Solving atomic multicast when groups crash

In this paper, we study the atomic multicast problem, a fundamental abstraction for building faulttolerant systems. In the atomic multicast problem, the system is divided into non-empty and disjoint groups of processes. Multicast messages may be addressed to any subset of groups, each message possibly being multicast to a different subset. Several papers previously studied this problem either in local area networks [3, 9, 20] or wide area networks [13, 21]. However, none of them considered atomic multicast when groups may crash. We present two atomic multicast algorithms that tolerate the crash of groups. The first algorithm tolerates an arbitrary number of failures, is genuine (i.e., to deliver a message m, only addressees of m are involved in the protocol), and uses the perfect failures detector P. We show that among realistic failure detectors, i.e., those that do not predict the future, P is necessary to solve genuine atomic multicast if we do not bound the number of processes that may fail. Thus, P is the weakest realistic failure detector for solving genuine atomic multicast when an arbitrary number of processes may crash. Our second algorithm is non-genuine and less resilient to process failures than the first algorithm but has several advantages: (i) it requires perfect failure detection within groups only, and not across the system, (ii) as we show in the paper it can be modified to rely on unreliable failure detection at the cost of a weaker liveness guarantee, and (iii) it is fast, messages addressed to multiple groups may be delivered within two inter-group message delays only

Taphonomy and chronosequence of the 709 ka Kalinga site formation (Luzon Island, Philippines)

The recently described site of Kalinga in the Philippines adds to our understanding of Early-Middle Pleistocene hominin behaviour. Yet, disentangling the natural from the anthropogenic modifications that have taken place in such an old archaeological site is challenging. In this paper we use a set of taphonomic tools at hand to rectify the distortion made by natural processes during the formation of the Kalinga site. From the description of the ribs completeness, surface damages and scattering in the excavation, one can reconstruct the butchery, transport and deposition sequence of the rhino carcass and its post-depositional disturbances and diagenetic evolution of the site. We conclude that the rhino and the stone artefacts potentially used to deflesh the carcass were transported by a mudflow from its butchery place over a few meters only and got stuck and mixed with an older faunal assemblage that was transported by a small stream.Materials and methods Results Discussion and concluding remarks: Death and butchery of the rhino ; Transport and deposition ; Post‑depositional evolution of the site and diagenesis ; The relative age of the stone artefact

In Vivo Determination of Fluctuating Forces during Endosome Trafficking Using a Combination of Active and Passive Microrheology

BACKGROUND: Regulation of intracellular trafficking is a central issue in cell biology. The forces acting on intracellular vesicles (endosomes) can be assessed in living cells by using a combination of active and passive microrheology. METHODOLOGY/PRINCIPAL FINDINGS: This dual approach is based on endosome labeling with magnetic nanoparticles. The resulting magnetic endosomes act both as probes that can be manipulated with external magnetic fields to infer the viscoelastic modulus of their surrounding microenvironment, and as biological vehicles that are trafficked along the microtubule network by means of forces generated by molecular motors. The intracellular viscoelastic modulus exhibits power law dependence with frequency, which is microtubule and actin-dependent. The mean square displacements of endosomes do not follow the predictions of the fluctuation-dissipation theorem, which offers evidence for active force generation. Microtubule disruption brings the intracellular medium closer to thermal equilibrium: active forces acting on the endosomes depend on microtubule-associated motors. The power spectra of these active forces, deduced through the use of a generalized Langevin equation, show a power law decrease with frequency and reveal an actin-dependent persistence of the force with time. Experimental spectra have been reproduced by a simple model consisting in a series of force steps power-law distributed in time. This model enlightens the role of the cytoskeleton dependent force exerted on endosomes to perform intracellular trafficking. CONCLUSIONS/SIGNIFICANCE: In this work, the influence of cytoskeleton components and molecular motors on intracellular viscoelasticity and transport is addressed. The use of an original probe, the magnetic endosome, allows retrieving the power spectrum of active forces on these organelles thanks to interrelated active and passive measures. Finally a computational model gives estimates of the force itself and hence of the number of the motors pulling on endosomes

FE65 Binds Teashirt, Inhibiting Expression of the Primate-Specific Caspase-4

The Alzheimer disease (AD) amyloid protein precursor (APP) can bind the FE65 adaptor protein and this complex can regulate gene expression. We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex. We screened stable cell lines with a macroarray focusing on AD-related genes and identified CASP4, encoding caspase-4, as a target of this silencing complex. Chromatin immunoprecipitation showed a direct interaction of FE65 and Teashirt3 with the promoter region of CASP4. Expression studies in postmortem samples demonstrated decreasing expression of Teashirt and increasing expression of caspase-4 with progressive cognitive decline. Importantly, there were significant increases in caspase-4 expression associated with even the earliest neuritic plaque changes in AD. We evaluated a case-control cohort and observed evidence for a genetic association between the Teashirt genes TSHZ1 and TSHZ3 and AD, with the TSHZ3 SNP genotype correlating with expression of Teashirt3. The results were consistent with a model in which reduced expression of Teashirt3, mediated by genetic or other causes, increases caspase-4 expression, leading to progression of AD. Thus the cell biological, gene expression and genetic data support a role for Teashirt/caspase-4 in AD biology. As caspase-4 shows evidence of being a primate-specific gene, current models of AD and other neurodegenerative conditions may be incomplete because of the absence of this gene in the murine genome

Management system for optimizing public transport networks: GPS record

As cities continue to grow in size and population, the design of public transport networks becomes complicated, given the wide diversity in the origins and destinations of users [1], as well as the saturation of vehicle infrastructure in large cities despite their attempts to adapt it according to population distribution. This indicates that, in order to reduce users’ travel time, it is necessary to implement alternative road solutions to the use of cars, increasing investment in public transportation [2, 3] by conducting a comprehensive analysis of the state of transportation. This situation has made appear the solutions and development oriented to transportation based on Internet of Things (IoT) which allows, in a first stage, monitoring of public transport systems, in order to optimize the deployment of transport units and thus reduce the time of transfer of users through the cities [4]. These solution proposals are focused on information collected from user resources (data collected through smart phones) to create a common database [5]. The present study proposes the development of an intelligent monitoring and management system for public transportation networks using a hybrid communication architecture based on wireless node networks using IPv6 and cellular networks (LTE, LTE-M)

A maximum entropy approach to detect close-in giant planets around active stars

Context: The high spot coverage of young active stars is responsible for distortions of spectral lines that hamper the detection of close-in planets through radial velocity methods. Aims: We aim to progress towards more efficient exoplanet detection around active stars by optimizing the use of Doppler imaging in radial velocity measurements. Methods: We propose a simple method to simultaneously extract a brightness map and a set of orbital parameters through a tomographic inversion technique derived from classical Doppler mapping. Based on the maximum entropy principle, the underlying idea is to determine the set of orbital parameters that minimizes the information content of the resulting Doppler map. We carry out a set of numerical simulations to perform a preliminary assessment of the robustness of our method, using an actual Doppler map of the very active star HR 1099 to produce a realistic synthetic data set for various sets of orbital parameters of a single planet in a circular orbit. Results: Using a simulated time series of 50 line profiles affected by a peak-to-peak activity jitter of 2.5 km s, in most cases we are able to recover the radial velocity amplitude, orbital phase, and orbital period of an artificial planet down to a radial velocity semi-amplitude of the order of the radial velocity scatter due to the photon noise alone (about 50 m s in our case). One noticeable exception occurs when the planetary orbit is close to co-rotation, in which case significant biases are observed in the reconstructed radial velocity amplitude, while the orbital period and phase remain robustly recovered. Conclusions: The present method constitutes a very simple way to extract orbital parameters from heavily distorted line profiles of active stars, when more classical radial velocity detection methods generally fail. It is easily adaptable to most existing Doppler imaging codes, paving the way towards a systematic search for close-in planets orbiting young, rapidly-rotating stars

Evaluations of the effect of sodium metabisulfite on the stability and dissolution rates of various model drugs from the extended release polyethylene oxide matrices

Purpose: This study examines the effect of sodium metabisulfite (SMB) as an antioxidant on the stability and release of various model drugs namely propranolol HCl, theophylline and zonisamide from the polyethylene oxide (PEO) tablets. The antioxidant was used to minimise degradation and instability of the manufactured tablets when stored at 40°C (55±5 % RH) over 8 weeks. Method: Multiple batches of tablets weighing 240 mg (50% w/w) with a ratio of 1:1 drug: polymer and 1% (w/w) sodium metabisulfite containing different model drugs and various molecular weights of PEO 750 and 303 were produced. Results: The results indicated that the use of sodium metabisulfite marginally assisted in reducing drug release and degradation via oxidation in propranolol HCl tablets containing both PEO 750 and 303. In the case of poorly and semi-soluble drugs (zonisamide and theophylline) the formulations with both PEO showed entirely superimposable phenomenon and different release profiles compared to control samples (matrices without SMB). DSC study demonstrated the modifications of the polymer due to degradation and observed the effect of SMB on the thermal degradation of the PEO matrices. Conclusion: The use of antioxidant has assisted in retaining the stability of the manufactured tablets with different model drugs especially those with the highly soluble drug that are susceptible to rapid degradation. This has been reflected by an extended release profile of various drugs used at various stages of the storage time up to 8 weeks

