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: Surface nuclear magnetic resonance (surface-NMR) is a promising technique for exploring shallow subsurface aquifer structures. Surface-NMR can be applied in environments that are characterized as a 1-D layered Earth. The technique utilizes a single loop and is referred to as magnetic resonance sounding. The technique referred to as magnetic resonance tomography (MRT) allows complex 2-D aquifer structures to be explored. Currently, MRT requires multiple loops and a roll along measurement scheme, which causes long survey time. We propose a loop layout using an elongated transmitter and an in-loop receiver arrays (ETRA) to conduct a 2-D survey with just one measurement. We present a comprehensive comparison between the new layout and the common approaches based on sensitivity and resolution analyses and show synthetic and field data. The results show that ETRA generates subsurface images at sufficient resolution with significantly lower survey times than other loop layouts.

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 studied ionospheric responses to the 2012 April 11 M w 8.6 North Sumatra earthquake using total electron content (TEC) measurements with the regional Global Navigation Satellite System network. This earthquake ruptured the oceanic lithosphere off the Indian Ocean coast of North Sumatra, and is known as the largest strike-slip earthquake ever recorded. Coseismic ionospheric disturbances (CIDs) with rapid TEC enhancement of a few TEC units propagated northward with a speed of acoustic waves (~1 km s –1 ). Resonant atmospheric oscillation with a frequency ~4 mHz have been found as monochromatic oscillation of TEC lasting for an hour after the main shock and the largest aftershock. We compared CID amplitudes of 21 earthquakes world-wide with moment magnitudes ( M w ) 6.6–9.2. They roughly obeyed a law such that CID amplitude increases by two orders of magnitude for the M w increase of three. The 2012 North Sumatra earthquakes slightly deviated negatively from the trend possibly reflecting their strike-slip mechanisms, that is small vertical crustal movements for their magnitudes.

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: Broad-band magnetic susceptibility (MS) measurement, a novel magnetic method capable of quantifying a narrow grain size distribution (GSD) of superparamagnetic (SP) particles by measuring low-field MS at a number of frequency steps spanning four orders of magnitude, has been tested in a loess/palaeosol section at Luochuan in the Chinese Loess Plateau. The studied succession consists of sequences from the latest palaeosol unit (S0) to the upper part of the loess unit (L2), spanning the last glacial–interglacial cycle. Reconstructed GSDs consist of volume fractions on the order of 10 –24 m 3 , and the mean GSDs are modal but with distinctive skewness among the loess, the weakly developed palaeosols (weak palaeosols), and the mature palaeosols. This indicates that the mean volume of SP particles in this loess/palaeosol sequence tends to increase during the transition from loess -〉 weak palaeosol -〉 palaeosol, an indication of grain growth as pedogenesis progresses. Total frequency dependence, or TFD(per cent), the difference between 130 at the lowest (130 Hz) and 500k at the highest (500 kHz) frequencies normalized to 130 , is judged to be a more suitable index than previous frequency dependence parameters for the concentration of SP particles. TFD(per cent) has a strong correlation with 130 , showing a continuous ‘growth curve’ with the rate of increase being highest for the loess, moderate for the weak palaeosols, and saturated for the palaeosols. The characteristic curve suggests that smaller SP particles are preferentially formed in the earlier stage of pedogenesis rather than the later phase when even larger particles are formed in mature palaeosols. These results demonstrate that the broad-band MS measurement method will be useful for the quantitative assessment of magnetic nanoparticles in soils and sediments.

Description: Environmental magnetism can provide simple and fast methods to semi-quantify the contamination levels by heavy metals in urban areas from the relationships between the magnetic properties and the heavy metal concentrations. The aim of this study is to explore the interpretation of selected magnetic parameters as proxies for the evaluation of heavy metal contamination in urban dusts. Dust samples were collected from different districts of Nanjing, Southeast China. The magnetic properties of dusts were analysed and heavy metal (Fe, Al, As, Ba, Cd, Cr, Co, Cu, Hg, Mn, Mo, Ni, Pb, Sr, V and Zn) concentrations were measured. Magnetic minerals, mainly from anthropogenic activities, are dominated by coarse stable single domain-grained ferrimagnetic minerals. The – T curves indicated that the main magnetic minerals are magnetite and hematite. Magnetic properties exhibited similar spatial distribution and significant positive correlations with the concentrations of most metals and with the pollution load index. Magnetic properties had a strong link with the abundance of heavy metals derived from industrial emission and traffic activities, whereas there was a poor correlation with the concentrations of metals from multi-sources such as commercial/domestic sources and natural processes. Besides the low-frequency magnetic susceptibility ( LF ) and the saturation isothermal remanent magnetization, other magnetic parameters can be considered as efficient indicators in the assessment of heavy metal contamination. The linkage between the magnetic properties and heavy metal concentrations in street dusts depends on the sources and nature of their magnetic fraction. Environmental magnetism analyses may provide simple and rapid methods for the assessment of heavy metal contamination in urban street dusts.

Description: We present in this paper an alternative approach to modelling and inversion of surface nuclear magnetic resonance (sNMR) data that has numerous attractive characteristics. By considering the forward and inverse problem in the frequency-domain (FD) it is possible to heavily truncate the band-limited data set with no appreciable loss of information. Furthermore, it introduces a natural method of signal demodulating and sidesteps the rotating frame transformation, which can be difficult to apply to large volumes. By instead remaining in the laboratory frame, phase shifts due to off-resonance transmission and static variation in the Larmor frequencies become simpler to account for. For these reasons, we present the first practical scheme for comprehensively inverting the complex sNMR data set. The use of complex data allows for improved depth and decay constant resolution. However, it requires the knowledge of subsurface electrical conductivity, and by corollary the ability to accurately model those effects in the sNMR record. Finally, the complex FD signal is sensitive to dephasing of the sNMR record due to static magnetic field inhomogeneity. We illustrate the ability to detect dephasing in synthetic and field data and demonstrate an effective inversion which is able to solve for static dephasing effects. This results in better estimation of meaningful decay constants as well as reduced error in extrapolated initial signal amplitude. Both of these parameters are critical for using sNMR in applications requiring estimation of hydraulic parameters.

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: We report a palaeomagnetic investigation of the last full geomagnetic field reversal, the Matuyama-Brunhes (M-B) transition, as preserved in a continuous sequence of exposed lacustrine sediments in the Apennines of Central Italy. The palaeomagnetic record provides the most direct evidence for the tempo of transitional field behaviour yet obtained for the M-B transition. 40 Ar/ 39 Ar dating of tephra layers bracketing the M-B transition provides high-accuracy age constraints and indicates a mean sediment accumulation rate of about 0.2 mm yr –1 during the transition. Two relative palaeointensity (RPI) minima are present in the M-B transition. During the terminus of the upper RPI minimum, a directional change of about 180 ° occurred at an extremely fast rate, estimated to be less than 2 ° per year, with no intermediate virtual geomagnetic poles (VGPs) documented during the transit from the southern to northern hemisphere. Thus, the entry into the Brunhes Normal Chron as represented by the palaeomagnetic directions and VGPs developed in a time interval comparable to the duration of an average human life, which is an order of magnitude more rapid than suggested by current models. The reported investigation therefore provides high-resolution integrated palaeomagnetic and radioisotopic data that document the fine details of the anatomy and tempo of the M-B transition in Central Italy that in turn are crucial for a better understanding of Earth's magnetic field, and for the development of more sophisticated models that are able to describe its global structure and behaviour.

