TY - CHAP AB - Here we describe the in vivo DNA assembly approach, where molecular cloning procedures are performed using an E. coli recA-independent recombination pathway, which assembles linear fragments of DNA with short homologous termini. This pathway is present in all standard laboratory E. coli strains and, by bypassing the need for in vitro DNA assembly, allows simplified molecular cloning to be performed without the plasmid instability issues associated with specialized recombination-cloning bacterial strains. The methodology requires specific primer design and can perform all standard plasmid modifications (insertions, deletions, mutagenesis, and sub-cloning) in a rapid, simple, and cost-efficient manner, as it does not require commercial kits or specialized bacterial strains. Additionally, this approach can be used to perform complex procedures such as multiple modifications to a plasmid, as up to 6 linear fragments can be assembled in vivo by this recombination pathway. Procedures generally require less than 3 h, involving PCR amplification, DpnI digestion of template DNA, and transformation, upon which circular plasmids are assembled. In this chapter we describe the requirements, procedure, and potential pitfalls when using this technique, as well as protocol variations to overcome the most common issues. AU - Arroyo-Urea, Sandra AU - Watson, Jake AU - García-Nafría, Javier ED - Scarlett, Garry ID - 12720 SN - 1064-3745 T2 - DNA Manipulation and Analysis TI - Molecular Cloning Using In Vivo DNA Assembly VL - 2633 ER - TY - CONF AB - Asynchronous programming has gained significant popularity over the last decade: support for this programming pattern is available in many popular languages via libraries and native language implementations, typically in the form of coroutines or the async/await construct. Instead of programming via shared memory, this concept assumes implicit synchronization through message passing. The key data structure enabling such communication is the rendezvous channel. Roughly, a rendezvous channel is a blocking queue of size zero, so both send(e) and receive() operations wait for each other, performing a rendezvous when they meet. To optimize the message passing pattern, channels are usually equipped with a fixed-size buffer, so sends do not suspend and put elements into the buffer until its capacity is exceeded. This primitive is known as a buffered channel. This paper presents a fast and scalable algorithm for both rendezvous and buffered channels. Similarly to modern queues, our solution is based on an infinite array with two positional counters for send(e) and receive() operations, leveraging the unconditional Fetch-And-Add instruction to update them. Yet, the algorithm requires non-trivial modifications of this classic pattern, in order to support the full channel semantics, such as buffering and cancellation of waiting requests. We compare the performance of our solution to that of the Kotlin implementation, as well as against other academic proposals, showing up to 9.8× speedup. To showcase its expressiveness and performance, we also integrated the proposed algorithm into the standard Kotlin Coroutines library, replacing the previous channel implementations. AU - Koval, Nikita AU - Alistarh, Dan-Adrian AU - Elizarov, Roman ID - 12735 SN - 9798400700156 T2 - Proceedings of the ACM SIGPLAN Symposium on Principles and Practice of Parallel Programming TI - Fast and scalable channels in Kotlin Coroutines ER - TY - GEN AB - Although a wide variety of handcrafted concurrent data structures have been proposed, there is considerable interest in universal approaches (Universal Constructions or UCs) for building concurrent data structures. UCs (semi-)automatically convert a sequential data structure into a concurrent one. The simplest approach uses locks [3, 6] that protect a sequential data structure and allow only one process to access it at a time. However, the resulting data structure is blocking. Most work on UCs instead focuses on obtaining non-blocking progress guarantees such as obstruction-freedom, lock-freedom or wait-freedom. Many non-blocking UCs have appeared. Key examples include the seminal wait-free UC [2] by Herlihy, a NUMA-aware UC [10] by Yi et al., and an efficient UC for large objects [1] by Fatourou et al. AU - Aksenov, Vitaly AU - Brown, Trevor A AU - Fedorov, Alexander AU - Kokorin, Ilya ID - 12736 SN - 9798400700156 T2 - Proceedings of the ACM SIGPLAN Symposium on Principles and Practice of Parallel Programming TI - Unexpected scaling in path copying trees ER - TY - CONF AB - Dynamic programming (DP) is one of the fundamental paradigms in algorithm design. However, many DP algorithms have to fill in large DP tables, represented by two-dimensional arrays, which causes at least quadratic running times and space usages. This has led to the development of improved algorithms for special cases when the DPs satisfy additional properties like, e.g., the Monge property or total monotonicity. In this paper, we consider a new condition which assumes (among some other technical assumptions) that the rows of the DP table are monotone. Under this assumption, we introduce a novel data structure for computing (1 + ϵ)-approximate DP solutions in near-linear time and space in the