter region, upstream of the -10 and -35 RNA polymerase binding motif, predicted variation in LacZ activity at full induction, using a thermodynamic model of polymerase binding (Tugrul, 2016). However, neither variation in LacZ activity, nor RNA polymerase binding predicted by the model correlated with variation in growth rate. Lac operons of human and environmental isolates did not differ systematically in either growth rate on lactose or LacZ protein activity, suggesting that these lac operons have been exposed to similar selection pressures. We thus have no evidence that the phenotypic variation we measured is relevant for fitness.
To start assessing the effect of genomic background on the growth phenotype conferred by the lac operon, I compared growth on minimal medium with lactose between lac operon constructs and the corresponding original isolates, I found that maximal growth rate was determined by genomic background, with almost all backgrounds conferring higher growth rates than lab strain K12 MG1655. However, I found no evidence that the lactose concentration at which growth was half maximal depended on genomic background.},
author = {Jesse, Fabienne},
pages = {87},
publisher = {IST Austria},
title = {{The lac operon in the wild}},
doi = {10.15479/AT:ISTA:th_857},
year = {2017},
}
@phdthesis{838,
abstract = {In this thesis we discuss the exact security of message authentications codes HMAC , NMAC , and PMAC . NMAC is a mode of operation which turns a fixed input-length keyed hash function f into a variable input-length function. A practical single-key variant of NMAC called HMAC is a very popular and widely deployed message authentication code (MAC). PMAC is a block-cipher based mode of operation, which also happens to be the most famous fully parallel MAC. NMAC was introduced by Bellare, Canetti and Krawczyk Crypto’96, who proved it to be a secure pseudorandom function (PRF), and thus also a MAC, under two assumptions. Unfortunately, for many instantiations of HMAC one of them has been found to be wrong. To restore the provable guarantees for NMAC , Bellare [Crypto’06] showed its security without this assumption. PMAC was introduced by Black and Rogaway at Eurocrypt 2002. If instantiated with a pseudorandom permutation over n -bit strings, PMAC constitutes a provably secure variable input-length PRF. For adversaries making q queries, each of length at most ` (in n -bit blocks), and of total length σ ≤ q` , the original paper proves an upper bound on the distinguishing advantage of O ( σ 2 / 2 n ), while the currently best bound is O ( qσ/ 2 n ). In this work we show that this bound is tight by giving an attack with advantage Ω( q 2 `/ 2 n ). In the PMAC construction one initially XORs a mask to every message block, where the mask for the i th block is computed as τ i := γ i · L , where L is a (secret) random value, and γ i is the i -th codeword of the Gray code. Our attack applies more generally to any sequence of γ i ’s which contains a large coset of a subgroup of GF (2 n ). As for NMAC , our first contribution is a simpler and uniform proof: If f is an ε -secure PRF (against q queries) and a δ - non-adaptively secure PRF (against q queries), then NMAC f is an ( ε + `qδ )-secure PRF against q queries of length at most ` blocks each. We also show that this ε + `qδ bound is basically tight by constructing an f for which an attack with advantage `qδ exists. Moreover, we analyze the PRF-security of a modification of NMAC called NI by An and Bellare that avoids the constant rekeying on multi-block messages in NMAC and allows for an information-theoretic analysis. We carry out such an analysis, obtaining a tight `q 2 / 2 c bound for this step, improving over the trivial bound of ` 2 q 2 / 2 c . Finally, we investigate, if the security of PMAC can be further improved by using τ i ’s that are k -wise independent, for k > 1 (the original has k = 1). We observe that the security of PMAC will not increase in general if k = 2, and then prove that the security increases to O ( q 2 / 2 n ), if the k = 4. Due to simple extension attacks, this is the best bound one can hope for, using any distribution on the masks. Whether k = 3 is already sufficient to get this level of security is left as an open problem. Keywords: Message authentication codes, Pseudorandom functions, HMAC, PMAC. },
author = {Rybar, Michal},
pages = {86},
publisher = {IST Austria},
title = {{(The exact security of) Message authentication codes}},
doi = {10.15479/AT:ISTA:th_828},
year = {2017},
}
@phdthesis{992,
abstract = {An instance of the Constraint Satisfaction Problem (CSP) is given by a finite set of
variables, a finite domain of labels, and a set of constraints, each constraint acting on
a subset of the variables. The goal is to find an assignment of labels to its variables
that satisfies all constraints (or decide whether one exists). If we allow more general
“soft” constraints, which come with (possibly infinite) costs of particular assignments,
we obtain instances from a richer class called Valued Constraint Satisfaction Problem
(VCSP). There the goal is to find an assignment with minimum total cost.
