ALBERT

Description: Revealing the clonal composition of a single tumor is essential for identifying cell subpopulations with metastatic potential in primary tumors or with resistance to therapies in metastatic tumors. Sequencing technologies provide only an overview of the aggregate of numerous cells. Computational approaches to de-mix a collective signal composed of the aberrations of a mixed cell population of a tumor sample into its individual components are not available. We propose an evolutionary framework for deconvolving data from a single genome-wide experiment to infer the composition, abundance and evolutionary paths of the underlying cell subpopulations of a tumor. We have developed an algorithm (TrAp) for solving this mixture problem. In silico analyses show that TrAp correctly deconvolves mixed subpopulations when the number of subpopulations and the measurement errors are moderate. We demonstrate the applicability of the method using tumor karyotypes and somatic hypermutation data sets. We applied TrAp to Exome-Seq experiment of a renal cell carcinoma tumor sample and compared the mutational profile of the inferred subpopulations to the mutational profiles of single cells of the same tumor. Finally, we deconvolve sequencing data from eight acute myeloid leukemia patients and three distinct metastases of one melanoma patient to exhibit the evolutionary relationships of their subpopulations.

Description: MicroRNAs (miRNAs) constitute an important class of small regulatory RNAs that are derived from distinct hairpin precursors (pre-miRNAs). In contrast to mature miRNAs, which have been characterized in numerous genome-wide studies of different organisms, research on global profiling of pre-miRNAs is limited. Here, using massive parallel sequencing, we have performed global characterization of both mouse mature and precursor miRNAs. In total, 87 369 704 and 252 003 sequencing reads derived from 887 mature and 281 precursor miRNAs were obtained, respectively. Our analysis revealed new aspects of miRNA/pre-miRNA processing and modification, including eight Ago2-cleaved pre-miRNAs, eight new instances of miRNA editing and exclusively 5' tailed mirtrons. Furthermore, based on the sequences of both mature and precursor miRNAs, we developed a miRNA discovery pipeline, miRGrep, which does not rely on the availability of genome reference sequences. In addition to 239 known mouse pre-miRNAs, miRGrep predicted 41 novel ones with high confidence. Similar as known ones, the mature miRNAs derived from most of these novel loci showed both reduced abundance following Dicer knockdown and the binding with Argonaute2. Evaluation on data sets obtained from Caenorhabditis elegans and Caenorhabditis sp.11 demonstrated that miRGrep could be widely used for miRNA discovery in metazoans, especially in those without genome reference sequences.

Description: It is a challenge to classify protein-coding or non-coding transcripts, especially those re-constructed from high-throughput sequencing data of poorly annotated species. This study developed and evaluated a powerful signature tool, Coding-Non-Coding Index (CNCI), by profiling adjoining nucleotide triplets to effectively distinguish protein-coding and non-coding sequences independent of known annotations. CNCI is effective for classifying incomplete transcripts and sense–antisense pairs. The implementation of CNCI offered highly accurate classification of transcripts assembled from whole-transcriptome sequencing data in a cross-species manner, that demonstrated gene evolutionary divergence between vertebrates, and invertebrates, or between plants, and provided a long non-coding RNA catalog of orangutan. CNCI software is available at http://www.bioinfo.org/software/cnci .

Description: Combinatorial transcription factor (TF) binding is essential for cell-type-specific gene regulation. However, much remains to be learned about the mechanisms of TF interactions, including to what extent constrained spacing and orientation of interacting TFs are critical for regulatory element activity. To examine the relative prevalence of the ‘enhanceosome’ versus the ‘TF collective’ model of combinatorial TF binding, a comprehensive analysis of TF binding site sequences in large scale datasets is necessary. We developed a motif-pair discovery pipeline to identify motif co-occurrences with preferential distance(s) between motifs in TF-bound regions. Utilizing a compendium of 289 mouse haematopoietic TF ChIP-seq datasets, we demonstrate that haematopoietic-related motif-pairs commonly occur with highly conserved constrained spacing and orientation between motifs. Furthermore, motif clustering revealed specific associations for both heterotypic and homotypic motif-pairs with particular haematopoietic cell types. We also showed that disrupting the spacing between motif-pairs significantly affects transcriptional activity in a well-known motif-pair—E-box and GATA, and in two previously unknown motif-pairs with constrained spacing—Ets and Homeobox as well as Ets and E-box. In this study, we provide evidence for widespread sequence-specific TF pair interaction with DNA that conforms to the ‘enhanceosome’ model, and furthermore identify associations between specific haematopoietic cell-types and motif-pairs.

Description: We present high-resolution tomographic images in source areas of 26 large crustal earthquakes ( M 6.0–7.2) which occurred in Northeast Japan (Tohoku) during the past 120 yr from 1894 to 2014. Prominent low-velocity (low- V ) and high Poisson's ratio (high- ) anomalies are revealed in the crust and mantle wedge under the source areas. Beneath the volcanic front and backarc areas, the low- V and high- zones reflect arc-magma related high-temperature anomalies which are produced by joint effects of corner flow in the mantle wedge and fluids from dehydration of the subducting Pacific slab. The hot anomalies cause locally thinning and weakening of the brittle seismogenic layer above them. Low-frequency micro-earthquakes are observed in the lower crust and uppermost mantle in or around the low- V zones, which reflect ascending of arc magma and fluids from the mantle wedge to the crust. No volcano and magma exist in the forearc area due to low temperature there, hence the low- V zones in the forearc reflect fluids from the slab dehydration. The ascending fluids may have produced a ‘water wall’ in the mantle wedge and crust beneath the forearc area. When the water enters active faults in the crust, the fault-zone friction is reduced and so large earthquakes can be induced. These results indicate that the nucleation of a large earthquake is not entirely a mechanical process, but is closely associated with subduction dynamics and physical and chemical properties of rocks in the crust and upper mantle. In particular, arc magma and fluids play an important role in the seismogenesis.

Description: Homologous non-coding RNAs frequently exhibit domain insertions, where a branch of secondary structure is inserted in a sequence with respect to its homologs. Dynamic programming algorithms for common secondary structure prediction of multiple RNA homologs, however, do not account for these domain insertions. This paper introduces a novel dynamic programming algorithm methodology that explicitly accounts for the possibility of inserted domains when predicting common RNA secondary structures. The algorithm is implemented as Dynalign II, an update to the Dynalign software package for predicting the common secondary structure of two RNA homologs. This update is accomplished with negligible increase in computational cost. Benchmarks on ncRNA families with domain insertions validate the method. Over base pairs occurring in inserted domains, Dynalign II improves accuracy over Dynalign, attaining 80.8% sensitivity (compared with 14.4% for Dynalign) and 91.4% positive predictive value (PPV) for tRNA; 66.5% sensitivity (compared with 38.9% for Dynalign) and 57.0% PPV for RNase P RNA; and 50.1% sensitivity (compared with 24.3% for Dynalign) and 58.5% PPV for SRP RNA. Compared with Dynalign, Dynalign II also exhibits statistically significant improvements in overall sensitivity and PPV. Dynalign II is available as a component of RNAstructure, which can be downloaded from http://rna.urmc.rochester.edu/RNAstructure.html .

Description: Sequence elements, at all levels—DNA, RNA and protein, play a central role in mediating molecular recognition and thereby molecular regulation and signaling. Studies that focus on measuring and investigating sequence-based recognition make use of statistical and computational tools, including approaches to searching sequence motifs. State-of-the-art motif searching tools are limited in their coverage and ability to address large motif spaces. We develop and present statistical and algorithmic approaches that take as input ranked lists of sequences and return significant motifs. The efficiency of our approach, based on suffix trees, allows searches over motif spaces that are not covered by existing tools. This includes searching variable gap motifs—two half sites with a flexible length gap in between—and searching long motifs over large alphabets. We used our approach to analyze several high-throughput measurement data sets and report some validation results as well as novel suggested motifs and motif refinements. We suggest a refinement of the known estrogen receptor 1 motif in humans, where we observe gaps other than three nucleotides that also serve as significant recognition sites, as well as a variable length motif related to potential tyrosine phosphorylation.

Description: Cataloging the association of transcripts to genetic variants in recent years holds the promise for functional dissection of regulatory structure of human transcription. Here, we present a novel approach, which aims at elucidating the joint relationships between transcripts and single-nucleotide polymorphisms (SNPs). This entails detection and analysis of modules of transcripts, each weakly associated to a single genetic variant, together exposing a high-confidence association signal between the module and this ‘main’ SNP. To explore how transcripts in a module are related to causative loci for that module, we represent such dependencies by a graphical model. We applied our method to the existing data on genetics of gene expression in the liver. The modules are significantly more, larger and denser than found in permuted data. Quantification of the confidence in a module as a likelihood score, allows us to detect transcripts that do not reach genome-wide significance level. Topological analysis of each module identifies novel insights regarding the flow of causality between the main SNP and transcripts. We observe similar annotations of modules from two sources of information: the enrichment of a module in gene subsets and locus annotation of the genetic variants. This and further phenotypic analysis provide a validation for our methodology.

Description: Phase variation of surface structures occurs in diverse bacterial species due to stochastic, high frequency, reversible mutations. Multiple genes of Campylobacter jejuni are subject to phase variable gene expression due to mutations in polyC/G tracts. A modal length of nine repeats was detected for polyC/G tracts within C. jejuni genomes. Switching rates for these tracts were measured using chromosomally-located reporter constructs and high rates were observed for cj1139 (G8) and cj0031 (G9). Alteration of the cj1139 tract from G8 to G11 increased mutability 10-fold and changed the mutational pattern from predominantly insertions to mainly deletions. Using a multiplex PCR, major changes were detected in ‘on/off’ status for some phase variable genes during passage of C. jejuni in chickens. Utilization of observed switching rates in a stochastic, theoretical model of phase variation demonstrated links between mutability and genetic diversity but could not replicate observed population diversity. We propose that modal repeat numbers have evolved in C. jejuni genomes due to molecular drivers associated with the mutational patterns of these polyC/G repeats, rather than by selection for particular switching rates, and that factors other than mutational drift are responsible for generating genetic diversity during host colonization by this bacterial pathogen.

Description: Control of translation in eukaryotes is complex, depending on the binding of various factors to mRNAs. Available data for subsets of mRNAs that are translationally up- and down-regulated in yeast eIF4E-binding protein (4E-BP) deletion mutants are coupled with reported mRNA secondary structure measurements to investigate whether 5'-UTR secondary structure varies between the subsets. Genes with up-regulated translational efficiencies in the caf20 mutant have relatively high averaged 5'-UTR secondary structure. There is no apparent wide-scale correlation of RNA-binding protein preferences with the increased 5'-UTR secondary structure, leading us to speculate that the secondary structure itself may play a role in differential partitioning of mRNAs between eIF4E/4E-BP repression and eIF4E/eIF4G translation initiation. Both Caf20p and Eap1p contain stretches of positive charge in regions of predicted disorder. Such regions are also present in eIF4G and have been reported to associate with mRNA binding. The pattern of these segments, around the canonical eIF4E-binding motif, varies between each 4E-BP and eIF4G. Analysis of gene ontology shows that yeast proteins containing predicted disordered segments, with positive charge runs, are enriched for nucleic acid binding. We propose that the 4E-BPs act, in part, as differential, flexible, polyelectrostatic scaffolds for mRNAs.

Description: The activation of cryptic 5' splice sites (5' SSs) is often related to human hereditary diseases. The DNA-based mutation screening strategies are commonly used to recognize the cryptic 5' SSs, because features of the local DNA sequence can influence the choice of cryptic 5' SSs. To improve the identification of the cryptic 5' SSs, we developed a structure-based method, named SPO (structure profiles and odds measure), which combines two parameters, the structural feature derived from hydroxyl radical cleavage pattern and odds measure, to assess the likelihood of a cryptic 5' SS activation in competing with its paired authentic 5' SS. Compared to the current tools for identifying activated cryptic 5' SSs, the SPO algorithm achieves higher prediction accuracy than the other methods, including MaxEnt, MDD, Markov model, weight matrix model, Shapiro and Senapathy matrix, R i and G . In addition, the predicted SPO scores from the SPO algorithm exhibited a greater degree of correlation with the strength of cryptic 5' SS activation than that measured from the other seven methods. In conclusion, the SPO algorithm provides an optimal identification of cryptic 5' SSs, can be applied in designing mutagenesis experiments for various splicing events and may be helpful to investigate the relationship between structural variants and human hereditary diseases.

