ALBERT

Description: The mineralocorticoid receptor (MR) is a ligand-induced transcription factor belonging to the steroid receptor family and involved in water-electrolyte homeostasis, blood pressure regulation, inflammation and fibrosis in the renocardiovascular system. The MR shares a common hormone-response-element with the glucocorticoid receptor but nevertheless elicits MR-specific effects including enhanced epidermal growth factor receptor (EGFR) expression via unknown mechanisms. The EGFR is a receptor tyrosine kinase that leads to activation of MAP kinases, but that can also function as a signal transducer for other signaling pathways. In the present study, we mechanistically investigate the interaction between a newly discovered MR- but not glucocorticoid receptor- responsive-element (=MRE1) of the EGFR promoter, specificity protein 1 (SP1) and MR to gain general insights into MR-specificity. Biological relevance of the interaction for EGFR expression and consequently for different signaling pathways in general is demonstrated in human, rat and murine vascular smooth muscle cells and cells of EGFR knockout mice. A genome-wide promoter search for identical binding regions followed by quantitative PCR validation suggests that the identified MR-SP1–MRE1 interaction might be applicable to other genes. Overall, a novel principle of MR-specific gene expression is explored that applies to the pathophysiologically relevant expression of the EGFR and potentially also to other genes.

Description: Selective inhibitory crosstalk has been known to occur within the signaling pathways of the dioxin (AhR) and estrogen (ERα) receptors. More specifically, ERα represses a cytochrome P450-encoding gene ( CYP1A1 ) that converts cellular estradiol into a metabolite that inhibits the cell cycle, while it has no effect on a P450-encoding gene ( CYP1B1 ) that converts estrodiol into a genotoxic product. Here we show that ERα represses CYP1A1 by targeting the Dnmt3B DNA methyltransferase and concomitant DNA methylation of the promoter. We also find that histone H2A.Z can positively contribute to CYP1A1 gene expression, and its presence at that gene is inversely correlated with DNA methylation. Taken together, our results provide a framework for how ERα can repress transcription, and how that impinges on the production of an enzyme that generates genotoxic estradiol metabolites, and potential breast cancer progression. Finally, our results reveal a new mechanism for how H2A.Z can positively influence gene expression, which is by potentially competing with DNA methylation events in breast cancer cells.

Description: TFIIIB and TFIIIC are multi-subunit factors required for transcription by RNA polymerase III. We present a genome-wide high-resolution footprint map of TFIIIB–TFIIIC complexes in Saccharomyces cerevisiae , obtained by paired-end sequencing of micrococcal nuclease-resistant DNA. On tRNA genes, TFIIIB and TFIIIC form stable complexes with the same distinctive occupancy pattern but in mirror image, termed ‘bootprints’. Global analysis reveals that the TFIIIB–TFIIIC transcription complex exhibits remarkable structural elasticity: tRNA genes vary significantly in length but remain protected by TFIIIC. Introns, when present, are markedly less protected. The RNA polymerase III transcription terminator is flexibly accommodated within the transcription complex and, unexpectedly, plays a major structural role by delimiting its 3'-boundary. The ETC sites, where TFIIIC binds without TFIIIB, exhibit different bootprints, suggesting that TFIIIC forms complexes involving other factors. We confirm six ETC sites and report a new site ( ETC10 ). Surprisingly, TFIIIC, but not TFIIIB, interacts with some centromeric nucleosomes, suggesting that interactions between TFIIIC and the centromere may be important in the 3D organization of the nucleus.

Description: The process of DNA mismatch repair is initiated when MutS recognizes mismatched DNA bases and starts the repair cascade. The Escherichia coli MutS protein exists in an equilibrium between dimers and tetramers, which has compromised biophysical analysis. To uncouple these states, we have generated stable dimers and tetramers, respectively. These proteins allowed kinetic analysis of DNA recognition and structural analysis of the full-length protein by X-ray crystallography and small angle X-ray scattering. Our structural data reveal that the tetramerization domains are flexible with respect to the body of the protein, resulting in mostly extended structures. Tetrameric MutS has a slow dissociation from DNA, which can be due to occasional bending over and binding DNA in its two binding sites. In contrast, the dimer dissociation is faster, primarily dependent on a combination of the type of mismatch and the flanking sequence. In the presence of ATP, we could distinguish two kinetic groups: DNA sequences where MutS forms sliding clamps and those where sliding clamps are not formed efficiently. Interestingly, this inability to undergo a conformational change rather than mismatch affinity is correlated with mismatch repair.

Description: Phosphorylation of histone H4 serine 47 (H4S47ph) is catalyzed by Pak2, a member of the p21-activated serine/threonine protein kinase (Pak) family and regulates the deposition of histone variant H3.3. However, the phosphatase(s) involved in the regulation of H4S47ph levels was unknown. Here, we show that three phosphatases (PP1α, PP1β and Wip1) regulate H4S47ph levels and H3.3 deposition. Depletion of each of the three phosphatases results in increased H4S47ph levels. Moreover, PP1α, PP1β and Wip1 bind H3-H4 in vitro and in vivo , whereas only PP1α and PP1β, but not Wip1, interact with Pak2 in vivo . These results suggest that PP1α, PP1β and Wip1 regulate the levels of H4S47ph through directly acting on H4S47ph, with PP1α and PP1β also likely regulating the activity of Pak2. Finally, depletion of PP1α, PP1β and Wip1 leads to increased H3.3 occupancy at candidate genes tested, elevated H3.3 deposition and enhanced association of H3.3 with its chaperones HIRA and Daxx. These results reveal a novel role of three phosphatases in chromatin dynamics in mammalian cells.

Description: Previously we identified Rrp1 and Rrp2 as two proteins required for the Sfr1/Swi5-dependent branch of homologous recombination (HR) in Schizosaccharomyces pombe . Here we use a yeast two-hybrid approach to demonstrate that Rrp1 and Rrp2 can interact with each other and with Swi5, an HR mediator protein. Rrp1 and Rrp2 form co-localizing methyl methanesulphonate–induced foci in nuclei, further suggesting they function as a complex. To place the Rrp1/2 proteins more accurately within HR sub-pathways, we carried out extensive epistasis analysis between mutants defining Rrp1/2, Rad51 (recombinase), Swi5 and Rad57 (HR-mediators) plus the anti-recombinogenic helicases Srs2 and Rqh1. We confirm that Rrp1 and Rrp2 act together with Srs2 and Swi5 and independently of Rad57 and show that Rqh1 also acts independently of Rrp1/2. Mutants devoid of Srs2 are characterized by elevated recombination frequency with a concomitant increase in the percentage of conversion-type recombinants. Strains devoid of Rrp1 or Rrp2 did not show a change in HR frequency, but the number of conversion-type recombinants was increased, suggesting a possible function for Rrp1/2 with Srs2 in counteracting Rad51 activity. Our data allow us to propose a model placing Rrp1 and Rrp2 functioning together with Swi5 and Srs2 in a synthesis-dependent strand annealing HR repair pathway.

Description: In eukaryotic cells, gene expression is mediated by enhancer activation of RNA polymerase at distant promoters. Recently, distinctions between enhancers and promoters have been blurred by the discovery that enhancers are associated with RNA polymerase and are sites of RNA synthesis. Here, we present an analysis of the insulin-like growth factor 2/H19 muscle enhancer. This enhancer includes a short conserved core element that is organized into chromatin typical of mammalian enhancers, binds tissue-specific transcription factors and functions on its own in vitro to activate promoter transcription. However, in a chromosomal context, this element is not sufficient to activate distant promoters. Instead, enhancer function also requires transcription in cis of a long non-coding RNA, Nctc1 . Thus, the insulin-like growth factor 2/H19 enhancer is an active transcriptional complex whose own transcription is essential to its function.

Description: Evolutionarily conserved RNA secondary structures are a robust indicator of purifying selection and, consequently, molecular function. Evaluating their genome-wide occurrence through comparative genomics has consistently been plagued by high false-positive rates and divergent predictions. We present a novel benchmarking pipeline aimed at calibrating the precision of genome-wide scans for consensus RNA structure prediction. The benchmarking data obtained from two refined structure prediction algorithms, RNAz and SISSIz, were then analyzed to fine-tune the parameters of an optimized workflow for genomic sliding window screens. When applied to consistency-based multiple genome alignments of 35 mammals, our approach confidently identifies 〉4 million evolutionarily constrained RNA structures using a conservative sensitivity threshold that entails historically low false discovery rates for such analyses (5–22%). These predictions comprise 13.6% of the human genome, 88% of which fall outside any known sequence-constrained element, suggesting that a large proportion of the mammalian genome is functional. As an example, our findings identify both known and novel conserved RNA structure motifs in the long noncoding RNA MALAT1 . This study provides an extensive set of functional transcriptomic annotations that will assist researchers in uncovering the precise mechanisms underlying the developmental ontologies of higher eukaryotes.

Description: The p53 core domain binds to response elements (REs) that contain two continuous half-sites as a cooperative tetramer, but how p53 recognizes discontinuous REs is not well understood. Here we describe the crystal structure of the p53 core domain bound to a naturally occurring RE located at the promoter of the Bcl-2-associated X protein (BAX) gene, which contains a one base-pair insertion between the two half-sites. Surprisingly, p53 forms a tetramer on the BAX-RE that is nearly identical to what has been reported on other REs with a 0-bp spacer. Each p53 dimer of the tetramer binds in register to a half-site and maintains the same protein–DNA interactions as previously observed, and the two dimers retain all the protein–protein contacts without undergoing rotation or translation. To accommodate the additional base pair, the DNA is deformed and partially disordered around the spacer region, resulting in an apparent unwinding and compression, such that the interactions between the dimers are maintained. Furthermore, DNA deformation within the p53-bound BAX-RE is confirmed in solution by site-directed spin labeling measurements. Our results provide a structural insight into the mechanism by which p53 binds to discontinuous sites with one base-pair spacer.

