Fully Dynamic Maintenance of Arc-Flags in Road Networks

International audienceThe problem of finding best routes in road networks can be solved by applying Dijkstra's shortest paths algorithm. Unfortunately, road networks deriving from real-world applications are huge yielding unsustainable times to compute shortest paths. For this reason, great research efforts have been done to accelerate Dijkstra's algorithm on road networks. These efforts have led to the development of a number of speed-up techniques, as for example Arc-Flags, whose aim is to compute additional data in a preprocessing phase in order to accelerate the shortest paths queries in an on-line phase. The main drawback of most of these techniques is that they do not work well in dynamic scenarios. In this paper we propose a new algorithm to update the Arc-Flags of a graph subject to edge weight decrease operations. To check the practical performances of the new algorithm we experimentally analyze it, along with a previously known algorithm for edge weight increase operations, on real-world road networks subject to fully dynamic sequences of operations. Our experiments show a significant speed-up in the updating phase of the Arc-Flags, at the cost of a small space and time overhead in the preprocessing phase

Distance Oracles for Time-Dependent Networks

We present the first approximate distance oracle for sparse directed networks with time-dependent arc-travel-times determined by continuous, piecewise linear, positive functions possessing the FIFO property. Our approach precomputes $(1+\epsilon)-$approximate distance summaries from selected landmark vertices to all other vertices in the network. Our oracle uses subquadratic space and time preprocessing, and provides two sublinear-time query algorithms that deliver constant and $(1+\sigma)-$approximate shortest-travel-times, respectively, for arbitrary origin-destination pairs in the network, for any constant $\sigma > \epsilon$. Our oracle is based only on the sparsity of the network, along with two quite natural assumptions about travel-time functions which allow the smooth transition towards asymmetric and time-dependent distance metrics.Comment: A preliminary version appeared as Technical Report ECOMPASS-TR-025 of EU funded research project eCOMPASS (http://www.ecompass-project.eu/). An extended abstract also appeared in the 41st International Colloquium on Automata, Languages, and Programming (ICALP 2014, track-A

Scanning Electron Microscopy in Bone Pathology: Review of Methods, Potential and Applications

This article reviews the applications of SEM methods to human bone pathologies referring to studies made at UCL. We consider the methods which may be most suitable; these prove to be not routine in the context of most bio-medical applications of SEM. Valuable information can be obtained from a bone sample if its edges are ground flat, before making either (a) a matrix surface preparation by washing away all the cells or (b) a mineralising front preparation, by also dissolving the osteoid -for which hydrogen peroxide is recommended to produce a robust specimen. BSE contrast from a cut block surface can be used to measure bone phase volume. SE contrasts from natural surfaces (trabeculae, canals and lacunae) can be used to study forming, resting and resorbing* surfaces both qualitatively and quantitatively (*except in the case of histological osteomalacia, where the existence of osteoid will go undetected and reversal lines will be difficult to distinguish from recently resorbed surfaces). We also recommend the use of PMMA embedded bone blocks, which can be used as obtained from the pathologist, but are better embedded by a more rigorous procedure. BSE image analysis can be used to quantitate bone density fractions opening up a completely new investigative method for the future. Osteoid can be measured automatically using CL if the bone sample is block stained with brilliant sulphaflavine before embedding or if a scintillant is added to the embeddant. We give examples of observations made from a number of bone diseases: vitamin D resistant rickets, ostegenesis imperfecta; osteomalacia; osteoporosis; hyperparathyroidism; fluorosis; Paget \u27s disease; tumour metastasis to bone

Direct recording and molecular identification of the calcium channel of primary cilia

Summary A primary cilium is a solitary slender non-motile protuberance of structured microtubules (9+0) enclosed by plasma membrane1. Housing components of the cell division apparatus between cell divisions, they also serve as specialized compartments for calcium signaling2 and Hedgehog (Hh) signaling pathways3. Specialized sensory cilia such as retinal photoreceptors and olfactory cilia employ diverse ion channels4-7. An ion current has been measured from primary cilia of kidney cells8 but the responsible genes have not been identified. The polycystin proteins (PC, PKD), identified in linkage studies of polycystic kidney disease9, are candidate channels divided into two structural classes: 11-transmembrane (TM) proteins (PKD1, PKD1-L1 and PKD1-L2) remarkable for a large extracellular N-terminus of putative cell adhesion domains and a GPCR proteolytic site, and the 6-TM channel proteins (PKD2, PKD2-L1, PKD2-L2; TRPPs). Evidence suggests that the PKD1s associate with the PKD2s via coiled-coil domains10-12. Here, we employ a transgenic mouse in which only cilia express a fluorophore and employ it to directly record from primary cilia and demonstrate that PKD1-L1 and PKD2-L1 form ion channels at high densities in several cell types. In conjunction with the companion manuscript2, we show that the PKD1-L1/PKD2-L1 heteromeric channel establishes the cilia as a unique calcium compartment within cells that modulates established Hedgehog pathways

