Pharmacological Therapy in the Heart as an Alternative to Cellular Therapy: A Place for the Brain Natriuretic Peptide?

The discovery that stem cells isolated from different organs have the ability to differentiate into mature beating cardiomyocytes has fostered considerable interest in developing cellular regenerative therapies to treat cardiac diseases associated with the loss of viable myocardium. Clinical studies evaluating the potential of stem cells (from heart, blood, bone marrow, skeletal muscle, and fat) to regenerate the myocardium and improve its functional status indicated that although the method appeared generally safe, its overall efficacy has remained modest. Several issues raised by these studies were notably related to the nature and number of injected cells, as well as the route and timing of their administration, to cite only a few. Besides the direct administration of cardiac precursor cells, a distinct approach to cardiac regeneration could be based upon the stimulation of the heart's natural ability to regenerate, using pharmacological approaches. Indeed, differentiation and/or proliferation of cardiac precursor cells is controlled by various endogenous mediators, such as growth factors and cytokines, which could thus be used as pharmacological agents to promote regeneration. To illustrate such approach, we present recent results showing that the exogenous administration of the natriuretic peptide BNP triggers "endogenous" cardiac regeneration, following experimental myocardial infarction

Fermi-surface transformation across the pseudogap critical point of the cuprate superconductor La1.6−x_{1.6-x}Nd0.4_{0.4}Srx_{x}CuO4_4

The electrical resistivity $\rho$ and Hall coefficient R$_H$ of the tetragonal single-layer cuprate Nd-LSCO were measured in magnetic fields up to $H = 37.5$ T, large enough to access the normal state at $T \to 0$, for closely spaced dopings $p$ across the pseudogap critical point at $p^\star = 0.235$. Below $p^\star$, both coefficients exhibit an upturn at low temperature, which gets more pronounced with decreasing $p$. Taken together, these upturns show that the normal-state carrier density $n$ at $T = 0$ drops upon entering the pseudogap phase. Quantitatively, it goes from $n = 1 + p$ at $p = 0.24$ to $n = p$ at $p = 0.20$. By contrast, the mobility does not change appreciably, as revealed by the magneto-resistance. The transition has a width in doping and some internal structure, whereby R$_H$ responds more slowly than $\rho$ to the opening of the pseudogap. We attribute this difference to a Fermi surface that supports both hole-like and electron-like carriers in the interval $0.2 < p < p^\star$, with compensating contributions to R$_H$. Our data are in excellent agreement with recent high-field data on YBCO and LSCO. The quantitative consistency across three different cuprates shows that a drop in carrier density from $1 + p$ to $p$ is a universal signature of the pseudogap transition at $T=0$. We discuss the implication of these findings for the nature of the pseudogap phase.Comment: 11 pages, 12 figure

Two types of nematicity in the phase diagram of the cuprate superconductor YBa2_2Cu3_3Oy_y

Nematicity has emerged as a key feature of cuprate superconductors, but its link to other fundamental properties such as superconductivity, charge order and the pseudogap remains unclear. Here we use measurements of transport anisotropy in YBa$_2$Cu$_3$O$_y$ to distinguish two types of nematicity. The first is associated with short-range charge-density-wave modulations in a doping region near $p = 0.12$. It is detected in the Nernst coefficient, but not in the resistivity. The second type prevails at lower doping, where there are spin modulations but no charge modulations. In this case, the onset of in-plane anisotropy - detected in both the Nernst coefficient and the resistivity - follows a line in the temperature-doping phase diagram that tracks the pseudogap energy. We discuss two possible scenarios for the latter nematicity.Comment: 8 pages and 7 figures. Main text and supplementary material now combined into single articl

Anisotropy of the Seebeck Coefficient in the Cuprate Superconductor YBa2_{2}Cu3_{3}Oy_{y}: Fermi-Surface Reconstruction by Bidirectional Charge Order

The Seebeck coefficient $S$ of the cuprate YBa$_{2}$Cu$_{3}$O$_{y}$ was measured in magnetic fields large enough to suppress superconductivity, at hole dopings $p = 0.11$ and $p = 0.12$, for heat currents along the $a$ and $b$ directions of the orthorhombic crystal structure. For both directions, $S/T$ decreases and becomes negative at low temperature, a signature that the Fermi surface undergoes a reconstruction due to broken translational symmetry. Above a clear threshold field, a strong new feature appears in $S_{\rm b}$, for conduction along the $b$ axis only. We attribute this feature to the onset of 3D-coherent unidirectional charge-density-wave modulations seen by x-ray diffraction, also along the $b$ axis only. Because these modulations have a sharp onset temperature well below the temperature where $S/T$ starts to drop towards negative values, we infer that they are not the cause of Fermi-surface reconstruction. Instead, the reconstruction must be caused by the quasi-2D bidirectional modulations that develop at significantly higher temperature.Comment: 7 pages, 5 figure

