@article{1269,
abstract = {Plants are continuously exposed to a myriad of external signals such as fluctuating nutrients availability, drought, heat, cold, high salinity, or pathogen/pest attacks that can severely affect their development, growth, and fertility. As sessile organisms, plants must therefore be able to sense and rapidly react to these external inputs, activate efficient responses, and adjust development to changing conditions. In recent years, significant progress has been made towards understanding the molecular mechanisms underlying the intricate and complex communication between plants and the environment. It is now becoming increasingly evident that hormones have an important regulatory role in plant adaptation and defense mechanisms.},
author = {Benková, Eva},
journal = {Plant Molecular Biology},
number = {6},
pages = {597},
publisher = {Springer},
title = {{Plant hormones in interactions with the environment}},
doi = {10.1007/s11103-016-0501-8},
volume = {91},
year = {2016},
}
@inproceedings{948,
abstract = {Experience constantly shapes neural circuits through a variety of plasticity mechanisms. While the functional roles of some plasticity mechanisms are well-understood, it remains unclear how changes in neural excitability contribute to learning. Here, we develop a normative interpretation of intrinsic plasticity (IP) as a key component of unsupervised learning. We introduce a novel generative mixture model that accounts for the class-specific statistics of stimulus intensities, and we derive a neural circuit that learns the input classes and their intensities. We will analytically show that inference and learning for our generative model can be achieved by a neural circuit with intensity-sensitive neurons equipped with a specific form of IP. Numerical experiments verify our analytical derivations and show robust behavior for artificial and natural stimuli. Our results link IP to non-trivial input statistics, in particular the statistics of stimulus intensities for classes to which a neuron is sensitive. More generally, our work paves the way toward new classification algorithms that are robust to intensity variations.},
author = {Monk, Travis and Savin, Cristina and Lücke, Jörg},
location = {Barcelona, Spaine},
pages = {4285 -- 4293},
publisher = {Neural Information Processing Systems},
title = {{Neurons equipped with intrinsic plasticity learn stimulus intensity statistics}},
volume = {29},
year = {2016},
}
@phdthesis{1130,
abstract = {In this thesis we present a computer-aided programming approach to concurrency. Our approach
helps the programmer by automatically fixing concurrency-related bugs, i.e. bugs that occur
when the program is executed using an aggressive preemptive scheduler, but not when using a
non-preemptive (cooperative) scheduler. Bugs are program behaviours that are incorrect w.r.t.
a specification. We consider both user-provided explicit specifications in the form of assertion
statements in the code as well as an implicit specification. The implicit specification is inferred
from the non-preemptive behaviour. Let us consider sequences of calls that the program makes
to an external interface. The implicit specification requires that any such sequence produced
under a preemptive scheduler should be included in the set of sequences produced under a
non-preemptive scheduler.
We consider several semantics-preserving fixes that go beyond atomic sections typically
explored in the synchronisation synthesis literature. Our synthesis is able to place locks, barriers
and wait-signal statements and last, but not least reorder independent statements. The latter
may be useful if a thread is released to early, e.g., before some initialisation is completed. We
guarantee that our synthesis does not introduce deadlocks and that the synchronisation inserted
is optimal w.r.t. a given objective function.
We dub our solution trace-based synchronisation synthesis and it is loosely based on
counterexample-guided inductive synthesis (CEGIS). The synthesis works by discovering a
trace that is incorrect w.r.t. the specification and identifying ordering constraints crucial to trigger
the specification violation. Synchronisation may be placed immediately (greedy approach) or
delayed until all incorrect traces are found (non-greedy approach). For the non-greedy approach
we construct a set of global constraints over synchronisation placements. Each model of the
global constraints set corresponds to a correctness-ensuring synchronisation placement. The
placement that is optimal w.r.t. the given objective function is chosen as the synchronisation
solution.
We evaluate our approach on a number of realistic (albeit simplified) Linux device-driver
benchmarks. The benchmarks are versions of the drivers with known concurrency-related bugs.
For the experiments with an explicit specification we added assertions that would detect the bugs
in the experiments. Device drivers lend themselves to implicit specification, where the device and
the operating system are the external interfaces. Our experiments demonstrate that our synthesis
method is precise and efficient. We implemented objective functions for coarse-grained and
fine-grained locking and observed that different synchronisation placements are produced for
our experiments, favouring e.g. a minimal number of synchronisation operations or maximum
concurrency.},
author = {Tarrach, Thorsten},
pages = {151},
publisher = {IST Austria},
title = {{Automatic synthesis of synchronisation primitives for concurrent programs}},
year = {2016},
}
@article{1432,
abstract = {CA3–CA3 recurrent excitatory synapses are thought to play a key role in memory storage and pattern completion. Whether the plasticity properties of these synapses are consistent with their proposed network functions remains unclear. Here, we examine the properties of spike timing-dependent plasticity (STDP) at CA3–CA3 synapses. Low-frequency pairing of excitatory postsynaptic potentials (EPSPs) and action potentials (APs) induces long-term potentiation (LTP), independent of temporal order. The STDP curve is symmetric and broad (half-width ~150 ms). Consistent with these STDP induction properties, AP–EPSP sequences lead to supralinear summation of spine [Ca2+] transients. Furthermore, afterdepolarizations (ADPs) following APs efficiently propagate into dendrites of CA3 pyramidal neurons, and EPSPs summate with dendritic ADPs. In autoassociative network models, storage and recall are more robust with symmetric than with asymmetric STDP rules. Thus, a specialized STDP induction rule allows reliable storage and recall of information in the hippocampal CA3 network.},
author = {Mishra, Rajiv Kumar and Kim, Sooyun and Guzmán, José and Jonas, Peter M},
journal = {Nature Communications},
publisher = {Nature Publishing Group},
title = {{Symmetric spike timing-dependent plasticity at CA3–CA3 synapses optimizes storage and recall in autoassociative networks}},
doi = {10.1038/ncomms11552},
volume = {7},
year = {2016},
}
@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{1129,
abstract = {Directed cell migration is a hallmark feature, present in almost all multi-cellular
organisms. Despite its importance, basic questions regarding force transduction
or directional sensing are still heavily investigated. Directed migration of cells
guided by immobilized guidance cues - haptotaxis - occurs in key-processes,
such as embryonic development and immunity (Middleton et al., 1997; Nguyen
et al., 2000; Thiery, 1984; Weber et al., 2013). Immobilized guidance cues
comprise adhesive ligands, such as collagen and fibronectin (Barczyk et al.,
2009), or chemokines - the main guidance cues for migratory leukocytes
(Middleton et al., 1997; Weber et al., 2013). While adhesive ligands serve as
attachment sites guiding cell migration (Carter, 1965), chemokines instruct
haptotactic migration by inducing adhesion to adhesive ligands and directional
guidance (Rot and Andrian, 2004; Schumann et al., 2010). Quantitative analysis
of the cellular response to immobilized guidance cues requires in vitro assays
that foster cell migration, offer accurate control of the immobilized cues on a
subcellular scale and in the ideal case closely reproduce in vivo conditions. The
exploration of haptotactic cell migration through design and employment of such
assays represents the main focus of this work.
Dendritic cells (DCs) are leukocytes, which after encountering danger
signals such as pathogens in peripheral organs instruct naïve T-cells and
consequently the adaptive immune response in the lymph node (Mellman and
Steinman, 2001). To reach the lymph node from the periphery, DCs follow
haptotactic gradients of the chemokine CCL21 towards lymphatic vessels
(Weber et al., 2013). Questions about how DCs interpret haptotactic CCL21
gradients have not yet been addressed. The main reason for this is the lack of
an assay that offers diverse haptotactic environments, hence allowing the study
of DC migration as a response to different signals of immobilized guidance cue.
