@misc{5402,
abstract = {Linearizability requires that the outcome of calls by competing threads to a concurrent data structure is the same as some sequential execution where each thread has exclusive access to the data structure. In an ordered data structure, such as a queue or a stack, linearizability is ensured by requiring threads commit in the order dictated by the sequential semantics of the data structure; e.g., in a concurrent queue implementation a dequeue can only remove the oldest element.
In this paper, we investigate the impact of this strict ordering, by comparing what linearizability allows to what existing implementations do. We first give an operational definition for linearizability which allows us to build the most general linearizable implementation as a transition system for any given sequential specification. We then use this operational definition to categorize linearizable implementations based on whether they are bound or free. In a bound implementation, whenever all threads observe the same logical state, the updates to the logical state and the temporal order of commits coincide. All existing queue implementations we know of are bound. We then proceed to present, to the best of our knowledge, the first ever free queue implementation. Our experiments show that free implementations have the potential for better performance by suffering less from contention.},
author = {Henzinger, Thomas A and Sezgin, Ali},
issn = {2664-1690},
pages = {16},
publisher = {IST Austria},
title = {{How free is your linearizable concurrent data structure?}},
doi = {10.15479/AT:IST-2013-123-v1-1},
year = {2013},
}
@techreport{5407,
abstract = {This document is created as a part of the project “Repository for Research Data at IST Austria”. It summarises the mandatory features, which need to be fulfilled to provide an institutional repository as a platform and also a service to the scientists at the institute. It also includes optional features, which would be of strong benefit for the scientists and would increase the usage of the repository, and hence the visibility of research at IST Austria.},
author = {Porsche, Jana},
publisher = {IST Austria},
title = {{Technical requirements and features}},
year = {2013},
}
@inproceedings{1385,
abstract = {It is often difficult to correctly implement a Boolean controller for a complex system, especially when concurrency is involved. Yet, it may be easy to formally specify a controller. For instance, for a pipelined processor it suffices to state that the visible behavior of the pipelined system should be identical to a non-pipelined reference system (Burch-Dill paradigm). We present a novel procedure to efficiently synthesize multiple Boolean control signals from a specification given as a quantified first-order formula (with a specific quantifier structure). Our approach uses uninterpreted functions to abstract details of the design. We construct an unsatisfiable SMT formula from the given specification. Then, from just one proof of unsatisfiability, we use a variant of Craig interpolation to compute multiple coordinated interpolants that implement the Boolean control signals. Our method avoids iterative learning and back-substitution of the control functions. We applied our approach to synthesize a controller for a simple two-stage pipelined processor, and present first experimental results.},
author = {Hofferek, Georg and Gupta, Ashutosh and Könighofer, Bettina and Jiang, Jie and Bloem, Roderick},
booktitle = {2013 Formal Methods in Computer-Aided Design},
location = {Portland, OR, United States},
pages = {77 -- 84},
publisher = {IEEE},
title = {{Synthesizing multiple boolean functions using interpolation on a single proof}},
doi = {10.1109/FMCAD.2013.6679394},
year = {2013},
}
@misc{5399,
abstract = {In this work we present a flexible tool for tumor progression, which simulates the evolutionary dynamics of cancer. Tumor progression implements a multi-type branching process where the key parameters are the fitness landscape, the mutation rate, and the average time of cell division. The fitness of a cancer cell depends on the mutations it has accumulated. The input to our tool could be any fitness landscape, mutation rate, and cell division time, and the tool produces the growth dynamics and all relevant statistics.},
author = {Reiter, Johannes and Bozic, Ivana and Chatterjee, Krishnendu and Nowak, Martin},
issn = {2664-1690},
pages = {17},
publisher = {IST Austria},
title = {{TTP: Tool for Tumor Progression}},
doi = {10.15479/AT:IST-2013-104-v1-1},
year = {2013},
}
@inproceedings{2181,