Description: Determining the taxonomic affiliation of sequences assembled from metagenomes remains a major bottleneck that affects research across the fields of environmental, clinical and evolutionary microbiology. Here, we introduce MyTaxa, a homology-based bioinformatics framework to classify metagenomic and genomic sequences with unprecedented accuracy. The distinguishing aspect of MyTaxa is that it employs all genes present in an unknown sequence as classifiers, weighting each gene based on its (predetermined) classifying power at a given taxonomic level and frequency of horizontal gene transfer. MyTaxa also implements a novel classification scheme based on the genome-aggregate average amino acid identity concept to determine the degree of novelty of sequences representing uncharacterized taxa, i.e. whether they represent novel species, genera or phyla. Application of MyTaxa on in silico generated (mock) and real metagenomes of varied read length (100–2000 bp) revealed that it correctly classified at least 5% more sequences than any other tool. The analysis also showed that ~10% of the assembled sequences from human gut metagenomes represent novel species with no sequenced representatives, several of which were highly abundant in situ such as members of the Prevotella genus. Thus, MyTaxa can find several important applications in microbial identification and diversity studies.

Description: Increasing numbers of protein structures are solved each year, but many of these structures belong to proteins whose sequences are homologous to sequences in the Protein Data Bank. Nevertheless, the structures of homologous proteins belonging to the same family contain useful information because functionally important residues are expected to preserve physico-chemical, structural and energetic features. This information forms the basis of our method, which detects RNA-binding residues of a given RNA-binding protein as those residues that preserve physico-chemical, structural and energetic features in its homologs. Tests on 81 RNA-bound and 35 RNA-free protein structures showed that our method yields a higher fraction of true RNA-binding residues (higher precision) than two structure-based and two sequence-based machine-learning methods. Because the method requires no training data set and has no parameters, its precision does not degrade when applied to ‘novel’ protein sequences unlike methods that are parameterized for a given training data set. It was used to predict the ‘unknown’ RNA-binding residues in the C-terminal RNA-binding domain of human CPEB3. The two predicted residues, F430 and F474, were experimentally verified to bind RNA, in particular F430, whose mutation to alanine or asparagine nearly abolished RNA binding. The method has been implemented in a webserver called DR_bind1, which is freely available with no login requirement at http://drbind.limlab.ibms.sinica.edu.tw .

Description: For a period of about 1 yr between the summers of 2010 and 2011, 25 broad-band seismographs were deployed in a roughly linear array across the eastern end of the Qaidam basin and the Qilian Shan in the northeastern Tibetan plateau. This region is probably the most suitable place to study the ongoing convergence interaction between the high Tibetan plateau and the main Asian continental plate. Low-frequency P receiver function analysis of the data provides an image of the crust and mantle down to 700 km depth. In addition to the Moho at 45–65 km depth beneath the profile, the 410 and 660 km discontinuities bounding the mantle transition zone can be identified at 400–410 and 650–660 km depths, respectively. A possible increase in temperature in the upper mantle thought to exist beneath the northern part of the high Tibetan plateau is thus confined to this part of the plateau and lower upper-mantle temperatures similar to those beneath southern Tibet occur beneath the Qaidam basin and Qilian Shan. When higher frequencies are included in the P receiver function analysis, a positive Ps converter dipping down to the south from 70–75 km depth at 37.9°N to about 110 km depth at 36°N is imaged. As this feature is only seen in high-frequency images and not in the low-frequency image, it is modelled as the positive Ps conversion from the base of an approximately 5-km-thick anisotropic layer at the top of the Asian mantle lithosphere which is currently subducting. This south-dipping converter continues to the south on the INDEPTH IV profile. S receiver function analysis completes the image of the structure below the Qilian Shan profile with the identification of the lithosphere–asthenosphere boundary (LAB). The LAB of the Asian Plate is identified for a reference slowness of 6.4 s deg –1 at 12–14 s (105–125 km depth) between 38 and 41°N below the northern part of the S receiver function profile. To the south it increases in depth such that it is at about 19 s (170 km depth) between 34 and 35°N at the southern end of the profile. The LAB of the Asian Plate occurs at similar depths on the INDEPTH IV profile at the latitudes where the INDEPTH IV and Qilian Shan profiles overlap. As on the INDEPTH IV profile to the south, between 34 and 35°N at the southern end of the Qilian Shan profile there is evidence from the S receiver functions for the LAB of a separate Tibetan Plate.

Description: Nanotechnology and synthetic biology currently constitute one of the most innovative, interdisciplinary fields of research, poised to radically transform society in the 21st century. This paper concerns the synthetic design of ribonucleic acid molecules, using our recent algorithm, RNAiFold , which can determine all RNA sequences whose minimum free energy secondary structure is a user-specified target structure. Using RNAiFold , we design ten cis -cleaving hammerhead ribozymes, all of which are shown to be functional by a cleavage assay. We additionally use RNAiFold to design a functional cis -cleaving hammerhead as a modular unit of a synthetic larger RNA. Analysis of kinetics on this small set of hammerheads suggests that cleavage rate of computationally designed ribozymes may be correlated with positional entropy, ensemble defect, structural flexibility/rigidity and related measures. Artificial ribozymes have been designed in the past either manually or by SELEX (Systematic Evolution of Ligands by Exponential Enrichment); however, this appears to be the first purely computational design and experimental validation of novel functional ribozymes. RNAiFold is available at http://bioinformatics.bc.edu/clotelab/RNAiFold/ .

Description: Lower and upper bounds for present deformation rates across faults in central California between the San Andreas Fault and Pacific coast are estimated from a new Global Positioning System (GPS) velocity field for central, western California in light of geodetic evidence presented in a companion paper for slow, but significant deformation within the Pacific Plate between young seafloor in the eastern Pacific and older seafloor elsewhere on the plate. Transects of the GPS velocity field across the San Andreas Fault between Parkfield and San Juan Buatista, where fault slip is dominated by creep and the velocity field thus reveals the off-fault deformation, show that GPS sites in westernmost California move approximately parallel to the fault at an average rate of 3.4 ± 0.4 mm yr –1 relative to the older interior of the Pacific Plate, but only 1.8 ± 0.6 mm yr –1 if the Pacific Plate frame of reference is corrected for deformation within the plate. Modelled interseismic elastic deformation from the weakly coupled creeping segment of the San Andreas Fault is an order-of-magnitude too small to explain the southeastward motions of coastal sites in western California. Similarly, models that maximize residual viscoelastic deformation from the 1857 Fort Tejon and 1906 San Francisco earthquakes mismatch both the rates and directions of GPS site motions in central California relative to the Pacific Plate. Neither thus explains the site motions southwest of the San Andreas fault, indicating that the site motions measure deformation across faults and folds outboard of the San Andreas Fault. The non-zero site velocities thus constitute strong evidence for active folding and faulting outboard from the creeping segment of the San Andreas Fault and suggest limits of 0–2 mm yr –1 for the Rinconada Fault slip rate and 1.8 ± 0.6 to 3.4 ± 0.4 mm yr –1 for the slip rates integrated across near-coastal faults such as the Hosgri, San Gregorio and San Simeon faults.

Description: We combine new, well-determined GPS velocities from Clarion, Guadalupe and Socorro islands on young seafloor in the eastern Pacific basin with newly estimated velocities for 26 GPS sites from older seafloor in the central, western and southern parts of the Pacific Plate to test for deformation within the interior of the Pacific Plate and estimate the viscosity of the asthenosphere below the plate. Relative to a Pacific Plate reference frame defined from the velocities of the 26 GPS sites in other areas of the Pacific Plate, GPS sites on Clarion and Guadalupe islands in the eastern Pacific move 1.2 ± 0.6 mm yr –1 (1) towards S09°W ± 38° and 1.9 ± 0.3 mm yr –1 towards S19°E ± 10°, respectively. The two velocities, which are consistent within their 95 per cent uncertainties, both differ significantly from Pacific Plate motion. Transient volcanic deformation related to a 1993–1996 eruption of the Socorro Island shield volcano renders our GPS velocity from that island unreliable for the tectonic analysis although its motion is also southward like those of Clarion and Guadalupe islands. We test but reject the possibilities that drift of Earth's origin in ITRF2008 or unmodelled elastic offsets due to large-magnitude earthquakes around the Pacific rim since 1993 can be invoked to explain the apparent slow southward motions of Clarion and Guadalupe islands. Similarly, corrections to the Pacific Plate GPS velocity field for possible viscoelastic deformation triggered by large-magnitude earthquakes since 1950 also fail to explain the southward motions of the two islands. Viscoelastic models with prescribed asthenospheric viscosities lower than 1  x 10 19 Pa s instead introduce statistically significant inconsistencies into the Pacific Plate velocity field, suggesting that the viscosity of the asthenosphere below the plate is higher than 1  x 10 19 Pa s. Elastic deformation from locked Pacific–North America Plate boundary faults is also too small to explain the southward motions of the two islands. Horizontal thermal contraction of the plate interior may explain the motion observed at Clarion and Guadalupe islands, as might long-term tectonic deformation of the plate interior.

Description: In this study, a new method for computing the sensitivity of the glacial isostatic adjustment (GIA) forward solution with respect to the Earth's mantle viscosity, the so-called the forward sensitivity method (FSM), and a method for computing the gradient of data misfit with respect to viscosity parameters, the so-called adjoint-state method (ASM), are presented. These advanced formal methods complement each other in the inverse modelling of GIA-related observations. When solving this inverse problem, the first step is to calculate the forward sensitivities by the FSM and use them to fix the model parameters that do not affect the forward model solution, as well as identifying and removing redundant parts of the inferred viscosity structure. Once the viscosity model is optimized in view of the forward sensitivities, the minimization of the data misfit with respect to the viscosity parameters can be carried out by a gradient technique which makes use of the ASM. The aim is this paper is to derive the FSM and ASM in the forms that are closely associated with the forward solver of GIA developed by Martinec. Since this method is based on a continuous form of the forward model equations, which are then discretized by spectral and finite elements, we first derive the continuous forms of the FSM and ASM and then discretize them by the spectral and finite elements used in the discretization of the forward model equations. The advantage of this approach is that all three methods (forward, FSM and ASM) have the same matrix of equations and use the same methodology for the implementation of the time evolution of stresses. The only difference between the forward method and the FSM and ASM is that the different numerical differencing schemes for the time evolution of the Maxwell and generalized Maxwell viscous stresses are applied in the respective methods. However, it requires only a little extra computational time for carrying out the FSM and ASM numerically. An straightforward approach to compute the gradient of the data misfit is the brute-force method, whereby the partial derivatives of the misfit with respect to model parameters are approximated by the centred difference of two forward model runs. Although the brute-force method is useful for computing the gradient of the data misfit with respect to a small number of model parameters, it becomes expensive for a viscosity model with a large number of parameters. The ASM offers an efficient alternative for computing the gradient of the misfit since the computational time of the ASM is independent of the number of viscosity parameters. The ASM is thus highly efficient for calculating the gradient of the misfit for models with large numbers of parameters. However, the forward-model solution for each time step must be stored, hence the memory demands scale linearly with the number of time steps. This is the main drawback of the ASM.