static setting, and with polylogarithmic update times when the DP entries change dynamically. To the best of our knowledge, our new condition is incomparable to previous conditions and is the first which allows to derive dynamic algorithms based on existing DPs. Instead of using two-dimensional arrays to store the DP tables, we store the rows of the DP tables using monotone piecewise constant functions. This allows us to store length-n DP table rows with entries in [0, W] using only polylog(n, W) bits, and to perform operations, such as (min, +)-convolution or rounding, on these functions in polylogarithmic time. We further present several applications of our data structure. For bicriteria versions of k-balanced graph partitioning and simultaneous source location, we obtain the first dynamic algorithms with subpolynomial update times, as well as the first static algorithms using only near-linear time and space. Additionally, we obtain the currently fastest algorithm for fully dynamic knapsack. AU - Henzinger, Monika H AU - Neumann, Stefan AU - Räcke, Harald AU - Schmid, Stefan ID - 12760 SN - 1868-8969 T2 - 40th International Symposium on Theoretical Aspects of Computer Science TI - Dynamic maintenance of monotone dynamic programs and applications VL - 254 ER - TY - THES AB - The process of detecting and evaluating sensory information to guide behaviour is termed perceptual decision-making (PDM), and is critical for the ability of an organism to interact with its external world. Individuals with autism, a neurodevelopmental condition primarily characterised by social and communication difficulties, frequently exhibit altered sensory processing and PDM difficulties are widely reported. Recent technological advancements have pushed forward our understanding of the genetic changes accompanying this condition, however our understanding of how these mutations affect the function of specific neuronal circuits and bring about the corresponding behavioural changes remains limited. Here, we use an innate PDM task, the looming avoidance response (LAR) paradigm, to identify a convergent behavioural abnormality across three molecularly distinct genetic mouse models of autism (Cul3, Setd5 and Ptchd1). Although mutant mice can rapidly detect threatening visual stimuli, their responses are consistently delayed, requiring longer to initiate an appropriate response than their wild-type siblings. Mutant animals show abnormal adaptation in both their stimulus- evoked escape responses and exploratory dynamics following repeated stimulus presentations. Similarly delayed behavioural responses are observed in wild-type animals when faced with more ambiguous threats, suggesting the mutant phenotype could arise from a dysfunction in the flexible control of this PDM process. Our knowledge of the core neuronal circuitry mediating the LAR facilitated a detailed dissection of the neuronal mechanisms underlying the behavioural impairment. In vivo extracellular recording revealed that visual responses were unaffected within a key brain region for the rapid processing of visual threats, the superior colliculus (SC), indicating that the behavioural delay was unlikely to originate from sensory impairments. Delayed behavioural responses were recapitulated in the Setd5 model following optogenetic stimulation of the excitatory output neurons of the SC, which are known to mediate escape initiation through the activation of cells in the underlying dorsal periaqueductal grey (dPAG). In vitro patch-clamp recordings of dPAG cells uncovered a stark hypoexcitability phenotype in two out of the three genetic models investigated (Setd5 and Ptchd1), that in Setd5, is mediated by the misregulation of voltage-gated potassium channels. Overall, our results show that the ability to use visual information to drive efficient escape responses is impaired in three diverse genetic mouse models of autism and that, in one of the models studied, this behavioural delay likely originates from differences in the intrinsic excitability of a key subcortical node, the dPAG. Furthermore, this work showcases the use of an innate behavioural paradigm to mechanistically dissect PDM processes in autism. AU - Burnett, Laura ID - 12716 SN - 2663-337X TI - To flee, or not to flee? Using innate defensive behaviours to investigate rapid perceptual decision-making through subcortical circuits in mouse models of autism ER - TY - CONF AB - The main idea behind BUBAAK is to run multiple program analyses in parallel and use runtime monitoring and enforcement to observe and control their progress in real time. The analyses send information about (un)explored states of the program and discovered invariants to a monitor. The monitor processes the received data and can force an analysis to stop the search of certain program parts (which have already been analyzed by other analyses), or to make it utilize a program invariant found by another analysis. At SV-COMP 2023, the implementation of data exchange between the monitor and the analyses was not yet completed, which is why BUBAAK only ran several analyses in parallel, without any coordination. Still, BUBAAK won the meta-category FalsificationOverall and placed very well in several other (sub)-categories of the competition. AU - Chalupa, Marek AU - Henzinger, Thomas A ID - 12854 SN - 0302-9743 T2 - Tools and Algorithms for the Construction and Analysis of Systems TI - Bubaak: Runtime monitoring of program verifiers VL - 13994 ER - TY - GEN AB - We present a formula for the signed area of a spherical polygon via prequantization. In contrast to the traditional formula based on the Gauss-Bonnet theorem that requires measuring angles, the new formula mimics Green's theorem and is applicable to a wider range of degenerate spherical curves and polygons. AU - Chern, Albert AU - Ishida, Sadashige ID - 12846 T2 - arXiv TI - Area formula for spherical polygons via prequantization ER - TY - CONF AB - As the complexity and criticality of software increase every year, so does the importance of run-time monitoring. Third-party monitoring, with limited knowledge of the monitored software, and best-effort monitoring, which keeps pace with the monitored software, are especially valuable, yet underexplored areas of run-time monitoring. Most existing monitoring frameworks do not support their combination because they either require access to the monitored code for instrumentation purposes or the processing of all observed events, or both. We present a middleware framework, VAMOS, for the run-time monitoring of software which is explicitly designed to support third-party and best-effort scenarios. The design goals of VAMOS are (i) efficiency (keeping pace at low overhead), (ii) flexibility (the ability to monitor black-box code through a variety of different event channels, and the connectability to monitors written in different specification languages), and (iii) ease-of-use. To achieve its goals, VAMOS combines aspects of event broker and event recognition systems with aspects of stream processing systems. We implemented a prototype toolchain for VAMOS and conducted experiments including a case study of monitoring for data races. The results indicate that VAMOS enables writing useful yet efficient monitors, is compatible with a variety of event sources and monitor specifications, and simplifies key aspects of setting up a monitoring system from scratch. AU - Chalupa, Marek AU - Mühlböck, Fabian AU - Muroya Lei, Stefanie AU - Henzinger, Thomas A ID - 12856 SN - 0302-9743 T2 - Fundamental Approaches to Software Engineering TI - Vamos: Middleware for best-effort third-party monitoring VL - 13991 ER - TY - GEN AB - As the complexity and criticality of software increase every year, so does the importance of run-time monitoring. Third-party monitoring, with limited knowledge of the monitored software, and best-effort monitoring, which keeps pace with the monitored software, are especially valuable, yet underexplored areas of run-time monitoring. Most existing monitoring frameworks do not support their combination because they either require access to the monitored code for instrumentation purposes or the processing of all observed events, or both. We present a middleware framework, VAMOS, for the run-time monitoring of software which is explicitly designed to support third-party and best-effort scenarios. The design goals of VAMOS are (i) efficiency (keeping pace at low overhead), (ii) flexibility (the ability to monitor black-box code through a variety of different event channels, and the connectability to monitors written in different specification languages), and (iii) ease-of-use. To achieve its goals, VAMOS combines aspects of event broker and event recognition systems with aspects of stream processing systems. We implemented a prototype toolchain for VAMOS and conducted experiments including a case study of monitoring for data races. The results indicate that VAMOS enables writing useful yet efficient monitors, is compatible with a variety of event sources and monitor specifications, and simplifies key aspects of setting up a monitoring system from scratch. AU - Chalupa, Marek AU - Mühlböck, Fabian AU - Muroya Lei, Stefanie AU - Henzinger, Thomas A ID - 12407 KW - runtime monitoring KW - best effort KW - third party TI - VAMOS: Middleware for Best-Effort Third-Party Monitoring ER - TY - CHAP AB - Autism spectrum disorder (ASD) and epilepsy are frequently comorbid neurodevelopmental disorders. Extensive research has demonstrated shared pathological pathways, etiologies, and phenotypes. Many risk factors for these disorders, like genetic mutations and environmental pressures, are linked to changes in childhood brain development, which is a critical period for their manifestation. Decades of research have yielded many signatures for ASD and epilepsy, some shared and others unique or opposing. The anatomical, physiological, and behavioral correlates of these disorders are discussed in this chapter in the context of understanding shared pathological pathways. We end with important takeaways on the presentation, prevention, intervention, and policy changes for ASD and epilepsy. This chapter aims to explore the complexity of these disorders, both in etiology and phenotypes, with the further goal of appreciating the expanse of unknowns still to explore about the brain. AU - Currin, Christopher AU - Beyer, Chad ED - Halpern-Felsher, Bonnie ID - 12866 SN - 9780128188736 T2 - Encyclopedia of Child and Adolescent Health TI - Altered childhood brain development in autism and epilepsy ER -