Description: RNA-based therapeutic approaches using splice-switching oligonucleotides have been successfully applied to rescue dystrophin in Duchenne muscular dystrophy (DMD) preclinical models and are currently being evaluated in DMD patients. Although the modular structure of dystrophin protein tolerates internal deletions, many mutations that affect nondispensable domains of the protein require further strategies. Among these, trans -splicing technology is particularly attractive, as it allows the replacement of any mutated exon by its normal version as well as introducing missing exons or correcting duplication mutations. We have applied such a strategy in vitro by using cotransfection of pre– trans -splicing molecule (PTM) constructs along with a reporter minigene containing part of the dystrophin gene harboring the stop-codon mutation found in the mdx mouse model of DMD. Optimization of the different functional domains of the PTMs allowed achieving accurate and efficient trans -splicing of up to 30% of the transcript encoded by the cotransfected minigene. Optimized parameters included mRNA stabilization, choice of splice site sequence, inclusion of exon splice enhancers and artificial intronic sequence. Intramuscular delivery of adeno-associated virus vectors expressing PTMs allowed detectable levels of dystrophin in mdx and mdx4Cv , illustrating that a given PTM can be suitable for a variety of mutations.

Description: We give explicit atomic bases of arbitrary coefficient-free cluster algebras of types A and à . This entails showing that the minimal elements of the positive semiring of these cluster algebras form a linear basis over the integers for the cluster algebra.

Description: We prove that strongly F -regular and F -pure singularities satisfy Bertini-type theorems (including in the context of pairs) by building upon a framework of Cumino, Greco and Manaresi (compare with the work of Jouanolou and Spreafico). We also prove that F -injective singularities fail to satisfy even the most basic Bertini-type results.

Description: This is the second of a pair of papers on the Delta-group structure on the braid and mapping class groups of a surface. We obtain a description of the homotopy groups of these Delta-groups and generalize to an arbitrary surface the Berrick–Cohen–Wong–Wu exact sequence relating the Brunnian braid groups of the 2-sphere to its homotopy groups. We prove a similar result for Brunnian mapping class groups.

Description: We construct a geometric realization of the Khovanov–Lauda–Rouquier algebra R associated with a symmetric Borcherds–Cartan matrix A = ( a ij ) i , j I via quiver varieties. As an application, if a ii != 0 for any i I , we prove that there exists a one-to-one correspondence between Kashiwara's lower global basis (or Lusztig's canonical basis) of U A – (g) (respectively, V A ( )) and the set of isomorphism classes of indecomposable projective graded modules over R (respectively, R ).

Description: The purpose of this paper is to study the nature of quasi-invariant measures for finitely generated non-discrete subgroups of Diff ( S 1 ). For this, we apply ideas involving the closure of these groups to find out that the regularity of the measure depends on a ‘measurable version’ of well-known problems concerning stable self-intersection of Cantor sets. As applications, we prove that every d -quasiconformal probability measure for a non-solvable and non-discrete group must be absolutely continuous. Concerning singular quasi-invariant measures, it is also proved that their associated Hausdorff measures must either be zero or of infinite mass, a result contrasting with the case of dynamically defined Cantor sets and also applicable to the examples of singular stationary measures constructed by Kaimanovich and Le Prince. As a further application of our methods, a theorem of rigidity for measurable conjugations between groups as above is obtained.

Description: We study the space of period polynomials associated with modular forms of integral weight for finite-index subgroups of the modular group. For the modular group, this space is endowed with a pairing, corresponding to the Petersson inner product on modular forms via a formula of Haberland, and with an action of Hecke operators, defined algebraically by Zagier. We generalize Haberland's formula to (not necessarily cuspidal) modular forms for finite-index subgroups, and we show that it conceals two stronger formulas. We extend the action of Hecke operators to period polynomials of modular forms, we show that the pairing on period polynomials appearing in Haberland's formula is nondegenerate, and we determine the adjoints of Hecke operators with respect to it. We give a few applications for 1 ( N ): an extension of the Eichler–Shimura isomorphism to the entire space of modular forms; the determination of the relations satisfied by the even and odd parts of period polynomials associated with cusp forms, which are independent of the period relations; and an explicit formula for Fourier coefficients of Hecke eigenforms in terms of their period polynomials, generalizing the Coefficient theorem of Manin.

Description: This study develops a spectral theory of the interior transmission problem (ITP) for heterogeneous and anisotropic elastic solids. The subject is central to the so-called qualitative methods for inverse scattering involving penetrable obstacles. Although simply stated as a coupled pair of elastodynamic wave equations, the ITP for elastic bodies is neither self-adjoint nor elliptic. To help deal with such impediments, earlier studies have established the well-posedness of an elastodynamic ITP under notably restrictive assumptions on the contrast in elastic and mass density parameters between the scatterer and the background solid. Due to lack of self-adjointness of the problem, these analyses were further successful in substantiating the discreteness of the relevant eigenvalue spectrum but not its existence. The aim of this work is to provide a systematic treatment of the ITP for elastic bodies that transcends the limitations of earlier analyses. Considering a broad range of material-contrast configurations, this paper investigates the questions of the solvability of the ITP, the discreteness of its eigenvalues and, for the first time, of the existence of such eigenvalue spectrum. Necessitated by the breadth of material configurations studied, the relevant claims are established via a suite of variational formulations, each customized to meet the needs of a particular subclass of eigenvalue problems.

Description: Rayleigh–Stokes problems have in recent years received much attention due to their importance in physics. In this article, we focus on the variable-order Rayleigh–Stokes problem for a heated generalized second grade fluid with fractional derivative. Implicit and explicit numerical methods are developed to solve the problem. The convergence, stability of the numerical methods and solvability of the implicit numerical method are discussed via Fourier analysis. Moreover, a numerical example is given and the results support the effectiveness of the theoretical analysis.

Description: In this paper, the rigorous linking of exact stochastic models to mean-field approximations is studied. Using a continuous-time Markov chain, we start from the exact formulation of a simple epidemic model on a certain class of networks, including completely connected and regular random graphs, and rigorously derive the well-known mean-field approximation that is usually justified based on biological hypotheses. We propose a unifying framework that incorporates and discusses the details of two existing proofs and we put forward a new ordinary differential equation (ODE)-based proof. The more well-known proof is based on a first-order partial differential equation approximation, while the other, more technical one, uses Martingale and Semigroup theory. We present the main steps of both proofs to investigate their applicability in different modelling contexts and to make these ideas more accessible to a broader group of applied researchers. The main result of the paper is a new ODE-based proof that may serve as a building block to prove similar convergence results for more complex networks. The new proof is based on deriving a countable system of ODEs for the moments of a distribution of interest and proving a perturbation theorem for this infinite system.

Description: In this paper, we extend certain key results from the classical theory of isotropic elasticity to the generalized theory of elasticity for decagonal quasicrystaline composites. These results include: (i) the dependence of the solution on the number of elastic constants, (ii) Green's functions for bimaterials consisting of two bonded half-planes, (iii) Green's functions for a circular elastic inclusion, (iv) the oscillatory singular stress field in the vicinity of an interface crack tip and (v) the inverse problem corresponding to the design of harmonic shapes.

Description: The note develops an approximate approach to mixed boundary value problems in linear elasticity starting from an explicit asymptotic model for the Rayleigh surface wave. It is demonstrated that the original vector mixed problem may be reduced to a scalar problem for the Laplace equation. As an illustration, the steady-state motion of a rigid stamp is analysed. Comparison of asymptotic and exact results is presented.

Description: Thanks to the microarray technology, our understanding of transcriptome evolution at the genome level has been considerably advanced in the past decade. Yet, further investigation was challenged by several technical limitations of this technology. Recent innovation of next-generation sequencing, particularly the invention of RNA-seq technology, has shed insightful lights on resolving this problem. Though a number of statistical and computational methods have been developed to analyze RNA-seq data, the analytical framework specifically designed for evolutionary genomics remains an open question. In this article we develop a new method for estimating the genome expression distance from the RNA-seq data, which has explicit interpretations under the model of gene expression evolution. Moreover, this distance measure takes the data overdispersion, gene length variation, and sequencing depth variation into account so that it can be applied to multiple genomes from different species. Using mammalian RNA-seq data as example, we demonstrated that this expression distance is useful in phylogenomic analysis.

Description: The control of RNA splicing is often modulated by exonic motifs near splice sites. Chief among these are exonic splice enhancers (ESEs). Well-described ESEs in mammals are purine rich and cause predictable skews in codon and amino acid usage toward exonic ends. Looking across species, those with relatively abundant intronic sequence are those with the more profound end of exon skews, indicative of exonization of splice site recognition. To date, the only intron-rich species that have been analyzed are mammals, precluding any conclusions about the likely ancestral condition. Here, we examine the patterns of codon and amino acid usage in the vicinity of exon–intron junctions in the brown alga Ectocarpus siliculosus , a species with abundant large introns, known SR proteins, and classical splice sites. We find that amino acids and codons preferred/avoided at both 3' and 5' ends in Ectocarpus , of which there are many, tend, on average, to also be preferred/avoided at the same exon ends in humans. Moreover, the preferences observed at the 5' ends of exons are largely the same as those at the 3' ends, a symmetry trend only previously observed in animals. We predict putative hexameric ESEs in Ectocarpus and show that these are purine rich and that there are many more of these identified as functional ESEs in humans than expected by chance. These results are consistent with deep phylogenetic conservation of SR protein binding motifs. Assuming codons preferred near boundaries are "splice optimal" codons, in Ectocarpus , unlike Drosophila, splice optimal and translationally optimal codons are not mutually exclusive. The exclusivity of translationally optimal and splice optimal codon sets is thus not universal.

Description: We show the existence and uniqueness of a solution for the nonlocal vector-valued Allen–Cahn variational inequality in a formulation involving Lagrange multipliers for local and nonlocal constraints. Furthermore, we propose and analyse a primal–dual active set (PDAS) method for local and nonlocal vector-valued Allen–Cahn variational inequalities. The local convergence behaviour of the PDAS algorithm is studied by interpreting the approach as a semismooth Newton method and numerical simulations are presented demonstrating its efficiency.

Description: In this paper, we will present a generalized convolution quadrature for solving linear parabolic and hyperbolic evolution equations. The original convolution quadrature method by Lubich works very nicely for equidistant time steps while the generalization of the method and its analysis to nonuniform time stepping is by no means obvious. We will introduce the generalized convolution quadrature allowing for variable time steps and develop a theory for its error analysis. This method opens the door for further development towards adaptive time stepping for evolution equations. As the main application of our new theory, we will consider the wave equation in exterior domains which is formulated as a retarded boundary integral equation.