Gγ1, a Downstream Target for the hmgcr-Isoprenoid Biosynthetic Pathway, Is Required for Releasing the Hedgehog Ligand and Directing Germ Cell Migration

The isoprenoid biosynthetic pathway leading from the production of mevalonate by HMGCoA reductase (Hmgcr) to the geranylation of the G protein subunit, Gγ1, plays an important role in cardiac development in the fly. Hmgcr has also been implicated in the release of the signaling molecule Hedgehog (Hh) from hh expressing cells and in the production of an attractant that directs primordial germ cells to migrate to the somatic gonadal precursor cells (SGPs). The studies reported here indicate that this same hmgcr→Gγ1 pathway provides a novel post-translational mechanism for modulating the range and activity of the Hh signal produced by hh expressing cells. We show that, like hmgcr, gγ1 and quemao (which encodes the enzyme, geranylgeranyl diphosphate synthetase, that produces the substrate for geranylation of Gγ1) are components of the hh signaling pathway and are required for the efficient release of the Hh ligand from hh expressing cells. We also show that the hmgcr→Gγ1 pathway is linked to production of the germ cell attractant by the SGPs through its ability to enhance the potency of the Hh signal. We show that germ cell migration is disrupted by the loss or gain of gγ1 activity, by trans-heterozygous combinations between gγ1 and either hmgcr or hh mutations, and by ectopic expression of dominant negative Gγ1 proteins that cannot be geranylated

A Genome-Wide RNAi Screen Identifies Regulators of Cholesterol-Modified Hedgehog Secretion in Drosophila

Hedgehog (Hh) proteins are secreted molecules that function as organizers in animal development. In addition to being palmitoylated, Hh is the only metazoan protein known to possess a covalently-linked cholesterol moiety. The absence of either modification severely disrupts the organization of numerous tissues during development. It is currently not known how lipid-modified Hh is secreted and released from producing cells. We have performed a genome-wide RNAi screen in Drosophila melanogaster cells to identify regulators of Hh secretion. We found that cholesterol-modified Hh secretion is strongly dependent on coat protein complex I (COPI) but not COPII vesicles, suggesting that cholesterol modification alters the movement of Hh through the early secretory pathway. We provide evidence that both proteolysis and cholesterol modification are necessary for the efficient trafficking of Hh through the ER and Golgi. Finally, we identified several putative regulators of protein secretion and demonstrate a role for some of these genes in Hh and Wingless (Wg) morphogen secretion in vivo. These data open new perspectives for studying how morphogen secretion is regulated, as well as provide insight into regulation of lipid-modified protein secretion

Rare and Frequent Promoter Methylation, Respectively, of TSHZ2 and 3 Genes That Are Both Downregulated in Expression in Breast and Prostate Cancers

Neoplastic cells harbor both hypomethylated and hypermethylated regions of DNA. Whereas hypomethylation is found mainly in repeat sequences, regional hypermethylation has been linked to the transcriptional silencing of certain tumor suppressor genes. We attempted to search for candidate genes involved in breast/prostate carcinogenesis, using the criteria that they should be expressed in primary cultures of normal breast/prostate epithelial cells but are frequently downregulated in breast/prostate cancer cell lines and that their promoters are hypermethylated.We identified several dozens of candidates among 194 homeobox and related genes using Systematic Multiplex RT-PCR and among 23,000 known genes and 23,000 other expressed sequences in the human genome by DNA microarray hybridization. An additional examination, by real-time qRT-PCR of clinical specimens of breast cancer, further narrowed the list of the candidates. Among them, the most frequently downregulated genes in tumors were NP_775756 and ZNF537, from the homeobox gene search and the genome-wide search, respectively. To our surprise, we later discovered that these genes belong to the same gene family, the 3-member Teashirt family, bearing the new names of TSHZ2 and TSHZ3. We subsequently determined the methylation status of their gene promoters. The TSHZ3 gene promoter was found to be methylated in all the breast/prostate cancer cell lines and some of the breast cancer clinical specimens analyzed. The TSHZ2 gene promoter, on the other hand, was unmethylated except for the MDA-MB-231 breast cancer cell line. The TSHZ1 gene was always expressed, and its promoter was unmethylated in all cases.TSHZ2 and TSHZ3 genes turned out to be the most interesting candidates for novel tumor suppressor genes. Expression of both genes is downregulated. However, differential promoter methylation suggests the existence of distinctive mechanisms of transcriptional inactivation for these genes