33 research outputs found

    Development and Validation of a Tokamak Skin Effect Transformer model

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    A control oriented, lumped parameter model for the tokamak transformer including the slow flux penetration in the plasma (skin effect transformer model) is presented. The model does not require detailed or explicit information about plasma profiles or geometry. Instead, this information is lumped in system variables, parameters and inputs. The model has an exact mathematical structure built from energy and flux conservation theorems, predicting the evolution and non linear interaction of the plasma current and internal inductance as functions of the primary coil currents, plasma resistance, non-inductive current drive and the loop voltage at a specific location inside the plasma (equilibrium loop voltage). Loop voltage profile in the plasma is substituted by a three-point discretization, and ordinary differential equations are used to predict the equilibrium loop voltage as function of the boundary and resistive loop voltages. This provides a model for equilibrium loop voltage evolution, which is reminiscent of the skin effect. The order and parameters of this differential equation are determined empirically using system identification techniques. Fast plasma current modulation experiments with Random Binary Signals (RBS) have been conducted in the TCV tokamak to generate the required data for the analysis. Plasma current was modulated in Ohmic conditions between 200kA and 300kA with 30ms rise time, several times faster than its time constant L/R\approx200ms. The model explains the most salient features of the plasma current transients without requiring detailed or explicit information about resistivity profiles. This proves that lumped parameter modeling approach can be used to predict the time evolution of bulk plasma properties such as plasma inductance or current with reasonable accuracy; at least in Ohmic conditions without external heating and current drive sources

    The taxanes: toxicity and quality of life considerations in advanced ovarian cancer

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    The taxanes paclitaxel and docetaxel show good activity in the management of advanced ovarian cancer when used in conjunction with platinum agents. Accumulating evidence from clinical studies, particularly the latest results from the phase III comparative SCOTROC study, indicates that the two drugs confer similar rates of tumour response and survival in women with this condition. However, it is clear that paclitaxel and docetaxel differ in their tolerability profiles and in other respects, and cannot be regarded as directly equivalent drugs. In particular, paclitaxel is associated with significant neurotoxicity; peripheral neuropathy has also been reported with docetaxel, but to a lesser extent. Neutropenia appears more prevalent with docetaxel than with paclitaxel, although clinical trial data show that this adverse effect is manageable and need not compromise dose delivery. Docetaxel is also associated with potential benefits accruing from shorter infusion times and lack of need for premedication with intravenous histamine H1 and H2 antagonists. Emerging quality of life data are expected to shed further light on the overall benefit of chemotherapy in women with advanced ovarian cancer in general, and on taxane−platinum combinations in particular

    First-line treatment for advanced ovarian cancer: paclitaxel, platinum and the evidence

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    Four large randomised trials of paclitaxel in combination with platinum against a platinum-based control treatment have now been published in full, representing around 88% (3588 out of 4057) of patients randomised into the eight known trials of this question. There is substantial heterogeneity in the results of these four trials. Four main explanations for this heterogeneity have been proposed: differences in the extent and timing of ‘crossover’ to taxanes in the control groups; differences in the types of patient included; differences in the effectiveness of the research regimens used; differences in the effectiveness of the control regimens used. In this study we examine whether any of these explanations is consistent with the pattern of results seen in these trials. Each explanation suggests that a particular characteristic of each trial was responsible for the results observed. For each explanation the trials were split into groups according to that characteristic, in order to partition the total heterogeneity into that seen ‘within’ and ‘between’ groups of trials. If a particular explanation was consistent with the pattern of results, we would expect to see relatively little heterogeneity within each group of trial results viewed in this way, with most of the heterogeneity being between groups which are dissimilar with respect to the key characteristic. Heterogeneity ‘within’ and ‘between’ groups was formally compared using the F-ratio. If any explanation appeared to be consistent with the results of the trials, it was considered whether the explanation was also consistent with other evidence available about these regimens. Only one explanation appeared to be consistent with the pattern of results seen in these trials, and that was differences in effectiveness of the control arms used in these trials. This suggests that the very positive results in favour of paclitaxel/cisplatin seen in two of the trials may have been due to the use of a suboptimal control arm. There is no direct evidence about the relative effectiveness of the control arms used in these trials, but indirect evidence is consistent with the conclusion that the cyclophosphamide/cisplatin regimen used in two of the trials may be less effective than the control regimens used in the other trials. Specific concerns about the choice of a cyclophosphamide/cisplatin control arm in the first of these trials to report were raised before the results of the other trials were known, i.e. before any heterogeneity had been observed. Further investigation of this question would be useful. In the meantime, given all of the randomised evidence on the efficacy and toxicity associated with the regimens used in these trials, we conclude that single agent carboplatin is a safe and effective first-line treatment for women with advanced ovarian cancer