Description: We address the error control of Galerkin discretization (in space) of linear second-order hyperbolic problems. More specifically, we derive a posteriori error bounds in the L ( L 2 ) norm for finite element methods for the linear wave equation, under minimal regularity assumptions. The theory is developed for both the space-discrete case and for an implicit fully discrete scheme. The derivation of these bounds relies crucially on carefully constructed space and time reconstructions of the discrete numerical solutions, in conjunction with a technique introduced by Baker (1976, Error estimates for finite element methods for second-order hyperbolic equations. SIAM J. Numer. Anal. , 13 , 564–576) in the context of a priori error analysis of Galerkin discretization of the wave problem in weaker-than-energy spatial norms.

Description: The surface finite element method can be used to approximate curvatures on embedded hypersurfaces and to discretize geometric partial differential equations. In this paper, we present a definition of discrete Ricci curvature on polyhedral hypersurfaces of arbitrary dimension based on the discretization of a weak formulation with isoparametric finite elements. We prove that for a piecewise quadratic approximation of a two- or three-dimensional hypersurface R n +1 , this definition approximates the Ricci curvature of with a linear order of convergence in the L 2 ( ) norm. By using a smoothing scheme in the case of a piecewise linear approximation of , we still get a convergence of order 2/3 in the L 2 ( ) norm and of order 1/3 in the W 1, 2 ( ) norm.

Description: We give general conditions which guarantee that the sequence generated by a descent algorithm converges to an equilibrium point. The convergence result is based on the Lojasiewicz gradient inequality; optimal convergence rates are also derived, as well as a stability result. We show how our results apply to a large variety of standard time discretizations of gradient-like flows. Schemes with variable time step are considered and optimal conditions on the maximal step size are derived. Applications to time and space discretizations of the Allen–Cahn equation, the sine–Gordon equation and a damped wave equation are given.

Description: This paper presents quadratic finite-volume methods for elliptic and parabolic problems on quadrilateral meshes that use Barlow points (optimal stress points) for dual partitions. Introducing Barlow points into the finite-volume formulations results in better approximation properties at the cost of loss of symmetry. The novel ‘symmetrization’ technique adopted in this paper allows us to derive optimal-order error estimates in the H 1 - and L 2 -norms for elliptic problems and in the L ( H 1 )- and L ( L 2 )-norms for parabolic problems. Superconvergence of the difference between the gradients of the finite-volume solution and the interpolant can also be derived. Numerical results confirm the proved error estimates.

Description: A linear parabolic differential equation on a moving surface is discretized in space by evolving-surface finite elements and in time by backward difference formulas (BDFs). Using results from Dahlquist's G-stability theory and Nevanlinna & Odeh's multiplier technique together with properties of the spatial semidiscretization, stability of the full discretization is proved for BDF methods up to order 5 and optimal-order convergence is shown. Numerical experiments illustrate the behaviour of the fully discrete method.

Description: In this article, we develop the a priori and a posteriori error analysis of hp -version interior penalty discontinuous Galerkin finite element methods for strongly monotone quasi-Newtonian fluid flows in a bounded Lipschitz domain R d , d = 2, 3. In the latter case, computable upper and lower bounds on the error are derived in terms of a natural energy norm, which are explicit in the local mesh size and local polynomial degree of the approximating finite element method. A series of numerical experiments illustrate the performance of the proposed a posteriori error indicators within an automatic hp -adaptive refinement algorithm.

Description: In recent years, it has become increasingly clear that the critical issue in gradient methods is the choice of the step length, whereas using gradient as the search direction may lead to very effective algorithms, whose surprising behaviour has only been partially explained, mostly in terms of the spectrum of the Hessian matrix. On the other hand, the convergence of the classical Cauchy steepest descent (SD) method has been analysed extensively and related to the spectral properties of the Hessian matrix, but the connection with the spectrum of the Hessian has not been exploited much to modify the method in order to improve its behaviour. In this work, we show how, for convex quadratic problems, moving from some theoretical properties of the SD method, second-order information provided by the step length can be exploited to dramatically improve the usually poor practical behaviour of this method. This allows us to achieve computational results comparable with those of the Barzilai and Borwein algorithm, with the further advantage of monotonic behaviour.

Description: We proposed two multiparty quantum secret sharing schemes based on n -particle Greenberger–Horne–Zeilinger-states (GHZ states), which are transformed from Einstein–Podolsky–Rosen pairs by entanglement swapping. In our schemes, the dealer imposes messages by performing local unitary operations ( I, x, i y, z ) on the n -particle GHZ state she holds, and the agents collaborate to deduce the dealer's messages by performing local unitary operations on their own qubit. The amount of dealer's secret message is positively related with the number of agents. The need of qubits is one-third less than the former schemes and, also, they can be reused for the next new round. The scheme (II) does not have to pre-share the code table, which increases the security without the risk of being stolen.

Description: Automatic fare collection (AFC) systems calculate the fare that the users must pay depending on the time of service (time-based) or the points of entrance and exit of the system (distance-based). The progressive introduction of Information and Communication Technologies allows the use of electronic tickets, which helps us to reduce costs and improve the control of the infrastructures. Nevertheless, these systems must be secure against possible fraud and they must also preserve users’ privacy. Therefore, we have studied the security requirements for the time-based and distance-based systems and we have proposed a protocol for each of the AFC systems. 1 The protocols offer strong privacy for honest users, i.e. the service provider is not able to disclose the identity of its users and, moreover, different journeys of the same user are not linkable between them. However, anonymity for users could be revoked if they misbehave. The protocols have been implemented in Android and its performance has been evaluated in two Android smartphones. The results remark that protocols are suitable to be used on an AFC system with a medium class mobile device although they offer a better experience with a high-class smartphone. The appearance in the market of more powerful mobile devices suggests a better usability of our proposal in a near future.

Description: Accurately locating unknown nodes is a critical issue in the study of wireless sensor networks (WSNs). Many localization approaches have been proposed based on anchor nodes, which are assumed to know their locations by manual placement or additional equipments such as global positioning system. However, none of these approaches can work properly under the adversarial scenario. In this paper, we propose a novel scheme called two-step secure localization (TSSL) stand against many typical malicious attacks, e.g. wormhole attack and location spoofing attack. TSSL detects malicious nodes step by step. First, anchor nodes collaborate with each other to identify suspicious nodes by checking their coordinates, identities and time of sending information. Then, by using a modified mesh generation scheme, malicious nodes are isolated and the WSN is divided into areas with different trust grades. Finally, a novel localization algorithm based on the arrival time difference of localization information is adopted to calculate locations of unknown nodes. Simulation results show that the TSSL detects malicious nodes effectively and the localization algorithm accomplishes localization with high localization accuracy.

Description: Distance-bounding protocols form a family of challenge–response authentication protocols that have been introduced to thwart relay attacks. They enable a verifier to authenticate and to establish an upper bound on the physical distance to an untrusted prover. We provide a detailed security analysis of a family of such protocols. More precisely, we show that the secret key shared between the verifier and the prover can be leaked after a number of nonce repetitions. The leakage probability, while exponentially decreasing with the nonce length, is only weakly dependent on the key length. Our main contribution is a high probability bound on the number of sessions required for the attacker to discover the secret, and an experimental analysis of the attack under noisy conditions. Both of these show that the attack's success probability mainly depends on the length of the used nonces rather than the length of the shared secret key. The theoretical bound could be used by practitioners to appropriately select their security parameters. While longer nonces can guard against this type of attack, we provide a possible countermeasure which successfully combats these attacks even when short nonces are used.

Description: In threshold public-key encryption (TPKE), the decryption key is divided into n shares, each one of which is given to a different decryption user in order to avoid single points of failure. A robust TPKE is that if threshold decryption of a valid ciphertext fails, the combiner can identify the decryption users that supplied invalid partial decryption shares. In this paper, we propose a practical and efficient TPKE scheme which is robust and non-interactive. Security against chosen-ciphertext attacks (CCAs) can be proved in the standard model under the hashed Diffie–Hellman assumption in bilinear groups. The security reduction is tight and simple. We use an instantiation hash function of the Kiltz's key encapsulation mechanism and Lai et al. 's chosen-ciphertext secure technique to construct a TPKE scheme. Moreover, our scheme is more simple and shown to be more efficient than currently existing CCA-secure TPKE schemes.

Description: The advances in the digital world (e.g. the Internet, Communications, etc.) are closing the gap between consumers and providers, in both Business to Consumer and Business to Business environments. Through the Internet, providers can offer their products directly to consumers, which increase their choices and allow them to contract a set of different services/products from different providers. But sometimes the consumer needs an all-or-nothing exchange with these providers: an atomic exchange. The consumer has negotiated/obtained a set of conditions that are only met if she acquires all the services/products. Thus, we need an Atomic Multi-Two-Party contract signing protocol. Even though digital signature of contracts is a topic that has been widely studied, it lacks a solution when applied to Atomic Multi-Two-Party scenarios. Here, we propose the first solution to solve this problem.

Description: Key-evolving cryptography is intended to mitigate the damage in case of a secret key compromise, one of the severest security threats to actual cryptographic schemes. In the public-key setting, the essential idea of key-evolving lies in updating the private key with time, while maintaining the same public key. Key evolution in encryption and signing has been well studied, especially in the identity-based (ID-based) setting where an entity's public key can be derived from that entity's identity information. From a more practical standpoint, however, one would like to use the primitive signcryption in the hierarchical ID-based setting. In this paper, we propose the first key-evolving hierarchical ID-based signcryption scheme that is scalable and joining-time-oblivious and allows secret keys to be updated autonomously. The security proofs of our construction depend on the bilinear Diffie–Hellman assumption and the computational Diffie–Hellman assumption in the random oracle model. To be specific, our proposal not only achieves the fundamental goals of confidentiality and authenticity, but also enjoys desirable properties of non-repudiation, ciphertext anonymity and strong forward security. Compared with the conventional sign-then-encrypt approach, our construction provides better efficiency in terms of the computation cost and the communication overhead.