In this thesis, we focus (assuming that P
6
=
NP) on classifying computational com-
plexity of CSPs and VCSPs under certain restricting conditions. Two results are the core
content of the work. In one of them, we consider VCSPs parametrized by a constraint
language, that is the set of “soft” constraints allowed to form the instances, and finish
the complexity classification modulo (missing pieces of) complexity classification for
analogously parametrized CSP. The other result is a generalization of Edmonds’ perfect
matching algorithm. This generalization contributes to complexity classfications in two
ways. First, it gives a new (largest known) polynomial-time solvable class of Boolean
CSPs in which every variable may appear in at most two constraints and second, it
settles full classification of Boolean CSPs with planar drawing (again parametrized by a
constraint language).},
author = {Rolinek, Michal},
pages = {97},
publisher = {IST Austria},
title = {{Complexity of constraint satisfaction}},
doi = {10.15479/AT:ISTA:th_815},
year = {2017},
}
@phdthesis{938,
abstract = {The thesis encompasses several topics of plant cell biology which were studied in the model plant Arabidopsis thaliana. Chapter 1 concerns the plant hormone auxin and its polar transport through cells and tissues. The highly controlled, directional transport of auxin is facilitated by plasma membrane-localized transporters. Transporters from the PIN family direct auxin transport due to their polarized localizations at cell membranes. Substantial effort has been put into research on cellular trafficking of PIN proteins, which is thought to underlie their polar distribution. I participated in a forward genetic screen aimed at identifying novel regulators of PIN polarity. The screen yielded several genes which may be involved in PIN polarity regulation or participate in polar auxin transport by other means. Chapter 2 focuses on the endomembrane system, with particular attention to clathrin-mediated endocytosis. The project started with identification of several proteins that interact with clathrin light chains. Among them, I focused on two putative homologues of auxilin, which in non-plant systems is an endocytotic factor known for uncoating clathrin-coated vesicles in the final step of endocytosis. The body of my work consisted of an in-depth characterization of transgenic A. thaliana lines overexpressing these putative auxilins in an inducible manner. Overexpression of these proteins leads to an inhibition of endocytosis, as documented by imaging of cargoes and clathrin-related endocytic machinery. An extension of this work is an investigation into a concept of homeostatic regulation acting between distinct transport processes in the endomembrane system. With auxilin overexpressing lines, where endocytosis is blocked specifically, I made observations on the mutual relationship between two opposite trafficking processes of secretion and endocytosis. In Chapter 3, I analyze cortical microtubule arrays and their relationship to auxin signaling and polarized growth in elongating cells. In plants, microtubules are organized into arrays just below the plasma membrane, and it is thought that their function is to guide membrane-docked cellulose synthase complexes. These, in turn, influence cell wall structure and cell shape by directed deposition of cellulose fibres. In elongating cells, cortical microtubule arrays are able to reorient in relation to long cell axis, and these reorientations have been linked to cell growth and to signaling of growth-regulating factors such as auxin or light. In this chapter, I am addressing the causal relationship between microtubule array reorientation, growth, and auxin signaling. I arrive at a model where array reorientation is not guided by auxin directly, but instead is only controlled by growth, which, in turn, is regulated by auxin.},
author = {Adamowski, Maciek},
pages = {117},
publisher = {IST Austria},
title = {{Investigations into cell polarity and trafficking in the plant model Arabidopsis thaliana }},
doi = {10.15479/AT:ISTA:th_842},
year = {2017},
}
@phdthesis{839,
abstract = {This thesis describes a brittle fracture simulation method for visual effects applications. Building upon a symmetric Galerkin boundary element method, we first compute stress intensity factors following the theory of linear elastic fracture mechanics. We then use these stress intensities to simulate the motion of a propagating crack front at a significantly higher resolution than the overall deformation of the breaking object. Allowing for spatial variations of the material's toughness during crack propagation produces visually realistic, highly-detailed fracture surfaces. Furthermore, we introduce approximations for stress intensities and crack opening displacements, resulting in both practical speed-up and theoretically superior runtime complexity compared to previous methods. While we choose a quasi-static approach to fracture mechanics, ignoring dynamic deformations, we also couple our fracture simulation framework to a standard rigid-body dynamics solver, enabling visual effects artists to simulate both large scale motion, as well as fracturing due to collision forces in a combined system. As fractures inside of an object grow, their geometry must be represented both in the coarse boundary element mesh, as well as at the desired fine output resolution. Using a boundary element method, we avoid complicated volumetric meshing operations. Instead we describe a simple set of surface meshing operations that allow us to progressively add cracks to the mesh of an object and still re-use all previously computed entries of the linear boundary element system matrix. On the high resolution level, we opt for an implicit surface representation. We then describe how to capture fracture surfaces during crack propagation, as well as separate the individual fragments resulting from the fracture process, based on this implicit representation. We show results obtained with our method, either solving the full boundary element system in every time step, or alternatively using our fast approximations. These results demonstrate that both of these methods perform well in basic test cases and produce realistic fracture surfaces. Furthermore we show that our fast approximations substantially out-perform the standard approach in more demanding scenarios. Finally, these two methods naturally combine, using the full solution while the problem size is manageably small and switching to the fast approximations later on. The resulting hybrid method gives the user a direct way to choose between speed and accuracy of the simulation. },
author = {Hahn, David},
pages = {124},
publisher = {IST Austria},
title = {{Brittle fracture simulation with boundary elements for computer graphics}},
doi = {10.15479/AT:ISTA:th_855},
year = {2017},
}
@phdthesis{821,
abstract = {This dissertation focuses on algorithmic aspects of program verification, and presents modeling and complexity advances on several problems related to the
static analysis of programs, the stateless model checking of concurrent programs, and the competitive analysis of real-time scheduling algorithms.