abstract = {There is a trade-off between performance and correctness in implementing concurrent data structures. Better performance may be achieved at the expense of relaxing correctness, by redefining the semantics of data structures. We address such a redefinition of data structure semantics and present a systematic and formal framework for obtaining new data structures by quantitatively relaxing existing ones. We view a data structure as a sequential specification S containing all "legal" sequences over an alphabet of method calls. Relaxing the data structure corresponds to defining a distance from any sequence over the alphabet to the sequential specification: the k-relaxed sequential specification contains all sequences over the alphabet within distance k from the original specification. In contrast to other existing work, our relaxations are semantic (distance in terms of data structure states). As an instantiation of our framework, we present two simple yet generic relaxation schemes, called out-of-order and stuttering relaxation, along with several ways of computing distances. We show that the out-of-order relaxation, when further instantiated to stacks, queues, and priority queues, amounts to tolerating bounded out-of-order behavior, which cannot be captured by a purely syntactic relaxation (distance in terms of sequence manipulation, e.g. edit distance). We give concurrent implementations of relaxed data structures and demonstrate that bounded relaxations provide the means for trading correctness for performance in a controlled way. The relaxations are monotonic which further highlights the trade-off: increasing k increases the number of permitted sequences, which as we demonstrate can lead to better performance. Finally, since a relaxed stack or queue also implements a pool, we actually have new concurrent pool implementations that outperform the state-of-the-art ones.},
author = {Henzinger, Thomas A and Kirsch, Christoph and Payer, Hannes and Sezgin, Ali and Sokolova, Ana},
booktitle = {Proceedings of the 40th annual ACM SIGPLAN-SIGACT symposium on Principles of programming language},
isbn = {978-1-4503-1832-7},
location = {Rome, Italy},
pages = {317 -- 328},
publisher = {ACM},
title = {{Quantitative relaxation of concurrent data structures}},
doi = {10.1145/2429069.2429109},
year = {2013},
}
@inproceedings{2237,
abstract = {We describe new extensions of the Vampire theorem prover for computing tree interpolants. These extensions generalize Craig interpolation in Vampire, and can also be used to derive sequence interpolants. We evaluated our implementation on a large number of examples over the theory of linear integer arithmetic and integer-indexed arrays, with and without quantifiers. When compared to other methods, our experiments show that some examples could only be solved by our implementation.},
author = {Blanc, Régis and Gupta, Ashutosh and Kovács, Laura and Kragl, Bernhard},
location = {Stellenbosch, South Africa},
pages = {173 -- 181},
publisher = {Springer},
title = {{Tree interpolation in Vampire}},
doi = {10.1007/978-3-642-45221-5_13},
volume = {8312},
year = {2013},
}
@article{2299,
abstract = {The standard hardware design flow involves: (a) design of an integrated circuit using a hardware description language, (b) extensive functional and formal verification, and (c) logical synthesis. However, the above-mentioned processes consume significant effort and time. An alternative approach is to use a formal specification language as a high-level hardware description language and synthesize hardware from formal specifications. Our work is a case study of the synthesis of the widely and industrially used AMBA AHB protocol from formal specifications. Bloem et al. presented the first formal specifications for the AMBA AHB Arbiter and synthesized the AHB Arbiter circuit. However, in the first formal specification some important assumptions were missing. Our contributions are as follows: (a) We present detailed formal specifications for the AHB Arbiter incorporating the missing details, and obtain significant improvements in the synthesis results (both with respect to the number of gates in the synthesized circuit and with respect to the time taken to synthesize the circuit), and (b) we present formal specifications to generate compact circuits for the remaining two main components of AMBA AHB, namely, AHB Master and AHB Slave. Thus with systematic description we are able to automatically and completely synthesize an important and widely used industrial protocol.},
author = {Godhal, Yashdeep and Chatterjee, Krishnendu and Henzinger, Thomas A},
journal = {International Journal on Software Tools for Technology Transfer},
number = {5-6},
pages = {585 -- 601},
publisher = {Springer},
title = {{Synthesis of AMBA AHB from formal specification: A case study}},
doi = {10.1007/s10009-011-0207-9},
volume = {15},
year = {2013},
}
@article{2814,
abstract = {We study the problem of generating a test sequence that achieves maximal coverage for a reactive system under test. We formulate the problem as a repeated game between the tester and the system, where the system state space is partitioned according to some coverage criterion and the objective of the tester is to maximize the set of partitions (or coverage goals) visited during the game. We show the complexity of the maximal coverage problem for non-deterministic systems is PSPACE-complete, but is NP-complete for deterministic systems. For the special case of non-deterministic systems with a re-initializing "reset" action, which represent running a new test input on a re-initialized system, we show that the complexity is coNP-complete. Our proof technique for reset games uses randomized testing strategies that circumvent the exponentially large memory requirement of deterministic testing strategies. We also discuss the memory requirement for deterministic strategies and extensions of our results to other models, such as pushdown systems and timed systems.},