Description: Cooperative Intelligent Transportation Systems (ITS) will turn up to us with safer and more efficient driving environments as well as convenient and infotainment features for future ITS stations. ETSI and ISO are completing the standardization of the building blocks of a reference communication architecture for cooperative ITS. Future ITS stations complying with this set of standards deployed in vehicles, at the roadside infrastructures and within the Internet are expected to communicate with each other through a combination of ITS dedicated communication protocols and legacy Internet protocols. However, in spite of the wide adoption of IPv6 for cooperative ITS communications, relatively little attention has been paid to the security issues related to IPv6 signaling and IPv6 transport communications. In this paper, we present our position on the emerging and urgent IPv6-related security issues that occur in communications between ITS stations complying with the ITS station reference architecture under standardization within ETSI TC ITS and ISO TC204.

Description: Autonomous retrotransposons lacking long terminal repeats (LTR) account for much of the variation in genome size and structure among vertebrates. Mammalian genomes contain hundreds of thousands of non-LTR retrotransposon copies, mostly resulting from the amplification of a single clade known as L1. The genomes of teleost fish and squamate reptiles contain a much more diverse array of non-LTR retrotransposon families, whereas copy number is relatively low. The majority of non-LTR retrotransposon insertions in nonmammalian vertebrates also appear to be very recent, suggesting strong purifying selection limits the accumulation of non-LTR retrotransposon copies. It is however unclear whether this turnover model, originally proposed in Drosophila , applies to nonmammalian vertebrates. Here, we studied the population dynamics of L1 in the green anole lizard ( Anolis carolinensis ). We found that although most L1 elements are recent in this genome, truncated insertions accumulate readily, and many are fixed at both the population and species level. In contrast, full-length L1 insertions are found at lower population frequencies, suggesting that the turnover model only applies to longer L1 elements in Anolis . We also found that full-length L1 inserts are more likely to be fixed in populations of small effective size, suggesting that the strength of purifying selection against deleterious alleles is highly dependent on host demographic history. Similar mechanisms seem to be controlling the fate of non-LTR retrotransposons in both Anolis and teleostean fish, which suggests that mammals have considerably diverged from the ancestral vertebrate in terms of how they interact with their intragenomic parasites.

Description: A requirement for advancing antibody-based medicine is the development of proteins that can bind with high affinity to a specific epitope related to a critical protein activity site. As a part of generating such proteins, we have succeeded in creating a binding protein without changing epitope by complementarity-determining region 3 (CDR3) grafting (Inoue et al. , Affinity transfer to a human protein by CDR3 grafting of camelid VHH. Protein Sci. 20, 1971–1981). However, the affinity of the target-binding protein was low. In this manuscript, the affinity maturation of a target-binding protein was examined using CDR3-grafted camelid single domain antibody (VHH) as a model protein. Several amino acids in the CDR1 and CDR2 regions of VHH were mutated to tyrosines and/or serines and screened for affinity-matured proteins by using in silico analysis. The mutation of two amino acids in the CDR2 region to arginine and/or aspartic acid increased the affinity by decreasing the dissociation rate. The affinity of designed mutant increased by ~20-fold over that of the original protein. In the present study, candidate mutants were narrowed down using in silico screening and computational modelling, thus avoiding much in vitro analytical effort. Therefore, the method used in this study is expected to be one of the useful for promoting affinity maturation of antibodies.

Description: A method was previously established for evaluating Asn deamidation by matrix-assisted laser desorption/ionization time of flight-mass spectrometry using endoproteinase Asp-N. In this study, we demonstrated that this method could be applied to the identification of the deamidation site of the humanized fragment antigen-binding (Fab). First, a system for expressing humanized Fab from methylotrophic yeast Pichia pastoris was constructed, resulting in the preparation of ~30 mg of the purified humanized Fab from 1 l culture. Analysis of the L-chain derived from recombinant humanized Fab that was heated at pH 7 and 100°C for 1 h showed the deamidation at Asn138 in the constant region. Then, we prepared L-N138D Fab and L-N138A Fab and examined their properties. The circular dichroism (CD) spectrum of the L-N138D Fab was partially different from that of the wild-type Fab. The measurement of the thermostability showed that L-N138D caused a significant decrease in the thermostability of Fab. On the other hand, the CD spectrum and thermostability of L-N138A Fab showed the same behaviour as the wild-type Fab. Thus, it was suggested that the introduction of a negative charge at position 138 in the L-chain by the deamidation significantly affected the stability of humanized Fab.

Description: The tripartite motif (TRIM) or RBCC proteins are characterized by the TRIM composed of a RING finger, B-box and coiled-coil domains. TRIM proteins often play roles in the post-translational protein modification, including ubiquitylation and other ubiquitin-like modifications. Evidence has accumulated in regard to the contribution of TRIM proteins to diverse cellular processes, including such as cell cycle progression, apoptosis, immunity and transcriptional regulation. In particular, some of the TRIM proteins have been characterized to exert oncogenic or tumour suppressor-like functions depending on the context. A recent report by Inoue and his colleagues has revealed that Terf/TRIM17 stimulates the degradation of a kinetochore protein ZWINT and regulates the proliferation of breast cancer cells. Terf has also been paid attention as a factor promoting neuronal apoptosis, by degrading a Bcl2-like anti-apoptotic protein Mcl-1. Like aircraft trim tabs, TRIM proteins trim the balance of homoeostasis by modulating various biological pathways through protein–protein interactions.

Description: Cyclin-dependent kinase (CDK) that plays a central role in preventing re-replication of DNA phosphorylates several replication proteins to inactivate them. MCM4 in MCM2-7 and RPA2 in RPA are phosphorylated with CDK in vivo . There are inversed correlations between the phosphorylation of these proteins and their chromatin binding. Here, we examined in vitro phosphorylation of human replication proteins of MCM2-7, RPA, TRESLIN, CDC45 and RECQL4 with CDK2/cyclinE, CDK2/cyclinA, CDK1/cyclinB, CHK1, CHK2 and CDC7/DBF4 kinases. MCM4, RPA2, TRESLIN and RECQL4 were phosphorylated with CDKs. Effect of the phosphorylation by CDK2/cyclinA on DNA-binding abilities of MCM2-7 and RPA was examined by gel-shift analysis. The phosphorylation of RPA did not affect its DNA-binding ability but that of MCM4 inhibited the ability of MCM2-7. Change of six amino acids of serine and threonine to alanines in the amino-terminal region of MCM4 rendered the mutant MCM2-7 insensitive to the inhibition with CDK. These biochemical data suggest that phosphorylation of MCM4 at these sites by CDK plays a direct role in dislodging MCM2-7 from chromatin and/or preventing re-loading of the complex to chromatin.

Description: To determine the effects of alcohols on the low-frequency local motions that control slow changes in structural dynamics of native-like compact states of proteins, we have studied the effects of alcohols on structural fluctuation of M80-containing -loop by measuring the rate of thermally driven CO dissociation from a natively folded carbonmonoxycytochrome c under varying concentrations of alcohols (methanol, ethanol, 1-propanol, 2-propanol, 3°-butanol, 2,2,2-trifluoroethanol). As alcohol is increased, the rate coefficient of CO dissociation ( k diss ) first decreases in subdenaturing region and then increases on going from subdenaturing to denaturing milieu. This decrease in k diss is more for 2,2,2-trifluroethanol and 1-propanol and least for methanol, indicating that the first phase of motional constraint is due to the hydrophobicity of alcohols and intramolecular protein cross-linking effect of alcohols, which results in conformational entropy loss of protein. The thermal denaturation midpoint for ferrocytochrome c decreases with increase in alcohol, indicating that alcohol decrease the global stability of protein. The stabilization free energy ( G ) in alcohols’ solution was calculated from the slope of the Wyman–Tanford plot and water activity. The m -values obtained from the slope of G versus alcohols plot were found to be more negative for longer and linear chain alcohols, indicating destabilization of proteins by alcohols through disturbance of hydrophobic interactions and hydrogen bonding.

Description: Ubiquitination is a post-translational modification involved in the regulation of a broad variety of cellular functions, such as protein degradation and signal transduction, including nuclear factor-B (NF-B) signalling. NF-B is crucial for inflammatory and immune responses, and aberrant NF-B signalling is implicated in multiple disorders. We found that linear ubiquitin chain assembly complex (LUBAC), composed of HOIL-1L, HOIP and SHARPIN, generates a novel type of Met1 (M1)-linked linear polyubiquitin chain and specifically regulates the canonical NF-B pathway. Moreover, specific deubiquitinases, such as CYLD, A20 (TNFAIP3) and OTULIN/gumby, inhibit LUBAC-induced NF-B activation by different molecular mechanisms, and several M1-linked ubiquitin-specific binding domains have been structurally defined. LUBAC and these linear ubiquitination-regulating factors contribute to immune and inflammatory processes and apoptosis. Functional impairments of these factors are correlated with multiple disorders, including autoinflammation, immunodeficiencies, dermatitis, B-cell lymphomas and Parkinson’s disease. This review summarizes the molecular basis and the pathophysiological implications of the linear ubiquitination-mediated NF-B activation pathway regulation by LUBAC.

Description: We screened circadian-regulated genes in rat cartilage by using a DNA microarray analysis. In rib growth-plate cartilage, numerous genes showed statistically significant circadian mRNA expression under both 12:12 h light–dark and constant darkness conditions. Type II collagen and aggrecan genes—along with several genes essential for post-translational modifications of collagen and aggrecan, including prolyl 4-hydroxylase 1, lysyl oxidase, lysyl oxidase-like 2 and 3'-phosphoadenosine 5'-phosphosulphate synthase 2—showed the same circadian phase. In addition, the mRNA level of SOX9, a master transcription factor for the synthesis of type II collagen and aggrecan, has a similar phase of circadian rhythms. The circadian expression of the matrix-related genes may be critical in the development and the growth of various cartilages, because similar circadian expression of the matrix-related genes was observed in hip joint cartilage. However, the circadian phase of the major matrix-related genes in the rib permanent cartilage was almost the converse of that in the rib growth-plate cartilage under light–dark conditions. We also found that half of the oscillating genes had conserved clock-regulatory elements, indicating contribution of the elements to the clock outputs. These findings suggest that the synthesis of the cartilage matrix macromolecules is controlled by cell-autonomous clocks depending upon the in vivo location of cartilage.

