The dust and gas content of the Crab Nebula

We have constructed MOCASSIN photoionization plus dust radiative transfer models for the Crab Nebula core-collapse supernova (CCSN) remnant, using either smooth or clumped mass distributions, in order to determine the chemical composition and masses of the nebular gas and dust. We computed models for several different geometries suggested for the nebular matter distribution but found that the observed gas and dust spectra are relatively insensitive to these geometries, being determined mainly by the spectrum of the pulsar wind nebula which ionizes and heats the nebula. Smooth distribution models are ruled out since they require 16-49 Msun of gas to fit the integrated optical nebular line fluxes, whereas our clumped models re quire 7.0 Msun of gas. A global gas-phase C/O ratio of 1.65 by number is derived, along with a He/H number ratio of 1.85, neither of which can be matched by current CCSN yield predictions. A carbonaceous dust composition is favoured by the observed gas-phase C/O ratio: amorphous carbon clumped model fits to the Crab's Herschel and Spitzer infrared spectral energy distribution imply the presence of 0.18-0.27 Msun of dust, corresponding to a gas to dust mass ratio of 26-39. Mixed dust chemistry models can also be accommodated, comprising 0.11-0.13 Msun of amorphous carbon and 0.39-0.47 Msun of silicates. Power-law grain size distributions with mass distributions that are weighted towards the largest grain radii are derived, favouring their longer-term survival when they eventually interact with the interstellar medium. The total mass of gas plus dust in the Crab Nebula is 7.2 +/- 0.5 Msun, consistent with a progenitor star mass of 9 Msun.Comment: Accepted in Ap

Multiscale modelling of tumour growth and therapy: the influence of vessel normalisation on chemotherapy

Following the poor clinical results of antiangiogenic drugs, particularly when applied in isolation, tumour biologists and clinicians are now turning to combinations of therapies in order to obtain better results. One of these involves vessel normalisation strategies. In this paper, we investigate the effects on tumour growth of combinations of antiangiogenic and standard cytotoxic drugs, taking into account vessel normalisation. An existing multiscale framework is extended to include new elements such as tumour-induced vessel dematuration. Detailed simulations of our multiscale framework allow us to suggest one possible mechanism for the observed vessel normalisation-induced improvement in the efficacy of cytotoxic drugs: vessel dematuration produces extensive regions occupied by quiescent (oxygen-starved) cells which the cytotoxic drug fails to kill. Vessel normalisation reduces the size of these regions, thereby allowing the chemotherapeutic agent to act on a greater number of cells

Oscillatory dynamics in a model of vascular tumour growth -- implications for chemotherapy

Background\ud \ud Investigations of solid tumours suggest that vessel occlusion may occur when increased pressure from the tumour mass is exerted on the vessel walls. Since immature vessels are frequently found in tumours and may be particularly sensitive, such occlusion may impair tumour blood flow and have a negative impact on therapeutic outcome. In order to study the effects that occlusion may have on tumour growth patterns and therapeutic response, in this paper we develop and investigate a continuum model of vascular tumour growth.\ud Results\ud \ud By analysing a spatially uniform submodel, we identify regions of parameter space in which the combination of tumour cell proliferation and vessel occlusion give rise to sustained temporal oscillations in the tumour cell population and in the vessel density. Alternatively, if the vessels are assumed to be less prone to collapse, stable steady state solutions are observed. When spatial effects are considered, the pattern of tumour invasion depends on the dynamics of the spatially uniform submodel. If the submodel predicts a stable steady state, then steady travelling waves are observed in the full model, and the system evolves to the same stable steady state behind the invading front. When the submodel yields oscillatory behaviour, the full model produces periodic travelling waves. The stability of the waves (which can be predicted by approximating the system as one of λ-ω type) dictates whether the waves develop into regular or irregular spatio-temporal oscillations. Simulations of chemotherapy reveal that treatment outcome depends crucially on the underlying tumour growth dynamics. In particular, if the dynamics are oscillatory, then therapeutic efficacy is difficult to assess since the fluctuations in the size of the tumour cell population are enhanced, compared to untreated controls.\ud Conclusions\ud \ud We have developed a mathematical model of vascular tumour growth formulated as a system of partial differential equations (PDEs). Employing a combination of numerical and analytical techniques, we demonstrate how the spatio-temporal dynamics of the untreated tumour may influence its response to chemotherapy.\ud Reviewers\ud \ud This manuscript was reviewed by Professor Zvia Agur and Professor Marek Kimmel