author = {Chatterjee, Krishnendu and Alfaro, Luca and Majumdar, Ritankar},
journal = {International Journal of Foundations of Computer Science},
number = {2},
pages = {165 -- 185},
publisher = {World Scientific Publishing},
title = {{The complexity of coverage}},
doi = {10.1142/S0129054113400066},
volume = {24},
year = {2013},
}
@inproceedings{2819,
abstract = {We introduce quantatitive timed refinement metrics and quantitative timed simulation functions, incorporating zenoness checks, for timed systems. These functions assign positive real numbers between zero and infinity which quantify the timing mismatches between two timed systems, amongst non-zeno runs. We quantify timing mismatches in three ways: (1) the maximum timing mismatch that can arise, (2) the "steady-state" maximum 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 functions to within any desired degree of accuracy. In order to compute the values of the quantitative simulation functions, 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 for player 1, and then use these algorithms to compute the values of the quantitative timed simulation functions. },
author = {Chatterjee, Krishnendu and Prabhu, Vinayak},
booktitle = {Proceedings of the 16th International Conference on Hybrid Systems: Computation and Control},
location = {Philadelphia, PA USA},
pages = {273 -- 282},
publisher = {Springer},
title = {{Quantitative timed simulation functions and refinement metrics for real-time systems}},
doi = {10.1145/2461328.2461370},
volume = {1},
year = {2013},
}
@article{2282,
abstract = {Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the enveloping cell layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish epiboly. The control of EVL cell-division orientation by tension involves cell elongation and requires myosin II activity to align the mitotic spindle with the main tension axis. We also found that in the absence of tension-oriented cell divisions and in the presence of increased tissue tension, EVL cells undergo ectopic fusions, suggesting that the reduction of tension anisotropy by oriented cell divisions is required to prevent EVL cells from fusing. We conclude that cell-division orientation by tension constitutes a key mechanism for limiting tension anisotropy and thus promoting tissue spreading during EVL epiboly.},
author = {Campinho, Pedro and Behrndt, Martin and Ranft, Jonas and Risler, Thomas and Minc, Nicolas and Heisenberg, Carl-Philipp J},
journal = {Nature Cell Biology},
pages = {1405 -- 1414},
publisher = {Nature Publishing Group},
title = {{Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly}},
doi = {10.1038/ncb2869},
volume = {15},
year = {2013},
}
@inproceedings{2446,
abstract = {The model-checking problem for probabilistic systems crucially relies on the translation of LTL to deterministic Rabin automata (DRW). Our recent Safraless translation [KE12, GKE12] for the LTL(F,G) fragment produces smaller automata as compared to the traditional approach. In this work, instead of DRW we consider deterministic automata with acceptance condition given as disjunction of generalized Rabin pairs (DGRW). The Safraless translation of LTL(F,G) formulas to DGRW results in smaller automata as compared to DRW. We present algorithms for probabilistic model-checking as well as game solving for DGRW conditions. Our new algorithms lead to improvement both in terms of theoretical bounds as well as practical evaluation. We compare PRISM with and without our new translation, and show that the new translation leads to significant improvements.},
author = {Chatterjee, Krishnendu and Gaiser, Andreas and Kretinsky, Jan},
location = {St. Petersburg, Russia},
pages = {559 -- 575},
publisher = {Springer},
title = {{Automata with generalized Rabin pairs for probabilistic model checking and LTL synthesis}},
doi = {10.1007/978-3-642-39799-8_37},
volume = {8044},
year = {2013},
}
@phdthesis{1405,
abstract = {Motivated by the analysis of highly dynamic message-passing systems, i.e. unbounded thread creation, mobility, etc. we present a framework for the analysis of depth-bounded systems. Depth-bounded systems are one of the most expressive known fragment of the π-calculus for which interesting verification problems are still decidable. Even though they are infinite state systems depth-bounded systems are well-structured, thus can be analyzed algorithmically. We give an interpretation of depth-bounded systems as graph-rewriting systems. This gives more flexibility and ease of use to apply depth-bounded systems to other type of systems like shared memory concurrency.