In this work, we developed an in vitro assay that enables us to
quantitatively assess DC haptotaxis, by combining precisely controllable
chemokine photo-patterning with physically confining migration conditions. With this tool at hand, we studied the influence of CCL21 gradient properties and
concentration on DC haptotaxis. We found that haptotactic gradient sensing
depends on the absolute CCL21 concentration in combination with the local
steepness of the gradient. Our analysis suggests that the directionality of
migrating DCs is governed by the signal-to-noise ratio of CCL21 binding to its
receptor CCR7. Moreover, the haptotactic CCL21 gradient formed in vivo
provides an optimal shape for DCs to recognize haptotactic guidance cue.
By reconstitution of the CCL21 gradient in vitro we were also able to
study the influence of CCR7 signal termination on DC haptotaxis. To this end,
we used DCs lacking the G-protein coupled receptor kinase GRK6, which is
responsible for CCL21 induced CCR7 receptor phosphorylation and
desensitization (Zidar et al., 2009). We found that CCR7 desensitization by
GRK6 is crucial for maintenance of haptotactic CCL21 gradient sensing in vitro
and confirm those observations in vivo.
In the context of the organism, immobilized haptotactic guidance cues
often coincide and compete with soluble chemotactic guidance cues. During
wound healing, fibroblasts are exposed and influenced by adhesive cues and
soluble factors at the same time (Wu et al., 2012; Wynn, 2008). Similarly,
migrating DCs are exposed to both, soluble chemokines (CCL19 and truncated
CCL21) inducing chemotactic behavior as well as the immobilized CCL21. To
quantitatively assess these complex coinciding immobilized and soluble
guidance cues, we implemented our chemokine photo-patterning technique in a
microfluidic system allowing for chemotactic gradient generation. To validate
the assay, we observed DC migration in competing CCL19/CCL21
environments.
Adhesiveness guided haptotaxis has been studied intensively over the
last century. However, quantitative studies leading to conceptual models are
largely missing, again due to the lack of a precisely controllable in vitro assay. A
requirement for such an in vitro assay is that it must prevent any uncontrolled
cell adhesion. This can be accomplished by stable passivation of the surface. In
addition, controlled adhesion must be sustainable, quantifiable and dose
dependent in order to create homogenous gradients. Therefore, we developed a novel covalent photo-patterning technique satisfying all these needs. In
combination with a sustainable poly-vinyl alcohol (PVA) surface coating we
were able to generate gradients of adhesive cue to direct cell migration. This
approach allowed us to characterize the haptotactic migratory behavior of
zebrafish keratocytes in vitro. Furthermore, defined patterns of adhesive cue
allowed us to control for cell shape and growth on a subcellular scale.},
author = {Schwarz, Jan},
pages = {178},
publisher = {IST Austria},
title = {{Quantitative analysis of haptotactic cell migration}},
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{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{1131,
abstract = {Evolution of gene regulation is important for phenotypic evolution and diversity. Sequence-specific binding of regulatory proteins is one of the key regulatory mechanisms determining gene expression. Although there has been intense interest in evolution of regulatory binding sites in the last decades, a theoretical understanding is far from being complete. In this thesis, I aim at a better understanding of the evolution of transcriptional regulatory binding sequences by using biophysical and population genetic models.
In the first part of the thesis, I discuss how to formulate the evolutionary dynamics of binding se- quences in a single isolated binding site and in promoter/enhancer regions. I develop a theoretical framework bridging between a thermodynamical model for transcription and a mutation-selection-drift model for monomorphic populations. I mainly address the typical evolutionary rates, and how they de- pend on biophysical parameters (e.g. binding length and specificity) and population genetic parameters (e.g. population size and selection strength).
In the second part of the thesis, I analyse empirical data for a better evolutionary and biophysical understanding of sequence-specific binding of bacterial RNA polymerase. First, I infer selection on regulatory and non-regulatory binding sites of RNA polymerase in the E. coli K12 genome. Second, I infer the chemical potential of RNA polymerase, an important but unknown physical parameter defining the threshold energy for strong binding. Furthermore, I try to understand the relation between the lac promoter sequence diversity and the LacZ activity variation among 20 bacterial isolates by constructing a simple but biophysically motivated gene expression model. Lastly, I lay out a statistical framework to predict adaptive point mutations in de novo promoter evolution in a selection experiment.},
author = {Tugrul, Murat},
pages = {89},
publisher = {IST Austria},
title = {{Evolution of transcriptional regulatory sequences}},
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{1124,
author = {Morri, Maurizio},
pages = {129},
publisher = {IST Austria},
title = {{Optical functionalization of human class A orphan G-protein coupled receptors}},
year = {2016},
}
@article{1183,
abstract = {Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.},
author = {Tarlungeanu, Dora-Clara and Deliu, Elena and Dotter, Christoph and Kara, Majdi and Janiesch, Philipp and Scalise, Mariafrancesca and Galluccio, Michele and Tesulov, Mateja and Morelli, Emanuela and Sönmez, Fatma and Bilgüvar, Kaya and Ohgaki, Ryuichi and Kanai, Yoshikatsu and Johansen, Anide and Esharif, Seham and Ben Omran, Tawfeg and Topcu, Meral and Schlessinger, Avner and Indiveri, Cesare and Duncan, Kent and Caglayan, Ahmet and Günel, Murat and Gleeson, Joseph and Novarino, Gaia},
journal = {Cell},
number = {6},
pages = {1481 -- 1494},
publisher = {Cell Press},
title = {{Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder}},
doi = {10.1016/j.cell.2016.11.013},
volume = {167},
year = {2016},
}
@article{1321,
abstract = {Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion.},
author = {Leithner, Alexander F and Eichner, Alexander and Müller, Jan and Reversat, Anne and Brown, Markus and Schwarz, Jan and Merrin, Jack and De Gorter, David and Schur, Florian and Bayerl, Jonathan and De Vries, Ingrid and Wieser, Stefan and Hauschild, Robert and Lai, Frank and Moser, Markus and Kerjaschki, Dontscho and Rottner, Klemens and Small, Victor and Stradal, Theresia and Sixt, Michael K},
journal = {Nature Cell Biology},
pages = {1253 -- 1259},
publisher = {Nature Publishing Group},
title = {{Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes}},
doi = {10.1038/ncb3426},
volume = {18},
year = {2016},
}
@article{1100,
abstract = {During metazoan development, the temporal pattern of morphogen signaling is critical for organizing cell fates in space and time. Yet, tools for temporally controlling morphogen signaling within the embryo are still scarce. Here, we developed a photoactivatable Nodal receptor to determine how the temporal pattern of Nodal signaling affects cell fate specification during zebrafish gastrulation. By using this receptor to manipulate the duration of Nodal signaling in vivo by light, we show that extended Nodal signaling within the organizer promotes prechordal plate specification and suppresses endoderm differentiation. Endoderm differentiation is suppressed by extended Nodal signaling inducing expression of the transcriptional repressor goosecoid (gsc) in prechordal plate progenitors, which in turn restrains Nodal signaling from upregulating the endoderm differentiation gene sox17 within these cells. Thus, optogenetic manipulation of Nodal signaling identifies a critical role of Nodal signaling duration for organizer cell fate specification during gastrulation.},
author = {Sako, Keisuke and Pradhan, Saurabh and Barone, Vanessa and Inglés Prieto, Álvaro and Mueller, Patrick and Ruprecht, Verena and Capek, Daniel and Galande, Sanjeev and Janovjak, Harald L and Heisenberg, Carl-Philipp J},
journal = {Cell Reports},
number = {3},
pages = {866 -- 877},
publisher = {Cell Press},
title = {{Optogenetic control of nodal signaling reveals a temporal pattern of nodal signaling regulating cell fate specification during gastrulation}},
doi = {10.1016/j.celrep.2016.06.036},
volume = {16},
year = {2016},
}
@inproceedings{1437,
abstract = {We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural problems that arise in program analysis. We consider that each component of the concurrent system is a graph with constant treewidth, a property satisfied by the controlflow graphs of most programs. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis. The study of multiple queries allows us to consider the tradeoff between the resource usage of the one-time preprocessing and for each individual query. The traditional approach constructs the product graph of all components and applies the best-known graph algorithm on the product. In this approach, even the answer to a single query requires the transitive closure (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time. Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time, each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results showing that the worst-case running time of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (i.e., improving the worst-case bound for the shortest path problem in general graphs). Preliminary experimental results show that our algorithms perform favorably on several benchmarks.},
author = {Chatterjee, Krishnendu and Goharshady, Amir and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas},
location = {St. Petersburg, FL, USA},
pages = {733 -- 747},
publisher = {ACM},
title = {{Algorithms for algebraic path properties in concurrent systems of constant treewidth components}},
doi = {10.1145/2837614.2837624},
volume = {20-22},
year = {2016},
}
@inproceedings{1386,
abstract = {We consider nondeterministic probabilistic programs with the most basic liveness property of termination. We present efficient methods for termination analysis of nondeterministic probabilistic programs with polynomial guards and assignments. Our approach is through synthesis of polynomial ranking supermartingales, that on one hand significantly generalizes linear ranking supermartingales and on the other hand is a counterpart of polynomial ranking-functions for proving termination of nonprobabilistic programs. The approach synthesizes polynomial ranking-supermartingales through Positivstellensatz's, yielding an efficient method which is not only sound, but also semi-complete over a large subclass of programs. We show experimental results to demonstrate that our approach can handle several classical programs with complex polynomial guards and assignments, and can synthesize efficient quadratic ranking-supermartingales when a linear one does not exist even for simple affine programs.},
author = {Chatterjee, Krishnendu and Fu, Hongfei and Goharshady, Amir},
location = {Toronto, Canada},
pages = {3 -- 22},
publisher = {Springer},
title = {{Termination analysis of probabilistic programs through Positivstellensatz's}},
doi = {10.1007/978-3-319-41528-4_1},
volume = {9779},
year = {2016},
}
@article{2271,
abstract = {A class of valued constraint satisfaction problems (VCSPs) is characterised by a valued constraint language, a fixed set of cost functions on a finite domain. Finite-valued constraint languages contain functions that take on rational costs and general-valued constraint languages contain functions that take on rational or infinite costs. An instance of the problem is specified by a sum of functions from the language with the goal to minimise the sum. This framework includes and generalises well-studied constraint satisfaction problems (CSPs) and maximum constraint satisfaction problems (Max-CSPs).
