Affinity retardation chromatography: characterization of the method and its application. The description of low affinity laminin self-interactions.

Affinity retardation chromatography (ARC), a method for the examination of low-affinity interactions, is mathematically described in order to characterize the method itself and to estimate binding coefficients of self-assembly domains of basement membrane protein laminin. Affinity retardation was determined by comparing the elutions on a "binding" and on a "nonreacting" column. It depends on the binding coefficient, the concentrations of both ligands, and the nonbinding elution position. Half maximal binding of the NH2-terminal domain of laminin B1-short arm to the A- and/or B2-short arms was estimated to occur at 10-17 microM for noncooperative and at < or = 3 microM for cooperative binding. A model of the laminin polymerization, postulating two levels of cooperative binding behavior, is described.

Maximal acceleration of calcium release refractoriness by β-adrenergic stimulation requires dual activation of protein kinase A and CaMKII in mouse ventricular myocytes

Time-dependent refractoriness of calcium (Ca2+) release in cardiac myocytes is an important factor in determining whether pro-arrhythmic release patterns develop. At the subcellular level of the Ca2+ spark, recent studies have suggested that recovery of spark amplitude is controlled by local sarcoplasmic reticulum (SR) refilling whereas refractoriness of spark triggering depends on both refilling and the sensitivity of the ryanodine receptor (RyR) release channels that produce sparks. Here we studied regulation of Ca2+ spark refractoriness in mouse ventricular myocytes by examining how β-adrenergic stimulation influenced sequences of Ca2+ sparks originating from individual RyR clusters. Our protocol allowed us to separately measure recovery of spark amplitude and delays between successive sparks, and data were interpreted quantitatively through simulations with a stochastic mathematical model. We found that, compared with spark sequences measured under control conditions: (1) β-adrenergic stimulation with isoproterenol accelerated spark amplitude recovery and decreased spark-to-spark delays; (2) activating protein kinase A (PKA) with forskolin accelerated amplitude recovery but did not affect spark-to-spark delays; (3) inhibiting PKA with H89 retarded amplitude recovery and increased spark- to-spark delays; (4) preventing phosphorylation of the RyR at serine 2808 with a knock-in mouse prevented the decrease in spark-to-spark delays seen with β-adrenergic stimulation; (5) inhibiting either PKA or Ca2+/calmodulin-dependent protein kinase II (CaMKII) during β-adrenergic stimulation prevented the decrease in spark-to-spark delays seen) without inhibition. The results suggest that activation of either PKA or CaMKII is sufficient to speed SR refilling, but activation of both kinases appears necessary to observe increased RyR sensitivity. The data provide novel insight into β-adrenergic regulation of Ca2+ release refractoriness in mouse myocytes.

Short-arc tracklet association for geostationary objects

Measurement association and initial orbit determination is a fundamental task when building up a database of space objects. This paper proposes an efficient and robust method to determine the orbit using the available information of two tracklets, i.e. their line-of-sights and their derivatives. The approach works with a boundary-value formulation to represent hypothesized orbital states and uses an optimization scheme to find the best fitting orbits. The method is assessed and compared to an initial-value formulation using a measurement set taken by the Zimmerwald Small Aperture Robotic Telescope of the Astronomical Institute at the University of Bern. False associations of closely spaced objects on similar orbits cannot be completely eliminated due to the short duration of the measurement arcs. However, the presented approach uses the available information optimally and the overall association performance and robustness is very promising. The boundary-value optimization takes only around 2% of computational time when compared to optimization approaches using an initial-value formulation. The full potential of the method in terms of run-time is additionally illustrated by comparing it to other published association methods.

A boundary value problem approach to too-short arc optical track association

Given a short-arc optical observation with estimated angle-rates, the admissible region is a compact region in the range / range-rate space defined such that all likely and relevant orbits are contained within it. An alternative boundary value problem formulation has recently been proposed where range / range hypotheses are generated with two angle measurements from two tracks as input. In this paper, angle-rate information is reintroduced as a means to eliminate hypotheses by bounding their constants of motion before a more computationally costly Lambert solver or differential correction algorithm is run.

