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Biomedical subjects

Andrew Harrison

Publications and source records attributed to Andrew Harrison.

At least 19 recordsLinked to original sources

HiCPotts: An R/Bioconductor package to identify significant interactions in chromosome conformation capture data and model sources of bias.

MOTIVATION: Chromosome Conformation Capture methods, including Hi-C, micro-C or Capture-C, are used to map chromatin interactions genome-wide. Most of the existing computational methods do not account for sources of bias (such as DNA accessibility, GC content or TE content) in the data. RESULTS: We previously developed ZipHiC, a Bayesian method based on the hidden Markov random field (HMRF) model and the Approximate Bayesian Computation (ABC), that uses zero-inflated Poisson distribution to model the noise, signal and false signal of the data and showed that this approach was able to detect bias from DNA accessibility, GC content and TE content in both Hi-C and micro-C data. Here, we present HiCPotts, another Bayesian method based on the HMRF model and the ABC that uses a zero-inflated Negative Binomial distribution instead to model the noise and signal of the data. We systematically show that HiCPotts reduces false positives and increases recovery of true interactions compared to ZipHiC, but also compared to other methods such as FastHiC, Juicer and HiCExplorer. Most importantly, we provide an R/Bioconductor package that allows modelling the noise, signal and false signal using various distributions such as the zero-inflated Negative Binomial (ZINB) and the zero-inflated Poisson distribution (ZIP). AVAILABILITY AND IMPLEMENTATION: https://bioconductor.org/packages/HiCPotts/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Approximate Bayesian Computation↗

Synthesis of ordered mesoporous Fe3O4 and gamma-Fe2O3 with crystalline walls using post-template reduction/oxidation.

Ordered mesoporous Fe(3)O(4) with crystalline walls (inverse spinel structure) has been synthesized for the first time, representing to the best of our knowledge, the first synthesis of a reduced mesoporous iron oxide. Synthesis was achieved by reducing ordered mesoporous alpha-Fe(2)O(3) (corundum structure) to Fe(3)O(4) spinel then to gamma-Fe(2)O(3) by oxidation, while preserving the ordered mesostructure and crystalline walls throughout. Such solid/solid transformations demonstrate the stability of the mesostructure to structural phase transitions from the hexagonal close packed oxide subarray of alpha-Fe(2)O(3) (corundum structure) to the cubic close packed subarray of Fe(3)O(4) spinel and gamma-Fe(2)O(3). Preliminary magnetic measurements reveal that the spins in both Fe(3)O(4) and gamma-Fe(2)O(3) are frozen at 295 K, despite the wall thickness (7 nm) being less than the lower limit for such freezing in corresponding nanoparticles (>8 nm).

Journal Article↗

Structural and magnetic properties of [BDTA]2[MCl4] [M = Cu (1), Co (2), and Mn (3)], revealing an S = 1/2 square-lattice antiferromagnet with weak magnetic exchange.

We report the synthesis and structural and magnetic characterization of model square or rectangular antiferromagnets [BDTA]2[MCl4] [BDTA = benzo-1,3,2-dithiazolyl; M = Cu (1), Co (2), and Mn (3)]. All of these compounds display a molecular structure of sandwich layers of [MCl4]2- between two sheets of [BDTA]+ molecules. Consideration of likely superexchange pathways suggests that 1 presents a model square lattice of S = 1/2 moments, while 2 and 3 present model rectangular lattices with S = 3/2 and 5/2, respectively. Magnetic susceptibility measurements indicate that all of these materials have modest antiferromagnetic exchange fields, with near-neighbor exchange J/k(B) running from 0.018(1) through 0.35(3) to 2.10(2) K as M runs from Mn to Co to Cu. No signature of any three-dimensional magnetic ordering could be observed down to 1.8 K. 1 is of particular interest because it belongs to a similar class of magnets as the high-Tc superconducting cuprates but has a much smaller exchange field; it has been proposed that the application of a magnetic field to this type of magnet can induce novel quantum states in this class of magnet, but the observation of such states is only experimentally feasible for small exchange. More detailed characterization of 1 by heat capacity measurements showed a broad cusp centered at 1.3 K in the absence of an applied magnetic field but failed to observe any sign of long-range order down to 0.33 K; this suggests that interplane magnetic exchange is weak.

Journal Article↗

Ordered mesoporous Fe2O3 with crystalline walls.