Primary cilia are specialized calcium signaling organelles

Summary Primary cilia are solitary nonmotile extensions of the centriole found on nearly all nucleated eukaryotic cells between cell divisions. Only ∼200-300 nm in diameter and a few microns long, they are separated from the cytoplasm by the ciliary neck and basal body. Often called sensory cilia, they are hypothesized to receive chemical and mechanical stimuli and initiate specific cellular signal transduction pathways. When activated by a ligand, Hedgehog (Hh) pathway proteins, such as Gli2 and Smoothened (Smo), translocate from the cell into the cilium1,2. Mutations in primary ciliary proteins are associated with severe developmental defects3. The ionic conditions, permeability of the primary cilia membrane, and effectiveness of the diffusion barriers between the cilia and cell body are unknown. Here we show that cilia are a unique calcium compartment regulated by a heteromeric TRP channel, PKD1-L1/PKD2-L1. In contrast to the hypothesis that polycystin (PKD) channels initiate changes in ciliary calcium that are conducted into the cytoplasm4, we show that changes in ciliary calcium concentration ([Ca2+]cilia) occur without substantially altering global cytoplasmic calcium ([Ca2+]cyto). PKD1-L1/PKD2-L1 acts as a ciliary calcium channel controlling [Ca2+]cilia and thereby modifying Smo-activated Gli2 translocation and Gli1 expression

Pelvic Girdle Reconstruction Based on Spinal Fusion and Ischial Screw Fixation in a Case of Aneurysmal Bone Cyst

A case of lytic lesion of the pelvis in a 23-year-old woman is presented. A biopsy led to the diagnosis aneurysmal bone cyst (ABC). Due to the histologically very aggressive growth of the tumor, a low malignant osteosarcoma could not be excluded. In an initial operation the tumour, affecting the sacrum, the iliac crest and the lower lumbar spine was resected. Temporary restabilisation of the pelvic ring was achieved by a titanium plate. The histological examination of the entire tumour confirmed the diagnosis ABC. After 6 months, the MRI showed no recurrence. The observed tilt of the spine to the operated side on the sacral base prompted a second surgical procedure: a transpedicular fixation of L5 and L4 was connected via bent titanium stems to the ischium, where the fixation was achieved by two screws. This construction allowed the correction of the base angle and yielded a stable closure of the pelvic ring. The patient has now been followed for 6 years: the bone grafts have been incorporated and, in spite of radiological signs of screw loosening in the ischium, the patient is fully rehabilitated and free of symptoms. Pedicle screws in the lower spine can be recommended for fixation of a pelvic ring discontinuity

Tractable Pathfinding for the Stochastic On-Time Arrival Problem

We present a new and more efficient technique for computing the route that maximizes the probability of on-time arrival in stochastic networks, also known as the path-based stochastic on-time arrival (SOTA) problem. Our primary contribution is a pathfinding algorithm that uses the solution to the policy-based SOTA problem---which is of pseudo-polynomial-time complexity in the time budget of the journey---as a search heuristic for the optimal path. In particular, we show that this heuristic can be exceptionally efficient in practice, effectively making it possible to solve the path-based SOTA problem as quickly as the policy-based SOTA problem. Our secondary contribution is the extension of policy-based preprocessing to path-based preprocessing for the SOTA problem. In the process, we also introduce Arc-Potentials, a more efficient generalization of Stochastic Arc-Flags that can be used for both policy- and path-based SOTA. After developing the pathfinding and preprocessing algorithms, we evaluate their performance on two different real-world networks. To the best of our knowledge, these techniques provide the most efficient computation strategy for the path-based SOTA problem for general probability distributions, both with and without preprocessing.Comment: Submission accepted by the International Symposium on Experimental Algorithms 2016 and published by Springer in the Lecture Notes in Computer Science series on June 1, 2016. Includes typographical corrections and modifications to pre-processing made after the initial submission to SODA'15 (July 7, 2014

Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age

Retrospective histologic analyses of bone biopsies and of post mortem samples from normal persons of different age groups, and of bone biopsies of age- and sex-matched groups of patients with primary osteoporosis and aplastic anemia show characteristic age dependent as well as pathologic changes including atrophy of osseous trabeculae and of hematopoiesis, and changes in the sinusoidal and arterial capillary compartments. These results indicate the possible role of a microvascular defect in the pathogenesis of osteoporosis and aplastic anemia

Advanced Multilevel Node Separator Algorithms

A node separator of a graph is a subset S of the nodes such that removing S and its incident edges divides the graph into two disconnected components of about equal size. In this work, we introduce novel algorithms to find small node separators in large graphs. With focus on solution quality, we introduce novel flow-based local search algorithms which are integrated in a multilevel framework. In addition, we transfer techniques successfully used in the graph partitioning field. This includes the usage of edge ratings tailored to our problem to guide the graph coarsening algorithm as well as highly localized local search and iterated multilevel cycles to improve solution quality even further. Experiments indicate that flow-based local search algorithms on its own in a multilevel framework are already highly competitive in terms of separator quality. Adding additional local search algorithms further improves solution quality. Our strongest configuration almost always outperforms competing systems while on average computing 10% and 62% smaller separators than Metis and Scotch, respectively