First, we develop an adequate domain of limits for depth-bounded systems, a prerequisite for the effective representation of downward-closed sets. Downward-closed sets are needed by forward saturation-based algorithms to represent potentially infinite sets of states. Then, we present an abstract interpretation framework to compute the covering set of well-structured transition systems. Because, in general, the covering set is not computable, our abstraction over-approximates the actual covering set. Our abstraction captures the essence of acceleration based-algorithms while giving up enough precision to ensure convergence. We have implemented the analysis in the PICASSO tool and show that it is accurate in practice. Finally, we build some further analyses like termination using the covering set as starting point.},
author = {Zufferey, Damien},
pages = {134},
publisher = {IST Austria},
title = {{Analysis of dynamic message passing programs}},
year = {2013},
}
@article{2939,
abstract = {In this paper, we present the first output-sensitive algorithm to compute the persistence diagram of a filtered simplicial complex. For any Γ > 0, it returns only those homology classes with persistence at least Γ. Instead of the classical reduction via column operations, our algorithm performs rank computations on submatrices of the boundary matrix. For an arbitrary constant δ ∈ (0, 1), the running time is O (C (1 - δ) Γ R d (n) log n), where C (1 - δ) Γ is the number of homology classes with persistence at least (1 - δ) Γ, n is the total number of simplices in the complex, d its dimension, and R d (n) is the complexity of computing the rank of an n × n matrix with O (d n) nonzero entries. Depending on the choice of the rank algorithm, this yields a deterministic O (C (1 - δ) Γ n 2.376) algorithm, an O (C (1 - δ) Γ n 2.28) Las-Vegas algorithm, or an O (C (1 - δ) Γ n 2 + ε{lunate}) Monte-Carlo algorithm for an arbitrary ε{lunate} > 0. The space complexity of the Monte-Carlo version is bounded by O (d n) = O (n log n).},
author = {Chen, Chao and Kerber, Michael},
journal = {Computational Geometry: Theory and Applications},
number = {4},
pages = {435 -- 447},
publisher = {Elsevier},
title = {{An output sensitive algorithm for persistent homology}},
doi = {10.1016/j.comgeo.2012.02.010},
volume = {46},
year = {2013},
}
@phdthesis{1406,
abstract = {Epithelial spreading is a critical part of various developmental and wound repair processes. Here we use zebrafish epiboly as a model system to study the cellular and molecular mechanisms underlying the spreading of epithelial sheets. During zebrafish epiboly the enveloping cell layer (EVL), a simple squamous epithelium, spreads over the embryo to eventually cover the entire yolk cell by the end of gastrulation. The EVL leading edge is anchored through tight junctions to the yolk syncytial layer (YSL), where directly adjacent to the EVL margin a contractile actomyosin ring is formed that is thought to drive EVL epiboly. The prevalent view in the field was that the contractile ring exerts a pulling force on the EVL margin, which pulls the EVL towards the vegetal pole. However, how this force is generated and how it affects EVL morphology still remains elusive. Moreover, the cellular mechanisms mediating the increase in EVL surface area, while maintaining tissue integrity and function are still unclear. Here we show that the YSL actomyosin ring pulls on the EVL margin by two distinct force-generating mechanisms. One mechanism is based on contraction of the ring around its circumference, as previously proposed. The second mechanism is based on actomyosin retrogade flows, generating force through resistance against the substrate. The latter can function at any epiboly stage even in situations where the contraction-based mechanism is unproductive. Additionally, we demonstrate that during epiboly the EVL is subjected to anisotropic tension, which guides the orientation of EVL cell division along the main axis (animal-vegetal) of tension. The influence of tension in cell division orientation involves cell elongation and requires myosin-2 activity for proper spindle alignment. Strikingly, we reveal that tension-oriented cell divisions release anisotropic tension within the EVL and that in the absence of such divisions, EVL cells undergo ectopic fusions. We conclude that forces applied to the EVL by the action of the YSL actomyosin ring generate a tension anisotropy in the EVL that orients cell divisions, which in turn limit tissue tension increase thereby facilitating tissue spreading.},
author = {Campinho, Pedro},
pages = {123},
publisher = {IST Austria},
title = {{Mechanics of zebrafish epiboly: Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading}},
year = {2013},
}
@inproceedings{2238,
abstract = {We study the problem of achieving a given value in Markov decision processes (MDPs) with several independent discounted reward objectives. We consider a generalised version of discounted reward objectives, in which the amount of discounting depends on the states visited and on the objective. This definition extends the usual definition of discounted reward, and allows to capture the systems in which the value of different commodities diminish at different and variable rates.
