Towards Understanding The B[e] Phenomenon: IV. Modeling of IRAS 00470+6429

FS CMa type stars are a recently described group of objects with the B[e] phenomenon that exhibit strong emission-line spectra and strong IR excesses. In this paper we report the first attempt for a detailed modeling of IRAS 00470+6429, for which we have the best set of observations. Our modeling is based on two key assumptions: the star has a main-sequence luminosity for its spectral type (B2) and the circumstellar envelope is bimodal, composed of a slowly outflowing disk-like wind and a fast polar wind. Both outflows are assumed to be purely radial. We adopt a novel approach to describe the dust formation site in the wind that employs timescale arguments for grain condensation and a self-consistent solution for the dust destruction surface. With the above assumptions we were able to reproduce satisfactorily many observational properties of IRAS 00470+6429, including the H line profiles and the overall shape of the spectral energy distribution. Our adopted recipe for dust formation proved successful in reproducing the correct amount of dust formed in the circumstellar envelope. Possible shortcomings of our model, as well as suggestions for future improvements, are discussed.Comment: 11 pages, 7 figures, accepted for publication in The Astrophysical Journa

Acoustic spectral analysis and testing techniques

Subjects covered in four reports are described including: (1) mathematical techniques for combining decibel levels of octaves or constant bandwidth: (2) techniques for determining equation for power spectral density function; (3) computer program to analyze acoustical test data; and (4) computer simulation of horn responses utilizing hyperbolic horn theory

Polarization and kinematics in Cygnus A

From optical spectropolarimetry of Cygnus A we conclude that the scattering medium in the ionization cones in Cygnus A is moving outward at a speed of 170+-34 km/s, and that the required momentum can be supplied by the radiation pressure of an average quasar. Such a process could produce a structure resembling the observed ionization cones, which are thought to result from shadowing by a circumnuclear dust torus. We detect a polarized red wing in the [O III] emission lines arising from the central kiloparsec of Cygnus A. This wing is consistent with line emission created close to the boundary of the broad-line region.Comment: 5 pages, accepted for publication in MNRAS letter

Constraining the star formation rate in the Solar neighbourhood with star clusters

This paper investigates the star formation rate (SFR) in the Solar neighbourhood. First, we build the local age distribution function (ADF) with an updated sample of 442 star clusters located at less than 1\,kpc from the Sun. Next, we define the SFR, compute the individual mass evolution of a population of artificial clusters covering the broad range of parameters observed in actual clusters, and assume 100\,\ms\ as the low-mass limit for effective cluster observation. This leads to a simulated ADF, which is compared to the low-noise Solar neighbourhood ADF. The best match corresponds to a non-constant SFR presenting two conspicuous excesses for ages $\le9$\,Myr and between 220-600\,Myr (the local starburst). The average formation rate is \bar{SFR}\approx(2500\pm500)\,\mmy, corresponding to the average surface formation rate \bar{\ssfr}\approx(790\pm160)\,\mmk. These values are consistent with the formation rate inferred from embedded clusters (ECs), but much lower (\la16%) than that implied by field stars. Both the local starburst and the recent star formation period require $SFR\sim2\times\bar{SFR}$ to be described. The simulations show that $91.2\pm2.7$ of the clusters created in the Solar neighbourhood do not survive the first 10\,Myr, which is consistent with the rate of EC dissolution.Comment: Accepted by MNRA

The behavioural and neural effects of cannabinoids: Studies using Lewis and Wistar strain rats