Modelling the response of vascular tumours to chemotherapy: A multiscale approach

An existing multiscale model is extended to study the response of a vascularised tumour to treatment with chemotherapeutic drugs which target proliferating cells. The underlying hybrid cellular automaton model couples tissue-level processes (e.g. blood flow, vascular adaptation, oxygen and drug transport) with cellular and subcellular phenomena (e.g. competition for space, progress through the cell cycle, natural cell death and drug-induced cell kill and the expression of angiogenic factors). New simulations suggest that, in the absence of therapy, vascular adaptation induced by angiogenic factors can stimulate spatio-temporal oscillations in the tumour's composition.\ud \ud Numerical simulations are presented and show that, depending on the choice of model parameters, when a drug which kills proliferating cells is continuously infused through the vasculature, three cases may arise: the tumour is eliminated by the drug; the tumour continues to expand into the normal tissue; or, the tumour undergoes spatio-temporal oscillations, with regions of high vascular and tumour cell density alternating with regions of low vascular and tumour cell density. The implications of these results and possible directions for future research are also discussed

The impact of cell crowding and active cell movement on vascular tumour growth

A multiscale model for vascular tumour growth is presented which includes systems of ordinary differential equations for the cell cycle and regulation of apoptosis in individual cells, coupled to partial differential equations for the spatio-temporal dynamics of nutrient and key signalling chemicals. Furthermore, these subcellular and tissue layers are incorporated into a cellular automaton framework for cancerous and normal tissue with an embedded vascular network. The model is the extension of previous work and includes novel features such as cell movement and contact inhibition. We presented a detailed simulation study of the effects of these additions on the invasive behaviour of tumour cells and the tumour's response to chemotherapy. In particular, we find that cell movement alone increases the rate of tumour growth and expansion, but that increasing the tumour cell carrying capacity leads to the formation of less invasive dense hypoxic tumours containing fewer tumour cells. However, when an increased carrying capacity is combined with significant tumour cell movement, the tumour grows and spreads more rapidly, accompanied by large spatio-temporal fluctuations in hypoxia, and hence in the number of quiescent cells. Since, in the model, hypoxic/quiescent cells produce VEGF which stimulates vascular adaptation, such fluctuations can dramatically affect drug delivery and the degree of success of chemotherapy

High-frequency high-voltage high-power DC-to-DC converters

The current and voltage waveshapes associated with the power transitor and the power diode in an example current-or-voltage step-up (buck-boost) converter were analyzed to highlight the problems and possible tradeoffs involved in the design of high voltage high power converters operating at switching frequencies in the range of 100 Khz. Although the fast switching speeds of currently available power diodes and transistors permit converter operation at high switching frequencies, the resulting time rates of changes of current coupled with parasitic inductances in series with the semiconductor switches, produce large repetitive voltage transients across the semiconductor switches, potentially far in excess of the device voltage ratings. The need is established for semiconductor switch protection circuitry to control the peak voltages appearing across the semiconductor switches, as well as to provide the waveshaping action require for a given semiconductor device. The possible tradeoffs, as well as the factors affecting the tradeoffs that must be considered in order to maximize the efficiency of the converters are enumerated

Analysis of transistor and snubber turn-off dynamics in high-frequency high-voltage high-power converters

