Modeling the Thermosphere as a Driven-Dissipative Thermodynamic System

Thermospheric density impacts satellite position and lifetime through atmospheric drag. More accurate specification of thermospheric temperature, a key input to current models such as the High Accuracy Satellite Drag Model (HASDM), can decrease model density errors. Building on Burke et al. s driven-dissipative model (2009) the arithmetic mean temperature, T1/2 , defined by Jacchia, 1977 (J77), is modeled using the magnetospheric electric field as a driver. Three methods of treating the UV contribution to T1/2 (T1/2UV) are tested. Two model parameters, the coupling and relaxation constants, are adjusted for 38 storms from 2002 - 2008 to minimize modeled T1/2 errors. Observed T1/2 values are derived from densities and heights measured by the GRACE satellite. It is found that allowing T1/2 UV to vary produces the lowest errors for 27 of 38 storms in the sample and 27 of 28 storms with decreasing UV contributions. Treating T1/2UV as a constant produces the lowest errors for 7 of 10 storms with increasing UV contributions

Two-dimensional protein crystallization via metal-ion coordination by naturally occurring surface histidines

A powerful and potentially general approach to the targeting and crystallization of proteins on lipid interfaces through coordination of surface histidine residues to lipid-chelated divalent metal ions is presented. This approach, which should be applicable to the crystallization of a wide range of naturally occurring or engineered proteins, is illustrated here by the crystallization of streptavidin on a monolayer of an iminodiacetate-Cu(II) lipid spread at the air-water interface. This method allows control of the protein orientation at interfaces, which is significant for the facile production of highly ordered protein arrays and for electron density mapping in structural analysis of two-dimensional crystals. Binding of native streptavidin to the iminodiacetate-Cu lipids occurs via His-87, located on the protein surface near the biotin binding pocket. The two-dimensional streptavidin crystals show a previously undescribed microscopic shape that differs from that of crystals formed beneath biotinylated lipids

Modeling the Thermosphere as a Driven-dissipative Thermodynamic System

Thermospheric density impacts satellite position and lifetime through atmospheric drag. More accurate specification of thermospheric temperature, a key input to current models such as the High Accuracy Satellite Drag Model, can decrease model density errors. This paper improves the model of Burke et al. (2009) to model thermospheric temperatures using the magnetospheric convective electric field as a driver. In better alignment with Air Force satellite tracking operations, we model the arithmetic mean temperature, T 1/2, defined by the Jacchia (1977) model as the mean of the daytime maximum and nighttime minimum exospheric temperatures occurring in opposite hemispheres at a given time, instead of the exospheric temperature used by Burke et al. (2009). Two methods of treating the solar ultraviolet (UV) contribution to T 1/2 are tested. Two model parameters, the coupling and relaxation constants, are optimized for 38 storms from 2002 to 2008. Observed T 1/2 values are derived from densities and heights measured by the Gravity Recovery and Climate Experiment satellite. The coupling and relaxation constants were found to vary over the solar cycle and are fit as functions of F 10.7a, the 162 day average of the F 10.7 index. Model results show that allowing temporal UV variation decreased model T 1/2 errors for storms with decreasing UV over the storm period but increased T 1/2 errors for storms with increasing UV. Model accuracy was found to be improved by separating storms by type (coronal mass ejection or co‐rotating interaction region). The model parameter fits established will be useful for improving satellite drag forecasts

Relationships between coronary heart disease risk factors and serum ionized calcium in Kennedy Space Center Cohort

Kennedy Space Center (KSC) employees are reported to be at high risk for coronary heart disease (CHD). Risk factors for CHD include high serum total cholesterol levels, low levels of high-density lipoprotein cholesterol (HDLC), elevated triglyceride, smoking, inactivity, high blood pressure, being male, and being older. Higher dietary and/or serum calcium Ca(++) may be related to a lower risk for CHD. Fifty men and 37 women participated. Subjects were tested in the morning after fasting 12 hours. Information relative to smoking and exercise habits was obtained; seated blood pressures were measured; and blood drawn. KCS men had higher risk values than KCS women as related to HDLC, triglycerides, systolic blood pressure, and diastolic blood pressure. Smoking and nonsmoking groups did not differ for other risk factors or for serum Ca(++) levels. Exercise and sedentary groups differed in total cholesterol and triglyceride levels. Serum Ca(++) levels were related to age, increasing with age in the sedentary group and decreasing in the exercisers, equally for men and women. It is concluded that these relationships may be significant to the risk of CHD and/or the risk of bone demineralization in an aging population

Aspirin commits yeast cells to apoptosis depending on carbon source

The effect of aspirin on the growth of a wild-type Saccharomyces cerevisiae strain (EG103), containing both copper,zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD), a strain deficient in MnSOD (EG110) and a strain deficient in CuZnSOD (EG118) was measured in media containing different carbon sources. Aspirin inhibited the fermentative growth of all three strains in glucose medium. It inhibited the non-fermentative growth of the MnSOD-deficient strain very drastically in ethanol medium and had no effect on this strain in glycerol or acetate medium. The non-fermentative growth of the other two strains was not affected by aspirin. The growth inhibition of strain EG110 was associated with early necrosis in glucose medium and late apoptosis in ethanol medium. The apoptosis was preceded by a pronounced loss of cell viability. The growth inhibitory effect of aspirin was not reversed by the antioxidants N-acetylcysteine and vitamin E. Furthermore, aspirin itself appeared to act as an antioxidant until the onset of overt apoptosis, when a moderate increase in the intracellular oxidation level occurred. This suggested that reactive oxygen species probably do not play a primary role in the apoptosis of cells exposed to aspirin.peer-reviewe