Positive braids of maximal signature

We characterise positive braid links with positive Seifert form via a finite number of forbidden minors. From this we deduce a one-to-one correspondence between prime positive braid links with positive Seifert form and simply laced Dynkin diagrams, as well as a simple classification of alternating positive braid knots.

Improved VMAT planning for head and neck tumors with an advanced optimization algorithm

OBJECTIVE In this study, the "Progressive Resolution Optimizer PRO3" (Varian Medical Systems) is compared to the previous version "PRO2" with respect to its potential to improve dose sparing to the organs at risk (OAR) and dose coverage of the PTV for head and neck cancer patients. MATERIALS AND METHODS For eight head and neck cancer patients, volumetric modulated arc therapy (VMAT) treatment plans were generated in this study. All cases have 2-3 phases and the total prescribed dose (PD) was 60-72Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54Gy, and complex PTV structures with an overlap to the parotids. Optimization was performed based on planning objectives for the PTV according to ICRU83, and with minimal dose to spinal cord, and parotids outside PTV. In order to assess the quality of the optimization algorithms, an identical set of constraints was used for both, PRO2 and PRO3. The resulting treatment plans were investigated with respect to dose distribution based on the analysis of the dose volume histograms. RESULTS For the phase 1 plans (PD=54Gy) the near maximum dose D2% of the spinal cord, could be minimized to 22±5 Gy with PRO3, as compared to 32±12Gy with PRO2, averaged for all patients. The mean dose to the parotids was also lower in PRO3 plans compared to PRO2, but the differences were less pronounced. A PTV coverage of V95%=97±1% could be reached with PRO3, as compared to 86±5% with PRO2. In clinical routine, these PRO2 plans would require modifications to obtain better PTV coverage at the cost of higher OAR doses. CONCLUSION A comparison between PRO3 and PRO2 optimization algorithms was performed for eight head and neck cancer patients. In general, the quality of VMAT plans for head and neck patients are improved with PRO3 as compared to PRO2. The dose to OARs can be reduced significantly, especially for the spinal cord. These reductions are achieved with better PTV coverage as compared to PRO2. The improved spinal cord sparing offers new opportunities for all types of paraspinal tumors and for re-irradiation of recurrent tumors or second malignancies.

Impact of the arc length on GNSS analysis results

Homogeneously reprocessed combined GPS/GLONASS 1- and 3-day solutions from 1994 to 2013, generated by the Center for Orbit Determination in Europe (CODE) in the frame of the second reprocessing campaign REPRO-2 of the International GNSS Service, as well as GPS- and GLONASS-only 1- and 3-day solutions for the years 2009 to 2011 are analyzed to assess the impact of the arc length on the estimated Earth Orientation Parameters (EOP, namely polar motion and length of day), on the geocenter, and on the orbits. The conventional CODE 3-day solutions assume continuity of orbits, polar motion components, and of other parameters at the day boundaries. An experimental 3-day solution, which assumes continuity of the orbits, but independence from day to day for all other parameters, as well as a non-overlapping 3-day solution, is included into our analysis. The time series of EOPs, geocenter coordinates, and orbit misclosures, are analyzed. The long-arc solutions were found to be superior to the 1-day solutions: the RMS values of EOP and geocenter series are typically reduced between 10 and 40 %, except for the polar motion rates, where RMS reductions by factors of 2–3 with respect to the 1-day solutions are achieved for the overlapping and the non-overlapping 3-day solutions. In the low-frequency part of the spectrum, the reduction is even more important. The better performance of the orbits of 3-day solutions with respect to 1-day solutions is also confirmed by the validation with satellite laser ranging.