Description: Human chromosome 7 open reading frame 24 (C7orf24)/-glutamyl cyclotransferase has been suggested to be a potential diagnostic marker for several cancers, including carcinomas in the bladder urothelium, breast and endometrial epithelium. We here investigated the epigenetic regulation of the human C7orf24 promoter in normal diploid ARPE-19 and IMR-90 cells and in the MCF-7 and HeLa cancer cell lines to understand the transcriptional basis for the malignant-associated high expression of C7orf24. Chromatin immunoprecipitation analysis revealed that histone modifications associated with active chromatin were enriched in the proximal region but not in the distal region of the C7orf24 promoter in HeLa and MCF-7 cells. In contrast, elevated levels of histone modifications leading to transcriptional repression and accumulation of heterochromatin proteins in the C7orf24 promoter were observed in the ARPE-19 and IMR-90 cells, compared to the levels in HeLa and MCF-7 cancer cells. In parallel, the CpG island of the C7orf24 promoter was methylated to a greater extent in the normal cells than in the cancer cells. These results suggest that the transcriptional silencing of the C7orf24 gene in the non-malignant cells is elicited through heterochromatin formation in its promoter region; aberrant expression of C7orf24 associated with malignant alterations results from changes in chromatin dynamics.

Description: Abscisic acid (ABA) is a stress-inducible plant hormone comprising an inevitable component of the human diet. Recently, stress-induced accumulation of autocrine ABA was shown in humans, as well as ABA-mediated modulation of a number of disease-associated systems. Now, the application of a chemical proteomics approach to gain further insight into ABA mechanisms of action in mammalian cells is reported. An ABA mimetic photoaffinity probe was applied to intact mammalian insulinoma and embryonic cells, leading to the identification of heat shock protein 70 (HSP70) family members, (including GRP78 and HSP70-2) as putative human ABA-binding proteins. In vitro characterization of the ABA–HSP70 interactions yielded K d s in the 20–60 µM range, which decreased several fold in the presence of co-chaperone. However, ABA was found to have only variable- and co-chaperone-independent effects on the ATPase activity of these proteins. The potential implications of these ABA–HSP70 interactions are discussed with respect to the intracellular protein folding and extracellular receptor-like activities of these stress-inducible proteins. While mechanistic and functional relevance remain enigmatic, we conclude that ABA can bind to human HSP70 family members with physiologically relevant affinities and in a co-chaperone-dependent manner.

Description: I begin by drawing a parallel between the intuitionistic understanding of quantification over all natural numbers and the generality relativist understanding of quantification over absolutely everything. I then argue that adoption of an intuitionistic reading of relativism not only provides an immediate reply to the absolutist's charge of incoherence but it also throws a new light on the debates surrounding absolute generality.

Description: In Plato's Phaedrus , Socrates offers two speeches, the first portraying madness as mere disease, the second celebrating madness as divine inspiration. Each speech is correct, says Socrates, though neither is complete. The two kinds of madness are like the left and right sides of a living body: no account that focuses on just one half can be adequate. In a recent paper, Hugh Benson gives a left-handed speech about a psychic condition endemic among mathematicians: dianoia . Benson acknowledges that his account is one-sided, but only hints at the virtues of right-handed dianoia . This note sketches a somewhat fuller picture.

Description: In a recent paper, Aidan Lyon and Mark Colyvan have proposed an explanation of the structure of the bee's honeycomb based on the mathematical Honeycomb Conjecture. This explanation has instantly become one of the standard examples in the philosophical debate on mathematical explanations of physical phenomena. In this critical note, I argue that the explanation is not scientifically adequate. The reason for this is that the explanation fails to do justice to the essentially three-dimensional structure of the bee's honeycomb.

Description: Hilary Putnam first published the consistency objection against Ludwig Wittgenstein’s account of mathematics in 1979. In 1983, Putnam and Benacerraf raised this objection against all conventionalist accounts of mathematics. I discuss the 1979 version and the scenario argument, which supports the key premise of the objection. The wide applicability of this objection is not apparent; I thus raise it against an imaginary axiomatic theory T similar to Peano arithmetic in all relevant aspects. I argue that a conventionalist can explain the consistency of T and suggest that an analogous explanation can be provided for the consistency of Peano arithmetic.

Description: In this paper I examine some difficulties with the argument presented as a topological sorites in Z. Weber and M. Colyvan, ‘A topological sorites’, Journal of Philosophy 107, 311–325. In particular, I suggest that the argument may be used to support the claim that sorites-type paradoxes cannot arise in a cohesive environment.

Description: Mistaken reasons for thinking diagrammatic proofs aren't rigorous are explored. The main result is that a confusion between the contents of a proof procedure (what's expressed by the referential elements in a proof procedure) and the unarticulated mathematical aspects of a proof procedure (how that proof procedure is enabled) gives the impression that diagrammatic proofs are less rigorous than language proofs. An additional (and independent) factor is treating the impossibility of naturally generalizing a diagrammatic proof procedure as an indication of lack of rigor.

Description: This paper examines the ontological commitments of the second-order language of arithmetic and argues that they do not extend beyond the first-order language. Then, building on an argument by George Boolos, we develop a Tarski-style definition of a truth predicate for the second-order language of arithmetic that does not involve the assignment of sets to second-order variables but rather uses the same class of assignments standardly used in a definition for the first-order language.

Description: This note has three goals. First, we discuss a presentation of Bertrand's paradox in a recent issue of Philosophia Mathematica , which we believe to be a subtle but important misinterpretation of the problem. We compare claims made about Bertrand with his 1889 Calcul des Probabilités . Second, we use this source to understand Bertrand's true intention in describing what we now call his paradox, comparing it both to another problem he describes in the same section and to a modern treatment. Finally, we briefly consider the importance of knowing when a specific example represents a general case.

Description: Motivation: Residue–residue contacts across the transmembrane helices dictate the three-dimensional topology of alpha-helical membrane proteins. However, contact determination through experiments is difficult because most transmembrane proteins are hard to crystallize. Results: We present a novel method (MemBrain) to derive transmembrane inter-helix contacts from amino acid sequences by combining correlated mutations and multiple machine learning classifiers. Tested on 60 non-redundant polytopic proteins using a strict leave-one-out cross-validation protocol, MemBrain achieves an average accuracy of 62%, which is 12.5% higher than the current best method from the literature. When applied to 13 recently solved G protein-coupled receptors, the MemBrain contact predictions helped increase the TM-score of the I-TASSER models by 37% in the transmembrane region. The number of foldable cases (TM-score 〉0.5) increased by 100%, where all G protein-coupled receptor templates and homologous templates with sequence identity 〉30% were excluded. These results demonstrate significant progress in contact prediction and a potential for contact-driven structure modeling of transmembrane proteins. Availability: www.csbio.sjtu.edu.cn/bioinf/MemBrain/ Contact: hbshen@sjtu.edu.cn or zhng@umich.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: Identification of protein–ligand binding sites is critical to protein function annotation and drug discovery. However, there is no method that could generate optimal binding site prediction for different protein types. Combination of complementary predictions is probably the most reliable solution to the problem. Results: We develop two new methods, one based on binding-specific substructure comparison (TM-SITE) and another on sequence profile alignment (S-SITE), for complementary binding site predictions. The methods are tested on a set of 500 non-redundant proteins harboring 814 natural, drug-like and metal ion molecules. Starting from low-resolution protein structure predictions, the methods successfully recognize 〉51% of binding residues with average Matthews correlation coefficient (MCC) significantly higher (with P -value 〈10 –9 in student t -test) than other state-of-the-art methods, including COFACTOR, FINDSITE and ConCavity. When combining TM-SITE and S-SITE with other structure-based programs, a consensus approach (COACH) can increase MCC by 15% over the best individual predictions. COACH was examined in the recent community-wide COMEO experiment and consistently ranked as the best method in last 22 individual datasets with the Area Under the Curve score 22.5% higher than the second best method. These data demonstrate a new robust approach to protein–ligand binding site recognition, which is ready for genome-wide structure-based function annotations. Availability: http://zhanglab.ccmb.med.umich.edu/COACH/ Contact: zhng@umich.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: The nucleosome is the basic repeating unit of chromatin. It contains two copies each of the four core histones H2A, H2B, H3 and H4 and about 147 bp of DNA. The residues of the histone proteins are subject to numerous post-translational modifications, such as methylation or acetylation. Chromatin immunoprecipitiation followed by sequencing (ChIP-seq) is a technique that provides genome-wide occupancy data of these modified histone proteins, and it requires appropriate computational methods. Results: We present NucHunter, an algorithm that uses the data from ChIP-seq experiments directed against many histone modifications to infer positioned nucleosomes. NucHunter annotates each of these nucleosomes with the intensities of the histone modifications. We demonstrate that these annotations can be used to infer nucleosomal states with distinct correlations to underlying genomic features and chromatin-related processes, such as transcriptional start sites, enhancers, elongation by RNA polymerase II and chromatin-mediated repression. Thus, NucHunter is a versatile tool that can be used to predict positioned nucleosomes from a panel of histone modification ChIP-seq experiments and infer distinct histone modification patterns associated to different chromatin states. Availability: The software is available at http://epigen.molgen.mpg.de/nuchunter/ . Contact: chung@molgen.mpg.de Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: In biomedical research a growing number of platforms and technologies are used to measure diverse but related information, and the task of clustering a set of objects based on multiple sources of data arises in several applications. Most current approaches to multisource clustering either independently determine a separate clustering for each data source or determine a single ‘joint’ clustering for all data sources. There is a need for more flexible approaches that simultaneously model the dependence and the heterogeneity of the data sources. Results: We propose an integrative statistical model that permits a separate clustering of the objects for each data source. These separate clusterings adhere loosely to an overall consensus clustering, and hence they are not independent. We describe a computationally scalable Bayesian framework for simultaneous estimation of both the consensus clustering and the source-specific clusterings. We demonstrate that this flexible approach is more robust than joint clustering of all data sources, and is more powerful than clustering each data source independently. We present an application to subtype identification of breast cancer tumor samples using publicly available data from The Cancer Genome Atlas. Availability: R code with instructions and examples is available at http://people.duke.edu/%7Eel113/software.html . Contact: Eric.Lock@duke.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: More and more evidences have indicated that long–non-coding RNAs (lncRNAs) play critical roles in many important biological processes. Therefore, mutations and dysregulations of these lncRNAs would contribute to the development of various complex diseases. Developing powerful computational models for potential disease-related lncRNAs identification would benefit biomarker identification and drug discovery for human disease diagnosis, treatment, prognosis and prevention. Results : In this article, we proposed the assumption that similar diseases tend to be associated with functionally similar lncRNAs. Then, we further developed the method of Laplacian Regularized Least Squares for LncRNA–Disease Association (LRLSLDA) in the semisupervised learning framework. Although known disease–lncRNA associations in the database are rare, LRLSLDA still obtained an AUC of 0.7760 in the leave-one-out cross validation, significantly improving the performance of previous methods. We also illustrated the performance of LRLSLDA is not sensitive (even robust) to the parameters selection and it can obtain a reliable performance in all the test classes. Plenty of potential disease–lncRNA associations were publicly released and some of them have been confirmed by recent results in biological experiments. It is anticipated that LRLSLDA could be an effective and important biological tool for biomedical research. Availability: The code of LRLSLDA is freely available at http://asdcd.amss.ac.cn/Software/Details/2 . Contact: xingchen@amss.ac.cn or yangy@amt.ac.cn Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: Genomic repositories are rapidly growing, as witnessed by the 1000 Genomes or the UK10K projects. Hence, compression of multiple genomes of the same species has become an active research area in the past years. The well-known large redundancy in human sequences is not easy to exploit because of huge memory requirements from traditional compression algorithms. Results: We show how to obtain several times higher compression ratio than of the best reported results, on two large genome collections (1092 human and 775 plant genomes). Our inputs are variant call format files restricted to their essential fields. More precisely, our novel Ziv-Lempel-style compression algorithm squeezes a single human genome to ~400 KB. The key to high compression is to look for similarities across the whole collection, not just against one reference sequence, what is typical for existing solutions. Availability: http://sun.aei.polsl.pl/tgc (also as Supplementary Material) under a free license. Supplementary data: Supplementary data are available at Bioinformatics online. Contact: sebastian.deorowicz@polsl.pl

