@phdthesis{819,
abstract = {Contagious diseases must transmit from infectious to susceptible hosts in order to reproduce. Whilst vectored pathogens can rely on intermediaries to find new hosts for them, many infectious pathogens require close contact or direct interaction between hosts for transmission. Hence, this means that conspecifics are often the main source of infection for most animals and so, in theory, animals should avoid conspecifics to reduce their risk of infection. Of course, in reality animals must interact with one another, as a bare minimum, to mate. However, being social provides many additional benefits and group living has become a taxonomically diverse and widespread trait. How then do social animals overcome the issue of increased disease? Over the last few decades, the social insects (ants, termites and some bees and wasps) have become a model system for studying disease in social animals. On paper, a social insect colony should be particularly susceptible to disease, given that they often contain thousands of potential hosts that are closely related and frequently interact, as well as exhibiting stable environmental conditions that encourage microbial growth. Yet, disease outbreaks appear to be rare and attempts to eradicate pest species using pathogens have failed time and again. Evolutionary biologists investigating this observation have discovered that the reduced disease susceptibility in social insects is, in part, due to collectively performed disease defences of the workers. These defences act like a “social immune system” for the colony, resulting in a per capita decrease in disease, termed social immunity. Our understanding of social immunity, and its importance in relation to the immunological defences of each insect, continues to grow, but there remain many open questions. In this thesis I have studied disease defence in garden ants. In the first data chapter, I use the invasive garden ant, Lasius neglectus, to investigate how colonies mitigate lethal infections and prevent them from spreading systemically. I find that ants have evolved ‘destructive disinfection’ – a behaviour that uses endogenously produced acidic poison to kill diseased brood and to prevent the pathogen from replicating. In the second experimental chapter, I continue to study the use of poison in invasive garden ant colonies, finding that it is sprayed prophylactically within the nest. However, this spraying has negative effects on developing pupae when they have had their cocoons artificially removed. Hence, I suggest that acidic nest sanitation may be maintaining larval cocoon spinning in this species. In the next experimental chapter, I investigated how colony founding black garden ant queens (Lasius niger) prevent disease when a co-foundress dies. I show that ant queens prophylactically perform undertaking behaviours, similar to those performed by the workers in mature nests. When a co-foundress was infected, these undertaking behaviours improved the survival of the healthy queen. In the final data chapter, I explored how immunocompetence (measured as antifungal activity) changes as incipient black garden ant colonies grow and mature, from the solitary queen phase to colonies with several hundred workers. Queen and worker antifungal activity varied throughout this time period, but despite social immunity, did not decrease as colonies matured. In addition to the above data chapters, this thesis includes two co-authored reviews. In the first, we examine the state of the art in the field of social immunity and how it might develop in the future. In the second, we identify several challenges and open questions in the study of disease defence in animals. We highlight how social insects offer a unique model to tackle some of these problems, as disease defence can be studied from the cell to the society. },
author = {Pull, Christopher},
pages = {122},
publisher = {IST Austria},
title = {{Disease defence in garden ants}},
doi = {10.15479/AT:ISTA:th_861},
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{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{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{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{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{961,
abstract = {Cell-cell contact formation constitutes the first step in the emergence of multicellularity in evolution, thereby allowing the differentiation of specialized cell types. In metazoan development, cell-cell contact formation is thought to influence cell fate specification, and cell fate specification has been implicated in cell-cell contact formation. However, remarkably little is yet known about whether and how the interaction and feedback between cell-cell contact formation and cell fate specification affect development. Here we identify a positive feedback loop between cell-cell contact duration, morphogen signaling and mesendoderm cell fate specification during zebrafish gastrulation. We show that long lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for proper ppl cell fate specification. We further show that Nodal signalling romotes ppl cell-cell contact duration, thereby generating an effective positive feedback loop between ppl cell-cell contact duration and cell fate specification. Finally, by using a combination of theoretical modeling and experimentation, we show that this feedback loop determines whether anterior axial mesendoderm cells become ppl progenitors or, instead, turn into endoderm progenitors. Our findings reveal that the gene regulatory networks leading to cell fate diversification within the developing embryo are controlled by the interdependent activities of cell-cell signaling and contact formation.},
