Glacial thermohaline circulation states of the northern Atlantic: The compatibility of modelling and observations

We present 3He data froma repeat section across Drake Passage, fromthree sections off the South American continent in the Pacific, at 28?S, 35?S, and 43?S, and fromthree sections in the Atlantic, eastward of the Malvinas, close to 35?W, and near the Greenwich Meridian. In Drake Passage, a distinct high-3He signal is observed that is centered just above the boundary of the Lower and the Upper Circumpolar Deep Water (LCDW, UCDW), and is concentrated towards the northern continental slope. 3He concentrations in the Antarctic Circumpolar Current (ACC) upstream of Drake Passage (World Ocean Circulation Experiment section P19 at 88?W) are markedly lower than those found in Drake Passage, and a regional source of primordial helium in the path of the ACC that might cause the high-3He feature can be ruled out. We explain the feature by addition of high-3He waters present at the 43?S Pacific section. This supports a previous, similar interpretation of a low-salinity anomaly in Drake Passage (Naveira Garabato et al., Deep- Sea Research I 49 (2002) 681), that is strongly related to the high-3He feature. Employing multiparameter water mass analysis (including 3He as a parameter), we find that deep waters as met at the 43?S Pacific section, flowing south along the South American continental slope, contribute substantially to the ACC waters in Drake Passage (fractions exceed 50% locally). Lesser, but laterally more extended contributions are found east of the Malvinas, and still smaller ones are present at 35?W and at the Greenwich Meridian. Using velocity measurements from one of the two Drake Passage sections, we estimate the volume transport of these waters to be 7.071.2 Sv, but the average transport may be somewhat lower as the other realization had a less pronounced signal. The enhanced 3He signature in Drake Passage is essentially confined north of the Polar Front. Further downstreamthe signature crosses this front, to the extent that at 35?W the contributions south and north of it are of similar magnitude. At the same time, the 3He levels north of the front are reduced due to a substantial admixture of low-3He North Atlantic Deep Water, such that 3He becomes highest south of the front. The flow of Southeast Pacific deep slope waters entering the ACC constitutes the predominant exit pathway of the primordial helium released in the deep Pacific, and represents a considerable fraction of the deep water return flow fromthe Pacific into the ACC. Therefore and also because the density range of the added deep slope waters is intermediate between those of UCDW and LCDW, they must be considered a distinct water mass. r 2003 Elsevier Ltd. All rights reserved

Telemonitoring after discharge from hospital with heart failure: cost-effectiveness modelling of alternative service designs.

Objectives To estimate the cost-effectiveness of remote monitoring strategies versus usual care for adults recently discharged after a heart failure (HF) exacerbation. Design Decision analysis modelling of cost-effectiveness using secondary data sources. Setting Acute hospitals in the UK. Patients Patients recently discharged (within 28 days) after a HF exacerbation. Interventions Structured telephone support (STS) via human to machine (STS HM) interface, (2) STS via human to human (STS HH) contact and (3) home telemonitoring (TM), compared with (4) usual care. Main outcome measures The incremental cost per quality-adjusted life year (QALY) gained by each strategy compared to the next most effective alternative and the probability of each strategy being cost-effective at varying willingness to pay per QALY gained. Results TM was the most cost-effective strategy in the scenario using these base case costs. Compared with usual care, TM had an estimated incremental cost effectiveness ratio (ICER) of £11 873/QALY, whereas STS HH had an ICER of £228 035/QALY against TM. STS HM was dominated by usual care. Threshold analysis suggested that the monthly cost of TM has to be higher than £390 to have an ICER greater than £20 000/QALY against STS HH. Scenario analyses performed using higher costs of usual care, higher costs of STS HH and lower costs of TM do not substantially change the conclusions. Conclusions Cost-effectiveness analyses suggest that TM was an optimal strategy in most scenarios, but there is considerable uncertainty in relation to clear descriptions of the interventions and robust estimation of costs

Nanozyme-amplified lateral flow immunoassay for molecular signature detection of cardiovascular diseases

Point-of-care (PoC) devices offer the opportunity to decentralize the analysis of biomarkers in biological fluids thus providing patients with more personalized medicine. The golden standard of PoC platforms are lateral flow assays since they are low cost, quick to perform and user-friendly [1]. Here we show the use of a nanozyme-mediated signal readout on a multiplexed PoC lateral flow immunoassay for the diagnosis of cardiovascular diseases. Our aim has been to expand the application of this ultrasensitive detection method towards the development of a multiplexed PoC assay for cardiovascular-related biomarkers to support triage of myocardial injury

