Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of Therapeutics for Heart Failure : Expedited Commentary

Despite significant advances in the treatment of chronic heart failure during the past 30 years, there is a broad consensus that new treatments are needed because morbidity and mortality in this disorder remain unacceptably high. Nevertheless, the development of new drugs for chronic heart failure has waned during the past 20 years; the quantity of novel agents in clinical testing and the number of welldesigned clinical trials have diminished to a small fraction of that seen in the 1980s and 1990s. Some have suggested that investment in heart failure has declined because the primary mechanisms of the disorder are poorly understood, because the promising results of phase II trials are frequently not confirmed in large-scale definitive studies, and because the large-scale clinical trials needed for regulatory approval have often become prohibitively expensive. We know that clinical research in heart failure is extremely challenging, and so we beg innovators in the pharmaceutical and device industries to be patient, and we plead with sponsors to invest in large-scale investigations because the need is so great. Yet, when we critically examine how we react to data, it may not be too surprising that meaningful clinical trials in heart failure are becoming increasingly scarce. Do cardiologists act as if the results of clinical trials in heart failure really matter?
An experimental study into the rheology of synthetic polycrystalline coesite aggregates

Coesite has been found as a relic in ultrahigh pressure metamorphic (UHPM) crust worldwide and is expected to play a major role in the mechanical behavior of continental crust at UHPM conditions. We performed triaxial compression tests on synthetic polycrystalline coesitite in a solid medium apparatus at confining pressures of 3.1 to 3.7 GPa, temperatures of 700° to ∼1160°C, and strain rates betweeen 6×10−7 and 1×10−3 s−1. The problem of the limited stress resolution of the solid medium apparatus was addressed by applying two extreme friction corrections that yield lower and upper bounds to the differential stress. The correlation between the mechanical data and the microstructural record of the deformed samples, as a function of temperature and imposed strain rate, is consistent with deformation by dislocation creep. We deduced parameters of a power law as n ≈ 3±1 and Q ≈ 275±50 kJ mol−1. Extrapolation of the experimental data to natural conditions cannot be constrained by comparison with natural microstructures, due to the lack of preserved coesite other than as single crystal inclusions. Nevertheless, the extrapolation indicates a low strength (of order 10 MPa) for natural strain rates at typical UHPM conditions. Absent deformation of the UHPM Brossasco granite (Dora Maira Massif, Western Alps) thus implies low stresses; deformation must have been localized in very weak shear zones during burial and exhumation.
Mixture Models With a Prior on the Number of Components

ABSTRACT A natural Bayesian approach for mixture models with an unknown number of components is to take the usual finite mixture model with symmetric Dirichlet weights, and put a prior on the number of components—that is, to use a mixture of finite mixtures (MFM). The most commonly used method of inference for MFMs is reversible jump Markov chain Monte Carlo, but it can be nontrivial to design good reversible jump moves, especially in high-dimensional spaces. Meanwhile, there are samplers for Dirichlet process mixture (DPM) models that are relatively simple and are easily adapted to new applications. It turns out that, in fact, many of the essential properties of DPMs are also exhibited by MFMs—an exchangeable partition distribution, restaurant process, random measure representation, and stick-breaking representation—and crucially, the MFM analogues are simple enough that they can be used much like the corresponding DPM properties. Consequently, many of the powerful methods developed for inference in DPMs can be directly applied to MFMs as well; this simplifies the implementation of MFMs and can substantially improve mixing. We illustrate with real and simulated data, including high-dimensional gene expression data used to discriminate cancer subtypes. Supplementary materials for this article are available online.
Mechanism-based inhibition of human persulfide dioxygenase by (cid:2) -glutamyl-homocysteinyl-glycine