author = {Barone, Vanessa},
pages = {109},
publisher = {IST Austria},
title = {{Cell adhesion and cell fate: An effective feedback loop during zebrafish gastrulation}},
doi = {10.15479/AT:ISTA:th_825},
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{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{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{837,
abstract = {The hippocampus is a key brain region for memory and notably for spatial memory, and is needed for both spatial working and reference memories. Hippocampal place cells selectively discharge in specific locations of the environment to form mnemonic represen tations of space. Several behavioral protocols have been designed to test spatial memory which requires the experimental subject to utilize working memory and reference memory. However, less is known about how these memory traces are presented in the hippo campus, especially considering tasks that require both spatial working and long -term reference memory demand. The aim of my thesis was to elucidate how spatial working memory, reference memory, and the combination of both are represented in the hippocampus. In this thesis, using a radial eight -arm maze, I examined how the combined demand on these memories influenced place cell assemblies while reference memories were partially updated by changing some of the reward- arms. This was contrasted with task varian ts requiring working or reference memories only. Reference memory update led to gradual place field shifts towards the rewards on the switched arms. Cells developed enhanced firing in passes between newly -rewarded arms as compared to those containing an unchanged reward. The working memory task did not show such gradual changes. Place assemblies on occasions replayed trajectories of the maze; at decision points the next arm choice was preferentially replayed in tasks needing reference memory while in the pure working memory task the previously visited arm was replayed. Hence trajectory replay only reflected the decision of the animal in tasks needing reference memory update. At the reward locations, in all three tasks outbound trajectories of the current arm were preferentially replayed, showing the animals’ next path to the center. At reward locations trajectories were replayed preferentially in reverse temporal order. Moreover, in the center reverse replay was seen in the working memory task but in the other tasks forward replay was seen. Hence, the direction of reactivation was determined by the goal locations so that part of the trajectory which was closer to the goal was reactivated later in an HSE while places further away from the goal were reactivated earlier. Altogether my work demonstrated that reference memory update triggers several levels of reorganization of the hippocampal cognitive map which are not seen in simpler working memory demand s. Moreover, hippocampus is likely to be involved in spatial decisions through reactivating planned trajectories when reference memory recall is required for such a decision. },
author = {Xu, Haibing},
pages = {93},
publisher = {IST Austria},
title = {{Reactivation of the hippocampal cognitive map in goal-directed spatial tasks}},
doi = {10.15479/AT:ISTA:th_858},
year = {2017},
}
@phdthesis{1396,
abstract = {CA3 pyramidal neurons are thought to pay a key role in memory storage and pattern completion by activity-dependent synaptic plasticity between CA3-CA3 recurrent excitatory synapses. To examine the induction rules of synaptic plasticity at CA3-CA3 synapses, we performed whole-cell patch-clamp recordings in acute hippocampal slices from rats (postnatal 21-24 days) at room temperature. Compound excitatory postsynaptic potentials (ESPSs) were recorded by tract stimulation in stratum oriens in the presence of 10 µM gabazine. High-frequency stimulation (HFS) induced N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP). Although LTP by HFS did not requier postsynaptic spikes, it was blocked by Na+-channel blockers suggesting that local active processes (e.g.) dendritic spikes) may contribute to LTP induction without requirement of a somatic action potential (AP). We next examined the properties of spike timing-dependent plasticity (STDP) at CA3-CA3 synapses. Unexpectedly, low-frequency pairing of EPSPs and backpropagated action potentialy (bAPs) induced LTP, independent of temporal order. The STDP curve was symmetric and broad, with a half-width of ~150 ms. Consistent with these specific STDP induction properties, post-presynaptic sequences led to a supralinear summation of spine [Ca2+] transients. Furthermore, in autoassociative network models, storage and recall was substantially more robust with symmetric than with asymmetric STDP rules. In conclusion, we found associative forms of LTP at CA3-CA3 recurrent collateral synapses with distinct induction rules. LTP induced by HFS may be associated with dendritic spikes. In contrast, low frequency pairing of pre- and postsynaptic activity induced LTP only if EPSP-AP were temporally very close. Together, these induction mechanisms of synaptiic plasticity may contribute to memory storage in the CA3-CA3 microcircuit at different ranges of activity.},
