Locating Depots for Capacitated Vehicle Routing

We study a location-routing problem in the context of capacitated vehicle routing. The input is a set of demand locations in a metric space and a fleet of k vehicles each of capacity Q. The objective is to locate k depots, one for each vehicle, and compute routes for the vehicles so that all demands are satisfied and the total cost is minimized. Our main result is a constant-factor approximation algorithm for this problem. To achieve this result, we reduce to the k-median-forest problem, which generalizes both k-median and minimum spanning tree, and which might be of independent interest. We give a (3+c)-approximation algorithm for k-median-forest, which leads to a (12+c)-approximation algorithm for the above location-routing problem, for any constant c>0. The algorithm for k-median-forest is just t-swap local search, and we prove that it has locality gap 3+2/t; this generalizes the corresponding result known for k-median. Finally we consider the "non-uniform" k-median-forest problem which has different cost functions for the MST and k-median parts. We show that the locality gap for this problem is unbounded even under multi-swaps, which contrasts with the uniform case. Nevertheless, we obtain a constant-factor approximation algorithm, using an LP based approach.Comment: 12 pages, 1 figur

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

Stochastic Vehicle Routing with Recourse

We study the classic Vehicle Routing Problem in the setting of stochastic optimization with recourse. StochVRP is a two-stage optimization problem, where demand is satisfied using two routes: fixed and recourse. The fixed route is computed using only a demand distribution. Then after observing the demand instantiations, a recourse route is computed -- but costs here become more expensive by a factor lambda. We present an O(log^2 n log(n lambda))-approximation algorithm for this stochastic routing problem, under arbitrary distributions. The main idea in this result is relating StochVRP to a special case of submodular orienteering, called knapsack rank-function orienteering. We also give a better approximation ratio for knapsack rank-function orienteering than what follows from prior work. Finally, we provide a Unique Games Conjecture based omega(1) hardness of approximation for StochVRP, even on star-like metrics on which our algorithm achieves a logarithmic approximation.Comment: 20 Pages, 1 figure Revision corrects the statement and proof of Theorem 1.

Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture

Full-length mRNAs transfer between adjacent mammalian cells via direct cell-to-cell connections called tunneling nanotubes (TNTs). However, the extent of mRNA transfer at the transcriptome-wide level (the 'transferome') is unknown. Here, we analyzed the transferome in an human-mouse cell co-culture model using RNA-sequencing. We found that mRNA transfer is non-selective, prevalent across the human transcriptome, and that the amount of transfer to mouse embryonic fibroblasts (MEFs) strongly correlates with the endogenous level of gene expression in donor human breast cancer cells. Typically, <1% of endogenous mRNAs undergo transfer. Non-selective, expression-dependent RNA transfer was further validated using synthetic reporters. RNA transfer appears contact-dependent via TNTs, as exemplified for several mRNAs. Notably, significant differential changes in the native MEF transcriptome were observed in response to co-culture, including the upregulation of multiple cancer and cancer-associated fibroblast-related genes and pathways. Together, these results lead us to suggest that TNT-mediated RNA transfer could be a phenomenon of physiological importance under both normal and pathogenic conditions

RNA-controlled nucleocytoplasmic shuttling of mRNA decay factors regulates mRNA synthesis and a novel mRNA decay pathway

mRNA level is controlled by factors that mediate both mRNA synthesis and decay, including the 5' to 3' exonuclease Xrn1. Here we show that nucleocytoplasmic shuttling of several yeast mRNA decay factors plays a key role in determining both mRNA synthesis and decay. Shuttling is regulated by RNAcontrolled binding of the karyopherin Kap120 to two nuclear localization sequences (NLSs) in Xrn1, location of one ofwhich is conserved fromyeast to human. The decaying RNA binds and masks NLS1, establishing a link between mRNA decay and Xrn1 shuttling. Preventing Xrn1 import, either by deleting KAP120 or mutating the two Xrn1 NLSs, compromises transcription and, unexpectedly, also cytoplasmic decay, uncovering a cytoplasmic decay pathway that initiates in the nucleus.MostmRNAs are degraded by both pathways - the ratio between them represents a full spectrum. Importantly, Xrn1 shuttling is required for proper responses to environmental changes, e.g., fluctuating temperatures, involving proper changes in mRNA abundance and in cell proliferation rate

Joint transmitter selection and resource management strategy based on low probability of intercept optimization for distributed radar networks

In this paper, a joint transmitter selection and resource management (JTSRM) strategy based on low probability of intercept (LPI) is proposed for target tracking in distributed radar network system. The basis of the JTSRM strategy is to utilize the optimization technique to control transmitting resources of radar networks in order to improve the LPI performance, while guaranteeing a specified target tracking accuracy. The weighted intercept probability and transmit power of radar networks is defined and subsequently employed as the optimization criterion for the JTSRM strategy. The resulting optimization problem is to minimize the LPI performance criterion of radar networks by optimizing the revisit interval, dwell time, transmitter selection, and transmit power subject to a desired target tracking performance and some resource constraints. An efficient and fast three‐step solution technique is also developed to solve this problem. The presented mechanism implements the optimal working parameters based on the feedback information in the tracking recursion cycle in order to improve the LPI performance for radar networks. Numerical simulations are provided to verify the superior performance of the proposed JTSRM strategy

