Theory of Scanning Tunneling Spectroscopy of a Magnetic Adatom on a Metallic Surface

A comprehensive theory is presented for the voltage, temperature, and spatial dependence of the tunneling current between a scanning tunneling microscope (STM) tip and a metallic surface with an individual magnetic adatom. Modeling the adatom by a nondegenerate Anderson impurity, a general expression is derived for a weak tunneling current in terms of the dressed impurity Green function, the impurity-free surface Green function, and the tunneling matrix elements. This generalizes Fano's analysis to the interacting case. The differential-conductance lineshapes seen in recent STM experiments with the tip directly over the magnetic adatom are reproduced within our model, as is the rapid decay, \sim 10\AA, of the low-bias structure as one moves the tip away from the adatom. With our simple model for the electronic structure of the surface, there is no dip in the differential conductance at approximately one lattice spacing from the magnetic adatom, but rather we see a resonant enhancement. The formalism for tunneling into small clusters of magnetic adatoms is developed.Comment: 12 pages, 9 figures; to appear in Phys. Rev.

AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons

Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha 2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. in contrast, AgRPa2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha 2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus

Statistical mechanics of the random K-SAT model

The Random K-Satisfiability Problem, consisting in verifying the existence of an assignment of N Boolean variables that satisfy a set of M=alpha N random logical clauses containing K variables each, is studied using the replica symmetric framework of diluted disordered systems. We present an exact iterative scheme for the replica symmetric functional order parameter together for the different cases of interest K=2, K>= 3 and K>>1. The calculation of the number of solutions, which allowed us [Phys. Rev. Lett. 76, 3881 (1996)] to predict a first order jump at the threshold where the Boolean expressions become unsatisfiable with probability one, is thoroughly displayed. In the case K=2, the (rigorously known) critical value (alpha=1) of the number of clauses per Boolean variable is recovered while for K>=3 we show that the system exhibits a replica symmetry breaking transition. The annealed approximation is proven to be exact for large K.Comment: 34 pages + 1 table + 8 fig., submitted to Phys. Rev. E, new section added and references update

Replication of Extended Lifespan Phenotype in Mice with Deletion of Insulin Receptor Substrate 1

We previously reported that global deletion of insulin receptor substrate protein 1 (Irs1) extends lifespan and increases resistance to several age-related pathologies in female mice. However, no effect on lifespan was observed in male Irs1 null mice. We suggested at the time that the lack of any effect in males might have been due to a sample size issue. While such lifespan studies are essential to our understanding of the aging process, they are generally based on survival curves derived from single experiments, primarily due to time and economic constraints. Consequently, the robustness of such findings as a basis for further investigation has been questioned. We have therefore measured lifespan in a second, separate cohort of Irs1 null female mice, and show that, consistent with our previous finding, global deletion of Irs1 significantly extends lifespan in female mice. In addition, an augmented and completed study demonstrates lifespan extension in male Irs1 null mice. Therefore, we show that reduced IRS1-dependent signalling is a robust mechanism through which mammalian lifespan can be modulated

HST/NICMOS detection of a partially embedded, intermediate-mass pre-main-sequence population in the 30 Doradus Nebula

We present the detection of an intermediate-mass pre-main-sequence population embedded in the nebular filaments surrounding the 30 Doradus region in the Large Magellanic Cloud (LMC) using HST/NICMOS. In addition to four previously known luminous Class I infrared ``protostars,'' the NICMOS data reveal 20 new sources with intrinsic infrared excess similar to Galactic pre-main sequence stars. Based on their infrared brightness, these objects can be identified as the LMC equivalent of Galactic pre-main sequence stars. The faintest LMC Young Stellar Objects in the sample have colors similar to T Tauri and have about the same brightness as T Tauri if placed at the distance of the LMC. We find no evidence for a lower-mass cut-off in the initial mass function. Instead, the whole spectrum of stellar masses from pre-main sequence stars with ~1.5Mo to massive O stars still embedded in dense knots appears to be present in the nebular filaments. The majority of the young stellar objects can be found to the north of the central starburst cluster R136. This region is very likely evolving into an OB association.Comment: 9 pages, 4 figures, uses emulateapj.sty and psfig.sty. accepted for publication in the Astronomical Journal (August 2001 issue

Hubble Space Telescope imaging of a peculiar stellar complex in NGC 6946

The stellar populations in a stellar complex in NGC 6946 are analyzed on images taken with the Wide Field Planetary Camera 2 on board the Hubble Space Telescope. The complex is peculiar by its very high density of stars and clusters and semicircular shape. Its physical dimensions are about the same as for the local Gould Belt, but the stellar density is 1 - 2 orders of magnitude higher. In addition to an extremely luminous, 15 Myr old cluster discussed in an earlier paper, accounting for about 17% of the integrated V-band light, we identify 18 stellar clusters within the complex with luminosities similar to the brightest open clusters in the Milky Way. The color-magnitude diagram of individual stars in the complex shows a paucity of red supergiants compared to model predictions in the 10-20 Myr age range for a uniform star formation rate. We thus find tentative evidence for a gap in the dispersed star formation history, with a concentration of star formation into a young globular cluster during this gap. Confirmation of this result must, however, await a better understanding of the late evolution of stars in the corresponding mass range (> 12 Msun). A reddening map based on individual reddenings for 373 early-type stars is presented, showing significant variations in the absorption across the complex. These may be responsible for some of the arc-like structures previously identified on ground-based images. We finally discuss various formation scenarios for the complex and the star clusters within it.Comment: 51 pages, including 19 figures and 4 tables. Accepted for publication in Ap

Global Methylation Patterns in Idiopathic Pulmonary Fibrosis

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is characterized by profound changes in the lung phenotype including excessive extracellular matrix deposition, myofibroblast foci, alveolar epithelial cell hyperplasia and extensive remodeling. The role of epigenetic changes in determining the lung phenotype in IPF is unknown. In this study we determine whether IPF lungs exhibit an altered global methylation profile.\ud \ud METHODOLOGY/PRINCIPAL FINDINGS: Immunoprecipitated methylated DNA from 12 IPF lungs, 10 lung adenocarcinomas and 10 normal histology lungs was hybridized to Agilent human CpG Islands Microarrays and data analysis was performed using BRB-Array Tools and DAVID Bioinformatics Resources software packages. Array results were validated using the EpiTYPER MassARRAY platform for 3 CpG islands. 625 CpG islands were differentially methylated between IPF and control lungs with an estimated False Discovery Rate less than 5%. The genes associated with the differentially methylated CpG islands are involved in regulation of apoptosis, morphogenesis and cellular biosynthetic processes. The expression of three genes (STK17B, STK3 and HIST1H2AH) with hypomethylated promoters was increased in IPF lungs. Comparison of IPF methylation patterns to lung cancer or control samples, revealed that IPF lungs display an intermediate methylation profile, partly similar to lung cancer and partly similar to control with 402 differentially methylated CpG islands overlapping between IPF and cancer. Despite their similarity to cancer, IPF lungs did not exhibit hypomethylation of long interspersed nuclear element 1 (LINE-1) retrotransposon while lung cancer samples did, suggesting that the global hypomethylation observed in cancer was not typical of IPF.\ud \ud CONCLUSIONS/SIGNIFICANCE: Our results provide evidence that epigenetic changes in IPF are widespread and potentially important. The partial similarity to cancer may signify similar pathogenetic mechanisms while the differences constitute IPF or cancer specific changes. Elucidating the role of these specific changes will potentially allow better understanding of the pathogenesis of IPF.\ud \u