Chain folding and A:T pairing in human telomeric DNA: a model-building and molecular dynamics study

The various types of chain folding and possible intraloop as well as interloop base pairing in human telomeric DNA containing d(TTAG(3)) repeats have been investigated by model-building, molecular mechanics, and molecular dynamics techniques. Model-building and molecular mechanics studies indicate that it is possible to build a variety of energetically favorable folded-back structures with the two TTA loops on same side and the 5' end thymines in the two loops forming TATA tetrads involving a number of different intraloop as well as interloop A:T pairing schemes. In these folded-back structures, although both intraloop and interloop Watson-Crick pairing is feasible, no structure is possible with interloop Hoogsteen pairing. MD studies of representative structures indicate that the guanine-tetraplex stem is very rigid and, while the loop regions are relatively much more flexible, most of the hydrogen bonds remain intact throughout the 350-ps in vacuo simulation. The various possible TTA loop structures, although they are energetically similar, have characteristic inter proton distances, which could give rise to unique cross-peaks in two-dimensional nuclear Overhauser effect spectroscopy (NOESY) experiments. These folded-back structures with A:T pairings in the loop region help in rationalizing the data from chemical probing and other biochemical studies on human telomeric DNA.

Precoding with X-codes to increase capacity with discrete input alphabets

We consider Gaussian multiple-input multiple-output (MIMO) channels with discrete input alphabets. We propose a non-diagonal precoder based on X-Codes in to increase the mutual information. The MIMO channel is transformed into a set of parallel subchannels using Singular Value Decomposition (SVD) and X-codes are then used to pair the subchannels. X-Codes are fully characterized by the pairings and the 2 × 2 real rotation matrices for each pair (parameterized with a single angle). This precoding structure enables to express the total mutual information as a sum of the mutual information of all the pairs. The problem of finding the optimal precoder with the above structure, which maximizes the total mutual information, is equivalent to i) optimizing the rotation angle and the power allocation within each pair and ii) finding the optimal pairing and power allocation among the pairs. It is shown that the mutual information achieved with the proposed pairing scheme is very close to that achieved with the optimal precoder by Cruz et al., and significantly better than mercury/waterfilling strategy by Lozano et al.. Our approach greatly simplifies both the precoder optimization and the detection complexity, making it suitable for practical applications.

Precoding by Pairing Subchannels to Increase MIMO Capacity With Discrete Input Alphabets

We consider Gaussian multiple-input multiple-output (MIMO) channels with discrete input alphabets. We propose a non-diagonal precoder based on the X-Codes in 1] to increase the mutual information. The MIMO channel is transformed into a set of parallel subchannels using singular value decomposition (SVD) and X-Codes are then used to pair the subchannels. X-Codes are fully characterized by the pairings and a 2 x 2 real rotation matrix for each pair (parameterized with a single angle). This precoding structure enables us to express the total mutual information as a sum of the mutual information of all the pairs. The problem of finding the optimal precoder with the above structure, which maximizes the total mutual information, is solved by: i) optimizing the rotation angle and the power allocation within each pair and ii) finding the optimal pairing and power allocation among the pairs. It is shown that the mutual information achieved with the proposed pairing scheme is very close to that achieved with the optimal precoder by Cruz et al., and is significantly better than Mercury/waterfilling strategy by Lozano et al. Our approach greatly simplifies both the precoder optimization and the detection complexity, making it suitable for practical applications.