Description: The anisotropy of magnetic susceptibility (AMS) of soft rocks was measured in order to distinguish between the effect of remote and local strain fields, determine the size of the related inelastic damage zone and resolve the fault-plane solutions of past earthquakes. The AMS fabrics were explored next to late Pleistocene syndepositional normal faults (total displacement up to ~3.5 m) that cross soft lacustrine rocks within the seismically active Dead Sea basin. ‘Deposition fabrics’ prevail meters away from the fault planes and are characterized by scattered maximum and intermediate principal AMS axes. ‘Deformation fabrics’ are detected up to tens of centimetres from the fault planes and are characterized by well-grouped AMS axes, in which one of the principal axes is parallel to the strike of the nearby fault. Variations in the AMS fabrics and magnetic lineations define the size of the inelastic damage zone around the faults. The results demonstrate that the deformation-driven magnetic fabrics and the associated inelastic damage zones are compatible with coseismic dynamic faulting and the effects of the local strain field during earthquakes. Most of the AMS fabrics show a conspicuous similarity to that of the fault-plane solutions, i.e., the principal AMS axes and instantaneous strain ellipsoids are coaxial. These results suggest a novel application of the AMS method for defining the shape and size of the damage zones surrounding dynamic faults and determining the full tensor of the local strain field.

Description: Very low frequency (VLF) electromagnetic waves that penetrate conductive magma-filled dykes generate secondary fields on the surface that can be used to invert for dyke properties. The model used for the interpretation calculates currents induced in a conductive strip by an inducing field that decays exponentially with depth due to the conductivity of the surrounding medium. The differential equations are integrated to give an inhomogeneous Fredholm equation of the second kind with a kernel consisting of a modified Bessel function of the second kind. Numerical methods are typically used to solve for the induced currents in the strip. In this paper, we apply a modified Galerkin–Chebyshev method, which involves separating the kernel into source and field spectra and integrating the source terms to obtain a matrix equation for the unknown coefficients. The incident wave is expressed as a Chebyshev series. The modified Bessel function is separated into a logarithmic singularity and a non-singular remainder, both of which are expanded in complex Chebyshev polynomials. The Chebyshev coefficients for the remainder are evaluated using a fast Fourier transform, while the logarithmic term and incident field have analytic series. The deconvolution then involves a matrix inversion. The results depend on the ratio of strip-size to skin-depth. For infinite skin-depth and a singular conductivity distribution given by $\tau _0 a/\sqrt{a^2 - z^2 }$ (where 0 is the conductance, a is the half-length and z the distance from the centre), Parker gives an analytic solution. We present a similar analytic series solution for the finite skin-depth case, where the size to skin depth ratio is small. Results are presented for different ratios of size to skin depth that can be compared with numerical solutions. We compare full-space and half-space solutions. A fit of the model to VLF data taken above a magma filled dykes in Hawaii and Mt Etna demonstrates that while properties such as depth to top, conductivity ratio, tilt and dip can be determined, the depth to bottom is indeterminate due to the exponential decay of the inducing field.

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: Correlated data errors (noise) are common in magnetotelluric (MT) data, but MT inversions typically neglect error correlations without investigating the impact of this simplification on inversion results. This paper examines effects of neglecting frequency- and spatially correlated noise on MT inversion, based on a nonlinear Bayesian formulation which quantifies the uncertainties of inversion results in terms of marginal posterior probability densities and credibility intervals. To do so, data with frequency- and spatially correlated noise of differing degrees are generated for several layered (1-D) synthetic cases. Bayesian MT inversions are carried out for these data sets with and without accounting for error correlation (i.e. applying full and diagonal covariance matrices, respectively, in the inversion), and the results are compared. For cases with noise that is strongly correlated over frequency or space, parameter uncertainties estimated using the diagonal-covariance simplification (neglecting error correlations) are found to often be significantly underestimated compared with results computed using the full covariance matrix.

Description: We report a new method to infer continuous time-series of the declination, inclination and intensity of the magnetic field from archaeomagnetic data. Adopting a Bayesian perspective, we need to specify a priori knowledge about the time evolution of the magnetic field. It consists in a time correlation function that we choose to be compatible with present knowledge about the geomagnetic time spectra. The results are presented as distributions of possible values for the declination, inclination or intensity. We find that the methodology can be adapted to account for the age uncertainties of archaeological artefacts and we use Markov chain Monte Carlo to explore the possible dates of observations. We apply the method to intensity data sets from Mari, Syria and to intensity and directional data sets from Paris, France. Our reconstructions display more rapid variations than previous studies and we find that the possible values of geomagnetic field elements are not necessarily normally distributed. Another output of the model is better age estimates of archaeological artefacts.

Description: We present a rigorous method for interpolation of electric and magnetic fields close to an interface with a conductivity contrast. The method takes into account not only a well-known discontinuity in the normal electric field, but also discontinuity in all the normal derivatives of electric and magnetic tangential fields. The proposed method is applied to marine 3-D controlled-source electromagnetic modelling (CSEM) where sources and receivers are located close to the seafloor separating conductive seawater and resistive formation. For the finite-difference scheme based on the Yee grid, the new interpolation is demonstrated to be much more accurate than alternative methods (interpolation using nodes on one side of the interface or interpolation using nodes on both sides, but ignoring the derivative jumps). The rigorous interpolation can handle arbitrary orientation of interface with respect to the grid, which is demonstrated on a marine CSEM example with a dipping seafloor. The interpolation coefficients are computed by minimizing a misfit between values at the nearest nodes and linear expansions of the continuous field components in the coordinate system aligned with the interface. The proposed interpolation operators can handle either uniform or non-uniform grids and can be applied to interpolation for both sources and receivers.

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: According to field observations, electromagnetic (EM) signals accompanying seismic waves can be recorded. The orders of magnitude of observed coseismic electric and magnetic signals associated with earthquakes are usually around 1 to 10 1 mV km –1 and 10 –2 to 1 nT, respectively. In this paper, we carry out numerical simulation of coseismic EM signals associated with seismic waves due to electrokinetic effect and compare with field observations. The seismic source is represented by a finite fault measuring 15 x 9 km 2 with a max slip displacement 1.5 m, corresponding to a M w 5.9 earthquake. While using the EM surface boundary condition of continuous horizontal EM components, the magnetic signals only accompany the late-arriving S waves at receiver near the ground surface. This is obviously different from field observations. Thus, we adopt another EM surface boundary condition which assumes the ground surface carries surface charge. For the used half-space model, a surface-charge density magnitude | Q sc | in excess of 10 –4 C m –2 is sufficient to make horizontal magnetic components clearly show up at the whole time duration of seismic waves. When | Q sc | increases, the contribution of surface-charge density to coseismic EM signals becomes more and more dominant comparing with that of the seismically induced streaming-current. We estimate the Q sc expected at the Earth's surface might be a value between –5 x 10 –4 and –0.1 C m –2 by the comparison between numerical results and field observations. The vertical magnetic signals only accompany the late-arriving seismic waves, because they are theoretically only induced by SH wave. The field observation results of vertical magnetic signals may be resulted from the scattering effect or the seismic dynamo effect. We conclude that electrokinetic effect combined with surface-charge assumption is one possible generation mechanism of the observed coseismic EM signals.

Description: Fifteen sites of lava flows from Martinique Island (FWI) have been selected to document the geomagnetic field in the Caribbean area over the past 2.5 Ma and further constrain the time-averaged field during this period. Identical characteristic directions were isolated using both AF and thermal stepwise demagnetization techniques in all flows. Nine mean-site directions have a normal polarity, while three others are reversed. The mean geomagnetic pole position obtained after reducing all directions to the same polarity is indistinguishable from the present north geographic pole. The dispersion is at least 8° larger than the values derived from the time-averaged field models and remains unexplained otherwise than resulting from the relatively small number of directions. The other three flows are characterized by large deviations from the expected north–south direction. One lava flow dated at 1.69 Ma (±0.02 Ma) is likely associated with a transitional field during the Gilsà subchron. The lava flow dated at 770 ka (±11 ka) coincides with the age of the Brunhes-Matuyama geomagnetic reversal and is also coeval with another intermediate flow of the same age found at Guadeloupe Island. The 617 ka (±52 ka) old unit is characterized by reversed directions that are evidently not related to the last reversal, but with other reversed polarity and transitional lava flows of the same age recorded, respectively at Mexico and La Palma island. We infer that the presence of reversed directions with the same age at distinct localities confirms that a short episode of reversed polarity has occurred during this period.

