A group membership algorithm with a practical specification

Presents a solvable specification and gives an algorithm for the group membership problem in asynchronous systems with crash failures. Our specification requires processes to maintain a consistent history in their sequences of views. This allows processes to order failures and recoveries in time and simplifies the programming of high level applications. Previous work has proven that the group membership problem cannot be solved in asynchronous systems with crash failures. We circumvent this impossibility result building a weaker, yet nontrivial specification. We show that our solution is an improvement upon previous attempts to solve this problem using a weaker specification. We also relate our solution to other methods and give a classification of progress properties that can be achieved under different models

Genome-wide polyadenylation site mapping datasets in the rice blast fungus Magnaporthe oryzae

Polyadenylation plays an important role in gene regulation, thus affecting a wide variety of biological processes. In the rice blast fungus Magnaporthe oryzae the cleavage factor I protein Rpb35 is required for pre-mRNA polyadenylation and fungal virulence. Here we present the bioinformatic approach and output data related to a global survey of polyadenylation site usage in M. oryzae wild-type and Delta rbp35 strains under a variety of nutrient conditions, some of which simulate the conditions experienced by the fungus during part of its infection cycle

Optical Properties and Structure of Most Stable Subnanometer (ZnAs2)n Clusters

ZnAs2 nanoclusters were fabricated by incorporation into pores of zeolite Na-X and by laser ablation. Absorption and photoluminescence spectra of ZnAs2 nanoclusters in zeolite were measured at the temperatures of 4.2, 77 and 293 K. Both absorption and PL spectra consist of two bands which demonstrate the blue shift from the line of free exciton in bulk crystal. We performed the calculations aimed to find the most stable clusters in the size region up to size of the zeolite Na-X supercage. The most stable clusters are (ZnAs2)6 and (ZnAs2)8 with binding energies of 7.181 eV and 8.012 eV per (ZnAs2)1 formula unit respectively. Therefore, we attributed two bands observed in absorption and PL spectra to these stable clusters. The measured Raman spectrum of ZnAs2 clusters in zeolite was explained to be originated from (ZnAs2)6 and (ZnAs2)8 clusters as well. The PL spectrum of ZnAs2 clusters produced by laser ablation consists of a single band which has been attributed to emission of (ZnAs2)8 cluster.Comment: Article accepted for publication in Physica B: Physics of Condensed Matte

Diffuse charge and Faradaic reactions in porous electrodes

Porous electrodes instead of flat electrodes are widely used in electrochemical systems to boost storage capacities for ions and electrons, to improve the transport of mass and charge, and to enhance reaction rates. Existing porous electrode theories make a number of simplifying assumptions: (i) The charge-transfer rate is assumed to depend only on the local electrostatic potential difference between the electrode matrix and the pore solution, without considering the structure of the double layer (DL) formed in between; (ii) the charge-transfer rate is generally equated with the salt-transfer rate not only at the nanoscale of the matrix-pore interface, but also at the macroscopic scale of transport through the electrode pores. In this paper, we extend porous electrode theory by including the generalized Frumkin-Butler-Volmer model of Faradaic reaction kinetics, which postulates charge transfer across the molecular Stern layer located in between the electron-conducting matrix phase and the plane of closest approach for the ions in the diffuse part of the DL. This is an elegant and purely local description of the charge-transfer rate, which self-consistently determines the surface charge and does not require consideration of reference electrodes or comparison with a global equilibrium. For the description of the DLs, we consider the two natural limits: (i) the classical Gouy-Chapman-Stern model for thin DLs compared to the macroscopic pore dimensions, e.g., for high-porosity metallic foams (macropores >50 nm) and (ii) a modified Donnan model for strongly overlapping DLs, e.g., for porous activated carbon particles (micropores <2 nm). Our theory is valid for electrolytes where both ions are mobile, and it accounts for voltage and concentration differences not only on the macroscopic scale of the full electrode, but also on the local scale of the DL. The model is simple enough to allow us to derive analytical approximations for the steady-state and early transients. We also present numerical solutions to validate the analysis and to illustrate the evolution of ion densities, pore potential, surface charge, and reaction rates in response to an applied voltage

Multilayer regulatory mechanisms control cleavage factor I proteins in filamentous fungi

Cleavage factor I (CFI) proteins are core components of the polyadenylation machinery that can regulate several steps of mRNA life cycle, including alternative polyadenylation, splicing, export and decay. Here, we describe the regulatory mechanisms that control two fungal CFI protein classes in Magnaporthe oryzae: Rbp35/CfI25 complex and Hrp1. Using mutational, genetic and biochemical studies we demonstrate that cellular concentration of CFI mRNAs is a limited indicator of their protein abundance. Our results suggest that several post-transcriptional mechanisms regulate Rbp35/CfI25 complex and Hrp1 in the rice blast fungus, some of which are also conserved in other ascomycetes. With respect to Rbp35, these include C-terminal processing, RGG-dependent localization and cleavage, C-terminal autoregulatory domain and regulation by an upstream open reading frame of Rbp35-dependent TOR signalling pathway. Our proteomic analyses suggest that Rbp35 regulates the levels of proteins involved in melanin and phenylpropanoids synthesis, among others. The drastic reduction of fungal CFI proteins in carbon-starved cells suggests that the pre-mRNA processing pathway is altered. Our findings uncover broad and multilayer regulatory mechanisms controlling fungal polyadenylation factors, which have profound implications in pre-mRNA maturation. This area of research offers new avenues for fungicide design by targeting fungal-specific proteins that globally affect thousands of mRNAs

Social capital: a roadmap of theoretical and empirical contributions and limitations

The general idea of social capital is that relationships matter. In this sense, the trust, cooperation and reciprocity involved in these relationships can have a positive impact on the wealth of society by reducing transaction costs, facilitating collective actions, and lowering opportunistic behavior. This work sheds light on the different theoretical and empirical problems that a scholar is likely to face in dealing with social capital research and analysis. We propose a critical roadmap of the social capital theories and applications for a general audience, nonusers included, with particular attention to the works of political and social economists. We provide a critical debate on the different definitions and measures produced, the theoretical frameworks developed, and the empirical techniques adopted so far in the analysis of the impact of social capital on socio-economic outcomes. We turn to the limitations of these techniques and suggest some basic strategies to reduce the magnitude of these limitations

Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons

Two mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na(+)-dependent K(+) (K(Na)) channels. Progress in understanding K(Na) channels has been hampered by the absence of specific tools and methods for rigorous K(Na) identification in native cells. Here, we report the genetic disruption of both Kcnt1 and Kcnt2, confirm the loss of Slo2.2 and Slo2.1 protein, respectively, in KO animals, and define tissues enriched in Slo2 expression. Noting the prevalence of Slo2.2 in dorsal root ganglion, we find that KO of Slo2.2, but not Slo2.1, results in enhanced itch and pain responses. In dissociated small diameter DRG neurons, KO of Slo2.2, but not Slo2.1, abolishes K(Na) current. Utilizing isolectin B4+ neurons, the absence of K(Na) current results in an increase in action potential (AP) firing and a decrease in AP threshold. Activation of K(Na) acts as a brake to initiation of the first depolarization-elicited AP with no discernible effect on afterhyperpolarizations. DOI: http://dx.doi.org/10.7554/eLife.10013.00

Epileptogenic potential of mefloquine chemoprophylaxis: a pathogenic hypothesis

<p>Abstract</p> <p>Background</p> <p>Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but prescribing it requires careful attention in order to rule out contraindications to its use. Contraindications include a history of certain neurological conditions that might increase the risk of seizure and other adverse events. The precise pathophysiological mechanism by which mefloquine might predispose those with such a history to seizure remains unclear.</p> <p>Presentation of the hypothesis</p> <p>Studies have demonstrated that mefloquine at doses consistent with chemoprophylaxis accumulates at high levels in brain tissue, which results in altered neuronal calcium homeostasis, altered gap-junction functioning, and contributes to neuronal cell death. This paper reviews the scientific evidence associating mefloquine with alterations in neuronal function, and it suggests the novel hypothesis that among those with the prevalent EPM1 mutation, inherited and mefloquine-induced impairments in neuronal physiologic safeguards might increase risk of GABAergic seizure during mefloquine chemoprophylaxis.</p> <p>Testing and implications of the hypothesis</p> <p>Consistent with case reports of tonic-clonic seizures occurring during mefloquine chemoprophylaxis among those with family histories of epilepsy, it is proposed here that a new contraindication to mefloquine use be recognized for people with EPM1 mutation and for those with a personal history of myoclonus or ataxia, or a family history of degenerative neurologic disorder consistent with EPM1. Recommendations and directions for future research are presented.</p

Characterization of PTZ-Induced Seizure Susceptibility in a Down Syndrome Mouse Model That Overexpresses CSTB

Down syndrome (DS) is a complex genetic syndrome characterized by intellectual disability, dysmorphism and variable additional physiological traits. Current research progress has begun to decipher the neural mechanisms underlying cognitive impairment, leading to new therapeutic perspectives. Pentylenetetrazol (PTZ) has recently been found to have positive effects on learning and memory capacities of a DS mouse model and is foreseen to treat DS patients. But PTZ is also known to be a convulsant drug at higher dose and DS persons are more prone to epileptic seizures than the general population. This raises concerns over what long-term effects of treatment might be in the DS population. The cause of increased propensity for epilepsy in the DS population and which Hsa21 gene(s) are implicated remain unknown. Among Hsa21 candidate genes in epilepsy, CSTB, coding for the cystein protease inhibitor cystatin B, is involved in progressive myoclonus epilepsy and ataxia in both mice and human. Thus we aim to evaluate the effect of an increase in Cstb gene dosage on spontaneous epileptic activity and susceptibility to PTZ-induced seizure. To this end we generated a new mouse model trisomic for Cstb by homologous recombination. We verified that increasing copy number of Cstb from Trisomy (Ts) to Tetrasomy (Tt) was driving overexpression of the gene in the brain, we checked transgenic animals for presence of locomotor activity and electroencephalogram (EEG) abnormalities characteristic of myoclonic epilepsy and we tested if those animals were prone to PTZ-induced seizure. Overall, the results of the analysis shows that an increase in Cstb does not induce any spontaneous epileptic activity and neither increase or decrease the propensity of Ts and Tt mice to myoclonic seizures suggesting that Ctsb dosage should not interfere with PTZ-treatment

Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass $M>70$ $M_\odot$) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities $0 < e \leq 0.3$ at $0.33$ Gpc$^{-3}$ yr$^{-1}$ at 90\% confidence level.Comment: 24 pages, 5 figure