Autoinsertion of soluble oligomers of Alzheimer's Aβ(1–42) peptide into cholesterol-containing membranes is accompanied by relocation of the sterol towards the bilayer surface

BACKGROUND: Soluble Alzheimer's Aβ oligomers autoinsert into neuronal cell membranes, contributing to the pathology of Alzheimer's Disease (AD), and elevated serum cholesterol is a risk factor for AD, but the reason is unknown. We investigated potential connections between these two observations at the membrane level by testing the hypothesis that Aβ(1–42) relocates membrane cholesterol. RESULTS: Oligomers of Aβ(1–42), but not the monomeric peptide, inserted into cholesterol-containing phosphatidylcholine monolayers with an anomalously low molecular insertion area, suggesting concurrent lipid rearrangement. Membrane neutron diffraction, including isomorphous replacement of specific lipid hydrogens with highly-scattering deuterium, showed that Aβ(1–42) insertion was accompanied by outward displacement of membrane cholesterol, towards the polar surfaces of the bilayer. Changes in the generalised polarisation of laurdan confirmed that the structural changes were associated with a functional alteration in membrane lipid order. CONCLUSION: Cholesterol is known to regulate membrane lipid order, and this can affect a wide range of membrane mechanisms, including intercellular signalling. Previously unrecognised Aβ-dependent rearrangement of the membrane sterol could have an important role in AD

Signet-Ring Cell Carcinoma Arising in the Gastric Stump After Duodenopancreatectomy for Ductal Adenocarcinoma of the Pancreas: A Case Report

The development of malignancy in the gastric stump following surgery for peptic ulcer disease is well recognized. There are also few reports on carcinomas occurring after surgery for malignant gastric disease. However, carcinoma of the gastric stump after duodenopancreatectomy is extremely rare. We describe what we believe to be an unusual case of signet-ring cell carcinoma of the gastric stump developing at the anastomotic site 5 years after duodenopancreatectomy for ductal adenocarcinoma of the pancreatic head. We performed remnant gastrectomy and Roux-en-Y gastrojejunostomy as a curative resection. This experience clearly underlies that g astric stump carcinoma (GSC) may mimic metastatic disease recurrence leading to diagnostic confusion after surgery for malignancy. Although an increased risk of gastric stump carcinoma after pancreatoduodenectomy for pancreatic cancer has not been established, the possibility of such a complication should be kept in mind when evaluating patients after gastric resection who present with symptoms of metastatic disease recurrence years after the primary operation. Investigations should be independent of the entity of the primary disease or its localization, since GSC may well be amenable to surgical cure as demonstrated in the presented case. Outpatient follow up results of the last four years indicated no recurrence in this case

Nitrogen fixation rates in the Guinea Dome and the equatorial upwelling regions in the Atlantic Ocean

Biological nitrogen fixation is a key process balancing the loss of combined nitrogen in the marine nitrogen cycle. Its relevance in upwelling or high nutrient regions is still unclear, with the few available studies in these regions of the ocean reporting rates that vary widely from below detection limit to > 100 nmol N L−1 d−1. In the eastern tropical Atlantic Ocean, two open ocean upwelling systems are active in boreal summer. One is the seasonal equatorial upwelling, where the residual phosphorus associated with aged upwelled waters is suggested to enhance nitrogen fixation in this season. The other is the Guinea Dome, a thermal upwelling dome. We conducted two surveys along 23° W across the Guinea Dome and the Equator from 15° N to 5° S in September 2015 and August–September 2016 with high latitudinal resolution (20–60 nm between stations). The abundance of Trichodesmium colonies was characterized by an Underwater Vision Profiler 5 and the total biological nitrogen fixation in the euphotic layer was measured using the 15N2 technique. The highest abundances of Trichodesmium colonies were found in the area of the Guinea Dome (9°–15° N) with a maximum of 3 colonies L−1 near the surface. By contrast, colonies were almost absent in the Equatorial band between 2° N and 5° S. The highest nitrogen fixation rate was measured at the northern edge of the Guinea Dome in 2016 (ca. 31 nmol N L−1 d−1). In this region, where diazotrophs thrived on a sufficient supply of both phosphorus and iron, a patchy distribution was unveiled by our increased spatial resolution scheme. In the Equatorial band, rates were considerably lower, ranging from below detection limit to ca. 4 nmol N L−1 d−1, with a clear difference in magnitude between 2015 (rates close to zero) and 2016 (average rates around 2 nmol N L−1 d−1). This difference seemed triggered by a contrasting supply of phosphorus between years. Our study stresses the importance of surveys with sampling at fine-scale spatial resolution, and shows unexpected high variability in the rates of nitrogen fixation in the Guinea Dome, a region where diazotrophy is a significant process supplying new nitrogen into the euphotic layer.publishedVersio

