Nitric oxide and peroxynitrite in health and disease

The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review

Inequalities that test locality in quantum mechanics

Quantum theory violates Bell's inequality, but not to the maximum extent that is logically possible. We derive inequalities (generalizations of Cirel'son's inequality) that quantify the upper bound of the violation, both for the standard formalism and the formalism of generalized observables (POVMs). These inequalities are quantum analogues of Bell inequalities, and they can be used to test the quantum version of locality. We discuss the nature of this kind of locality. We also go into the relation of our results to an argument by Popescu and Rohrlich (Found. Phys. 24, 379 (1994)) that there is no general connection between the existence of Cirel'son's bound and locality.Comment: 5 pages, 1 figure; the argument has been made clearer in the revised version; 1 reference adde

Characterization of aerosol associated with enhanced small particle number concentrations in a suburban forested environment

Two elevated particle number/mass growth events associated with Aitken‐mode particles were observed during a sampling campaign (13–29 September 2004) at the Duke University Free‐Air CO2 Enrichment facility, a forested field site located in suburban central North Carolina. Aerosol growth rates between 1.2 and 4.9 nm hr−1 were observed, resulting in net increases in geometric mean diameter of 21 and 37 nm during events. Growth was dominated by addition of oxidized organic compounds. Campaign‐average aerosol mass concentrations measured by an Aerodyne quadrupole aerosol mass spectrometer (Q‐AMS) were 1.9 ± 1.6 (σ), 1.6 ± 1.9, 0.1 ± 0.1, and 0.4 ± 0.4 μg m−3 for organic mass (OM), sulfate, nitrate, and ammonium, respectively. These values represent 47%, 40%, 3%, and 10%, respectively, of the measured submicron aerosol mass. Based on Q‐AMS spectra, OM was apportioned to hydrocarbon‐like organic aerosol (HOA, likely representing primary organic aerosol) and two types of oxidized organic aerosol (OOA‐1 and OOA‐2), which constituted on average 6%, 58%, and 36%, respectively, of the apportioned OM. OOA‐1 probably represents aged, regional secondary organic aerosol (SOA), while OOA‐2 likely reflects less aged SOA. Organic aerosol characteristics associated with the events are compared to the campaign averages. Particularly in one event, the contribution of OOA‐2 to overall OM levels was enhanced, indicating the likelihood of less aged SOA formation. Statistical analyses investigate the relationships between HOA, OOA‐1, OOA‐2, other aerosol components, gas‐phase species, and meteorological data during the campaign and individual events. No single variable clearly controls the occurrence of a particle growth event

Stability of undissociated screw dislocations in zinc-blende covalent materials from first principle simulations

The properties of perfect screw dislocations have been investigated for several zinc-blende materials such as diamond, Si, $\beta$-SiC, Ge and GaAs, by performing first principles calculations. For almost all elements, a core configuration belonging to shuffle set planes is favored, in agreement with low temperature experiments. Only for diamond, a glide configuration has the lowest defect energy, thanks to an sp$^2$ hybridization in the core

A composite HII region luminosity function in H alpha of unprecedented statistical weight

Context. Statistical properties of HII region populations in disk galaxies yield important clues to the physics of massive star formation. Aims. We present a set of HII region catalogues and luminosity functions for a sample of 56 spiral galaxies in order to derive the most general form of their luminosity function. Methods. HII region luminosity functions are derived for individual galaxies which, after photometric calibration, are summed to form a total luminosity function comprising 17,797 HII regions from 53 galaxies. Results. The total luminosity function, above its lower limit of completeness, is clearly best fitted by a double power law with a significantly steeper slope for the high luminosity portion of the function. This change of slope has been reported in the literature for individual galaxies, and occurs at a luminosity of log L = 38.6\pm0.1 (L in erg/s) which has been termed the Stromgren luminosity. A steep fall off in the luminosity function above log L = 40 is also noted, and is related to an upper limit to the luminosities of underlying massive stellar clusters. Detailed data are presented for the individual sample galaxies. Conclusions. The luminosity functions of HII regions in spiral galaxies show a two slope power law behaviour, with a significantly steeper slope for the high luminosity branch. This can be modelled by assuming that the high luminosity regions are density bounded, though the scenario is complicated by the inhomogeneity of the ionized interstellar medium. The break, irrespective of its origin, is of potential use as a distance indicator for disc galaxies.Comment: Accepted for publication as a Letter in Astronomy & Astrophysics. Latex with postscript figures. Online-only tables and figures are included in this preprint. The HII region catalogues for 56 galaxies will be published electronically on the CDS but are available also on request from the author

Quantification and expert evaluation of evidence for chemopredictive biomarkers to personalize cancer treatment.

Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines. We focused on studies that investigated changes in gene or protein expression as predictors of drug sensitivity or resistance. We considered an evidence framework that ranked studies from high level I evidence for randomized controlled trials to low level IV evidence for pre-clinical studies and patient case studies.We found that further in-depth analysis will be required to explore methodological issues, inconsistencies between studies, and tumor specific effects present even within high evidence level studies. Some of these nuances will lend themselves to automation, others will require manual curation. However, the comprehensive cataloging and analysis of dispersed public data utilizing an evidence framework provides a high level perspective on clinical actionability of these protein biomarkers. This framework and perspective will ultimately facilitate clinical trial design as well as therapeutic decision-making for individual patients