Our main result is a precise algebraic characterisation of valued constraint languages whose instances can be solved exactly by the basic linear programming relaxation (BLP). For a general-valued constraint language Γ, BLP is a decision procedure for Γ if and only if Γ admits a symmetric fractional polymorphism of every arity. For a finite-valued constraint language Γ, BLP is a decision procedure if and only if Γ admits a symmetric fractional polymorphism of some arity, or equivalently, if Γ admits a symmetric fractional polymorphism of arity 2.
Using these results, we obtain tractability of several novel and previously widely-open classes of VCSPs, including problems over valued constraint languages that are: (1) submodular on arbitrary lattices; (2) bisubmodular (also known as k-submodular) on arbitrary finite domains; (3) weakly (and hence strongly) tree-submodular on arbitrary trees. },
author = {Kolmogorov, Vladimir and Thapper, Johan and Živný, Stanislav},
journal = {SIAM Journal on Computing},
number = {1},
pages = {1 -- 36},
publisher = {SIAM},
title = {{The power of linear programming for general-valued CSPs}},
doi = {10.1137/130945648},
volume = {44},
year = {2015},
}
@article{802,
abstract = {Glycoinositolphosphoceramides (GIPCs) are complex sphingolipids present at the plasma membrane of various eukaryotes with the important exception of mammals. In fungi, these glycosphingolipids commonly contain an alpha-mannose residue (Man) linked at position 2 of the inositol. However, several pathogenic fungi additionally synthesize zwitterionic GIPCs carrying an alpha-glucosamine residue (GlcN) at this position. In the human pathogen Aspergillus fumigatus, the GlcNalpha1,2IPC core (where IPC is inositolphosphoceramide) is elongated to Manalpha1,3Manalpha1,6GlcNalpha1,2IPC, which is the most abundant GIPC synthesized by this fungus. In this study, we identified an A. fumigatus N-acetylglucosaminyltransferase, named GntA, and demonstrate its involvement in the initiation of zwitterionic GIPC biosynthesis. Targeted deletion of the gene encoding GntA in A. fumigatus resulted in complete absence of zwitterionic GIPC; a phenotype that could be reverted by episomal expression of GntA in the mutant. The N-acetylhexosaminyltransferase activity of GntA was substantiated by production of N-acetylhexosamine-IPC in the yeast Saccharomyces cerevisiae upon GntA expression. Using an in vitro assay, GntA was furthermore shown to use UDP-N-acetylglucosamine as donor substrate to generate a glycolipid product resistant to saponification and to digestion by phosphatidylinositol-phospholipase C as expected for GlcNAcalpha1,2IPC. Finally, as the enzymes involved in mannosylation of IPC, GntA was localized to the Golgi apparatus, the site of IPC synthesis.},
author = {Engel, Jakob and Schmalhorst, Philipp S and Kruger, Anke and Muller, Christina and Buettner, Falk and Routier, Françoise},
journal = {Glycobiology},
number = {12},
pages = {1423 -- 1430},
publisher = {Oxford University Press},
title = {{Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis}},
doi = {10.1093/glycob/cwv059},
volume = {25},
year = {2015},
}
@article{1686,
author = {Kiermaier, Eva and Sixt, Michael K},
journal = {Science},
number = {6252},
pages = {1055 -- 1056},
publisher = {American Association for the Advancement of Science},
title = {{Fragmented communication between immune cells: Neutrophils blaze a trail with migratory cues for T cells to follow to sites of infection}},
doi = {10.1126/science.aad0867},
volume = {349},
year = {2015},
}
@article{1687,
abstract = {Guided cell movement is essential for development and integrity of animals and crucially involved in cellular immune responses. Leukocytes are professional migratory cells that can navigate through most types of tissues and sense a wide range of directional cues. The responses of these cells to attractants have been mainly explored in tissue culture settings. How leukocytes make directional decisions in situ, within the challenging environment of a tissue maze, is less understood. Here we review recent advances in how leukocytes sense chemical cues in complex tissue settings and make links with paradigms of directed migration in development and Dictyostelium discoideum amoebae.},
author = {Sarris, Milka and Sixt, Michael K},
journal = {Current Opinion in Cell Biology},
number = {10},
pages = {93 -- 102},
publisher = {Elsevier},
title = {{Navigating in tissue mazes: Chemoattractant interpretation in complex environments}},
doi = {10.1016/j.ceb.2015.08.001},
volume = {36},
year = {2015},
}
@article{1688,
abstract = {We estimate the selection constant in the following geometric selection theorem by Pach: For every positive integer d, there is a constant (Formula presented.) such that whenever (Formula presented.) are n-element subsets of (Formula presented.), we can find a point (Formula presented.) and subsets (Formula presented.) for every i∈[d+1], each of size at least cdn, such that p belongs to all rainbowd-simplices determined by (Formula presented.) simplices with one vertex in each Yi. We show a super-exponentially decreasing upper bound (Formula presented.). The ideas used in the proof of the upper bound also help us to prove Pach’s theorem with (Formula presented.), which is a lower bound doubly exponentially decreasing in d (up to some polynomial in the exponent). For comparison, Pach’s original approach yields a triply exponentially decreasing lower bound. On the other hand, Fox, Pach, and Suk recently obtained a hypergraph density result implying a proof of Pach’s theorem with (Formula presented.). In our construction for the upper bound, we use the fact that the minimum solid angle of every d-simplex is super-exponentially small. This fact was previously unknown and might be of independent interest. For the lower bound, we improve the ‘separation’ part of the argument by showing that in one of the key steps only d+1 separations are necessary, compared to 2d separations in the original proof. We also provide a measure version of Pach’s theorem.},
author = {Karasev, Roman and Kynčl, Jan and Paták, Pavel and Patakova, Zuzana and Tancer, Martin},
journal = {Discrete & Computational Geometry},
number = {3},
pages = {610 -- 636},
publisher = {Springer},
title = {{Bounds for Pach's selection theorem and for the minimum solid angle in a simplex}},
doi = {10.1007/s00454-015-9720-z},
volume = {54},
year = {2015},
}
@inproceedings{1689,
abstract = {We consider the problem of computing the set of initial states of a dynamical system such that there exists a control strategy to ensure that the trajectories satisfy a temporal logic specification with probability 1 (almost-surely). We focus on discrete-time, stochastic linear dynamics and specifications given as formulas of the Generalized Reactivity(1) fragment of Linear Temporal Logic over linear predicates in the states of the system. We propose a solution based on iterative abstraction-refinement, and turn-based 2-player probabilistic games. While the theoretical guarantee of our algorithm after any finite number of iterations is only a partial solution, we show that if our algorithm terminates, then the result is the set of satisfying initial states. Moreover, for any (partial) solution our algorithm synthesizes witness control strategies to ensure almost-sure satisfaction of the temporal logic specification. We demonstrate our approach on an illustrative case study.},
author = {Svoreňová, Mária and Kretinsky, Jan and Chmelik, Martin and Chatterjee, Krishnendu and Cěrná, Ivana and Belta, Cǎlin},
booktitle = {Proceedings of the 18th International Conference on Hybrid Systems: Computation and Control},
location = {Seattle, WA, United States},
pages = {259 -- 268},
publisher = {ACM},
title = {{Temporal logic control for stochastic linear systems using abstraction refinement of probabilistic games}},