Hydrogen sulfide (H 2 S) is a signaling molecule with many beneficial effects. However, its cellular concentration is strictly regulated to avoid toxicity. Persulfide dioxygenase (PDO or ETHE1) is a mononuclear non-heme iron–containing protein in the sulfide oxidation pathway catalyzing the conversion of GSH persulfide (GSSH) to sulfite and GSH. PDO mutations result in the autosomal-recessive disorder ethylmalonic encephalopathy (EE). Here, we developed (cid:2) -glutamyl-homocystei-nyl-glycine (GHcySH), in which the cysteinyl moiety in GSH is substituted with homocysteine, as a mechanism-based PDO inhibitor.HumanPDOusedGHcySHasanalternativesubstrate andconvertedittoGHcy-SO 2 H,mimickingGS-SO 2 H,theputa-tive oxygenated intermediate formed with the natural substrate. Because GHcy-SO 2 H contains a C–S bond rather than an S–S bond in GS-SO 2 H, it failed to undergo the final hydrolysis step in the catalytic cycle, leading to PDO inhibition. We also characterized
Sedimentology and budget of a Recent carbonate mound, Florida Keys

The sedimentology of a Recent carbonate mound is investigated to further our understanding of mound building communities, surface and subsurface mound sediments, and the overall sediment budget of mounds. Nine sedimentary facies of the surface of Tavernier mound, Florida Keys are described. These sediments are composed of Neogoniolithon, Halimeda, Porites, mollusc and foraminiferal grains, and lime mud. Muds rich in aragonite and high magnesian calcite show little mineralogical variation over the mound surface. Geochemical evidence suggests that the mud is mainly formed from breakdown of codiacean algae and Thalassia blade epibionts. Production rates of the facies are established from in situ growth rate experiments and standing-crop surveys. Annual calcium carbonate production is c. 500gm-2, intermediate between reef and other bay and lagoonal environment production rates in the Caribbean. The internal structure of the mound, studied from piston cores and sediment probes, indicates that seven facies can be identified. Five of these can be related to the present-day facies, and occur in the upper part of the mound (gravel-mound stage). The remaining two facies, characterized by molluscs and aragonite-rich muds, occur in the lower part of the mound (mud-mound stage), and are most similar to facies from typical Florida Bay mud mounds. Mangrove peats within the mound indicate former intertidal areas and C14 dates from these peats provide a time framework for mound sedimentation. The mound appears to have formed because of an initial valley in the Pleistocene surface which accumulated mud in a shallow embayment during the Holocene transgression. A sediment budget for the mound is presented which compares production rates from present-day facies with subsurface sediment masses. During the mud mound stage production rates were similar to accumulation rates and the mound was similar to the present-day mounds of Florida Bay. During the gravel mound stage (3400 yr BP-present day), conditions were more normal marine and the establishment of Porites and Neogoniolithon on the mound increased production rates 10% over accumulation rates. This excess sediment is thought to be transported off the mound to the surrounding seabed. Models are proposed which divide carbonate mounds on the basis of internal versus external sediment supply. Comparisons are made with other Recent and ancient mounds. Similarities exist between the roles of the biotic components of late Palaeozoic mounds but major differences are found when structures and early diagenesis are compared.
Decapod burrows in mangrove-channel and back-reef environments at the Atlantic Barrier Reef, Belize

Burrows of decapod crustaceans were investigated by in situ resin casting in various mangrove and back‐reef environments. Alpheid shrimps (A. floridanus and A. heterochaelis) were the most numerous burrowing shrimps in soft muddy sediments of mangrove channels. Their burrows consist either of a single U or a series of U's inhabited by a pair of shrimp or are Y‐shaped and inhabited by a single shrimp and a gobiid associate. Large mounds and deep funnels are produced by the thalassinidean Glypturus acanthochirus, both in bare sediments of mangrove channels and in back‐reef subtidal sediments. Their burrows consist of a spiral with several radiating branches leading to the surface and deeper blind chambers often filled with shell particles reaching to a depth of over 160 cm. The thalassinidean Neocallichirus grandimana inhabits the intertidal of protected back‐reef sands; it occupies shallow, mainly horizontal burrows. Corallia‐nassa longiventris, characteristic of coarse sediments of the intertidal and shal.
Objective air temperature mapping for the Iberian Peninsula using spatial interpolation and GIS

