Living with Oxygen

Work on the electronic structures of metal–oxo complexes began in Copenhagen over 50 years ago. This work led to the prediction that tetragonal multiply bonded transition metal–oxos would not be stable beyond the iron–ruthenium–osmium oxo wall in the periodic table and that triply bonded metal–oxos could not be protonated, even in the strongest Brønsted acids. In this theory, only double bonded metal–oxos could attract protons, with basicities being a function of the electron donating ability of ancillary ligands. Such correlations of electronic structure with reactivity have gained importance in recent years, most notably owing to the widespread recognition that high-valent iron–oxos are intermediates in biological reactions critical to life on Earth. In this Account, we focus attention on the oxygenations of inert organic substrates by cytochromes P450, as these reactions involve multiply bonded iron–oxos. We emphasize that P450 iron–oxos are strong oxidants, so strong that they would destroy nearby amino acids if substrates are not oxygenated rapidly; it is our view that these high-valent iron–oxos are such dangerous reactive oxygen species that Nature surely found ways to disable them. Looking more deeply into this matter, mainly by examining many thousands of structures in the Protein Data Bank, we have found that P450s and other enzymes that require oxygen for function have chains of tyrosines and tryptophans that extend from active-site regions to protein surfaces. Tyrosines are near the heme active sites in bacterial P450s, whereas tryptophan is closest in most human enzymes. High-valent iron–oxo survival times taken from hole hopping maps range from a few nanoseconds to milliseconds, depending on the distance of the closest Trp or Tyr residue to the heme. In our proposed mechanism, multistep hole tunneling (hopping) through Tyr/Trp chains guides the damaging oxidizing hole to the protein surface, where it can be quenched by soluble protein or small molecule reductants. As the Earth’s oxygenic atmosphere is believed to have developed about 2.5 billion years ago, the increase in occurrence frequency of tyrosine and tryptophan since the last universal evolutionary ancestor may be in part a consequence of enzyme protective functions that developed to cope with the environmental toxin, O_2

Practical Modeling Concepts for Connective Tissue Stem Cell and Progenitor Compartment Kinetics

Stem cell activation and development is central to skeletal development, maintenance, and repair, as it is for all tissues. However, an integrated model of stem cell proliferation, differentiation, and transit between functional compartments has yet to evolve. In this paper, the authors review current concepts in stem cell biology and progenitor cell growth and differentiation kinetics in the context of bone formation. A cell-based modeling strategy is developed and offered as a tool for conceptual and quantitative exploration of the key kinetic variables and possible organizational hierarchies in bone tissue development and remodeling, as well as in tissue engineering strategies for bone repair

Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map

Peer reviewedPublisher PD

Secondary Scoliosis from a Retroperitoneal Ganglioneuroma in a 9-year-old Female: Case Report

Ganglioneuromas are rare benign tumors that tend to be asymptomatic until large enough to compress adjacent structures. These tumors are often found during childhood during evaluations for other pathologies. Retroperitoneal ganglioneuromas may be a secondary cause of scoliosis. Here, we present a case of a child who was found to have a retroperitoneal ganglioneuroma during an evaluation for scoliosis.

Intentional and unintentional medication non-adherence in hypertension: the role of health literacy, empowerment and medication beliefs

Background: Medication non-adherence is a major public health issue, creating obstacles to effective treatment of hypertension. Examining the underlying factors of deliberate and non-deliberate non-adherence is crucial to address this problem. Thus, the goal of the present study is to assess the socio-demographic, clinical and psychological determinants of intentional and unintentional non-adherence. Design and methods: A cross-sectional survey was conducted between March, 2015 and April, 2016. The sample consisted of hypertension patients holding at least one medical prescription (N=109). Measurements assessed patients’ medication adherence, health literacy, empowerment, self-efficacy, medication beliefs, and patients’ acceptance of their doctor’s advice, socio-demographic and clinical characteristics. Results: Patients who occasionally engaged in either intentional or unintentional non-adherence reported to have lower adherence selfefficacy, higher medication concern beliefs, lower meaningfulness scores and were less likely to accept the doctor’s treatment recommendations. Patients who occasionally engaged in unintentional nonadherence were younger and had experienced more side effects compared to completely adherent patients. Adherence self-efficacy was a mediator of the effect of health literacy on patients’ medication adherence and acceptance of the doctor’s advice was a covariate. Conclusions: Regarding the research implications, health literacy and adherence self-efficacy should be assessed simultaneously when investigating the factors of non-adherence. Regarding the practical implications, adherence could be increased if physicians i) doublecheck whether their patients accept the treatment advice given and ii) if they address patients’ concerns about medications. These steps could be especially important for patients characterized with lower self-efficacy, as they are more likely to engage in occasional nonadherence

