High sensitivity, contemporary and point-of-care cardiac troponin assays: educational aids developed by the IFCC Committee on Clinical Application of Cardiac Bio-Markers.

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) formed a Task Force on the Application of Cardiac Bio-markers (TF-CB) in 2008, re-designated in 2018 as a committee (C-CB), to produce educational materials on cardiac biomarkers. Established in June 2017, definitive tables covering the majority of high-sensitivity, contemporary and point-of-care (POC) cTn assays have been developed by the C-CB and are available on the IFCC website. These tables provide extensive information about assays' analytical characteristics and encompass information on diagnostic discriminants, particularly the 99th percentiles, as provided by the manufacturers

Obtaining reliable source locations with time reverse imaging: limits to array design, velocity models and signal-to-noise ratios

Time reverse imaging (TRI) is evolving into a standard technique for locating and characterising seismic events. In recent years, TRI has been employed for a wide range of applications from the lab scale, to the field scale and up to the global scale. No identification of events or their onset times is necessary when locating events with TRI; therefore, it is especially suited for locating quasi-simultaneous events and events with a low signal-to-noise ratio. However, in contrast to more regularly applied localisation methods, the prerequisites for applying TRI are not sufficiently known.To investigate the significance of station distributions, complex velocity models and signal-to-noise ratios with respect to location accuracy, numerous simulations were performed using a finite difference code to propagate elastic waves through three-dimensional models. Synthetic seismograms were reversed in time and reinserted into the model. The time-reversed wave field back propagates through the model and, in theory, focuses at the source location. This focusing was visualised using imaging conditions. Additionally, artificial focusing spots were removed using an illumination map specific to the set-up. Successful locations were sorted into four categories depending on their reliability. Consequently, individual simulation set-ups could be evaluated by their ability to produce reliable source locations.Optimal inter-station distances, minimum apertures, relations between the array and source locations, heterogeneities of inter-station distances and the total number of stations were investigated for different source depths and source types. Additionally, the accuracy of the locations was analysed when using a complex velocity model or a low signal-to-noise ratio.Finally, an array in southern California was investigated regarding its ability to locate seismic events at specific target depths while using the actual velocity model for that region. In addition, the success rate with recorded data was estimated.Knowledge about the prerequisites for using TRI enables the estimation of success rates for a given problem. Furthermore, it reduces the time needed to adjust stations to achieve more reliable locations and provides a foundation for designing arrays for applying TRI.</p

Free and smooth boundaries in 2-D finite-difference schemes for transient elastic waves

A method is proposed for accurately describing arbitrary-shaped free boundaries in single-grid finite-difference schemes for elastodynamics, in a time-domain velocity-stress framework. The basic idea is as follows: fictitious values of the solution are built in vacuum, and injected into the numerical integration scheme near boundaries. The most original feature of this method is the way in which these fictitious values are calculated. They are based on boundary conditions and compatibility conditions satisfied by the successive spatial derivatives of the solution, up to a given order that depends on the spatial accuracy of the integration scheme adopted. Since the work is mostly done during the preprocessing step, the extra computational cost is negligible. Stress-free conditions can be designed at any arbitrary order without any numerical instability, as numerically checked. Using 10 grid nodes per minimal S-wavelength with a propagation distance of 50 wavelengths yields highly accurate results. With 5 grid nodes per minimal S-wavelength, the solution is less accurate but still acceptable. A subcell resolution of the boundary inside the Cartesian meshing is obtained, and the spurious diffractions induced by staircase descriptions of boundaries are avoided. Contrary to what occurs with the vacuum method, the quality of the numerical solution obtained with this method is almost independent of the angle between the free boundary and the Cartesian meshing.Comment: accepted and to be published in Geophys. J. In

Bubble generation in a twisted and bent DNA-like model

The DNA molecule is modeled by a parabola embedded chain with long-range interactions between twisted base pair dipoles. A mechanism for bubble generation is presented and investigated in two different configurations. Using random normally distributed initial conditions to simulate thermal fluctuations, a relationship between bubble generation, twist and curvature is established. An analytical approach supports the numerical results.Comment: 7 pages, 8 figures. Accepted for Phys. Rev. E (in press

Streptococcus pyogenes pSM19035 requires dynamic assembly of ATP-bound ParA and ParB on parS DNA during plasmid segregation

The accurate partitioning of Firmicute plasmid pSM19035 at cell division depends on ATP binding and hydrolysis by homodimeric ATPase δ2 (ParA) and binding of ω2 (ParB) to its cognate parS DNA. The 1.83 Å resolution crystal structure of δ2 in a complex with non-hydrolyzable ATPγS reveals a unique ParA dimer assembly that permits nucleotide exchange without requiring dissociation into monomers. In vitro, δ2 had minimal ATPase activity in the absence of ω2 and parS DNA. However, stoichiometric amounts of ω2 and parS DNA stimulated the δ2 ATPase activity and mediated plasmid pairing, whereas at high (4:1) ω2 : δ2 ratios, stimulation of the ATPase activity was reduced and δ2 polymerized onto DNA. Stimulation of the δ2 ATPase activity and its polymerization on DNA required ability of ω2 to bind parS DNA and its N-terminus. In vivo experiments showed that δ2 alone associated with the nucleoid, and in the presence of ω2 and parS DNA, δ2 oscillated between the nucleoid and the cell poles and formed spiral-like structures. Our studies indicate that the molar ω2 : δ2 ratio regulates the polymerization properties of (δ•ATP•Mg2+)2 on and depolymerization from parS DNA, thereby controlling the temporal and spatial segregation of pSM19035 before cell division