doi = {10.1145/2728606.2728608},
year = {2015},
}
@inproceedings{1690,
abstract = {A number of powerful and scalable hybrid systems model checkers have recently emerged. Although all of them honor roughly the same hybrid systems semantics, they have drastically different model description languages. This situation (a) makes it difficult to quickly evaluate a specific hybrid automaton model using the different tools, (b) obstructs comparisons of reachability approaches, and (c) impedes the widespread application of research results that perform model modification and could benefit many of the tools. In this paper, we present Hyst, a Hybrid Source Transformer. Hyst is a source-to-source translation tool, currently taking input in the SpaceEx model format, and translating to the formats of HyCreate, Flow∗, or dReach. Internally, the tool supports generic model-to-model transformation passes that serve to both ease the translation and potentially improve reachability results for the supported tools. Although these model transformation passes could be implemented within each tool, the Hyst approach provides a single place for model modification, generating modified input sources for the unmodified target tools. Our evaluation demonstrates Hyst is capable of automatically translating benchmarks in several classes (including affine and nonlinear hybrid automata) to the input formats of several tools. Additionally, we illustrate a general model transformation pass based on pseudo-invariants implemented in Hyst that illustrates the reachability improvement.},
author = {Bak, Stanley and Bogomolov, Sergiy and Johnson, Taylor},
location = {Seattle, WA, United States},
pages = {128 -- 133},
publisher = {Springer},
title = {{HYST: A source transformation and translation tool for hybrid automaton models}},
doi = {10.1145/2728606.2728630},
year = {2015},
}
@inproceedings{1691,
abstract = {We consider a case study of the problem of deploying an autonomous air vehicle in a partially observable, dynamic, indoor environment from a specification given as a linear temporal logic (LTL) formula over regions of interest. We model the motion and sensing capabilities of the vehicle as a partially observable Markov decision process (POMDP). We adapt recent results for solving POMDPs with parity objectives to generate a control policy. We also extend the existing framework with a policy minimization technique to obtain a better implementable policy, while preserving its correctness. The proposed techniques are illustrated in an experimental setup involving an autonomous quadrotor performing surveillance in a dynamic environment.},
author = {Svoreňová, Mária and Chmelik, Martin and Leahy, Kevin and Eniser, Hasan and Chatterjee, Krishnendu and Cěrná, Ivana and Belta, Cǎlin},
booktitle = {Proceedings of the 18th International Conference on Hybrid Systems: Computation and Control},
location = {Seattle, WA, United States},
pages = {233 -- 238},
publisher = {ACM},
title = {{Temporal logic motion planning using POMDPs with parity objectives: Case study paper}},
doi = {10.1145/2728606.2728617},
year = {2015},
}
@inproceedings{1692,
abstract = {Computing an approximation of the reachable states of a hybrid system is a challenge, mainly because overapproximating the solutions of ODEs with a finite number of sets does not scale well. Using template polyhedra can greatly reduce the computational complexity, since it replaces complex operations on sets with a small number of optimization problems. However, the use of templates may make the over-approximation too conservative. Spurious transitions, which are falsely considered reachable, are particularly detrimental to performance and accuracy, and may exacerbate the state explosion problem. In this paper, we examine how spurious transitions can be avoided with minimal computational effort. To this end, detecting spurious transitions is reduced to the well-known problem of showing that two convex sets are disjoint by finding a hyperplane that separates them. We generalize this to owpipes by considering hyperplanes that evolve with time in correspondence to the dynamics of the system. The approach is implemented in the model checker SpaceEx and demonstrated on examples.},
author = {Frehse, Goran and Bogomolov, Sergiy and Greitschus, Marius and Strump, Thomas and Podelski, Andreas},
booktitle = {Proceedings of the 18th International Conference on Hybrid Systems: Computation and Control},
isbn = {978-1-4503-3433-4},
location = {Seattle, WA, United States},
pages = {149 -- 158},
publisher = {ACM},
title = {{Eliminating spurious transitions in reachability with support functions}},
doi = {10.1145/2728606.2728622},
year = {2015},
}
@article{1693,
abstract = {Quantum interference between energetically close states is theoretically investigated, with the state structure being observed via laser spectroscopy. In this work, we focus on hyperfine states of selected hydrogenic muonic isotopes, and on how quantum interference affects the measured Lamb shift. The process of photon excitation and subsequent photon decay is implemented within the framework of nonrelativistic second-order perturbation theory. Due to its experimental interest, calculations are performed for muonic hydrogen, deuterium, and helium-3. We restrict our analysis to the case of photon scattering by incident linear polarized photons and the polarization of the scattered photons not being observed. We conclude that while quantum interference effects can be safely neglected in muonic hydrogen and helium-3, in the case of muonic deuterium there are resonances with close proximity, where quantum interference effects can induce shifts up to a few percent of the linewidth, assuming a pointlike detector. However, by taking into account the geometry of the setup used by the CREMA collaboration, this effect is reduced to less than 0.2% of the linewidth in all possible cases, which makes it irrelevant at the present level of accuracy. © 2015 American Physical Society.},
author = {Amaro, Pedro and Franke, Beatrice and Krauth, Julian and Diepold, Marc and Fratini, Filippo and Safari, Laleh and Machado, Jorge and Antognini, Aldo and Kottmann, Franz and Indelicato, Paul and Pohl, Randolf and Santos, José},
journal = {Physical Review A},
number = {2},
publisher = {American Physical Society},
title = {{Quantum interference effects in laser spectroscopy of muonic hydrogen, deuterium, and helium-3}},
doi = {10.1103/PhysRevA.92.022514},
volume = {92},
year = {2015},
}
@article{1694,
abstract = {
We introduce quantitative timed refinement and timed simulation (directed) metrics, incorporating zenoness checks, for timed systems. These metrics assign positive real numbers which quantify the timing mismatches between two timed systems, amongst non-zeno runs. We quantify timing mismatches in three ways: (1) the maximal timing mismatch that can arise, (2) the “steady-state” maximal timing mismatches, where initial transient timing mismatches are ignored; and (3) the (long-run) average timing mismatches amongst two systems. These three kinds of mismatches constitute three important types of timing differences. Our event times are the global times, measured from the start of the system execution, not just the time durations of individual steps. We present algorithms over timed automata for computing the three quantitative simulation distances to within any desired degree of accuracy. In order to compute the values of the quantitative simulation distances, we use a game theoretic formulation. We introduce two new kinds of objectives for two player games on finite-state game graphs: (1) eventual debit-sum level objectives, and (2) average debit-sum level objectives. We present algorithms for computing the optimal values for these objectives in graph games, and then use these algorithms to compute the values of the timed simulation distances over timed automata.