Description: Presently, most loess/palaeosol magnetic susceptibility records are interpreted as following either the wind-vigour model or the pedogenic enhancement model. However redoxomorphic processes induced by waterlogging, often referred to gleying in the loess literature, are also known to alter loess deposits but their impact on loess/palaeosol magnetic susceptibility records has received little attention. The reported rock magnetic study aims to characterize the mineral magnetic response of loess to waterlogging-induced redoxomorphic processes, thus improving our understanding of mineral magnetic changes within loess deposits with respect to environmental and climate conditions. The Nussloch loess-palaeosol deposit (Rhine Valley, Germany) was targeted because it is one of the best-studied Pleniglacial deposits for Western Europe in which numerous tundra gley intervals have been identified. Moreover, a comprehensive high-resolution environmental magnetism study has never been undertaken for this site. Various rock magnetism experiments were conducted at both room and low temperatures to characterise the composition, concentration and relative magnetic grain size of the mineral magnetic assemblage. The relative changes in magnetic parameters within the investigated loess interval are primarily controlled by (1) varying concentrations of coarse-grained ferrimagnetic particles of detrital (aeolian) origin and (2) dissolution of fine-grained ferrimagnetic particles related to in situ post-depositional alteration promoted by waterlogging-induced redoxomorphic processes. Goethite is found to be ubiquitous throughout the studied interval and is argued to have both a primary (aeolian) and secondary ( in situ ) origin. We conclude, that redoxomorphic processes induced by waterlogging, if present, will hinder the interpretation of magnetic susceptibility variations within loess and palaeosol deposits following the expected relationships dictated by the wind-vigour and the pedogenic enhancement magnetism models.

Description: Palaeosecular variation (PSV), as estimated from the scatter of remanent magnetization directions or poles, can be used to shed light to processes in the geodynamo, and potentially, to model the growth of the solid inner core. To understand the temporal aspects of the geomagnetic field behavior in the far past, we have calculated the scatter of palaeomagnetic poles (S) from a set of 55 high-quality observations derived from a new Precambrian paleomagnetic data compilation. Our analysis supports former Phanerozoic and Precambrian analyses of PSV, which favour a lower reversal rate, a higher stability of the geodynamo and a substantially smaller size of the inner core prior to 1.5 billion years ago.

Description: A palaeomagnetic study has been carried out in 29 cores drilled at six different sites from the volcanic products of Lomo Negro eruption (El Hierro, Canary Islands, Spain). Systematic thermal and alternating field demagnetization of the samples’ natural remanent magnetization revealed a northward, stable palaeomagnetic direction similar in all the samples. Rock magnetic experiments indicate that this palaeomagnetic component is carried by a mixture of high-Ti and low-Ti titanomagnetite crystals typical of basaltic lithologies that have experienced a significant degree of oxyexsolution during subaerial cooling. The well constrained palaeomagnetic direction of Lomo Negro lavas was used to perform a palaeomagnetic dating of the volcanic event, using the SHA.DIF.14k global geomagnetic model restricted for the last 3000 yr. It can be unambiguously concluded that Lomo Negro eruption occurred well before the previously proposed date of 1793 AD, with three different age ranges being statistically possible during the last 3 ka: 115 BC-7 AD, 410–626 AD and 1499–1602 AD. The calibration of a previously published non-calibrated 14 C dating suggests a XVI c. date for Lomo Negro eruption. This conclusion leaves open the possibility that the seismic crisis occurred at El Hierro in 1793 AD was related to an intrusive magmatic event that either did not reach the surface or either culminated in an unregistered submarine eruption similar to the one occurred in 2011–2012 at the southern off-shore ridge of the island.

Description: We have performed an extended palaeomagnetic study of the Oslo Graben volcanics, compared to the study of half a century ago by van Everdingen, using modern techniques and a four times larger amount of sites, plus additional rock magnetic experiments. We conclude that the average direction ( D = 204.0, I = –37.9, k = 46.9, α 95 = 2.0) and associated palaeomagnetic pole ( = 48.3, = 155.5, K = 52.2, A 95 = 1.9) of the Krokskogen and Vestfold volcanics together are statistically identical to those of the earlier study. This gives confidence in the fact that older palaeomagnetic studies can be reliable and robust, even though methods have improved. Our larger number of samples, and better age constraints, enable us to separate the data into two major intervals: the younger, on average, Krokskogen area and the older Vestfold area. The results show firstly that palaeolatitudes are slightly higher than predicted by the latest apparent polar wander path (APWP) for Eurasia by Torsvik et al. These data support an early Permian Pangaea A configuration and do not necessitate a Pangaea B configuration. The larger data set also allows us to assess the distribution of the characteristic remanent magnetization directions of the Oslo Graben in terms of geomagnetic field behaviour, which were acquired during a long period of dominantly single polarity the Permo-Carboniferous Reversed Superchron (PCRS). The distributions show a significantly lower virtual geomagnetic pole (VGP) scatter at the observed (low) latitudes than expected from a compilation from lavas of the last 5 Myr. The data do however show excellent agreement with the scatter observed both during the Cretaceous Normal Superchron and the PCRS. A comparison of the directional distributions in terms of elongation is less discriminating, since the large errors in all cases allow a fit to the predicted elongation/inclination behaviour of the TK03.GAD model.

Description: We illustrate a new imaging method to estimate the depth to the sources of potential fields and the structural index. The method consists of applying the Depth from EXtreme Point (DEXP) transformation to the ratio (R) between two different-order partial derivatives of the field. While the scaling function of the potential field depends on the structural index, we show that the scaling function of R merely depends on the difference between the two used orders of differentiation. This allows three main features to be established for the DEXP transformation of R: (1) it is independent from the structural index; (2) the estimation of the source depths is fully automatic, simply consisting in the search of position of the extreme points of the DEXP image and (3) the structural index of each source is finally determined from the scaling function or the extreme points using the estimated depth. Besides the well-known characteristics of the DEXP transformation, such as high-resolution and stability, the DEXP transformation of R enjoys one more relevant feature: it can be applied to multisource cases, yielding simultaneously correct estimations of structural index and depth for each source in the same image. However, while the DEXP transformation is a linear transformation of the field, the DEXP transformation of R is non-linear, and a procedure is described to circumvent the non-linear effects. The method is tested with synthetic examples and the estimated source parameters show a good agreement with the true values. The method was applied also to real magnetic data from the Pima copper mine, Arizona, USA, Hamrawien area, Egypt and Cataldere, Bala district of Turkey. The results are consistent with the known information about the causative sources.

Description: Variational data assimilation (4DVar) is a powerful technique for tuning dynamic models to observations, in order not only to forecast future time evolution of the system, but to make inferences about quantities that are otherwise unconstrained by observation. We apply this technique, well-grounded in meteorology and oceanography, to the Earth's core where incompressible fluid motions in an electrically conducting medium are responsible for magnetic field generation. Our dynamic model's momentum equation neglects inertia such that the entire evolution depends only on the structure of the initial magnetic field; time evolution of the system is solely governed by the equation of magnetic induction. Nevertheless the dynamic system encompasses the effects of rotation, Lorentz forces and viscosity and aims to mimic a reasonable force-balance in the Earth's core. Building on the work of Li et al. , in order to optimize the data-fit subject to the dynamics, we further develop the mathematical structure of the adjoint equations of the system. We address the feasibility of recovering 3-D spatial properties of the system using only time-varying 2-D observations of different character. Using closed-loop testing, we demonstrate the retrievability of the initial state (and thus the entire trajectory) of the system over convective timescales, when sampling in regions in which magnetic induction dominates over diffusion. The results suggest the possibility of retrieving the entire trajectory of the dynamo system of the Earth using the 400-yr model of secular variation gufm1 .