Advanced radiometric and interferometric milimeter-wave scene simulations

Smart munitions and weapons utilize various imaging sensors (including passive IR, active and passive millimeter-wave, and visible wavebands) to detect/identify targets at short standoff ranges and in varied terrain backgrounds. In order to design and evaluate these sensors under a variety of conditions, a high-fidelity scene simulation capability is necessary. Such a capability for passive millimeter-wave scene simulation exists at TRW. TRW's Advanced Radiometric Millimeter-Wave Scene Simulation (ARMSS) code is a rigorous, benchmarked, end-to-end passive millimeter-wave scene simulation code for interpreting millimeter-wave data, establishing scene signatures and evaluating sensor performance. In passive millimeter-wave imaging, resolution is limited due to wavelength and aperture size. Where high resolution is required, the utility of passive millimeter-wave imaging is confined to short ranges. Recent developments in interferometry have made possible high resolution applications on military platforms. Interferometry or synthetic aperture radiometry allows the creation of a high resolution image with a sparsely filled aperture. Borrowing from research work in radio astronomy, we have developed and tested at TRW scene reconstruction algorithms that allow the recovery of the scene from a relatively small number of spatial frequency components. In this paper, the TRW modeling capability is described and numerical results are presented

Presentation of the ERFB Bitumenized Waste Drum Retrieval Facility

The bitumenized waste drum facility (ERFB) is built on the Marcoule site and is intended to handle the historic bitumenized waste of the site, that were conditioned in metallic drums. The purpose of the facility is to retrieve the drums stored in pits, condition them in stainless steel overpacks and produce packages ready to be shipped to the multipurpose interim storage (EIP) facility. The ERBF includes a mobile frame structure capable to shift from one pit to another. It is used to recover drums and characterizes them (weight, radiological properties, etc.) and to repack them according to their state. The first operation results are provided

Oxygen Utilization and Downward Carbon Flux in an Oxygen-Depleted Eddy in the Eastern Tropical North Atlantic

The occurrence of mesoscale eddies that develop suboxic environments at shallow depth (about 40–100 m) has recently been reported for the eastern tropical North Atlantic (ETNA). Their hydrographic structure suggests that the water mass inside the eddy is well isolated from ambient waters supporting the development of severe near-surface oxygen deficits. So far, hydrographic and biogeochemical characterization of these eddies was limited to a few autonomous surveys, with the use of moorings, underwater gliders and profiling floats. In this study we present results from the first dedicated biogeochemical survey of one of these eddies conducted in March 2014 near the Cape Verde Ocean Observatory (CVOO). During the survey the eddy core showed oxygen concentrations as low as 5 µmol kg−1 with a pH of around 7.6 at approximately 100 m depth. Correspondingly, the aragonite saturation level dropped to 1 at the same depth, thereby creating unfavorable conditions for calcifying organisms. To our knowledge, such enhanced acidity within near-surface waters has never been reported before for the open Atlantic Ocean. Vertical distributions of particulate organic matter and dissolved organic matter (POM and DOM), generally showed elevated concentrations in the surface mixed layer (0–70 m), with DOM also accumulating beneath the oxygen minimum. With the use of reference data from the upwelling region where these eddies are formed, the oxygen utilization rate was calculated by determining oxygen consumption through the remineralization of organic matter. Inside the core, we found these rates were almost 1 order of magnitude higher (apparent oxygen utilization rate (aOUR); 0.26 µmol kg−1 day−1) than typical values for the open North Atlantic. Computed downward fluxes for particulate organic carbon (POC), were around 0.19 to 0.23 g C m−2 day−1 at 100 m depth, clearly exceeding fluxes typical for an oligotrophic open-ocean setting. The observations support the view that the oxygen-depleted eddies can be viewed as isolated, westwards propagating upwelling systems of their own, thereby represent re-occurring alien biogeochemical environments in the ETNA