},
author = {Chatterjee, Krishnendu and Prabhu, Vinayak},
journal = {IEEE Transactions on Automatic Control},
number = {9},
pages = {2291 -- 2306},
publisher = {IEEE},
title = {{Quantitative temporal simulation and refinement distances for timed systems}},
doi = {10.1109/TAC.2015.2404612},
volume = {60},
year = {2015},
}
@article{1695,
abstract = {We give a comprehensive introduction into a diagrammatic method that allows for the evaluation of Gutzwiller wave functions in finite spatial dimensions. We discuss in detail some numerical schemes that turned out to be useful in the real-space evaluation of the diagrams. The method is applied to the problem of d-wave superconductivity in a two-dimensional single-band Hubbard model. Here, we discuss in particular the role of long-range contributions in our diagrammatic expansion. We further reconsider our previous analysis on the kinetic energy gain in the superconducting state.},
author = {Kaczmarczyk, Jan and Schickling, Tobias and Bünemann, Jörg},
journal = {Physica Status Solidi (B): Basic Solid State Physics},
number = {9},
pages = {2059 -- 2071},
publisher = {Wiley},
title = {{Evaluation techniques for Gutzwiller wave functions in finite dimensions}},
doi = {10.1002/pssb.201552082},
volume = {252},
year = {2015},
}
@article{1696,
abstract = {The recently proposed diagrammatic expansion (DE) technique for the full Gutzwiller wave function (GWF) is applied to the Anderson lattice model. This approach allows for a systematic evaluation of the expectation values with full Gutzwiller wave function in finite-dimensional systems. It introduces results extending in an essential manner those obtained by means of the standard Gutzwiller approximation (GA), which is variationally exact only in infinite dimensions. Within the DE-GWF approach we discuss the principal paramagnetic properties and their relevance to heavy-fermion systems. We demonstrate the formation of an effective, narrow f band originating from atomic f-electron states and subsequently interpret this behavior as a direct itineracy of f electrons; it represents a combined effect of both the hybridization and the correlations induced by the Coulomb repulsive interaction. Such a feature is absent on the level of GA, which is equivalent to the zeroth order of our expansion. Formation of the hybridization- and electron-concentration-dependent narrow f band rationalizes the common assumption of such dispersion of f levels in the phenomenological modeling of the band structure of CeCoIn5. Moreover, it is shown that the emerging f-electron direct itineracy leads in a natural manner to three physically distinct regimes within a single model that are frequently discussed for 4f- or 5f-electron compounds as separate model situations. We identify these regimes as (i) the mixed-valence regime, (ii) Kondo/almost-Kondo insulating regime, and (iii) the Kondo-lattice limit when the f-electron occupancy is very close to the f-state half filling, ⟨nˆf⟩→1. The nonstandard features of the emerging correlated quantum liquid state are stressed.},
author = {Wysokiński, Marcin and Kaczmarczyk, Jan and Spałek, Jozef},
journal = {Physical Review B},
number = {12},
publisher = {American Physical Society},
title = {{Gutzwiller wave function solution for Anderson lattice model: Emerging universal regimes of heavy quasiparticle states}},
doi = {10.1103/PhysRevB.92.125135},
volume = {92},
year = {2015},
}
@article{1697,
abstract = {Motion tracking is a challenge the visual system has to solve by reading out the retinal population. It is still unclear how the information from different neurons can be combined together to estimate the position of an object. Here we recorded a large population of ganglion cells in a dense patch of salamander and guinea pig retinas while displaying a bar moving diffusively. We show that the bar’s position can be reconstructed from retinal activity with a precision in the hyperacuity regime using a linear decoder acting on 100+ cells. We then took advantage of this unprecedented precision to explore the spatial structure of the retina’s population code. The classical view would have suggested that the firing rates of the cells form a moving hill of activity tracking the bar’s position. Instead, we found that most ganglion cells in the salamander fired sparsely and idiosyncratically, so that their neural image did not track the bar. Furthermore, ganglion cell activity spanned an area much larger than predicted by their receptive fields, with cells coding for motion far in their surround. As a result, population redundancy was high, and we could find multiple, disjoint subsets of neurons that encoded the trajectory with high precision. This organization allows for diverse collections of ganglion cells to represent high-accuracy motion information in a form easily read out by downstream neural circuits.},
author = {Marre, Olivier and Botella Soler, Vicente and Simmons, Kristina and Mora, Thierry and Tkacik, Gasper and Berry, Michael},
journal = {PLoS Computational Biology},
number = {7},
publisher = {Public Library of Science},
title = {{High accuracy decoding of dynamical motion from a large retinal population}},
doi = {10.1371/journal.pcbi.1004304},
volume = {11},
year = {2015},
}
@article{1698,
abstract = {In mean-payoff games, the objective of the protagonist is to ensure that the limit average of an infinite sequence of numeric weights is nonnegative. In energy games, the objective is to ensure that the running sum of weights is always nonnegative. Multi-mean-payoff and multi-energy games replace individual weights by tuples, and the limit average (resp., running sum) of each coordinate must be (resp., remain) nonnegative. We prove finite-memory determinacy of multi-energy games and show inter-reducibility of multi-mean-payoff and multi-energy games for finite-memory strategies. We improve the computational complexity for solving both classes with finite-memory strategies: we prove coNP-completeness improving the previous known EXPSPACE bound. For memoryless strategies, we show that deciding the existence of a winning strategy for the protagonist is NP-complete. We present the first solution of multi-mean-payoff games with infinite-memory strategies: we show that mean-payoff-sup objectives can be decided in NP∩coNP, whereas mean-payoff-inf objectives are coNP-complete.},
author = {Velner, Yaron and Chatterjee, Krishnendu and Doyen, Laurent and Henzinger, Thomas A and Rabinovich, Alexander and Raskin, Jean},
journal = {Information and Computation},
number = {4},
pages = {177 -- 196},
publisher = {Elsevier},
title = {{The complexity of multi-mean-payoff and multi-energy games}},
doi = {10.1016/j.ic.2015.03.001},
volume = {241},
year = {2015},
}
@article{1699,
abstract = {By hybridization and backcrossing, alleles can surmount species boundaries and be incorporated into the genome of a related species. This introgression of genes is of particular evolutionary relevance if it involves the transfer of adaptations between populations. However, any beneficial allele will typically be associated with other alien alleles that are often deleterious and hamper the introgression process. In order to describe the introgression of an adaptive allele, we set up a stochastic model with an explicit genetic makeup of linked and unlinked deleterious alleles. Based on the theory of reducible multitype branching processes, we derive a recursive expression for the establishment probability of the beneficial allele after a single hybridization event. We furthermore study the probability that slightly deleterious alleles hitchhike to fixation. The key to the analysis is a split of the process into a stochastic phase in which the advantageous alleles establishes and a deterministic phase in which it sweeps to fixation. We thereafter apply the theory to a set of biologically relevant scenarios such as introgression in the presence of many unlinked or few closely linked deleterious alleles. A comparison to computer simulations shows that the approximations work well over a large parameter range.},
author = {Uecker, Hildegard and Setter, Derek and Hermisson, Joachim},
journal = {Journal of Mathematical Biology},
number = {7},
pages = {1523 -- 1580},
publisher = {Springer},
title = {{Adaptive gene introgression after secondary contact}},
doi = {10.1007/s00285-014-0802-y},
volume = {70},
year = {2015},
}
@article{1700,
abstract = {We use the dual boson approach to reveal the phase diagram of the Fermi-Hubbard model with long-range dipole-dipole interactions. By using a large-scale finite-temperature calculation on a 64×64 square lattice we demonstrate the existence of a novel phase, possessing an "ultralong-range" order. The fingerprint of this phase - the density correlation function - features a nontrivial behavior on a scale of tens of lattice sites. We study the properties and the stability of the ultralong-range-ordered phase, and show that it is accessible in modern experiments with ultracold polar molecules and magnetic atoms.},