author = {Mishra, Rajiv Kumar},
pages = {83},
publisher = {IST Austria},
title = {{Synaptic plasticity rules at CA3-CA3 recurrent synapses in hippocampus}},
year = {2016},
}
@phdthesis{1397,
abstract = {We study partially observable Markov decision processes (POMDPs) with objectives used in verification and artificial intelligence. The qualitative analysis problem given a POMDP and an objective asks whether there is a strategy (policy) to ensure that the objective is satisfied almost surely (with probability 1), resp. with positive probability (with probability greater than 0). For POMDPs with limit-average payoff, where a reward value in the interval [0,1] is associated to every transition, and the payoff of an infinite path is the long-run average of the rewards, we consider two types of path constraints: (i) a quantitative limit-average constraint defines the set of paths where the payoff is at least a given threshold L1 = 1. Our main results for qualitative limit-average constraint under almost-sure winning are as follows: (i) the problem of deciding the existence of a finite-memory controller is EXPTIME-complete; and (ii) the problem of deciding the existence of an infinite-memory controller is undecidable. For quantitative limit-average constraints we show that the problem of deciding the existence of a finite-memory controller is undecidable. We present a prototype implementation of our EXPTIME algorithm. For POMDPs with w-regular conditions specified as parity objectives, while the qualitative analysis problems are known to be undecidable even for very special case of parity objectives, we establish decidability (with optimal complexity) of the qualitative analysis problems for POMDPs with parity objectives under finite-memory strategies. We establish optimal (exponential) memory bounds and EXPTIME-completeness of the qualitative analysis problems under finite-memory strategies for POMDPs with parity objectives. Based on our theoretical algorithms we also present a practical approach, where we design heuristics to deal with the exponential complexity, and have applied our implementation on a number of well-known POMDP examples for robotics applications. For POMDPs with a set of target states and an integer cost associated with every transition, we study the optimization objective that asks to minimize the expected total cost of reaching a state in the target set, while ensuring that the target set is reached almost surely. We show that for general integer costs approximating the optimal cost is undecidable. For positive costs, our results are as follows: (i) we establish matching lower and upper bounds for the optimal cost, both double and exponential in the POMDP state space size; (ii) we show that the problem of approximating the optimal cost is decidable and present approximation algorithms that extend existing algorithms for POMDPs with finite-horizon objectives. We show experimentally that it performs well in many examples of interest. We study more deeply the problem of almost-sure reachability, where given a set of target states, the question is to decide whether there is a strategy to ensure that the target set is reached almost surely. While in general the problem EXPTIME-complete, in many practical cases strategies with a small amount of memory suffice. Moreover, the existing solution to the problem is explicit, which first requires to construct explicitly an exponential reduction to a belief-support MDP. We first study the existence of observation-stationary strategies, which is NP-complete, and then small-memory strategies. We present a symbolic algorithm by an efficient encoding to SAT and using a SAT solver for the problem. We report experimental results demonstrating the scalability of our symbolic (SAT-based) approach. Decentralized POMDPs (DEC-POMDPs) extend POMDPs to a multi-agent setting, where several agents operate in an uncertain environment independently to achieve a joint objective. In this work we consider Goal DEC-POMDPs, where given a set of target states, the objective is to ensure that the target set is reached with minimal cost. We consider the indefinite-horizon (infinite-horizon with either discounted-sum, or undiscounted-sum, where absorbing goal states have zero-cost) problem. We present a new and novel method to solve the problem that extends methods for finite-horizon DEC-POMDPs and the real-time dynamic programming approach for POMDPs. We present experimental results on several examples, and show that our approach presents promising results. In the end we present a short summary of a few other results related to verification of MDPs and POMDPs.},
