Monoclinic and Correlated Metal Phase in VO_2 as Evidence of the Mott Transition: Coherent Phonon Analysis

In femtosecond pump-probe measurements, the appearance of coherent phonon oscillations at 4.5 THz and 6.0 THz indicating the rutile metal phase of VO_2 does not occur simultaneously with the first-order metal-insulator transition (MIT) near 68^oC. The monoclinic and correlated metal(MCM) phase between the MIT and the structural phase transition (SPT) is generated by a photo-assisted hole excitation which is evidence of the Mott transition. The SPT between the MCM phase and the rutile metal phase occurs due to subsequent Joule heating. The MCM phase can be regarded as an intermediate non-equilibrium state.Comment: 4 pages, 2 figure

DJ-1 interacts with and regulates paraoxonase-2, an enzyme critical for neuronal survival in response to oxidative stress.

Loss-of-function mutations in DJ-1 (PARK7) gene account for about 1% of all familial Parkinson's disease (PD). While its physiological function(s) are not completely clear, DJ-1 protects neurons against oxidative stress in both in vitro and in vivo models of PD. The molecular mechanism(s) through which DJ-1 alleviates oxidative stress-mediated damage remains elusive. In this study, we identified Paraoxonase-2 (PON2) as an interacting target of DJ-1. PON2 activity is elevated in response to oxidative stress and DJ-1 is crucial for this response. Importantly, we showed that PON2 deficiency hypersensitizes neurons to oxidative stress induced by MPP+ (1-methyl-4-phenylpyridinium). Conversely, over-expression of PON2 protects neurons in this death paradigm. Interestingly, PON2 effectively rescues DJ-1 deficiency-mediated hypersensitivity to oxidative stress. Taken together, our data suggest a model by which DJ-1 exerts its antioxidant activities, at least partly through regulation of PON2

Observation of Mott Transition in VO_2 Based Transistors

An abrupt Mott metal-insulator transition (MIT) rather than the continuous Hubbard MIT near a critical on-site Coulomb energy U/U_c=1 is observed for the first time in VO_2, a strongly correlated material, by inducing holes of about 0.018% into the conduction band. As a result, a discontinuous jump of the density of states on the Fermi surface is observed and inhomogeneity inevitably occurs. The gate effect in fabricated transistors is clear evidence that the abrupt MIT is induced by the excitation of holes.Comment: 4 pages, 4 figure

Circumstellar molecular composition of the oxygen-rich AGB star IK~Tau: II. In-depth non-LTE chemical abundance analysis

Aims: Little information exists on the circumstellar molecular abundance stratifications of many molecules. The aim is to study the circumstellar chemical abundance pattern of 11 molecules and isotopologs ($^{12}$CO, $^{13}$CO, SiS, $^{28}$SiO, $^{29}$SiO, $^{30}$SiO, HCN, CN, CS, SO, SO$_2$) in the oxygen-rich evolved star IK~Tau. Methods: We have performed an in-depth analysis of a large number of molecular emission lines excited in the circumstellar envelope around IK~Tau. The analysis is done based on a non-local thermodynamic equilibrium (non-LTE) radiative transfer analysis, which calculates the temperature and velocity structure in a self-consistent way. The chemical abundance pattern is coupled to theoretical outer wind model predictions including photodestruction and cosmic ray ionization. Not only the integrated line intensities, but also the line shapes, are used as diagnostic tool to study the envelope structure. Results: The deduced wind acceleration is much slower than predicted from classical theories. SiO and SiS are depleted in the envelope, possibly due to the adsorption onto dust grains. For HCN and CS a clear difference with respect to inner wind non-equilibrium predictions is found, either indicating uncertainties in the inner wind theoretical modeling or the possibility that HCN and CS (or the radical CN) participate in the dust formation. The low signal-to-noise profiles of SO and CN prohibit an accurate abundance determination; the modeling of high-excitation SO$_2$ lines is cumbersome, possibly related to line misidentifications or problems with the collisional rates. The SiO isotopic ratios ($^{29}$SiO/$^{28}$SiO and $^{30}$SiO/$^{28}$SiO) point toward an enhancement in $^{28}$SiO compared to results of classical stellar evolution codes. Predictions for H$_2$O lines in the spectral range of the Herschel/HIFI mission are performed. [abbreviated]Comment: 24 pagees, accepted for publication in Astronomy & Astrophysic

