A discrete MMAP for analysing the behaviour of a multi-state complex dynamic system subject to multiple events.

A complex multi-state system subject to different types of failures, repairable and/or nonrepairable, external shocks and preventive maintenance is modelled by considering a discrete Markovian arrival process with marked arrivals (D-MMAP). The internal performance of the system is composed of several degradation states partitioned into minor and major damage states according to the risk of failure. Random external events can produce failures throughout the system. If an external shock occurs, there may be an aggravation of the internal degradation, cumulative external damage or extreme external failure. The internal performance and the cumulative external damage are observed by random inspection. If major degradation is observed, the unit goes to the repair facility for preventive maintenance. If a repairable failure occurs then the system goes to corrective repair with different time distributions depending on the failure state. Time distributions for corrective repair and preventive maintenance depend on the failure state. Rewards and costs depending on the state at which the device failed or was inspected are introduced. The system is modelled and several measures of interest are built into transient and stationary regimes. A preventive maintenance policy is shown to determine the effectiveness of preventive maintenance and the optimum state of internal and cumulative external damage at which preventive maintenance should be taken into account. A numerical example is presented, revealing the efficacy of the model. Correlations between the numbers of different events over time and in non-overlapping intervals are calculated. The results are expressed in algorithmic-matrix form and are implemented computationally with Matlab.Junta de Andalucía, Spain, under the grant FQM307Ministerio de Economía y Competitividad, España, MTM2017-88708-PEuropean Regional Development Fund (ERDF

The evolutionary history of Drosophila buzzatii. XVII. Double mating and sperm predominance

Sperm predominance in males and double mating in females have been studied in 2 stocks of the cactophilic species Drosophila buzzatii. The relationship between double mating and total productivity of females was also ascertained. Our results show high values of sperm predominance and double mating. Moreover, female productivity is increased with a second mate. These results are discussed in relation to the mating strategy of this species.On a étudié la prédominance du sperme chez les mâles et le double accouplement chez les femelles dans 2 souches de l'espèce cactophile Drosophila buzzatii. La relation entre le double accouplement et la productivité totale des femelles a été aussi recherchée. Nos résultats montrent des valeurs élevées pour la prédominance du sperme et pour le double accouplement. De plus, on constate que la productivité des femelles est augmentée par un deuxième accouplement. Ces résultats sont discutés par rapport à la stratégie d'accouplement de cette espèce

Mind the numt: Finding informative mitochondrial markers in a giant grasshopper genome

H2020 Marie Sklodowska-Curie Actions, Grant/Award Number: 658706; Ministerio de Ciencia, Innovacion y Universidades, Grant/Award Number: PID2019-104952GB-I00/AEI/10.13039/501100011033The barcoding of the mitochondrial COX1 gene has been instrumental in cataloguing the tree of life, and in providing insights in the phylogeographic history of species. Yet, this strategy has encountered difficulties in major clades characterized by large genomes, which contain a high frequency of nuclear pseudogenes originating from the mitochondrial genome (numts). Here, we use the meadow grasshopper (Chorthippus parallelus), which possesses a giant genome of ~13 Gb, to identify mitochondrial genes that are underrepresented as numts, and test their use as informative phylogeographic markers. We recover the same full mitochondrial sequence using both whole genome and transcriptome sequencing, including functional protein‐coding genes and tRNAs. We show that a region of the mitogenome containing the COX1 gene, typically used in DNA barcoding, has disproportionally higher diversity and coverage than the rest of the mitogenome, consistent with multiple insertions of that region into the nuclear genome. By designing new markers in regions of less elevated diversity and coverage, we identify two mitochondrial genes that are less likely to be duplicated as numts. We show that, while these markers show high levels of incomplete lineage sorting between subspecies, as expected for mitochondrial genes, genetic variation reflects their phylogeographic history accurately. These findings allow us to identify useful mitochondrial markers for future studies in C. parallelus, an important biological system for evolutionary biology. More generally, this study exemplifies how non‐PCR‐based methods using next‐generation sequencing can be used to avoid numts in species characterized by large genomes, which have remained challenging to study in taxonomy and evolution.H2020 Marie Sklodowska-Curie Actions 658706Ministerio de Ciencia, Innovacion y Universidades PID2019-104952GB-I00/AEI/10.13039/50110001103