author = {Chmelik, Martin},
pages = {232},
publisher = {IST Austria},
title = {{Algorithms for partially observable markov decision processes}},
year = {2016},
}
@phdthesis{1398,
abstract = {Hybrid zones represent evolutionary laboratories, where recombination brings together alleles in combinations which have not previously been tested by selection. This provides an excellent opportunity to test the effect of molecular variation on fitness, and how this variation is able to spread through populations in a natural context. The snapdragon Antirrhinum majus is polymorphic in the wild for two loci controlling the distribution of yellow and magenta floral pigments. Where the yellow A. m. striatum and the magenta A. m. pseudomajus meet along a valley in the Spanish Pyrenees they form a stable hybrid zone Alleles at these loci recombine to give striking transgressive variation for flower colour. The sharp transition in phenotype over ~1km implies strong selection maintaining the hybrid zone. An indirect assay of pollinator visitation in the field found that pollinators forage in a positive-frequency dependent manner on Antirrhinum, matching previous data on fruit set. Experimental arrays and paternity analysis of wild-pollinated seeds demonstrated assortative mating for pigmentation alleles, and that pollinator behaviour alone is sufficient to explain this pattern. Selection by pollinators should be sufficiently strong to maintain the hybrid zone, although other mechanisms may be at work. At a broader scale I examined evolutionary transitions between yellow and anthocyanin pigmentation in the tribe Antirrhinae, and found that selection has acted strate that pollinators are a major determinant of reproductive success and mating patterns in wild Antirrhinum.},
author = {Ellis, Thomas},
pages = {130},
publisher = {IST Austria},
title = {{The role of pollinator-mediated selection in the maintenance of a flower color polymorphism in an Antirrhinum majus hybrid zone}},
doi = {10.15479/AT:ISTA:TH_526 },
year = {2016},
}
@phdthesis{1121,
abstract = {Horizontal gene transfer (HGT), the lateral acquisition of genes across existing species
boundaries, is a major evolutionary force shaping microbial genomes that facilitates
adaptation to new environments as well as resistance to antimicrobial drugs. As such,
understanding the mechanisms and constraints that determine the outcomes of HGT
events is crucial to understand the dynamics of HGT and to design better strategies to
overcome the challenges that originate from it.
Following the insertion and expression of a newly transferred gene, the success of an
HGT event will depend on the fitness effect it has on the recipient (host) cell. Therefore,
predicting the impact of HGT on the genetic composition of a population critically
depends on the distribution of fitness effects (DFE) of horizontally transferred genes.
However, to date, we have little knowledge of the DFE of newly transferred genes, and
hence little is known about the shape and scale of this distribution.
It is particularly important to better understand the selective barriers that determine
the fitness effects of newly transferred genes. In spite of substantial bioinformatics
efforts to identify horizontally transferred genes and selective barriers, a systematic
experimental approach to elucidate the roles of different selective barriers in defining
the fate of a transfer event has largely been absent. Similarly, although the fact that
environment might alter the fitness effect of a horizontally transferred gene may seem
obvious, little attention has been given to it in a systematic experimental manner.
In this study, we developed a systematic experimental approach that consists of
transferring 44 arbitrarily selected Salmonella typhimurium orthologous genes into an
Escherichia coli host, and estimating the fitness effects of these transferred genes at a
constant expression level by performing competition assays against the wild type.
In chapter 2, we performed one-to-one competition assays between a mutant strain
carrying a transferred gene and the wild type strain. By using flow cytometry we
estimated selection coefficients for the transferred genes with a precision level of 10-3,and obtained the DFE of horizontally transferred genes. We then investigated if these
fitness effects could be predicted by any of the intrinsic properties of the genes, namely,
functional category, degree of complexity (protein-protein interactions), GC content,
codon usage and length. Our analyses revealed that the functional category and length
of the genes act as potential selective barriers. Finally, using the same procedure with
the endogenous E. coli orthologs of these 44 genes, we demonstrated that gene dosage is
the most prominent selective barrier to HGT.
