Algebraic analysis of the SSS stream cipher

Both the SSS and SOBER-t32 stream cipher designs use a single word-based shift register and a nonlinear filter function to produce keystream. In this paper we show that the algebraic attack method previously applied to SOBER-t32 is prevented from succeeding on SSS by the use of the key dependent substitution box (SBox) in the nonlinear filter of SSS. Additional assumptions and modifications to the SSS cipher in an attempt to enable algebraic analysis result in other difficulties that also render the algebraic attack infeasible. Based on these results, we conclude that a well chosen key-dependent substitution box used in the nonlinear filter of the stream cipher provides resistance against such algebraic attacks.

Association between prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data

Background: Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease. Objectives: We performed a comprehensive analysis of association of variants in the KLK15 gene with prostate cancer risk and aggressiveness by genotyping tagSNPs, as well as putative functional SNPs identified by extensive bioinformatics analysis. Methods and Data Sources: Twelve out of 22 SNPs, selected on the basis of linkage disequilibrium pattern, were analyzed in an Australian sample of 1,011 histologically verified prostate cancer cases and 1,405 ethnically matched controls. Replication was sought from two existing genome wide association studies (GWAS): the Cancer Genetic Markers of Susceptibility (CGEMS) project and a UK GWAS study. Results: Two KLK15 SNPs, rs2659053 and rs3745522, showed evidence of association (p, 0.05) but were not present on the GWAS platforms. KLK15 SNP rs2659056 was found to be associated with prostate cancer aggressiveness and showed evidence of association in a replication cohort of 5,051 patients from the UK, Australia, and the CGEMS dataset of US samples. A highly significant association with Gleason score was observed when the data was combined from these three studies with an Odds Ratio (OR) of 0.85 (95% CI = 0.77-0.93; p = 2.7610 24). The rs2659056 SNP is predicted to alter binding of the RORalpha transcription factor, which has a role in the control of cell growth and differentiation and has been suggested to control the metastatic behavior of prostate cancer cells. Conclusions: Our findings suggest a role for KLK15 genetic variation in the etiology of prostate cancer among men of European ancestry, although further studies in very large sample sets are necessary to confirm effect sizes.

A world map of knowledge in the making : Wikipedia's Inter-Language Linkage as a dependency explorer of global knowledge accumulation

Analysis of Wikipedia's inter-language links provides insight into a new mechanism of knowledge sharing and linking worldwide.

Speaker linking using complete-linkage clustering

Speaker diarization determines instances of the same speaker within a recording. Extending this task to a collection of recordings for linking together segments spoken by a unique speaker requires speaker linking. In this paper we propose a speaker linking system using linkage clustering and state-of-the-art speaker recognition techniques. We evaluate our approach against two baseline linking systems using agglomerative cluster merging (AC) and agglomerative clustering with model retraining (ACR). We demonstrate that our linking method, using complete-linkage clustering, provides a relative improvement of 20% and 29% in attribution error rate (AER), over the AC and ACR systems, respectively.

Speaker attribution of multiple telephone conversations using a complete-linkage clustering approach

In this paper we propose and evaluate a speaker attribution system using a complete-linkage clustering method. Speaker attribution refers to the annotation of a collection of spoken audio based on speaker identities. This can be achieved using diarization and speaker linking. The main challenge associated with attribution is achieving computational efficiency when dealing with large audio archives. Traditional agglomerative clustering methods with model merging and retraining are not feasible for this purpose. This has motivated the use of linkage clustering methods without retraining. We first propose a diarization system using complete-linkage clustering and show that it outperforms traditional agglomerative and single-linkage clustering based diarization systems with a relative improvement of 40% and 68%, respectively. We then propose a complete-linkage speaker linking system to achieve attribution and demonstrate a 26% relative improvement in attribution error rate (AER) over the single-linkage speaker linking approach.

Mapping quantitative trait loci in a wild population using linkage and linkage disequilibrium analyses

Historical information can be used, in addition to pedigree, traits and genotypes, to map quantitative trait locus (QTL) in general populations via maximum likelihood estimation of variance components. This analysis is known as linkage disequilibrium (LD) and linkage mapping, because it exploits both linkage in families and LD at the population level. The search for QTL in the wild population of Soay sheep on St. Kilda is a proof of principle. We analysed the data from a previous study and confirmed some of the QTLs reported. The most striking result was the confirmation of a QTL affecting birth weight that had been reported using association tests but not when using linkage-based analyses. Copyright © Cambridge University Press 2010.

