Grøstl – a SHA-3 candidate

Grøstl is a SHA-3 candidate proposal. Grøstl is an iterated hash function with a compression function built from two fixed, large, distinct permutations. The design of Grøstl is transparent and based on principles very different from those used in the SHA-family. The two permutations are constructed using the wide trail design strategy, which makes it possible to give strong statements about the resistance of Grøstl against large classes of cryptanalytic attacks. Moreover, if these permutations are assumed to be ideal, there is a proof for the security of the hash function. Grøstl is a byte-oriented SP-network which borrows components from the AES. The S-box used is identical to the one used in the block cipher AES and the diffusion layers are constructed in a similar manner to those of the AES. As a consequence there is a very strong confusion and diffusion in Grøstl. Grøstl is a so-called wide-pipe construction where the size of the internal state is significantly larger than the size of the output. This has the effect that all known, generic attacks on the hash function are made much more difficult. Grøstl has good performance on a wide range of platforms and counter-measures against side-channel attacks are well-understood from similar work on the AES.

Grøstl - a SHA-3 candidate

Grøstl is a SHA-3 candidate proposal. Grøstl is an iterated hash function with a compression function built from two �fixed, large, distinct permutations. The design of Grøstl is transparent and based on principles very different from those used in the SHA-family. The two permutations are constructed using the wide trail design strategy, which makes it possible to give strong statements about the resistance of Grøstl against large classes of cryptanalytic attacks. Moreover, if these permutations are assumed to be ideal, there is a proof for the security of the hash function. Grøstl is a byte-oriented SP-network which borrows components from the AES. The S-box used is identical to the one used in the block cipher AES and the diffusion layers are constructed in a similar manner to those of the AES. As a consequence there is a very strong confusion and diffusion in Grøstl

Performance-Based Quality Assurance/Quality Control (QA/QC) Acceptance Procedures for In-Place Soil Testing Phase 3

One of the objectives of this study was to evaluate soil testing equipment based on its capability of measuring in-place stiffness or modulus values. As design criteria transition from empirical to mechanistic-empirical, soil test methods and equipment that measure properties such as stiffness and modulus and how they relate to Florida materials are needed. Requirements for the selected equipment are that they be portable, cost effective, reliable, a ccurate, and repeatable. A second objective is that the selected equipment measures soil properties without the use of nuclear materials.The current device used to measure soil compaction is the nuclear density gauge (NDG). Equipment evaluated in this research included lightweight deflectometers (LWD) from different manufacturers, a dynamic cone penetrometer (DCP), a GeoGauge, a Clegg impact soil tester (CIST), a Briaud compaction device (BCD), and a seismic pavement analyzer (SPA). Evaluations were conducted over ranges of measured densities and moistures.Testing (Phases I and II) was conducted in a test box and test pits. Phase III testing was conducted on materials found on five construction projects located in the Jacksonville, Florida, area. Phase I analyses determined that the GeoGauge had the lowest overall coefficient of variance (COV). In ascending order of COV were the accelerometer-type LWD, the geophone-type LWD, the DCP, the BCD, and the SPA which had the highest overall COV. As a result, the BCD and the SPA were excluded from Phase II testing.In Phase II, measurements obtained from the selected equipment were compared to the modulus values obtained by the static plate load test (PLT), the resilient modulus (MR) from laboratory testing, and the NDG measurements. To minimize soil and moisture content variability, the single spot testing sequence was developed. At each location, test results obtained from the portable equipment under evaluation were compared to the values from adjacent NDG, PLT, and laboratory MR measurements. Correlations were developed through statistical analysis. Target values were developed for various soils for verification on similar soils that were field tested in Phase III. The single spot testing sequence also was employed in Phase III, field testing performed on A-3 and A-2-4 embankments, limerock-stabilized subgrade, limerock base, and graded aggregate base found on Florida Department of Transportation construction projects. The Phase II and Phase III results provided potential trend information for future research—specifically, data collection for in-depth statistical analysis for correlations with the laboratory MR for specific soil types under specific moisture conditions. With the collection of enough data, stronger relationships could be expected between measurements from the portable equipment and the MR values. Based on the statistical analyses and the experience gained from extensive use of the equipment, the combination of the DCP and the LWD was selected for in-place soil testing for compaction control acceptance. Test methods and developmental specifications were written for the DCP and the LWD. The developmental specifications include target values for the compaction control of embankment, subgrade, and base materials.

Provisioning a 3.3 MW PhotoVoltaic generation system onto a distribution authority’s 11 kV rural feeder

This paper describes part of an engineering study that was undertaken to demonstrate that a multi-megawatt Photovoltaic (PV) generation system could be connected to a rural 11 kV feeder without creating power quality issues for other consumers. The paper concentrates solely on the voltage regulation aspect of the study as this was the most innovative part of the study. The study was carried out using the time-domain software package, PSCAD/EMTDC. The software model included real time data input of actual measured load and scaled PV generation data, along with real-time substation voltage regulator and PV inverter reactive power control. The outputs from the model plot real-time voltage, current and power variations throughout the daily load and PV generation variations. Other aspects of the study not described in the paper include the analysis of harmonics, voltage flicker, power factor, voltage unbalance and system losses.

Hole mobility of 3.56 cm2V−1s−1accomplished using more extended dithienothiophene with furan flanked diketopyrrolopyrrole polymer

A highly extended dithienothiophene comonomer building block was used in combination with highly fused aromatic furan substituted diketopyrrolopyrrole for the synthesis of novel donor–acceptor alternating copolymer PDPPF-DTT. Upon testing PDPPF-DTT as a channel semiconductor in top contact bottom gate organic field effect transistors (OFETs), it was found to exhibit p-channel behaviour. The highest hole mobility of 3.56 cm2 V−1 s−1 was reported for PDPPF-DTT. To our knowledge, this is the highest mobility reported so far for the furan flanked diketopyrrolopyrrole class of copolymers using conventional device geometry with straightforward processing.

Bayesian refinement of association signals for 14 loci in 3 common diseases

To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves' disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal. Very few SNPs in our credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases. Our results also show the value of more detailed mapping to target sequences for functional studies. © 2012 Nature America, Inc. All rights reserved.

Interleukin-23 mediates the intestinal response to microbial β-1,3-glucan and the development of spondyloarthritis pathology in SKG mice

Objective Spondyloarthritides (SpA) occur in 1% of the population and include ankylosing spondylitis (AS) and arthropathy of inflammatory bowel disease (IBD), with characteristic spondylitis, arthritis, enthesitis, and IBD. Genetic studies implicate interleukin-23 (IL-23) receptor signaling in the development of SpA and IBD, and IL-23 overexpression in mice is sufficient for enthesitis, driven by entheseal-resident T cells. However, in genetically prone individuals, it is not clear where IL-23 is produced and how it drives the SpA syndrome, including IBD or subclinical gut inflammation of AS. Moreover, it is unclear why specific tissue involvement varies between patients with SpA. We undertook this study to determine the location of IL-23 production and its role in SpA pathogenesis in BALB/c ZAP-70W163C-mutant (SKG) mice injected intraperitoneally with β-1,3-glucan (curdlan). Methods Eight weeks after curdlan injection in wild-type or IL-17A-/- SKG or BALB/c mice, pathology was scored in tissue sections. Mice were treated with anti-IL-23 or anti-IL-22. Cytokine production and endoplasmic reticulum (ER) stress were determined in affected organs. Results In curdlan-treated SKG mice, arthritis, enthesitis, and ileitis were IL-23 dependent. Enthesitis was specifically dependent on IL-17A and IL-22. IL-23 was induced in the ileum, where it amplified ER stress, goblet cell dysfunction, and proinflammatory cytokine production. IL-17A was pathogenic, while IL-22 was protective against ileitis. IL-22+CD3- innate-like cells were increased in lamina propria mononuclear cells of ileitis-resistant BALB/c mice, which developed ileitis after curdlan injection and anti-IL-22. Conclusion In response to systemic β-1,3-glucan, intestinal IL-23 provokes local mucosal dysregulation and cytokines driving the SpA syndrome, including IL-17/IL-22-dependent enthesitis. Innate IL-22 production promotes ileal tolerance.

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with diseaseIRGM for Crohns disease, HLA for Crohns disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetesalthough in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases. © 2010 Macmillan Publishers Limited. All rights reserved.

Partial epilepsy syndrome in a Gypsy family linked to 5q31.3-q32

PURPOSE The restricted genetic diversity and homogeneous molecular basis of Mendelian disorders in isolated founder populations have rarely been explored in epilepsy research. Our long-term goal is to explore the genetic basis of epilepsies in one such population, the Gypsies. The aim of this report is the clinical and genetic characterization of a Gypsy family with a partial epilepsy syndrome. METHODS Clinical information was collected using semistructured interviews with affected subjects and informants. At least one interictal electroencephalography (EEG) recording was performed for each patient and previous data obtained from records. Neuroimaging included structural magnetic resonance imaging (MRI). Linkage and haplotype analysis was performed using the Illumina IVb Linkage Panel, supplemented with highly informative microsatellites in linked regions and Affymetrix SNP 5.0 array data. RESULTS We observed an early-onset partial epilepsy syndrome with seizure semiology strongly suggestive of temporal lobe epilepsy (TLE), with mild intellectual deficit co-occurring in a large proportion of the patients. Psychiatric morbidity was common in the extended pedigree but did not cosegregate with epilepsy. Linkage analysis definitively excluded previously reported loci, and identified a novel locus on 5q31.3-q32 with an logarithm of the odds (LOD) score of 3 corresponding to the expected maximum in this family. DISCUSSION The syndrome can be classified as familial temporal lobe epilepsy (FTLE) or possibly a new syndrome with mild intellectual deficit. The linked 5q region does not contain any ion channel-encoding genes and is thus likely to contribute new knowledge about epilepsy pathogenesis. Identification of the mutation in this family and in additional patients will define the full phenotypic spectrum.

The use of an acetoacetyl-CoA synthase in place of a -ketothiolase enhances poly-3-hydroxybutyrate production in sugarcane mesophyll cells

Engineering the production of polyhydroxyalkanoates (PHAs) into high biomass bioenergy crops has the potential to provide a sustainable supply of bioplastics and energy from a single plant feedstock. One of the major challenges in engineering C-4 plants for the production of poly[(R)-3-hydroxybutyrate] (PHB) is the significantly lower level of polymer produced in the chloroplasts of mesophyll (M) cells compared to bundle sheath (BS) cells, thereby limiting the full PHB yield-potential of the plant. In this study, we provide evidence that the access to substrate for PHB synthesis may limit polymer production in M chloroplasts. Production of PHB in M cells of sugarcane is significantly increased by replacing -ketothiolase, the first enzyme in the bacterial PHA pathway, with acetoacetyl-CoA synthase. This novel pathway enabled the production of PHB reaching an average of 6.3% of the dry weight of total leaf biomass, with levels ranging from 3.6 to 11.8% of the dry weight (DW) of individual leaves. These yields are more than twice the level reported in PHB-producing sugarcane containing the -ketothiolase and illustrate the importance of producing polymer in mesophyll plastids to maximize yield. The molecular weight of the polymer produced was greater than 2x10(6)Da. These results are a major step forward in engineering a high biomass C-4 grass for the commercial production of PHB.

Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3

We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 x 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 x 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.

A reanalysis of 409 European-Ancestry and African American schizophrenia pedigrees reveals significant linkage to 8p23.3 with evidence of locus heterogeneity

The detection and replication of schizophrenia risk loci can require substantial sample sizes, which has prompted various collaborative efforts for combining multiple samples. However, pooled samples may comprise sub-samples with substantial population genetic differences, including allele frequency differences. We investigated the impact of population differences via linkage reanalysis of Molecular Genetics of Schizophrenia 1 (MGS1) affected sibling-pair data, comprising two samples of distinct ancestral origin: European (EA: 263 pedigrees) and African-American (AA: 146 pedigrees). To exploit the linkage information contained within these distinct continental samples, we performed separate analyses of the individual samples, allowing for within-sample locus heterogeneity, and the pooled sample, allowing for both within-sample and between-sample heterogeneity. Significance levels, corrected for the multiple tests, were determined empirically. For all suggestive peaks, stronger linkage evidence was obtained in either the EA or AA sample than the combined sample, regardless of how heterogeneity was modeled for the latter. Notably, we report genomewide significant linkage of schizophrenia to 8p23.3 and evidence for a second, independent susceptibility locus, reaching suggestive linkage, 29 cM away on 8p21.3. We also detected suggestive linkage on chromosomes 5p13.3 and 7q36.2. Many regions showed pronounced differences in the extent of linkage between the EA and AA samples. This reanalysis highlights the potential impact of population differences upon linkage evidence in pooled data and demonstrates a useful approach for the analysis of samples drawn from distinct continental groups.

Familial isolated hyperparathyroidism is linked to a 1.7 Mb region on chromosome 2p13.3-14

BACKGROUND: Familial isolated hyperparathyroidism (FIHP) is an autosomal dominantly inherited form of primary hyperparathyroidism. Although comprising only about 1% of cases of primary hyperparathyroidism, identification and functional analysis of a causative gene for FIHP is likely to advance our understanding of parathyroid physiology and pathophysiology. METHODS: A genome-wide screen of DNA from seven pedigrees with FIHP was undertaken in order to identify a region of genetic linkage with the disorder. RESULTS: Multipoint linkage analysis identified a region of suggestive linkage (LOD score 2.68) on chromosome 2. Fine mapping with the addition of three other families revealed significant linkage adjacent to D2S2368 (maximum multipoint LOD score 3.43). Recombination events defined a 1.7 Mb region of linkage between D2S2368 and D2S358 in nine pedigrees. Sequencing of the two most likely candidate genes in this region, however, did not identify a gene for FIHP. CONCLUSIONS: We conclude that a causative gene for FIHP lies within this interval on chromosome 2. This is a major step towards eventual precise identification of a gene for FIHP, likely to be a key component in the genetic regulation of calcium homeostasis.

Plasma polymer and biomolecule modification of 3-D scaffolds for tissue engineering

Plasma polymerization was used to coat a melt electrospun polycaprolactone scaffold to improve cell attachment and organization. Plasma polymerization was performed using an amine containing monomer, allylamine, which then allowed for the subsequent immobilization of biomolecules i.e. heparin and fibroblast growth factor-2. The stability of the plasma polymerized amine-coating was demonstrated by X-ray photoelectron spectroscopy analysis and imaging time-of-flight secondary ion mass spectrometry revealed that a uniform plasma amine-coating was deposited throughout the scaffold. Based upon comparison with controls it was evident that the combination scaffold aided cell ingress and the formation of distinct fibroblast and keratinocyte layers.