44 research outputs found

    Assessing the Role of Compaction in the Formation of Adcumulates: a Microstructural Perspective

    Get PDF
    The formation of adcumulates necessitates the continued growth of primocrysts down to low porosities. Gravitationally driven viscous compaction at the base of a crystal mushy layer on the magma chamber floor, driven by the weight of the mushy layer itself, is commonly suggested as a significant process acting to drive out interstitial liquid and promote adcumulate formation. Compaction necessitates viscous deformation, by either dislocation creep or diffusion-controlled processes such as pressure-solution: many studies suggest that the foliations preserved in cumulates are a consequence of recrystallization during compaction, completely overprinting primary magmatic fabrics. We test the compaction hypothesis by looking for microstructural evidence of viscous deformation. A detailed examination of cumulates from the Skaergaard intrusion, East Greenland, demonstrates only limited crystal plastic deformation, with no correlation between the extent of dislocation creep and the calculated volume fraction of trapped liquid left in the cumulates. Although the evidence for diffusion-controlled deformation is often cryptic, there is an anti-correlation between apparent aspect ratio of plagioclase and the extent of adcumulate crystallization, contradicting previous hypotheses involving transposition of original magmatic fabrics by dissolution–reprecipitation. This is supported by the spatial distribution of compositional zoning in plagioclase, which demonstrates that pressure-solution or related diffusion-controlled processes were insufficient to obscure primary magmatic fabrics. The Skaergaard adcumulates did not form by viscous compaction. Instead we suggest that they formed by primary processes involving mass transport in a thin mushy layer. Compaction is most likely to occur in slowly cooled intrusions in which the bulk magma crystallizes abundant dense minerals. We present preliminary observations of microstructures in norites from the lower Main Zone of the Bushveld Intrusion, South Africa, and in plagioclase-rich cumulates from the Fe–Ti oxide-rich Baima Intrusion, SW China. The evidence for dislocation creep in both intrusions is unambiguous, although deformation was insuffi- cient to obliterate all traces of the primary magmatic fabrics and unlikely to have been sufficient to significantly reduce the volume of interstitial liquid.This work was supported by the Natural Environment Research Council [grant numbers NE/J021520/1 and NE/M000060/1] and a Royal Society International Joint Project grant. Z.V. is supported by a Marie SkłodowskaCurie Individual European Fellow grant

    Redox-freezing and nucleation of diamond via magnetite formation in the Earth’s mantle

    Get PDF
    Diamonds and their inclusions are unique probes into the deep Earth, tracking the deep carbon cycle to >800 km. Understanding the mechanisms of carbon mobilization and freezing is a prerequisite for quantifying the fluxes of carbon in the deep Earth. Here we show direct evidence for the formation of diamond by redox reactions involving FeNi sulfides. Transmission Kikuchi Diffraction identifies an arrested redox reaction from pyrrhotite to magnetite included in diamond. The magnetite corona shows coherent epitaxy with relict pyrrhotite and diamond, indicating that diamond nucleated on magnetite. Furthermore, structures inherited from h-Fe3O4 define a phase transformation at depths of 320–330 km, the base of the Kaapvaal lithosphere. The oxidation of pyrrhotite to magnetite is an important trigger of diamond precipitation in the upper mantle, explaining the presence of these phases in diamonds

    Predicting Outcomes of Prostate Cancer Immunotherapy by Personalized Mathematical Models

    Get PDF
    Therapeutic vaccination against disseminated prostate cancer (PCa) is partially effective in some PCa patients. We hypothesized that the efficacy of treatment will be enhanced by individualized vaccination regimens tailored by simple mathematical models.We developed a general mathematical model encompassing the basic interactions of a vaccine, immune system and PCa cells, and validated it by the results of a clinical trial testing an allogeneic PCa whole-cell vaccine. For model validation in the absence of any other pertinent marker, we used the clinically measured changes in prostate-specific antigen (PSA) levels as a correlate of tumor burden. Up to 26 PSA levels measured per patient were divided into each patient's training set and his validation set. The training set, used for model personalization, contained the patient's initial sequence of PSA levels; the validation set contained his subsequent PSA data points. Personalized models were simulated to predict changes in tumor burden and PSA levels and predictions were compared to the validation set. The model accurately predicted PSA levels over the entire measured period in 12 of the 15 vaccination-responsive patients (the coefficient of determination between the predicted and observed PSA values was R(2) = 0.972). The model could not account for the inconsistent changes in PSA levels in 3 of the 15 responsive patients at the end of treatment. Each validated personalized model was simulated under many hypothetical immunotherapy protocols to suggest alternative vaccination regimens. Personalized regimens predicted to enhance the effects of therapy differed among the patients.Using a few initial measurements, we constructed robust patient-specific models of PCa immunotherapy, which were retrospectively validated by clinical trial results. Our results emphasize the potential value and feasibility of individualized model-suggested immunotherapy protocols

    FOXP3 Expression Is Upregulated in CD4+T Cells in Progressive HIV-1 Infection and Is a Marker of Disease Severity

    Get PDF
    Understanding the role of different classes of T cells during HIV infection is critical to determining which responses correlate with protective immunity. To date, it is unclear whether alterations in regulatory T cell (Treg) function are contributory to progression of HIV infection.FOXP3 expression was measured by both qRT-PCR and by flow cytometry in HIV-infected individuals and uninfected controls together with expression of CD25, GITR and CTLA-4. Cultured peripheral blood mononuclear cells were stimulated with anti-CD3 and cell proliferation was assessed by CFSE dilution.HIV infected individuals had significantly higher frequencies of CD4(+)FOXP3(+) T cells (median of 8.11%; range 1.33%-26.27%) than healthy controls (median 3.72%; range 1.3-7.5%; P = 0.002), despite having lower absolute counts of CD4(+)FOXP3(+) T cells. There was a significant positive correlation between the frequency of CD4(+)FOXP3(+) T cells and viral load (rho = 0.593 P = 0.003) and a significant negative correlation with CD4 count (rho = -0.423 P = 0.044). 48% of our patients had CD4 counts below 200 cells/microl and these patients showed a marked elevation of FOXP3 percentage (median 10% range 4.07%-26.27%). Assessing the mechanism of increased FOXP3 frequency, we found that the high FOXP3 levels noted in HIV infected individuals dropped rapidly in unstimulated culture conditions but could be restimulated by T cell receptor stimulation. This suggests that the high FOXP3 expression in HIV infected patients is likely due to FOXP3 upregulation by individual CD4(+) T cells following antigenic or other stimulation.FOXP3 expression in the CD4(+) T cell population is a marker of severity of HIV infection and a potential prognostic marker of disease progression

    Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

    Get PDF
    Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

    Reconstructing grain-shape statistics from electron back-scatter diffraction microscopy

    No full text
    Reconstructing the three-dimensional (3D) size and shape distribution of randomly oriented grains using only images of cross sections remains an important challenge. Even for ellipsoids, a solution is only possible when they are solids of revolution, and may still be numerically unstable. Here we show that crystallographic orientation data, for example from electron back-scatter diffraction (EBSD), provides enough additional information to obtain moments of the 3D grain distribution, provided grain shapes can be assumed to align with crystal axes. We show that this moment method can give an average 3D grain size and shape (with error estimate) which is rigorous for ellipsoids and a good approximation for cuboidal grains, indicating that it may be a useful technique for polycrystalline materials in general. High throughput image analysis and EBSD now make the necessary sample sizes practical. We illustrate by applying the method to a basaltic rock specimen
    corecore