Alpha-Fe(2)O(3) has been synthesized with an ordered mesoporous structure and crystalline walls that exhibit a near-single crystal-like order. The unique magnetic behavior of the material, distinct from bulk nanoparticles of alpha-Fe(2)O(3) or mesoporous Fe(2)O(3) with disordered walls, has been established. Magnetic susceptibility, Mössbauer, and neutron diffraction data show that the material possesses the same long-range magnetic order as bulk alpha-Fe(2)O(3), despite the wall thickness being less than the 8 nm limit below which magnetic ordering breaks down in nanoparticulate alpha-Fe(2)O(3), yet the Morin transition of bulk alpha-Fe(2)O(3) is absent. It is also shown by TEM, PXRD, and EXAFS that alpha-Fe(2)O(3) with the same ordered mesoporous structure but disordered walls contains small crystalline domains. Mössbauer and magnetic susceptibility data demonstrate that this material exhibits no long-range magnetic order but superparamagnetic behavior.

Journal Article↗

Functional data analysis of knee joint kinematics in the vertical jump.

Understanding of the motor development process is usually based on descriptive studies using either cross-sectional or longitudinal designs. These data typically consist of sets of measurements on groups of individuals gathered during the performance of a single task. A natural approach is to represent the set of measurements for an individual as a single entity, a function. In practice, however, this approach is seldom applied. Typically, the analysis proceeds by reducing what are intrinsically functional responses to a single summary measurement and then using this to draw conclusions. As a result, many potentially informative data are ignored. Functional data analysis (FDA) is an emerging field in statistics that focuses on treating an entire sequence of measurements for an experimental unit as a single function. Therefore, functional data analysis appears to be inherently suitable for analysing kinematic data. In this paper, the key concepts and procedures of functional data analysis are introduced and illustrated using data obtained from a cross-sectional study on the development of the vertical jump.

Biomechanical Phenomena↗

Comparisons of annotation predictions for affymetrix GeneChips.

We have compared Affymetrix and Bioconductor annotations for the MOE430A (mouse) GeneChip array. The mappings of probe sets to LocusLink identifiers (LocusIDs) were found to be dynamic, with many changes between successive releases of annotation for both Affymetrix and Bioconductor. There are 49 probe sets that are assigned to one LocusID by Affymetrix and to a different LocusID by Bioconductor from mid-2004 onwards. For virtually all of these examples, the Affymetrix annotation was found to be the one that is in agreement with the current gene prediction. Reference sequence (RefSeq) identifiers are considered to be the gold standard of annotations. However, we could not use these identifiers to discriminate between the accuracy of Bioconductor and Affymetrix because not all of the probes map to the RefSeq transcript to which the probe set is assigned. Moreover, in some cases, probes align to regions downstream of the 3' end of a RefSeq transcript. Adjacent genes were found to be a major cause of discrepancies between the Bioconductor and Affymetrix assignments. Case studies of several probe sets indicated that incorrect assignments are caused by the UniGene cluster assignments of expressed sequence tags representing the probe sets, and by errors in GenBank sequences. Our results indicate that there are a number of errors remaining in the annotation sources used by the microarray community.

DNA↗

Mobile peer-to-grid architecture for paramedical emergency operations.

In this paper we describe a distributed architecture that could be used to link emergency medical centres, hospitals, telephone operators, and ambulances into a hybrid Peer-to-Peer (P2P) and Grid system for the sharing of information and transport of data. Distributed computing techniques can be used to connect static and mobile systems, bringing the different tools, expertise and databases together to aggregate patient data "on-the-fly" and then integrate it into a situation and context-specific patient-centred virtual environment. The scenario presented in this paper encapsulates connecting mobile tools and medical devices from ambulances, enabling data transfer to medical centres, and aggregating patient data from numerous sources. The proposed P2G (Peer-to-Grid) framework consolidates Peer-to-Peer and Grid computing research by addressing the mobility of transiently connected devices while supporting interactive configurability of components for dynamic data-driven distributed paramedical scenarios.

Allied Health Personnel↗

TNF inhibitors for inflammatory arthritis in New Zealand.

For the vast majority of the estimated 100,000 New Zealanders who suffer from rheumatoid arthritis (RA), relatively inexpensive disease-modifying antirheumatic drugs (DMARD) regimens are sufficient to control inflammatory disease and maintain long-term function. Some DMARDs have been shown to slow, but not arrest, the progression of erosions. All but a few of those who suffer from ankylosing spondylitis (AS) can manage full social participation with non-steroidal anti-inflammatory drugs (NSAIDs) and an exercise regimen. For the small subset of arthritis sufferers who have disabling pain and progressive damage from uncontrolled inflammatory disease, the advent of the biological era offered great promise. In most of the developed world, this promise is being delivered to patients with an expanding range of diseases including RA, AS, and psoriatic arthritis, but central government (PHARMAC) funding for TNF inhibitors in New Zealand has until recently been limited to etanercept for approximately 40 patients with juvenile inflammatory arthritis.

Adalimumab↗

The CATH Domain Structure Database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis.

