Automated Expected Amortised Cost Analysis of Probabilistic Data Structures

In this paper, we present the first fully-automated expected amortised cost analysis of self-adjusting data structures, that is, of randomised splay trees, randomised splay heaps and randomised meldable heaps, which so far have only (semi-) manually been analysed in the literature. Our analysis is stated as a type-and-effect system for a first-order functional programming language with support for sampling over discrete distributions, non-deterministic choice and a ticking operator. The latter allows for the specification of fine-grained cost models. We state two soundness theorems based on two different -- but strongly related -- typing rules of ticking, which account differently for the cost of non-terminating computations. Finally we provide a prototype implementation able to fully automatically analyse the aforementioned case studies.Comment: 39 page

Synthesis and characterization of nanocrystalline U1−x_{1-x}Pux_{x}O2(+y)_{2(+y)} mixed oxides

We report here the first synthesis of mixed oxide U$_{1-x}$Pu$_{x}$O$_{2(+y)}$ nanoparticles. The obtained nanopowders were characterized by X-ray diffraction, thermal ionization mass spectrometry, transmission electron microscopy, Raman spectroscopy, and U M$_{4}$ edge high-energy-resolution X-ray absorption near edge structure (HR-XANES). The HR-XANES spectra give evidence for the partial oxidation of U$^{IV}$ to U$^{V}$. This novel route toward the formation of actinide–actinide solid solution opens research opportunities that are not accessible using bulk materials. We give details on the X-ray diffraction study on plutonium oxalate hexahydrate, as a reagent for the synthesis of such nanoparticles

Alternating runtime and size complexity analysis of integer programs

We present a modular approach to automatic complexity analysis. Based on a novel alternation between finding symbolic time bounds for program parts and using these to infer size bounds on program variables, we can restrict each analysis step to a small part of the program while maintaining a high level of precision. Extensive experiments with the implementation of our method demonstrate its performance and power in comparison with other tools

Nuclear envelope protein Lem2 is required for mouse development and regulates MAP and AKT kinases

The nuclear lamina, along with associated nuclear membrane proteins, is a nexus for regulating signaling in the nucleus. Numerous human diseases arise from mutations in lamina proteins, and experimental models for these disorders have revealed aberrant regulation of various signaling pathways. Previously, we reported that the inner nuclear membrane protein Lem2, which is expressed at high levels in muscle, promotes the differentiation of cultured myoblasts by attenuating ERK signaling. Here, we have analyzed mice harboring a disrupted allele for the Lem2 gene (Lemd2). No gross phenotypic defects were seen in heterozygotes, although muscle regeneration induced by cardiotoxin was delayed. By contrast, homozygous Lemd2 knockout mice died by E11.5. Although many normal morphogenetic hallmarks were observed in E10.5 knockout embryos, most tissues were substantially reduced in size. This was accompanied by activation of multiple MAP kinases (ERK1/2, JNK, p38) and AKT. Knockdown of Lem2 expression in C2C12 myoblasts also led to activation of MAP kinases and AKT. These findings indicate that Lemd2 plays an essential role in mouse embryonic development and that it is involved in regulating several signaling pathways. Since increased MAP kinase and AKT/mTORC signaling is found in other animal models for diseases linked to nuclear lamina proteins, LEMD2 should be considered to be another candidate gene for human disease

Tight polynomial bounds for Loop programs in polynomial space

We consider the following problem: given a program, find tight asymptotic bounds on the values of some variables at the end of the computation (or at any given program point) in terms of its input values. We focus on the case of polynomially-bounded variables, and on a weak programming language for which we have recently shown that tight bounds for polynomially-bounded variables are computable. These bounds are sets of multivariate polynomials. While their computability has been settled, the complexity of this program-analysis problem remained open. In this paper, we show the problem to be PSPACE-complete. The main contribution is a new, space-efficient analysis algorithm. This algorithm is obtained in a few steps. First, we develop an algorithm for univariate bounds, a sub-problem which is already PSPACE-hard. Then, a decision procedure for multivariate bounds is achieved by reducing this problem to the univariate case; this reduction is orthogonal to the solution of the univariate problem and uses observations on the geometry of a set of vectors that represent multivariate bounds. Finally, we transform the univariate-bound algorithm to produce multivariate bounds

Biallelic variants in coenzyme Q10 biosynthesis pathway genes cause a retinitis pigmentosa phenotype

The aim of this study was to investigate coenzyme Q10 (CoQ10) biosynthesis pathway defects in inherited retinal dystrophy. Individuals affected by inherited retinal dystrophy (IRD) underwent exome or genome sequencing for molecular diagnosis of their condition. Following negative IRD gene panel analysis, patients carrying biallelic variants in CoQ10 biosynthesis pathway genes were identified. Clinical data were collected from the medical records. Haplotypes harbouring the same missense variant were characterised from family genome sequencing (GS) data and direct Sanger sequencing. Candidate splice variants were characterised using Oxford Nanopore Technologies single molecule sequencing. The CoQ10 status of the human plasma was determined in some of the study patients. 13 individuals from 12 unrelated families harboured candidate pathogenic genotypes in the genes: PDSS1, COQ2, COQ4 and COQ5. The PDSS1 variant c.589 A > G was identified in three affected individuals from three unrelated families on a possible ancestral haplotype. Three variants (PDSS1 c.468-25 A > G, PDSS1 c.722-2 A > G, COQ5 c.682-7 T > G) were shown to lead to cryptic splicing. 6 affected individuals were diagnosed with non-syndromic retinitis pigmentosa and 7 had additional clinical findings. This study provides evidence of CoQ10 biosynthesis pathway gene defects leading to non-syndromic retinitis pigmentosa in some cases. Intronic variants outside of the canonical splice-sites represent an important cause of disease. RT-PCR nanopore sequencing is effective in characterising these splice defects

Peak Cost Analysis of Distributed Systems (Author's version)

We present a novel static analysis to infer the peak cost of distributed systems. The different locations of a distributed system communicate and coordinate their actions by posting tasks among them. Thus, the amount of work that each location has to perform can greatly vary along the execution depending on: (1) the amount of tasks posted to its queue, (2) their respective costs, and (3) the fact that they may be posted in parallel and thus be pending to execute simultaneously. The peak cost of a distributed location refers to the maximum cost that it needs to carry out along its execution. Inferring the peak cost is challenging because it increases and decreases along the execution, unlike the standard notion of total cost which is cumulative. Our key contribution is the novel notion of quantified queue configuration which captures the worst-case cost of the tasks that may be simultaneously pending to execute at each location along the execution. A prototype implementation demonstrates the accuracy and feasibility of the proposed peak cost analysis