author = {Van Loon, Erik and Katsnelson, Mikhail and Lemeshko, Mikhail},
journal = {Physical Review B},
number = {8},
publisher = {American Physical Society},
title = {{Ultralong-range order in the Fermi-Hubbard model with long-range interactions}},
doi = {10.1103/PhysRevB.92.081106},
volume = {92},
year = {2015},
}
@article{1701,
abstract = {The activity of a neural network is defined by patterns of spiking and silence from the individual neurons. Because spikes are (relatively) sparse, patterns of activity with increasing numbers of spikes are less probable, but, with more spikes, the number of possible patterns increases. This tradeoff between probability and numerosity is mathematically equivalent to the relationship between entropy and energy in statistical physics. We construct this relationship for populations of up to N = 160 neurons in a small patch of the vertebrate retina, using a combination of direct and model-based analyses of experiments on the response of this network to naturalistic movies. We see signs of a thermodynamic limit, where the entropy per neuron approaches a smooth function of the energy per neuron as N increases. The form of this function corresponds to the distribution of activity being poised near an unusual kind of critical point. We suggest further tests of criticality, and give a brief discussion of its functional significance. },
author = {Tkacik, Gasper and Mora, Thierry and Marre, Olivier and Amodei, Dario and Palmer, Stephanie and Berry Ii, Michael and Bialek, William},
journal = {PNAS},
number = {37},
pages = {11508 -- 11513},
publisher = {National Academy of Sciences},
title = {{Thermodynamics and signatures of criticality in a network of neurons}},
doi = {10.1073/pnas.1514188112},
volume = {112},
year = {2015},
}
@article{1703,
abstract = {Vegetation clearing and land-use change have depleted many natural plant communities to the point where restoration is required. A major impediment to the success of rebuilding complex vegetation communities is having regular access to sufficient quantities of high-quality seed. Seed-production areas (SPAs) can help generate this seed, but these must be underpinned by a broad genetic base to maximise the evolutionary potential of restored populations. However, genetic bottlenecks can occur at the collection, establishment and production stages in SPAs, requiring genetic evaluation. This is especially relevant for species that may take many years before a return on SPA investment is realised. Two recently established yellow box (Eucalyptus melliodora A.Cunn. ex Schauer, Myrtaceae) SPAs were evaluated to determine whether genetic bottlenecks had occurred between seed collection and SPA establishment. No evidence was found to suggest that a significant loss of genetic diversity had occurred at this stage, although there was a significant difference in diversity between the two SPAs. Complex population genetic structure was also observed in the seed used to source the SPAs, with up to eight groups identified. Plant survival in the SPAs was influenced by seed collection location but not by SPA location and was not associated with genetic diversity. There were also no associations between genetic diversity and plant growth. These data highlighted the importance of chance events when establishing SPAs and indicated that the two yellow box SPAs are likely to provide genetically diverse seed sources for future restoration projects, especially by pooling seed from both SPAs.},
author = {Broadhurst, Linda and Fifield, Graham and Vanzella, Bindi and Pickup, Melinda},
journal = {Australian Journal of Botany},
number = {5},
pages = {455 -- 466},
publisher = {CSIRO},
title = {{An evaluation of the genetic structure of seed sources and the maintenance of genetic diversity during establishment of two yellow box (Eucalyptus melliodora) seed-production areas}},
doi = {10.1071/BT15023},
volume = {63},
year = {2015},
}
@article{1704,
abstract = {Given a convex function (Formula presented.) and two hermitian matrices A and B, Lewin and Sabin study in (Lett Math Phys 104:691–705, 2014) the relative entropy defined by (Formula presented.). Among other things, they prove that the so-defined quantity is monotone if and only if (Formula presented.) is operator monotone. The monotonicity is then used to properly define (Formula presented.) for bounded self-adjoint operators acting on an infinite-dimensional Hilbert space by a limiting procedure. More precisely, for an increasing sequence of finite-dimensional projections (Formula presented.) with (Formula presented.) strongly, the limit (Formula presented.) is shown to exist and to be independent of the sequence of projections (Formula presented.). The question whether this sequence converges to its "obvious" limit, namely (Formula presented.), has been left open. We answer this question in principle affirmatively and show that (Formula presented.). If the operators A and B are regular enough, that is (A − B), (Formula presented.) and (Formula presented.) are trace-class, the identity (Formula presented.) holds.},
author = {Deuchert, Andreas and Hainzl, Christian and Seiringer, Robert},
journal = {Letters in Mathematical Physics},
number = {10},
pages = {1449 -- 1466},
publisher = {Springer},
title = {{Note on a family of monotone quantum relative entropies}},
doi = {10.1007/s11005-015-0787-5},
volume = {105},
year = {2015},
}
@inproceedings{1706,
abstract = {We consider a problem of learning kernels for use in SVM classification in the multi-task and lifelong scenarios and provide generalization bounds on the error of a large margin classifier. Our results show that, under mild conditions on the family of kernels used for learning, solving several related tasks simultaneously is beneficial over single task learning. In particular, as the number of observed tasks grows, assuming that in the considered family of kernels there exists one that yields low approximation error on all tasks, the overhead associated with learning such a kernel vanishes and the complexity converges to that of learning when this good kernel is given to the learner.},
author = {Pentina, Anastasia and Ben David, Shai},
location = {Banff, AB, Canada},
pages = {194 -- 208},
publisher = {Springer},
title = {{Multi-task and lifelong learning of kernels}},
doi = {10.1007/978-3-319-24486-0_13},
volume = {9355},
year = {2015},
}
@article{1709,
abstract = {The competition for resources among cells, individuals or species is a fundamental characteristic of evolution. Biological all-pay auctions have been used to model situations where multiple individuals compete for a single resource. However, in many situations multiple resources with various values exist and single reward auctions are not applicable. We generalize the model to multiple rewards and study the evolution of strategies. In biological all-pay auctions the bid of an individual corresponds to its strategy and is equivalent to its payment in the auction. The decreasingly ordered rewards are distributed according to the decreasingly ordered bids of the participating individuals. The reproductive success of an individual is proportional to its fitness given by the sum of the rewards won minus its payments. Hence, successful bidding strategies spread in the population. We find that the results for the multiple reward case are very different from the single reward case. While the mixed strategy equilibrium in the single reward case with more than two players consists of mostly low-bidding individuals, we show that the equilibrium can convert to many high-bidding individuals and a few low-bidding individuals in the multiple reward case. Some reward values lead to a specialization among the individuals where one subpopulation competes for the rewards and the other subpopulation largely avoids costly competitions. Whether the mixed strategy equilibrium is an evolutionarily stable strategy (ESS) depends on the specific values of the rewards.},
author = {Reiter, Johannes and Kanodia, Ayush and Gupta, Raghav and Nowak, Martin and Chatterjee, Krishnendu},
journal = {Proceedings of the Royal Society of London Series B Biological Sciences},
number = {1812},
publisher = {Royal Society},
title = {{Biological auctions with multiple rewards}},
doi = {10.1098/rspb.2015.1041},
volume = {282},
year = {2015},
}
@article{1710,
