Fuzzy Fibers: Uncertainty in dMRI Tractography

Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI) allows for noninvasive reconstruction of fiber bundles in the human brain. In this chapter, we discuss sources of error and uncertainty in this technique, and review strategies that afford a more reliable interpretation of the results. This includes methods for computing and rendering probabilistic tractograms, which estimate precision in the face of measurement noise and artifacts. However, we also address aspects that have received less attention so far, such as model selection, partial voluming, and the impact of parameters, both in preprocessing and in fiber tracking itself. We conclude by giving impulses for future research

Fair Near Neighbor Search: Independent Range Sampling in High Dimensions. PODS

Similarity search is a fundamental algorithmic primitive, widely used in many computer science disciplines. There are several variants of the similarity search problem, and one of the most relevant is the $r$-near neighbor ($r$-NN) problem: given a radius $r>0$ and a set of points $S$, construct a data structure that, for any given query point $q$, returns a point $p$ within distance at most $r$ from $q$. In this paper, we study the $r$-NN problem in the light of fairness. We consider fairness in the sense of equal opportunity: all points that are within distance $r$ from the query should have the same probability to be returned. In the low-dimensional case, this problem was first studied by Hu, Qiao, and Tao (PODS 2014). Locality sensitive hashing (LSH), the theoretically strongest approach to similarity search in high dimensions, does not provide such a fairness guarantee. To address this, we propose efficient data structures for $r$-NN where all points in $S$ that are near $q$ have the same probability to be selected and returned by the query. Specifically, we first propose a black-box approach that, given any LSH scheme, constructs a data structure for uniformly sampling points in the neighborhood of a query. Then, we develop a data structure for fair similarity search under inner product that requires nearly-linear space and exploits locality sensitive filters. The paper concludes with an experimental evaluation that highlights (un)fairness in a recommendation setting on real-world datasets and discusses the inherent unfairness introduced by solving other variants of the problem.Comment: Proceedings of the 39th ACM SIGMOD-SIGACT-SIGAI Symposium on Principles of Database Systems (PODS), Pages 191-204, June 202

LNCS

We introduce the monitoring of trace properties under assumptions. An assumption limits the space of possible traces that the monitor may encounter. An assumption may result from knowledge about the system that is being monitored, about the environment, or about another, connected monitor. We define monitorability under assumptions and study its theoretical properties. In particular, we show that for every assumption A, the boolean combinations of properties that are safe or co-safe relative to A are monitorable under A. We give several examples and constructions on how an assumption can make a non-monitorable property monitorable, and how an assumption can make a monitorable property monitorable with fewer resources, such as integer registers

C7orf59/LAMTOR4 phosphorylation and structural flexibility modulate ragulator assembly

Ragulator is a pentamer composed of p18, MP1, p14, C7orf59, and hepatitis B virus X-interacting protein (HBXIP; LAMTOR 1-5) which acts as a lysosomal scaffold of the Rag GTPases in the amino acid sensitive branch of TORC1 signaling. Here, we present the crystal structure of human HBXIP-C7orf59 dimer (LAMTOR 4/5) at 2.9 angstrom and identify a phosphorylation site on C7orf59 which modulates its interaction with p18. Additionally, we demonstrate the requirement of HBXIP-C7orf59 to stabilize p18 and allow further binding of MP1-p14. The structure of the dimer revealed an unfolded N terminus in C7orf59 (residues 1-15) which was shown to be essential for p18 binding. Full-length p18 does not interact stably with MP1-p14 in the absence of HBXIP-C7orf59, but deletion of p18 residues 108-161 rescues MP1-p14 binding. C7orf59 was phosphorylated by protein kinase A (PKA) in vitro and mutation of the conserved Ser67 residue to aspartate prevented phosphorylation and negatively affected the C7orf59 interaction with p18 both in cell culture and in vitro. C7orf59 Ser67 was phosphorylated in human embryonic kidney 293T cells. PKA activation with forskolin induced dissociation of p18 from C7orf59, which was prevented by the PKA inhibitor H-89. Our results highlight the essential role of HBXIP-C7orf59 dimer as a nucleator of pentameric Ragulator and support a sequential model of Ragulator assembly in which HBXIP-C7orf59 binds and stabilizes p18 which allows subsequent binding of MP1-p149915891602CNPQ - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2014/12445-0; 2017/21455-7; 2014/17264-3190174/2012-

Software Model Checking with Explicit Scheduler and Symbolic Threads

In many practical application domains, the software is organized into a set of threads, whose activation is exclusive and controlled by a cooperative scheduling policy: threads execute, without any interruption, until they either terminate or yield the control explicitly to the scheduler. The formal verification of such software poses significant challenges. On the one side, each thread may have infinite state space, and might call for abstraction. On the other side, the scheduling policy is often important for correctness, and an approach based on abstracting the scheduler may result in loss of precision and false positives. Unfortunately, the translation of the problem into a purely sequential software model checking problem turns out to be highly inefficient for the available technologies. We propose a software model checking technique that exploits the intrinsic structure of these programs. Each thread is translated into a separate sequential program and explored symbolically with lazy abstraction, while the overall verification is orchestrated by the direct execution of the scheduler. The approach is optimized by filtering the exploration of the scheduler with the integration of partial-order reduction. The technique, called ESST (Explicit Scheduler, Symbolic Threads) has been implemented and experimentally evaluated on a significant set of benchmarks. The results demonstrate that ESST technique is way more effective than software model checking applied to the sequentialized programs, and that partial-order reduction can lead to further performance improvements.Comment: 40 pages, 10 figures, accepted for publication in journal of logical methods in computer scienc

MSH2/MSH6 Complex Promotes Error-Free Repair of AID-Induced dU:G Mispairs as well as Error-Prone Hypermutation of A:T Sites

Mismatch repair of AID-generated dU:G mispairs is critical for class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The generation of a previously unavailable Msh2−/−Msh6−/− mouse has for the first time allowed us to examine the impact of the complete loss of MutSα on lymphomagenesis, CSR and SHM. The onset of T cell lymphomas and the survival of Msh2−/−Msh6−/− and Msh2−/−Msh6−/−Msh3−/− mice are indistinguishable from Msh2−/− mice, suggesting that MSH2 plays the critical role in protecting T cells from malignant transformation, presumably because it is essential for the formation of stable MutSα heterodimers that maintain genomic stability. The similar defects on switching in Msh2−/−, Msh2−/−Msh6−/− and Msh2−/−Msh6−/−Msh3−/− mice confirm that MutSα but not MutSβ plays an important role in CSR. Analysis of SHM in Msh2−/−Msh6−/− mice not only confirmed the error-prone role of MutSα in the generation of strand biased mutations at A:T bases, but also revealed an error-free role of MutSα when repairing some of the dU:G mispairs generated by AID on both DNA strands. We propose a model for the role of MutSα at the immunoglobulin locus where the local balance of error-free and error-prone repair has an impact in the spectrum of mutations introduced during Phase 2 of SHM