We describe a group of alloys that exhibit "super" properties, such as ultralow elastic modulus, ultrahigh strength, super elasticity, and super plasticity, at room temperature and that show Elinvar and Invar behavior. These "super" properties are attributable to a dislocation-free plastic deformation mechanism. In cold-worked alloys, this mechanism forms elastic strain fields of hierarchical structure that range in size from the nanometer scale to several tens of micrometers. The resultant elastic strain energy leads to a number of enhanced material properties.Mechanical properties, such as strength, of metallic materials are strongly affected by metallurgical processes such as heat treatment and plastic working, which bring modifications in the microstructure. On the other hand, these processes have no substantial effect on physical properties such as elastic modulus and thermal expansion. The reason for this is that the changes that can be affected by plastic working and heat treatment do not extend to interatomic bonds or electronic states.We present a group of alloys that exhibit multiple "super" properties and drastic changes in physical properties after plastic working at room temperature. These alloys simultaneously offer super elasticity, super strength, super coldworkability, and Invar and Elinvar properties. The alloys consist of Group IVa and Va elements and oxygen and share the following three electronic magic numbers: (i) a compositional average valence electron number [electron/atom (e/a) ratio] of about 4.24; (ii) a bond order (Bo value) of about 2.87 based on the DV-X␣ cluster method, which represents the bonding strength (1-3); and (iii) a "d" electron-orbital energy level (Md value) of about 2.45 eV, representing electronegativity. The properties emerge only when all three of these magic numbers are satisfied simultaneously. Various alloy composition combinations meet these criteria, such as Ti-12Ta-9Nb-3V-6Zr-O and Ti23Nb-0.7Ta-2Zr-O [mole percent (mol %)], wherein each alloy has a simple body-centered cubic (bcc) crystal structure. In order to exhibit these properties, each alloy system requires substantial cold working and the presence of a certain amount of oxygen, restricted to an oxygen concentration of 0.7 to 3.0 mol %.Typical properties of the alloys are shown in Fig. 1 for samples before and after cold swaging with 90% reduction in area (4). Tensile stress-strain curves shown in Fig. 1A indicate that cold working substantially decreases the elastic modulus and increases the yield strength and confirm nonlinearity in the elastic range, with the gradient of each curve decreasing continuously to about 1/3 its original value near the elastic limit. As a result of this decrease in elastic modulus and nonlinearity, elastic deformability after cold working reaches 2.5%, which is at least double the value before cold working. Generally, large elastic deformations that occur in so-called "super-elastic alloys" are known to be reversible martensitic transformations resulting from deformation, d...

Chung et al. show that the myomitokine GDF15 can act to modulate oxidative and lipolytic function in a non–cell-autonomous manner, thereby regulating systemic energy homeostasis in skeletal muscle-specific Crif1-deficient mice. This pathway may be a potential therapeutic target for preventing the onset of obesity and insulin resistance.

SU11248 is a highly effective tyrosine kinase inhibitor of the RET/PTC oncogenic kinase.

OBJECTIVENicotinamide adenine dinucleotides (NAD+ and NADH) play a crucial role in cellular energy metabolism, and a dysregulated NAD+-to-NADH ratio is implicated in metabolic syndrome. However, it is still unknown whether a modulating intracellular NAD+-to-NADH ratio is beneficial in treating metabolic syndrome. We tried to determine whether pharmacological stimulation of NADH oxidation provides therapeutic effects in rodent models of metabolic syndrome.RESEARCH DESIGN AND METHODSWe used β-lapachone (βL), a natural substrate of NADH:quinone oxidoreductase 1 (NQO1), to stimulate NADH oxidation. The βL-induced pharmacological effect on cellular energy metabolism was evaluated in cells derived from NQO1-deficient mice. In vivo therapeutic effects of βL on metabolic syndrome were examined in diet-induced obesity (DIO) and ob/ob mice.RESULTSNQO1-dependent NADH oxidation by βL strongly provoked mitochondrial fatty acid oxidation in vitro and in vivo. These effects were accompanied by activation of AMP-activated protein kinase and carnitine palmitoyltransferase and suppression of acetyl-coenzyme A (CoA) carboxylase activity. Consistently, systemic βL administration in rodent models of metabolic syndrome dramatically ameliorated their key symptoms such as increased adiposity, glucose intolerance, dyslipidemia, and fatty liver. The treated mice also showed higher expressions of the genes related to mitochondrial energy metabolism (PPARγ coactivator-1α, nuclear respiratory factor-1) and caloric restriction (Sirt1) consistent with the increased mitochondrial biogenesis and energy expenditure.CONCLUSIONSPharmacological activation of NADH oxidation by NQO1 resolves obesity and related phenotypes in mice, opening the possibility that it may provide the basis for a new therapy for the treatment of metabolic syndrome.