Description: While mRNA stability has been demonstrated to control rates of translation, generating both global and local synonymous codon biases in many unicellular organisms, this explanation cannot adequately explain why codon bias strongly tracks neighboring intergene GC content; suggesting that structural dynamics of DNA might also influence codon choice. Because minor groove width is highly governed by 3-base periodicity in GC, the existence of triplet-based codons might imply a functional role for the optimization of local DNA molecular dynamics via GC content at synonymous sites (GC3). We confirm a strong association between GC3-related intrinsic DNA flexibility and codon bias across 24 different prokaryotic multiple whole-genome alignments. We develop a novel test of natural selection targeting synonymous sites and demonstrate that GC3-related DNA backbone dynamics have been subject to moderate selective pressure, perhaps contributing to our observation that many genes possess extreme DNA backbone dynamics for their given protein space. This dual function of codons may impose universal functional constraints affecting the evolution of synonymous and non-synonymous sites. We propose that synonymous sites may have evolved as an ‘accessory’ during an early expansion of a primordial genetic code, allowing for multiplexed protein coding and structural dynamic information within the same molecular context.

Description: Relative to the gravitational potential energy of the Earth's monopole, the multipole energy has received far less attention. In this paper, we recapitulate the basic physics from first principles and derive the formulas for multipole energies in analogy to classical electrostatic theory. We focus on the zonal quadrupole energy associated with the Earth's oblateness, the dominant term in Earth's gravity field apart from the monopole. We find the gravitational energy E oblateness 10 –6 | E monopole | = +2.5 x 10 26 J. We examine the implications of E oblateness and its changes associated with long-term ‘secular’ decreases in the oblateness parameter J 2 . We find the rate of loss of E oblateness due to the Earth rounding induced by the present-day GIA is about –200 GW, an amount quite significant in the kinetic energy budget of the mantle heat engine that drives the plate tectonics that has been estimated to be ~1 TW. We also assert that the tidal braking and the global earthquake dislocations, both resulting in Earth rounding on long-term geological timescales, are accompanied with a secular decrease of E oblateness at nearly the same rate of several GW.

Description: Large-scale chemical lateral heterogeneities are inferred in the Earth's lowermost mantle by seismological studies. We explore the model space of thermochemical convection that can maintain reservoirs of dense material for a long period of time, by using similar analysis in 3-D spherical geometry. In this study, we focus on the parameters thought to be important in controlling the stability and structure of primordial dense reservoirs in the lower mantle, including the chemical density contrast between the primordial dense material and the regular mantle material (buoyancy ratio), thermal and chemical viscosity contrasts, volume fraction of primordial dense material and the Clapeyron slope of the phase transition at 660 km depth. We find that most of the findings from the 3-D Cartesian study still apply to 3-D spherical cases after slight modifications. Varying buoyancy ratio leads to different flow patterns, from rapid upwelling to stable layering; and large thermal viscosity contrasts are required to generate long wavelength chemical structures in the lower mantle. Chemical viscosity contrasts in a reasonable range have a second-order role in modifying the stability of the dense anomalies. The volume fraction of the initial primordial dense material does not effect the results with large thermal viscosity contrasts, but has significant effects on calculations with intermediate and small thermal viscosity contrasts. The volume fraction of dense material at which the flow pattern changes from unstable to stable depends on buoyancy ratio and thermal viscosity contrast. An endothermic phase transition at 660 km depth acts as a ‘filter’ allowing cold slabs to penetrate while blocking most of the dense material from penetrating to the upper mantle.

Description: Relative sea level curves contain coupled information about absolute sea level change and vertical lithospheric movement. Such curves may be constructed based on, for example tide gauge data for the most recent times and different types of geological data for ancient times. Correct account for vertical lithospheric movement is essential for estimation of reliable values of absolute sea level change from relative sea level data and vise versa. For modern times, estimates of vertical lithospheric movement may be constrained by data (e.g. GPS-based measurements), which are independent from the relative sea level data. Similar independent data do not exist for ancient times. The purpose of this study is to test two simple inversion approaches for simultaneous estimation of lithospheric uplift rates and absolute sea level change rates for ancient times in areas where a dense coverage of relative sea level data exists and well-constrained average lithospheric movement values are known from, for example glacial isostatic adjustment (GIA) models. The inversion approaches are tested and used for simultaneous estimation of lithospheric uplift rates and absolute sea level change rates in southwest Scandinavia from modern relative sea level data series that cover the period from 1900 to 2000. In both approaches, a priori information is required to solve the inverse problem. A priori information about the average vertical lithospheric movement in the area of interest is critical for the quality of the obtained results. The two tested inversion schemes result in estimated absolute sea level rise of ~1.2/1.3 mm yr –1 and vertical uplift rates ranging from approximately –1.4/–1.2 mm yr –1 (subsidence) to about 5.0/5.2 mm yr –1 if an a priori value of 1 mm yr –1 is used for the vertical lithospheric movement throughout the study area. In case the studied time interval is broken into two time intervals (before and after 1970), absolute sea level rise values of ~0.8/1.2 mm yr –1 (before 1970) and ~2.0 mm yr –1 (after 1970) are found. The uplift patterns resulting from the different inversions suggest that the lithospheric post-GIA response changes near the border between the Danish Basin and the Fennoscandian Shield. The obtained patterns of vertical lithospheric movement rates are comparable to results from other studies based on different and similar data types. Main differences between the inversion results and the results from other studies are caused by factors such as the simplifications included in the inversion approach, such as neglecting local sea level variation caused by the dominant wind patterns, and the a priori values chosen for the vertical uplift rates. The tests of the inversion schemes reveal that realistic values of absolute sea level rise and lithospheric uplift may be simultaneously estimated provided that reliable prior knowledge regarding the overall lithospheric uplift in the study area is available beforehand. In the presented parametrizations, only one absolute sea level change rate value is estimated for each studied time interval while several vertical movement rates are found, and the inverse estimate of absolute sea level change rate is practically insensitive with respect to the choice of a priori value of absolute sea level change, as long as the uncertainty assigned to this a priori value is kept sufficiently high.

Description: In 1356, a magnitude 6–7 earthquake occurred near Basel, in Switzerland. But recent compilations of GPS measurements reveal that measured horizontal deformation rates in northwestern continental Europe are smaller than error bars on the measurements, proving present tectonic activity, if any, is very small in this area. We propose to reconcile these apparently antinomic observations with a mechanical model of the lithosphere that takes into account the geometry of the lithosphere–asthenosphere boundary, assuming that the only loading mechanism is gravity. The lithosphere is considered to be an elastoplastic material satisfying a Von Mises plasticity criterion. The model, which is 400 km long, 360 km wide and 230 km thick, is centred near Belfort in eastern France, with its width oriented parallel to the N145°E direction. It also takes into account the real topography of both the ground surface and that of the Moho discontinuity. Not only does the model reproduce observed principal stress directions orientations, it also identifies a plastic zone that fits roughly the most seismically active domain of the region. Interestingly, a somewhat similar stress map may be produced by considering an elastic lithosphere and an ad-hoc horizontal ‘tectonic’ stress field. However, for the latter model, examination of the plasticity criterion suggests that plastic deformation should have taken place. It is concluded that the present-day stress field in this region is likely controlled by gravity and rheology, rather than by active Alpine tectonics.

Description: We have investigated variations in transition zone thickness under the Borborema Province of NE Brazil by migrating and stacking teleseismic P -wave receiver functions at 32 seismic stations in the region. The Borborema Province represents the western portion of a larger Neoproterozoic mobile belt that occupied much of northern Gondwana, where extensional processes in the Mesozoic lead to the formation of a number of intracontinental basins and ultimately continental breakup. Episodes of intraplate volcanism and uplift marked the evolution of the Province during the Cenozoic, but it is unclear whether those episodes originated from shallow or deep-seated magmatic sources. On one hand, the elliptical shape of the uplifted area, the stress pattern of the Cenozoic deformation and the time overlap between uplift and volcanism suggest doming from thermal activation due to a deep-seated mantle plume. On the other hand, geochronological dates of volcanic bodies in the Province are better understood if resulting from lithospheric erosion by a shallow, small-scale convection cell. Large temperature anomalies are expected to be associated with mantle upwellings, and constraints on the depth extent of the upwellings can be obtained from transition zone thickness. Thinning of the transition zone with respect to its nominal 250 km value is considered diagnostic for positive temperature anomalies, while thickening is considered diagnostic for negative anomalies. Our results show that transition zone thickness is normal, around 250 km, throughout the Province and suggest that thermal perturbations—if present—are confined to the upper mantle. We argue that our results are consistent with a local, shallow magmatic source for the Cenozoic intraplate volcanism of the Borborema Province, although other proposed scenarios—such as channeling of upwelling plume material along lithospheric thin spots—cannot be ruled out with our analysis.

Description: The thermophilic fungus Chaetomium thermophilum holds great promise for structural biology. To increase the efficiency of its biochemical and structural characterization and to explore its thermophilic properties beyond those of individual proteins, we obtained transcriptomics and proteomics data, and integrated them with computational annotation methods and a multitude of biochemical experiments conducted by the structural biology community. We considerably improved the genome annotation of Chaetomium thermophilum and characterized the transcripts and expression of thousands of genes. We furthermore show that the composition and structure of the expressed proteome of Chaetomium thermophilum is similar to its mesophilic relatives. Data were deposited in a publicly available repository and provide a rich source to the structural biology community.

Description: Standard techniques for computed tomography imaging are not directly applicable to a carbonate rock because of the geometric complexity of its pore space. In this study, we first characterized the pore structure in Majella limestone with 30 per cent porosity. Microtomography data acquired on this rock was partitioned into three distinct domains: macropores, solid grains, and an intermediate domain made up of voxels of solid embedded with micropores below the resolution. A morphological analysis of the microtomography images shows that in Majella limestone both the solid and intermediate domains are interconnected in a manner similar to that reported previously in a less porous limestone. We however show that the macroporosity in Majella limestone is fundamentally different, in that it has a percolative backbone which may contribute significantly to its permeability. We then applied for the first time 3-D-volumetric digital image correlation (DIC) to characterize the mode of mechanical failure in this limestone. Samples were triaxially deformed over a wide range of confining pressures. Tomography imaging was performed on these samples before and after deformation. Inelastic compaction was observed at all tested pressures associated with both brittle and ductile behaviors. Our DIC analysis reveals the structure of compacting shear bands in Majella limestone deformed in the transitional regime. It also indicates an increase of geometric complexity with increasing confinement—from a planar shear band, to a curvilinear band, and ultimately to a diffuse multiplicity of bands, before shear localization is inhibited as the failure mode completes the transition to delocalized cataclastic flow.

Description: Wide-angle reflection/refraction seismic profiles were recorded across the Cyprus Arc, the plate boundary between the African Plate and the Aegean–Anatolian microplate, from the Eratosthenes Seamount to the Hecataeus Rise immediately south of Cyprus. The resultant models were able to resolve detail of significant lateral velocity variations, though the deepest crust and Moho are not well resolved from the seismic data alone. Conclusions from the modelling suggest that (i) Eratosthenes Seamount consists of continental crust but exhibits a laterally variable velocity structure with a thicker middle crust and thinner lower crust to the northeast; (ii) the Hecataeus Rise has a thick sedimentary rock cover on an indeterminate crust (likely continental) and the crust is significantly thinner than Eratosthenes Seamount based on gravity modelling; (iii) high velocity basement blocks, coincident with highs in the magnetic field, occur in the deep water between Eratosthenes and Hecataeus, and are separated and bounded by deep low-velocity troughs and (iv) one of the high velocity blocks runs parallel to the Cyprus Arc, while the other two appear linked based on the magnetic data and run NW–SE, parallel to the margin of the Hecataeus Rise. The high velocity block beneath the edge of Eratosthenes Seamount is interpreted as an older magmatic intrusion while the linked high velocity blocks along Hecataeus Rise are interpreted as deformed remnant Tethyan oceanic crust or mafic intrusives from the NNW–SSE oriented transform margin marking the northern boundary of Eratosthenes Seamount. Eratosthenes Seamount, the northwestern limit of rifted continental crust from the Levant Margin, is part of a jagged rifted margin transected by transform faults on the northern edge of the lower African Plate that is being obliquely subducted under the Aegean–Anatolian upper plate. The thicker crust of Eratosthenes Seamount may be acting as an asperity on the subducting slab, locally locking up subduction of the Cyprus Arc on its northern margin, while deformed Tethyan oceanic crust remains trapped between its northeastern margin and the Hecataeus Rise.

Description: We present an up-to-date high resolution picture of the ongoing crustal deformation field of Italy, based on an extensive combination of permanent and non-permanent GPS observations carried out since 1994. In addition, we present an updated map of contemporary S Hmax orientations computed by a multidisciplinary data set of well-constrained stress indicators, including both published results and novel analyses. The comparison of stress and geodetic strain-rates directions reveals that both patterns are near-parallel over a large part of the investigated area, highlighting that crustal stress and surface deformation are driven by the same mechanism. The comparison of the azimuthal patterns of surface strain and mantle deformation shows a modest correlation on the Alps and a low correlation along the Apennines chain and the Calabro-Peloritan Arc. Along the Apennines chain, this feature suggests the occurrence of significant strain partitioning and crust–mantle mechanical decoupling. Along the Calabro-Peloritan Arc, the apparent low correlation reflects a different mantle–crust mechanism of deformation to the ongoing subduction and rollback of the Ionian slab. In addition, the superposition of regional/local effects related to second-order sources (crustal lateral density changes, strength contrasts), which at regional/local scale modulate the crustal stress/strain-rate pattern, cannot be ruled out.

Description: A series of linear analysis was performed on the onset of thermal convection of highly compressible fluids, in order to deepen the fundamental insights into the mantle convection of massive super-Earths in the presence of strong adiabatic compression. We consider the temporal evolution (growth or decay) of an infinitesimal perturbation superimposed to a highly compressible fluid which is in a hydrostatic (motionless) and conductive state in a basally heated horizontal layer. As a model of pressure-dependence in material properties, we employed an exponential decrease in thermal expansivity α and exponential increase in (reference) density with depth. The linearized equations for conservation of mass, momentum and internal (thermal) energy are numerically solved for the critical Rayleigh number as well as the vertical profiles of eigenfunctions for infinitesimal perturbations. The above calculations are repeatedly carried out by systematically varying (i) the dissipation number (Di), (ii) the temperature at the top surface and (iii) the magnitude of pressure-dependence in α and . Our analysis demonstrated that the onset of thermal convection is strongly affected by the adiabatic compression, in response to the changes in the static stability of thermal stratification in the fluid layer. For sufficiently large Di where a thick sublayer of stable stratification develops in the layer, for example, the critical Rayleigh number explosively increases with Di, together with drastic decreases in the length scales of perturbations both in vertical and horizontal directions. In particular, for very large Di, a thick ‘stratosphere’ occurs in the fluid layer where the vertical motion is significantly suppressed, resulting in a shrink of the incipient convection in a thin sublayer of unstable thermal stratification. In addition, when Di exceeds a threshold value above which a thermal stratification becomes stable in the entire layer, no perturbation is allowed to grow with time regardless of the Rayleigh number and/or the horizontal wavelength. We also found that the effect of adiabatic compression becomes prominent for higher temperature at the top surface of the fluid layer. These findings may imply the crucial importance of adiabatic compression in understanding the dynamics and evolution of the mantles of massive super-Earths, particularly for those orbiting their parent stars very closely.

Description: In this paper, we propose an approach to compute the coseismic Earth's volume change based on a spherical-Earth elastic dislocation theory. We present a general expression of the Earth's volume change for three typical dislocations: the shear, tensile and explosion sources. We conduct a case study for the 2004 Sumatra earthquake ( M w 9.3), the 2010 Chile earthquake ( M w 8.8), the 2011 Tohoku-Oki earthquake ( M w 9.0) and the 2013 Okhotsk Sea earthquake ( M w 8.3). The results show that mega-thrust earthquakes make the Earth expand and earthquakes along a normal fault make the Earth contract. We compare the volume changes computed for finite fault models and a point source of the 2011 Tohoku-Oki earthquake ( M w 9.0). The big difference of the results indicates that the coseismic changes in the Earth's volume (or the mean radius) are strongly dependent on the earthquakes’ focal mechanism, especially the depth and the dip angle. Then we estimate the cumulative volume changes by historical earthquakes ( M w ≥ 7.0) since 1960, and obtain an Earth mean radius expanding rate about 0.011 mm yr –1 .

Description: The Joint BioEnergy Institute Inventory of Composable Elements (JBEI-ICEs) is an open source registry platform for managing information about biological parts. It is capable of recording information about ‘legacy’ parts, such as plasmids, microbial host strains and Arabidopsis seeds, as well as DNA parts in various assembly standards. ICE is built on the idea of a web of registries and thus provides strong support for distributed interconnected use. The information deposited in an ICE installation instance is accessible both via a web browser and through the web application programming interfaces, which allows automated access to parts via third-party programs. JBEI-ICE includes several useful web browser-based graphical applications for sequence annotation, manipulation and analysis that are also open source. As with open source software, users are encouraged to install, use and customize JBEI-ICE and its components for their particular purposes. As a web application programming interface, ICE provides well-developed parts storage functionality for other synthetic biology software projects. A public instance is available at public-registry.jbei.org, where users can try out features, upload parts or simply use it for their projects. The ICE software suite is available via Google Code, a hosting site for community-driven open source projects.

Description: We present the crustal resistivity structure of the Pamir and Southern Tian Shan orogenic belts at the northwestern promontory of the India–Asia collision zone. The magnetotelluric (MT) data were recorded along a roughly north–south trending, 350 km long corridor from the Pamir Plateau in southern Tajikistan across the Pamir frontal ranges, the Alai Valley and the southwestern Tian Shan to Osh in the Kyrgyz part of the Fergana Basin. In total, we measured at 178 sites, whereof 26 combine broad band and long period recordings. One of the most intriguing features of the 2-D and 3-D inversion results is a laterally extended zone of high electrical conductivity below the Pamir Plateau, with resistivities below 1 m, starting at a depth of ~10–15 km. The high conductivity can be explained with the presence of partially molten rocks at middle to lower crustal levels, possibly related to ongoing migmatization and/or middle/lower crustal flow underneath the Southern Pamir. This interpretation is consistent with a low velocity zone found from local earthquake tomography, relatively high v p / v s ratios, elevated surface heat flow, and thermomechanical modelling suggesting that melting temperatures are reached in the felsic middle crust. In the upper crust of the Pamir and Tian Shan, the Palaeozoic–Mesozoic suture zones appear as electrically conductive, whereas the compact metamorphic rocks of the Muskol-Shatput Dome of the Central Pamir are highly resistive. The intra-montane basin of the Alai Valley—sandwiched between the Pamir and Tian Shan—exhibits a generally conductive upper crust that bifurcates into two conductors at depth. One of them connects to the active Main Pamir Thrust, which is absorbing most of today's convergence between the Pamir and the Tian Shan. Several deeper zones of high conductivity in the middle and lower crust of Central and Northern Pamir likely record fluid release due to metamorphism associated with active continental subduction/delamination.

Description: A new model of the deglaciation history of Antarctica over the past 25 kyr has been developed, which we refer to herein as ICE-6G_C (VM5a). This revision of its predecessor ICE-5G (VM2) has been constrained to fit all available geological and geodetic observations, consisting of: (1) the present day uplift rates at 42 sites estimated from GPS measurements, (2) ice thickness change at 62 locations estimated from exposure-age dating, (3) Holocene relative sea level histories from 12 locations estimated on the basis of radiocarbon dating and (4) age of the onset of marine sedimentation at nine locations along the Antarctic shelf also estimated on the basis of 14 C dating. Our new model fits the totality of these data well. An additional nine GPS-determined site velocities are also estimated for locations known to be influenced by modern ice loss from the Pine Island Bay and Northern Antarctic Peninsula regions. At the 42 locations not influenced by modern ice loss, the quality of the fit of postglacial rebound model ICE-6G_C (VM5A) is characterized by a weighted root mean square residual of 0.9 mm yr –1 . The Southern Antarctic Peninsula is inferred to be rising at 2 mm yr –1 , requiring there to be less Holocene ice loss there than in the prior model ICE-5G (VM2). The East Antarctica coast is rising at approximately 1 mm yr –1 , requiring ice loss from this region to have been small since Last Glacial Maximum. The Ellsworth Mountains, at the base of the Antarctic Peninsula, are inferred to be rising at 5–8 mm yr –1 , indicating large ice loss from this area during deglaciation that is poorly sampled by geological data. Horizontal deformation of the Antarctic Plate is minor with two exceptions. First, O'Higgins, at the tip of the Antarctic Peninsula, is moving southeast at a significant 2 mm yr –1 relative to the Antarctic Plate. Secondly, the margins of the Ronne and Ross Ice Shelves are moving horizontally away from the shelf centres at an approximate rate of 0.8 mm yr –1 , in viscous response to the early Holocene unloading of ice from the current locations of the ice shelf centers. ICE-6G_C (VM5A) fits the horizontal observations well (wrms residual speed of 0.7 mm yr –1 ), there being no need to invoke any influence of lateral variation in mantle viscosity. ICE-6G_C (VM5A) differs in several respects from the recently published W12A model of Whitehouse et al. First, the upper-mantle viscosity in VM5a is 5 10 20 Pa s, half that in W12A. The VM5a profile, which is identical to that inferred on the basis of the Fennoscandian relaxation spectrum, North American relative sea level histories and Earth rotation constraints, when coupled with the revised ICE-6G_C deglaciation history, fits all of the available constraints. Secondly, the net contribution of Antarctica ice loss to global sea level rise is 13.6 m, 2/3 greater than the 8 m in W12A. Thirdly, ice loss occurs quickly from 12 to 5 ka, and the contribution to global sea level rise during Meltwater Pulse 1B (11.5 ka) is large (5 m), consistent with sedimentation constraints from cores from the Antarctica ice shelf. Fourthly, in ICE-6G_C there is no ice gain in the East Antarctica interior, as there is in W12A. Finally, the new model of Antarctic deglaciation reconciles the global constraint upon the global mass loss during deglaciation provided by the Barbados record of relative sea level history when coupled with the Northern Hemisphere counterpart of this new model.

Description: Shotgun metagenome sequencing has become a fast, cheap and high-throughput technology for characterizing microbial communities in complex environments and human body sites. However, accurate identification of microorganisms at the strain/species level remains extremely challenging. We present a novel k -mer-based approach, termed GSMer, that identifies genome-specific markers (GSMs) from currently sequenced microbial genomes, which were then used for strain/species-level identification in metagenomes. Using 5390 sequenced microbial genomes, 8 770 321 50-mer strain-specific and 11 736 360 species-specific GSMs were identified for 4088 strains and 2005 species (4933 strains), respectively. The GSMs were first evaluated against mock community metagenomes, recently sequenced genomes and real metagenomes from different body sites, suggesting that the identified GSMs were specific to their targeting genomes. Sensitivity evaluation against synthetic metagenomes with different coverage suggested that 50 GSMs per strain were sufficient to identify most microbial strains with ≥0.25 x coverage, and 10% of selected GSMs in a database should be detected for confident positive callings. Application of GSMs identified 45 and 74 microbial strains/species significantly associated with type 2 diabetes patients and obese/lean individuals from corresponding gastrointestinal tract metagenomes, respectively. Our result agreed with previous studies but provided strain-level information. The approach can be directly applied to identify microbial strains/species from raw metagenomes, without the effort of complex data pre-processing.