Hydrological Drivers of Bedload Transport in an Alpine Watershed

Understanding and predicting bedload transport is an important element of watershed management. Yet, predictions of bedload remain uncertain by up to several order(s) of magnitude. In this contribution, we use a 5-year continuous time series of streamflow and bedload transport monitoring in a 13.4-km2 snow-dominated Alpine watershed in the Western Swiss Alps to investigate hydrological drivers of bedload transport. Following a calibration of the bedload sensors, and a quantification of the hydraulic forcing of streamflow upon bedload, a hydrological analysis is performed to identify daily flow hydrographs influenced by different hydrological drivers: rainfall, snowmelt, and combined rain and snowmelt events. We then quantify their respective contribution to bedload transport. Results emphasize the importance of combined rain and snowmelt events, for both annual bedload volumes (77% on average) and peaks in bedload transport rate. A non-negligible, but smaller, amount of bedload transport may occur during late summer and autumn storms, once the snowmelt contribution and baseflow have significantly decreased (9% of the annual volume on average). Although rainfall-driven changes in flow hydrographs are responsible for a large majority of the annual bedload volumes (86% on average), the identified melt-only events also represent a substantial contribution (14% on average). The results of this study help to improve current predictions of bedload transport through a better understanding of the bedload magnitude-frequency relationship under different hydrological conditions. We further discuss how bedload transport could evolve under a changing climate through its effects on Alpine watershed hydrology

Evidence for a small hole pocket in the Fermi surface of underdoped YBa2Cu3Oy

The Fermi surface of a metal is the fundamental basis from which its properties can be understood. In underdoped cuprate superconductors, the Fermi surface undergoes a reconstruction that produces a small electron pocket, but whether there is another, as yet undetected portion to the Fermi surface is unknown. Establishing the complete topology of the Fermi surface is key to identifying the mechanism responsible for its reconstruction. Here we report the discovery of a second Fermi pocket in underdoped YBa2Cu3Oy, detected as a small quantum oscillation frequency in the thermoelectric response and in the c-axis resistance. The field-angle dependence of the frequency demonstrates that it is a distinct Fermi surface and the normal-state thermopower requires it to be a hole pocket. A Fermi surface consisting of one electron pocket and two hole pockets with the measured areas and masses is consistent with a Fermi-surface reconstruction caused by the charge-density-wave order observed in YBa2Cu3Oy, provided other parts of the reconstructed Fermi surface are removed by a separate mechanism, possibly the pseudogap.Comment: 23 pages, 5 figure

Field-dependent heat transport in the Kondo insulator SmB6 : phonons scattered by magnetic impurities

The thermal conductivity $\kappa$ of the Kondo insulator SmB$_6$ was measured at low temperature, down to 70 mK, in magnetic fields up to 15 T, on single crystals grown using both the floating-zone and the flux methods. The residual linear term $\kappa_0/T$ at $T \to 0$ is found to be zero in all samples, for all magnetic fields, in agreement with previous studies. There is therefore no clear evidence of fermionic heat carriers. In contrast to some prior data, we observe a large enhancement of $\kappa(T)$ with increasing field. The effect of field is anisotropic, depending on the relative orientation of field and heat current (parallel or perpendicular), and with respect to the cubic crystal structure. We interpret our data in terms of heat transport predominantly by phonons, which are scattered by magnetic impurities.Comment: publish versio

Pseudogap phase of cuprate superconductors confined by Fermi surface topology

The properties of cuprate high-temperature superconductors are largely shaped by competing phases whose nature is often a mystery. Chiefly among them is the pseudogap phase, which sets in at a doping $p^*$ that is material-dependent. What determines $p^*$ is currently an open question. Here we show that the pseudogap cannot open on an electron-like Fermi surface, and can only exist below the doping $p_{FS}$ at which the large Fermi surface goes from hole-like to electron-like, so that $p^*$ $\leq$ $p_{FS}$. We derive this result from high-magnetic-field transport measurements in La$_{1.6-x}$Nd$_{0.4}$Sr$_x$CuO$_4$ under pressure, which reveal a large and unexpected shift of $p^*$ with pressure, driven by a corresponding shift in $p_{FS}$. This necessary condition for pseudogap formation, imposed by details of the Fermi surface, is a strong constraint for theories of the pseudogap phase. Our finding that $p^*$ can be tuned with a modest pressure opens a new route for experimental studies of the pseudogap.Comment: 15 pages, 5 figures, 7 supplemental figure

Wiedemann-Franz law and abrupt change in conductivity across the pseudogap critical point of a cuprate superconductor

The thermal conductivity $\kappa$ of the cuprate superconductor La$_{1.6-x}$Nd$_{0.4}$Sr$_x$CuO$_4$ was measured down to 50 mK in seven crystals with doping from $p=0.12$ to $p=0.24$, both in the superconducting state and in the magnetic field-induced normal state. We obtain the electronic residual linear term $\kappa_0/T$ as $T \to 0$ across the pseudogap critical point $p^{\star}= 0.23$. In the normal state, we observe an abrupt drop in $\kappa_0/T$ upon crossing below $p^{\star}$, consistent with a drop in carrier density $n$ from $1 + p$ to $p$, the signature of the pseudogap phase inferred from the Hall coefficient. A similar drop in $\kappa_0/T$ is observed at $H=0$, showing that the pseudogap critical point and its signatures are unaffected by the magnetic field. In the normal state, the Wiedemann-Franz law, $\kappa_0/T=L_0/\rho(0)$, is obeyed at all dopings, including at the critical point where the electrical resistivity $\rho(T)$ is $T$-linear down to $T \to 0$. We conclude that the non-superconducting ground state of the pseudogap phase at $T=0$ is a metal whose fermionic excitations carry heat and charge as conventional electrons do.Comment: 10 pages, including Supplementary Materia