PocketAlign A Novel Algorithm for Aligning Binding Sites in Protein Structures

A fundamental task in bioinformatics involves a transfer of knowledge from one protein molecule onto another by way of recognizing similarities. Such similarities are obtained at different levels, that of sequence, whole fold, or important substructures. Comparison of binding sites is important to understand functional similarities among the proteins and also to understand drug cross-reactivities. Current methods in literature have their own merits and demerits, warranting exploration of newer concepts and algorithms, especially for large-scale comparisons and for obtaining accurate residue-wise mappings. Here, we report the development of a new algorithm, PocketAlign, for obtaining structural superpositions of binding sites. The software is available as a web-service at http://proline.physicslisc.emetin/pocketalign/. The algorithm encodes shape descriptors in the form of geometric perspectives, supplemented by chemical group classification. The shape descriptor considers several perspectives with each residue as the focus and captures relative distribution of residues around it in a given site. Residue-wise pairings are computed by comparing the set of perspectives of the first site with that of the second, followed by a greedy approach that incrementally combines residue pairings into a mapping. The mappings in different frames are then evaluated by different metrics encoding the extent of alignment of individual geometric perspectives. Different initial seed alignments are computed, each subsequently extended by detecting consequential atomic alignments in a three-dimensional grid, and the best 500 stored in a database. Alignments are then ranked, and the top scoring alignments reported, which are then streamed into Pymol for visualization and analyses. The method is validated for accuracy and sensitivity and benchmarked against existing methods. An advantage of PocketAlign, as compared to some of the existing tools available for binding site comparison in literature, is that it explores different schemes for identifying an alignment thus has a better potential to capture similarities in ligand recognition abilities. PocketAlign, by finding a detailed alignment of a pair of sites, provides insights as to why two sites are similar and which set of residues and atoms contribute to the similarity.

PocketMatch (version 2.0): A parallel algorithm for the detection of structural similarities between protein ligand binding-sites

Knowledge of protein-ligand interactions is essential to understand several biological processes and important for applications ranging from understanding protein function to drug discovery and protein engineering. Here, we describe an algorithm for the comparison of three-dimensional ligand-binding sites in protein structures. A previously described algorithm, PocketMatch (version 1.0) is optimised, expanded, and MPI-enabled for parallel execution. PocketMatch (version 2.0) rapidly quantifies binding-site similarity based on structural descriptors such as residue nature and interatomic distances. Atomic-scale alignments may also be obtained from amino acid residue pairings generated. It allows an end-user to compute database-wide, all-to-all comparisons in a matter of hours. The use of our algorithm on a sample dataset, performance-analysis, and annotated source code is also included.

Fault Attacks on Pairing-Based Protocols Revisited

Several papers have studied fault attacks on computing a pairing value e(P, Q), where P is a public point and Q is a secret point. In this paper, we observe that these attacks are in fact effective only on a small number of pairing-based protocols, and that too only when the protocols are implemented with specific symmetric pairings. We demonstrate the effectiveness of the fault attacks on a public-key encryption scheme, an identity-based encryption scheme, and an oblivious transfer protocol when implemented with a symmetric pairing derived from a supersingular elliptic curve with embedding degree 2.

Effects of unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm on synaptic plasticity in the hippocampal CA1 area in vivo

Repeated vivid recalls or flashbacks of traumatic memories and memory deficits are the cardinal features of post-traumatic stress disorder (PTSD). The underlying mechanisms are not fully understood yet. Here, we examined the effects of very strong fear conditioning (20 pairings of a light with a 1.5-mA, 0.5-s foot shock) and subsequent reexposure to the conditioning context (chamber A), a similar context (chamber B), and/or to the fear conditioned stimulus (CS) (a light) on synaptic plasticity in the hippocampal CA1 area in anesthetized Sprague-Dawley rats. The conditioning procedure resulted in very strong conditioned fear, as reflected by high levels of persistent freezing, to both the contexts and to the CS, 24 h after fear conditioning. The induction of long-term potentiation ON was blocked immediately after fear conditioning. It was still markedly impaired 24 h after fear conditioning; reexposure to the conditioning chamber A (CA) or to a similar chamber 13 (CB) did not affect the impairment. However, presentation of the CS in the CA exacerbated the impairment of LTP, whereas the CS presentation in a CB ameliorated the impairment so that LTP induction did not differ from that of control groups. The induction of long-term depression (LTD) was facilitated immediately, but not 24 h, after fear conditioning. Only reexposure to the CS in the CA, but not reexposure to either chamber A or B alone, or the CS in chamber B, 24 h after conditioning, reinstated the facilitation of LTD induction. These data demonstrate that unconditioned and conditioned aversive stimuli in an intense fear conditioning paradigm can have profound effects on hippocampal synaptic plasticity, which may aid to understand the mechanisms underlying impairments of hippocampus-dependent memory by stress or in PTSD. (c) 2005 Wiley-Liss, Inc.