In chapter 3, using the same set of genes we investigated the role of environment on the
success of HGT events. Under six different environments with different levels of stress
we performed more complex competition assays, where we mixed all 44 mutant strains
carrying transferred genes with the wild type strain. To estimate the fitness effects of
genes relative to wild type we used next generation sequencing. We found that the DFEs
of horizontally transferred genes are highly dependent on the environment, with
abundant gene–by-environment interactions. Furthermore, we demonstrated a
relationship between average fitness effect of a gene across all environments and its
environmental variance, and thus its predictability. Finally, in spite of the fitness effects
of genes being highly environment-dependent, we still observed a common shape of
DFEs across all tested environments.},
author = {Acar, Hande},
pages = {75},
publisher = {IST Austria},
title = {{Selective barriers to horizontal gene transfer}},
year = {2016},
}
@phdthesis{1122,
abstract = {Computer graphics is an extremely exciting field for two reasons. On the one hand,
there is a healthy injection of pragmatism coming from the visual effects industry
that want robust algorithms that work so they can produce results at an increasingly
frantic pace. On the other hand, they must always try to push the envelope and
achieve the impossible to wow their audiences in the next blockbuster, which means
that the industry has not succumb to conservatism, and there is plenty of room to
try out new and crazy ideas if there is a chance that it will pan into something
useful.
Water simulation has been in visual effects for decades, however it still remains
extremely challenging because of its high computational cost and difficult artdirectability.
The work in this thesis tries to address some of these difficulties.
Specifically, we make the following three novel contributions to the state-of-the-art
in water simulation for visual effects.
First, we develop the first algorithm that can convert any sequence of closed
surfaces in time into a moving triangle mesh. State-of-the-art methods at the time
could only handle surfaces with fixed connectivity, but we are the first to be able to
handle surfaces that merge and split apart. This is important for water simulation
practitioners, because it allows them to convert splashy water surfaces extracted
from particles or simulated using grid-based level sets into triangle meshes that can
be either textured and enhanced with extra surface dynamics as a post-process.
We also apply our algorithm to other phenomena that merge and split apart, such
as morphs and noisy reconstructions of human performances.
Second, we formulate a surface-based energy that measures the deviation of a
water surface froma physically valid state. Such discrepancies arise when there is a
mismatch in the degrees of freedom between the water surface and the underlying
physics solver. This commonly happens when practitioners use a moving triangle
mesh with a grid-based physics solver, or when high-resolution grid-based surfaces
are combined with low-resolution physics. Following the direction of steepest
descent on our surface-based energy, we can either smooth these artifacts or turn
them into high-resolution waves by interpreting the energy as a physical potential.
Third, we extend state-of-the-art techniques in non-reflecting boundaries to handle spatially and time-varying background flows. This allows a novel new
workflow where practitioners can re-simulate part of an existing simulation, such
as removing a solid obstacle, adding a new splash or locally changing the resolution.
Such changes can easily lead to new waves in the re-simulated region that would
reflect off of the new simulation boundary, effectively ruining the illusion of a
seamless simulation boundary between the existing and new simulations. Our
non-reflecting boundaries makes sure that such waves are absorbed.},
author = {Bojsen-Hansen, Morten},
pages = {114},
publisher = {IST Austria},
title = {{Tracking, correcting and absorbing water surface waves}},
doi = {10.15479/AT:ISTA:th_640},
year = {2016},
}
@phdthesis{1123,
abstract = {Motivated by topological Tverberg-type problems in topological combinatorics and by classical
results about embeddings (maps without double points), we study the question whether a finite
simplicial complex K can be mapped into Rd without triple, quadruple, or, more generally, r-fold points (image points with at least r distinct preimages), for a given multiplicity r ≤ 2. In particular, we are interested in maps f : K → Rd that have no global r -fold intersection points, i.e., no r -fold points with preimages in r pairwise disjoint simplices of K , and we seek necessary and sufficient conditions for the existence of such maps.
We present higher-multiplicity analogues of several classical results for embeddings, in particular of the completeness of the Van Kampen obstruction for embeddability of k -dimensional
complexes into R2k , k ≥ 3. Speciffically, we show that under suitable restrictions on the dimensions(viz., if dimK = (r ≥ 1)k and d = rk \ for some k ≥ 3), a well-known deleted product criterion (DPC ) is not only necessary but also sufficient for the existence of maps without global r -fold points. Our main technical tool is a higher-multiplicity version of the classical Whitney trick , by which pairs of isolated r -fold points of opposite sign can be eliminated by local modiffications of the map, assuming codimension d – dimK ≥ 3.