Our contributions can be broadly grouped into five categories.
Our first contribution is a set of new algorithms and data structures for the quantitative and data-flow analysis of programs, based on the graph-theoretic notion of treewidth.
It has been observed that the control-flow graphs of typical programs have special structure, and are characterized as graphs of small treewidth.
We utilize this structural property to provide faster algorithms for the quantitative and data-flow analysis of recursive and concurrent programs.
In most cases we make an algebraic treatment of the considered problem,
where several interesting analyses, such as the reachability, shortest path, and certain kind of data-flow analysis problems follow as special cases.
We exploit the constant-treewidth property to obtain algorithmic improvements for on-demand versions of the problems,
and provide data structures with various tradeoffs between the resources spent in the preprocessing and querying phase.
We also improve on the algorithmic complexity of quantitative problems outside the algebraic path framework,
namely of the minimum mean-payoff, minimum ratio, and minimum initial credit for energy problems.
Our second contribution is a set of algorithms for Dyck reachability with applications to data-dependence analysis and alias analysis.
In particular, we develop an optimal algorithm for Dyck reachability on bidirected graphs, which are ubiquitous in context-insensitive, field-sensitive points-to analysis.
Additionally, we develop an efficient algorithm for context-sensitive data-dependence analysis via Dyck reachability,
where the task is to obtain analysis summaries of library code in the presence of callbacks.
Our algorithm preprocesses libraries in almost linear time, after which the contribution of the library in the complexity of the client analysis is (i)~linear in the number of call sites and (ii)~only logarithmic in the size of the whole library, as opposed to linear in the size of the whole library.
Finally, we prove that Dyck reachability is Boolean Matrix Multiplication-hard in general, and the hardness also holds for graphs of constant treewidth.
This hardness result strongly indicates that there exist no combinatorial algorithms for Dyck reachability with truly subcubic complexity.
Our third contribution is the formalization and algorithmic treatment of the Quantitative Interprocedural Analysis framework.
In this framework, the transitions of a recursive program are annotated as good, bad or neutral, and receive a weight which measures
the magnitude of their respective effect.
The Quantitative Interprocedural Analysis problem asks to determine whether there exists an infinite run of the program where the long-run ratio of the bad weights over the good weights is above a given threshold.
We illustrate how several quantitative problems related to static analysis of recursive programs can be instantiated in this framework,
and present some case studies to this direction.
Our fourth contribution is a new dynamic partial-order reduction for the stateless model checking of concurrent programs. Traditional approaches rely on the standard Mazurkiewicz equivalence between traces, by means of partitioning the trace space into equivalence classes, and attempting to explore a few representatives from each class.
We present a new dynamic partial-order reduction method called the Data-centric Partial Order Reduction (DC-DPOR).
Our algorithm is based on a new equivalence between traces, called the observation equivalence.
DC-DPOR explores a coarser partitioning of the trace space than any exploration method based on the standard Mazurkiewicz equivalence.
Depending on the program, the new partitioning can be even exponentially coarser.
Additionally, DC-DPOR spends only polynomial time in each explored class.
Our fifth contribution is the use of automata and game-theoretic verification techniques in the competitive analysis and synthesis of real-time scheduling algorithms for firm-deadline tasks.
On the analysis side, we leverage automata on infinite words to compute the competitive ratio of real-time schedulers subject to various environmental constraints.