Dc to dc converters which operate reliably and efficiently at switching frequencies high enough to effect substantial reductions in the size and weight of converter energy storage elements are studied. A two winding current or voltage stepup (buck boost) dc-to-dc converter power stage submodule designed to operate in the 2.5-kW range, with an input voltage range of 110 to 180 V dc, and an output voltage of 250 V dc is emphasized. In order to assess the limitations of present day component and circuit technologies, a design goal switching frequency of 10 kHz was maintained. The converter design requirements represent a unique combination of high frequency, high voltage, and high power operation. The turn off dynamics of the primary circuit power switching transistor and its associated turn off snubber circuitry are investigated

Deep-space navigation applications of improved ground-based optical astrometry

Improvements in ground-based optical astrometry will eventually be required for navigation of interplanetary spacecraft when these spacecraft communicate at optical wavelengths. Although such spacecraft may be some years off, preliminary versions of the astrometric technology can also be used to obtain navigational improvements for the Galileo and Cassini missions. This article describes a technology-development and observational program to accomplish this, including a cooperative effort with U.S. Naval Observatory Flagstaff Station. For Galileo, Earth-based astrometry of Jupiter's Galilean satellites may improve their ephemeris accuracy by a factor of 3 to 6. This would reduce the requirements for onboard optical navigation pictures, so that more of the data transmission capability (currently limited by high-gain antenna deployment problems) can be used for science data. Also, observations of European Space Agency (ESA) Hipparcos stars with asteroid 243 Ida may provide significantly improved navigation accuracy for a planned August 1993 Galileo spacecraft encounter

Systems analysis for ground-based optical navigation

Deep-space telecommunications systems will eventually operate at visible or near-infrared regions to provide increased information return from interplanetary spacecraft. This would require an onboard laser transponder in place of (or in addition to) the usual microwave transponder, as well as a network of ground-based and/or space-based optical observing stations. This article examines the expected navigation systems to meet these requirements. Special emphasis is given to optical astrometric (angular) measurements of stars, solar system target bodies, and (when available) laser-bearing spacecraft, since these observations can potentially provide the locations of both spacecraft and target bodies. The role of astrometry in the navigation system and the development options for astrometric observing systems are also discussed

Cognitive performance in multiple system atrophy

The cognitive performance of a group of patients with multiple system atrophy (MSA) of striato-nigral predominance was compared with that of age and IQ matched control subjects, using three tests sensitive to frontal lobe dysfunction and a battery sensitive to memory and learning deficits in Parkinson's disease and dementia of the Alzheimer type. The MSA group showed significant deficits in all three of the tests previously shown to be sensitive to frontal lobe dysfunction. Thus, a significant proportion of patients from the MSA group failed an attentional set-shifting test, specifically at the stage when an extra-dimensional shift was required. They were also impaired in a subject-ordered test of spatial working memory. The MSA group showed deficits mostly confined to measures of speed of thinking, rather than accuracy, on the Tower of London task. These deficits were seen in the absence of consistent impairments in language or visual perception. Moreover, the MSA group showed no significant deficits in tests of spatial and pattern recognition previously shown to be sensitive to patients early in the course of probable Alzheimer's disease and only a few patients exhibited impairment on the Warrington Recognition Memory Test. There were impairments on other tests of visual memory and learning relative to matched controls, but these could not easily be related to fundamental deficits of memory or learning. Thus, on a matching-to-sample task the patients were impaired at simultaneous but not delayed matching to sample, whereas difficulties in a pattern-location learning task were more evident at its initial, easier stages. The MSA group showed no consistent evidence of intellectual deterioration as assessed from their performance on subtests of the Wechsler Adult Intelligence Scale (WAIS) and the National Adult Reading Test (NART). Consideration of individual cases showed that there was some heterogeneity in the pattern of deficits in the MSA group, with one patient showing no impairment, even in the face of considerable physical disability. The results show a distinctive pattern of cognitive deficits, unlike those previously seen using the same tests in patients with Parkinson's and Alzheimer's diseases, and suggesting a prominent frontal-lobe-like component. The implications for concepts of 'subcortical' dementia and 'fronto-striatal' cognitive dysfunction are considered