Densest Subgraph in Dynamic Graph Streams

In this paper, we consider the problem of approximating the densest subgraph in the dynamic graph stream model. In this model of computation, the input graph is defined by an arbitrary sequence of edge insertions and deletions and the goal is to analyze properties of the resulting graph given memory that is sub-linear in the size of the stream. We present a single-pass algorithm that returns a $(1+\epsilon)$ approximation of the maximum density with high probability; the algorithm uses O(\epsilon^{-2} n \polylog n) space, processes each stream update in \polylog (n) time, and uses \poly(n) post-processing time where $n$ is the number of nodes. The space used by our algorithm matches the lower bound of Bahmani et al.~(PVLDB 2012) up to a poly-logarithmic factor for constant $\epsilon$. The best existing results for this problem were established recently by Bhattacharya et al.~(STOC 2015). They presented a $(2+\epsilon)$ approximation algorithm using similar space and another algorithm that both processed each update and maintained a $(4+\epsilon)$ approximation of the current maximum density in \polylog (n) time per-update.Comment: To appear in MFCS 201

Capacitated Vehicle Routing with Non-Uniform Speeds

The capacitated vehicle routing problem (CVRP) involves distributing (identical) items from a depot to a set of demand locations, using a single capacitated vehicle. We study a generalization of this problem to the setting of multiple vehicles having non-uniform speeds (that we call Heterogenous CVRP), and present a constant-factor approximation algorithm. The technical heart of our result lies in achieving a constant approximation to the following TSP variant (called Heterogenous TSP). Given a metric denoting distances between vertices, a depot r containing k vehicles with possibly different speeds, the goal is to find a tour for each vehicle (starting and ending at r), so that every vertex is covered in some tour and the maximum completion time is minimized. This problem is precisely Heterogenous CVRP when vehicles are uncapacitated. The presence of non-uniform speeds introduces difficulties for employing standard tour-splitting techniques. In order to get a better understanding of this technique in our context, we appeal to ideas from the 2-approximation for scheduling in parallel machine of Lenstra et al.. This motivates the introduction of a new approximate MST construction called Level-Prim, which is related to Light Approximate Shortest-path Trees. The last component of our algorithm involves partitioning the Level-Prim tree and matching the resulting parts to vehicles. This decomposition is more subtle than usual since now we need to enforce correlation between the size of the parts and their distances to the depot

Capacitated Center Problems with Two-Sided Bounds and Outliers

In recent years, the capacitated center problems have attracted a lot of research interest. Given a set of vertices $V$, we want to find a subset of vertices $S$, called centers, such that the maximum cluster radius is minimized. Moreover, each center in $S$ should satisfy some capacity constraint, which could be an upper or lower bound on the number of vertices it can serve. Capacitated $k$-center problems with one-sided bounds (upper or lower) have been well studied in previous work, and a constant factor approximation was obtained. We are the first to study the capacitated center problem with both capacity lower and upper bounds (with or without outliers). We assume each vertex has a uniform lower bound and a non-uniform upper bound. For the case of opening exactly $k$ centers, we note that a generalization of a recent LP approach can achieve constant factor approximation algorithms for our problems. Our main contribution is a simple combinatorial algorithm for the case where there is no cardinality constraint on the number of open centers. Our combinatorial algorithm is simpler and achieves better constant approximation factor compared to the LP approach

Algorithms for Colourful Simplicial Depth and Medians in the Plane

The colourful simplicial depth of a point x in the plane relative to a configuration of n points in k colour classes is exactly the number of closed simplices (triangles) with vertices from 3 different colour classes that contain x in their convex hull. We consider the problems of efficiently computing the colourful simplicial depth of a point x, and of finding a point, called a median, that maximizes colourful simplicial depth. For computing the colourful simplicial depth of x, our algorithm runs in time O(n log(n) + k n) in general, and O(kn) if the points are sorted around x. For finding the colourful median, we get a time of O(n^4). For comparison, the running times of the best known algorithm for the monochrome version of these problems are O(n log(n)) in general, improving to O(n) if the points are sorted around x for monochrome depth, and O(n^4) for finding a monochrome median.Comment: 17 pages, 8 figure

A Comparison between the Zero Forcing Number and the Strong Metric Dimension of Graphs

