Endodontic 'solutions' part 1:A literature review on the use of endodontic lubricants, irrigants and medicaments

Endodontic lubricants, irrigants and medicaments help prepare and disinfect root canal systems (RCS) but primary and secondary cases involve different microbes and therefore it is unlikely that one protocol will be effective for both case types. Each individual 'solution' or sequence of 'solutions' could play a significant role in each case type, but there are no detailed published guidelines in existence. To help inform clinical practice it was decided to undertake a literature review followed by a UK and Republic of Ireland wide audit on current endodontic 'solution' usage within dental schools. The literature review was undertaken under the following headings: pre-op oral rinse; file lubricants; root canal irrigants and intracanal medicaments and provides an evidence base for protocol development for both primary and retreatment cases. The audit project and the protocols developed from the findings of both the literature review and audit will be presented in Part 2.

Identification of benzimidazole resistance in Cladobotryum dendroides using a PCR-based method

Cladobotryutn dendroides, causal agent of cobweb disease of Agaricus bisporus, has become increasingly resistant to methylbenzimidazole carbamate (MBC) fungicides following the extensive use of MBC in cultivated mushroom production in Ireland. Of 38 isolates of C. dendroides obtained from Irish mushroom units, 34 were resistant to carbendazim. Primers based on conserved regions of the -tubulin gene were used to amplify and sequence a portion of the -tubulin gene in C. dendroides. A point mutation was detected at codon 50 in isolates resistant to benzimidazole fungicides, causing an amino acid substitution from tyrosine to cysteine. Species-specific PCR primers were designed to amplify the region of the -tubulin gene containing this substitution. The point mutation removed an Ace I restriction site in the -tubulin gene sequence of resistant isolates. Digestion of the PCR product with Ace I thus provides a rapid diagnostic test to differentiate sensitive and resistant isolates of this fungus. EMBL accession number: YI2256.

Purification of a cathepsin L-like proteinase secreted by adult Fasciola hepatica

A cysteine proteinase released in vitro by Fasciola hepatica was purified to homogeneity by Sephacryl S-200 gel filtration chromatography followed by QAE-Sephadex chromatography. The purified enzyme resolves as a single band with an apparent molecular size of 27 kDa on reducing SDS-polyacrylamide gel electrophoresis; however, under non-reducing conditions it migrates as multiple bands, each with enzymatic activity, in the apparent molecular size range 60-90 kDa. The sequence of the first 20 N-terminal amino acids of the enzyme shows considerable homology with cathepsin L-like proteinases. Immunolocalisation studies revealed that the cathepsin L-like proteinase is concentrated within vesicles in the gut epithelial cells of liver fluke.

A composite pollen-based stratotype for inter-regional evaluation of climatic events in New Zealand over the past 30,000 years (NZ-INTIMATE project)

Our review of paleoclimate information for New Zealand pertaining to the past 30,000 years has identified a general sequence of climatic events, spanning the onset of cold conditions marking the final phase of the Last Glaciation, through to the emergence to full interglacial conditions in the early Holocene. In order to facilitate more detailed assessments of climate variability and any leads or lags in the timing of climate changes across the region, a composite stratotype is proposed for New Zealand. The stratotype is based on terrestrial stratigraphic records and is intended to provide a standard reference for the intercomparison and evaluation of climate proxy records. We nominate a specific stratigraphic type record for each climatic event, using either natural exposure or drill core stratigraphic sections. Type records were selected on thebasis of having very good numerical age control and a clear proxy record. In all cases the main proxy of the type record is subfossil pollen. The type record for the period from ca 30 to ca 18 calendar kiloyears BP (cal. ka BP) is designated in lake-bed sediments from a small morainic kettle lake (Galway tarn) in western South Island. The Galway tarn type record spans a period of full glacial conditions (Last Glacial Coldest Period, LGCP) within the Otira Glaciation, and includes three cold stadials separated by two cool interstadials. The type record for the emergence from glacial conditions following the termination of the Last Glaciation (post-Termination amelioration) is in a core of lake sediments from a maar (Pukaki volcanic crater) in Auckland, northern North Island, and spans from ca 18 to 15.64±0.41 cal. ka BP. The type record for the Lateglacial period is an exposure of interbedded peat and mud at montane Kaipo bog, eastern North Island. In this high-resolution type record, an initial mild period was succeeded at 13.74±0.13 cal. ka BP by a cooler period, which after 12.55±0.14 cal. ka BP gave way to a progressive ascent to full interglacial conditions that were achieved by 11.88±0.18 cal. ka BP. Although a type section is not formally designated for the Holocene Interglacial (11.88±0.18 cal. ka BP to the present day), the sedimentary record of Lake Maratoto on the Waikato lowlands, northwestern North Island, is identified as a prospective type section pending the integration and updating of existing stratigraphic and proxy datasets, and age models. The type records are interconnected by one or more dated tephra layers, the ages of which are derived from Bayesian depositional modelling and OxCal-based calibrations using the IntCal09 dataset. Along with the type sections and the Lake Maratoto record, important, well-dated terrestrial reference records are provided for each climate event. Climate proxies from these reference records include pollen flora, stable isotopes from speleothems, beetle and chironomid fauna, and glacier moraines. The regional composite stratotype provides a benchmark against which to compare other records and proxies. Based on the composite stratotype, we provide an updated climate event stratigraphic classification for the New Zealand region. © 2013 Elsevier Ltd.

Ordering the cytochrome c-initiated caspase cascade:hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner

Exit of cytochrome c from mitochondria into the cytosol has been implicated as an important step in apoptosis. In the cytosol, cytochrome c binds to the CED-4 homologue, Apaf-1, thereby triggering Apaf-1-mediated activation of caspase-9. Caspase-9 is thought to propagate the death signal by triggering other caspase activation events, the details of which remain obscure. Here, we report that six additional caspases (caspases-2, -3, -6, -7, -8, and -10) are processed in cell-free extracts in response to cytochrome c, and that three others (caspases-1, -4, and -5) failed to be activated under the same conditions. In vitro association assays confirmed that caspase-9 selectively bound to Apaf-1, whereas caspases-1, -2, -3, -6, -7, -8, and -10 did not. Depletion of caspase-9 from cell extracts abrogated cytochrome c-inducible activation of caspases-2, -3, -6, -7, -8, and -10, suggesting that caspase-9 is required for all of these downstream caspase activation events. Immunodepletion of caspases-3, -6, and -7 from cell extracts enabled us to order the sequence of caspase activation events downstream of caspase-9 and reveal the presence of a branched caspase cascade. Caspase-3 is required for the activation of four other caspases (-2, -6, -8, and -10) in this pathway and also participates in a feedback amplification loop involving caspase-9.

Temper outbursts in Prader-Willi syndrome: causes, behavioural and emotional sequence and responses by carers

Background: Temper outbursts are common in Prader-Willi syndrome but rarely described in detail. This study investigated the phenomenology of temper outbursts in terms of antecedents, sequence of behaviours and emotions and intervention strategies used.

Method: A semi-structured interview about temper outbursts was conducted with the main carers of seven children (9.5 to 16.7 years) and seven adults (24.7 to 47.10 years) with Prader-Willi syndrome (10 male, 4 female). Reliability and validity of the interview results was established.

Results: Various setting events increased and reduced the likelihood of temper outbursts. The most common antecedent was a change to routine or expectation. There were marked similarities in the sequence of behaviours and emotions during temper outbursts, with anger rising quickly followed by expressions of remorse and distress at the end of an outburst.

Discussion: The sequence of behaviours and emotions within outbursts was similar to that described in temper tantrums in typical development. Cognitive and emotional processes are likely to be important in the understanding of temper outbursts with implications for early intervention.

Stated choices and benefit estimates in the context of traffic calming schemes:Utility maximization, regret minimization, or both?

This paper proposes a discrete mixture model which assigns individuals, up to a probability, to either a class of random utility (RU) maximizers or a class of random regret (RR) minimizers, on the basis of their sequence of observed choices. Our proposed model advances the state of the art of RU-RR mixture models by (i) adding and simultaneously estimating a membership model which predicts the probability of belonging to a RU or RR class; (ii) adding a layer of random taste heterogeneity within each behavioural class; and (iii) deriving a welfare measure associated with the RU-RR mixture model and consistent with referendum-voting, which is the adequate mechanism of provision for such local public goods. The context of our empirical application is a stated choice experiment concerning traffic calming schemes. We find that the random parameter RU-RR mixture model not only outperforms its fixed coefficient counterpart in terms of fit-as expected-but also in terms of plausibility of membership determinants of behavioural class. In line with psychological theories of regret, we find that, compared to respondents who are familiar with the choice context (i.e. the traffic calming scheme), unfamiliar respondents are more likely to be regret minimizers than utility maximizers. © 2014 Elsevier Ltd.

Biochemical characterisation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) from the liver fluke, Fasciola hepatica

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyses one of the two steps in glycolysis which generate the reduced coenzyme NADH. This reaction precedes the two ATP generating steps. Thus, inhibition of GAPDH will lead to substantially reduced energy generation. Consequently, there has been considerable interest in developing GAPDH inhibitors as anti-cancer and anti-parasitic agents. Here, we describe the biochemical characterisation of GAPDH from the common liver fluke Fasciola hepatica (FhGAPDH). The primary sequence of FhGAPDH is similar to that from other trematodes and the predicted structure shows high similarity to those from other animals including the mammalian hosts. FhGAPDH lacks a binding pocket which has been exploited in the design of novel antitrypanosomal compounds. The protein can be expressed in, and purified from Escherichia coli; the recombinant protein was active and showed no cooperativity towards glyceraldehyde 3-phosphate as a substrate. In the absence of ligands, FhGAPDH was a mixture of homodimers and tetramers, as judged by protein-protein crosslinking and analytical gel filtration. The addition of either NAD(+) or glyceraldehyde 3-phosphate shifted this equilibrium towards a compact dimer. Thermal scanning fluorimetry demonstrated that this form was considerably more stable than the unliganded one. These responses to ligand binding differ from those seen in mammalian enzymes. These differences could be exploited in the discovery of reagents which selectively disrupt the function of FhGAPDH.

Nonlocality of two- and three-mode continuous variable systems

We address the nonlocality of fully inseparable three-mode Gaussian states generated either by bilinear three-mode Hamiltonians or by a sequence of bilinear two-mode Hamiltonians. Two different tests revealing nonlocality are considered, in which the dichotomic Bell operator is represented by the displaced parity and by the pseudospin operator respectively. Three-mode states are also considered as a conditional source of two-mode non-Gaussian states, whose nonlocality properties are analysed. We found that the non-Gaussian character of the conditional states allows violation of Bell's inequalities (by parity and pseudospin tests) stronger than with a conventional twin-beam state. However, the non-Gaussian character is not sufficient to reveal nonlocality through a dichotomized quadrature measurement strategy.

The chronostratigraphy of the Haua Fteah cave (Cyrenaica, northeast Libya)

The 1950s excavations by Charles McBurney in the Haua Fteah, a large karstic cave on the coast of northeast Libya, revealed a deep sequence of human occupation. Most subsequent research on North African prehistory refers to his discoveries and interpretations, but the chronology of its archaeological and geological sequences has been based on very early age determinations. This paper reports on the initial results of a comprehensive multi-method dating program undertaken as part of new work at the site, involving radiocarbon dating of charcoal, land snails and marine shell, cryptotephra investigations, optically stimulated luminescence (OSL) dating of sediments, and electron spin resonance (ESR) dating of tooth enamel. The dating samples were collected from the newly exposed and cleaned faces of the upper 7.5m of the ~14.0m-deep McBurney trench, which contain six of the seven major cultural phases that he identified. Despite problems of sediment transport and reworking, using a Bayesian statistical model the new dating program establishes a robust framework for the five major lithostratigraphic units identified in the stratigraphic succession, and for the major cultural units. The age of two anatomically modern human mandibles found by McBurney in Layer XXXIII near the base of his Levalloiso-Mousterian phase can now be estimated to between 73 and 65ka (thousands of years ago) at the 95.4% confidence level, within Marine Isotope Stage (MIS) 4. McBurney's Layer XXV, associated with Upper Palaeolithic Dabban blade industries, has a clear stratigraphic relationship with Campanian Ignimbrite tephra. Microlithic Oranian technologies developed following the climax of the Last Glacial Maximum and the more microlithic Capsian in the Younger Dryas. Neolithic pottery and perhaps domestic livestock were used in the cave from the mid Holocene but there is no certain evidence for plant cultivation until the Graeco-Roman period. © 2013 Elsevier Ltd.

CHARACTERIZATION OF THE AU SURFACE-STRUCTURE OF AL-L-AU LIGHT-EMITTING TUNNEL-JUNCTIONS

Visible light is emitted from the Au-air interface of Al-I-Au thin-film tunnel junctions (deposited over a thin layer of CaF2 on glass) as a result of the decay of surface plasmon polaritons (SPPs). We show the surface topography of such a Au film and relate its large-scale features to the outcoupling of fast SPP's to photons. The absence of short-scale roughness features is explained by thier disappearance through surface diffusion. To confirm this a controlled sequence of 5-nm, 20-ms scanning tunneling microscope (STM) W tip crashes has been used to produce indentations 3 nm deep with a lateral dimension of 5-7 nm on a Au crystal in air at room temperature. Four sequences of indentations were drawn in the form of a square box. Right from the start, feature decay is observed and over a period of 2 h a succession of images shows that the structure disappears into the background as a result of surface diffusion. The surface diffusion constant is estimated to be 10(-18) cm2 s-1. The lack of light output via slow mode SPPs is an inevitable consequence of surface annealing.

The latest LGM culmination of the Garda Glacier (Italian Alps) and the onset of glacial termination. Age of glacial collapse and vegetation chronosequence

In the deglacial sequence of the largest end moraine system of the Italian Alps, we focused on the latest culmination of the Last Glacial Maximum, before a sudden downwasting of the piedmontane lobe occupying the modern lake basin. We obtained a robust chronology for this culmination and for the subsequent deglacial history by cross-radiocarbon dating of a proximal fluvioglacial plain and of a deglacial continuous lake sedimentation. We used reworked dinocysts to locate sources of glacial abrasion and to mark the input of glacial meltwater until depletion. The palynological record from postglacial lake sediments provided the first vegetation chronosequence directly reacting to the early Lateglacial withdrawal so far documented in the Alps.

Glacier collapse occurred soon after 17.46 +/- 0.2 ka cal BP, which is, the Manerba advance culmination. Basin deglaciation of several overdeepened foreland piedmont lakes on southern and northern sides of the Alps appears to be synchronous at millennial scale and near-synchronous with large-scale glacial retreat at global scale. The pioneering succession shows a first afforestation step at a median modeled age of 64 years after deglaciation, while rapid tree growth lagged 7 centuries. Between 16.4 +/- 0.16 and 15.5 +/- 0.16 ka cal BP, a regressive phase interrupted forest growth marking a Lateglacial phase of continental-dry climate predating GI-1. This event, spanning the most advanced phases of North-Atlantic H1, is consistently radiocarbon-framed at three deglacial lake records so far investigated on the Italian side of the Alps. Relationships with the Gschnitz stadial from the Alpine record of Lateglacial advances are discussed

The Host Defence Peptide LL-37 is Susceptible to Proteolytic Degradation by Wound Fluid Isolated from Foot Ulcers of Diabetic Patients

The pleiotropic effects of host defence peptides (HDPs), including the ability to kill microorganisms, enhance re-epithelialisation and increase angiogenesis, indicates a role for these important peptides as potential therapeutic agents in the treatment of chronic, non-healing wounds. However, the maintenance of peptide integrity, through resistance to degradation by the array of proteinases present at the wound site, is a prerequisite for clinical success. In this study we explored the degradation of exogenous LL-37, one such HDP, by wound fluid from diabetic foot ulcers to determine its susceptibility to proteolytic degradation. Our results suggest that LL-37 is unstable in the diabetic foot ulcer microenvironment. Following overnight treatment with wound fluid, LL-37 was completely degraded. Analysis of cleavage sites suggested potential involvement of both host- and bacterial-derived proteinases. The degradation products were shown to retain some antibacterial activity against Pseudomonas aeruginosa but were inactive against Staphylococcus aureus. In conclusion, our data suggest that stabilising selected peptide bonds within the sequence of LL-37 would represent an avenue for future research prior to clinical studies to address its potential as an exogenously-applied therapeutic in diabetic wounds. 

Conceptual Design and Workspace Analysis of an Exechon-inspired Parallel Kinematic Machine

Inspired by the commercial application of the Exechon machine, this paper proposed a novel parallel kinematic machine (PKM) named Exe-Variant. By exchanging the sequence of kinematic pairs in each limb of the Exechon machine, the Exe-Variant PKM claims an arrangement of 2UPR/1SPR topology and consists of two identical UPR limbs and one SPR limb. The inverse kinematics of the 2UPR/1SPR parallel mechanism was firstly analyzed based on which a conceptual design of the Exe-Variant was carried out. Then an algorithm of reachable workspace searching for the Exe-Variant and the Exchon was proposed. Finally, the workspaces of two example systems of the Exechon and the Exe-Variant with approximate dimensions were numerically simulated and compared. The comparison shows that the Exe-Variant possesses a competitive workspace with the Exechon machine, indicating it can be used as a promising reconfigurable module in a hybrid 5-DOF machine tool system.

Initial growth stages of epitaxial BaTiO3 films on vicinal SrTiO3 (001) substrate surfaces

The initial growth mechanism of epitaxial BaTiO3 films is studied by combined application of atomic force microscopy, cross sectional high-resolution transmission electron microscopy, and x-ray diffraction. Epitaxial BaTiO3 thin films were grown by pulsed laser deposition on vicinal Nb-doped SrTiO3 (SrTiO3:Nb) (001) substrates with well-defined terraces. X-ray diffraction and cross sectional high-resolution transmission electron microscopy investigations revealed well-defined epitaxial films and a sharp interface between BaTiO3 films and SrTiO3:Nb substrates. The layer-then-island (Stranski-Krastanov mode) growth mechanism observed by analyzing the morphology of a sequence of films with increasing amount of deposited material has been confirmed by microstructure investigations. (C) 2002 American Institute of Physics.