Genetic origins of social networks in rhesus macaques

This is the final version of the article. Available from the publisher via the DOI in this record.Sociality is believed to have evolved as a strategy for animals to cope with their environments. Yet the genetic basis of sociality remains unclear. Here we provide evidence that social network tendencies are heritable in a gregarious primate. The tendency for rhesus macaques, Macaca mulatta, to be tied affiliatively to others via connections mediated by their social partners - analogous to friends of friends in people - demonstrated additive genetic variance. Affiliative tendencies were predicted by genetic variation at two loci involved in serotonergic signalling, although this result did not withstand correction for multiple tests. Aggressive tendencies were also heritable and were related to reproductive output, a fitness proxy. Our findings suggest that, like humans, the skills and temperaments that shape the formation of multi-agent relationships have a genetic basis in nonhuman primates, and, as such, begin to fill the gaps in our understanding of the genetic basis of sociality.We thank Bonn Aure, Jacqueline Buhl, Monica Carlson, Matthew McConnell, Elizabeth Maldonado, David Paulsen, Cecilia Penedo & the Caribbean Primate Research Center (CPRC) for assistance, and Roger Mundry for the use of PSAM software. The authors were supported by NIMH grant R01-MH089484, an Incubator Award from the Duke Institute for Brain Sciences, and a Duke Center for Interdisciplinary Decision Sciences Fellowship to LJNB. The CPRC is supported by grant 8-P40 OD012217-25 from the National Center for Research Resources (NCRR) and the Office of Research Infrastructure Programs (ORIP) of the National Institutes of Health

Mexico City and the biogeochemistry of global urbanization

Mexico City is far advanced in its urban evolution, and cities in currently developing nations may soon follow a similar course. This paper investigates the strengths and weaknesses of infrastructures for the emerging megacities. The major driving force for infrastructure change in Mexico City is concern over air quality. Air chemistry data from recent field campaigns have been used to calculate fluxes in the atmosphere of the Valley of Mexico, for compounds that are important to biogeochemistry including methane (CH4), carbon monoxide (CO), nonmethane hydrocarbons (NMHCs), ammonia (NH3), sulfur dioxide (SO2), nitrogen oxides (NOx and NOy), soot, and dust. Leakage of liquified petroleum gas approached 10% during sampling periods, and automotive pollutant sources in Mexico City were found to match those in developed cities, despite a lower vehicle-to-person ratio of 0.1. Ammonia is released primarily from residential areas, at levels sufficient to titrate pollutant acids into particles across the entire basin. Enhancements of reduced nitrogen and hydrocarbons in the vapor phase skew the distribution of NOy species towards lower average deposition velocities. Partly as a result, downwind nutrient deposition occurs on a similar scale as nitrogen fixation across Central America, and augments marine nitrate upwelling. Dust suspension from unpaved roads and from the bed of Lake Texcoco was found to be comparable to that occurring on the periphery of the Sahara, Arabian, and Gobi deserts. In addition, sodium chloride (NaCl) in the dust may support heterogeneous chlorine oxide (ClOx) chemistry. The insights from our Mexico City analysis have been tentatively applied to the upcoming urbanization of Asia

Monitoring blood potassium concentration in hemodialysis patients by quantifying T-wave morphology dynamics.

We investigated the ability of time-warping-based ECG-derived markers of T-wave morphology changes in time ([Formula: see text]) and amplitude ([Formula: see text]), as well as their non-linear components ([Formula: see text] and [Formula: see text]), and the heart rate corrected counterpart ([Formula: see text]), to monitor potassium concentration ([Formula: see text]) changes ([Formula: see text]) in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). We compared the performance of the proposed time-warping markers, together with other previously proposed [Formula: see text] markers, such as T-wave width ([Formula: see text]) and T-wave slope-to-amplitude ratio ([Formula: see text]), when computed from standard ECG leads as well as from principal component analysis (PCA)-based leads. 48-hour ECG recordings and a set of hourly-collected blood samples from 29 ESRD-HD patients were acquired. Values of [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] were calculated by comparing the morphology of the mean warped T-waves (MWTWs) derived at each hour along the HD with that from a reference MWTW, measured at the end of the HD. From the same MWTWs [Formula: see text] and [Formula: see text] were also extracted. Similarly, [Formula: see text] was calculated as the difference between the [Formula: see text] values at each hour and the [Formula: see text] reference level at the end of the HD session. We found that [Formula: see text] and [Formula: see text] showed higher correlation coefficients with [Formula: see text] than [Formula: see text]-Spearman's ([Formula: see text]) and Pearson's (r)-and [Formula: see text]-Spearman's ([Formula: see text])-in both SL and PCA approaches being the intra-patient median [Formula: see text] and [Formula: see text] in SL and [Formula: see text] and [Formula: see text] in PCA respectively. Our findings would point at [Formula: see text] and [Formula: see text] as the most suitable surrogate of [Formula: see text], suggesting that they could be potentially useful for non-invasive monitoring of ESRD-HD patients in hospital, as well as in ambulatory settings. Therefore, the tracking of T-wave morphology variations by means of time-warping analysis could improve continuous and remote [Formula: see text] monitoring of ESRD-HD patients and flagging risk of [Formula: see text]-related cardiovascular events

Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration

Human genetic studies have suggested that polymorphisms of the GABRA2 gene encoding the GABA(A) α2-subunit are associated with ethanol dependence. Variations in this gene also convey sensitivity to the subjective effects of ethanol, indicating a role in mediating ethanol-related behaviours. We therefore investigated the consequences of deleting the α2-subunit on the ataxic and rewarding properties of ethanol in mice. Ataxic and sedative effects of ethanol were explored in GABA(A) α2-subunit wildtype (WT) and knockout (KO) mice using a Rotarod apparatus, wire hang and the duration of loss of righting reflex. Following training, KO mice showed shorter latencies to fall than WT littermates under ethanol (2 g/kg i.p.) in both Rotarod and wire hang tests. After administration of ethanol (3.5 g/kg i.p.), KO mice took longer to regain the righting reflex than WT mice. To ensure the acute effects are not due to the gabra2 deletion affecting pharmacokinetics, blood ethanol concentrations were measured at 20 minute intervals after acute administration (2 g/kg i.p.), and did not differ between genotypes. To investigate ethanol's rewarding properties, WT and KO mice were trained to lever press to receive increasing concentrations of ethanol on an FR4 schedule of reinforcement. Both WT and KO mice self-administered ethanol at similar rates, with no differences in the numbers of reinforcers earned. These data indicate a protective role for α2-subunits, against the acute sedative and ataxic effects of ethanol. However, no change was observed in ethanol self administration, suggesting the rewarding effects of ethanol remain unchange

S100A7 (Psoriasin), highly expressed in Ductal Carcinoma In Situ (DCIS), is regulated by IFN-gamma in mammary epithelial cells

<p>Abstract</p> <p>Background</p> <p>The aim of the present work was to explore signal transduction pathways used in the regulation of S100A7 (psoriasin). Members of the S100 gene family participate in many important cellular functions. Psoriasin, S100A8 (calgranulin A) and S100A9 (calgranulin B) are expressed in ductal carcinoma <it>in situ </it>(DCIS), as well as in the hyperproliferative skin disease, psoriasis. In the latter condition, a disturbance in the STAT pathway has recently been reported. This pathway is implicated in the regulation of IFN-gamma, widely recognized as a key cytokine in psoriasis. IFN-gamma also exerts anti-tumor action in a number of tumor cell types, including breast cancer. We therefore examined the effect of IFN-gamma and STAT-signaling on the psoriasin expression.</p> <p>Methods</p> <p>We established a TAC2 mouse mammary epithelial cell line with tetracycline-inducible psoriasin expression (Tet-Off). Viability in cell culture was estimated using MTS assay. Protein and gene expression were evaluated by Western blotting and quantitative real-time PCR. Statistical analyses were assessed using a one-tailed, paired t-test.</p> <p>Results</p> <p>We report the downregulation of psoriasin by IFN-gamma in the MDA-MB-468 breast cancer cell line, as well as the downregulation of psoriasin induced by anoikis in cell lines derived from different epithelial tissues. In contrast, IFN-gamma had no suppressive effect on calgranulin A or calgranulin B. IFN-gamma is an important activator of the STAT1 pathway and we confirmed an active signaling pathway in the cell lines that responded to IFN-gamma treatment. In contrast, in the SUM190 breast carcinoma cell line, IFN-gamma did not suppress the expression of endogenous psoriasin. Moreover, a reduced phosphorylation of the STAT1 protein was observed. We showed that IFN-gamma treatment and the inhibition of the transcription factor NFkappaB had a synergistic effect on psoriasin levels. Finally, in TAC2 cells with tetracycline-induced psoriasin expression, we observed the increased viability of psoriasin-expressing cells after IFN-gamma treatment.</p> <p>Conclusion</p> <p>Our data support the possibility that psoriasin expression is transcriptionally suppressed by IFN-gamma and that this effect is likely to be mediated by the activation of the STAT1 signaling pathway. The increased viability of psoriasin-expressing cells after IFN-gamma exposure suggests that psoriasin expression leads to the development of an apoptosis-resistant phenotype.</p