    Interplay between octupole and quasiparticle excitations in 178Hg and 180Hg

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    Excited structures in the Z = 80, 178Hg (N = 98), and 180Hg (N = 100) isotopes have been investigated with the Gammasphere spectrometer in conjunction with the recoil-decay tagging technique. The present data extend the previously known ground-state bands to higher spin and excitation energy. Negative parity bands with a complex decay towards the low spin states arising from both the prolate-deformed and the nearly spherical coexisting minima have been observed for the first time in both nuclei. It is shown that these sequences have characteristics in common with negative-parity bands in the heavier even-even Hg isotopes as well as in the Os and Pt isotones. These structures are interpreted as being associated at low spin with an octupole vibration which is crossed at moderate frequency by a shape driving, two-quasiproton excitation

    Quantitative Fitness Analysis Shows That NMD Proteins and Many Other Protein Complexes Suppress or Enhance Distinct Telomere Cap Defects

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    To better understand telomere biology in budding yeast, we have performed systematic suppressor/enhancer analyses on yeast strains containing a point mutation in the essential telomere capping gene CDC13 (cdc13-1) or containing a null mutation in the DNA damage response and telomere capping gene YKU70 (yku70Δ). We performed Quantitative Fitness Analysis (QFA) on thousands of yeast strains containing mutations affecting telomere-capping proteins in combination with a library of systematic gene deletion mutations. To perform QFA, we typically inoculate 384 separate cultures onto solid agar plates and monitor growth of each culture by photography over time. The data are fitted to a logistic population growth model; and growth parameters, such as maximum growth rate and maximum doubling potential, are deduced. QFA reveals that as many as 5% of systematic gene deletions, affecting numerous functional classes, strongly interact with telomere capping defects. We show that, while Cdc13 and Yku70 perform complementary roles in telomere capping, their genetic interaction profiles differ significantly. At least 19 different classes of functionally or physically related proteins can be identified as interacting with cdc13-1, yku70Δ, or both. Each specific genetic interaction informs the roles of individual gene products in telomere biology. One striking example is with genes of the nonsense-mediated RNA decay (NMD) pathway which, when disabled, suppress the conditional cdc13-1 mutation but enhance the null yku70Δ mutation. We show that the suppressing/enhancing role of the NMD pathway at uncapped telomeres is mediated through the levels of Stn1, an essential telomere capping protein, which interacts with Cdc13 and recruitment of telomerase to telomeres. We show that increased Stn1 levels affect growth of cells with telomere capping defects due to cdc13-1 and yku70Δ. QFA is a sensitive, high-throughput method that will also be useful to understand other aspects of microbial cell biology

    Green Managerialism and the Erosion of Meaning

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    In this chapter, Simon P. James argues that nature can be harmed, degraded, destroyed, but also restored, preserved or in some other way looked after, but that this also holds true of nature’s meanings. It is in many cases possible to look after or ‘cultivate’ the political, religious, personal, mythic and historical meanings of natural things, events, processes and places. James argues that it is not simply the case that nature’s meanings can be cultivated: there is sometimes a need for such cultivation. In support of this claim, he considers the modern tendency to talk, write and presumably think about our relations with nature in a ‘managerial’ way – in terms, that is, of the all-too-familiar idiom of objectives, targets, key performance indicators, and the like. This sort of approach is, he suggests, poorly equipped to do justice to nature’s semantic richness. Hence, in light of the increasing tendency to conceive environmental issues in a myopically managerial way, there is, James contends, a special need to look after or cultivate nature’s meanings
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