1,984 research outputs found

    Coded Merkle Tree: Solving Data Availability Attacks in Blockchains

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    In this paper, we propose coded Merkle tree (CMT), a novel hash accumulator that offers a constant-cost protection against data availability attacks in blockchains, even if the majority of the network nodes are malicious. A CMT is constructed using a family of sparse erasure codes on each layer, and is recovered by iteratively applying a peeling-decoding technique that enables a compact proof for data availability attack on any layer. Our algorithm enables any node to verify the full availability of any data block generated by the system by just downloading a Θ(1)\Theta(1) byte block hash commitment and randomly sampling Θ(logb)\Theta(\log b) bytes, where bb is the size of the data block. With the help of only one connected honest node in the system, our method also allows any node to verify any tampering of the coded Merkle tree by just downloading Θ(logb)\Theta(\log b) bytes. We provide a modular library for CMT in Rust and Python and demonstrate its efficacy inside the Parity Bitcoin client.Comment: To appear in Financial Cryptography and Data Security (FC) 202

    Perspectives from deductible plan enrollees: plan knowledge and anticipated care-seeking changes

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    <p>Abstract</p> <p>Background</p> <p>Consumer directed health care proposes that patients will engage as informed consumers of health care services by sharing in more of their medical costs, often through deductibles. We examined knowledge of deductible plan details among new enrollees, as well as anticipated care-seeking changes in response to the deductible.</p> <p>Methods</p> <p>In a large integrated delivery system with a range of deductible-based health plans which varied in services included or exempted from deductible, we conducted a mixed-method, cross-sectional telephone interview study.</p> <p>Results</p> <p>Among 458 adults newly enrolled in a deductible plan (71% response rate), 51% knew they had a deductible, 26% knew the deductible amount, and 6% knew which medical services were included or exempted from their deductible. After adjusting for respondent characteristics, those with more deductible-applicable services and those with lower self-reported health status were significantly more likely to know they had a deductible. Among those who knew of their deductible, half anticipated that it would cause them to delay or avoid medical care, including avoiding doctor's office visits and medical tests, even services that they believed were medically necessary. Many expressed concern about their costs, anticipating the inability to afford care and expressing the desire to change plans.</p> <p>Conclusion</p> <p>Early in their experience with a deductible, patients had limited awareness of the deductible and little knowledge of the details. Many who knew of the deductible reported that it would cause them to delay or avoid seeking care and were concerned about their healthcare costs.</p

    Electric Field Effects on Graphene Materials

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    Understanding the effect of electric fields on the physical and chemical properties of two-dimensional (2D) nanostructures is instrumental in the design of novel electronic and optoelectronic devices. Several of those properties are characterized in terms of the dielectric constant which play an important role on capacitance, conductivity, screening, dielectric losses and refractive index. Here we review our recent theoretical studies using density functional calculations including van der Waals interactions on two types of layered materials of similar two-dimensional molecular geometry but remarkably different electronic structures, that is, graphene and molybdenum disulphide (MoS2_2). We focus on such two-dimensional crystals because of they complementary physical and chemical properties, and the appealing interest to incorporate them in the next generation of electronic and optoelectronic devices. We predict that the effective dielectric constant (ε\varepsilon) of few-layer graphene and MoS2_2 is tunable by external electric fields (EextE_{\rm ext}). We show that at low fields (Eext<0.01E_{\rm ext}^{}<0.01 V/\AA) ε\varepsilon assumes a nearly constant value \sim4 for both materials, but increases at higher fields to values that depend on the layer thickness. The thicker the structure the stronger is the modulation of ε\varepsilon with the electric field. Increasing of the external field perpendicular to the layer surface above a critical value can drive the systems to an unstable state where the layers are weakly coupled and can be easily separated. The observed dependence of ε\varepsilon on the external field is due to charge polarization driven by the bias, which show several similar characteristics despite of the layer considered.Comment: Invited book chapter on Exotic Properties of Carbon Nanomatter: Advances in Physics and Chemistry, Springer Series on Carbon Materials. Editors: Mihai V. Putz and Ottorino Ori (11 pages, 4 figures, 30 references

    The effect of high dose antibiotic impregnated cement on rate of surgical site infection after hip hemiarthroplasty for fractured neck of femur : a protocol for a double-blind quasi randomised controlled trial

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    Background: Mortality following hip hemiarthroplasty is in the range of 10-40% in the first year, with much attributed to post-operative complications. One such complication is surgical site infection (SSI), which at the start of this trial affected 4.68% of patients in the UK having this operation. Compared to SSI rates of elective hip surgery, at less than 1%, this figure is elevated. The aim of this quasi randomised controlled trial (RCT) is to determine if high dose antibiotic impregnated cement can reduce the SSI in patients at 12-months after hemiarthroplasty for intracapsular fractured neck of femur. Methods: 848 patients with an intracapsular fractured neck of femur requiring a hip hemiarthroplasty are been recruited into this two-centre double-blind quasi RCT. Participants were recruited before surgery and quasi randomised to standard care or intervention group. Participants, statistician and outcome assessors were blind to treatment allocation throughout the study. The intervention consisted of high dose antibiotic impregnated cement consisting of 1 gram Clindamycin and 1 gram of Gentamicin. The primary outcome is Health Protection Agency (HPA) defined deep surgical site infection at 12 months. Secondary outcomes include HPA defined superficial surgical site infection at 30 days, 30 and 90-day mortality, length of hospital stay, critical care stay, and complications. Discussion: Large randomised controlled trials assessing the effectiveness of a surgical intervention are uncommon, particularly in the speciality of orthopaedics. The results from this trial will inform evidence-based recommendations for antibiotic impregnated cement in the management of patients with a fractured neck of femur undergoing a hip hemiarthroplasty. If high dose antibiotic impregnated cement is found to be an effective intervention, implementation into clinical practice could improve long-term outcomes for patients undergoing hip hemiarthroplasty

    Quantum Control at the Boundary

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    We present a scheme for controlling the state of a quantum system by modifying the boundary conditions. This constitutes an infinite-dimensional control problem. We provide conditions for the existence of solutions of the dynamics and prove that this system is approximately controllable

    Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus During Macrophage Cell Death.