We establish results for two prominent subclasses of the problem, namely state-discount models where the discount factors are only dependent on the state of the MDP (and independent of the objective), and reward-discount models where they are only dependent on the objective (but not on the state of the MDP). For the state-discount models we use a straightforward reduction to expected total reward and show that the problem whether a value is achievable can be solved in polynomial time. For the reward-discount model we show that memory and randomisation of the strategies are required, but nevertheless that the problem is decidable and it is sufficient to consider strategies which after a certain number of steps behave in a memoryless way.
For the general case, we show that when restricted to graphs (i.e. MDPs with no randomisation), pure strategies and discount factors of the form 1/n where n is an integer, the problem is in PSPACE and finite memory suffices for achieving a given value. We also show that when the discount factors are not of the form 1/n, the memory required by a strategy can be infinite.
},
author = {Chatterjee, Krishnendu and Forejt, Vojtěch and Wojtczak, Dominik},
location = {Stellenbosch, South Africa},
pages = {228 -- 242},
publisher = {Springer},
title = {{Multi-objective discounted reward verification in graphs and MDPs}},
doi = {10.1007/978-3-642-45221-5_17},
volume = {8312},
year = {2013},
}
@article{2283,
abstract = {Pathogens exert a strong selection pressure on organisms to evolve effective immune defences. In addition to individual immunity, social organisms can act cooperatively to produce collective defences. In many ant species, queens have the option to found a colony alone or in groups with other, often unrelated, conspecifics. These associations are transient, usually lasting only as long as each queen benefits from the presence of others. In fact, once the first workers emerge, queens fight to the death for dominance. One potential advantage of co-founding may be that queens benefit from collective disease defences, such as mutual grooming, that act against common soil pathogens. We test this hypothesis by exposing single and co-founding queens to a fungal parasite, in order to assess whether queens in co-founding associations have improved survival. Surprisingly, co-foundresses exposed to the entomopathogenic fungus Metarhizium did not engage in cooperative disease defences, and consequently, we find no direct benefit of multiple queens on survival. However, an indirect benefit was observed, with parasite-exposed queens producing more brood when they co-founded, than when they were alone. We suggest this is due to a trade-off between reproduction and immunity. Additionally, we report an extraordinary ability of the queens to tolerate an infection for long periods after parasite exposure. Our study suggests that there are no social immunity benefits for co-founding ant queens, but that in parasite-rich environments, the presence of additional queens may nevertheless improve the chances of colony founding success.},
author = {Pull, Christopher and Hughes, William and Brown, Markus},
journal = {Naturwissenschaften},
number = {12},
pages = {1125 -- 1136},
publisher = {Springer},
title = {{Tolerating an infection: an indirect benefit of co-founding queen associations in the ant Lasius niger }},
doi = {10.1007/s00114-013-1115-5},
volume = {100},
year = {2013},
}
@proceedings{2288,
abstract = {This book constitutes the proceedings of the 11th International Conference on Computational Methods in Systems Biology, CMSB 2013, held in Klosterneuburg, Austria, in September 2013. The 15 regular papers included in this volume were carefully reviewed and selected from 27 submissions. They deal with computational models for all levels, from molecular and cellular, to organs and entire organisms.},
editor = {Gupta, Ashutosh and Henzinger, Thomas A},
isbn = {978-3-642-40707-9},
location = {Klosterneuburg, Austria},
publisher = {Springer},
title = {{Computational Methods in Systems Biology}},
doi = {10.1007/978-3-642-40708-6},
volume = {8130},
year = {2013},
}
@article{2290,
