The Complexity of Drawing a Graph in a Polygonal Region

We prove that the following problem is complete for the existential theory of the reals: Given a planar graph and a polygonal region, with some vertices of the graph assigned to points on the boundary of the region, place the remaining vertices to create a planar straight-line drawing of the graph inside the region. This strengthens an NP-hardness result by Patrignani on extending partial planar graph drawings. Our result is one of the first showing that a problem of drawing planar graphs with straight-line edges is hard for the existential theory of the reals. The complexity of the problem is open in the case of a simply connected region. We also show that, even for integer input coordinates, it is possible that drawing a graph in a polygonal region requires some vertices to be placed at irrational coordinates. By contrast, the coordinates are known to be bounded in the special case of a convex region, or for drawing a path in any polygonal region.Comment: Appears in the Proceedings of the 26th International Symposium on Graph Drawing and Network Visualization (GD 2018

The Glucuronyltransferase GlcAT-P Is Required for Stretch Growth of Peripheral Nerves in Drosophila

During development, the growth of the animal body is accompanied by a concomitant elongation of the peripheral nerves, which requires the elongation of integrated nerve fibers and the axons projecting therein. Although this process is of fundamental importance to almost all organisms of the animal kingdom, very little is known about the mechanisms regulating this process. Here, we describe the identification and characterization of novel mutant alleles of GlcAT-P, the Drosophila ortholog of the mammalian glucuronyltransferase b3gat1. GlcAT-P mutants reveal shorter larval peripheral nerves and an elongated ventral nerve cord (VNC). We show that GlcAT-P is expressed in a subset of neurons in the central brain hemispheres, in some motoneurons of the ventral nerve cord as well as in central and peripheral nerve glia. We demonstrate that in GlcAT-P mutants the VNC is under tension of shorter peripheral nerves suggesting that the VNC elongates as a consequence of tension imparted by retarded peripheral nerve growth during larval development. We also provide evidence that for growth of peripheral nerve fibers GlcAT-P is critically required in hemocytes; however, glial cells are also important in this process. The glial specific repo gene acts as a modifier of GlcAT-P and loss or reduction of repo function in a GlcAT-P mutant background enhances VNC elongation. We propose a model in which hemocytes are required for aspects of glial cell biology which in turn affects the elongation of peripheral nerves during larval development. Our data also identifies GlcAT-P as a first candidate gene involved in growth of integrated peripheral nerves and therefore establishes Drosophila as an amenable in-vivo model system to study this process at the cellular and molecular level in more detail

The DAC system and associations with acute leukemias and myelodysplastic syndromes

Imbalances of histone acetyltransferase (HAT) and deacetylase activity (DAC) that result in deregulated gene expression are commonly observed in leukemias. These alterations provide the basis for novel therapeutic approaches that target the epigenetic mechanisms implicated in leukemogenesis. As the acetylation status of histones has been linked to transcriptional regulation of genes involved particularly in differentiation and apoptosis, DAC inhibitors (DACi) have attracted considerable attention for treatment of hematologic malignancies. DACi encompass a structurally diverse family of compounds that are being explored as single agents as well as in combination with chemotherapeutic drugs, small molecule inhibitors of signaling pathways and hypomethylating agents. While DACi have shown clear evidence of activity in acute myeloid leukemia, myelodysplastic syndromes and lymphoid malignancies, their precise role in treatment of these different entities remain to be elucidated. Successful development of these compounds as elements of novel targeted treatment strategies for leukemia will require that clinical studies be performed in conjunction with translational research including efforts to identify predictive biomarkers

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

A genetic programming approach to development of clinical prediction models: A case study in symptomatic cardiovascular disease

BACKGROUND:Genetic programming (GP) is an evolutionary computing methodology capable of identifying complex, non-linear patterns in large data sets. Despite the potential advantages of GP over more typical, frequentist statistical approach methods, its applications to survival analyses are rare, at best. The aim of this study was to determine the utility of GP for the automatic development of clinical prediction models. METHODS:We compared GP against the commonly used Cox regression technique in terms of the development and performance of a cardiovascular risk score using data from the SMART study, a prospective cohort study of patients with symptomatic cardiovascular disease. The composite endpoint was cardiovascular death, non-fatal stroke, and myocardial infarction. A total of 3,873 patients aged 19-82 years were enrolled in the study 1996-2006. The cohort was split 70:30 into derivation and validation sets. The derivation set was used for development of both GP and Cox regression models. These models were then used to predict the discrete hazards at t = 1, 3, and 5 years. The predictive ability of both models was evaluated in terms of their risk discrimination and calibration using the validation set. RESULTS:The discrimination of both models was comparable. At time points t = 1, 3, and 5 years the C-index was 0.59, 0.69, 0.64 and 0.66, 0.70, 0.70 for the GP and Cox regression models respectively. At the same time points, the calibration of both models, which was assessed using calibration plots and the generalization of the Hosmer-Lemeshow test statistic, was also comparable, but with the Cox model being better calibrated to the validation data. CONCLUSION:Using empirical data, we demonstrated that a prediction model developed automatically by GP has predictive ability comparable to that of manually tuned Cox regression. The GP model was more complex, but it was developed in a fully automated way and comprised fewer covariates. Furthermore, it did not require the expertise normally needed for its derivation, thereby alleviating the knowledge elicitation bottleneck. Overall, GP demonstrated considerable potential as a method for the automated development of clinical prediction models for diagnostic and prognostic purposes

Winter desiccation and rapid changes in the live fuel moisture content of Calluna vulgaris

<p>Background: Dramatic reductions in early-spring Calluna vulgaris moisture content have been linked to extreme fire hazard and plant die-back.</p> <p>Aims: To investigate spatial and temporal variation in the fuel moisture content of Calluna vulgaris.</p> <p>Methods: Calluna vulgaris plants were sampled in different sites and seasons to examine vertical profiles in moisture content. Live moisture content was monitored throughout autumn 2003 and spring 2004. Changes were compared to trends in temperature, soil resistance and rainfall. The effect of exposure was examined by comparing shoot moisture content in sheltered and exposed locations.</p> <p>Results: Significant spatial and temporal variation in moisture content was observed. In spring rapid fluctuations in moisture coincided with periods of dry weather, low temperatures and frozen ground. Shoots from exposed locations had significantly lower moisture content when the ground was frozen.</p> <p>Conclusions: Significant declines in the live fuel moisture content of Calluna vulgaris are associated with physiological drought caused by cold, clear conditions and frozen ground. Over-winter damage to leaf cuticles reduces the ability of the plant to regulate water loss. Changes in moisture content can be rapid, and managers should be aware of the potential for extreme fire behaviour.</p&gt