Description: We investigate polarity reversals in the geodynamo using a rotating, convection-driven dynamo model. As the flow in rapidly rotating convection is dominated by columns aligned with the axis of rotation, the focus is on the dynamics of columnar vortices. By studying the growth of a seed magnetic field to a stable axial dipole field, we show that the magnetic field acts in ways that significantly enhance the relative helicity between cyclonic and anticyclonic vortices. This flow asymmetry is the hallmark of a dipolar dynamo. Strong buoyancy, on the other hand, offsets the effect of the magnetic field, establishing parity between positive and negative vortices. As the dipole field is deprived of the helicity required to support itself, the dynamo is pushed into a reversing state. This is a likely regime for polarity reversals in the Earth's core. The integral lengthscale at which buoyancy injects energy is not significantly different from the convective flow lengthscale, which implies that buoyancy does not feed vortices at the small scales where non-linear inertia is present. The lengthscale at which the Lorentz force acts in the reversing dynamo is small, which may allow the passive presence of non-linear inertia in the small scales.

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: A new methodology to estimate magnetotelluric (MT) tensor relationships, called Estimation of Local transfer-functIons by Combining Interstation Transfer-functions (ELICIT), is proposed whereby the MT tensor relationships of the local site are derived using only interstation transfer functions. The MT impedance tensor and the geomagnetic transfer function at the local site are characterised by combining interstation tensor relationships between electric and magnetic fields at the local site with the horizontal magnetic fields acquired at a neighbouring site. The main property of the proposed method is that the employed interstation transfer functions are independently constrained, without the need to acquire the electric and the magnetic fields at the local site simultaneously to recover the local MT tensor relationships. Due to this property, the ELICIT method offers new possibilities for MT data acquisition and processing, providing significant improvements when the magnetic time-series at the local site are affected by local noise or are truncated. Error analysis shows that, even when magnetic fields are truncated, the quality of the results obtained following the ELICIT method are similar to those we would obtain if the magnetic fields had not been truncated. Another important property is that different neighbouring sites can be used to recover the tensor relationships at the local site. Averaging of results obtained using different neighbouring sites can be performed to improve the statistics. For our example data, when the ELICIT method is used to improve the statistics, errors of the estimates for periods between 1000 and 20 000 s periodicities are clearly reduced. All interstation transfer functions are calculated doing remote reference and the bootstrap method is used to compute the errors, when necessary. Long period magnetotelluric data acquired in the Pyrenees and in the Atlas Mountains in Morocco, and magnetic data provided by Fürstenfeldbruck magnetic observatory have been used to test the proposed ELICIT method, with positive results. Due to the lack of requirement that the electric and the magnetic fields of the local site be acquired simultaneously, the proposed method also offers new possibilities for MT data acquisition, optimizing the available instrumentation.

Description: The robust statistical model of a Gaussian core contaminated by outlying data that underlies robust estimation of the magnetotelluric (MT) response function has been re-examined. The residuals from robust estimators are systematically long tailed compared to a distribution based on the Gaussian, and hence are inconsistent with the robust model. Instead, MT data are pervasively described by the alpha stable distribution family whose variance and sometimes mean are undefined. A maximum likelihood estimator (MLE) that exploits the stable nature of MT data is formulated, and its two-stage implementation in which stable parameters are first fit to the data and then the MT responses are solved for is described. The MLE is shown to be inherently robust, but differs from the conventional robust estimator because it is based on a model derived from the data, while robust estimators are ad hoc , being based on the robust model that is inconsistent with actual data. Propriety versus impropriety of the complex MT response was investigated, and a likelihood ratio test for propriety and its null distribution was established. The Cramér-Rao lower bounds for the covariance matrix of proper and improper MT responses were specified. The MLE was applied to exemplar long period and broad-band data sets from South Africa. Both are shown to be significantly stably distributed using the Kolmogorov–Smirnov goodness of fit and Ansari-Bradley non-parametric dispersion tests. Impropriety of the MT responses at both sites is pervasive, hence the improper Cramér-Rao bound was used to estimate the MLE covariance. The MLE is shown to be nearly unbiased and well described by a Gaussian distribution based on bootstrap simulation. The MLE was compared to a conventional robust estimator, establishing that the standard errors of the former are systematically smaller than for the latter and that the standardized differences between them exhibit excursions that are both too frequent and too large to be described by a Gaussian model. This is ascribed to pervasive bias of the robust estimator that is to some degree obscured by their systematically large confidence bounds. Finally, a series of topics for further investigation is proposed.

Description: Broad-band and long period magnetotelluric (MT) data were acquired at 39 stations along five NNW-SSE profiles crossing the Iapetus Suture Zone (ISZ) in Ireland. Regional strike analyses indicate that the vast majority of the MT data is consistent with an assumption of a 2-D geo-electric strike direction. Strike is N52°E for the three easternmost profiles and N75°E for the two westernmost profiles; these directions correlate well with the observed predominant geological strike of the study region. 2-D inversions of the galvanic distortion-corrected TE and TM mode data from each profile are shown and discussed. As mapped geological variations between the neighbouring profiles suggest a heterogeneous subsurface, it is important to verify the robustness of the presence and geometries of prominent conductivity anomalies by employing 3-D forward and inverse modelling. A high conductivity layer (resistivity of 1–10 m), found at middle to lower crustal depths and presumed to be indicative of metamorphosed graphitic sediments rich in sulphides deposited during the convergence of the Laurentian and Avalonian continents, essentially constitutes the electrical signature of the ISZ. Shallow conductors observed are probably due to black shales that were widely deposited within the sedimentary accretionary wedge during Ordovician time. We interpret the moderately low resistivity at shallow depths from west to east across Ireland as indicative of an increase in maturity of the black shales in the easterly direction. From our conductivity models the southern extent of the ISZ is inferred to lie between the Navan Silvermines Fault and the Navan Tipperary Line, and shows clear resistivity contrast along all the profiles at the southern MT stations. The change in resistivity deduced from the 2-D models is spatially related to the composition of Lower Palaeozoic Ordovician, Silurian, Devonian and Carboniferous rocks. At upper mantle depths of about 60 km, a high conductivity block below the central MT stations is found to lie within the accretionary wedge of the Iapetus suture, and the location of the conductive anomaly corroborates reasonably well with the inferred spreading head of the putative Iceland plume-related magmatic intrusion. The low resistivity upper crust beneath the ISZ is indeed rich in Ordovician rocks with black shale content in the eastern as well as the central part; the western part is largely underlain by a highly resistive block of volcanic and metamorphosed rocks forming crystalline basement.

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: This paper presents new directional archeomagnetic data from nine Meso-/Neolithic fireplaces, sampled in a cave shelter, at Arconciel, in western Switzerland. Rock magnetic measurements indicate a homogenous magnetic mineralogy in all fireplaces, with magnetite as the main magnetic carrier. The remanent magnetization is stable and generally shows one characteristic directional component. Nine new directions, which were obtained from Arconciel, are combined with 356 other archeomagnetic data from a circular area with a radius of 700 km around this site, to obtain a penalized least square spline fit for the past 9000 yr. We found in general good agreement with other local compilations, such as the Balkan curve, the regional SCHA.DIF.8k model and with lake sediments from UK, Fennoscandia and Switzerland. Nevertheless, a time lag of several centuries is observed for a declination maximum between the archeomagnetic spline fit and the other European data records around 5900 BC. This time lag is also observed in the Swiss lake sediment record; therefore we interpret this shift as a local feature of the Earth's magnetic field.