abstract = {We consider the hollow on the half-plane {(x, y) : y ≤ 0} ⊂ ℝ2 defined by a function u : (-1, 1) → ℝ, u(x) < 0, and a vertical flow of point particles incident on the hollow. It is assumed that u satisfies the so-called single impact condition (SIC): each incident particle is elastically reflected by graph(u) and goes away without hitting the graph of u anymore. We solve the problem: find the function u minimizing the force of resistance created by the flow. We show that the graph of the minimizer is formed by two arcs of parabolas symmetric to each other with respect to the y-axis. Assuming that the resistance of u ≡ 0 equals 1, we show that the minimal resistance equals π/2 - 2arctan(1/2) ≈ 0.6435. This result completes the previously obtained result [SIAM J. Math. Anal., 46 (2014), pp. 2730-2742] stating in particular that the minimal resistance of a hollow in higher dimensions equals 0.5. We additionally consider a similar problem of minimal resistance, where the hollow in the half-space {(x1,...,xd,y) : y ≤ 0} ⊂ ℝd+1 is defined by a radial function U satisfying the SIC, U(x) = u(|x|), with x = (x1,...,xd), u(ξ) < 0 for 0 ≤ ξ < 1, and u(ξ) = 0 for ξ ≥ 1, and the flow is parallel to the y-axis. The minimal resistance is greater than 0.5 (and coincides with 0.6435 when d = 1) and converges to 0.5 as d → ∞.},
author = {Akopyan, Arseniy and Plakhov, Alexander},
journal = {Society for Industrial and Applied Mathematics},
number = {4},
pages = {2754 -- 2769},
publisher = {SIAM},
title = {{Minimal resistance of curves under the single impact assumption}},
doi = {10.1137/140993843},
volume = {47},
year = {2015},
}
@article{1712,
abstract = {The majority of immune cells in Drosophila melanogaster are plasmatocytes; they carry out similar functions to vertebrate macrophages, influencing development as well as protecting against infection and cancer. Plasmatocytes, sometimes referred to with the broader term of hemocytes, migrate widely during embryonic development and cycle in the larvae between sessile and circulating positions. Here we discuss the similarities of plasmatocyte developmental migration and its functions to that of vertebrate macrophages, considering the recent controversy regarding the functions of Drosophila PDGF/VEGF related ligands. We also examine recent findings on the significance of adhesion for plasmatocyte migration in the embryo, as well as proliferation, trans-differentiation, and tumor responses in the larva. We spotlight parallels throughout to vertebrate immune responses.},
author = {Ratheesh, Aparna and Belyaeva, Vera and Siekhaus, Daria E},
journal = {Current Opinion in Cell Biology},
number = {10},
pages = {71 -- 79},
publisher = {Elsevier},
title = {{Drosophila immune cell migration and adhesion during embryonic development and larval immune responses}},
doi = {10.1016/j.ceb.2015.07.003},
volume = {36},
year = {2015},
}
@inproceedings{1714,
abstract = {We present a flexible framework for the automated competitive analysis of on-line scheduling algorithms for firm-deadline real-time tasks based on multi-objective graphs: Given a task set and an on-line scheduling algorithm specified as a labeled transition system, along with some optional safety, liveness, and/or limit-average constraints for the adversary, we automatically compute the competitive ratio of the algorithm w.r.t. A clairvoyant scheduler. We demonstrate the flexibility and power of our approach by comparing the competitive ratio of several on-line algorithms, including Dover, that have been proposed in the past, for various task sets. Our experimental results reveal that none of these algorithms is universally optimal, in the sense that there are task sets where other schedulers provide better performance. Our framework is hence a very useful design tool for selecting optimal algorithms for a given application.},
author = {Chatterjee, Krishnendu and Pavlogiannis, Andreas and Kößler, Alexander and Schmid, Ulrich},
booktitle = {Real-Time Systems Symposium},
location = {Rome, Italy},
number = {January},
pages = {118 -- 127},
publisher = {IEEE},
title = {{A framework for automated competitive analysis of on-line scheduling of firm-deadline tasks}},
doi = {10.1109/RTSS.2014.9},
volume = {2015},
year = {2015},
}
@article{1730,
abstract = {How much cutting is needed to simplify the topology of a surface? We provide bounds for several instances of this question, for the minimum length of topologically non-trivial closed curves, pants decompositions, and cut graphs with a given combinatorial map in triangulated combinatorial surfaces (or their dual cross-metric counterpart). Our work builds upon Riemannian systolic inequalities, which bound the minimum length of non-trivial closed curves in terms of the genus and the area of the surface. We first describe a systematic way to translate Riemannian systolic inequalities to a discrete setting, and vice-versa. This implies a conjecture by Przytycka and Przytycki (Graph structure theory. Contemporary Mathematics, vol. 147, 1993), a number of new systolic inequalities in the discrete setting, and the fact that a theorem of Hutchinson on the edge-width of triangulated surfaces and Gromov’s systolic inequality for surfaces are essentially equivalent. We also discuss how these proofs generalize to higher dimensions. Then we focus on topological decompositions of surfaces. Relying on ideas of Buser, we prove the existence of pants decompositions of length O(g^(3/2)n^(1/2)) for any triangulated combinatorial surface of genus g with n triangles, and describe an O(gn)-time algorithm to compute such a decomposition. Finally, we consider the problem of embedding a cut graph (or more generally a cellular graph) with a given combinatorial map on a given surface. Using random triangulations, we prove (essentially) that, for any choice of a combinatorial map, there are some surfaces on which any cellular embedding with that combinatorial map has length superlinear in the number of triangles of the triangulated combinatorial surface. There is also a similar result for graphs embedded on polyhedral triangulations.},
author = {Colin De Verdière, Éric and Hubard, Alfredo and De Mesmay, Arnaud N},
journal = {Discrete & Computational Geometry},
number = {3},
pages = {587 -- 620},
publisher = {Springer},
title = {{Discrete systolic inequalities and decompositions of triangulated surfaces}},
doi = {10.1007/s00454-015-9679-9},
volume = {53},
year = {2015},
}
@article{1731,
abstract = {We consider two-player zero-sum games on graphs. These games can be classified on the basis of the information of the players and on the mode of interaction between them. On the basis of information the classification is as follows: (a) partial-observation (both players have partial view of the game); (b) one-sided complete-observation (one player has complete observation); and (c) complete-observation (both players have complete view of the game). On the basis of mode of interaction we have the following classification: (a) concurrent (both players interact simultaneously); and (b) turn-based (both players interact in turn). The two sources of randomness in these games are randomness in transition function and randomness in strategies. In general, randomized strategies are more powerful than deterministic strategies, and randomness in transitions gives more general classes of games. In this work we present a complete characterization for the classes of games where randomness is not helpful in: (a) the transition function probabilistic transition can be simulated by deterministic transition); and (b) strategies (pure strategies are as powerful as randomized strategies). As consequence of our characterization we obtain new undecidability results for these games. },
author = {Chatterjee, Krishnendu and Doyen, Laurent and Gimbert, Hugo and Henzinger, Thomas A},
journal = {Information and Computation},
number = {12},
pages = {3 -- 16},
publisher = {Elsevier},
title = {{Randomness for free}},
doi = {10.1016/j.ic.2015.06.003},
volume = {245},
year = {2015},
}
@inproceedings{1732,
abstract = {We consider partially observable Markov decision processes (POMDPs), that are a standard framework for robotics applications to model uncertainties present in the real world, with temporal logic specifications. All temporal logic specifications in linear-time temporal logic (LTL) can be expressed as parity objectives. We study the qualitative analysis problem for POMDPs with parity objectives that asks whether there is a controller (policy) to ensure that the objective holds with probability 1 (almost-surely). While the qualitative analysis of POMDPs with parity objectives is undecidable, recent results show that when restricted to finite-memory policies the problem is EXPTIME-complete. While the problem is intractable in theory, we present a practical approach to solve the qualitative analysis problem. We designed several heuristics to deal with the exponential complexity, and have used our implementation on a number of well-known POMDP examples for robotics applications. Our results provide the first practical approach to solve the qualitative analysis of robot motion planning with LTL properties in the presence of uncertainty.},
author = {Chatterjee, Krishnendu and Chmelik, Martin and Gupta, Raghav and Kanodia, Ayush},
location = {Seattle, WA, United States},
pages = {325 -- 330},
publisher = {IEEE},
title = {{Qualitative analysis of POMDPs with temporal logic specifications for robotics applications}},