abstract = {The plant hormone indole-acetic acid (auxin) is essential for many aspects of plant development. Auxin-mediated growth regulation typically involves the establishment of an auxin concentration gradient mediated by polarly localized auxin transporters. The localization of auxin carriers and their amount at the plasma membrane are controlled by membrane trafficking processes such as secretion, endocytosis, and recycling. In contrast to endocytosis or recycling, how the secretory pathway mediates the localization of auxin carriers is not well understood. In this study we have used the differential cell elongation process during apical hook development to elucidate the mechanisms underlying the post-Golgi trafficking of auxin carriers in Arabidopsis. We show that differential cell elongation during apical hook development is defective in Arabidopsis mutant echidna (ech). ECH protein is required for the trans-Golgi network (TGN)-mediated trafficking of the auxin influx carrier AUX1 to the plasma membrane. In contrast, ech mutation only marginally perturbs the trafficking of the highly related auxin influx carrier LIKE-AUX1-3 or the auxin efflux carrier PIN-FORMED-3, both also involved in hook development. Electron tomography reveals that the trafficking defects in ech mutant are associated with the perturbation of secretory vesicle genesis from the TGN. Our results identify differential mechanisms for the post-Golgi trafficking of de novo-synthesized auxin carriers to plasma membrane from the TGN and reveal how trafficking of auxin influx carriers mediates the control of differential cell elongation in apical hook development.},
author = {Boutté, Yohann and Jonsson, Kristoffer and Mcfarlane, Heather and Johnson, Errin and Gendre, Delphine and Swarup, Ranjan and Friml, Jirí and Samuels, Lacey and Robert, Stéphanie and Bhalerao, Rishikesh},
journal = {PNAS},
number = {40},
pages = {16259 -- 16264},
publisher = {National Academy of Sciences},
title = {{ECHIDNA mediated post Golgi trafficking of auxin carriers for differential cell elongation}},
doi = {10.1073/pnas.1309057110},
volume = {110},
year = {2013},
}
@article{2264,
abstract = {Faithful progression through the cell cycle is crucial to the maintenance and developmental potential of stem cells. Here, we demonstrate that neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs) employ a zinc-finger transcription factor specificity protein 2 (Sp2) as a cell cycle regulator in two temporally and spatially distinct progenitor domains. Differential conditional deletion of Sp2 in early embryonic cerebral cortical progenitors, and perinatal olfactory bulb progenitors disrupted transitions through G1, G2 and M phases, whereas DNA synthesis appeared intact. Cell-autonomous function of Sp2 was identified by deletion of Sp2 using mosaic analysis with double markers, which clearly established that conditional Sp2-null NSCs and NPCs are M phase arrested in vivo. Importantly, conditional deletion of Sp2 led to a decline in the generation of NPCs and neurons in the developing and postnatal brains. Our findings implicate Sp2-dependent mechanisms as novel regulators of cell cycle progression, the absence of which disrupts neurogenesis in the embryonic and postnatal brain.},
author = {Liang, Huixuan and Xiao, Guanxi and Yin, Haifeng and Hippenmeyer, Simon and Horowitz, Jonathan and Ghashghaei, Troy},
journal = {Development},
number = {3},
pages = {552 -- 561},
publisher = {Company of Biologists},
title = {{Neural development is dependent on the function of specificity protein 2 in cell cycle progression}},
doi = {10.1242/dev.085621 },
volume = {140},
year = {2013},
}
@article{2303,
abstract = {MADM (Mosaic Analysis with Double Markers) technology offers a genetic approach in mice to visualize and concomitantly manipulate genetically defined cells at clonal level and single cell resolution. MADM employs Cre recombinase/loxP-dependent interchromosomal mitotic recombination to reconstitute two split marker genes—green GFP and red tdTomato—and can label sparse clones of homozygous mutant cells in one color and wild-type cells in the other color in an otherwise unlabeled background. At present, major MADM applications include lineage tracing, single cell labeling, conditional knockouts in small populations of cells and induction of uniparental chromosome disomy to assess effects of genomic imprinting. MADM can be applied universally in the mouse with the sole limitation being the specificity of the promoter controlling Cre recombinase expression. Here I review recent developments and extensions of the MADM technique and give an overview of the major discoveries and progresses enabled by the implementation of the novel genetic MADM tools.},
author = {Hippenmeyer, Simon},
journal = {Frontiers in Biology},
number = {6},
pages = {557 -- 568},
publisher = {Springer},
title = {{Dissection of gene function at clonal level using mosaic analysis with double markers}},
doi = {10.1007/s11515-013-1279-6},
volume = {8},
year = {2013},
}