The \emph{zero forcing number}, $Z(G)$, of a graph $G$ is the minimum cardinality of a set $S$ of black vertices (whereas vertices in $V(G)-S$ are colored white) such that $V(G)$ is turned black after finitely many applications of "the color-change rule": a white vertex is converted black if it is the only white neighbor of a black vertex. The \emph{strong metric dimension}, $sdim(G)$, of a graph $G$ is the minimum among cardinalities of all strong resolving sets: $W \subseteq V(G)$ is a \emph{strong resolving set} of $G$ if for any $u, v \in V(G)$, there exists an $x \in W$ such that either $u$ lies on an $x-v$ geodesic or $v$ lies on an $x-u$ geodesic. In this paper, we prove that $Z(G) \le sdim(G)+3r(G)$ for a connected graph $G$, where $r(G)$ is the cycle rank of $G$. Further, we prove the sharp bound $Z(G) \leq sdim(G)$ when $G$ is a tree or a unicyclic graph, and we characterize trees $T$ attaining $Z(T)=sdim(T)$. It is easy to see that $sdim(T+e)-sdim(T)$ can be arbitrarily large for a tree $T$; we prove that $sdim(T+e) \ge sdim(T)-2$ and show that the bound is sharp.Comment: 8 pages, 5 figure

Clinical relevance of postzygotic mosaicism in Cornelia de Lange syndrome and purifying selection of NIPBL variants in blood

Postzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of patients with a positive molecular diagnosis. It is worth noting that most of the affected individuals with mosaicism have a clinical phenotype at least as severe as those with constitutive pathogenic variants. However, the type of genetic change does not vary between germline and somatic events and, even in the presence of mosaicism, missense substitutions are located preferentially within the HEAT repeat domain of NIPBL. In conclusion, the high prevalence of mosaicism in CdLS as well as the disparity in tissue distribution provide a novel orientation for the clinical management and genetic counselling of families

Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets

<p>Abstract</p> <p>Background:</p> <p><it>Mycobacterium tuberculosis </it>continues to be a major pathogen in the third world, killing almost 2 million people a year by the most recent estimates. Even in industrialized countries, the emergence of multi-drug resistant (MDR) strains of tuberculosis hails the need to develop additional medications for treatment. Many of the drugs used for treatment of tuberculosis target metabolic enzymes. Genome-scale models can be used for analysis, discovery, and as hypothesis generating tools, which will hopefully assist the rational drug development process. These models need to be able to assimilate data from large datasets and analyze them.</p> <p>Results:</p> <p>We completed a bottom up reconstruction of the metabolic network of <it>Mycobacterium tuberculosis </it>H37Rv. This functional <it>in silico </it>bacterium, <it>iNJ</it>661, contains 661 genes and 939 reactions and can produce many of the complex compounds characteristic to tuberculosis, such as mycolic acids and mycocerosates. We grew this bacterium <it>in silico </it>on various media, analyzed the model in the context of multiple high-throughput data sets, and finally we analyzed the network in an 'unbiased' manner by calculating the Hard Coupled Reaction (HCR) sets, groups of reactions that are forced to operate in unison due to mass conservation and connectivity constraints.</p> <p>Conclusion:</p> <p>Although we observed growth rates comparable to experimental observations (doubling times ranging from about 12 to 24 hours) in different media, comparisons of gene essentiality with experimental data were less encouraging (generally about 55%). The reasons for the often conflicting results were multi-fold, including gene expression variability under different conditions and lack of complete biological knowledge. Some of the inconsistencies between <it>in vitro </it>and <it>in silico </it>or <it>in vivo </it>and <it>in silico </it>results highlight specific loci that are worth further experimental investigations. Finally, by considering the HCR sets in the context of known drug targets for tuberculosis treatment we proposed new alternative, but equivalent drug targets.</p

Neocortical Axon Arbors Trade-off Material and Conduction Delay Conservation

The brain contains a complex network of axons rapidly communicating information between billions of synaptically connected neurons. The morphology of individual axons, therefore, defines the course of information flow within the brain. More than a century ago, Ramón y Cajal proposed that conservation laws to save material (wire) length and limit conduction delay regulate the design of individual axon arbors in cerebral cortex. Yet the spatial and temporal communication costs of single neocortical axons remain undefined. Here, using reconstructions of in vivo labelled excitatory spiny cell and inhibitory basket cell intracortical axons combined with a variety of graph optimization algorithms, we empirically investigated Cajal's conservation laws in cerebral cortex for whole three-dimensional (3D) axon arbors, to our knowledge the first study of its kind. We found intracortical axons were significantly longer than optimal. The temporal cost of cortical axons was also suboptimal though far superior to wire-minimized arbors. We discovered that cortical axon branching appears to promote a low temporal dispersion of axonal latencies and a tight relationship between cortical distance and axonal latency. In addition, inhibitory basket cell axonal latencies may occur within a much narrower temporal window than excitatory spiny cell axons, which may help boost signal detection. Thus, to optimize neuronal network communication we find that a modest excess of axonal wire is traded-off to enhance arbor temporal economy and precision. Our results offer insight into the principles of brain organization and communication in and development of grey matter, where temporal precision is a crucial prerequisite for coincidence detection, synchronization and rapid network oscillations

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic