Improving fluid registration through white matter segmentation in a twin study design

Robust and automatic non-rigid registration depends on many parameters that have not yet been systematically explored. Here we determined how tissue classification influences non-linear fluid registration of brain MRI. Twin data is ideal for studying this question, as volumetric correlations between corresponding brain regions that are under genetic control should be higher in monozygotic twins (MZ) who share 100% of their genes when compared to dizygotic twins (DZ) who share half their genes on average. When these substructure volumes are quantified using tensor-based morphometry, improved registration can be defined based on which method gives higher MZ twin correlations when compared to DZs, as registration errors tend to deplete these correlations. In a study of 92 subjects, higher effect sizes were found in cumulative distribution functions derived from statistical maps when performing tissue classification before fluid registration, versus fluidly registering the raw images. This gives empirical evidence in favor of pre-segmenting images for tensor-based morphometry.

Genetic variation within two sympatric spotted gum eucalypts exceeds between taxa variation

Population substructure and hybridization, among other factors, have the potential to cause erroneous associations in linkage disequilibrium (LD) mapping. Two closely related spotted gum eucalypts, Corymbia variegata and C. henryi (Myrtaceae) occur in sympatry in the east coast of Australia and potentially interbreed. They are morphologically similar but are distinguished as separate species based on capsule and foliage size. To determine whether they hybridize in nature and its implications for LD mapping, we investigated the level of molecular divergence between the two species at two sympatric locations separated by 300 kilometres. Very few individuals of intermediate morphology were identified, despite the two species occurring only metres apart. Analysis of genetic structure using 12 microsatellite loci showed that genetic differentiation between populations of the same species at different locations (FST = 0.07 for both species; p = 0.0001) was significantly higher than that observed between species at each location (mean FST = 0.02 and 0.04 for Cherry tree and Bunyaville respectively; p = 0.0001; all Mann-Whitney U-test p ≤ 0.01). No species-specific alleles or significant allele frequency differences were detected within a site, suggesting recurrent local gene flow between the two species. The lack of significant allele frequency differences implies no population stratification along taxonomic lines. This suggested that there is little concern for cryptic hybridization when sampling from sites of sympatry for LD mapping.

Genetic Heterogeneity in Autism Spectrum Disorders in a Population Isolate

Positional cloning has enabled hypothesis-free, genome-wide scans for genetic factors contributing to disorders or traits. Traditionally linkage analysis has been used to identify regions of interest, followed by meticulous fine mapping and candidate gene screening using association methods and finally sequencing of regions of interest. More recently, genome-wide association analysis has enabled a more direct approach to identify specific genetic variants explaining a part of the variance of the phenotype of interest. Autism spectrum disorders (ASDs) are a group of childhood onset neuropsychiatric disorders with shared core symptoms but varying severity. Although a strong genetic component has been established in ASDs, genetic susceptibility factors have largely eluded characterization. Here, we have utilized modern molecular genetic methods combined with the advantages provided by the special population structure in Finland to identify genetic risk factors for ASDs. The results of this study show that numerous genetic risk factors exist for ASDs even within a population isolate. Stratification based on clinical phenotype resulted in encouraging results, as previously identified linkage to 3p14-p24 was replicated in an independent family set of families with Asperger syndrome, but no other ASDs. Fine-mapping of the previously identified linkage peak for ASDs at 3q25-q27 revealed association between autism and a subunit of the 5-hydroxytryptamine receptor 3C (HTR3C). We also used dense, genome-wide single nucleotide polymorphism (SNP) data to characterize the population structure of Finns. We observed significant population substructure which correlates with the known history of multiple consecutive bottle-necks experienced by the Finnish population. We used this information to ascertain a genetically homogenous subset of autism families to identify possible rare, enriched risk variants using genome-wide SNP data. No rare enriched genetic risk factors were identified in this dataset, although a subset of families could be genealogically linked to form two extended pedigrees. The lack of founder mutations in this isolated population suggests that the majority of genetic risk factors are rare, de novo mutations unique to individual nuclear families. The results of this study are consistent with others in the field. The underlying genetic architecture for this group of disorders appears highly heterogeneous, with common variants accounting for only a subset of genetic risk. The majority of identified risk factors have turned out to be exceedingly rare, and only explain a subset of the genetic risk in the general population in spite of their high penetrance within individual families. The results of this study, together with other results obtained in this field, indicate that family specific linkage, homozygosity mapping and resequencing efforts are needed to identify these rare genetic risk factors.

Revisiting genetic structuring in spotted gums (genus Corymbia section Maculatae) focusing on C. maculata, an early diverged, insular lineage

Species delineation in the spotted gum complex was revisited focusing on Corymbia maculata. This study expands the range of C. maculata analysed with microsatellite markers to include populations from the north of the species range. It supported earlier findings that it is a cohesive genetic entity, well resolved from northern spotted gum taxa, Corymbia citriodora and Corymbia henryi; and inferences that its insularity is due to early lineage divergence and historical isolation. The northern extent of C. maculata sampled, as defined by chloroplast and nuclear genomes predominantly of C. maculata character, was the location of Kiwarrak, south of the Manning River near Taree in New South Wales. Trees from a recognised intergrade zone at the Yarratt locality, around 26 km north of Kiwarrak, also possessed a uniquely C. maculata chloroplast haplotype, but their nuclear genomes were predominantly of northern taxa ancestry. Range expansion of northern taxa leading to southerly gene movement into populations formerly C. maculata, would account for this apparent instance of chloroplast capture. Two subpopulations were identified in C. maculata, a northern population of which the Ourimbah locality was the most southerly studied, and a southern population of which Wingello was the most northerly locality studied. Diminished levels of northern taxa ancestry, i.e. C. citriodora or C. henryi, in individuals from the southern, relative to the northern subpopulation of C. maculata, suggested that secondary contact with northern taxa contributes to its substructure.

Lignin biosynthesis in Norway spruce: from a model system to the tree

Lignin is a hydrophobic polymer that is synthesised in the secondary cell walls of all vascular plants. It enables water conduction through the stem, supports the upright growth habit and protects against invading pathogens. In addition, lignin hinders the utilisation of the cellulosic cell walls of plants in pulp and paper industry and as forage. Lignin precursors are synthesised in the cytoplasm through the phenylpropanoid pathway, transported into the cell wall and oxidised by peroxidases or laccases to phenoxy radicals that couple to form the lignin polymer. This study was conducted to characterise the lignin biosynthetic pathway in Norway spruce (Picea abies (L.) Karst.). We focused on the less well-known polymerisation stage, to identify the enzymes and the regulatory mechanisms that are involved. Available data for lignin biosynthesis in gymnosperms is scarce and, for example, the latest improvements in precursor biosynthesis have only been verified in herbaceous plants. Therefore, we also wanted to study in detail the roles of individual gene family members during developmental and stress-induced lignification, using EST sequencing and real-time RT-PCR. We used, as a model, a Norway spruce tissue culture line that produces extracellular lignin into the culture medium, and showed that lignin polymerisation in the tissue culture depends on peroxidase activity. We identified in the culture medium a significant NADH oxidase activity that could generate H2O2 for peroxidases. Two basic culture medium peroxidases were shown to have high affinity to coniferyl alcohol. Conservation of the putative substrate-binding amino acids was observed when the spruce peroxidase sequences were compared with other peroxidases with high affinity to coniferyl alcohol. We also used different peroxidase fractions to produce synthetic in vitro lignins from coniferyl alcohol; however, the linkage pattern of the suspension culture lignin could not be reproduced in vitro with the purified peroxidases, nor with the full complement of culture medium proteins. This emphasised the importance of the precursor radical concentration in the reaction zone, which is controlled by the cells through the secretion of both the lignin precursors and the oxidative enzymes to the apoplast. In addition, we identified basic peroxidases that were reversibly bound to the lignin precipitate. They could be involved, for example, in the oxidation of polymeric lignin, which is required for polymer growth. The dibenzodioxocin substructure was used as a marker for polymer oxidation in the in vitro polymerisation studies, as it is a typical substructure in wood lignin and in the suspension culture lignin. Using immunolocalisation, we found the structure mainly in the S2+S3 layers of the secondary cell walls of Norway spruce tracheids. The structure was primarily formed during the late phases of lignification. Contrary to the earlier assumptions, it appears to be a terminal structure in the lignin macromolecule. Most lignin biosynthetic enzymes are encoded for by several genes, all of which may not participate in lignin biosynthesis. In order to identify the gene family members that are responsible for developmental lignification, ESTs were sequenced from the lignin-forming tissue culture and developing xylem of spruce. Expression of the identified lignin biosynthetic genes was studied using real-time RT-PCR. Candidate genes for developmental lignification were identified by a coordinated, high expression of certain genes within the gene families in all lignin-forming tissues. However, such coordinated expression was not found for peroxidase genes. We also studied stress-induced lignification either during compression wood formation by bending the stems or after Heterobasidion annosum infection. Based on gene expression profiles, stress-induced monolignol biosynthesis appeared similar to the developmental process, and only single PAL and C3H genes were specifically up-regulated by stress. On the contrary, the up-regulated peroxidase genes differed between developmental and stress-induced lignification, indicating specific responses.

Redefine: Runtime Reconfigurable Polymorphic ASIC

Emerging embedded applications are based on evolving standards (e.g., MPEG2/4, H.264/265, IEEE802.11a/b/g/n). Since most of these applications run on handheld devices, there is an increasing need for a single chip solution that can dynamically interoperate between different standards and their derivatives. In order to achieve high resource utilization and low power dissipation, we propose REDEFINE, a polymorphic ASIC in which specialized hardware units are replaced with basic hardware units that can create the same functionality by runtime re-composition. It is a ``future-proof'' custom hardware solution for multiple applications and their derivatives in a domain. In this article, we describe a compiler framework and supporting hardware comprising compute, storage, and communication resources. Applications described in high-level language (e.g., C) are compiled into application substructures. For each application substructure, a set of compute elements on the hardware are interconnected during runtime to form a pattern that closely matches the communication pattern of that particular application. The advantage is that the bounded CEs are neither processor cores nor logic elements as in FPGAs. Hence, REDEFINE offers the power and performance advantage of an ASIC and the hardware reconfigurability and programmability of that of an FPGA/instruction set processor. In addition, the hardware supports custom instruction pipelining. Existing instruction-set extensible processors determine a sequence of instructions that repeatedly occur within the application to create custom instructions at design time to speed up the execution of this sequence. We extend this scheme further, where a kernel is compiled into custom instructions that bear strong producer-consumer relationship (and not limited to frequently occurring sequences of instructions). Custom instructions, realized as hardware compositions effected at runtime, allow several instances of the same to be active in parallel. A key distinguishing factor in majority of the emerging embedded applications is stream processing. To reduce the overheads of data transfer between custom instructions, direct communication paths are employed among custom instructions. In this article, we present the overview of the hardware-aware compiler framework, which determines the NoC-aware schedule of transports of the data exchanged between the custom instructions on the interconnect. The results for the FFT kernel indicate a 25% reduction in the number of loads/stores, and throughput improves by log(n) for n-point FFT when compared to sequential implementation. Overall, REDEFINE offers flexibility and a runtime reconfigurability at the expense of 1.16x in power and 8x in area when compared to an ASIC. REDEFINE implementation consumes 0.1x the power of an FPGA implementation. In addition, the configuration overhead of the FPGA implementation is 1,000x more than that of REDEFINE.

Modeling of concrete cracking-A hybrid technique of using displacement discontinuity element method and direct boundary element method

This paper presents a new approach by making use of a hybrid method of using the displacement discontinuity element method and direct boundary element method to model concrete cracking by incorporating fictitious crack model. Fracture mechanics approach is followed using the Hillerborg's fictitious crack model. A boundary element based substructure method and a hybrid technique of using displacement discontinuity element method and direct boundary element method are compared in this paper. In order to represent the process zone ahead of the crack, closing forces are assumed to act in such a way that they obey a linear normal stress-crack opening displacement law. Plain concrete beams with and without initial crack under three-point loading were analyzed by both the methods. The numerical results obtained were shown to agree well with the results from existing finite element method. The model is capable of reproducing the whole range of load-deflection response including strain-softening and snap-back behavior as illustrated in the numerical examples. (C) 2011 Elsevier Ltd. All rights reserved.

PocketAnnotate: towards site-based function annotation

A computational pipeline PocketAnnotate for functional annotation of proteins at the level of binding sites has been proposed in this study. The pipeline integrates three in-house algorithms for site-based function annotation: PocketDepth, for prediction of binding sites in protein structures; PocketMatch, for rapid comparison of binding sites and PocketAlign, to obtain detailed alignment between pair of binding sites. A novel scheme has been developed to rapidly generate a database of non-redundant binding sites. For a given input protein structure, putative ligand-binding sites are identified, matched in real time against the database and the query substructure aligned with the promising hits, to obtain a set of possible ligands that the given protein could bind to. The input can be either whole protein structures or merely the substructures corresponding to possible binding sites. Structure-based function annotation at the level of binding sites thus achieved could prove very useful for cases where no obvious functional inference can be obtained based purely on sequence or fold-level analyses. An attempt has also been made to analyse proteins of no known function from Protein Data Bank. PocketAnnotate would be a valuable tool for the scientific community and contribute towards structure-based functional inference. The web server can be freely accessed at http://proline.biochem.iisc.ernet.in/pocketannotate/.

An experiment that shaped the physics of the century

In this article it is pointed out how the different layers of substructure of matter were revealed to us by experiments which were essentially very similar to the famous α-particle scattering experiment performed by Rutherford. This experiment, which revealed the nuclear structure of an atom, paved the way towards our current understanding of the fundamental constituents of matter and shaped the course of physics for the 20th century.

Looking for an invisible Higgs signal at the LHC

While the recent discovery of a Higgs-like boson at the LHC is an extremely important and encouraging step towards the discovery of the complete Standard Model (SM), the current information on this state does not rule out possibility of beyond standard model (BSM) physics. In fact the current data can still accommodate reasonably large values of the branching fractions of the Higgs into a channel with `invisible' decay products, such a channel being also well motivated theoretically. In this study we revisit the possibility of detecting the Higgs in this invisible channel for both choices of the LHC energies, 8 and 14 TeV, for two production modes; vector boson fusion (VBF) and associated production (ZH). We perform a comprehensive collider analysis for all the above channels and project the reach of LHC to constrain the invisible decay branching fraction for both 8 and 14 TeV energies. For the ZH case we consider decays of the Z boson into a pair of leptons as well as a b (b) over bar pair. For the VBF channel the sensitivity is found to be more than 5 sigma for both the energies up to an invisible branching ratio (Br-inv) similar to 0.80, with luminosities similar to 20/30 fb(-1). The sensitivity is further extended to values of Br-inv similar to 0.25 for 300 fb(-1) at 14 TeV. However the reach is found to be more modest for the ZH mode with leptonic final state; with about 3.5 sigma for the planned luminosity at 8 TeV, reaching 8 sigma only for 14 TeV for 50 fb(-1). In spite of the much larger branching ratio (BR) of the Z into a b (b) over bar channel compared to the dilepton case, the former channel, can provide useful reach up to Br-inv greater than or similar to 0.75, only for the higher luminosity (300 fb(-1)) option using both jet-substructure and jet clustering methods. (C) 2013 Elsevier B.V. All rights reserved.