This study presents an objective mapping of monthly mean air temperature over the Iberian Peninsula using the spatial interpolation of climatological data. The research focuses on an interpolation method (multiple regression with residual correction) that combines statistical global analysis with a local interpolation (splines and inverse distance weighting). Geographical information (the independent variables) is used to predict air temperature (the dependent variable) through the regression relationship and to test several approaches. A comprehensive GIS implementation makes it possible to address many cartographic issues and to produce mean minimum, mean and mean maximum air temperature surfaces for the entire Iberian Peninsula. The spatial resolution of the maps is 200 m and their temporal resolution is monthly and annual. An associated error level obtained through validation tests with independent data is computed for each map. These validation tests show that the best results have an average R2 (mean of all months) of 0.91 (mean temperature), 0.87 (mean maximum temperature) and 0.83 (mean minimum temperature). When the objective is to map a large area, best results are obtained when the model uses all stations of the Iberian Peninsula together (general peninsular model) and not when using different local subsets (hydrographical basins regional models). However, when the objective is mapping a regional area, basin models produce better outcomes than the general model being applied to these regional areas. Copyright © 2007 Royal Meteorological Society
Mathematical Modeling of Water Flow for Irrigation in a Permeable Pipe of Elliptical Cross-section

An unsteady incompressible fully developed flow in a horizontal flexible and permeable annular pipe of elliptic cross-section under the action of gravity is studied. The solution is obtained through a homogenization method by employing a small scale separation parameter that approximates the pipe in the form of a series. The results in terms of velocity and pressure distributions and mass flow rate inside the pipe and through the pipe wall are presented and discussed. It is shown that the pipe thickness has no influence on the water flow through the pores. We also propose that for the efficient use of water for irrigation, the elliptical pipe should be laid in a vertical position.
Moisture equilibrium in the vertical in swelling soils. I. Basic theory

The classical methodology of the scalar potential is used to develop the theory of equilibrium moisture distribution in the vertical in swelling soils. In addition to the well-known moisture potential O and the gravitational potential -z (z being the vertical ordinate, taken positive downward), the total potential O includes a further component U, the overburden potential. It is shown that U = de/de [P(Zo) + ? zzo] (A) where e is the void ratio, 6 is the moisture ratio, P(zJ is the load (if any) at the surface z = z,, and y is the apparent wet specific gravity. The equilibrium condition that O be constant in depth reduces to a first-order differential equation, the solutions of which represent equilibrium moisture profiles. The singular solution e = ept for all z > zo (B) separates two distinct classes of non-singular solutions. ep, designated the pycnotatic point, is the moisture ratio at which a assumes its maximum value. Swelling soils satisfying certain conditions (which appear to be theoretically reasonable and agree with the data of soil physics and soil mechanics) possess one, and only one, pycnotatic point. In such soils, then, three distinct types of equilibrium profile occur: (i) Hydric profiles, for which the surface moisture ratio eo > ep. 6 decreases with increasing z, asymptotically approaching 8, at great depths. (ii) Pycnotaticprojiles, for which 8, = aP and equation (B) is satisfied. (iii) Xeric profiles, for which eo < ep. e increases with z, asymptotically approaching ep at great depths. The physical significance of this result is discussed with the aid of calculations for an illustrative example. The hydrology of swelling soils is entirely different in character from classical hydrological behaviour, which ignores the consequences of volume change. Contrary to a common notion, the effects of overburden potential manifest themselves right to the surface of the soil: it is not the magnitude of n, but that of dU/dz, which is important. The effect of swelling on the behaviour of the soil water may be crudely summarized as follows: Gravity operates completely in reverse to the expectations of classical theory in the 'normal' part of the hydric range; its effect diminishes to zero at the pycnotatic point; and it approaches classical behaviour at the dry end of the xeric range. Applications of the analysis to equilibrium states in hydrology and soil mechanics are treated in Part II. In later papers the concept of the overburden potential is applied to steady vertical flows and to infiltration in swelling soils.
Title: Cholinergic Modulation Shifts the Response of CA1 Pyramidal Cells to Depolarizing Ramps via 1 TRPM4 Channels with Potential Implications for Place Field Firing