Description: Motivation:  Biological systems are understood through iterations of modeling and experimentation. Not all experiments, however, are equally valuable for predictive modeling. This study introduces an efficient method for experimental design aimed at selecting dynamical models from data. Motivated by biological applications, the method enables the design of crucial experiments: it determines a highly informative selection of measurement readouts and time points. Results:  We demonstrate formal guarantees of design efficiency on the basis of previous results. By reducing our task to the setting of graphical models, we prove that the method finds a near-optimal design selection with a polynomial number of evaluations. Moreover, the method exhibits the best polynomial-complexity constant approximation factor, unless P = NP. We measure the performance of the method in comparison with established alternatives, such as ensemble non-centrality, on example models of different complexity. Efficient design accelerates the loop between modeling and experimentation: it enables the inference of complex mechanisms, such as those controlling central metabolic operation. Availability:  Toolbox ‘NearOED’ available with source code under GPL on the Machine Learning Open Source Software Web site (mloss.org). Contact:   busettoa@inf.ethz.ch Supplementary information:   Supplementary data are available at Bioinformatics online.

Description: : Small RNA deep sequencing is widely used to characterize non-coding RNAs (ncRNAs) differentially expressed between two conditions, e.g. healthy and diseased individuals and to reveal insights into molecular mechanisms underlying condition-specific phenotypic traits. The ncRNAome is composed of a multitude of RNAs, such as transfer RNA, small nucleolar RNA and microRNA (miRNA), to name few. Here we present omiRas, a Web server for the annotation, comparison and visualization of interaction networks of ncRNAs derived from next-generation sequencing experiments of two different conditions. The Web tool allows the user to submit raw sequencing data and results are presented as: (i) static annotation results including length distribution, mapping statistics, alignments and quantification tables for each library as well as lists of differentially expressed ncRNAs between conditions and (ii) an interactive network visualization of user-selected miRNAs and their target genes based on the combination of several miRNA–mRNA interaction databases. Availability and Implementation: The omiRas Web server is implemented in Python, PostgreSQL, R and can be accessed at: http://tools.genxpro.net/omiras/ . Contact: rotter@genxpro.de Supplementary Information: Supplementary data are available at Bioinformatics online.

Description: : We present PARSEC (PAtteRn Search and Contextualization), a new open source platform for guided discovery, allowing localization and biological characterization of short genomic sites in entire eukaryotic genomes. PARSEC can search for a sequence or a degenerated pattern. The retrieved set of genomic sites can be characterized in terms of (i) conservation in model organisms, (ii) genomic context (proximity to genes) and (iii) function of neighboring genes. These modules allow the user to explore, visualize, filter and extract biological knowledge from a set of short genomic regions such as transcription factor binding sites. Availability: Web site implemented in Java, JavaScript and C++, with all major browsers supported. Freely available at lbgi.fr/parsec. Source code is freely available at sourceforge.net/projects/genomicparsec. Contact: odile.lecompte@unistra.fr Supplementary information: Supplementary data are available at Bioinformatics online.

Description: : At the rate that prokaryotic genomes can now be generated, comparative genomics studies require a flexible method for quickly and accurately predicting orthologs among the rapidly changing set of genomes available. SPOCS implements a graph-based ortholog prediction method to generate a simple tab-delimited table of orthologs and in addition, html files that provide a visualization of the predicted ortholog/paralog relationships to which gene/protein expression metadata may be overlaid. Availability and Implementation: A SPOCS web application is freely available at http://cbb.pnnl.gov/portal/tools/spocs.html . Source code for Linux systems is also freely available under an open source license at http://cbb.pnnl.gov/portal/software/spocs.html ; the Boost C++ libraries and BLAST are required. Contact: leeann.mccue@pnnl.gov

Description: : Automated image processing has allowed cell migration research to evolve to a high-throughput research field. As a consequence, there is now an unmet need for data management in this domain. The absence of a generic management system for the quantitative data generated in cell migration assays results in each dataset being treated in isolation, making data comparison across experiments difficult. Moreover, by integrating quality control and analysis capabilities into such a data management system, the common practice of having to manually transfer data across different downstream analysis tools will be markedly sped up and made more robust. In addition, access to a data management solution creates gateways for data standardization, meta-analysis and structured public data dissemination. We here present CellMissy, a cross-platform data management system for cell migration data with a focus on wound healing data. CellMissy simplifies and automates data management, storage and analysis from the initial experimental set-up to data exploration. Availability and implementation: CellMissy is a cross-platform open-source software developed in Java. Source code and cross-platform binaries are freely available under the Apache2 open source license at http://cellmissy.googlecode.com . Contact: lennart.martens@ugent.be Supplementary Information: Supplementary data are available at Bioinformatics online.

Description: Motivation: With the expansion of high-throughput technologies, understanding different kinds of genome-level data is a common task. MicroRNA (miRNA) is increasingly profiled using high-throughput technologies (microarrays or next-generation sequencing). The downstream analysis of miRNA targets can be difficult. Although there are many databases and algorithms to predict miRNA targets, there are few tools to integrate miRNA–gene interaction data into high-throughput genomic analyses. Results: We present targetHub, a CouchDB database of miRNA–gene interactions. TargetHub provides a programmer-friendly interface to access miRNA targets. The Web site provides RESTful access to miRNA–gene interactions with an assortment of gene and miRNA identifiers. It can be a useful tool to integrate miRNA target interaction data directly into high-throughput bioinformatics analyses. Availability: TargetHub is available on the web at http://app1.bioinformatics.mdanderson.org/tarhub/_design/basic/index.html . Contact: coombes.3@osu.edu

Description: Increasing evidence from sequence data from various environments, including the human gut, suggests the existence of a previously unknown putative seventh order of methanogens. The first genomic data from members of this lineage, Methanomassiliicoccus luminyensis and " Candidatus Methanomethylophilus alvus," provide insights into its evolutionary history and metabolic features. Phylogenetic analysis of ribosomal proteins robustly indicates a monophyletic group independent of any previously known methanogenic order, which shares ancestry with the Marine Benthic Group D, the Marine Group II, the DHVE2 group, and the Thermoplasmatales. This phylogenetic position, along with the analysis of enzymes involved in core methanogenesis, strengthens a single ancient origin of methanogenesis in the Euryarchaeota and indicates further multiple independent losses of this metabolism in nonmethanogenic lineages than previously suggested. Genomic analysis revealed an unprecedented loss of the genes coding for the first six steps of methanogenesis from H 2 /CO 2 and the oxidative part of methylotrophic methanogenesis, consistent with the fact that M. luminyensis and " Ca. M. alvus" are obligate H 2 -dependent methylotrophic methanogens. Genomic data also suggest that these methanogens may use a large panel of methylated compounds. Phylogenetic analysis including homologs retrieved from environmental samples indicates that methylotrophic methanogenesis (regardless of dependency on H 2 ) is not restricted to gut representatives but may be an ancestral characteristic of the whole order, and possibly also of ancient origin in the Euryarchaeota. 16S rRNA and McrA trees show that this new order of methanogens is very diverse and occupies environments highly relevant for methane production, therefore representing a key lineage to fully understand the diversity and evolution of methanogenesis.

Description: Resistive forces along convergent plate boundaries have a major impact on surface deformation, most visibly at collisional plate boundaries. Although quantification of these forces is key to understanding the evolution and present state of mountain belts, they remain highly uncertain due to the complexity of plate boundary structures and rheologies. In previous studies of the Eurasian Plate, we have analysed the balance of plate boundary forces, tractions resulting from lithosphere–mantle coupling, and intraplate variations in topography and density structure. This yielded a range of acceptable force distributions. In this study, we investigate to which extent the observed present-day stress field provides further constraints on the distribution of forces. We address the dynamics of the Eurasian Plate as a whole. This enables us to base our analysis on mechanical equilibrium of a tectonic plate and to evaluate all forces as part of an internally consistent set of forces driving and deforming Eurasia. We incorporate tractions from convective mantle flow modelling in a lithospheric model in which edge and lithospheric body forces are modelled explicitly and compute resulting stresses in a homogeneous elastic thin shell. Intraplate stress observations used are from the World Stress Map project. Eurasia's stress field turns out to be particularly sensitive to the distribution of collision forces on the plate's southern margin and, to a much lesser extent, to lithospheric density structure and tractions from mantle flow. Stress observations require collision forces on the India–Eurasia boundary of 7.0–10.5 TN m –1 and on the Arabia–Eurasia boundary of 1.3–2.7 TN m –1 . Implication of mechanical equilibrium of the plate is that forces on the contacts with the African and Australian plates amount to 1.0–2.5 and 0–1.3 TN m –1 , respectively. We use our results to assess the validity of the classical view that the mean elevation of an orogenic plateau can be taken as a measure of the magnitude of the compressive (in this case: collision-related) forces involved. For both the Tibetan and the Iranian plateaus, two plateaus with significantly different average elevations, we find that the horizontal force derived from the excess gravitational potential energy (collapse force) is in balance with the collision force.