Description: The Himalaya is the result of the on-going convergence and collision of India and Asia. The internal configuration and processes that govern the rise of the Himalayan Mountains and Tibetan Plateau are crucial to understand continental collision zones. However, knowledge of the prior configuration of the colliding plates is equally important, since inherited (pre-orogenic/basement) structures can undeniably influence the development of the orogenic architecture throughout the orogen's cycle of collision and eventual collapse. Three northeast-trending palaeotopographic ridges of faulted Precambrian Indian basement underlie the Ganga basin south of the Himalaya. Our paper illustrates a crustal-scale fault origin for these ridges and succeeds in determining how far north beneath the Himalayan system they extend and how they ultimately govern the location of upper crustal faults in southern Tibet. Spectrally filtered EGM2008 Bouguer gravity data and edges in its horizontal gradient at different source depths (‘gravity worms’) over northern Peninsular India, the Himalaya and southern Tibet reveal several continuous Himalayan cross-strike discontinuities interpreted to represent crustal faults. Gravity lineaments in Peninsular India coincide with edges of the Precambrian basement ridges and megakinks up to 100 km wide develop in foreland cover sequences between the interpreted basement faults. The interpreted basement faults project northward beneath the Himalayan system and southern Tibet. Our results suggest that several active Himalayan cross-strike faults, such as the ones related to many graben in southern Tibet, are rooted in the underplated Indian lower crust or step en échelon along interpreted basement faults. Our interpretation thus suggests that south Tibet graben are spatially related to deep-seated crustal-scale faults rooted in the underplated Indian crust. These major discontinuities partition the Himalayan range into distinct zones, and could ultimately contribute to lateral variability in tectonic evolution along the orogen's strike.

Description: We explore the impact of deep ductile shear zones on post-seismic deformation following a finite length strike-slip earthquake. We show that the pattern of post-seismic vertical surface deformation surrounding the fault is a discriminant for the existence of high viscosities immediately below the seismogenic layer, regardless of whether the model contains purely distributed creep or also includes a component of localized creep at subseismogenic depths. Post-seismic deformation characterized by initially fast relaxation followed by a slower relaxation is predicted by models that include both localized creep in a subseismogenic shear zone and distributed creep in the surrounding region, even if they only contain steady Maxwell viscoelasticity. This post-seismic deformation is similar to that in models that approximate the ductile lithosphere and/or asthenosphere with Burgers viscoelasticity. We find that the post-seismic deformation following the 1997 M w 7.6 Manyi, China, earthquake, is consistent with a post-seismic model composed of a lower Maxwell viscoelastic region with viscosity 10 19 Pa s and a 5 km wide, Maxwell viscoelastic shear zone with viscosity 10 18 Pa s beneath the fault.

Description: The Amundsen Sea Embayment of West Antarctica represents a key component in the tectonic history of Antarctic–New Zealand continental breakup. The region played a major role in the plate-kinematic development of the southern Pacific from the inferred collision of the Hikurangi Plateau with the Gondwana subduction margin at approximately 110–100 Ma to the evolution of the West Antarctic Rift System. However, little is known about the crustal architecture and the tectonic processes creating the embayment. During two ‘RV Polarstern’ expeditions in 2006 and 2010 a large geophysical data set was collected consisting of seismic-refraction and reflection data, ship-borne gravity and helicopter-borne magnetic measurements. Two P -wave velocity–depth models based on forward traveltime modelling of nine ocean bottom hydrophone recordings provide an insight into the lithospheric structure beneath the Amundsen Sea Embayment. Seismic-reflection data image the sedimentary architecture and the top-of-basement. The seismic data provide constraints for 2-D gravity modelling, which supports and complements P -wave modelling. Our final model shows 10–14-km-thick stretched continental crust at the continental rise that thickens to as much as 28 km beneath the inner shelf. The homogenous crustal architecture of the continental rise, including horst and graben structures are interpreted as indicating that wide-mode rifting affected the entire region. We observe a high-velocity layer of variable thickness beneath the margin and related it, contrary to other ‘normal volcanic type margins’, to a proposed magma flow along the base of the crust from beneath eastern Marie Byrd Land—West Antarctica to the Marie Byrd Seamount province. Furthermore, we discuss the possibility of upper mantle serpentinization by seawater penetration at the Marie Byrd Seamount province. Hints of seaward-dipping reflectors indicate some degree of volcanism in the area after break-up. A set of gravity anomaly data indicate several phases of fully developed and failed rift systems, including a possible branch of the West Antarctic Rift System in the Amundsen Sea Embayment.

Description: Geophysical data are the main source of information about the subsurface. Geophysical techniques are, however, highly non-unique in determining specific physical parameters and boundaries of subsurface objects. To obtain actual physical information, an inversion process is often applied, in which measurements at or above the Earth surface are inverted into a 2- or 3-D subsurface spatial distribution of the physical property. Interpreting these models into structural objects, related to physical processes, requires a priori knowledge and expert analysis which is susceptible to subjective choices and is therefore often non-repeatable. In this research, we implemented a recently introduced object-based approach to interpret the 3-D inversion results of a single geophysical technique using the available a priori information and the physical and geometrical characteristics of the interpreted objects. The introduced methodology is semi-automatic and repeatable, and allows the extraction of subsurface structures using 3-D object-oriented image analysis (3-D OOA) in an objective knowledge–based classification scheme. The approach allows for a semi-objective setting of thresholds that can be tested and, if necessary, changed in a very fast and efficient way. These changes require only changing the thresholds used in a so-called ruleset, which is composed of algorithms that extract objects from a 3-D data cube. The approach is tested on a synthetic model, which is based on a priori knowledge on objects present in the study area (Tanzania). Object characteristics and thresholds were well defined in a 3-D histogram of velocity versus depth, and objects were fully retrieved. The real model results showed how 3-D OOA can deal with realistic 3-D subsurface conditions in which the boundaries become fuzzy, the object extensions become unclear and the model characteristics vary with depth due to the different physical conditions. As expected, the 3-D histogram of the real data was substantially more complex. Still, the 3-D OOA-derived objects were extracted based on their velocity and their depth location. Spatially defined boundaries, based on physical variations, can improve the modelling with spatially dependent parameter information. With 3-D OOA, the non-uniqueness on the location of objects and their physical properties can be potentially significantly reduced.

Description: We estimate Eurasia-North America Plate motion rotations at ~1-Myr intervals for the past 20 Myr from more than 11 000 crossings of 21 magnetic reversals from Chron 1n (0.78 Ma) to C6no (19.72 Ma) and flow lines digitized from the Charlie Gibbs, Bight and Molloy fracture zones and transform faults. Adjusted for outward displacement, the 21 best-fitting rotations determined from a simultaneous inversion of the numerous kinematic data reconstruct the reversal crossings with weighted root mean square misfits of only 1–2 km and 0.2–7 km for the transform fault and fracture zone crossings. The new rotations clearly define a ~1000 km southward shift of the rotation pole and 20 per cent slowdown in seafloor spreading rates between 7 and 6 Ma, preceded by apparently steady plate motion from 19.7 to ~7 Ma. Data for times since C3An.2 (6.7 Ma) are well fit by a stationary pole of rotation and constant rate of angular opening, consistent with steady motion since 6.7 Ma. The southward shift of the rotation pole at 7–6 Ma implies that Eurasia-North America motion in northeastern Asia changed from slowly convergent before 7 Ma to slowly divergent afterward. Crossings of magnetic reversals C1n through C3An.1 (6.0 Ma) are well fit everywhere in the Arctic basin and south to the Azores triple junction, indicating that the Eurasia and North America plates have not deformed along their mutual boundary since at least 6.0 Ma. However, the new rotations systematically overrotate magnetic lineations older than C3An.1 (6.0 Ma) within 200 km of the Azores triple junction and also overrotate lineations older than C5n along the Gakkel Ridge in the Arctic Basin. Barring misidentifications of the magnetic anomalies in those areas, the pattern and magnitude of the systematic misfits imply that slow (~1 mm yr –1 ) distributed or microplate deformation occurred in one or both regions.

Description: Here we inverted the GPS data to infer the coseismic slip of the Tohoku-Oki earthquake and the time-dependent afterslip distribution in the 4 months following the main shock. The Tohoku-Oki earthquake showed an unexpected magnitude and a characteristic depth-dependent differentiation of seismic energy radiation. In this context the estimation and comparison of the distribution of the fault portions that slip coseismically and post-seismically contribute to a better understanding of the variation of frictional characteristics of the plate interface. The inferred coseismic slip extends in a relatively compact region located updip from the hypocentre and reaches its highest value (about 60 m) near the trench. Afterslip occurs mostly outside the coseismic rupture and is distributed in two main modal centres. It reaches its largest values in an area located downdip of the coseismic slip and extends to a depth of 80 km. In the depth range between 30 and 50 km afterslip overlaps the portion of the fault that experienced historical moderate earthquakes, high-frequency seismic radiation and thrust-type aftershocks. The behaviour of this area can be explained by a rheologically heterogeneous region made of a ductile fault matrix interspersed with compact brittle asperities. On the contrary, the region beneath 50–60 km depth is probably characterized by a fully velocity strengthening behaviour. Southern afterslip, located off-Chiba Prefecture, is probably related to the M w 7.9 Ibaraki-Oki aftershock. The northward extension of the afterslip stops at a latitude of about 40°N, just south of the off-Aomori region. This may be related to three large events occurred in this area during the last century and the consequent strong coupling or complete depletion of the accumulated strain that characterize this region.

Description: We present a revised interpretation of magnetic anomalies and fracture zones on the Southwest Indian Ridge (SWIR; Africa–Antarctica) and the Southeast Indian Ridge (SEIR; Capricorn–Antarctica) and use them to calculate 2-plate finite rotations for anomalies 34 to 20 (84 to 43 Ma). Central Indian Ridge (CIR; Capricorn–Africa) rotations are calculated by summing the SWIR and SEIR rotations. These rotations provide a high-resolution record of changes in the motion of India and Africa at the time of the onset of the Reunion plume head. An analysis of the relative velocities of India, Africa and Antarctica leads to a refinement of previous observations that the speedup of India relative to the mantle was accompanied by a slowdown of Africa. The most rapid slowdown of Africa occurs around Chron 32Ay (71 Ma), the time when India's motion relative to Africa notably starts to accelerate. Using the most recent Geomagnetic Polarity Timescale (GTS12) we show that India's velocity relative to Africa was characterized by an acceleration from roughly 60 to 180 mm yr –1 between 71 and 66 Ma, a short pulse of superfast motion (~180 mm yr –1 ) between 66 and 63 Ma, an abrupt slowdown to 120 mm yr –1 between 63 and 62 Ma, and then a long period (63 to 47 Ma) of gradual slowing, but still fast motion (~100 mm yr –1 ), which ends with a rapid slowdown after Chron 21o (47 Ma). Changes in the velocities of Africa and India with respect to the mantle follow a similar pattern. The fastest motion of India relative to the mantle, ~220 mm yr –1 , occurs during Chron 29R. The SWIR rotations constrain three significant changes in the migration path of the Africa–Antarctic stage poles: following Chron 33y (73 Ma), following Chron 31y (68 Ma), and following Chron 24o (54 Ma). The change in the migration path of the SWIR stage poles following Chron 33y is coincident with the most rapid slowdown in Africa's motion. The change in the migration path after Chron 31y, although coincident with the most rapid acceleration of India's northward motion, may be related to changes in ridge push forces on the SWIR associated with the onset of extension along the Bain transform fault zone. The initial slowdown in India's motion relative to Africa between 63 and 62 Ma is more abrupt than predictions based on published plume head force models, suggesting it might have been caused by a change in plate boundary forces. The abrupt change in the migration path of the SWIR stage poles after Chron 24o is not associated with major changes in the velocities of either Africa or India and may reflect Atlantic basin plate motion changes associated with the arrival at the Earth's surface of the Iceland plume head. The abruptness of India's slowdown after Chron 21o is consistent with a collision event.