Candidate gene analysis for quantitative traits using the transmission disequilibrium test : the example of the melanocortin 4-receptor in pigs

Population-wide associations between loci due to linkage disequilibrium can be used to map quantitative trait loci (QTL) with high resolution. However, spurious associations between markers and QTL can also arise as a consequence of population stratification. Statistical methods that cannot differentiate between loci associations due to linkage disequilibria from those caused in other ways can render false-positive results. The transmission-disequilibrium test (TDT) is a robust test for detecting QTL. The TDT exploits within-family associations that are not affected by population stratification. However, some TDTs are formulated in a rigid-form, with reduced potential applications. In this study we generalize TDT using mixed linear models to allow greater statistical flexibility. Allelic effects are estimated with two independent parameters: one exploiting the robust within-family information and the other the potentially biased between-family information. A significant difference between these two parameters can be used as evidence for spurious association. This methodology was then used to test the effects of the fourth melanocortin receptor (MC4R) on production traits in the pig. The new analyses supported the previously reported results; i.e., the studied polymorphism is either causal of in very strong linkage disequilibrium with the causal mutation, and provided no evidence for spurious association.

A multivariate approach to bidding strategies

A multivariate approach to bidding strategy is presented in comparison with previous standard approaches. An optimal formulation is derived and a method of parameter estimation proposed. A case study illustrates the derivation of optimal and other strategic mark up values against a single bidder. Concluding remarks concern extensions to multiple competitors differing levels of information, and sensitivity analysis.

Analysis of stream cipher based authenticated encryption schemes

Authenticated Encryption (AE) is the cryptographic process of providing simultaneous confidentiality and integrity protection to messages. This approach is more efficient than applying a two-step process of providing confidentiality for a message by encrypting the message, and in a separate pass providing integrity protection by generating a Message Authentication Code (MAC). AE using symmetric ciphers can be provided by either stream ciphers with built in authentication mechanisms or block ciphers using appropriate modes of operation. However, stream ciphers have the potential for higher performance and smaller footprint in hardware and/or software than block ciphers. This property makes stream ciphers suitable for resource constrained environments, where storage and computational power are limited. There have been several recent stream cipher proposals that claim to provide AE. These ciphers can be analysed using existing techniques that consider confidentiality or integrity separately; however currently there is no existing framework for the analysis of AE stream ciphers that analyses these two properties simultaneously. This thesis introduces a novel framework for the analysis of AE using stream cipher algorithms. This thesis analyzes the mechanisms for providing confidentiality and for providing integrity in AE algorithms using stream ciphers. There is a greater emphasis on the analysis of the integrity mechanisms, as there is little in the public literature on this, in the context of authenticated encryption. The thesis has four main contributions as follows. The first contribution is the design of a framework that can be used to classify AE stream ciphers based on three characteristics. The first classification applies Bellare and Namprempre's work on the the order in which encryption and authentication processes take place. The second classification is based on the method used for accumulating the input message (either directly or indirectly) into the into the internal states of the cipher to generate a MAC. The third classification is based on whether the sequence that is used to provide encryption and authentication is generated using a single key and initial vector, or two keys and two initial vectors. The second contribution is the application of an existing algebraic method to analyse the confidentiality algorithms of two AE stream ciphers; namely SSS and ZUC. The algebraic method is based on considering the nonlinear filter (NLF) of these ciphers as a combiner with memory. This method enables us to construct equations for the NLF that relate the (inputs, outputs and memory of the combiner) to the output keystream. We show that both of these ciphers are secure from this type of algebraic attack. We conclude that using a keydependent SBox in the NLF twice, and using two different SBoxes in the NLF of ZUC, prevents this type of algebraic attack. The third contribution is a new general matrix based model for MAC generation where the input message is injected directly into the internal state. This model describes the accumulation process when the input message is injected directly into the internal state of a nonlinear filter generator. We show that three recently proposed AE stream ciphers can be considered as instances of this model; namely SSS, NLSv2 and SOBER-128. Our model is more general than a previous investigations into direct injection. Possible forgery attacks against this model are investigated. It is shown that using a nonlinear filter in the accumulation process of the input message when either the input message or the initial states of the register is unknown prevents forgery attacks based on collisions. The last contribution is a new general matrix based model for MAC generation where the input message is injected indirectly into the internal state. This model uses the input message as a controller to accumulate a keystream sequence into an accumulation register. We show that three current AE stream ciphers can be considered as instances of this model; namely ZUC, Grain-128a and Sfinks. We establish the conditions under which the model is susceptible to forgery and side-channel attacks.

Postpartum care for Aboriginal and non-Aboriginal women with Gestational Diabetes Mellitus across urban, rural and remote locations : a protocol for a cohort linkage study

Background: Gestational diabetes mellitus (GDM) is increasing, along with obesity and type 2 diabetes (T2DM), with Aboriginal and Torres Strait Islander people* in Australia particularly affected. GDM causes serious complications in pregnancy, birth, and the longer term, for both women and their infants. Women diagnosed with GDM have an eightfold risk of developing T2DM after pregnancy, compared with women who have not had GDM. Indigenous women have an even higher risk, at a younger age, and progress more quickly from GDM to T2DM, compared to non-Indigenous women. If left undetected and untreated, T2DM can lead to heart disease, stroke, renal disease, kidney failure, amputations and blindness. A GDM diagnosis offers a ‘window of opportunity’ for diabetes health interventions and it is vital that acceptable and effective prevention, treatment, and post-pregnancy care are provided. Low rates of post-pregnancy screening for T2DM are reported among non-Aboriginal women in Australia and among Indigenous women in other countries, however data for Aboriginal women are scarce. Breastfeeding, a healthy diet, and exercise can also help to prevent T2DM, and together with T2DM screening are recommended elements of ‘post-pregnancy care’ for women with GDM, This paper describes methods for a data linkage study to investigate rates of post-pregnancy care among women with GDM. Methods/Design: This retrospective cohort includes all women who gave birth at Cairns Base Hospital in Far North Queensland, Australia, from 2004 to 2010, coded as having GDM in the Cairns Base Hospital Clinical Coding system. Data linkage is being conducted with the Queensland Perinatal Data Collection, and three laboratories. Hospital medical records are being reviewed to validate the accuracy of GDM case ascertainment, and gather information on breastfeeding and provision of dietary advice. Multiple logistic regression is being used to compare post-pregnancy care between Aboriginal and non-Aboriginal women, while adjusting for other factors may impact on post-pregnancy care. Survival analysis is being used to estimate the rates of progression from GDM to T2DM. Discussion: There are challenges to collecting post-pregnancy data for women with GDM. However, research is urgently needed to ensure adequate post-pregnancy care is provided for women with GDM in Australia.

Functional analysis of missense variants in the TRESK (KCNK18) K+ channel

A loss of function mutation in the TRESK K2P potassium channel (KCNK18), has recently been linked with typical familial migraine with aura. We now report the functional characterisation of additional TRESK channel missense variants identified in unrelated patients. Several variants either had no apparent functional effect, or they caused a reduction in channel activity. However, the C110R variant was found to cause a complete loss of TRESK function, yet is present in both sporadic migraine and control cohorts, and no variation in KCNK18 copy number was found. Thus despite the previously identified association between loss of TRESK channel activity and migraine in a large multigenerational pedigree, this finding indicates that a single non-functional TRESK variant is not alone sufficient to cause typical migraine and highlights the genetic complexity of this disorder. Migraine is a common, disabling neurological disorder with a genetic, environmental and in some cases hormonal component. It is characterized by attacks of severe, usually unilateral and throbbing headache, can be accompanied by nausea, vomiting and photophobia and is clinically divided into two main subtypes, migraine with aura (MA) when a migraine is accompanied by transient and reversible focal neurological symptoms and migraine without aura (MO)1. The multifactorial and clinical heterogeneity of the disorder have considerably hindered the identification of common migraine susceptibility genes and most of our current understanding comes from the studies of familial hemiplegic migraine (FHM), a rare monogenic autosomal dominant form of MA2. So far, the three susceptibility genes that have been convincingly identified in FHM families all encode ion channels or transporters: CACNA1A encoding the α1 subunit of the Cav2.1 calcium channel3, SCN1A encoding the Nav1.1 sodium channel4 and ATP1A2 encoding the α2 subunit of the Na+/K+ pump5. It is believed that mutations in these genes may lead to increased efflux of glutamate and potassium in the synapse and thereby cause migraine by rendering the brain more susceptible to cortical spreading depression (CSD)6 which is thought to play a role in initiating a migraine attack7,8. However, these genes have not to date been implicated in common forms of migraine9. Nevertheless, current opinion suggests that typical migraine, like FHM, is also disorder of neuronal excitability, ion homeostasis and neurotransmitter release10,11,12. Mutations in the SLC4A4 gene encoding the sodium-bicarbonate cotransporter NBCe1, have recently been implicated in several different forms of migraine13, and a variety of genes involved in glutamate homeostasis (PGCP, MTDH14 and LRP115) and a cation channel (TRPM8)15 have also recently been implicated in migraine via genome-wide association studies. Ion channels are therefore highly likely to play an important role in the pathogenesis of typical migraine. TRESK (KCNK18), is a member of the two-pore domain (K2P) family of potassium channels involved in the control of cellular electrical excitability16. Regulation of TRESK activity by the calcium-dependent phosphatase calcineurin17, as well as its expression in dorsal root ganglia (DRG)18 and trigeminal ganglia (TG)19,20 has led to a proposed role for this channel in a variety of pain pathways. In a recent study, a frameshift mutation (F139Wfsx24) in TRESK was identified in a large multigenerational pedigree where it co-segregated perfectly with typical MA and a significant genome-wide linkage LOD score of 3.0. Furthermore, functional analysis revealed that this mutation caused a complete loss of TRESK function and that the truncated subunit was also capable of down regulating wild-type channel function. This therefore highlighted KCNK18 as potentially important candidate gene and suggested that TRESK dysfunction might play a possible role in the pathogenesis of familial migraine with visual aura20. Additional screening for KCNK18 mutations in unrelated sporadic migraine and control cohorts also identified a number of other missense variants; R10G, A34V, C110R, S231P and A233V20. The A233V variant was found only in the control cohort, whilst A34V was identified in a single Australian migraine proband for which family samples were not available, but it was not detected in controls. By contrast, the R10G, C110R, and S231P variants were found in both migraineurs and controls in both cohorts. In this study, we have investigated the functional effect of these variants to further probe the potential association of TRESK dysfunction with typical migraine.