identity based threshold proxy signature

IEEE Computer Society

基于身份的移动网动态群组密钥协商方案

群组密钥协商是群组通信中非常重要的基本工具，如何得到一个安全有效的密钥协商协议是当前密码学研究中的一个重要问题。基于双线性对和随机预言模型，针对移动网络提出了一个动态群组密钥协商方案。此方案就计算复杂度和通信复杂度而言都是高效的，而且满足密钥协商所需耍的安全要求。

What children learn from adults’ utterances: an ephemeral lexical boost and persistent syntactic priming in adult–child dialogue

We show that children’s syntactic production is immediately affected by individual experiences of structures and verb–structure pairings within a dialogue, but that these effects have different timecourses. In a picture-matching game, three- to four-year-olds were more likely to describe a transitive action using a passive immediately after hearing the experimenter produce a passive than an active (abstract priming), and this tendency was stronger when the verb was repeated (lexical boost). The lexical boost disappeared after two intervening utterances, but the abstract priming effect persisted. This pattern did not differ significantly from control adults. Children also showed a cumulative priming effect. Our results suggest that whereas the same mechanism may underlie children’s immediate syntactic priming and long-term syntactic learning, different mechanisms underlie the lexical boost versus long-term learning of verb–structure links. They also suggest broad continuity of syntactic processing in production between this age group and adults.

Microbial spatial variability: An example from the Celtic Sea

In July 2004, dominant populations of microbial ultraplankton (<5 μm), in the surface of the Celtic Sea (between UK and Eire), were repeatedly mapped using flow cytometry, at 1.5 km resolution over a region of diameter 100 km. The numerically dominant representatives of all basic functional types were enumerated including one group of phototrophic bacteria (Syn), two groups of phytoplankton (PP, NP), three groups of heterotrophic bacterioplankton (HB) and the regionally dominant group of heterotrophic protists (HP). The distributions of all organisms showed strong spatial variability with little relation to variability in physical fields such as salinity and temperature. Furthermore, there was little agreement between distributions of different organisms. The only linear correlation consistently explaining more than 50% of the variance between any pairing of the organism groups enumerated is between two different groups of HB. Specifically, no linear, or non-linear, relationship is found between any pairings of SYB, PP or HB groups with their protist predators HP. Looking for multiple dependencies, factor analysis reveals three groupings: Syn, PP and low nucleic acid content HB (LNA); high nucleic acid content HB (HNA); HP and NP. Even the manner in which the spatial variability of Syn, PP and HB abundance varies as a function of lengthscale (represented by a semivariogram) differs significantly from that for HP. In summary, although all microbial planktonic groups enumerated are present and numerically dominant throughout the region studied, at face value the relationships between them seem weak. Nevertheless, the behaviour of a simple, illustrative ecological model, with strongly interacting phototrophs and heterotrophs, with stochastic forcing, is shown to be consistent with the observed poor correlations and differences in how spatial variability varies with lengthscale. Thus, our study suggests that a comparison of microbial abundances alone may not discern strong underlying trophic interactions. Specific knowledge of these processes, in particular grazing, will be required to explain the causes of the observed microbial spatial variability and its resulting consequences for the functioning of the ecosystem.

Shark personalities? Repeatability of social network traits in a widely distributed predatory fish. Behavioral Ecology and Sociobiology, 68, 1995-2003.

Interest in animal personalities has generated a burgeoning literature on repeatability in individual traits such as boldness or exploration through time or across different contexts. Yet, repeatability can be influenced by the interactive social strategies of individuals, for example, consistent inter-individual variation in aggression is well documented. Previous work has largely focused on the social aspects of repeatability in animal behaviour by testing individuals in dyadic pairings. Under natural conditions, individuals interact in a heterogeneous polyadic network. However, the extent to which there is repeatability of social traits at this higher order network level remains unknown. Here, we provide the first empirical evidence of consistent and repeatable animal social networks. Using a model species of shark, a taxonomic group in which repeatability in behaviour has yet to be described, we repeatedly quantified the social networks of ten independent shark groups across different habitats, testing repeatability in individual network position under changing environments. To understand better the mechanisms behind repeatable social behaviour, we also explored the coupling between individual preferences for specific group sizes and social network position. We quantify repeatability in sharks by demonstrating that despite changes in aggregation measured at the group level, the social network position of individuals is consistent across treatments. Group size preferences were found to influence the social network position of individuals in small groups but less so for larger groups suggesting network structure, and thus, repeatability was driven by social preference over aggregation tendency.