doi = {10.1109/ICRA.2015.7139019},
year = {2015},
}
@article{1734,
abstract = {Facial appearance capture is now firmly established within academic research and used extensively across various application domains, perhaps most prominently in the entertainment industry through the design of virtual characters in video games and films. While significant progress has occurred over the last two decades, no single survey currently exists that discusses the similarities, differences, and practical considerations of the available appearance capture techniques as applied to human faces. A central difficulty of facial appearance capture is the way light interacts with skin-which has a complex multi-layered structure-and the interactions that occur below the skin surface can, by definition, only be observed indirectly. In this report, we distinguish between two broad strategies for dealing with this complexity. "Image-based methods" try to exhaustively capture the exact face appearance under different lighting and viewing conditions, and then render the face through weighted image combinations. "Parametric methods" instead fit the captured reflectance data to some parametric appearance model used during rendering, allowing for a more lightweight and flexible representation but at the cost of potentially increased rendering complexity or inexact reproduction. The goal of this report is to provide an overview that can guide practitioners and researchers in assessing the tradeoffs between current approaches and identifying directions for future advances in facial appearance capture.},
author = {Klehm, Oliver and Rousselle, Fabrice and Papas, Marios and Bradley, Derek and Hery, Christophe and Bickel, Bernd and Jarosz, Wojciech and Beeler, Thabo},
journal = {Computer Graphics Forum},
number = {2},
pages = {709 -- 733},
publisher = {Wiley-Blackwell},
title = {{Recent advances in facial appearance capture}},
doi = {10.1111/cgf.12594},
volume = {34},
year = {2015},
}
@article{1735,
abstract = {This work presents a method for efficiently simplifying the pressure projection step in a liquid simulation. We first devise a straightforward dimension reduction technique that dramatically reduces the cost of solving the pressure projection. Next, we introduce a novel change of basis that satisfies free-surface boundary conditions exactly, regardless of the accuracy of the pressure solve. When combined, these ideas greatly reduce the computational complexity of the pressure solve without compromising free surface boundary conditions at the highest level of detail. Our techniques are easy to parallelize, and they effectively eliminate the computational bottleneck for large liquid simulations.},
author = {Ando, Ryoichi and Thürey, Nils and Wojtan, Christopher J},
journal = {Computer Graphics Forum},
number = {2},
pages = {473 -- 480},
publisher = {Wiley},
title = {{A dimension-reduced pressure solver for liquid simulations}},
doi = {10.1111/cgf.12576},
volume = {34},
year = {2015},
}
@article{1789,
abstract = {Intellectual disability (ID) has an estimated prevalence of 2-3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants. To identify further genes involved in ID, we performed WES in 250 patients with unexplained ID and their unaffected parents and included exomes of 51 previously sequenced child-parents trios in the analysis. Exome analysis revealed de novo intragenic variants in SET domain-containing 5 (SETD5) in two patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splice-donor site. Chromosomal microarray diagnostics further identified four de novo non-recurrent microdeletions encompassing SETD5. CRISPR/Cas9 mutation modelling of the two intragenic variants demonstrated nonsense-mediated decay of the resulting transcripts, pointing to a loss-of-function (LoF) and haploinsufficiency as the common disease-causing mechanism of intragenic SETD5 sequence variants and SETD5-containing microdeletions. In silico domain prediction of SETD5, a predicted SET domain-containing histone methyltransferase (HMT), substantiated the presence of a SET domain and identified a novel putative PHD domain, strengthening a functional link to well-known histone-modifying ID genes. All six patients presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence variants contribute substantially to the microdeletion 3p25.3 phenotype. The present report of two SETD5 LoF variants in 301 patients demonstrates a prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID.},
author = {Kuechler, Alma and Zink, Alexander and Wieland, Thomas and Lüdecke, Hermann and Cremer, Kirsten and Salviati, Leonardo and Magini, Pamela and Najafi, Kimia and Zweier, Christiane and Czeschik, Johanna and Aretz, Stefan and Endele, Sabine and Tamburrino, Federica and Pinato, Claudia and Clementi, Maurizio and Gundlach, Jasmin and Maylahn, Carina and Mazzanti, Laura and Wohlleber, Eva and Schwarzmayr, Thomas and Kariminejad, Roxana and Schlessinger, Avner and Wieczorek, Dagmar and Strom, Tim and Novarino, Gaia and Engels, Hartmut},
journal = {European Journal of Human Genetics},
number = {6},
pages = {753 -- 760},
publisher = {Nature Publishing Group},
title = {{Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome}},
doi = {10.1038/ejhg.2014.165},
volume = {23},
year = {2015},
}
@article{1792,
abstract = {Motivated by recent ideas of Harman (Unif. Distrib. Theory, 2010) we develop a new concept of variation of multivariate functions on a compact Hausdorff space with respect to a collection D of subsets. We prove a general version of the Koksma-Hlawka theorem that holds for this notion of variation and discrepancy with respect to D. As special cases, we obtain Koksma-Hlawka inequalities for classical notions, such as extreme or isotropic discrepancy. For extreme discrepancy, our result coincides with the usual Koksma-Hlawka theorem. We show that the space of functions of bounded D-variation contains important discontinuous functions and is closed under natural algebraic operations. Finally, we illustrate the results on concrete integration problems from integral geometry and stereology.},
author = {Pausinger, Florian and Svane, Anne},
journal = {Journal of Complexity},
number = {6},
pages = {773 -- 797},
publisher = {Academic Press},
title = {{A Koksma-Hlawka inequality for general discrepancy systems}},
doi = {10.1016/j.jco.2015.06.002},
volume = {31},
year = {2015},
}
@article{1793,
abstract = {We present a software platform for reconstructing and analyzing the growth of a plant root system from a time-series of 3D voxelized shapes. It aligns the shapes with each other, constructs a geometric graph representation together with the function that records the time of growth, and organizes the branches into a hierarchy that reflects the order of creation. The software includes the automatic computation of structural and dynamic traits for each root in the system enabling the quantification of growth on fine-scale. These are important advances in plant phenotyping with applications to the study of genetic and environmental influences on growth.},
author = {Symonova, Olga and Topp, Christopher and Edelsbrunner, Herbert},
journal = {PLoS One},
number = {6},
publisher = {Public Library of Science},
title = {{DynamicRoots: A software platform for the reconstruction and analysis of growing plant roots}},
doi = {10.1371/journal.pone.0127657},
volume = {10},
year = {2015},
}
@article{1804,
abstract = {It is known that in classical fluids turbulence typically occurs at high Reynolds numbers. But can turbulence occur at low Reynolds numbers? Here we investigate the transition to turbulence in the classic Taylor-Couette system in which the rotating fluids are manufactured ferrofluids with magnetized nanoparticles embedded in liquid carriers. We find that, in the presence of a magnetic field transverse to the symmetry axis of the system, turbulence can occur at Reynolds numbers that are at least one order of magnitude smaller than those in conventional fluids. This is established by extensive computational ferrohydrodynamics through a detailed investigation of transitions in the flow structure, and characterization of behaviors of physical quantities such as the energy, the wave number, and the angular momentum through the bifurcations. A finding is that, as the magnetic field is increased, onset of turbulence can be determined accurately and reliably. Our results imply that experimental investigation of turbulence may be feasible by using ferrofluids. Our study of transition to and evolution of turbulence in the Taylor-Couette ferrofluidic flow system provides insights into the challenging problem of turbulence control.},
author = {Altmeyer, Sebastian and Do, Younghae and Lai, Ying},
journal = {Scientific Reports},
publisher = {Nature Publishing Group},
title = {{Transition to turbulence in Taylor-Couette ferrofluidic flow}},
doi = {10.1038/srep10781},
volume = {5},
year = {2015},
}