"Drop in" gastroscopy outpatient clinic - experience after 9 months

<p>Abstract</p> <p>Background</p> <p>Logistics handling referrals for gastroscopy may be more time consuming than the examination itself. For the patient, "drop in" gastroscopy may reduce uncertainty, inadequate therapy and time off work.</p> <p>Methods</p> <p>After an 8-9 month run-in period we asked patients, hospital staff and GPs to fill in a questionnaire to evaluate their experience with "drop in" gastroscopy and gastroscopy by appointment, respectively. The diagnostic gain was evaluated.</p> <p>Results</p> <p>112 patients had "drop in" gastroscopy and 101 gastroscopy by appointment. The number of "drop in" patients varied between 3 and 12 per day (mean 6.5). Mean time from first GP consultation to gastroscopy was 3.6 weeks in the "drop in" group and 14 weeks in the appointment group. The half-yearly number of outpatient gastroscopies increased from 696 before introducing "drop in" to 1022 after (47% increase) and the proportion of examinations with pathological findings increased from 42% to 58%. Patients and GPs expressed great satisfaction with "drop in". Hospital staff also acclaimed although it caused more unpredictable working days with no additional staff.</p> <p>Conclusions</p> <p>"Drop in" gastroscopy was introduced without increase in staff. The observed increase in gastroscopies was paralleled by a similar increase in pathological findings without any apparent disadvantages for other groups of patients. This should legitimise "drop in" outpatient gastroscopies, but it requires meticulous observation of possible unwanted effects when implemented.</p

Spectral properties of interacting magnetoelectric particles

The linear magnetoelectric (ME) effect provides a special route for linking magnetic and electric properties. In microwaves, a local ME effect appears due to the dynamical symmetry breakings of magnetic-dipolar modes (MDMs) in a ferrite disk particle. The fact that for MDMs in a ferrite disk one has evident both classical and quantum-like attributes, puts special demands on the methods used for study of interacting ME particles. A proper model for coupled particles should be based on the spectral characteristics of MDM oscillations and an analysis of the overlap integrals for interacting eigen oscillating ME elements. In this paper, we present theoretical studies of spectral properties of literally coupled of MDM ME disks. We show that there exists the "exchange" mechanism of interaction between the particles, which is distinctive from the magnetostatic interaction between magnetic dipoles. The spectral method proposed in this paper may further the development of a theory of ME "molecules" and realization of local ME composites.Comment: 26 pages, 3 figure

Synthesis, structural characterization, antimicrobial and cytotoxic effects of aziridine, 2-aminoethylaziridine and azirine complexes of copper(II) and palladium(II).

The synthesis, spectroscopic and X-ray structural characterization of copper(II) and palladium(II) complexes with aziridine ligands as 2-dimethylaziridine HNCH2CMe2 (a), the bidentate N-(2-aminoethyl)aziridines C2H4NC2H4NH2 (b) or CH2CMe2NCH2CMe2NH2 (c) as well as the unsaturated azirine NCH2CPh (d) are reported. Cleavage of the cyclometallated Pd(II) dimer [μ-Cl(C6H4CHMeNMe2-C,N)Pd]2 with ligand a yielded compound [Cl(NHCH2CMe2)(C6H4CHMe2NMe2-C,N)Pd] (1a). The reaction of the aziridine complex trans-[Cl2Pd(HNC2H4)2] with an excess of aziridine in the presence of AgOTf gave the ionic chelate complex trans-[(C2H4NC2H4NH2-N,N′)2Pd](OTf)2 (2b) which contains the new ligand b formed by an unexpected insertion and ring opening reaction of two aziridines (“aziridine dimerization”). CuCl2 reacted in pure HNC2H4 or HNCH2CMe2 (b) again by “dimerization” to give the tris-chelated ionic complex [Cu(C2H4NC2H4NH2-N,N′)3]Cl2 (3b) or the bis-chelated complex [CuCl(C2H2Me2NC2H2Me2NH2-N,N′)2]Cl (4c). By addition of 2H-3-phenylazirine (d) to PdCl2, trans-[Cl2Pd(NCH2CPh)2] (5d) was formed. All new compounds were characterized by NMR, IR and mass spectra and also by X-ray structure analyses (except 3b). Additionally the cytotoxic effects of these complexes were examined on HL-60 and NALM-6 human leukemia cells and melanoma WM-115 cells. The antimicrobial activity was also determined. The growth of Gram-positive bacterial strains (S. aureus, S. epidermidis, E. faecalis) was inhibited by almost all tested complexes at the concentrations of 37.5–300.0 μg mL−1. However, MIC values of complexes obtained for Gram-negative E. coli and P. aeruginosa, as well as for C. albicans yeast, mostly exceeded 300 μg mL−1. The highest antibacterial activity was achieved by complexes 1a and 2b. Complex 2b also inhibited the growth of Gram-negative bacteria. Graphical abstract: Synthesis, structural characterization, antimicrobial and cytotoxic effects of aziridine, 2-aminoethylaziridine and azirine complexes of copper(ii) and palladium(ii