Comparison of central versus peripheral delivery of pregabalin in neuropathic pain states

<p>Abstract</p> <p>Background</p> <p>Although pregabalin therapy is beneficial for neuropathic pain (NeP) by targeting the CaVα₂δ-1 subunit, its site of action is uncertain. Direct targeting of the central nervous system may be beneficial for the avoidance of systemic side effects.</p> <p>Results</p> <p>We used intranasal, intrathecal, and near-nerve chamber forms of delivery of varying concentrations of pregabalin or saline delivered over 14 days in rat models of experimental diabetic peripheral neuropathy and spinal nerve ligation. As well, radiolabelled pregabalin was administered to determine localization with different deliveries. We evaluated tactile allodynia and thermal hyperalgesia at multiple time points, and then analyzed harvested nervous system tissues for molecular and immunohistochemical changes in CaVα₂δ-1 protein expression. Both intrathecal and intranasal pregabalin administration at high concentrations relieved NeP behaviors, while near-nerve pregabalin delivery had no effect. NeP was associated with upregulation of CACNA2D1 mRNA and CaVα₂δ-1 protein within peripheral nerve, dorsal root ganglia (DRG), and dorsal spinal cord, but not brain. Pregabalin's effect was limited to suppression of CaVα₂δ-1 protein (but not CACNA2D1 mRNA) expression at the spinal dorsal horn in neuropathic pain states. Dorsal root ligation prevented CaVα₂δ-1 protein trafficking anterograde from the dorsal root ganglia to the dorsal horn after neuropathic pain initiation.</p> <p>Conclusions</p> <p>Either intranasal or intrathecal pregabalin relieves neuropathic pain behaviours, perhaps due to pregabalin's effect upon anterograde CaVα₂δ-1 protein trafficking from the DRG to the dorsal horn. Intranasal delivery of agents such as pregabalin may be an attractive alternative to systemic therapy for management of neuropathic pain states.</p

Cerebrospinal fluid penetration of meropenem in neurocritical care patients with proven or suspected ventriculitis: a prospective observational study

Background: Ventriculitis is a complication of temporary intraventricular drains. The limited penetration of meropenem into the cerebrospinal fluid (CSF) is well known. However, ventricular CSF pharmacokinetic data in patients with ventriculitis are lacking. The aim of this study was to evaluate meropenem pharmacokinetics in the serum and CSF of neurocritical care patients with proven or suspected ventriculitis. Methods: We conducted an observational pharmacokinetic study of neurocritical care patients with proven or suspected ventriculitis receiving meropenem. Multiple blood and CSF samples were taken and were described using nonparametric pharmacokinetic modelling with Pmetrics. Results: In total, 21 patients (median age 52 years, median weight 76 kg) were included. The median (range) of peak and trough concentrations in serum were 20.16 (4.40-69.00) mg/L and 2.54 (0.00-31.40) mg/L, respectively. The corresponding peak and trough concentrations in CSF were 1.20 (0.00-6.20) mg/L and 1.28 (0.00-4.10) mg/L, respectively, with a median CSF/serum ratio (range) of 0.09 (0.03-0.16). Median creatinine clearance ranged from 60. 7 to 217.6 ml/minute (median 122.5 ml/minute). A three-compartment linear population pharmacokinetic model was most appropriate. No covariate relationships could be supported for any of the model parameters. Meropenem demonstrated poor penetration into CSF, with a median CSF/serum ratio of 9 % and high interindividual pharmacokinetic variability. Conclusions: Administration of higher-than-standard doses of meropenem and therapeutic drug monitoring in both serum and CSF should be considered to individualise meropenem dosing in neurocritical care patients with ventriculitis

The New Urban Revival in the United States

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68657/2/10.1080_00420989320081901.pd

VennVax, a DNA-prime, peptide-boost multi-T-cell epitope poxvirus vaccine, induces protective immunity against vaccinia infection by T cell response alone

The potential for smallpox to be disseminated in a bioterror attack has prompted development of new, safer smallpox vaccination strategies. We designed and evaluated immunogenicity and efficacy of a T-cell epitope vaccine based on conserved and antigenic vaccinia/variola sequences, identified using bioinformatics and immunological methods. Vaccination in HLA transgenic mice using a DNA-prime/peptide-boost strategy elicited significant T cell responses to multiple epitopes. No antibody response pre-challenge was observed, neither against whole vaccinia antigens nor vaccine epitope peptides. Remarkably, 100% of vaccinated mice survived lethal vaccinia challenge, demonstrating that protective immunity to vaccinia does not require B cell priming