Description: In Christian religion the sunrise is of great symbolic importance. Therefore, many churches constructed in the Middle Ages point towards geographic East. Although ‘easting’ of churches actually refers to the alignment towards the azimuth of sunrise on the individual churches’ patron's day, deviation of nave alignment from the geographic East direction is often assumed to be caused by the use of magnetic compasses. Therefore, the church alignment could provide information about historical magnetic declination. We investigate 124 churches in Lower Austria and 68 in northern Germany to clarify this question as well as the ‘easting’ hypothesis. Church orientations are determined from georeferenced satellite images. Metadata such as the construction year, possible reconstructions and the church patron are gathered to determine the date when current church direction was appointed, and to perform sunrise calculations. However, due to uncertainties of construction years and the declining importance of orientation tradition after the 15th century several churches are excluded from the study. Thus, 32 churches with reliable metadata remain for evaluation in each region. The analysis reveals a preferred alignment of naves towards geographic East in Lower Austria and northern Germany. The construction and alignment of churches was often affected by the pre-existing buildings and streets or topography and natural surroundings. Therefore, deviations from geographic East are more likely caused by town or landscape. The mean deviations from magnetic East in both regions are large compared to the mean deviations from geographic East and sunrise azimuths. Hence, the use of compasses cannot be confirmed. Despite a few churches indicating orientation according to their patron's day, a general trend cannot be observed in the data reviewed.

Description: A new finite difference solution to the global geomagnetic induction problem is developed and tested, based on a modified Lorenz gauge of the magnetic vector and electric scalar potentials and implementing a novel, overset ‘Yin-Yang’ grid that avoids unnecessary mesh refinement at the geographic poles. Previously used in whole-earth mantle convection models, the overset grid is built from a pair of partially overlapping mid-latitude latitude–longitude (lat/lon) grids, one of which is rotated with respect to the other for complete coverage of the sphere. Because of this symmetry, only one set of finite difference templates is required for global discretization of the governing Maxwell equations, a redundancy that is exploited for computational efficiency and multithreaded parallelization. Comparisons between solutions obtained by the proposed method show excellent agreement with those obtained by independent integral equation methods for 1-D, 2-D and 3-D problem geometries. The computational footprint of the method is minimized through a (non-symmetric) matrix-free BiCG-STAB iterative solver which computes finite difference matrix coefficients ‘on the fly’ as needed, rather than pulling stored values from memory. Scaling of the matrix-free BiCG-STAB algorithm with problem size shows behaviour similar to that seen with the (symmetric) QMR algorithm used in the Cartesian case from which the present algorithm is based. The proposed method may therefore provide a competitive addition to the existing body of global-scale geomagnetic induction modelling algorithms, allowing for resource-efficient forward modelling as the kernel for large-scale computing such as inversion of geomagnetic response functions, computational hypothesis testing and parametric studies of mantle geodynamics and physiochemical state.

Description: We present a robust and scalable solver for time-harmonic Maxwell's equations for problems with large conductivity contrasts, wide range of frequencies, stretched grids and locally refined meshes. The solver is part of the fully distributed adaptive 3-D electromagnetic modelling scheme which employs the finite element method and unstructured non-conforming hexahedral meshes for spatial discretization using the open-source software deal.II. We use the complex-valued electric field formulation and split it into two real-valued equations for which we utilize an optimal block-diagonal pre-conditioner. Application of this pre-conditioner requires the solution of two smaller real-valued symmetric problems. We solve them by using either a direct solver or the conjugate gradient method pre-conditioned with the recently introduced auxiliary space technique. The auxiliary space pre-conditioner reformulates the original problem in form of several simpler ones, which are then solved using highly efficient algebraic multigrid methods. In this paper, we consider the magnetotelluric case and verify our numerical scheme by using COMMEMI 3-D models. Afterwards, we run a series of numerical experiments and demonstrate that the solver converges in a small number of iterations for a wide frequency range and variable problem sizes. The number of iterations is independent of the problem size, but exhibits a mild dependency on frequency. To test the stability of the method on locally refined meshes, we have implemented a residual-based a posteriori error estimator and compared it with uniform mesh refinement for problems up to 200 million unknowns. We test the scalability of the most time consuming parts of our code and show that they fulfill the strong scaling assumption as long as each MPI process possesses enough degrees of freedom to alleviate communication overburden. Finally, we refer back to a direct solver-based pre-conditioner and analyse its complexity in time. The results show that for multiple right-hand sides the direct solver-based pre-conditioner can still be faster for problems of medium size. On the other hand, it also shows non-linear growth in memory, whereas the auxiliary space method increases only linearly.

Description: The configuration of the Pangea supercontinent has been a topic of intense debate for almost half a century, a controversy that stems from discrepancies between the geology-based Pangea-A and the palaeomagnetically based Pangea-B. Recent palaeomagnetic compilations aimed at resolving this controversy have identified the poor quality of palaeomagnetic data from Gondwana for Permian times as a major obstacle. Specifically, the vast majority of Gondwanan poles come from sedimentary rocks that are prone to biases from compaction or are poorly dated. Here, we present a new palaeomagnetic pole for cratonic South America based on impact melts from the 254.7 ± 2.5 Ma Araguainha impact structure (AIS). The granite basement, the impact-generated melt sheet and veins were sampled at 28 sites (169 specimens) and provided a reliable palaeomagnetic record similar to that of volcanic rocks. Alternating field and thermal demagnetization indicate a stable characteristic remanent magnetization carried by both magnetite and haematite. All sites but one show a single palaeomagnetic direction of normal polarity with a mean direction of Dec = 357.4°; Inc = –38.9°; N  = 28; k  = 62.35; α 95  = 3.5°, yielding a palaeomagnetic pole (AIS) at Lat = –84.2; Lon = 326.6; K  = 83.5; A 95  = 3.6°; S B  = 9.6°. The new pole provides a firm constraint on the position of Gondwana which is consistent with the Pangea A configuration.

Description: Reconstructions of the Holocene geomagnetic field and how it varies on millennial timescales are important for understanding processes in the core but may also be used to study long-term solar-terrestrial relationships and as relative dating tools for geological and archaeological archives. Here, we present a new family of spherical harmonic geomagnetic field models spanning the past 9000 yr based on magnetic field directions and intensity stored in archaeological artefacts, igneous rocks and sediment records. A new modelling strategy introduces alternative data treatments with a focus on extracting more information from sedimentary data. To reduce the influence of a few individual records all sedimentary data are resampled in 50-yr bins, which also means that more weight is given to archaeomagnetic data during the inversion. The sedimentary declination data are treated as relative values and adjusted iteratively based on prior information. Finally, an alternative way of treating the sediment data chronologies has enabled us to both assess the likely range of age uncertainties, often up to and possibly exceeding 500 yr and adjust the timescale of each record based on comparisons with predictions from a preliminary model. As a result of the data adjustments, power has been shifted from quadrupole and octupole to higher degrees compared with previous Holocene geomagnetic field models. We find evidence for dominantly westward drift of northern high latitude high intensity flux patches at the core mantle boundary for the last 4000 yr. The new models also show intermittent occurrence of reversed flux at the edge of or inside the inner core tangent cylinder, possibly originating from the equator.

Description: Several recent studies have used palaeomagnetic estimates of the virtual axial dipole moment to construct a quantitative stochastic model for fluctuations and reversals in the Earth's dipole field. We investigate the physical significance of the terms in a standard stochastic (Langevin) model using output from a numerical geodynamo model. The first term, known as the drift term, characterizes the slow adjustment of the dipole field toward a time-averaged state. We find that the timescale for this slow adjustment is set by the magnetic decay time of dipole fluctuations. These fluctuations are typically be represented by the first few decay modes. The second term is often called the noise term because it characterizes the influence of short-period convective fluctuations in the core. We establish a connection between the noise term and the rms variation in magnetic induction. Applying these results to the palaeomagnetic field suggests that the rms variation in dipole generation exceeds the mean rate of generation. Such large fluctuations may be necessary to permit magnetic reversals. Palaeomagnetic estimates of the drift term favour a high electrical conductivity in the core. A lower bound on electrical conductivity is 0.6 x 10 6 S m –1 . Similarly, we establish an upper bound on turbulent magnetic diffusivity (0.8 m 2 s –1 ), although realistic estimates may be much less.

