Vibrational Relaxation of N2O (v2) by Atomic Oxygen Measured by Tunable Diode Laser Absorption Spectroscopy

Through the use of Transient Diode Laser Absorption Spectroscopy (TDLAS), the rate coefficient for the vibrational relaxation of N2O (ν2) by O(3P) at room temperature (32 ºC)) was determined to be (1.51 ± 0.11)x10-12 cm3molecule-1sec-1. A Q-switched, frequency quadrupled (266 nm) Nd:YAG laser pulse was used as the pump for this experiment. This pulse caused the photodissociation of O3 into O2 and O atoms.Excited oxygen (O(1D)) was collisionally quenched to ground state (O(3P)) by Ar and/or Xe. Photodissociation also caused a temperature jump within the system, exciting the ν2 state of N2O molecules. Population in the ν2 state was monitored through a TDLASobservation of a ν3 transition. Data were fit using a Visual Fortran 6.0 Global Fitting program. Analysis of room temperature data taken using only Ar to quench O atoms to the ground state gave the same rate coefficient as analysis of data taken using an Ar/Xe mixture, suggesting Ar alone is a sufficient bath gas. Experimentation was alsoperformed at -27 ºC and -82 ºC for a temperature dependence analysis. A linear regression analysis gave a rate coefficient dependence on temperature of ... for the rate coefficient of the vibrational relaxation of N2O (ν2) by atomic oxygen.

Vibrational Relaxation of 13CO2(v2) by Atomic Oxygen

Carbon dioxide (CO2) has been of recent interest due to the issue of greenhouse cooling in the upper atmosphere by species such as CO2 and NO. In the Earth’s upper atmosphere, between altitudes of 75 and 110 km, a collisional energy exchange occurs between CO2 and atomic oxygen, which promotes a population of ground state CO2 to the bend excited state. The relaxation of CO2 following this excitation is characterized by spontaneous emission of 15-μm. Most of this energy is emitted away from Earth. Due to the low density in the upper atmosphere, most of this energy is not reabsorbed and thus escapes into space, leading to a local cooling effect in the upper atmosphere. To determine the efficiency of the CO2- O atom collisional energy exchange, transient diode laser absorption spectroscopy was used to monitor the population of the first vibrationally excited state, 13CO2(0110) or ν2, as a function of time. The rate coefficient, kO(ν2), for the vibrational relaxation 13CO2 (ν2)-O was determined by fitting laboratory measurements using a home-written linear least squares algorithm. The rate coefficient, kO(ν2), of the vibrational relaxation of 13CO2(ν2), by atomic oxygen at room temperature was determined to be (1.6 ± 0.3 x 10-12 cm3 s-1), which is within the uncertainty of the rate coefficient previously found in this group for 12CO2(ν2) relaxation. The cold temperature kO(ν2) values were determined to be: (2.1 ± 0.8) x 10-12 cm3 s-1 at Tfinal = 274 K, (1.8 ± 0.3) x 10-12 cm3 s-1 at Tfinal = 239 K, (2 ± 1) x 10-12 cm3 s-1 at Tfinal = 208 K, and (1.7 ± 0.3) x 10-12 cm3 s-1 at Tfinal = 186 K. These data did not show a definitive negative temperature dependence comparable to that found for 12CO2 previously.

Vibrational Relaxation of O3(nu2) by O((3)P)

Laboratory measurements of the rate coefficient for quenching of O3(nu2) by ground-state atomic oxygen, kO(nu2), at room temperature are presented. kO(nu2) is currently not well known and is necessary for appropriate nonlocal thermodynamic equilibrium modeling of the upper mesosphere and lower thermosphere. In this work, a 266 nm laser pulse photolyzes a small amount of O3 in a slow-flowing gas mixture of O3, Xe, and Ar. This process simultaneously produces atomic oxygen and increases the temperature of the gas mixture slightly, thereby increasing the population in the O3(nu2) state. Transient diode laser absorption spectroscopy is used to monitor the populations of the O3(nu2) and ground vibrational states as the system re-equilibrates. Relaxation rates are measured over a range of quencher concentrations to extract the rate coefficient of interest. The value of kO(nu2) was determined to be (2.2 0.5) * 10(-12) cm(3) s(-1).

Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria

The Krebs cycle is of fundamental importance for the generation of the energetic and molecular needs of both prokaryotic and eukaryotic cells. Both enantiomers of metabolite 2-hydroxyglutarate are directly linked to this pivotal biochemical pathway and are found elevated not only in several cancers, but also in different variants of the neurometabolic disease 2-hydroxyglutaric aciduria. Recently we showed that cancer-associated IDH2 germline mutations cause one variant of 2-hydroxyglutaric aciduria. Complementary to these findings, we now report recessive mutations in SLC25A1, the mitochondrial citrate carrier, in 12 out of 12 individuals with combined D-2- and L-2-hydroxyglutaric aciduria. Impaired mitochondrial citrate efflux, demonstrated by stable isotope labeling experiments and the absence of SLC25A1 in fibroblasts harboring certain mutations, suggest that SLC25A1 deficiency is pathogenic. Our results identify defects in SLC25A1 as a cause of combined D-2- and L-2-hydroxyglutaric aciduria.

High-resolution computer simulation of the dynamics of isoelectric focusing using carrier ampholytes: focusing with concurrent electrophoretic mobilization is an isotachophoretic process

Focusing of four hemoglobins with concurrent electrophoretic mobilization was studied by computer simulation. A dynamic electrophoresis simulator was first used to provide a detailed description of focusing in a 100-carrier component, pH 6-8 gradient using phosphoric acid as anolyte and NaOH as catholyte. These results are compared to an identical simulation except that the catholyte contained both NaOH and NaCl. A stationary, steady-state distribution of carrier components and hemoglobins is produced in the first configuration. In the second, the chloride ion migrates into and through the separation space. It is shown that even under these conditions of chloride ion flux a pH gradient forms. All amphoteric species acquire a slight positive charge upon focusing and the whole pattern is mobilized towards the cathode. The cathodic gradient end is stable whereas the anodic end is gradually degrading due to the continuous accumulation of chloride. The data illustrate that the mobilization is a cationic isotachophoretic process with the sodium ion being the leading cation. The peak height of the hemoglobin zones decreases somewhat upon mobilization, but the zones retain a relatively sharp profile, thus facilitating detection. The electropherograms that would be produced by whole column imaging and by a single detector placed at different locations along the focusing column are presented and show that focusing can be commenced with NaCl present in the catholyte at the beginning of the experiment. However, this may require detector placement on the cathodic side of the catholyte/sample mixture interface.

Control of muscle relaxation during anesthesia: a novel approach for clinical routine

During general anesthesia drugs are administered to provide hypnosis, ensure analgesia, and skeletal muscle relaxation. In this paper, the main components of a newly developed controller for skeletal muscle relaxation are described. Muscle relaxation is controlled by administration of neuromuscular blocking agents. The degree of relaxation is assessed by supramaximal train-of-four stimulation of the ulnar nerve and measuring the electromyogram response of the adductor pollicis muscle. For closed-loop control purposes, a physiologically based pharmacokinetic and pharmacodynamic model of the neuromuscular blocking agent mivacurium is derived. The model is used to design an observer-based state feedback controller. Contrary to similar automatic systems described in the literature this controller makes use of two different measures obtained in the train-of-four measurement to maintain the desired level of relaxation. The controller is validated in a clinical study comparing the performance of the controller to the performance of the anesthesiologist. As presented, the controller was able to maintain a preselected degree of muscle relaxation with excellent precision while minimizing drug administration. The controller performed at least equally well as the anesthesiologist.

MULTIPLE DISEASES IN CARRIER PROBABILITY ESTIMATION: ACCOUNTING FOR SURVIVING ALL CANCERS OTHER THAN BREAST AND OVARY IN BRCAPRO

Mendelian models can predict who carries an inherited deleterious mutation of known disease genes based on family history. For example, the BRCAPRO model is commonly used to identify families who carry mutations of BRCA1 and BRCA2, based on familial breast and ovarian cancers. These models incorporate the age of diagnosis of diseases in relatives and current age or age of death. We develop a rigorous foundation for handling multiple diseases with censoring. We prove that any disease unrelated to mutations can be excluded from the model, unless it is sufficiently common and dependent on a mutation-related disease time. Furthermore, if a family member has a disease with higher probability density among mutation carriers, but the model does not account for it, then the carrier probability is deflated. However, even if a family only has diseases the model accounts for, if the model excludes a mutation-related disease, then the carrier probability will be inflated. In light of these results, we extend BRCAPRO to account for surviving all non-breast/ovary cancers as a single outcome. The extension also enables BRCAPRO to extract more useful information from male relatives. Using 1500 familes from the Cancer Genetics Network, accounting for surviving other cancers improves BRCAPRO’s concordance index from 0.758 to 0.762 (p = 0.046), improves its positive predictive value from 35% to 39% (p < 10−6) without impacting its negative predictive value, and improves its overall calibration, although calibration slightly worsens for those with carrier probability < 10%. Copyright c 2000 John Wiley & Sons, Ltd.

