Verifying Policy Enforcers

Policy enforcers are sophisticated runtime components that can prevent failures by enforcing the correct behavior of the software. While a single enforcer can be easily designed focusing only on the behavior of the application that must be monitored, the effect of multiple enforcers that enforce different policies might be hard to predict. So far, mechanisms to resolve interferences between enforcers have been based on priority mechanisms and heuristics. Although these methods provide a mechanism to take decisions when multiple enforcers try to affect the execution at a same time, they do not guarantee the lack of interference on the global behavior of the system. In this paper we present a verification strategy that can be exploited to discover interferences between sets of enforcers and thus safely identify a-priori the enforcers that can co-exist at run-time. In our evaluation, we experimented our verification method with several policy enforcers for Android and discovered some incompatibilities.Comment: Oliviero Riganelli, Daniela Micucci, Leonardo Mariani, and Yli\`es Falcone. Verifying Policy Enforcers. Proceedings of 17th International Conference on Runtime Verification (RV), 2017. (to appear

Generic Superlight Client for Permissionless Blockchains

We conduct a systematic study on the light client of permissionless blockchains, in the setting where the full nodes and the light clients are rational. Under such a game-theoretic model, we design a superlight-client protocol to enable a client to employ some relaying full nodes (e.g. two or one) to read the blockchain. The protocol is "generic", i.e., it can be deployed disregarding the underlying consensuses, and also "superlight", i.e., the computational cost of the light client to predicate the (non)existence of a transaction in the blockchain becomes a small constant. Since our protocol resolves a fundamental challenge of broadening the usage of blockchain technology, it captures a wide variety of important use-cases such as multi-chain wallets, DApp browsers and more

Expected Constant Round Byzantine Broadcast under Dishonest Majority

Byzantine Broadcast (BB) is a central question in distributed systems, and an important challenge is to understand its round complexity. Under the honest majority setting, it is long known that there exist randomized protocols that can achieve BB in expected constant rounds, regardless of the number of nodes $n$. However, whether we can match the expected constant round complexity in the corrupt majority setting --- or more precisely, when $f \geq n/2 + \omega(1)$ --- remains unknown, where $f$ denotes the number of corrupt nodes. In this paper, we are the first to resolve this long-standing question. We show how to achieve BB in expected $O((n/(n-f))^2)$ rounds. Our results hold under both a static adversary and a weakly adaptive adversary who cannot perform ``after-the-fact removal\u27\u27 of messages already sent by a node before it becomes corrupt

Ledger Combiners for Fast Settlement

Blockchain protocols based on variations of the longest-chain rule—whether following the proof-of-work paradigm or one of its alternatives—suffer from a fundamental latency barrier. This arises from the need to collect a sufficient number of blocks on top of a transaction-bearing block to guarantee the transaction’s stability while limiting the rate at which blocks can be created in order to prevent security-threatening forks. Our main result is a black-box security-amplifying combiner based on parallel composition of $m$ blockchains that achieves $\Theta(m)$-fold security amplification for conflict-free transactions or, equivalently, $\Theta(m)$-fold reduction in latency. Our construction breaks the latency barrier to achieve, for the first time, a ledger based purely on Nakamoto longest-chain consensus guaranteeing worst-case constant-time settlement for conflict-free transactions: settlement can be accelerated to a constant multiple of block propagation time with negligible error. Operationally, our construction shows how to view any family of blockchains as a unified, virtual ledger without requiring any coordination among the chains or any new protocol metadata. Users of the system have the option to inject a transaction into a single constituent blockchain or—if they desire accelerated settlement—all of the constituent blockchains. Our presentation and proofs introduce a new formalism for reasoning about blockchains, the dynamic ledger, and articulate our constructions as transformations of dynamic ledgers that amplify security. We also illustrate the versatility of this formalism by presenting robust-combiner constructions for blockchains that can protect against complete adversarial control of a minority of a family of blockchains

Association between ABO haplotypes and the risk of venous thrombosis: impact on disease risk estimation

Genetic risk score (GRS) analysis is a popular approach to derive individual risk prediction models for complex diseases. In venous thrombosis (VT), such type of analysis shall integrate information at the ABO blood group locus, which is one of the major susceptibility loci. However, there is no consensus about which single nucleotide polymorphisms (SNPs) must be investigated when properly assessing association between ABO locus and VT risk. Using comprehensive haplotype analyses of ABO blood group tagging SNPs in 5425 cases and 8445 controls from 6 studies, we demonstrate that using only rs8176719 (tagging O1) to correctly assess the impact of ABO locus on VT risk is suboptimal, because 5% of rs8176719-delG carriers do not have an increased risk of developing VT. Instead, we recommend the use of 4 SNPs, rs2519093 (tagging A1), rs1053878 (A2), rs8176743 (B), and rs41302905 (O2), when assessing the impact ofABOlocus on VT risk to avoid any risk misestimation. Compared with the O1 haplotype, the A2 haplotype is associated with a modest increase in VT risk (odds ratio, similar to 1.2), the A1 and B haplotypes are associated with an similar to 1.8-fold increased risk, whereas the O2 haplotype tends to be slightly protective (odds ratio, similar to 0.80). In addition, although the A1 and B blood groups are associated with increased von Willebrand factor and factor VIII plasma levels, only the A1 blood group is associated with ICAM levels, but in an opposite direction, leaving additional avenues to be explored to fully understand the spectrum of biological effects mediated by ABO locus on cardiovascular traits.Clinical epidemiolog

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Background Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. Objective We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. Methods We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses. Results We confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31). Conclusions We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA

Oncogenic Signaling Pathways in The Cancer Genome Atlas.

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy