1,251 research outputs found

    The role of elasticity in slab bending

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    International audiencePrevious studies showed that plate rheology exerts a dominant control on the shape and velocity of subducting plates. Here, we perform a systematic investigation of the role of elasticity in slab bending, using fully dynamic 2-D models where an elastic, viscoelastic, or viscoelastoplastic plate subducts freely into a purely viscous mantle. We derive a scaling relationship between the bending radius of viscoelastic slabs and the Deborah number, De, which is the ratio of Maxwell time over deformation time. We show that De controls the ratio of elastically stored energy over viscously dissipated energy and find that at De>10-2, substantially less energy is required to bend a viscoelastic slab to the same shape as a purely viscous slab with the same intrinsic viscosity. Elastically stored energy at higher De favors retreating modes of subduction via unbending, while trench advance only occurs for some cases with De 1, where most zones have low De 0.1. Slabs with De<10-2 either have very low viscosities or they may be yielding, in which case our De estimates may be underestimated by up to an order of magnitude, potentially pointing towards a significant role of elasticity in ∼60% of the subduction zones. In support of such a role of elasticity in subduction, we find that increasing De correlates with increasing proportion of larger seismic events in both instrumental and historic catalogues

    Microneedle-Assisted Delivery of Anti-Migraine Drugs Across Porcine Skin: Almotriptan Malate and Naratriptan Hydrochloride

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    Migraine is a common neurological disorder characterized by nausea, vomiting, photophobia, aching, fever, pain and chills. Triptans are selective serotonin agonists which can used to relieve migraine symptoms. Almotriptan malate and naratriptan hydrochloride are currently used for the management of migraine in the form of oral tablets. Oral tablets may be problematic for patients experiencing nausea and vomiting which are often associated with migraine. The microneedle-assisted transdermal drug delivery of these triptans may improve patient compliance. A vertical six-celled, static Franz diffusion cell system was used to conduct in vitro permeation experiments on porcine ear skin to determine the influence of microneedle-assisted transdermal delivery of both almotriptan malate and naratriptan hydrochloride. HPLC-MS analysis was performed using an Agilent 1200 series high performance liquid chromatography system in combination with an Agilent time of flight mass spectrometer (TOF-MS) system model 6230 (Agilent, Santa Clara, CA, USA). A reversed phase liquid chromatography column (Agilent Zorbax Eclipse Plus C18, 100 mm X 2.1 mm, 3.5 µm), was utilized for chromatographic separation. Confocal laser scanning microscopy was used to characterize the depth of the microchannels created after stainless-steel microneedle roller application. Transdermal flux of both triptans was calculated from the linear portion of the cumulative amount of drug permeated versus time curve. The mean passive flux of almotriptan malate was 13.044 ± 0.32 µg.cm2 .h, while the mean flux following microneedle roller application was 11.281 ± 0.22 µg.cm2 .h. The mean flux values for naratriptan hydrochloride for passive and after microneedle roller application was 0.88 ± 0.29 µg.cm2 .h and 4.18 ± 1.39 µg.cm2 .h, respectively. Statistical analysis was performed using the Student’s t-test (GradPad Prism 7). A statistically significant difference (p\u3c0.05) between microneedle-treated porcine skin samples compared to untreated skin samples was found for the transdermal flux values of naratriptan hydrochloride. Solid stainless-steel microneedle rollers enhanced the transdermal delivery of naratriptan hydrochloride. In contrast, transdermal flux values obtained for almotriptan malate indicate that differences between microneedle-treated and untreated skin samples was not statistically significant (p\u3e0.05)

    The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

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    The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm2/h) compared to passive delivery (12.83 ± 6.30 µg/cm2/h). For carbamazepine in 20% ethanol, passive transdermal flux of 7.85 ± 0.60 µg/cm2/h was observed compared to 10.85 ± 0.11 µg/cm2/h after microneedle treatment. Carbamazepine reconstituted in 30% ethanol resulted in only a 1.19-fold increase in drug permeation across porcine skin (36.73 ± 1.83 µg/cm2/h versus 30.74 ± 1.32 µg/cm2/h). Differences in flux values of untreated and microneedle-treated porcine skin using solid microneedles for the transdermal delivery of tiagabine were statistically significant. Although there were 1.38- and 1.19-fold increases in transdermal flux values of carbamazepine when applied as 20% and 30% ethanol solutions across microneedle-treated porcine skin, respectively, the increases were not statistically significant

    1H, 13C, and 15N resonance assignments for the tandem PHD finger motifs of human CHD4

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    The plant homeodomain (PHD) zinc finger is a structural motif of about 40–60 amino acid residues found in many eukaryotic proteins that are involved in chromatin-mediated gene regulation. The human chromodomain helicase DNA binding protein 4 (CHD4) is a multi-domain protein that harbours, at its N-terminal end, a pair of PHD finger motifs (dPHD) connected by a ~30 amino acid linker. This tandem PHD motif is thought to be involved in targeting CHD4 to chromatin via its interaction with histone tails. Here we report the 1H, 13C and 15N backbone and side-chain resonance assignment of the entire dPHD by heteronuclear multidimensional NMR spectroscopy. These assignments provide the starting point for the determination of the structure, dynamics and histone-binding properties of this tandem domain pair

    Pacific Plate slab pull and intraplate deformation in the early Cenozoic

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    Large tectonic plates are known to be susceptible to internal deformation, leading to a range of phenomena including intraplate volcanism. However, the space and time dependence of intraplate deformation and its relationship with changing plate boundary configurations, subducting slab geometries, and absolute plate motion is poorly understood. We utilise a buoyancy driven Stokes flow solver, BEM-Earth, to investigate the contribution of subducting slabs through time on Pacific Plate motion and plate-scale deformation, and how this is linked to intraplate volcanism. We produce a series of geodynamic models from 62 to 42 Ma in which the plates are driven by the attached subducting slabs and mantle drag/suction forces. We compare our modelled intraplate deformation history with those types of intraplate volcanism that lack a clear age progression. Our models suggest that changes in Cenozoic subduction zone topology caused intraplate deformation to trigger volcanism along several linear seafloor structures, mostly by reactivation of existing seamount chains, but occasionally creating new volcanic chains on crust weakened by fracture zones and extinct ridges. Around 55 Ma subduction of the Pacific-Izanagi ridge reconfigured the major tectonic forces acting on the plate by replacing ridge push with slab pull along its north-western perimeter, causing lithospheric extension along pre-existing weaknesses. Large scale deformation observed in the models coincides with the seamount chains of Hawaii, Louisville, Tokelau, and Gilbert during our modelled time period of 62 to 42 Ma. We suggest that extensional stresses between 72 and 52 Ma are the likely cause of large parts of the formation of the Gilbert chain and that localised extension between 62 and 42 Ma could cause late-stage volcanism along the Musicians Volcanic Ridges. Our models demonstrate that early Cenozoic changes in Pacific plate driving forces only cause relatively minor changes in Pacific absolute plate motions, and cannot be responsible for the Hawaii-Emperor Bend (HEB), confirming previous interpretations that the 47 Ma HEB does not reflect an absolute plate motion event

    Hepatosplenic Gamma/Delta T-Cell Lymphoma Masquerading as Alcoholic Hepatitis and Methadone Withdrawal

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    Hepatosplenic gamma/delta T-cell lymphoma is a rare neoplasm of mature gamma/delta T-cells with sinusoidal infiltration of spleen, liver, and bone marrow. Patients are predominantly adolescent and young adult males and usually present with marked hepatosplenomegaly. Pancytopenia is another common finding. Despite an initial response to treatment, patients have a median survival of one to two years. In this report, we document a case of alcoholic hepatitis and methadone withdrawal masquerading unsuspected, hepatosplenic gamma/delta T-cell lymphoma with unusual CD20 positivity

    Hydrogen production at high Faradaic efficiency by a bio-electrode based on TiO2 adsorption of a new [FeFe]-hydrogenase from Clostridium perfringens

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    © 2015 Elsevier B.V. The [FeFe]-hydrogenase CpHydA from Clostridium perfringens was immobilized by adsorption on anatase TiO2 electrodes for clean hydrogen production. The immobilized enzyme proved to perform direct electron transfer to and from the electrode surface and catalyses both H2 oxidation (H2 uptake) and H2 production (H2 evolution) with a current density for H2 evolution of about 2mAcm-1. The TiO2/CpHydA bioelectrode remained active for several days upon storage and when a reducing potential was set, H2 evolution occurred with a mean Faradaic efficiency of 98%. The high turnover frequency of H2 production and the tight coupling of electron transfer, resulting in a Faradaic efficiency close to 100%, support the exploitation of the novel TiO2/CpHydA stationary electrode as a powerful device for H2 production

    COMPARING ESTIMATION PROCEDURES FOR DOSE-RESPONSE FUNCTIONS

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    The dose-response design is often used in agricultural research when it is necessary to measure a biological response at various levels of an experimental factor. This type of problem is common in chemical and pesticide research, however, it can also occur in other disciplines such as plant, animal, soil, and environmental sciences. While the analysis of dose-response data usually involves fitting a regression curve, the primary objective often centers on the estimation of dose related percentiles such as the LD50 or LC50. These measures are useful for comparing the relative efficacy of various treatments, however, the estimation of the specified percentiles is not always straightforward. Traditional methodology has relied on inverted solutions or asymptotic theory for statistical inference. More recently, computer intensive methods have been used to model dose-response relationships and can be more appropriate than traditional methods in some situations. This paper examines both the traditional and modem approaches to estimating doseresponse functions as they apply to binomial data. The techniques will be demonstrated using mortality data collected on black vine weevil eggs exposed to an organic pesticide treatment

    Dual transcriptional-translational cascade permits cellular level tuneable expression control.

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    The ability to induce gene expression in a small molecule dependent manner has led to many applications in target discovery, functional elucidation and bio-production. To date these applications have relied on a limited set of protein-based control mechanisms operating at the level of transcription initiation. The discovery, design and reengineering of riboswitches offer an alternative means by which to control gene expression. Here we report the development and characterization of a novel tunable recombinant expression system, termed RiboTite, which operates at both the transcriptional and translational level. Using standard inducible promoters and orthogonal riboswitches, a multi-layered modular genetic control circuit was developed to control the expression of both bacteriophage T7 RNA polymerase and recombinant gene(s) of interest. The system was benchmarked against a number of commonly used E. coli expression systems, and shows tight basal control, precise analogue tunability of gene expression at the cellular level, dose-dependent regulation of protein production rates over extended growth periods and enhanced cell viability. This novel system expands the number of E. coli expression systems for use in recombinant protein production and represents a major performance enhancement over and above the most widely used expression systems

    Field induced transition of the S=1 antiferromagnetic chain with anisotropy

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    The ground state magnetization process of the S=1 antiferromagnetic chain with the easy-axis single-ion anisotropy described by negative DD is investigated. It is numerically found that a phase transition between two different gapless phases occurs at an intermediate magnetic field between the starting and saturation points of the magnetization for −1.49<D<−0.35-1.49<D<-0.35. The transition is similar to the spin flopping, but it is second-order and not accompanied with any significant anomalous behaviors in the magnetization curve. We also present the phase diagrams in the m-D and H-D planes which reveal a possible re-entrant transition.Comment: 6 pages, Revtex, with 6 eps figures, to appear in Phys. Rev. B (Sep. 1
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