An important guiding idea for our work was that suffciency of the DPC, together with an old
result of Özaydin's on the existence of equivariant maps, might yield an approach to disproving the remaining open cases of the the long-standing topological Tverberg conjecture , i.e., to construct maps from the N -simplex σN to Rd without r-Tverberg points when r not a prime power and
N = (d + 1)(r – 1). Unfortunately, our proof of the sufficiency of the DPC requires codimension d – dimK ≥ 3, which is not satisfied for K = σN .
In 2015, Frick [16] found a very elegant way to overcome this \codimension 3 obstacle" and
to construct the first counterexamples to the topological Tverberg conjecture for all parameters(d; r ) with d ≥ 3r + 1 and r not a prime power, by a reduction1 to a suitable lower-dimensional skeleton, for which the codimension 3 restriction is satisfied and maps without r -Tverberg points exist by Özaydin's result and sufficiency of the DPC.
In this thesis, we present a different construction (which does not use the constraint method) that yields counterexamples for d ≥ 3r , r not a prime power. },
author = {Mabillard, Isaac},
pages = {55},
publisher = {IST Austria},
title = {{Eliminating higher-multiplicity intersections: an r-fold Whitney trick for the topological Tverberg conjecture}},
year = {2016},
}
@phdthesis{1124,
author = {Morri, Maurizio},
pages = {129},
publisher = {IST Austria},
title = {{Optical functionalization of human class A orphan G-protein coupled receptors}},
year = {2016},
}
@phdthesis{1125,
abstract = {Natural environments are never constant but subject to spatial and temporal change on
all scales, increasingly so due to human activity. Hence, it is crucial to understand the
impact of environmental variation on evolutionary processes. In this thesis, I present
three topics that share the common theme of environmental variation, yet illustrate its
effect from different perspectives.
First, I show how a temporally fluctuating environment gives rise to second-order
selection on a modifier for stress-induced mutagenesis. Without fluctuations, when
populations are adapted to their environment, mutation rates are minimized. I argue
that a stress-induced mutator mechanism may only be maintained if the population is
repeatedly subjected to diverse environmental challenges, and I outline implications of
the presented results to antibiotic treatment strategies.
Second, I discuss my work on the evolution of dispersal. Besides reproducing
known results about the effect of heterogeneous habitats on dispersal, it identifies
spatial changes in dispersal type frequencies as a source for selection for increased
propensities to disperse. This concept contains effects of relatedness that are known
to promote dispersal, and I explain how it identifies other forces selecting for dispersal
and puts them on a common scale.
Third, I analyse genetic variances of phenotypic traits under multivariate stabilizing
selection. For the case of constant environments, I generalize known formulae of
equilibrium variances to multiple traits and discuss how the genetic variance of a focal
trait is influenced by selection on background traits. I conclude by presenting ideas and
preliminary work aiming at including environmental fluctuations in the form of moving
trait optima into the model.},
author = {Novak, Sebastian},
pages = {124},
publisher = {IST Austria},
title = {{Evolutionary proccesses in variable emvironments}},
year = {2016},
}
@phdthesis{1126,
abstract = {Traditionally machine learning has been focusing on the problem of solving a single
task in isolation. While being quite well understood, this approach disregards an
important aspect of human learning: when facing a new problem, humans are able to
exploit knowledge acquired from previously learned tasks. Intuitively, access to several
problems simultaneously or sequentially could also be advantageous for a machine
learning system, especially if these tasks are closely related. Indeed, results of many
empirical studies have provided justification for this intuition. However, theoretical
justifications of this idea are rather limited.
The focus of this thesis is to expand the understanding of potential benefits of information
transfer between several related learning problems. We provide theoretical
analysis for three scenarios of multi-task learning - multiple kernel learning, sequential
learning and active task selection. We also provide a PAC-Bayesian perspective on
lifelong learning and investigate how the task generation process influences the generalization
guarantees in this scenario. In addition, we show how some of the obtained
theoretical results can be used to derive principled multi-task and lifelong learning
algorithms and illustrate their performance on various synthetic and real-world datasets.},
author = {Pentina, Anastasia},
pages = {127},
publisher = {IST Austria},
title = {{Theoretical foundations of multi-task lifelong learning}},
doi = {10.15479/AT:ISTA:TH_776},
year = {2016},
}