1 TRPM4 Channels with Potential Implications for Place Field Firing 2 3 Abbreviated Title: Cholinergic Modulation Shifts the Response of CA1 Pyramidal Cells 4 5 Author Names and Affiliations: Crescent Combe, Carol Upchurch, Carmen C. Canavier* and Sonia 6 Gasparini* 7 Neuroscience Center of Excellence, and Department of Cell Biology and Anatomy, School of Medicine, 8 Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA 70112 9 10 * these authors jointly supervised this work 11 12 Corresponding author: Sonia Gasparini, Neuroscience Center, Louisiana State University Health 13 Sciences Center, New Orleans, 2020 Gravier St., New Orleans, LA 70112, sgaspa1@lsuhsc.edu 14
Static Response of Reinforced Soil Retaining Walls with Nonuniform Reinforcement

The structural response of reinforced-soil wall systems with more than one reinforcement type (nonuniform reinforcement) is investigated using a numerical approach. The selected reinforcement types and mechanical properties represent actual polyester geogrid and woven wire mesh products. The model walls are mainly of wrapped-face type and have different reinforcement lengths, arrangements, and stiffness values. Additional wall models with tiered and vertical gabion facings are included for comparison purposes. The numerical simulation of wall models has been carried out using a finite difference-based program and includes sequential construction of the wall and placement of reinforcement at uniform vertical spacing followed by a sloped surcharge. The wall lateral displacements and backcalculated lateral earth pressure coefficient behind the facing in all nonuniform reinforcement wall models show a clear dependence on relative stiffness values of reinforcement layers at different elevations. An equation is proposed that can be used to predict the maximum reinforcement load in nonuniform reinforced wrapped-face walls of given backfill types and reinforcement configurations similar to those investigated in this study.
Estrutura da vegetação caducifólia espinhosa (caatinga) de uma área do sertão central de Pernambuco

Vegetation structure of a "Caatinga" sensu stricto (thorny deciduous woodland) was studied in a lowland area at the municipalities of Floresta and Betânia, State of Pernambuco, Brazil. Height and perimeter of all woody plants to be found in 1 hectare were censured when stem perimeter at soil level was > 3 cm and the height > 1 m. A total of 3,140 individuals belonging to 28 plant species were registered with a basal area of 18.5 m2. In general, results from surveys at lowlands on plain areas presented smaller individual stem diameters than those located near streams or mountain range sites. Physiognomic differences in the caatinga sensu stricto on lowlands are related to differences on the density of plants with greater diameters. The diameter distribution of Caesalpinia gardneriana Benth. (Caesalpiniaceae) and Croton rhamnifolioides Pax & K. Hoffm. (Euphorbiaceae), the two most important tree species, indicate that these plant populations may be regenerating from former disturbance.
Comparisons of cloud microphysics with cloud condensation nuclei spectra over the summertime Southern Ocean

In spite of the many factors that determine cloud droplet concentrations, relationships were found between cloud condensation nuclei (CCN) and cloud droplet concentrations for the First Aerosol Characterization Experiment (ACE 1). Measurements were made in summertime stratocumulus clouds over the Southern Ocean far from anthropogenic sources. The closest relationship of CCN and droplet concentrations was found for CCN measured just below near-adiabatic cloud parcels. Moreover, an adiabatic droplet growth model successfully predicted these droplet concentrations from the CCN spectra and updraft velocities. Correlations of the averages of CCN and cloud droplet concentrations over the entirety of each of the flights were also good. The model also predicted, with reasonable accuracy, these flight-wide average droplet concentrations from flight-wide average CCN spectra and flight-wide average cloud updraft velocities. Drizzle was a major reason for the larger variations in droplet concentrations than in CCN concentrations. Vertical differences in CCN concentrations may have also affected cloud droplet concentrations. Despite variabilities in droplet concentrations, there was a clear relationship between CCN and droplet concentrations. Many of the inferred supersaturations (0.5 to 1.4%) in the “adiabatic” clouds ranged higher than some previous estimates (e.g., 0.2%) for stratus clouds. This may have been due to the cleaner air of the Southern Ocean but is more likely attributable to the more intensive analysis used in this study. Nonetheless, even where the inferred cloud supersaturations were lower (i.e., 0.2%), due to reductions of the droplet concentrations, there was still a relationship between CCN and droplet concentrations.
The geology and evolution of the Ballachulish Igneous Complex and Aureole