Description: We demonstrate that first differences of polar orbiting satellite magnetic data in the along-track direction can be used to obtain high resolution models of the lithospheric field. Along-track differences approximate the north–south magnetic field gradients for non-polar latitudes. In a test case, using 2 yr of low altitude data from the CHAMP satellite, we show that use of along-track differences of vector field data results in an enhanced recovery of the small scale lithospheric field, compared to the use of the vector field data themselves. We show that the along-track technique performs especially well in the estimation of near zonal spherical harmonic coefficients. Moreover, lithospheric field models determined using along-track differences are found to be less sensitive to the presence of unmodelled external field contributions and problems associated with the polar gap are ameliorated. Experiments in modelling the Earth's lithospheric magnetic field with along-track differences are presented here as a proof of concept. We anticipate that use of such along-track differences in combination with east–west field differences, as are now provided by the Swarm satellite constellation, will be important in building the next generation of lithospheric field models.

Description: We develop an singular value decomposition-based compression of the Green's function matrix of an electromagnetic integral equation forward solver for global geomagnetic induction, on top of an fast Fourier transform reduction of the system to a block-diagonal form. With this approach, the memory usage and CPU time of Krylov subspace iterative solutions are significantly reduced at a very small cost of accuracy, making the accelerated forward solver well suited for 3-D inversions as well as forward simulations with multiple sources.

Description: The Fisher distribution is central to palaeomagnetism but presents several problems when used to characterize geomagnetic field directions as observed in sequences of volcanic rocks. First, it introduces a shallowing effect when used to define the mean of any group of directional unit vectors. This is problematic because it can suggest the presence of persistent non-axial dipole components when none are present. More importantly, it fails to capture the observed ‘long tail’ in distributions of both directions and associated virtual geomagnetic poles in terms of angular distance from a central direction. To achieve a good fit to data, it therefore requires the introduction of a second distribution (and therefore the estimation of additional parameters) or the arbitrary removal of data. Here we present a new distribution to describe palaeomagnetic directions and demonstrate that it overcomes both of these problems, generating robust indicators of both the central direction (or pole position) and the spread of palaeomagnetic data as defined by unit vectors. Starting from the assumption that poles (or directions) have an expected colatitude, rather than a mean location, we derive the spherical exponential distribution. We demonstrate that this new distribution provides a good fit to palaeomagnetic data sets from seven large igneous provinces between 15 and 65 Ma and also those produced by numerical dynamo models. We also use it to derive a new shape parameter which may be used as a diagnostic tool for testing goodness of fit of models to data and use this to argue for a shift in geomagnetic behaviour between 5 and 15 Ma. Furthermore, we point out that this new statistic can be used to determine the most appropriate distribution to be used when constructing confidence limits for poles.

Description: Haematite pigment is a common constituent of sedimentary rocks, but its contribution to the natural remanent magnetization of rocks is poorly understood. Here, we describe magnetic properties of two distinct pigment types that produce a characteristic decorative ‘print stone’ found in the ~2.5 Ga Mount McRae Shale Formation, Hamersley Province, Western Australia. Distinct magnetic remanence directions observed in the Print Stone can be correlated to each pigment type. By comparison with the Australian apparent polar wander path, the remanence carried by uniformly distributed pigment can be dated to ~15–25 Ma, while two age options, the Mesoproterozoic (~1.5 Ga) or the middle Carboniferous (~320–310 Ma), are permissible for the remanence carried by the pigment responsible for the distinctive ‘newsprint’ pattern. Magnetic properties and demagnetization characteristics of the different pigment types overlap significantly, and thus are not predictive of the dominant remanence carrier. Magnetic characteristics of the uniformly distributed pigment vary significantly on short spatial scales. Strong local control on pigment formation raises the possibility that a primary remanent magnetization may survive locally in pockets within sedimentary red bed formations.

Description: Remanent magnetizations of magnetites between single-domain (SD) threshold size (0.1 μm) and 20 μm have SD-like intensities and coercivities. This paper shows for the first time that magnetite's induced magnetization also has pseudo-single-domain behaviour. The first part of the paper reports temperature-dependent initial susceptibility data, k 0 ( T ), of sized magnetites and assesses their granulometric potential. The second part transforms coercive force data, H c ( T ), for the same magnetites into simulated k 0 ( T ) curves. The third part considers k 0 ( T ) results of coarse-grained mafic rocks as candidate sources of deep-seated magnetic anomalies. High-temperature susceptibility k 0 measured with a Kappabridge for eight fractions of crushed natural magnetites (median sizes of 0.6, 1, 3, 6, 9, 14, 110 and 135 μm) shows a progressive increase in the height of the Hopkinson peak below the Curie point as grain size decreases. The trend is systematic and has granulometric potential in the 1–14 μm range. Self-demagnetization should produce almost flat k 0 ( T ) in grains larger than SD size but experimentally, well-defined Hopkinson peaks are not limited to the finest grains. 1-μm magnetites have a peak 1.5 times k 0 at 20 °C and 14-μm grains have a peak of 1.25. Only 110 and 135 μm grains have T -independent k 0 . Using an empirical relationship between coercive force H c and k 0 , H c ( T ) data for the sized magnetites were used to simulate k 0 ( T ) results. A hump in the k 0 heating curve around 250 °C was traced to annealing out internal strains, evident in H c data measured in first heatings. For sizes ≤6 μm, observed Hopkinson peaks were smaller than predicted, possibly because of a previously unrecognized grain-size dependence of the empirical constant relating H c and k 0 . Two crystalline rocks, a gabbro and a diabase, combine SD-like Hopkinson peaks and multidomain (MD) flat ramps in their k 0 ( T ) data. In the diabase, a Hopkinson peak is prominent in separated plagioclase grains containing submicron magnetite, but is masked in whole-rock data. The gabbro has a clear superposition of SD and MD k 0 ( T ) functions in its whole-rock data, with a Hopkinson peak of 1.35. If oceanic layer-3 gabbros have similar susceptibility enhancement above 500 °C, they could be more important magnetic anomaly sources than room-temperature k 0 measurements on dredged or fault-uplifted samples would suggest.

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: We investigate the influence of different thermal and velocity boundary conditions on numerical geodynamo models. We concentrate on the implications for magnetic field morphology, heat transport scaling laws, force balances and generation mechanisms. The field morphology most strongly depends on the local Rossby number, but there is some variation in the dipolarity of the field with boundary condition. Scaling laws also depend on the boundary conditions, but a diffusivity-free scaling is a good first order approximation for all our dipolar models. Our multipolar models, however, obey different scaling laws from dipolar models implying a different force balance in these models. We find that our dipolar models have a stronger degree of Lorentz–Coriolis balance compared to our multipolar models which have a stronger degree of Lorentz-inertial balance.The models with a stronger Lorentz–Coriolis dominance can be generated by either α, α 2 or α 2 mechanisms whereas the models with a stronger Lorentz-inertial balance are all α 2 dynamos. These results imply that some caution is necessary when extrapolating results from dynamo models to Earth-like parameters since the choice of boundary conditions can have important effects.

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: 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: Lake sediments are excellent sources of palaeoenvironmental and palaeoclimatic information because they provide continuous and high-resolution records. South America is of particular interest because it is the only landmass that stretches southward into the Pacific and Atlantic Oceans towards Antarctica. The aim of this study is to explore the relationship of magnetic parameters with elemental and palaeobiological data of Laguna Potrok Aike to develop a model of lake-level changes and related hydrological and climatic fluctuations. Magnetic measurements were performed on subsamples from 15 500 cal. BP to the present, and associated rock magnetic parameters were calculated to infer magnetic mineralogy, concentration and grain size. According to the model, parameters dependent on magnetic concentration and grain size are directly related to lake-level changes. During dry periods, the remanent coercivity displays high values, whereas the proportion of magnetite is relatively low. Low percentages of greigite are observed, indicating that the water of the lake was stratified at least four times during the studied period, at approximately 10 300, 8900, 8500 and 8300 cal. BP. The preservation of greigite by inhibiting its complete transformation into pyrite is associated with a rapid burial that occurs with high sedimentation rates. Thermal stratification could be caused by a slight cooling in the area triggered by a weakening of the Westerlies and/or low activity of the sun, sum to the effect of a flood of melt water in the North Atlantic.

