Seasonal variation of cesium 134 and cesium 137 in semidomestic reindeer in Norway after the Chernobyl accident

The Chernobyl accident had a great impact on the semidomestic reindeer husbandry in central Norway. Seasonal differences in habitat and diet resulted in large variations in observed radiocesium concentrations in reindeer after the Chernobyl accident. In three areas with high values of cesium-134 and cesium-137 in lichens, the main feed for reindeer in winter, reindeer were sampled every second month to monitor the seasonal variation and the decrease rate of the radioactivity. The results are based on measurements of cesium-134 and cesium-137 content in meat and blood and by whole-body monitoring of live animals. In 1987 the increase of radiocesium content in reindeer in Vågå were 4x from August to January. The mean reductions in radiocesium content from the winter 1986/87 to the winter 1987/88 were 32%, 50% and 43% in the areas of Vågå, Østre-Namdal and Lom respectively

The pathogenesis of pulmonary hypertension - an update

Elevation of the mean pulmonary arterial pressure to ≥25 mm Hg within the low-pressure system of the pulmonary circulation is defined as pulmonary hypertension. Pulmonary hypertension may be the consequence of various clinical and pathophysiological entities. Many of these conditions, however, result in a final common pathway of pathogenesis. This pathway is characterised by the triad of excessive vasoconstriction, microthrombosis and remodelling of pulmonary arteries. Remodelling is arguably the most important factor: its complex pathogenesis is not completely understood and no specific treatment directly targets vascular remodelling. This article aims to review the current understanding of the pathogenesis of pulmonary hypertension and to give insights in future developments in this evolving field

The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C

Opioids are some of the most efficacious analgesics used in humans. Prolonged administration of opioids, however, often causes the development of drug tolerance, thus limiting their effectiveness. To explore the molecular basis of those mechanisms that may contribute to opioid tolerance, we have isolated a cDNA for the human mu opioid receptor, the target of such opioid narcotics as morphine, codeine, methadone, and fentanyl. The receptor encoded by this cDNA is 400 amino acids long with 94% sequence similarity to the rat mu opioid receptor. Transient expression of this cDNA in COS-7 cells produced high-affinity binding sites to mu-selective agonists and antagonists. This receptor displays functional coupling to a recently cloned G-protein-activated K+ channel. When both proteins were expressed in Xenopus oocytes, functional desensitization developed upon repeated stimulation of the mu opioid receptor, as observed by a reduction in K+ current induced by the second mu receptor activation relative to that induced by the first. The extent of desensitization was potentiated by both the multifunctional calcium/calmodulin-dependent protein kinase and protein kinase C. These results demonstrate that kinase modulation is a molecular mechanism by which the desensitization of mu receptor signaling may be regulated at the cellular level, suggesting that this cellular mechanism may contribute to opioid tolerance in humans

Enhanced Thermal Stability and Reduced Aggregation in an Antibody Fab Fragment at Elevated Concentrations

The aggregation of protein therapeutics such as antibodies remains a major challenge in the biopharmaceutical industry. The present study aimed to characterize the impact of the protein concentration on the mechanisms and potential pathways for aggregation, using the antibody Fab fragment A33 as the model protein. Aggregation kinetics were determined for 0.05 to 100 mg/mL Fab A33, at 65 °C. A surprising trend was observed whereby increasing the concentration decreased the relative aggregation rate, ln(v) (% day-1), from 8.5 at 0.05 mg/mL to 4.4 at 100 mg/mL. The absolute aggregation rate (mol L-1 h-1) increased with the concentration following a rate order of approximately 1 up to a concentration of 25 mg/mL. Above this concentration, there was a transition to an apparently negative rate order of -1.1 up to 100 mg/mL. Several potential mechanisms were examined as possible explanations. A greater apparent conformational stability at 100 mg/mL was observed from an increase in the thermal transition midpoint (Tm) by 7-9 °C, relative to those at 1-4 mg/mL. The associated change in unfolding entropy (△Svh) also increased by 14-18% at 25-100 mg/mL, relative to those at 1-4 mg/mL, indicating reduced conformational flexibility in the native ensemble. Addition of Tween or the crowding agents Ficoll and dextran, showed that neither surface adsorption, diffusion limitations nor simple volume crowding affected the aggregation rate. Fitting of kinetic data to a wide range of mechanistic models implied a reversible two-state conformational switch mechanism from aggregation-prone monomers (N*) into non-aggregating native forms (N) at higher concentrations. kD measurements from DLS data also suggested a weak self-attraction while remaining colloidally stable, consistent with macromolecular self-crowding within weakly associated reversible oligomers. Such a model is also consistent with compaction of the native ensemble observed through changes in Tm and △Svh

Control Law Design for Perching an Agile MAV with Articulated Wings

This paper explores the use of variable wing dihedral and variable wing twist (in conjunction with a conventional horizontal elevator) to control an aircraft performing a perching maneuver. A choice of controller architecture wherein the dihedral is employed in the forward path and the elevator and twist are employed in the feedback path, is considered. The aircraft is modeled as a multivariable linear time-varying system. A specific perching trajectory is considered; and the open-loop aircraft is longitudinally unstable for a segment of this perching trajectory and lateral-directionally unstable for the entire perching trajectory. A multivariable time-varying controller is designed to efficiently stabilize the aircraft as well as reject longitudinal-lateral-directional wind disturbances, while closely tracking the reference perching trajectory