Micromechanisms of fracture and strengthening in free-standing Pt-aluminide bond coats under tensile loading

Free-standing Pt-aluminide (PtAl) bond coats exhibit a linear stress strain response under tensile loading and undergo brittle cleavage fracture at temperatures below the brittle-to-ductile transition temperature (BDTT). Above the BDTT, these coatings show yielding and fail in a ductile manner. In this paper, the various micromechanisms affecting the tensile fracture stress (FS) below the BDTT and yield strength (YS) above the BDTT in a PtAl bond coat have been ascertained and quantified at various temperatures. The micromechanisms have been identified by carrying out microtensile testing of stand-alone PtAl coating specimens containing different levels of Pt at temperatures between room temperature and 1100 degrees C and correlation of the corresponding fracture mechanisms with the deformation substructure in the coating. An important aspect of the influence of Pt on the tensile behavior, slip characteristics, FS/YS and BDTT in the PtAl coating has also been examined. The addition of Pt enhances the FS of the coating by Pt solid solution strengthening and imparts a concomitant increase in fracture toughness and yet causes a significant increase in the BDTT of the coating. Published by Elsevier Ltd. on behalf of Acta Materialia Inc.

Boosting Higgs CP properties via VH production at the Large Hadron Collider

We consider ZH and WH production at the Large Hadron Collider, where the Higgs decays to a b (b) over bar pair. We use jet substructure techniques to reconstruct the Higgs boson and construct angular observables involving leptonic decay products of the vector bosons. These efficiently discriminate between the tensor structure of the HVV vertex expected in the Standard Model and that arising from possible new physics, as quantified by higher dimensional operators. This can then be used to examine the CP nature of the Higgs as well as CP mixing effects in the HZZ and HWW vertices separately. (C) 2014 Elsevier B.V.

Microstructural Features of Hot Deformed Nb-1Zr-0.1C Alloy

Niobium-based alloys are well-established refractory materials; as a result of their high melting temperature and good creep properties, these alloys find their applications in nuclear reactors. The present study deals with a microstructural response of these materials during hot working. The evolution of microstructure and texture during high-temperature deformation has been investigated in the temperature range 1500-1700A degrees C and strain rate range of 0.001-0.1 s(-1). For each deformed sample, the microstructure has been examined in detail. The microstructural features clearly revealed the formation of a substructure and the occurrence of dynamic recrystallization in a proper temperature-strain rate window. At low strain rates, the necklace structure formation was more prominent.

Social insect colony as a biological regulatory system: modelling information flow in dominance networks

Social insects provide an excellent platform to investigate flow of information in regulatory systems since their successful social organization is essentially achieved by effective information transfer through complex connectivity patterns among the colony members. Network representation of such behavioural interactions offers a powerful tool for structural as well as dynamical analysis of the underlying regulatory systems. In this paper, we focus on the dominance interaction networks in the tropical social wasp Ropalidia marginata-a species where behavioural observations indicate that such interactions are principally responsible for the transfer of information between individuals about their colony needs, resulting in a regulation of their own activities. Our research reveals that the dominance networks of R. marginata are structurally similar to a class of naturally evolved information processing networks, a fact confirmed also by the predominance of a specific substructure-the `feed-forward loop'-a key functional component in many other information transfer networks. The dynamical analysis through Boolean modelling confirms that the networks are sufficiently stable under small fluctuations and yet capable of more efficient information transfer compared to their randomized counterparts. Our results suggest the involvement of a common structural design principle in different biological regulatory systems and a possible similarity with respect to the effect of selection on the organization levels of such systems. The findings are also consistent with the hypothesis that dominance behaviour has been shaped by natural selection to co-opt the information transfer process in such social insect species, in addition to its primal function of mediation of reproductive competition in the colony.

Response of shock wave deformation in AA5086 aluminum alloy

The AA5086 aluminum alloy sheets with different starting textures were subjected to shock wave deformation with an input impulse of similar to 0.2 Ns. Microstructural examination indicate no significant change in grain size; however, the evolution of substructure manifesting intra-granular misorientation was evident. The improvement in hardness indicates the absence of recovery and strain hardening during shock deformation. Shock deformed samples show characteristic texture evolution with high Brass {110}< 112 > component. The study demonstrates the viability of high velocity forming of AA5086 aluminum alloy sheet using shock wave. (C) 2014 Elsevier B.V. All rights reserved.