Simultaneous Embeddings with Few Bends and Crossings

A simultaneous embedding with fixed edges (SEFE) of two planar graphs $R$ and $B$ is a pair of plane drawings of $R$ and $B$ that coincide when restricted to the common vertices and edges of $R$ and $B$. We show that whenever $R$ and $B$ admit a SEFE, they also admit a SEFE in which every edge is a polygonal curve with few bends and every pair of edges has few crossings. Specifically: (1) if $R$ and $B$ are trees then one bend per edge and four crossings per edge pair suffice (and one bend per edge is sometimes necessary), (2) if $R$ is a planar graph and $B$ is a tree then six bends per edge and eight crossings per edge pair suffice, and (3) if $R$ and $B$ are planar graphs then six bends per edge and sixteen crossings per edge pair suffice. Our results improve on a paper by Grilli et al. (GD'14), which proves that nine bends per edge suffice, and on a paper by Chan et al. (GD'14), which proves that twenty-four crossings per edge pair suffice.Comment: Full version of the paper "Simultaneous Embeddings with Few Bends and Crossings" accepted at GD '1

Islamic Monetary Economics: Insights from the Literature

This chapter reviews critical early literature of Islamic monetary economics. The prohibition of Riba has imposed challenges on Islamic economists to come up with the viable alternatives to achieve Islamic monetary policy goals. Our extensive review of theoretical and empirical literature indicates that equity based profit- and loss-sharing instruments have been proposed for conducting open market operations in an interest-free economy. Theoretically, the central bank can achieve desired goals by controlling money supply and profit-sharing ratios. The findings from empirical literature suggest that money demand tend to be more stable in an interest-free economy. Whether monetary transmission works through Islamic banking channel is controversial, but the literature is growing. These findings are not surprising as majority Muslim countries lack sustainable and equitable economic growth. Moreover, these countries suffer from higher inflation and unemployment with little or no monetary freedom due to fixed exchange rate regime, shallow financial markets and strict capital control

Earthquake Rupture in Fault Zones With Along‐Strike Material Heterogeneity

Geological and geophysical observations reveal along‐strike fault zone heterogeneity on major strike‐slip faults, which can play a significant role in earthquake rupture propagation and termination. I present 2‐D dynamic rupture simulations to demonstrate rupture characteristics in such heterogeneous fault zone structure. The modeled rupture is nucleated in a damaged fault zone and propagates on a preexisting fault toward the zone of intact rocks. There is an intermediate range of nucleation lengths that only allow rupture to spontaneously propagate in the damaged fault zone but not in a homogeneous medium given the same stresses and frictional parameters. Rupture with an intermediate nucleation length tends to stop when it reaches the zone of intact rocks for uniform fault stress conditions, especially when the rupture propagation distance in the damaged fault zone is relatively short and when the damaged fault zone is relatively narrow or smooth in the fault‐normal direction. Pronounced small‐scale heterogeneity within the damaged fault zone also contributes to such early rupture termination. In asymmetric fault zones bisected by a bimaterial fault, rupture moving in the direction of slip of faster rocks tends to terminate under the same conditions as in symmetric fault zones, whereas rupture moving in the direction of slip of slower rocks can penetrate into the zone of intact rocks. A sufficiently large asperity located at the edge of the zone of intact rocks also allows break‐through rupture. The results suggest that the along‐strike fault zone heterogeneity can play a critical role in seismicity distribution.Plain Language SummaryNatural faults are surrounded by a zone of deformed rocks to accommodate strain localization. Such fault zone is not continuous along the fault, but rather includes segments of relatively damaged rocks adjacent to segments of relatively intact rocks. By simulating the dynamic interactions between fault stress, friction, and fault zone heterogeneities during the earthquake rupture process, I show that rupture is more likely to spontaneously propagate inside the damaged fault zone and stop when it reaches the relatively intact zone for uniform fault stress conditions. This phenomenon is less pronounced when the damaged fault zone becomes wider, sharper, and more damaged, indicating a higher likelihood of having large earthquakes that can penetrate into the relatively intact zone on more mature faults. The results suggest that a priori knowledge of the fault zone heterogeneity is critical for understanding the spatial distribution of earthquakes and the likelihood of having large earthquakes.Key PointsRupture nucleated in a damaged fault zone tends to terminate when it propagates along strike to an intact zone for uniform fault stressesRupture tends to penetrate into the relatively intact zone when the damaged fault zone becomes wider, sharper, and more damagedAn asperity at the edge of the relatively intact zone can facilitate rupture when its size is comparable to the nucleation half‐lengthPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147204/1/jgrb53125_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147204/2/jgrb53125.pd

Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells

IL-2 is the primary growth factor for promoting survival and proliferation of activated T cells that occurs following engagement of the Janus Kinase (JAK)1-3/and Signal Transducer and Activator of Transcription (STAT) 5 signaling pathway. STAT5 has two isoforms: STAT5A and STAT5B ( commonly referred to as STAT5) which, in T cells, play redundant roles transcribing cell cycle and survival genes. As such, inhibition of STAT5 by a variety of mechanisms can rapidly induce apoptosis in certain lymphoid tumor cells, suggesting that it and its target genes represent therapeutic targets to control certain lymphoid diseases. To search for these molecules we aligned IL-2 regulated genes detected by Affymetrix gene expression microarrays with the STAT5 cistrome identified by chip-on-ChIP analysis in an IL-2-dependent human leukemia cell line, Kit225. Select overlapping genes were then validated using qRT(2)PCR medium-throughput arrays in human PHA-activated PBMCs. Of 19 putative genes, one key regulator of T cell receptor signaling, PDE4B, was identified as a novel target, which was readily up-regulated at the protein level (3 h) in IL-2 stimulated, activated human PBMCs. Surprisingly, only purified CD8+ primary T-cells expressed PDE4B, but not CD4+ cells. Moreover, PDE4B was found to be highly expressed in CD4+ lymphoid cancer cells, which suggests that it may represent a physiological role unique to the CD8+ and lymphoid cancer cells and thus might represent a target for pharmaceutical intervention for certain lymphoid diseases

Aquatic Ecotoxicity Testing of Nanoparticles—The Quest To Disclose Nanoparticle Effects

The number of products on the market containing engineered nanoparticles (ENPs) has increased significantly, and concerns have been raised regarding their ecotoxicological effects. Environmental safety assessments as well as relevant and reliable ecotoxicological data are required for the safe and sustainable use of ENPs. Although the number of publications on the ecotoxicological effects and uptake of ENPs is rapidly expanding, the applicability of the reported data for hazard assessment is questionable. A major knowledge gap is whether nanoparticle effects occur when test organisms are exposed to ENPs in aquatic test systems. Filling this gap is not straightforward, because of the broad range of ENPs and the different behavior of ENPs compared to “ordinary” (dissolved) chemicals in the ecotoxicity test systems. The risk of generating false negatives, and false positives, in the currently used tests is high, and in most cases difficult to assess. This Review outlines some of the pitfalls in the aquatic toxicity testing of ENPs which may lead to misinterpretation of test results. Response types are also proposed to reveal potential nanoparticle effects in the aquatic test organisms

(Q)SAR Modelling of Nanomaterial Toxicity - A Critical Review

There is an increasing recognition that nanomaterials pose a risk to human health, and that the novel engineered nanomaterials (ENMs) in the nanotechnology industry and their increasing industrial usage poses the most immediate problem for hazard assessment, as many of them remain untested. The large number of materials and their variants (different sizes and coatings for instance) that require testing and ethical pressure towards non-animal testing means that expensive animal bioassay is precluded, and the use of (quantitative) structure activity relationships ((Q)SAR) models as an alternative source of hazard information should be explored. (Q)SAR modelling can be applied to fill the critical knowledge gaps by making the best use of existing data, prioritize physicochemical parameters driving toxicity, and provide practical solutions to the risk assessment problems caused by the diversity of ENMs. This paper covers the core components required for successful application of (Q)SAR technologies to ENMs toxicity prediction, and summarizes the published nano-(Q)SAR studies and outlines the challenges ahead for nano-(Q)SAR modelling. It provides a critical review of (1) the present status of the availability of ENMs characterization/toxicity data, (2) the characterization of nanostructures that meets the need of (Q)SAR analysis, (3) the summary of published nano-(Q)SAR studies and their limitations, (4) the in silico tools for (Q)SAR screening of nanotoxicity and (5) the prospective directions for the development of nano-(Q)SAR models

