Source‐to‐sink mass‐balance analysis of an ancient wave‐influenced sediment routing system: Middle Jurassic Brent Delta, Northern North Sea, offshore UK and Norway

Sediment mass-balance analysis provides key constraints on stratigraphic architecture and its controls. We use the data-rich Middle Jurassic Brent Delta sediment routing system in the proto-Viking Graben, Northern North Sea, to estimate sediment budgets and mass-balance between source areas and depositional sinks. Published studies are synthesised to provide an age-constrained sequence stratigraphic framework, consisting of four previously defined genetic sequences (J22, J24, J26, J32). Genetic sequence J32 (3.9 Myr) records transverse progradation of basin-margin deltas, sourced from the Shetland Platform to the west and Norwegian Landmass to the east. Genetic sequences J24 (1.1 Myr) and J26 (0.9 Myr) record the rapid progradation and subsequent aggradation of the Brent Delta along the basin axis, sourced from the uplifted Mid-North Sea High to the south, and the western and eastern source regions. Genetic sequence J32 (2.2 Myr) records the retreat of the Brent Delta. Sediment budgets for the four genetic sequences are estimated using palaeogeographical reconstructions, isopach maps, and sedimentological analysis of core and well-log data. The estimated net-depositional sediment budget for the mapped Brent Delta system is 2.0–2.8 Mt/year. Temporal variations in net-depositional sediment budget were driven by changes in tectonic boundary conditions, such as the onset of uplift before the deposition of genetic sequence J24. Over the same time period, the Shetland Platform, Norwegian Landmass and Mid-North Sea High source regions are estimated to have supplied 2.3–5.6, 5.0–14.1, and 2.8–9.4 Mt/year of sediment, respectively, using the BQART sediment load model and independent geometrical reconstruction of eroded volumes, which are constrained by isostatic uplift estimates based on the geochemistry of syn-depositional volcanic rocks. The net-depositional sediment budget in the sink is an order-of-magnitude smaller than the total sediment budget supplied by the source regions (13.9–23 Mt/year). This discrepancy suggests that along-shore transport by wave-generated currents into the coeval Faroe-Shetland Basin and/or down-dip transport by gravity flows into the coeval western Møre Basin played a key role in redistributing sediments away from the Brent Delta system

Four patients with a history of acute exacerbations of COPD: implementing the CHEST/Canadian Thoracic Society guidelines for preventing exacerbations

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Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

New structural analogues of curcumin exhibit potent growth suppressive activity in human colorectal carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Colorectal carcinoma is one of the major causes of morbidity and mortality in the Western World. Novel therapeutic approaches are needed for colorectal carcinoma. Curcumin, the active component and yellow pigment of turmeric, has been reported to have several anti-cancer activities including anti-proliferation, anti-invasion, and anti-angiogenesis. Clinical trials have suggested that curcumin may serve as a potential preventive or therapeutic agent for colorectal cancer.</p> <p>Methods</p> <p>We compared the inhibitory effects of curcumin and novel structural analogues, GO-Y030, FLLL-11, and FLLL-12, in three independent human colorectal cancer cell lines, SW480, HT-29, and HCT116. MTT cell viability assay was used to examine the cell viability/proliferation and western blots were used to determine the level of PARP cleavages. Half-Maximal inhibitory concentrations (IC₅₀) were calculated using Sigma Plot 9.0 software.</p> <p>Results</p> <p>Curcumin inhibited cell viability in all three of the human colorectal cancer cell lines studied with IC₅₀values ranging between 10.26 μM and 13.31 μM. GO-Y030, FLLL-11, and FLLL-12 were more potent than curcumin in the inhibition of cell viability in these three human colorectal cancer cell lines with IC₅₀values ranging between 0.51 μM and 4.48 μM. In addition, FLLL-11 and FLLL-12 exhibit low toxicity to WI-38 normal human lung fibroblasts with an IC-50 value greater than 1,000 μM. GO-Y030, FLLL-11, and FLLL-12 are also more potent than curcumin in the induction of apoptosis, as evidenced by cleaved PARP and cleaved caspase-3 in all three human colorectal cancer cell lines studied.</p> <p>Conclusion</p> <p>The results indicate that the three curcumin analogues studied exhibit more potent inhibitory activity than curcumin in human colorectal cancer cells. Thus, they may have translational potential as chemopreventive or therapeutic agents for colorectal carcinoma.</p

Perspective from a Younger Generation -- The Astro-Spectroscopy of Gisbert Winnewisser

Gisbert Winnewisser's astronomical career was practically coextensive with the whole development of molecular radio astronomy. Here I would like to pick out a few of his many contributions, which I, personally, find particularly interesting and put them in the context of newer results.Comment: 14 pages. (Co)authored by members of the MPIfR (Sub)millimeter Astronomy Group. To appear in the Proceedings of the 4th Cologne-Bonn-Zermatt-Symposium "The Dense Interstellar Medium in Galaxies" eds. S. Pfalzner, C. Kramer, C. Straubmeier, & A. Heithausen (Springer: Berlin

A pilot study for augmenting atomoxetine with methylphenidate: safety of concomitant therapy in children with attention-deficit/hyperactivity disorder