Description: Thin plate flexure theory provides an accurate model for the response of the lithosphere to vertical loads on horizontal length scales ranging from tens to hundreds of kilometres. Examples include flexure at seamounts, fracture zones, sedimentary basins and subduction zones. When applying this theory to real world situations, most studies assume a locally uniform plate thickness to enable simple Fourier transform solutions. However, in cases where the amplitude of the flexure is prominent, such as subduction zones, or there are rapid variations in seafloor age, such as fracture zones, these models are inadequate. Here we present a computationally efficient algorithm for solving the thin plate flexure equation for non-uniform plate thickness and arbitrary vertical load. The iterative scheme takes advantage of the 2-D fast Fourier transform to perform calculations in both the spatial and spectral domains, resulting in an accurate and computationally efficient solution. We illustrate the accuracy of the method through comparisons with known analytic solutions. Finally, we present results from three simple models demonstrating the differences in trench outer rise flexure when 2-D variations in plate rigidity and applied bending moment are taken into account. Although we focus our analysis on ocean trench flexure, the method is applicable to other 2-D flexure problems having spatial rigidity variations such as seamount loading of a thermally eroded lithosphere or flexure across the continental–oceanic crust boundary.

Description: Theory has been long established for computing the elastic response of a spherically symmetric terrestrial planetary body to both body tide and surface loading forces. However, for a planet with laterally heterogeneous mantle structure, the response is usually computed using a fully numerical approach. In this paper, we develop a semi-analytic method based on perturbation theory to solve for the elastic response of a planetary body with lateral heterogeneities in its mantle. We present a derivation of the governing equations for our second-order perturbation method and use them to study the high-order tidal effects caused by mode coupling between degree-2 body tide forcing and the laterally heterogeneous elastic structure of the mantle. We test our method by applying it to the Moon in which small long-wavelength lateral heterogeneities are assumed to exist in the elastic moduli of the lunar mantle. The tidal response of the Moon is determined mode by mode, for lateral heterogeneities with different depth ranges within the mantle and different horizontal scales. Our perturbation method solutions are compared with numerical results, showing remarkable agreement between the two methods. We conclude that our perturbation method provides accurate results and can be adapted to address a variety of forward and inverse response problems.

Description: Functional mechanisms of biomolecules often manifest themselves precisely in transient conformational substates. Researchers have long sought to structurally characterize dynamic processes in non-coding RNA, combining experimental data with computer algorithms. However, adequate exploration of conformational space for these highly dynamic molecules, starting from static crystal structures, remains challenging. Here, we report a new conformational sampling procedure, KGSrna, which can efficiently probe the native ensemble of RNA molecules in solution. We found that KGSrna ensembles accurately represent the conformational landscapes of 3D RNA encoded by NMR proton chemical shifts. KGSrna resolves motionally averaged NMR data into structural contributions; when coupled with residual dipolar coupling data, a KGSrna ensemble revealed a previously uncharacterized transient excited state of the HIV-1 trans-activation response element stem–loop. Ensemble-based interpretations of averaged data can aid in formulating and testing dynamic, motion-based hypotheses of functional mechanisms in RNAs with broad implications for RNA engineering and therapeutic intervention.

Description: Binding of transcription factors to their binding sites in promoter regions is the fundamental event in transcriptional gene regulation. When a transcription factor binding site is located within a nucleosome, the DNA has to partially unwrap from the nucleosome to allow transcription factor binding. This reduces the rate of transcription factor binding and is a known mechanism for regulation of gene expression via chromatin structure. Recently a second mechanism has been reported where transcription factor off-rates are dramatically increased when binding to target sites within the nucleosome. There are two possible explanations for such an increase in off-rate short of an active role of the nucleosome in pushing the transcription factor off the DNA: (i) for dimeric transcription factors the nucleosome can change the equilibrium between monomeric and dimeric binding or (ii) the nucleosome can change the equilibrium between specific and non-specific binding to the DNA. We explicitly model both scenarios and find that dimeric binding can explain a large increase in off-rate while the non-specific binding model cannot be reconciled with the large, experimentally observed increase. Our results suggest a general mechanism how nucleosomes increase transcription factor dissociation to promote exchange of transcription factors and regulate gene expression.

Description: Teleseismic data recorded at 13 broad-band seismological stations across northwest part of the Tethyan Himalaya and eastern Ladakh are analysed to determine the seismic characteristics of the crust and upper mantle beneath the northwest India–Asia collision zone. The receiver functions computed from teleseismic P- waveform for a wide range of backazimuth show strong azimuthal variation in the Indus suture zone (ISZ), the zone which marks the collision and subsequent subduction of both the Tethyan oceanic plate and Indian continental plate beneath Eurasia. The teleseismic waves piercing the ISZ do not show clear P -to- S ( Ps ) converted phase at the depth of Moho. In contrast, the waves piercing the Karakoram zone, Ladakh batholith and the Tethyan Himalayan region south of the ISZ clearly show the Moho converted Ps phase and corresponding inverted models reveal variation of crustal thickness from ~60 km beneath the Tethyan Himalaya to ~80 km beneath the Karakoram fault zone. A prominent intracrustal low velocity zone (IC-LVZ) is detected in the shear wave velocity models within the depth range ~15–40 km. The IC-LVZ identified at the stations both north and south of the ISZ can be interpreted as due to presence of fluid/partial melt. Our study provides compelling evidence that the mid-crustal low velocity zone does extend across the suture zone, in to the Tethyan Himalaya. The contact between this serpentinized ultramafic rocks and the eclogitized Indian continental crust in the suture zone is identified at ~47–50 km depth.

Description: The Tien Shan is the largest active intracontinental orogenic belt on Earth. To better understand the processes causing mountains to form at great distances from a plate boundary, we analyse passive source seismic data collected on 40 broad-band stations of the MANAS project (2005–2007) and 12 stations of the permanent KRNET seismic network to determine variations in crustal thickness and shear wave speed across the range. We jointly invert P - and S -wave receiver functions with surface wave observations from both earthquakes and ambient noise to reduce the ambiguity inherent in the images obtained from the techniques applied individually. Inclusion of ambient noise data improves constraints on the upper crust by allowing dispersion measurements to be made at shorter periods. Joint inversion can also reduce the ambiguity in interpretation by revealing the extent to which various features in the receiver functions are amplified or eliminated by interference from multiples. The resulting wave speed model shows a variation in crustal thickness across the range. We find that crustal velocities extend to ~75 km beneath the Kokshaal Range, which we attribute to underthrusting of the Tarim Basin beneath the southern Tien Shan. This result supports the plate model of intracontinental convergence. Crustal thickness elsewhere beneath the range is about 50 km, including beneath the Naryn Valley in the central Tien Shan where previous studies reported a shallow Moho. This difference apparently is the result of wave speed variations in the upper crust that were not previously taken into account. Finally, a high velocity lid appears in the upper mantle of the Central and Northern part of the Tien Shan, which we interpret as a remnant of material that may have delaminated elsewhere under the range.

Description: Errors in the satellite orbits are considered to be a limitation for Interferometric Synthetic Aperture Radar (InSAR) time-series techniques to accurately measure long-wavelength (〉50 km) ground displacements. Here we examine how orbital errors propagate into relative InSAR line-of-sight velocity fields and evaluate the contribution of orbital errors to the InSAR uncertainty. We express the InSAR uncertainty due to the orbital errors in terms of the standard deviations of the velocity gradients in range and azimuth directions (range and azimuth uncertainties). The range uncertainty depends on the magnitude of the orbital errors, the number and time span of acquisitions. Using reported orbital uncertainties we find range uncertainties of less than 1.5 mm yr –1  100 km –1 for ERS, less than 0.5 mm yr –1  100 km –1 for Envisat and ~0.2 mm yr –1  100 km –1 for TerraSAR-X and Sentinel-1. Under a conservative scenario, we find azimuth uncertainties of better than 1.5 mm yr –1  100 km –1 for older satellites (ERS and Envisat) and better than 0.5 mm yr –1  100 km –1 for modern satellites (TerraSAR-X and Sentinel-1). We validate the expected uncertainties using LOS velocity fields obtained from Envisat SAR imagery. We find residual gradients of 0.8 mm yr –1  100 km –1 or less in range and of 0.95 mm yr –1  100 km –1 or less in azimuth direction, which fall within the 1 to 2 uncertainties. The InSAR uncertainties due to the orbital errors are significantly smaller than generally expected. This shows the potential of InSAR systems to constrain long-wavelength geodynamic processes, such as continent-scale deformation across entire plate boundary zones.

Description: A method for subsurface recognition of blind geological bodies is presented using combined surface constraints and 3-D structural modelling that incorporates constraints from detailed mapping, and potential-field inversion modelling. This method is applied to the Mount Painter Province and demonstrates that addition of low density material is required to reconcile the gravity signature of the region. This method may be an effective way to construct 3-D models in regions of excellent structural control, and can be used to assess the validity of surface structures with 3-D architecture. Combined geological and potential-field constrained inversion modelling of the Mount Painter Province was conducted to assess the validity of the geological models of the region. Magnetic susceptibility constrained stochastic property inversions indicates that the northeast to southwest structural trend of the relatively magnetic meta-sedimentary rocks of the Radium Creek Group in the Mount Painter Inlier is reconcilable with the similar, northeast to southwest trending positive magnetic anomalies in the region. Radium Creek Group packages are the major contributor of the total magnetic response of the region. However field mapping and the results of initial density constrained stochastic property inversion modelling do not correlate with a large residual negative gravity anomaly central to the region. Further density constrained inversion modelling indicates that an additional large body of relatively low density material is needed within the model space to account for this negative density anomaly. Through sensitivity analysis of multiple geometrical and varied potential-field property inversions, the best-fitting model records a reduction in gravity rms misfit from 21.9 to 1.69 mGal, representing a reduction from 56 to 4.5 per cent in respect to the total dynamic range of 37.5 mGal of the residual anomaly. This best-fitting model incorporates a volumetrically significant source body of interpreted felsic, low density material (10 12 m 3 ) impinging on the central-west of the Mount Painter Inlier and overlying Neoproterozoic sequences, and the emplacement of more mafic affinities in the northeast and east. The spatial association and circular geometry of these granitoid bodies suggests an affinity with the Palaeozoic ~460–440 Ma British Empire Granite that outcrops in the Mount Painter Inlier. The intrusion of this additional material in the Palaeozoic could either be the product of; or contributed to, an increased local geotherm and heat flow in the region during the Palaeozoic.

Description: The Pacific and Australian plates in the South Island, New Zealand (NZ) converge at a rate of about 4 cm yr –1 . Accommodation of the continental part of this convergence in the lithospheric mantle is both poorly understood and currently controversial yet it is a problem of fundamental importance for understanding lithospheric thickening. End-member possibilities range from the classical model of asymmetric subduction to symmetric viscous thickening. Seismic tomography has the potential to image this process. However, tomographic images to date are poorly constrained due to the lack of appropriate earthquakes. Improved teleseismic tomography of the region has been achieved by increasing data coverage and applying a novel scheme of correcting for crustal structure by ray tracing through a newly created model of shallow shear wave velocity derived from the inversion of noise-based dispersion measurements. Our resulting models suggest the lithospheric mantle high velocities at the continental plate boundary extend no deeper than approximately 125 km, evidence against both previous models of viscous drip and typical asymmetric subduction zones. This high velocity core extends from north to south along the axis of South Island suggesting that mantle convergence is accommodated along the older, mid-Cenozoic, plate boundary. West of South Island, a high velocity west dipping zone may define the remnant Cretaceous subduction zone that has been distorted by Cenozoic transcurrent deformation. We present our new 3-D seismic velocity models together with a compatible tectonic model and discuss their implications for the nature of lithospheric evolution at this convergent boundary.