Description: Magma movement and fault slip alter the magnitude and orientation of the stress in the surrounding crust. Observations of a sequence of events clustered in space and time provide information about the triggering mechanism and stress interactions between magma intrusion, earthquakes and eruptions. We investigate the syn- and post-intrusion stress changes associated with the 2007 Gelei dyke intrusion episode and subsequent eruption of nearby Oldonyo Lengai. Previous studies produced a kinematic model of the 2007 June–August sequence involving ~1 m slip on a normal fault followed by the intrusion of the 7–10-km long Gelei dyke, collapse of a shallow graben and the deflation of the Gelei magma chamber. Immediately following this, the volcano Oldoinyo Lengai (〈10 km away) experienced a new phase of explosive activity lasting for several months. Here, we present new geodetic observations covering Gelei and Oldoinyo Lengai in 2008 September–2010. We show continued slip on graben-bounding faults above the Gelei dyke. The eruption of Oldoinyo Lengai was accompanied by the intrusion of a 4 km-long E–W-trending dyke followed by deflation of a shallow source directly below the summit of the volcano. Next, we use stress calculations to investigate a number of hypotheses linking these events. (1) Before the onset of surface deformation, a dyke sufficiently deep and narrow to be geodetically undetectable could still have produced sufficient stress changes to trigger slip on the normal fault (i.e. the sequence could have been magmatically driven). (2) Stresses at the dyke tip would have been sufficient to overcome the effect of continued slip on the normal fault, allowing the dyke to propagate upwards into a region of clamping. (3) The Gelei sequence would have produced a significant stress change on the chamber beneath Oldoinyo Lengai. These static stress calculations allow us to discuss the roles played by dynamic stress, deeper magmatic changes and background stresses throughout the sequence with implications for the stress triggering of both seismic and volcanic hazards.

Description: The relationships between magnetic susceptibility and pedogenic development are different in various regions of the world. For example, loess magnetic susceptibility shows a positive correlation with pedogenic development in Chinese Loess Plateau (CLP), while it displays a negative correlation with pedogenesis in Alaska and Siberia. To better understand the relationship between magnetic properties and pedogenic development, detailed sampling of Dashing Rocks loess section at Timaru, South Island, New Zealand, was carried out. Multiproxy magnetic parameters such as magnetic susceptibility, anhysteretic remanent magnetization, magnetic hysteresis loops, M s – T curves and – T curves were measured. The results show that the types of magnetic minerals are similar to CLP: magnetite, maghemite, goethite and hematite. However, great differences are found in their concentration: most minerals in the Dashing Rocks section are hard magnetic, such as goethite, the content of paramagnetic minerals is rather high, while the soft-magnetic mineral content is very low. Hard-magnetic and paramagnetic minerals increase with depth, but soft-magnetic minerals decrease with depth, and are absent in the lower part of the profile. Gammate soil structures and Fe/Mn nodules (or pans) are commonly observed in the section, indicating that high susceptibility magnetite and maghemite have been converted to goethite and migrated downward to enrich certain horizons during chemical weathering. This process leads to lower magnetic susceptibility values, possibly related to the source and the transformation of soft-magnetic minerals in a high soil moisture environment. The relationship between magnetic susceptibility and pedogenic development in Dashing Rocks loess section is therefore different from the simple positive and negative relationships in CLP and Siberia, respectively. The more complex relationships between magnetic properties and pedogenic development in New Zealand loess may be related to differing degrees of magnetic mineral transformation at different depths and at different times.

Description: Vehicle traffic is at present one of the major sources of environmental pollution in urban areas. Magnetic parameters are successfully applied in environmental studies to obtain detailed information about concentrations and quality of iron-bearing minerals. A general aim of this research was to investigate the magnetic, microstructural and mineralogical properties of dust extracted from the roadside snowpack accumulated on the side of an urban highway, northern Helsinki. Vertical snow profiles were taken at different distances (5, 10 and 15 m) from the road edge, during winter season 2010–2011. The temporal distribution of mass magnetic susceptibility () of the road dust shows that the concentration of magnetic particles increases in the snowpack during winter. Roadside snowpack preserves a large fraction of the magnetic particulate until the late stages of melting and this could be considered as one of the main factors responsible for the resuspension phenomenon observed in Nordic countries. The vertical distribution of and SIRM (saturation isothermal remanent magnetization)/ ratio may indicate the migration of magnetic particles down in the snowpack during melting conditions. Ultrafine to coarse-grained (superparamagnetic to multidomain) magnetite was identified as the primary magnetic mineral in all the studied road dust samples. The examined road dust contains significant amount of dia/paramagnetic minerals (e.g. quartz, albite, biotite) and the content of magnetite is relatively low (below 1 weight percent, wt%). The roadside snowpack is enriched in anthropogenic particles such as angular and spherical iron-oxides, tungsten-rich particles and sodium chloride. This study demonstrates the suitability of snow as an efficient collecting medium of magnetic particulates generated by anthropogenic activities.

Description: We explore the use of on-land GPS observations to detect deformation due to tsunami propagation near source regions of large interplate earthquakes. Here, we focus on the M w 9 Tohoku-oki earthquake, which occurred around 14:46 (JST) on 2011 March 11. We consider GPS data in the time span 14:54–15:22 (JST) along the Sanriku coast, where the tsunami had the largest amplitude. The displacement data shows the signatures of large aftershocks as well as post-seismic fault slip (afterslip). These effects are particularly evident in the east component. From the horizontal displacement vectors, we construct a simple fault model for the early phase of the afterslip. Mean slip velocity of the early afterslip reaches 0.1 mm s –1 . By compiling the early afterslip velocity of recent interplate earthquakes around that region, we find its increasing trend with the main shock magnitude. This scaling relation may reflect higher stressing rates at edges of larger main shock faults. Separately, we forward calculate land deformation due to tsunami height changes based on a tsunami simulation. Tsunami-induced deformation is only evident in the vertical direction at coastal GPS stations. The predicted subsidence amounts at some coastal stations can account for a large portion of the residuals between the observation and the modelled deformation due to the fault slip.

Description: Observations of the Earth's nutations provide constraints on the mechanical coupling at the core–mantle and inner core boundaries. An important physical mechanism that could be responsible for the observed dissipation is the electromagnetic (EM) coupling, to which this paper is devoted. Previous studies assumed that the main feature of the magnetic field that affects the EM coupling is its overall strength, its morphology being considered unimportant. In particular, these studies rely on the hypothesis that the contribution to the torque from all the non-dipolar components of the field can be approximated by the contribution that a uniform radial field with the same strength would have. In this study, we compute the EM torque for more realistic configurations of the magnetic field at the core boundaries and thereby assess the role of its spatial distribution on the strength of the EM torque. For field strengths typical of the core–mantle boundary (CMB), we show that the spatial distribution affects weakly the strength of the torque, with the approximation by a uniform field leading to an overestimation of the torque magnitude by ~15–20 per cent. However, for field strengths typical of the inner core boundary (ICB), the morphology of the field has a more significant influence on the EM torque and the approximation by a uniform field overestimates the torque by ~30–40 per cent. Assuming that EM coupling is responsible for the observed dissipation, we infer constraints on the strength of the radial magnetic field at both the CMB and ICB. We show how the unknown morphology of the magnetic field induces uncertainties on the estimated field strength at the ICB, which can take values anywhere in the range of ~9–16 mT. These very large values suggest that EM coupling at the ICB cannot be the only mechanism responsible for the observed dissipation.

Description: Variations in the degree-2 Stokes coefficients C 20 , C 21 and S 21 can be used to understand long- and short-term climate forcing. Here we derive changes in these coefficients for the period 2003 January–2012 April using Earth rotation data. Earth rotation data contain contributions from motion terms (the effects of winds and currents) and contributions from the effects of mass redistribution. We remove the effects of tides, atmospheric winds and oceanic currents from our data. We compare two different models of atmospheric and oceanic angular momentum for removing the effects of winds and currents: (1) using products from the National Centers for Environmental Prediction and (2) using data from the European Centre for Medium-range Weather Forecasts (ECMWF). We assess the quality of these motion models by comparing the two resulting sets of degree-2 Stokes coefficients to independent degree-2 estimates from satellite laser ranging (SLR), GRACE and a geophysical loading model. We find a good agreement between the coefficients from Earth rotation and the coefficients from other sources. In general, the agreement is better for the coefficients we obtain by removing winds and currents effects using the ECMWF model. In this case, we find higher correlations with the independent models and smaller scatters in differences. This fact holds in particular for C 20 and C 21 , whereas we cannot observe a significant difference for S 21 . At the annual and semiannual periods, our Earth rotation derived coefficients agree well with the estimates from the other sources, particularly for C 21 and S 21 . The slight discrepancies we obtain for C 20 can probably be explained by errors in the atmospheric models and are most likely the result of an over-/underestimation of the annual and semiannual contributions of atmospheric winds to the length-of-day excitation.

Description: Subduction zones are complex 3-D features in which one tectonic plate sinks underneath another into the deep mantle. During subduction the overriding plate (OP) remains in physical contact with the subducting plate and stresses generated at the subduction zone interface and by mantle flow force the OP to deform. We present results of 3-D dynamic laboratory models of subduction that include an OP. We introduce new interplate materials comprising homogeneous mixtures of petrolatum and paraffin oil to achieve progressive subduction. The rheology of these mixtures is characterized by measurements using a strain rate controlled rheometer. The results show that the strength of the mixture increases with petrolatum content, which can be used as a proxy for the degree of mechanical coupling along the subduction interface. Results of subduction experiments are presented with different degrees of mechanical coupling and the influence this has on the dynamics and kinematics of subduction. The modelling results show that variations in the degree of mechanical coupling between the plates have a major impact on subduction velocities, slab geometry and the rate of OP deformation. In all experiments the OP is displaced following trench migration and experiences overall extension localized in the plate interior. This suggests that OP deformation is driven primarily by the toroidal component of subduction-related mantle return flow. The subduction rate is always very slow in experiments with medium mechanical coupling, and subduction stops prematurely in experiments with very high coupling. This implies that the shear forces along the plate interface in natural subduction zone systems must be relatively low and do not vary significantly. Otherwise a higher variability in natural subduction velocities should be observed for mature, non-perturbed subduction zones. The required low shear force is likely controlled by the rheology of highly hydrated sedimentary and basaltic rocks.