Clinical validation of electromyography and acceleromyography as sensors for muscle relaxation

BACKGROUND AND OBJECTIVE: The aim of this study was to determine which of two clinically applied methods, electromyography or acceleromyography, was less affected by external disturbances, had a higher sensitivity and which would provide the better input signal for closed loop control of muscle relaxation. METHODS: In 14 adult patients, anaesthesia was induced with intravenous opioids and propofol. The response of the thumb to ulnar nerve stimulation was recorded on the same arm. Mivacurium was used for neuromuscular blockade. Under stable conditions of relaxation, the infusion-rate was decreased and the effects of turning the hand were investigated. RESULTS: Electromyography and acceleromyography both reflected the change of the infusion rate (P = 0.015 and P < 0.001, respectively). Electromyography was significantly less affected by the hand-turn (P = 0.008) than acceleromyography. While zero counts were detected with acceleromyography, electromyography could still detect at least one count in 51.1%. CONCLUSIONS: Electromyography is more reliable for use in daily practice as it is less influenced by external disturbances than acceleromyography.

High-resolution computer simulation of the dynamics of isoelectric focusing: in quest of more realistic input parameters for carrier ampholytes

The impact of the systematic variation of either DeltapK(a) or mobility of 140 biprotic carrier ampholytes on the conductivity profile of a pH 3-10 gradient was studied by dynamic computer simulation. A configuration with the greatest DeltapK(a) in the pH 6-7 range and uniform mobilities produced a conductivity profile consistent with that which is experimentally observed. A similar result was observed when the neutral (pI = 7) ampholyte is assigned the lowest mobility and mobilities of the other carriers are systematically increased as their pI's recede from 7. When equal DeltapK(a) values and mobilities are assigned to all ampholytes a conductivity plateau in the pH 5-9 region is produced which does not reflect what is seen experimentally. The variation in DeltapK(a) values is considered to most accurately reflect the electrochemical parameters of commercially available mixtures of carrier ampholytes. Simulations with unequal mobilities of the cationic and anionic species of the carrier ampholytes show either cathodic (greater mobility of the cationic species) or anodic (greater mobility of the anionic species) drifts of the pH gradient. The simulated cationic drifts compare well to those observed experimentally in a capillary in which the focusing of three dyes was followed by whole column optical imaging. The cathodic drift flattens the acidic portion of the gradient and steepens the basic part. This phenomenon is an additional argument against the notion that focused zones of carrier ampholytes have no electrophoretic flux.

Intimal proliferation and restenosis in paclitaxel-eluting stents with aminoparylene as carrier substance in swines

BACKGROUND: Polymer as carrier substance for drugeluting stents (DES) has been accused of inducing inflammation and hypersensitivity reactions leading to restenosis and stent thrombosis. Thus, a new paclitaxel-eluting stent (PES) with aminoparylene as a carrier substance is tested in the present study. METHODS: In 10 pigs, stents were implanted in the epicardial coronary arteries: 1) bare-metal stents (BMS, control stent); 2) cobalt-chromium stents (CCS); and 3) PES. Stent length was 15 mm, and diameter was 3 mm. The animals were restudied after 6 weeks. Quantitative coronary angiography was performed at baseline and follow up. Minimum luminal diameter (MLD) and late loss were calculated in all animals. Histologic vessel lumen, intimal proliferation and restenosis were determined by morphometry. Disruption of the lamina elastica interna (LEI) and inflammatory reactions were assessed by histology. RESULTS: The MLD at baseline was 2.83 +/- 0.28 mm, and at follow up it was 2.29 +/- 0.44 (p < 0.05; n = 30). Late loss and angiographic restenosis were smallest in the CCS and largest in the PES (ns). Neointimal proliferation was similar for all 3 stents, ranging between 1.38 and 1.64 mm(2) (ns). There was a significant correlation between disruption of the LEI and inflammatory reactions. CONCLUSIONS: PTs with aminoparylene as a carrier substance show similar late loss and angiographic restenosis to that of BM and CCS. The incidence of inflammatory reactions (35% of all histologic sections) is similar in all stents, but highest in PES. The mechanism of this reaction is unclear, but may be either due to the drug itself, the disruption of the LEI or to a hypersensitivity reaction.