The CATH database of protein domain structures (http://www.biochem.ucl.ac.uk/bsm/cath/) currently contains 43,229 domains classified into 1467 superfamilies and 5107 sequence families. Each structural family is expanded with sequence relatives from GenBank and completed genomes, using a variety of efficient sequence search protocols and reliable thresholds. This extended CATH protein family database contains 616,470 domain sequences classified into 23,876 sequence families. This results in the significant expansion of the CATH HMM model library to include models built from the CATH sequence relatives, giving a 10% increase in coverage for detecting remote homologues. An improved Dictionary of Homologous superfamilies (DHS) (http://www.biochem.ucl.ac.uk/bsm/dhs/) containing specific sequence, structural and functional information for each superfamily in CATH considerably assists manual validation of homologues. Information on sequence relatives in CATH superfamilies, GenBank and completed genomes is presented in the CATH associated DHS and Gene3D resources. Domain partnership information can be obtained from Gene3D (http://www.biochem.ucl.ac.uk/bsm/cath/Gene3D/). A new CATH server has been implemented (http://www.biochem.ucl.ac.uk/cgi-bin/cath/CathServer.pl) providing automatic classification of newly determined sequences and structures using a suite of rapid sequence and structure comparison methods. The statistical significance of matches is assessed and links are provided to the putative superfamily or fold group to which the query sequence or structure is assigned.

Databases, Nucleic Acid↗

Accelerometry-based feedback--can it improve movement consistency and performance in rowing?

The training and competition regimen of elite athletes demands rapid feedback about their performance. The aim of this study was to determine if real-time visual ipsative (comparison with oneself) feedback of instantaneous kinematic consistency improves overall kinematic consistency in rowing. Accelerometry-based data, representing the upper and lower body kinematics, were determined for 13 experienced rowers. Kinematic consistency data -- represented by percentage time outside the acceptable performance bandwidth, performance consistency -- represented by power-stroke dispersion, and several performance indicators were acquired for all the rowers for three 2000 m time trials on a RowPerfect ergometer with three different visual feedback interventions: no feedback, detailed feedback, and summary feedback. Results indicated significantly increased performance consistency for detailed feedback than for both no feedback (p < 0.01) and summary feedback (p < 0.05). No significant difference between summary feedback and no feedback was found (p = 0.173). We deemed feedback of detailed information to enhance kinematic consistency significantly more than both no feedback (p < 0.01) and summary feedback (p < 0.01) interventions, although summary feedback was shown to enhance kinematic consistency more than no feedback (p < 0.01). No improvements were found for performance-related parameters.

Acceleration↗

Synthesis and studies of a trinuclear Mn(II) carboxylate complex.

We report a carboxylate triangle consisting of three manganese(II) centres which is made from manganese(II) carbonate and pivalic acid. The magnetic exchange within the triangle is extremely weak, and antiferromagnetic. Several models have been used to fit the magnetic data, and the best fit uses two weak antiferromagnetic coupling constants of J(1)=-0.588 cm(-1) and J(2)=-0.855 cm(-1). Exchange interactions between the metal centres has been calculated using DFT adopting all the three possible Heisenberg models for a trinuclear system and the results are compared with experimental values. Spin density distribution is used to analyse the nature of the coupling between the metal centres. EPR spectroscopy has been used to explore the nature of the ground state. Recrystallisation of the trinuclear compound from MeCN gives a polymer, while oxidation in air leads to a known compound--an edge-sharing bitetrahedral (MnIII2MnII4) cage.

Journal Article↗

Provision of rheumatology services in New Zealand.

AIMS: To measure equity of access to rheumatology services and to assess the adequacy of the rheumatology workforce-compared with published recommended levels, United Kingdom levels, and previous New Zealand data; and to provide data to assist in workforce planning. METHODS: Data from of the central North Island of New Zealand were obtained during a review of rheumatology services in the Midland region. Complete national public-sector rheumatology workforce data were obtained in a separate survey. RESULTS: This study demonstrates wide geographical variation in outpatient (more than three-fold variation) and inpatient (more than six-fold variation) service volumes per capita between the District Health Boards of the Midland region. Outpatient waiting lists were not higher in underserviced areas. Nationally, there were 251,211 people for each full time equivalent (FTE) rheumatologist, compared with the 1999 level of 235,593 population per FTE, and well behind the UK recommendation of 85,000 people per FTE. CONCLUSIONS This study has demonstrated marked variation in access to rheumatology services based on geographical location, as well as evidence of a worsening shortage of rheumatologists in New Zealand.

Ambulatory Care↗

Synthesis of hybrid framework materials under "dry" hydrothermal conditions: crystal structure and magnetic properties of Mn(2)(H(2)PO(4))(2)(C(2)O(4)).

An exploration of the manganese oxalate-phosphoric acid-water system under hydrothermal conditions, and using "reagent" quantities only of water, has led to the isolation of a new mixed anion framework material Mn(2)(H(2)PO(4))(2)(C(2)O(4)). This material features continuous chains of cis edge-sharing MnO(6) octahedra, a motif which is unique among mixed phosphate-oxalate materials identified so far. These octahedral chains are linked into a three-dimensional framework via corner-sharing with H(2)PO(4) tetrahedra, with oxalate ions acting as a bis-bidentate ligand in the third direction. Magnetic susceptibility studies show that this material may be modeled as an antiferromagnetic, S = (5)/(2) Heisenberg chain, with weaker coupling between the chains.

Journal Article↗

Recognizing the fold of a protein structure.

This paper reports a graph-theoretic program, GRATH, that rapidly, and accurately, matches a novel structure against a library of domain structures to find the most similar ones. GRATH generates distributions of scores by comparing the novel domain against the different types of folds that have been classified previously in the CATH database of structural domains. GRATH uses a measure of similarity that details the geometric information, number of secondary structures and number of residues within secondary structures, that any two protein structures share. Although GRATH builds on well established approaches for secondary structure comparison, a novel scoring scheme has been introduced to allow ranking of any matches identified by the algorithm. More importantly, we have benchmarked the algorithm using a large dataset of 1702 non-redundant structures from the CATH database which have already been classified into fold groups, with manual validation. This has facilitated introduction of further constraints, optimization of parameters and identification of reliable thresholds for fold identification. Following these benchmarking trials, the correct fold can be identified with the top score with a frequency of 90%. It is identified within the ten most likely assignments with a frequency of 98%. GRATH has been implemented to use via a server (http://www.biochem.ucl.ac.uk/cgi-bin/cath/Grath.pl). GRATH's speed and accuracy means that it can be used as a reliable front-end filter for the more accurate, but computationally expensive, residue based structure comparison algorithm SSAP, currently used to classify domain structures in the CATH database. With an increasing number of structures being solved by the structural genomics initiatives, the GRATH server also provides an essential resource for determining whether newly determined structures are related to any known structures from which functional properties may be inferred.

Algorithms↗

Cationic assembly of metal complex aggregates: structural diversity, solution stability, and magnetic properties.

The tetradentate imino-carboxylate ligand [L](2)(-) chelates the equatorial sites of Ni(II) to give the complex [Ni(L)(MeOH)(2)] in which a Ni(II) center is bound in an octahedral coordination environment with MeOH ligands occupying the axial sites. Lanthanide (Ln) and Group II metal ions (M) template the aggregation of six [Ni(L)] fragments into the octahedral cage aggregates (M[Ni(L)](6))(x)(+) (1: M = Sr(II); x = 2,2: M = Ba(II); x = 2, 3: M = La(III); x = 3, 4: M = Ce(III); x = 3, 5: M = Pr(III); x = 3, and 6: M = Nd(III); x = 3). In the presence of Group I cations, however, aggregates composed of the alkali metal-oxide cations template various cage compounds. Thus, Na(+) forms the trigonal bipyramidal [Na(5)O](3+) core within a tricapped trigonal prismatic [Ni(L)](9) aggregate to give ((Na(5)O) subset [Ni(L)](9)(MeOH)(3))(BF(4))(2).OH.CH(3)OH, 7. Li(+) and Na(+) together form a mixed Li(+)/Na(+) core comprising distorted trigonal bipyramidal [Na(3)Li(2)O](3+) within an approximately anti-square prismatic [Ni(L)](8) cage in ((Na(3)Li(2)O) subset [Ni(L)](8)(CH(3)OH)(1.3)(BF(4))(0.7))(BF(4))(2.3).(CH(3)OH)(2.75).(C(4)H(10)O)(0.5), 8, while in the presence of Li(+), a tetrahedral [Li(4)O](2+) core within a hexanuclear open cage [Ni(L)](6) in ((Li(4)O) subset [Ni(L)](6)(CH(3)OH)(3))2ClO(4).1.85CH(3)OH, 9, is produced. In the presence of H(2)O, the Cs(+) cation induces the aggregation of the [Ni(L)(H(2)O)(2)] monomer to give the cluster Cs(2)[Ni(L)(H(2)O)(2)](6).2I.4CH(3)OH.5.25H(2)O, 10. Analysis by electronic spectroscopy and mass spectrometry indicates that in solution the trend in stability follows the order 1-6 > 7 > 8 approximately 9. Magnetic susceptibility data indicate that there is net antiferromagnetic exchange between magnetic centers within the cages.

Journal Article↗