Grace Pedley, Rollenbild, Hüftbild, in: Joan of Arc

Signatur des Originals: S 36/F09498

Maximal exercise hemodynamics and risk of mortality in apparently healthy men and women

The use of exercise electrocardiography (ECG) to detect latent coronary heart disease (CHD) is discouraged in apparently healthy populations because of low sensitivity. These recommendations however, are based on the efficacy of evaluation of ischemia (ST segment changes) with little regard for other measures of cardiac function that are available during exertion. The purpose of this investigation was to determine the association of maximal exercise hemodynamic responses with risk of mortality due to all-causes, cardiovascular disease (CVD), and coronary heart disease (CHD) in apparently healthy individuals. Study participants were 20,387 men (mean age = 42.2 years) and 6,234 women (mean age = 41.9 years) patients of a preventive medicine center in Dallas, TX examined between 1971 and 1989. During an average of 8.1 years of follow-up, there were 348 deaths in men and 66 deaths in women. In men, age-adjusted all-cause death rates (per 10,000 person years) across quartiles of maximal systolic blood pressure (SBP) (low to high) were: 18.2, 16.2, 23.8, and 24.6 (p for trend $<$0.001). Corresponding rates for maximal heart rate were: 28.9, 15.9, 18.4, and 15.1 (p trend $<$0.001). After adjustment for confounding variables including age, resting systolic pressure, serum cholesterol and glucose, body mass index, smoking status, physical fitness and family history of CVD, risks (and 95% confidence interval (CI)) of all-cause mortality for quartiles of maximal SBP, relative to the lowest quartile, were: 0.96 (0.70-1.33), 1.36 (1.01-1.85), and 1.37 (0.98-1.92) for quartiles 2-4 respectively. Similar risks for maximal heart rate were: 0.61 (0.44-0.85), 0.69 (0.51-0.93), and 0.60 (0.41-0.87). No associations were noted between maximal exercise rate-pressure product mortality. Similar results were seen for risk of CVD and CHD death. In women, similar trends in age-adjusted all-cause and CVD death rates across maximal SBP and heart rate categories were observed. Sensitivity of the exercise test in predicting mortality was enhanced when ECG results were evaluated together with maximal exercise SBP or heart rate with a concomitant decrease in specificity. Positive predictive values were not improved. The efficacy of the exercise test in predicting mortality in apparently healthy men and women was not enhanced by using maximal exercise hemodynamic responses. These results suggest that an exaggerated systolic blood pressure or an attenuated heart rate response to maximal exercise are risk factors for mortality in apparently healthy individuals. ^

Volumetric Modulated Arc Therapy Evaluation with the Radiological Physics Center Head and Neck Phantom

Validation of treatment plan quality and dose calculation accuracy is essential for new radiotherapy techniques, including volumetric modulated arc therapy (VMAT). VMAT delivers intensity modulated radiotherapy treatments while simultaneously rotating the gantry, adding an additional level of complexity to both the dose calculation and delivery of VMAT treatments compared to static gantry IMRT. The purpose of this project was to compare two VMAT systems, Elekta VMAT and Varian RapidArc, to the current standard of care, IMRT, in terms of both treatment plan quality and dosimetric delivery accuracy using the Radiological Physics Center (RPC) head and neck (H&N) phantom. Clinically relevant treatment plans were created for the phantom using typical prescription and dose constraints for Elekta VMAT (planned with Pinnacle3 Smart Arc) and RapidArc and IMRT (both planned with Eclipse). The treatment plans were evaluated to determine if they were clinically comparable using several dosimetric criteria, including ability to meet dose objectives, hot spots, conformity index, and homogeneity index. The planned treatments were delivered to the phantom and absolute doses and relative dose distributions were measured with thermoluminescent dosimeters (TLDs) and radiochromic film, respectively. The measured and calculated doses of each treatment were compared to determine if they were clinically acceptable based upon RPC criteria of ±7% dose difference and 4 mm distance-to-agreement. Gamma analysis was used to assess dosimetric accuracy, as well. All treatment plans were able to meet the dosimetric objectives set by the RPC and had similar hot spots in the normal tissue. The Elekta VMAT plan was more homogenous but less conformal than the RapidArc and IMRT plans. When comparing the measured and calculated doses, all plans met the RPC ±7%/4 mm criteria. The percent of points passing the gamma analysis for each treatment delivery was acceptable. Treatment plan quality of the Elekta VMAT, RapidArc and IMRT treatments were comparable for consistent dose prescriptions and constraints. Additionally, the dosimetric accuracy of the Elekta VMAT and RapidArc treatments was verified to be within acceptable tolerances.