Provenance and geochemistry of exotic clasts in conglomerates of the Oligocene Torehina Formation, Coromandel Peninsula, New Zealand

Non-marine pebble to cobble conglomerates of the lower Torehina Formation (Oligocene) crop out along western Coromandel Peninsula and overlie, with strong angular discordance, continental-margin metasedimentary rocks (Manaia Hill Group) of Mesozoic (Late Jurassic to ?Early Cretaceous) age. The conglomerates contain provenance information that identifies a pre-Oligocene depositional history obscured by the unconformable juxtaposition of these Tertiary and Mesozoic strata. Most clasts in the lower Torehina Formation are visually similar to local bedrock lithologies, including metamorphosed sandstones and argillites, but are kaolinitic and contain more detrital and authigenic chert, quartz, and potash feldspar. Local derivation of these clasts seems unlikely. By comparing geochemical ratios with those defined for continental margin sandstones, and well characterised New Zealand tectonic terranes, we interpret the majority of clasts in the lower Torehina Formation to have been derived from a dissected orogen, with mixtures of felsic and volcanogenic-derived sediment. The most likely sources are the Waipapa and Torlesse Terranes. The remaining 20–30% of the clasts in the lower Torehina Formation were originally friable, are coarse grained, and appear to be lithologically exotic relative to known metamorphosed sandstones in basement terrane sources on North Island. Some clasts contain coal laminae and particles, and all contain detrital kaolinite as lithic fragments and matrix. Such characteristics imply a non-marine to marginal-marine source containing sediment derived from strongly weathered granite or granodiorite. Mechanical fragility implies a likely proximal, easily erodible source. We propose that this group of clasts was derived from an Upper Cretaceous sedimentary cover, either part of a locally developed basin fill or part of a once regionally extensive cover on North Island. Either case defines a more widely distributed Cretaceous source than found today

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Strain analysis of a seismically imaged mass‐transport complex, offshore Uruguay

Strain style, magnitude and distribution within mass‐transport complexes (MTCs) are important for understanding the process evolution of submarine mass flows and for estimating their runout distances. Structural restoration and quantification of strain in gravitationally driven passive margins have been shown to approximately balance between updip extensional and downdip contractional domains; such an exercise has not yet been attempted for MTCs. We here interpret and structurally restore a shallowly buried (c. 1,500 mbsf) and well‐imaged MTC, offshore Uruguay using a high‐resolution (12.5 m vertical and 15 × 12.5 m horizontal resolution) three‐dimensional seismic‐reflection survey. This allows us to characterise and quantify vertical and lateral strain distribution within the deposit. Detailed seismic mapping and attribute analysis shows that the MTC is characterised by a complicated array of kinematic indicators, which vary spatially in style and concentration. Seismic‐attribute extractions reveal several previously undocumented fabrics preserved in the MTC, including internal shearing in the form of sub‐orthogonal shear zones, and fold‐thrust systems within the basal shear zone beneath rafted‐blocks. These features suggest multiple transport directions and phases of flow during emplacement. The MTC is characterised by a broadly tripartite strain distribution, with extensional (e.g. normal faults), translational and contractional (e.g. folds and thrusts) domains, along with a radial frontally emergent zone. We also show how strain is preferentially concentrated around intra‐MTC rafted‐blocks due to their kinematic interactions with the underlying basal shear zone. Overall, and even when volume loss within the frontally emergent zone is included, a strain deficit between the extensional and contractional domains (c. 3%–14%) is calculated. We attribute this to a combination of distributed, sub‐seismic, ‘cryptic’ strain, likely related to de‐watering, grain‐scale deformation and related changes in bulk sediment volume. This work has implications for assessing MTCs strain distribution and provides a practical approach for evaluating structural interpretations within such deposits

Amorphous formulations of indomethacin and griseofulvin prepared by electrospinning