Synopsis The Ballachulish Igneous Complex and Aureole is one of the world’s most intensively studied plutonic-metamorphic complexes. The 412 ± 28 Ma igneous complex was emplaced at a depth of about 10 km in regionally deformed and metamorphosed mica schists, quartzites and siliceous carbonates belonging to the Dalradian Supergroup. The intrusion is exposed over an area of c. 7.5 × 4.5 km2 and is roughly cylinder-shaped to about 4 km beneath the surface, with the exception of two areas where the intrusion lies shallowly beneath the country rocks. The intrusion consists of an outer orthopyroxene-bearing diorite shell (emplacement temperature c. 1100°C) surrounding a central body of granite (emplacement temperature c. 850°C), the latter emplaced when the central portion of the diorite was still partially molten. A small, late leucocratic body in the centre of the granite is associated with weak Cu–Mo mineralization. The different intrusive phases represent separate magma batches which underwent little physical or chemical interaction during emplacement. A well-developed contact aureole surrounds the intrusive complex. Isograds in pelitic rocks, the most abundant rock type in the aureole, can be mapped around the intrusion and range from development of cordierite ‘spots’ (c. 550°C) up to anatectic migmatization (700–800°C). Isograds in siliceous carbonates rocks range from development of talc (< 480°C) up to periclase formation (c. 750°C). In the quartzites, recrystallization and coarsening of clastic quartz occurs, and clastic feldspar grains develop a high-temperature structural state, as the contact is approached. The agreement of the sequence and spacing of isograds in pelites, siliceous carbonates and quartzites with equilibrium phase diagrams indicates no significant kinetic control on the positioning of isograds, although some metamorphic processes appear to have been kinetically controlled. The contact metamorphism was mainly caused by intrusion of the diorite phase, with the later granite having little effect. Variations in width of the aureole are mainly due to variations in shape of the intrusion, temperature of the different intrusive phases, and the relative proportions of quartzite and pelite in the country rocks. The duration of the contact metamorphic event, for temperatures above conditions of the cordierite isograd (c. 550°C), was about 500 ka, whereas rocks were hot enough to be partially molten (temperatures above ca. 660°C) for about 270 ka. With the exception of some extensively fluid-fluxed partial melting on the west flank of the complex (Chaotic Zone), fluid communication between the intrusion and aureole was generally limited. Fluid fluxes in siliceous carbonates from the inner aureole on the east flank ranged from 100–1000 moles fluid cm−2. There is no evidence for the development of a large-scale hydrothermal circulation system.
Interference Pattern and Propagation of the M2 Internal Tide South of the Hawaiian Ridge

Abstract Most of the M2 internal tide energy generated at the Hawaiian Ridge radiates away in modes 1 and 2, but direct observation of these propagating waves is complicated by the complexity of the bathymetry at the generation region and by the presence of interference patterns. Observations from satellite altimetry, a tomographic array, and the R/P FLIP taken during the Farfield Program of the Hawaiian Ocean Mixing Experiment (HOME) are found to be in good agreement with the output of a high-resolution primitive equation model, simulating the generation and propagation of internal tides. The model shows that different modes are generated with different amplitudes along complex topography. Multiple sources produce internal tides that sum constructively and destructively as they propagate. The major generation sites can be identified using a simplified 2D idealized knife-edge ridge model. Four line sources located on the Hawaiian Ridge reproduce the interference pattern of sea surface height and energy fl.