High-dose clevudine impairs mitochondrial function and glucose-stimulated insulin secretion in INS-1E cells

<p>Abstract</p> <p>Background</p> <p>Clevudine is a nucleoside analog reverse transcriptase inhibitor that exhibits potent antiviral activity against hepatitis B virus (HBV) without serious side effects. However, mitochondrial myopathy has been observed in patients with chronic HBV infection taking clevudine. Moreover, the development of diabetes was recently reported in patients receiving long-term treatment with clevudine. In this study, we investigated the effects of clevudine on mitochondrial function and insulin release in a rat clonal β-cell line, INS-1E.</p> <p>Methods</p> <p>The mitochondrial DNA (mtDNA) copy number and the mRNA levels were measured by using quantitative PCR. MTT analysis, ATP/lactate measurements, and insulin assay were performed.</p> <p>Results</p> <p>Both INS-1E cells and HepG2 cells, which originated from human hepatoma, showed dose-dependent decreases in mtDNA copy number and cytochrome c oxidase-1 (Cox-1) mRNA level following culture with clevudine (10 μM-1 mM) for 4 weeks. INS-1E cells treated with clevudine had reduced total mitochondrial activities, lower cytosolic ATP contents, enhanced lactate production, and more lipid accumulation. Insulin release in response to glucose application was markedly decreased in clevudine-treated INS-1E cells, which might be a consequence of mitochondrial dysfunction.</p> <p>Conclusions</p> <p>Our data suggest that high-dose treatment with clevudine induces mitochondrial defects associated with mtDNA depletion and impairs glucose-stimulated insulin secretion in insulin-releasing cells. These findings partly explain the development of diabetes in patients receiving clevudine who might have a high susceptibility to mitochondrial toxicity.</p

Identification of hypoxanthine as a urine marker for non-Hodgkin lymphoma by low-mass-ion profiling

<p>Abstract</p> <p>Background</p> <p>Non-Hodgkin lymphoma (NHL) is a hematologic malignancy for which good diagnostic markers are lacking. Despite continued improvement in our understanding of NHL, efforts to identify diagnostic markers have yielded dismal results. Here, we translated low-mass-ion information in urine samples from patients with NHL into a diagnostic marker.</p> <p>Methods</p> <p>To minimize experimental error, we tested variable parameters before MALDI-TOF analysis of low-mass ions in urine. Urine from 30 controls and 30 NHL patients was analyzed as a training set for NHL prediction. All individual peak areas were normalized to total area up to 1000 m/z. The training set analysis was repeated four times. Low-mass peaks that were not affected by changes in experimental conditions were collected using MarkerView™ software. Human Metabolome Database (HMDB) searches and ESI LC-MS/MS analyses were used to identify low-mass ions that exhibited differential patterns in control and NHL urines. Identified low-mass ions were validated in a blinded fashion in 95 controls and 66 NHL urines to determine their ability to discriminate NHL patients from controls.</p> <p>Results</p> <p>The 30 highest-ranking low-mass-ion peaks were selected from the 60-urine training set, and three low-mass-ion peaks with high intensity were selected for identification. Of these, a 137.08-m/z ion showed lower mass-peak intensity in urines of NHL patients, a result that was validated in a 161-urine blind validation set (95 controls and 66 NHL urines). The 130.08-m/z ion was identified from HMDB searches and ESI LC-MS/MS analyses as hypoxanthine (HX). The HX concentration in urines of NHL patients was significantly decreased (P < 0.001) and was correlated with the mass-peak area of the 137.08-m/z ion. At an HX concentration cutoff of 17.4 μM, sensitivity and specificity were 79.2% and 78.4%, respectively.</p> <p>Conclusions</p> <p>The present study represents a good example of low-mass-ion profiling in the setting of disease screening using urine. This technique can be a powerful non-invasive diagnostic tool with high sensitivity and specificity for NHL screening. Furthermore, HX identified in the study may be a useful single urine marker for NHL screening.</p