Staphylococcus aureus α-Toxin Triggers the Synthesis of B-Cell Lymphoma 3 by Human Platelets

The frequency and severity of bacteremic infections has increased over the last decade and bacterial endovascular infections (i.e., sepsis or endocarditis) are associated with high morbidity and mortality. Bacteria or secreted bacterial products modulate platelet function and, as a result, affect platelet accumulation at sites of vascular infection and inflammation. However, whether bacterial products regulate synthetic events in platelets is not known. In the present study, we determined if prolonged contact with staphylococcal α-toxin signals platelets to synthesize B-cell lymphoma (Bcl-3), a protein that regulates clot retraction in murine and human platelets. We show that α-toxin induced αIIbβ3-dependent aggregation (EC50 2.98 µg/mL ± 0.64 µg/mL) and, over time, significantly altered platelet morphology and stimulated de novo accumulation of Bcl-3 protein in platelets. Adherence to collagen or fibrinogen also increased the expression of Bcl-3 protein by platelets. α-toxin altered Bcl-3 protein expression patterns in platelets adherent to collagen, but not fibrinogen. Pretreatment of platelets with inhibitors of protein synthesis or the mammalian Target of Rapamycin (mTOR) decreased Bcl-3 protein expression in α-toxin stimulated platelets. In conclusion, Staphylococcus aureus-derived α-toxin, a pore forming exotoxin, exerts immediate (i.e., aggregation) and prolonged (i.e., protein synthesis) responses in platelets, which may contribute to increased thrombotic events associated with gram-positive sepsis or endocarditis

An mRNA decapping mutant deficient in P body assembly limits mRNA stabilization in response to osmotic stress

Yeast is exposed to changing environmental conditions and must adapt its genetic program to provide a homeostatic intracellular environment. An important stress for yeast in the wild is high osmolarity. A key response to this stress is increased mRNA stability primarily by the inhibition of deadenylation. We previously demonstrated that mutations in decapping activators (edc3∆ lsm4∆C), which result in defects in P body assembly, can destabilize mRNA under unstressed conditions. We wished to examine whether mRNA would be destabilized in the edc3∆ lsm4∆C mutant as compared to the wild-type in response to osmotic stress, when P bodies are intense and numerous. Our results show that the edc3∆ lsm4∆C mutant limits the mRNA stability in response to osmotic stress, while the magnitude of stabilization was similar as compared to the wild-type. The reduced mRNA stability in the edc3∆ lsm4∆C mutant was correlated with a shorter PGK1 poly(A) tail. Similarly, the MFA2 mRNA was more rapidly deadenylated as well as significantly stabilized in the ccr4∆ deadenylation mutant in the edc3∆ lsm4∆C background. These results suggest a role for these decapping factors in stabilizing mRNA and may implicate P bodies as sites of reduced mRNA degradation

Substrate specificity of the TRAMP nuclear surveillance complexes

During nuclear surveillance in yeast and human cells, the RNA exosome functions together with the TRAMP complexes. Here, the authors defined the protein composition of the TRAMP complexes and identified specific RNA binding sites for the different TRAMP components

Global Self-Organization of the Cellular Metabolic Structure

Background: Over many years, it has been assumed that enzymes work either in an isolated way, or organized in small catalytic groups. Several studies performed using "metabolic networks models'' are helping to understand the degree of functional complexity that characterizes enzymatic dynamic systems. In a previous work, we used "dissipative metabolic networks'' (DMNs) to show that enzymes can present a self-organized global functional structure, in which several sets of enzymes are always in an active state, whereas the rest of molecular catalytic sets exhibit dynamics of on-off changing states. We suggested that this kind of global metabolic dynamics might be a genuine and universal functional configuration of the cellular metabolic structure, common to all living cells. Later, a different group has shown experimentally that this kind of functional structure does, indeed, exist in several microorganisms. Methodology/Principal Findings: Here we have analyzed around 2.500.000 different DMNs in order to investigate the underlying mechanism of this dynamic global configuration. The numerical analyses that we have performed show that this global configuration is an emergent property inherent to the cellular metabolic dynamics. Concretely, we have found that the existence of a high number of enzymatic subsystems belonging to the DMNs is the fundamental element for the spontaneous emergence of a functional reactive structure characterized by a metabolic core formed by several sets of enzymes always in an active state. Conclusions/Significance: This self-organized dynamic structure seems to be an intrinsic characteristic of metabolism, common to all living cellular organisms. To better understand cellular functionality, it will be crucial to structurally characterize these enzymatic self-organized global structures.Supported by the Spanish Ministry of Science and Education Grants MTM2005-01504, MTM2004-04665, partly with FEDER funds, and by the Basque Government, Grant IT252-07