Description: Measurement of magnetic vector or tensor quantities, namely of field or field gradient, delivers more details of the underlying geological setting in geomagnetic prospection than a scalar measurement of a single component or of the scalar total magnetic intensity. Currently, highest measurement resolutions are achievable with superconducting quantum interference device (SQUID)-based systems. Due to technological limitations, it is necessary to suppress the parasitic magnetic field response from the SQUID gradiometer signals, which are a superposition of one tensor component and all three orthogonal magnetic field components. This in turn requires an accurate estimation of the local magnetic field. Such a measurement can itself be achieved via three additional orthogonal SQUID reference magnetometers. It is the calibration of such a SQUID reference vector magnetometer system that is the subject of this paper. A number of vector magnetometer calibration methods are described in the literature. We present two methods that we have implemented and compared, for their suitability of rapid data processing and integration into a full tensor magnetic gradiometry, SQUID-based, system. We conclude that the calibration routines must necessarily model fabrication misalignments, field offset and scale factors, and include comparison with a reference magnetic field. In order to enable fast processing on site, the software must be able to function as a stand-alone toolbox.

Description: Motional induction in the ocean by tides has long been observed by both land and satellite measurements of magnetic fields. While these signals are weak (~10 nT) when compared to the main magnetic field, their persistent nature makes them important for consideration during geomagnetic field modelling. Previous studies have reported several discrepancies between observations and numerical predictions of the tidal magnetic signals and those studies were inconclusive of the source of the error. We address this issue by (1) analysing magnetometer data from ocean-bottom stations, where the low-noise and high-signal environment is most suitable for detecting the weak tidal magnetic signals, (2) by numerically predicting the magnetic field with a spatial resolution that is 16 times higher than the previous studies and (3) by using four different models of upper-mantle conductivity. We use vector magnetic data from six ocean-bottom electromagnetic (OBEM) stations located in the Northwestern Pacific Ocean. The OBEM tidal amplitudes were derived using an iteratively re-weighted least-squares (IRLS) method and by limiting the analysis of lunar semidiurnal (M2), lunar elliptic semidinurnal (N2) and diurnal (O1) tidal modes to the night-time. Using a 3-D electromagnetic induction solver and the TPX07.2 tidal model, we predict the tidal magnetic signal. We use earth models with non-uniform oceans and four 1-D mantle sections underneath taken from Kuvshinov and Olsen, Shimizu et al. and Baba et al. to compare the effect of upper-mantle conductivity. We find that in general, the predictions and observations match within 10–70 per cent across all the stations for each of the tidal modes. The median normalized percent difference (NPD) between observed and predicted amplitudes for the tidal modes M2, N2 and O1 were 15 per cent, 47 per cent and 98 per cent, respectively, for all the stations and models. At the majority of stations, and for each of the tidal modes, the higher resolution (0.25° 0.25°) modelling gave amplitudes consistently closer to the observations than the lower resolution (1° 1°) modelling. The difference in lithospheric resistance east and west of the Izu–Bonin trench system seems to be affecting the model response and observations in the O1 tidal mode. This response is not seen in the M2 and N2 modes, thereby indicating that the O1 mode is more sensitive to lithospheric resistance.

Description: Magnetotelluric observations over one or 2-D structures that are distorted by 3-D electro-galvanic effects, need to be corrected for their proper conversion into reliable images of the subsurface electrical resistivity distribution. One of the most widely used approaches for correcting the data is the Groom–Bailey decomposition of the impedance tensor in terms of the unknown parameters of strike, twist and shear, along with the also unknown 2-D impedances. The standard approach for recovering the 2-D impedances is to solve numerically for all the unknowns as a non-linear inverse problem. In this work, we pose the recovery of the undistorted impedances in terms of a quadratic equation whose solutions filter out the distortions after a final tune for the appropriate shear parameter. The formula relies on two known invariants of the impedance tensor, the series and parallel invariants that have special immunity to some of the distorting parameters. Compared with the standard numerical recovery, the analytical solution provides more accurate results; they are clear-cut for both amplitudes and phases. The recovered amplitudes of the impedance are independent of strike, twist and shear, and the phases, in addition, of static effects. The recovery formula is transparent to random noise; hence the data preserve the original uncertainties. The applications to individual soundings of the COPROD2S1 data set and to a profile over a seismogenic region in Baja California, illustrate the effectiveness of the approach.

Description: Great progress has been made in the numerical simulation of planetary dynamos, though these numerical experiments still operate in a regime very far from the planets. For example, it seems unlikely that viscous forces are at all significant in planetary interiors, yet some of the simulations display a significant dependence on viscosity, and indeed in some of the simulations the dynamo mechanism is itself viscously driven, taking the form of helical Ekman pumping within columnar convection rolls. Given the similarity of the external magnetic fields observed in the terrestrial planets and gas giants, and the extremely small value of the Ekman number in all such cases, it seems natural to suppose that the underlying dynamo mechanism in these planets is simple, robust, independent of viscosity and insensitive to mechanical boundary conditions. A key step to identifying this mechanism is to determine the source of helicity in planetary cores, which itself should be robust, independent of viscosity and insensitive to boundary conditions. In this paper, we explore the possibility that the helicity in the core of the Earth arises from the spontaneous emission of inertial waves, driven by the equatorial heat flux in the outer core. We also ask if a similar mechanism might operate in other planets, and perhaps act to supplement the helicity driven by Ekman pumping in the (viscous) numerical simulations. We demonstrate that such waves do indeed produce the required helicity distribution outside the tangent cylinder. Moreover, we show that these waves inevitably propagate along the axis of the columnar vortices, and indeed they are the very mechanism by which the columnar vortices form in the first place and the means by which the columns subsequently evolve. We also calculate the emf induced by such axially propagating inertial waves and show that, in principle, this emf is sufficient to support a self-sustaining dynamo of the α 2 type. Finally, we derive the scaling laws for this kind of inertial-wave dynamo. We compare these predictions with the (imperfect) simulations, and also with what little we know about the Earth's core. The numerical experiments fall into two categories; the slowly rotating simulations which cannot sustain inertial waves at the small scales and the rapidly rotating (planet-like) ones which can. Our scaling laws are consistent with the latter class of simulations, and also with what we know about the Earth.

Description: The main sources of magnetic minerals in soils unaffected by anthropogenic pollution are iron oxides and hydroxides derived from parent materials through soil formation processes. Soil magnetic minerals can be used as indicators of environmental factors including soil forming processes, degree of pedogenesis, weathering processes and biological activities. In this study measurements of magnetic susceptibility are used to detect the presence and the concentration of soil magnetic minerals in topsoil and bulk samples in a small cultivated field, which forms a hydrological unit that can be considered to be representative of the rainfed agroecosystems of Mediterranean mountain environments. Additional magnetic studies such as isothermal remanent magnetization (IRM), anhysteretic remanent magnetization (ARM) and thermomagnetic measurements are used to identify and characterize the magnetic mineralogy of soil minerals. The objectives were to analyse the spatial variability of the magnetic parameters to assess whether topographic factors, soil redistribution processes, and soil properties such as soil texture, organic matter and carbonate contents analysed in this study, are related to the spatial distribution pattern of magnetic properties. The medians of mass specific magnetic susceptibility at low frequency ( lf ) were 36.0 and 31.1 10 –8 m 3 kg –1 in bulk and topsoil samples respectively. High correlation coefficients were found between the lf in topsoil and bulk core samples ( r  = 0.951, p  〈 0.01). In addition, volumetric magnetic susceptibility was measured in situ in the field ( is ) and values varied from 13.3 to 64.0 10 –5 SI. High correlation coefficients were found between lf in topsoil measured in the laboratory and volumetric magnetic susceptibility field measurements ( r  = 0.894, p  〈 0.01). The results obtained from magnetic studies such as IRM, ARM and thermomagnetic measurements show the presence of magnetite, which is the predominant magnetic carrier, and hematite. The predominance of superparamagnetic minerals in upper soil layers suggests enrichment in pedogenic minerals. The finer soil particles, the organic matter content and the magnetic susceptibility values are statistically correlated and their spatial variability is related to similar physical processes. Runoff redistributes soil components including magnetic minerals and exports fine particles out the field. This research contributed to further knowledge on the application of soil magnetic properties to derive useful information on soil processes in Mediterranean cultivated soils.