Self-assembled 2D Free-Standing Janus Nanosheets with Single-Layer Thickness

We report the thermodynamically controlled growth of solution-processable and free-standing nanosheets via peptide assembly in two dimensions. By taking advantage of self-sorting between peptide β-strands and hydrocarbon chains, we have demonstrated the formation of Janus 2D structures with single-layer thickness, which enable a predetermined surface heterofunctionalization. A controlled 2D-to-1D morphological transition was achieved by subtly adjusting the intermolecular forces. These nanosheets provide an ideal substrate for the engineering of guest components (e.g., proteins and nanoparticles), where enhanced enzyme activity was observed. We anticipate that sequence-specific programmed peptides will offer promise as design elements for 2D assemblies with face-selective functionalization

Employing defined bioconjugates to generate chemically functionalised gold nanoparticles for in vitro diagnostic applications

Novel methods for introducing chemical and biological functionality to the surface of gold nanoparticles serve to increase the utility of this class of nanomaterials across a range of applications. To date, methods for functionalising gold surfaces have relied upon uncontrollable non-specific adsorption, bespoke chemical linkers, or non-generalisable protein–protein interactions. Herein we report a versatile method for introducing functionality to gold nanoparticles by exploiting the strong interaction between chemically functionalised bovine serum albumin (f-BSA) and citrate-capped gold nanoparticles (AuNPs). We establish the generalisability of the method by introducing a variety of functionalities to gold nanoparticles using cheap, commercially available chemical linkers. The utility of this approach is further demonstrated through the conjugation of the monoclonal antibody Ontruzant to f-BSA–AuNPs using inverse electron-demand Diels–Alder (iEDDA) click chemistry, a hitherto unexplored chemistry for AuNP–IgG conjugation. Finally, we show that the AuNP–Ontruzant particles generated via f-BSA–AuNPs have a greater affinity for their target in a lateral flow format when compared to conventional physisorption, highlighting the potential of this technology for producing sensitive diagnostic tests

Design of Lipid-Based Nanocarriers via Cation Modulation of Ethanol-Interdigitated Lipid Membranes

Short-chain alcohols (i.e., ethanol) can induce membrane interdigitation in saturated-chain phosphatidylcholines (PCs). In this process, alcohol molecules intercalate between phosphate heads, increasing lateral separation and favoring hydrophobic interactions between opposing acyl chains, which interpenetrate forming an interdigitated phase. Unraveling mechanisms underlying the interactions between ethanol and model lipid membranes has implications for cell biology, biochemistry, and for the formulation of lipid-based nanocarriers. However, investigations of ethanol–lipid membrane systems have been carried out in deionized water, which limits their applicability. Here, using a combination of small- and wide-angle X-ray scattering, small-angle neutron scattering, and all-atom molecular dynamics simulations, we analyzed the effect of varying CaCl2 and NaCl concentrations on ethanol-induced interdigitation. We observed that while ethanol addition leads to the interdigitation of bulk phase 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers in the presence of CaCl2 and NaCl regardless of the salt concentration, the ethanol-induced interdigitation of vesicular DPPC depends on the choice of cation and its concentration. These findings unravel a key role for cations in the ethanol-induced interdigitation of lipid membranes in either bulk phase or vesicular form

Phytoestrogens

Collectively, plants contain several different families of natural products among which are compounds with weak estrogenic or antiestrogenic activity toward mammals. These compounds, termed phytoestrogens, include certain isoflavonoids, flavonoids, stilbenes, and lignans. The best-studied dietary phytoestrogens are the soy isoflavones and the flaxseed lignans. Their perceived health beneficial properties extend beyond hormone-dependent breast and prostate cancers and osteoporosis to include cognitive function, cardiovascular disease, immunity and inflammation, and reproduction and fertility. In the future, metabolic engineering of plants could generate novel and exquisitely controlled dietary sources with which to better assess the potential health beneficial effects of phytoestrogens

Surface dynamics and ligand-core interactions of quantum sized photoluminescent gold nanoclusters

Quantum-sized metallic clusters protected by biological ligands represent a new class of luminescent materials; yet the understanding of structural information and photoluminescence origin of these ultrasmall clusters remains a challenge. Herein we systematically study the surface ligand dynamics and ligand–metal core interactions of peptide-protected gold nanoclusters (AuNCs) with combined experimental characterizations and theoretical molecular simulations. We show that the peptide sequence plays an important role in determining the surface peptide structuring, interfacial water dynamics and ligand–Au core interaction, which can be tailored by controlling peptide acetylation, constituent amino acid electron donating/withdrawing capacity, aromaticity/hydrophobicity and by adjusting environmental pH. Specifically, emission enhancement is achieved through increasing the electron density of surface ligands in proximity to the Au core, discouraging photoinduced quenching, and by reducing the amount of surface-bound water molecules. These findings provide key design principles for understanding the surface dynamics of peptide-protected nanoparticles and maximizing the photoluminescence of metallic clusters through the exploitation of biologically relevant ligand properties