Following an array of optimization experiments, two series of electrospun polyvinylpyrrolidone (PVP) fibers were prepared. One set of fibers contained various loadings of indomethacin, known to form stable glasses, and the other griseofulvin (a poor glass former). Drug loadings of up to 33% w/w were achieved. Electron microscopy data showed the fibers largely to comprise smooth and uniform cylinders, with evidence for solvent droplets in some samples. In all cases, the drug was found to exist in the amorphous physical state in the fibers on the basis of X-ray diffraction and differential scanning calorimetry (DSC) measurements. Modulated temperature DSC showed that the relationship between a formulation’s glass transition temperature (<i>T</i>_g) and the drug loading follows the Gordon–Taylor equation, but not the Fox equation. The results of Gordon–Taylor analysis indicated that the drug/polymer interactions were stronger with indomethacin. The interactions between drug and polymer were explored in more detail using molecular modeling simulations and again found to be stronger with indomethacin; the presence of significant intermolecular forces was further confirmed using IR spectroscopy. The amorphous form of both drugs was found to be stable after storage of the fibers for 8 months in a desiccator (relative humidity <25%). Finally, the functional performance of the fibers was studied; in all cases, the drug-loaded fibers released their drug cargo very rapidly, offering accelerated dissolution over the pure drug

Periconceptional bread intakes indicate New Zealand's proposed mandatory folic acid fortification program may be outdated: results from a postpartum survey

Abstract Background In September 2009, a folic acid fortification mandate (135 μg/100 g bread) was to be implemented in New Zealand. However, due to political and manufacturer objection, fortification was deferred until May 2012. Based on estimates of bread consumption derived from a 1997 nationally representative survey, this program was intended to deliver a mean additional intake of 140 μg folic acid/d to women of childbearing age. Little is known about current bread consumption patterns in this target group. The aim of this study was to assess bread consumption among women prior to and during pregnancy with the intent to estimate periconceptional folic acid intakes that would be derived from bread if mandatory fortification were implemented as currently proposed. Methods A retrospective survey of 723 postpartum women in hospitals and birthing centres across New Zealand was conducted using a self-administered questionnaire on bread intake prior to and during pregnancy and maternal socio-demographic and obstetric characteristics. Results Median bread intake before conception (2 slices/d) was below that of previous data upon which the current fortification proposal was modeled (3-4 slices/d). If mandatory fortification is implemented as proposed, only 31% (95% CI = 24%-37%) of childbearing-age women would attain an additional folic acid intake of ≥ 140 μg/d, with a mean of 119 μg/d (95% CI = 107 μg/d-130 μg/d). Based on these data, a fortification level of 160 μg/100 g bread is required to achieve the targeted mean of 140 μg folic acid/d. Nonetheless, under the current proposal additional folic acid intakes would be greatest among the least advantaged segments of the target population: Pacific and indigenous Māori ethnic groups; those with increased parity, lower income and education; younger and single mothers; and women with unplanned pregnancies. Subgroups predicted to derive less than adequate folic acid intakes from the proposed policy were women of Asian descent and those with a postgraduate education. Conclusions This study provides insight on the ability of a fortification policy to benefit the groups at highest risk of poor folate intakes in a population. However, bread consumption among the target group of childbearing women appears to have declined since the data used in previous dietary modeling were collected. Thus, it seems prudent to re-model dietary folic acid intakes based on more recent national survey data prior to the implementation of a mandatory folic acid fortification policy.</p

GRaNIE and GRaNPA: inference and evaluation of enhancer-mediated gene regulatory networks

Enhancers play a vital role in gene regulation and are critical in mediating the impact of noncoding genetic variants associated with complex traits. Enhancer activity is a cell-type-specific process regulated by transcription factors (TFs), epigenetic mechanisms and genetic variants. Despite the strong mechanistic link between TFs and enhancers, we currently lack a framework for jointly analysing them in cell-type-specific gene regulatory networks (GRN). Equally important, we lack an unbiased way of assessing the biological significance of inferred GRNs since no complete ground truth exists. To address these gaps, we present GRaNIE (Gene Regulatory Network Inference including Enhancers) and GRaNPA (Gene Regulatory Network Performance Analysis). GRaNIE (https://git.embl.de/grp-zaugg/GR aNIE) builds enhancer-mediated GRNs based on covariation of chromatin accessibility and RNA-seq across samples (e.g. individuals), while GRaNPA (https://git.embl.de/grp-zaugg/GRaNPA) assesses the performance of GRNs for predicting cell-type-specific differential expression. We demonstrate their power by investigating gene regulatory mechanisms underlying the response of macrophages to infection, cancer and common genetic traits including autoimmune diseases. Finally, our methods identify the TF PURA as a putative regulator of pro-inflammatory macrophage polarisation