Description: The Frank-Kamenetskii (FK) approximation is a common method to represent the Arrhenius-type viscosity of planetary mantles because it reduces the viscosity contrast in the lithosphere to save computational resources and prevent numerical errors. In some cases, this approximation does not lead to satisfying results; for example, it can lead to a mobile-lid regime, whereas use of the Arrhenius law shows a thin stagnant lid. We therefore derive a new, more accurate approximation called ‘damped FK approximation’ for a temperature- and pressure-dependent viscosity. This damped FK approximation is a mixture between the standard first-order FK approximation and an approximation of second-order accuracy controlled by a damping parameter. Furthermore, the FK parameters are determined self-consistently at every time step. This study shows that the damped FK approximation represents the mantle flow of an Arrhenius-type viscosity for a much larger parameter space than for the standard first-order approximation. It can also be used to simulate terrestrial planets, such as super-Earths, with high pressure dependence of the viscosity, if the surface temperature does not exceed a specific threshold value and if a high enough damping parameter is used. We also test the FK approximation for plate tectonics simulations. The second-order FK approximation best represents the Arrhenius flow in the investigated parameter range. In particular, the dependence of the critical yield stress, at which the transition from the plate tectonics regime to the stagnant-lid regime can be observed, on the Rayleigh number can differ from the Arrhenius case (and the second-order FK approximation) when using a first-order FK approximation or rheology parameters in the Arrhenius law that differ from laboratory values to yield small viscosity contrasts. This finding may have strong implications for the prediction of plate tectonics on terrestrial planets.

Description: We propose new scaling laws for the properties of planetary dynamos. In particular, the Rossby number, the magnetic Reynolds number, the ratio of magnetic to kinetic energy, the Ohmic dissipation timescale and the characteristic aspect ratio of the columnar convection cells are all predicted to be power-law functions of two observable quantities: the magnetic dipole moment and the planetary rotation rate. The resulting scaling laws constitute a somewhat modified version of the scalings proposed by Christensen and Aubert. The main difference is that, in view of the small value of the Rossby number in planetary cores, we insist that the non-linear inertial term, ${\boldsymbol u} \cdot \nabla {\boldsymbol u}$ , is negligible. This changes the exponents in the power-laws which relate the various properties of the fluid dynamo to the planetary dipole moment and rotation rate. Our scaling laws are consistent with the available numerical evidence.

Description: Earlier studies at the large Vredefort impact structure since 1960 have shown that values of natural remanent magnetizations (NRMs) and, hence, Koenigsberger's Q values (ratio of remanent over induced magnetization), for different rock lithologies are elevated compared to the values for similar rock types around the world. Three origins for the high Q values have been suggested, namely shock by meteorite impact, enhanced plasma field and lightning strikes. We have studied whether laboratory lightning experiments can produce enhanced NRMs in the Vredefort target rocks. For comparison, we also included rocks from the Johannesburg dome, which is not a meteorite impact site. The results revealed increased NRMs, susceptibility and Q values of the rocks from both Vredefort and Johannesburg domes. Rock magnetic measurements and scanning electron microscope analyses of lightning pulsed and unpulsed samples showed that the lightning included changes in magnetic properties of the rocks. We suggest that in some samples lightning have changed magnetic mineralogy by oxidizing magnetite to maghemite. Indication of this oxidation came from the low-temperature variation of the remanent magnetization where we observed several hallmarks of maghemitization in samples treated by lightning strikes. Further indications of mineralogical changes include increased Curie points above the magnetite's Curie point (580 °C) and appearance of pronounced lower temperature (200–400 °C) phases in susceptibility versus temperature curves. These changes are interpreted to indicate partially oxidized magnetite (maghemitization) coupled with grain fragmentations and by this way grain size reduction. High-temperature hysteresis and REM (= NRM/saturation isothermal remanent magnetization) studies support these conclusions. Our results were analogous with the ones for lodestones and protolodestones where partially oxidized magnetite is thought to make magnetization more intense.

Description: Regeneration of the Earth's magnetic field by convection in the liquid core produces a broad spectrum of time variation. Relative palaeointensity measurements in marine sediments provide a detailed record over the past 2 Myr, but an explicit reconstruction of the underlying dynamics is not feasible. A more practical alternative is to construct a stochastic model from estimates of the virtual axial dipole moment. The deterministic part of the model (drift term) describes time-averaged behaviour, whereas the random part (diffusion term) characterizes complex interactions over convective timescales. We recover estimates of the drift and diffusion terms from the SINT2000 model of Valet et al. and the PADM2M model of Ziegler et al. The results are used in numerical solutions of the Fokker–Planck equation to predict statistical properties of the palaeomagnetic field, including the average rates of magnetic reversals and excursions. A physical interpretation of the stochastic model suggests that the timescale for adjustments in the axial dipole moment is set by the dipole decay time d . We obtain d = 29 kyr from the stochastic models, which falls within the expected range for the Earth's core. We also predict the amplitude of convective fluctuations in the core, and establish a physical connection to the rates of magnetic reversals and excursions. Chrons lasting longer than 10 Myr are unlikely under present-day conditions. However, long chrons become more likely if the diffusion term is reduced by a factor of 2. Such a change is accomplished by reducing the velocity fluctuations in the core by a factor of 2, which could be attributed to a shift in the spatial pattern of heat flux from the core or a reduction in the total core heat flow.

Description: Since King presented the ‘plates and spheres’ model in an attempt to investigate the origin of the inclination error in sediments, no one to date has conducted specific experiments designed to separate the individual contribution of platy and spherical particles to depositional remanent magnetizations (DRMs). It is commonly accepted that it is the flattening of plates, rather than the rolling of spheres that is the main source of inclination error in sediments. Recently, however, Bilardello et al. have shown that spheres alone may lead to significant amounts of shallowing. A comparison of experiments run in parallel using synthetic platy and spherical particles is presented. Experiments of the duration of 24 hr were run in 100 μT field intensity ( μ 0 H ) and varying field inclinations ( I F ) from vertical to horizontal. A systematic dependence of the magnetization on field inclination is apparent. Results indicate that magnetic moment measurements are more repeatable for spherical particles than for plates, yielding smaller uncertainties. Inclination measurements, however, are more repeatable for platy particles, with a more linear relationship of inclination error to applied field inclination. Moreover, plates yield smaller inclination error than spheres. A clear field inclination dependency of the inclination error also exists, with the error decreasing through field inclinations of 30°, 60° and 90°. A continuous acquisition experiment involving plates was also run up to 10 d of deposition in μ 0 H = 100 μT and I F = 60°. The acquisition curves for moment, inclination and thickness of depositing sediment are compared to the mean curves measured for spheres by Bilardello et al. under the same field conditions. No unequivocal evidence of compaction of the platy particles is observed, while the inclination error is acquired virtually instantaneously for all particles. These preliminary results contradict the widespread understanding that inclination shallowing is more prominent for platy particles (e.g. hematite) than it is for more spherical particles (e.g. magnetite). It is true that larger amounts of shallowing have been commonly observed in natural hematite-bearing rocks, but the overall ranges of shallowing are also larger. The particles used in these experiments may not be a reliable proxy for natural crystals and one must exercise caution when extrapolating to the natural scenarios; however, the results provide insight into the behaviour of differently shaped particles.

Description: Monoclinic 4C pyrrhotite (Fe 7 S 8 ) is ferrimagnetic due to an ordered defect structure with alternating vacancy and vacancy-free sublattices. Its low-temperature magnetic transition near 35 K is characterized by the distinct increase in coercivity and remanent magnetization. The increase of these parameters has been attributed to changes in the domain wall structure. We present static and dynamic magnetization data of a powder sample to study the domain-wall dynamics across the low-temperature transition. The amplitude-dependent ac susceptibility and the ferromagnetic resonance spectroscopy indicate that the hardening of the domain-wall pinning at the transition occurs simultaneously with the decrease in initial saturation remanent magnetization. These two effects are explained by the enhanced inhomogeneity of the bulk material caused by the persistency of the ordered vacancies and by newly formed defects due to localized distortion of Fe(II) sites in the vacancy-free sublattice. The generated localized defects are the link between the domain wall dynamics and the low-temperature transition in 4C pyrrhotite.

Description: Thermal anomalies associated with ore-mineralization (Pb–Cu–Zn and Fe) were studied using thermal infrared data collected over Mamandur polymetal prospect, India, with the aid of satellite, field, and laboratory measurements. Day and night ASTER data were analysed in conjunction with field measurements to estimate thermal inertia of the ore body, altered zones and country rocks. Representative samples collected from field were also analysed for thermal conductivity, diffusivity, and inertia using a self-fabricated setup. Spatial changes in thermal inertia were mapped by look up table (LUT) and advanced thermal inertia mapping (ATIM) approaches. Mineralized zones show very high thermal contrast ( T ) both in field (15–25°C) and satellite data (14.9–16.9 o C). They also exhibit the lowest thermal inertia in field-(2118–5474 J m –2 K –1 s –1/2 ) and satellite-based (3783–4037 J m –2 K –1 s –1/2 ) measurements. In non-mineralized areas, acidic rocks (granite, migmatite and granite gneiss) have lower inertia than basic rocks (basic granulite, dolerite and charnockite). Results estimated by LUT and ATIM approaches correlate very well at satellite ( R 2  = 0.97) and field ( R 2  = 0.89) scales. Similarly, field- and satellite-based results also have good correlation ( R 2  = 0.69–0.72). This study illustrates the potential of thermal inertia mapping in delineating ore bodies and deciphering the lithological changes even under veneer of soil.