Description: State of the art numerical models of the Geodynamo are still performed in a parameter regime extremely remote from the values relevant to the physics of the Earth's core. In order to establish a connection between dynamo modelling and the geophysical motivation, it is necessary to use scaling laws. Such scaling laws establish the dependence of essential quantities (such as the magnetic field strength) on measured or controlled quantities. They allow for a direct confrontation of advanced models with geophysical constraints. We combine a numerical approach, based on a multiple linear regression method in the form of power laws, applied to a database of 102 direct numerical simulations (courtesy of U. Christensen), and a physical approach, based on energetics and forces balances. We show that previous empirical scaling laws for the magnetic field strength essentially reflect the statistical balance between energy production and dissipation for saturated dynamos. Such power based scaling laws are thus necessarily valid for any dynamo in statistical equilibrium and applicable to any numerical model, irrespectively of the dynamo mechanism. We show that direct numerical fits can provide contradictory results owing to biases in the parameters space covered in the numerics and to the role of a priori hypothesis on the fraction of ohmic dissipation. We introduce predictive scaling laws, that is relations involving input parameters of the governing equations only. We guide our reasoning on physical considerations. We show that our predictive scaling laws can properly describe the numerical database and reflect the dominant forces balance at work in these numerical simulations. We highlight the dependence of the magnetic field strength on the rotation rate. Finally, our results stress that available numerical models operate in a viscous dynamical regime, which is not relevant to the Earth's core.

Description: High-quality palaeomagnetic data for the early Carboniferous of Central Asia are scarce and the palaeogeographic evolution of this area prior to final amalgamation of the region east of the Ural mountains is still rather obscure. Here, we present palaeomagnetic data for early Carboniferous deposits from two areas in the Kyrgyz North Tianshan (NTS). Detailed rock-magnetic analysis indicates the presence of magnetite and haematite as magnetic carriers in these red sediments. In the Kazakh basin section (KEL), we identify a high-temperature component (HTC) of magnetization during stepwise thermal demagnetization at temperatures of up to ~680 °C yielding a site mean direction of D  = 176.2°, I  = –36.4°, k  = 57.4 and α 95  = 8.9° after tilt correction. Two HTCs of magnetization were identified in samples from the Sonkul Basin (DUN) with maximum blocking temperatures of ~600 °C (magnetite) and ~680 °C (haematite). The magnetite component was also identified with alternating field demagnetization. The resulting site mean directions for these two components identified in 16 and 14 sites, respectively, are D  = 149.3°, I  = –50.3°, k  = 73.6 and α 95  = 4.3° for the magnetite and D  = 139.6°, I  = –35.1°, k  = 71.6 and α 95  = 4.7° for the haematite component. All three mean directions show a significant increase of the precision parameter k after tilt correction indicating acquisition of the high-temperature magnetization prior to the main folding event in the Jurassic. We explain the difference of the two components of DUN by a process of inclination bias due to compaction to which the platy haematite particles are more susceptible. Applying the elongation-inclination (E/I) method to directional data from over 100 individual samples from location DUN results in a negligible correction for the magnetite component (〈5°), whereas the inclination of the haematite component corrects from –35.0° to –50.3° ( f  = 0.6, error interval –41.4° to –57.9°), which is then equal to the uncorrected magnetite inclination. The small number of samples from section KEL does not allow application of the E/I technique and inclination correction based on high field anisotropy of isothermal remanent magnetization was applied, yielding a corrected inclination of –75.2° ± 4°. Assuming comparable degrees of compaction for both study areas and applying the flattening factor obtained in DUN on samples from KEL, however, would result in comparable inclinations. The identification of inclination shallowing at both sections indicates that the age of magnetization is close to the deposition age. Assuming a reversed polarity of the directions from both areas results in palaeolatitudes of ~30°N for section DUN and ~60°N for the anisotropy-based correction of section KEL. The large difference, however, is geologically very unlikely. The inclination of the magnetite component of DUN (unaffected by inclination shallowing) favours a palaeoposition of ~30°N. This is supported by the inclination shallowing corrected haematite component of DUN yielding a comparable inclination. Therefore, our results indicate that the NTS domain was situated at ~30°N in the early Carboniferous. Furthermore, the NTS zone was probably not connected to Baltica or Siberia prior to the late Palaeozoic.

Description: An exploratory 3-D model of the electrical conductivity structure of the Australian continent is presented. The model is derived from the inversion of vertical magnetic-field transfer functions from the Australia-wide Array of Geomagnetic Stations. Crustal conductivity anomalies evident in the model are consistent with those previously mapped by independent magnetometer array studies and new electrical structures are suggested in the upper mantle. The model represents a seamless continent-scale basis for further models likely to be derived from subsequent studies. The model reveals three upper-mantle enhanced-conductivity anomalies beneath Archaean cratonic regions and two upper-mantle anomalies beneath Phanerozoic terranes in eastern Australia. Two of these anomalies have been investigated by recent magnetotelluric (MT) surveys, one in the Yilgarn Craton–Officer Basin–Musgrave Block the other in the Gawler Craton region, and are consistent with the MT results. Across much of central Australia enhanced conductivity at depths of 50–100 km is observed in the model. This region corresponds well with a recognized seismic velocity gradient at 75–100 km. Conductivity differences are also observed beneath Archaean cratons in Western Australia. The Pilbara Craton is represented as an enhanced conductivity anomaly at about 100 km, corresponding well with the lower-velocity anomaly evident in surface wave tomography models. The Yilgarn Craton is imaged as a low-conductivity body, with conductivity two orders of magnitude lower than the Pilbara Craton, continuing to greater depths.

Description: This paper presents new directional archeomagnetic data from nine Meso-/Neolithic fireplaces, sampled in a cave shelter, at Arconciel, in western Switzerland. Rock magnetic measurements indicate a homogenous magnetic mineralogy in all fireplaces, with magnetite as the main magnetic carrier. The remanent magnetization is stable and generally shows one characteristic directional component. Nine new directions, which were obtained from Arconciel, are combined with 356 other archeomagnetic data from a circular area with a radius of 700 km around this site, to obtain a penalized least square spline fit for the past 9000 yr. We found in general good agreement with other local compilations, such as the Balkan curve, the regional SCHA.DIF.8k model and with lake sediments from UK, Fennoscandia and Switzerland. Nevertheless, a time lag of several centuries is observed for a declination maximum between the archeomagnetic spline fit and the other European data records around 5900 BC. This time lag is also observed in the Swiss lake sediment record; therefore we interpret this shift as a local feature of the Earth's magnetic field.

Description: We present a new approach for 2-D magnetotelluric forward numerical modelling in contrast to traditional numerical methods like finite elements or finite differences. The method used for solving the partial differential equations is based on a mesh-free technique which does not need an underlaying mesh or grid. We use the Meshless Local Petrov–Galerkin (MLPG) method in combination with radial basis functions to simulate the response of a given conductivity model to a plane-wave source. We compare the mesh-free solution with known simulation programs and simple analytical solutions. Furthermore, we discuss the new magnetotelluric modelling method in terms of implementation and stability. First, we study the convergence and discretization errors of the new method with a simple half-space conductivity model. Then we compare our mesh-free simulation results with simple 2-D conductivity models with the results of a well-known finite element program. In the end, we provide a smooth conductivity model calculated with the mesh-free approach. The modelling results, even with randomly distributed nodes, are in a good agreement with those obtained by the finite element method.

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.