Association analysis of chromosome 1 migraine candidate genes

Migraine with aura (MA) is a subtype of typical migraine. Migraine with aura (MA) also encompasses a rare severe subtype Familial Hemiplegic Migraine (FHM) with several known genetic loci. The type 2 FHM (FHM-2) susceptibility locus maps to chromosome 1q23 and mutations in the ATP1A2 gene at this site have recently been implicated. We have previously provided evidence of linkage of typical migraine (predominantly MA) to microsatellite markers on chromosome 1, in the 1q31 and 1q23 regions. In this study, we have undertaken a large genomic investigation involving candidate genes that lie within the chromosome 1q23 and 1q31 regions using an association analysis approach. Methods We have genotyped a large population of case-controls (243 unrelated Caucasian migraineurs versus 243 controls) examining a set of 5 single nucleotide polymorphisms (SNPs) and the Fas Ligand dinucleotide repeat marker, located within the chromosome 1q23 and 1q31 regions. Results Several genes have been studied including membrane protein (ATP 1 subtype A4 and FasL), cytoplasmic glycoprotein (CASQ 1) genes and potassium (KCN J9 and KCN J10) and calcium (CACNA1E) channel genes in 243 migraineurs (including 85% MA and 15% of migraine without aura (MO)) and 243 matched controls. After correction for multiple testing, chi-square results showed non-significant P values (P > 0.008) across all SNPs (and a CA repeat) tested in these different genes, however results with the KCN J10 marker gave interesting results (P = 0.02) that may be worth exploring further in other populations. Conclusion These results do not show a significant role for the tested candidate gene variants and also do not support the hypothesis that a common chromosome 1 defective gene influences both FHM and the more common forms of migraine.

An analysis of clinical characteristics in genetically linked migraine-affected pedigrees

Migraine is a common complex disorder characterized by severe recurrent headache and usually accompanied by nausea and vomiting. Previous studies in our laboratory have utilized three large multigenerational Australian pedigrees affected with migraine to indicate that the disease is genetically heterogeneous, with linkage results implicating genomic susceptibility regions on both chromosomes 19p and Xq. The present study explores the possibility of a correlation between genetic and clinical heterogeneity in these affected pedigrees. Specifically, the clinical characteristics of migraine including subtype, age of onset, frequency, duration, and disease symptoms were compared between the migraine pedigrees, and gender differences were also assessed. Our exploratory analyses revealed no significant differences in any of the clinical characteristics tested between the chromosome 19-linked family and the two X-linked families. Also, we did not detect any differences in male vs. female clinical features for these pedigrees. In conclusion, migraine is considered to be a clinically and genetically heterogeneous disorder; however, our study provided no conclusive evidence that variation in genomic susceptibility region is related to heterogeneity at the clinical level in these migraine-affected pedigrees.

Familial typical migraine: Significant linkage and localization of a gene to Xq24-28

In a previous study we found evidence for an X-linked genetic component for familial typical migraine in two large Australian white pedigrees, designated MF7 and MF14. Significant excess allele sharing was indicated by nonparametric linkage (NPL) analysis using GENEHUNTER (P=0.031 and P=0.012, respectively), with a combined analysis of the two pedigrees showing further increased evidence for linkage, producing a maximum NPL score of 2.87 (P=0.011 ) at DXS 1123 on Xq27. The present study was aimed at refining the localization of the migraine X-chromosomal component by typing additional markers, performing haplotype analysis and applying a more powerful technique in the analysis of linkage data from these two pedigrees. Results from the haplotype analyses, coupled with linkage analyses that produced a peak GENEHUNTER-PLUS LOD* score of 2.388 (P=0.0005), provide compelling evidence for the presence of a migraine susceptibility locus on chromosome Xq24-28.