An Evolutionary Algorithm to Generate Real Urban Traffic Flows

In this article we present a strategy based on an evolutionary algorithm to calculate the real vehicle ows in cities according to data from sensors placed in the streets. We have worked with a map imported from OpenStreetMap into the SUMO traffic simulator so that the resulting scenarios can be used to perform different optimizations with the confidence of being able to work with a traffic distribution close to reality. We have compared the results of our algorithm to other competitors and achieved results that replicate the real traffic distribution with a precision higher than 90%.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This research has been partially funded by project number 8.06/5.47.4142 in collaboration with the VSB-Technical University of Ostrava and Universidad de Málaga UMA/FEDER FC14-TIC36, programa de fortalecimiento de las capacidades de I+D+i en las universidades 2014-2015, de la Consejería de Economía, Innovación, Ciencia y Empleo, cofinanciado por el fondo europeo de desarrollo regional (FEDER). Also, partially funded by the Spanish MINECO project TIN2014-57341-R (http://moveon.lcc.uma.es). The authors would like to thank the FEDER of European Union for financial support via project Movilidad Inteligente: Wi-Fi, Rutas y Contaminación (maxCT) of the "Programa Operativo FEDER de Andalucía 2014-2020. We also thank all Agency of Public Works of Andalusia Regional Government staff and researchers for their dedication and professionalism. Daniel H. Stolfi is supported by a FPU grant (FPU13/00954) from the Spanish Ministry of Education, Culture and Sports

The safety of over-the-counter niacin. A randomized placebo-controlled trial [ISRCTN18054903]

BACKGROUND: Niacin is widely available over the counter (OTC). We sought to determine the safety of 500 mg immediate release niacin, when healthy individuals use them as directed. METHODS: 51 female and 17 male healthy volunteers (mean age 27 years SD 4.4) participated in a randomized placebo-controlled blinded trial of a single dose of an OTC, immediate-release niacin 500 mg (n = 33), or a single dose of placebo (n = 35) on an empty stomach. The outcomes measured were self-reported incidence of flushing and other adverse effects. RESULTS: 33 volunteers on niacin (100%) and 1 volunteer on placebo (3%) flushed (relative risk 35, 95% confidence interval (CI) 6.8–194.7). Mean time to flushing on niacin was 18.2 min (95% CI: 12.7–23.6); mean duration of flushing was 75.4 min (95% CI: 62.5–88.2). Other adverse effects occurred commonly in the niacin group: chills (51.5% vs. 0%, P < .0001), generalized pruritus (75% vs. 0%, P = <.001), gastrointestinal upset (30% vs. 3%, P = .005), and cutaneous tingling (30% vs. 0%, P = <.001). Six participants did not tolerate the adverse effects of niacin and 3 required medical attention. CONCLUSION: Clinicians counseling patients about niacin should alert patients not only about flushing but also about gastrointestinal symptoms, the most severe in this study. They should not trust that patients would receive information about these side effects or their prevention (with aspirin) from the OTC packet insert

Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules

Cytoplasmic dynein is a dimeric AAA+ motor protein that performs critical roles in eukaryotic cells by moving along microtubules using ATP. Here using cryo-electron microscopy we directly observe the structure of Dictyostelium discoideum dynein dimers on microtubules at near-physiological ATP concentrations. They display remarkable flexibility at a hinge close to the microtubule binding domain (the stalkhead) producing a wide range of head positions. About half the molecules have the two heads separated from one another, with both leading and trailing motors attached to the microtubule. The other half have the two heads and stalks closely superposed in a front-to-back arrangement of the AAA+ rings, suggesting specific contact between the heads. All stalks point towards the microtubule minus end. Mean stalk angles depend on the separation between their stalkheads, which allows estimation of inter-head tension. These findings provide a structural framework for understanding dynein’s directionality and unusual stepping behaviour

The human cytomegalovirus ul11 protein interacts with the receptor tyrosine phosphatase cd45, resulting in functional paralysis of t cells

Human cytomegalovirus (CMV) exerts diverse and complex effects on the immune system, not all of which have been attributed to viral genes. Acute CMV infection results in transient restrictions in T cell proliferative ability, which can impair the control of the virus and increase the risk of secondary infections in patients with weakened or immature immune systems. In a search for new immunomodulatory proteins, we investigated the UL11 protein, a member of the CMV RL11 family. This protein family is defined by the RL11 domain, which has homology to immunoglobulin domains and adenoviral immunomodulatory proteins. We show that pUL11 is expressed on the cell surface and induces intercellular interactions with leukocytes. This was demonstrated to be due to the interaction of pUL11 with the receptor tyrosine phosphatase CD45, identified by mass spectrometry analysis of pUL11-associated proteins. CD45 expression is sufficient to mediate the interaction with pUL11 and is required for pUL11 binding to T cells, indicating that pUL11 is a specific CD45 ligand. CD45 has a pivotal function regulating T cell signaling thresholds; in its absence, the Src family kinase Lck is inactive and signaling through the T cell receptor (TCR) is therefore shut off. In the presence of pUL11, several CD45-mediated functions were inhibited. The induction of tyrosine phosphorylation of multiple signaling proteins upon TCR stimulation was reduced and T cell proliferation was impaired. We therefore conclude that pUL11 has immunosuppressive properties, and that disruption of T cell function via inhibition of CD45 is a previously unknown immunomodulatory strategy of CMV

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

Effects of cadmium and zinc on Procambarus clarkii: Simulation of the Aznalcóllar mining spill

Female red swamp crayfish, Procambarus clarkii, were exposed for 21 days in the laboratory to different dissolved concentrations of zinc (1000 µg L–1 and 3000 µg L–1) and cadmium (10 µg L–1 and 30 µg L–1), determined in the Guadiamar River after the Aznalcóllar mining spill (SW Spain). Female gonadosomatic and hepatosomatic indexes were analyzed at the end of the bioassay, and a general decrease in the gonadosomatic index and increase in the hepatosomatic index were observed in individuals at the same maturation stage, exposed to increasing heavy metal concentrations. Only the decrease in the gonadosomatic index values was significant at the highest zinc concentration. Decreases in gonadosomatic indexes were associated with reduced fecundity

Environmental and developmental factors driving xylem anatomy and micro‐density in black spruce

Wood density is the product of carbon allocation for structural growth and reflects thetrade-off between mechanical support and water conductivity. We tested a conceptualframework based on the assumption that micro-density depends on direct and indirect rela-tionships with endogenous and exogenous factors. The dynamics of wood formation, including timings and rates of cell division, cell enlarge-ment, and secondary wall deposition, were assessed from microcores collected weeklybetween 2002 and 2016 from five black spruce stands located along a latitudinal gradient inQuebec, Canada. Cell anatomy and micro-density were recorded by anatomical analyses andX-ray measurements. Our structural equation model explained 80% of micro-density variation within the tree-ring with direct effects of wall thickness (σ=0.61), cell diameter (σ=-0.51), and photoperiod(σ=-0.26). Wood formation dynamics had an indirect effect on micro-density. Micro-densityincreased under longer periods of cell-wall deposition and shorter durations of enlargement. Our results fill a critical gap in understanding the relationships underlying micro-densityvariation in conifers. We demonstrated that short-term responses to environmental variationscould be overridden by plastic responses that modulate cell differentiation. Our results pointto wood formation dynamics as a reliable predictor of carbon allocation in trees