On the synthesis side, we introduce a new instance of two-player mean-payoff partial-information games, and show
how the synthesis of an optimal real-time scheduler can be reduced to computing winning strategies in this new type of games.},
author = {Pavlogiannis, Andreas},
pages = {418},
publisher = {IST Austria},
title = {{Algorithmic advances in program analysis and their applications}},
doi = {10.15479/AT:ISTA:th_854},
year = {2017},
}
@phdthesis{1155,
abstract = {This dissertation concerns the automatic verification of probabilistic systems and programs with arrays by statistical and logical methods. Although statistical and logical methods are different in nature, we show that they can be successfully combined for system analysis. In the first part of the dissertation we present a new statistical algorithm for the verification of probabilistic systems with respect to unbounded properties, including linear temporal logic. Our algorithm often performs faster than the previous approaches, and at the same time requires less information about the system. In addition, our method can be generalized to unbounded quantitative properties such as mean-payoff bounds. In the second part, we introduce two techniques for comparing probabilistic systems. Probabilistic systems are typically compared using the notion of equivalence, which requires the systems to have the equal probability of all behaviors. However, this notion is often too strict, since probabilities are typically only empirically estimated, and any imprecision may break the relation between processes. On the one hand, we propose to replace the Boolean notion of equivalence by a quantitative distance of similarity. For this purpose, we introduce a statistical framework for estimating distances between Markov chains based on their simulation runs, and we investigate which distances can be approximated in our framework. On the other hand, we propose to compare systems with respect to a new qualitative logic, which expresses that behaviors occur with probability one or a positive probability. This qualitative analysis is robust with respect to modeling errors and applicable to many domains. In the last part, we present a new quantifier-free logic for integer arrays, which allows us to express counting. Counting properties are prevalent in array-manipulating programs, however they cannot be expressed in the quantified fragments of the theory of arrays. We present a decision procedure for our logic, and provide several complexity results.},
author = {Daca, Przemyslaw},
pages = {163},
publisher = {IST Austria},
title = {{Statistical and logical methods for property checking}},
doi = {10.15479/AT:ISTA:TH_730},
year = {2017},
}
@phdthesis{1127,
abstract = {Plant hormone auxin and its transport between cells belong to the most important
mechanisms controlling plant development. Auxin itself could change localization of PINs and
thereby control direction of its own flow. We performed an expression profiling experiment
in Arabidopsis roots to identify potential regulators of PIN polarity which are transcriptionally
regulated by auxin signalling. We identified several novel regulators and performed a detailed
characterization of the transcription factor WRKY23 (At2g47260) and its role in auxin
feedback on PIN polarity. Gain-of-function and dominant-negative mutants revealed that
WRKY23 plays a crucial role in mediating the auxin effect on PIN polarity. In concordance,
typical polar auxin transport processes such as gravitropism and leaf vascular pattern
formation were disturbed by interfering with WRKY23 function.
In order to identify direct targets of WRKY23, we performed consequential expression
profiling experiments using a WRKY23 inducible gain-of-function line and dominant-negative
WRKY23 line that is defunct in PIN re-arrangement. Among several genes mostly related to
the groups of cell wall and defense process regulators, we identified LYSINE-HISTIDINE
TRANSPORTER 1 (LHT1; At5g40780), a small amino acid permease gene from the amino
acid/auxin permease family (AAAP), we present its detailed characterisation in auxin feedback
on PIN repolarization, identified its transcriptional regulation, we propose a potential
mechanism of its action. Moreover, we identified also a member of receptor-like protein
kinase LRR-RLK (LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN KINASE PROTEIN 1;
LRRK1; At1g05700), which also affects auxin-dependent PIN re-arrangement. We described
its transcriptional behaviour, subcellular localization. Based on global expression data, we
tried to identify ligand responsible for mechanism of signalling and suggest signalling partner
and interactors. Additionally, we described role of novel phytohormone group, strigolactone,
in auxin-dependent PIN re-arrangement, that could be a fundament for future studies in this
field.
Our results provide first insights into an auxin transcriptional network targeting PIN
localization and thus regulating plant development. We highlighted WRKY23 transcriptional
network and characterised its mediatory role in plant development. We identified direct
effectors of this network, LHT1 and LRRK1, and describe their roles in PIN re-arrangement and
PIN-dependent auxin transport processes.},
author = {Prat, Tomas},
pages = {131},
publisher = {IST Austria},
title = {{Identification of novel regulators of PIN polarity and development of novel auxin sensor}},
year = {2017},
}
@phdthesis{202,
abstract = {Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions.},
author = {Pleska, Maros},
pages = {126},
publisher = {IST Austria},
title = {{Biology of restriction-modification systems at the single-cell and population level}},
doi = {10.15479/AT:ISTA:th_916},
year = {2017},
}