Phonological oddballs in the focus of attention elicit a normal P3b in dyslexic adults

Difficulties in phonological processing have been proposed to be the core symptom of developmental dyslexia. Phoneme awareness tasks have been shown to both index and predict individual reading ability. In a previous experiment, we observed that dyslexic adults fail to display a P3a modulation for phonological deviants within an alliterated word stream when concentrating primarily on a lexical decision task [Fosker and Thierry, 2004, Neurosci. Lett. 357, 171-174]. Here we recorded the P3b oddball response elicited by initial phonemes within streams of alliterated words and pseudo-words when participants focussed directly on detecting the oddball phonemes. Despite significant verbal screening test differences between dyslexic adults and controls, the error rates, reactions times, and main components (P2, N2, P3a, and P3b) were indistinguishable across groups. The only difference between groups was found in the NI range, where dyslexic participants failed to show the modulations induced by phonological pairings (/b/-/p/ versus /r/ /g/) in controls. In light of previous P3a differences, these results suggest an important role for attention allocation in the manifestation of phonological deficits in developmental dyslexia. (c) 2005 Elsevier B.V. All rights reserved.

A structural analysis of G-quadruplex/ligand interactions

This focused review article discusses in detail, all available high-resolution small molecule ligand/G-quadruplex structural data derived from crystallographic and NMR based techniques, in an attempt to understand key factors in ligand binding and to highlight the biological importance of these complexes. In contrast to duplex DNA, G-quadruplexes are four-stranded nucleic acid structures folded from guanine rich repeat sequences stabilized by the stacking of guanine G-quartets and extensive Watson-Crick/Hoogsteen hydrogen bonding. Thermally stable, these topologies can play a role in telomere regulation and gene expression. The core structures of G-quadruplexes form stable scaffolds while the loops have been shown, by the addition of small molecule ligands, to be sufficiently adaptable to generate new and extended binding platforms for ligands to associate, either by extending G-quartet surfaces or by forming additional planar dinucleotide pairings. Many of these structurally characterised loop rearrangements were totally unexpected opening up new opportunities for the design of selective ligands. However these rearrangements do significantly complicate attempts to rationally design ligands against well defined but unbound topologies, as seen for the series of napthalene diimides complexes. Drawing together previous findings and with the introduction of two new crystallographic quadruplex/ligand structures we aim to expand the understanding of possible structural adaptations available to quadruplexes in the presence of ligands, thereby aiding in the design of new selective entities. (C) 2011 Elsevier Masson SAS. All rights reserved.

Marker-to-marker linkage disequilibrium on chromosomes 5q, 6p, and 8p in Irish high-density schizophrenia pedigrees

Linkage disequilibrium (LD) is a potentially powerful tool for the localization of disease genes for complex disorders. Most prior studies of the relationship between genetic distance and LD have examined only very short distances, focusing on the role of LD in fine-mapping and positional cloning. We examine here the relationship between marker-to-marker (M-M) LD and somewhat greater genetic distances. We analyzed 622 M-M pairings on chromosomes 6p, 8p, and 5q in 265 native Irish pedigrees ascertained for a high density of schizophrenia. LD, significant at the 5% level, was found for 96% of all M-M pairings within 0.5 cM, for 67% within 0.5-1 cM, for 35% within 1-2 cM, for 15% within 2-4 cM, for 8% within 5-10 cM, and for 7% above 10 cM. Thus, in Irish families selected for a high density of schizophrenia, M-M LD may be very common within 0.5 cM and frequent up to distances of 2 cM.