Finding k-Dissimilar Paths with Minimum Collective Length

Shortest path computation is a fundamental problem in road networks. However, in many real-world scenarios, determining solely the shortest path is not enough. In this paper, we study the problem of finding k-Dissimilar Paths with Minimum Collective Length (kDPwML), which aims at computing a set of paths from a source s to a target t such that all paths are pairwise dissimilar by at least \theta and the sum of the path lengths is minimal. We introduce an exact algorithm for the kDPwML problem, which iterates over all possible s-t paths while employing two pruning techniques to reduce the prohibitively expensive computational cost. To achieve scalability, we also define the much smaller set of the simple single-via paths, and we adapt two algorithms for kDPwML queries to iterate over this set. Our experimental analysis on real road networks shows that iterating over all paths is impractical, while iterating over the set of simple single-via paths can lead to scalable solutions with only a small trade-off in the quality of the results.Comment: Extended version of the SIGSPATIAL'18 paper under the same titl

Nuclear Factor-κB-Independent Anti-Inflammatory Action of Salicylate in Human Endothelial Cells

In contrast to aspirin, salicylate, its active metabolite, possesses profound anti-inflammatory properties without blocking cyclooxygenase. Inhibition of the transcription factor nuclear factor-κB (NF-κB) has been discussed to play a role in the anti-inflammatory profile of salicylate. However, NF-κB-independent effects of salicylate have been assumed but have up to now been poorly investigated. Therefore, the aim of the present study was to investigate NF-κB-independent anti-inflammatory mechanisms of salicylate in human umbilical vein endothelial cells using interleukin-4 (IL-4) as NF-κB-independent proinflammatory stimulus and P-selectin as inflammatory read-out parameter. Using quantitative real-time reverse transcriptionpolymerase chain reaction, we found that salicylate decreases IL-4-induced P-selectin expression. As judged by Western blot analysis, salicylate increased endothelial heme oxygenase-1 (HO-1) protein levels. Using both the HO-1 inhibitor tin(II) protoporphyrin IX and HO-1 antisense oligonucleotides, we causally linked the induction of HO-1 to the decrease of P-selectin. Moreover, we were interested in the signaling mechanisms leading to the up-regulation of HO-1 by salicylate. c-Jun NH2-terminal kinase (JNK) was found to be activated by salicylate, and we could causally link this activation to the induction of HO-1 by using the JNK inhibitor 1,9-pyrazoloanthrone. By applying activator protein-1 (AP-1) decoys, it was shown that the transcription factor AP-1 is crucially involved in the up-regulation of HO-1 downstream of JNK. In summary, our study introduces HO-1 as novel NF-κB-independent anti-inflammatory target of salicylate in human endothelial cells. Moreover, we elucidated the JNK/AP-1 pathway as crucial for the induction of HO-1 by salicylate

Metalloporphyrins inactivate caspase-3 and -8

Activation of caspases represents one of the earliest biochemical indicators for apoptotic cell death. Therefore, measurement of caspase activity is a widely used and generally accepted method to determine apoptosis in a wide range of in vivo and in vitro settings. Numerous publications characterize the role of the heme-catabolizing enzyme heme oxygenase-1 (HO-1) in regulating apoptotic processes. Different metalloporphyrins representing inducers and inhibitors of this enzyme are often used, followed by assessment of apoptotic cell death. In the present work, we found that caspase-3-like activity, as well as activity of caspase-8 measured in either Fas (CD95) ligand-treated Jurkat T-lymphocytes or by the use of recombinant caspase-3 or -8, was inhibited by different metalloporphyrins (cobalt(III) protoporphyrin IX, tin and zinc II) protoporphyrin-IX). Moreover, employing the mouse model of Fas-induced liver apoptosis these properties of porphyrins could also be demonstrated in vivo. The metalloporphyrins were shown to inhibit caspase-3-mediated PARP cleavage. Molecular modeling studies demonstrated that porphyrins can occupy the active site of caspase-3 in an energetically favorable manner and in a binding mode similar to that of known inhibitors. The data shown here introduce metalloporphyrins as direct inhibitors of caspase activity. This finding points to the need for careful employment of metalloporphyrins as modulators of HO-1

Lensing by Lyman Limit Systems: Determining the Mass to Gas Ratio

We present a new method to determine the total mass-to-neutral gas ratio in Lyman-limits systems. The method exploits the relation between the neutral hydrogen column density and the magnification of background sources due to the weak gravitational lensing that these systems induce. Because weak lensing does not provide a direct measure of mass, one must use this relation in a statistical sense to solve for the average mass-to-gas ratio and its distribution. We use a detailed mock catalog of quasars (sources) and Lyman-limit systems (lenses) to demonstrate the applicability of this approach through our ability to recover the parameter. This mock catalog also allows us to check for systematics in the method and to sketch its limitations. For a universal constant mass-to-gas ratio and a sample of N quasars, we obtain an unbiased estimate of its value with 95% confidence limits (independent of its actual value) of +/- 140 {10^5/N)^0.5.Comment: 20 pages, 11 figures submitted to Ap

Single-parameter non-adiabatic quantized charge pumping

Controlled charge pumping in an AlGaAs/GaAs gated nanowire by single-parameter modulation is studied experimentally and theoretically. Transfer of integral multiples of the elementary charge per modulation cycle is clearly demonstrated. A simple theoretical model shows that such a quantized current can be generated via loading and unloading of a dynamic quasi-bound state. It demonstrates that non-adiabatic blockade of unwanted tunnel events can obliterate the requirement of having at least two phase-shifted periodic signals to realize quantized pumping. The simple configuration without multiple pumping signals might find wide application in metrological experiments and quantum electronics.Comment: 4 pages, 4 figure