Changes in Local S4 Environment Provide a Voltage-sensing Mechanism for Mammalian Hyperpolarization–activated HCN Channels

The positively charged S4 transmembrane segment of voltage-gated channels is thought to function as the voltage sensor by moving charge through the membrane electric field in response to depolarization. Here we studied S4 movements in the mammalian HCN pacemaker channels. Unlike most voltage-gated channel family members that are activated by depolarization, HCN channels are activated by hyperpolarization. We determined the reactivity of the charged sulfhydryl-modifying reagent, MTSET, with substituted cysteine (Cys) residues along the HCN1 S4 segment. Using an HCN1 channel engineered to be MTS resistant except for the chosen S4 Cys substitution, we determined the reactivity of 12 S4 residues to external or internal MTSET application in either the closed or open state of the channel. Cys substitutions in the NH2-terminal half of S4 only reacted with external MTSET; the rates of reactivity were rapid, regardless of whether the channel was open or closed. In contrast, Cys substitutions in the COOH-terminal half of S4 selectively reacted with internal MTSET when the channel was open. In the open state, the boundary between externally and internally accessible residues was remarkably narrow (∼3 residues). This suggests that S4 lies in a water-filled gating canal with a very narrow barrier between the external and internal solutions, similar to depolarization-gated channels. However, the pattern of reactivity is incompatible with either classical gating models, which postulate a large translational or rotational movement of S4 within a gating canal, or with a recent model in which S4 forms a peripheral voltage-sensing paddle (with S3b) that moves within the lipid bilayer (the KvAP model). Rather, we suggest that voltage sensing is due to a rearrangement in transmembrane segments surrounding S4, leading to a collapse of an internal gating canal upon channel closure that alters the shape of the membrane field around a relatively static S4 segment

Tropical sea surface temperatures for the past four centuries reconstructed from coral archives

Most annually resolved climate reconstructions of the Common Era are based on terrestrial data, making it a challenge to independently assess how recent climate changes have affected the oceans. Here as part of the Past Global Changes Ocean2K project, we present four regionally calibrated and validated reconstructions of sea surface temperatures in the tropics, based on 57 published and publicly archived marine paleoclimate data sets derived exclusively from tropical coral archives. Validation exercises suggest that our reconstructions are interpretable for much of the past 400 years, depending on the availability of paleoclimate data within, and the reconstruction validation statistics for, each target region. Analysis of the trends in the data suggests that the Indian, western Pacific, and western Atlantic Ocean regions were cooling until modern warming began around the 1830s. The early 1800s were an exceptionally cool period in the Indo-Pacific region, likely due to multiple large tropical volcanic eruptions occurring in the early nineteenth century. Decadal-scale variability is a quasi-persistent feature of all basins. Twentieth century warming associated with greenhouse gas emissions is apparent in the Indian, West Pacific, and western Atlantic Oceans, but we find no evidence that either natural or anthropogenic forcings have altered El Ni ˜no–Southern Oscillation-related variance in tropical sea surface temperatures. Our marine-based regional paleoclimate reconstructions serve as benchmarks against which terrestrial reconstructions as well as climate model simulations can be compared and as a basis for studying the processes by which the tropical oceans mediate climate variability and change

Self-energy limited ion transport in sub-nanometer channels

The current-voltage characteristics of the alpha-Hemolysin protein pore during the passage of single-stranded DNA under varying ionic strength, C, are studied experimentally. We observe strong blockage of the current, weak super-linear growth of the current as a function of voltage, and a minimum of the current as a function of C. These observations are interpreted as the result of the ion electrostatic self-energy barrier originating from the large difference in the dielectric constants of water and the lipid bilayer. The dependence of DNA capture rate on C also agrees with our model.Comment: more experimental material is added. 4 pages, 7 figure

Statistical Mechanics of Torque Induced Denaturation of DNA

A unifying theory of the denaturation transition of DNA, driven by temperature T or induced by an external mechanical torque Gamma is presented. Our model couples the hydrogen-bond opening and the untwisting of the helicoidal molecular structure. We show that denaturation corresponds to a first-order phase transition from B-DNA to d-DNA phases and that the coexistence region is naturally parametrized by the degree of supercoiling sigma. The denaturation free energy, the temperature dependence of the twist angle, the phase diagram in the T,Gamma plane and isotherms in the sigma, Gamma plane are calculated and show a good agreement with experimental data.Comment: 5 pages, 3 figures, model improve