Near-infrared Brightness of the Galilean Satellites Eclipsed in Jovian Shadow: A New Technique to Investigate Jovian Upper Atmosphere

We have discovered that Europa, Ganymede and Callisto are bright around 1.5 {\mu}m even when not directly lit by sunlight, based on observations from the Hubble Space Telescope and the Subaru Telescope. The observations were conducted with non-sidereal tracking on Jupiter outside of the field of view to reduce the stray light subtraction uncertainty due to the close proximity of Jupiter. Their eclipsed luminosity was $10^{-6}$-$10^{-7}$ of their uneclipsed brightness, which is low enough that this phenomenon has been undiscovered until now. In addition, Europa in eclipse was <1/10 of the others at 1.5 {\mu}m, a potential clue to the origin of the source of luminosity. Likewise, Ganymede observations were attempted at 3.6 {\mu}m by the Spitzer Space Telescope but it was not detected, suggesting a significant wavelength dependence. The reason why they are luminous even when in the Jovian shadow is still unknown, but forward-scattered sunlight by haze in the Jovian upper atmosphere is proposed as the most plausible candidate. If this is the case, observations of these Galilean satellites while eclipsed by the Jovian shadow provide us a new technique to investigate Jovian atmospheric composition, and investigating the transmission spectrum of Jupiter by this method is important for investigating the atmosphere of extrasolar giant planets by transit spectroscopy.Comment: 7 pages, 3 figures, accepted to Ap

Pando: Personal Volunteer Computing in Browsers

The large penetration and continued growth in ownership of personal electronic devices represents a freely available and largely untapped source of computing power. To leverage those, we present Pando, a new volunteer computing tool based on a declarative concurrent programming model and implemented using JavaScript, WebRTC, and WebSockets. This tool enables a dynamically varying number of failure-prone personal devices contributed by volunteers to parallelize the application of a function on a stream of values, by using the devices' browsers. We show that Pando can provide throughput improvements compared to a single personal device, on a variety of compute-bound applications including animation rendering and image processing. We also show the flexibility of our approach by deploying Pando on personal devices connected over a local network, on Grid5000, a French-wide computing grid in a virtual private network, and seven PlanetLab nodes distributed in a wide area network over Europe.Comment: 14 pages, 12 figures, 2 table

A Bioeconomic Model of Little Fire Ant Wasmannia auropunctata in Hawaii

Reports were scanned in black and white at a resolution of 600 dots per inch and were converted to text using Adobe Paper Capture Plug-in.Wasmannia auropunctata, known as the Little Fire Ant (LFA), was first detected on the island of Hawai‘i (the Big Island) in 1999. It was most probably introduced through imports of contaminated potted plants from mainland USA. We estimate that LFA has now spread to over 4,000 locations on the Big Island and under current management efforts will spread rapidly inundating the Big Island in 15-20 years. Increased efforts in prevention, detections, and mitigation treatments will suppress existing infestations, reduce rate of spread and decrease long term management costs, damages, and human stings. Benefits from increased management are estimated to be $5 billion savings including$540 million in reduced damages and 2.1 billion fewer sting incidents over 35 years.This research was supported in part by the Tropical and Subtropical Agriculture Research (TSTAR) Program (Award Number 2010-34135-21228), The National institute of Food and Agriculture (NIFA), US Department of Agriculture (USDA

Irreducible triangulations of surfaces with boundary

A triangulation of a surface is irreducible if no edge can be contracted to produce a triangulation of the same surface. In this paper, we investigate irreducible triangulations of surfaces with boundary. We prove that the number of vertices of an irreducible triangulation of a (possibly non-orientable) surface of genus g>=0 with b>=0 boundaries is O(g+b). So far, the result was known only for surfaces without boundary (b=0). While our technique yields a worse constant in the O(.) notation, the present proof is elementary, and simpler than the previous ones in the case of surfaces without boundary