Description: We use continuous GPS measurements from 31 stations in southern Mexico to model coseismic slip and post-seismic deformation from the 2012 March 20 M w  = 7.5 Ometepec earthquake, the first large thrust earthquake to occur below central Mexico during the modern GPS era. Coseismic offsets ranging from ~280 mm near the epicentre to 5 mm or less at sites far from the epicentre are fit best by a rupture focused between ~15 and 35 km depth, consistent with an independent seismological estimate. The corresponding geodetic moment of 1.4 10 20 N·m is within 10 per cent of two independent seismic estimates. Transient post-seismic motion recorded by GPS sites as far as 300 km from the rupture has a different horizontal deformation gradient and opposite sense of vertical motion than do the coseismic offsets. A forward model of viscoelastic relaxation as a result of our new coseismic slip solution incorrectly predicts uplift in areas where post-seismic subsidence was recorded and indicates that viscoelastic deformation was no more than a few per cent of the measured post-seismic deformation. The deformation within 6 months of the earthquake was thus strongly dominated by fault afterslip. The post-seismic GPS time-series are well fit as logarithmically decaying fault afterslip on an area of the subduction interface up to 10 times larger than the earthquake rupture zone, extending as far as 220 km inland. Afterslip had a cumulative geodetic moment of 2.0 10 20 N·m, ~40 per cent larger than the Ometepec earthquake. Tests for the shallow and deep limits for the afterslip require that it included much of the earthquake rupture zone as well as regions of the subduction interface where slow slip events and non-volcanic tremor have been recorded and areas even farther downdip on the flat interface. Widespread afterslip below much of central Mexico suggests that most of the nearly flat subduction interface in this region is conditionally stable and thus contributes measurable transient deformation to large areas of Mexico south of and in the volcanic belt.

Description: We have derived a shallow subsurface 2-D tomographic P -wave velocity image of the Deccan Volcanic Province (DVP) of India using first-arrival traveltime data along a 90-km-long N–S trending seismic profile in the Deccan Syneclise region. The tomographic image depicts smooth velocity variations of Quaternary and Tertiary (2.0–3.0 km s –1 ) sediments, basalts/traps (5.0–5.5 km s –1 ), sub-trappean Mesozoic sediments (4.3–4.5 km s –1 ) as well as the basement (5.9–6.1 km s –1 ) geometry down to a maximum depth of 5.0 km. Due to Late Cretaceous volcanism and outpouring of basaltic lava flows, this region is affected by numerous dyke intrusions and thick basaltic trap (2–3 km) exposed on the surface and surrounded by graben structures due to deep basinal faults forming a large igneous province. Although sub-basalt imaging is a major challenge for the oil industry, with the help of tomographic imaging technique of first-arrival seismic refraction data, we were able to image sub-trappean Mesozoic sediments (〈0.75 km) deposited below the two sequences of thick basaltic flows above the basement. The imaged Mesozoic sediments are expected to contain hydrocarbon because of their wide extension in this sedimentary basin with suitable trapping mechanism due to basalts. The robustness of the velocity image is assessed through numerous tests like velocity perturbations, 2 estimates, rms residuals of traveltime fit, uncertainty estimates through computation of ray-density or hits and series of checkerboard resolution tests with velocity anomalies having different cell size. The thickness of the basalt and the sub-trappean Mesozoic sediments along with the basement geometry obtained from tomography are constrained through ray-trace modelling and pre-stack depth migration (PSDM) of the wide-angle reflection phases for different shot gathers along the profile.

Description: High-throughput sequencing technologies, including RNA-seq, have made it possible to move beyond gene expression analysis to study transcriptional events including alternative splicing and gene fusions. Furthermore, recent studies in cancer have suggested the importance of identifying transcriptionally altered loci as biomarkers for improved prognosis and therapy. While many statistical methods have been proposed for identifying novel transcriptional events with RNA-seq, nearly all rely on contrasting known classes of samples, such as tumor and normal. Few tools exist for the unsupervised discovery of such events without class labels. In this paper, we present SigFuge for identifying genomic loci exhibiting differential transcription patterns across many RNA-seq samples. SigFuge combines clustering with hypothesis testing to identify genes exhibiting alternative splicing, or differences in isoform expression. We apply SigFuge to RNA-seq cohorts of 177 lung and 279 head and neck squamous cell carcinoma samples from the Cancer Genome Atlas, and identify several cases of differential isoform usage including CDKN2A , a tumor suppressor gene known to be inactivated in a majority of lung squamous cell tumors. By not restricting attention to known sample stratifications, SigFuge offers a novel approach to unsupervised screening of genetic loci across RNA-seq cohorts. SigFuge is available as an R package through Bioconductor.

Description: Numerical experiments of convection with grain-damage are used to develop scaling laws for convective heat flow, mantle velocity and plate velocity across the stagnant lid and plate-tectonic regimes. Three main cases are presented in order of increasing complexity: a simple case wherein viscosity is only dependent on grain size, a case where viscosity depends on temperature and grain size, and finally a case where viscosity is temperature and grain size sensitive, and the grain-growth (or healing) is also temperature sensitive. In all cases, convection with grain-damage scales differently than Newtonian convection; whereas the Nusselt number (Nu), typically scales with the reference Rayleigh number, Ra 0 , to the 1/3 power, for grain-damage this exponent is larger because increasing Ra 0 also enhances damage. In addition, Nu, mantle velocity, and plate velocity are also functions of the damage to healing ratio, ( D / H ); increasing D / H increases Nu because more damage leads to more vigorous convection. For the fully realistic case, numerical results show stagnant lid convection, fully mobilized convection that resembles the temperature-independent viscosity case, and partially mobile or transitional convection, depending on D / H , Ra 0 , and the activation energies for viscosity and healing. Applying our scaling laws for the fully realistic case to Earth and Venus we demonstrate that increasing surface temperature dramatically decreases plate speed and heat flow, essentially shutting down plate tectonics, due to increased healing in lithospheric shear zones, as proposed previously. Contrary to many previous studies, the transitional regime between the stagnant lid and fully mobilized regimes is large, and the transition from stagnant lid to mobile convection is gradual and continuous. Thus planets could exhibit a full range of surface mobility, as opposed to the bimodal distribution of fully mobile lid planets and stagnant lid planets that is typically assumed.

Description: Three magnetotelluric (MT) profiles in northwestern Canada cross the central and western segments of Great Slave Lake shear zone (GSLsz), a continental scale strike-slip structure active during the Slave-Rae collision in the Proterozoic. Dimensionality analysis indicates that (i) the resistivity structure is approximately 2-D with a geoelectric strike direction close to the dominant geological strike of N45°E and that (ii) electrical anisotropy may be present in the crust beneath the two southernmost profiles. Isotropic and anisotropic 2-D inversion and isotropic 3-D inversions show different resistivity structures on different segments of the shear zone. The GSLsz is imaged as a high resistivity zone (〉5000  m) that is at least 20 km wide and extends to a depth of at least 50 km on the northern profile. On the southern two profiles, the resistive zone is confined to the upper crust and pierces an east-dipping crustal conductor. Inversions show that this dipping conductor may be anisotropic, likely caused by conductive materials filling a network of fractures with a preferred spatial orientation. These conductive regions would have been disrupted by strike-slip, ductile deformation on the GSLsz that formed granulite to greenschist facies mylonite belts. The pre-dominantly granulite facies mylonites are resistive and explain why the GSLsz appears as a resistive structure piercing the east-dipping anisotropic layer. The absence of a dipping anisotropic/conductive layer on the northern MT profile, located on the central segment of the GSLsz, is consistent with the lack of subduction at this location as predicted by geological and tectonic models.

Description: The coupling of chromosome conformation capture (3C) with next-generation sequencing technologies enables the high-throughput detection of long-range genomic interactions, via the generation of ligation products between DNA sequences, which are closely juxtaposed in vivo . These interactions involve promoter regions, enhancers and other regulatory and structural elements of chromosomes and can reveal key details of the regulation of gene expression. 3C-seq is a variant of the method for the detection of interactions between one chosen genomic element (viewpoint) and the rest of the genome. We present r3Cseq , an R/Bioconductor package designed to perform 3C-seq data analysis in a number of different experimental designs. The package reads a common aligned read input format, provides data normalization, allows the visualization of candidate interaction regions and detects statistically significant chromatin interactions, thus greatly facilitating hypothesis generation and the interpretation of experimental results. We further demonstrate its use on a series of real-world applications.

Description: The 3-D shear velocity structure beneath South India's Dharwar Craton determined from fundamental mode Rayleigh waves phase velocities reveals the existence of anomalously high velocity materials in the depth range of 50–100 km. Tomographic analysis of seismograms recorded on a network of 35 broad-band seismographs shows the uppermost mantle shear wave speeds to be as high as 4.9 km s –1 in the northwestern Dharwar Craton, decreasing both towards the south and the east. Below ~100 km, the shear wave speed beneath the Dharwar Craton is close to the global average shear wave speed at these depths. Limitations of usable Rayleigh phase periods, however, have restricted the analysis to depths of 120 km, precluding the delineation of the lithosphere–asthenosphere boundary in this region. However, pressure–temperature analysis of xenoliths in the region suggests a lithospheric thickness of at least ~185 km during the mid-Proterozoic period. The investigations were motivated by a search for seismic indicators in the shallow mantle beneath the distinctly different parts of the Dharwar Craton otherwise distinguished by their lithologies, ages and crustal structure. Since the ages of cratonic crust and of the associated mantle lithosphere around the globe have been found to be broadly similar and their compositions bimodal in time, any distinguishing features of the various parts of the Dharwar shallow mantle could thus shed light on the craton formation process responsible for stabilizing the craton during the Meso- and Neo-Archean.

Description: Frontier hydrocarbon development projects in the deepwater slopes of the Gulf of Mexico Basin, Santos Basin and Lower Congo Basin all require wells to cross ductile layers of autochthonous or allochthonous salt moving at peak rates of 100 mm yr –1 . The Couette–Poiseuille number is introduced here to help pinpoint the depth of shear stress reversal in such salt layers. For any well-planned through salt, the probable range of creep forces of moving salt needs to be taken into account when designing safety margins and load-factor tolerance of the well casing. Drag forces increase with wellbore diameter, but more significantly with effective viscosity and speed of the creeping salt layer. The potential drag forces on cased wellbores in moving salt sheets are estimated analytically using a range of salt viscosities (10 15 –10 19 Pa s) and creep rates (0–10 mm yr –1 ). Drag on perfectly rigid casing of infinite strength may reach up to 13 Giga Newton per meter wellbore length in salt having a viscosity of 10 19 Pa s. Well designers may delay stress accumulations due to salt drag when flexible casing accommodates some of the early displacement and strain. However, all creeping salt could displace, fracture and disconnect well casing, eventually. The shear strength of typical heavy duty well casing (about 1000 MPa) can be reached due to drag by moving salt. Internal flow of salt will then fracture the casing near salt entry and exit points, but the structural damage is likely to remain unnoticed early in the well-life when the horizontal shift of the wellbore is still negligibly small (at less than 1 cm yr –1 ). Disruption of casing and production flow lines within the anticipated service lifetime of a well remains a significant risk factor within distinct zones of low-viscosity salt which may reach ultrafast creep rates of 100 mm yr –1 .

Description: The Antarctic Peninsula (AP) consists of a long lived and uniquely well preserved magmatic arc system. The broad tectonic structure of the AP arc is well understood. However, magmatic processes occurring along the arc are only constrained by regional geophysical and relatively sparse geological data. Key questions remain about the timing, volume, and structural controls on magma emplacement. We present new high resolution aeromagnetic data across Adelaide Island, on the western margin of the AP revealing the complex structure of the AP arc/forearc boundary. Using digital enhancement, 2-D modelling and 3-D inversion we constrain the form of the magnetic sources at the arc/forearc boundary. Our interpretation of these magnetic data, guided by geological evidence and new zircon U-Pb dating, suggests significant Palaeogene to Neogene magmatism formed ~25 per cent of the upper crust in this region (~7500 km 3 ). Significant structural control on Neogene magma emplacement along the arc/forearc boundary is also revealed. We hypothesize that this Neogene magmatism reflects mantle return flow through a slab window generated by Late Palaeogene cessation of subduction south of Adelaide Island. This mantle process may have affected the final stages of arc magmatism along the AP margin.

