Hydrogen evolution reaction is an important process in electrochemical energy technologies. Herein, ruthenium and nitrogen codoped carbon nanowires are prepared as effective hydrogen evolution catalysts. The catalytic performance is markedly better than that of commercial platinum catalyst, with an overpotential of only −12 mV to reach the current density of 10 mV cm-2 in 1 M KOH and −47 mV in 0.1 M KOH. Comparisons with control experiments suggest that the remarkable activity is mainly ascribed to individual ruthenium atoms embedded within the carbon matrix, with minimal contributions from ruthenium nanoparticles. Consistent results are obtained in first-principles calculations, where RuCxNy moieties are found to show a much lower hydrogen binding energy than ruthenium nanoparticles, and a lower kinetic barrier for water dissociation than platinum. Among these, RuC2N2 stands out as the most active catalytic center, where both ruthenium and adjacent carbon atoms are the possible active sites.

This tutorial review describes recent progress in the development of homogeneous catalytic methodology for the direct generation of hydrogen gas from formic acid and alcohols.

Background-Cellular hypertrophy requires coordinated regulation of progrowth and antigrowth mechanisms. In cultured neonatal cardiomyocytes, Foxo transcription factors trigger an atrophy-related gene program that counters hypertrophic growth. However, downstream molecular events are not yet well defined. Methods and Results-Here, we report that expression of either Foxo1 or Foxo3 in cardiomyocytes attenuates calcineurin phosphatase activity and inhibits agonist-induced hypertrophic growth. Consistent with these results, Foxo proteins decrease calcineurin phosphatase activity and repress both basal and hypertrophic agonist-induced expression of MCIP1.4, a direct downstream target of the calcineurin/NFAT pathway. Furthermore, hearts from Foxo3-null mice exhibit increased MCIP1.4 abundance and a hypertrophic phenotype with normal systolic function at baseline. Together, these results suggest that Foxo proteins repress cardiac growth at least in part through inhibition of the calcineurin/NFAT pathway. Given that hypertrophic growth of the heart occurs in multiple contexts, our findings also suggest that certain hypertrophic signals are capable of overriding the antigrowth program induced by Foxo. Consistent with this, multiple hypertrophic agonists triggered inactivation of Foxo proteins in cardiomyocytes through a mechanism requiring the PI3K/Akt pathway. In addition, both Foxo1 and Foxo3 are phosphorylated and consequently inactivated in hearts undergoing hypertrophic growth induced by hemodynamic stress. Key Words: angiotensin Ⅲ calcineurin Ⅲ hypertrophy I n response to stress from neurohumoral activation, hypertension, or other myocardial injury, the heart initially compensates with an adaptive hypertrophic increase in mass. The resulting growth and remodeling response alters the balance between protein synthesis and protein degradation. In skeletal muscle, activation of progrowth signaling pathways is accompanied by deactivation of pathways that promote proteolysis. Prominent among the atrophy-inducing pathways are those governed by Forkhead box transcription factors, O subfamily (Foxo). Conclusions-This Clinical Perspective p 1168Foxo transcription factors regulate key physiological functions, including responses to stress, cell-cycle progression, protein degradation, and apoptosis. 1,2 There are 4 mammalian Foxo genes: Foxo1 (FKHR), Foxo3 (FKHRL1), Foxo4 (AFX), and Foxo6. The transcriptional activities of Foxo proteins are governed by posttranslational modifications such as phosphorylation and acetylation. With respect to myocyte growth and remodeling, Foxo proteins induce ubiquitin ligases and promote proteolysis in skeletal muscle. 3,4 In heart, a number of signaling cascades involving transcription factors, kinases, and G-protein-coupled receptors are implicated in the regulation of muscle growth (see reviews 5-7 ). Among these, the calcineurin/nuclear factor of activated T cells (NFAT) pathway has been shown to be a key signaling cascade that promotes cardiac hypertrophy. 8 It has been reported recently...