Insulin signaling inhibits the 5-HT(2C )receptor in choroid plexus via MAP kinase

BACKGROUND: G protein-coupled receptors (GPCRs) interact with heterotrimeric GTP-binding proteins (G proteins) to modulate acute changes in intracellular messenger levels and ion channel activity. In contrast, long-term changes in cellular growth, proliferation and differentiation are often mediated by tyrosine kinase receptors and certain GPCRs by activation of mitogen-activated protein (MAP) kinases. Complex interactions occur between these signaling pathways, but the specific mechanisms of such regulatory events are not well-understood. In particular it is not clear whether GPCRs are modulated by tyrosine kinase receptor-MAP kinase pathways. RESULTS: Here we describe tyrosine kinase receptor regulation of a GPCR via MAP kinase. Insulin reduced the activity of the 5-HT(2C )receptor in choroid plexus cells which was blocked by the MAP kinase kinase (MEK) inhibitor, PD 098059. We demonstrate that the inhibitory effect of insulin and insulin-like growth factor type 1 (IGF-1) on the 5-HT(2C )receptor is dependent on tyrosine kinase, RAS and MAP kinase. The effect may be receptor-specific: insulin had no effect on another GPCR that shares the same G protein signaling pathway as the 5-HT(2C )receptor. This effect is also direct: activated MAP kinase mimicked the effect of insulin, and removing a putative MAP kinase site from the 5-HT(2C )receptor abolished the effect of insulin. CONCLUSION: These results show that insulin signaling can inhibit 5-HT(2C )receptor activity and suggest that MAP kinase may play a direct role in regulating the function of a specific GPCR

Dynamical scaling and isotope effect in temporal evolution of mesoscopic structure during hydration of cement

The evolution of mesoscopic structure for cement-water mixtures turning into colloidal gels remains far from being understood. Recent neutron scattering investigations (Phys. Rev. Lett. 93, 255704 (2004); Phys. Rev. B. 72, 224208 (2005); Phys. Rev. B. 82, 064203 (2010)),, reveal the role of hydrogen bond in temporal evolution of the mesoscopic structure during hydration of cement which is the most consumed synthetic material. The present neutron scattering investigation on hydration of cement with a mixture of light and heavy water points to incomprehensibility of the temporal evolution of the mesoscopic structure in terms of earlier observations on hydration with pure light or heavy water. Unlike in the case of hydration with light water, disagreement has been observed with the hypothesis of dynamical scaling for hydration of cement with a mixture of the two types of water. The dynamics of evolution of the mesoscopic structure has been observed to be nonlinear in regard to the composition of hydration medium.Comment: 16 Pages, 5 Figure

A Transiting Planet of a Sun-like Star

A planet transits an 11th magnitude, G1V star in the constellation Corona Borealis. We designate the planet XO-1b, and the star, XO-1, also known as GSC 02041-01657. XO-1 lacks a trigonometric distance; we estimate it to be 200+-20 pc. Of the ten stars currently known to host extrasolar transiting planets, the star XO-1 is the most similar to the Sun in its physical characteristics: its radius is 1.0+-0.08 R_Sun, its mass is 1.0+-0.03 M_Sun, V sini < 3 km/s, and its metallicity [Fe/H] is 0.015+-0.04. The orbital period of the planet XO-1b is 3.941534+-0.000027 days, one of the longer ones known. The planetary mass is 0.90+-0.07 M_Jupiter, which is marginally larger than that of other transiting planets with periods between 3 and 4 days. Both the planetary radius and the inclination are functions of the spectroscopically determined stellar radius. If the stellar radius is 1.0+-0.08 R_Sun, then the planetary radius is 1.30+-0.11 R_Jupiter and the inclination of the orbit is 87.7+-1.2 degrees. We have demonstrated a productive international collaboration between professional and amateur astronomers that was important to distinguishing this planet from many other similar candidates.Comment: 31 pages, 9 figures, accepted for part 1 of Ap

Measurements of body fat is associated with markers of inflammation, insulin resistance and lipid levels in both overweight and in lean, healthy subjects

Background & aims: Low-grade inflammation is associated with fat mass in overweight. Whether this association exists in lean persons is unknown. Aims were to investigate associations between anthropometric measures of fat distribution and fat mass (% and kg) assessed by bioelectrical impedance analysis (BIA). Furthermore we wanted to investigate the relationship between fat mass and markers of insulin resistance, inflammation, and lipids in healthy subjects in different BMI categories. Methods: We compared 47 healthy overweight adults (BMI 26e40 kg/m2) and 40 lean (BMI 17e25 kg/ m2) matched for age and sex. Waist and hip circumferences, waist-to-hip ratio, waist-to-height ratio and triceps skinfold were used to evaluate fat distribution. BIA was used to estimate fat mass (% and kg). Markers of insulin resistance, lipids, inflammation and adipokines were measured. Results: Hip circumference was associated (P < 0.01) with BIA-assessed fat mass (%) in both groups (lean: regression coefficient B ¼ 0.4; overweight: B ¼ 0.5). An increase in hip circumference in all tertiles was associated with higher plasma levels of leptin, CRP and C-peptide in both groups. Conclusions: Fat mass may play a role in low-grade inflammation also in subjects within the normal range of BMI. Hip circumference may be a surrogate measure for fat mass in subjects in different BMI categories, and may be useful for identification of people with risk of developing overweight-related chronic disease