Description: The intrusion mechanism and internal structure of sills are still under debate. We present a detailed magnetic study, including anisotropy of magnetic susceptibility and rock magnetic analyses of a Cretaceous (94 Ma), 7-m-thick sill from the Lusitanian Basin in Portugal, the Foz da Fonte sill. The results, from both the top surface and a vertical profile, allow us to propose a model for the magmatic flow pattern and sense of flow. According to their location in the vertical profile, three magnetic fabric domains are identified: (1) at the borders, qualified as chilled margins (~0–50 cm), low anisotropies suggest that low velocity gradients and heterogeneous flow paths occurred during the initial emplacement stages; (2) in the centre of the sill, where low anisotropies are observed, low shear gradients and magma displacement close to pure translation is inferred and (3) in the intermediate zones, high anisotropy values are ascribed to zones having undergone high shear gradients. The mean magnetic lineations from the top surface and basal contact indicate an almost horizontal and NW–SE orientation (azimuth: 310°) which agrees with the preferred orientation of iron oxide grain clusters and with the elongation of vesicles considered as coaxial with the magma flow direction. Moreover, the magnetic foliation planes and the lineations show both a mirror imbrication relative to the average upper and lower border surfaces of the sill, pointing to a flow direction towards the SE. Based on these results and on the interpretation of two seismic reflection lines, we show that the Cabo Raso magnetic anomaly, located 25 km to NW of the FF-sill, is associated to Cretaceous magmatic intrusions from which the sill likely originated. This tectono-magmatic setting is discussed with respect to the West Iberia Late Cretaceous magmatism, integrating magnetic anomalies, isotope chronology and tectonics.

Description: Southern Mendoza and northern Neuquén Provinces, south of the Pampean Shallow Subduction region in western Argentina, are host to the 〈2 Myr Payunia Basaltic Province, which covers ~39 500 km 2 with primarily basaltic intraplate volcanism. This backarc igneous province can be explained by extension due to trench roll-back following steepening of a flat slab that existed in the middle to late Miocene. Magnetotelluric data collected at 37 sites from 67°W to 70°W and 35°S to 38°S are used to probe the source of the Payún Matrú basalts. These data, which require significantly 3-D structure, are inverted with a 3-D non-linear conjugate gradient algorithm that minimizes structure for a given data misfit. We identify two significant electrically conductive structures. One, called the SWAP (shallow western asthenospheric plume) approaches the surface beneath the Payún Matrú Caldera and the Trómen Volcano and dips westward towards the subducted Nazca slab. The second, called the DEEP (deep eastern plume) approaches the surface ~100 km to the southeast of Payún Matrú and dips steeply east to ~400 km depth while remaining above the subducted Nazca slab. We use a variety of model assessment techniques including forward modelling and constrained inversion to test the veracity of these features. We interpret the SWAP as the source of the 〈2 Myr intraplate volcanism. Our model assessment permits but does not require the SWAP to connect to the Nazca slab. The SWAP and DEEP are electrically connected only in the shallow crust, which is likely due to the Neuquén sedimentary basin and not a magmatic process. We propose that the SWAP and DEEP may have been more robustly connected in the past, but that the DEEP was decapitated to form the SWAP when shallow northwestward mantle flow resumed during steepening of the slab. The ~2 Myr basaltic volcanism is the result of this decapitated DEEP magma that had ponded below the crust until extension allowed eruption. The westward dip of the SWAP is interpreted to be the result of shear in the renewed mantle corner flow—this explains why the SWAP and Nazca slab can appear connected, yet there is no recent arc-signature magma in this region.

Description: This study presents the results of a deep seismic survey across the north Algerian margin, based on the combination of 2-D multichannel and wide-angle seismic data simultaneously recorded by 41 ocean bottom seismometers deployed along a north–south line extending 180 km off Jijel into the Algerian offshore basin, and 25 land stations deployed along a 100-km-long line, cutting through the Lesser Kabylia and the Tellian thrust-belt. The final model obtained using forward modelling of the wide-angle data and pre-stack depth migration of the seismic reflection data provides an unprecedented view of the sedimentary and crustal structure of the margin. The sedimentary layers in the Algerian basin are 3.75 km thick to the north and up to 4.5–5 km thick at the foot of the margin. They are characterized by seismic velocities from 1.9 to 3.8 km s –1 . Messinian salt formations are about 1 km thick in the study area, and are modelled and imaged using a velocity between 3.7 and 3.8 km s –1 . The crust in the deep sea basin is about 4.5 km thick and of oceanic origin, presenting two distinct layers with a high gradient upper crust (4.7–6.1 km s –1 ) and a low gradient lower crust (6.2–7.1 km s –1 ). The upper-mantle velocity is constrained to 7.9 km s –1 . The ocean–continent transition zone is very narrow between 15 and 20 km wide. The continental crust reaches 25 km thickness as imaged from the most landward station and thins to 5 km over a less than 70 km distance. The continental crust presents steep and asymmetric upper- and lower-crustal geometry, possibly due to either asymmetric rifting of the margin, an underplated body, or flow of lower crustal material towards the ocean basin. Present-time deformation, as imaged from three additional seismic profiles, is characterized by an interplay of gravity-driven mobile-salt creep and active thrusting at the foot of the tectonically inverted Algerian margin.

Description: Understanding the numerous functions that RNAs play in living cells depends critically on knowledge of their three-dimensional structure. Due to the difficulties in experimentally assessing structures of large RNAs, there is currently great demand for new high-resolution structure prediction methods. We present the novel method for the fully automated prediction of RNA 3D structures from a user-defined secondary structure. The concept is founded on the machine translation system. The translation engine operates on the RNA FRABASE database tailored to the dictionary relating the RNA secondary structure and tertiary structure elements. The translation algorithm is very fast. Initial 3D structure is composed in a range of seconds on a single processor. The method assures the prediction of large RNA 3D structures of high quality. Our approach needs neither structural templates nor RNA sequence alignment, required for comparative methods. This enables the building of unresolved yet native and artificial RNA structures. The method is implemented in a publicly available, user-friendly server RNAComposer. It works in an interactive mode and a batch mode. The batch mode is designed for large-scale modelling and accepts atomic distance restraints. Presently, the server is set to build RNA structures of up to 500 residues.

Description: Programmed –1 ribosomal frameshifting is employed in the expression of a number of viral and cellular genes. In this process, the ribosome slips backwards by a single nucleotide and continues translation of an overlapping reading frame, generating a fusion protein. Frameshifting signals comprise a heptanucleotide slippery sequence, where the ribosome changes frame, and a stimulatory RNA structure, a stem–loop or RNA pseudoknot. Antisense oligonucleotides annealed appropriately 3' of a slippery sequence have also shown activity in frameshifting, at least in vitro . Here we examined frameshifting at the U 6 A slippery sequence of the HIV gag/pol signal and found high levels of both –1 and –2 frameshifting with stem–loop, pseudoknot or antisense oligonucleotide stimulators. By examining –1 and –2 frameshifting outcomes on mRNAs with varying slippery sequence-stimulatory RNA spacing distances, we found that –2 frameshifting was optimal at a spacer length 1–2 nucleotides shorter than that optimal for –1 frameshifting with all stimulatory RNAs tested. We propose that the shorter spacer increases the tension on the mRNA such that when the tRNA detaches, it more readily enters the –2 frame on the U 6 A heptamer. We propose that mRNA tension is central to frameshifting, whether promoted by stem–loop, pseudoknot or antisense oligonucleotide stimulator.

Description: Understanding the categorization of human diseases is critical for reliably identifying disease causal genes. Recently, genome-wide studies of abnormal chromosomal locations related to diseases have mapped 〉2000 phenotype–gene relations, which provide valuable information for classifying diseases and identifying candidate genes as drug targets. In this article, a regularized non-negative matrix tri-factorization (R-NMTF) algorithm is introduced to co-cluster phenotypes and genes, and simultaneously detect associations between the detected phenotype clusters and gene clusters. The R-NMTF algorithm factorizes the phenotype–gene association matrix under the prior knowledge from phenotype similarity network and protein–protein interaction network, supervised by the label information from known disease classes and biological pathways. In the experiments on disease phenotype–gene associations in OMIM and KEGG disease pathways, R-NMTF significantly improved the classification of disease phenotypes and disease pathway genes compared with support vector machines and Label Propagation in cross-validation on the annotated phenotypes and genes. The newly predicted phenotypes in each disease class are highly consistent with human phenotype ontology annotations. The roles of the new member genes in the disease pathways are examined and validated in the protein–protein interaction subnetworks. Extensive literature review also confirmed many new members of the disease classes and pathways as well as the predicted associations between disease phenotype classes and pathways.

Description: The development of algorithms for designing artificial RNA sequences that fold into specific secondary structures has many potential biomedical and synthetic biology applications. To date, this problem remains computationally difficult, and current strategies to address it resort to heuristics and stochastic search techniques. The most popular methods consist of two steps: First a random seed sequence is generated; next, this seed is progressively modified (i.e. mutated) to adopt the desired folding properties. Although computationally inexpensive, this approach raises several questions such as (i) the influence of the seed; and (ii) the efficiency of single-path directed searches that may be affected by energy barriers in the mutational landscape. In this article, we present RNA-ensign , a novel paradigm for RNA design. Instead of taking a progressive adaptive walk driven by local search criteria, we use an efficient global sampling algorithm to examine large regions of the mutational landscape under structural and thermodynamical constraints until a solution is found. When considering the influence of the seeds and the target secondary structures, our results show that, compared to single-path directed searches, our approach is more robust, succeeds more often and generates more thermodynamically stable sequences. An ensemble approach to RNA design is thus well worth pursuing as a complement to existing approaches. RNA-ensign is available at http://csb.cs.mcgill.ca/RNAensign .

Description: Identifying cancer driver genes and pathways among all somatic mutations detected in a cohort of tumors is a key challenge in cancer genomics. Traditionally, this is done by prioritizing genes according to the recurrence of alterations that they bear. However, this approach has some known limitations, such as the difficulty to correctly estimate the background mutation rate, and the fact that it cannot identify lowly recurrently mutated driver genes. Here we present a novel approach, Oncodrive-fm, to detect candidate cancer drivers which does not rely on recurrence. First, we hypothesized that any bias toward the accumulation of variants with high functional impact observed in a gene or group of genes may be an indication of positive selection and can thus be used to detect candidate driver genes or gene modules. Next, we developed a method to measure this bias (FM bias) and applied it to three datasets of tumor somatic variants. As a proof of concept of our hypothesis we show that most of the highly recurrent and well-known cancer genes exhibit a clear FM bias. Moreover, this novel approach avoids some known limitations of recurrence-based approaches, and can successfully identify lowly recurrent candidate cancer drivers.

Description: For the first time, a deep seismic data set acquired in the frame of the Algerian–French SPIRAL program provides new insights regarding the origin of the westernmost Algerian margin and basin. We performed a tomographic inversion of traveltimes along a 100-km-long wide-angle seismic profile shot over 40 ocean bottom seismometers offshore Mostaganem (Northwestern Algeria). The resulting velocity model and multichannel seismic reflection profiles show a thin (3–4 km thick) oceanic crust. The narrow ocean–continent transition (less than 10 km wide) is bounded by vertical faults and surmounted by a narrow almost continuous basin filled with Miocene to Quaternary sediments. This fault system, as well as the faults organized in a negative-flower structure on the continent side, marks a major strike-slip fault system. The extremely sharp variation of the Moho depth (up to 45 ± 3°) beneath the continental border underscores the absence of continental extension in this area. All these features support the hypothesis that this part of the margin from Oran to Tenes, trending N65–N70°E, is a fossil subduction-transform edge propagator fault, vestige of the propagation of the edge of the Gibraltar subduction zone during the westward migration of the Alborán domain.