Virosome-Formulated Plasmodium falciparum AMA-1 & CSP Derived Peptides as Malaria Vaccine: Randomized Phase 1b Trial in Semi-Immune Adults & Children

BACKGROUND\ud \ud This trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children.\ud \ud METHODS\ud \ud The design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations. 10 adults and 40 children (aged 5-9 years) living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal®V on day 0 and 90.\ud \ud RESULTS\ud \ud No serious or severe adverse events (AEs) related to the vaccines were observed. The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal®V group compared to the PEV3B group (p = 0.014). In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal®V control group. Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children. As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (0.0035 episodes per day at risk for PEV3B vs. 0.0069 for Inflexal®V; RR  = 0.50 [95%-CI: 0.29-0.88], p = 0.02).\ud \ud CONCLUSION\ud \ud These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines.\ud \ud TRIAL REGISTRATION\ud \ud ClinicalTrials.gov NCT00513669

Regional Environmental Breadth Predicts Geographic Range and Longevity in Fossil Marine Genera

Geographic range is a good indicator of extinction susceptibility in fossil marine species and higher taxa. The widely-recognized positive correlation between geographic range and taxonomic duration is typically attributed to either accumulating geographic range with age or an extinction buffering effect, whereby cosmopolitan taxa persist longer because they are reintroduced by dispersal from remote source populations after local extinction. The former hypothesis predicts that all taxa within a region should have equal probabilities of extinction regardless of global distributions while the latter predicts that cosmopolitan genera will have greater survivorship within a region than endemics within the same region. Here we test the assumption that all taxa within a region have equal likelihoods of extinction.We use North American and European occurrences of marine genera from the Paleobiology Database and the areal extent of marine sedimentary cover in North America to show that endemic and cosmopolitan fossil marine genera have significantly different range-duration relationships and that broad geographic range and longevity are both predicted by regional environmental breadth. Specifically, genera that occur outside of the focal region are significantly longer lived and have larger geographic ranges and environmental breadths within the focal region than do their endemic counterparts, even after controlling for differences in sampling intensity. Analyses of the number of paleoenvironmental zones occupied by endemic and cosmopolitan genera suggest that the number of paleoenvironmental zones occupied is a key factor of geographic range that promotes genus survivorship.Wide environmental tolerances within a single region predict both broad geographic range and increased longevity in marine genera over evolutionary time. This result provides a specific driving mechanism for the spatial and temporal distributions of marine genera at regional and global scales and is consistent with the niche-breadth hypothesis operating on macroevolutionary timescales

Interaction between polymorphisms of the Human Leukocyte Antigen and HPV-16 Variants on the risk of invasive cervical cancer

<p>Abstract</p> <p>Background</p> <p>Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability.</p> <p>Methods</p> <p>We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for <it>HLA-DQA1</it>, <it>DRB1 </it>and <it>DQB1 </it>genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis.</p> <p>Results</p> <p>European (E), Asian-American (AA) and African (Af) variants were identified. Here we show that inverse association between <it>DQB1*05 </it>(adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39–1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers (OR = 0.27; 95%CI: 0.10–0.75). We observed similar proportions of <it>HLA DRB1*1302 </it>carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases (p = 0.03, Fisher exact test). A positive association with <it>DRB1*15 </it>was observed in both groups of women harboring either E (OR = 2.99; 95% CI: 1.13–7.86) or AA variants (OR = 2.34; 95% CI: 1.00–5.46). There was an inverse association between <it>DRB1*04 </it>and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the <it>E6 </it>gene (OR = 0.27; 95% CI: 0.08–0.96). An inverse association between <it>DQB1*05 </it>and cases carrying 350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15–0.89).</p> <p>Conclusion</p> <p>Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants.</p