History of depression and survival after acute myocardial infarction

Objective: To compare survival in post-myocardial (MI) participants from the Enhancing Recovery In Coronary Heart Disease (ENRICHD) clinical trial with a first episode of major depression (MD) and those with recurrent MID, which is a risk factor for mortality after acute MI. Recent reports suggest that the level of risk may depend on whether the comorbid MD is a first or a recurrent episode. Methods: Survival was compared over a median of 29 months in 370 patients with an initial episode of MD, 550 with recurrent MD, and 408 who were free of depression. Results: After adjusting for an all-cause mortality risk score, initial Beck Depression Inventory score, and the use of selective serotonin reuptake inhibitor antidepressants, patients with a first episode of MD had poorer survival (18.4% all-cause mortality) than those with recurrent MD (11.8%) (hazard ratio (HR)=1.4; 95% Confidence Interval (CI)=1.0-2.0; p=.05). Both first depression (HR=3.1; 95% CI=1.6-6.1; p=.001) and recurrent MD (HR=2.2; 95% CI=1.1-4.4; p=.03) had significantly poorer survival than did the nondepressed patients (3.4%). A secondary analysis of deaths classified as probably due to a cardiovascular cause resulted in similar HRs, but the difference between depression groups was not significant. Conclusions: Both initial and recurrent episodes of MD predict shorter survival after acute MI, but initial MD episodes are more strongly predictive than recurrent episodes. Exploratory analyses suggest that this cannot be explained by more severe heart disease at index, poorer response to depression treatment, or a higher risk of cerebrovascular disease in patients with initial MD episodes

The modulation of the gamma-ray emission from the binary LS 5039

Gamma-ray binaries, composed of a massive star and compact object, have been established as a new class of sources of very high energy (VHE) photons. The gamma-rays are produced by inverse Compton scattering of the stellar light by VHE electrons accelerated in the vicinity of the compact object. The VHE emission from LS 5039 displays an orbital modulation. The inverse Compton spectrum depends on the angle between the incoming and outgoing photon in the electron rest frame. Since the angle at which an observer sees the star and electrons changes with the orbit, a phase dependence of the spectrum is expected. The phase-dependent spectrum of LS 5039 is calculated, assuming a continuous injection of electrons. The shape of the electron distribution depends on the injected power-law and on the magnetic field intensity. Anisotropic scattering produces hard emission at inferior conjunction, when attenuation due to pair production of the VHE gamma-rays on star light is minimum. The computed lightcurve and spectra provide good fits to the HESS and EGRET observations, except at phases of maximum attenuation where pair cascade emission may be significant for HESS. Detailed predictions are made for a modulation in the GLAST energy range. The magnetic field intensity at periastron is 0.8+-0.2 G. Anisotropic inverse Compton scattering plays a major role in LS 5039. The derived magnetic field intensity, injection energy and slope suggest a rotation-powered pulsar wind nebula. Gamma-ray binaries are promising sources to study the environment of pulsars on small scales.Comment: 12 pages, 8 figures, accepted for publication in A&

Operon conservation and the evolution of trans-splicing in the phylum Nematoda

The nematode Caenorhabditis elegans is unique among model animals in that many of its genes are cotranscribed as polycistronic pre-mRNAs from operons. The mechanism by which these operonic transcripts are resolved into mature mRNAs includes trans-splicing to a family of SL2-like spliced leader exons. SL2-like spliced leaders are distinct from SL1, the major spliced leader in C. elegans and other nematode species. We surveyed five additional nematode species, representing three of the five major clades of the phylum Nematoda, for the presence of operons and the use of trans-spliced leaders in resolution of polycistronic pre-mRNAs. Conserved operons were found in Pristionchus pacificus, Nippostrongylus brasiliensis, Strongyloides ratti, Brugia malayi, and Ascaris suum. In nematodes closely related to the rhabditine C. elegans, a related family of SL2-like spliced leaders is used for operonic transcript resolution. However, in the tylenchine S. ratti operonic transcripts are resolved using a family of spliced leaders related to SL1. Non-operonic genes in S. ratti may also receive these SL1 variants. In the spirurine nematodes B. malayi and A. suum operonic transcripts are resolved using SL1. Mapping these phenotypes onto the robust molecular phylogeny for the Nematoda suggests that operons evolved before SL2-like spliced leaders, which are an evolutionary invention of the rhabditine lineage

Properties of Classical and Quantum Jensen-Shannon Divergence

Jensen-Shannon divergence (JD) is a symmetrized and smoothed version of the most important divergence measure of information theory, Kullback divergence. As opposed to Kullback divergence it determines in a very direct way a metric; indeed, it is the square of a metric. We consider a family of divergence measures (JD_alpha for alpha>0), the Jensen divergences of order alpha, which generalize JD as JD_1=JD. Using a result of Schoenberg, we prove that JD_alpha is the square of a metric for alpha lies in the interval (0,2], and that the resulting metric space of probability distributions can be isometrically embedded in a real Hilbert space. Quantum Jensen-Shannon divergence (QJD) is a symmetrized and smoothed version of quantum relative entropy and can be extended to a family of quantum Jensen divergences of order alpha (QJD_alpha). We strengthen results by Lamberti et al. by proving that for qubits and pure states, QJD_alpha^1/2 is a metric space which can be isometrically embedded in a real Hilbert space when alpha lies in the interval (0,2]. In analogy with Burbea and Rao's generalization of JD, we also define general QJD by associating a Jensen-type quantity to any weighted family of states. Appropriate interpretations of quantities introduced are discussed and bounds are derived in terms of the total variation and trace distance.Comment: 13 pages, LaTeX, expanded contents, added references and corrected typo