Multi-elemental alloy nanoparticles (MEA-NPs) hold great promise for catalyst discovery in a virtually unlimited compositional space. However, rational and controllable synthesize of these intrinsically complex structures remains a challenge. Here, we report the computationally aided, entropy-driven design and synthesis of highly efficient and durable catalyst MEA-NPs. The computational strategy includes prescreening of millions of compositions, prediction of alloy formation by density functional theory calculations, and examination of structural stability by a hybrid Monte Carlo and molecular dynamics method. Selected compositions can be efficiently and rapidly synthesized at high temperature (e.g., 1500 K, 0.5 s) with excellent thermal stability. We applied these MEA-NPs for catalytic NH 3 decomposition and observed outstanding performance due to the synergistic effect of multielemental mixing, their small size, and the alloy phase. We anticipate that the computationally aided rational design and rapid synthesis of MEA-NPs are broadly applicable for various catalytic reactions and will accelerate material discovery. Computationally aided, entropy-driven synthesis of highly efficient and durable multi-elemental alloy catalysts.(11), eaaz0510. 6 Sci Adv ARTICLE TOOLS

Insulin resistance and metabolic syndrome are rapidly expanding public health problems. Acting through the PI3K/Akt pathway, insulin and insulin-like growth factor-1 (IGF-1) inactivate FoxO transcription factors, a class of highly conserved proteins important in numerous physiological functions. However, even as FoxO is a downstream target of insulin, FoxO factors also control upstream signaling elements governing insulin sensitivity and glucose metabolism. Here, we report that sustained activation of either FoxO1 or FoxO3 in cardiac myocytes increases basal levels of Akt phosphorylation and kinase activity. FoxO-activated Akt directly interacts with and phosphorylates FoxO, providing feedback inhibition. We reported previously that FoxO factors attenuate cardiomyocyte calcineurin (PP2B) activity. We now show that calcineurin forms a complex with Akt and inhibition of calcineurin enhances Akt phosphorylation. In addition, FoxO activity suppresses protein phosphatase 2A (PP2A) and disrupts Akt-PP2A and Akt-calcineurin interactions. Repression of Akt-PP2A/B interactions and phosphatase activities contributes, at least in part, to FoxO-dependent increases in Akt phosphorylation and kinase activity. Resveratrol, an activator of Sirt1, increases the transcriptional activity of FoxO1 and triggers Akt phosphorylation in heart. Importantly, FoxO-mediated increases in Akt activity diminish insulin signaling, as manifested by reduced Akt phosphorylation, reduced membrane translocation of Glut4, and decreased insulintriggered glucose uptake. Also, inactivation of the gene coding for FoxO3 enhances insulin-dependent Akt phosphorylation. Taken together, this study demonstrates that changes in FoxO activity have a dose-responsive repressive effect on insulin signaling in cardiomyocytes through inhibition of protein phosphatases, which leads to altered Akt activation, reduced insulin sensitivity, and impaired glucose metabolism.cardiomyocyte ͉ calcineurin ͉ insulin resistance ͉ cardiomyopathy

The Parkes Multibeam Pulsar Survey has unlocked vast areas of the Galactic plane, which were previously invisible to earlier low-frequency and less-sensitive surveys. The survey has discovered more than 600 new pulsars so far, including many that are young and exotic. In this paper we report the discovery of 200 pulsars for which we present positional and spin-down parameters, dispersion measures, flux densities and pulse profiles. A large number of these new pulsars are young and energetic, and we review possible associations of gamma-ray sources with the sample of about 1300 pulsars for which timing solutions are known. Based on a statistical analysis, we estimate that about 19 +/- 6 associations are genuine. The survey has also discovered 12 pulsars with spin properties similar to those of the Vela pulsar, nearly doubling the known population of such neutron stars. Studying the properties of all known 'Vela-like' pulsars, we find their radio luminosities to be similar to normal pulsars, implying that they are very inefficient radio sources. Finally, we review the use of the newly discovered pulsars as Galactic probes and discuss the implications of the new NE2001 Galactic electron density model for the determination of pulsar distances and luminosities

The Parkes Multibeam Pulsar Survey is a sensitive survey of a strip of the Galactic plane with |b| < 5 • and 260 • < l < 50 • at 1374 MHz. Here we report the discovery of 120 new pulsars and subsequent timing observations, primarily using the 76-m Lovell radio telescope at Jodrell Bank. The main features of the sample of 370 published pulsars discovered during the multibeam survey are described. Furthermore, we highlight two pulsars: PSR J1734−3333, a young pulsar with the second highest surface magnetic field strength among the known radio pulsars, B s = 5.4 × 10 13 G, and PSR J1830−1135, the second slowest radio pulsar known, with a 6-s period.

Ruthenium dimer 6 (readily available in two steps from TsDPEN) is converted directly to monomeric asymmetric transfer hydrogenation catalyst 3 in situ under the conditions employed for ketone reduction. Catalyst 3 is a significantly more active catalyst for this application than the untethered derivative, exhibits higher enantioselectivities across a range of substrates, and appears to be highly stable to the reaction conditions. It is active at loadings of as low as 0.01 mol %, and reductions at the 0.1 mol % level are complete within 20 min at 80 degrees C without significant loss of enantioselectivity.