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    RATIONALE: Pulmonary aspergillosis is a lethal mould infection in the immunocompromised host. Understanding initial control of infection, and how this is altered in the immunocompromised host, is a key goal for understanding the pathogenesis of pulmonary aspergillosis. OBJECTIVES: To characterise the outcome of human macrophage infection with Aspergillus fumigatus, and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants. METHODS: We defined the outcome of human macrophage infection with Aspergillus fumigatus, and the impact of calcineurin inhibitors, through a combination of single cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies. MEASUREMENTS AND MAIN RESULTS: Macrophage phagocytosis of Aspergillus fumigatus enabled control of 90% of fungal germination. However fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell-cell transfer of Aspergillus fumigatus between macrophages which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein (VASP) envelope. Its relevance to the control of fungal germination was also shown by direct visualisation in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506/tacrolimus reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and hyphal escape. CONCLUSIONS: These observations identify programmed necrosis-dependent lateral transfer of Aspergillus fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host

    Tomato protoplast DNA transformation: physical linkage and recombination of exogenous DNA sequences

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    Tomato protoplasts have been transformed with plasmid DNA's, containing a chimeric kanamycin resistance gene and putative tomato origins of replication. A calcium phosphate-DNA mediated transformation procedure was employed in combination with either polyethylene glycol or polyvinyl alcohol. There were no indications that the tomato DNA inserts conferred autonomous replication on the plasmids. Instead, Southern blot hybridization analysis of seven kanamycin resistant calli revealed the presence of at least one kanamycin resistance locus per transformant integrated in the tomato nuclear DNA. Generally one to three truncated plasmid copies were found integrated into the tomato nuclear DNA, often physically linked to each other. For one transformant we have been able to use the bacterial ampicillin resistance marker of the vector plasmid pUC9 to 'rescue' a recombinant plasmid from the tomato genome. Analysis of the foreign sequences included in the rescued plasmid showed that integration had occurred in a non-repetitive DNA region. Calf-thymus DNA, used as a carrier in transformation procedure, was found to be covalently linked to plasmid DNA sequences in the genomic DNA of one transformant. A model is presented describing the fate of exogenously added DNA during the transformation of a plant cell. The results are discussed in reference to the possibility of isolating DNA sequences responsible for autonomous replication in tomato.

    Onion routing in deterministic delay tolerant networks

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    Aquest volum de Lecture notes in computer science, amb el títol Foundations and Practice of Security, recull les actes al 8th International Symposium on Foundations & Practice of Security que va tenir lloc a Clermont-Ferrand (France), del 16 al 28 d'octubre de 2015Deterministic DTNs are networks where the behavior is known in advance or where a repetitive action occurs over time like in public transportation networks. This work proposes the application of an onion routing approach to deterministic DTNs to achieve anonymous communications. We show how the prior stage of path selection in onion routing can be achieved using the information provided by deterministic networks

    How Chromatin Is Remodelled during DNA Repair of UV-Induced DNA Damage in Saccharomyces cerevisiae

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    Global genome nucleotide excision repair removes DNA damage from transcriptionally silent regions of the genome. Relatively little is known about the molecular events that initiate and regulate this process in the context of chromatin. We've shown that, in response to UV radiation–induced DNA damage, increased histone H3 acetylation at lysine 9 and 14 correlates with changes in chromatin structure, and these alterations are associated with efficient global genome nucleotide excision repair in yeast. These changes depend on the presence of the Rad16 protein. Remarkably, constitutive hyperacetylation of histone H3 can suppress the requirement for Rad7 and Rad16, two components of a global genome repair complex, during repair. This reveals the connection between histone H3 acetylation and DNA repair. Here, we investigate how chromatin structure is modified following UV irradiation to facilitate DNA repair in yeast. Using a combination of chromatin immunoprecipitation to measure histone acetylation levels, histone acetylase occupancy in chromatin, MNase digestion, or restriction enzyme endonuclease accessibility assays to analyse chromatin structure, and finally nucleotide excision repair assays to examine DNA repair, we demonstrate that global genome nucleotide excision repair drives UV-induced chromatin remodelling by controlling histone H3 acetylation levels in chromatin. The concerted action of the ATPase and C3HC4 RING domains of Rad16 combine to regulate the occupancy of the histone acetyl transferase Gcn5 on chromatin in response to UV damage. We conclude that the global genome repair complex in yeast regulates UV-induced histone H3 acetylation by controlling the accessibility of the histone acetyl transferase Gcn5 in chromatin. The resultant changes in histone H3 acetylation promote chromatin remodelling necessary for efficient repair of DNA damage. Recent evidence suggests that GCN5 plays a role in NER in human cells. Our work provides important insight into how GG-NER operates in chromatin

    Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance

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    Many important cellular processes are performed by molecular machines, composed of multiple proteins that physically interact to execute biological functions. An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. Staphylococcus aureus is a Gram-positive pathogen, renowned for its resistance to many commonly used antibiotics and prevalence in hospitals. Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus
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