<p>Abstract</p> <p>Background</p> <p>This study examined augmenting atomoxetine with extended-release methylphenidate in children whose attention-deficit/hyperactivity disorder (ADHD) previously failed to respond adequately to stimulant medication.</p> <p>Methods</p> <p>Children with ADHD and prior stimulant treatment (<it>N </it>= 25) received atomoxetine (1.2 mg/kg/day) plus placebo. After 4 weeks, patients who were responders (<it>n </it>= 4) were continued on atomoxetine/placebo while remaining patients were randomly assigned to either methylphenidate (ATX/MPH) (1.1 mg/kg/day) or placebo augmentation (ATX/PB) for another 6 weeks. Patients and sites were blind to timing of active augmentation. Safety measures included vital signs, weight, and adverse events. Efficacy was assessed by ADHD rating scales.</p> <p>Results</p> <p>Categorical increases in vital signs occurred for 5 patients (3 patients in ATX/MPH, 2 patients in ATX/PBO). Sixteen percent discontinued the study due to AE, but no difference between augmentation groups. Atomoxetine treatment was efficacious on outcome measures (<it>P </it>≤ .001), but methylphenidate did not enhance response.</p> <p>Conclusion</p> <p>Methylphenidate appears to be safely combined with atomoxetine, but conclusions limited by small sample. With atomoxetine treatment, 43% of patients achieved normalization on ADHD ratings.</p

Global Gene Expression Profiling Of Human Pleural Mesotheliomas: Identification of Matrix Metalloproteinase 14 (MMP-14) as Potential Tumour Target

BACKGROUND:The goal of our study was to molecularly dissect mesothelioma tumour pathways by mean of microarray technologies in order to identify new tumour biomarkers that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets. METHODOLOGY:We performed Affymetrix HGU133A plus 2.0 microarray analysis, containing probes for about 39,000 human transcripts, comparing 9 human pleural mesotheliomas with 4 normal pleural specimens. Stringent statistical feature selection detected a set of differentially expressed genes that have been further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes, never associated before to mesotheliom that could be involved in tumour progression. Notable is the identification of MMP-14, a member of matrix metalloproteinase family. In a cohort of 70 mesothelioma patients, we found by a multivariate Cox regression analysis, that the only parameter influencing overall survival was expression of MMP14. The calculated relative risk of death in MM patients with low MMP14 expression was significantly lower than patients with high MMp14 expression (P = 0.002). CONCLUSIONS:Based on the results provided, this molecule could be viewed as a new and effective therapeutic target to test for the cure of mesothelioma

Repurposing a photosynthetic antenna protein as a super-resolution microscopy label

Techniques such as Stochastic Optical Reconstruction Microscopy (STORM) and Structured Illumination Microscopy (SIM) have increased the achievable resolution of optical imaging, but few fluorescent proteins are suitable for super-resolution microscopy, particularly in the far-red and near-infrared emission range. Here we demonstrate the applicability of CpcA, a subunit of the photosynthetic antenna complex in cyanobacteria, for STORM and SIM imaging. The periodicity and width of fabricated nanoarrays of CpcA, with a covalently attached phycoerythrobilin (PEB) or phycocyanobilin (PCB) chromophore, matched the lines in reconstructed STORM images. SIM and STORM reconstructions of Escherichia coli cells harbouring CpcA-labelled cytochrome bd 1 ubiquinol oxidase in the cytoplasmic membrane show that CpcA-PEB and CpcA-PCB are suitable for super-resolution imaging in vivo. The stability, ease of production, small size and brightness of CpcA-PEB and CpcA-PCB demonstrate the potential of this largely unexplored protein family as novel probes for super-resolution microscopy

Teacher resilience in adverse contexts: issues of professionalism and professional identity

Teacher resilience is a construct that is relative, developmental and dynamic; it is socially constructed and depends on personal and professional dispositions. Issues of commitment, professionalism, and professional identity, for instance, need to be taken into account if teacher resilience is to be fully understood. In this chapter I draw upon a larger piece of research aimed at investigating teachers’ work and lives in challenging circumstances. Data were collected through a national survey (n=2702 teachers), focus group (n=99 teachers) and interviews to 11 school principals. Findings suggest the connection between teacher commitment and resilience which are associated with issues of school culture and leadership, a sense of vocation, and teachers’ beliefs and professional values. Factors and sources of teacher motivation and resilience are also identified within a context marked by teacher intensification, lack of trust, worsening of teaching conditions, lower social and economic status and legislative “tsunami”. The chapter ends with the discussion of the importance of relationships in the teaching profession and issues of motivation and professionalism which entails given ways of being and feeling as a teacher.Financial Support by CIEC (Research Centre on Child Studies, IE, UMinho; FCT R&D unit 317, Portugal) by the Strategic Project UID/CED/00317/2013, with financial support of National Funds through the FCT (Foundation for Science and Technology) and co-financed by European Regional Development Funds (FEDER) through the COMPETE 2020 - Competitiveness and Internationalization Operational Program (POCI) with the reference POCI-01-0145-FEDER-00756