Cannabis (known in its common forms as Cannabis sativa or Cannabis indica) is the most widely used illicit drug in the world and has been used for thousands of years for medicinal, religious and hedonistic purposes. In the last half of the 20th century the therapeutic uses of cannabis were largely ignored as most Western governments prohibited the use of the drug. Prohibition has come about largely as a result of the view that cannabis is a dangerous drug that poses major risks to both mental and physical health. However, this view is being increasingly challenged in recent years with a major popular movement towards decriminalization of cannabis occurring in some Western countries and a resurgence of interest in the medicinal properties of cannabis. Since Mechoulam and colleagues first isolated delta 9-tetrahydrocannabinol (delta 9-THC) as the main psychoactive constituent of cannabis, considerable advances have been made in the pharmacology of cannabis and cannabis-like drugs (cannabinoids). Central and peripheral cannabinoid receptors have been isolated and two endogenous ligands have been discovered. In addition, two cannabinoid receptor antagonists have been developed. However, our knowledge of the behavioural, neural and emotional effects of cannabis and the cannabinoids has often lagged behind our understanding of basic cannabinoid pharmacology. The present thesis attempts to further the understanding of the behavioural, neural and emotional effects of cannabinoids, using laboratory rats as subjects. A synthetic analogue of delta 9-THC (CP 55,940), is used as the primary pharmacological tool. The thesis offers a broad perspective with three major areas of investigation. These are: 1) the effects of CP 55,940 on anxiety-related behaviour (Chapters 2 and 3); 2) the effects of CP 55,940 on patterns of brain activation as indicated by c-fos expression (Chapter 4) and; 3) the addictive potential of CP 55,940 and its capacity to produce sensitization to the effects of other drugs such as cocaine (Chapters 5 and 6). A recurring theme throughout the thesis is that genetic factors may partially determine the behavioural, neural and emotional response to cannabinoids. To this end, the thesis compares Lewis and Wistar trains of rat in a wide variety of assays. Previous research has isolated Lewis rats as an "addiction-prone" and a "cannabinoid-preferring" strain, as they are more sensitive to the rewarding effects of various drugs of abuse including cannabinoids. Conversely, cannabinoids appear to have aversive effects in Wistar rats. A long-standing puzzle in cannabinoid research has been the question of why rats do not self-administer cannabis or cannabinoids. One likely reason is that cannabinoids have predominately aversive effects in rats. It is proposed here that these aversive effects arise because cannabinoids are anxiogenic agents in most rat strains. However some evidence indicates that the Lewis strain of rat are the only strain to find cannabinoids rewarding. It is hypothesised that Lewis rats may be more susceptible to the rewarding effects of cannabinoids because they are less susceptible to the anxiogenic effects of these compounds. In Chapters 2 and 3 the anxiogenic effects of the synthetic cannabinoid agonist CP 55,940 were compared in Lewis and Wistar rats in several different animal models of anxiety. In Chapter 2, the predatory odour avoidance, open area avoidance and conditioned ultrasonic vocalization (USV) models were utilised. In the predatory odour avoidance model, rats were exposed to cat odour in a rectangular arena and given the opportunity to hide in a small box. Both Lewis and Wistar rats displayed high levels of hiding during odour exposure. In Wistar but not Lewis rats, 50 �g/kg of CP 55,940 (i.p.) enhanced this avoidance response. Unfortunately, Lewis rats showed exceptionally high avoidance of the cat odour making it difficult to discern the effects of CP 55,940. To avoid this problem a second experiment was conducted, where rats were tested in the same arena as in the first experiment but with no cat odour present. Again in Wistar, but not Lewis rats, 25 and 50 �g/kg of CP 55,940 (i.p.) increased the avoidance of the open space. In the third experiment, Lewis and Wistar rats were placed in a chamber in which they had previously received footshock. Wistar but not Lewis rats re-exposed under the influence of 10, 25 or 50 �g/kg CP 55,940 (i.p.) emitted significantly more USVs than vehicle-treated rats. Thus, CP 55,940 clearly increased anxiety-related behaviour in Wistar rats but not Lewis rats, supporting the notion of a genetic predisposition towards cannabinoid-induced anxiety. In Chapter 3 the generality of the findings made in Chapter 2 were tested by utilising two further animal models of anxiety, the social interaction and light-dark emergence tests. From the results of Chapter 2, it could be claimed that Lewis rats were merely subsensitive to the effects of CP 55,940. Therefore a higher dose range (0, 25, 50 and 75 �g/kg i.p.) of CP 55,940 was employed in Chapter 3. In addition, the rotarod test was used to assess whether CP 55,940 has ataxic effects at these doses. In the first experiment, two unfamiliar rats were placed in a large arena and the time the rats spent socially interacting was recorded. CP 55,940 significantly reduced the total time rats spent socially interacting in Lewis (25 and 75 �g/kg) and Wistar rats (50 and 75 �g/kg). However, CP 55,940 has a significantly greater effect in Wistar rats compared to Lewis rats. In the second experiment, rats were placed in a small box within a large open arena and the latency to emerge from this box was measured. CP 55,940 increased emergence latency (at 75 �g/kg) and mean time per entry into the box (at 25 and 75 �g/kg) in Wistar but not Lewis rats. Furthermore, CP 55,940 caused a greater decrease in time spent in the open arena (at 25 and 75 �g/kg) and frequency of emergence (at 75 �g/kg) in Wistar rats in comparison to Lewis rats. In the third experiment, CP 55,940 (at 25, 50 and 75 �g/kg) caused mild incoordination only in Lewis rats as measured by the rotarod test. This finding argues against the assertion that the CP 55,940-induced anxiety-like behaviours in Wistar rats are merely a result of motoric impairment. Furthermore, it illustrates that Lewis rats are not generally subsensitive to the effects of CP 55,940. That is, when compared to other rat strains, Lewis rats may be more or less sensitive to the effects of CP 55,940 depending on what behaviour is being assessed. From the results of Chapters 2 and 3 it can be seen that Lewis rats are less sensitive to the anxiogenic effects of CP 55,940 than Wistar rats. In Chapter 4 it was hypothesised that in Lewis rats the effects of CP 55,940 on neural substrates of reward far outweigh the effects the compound has on neural substrates mediating anxiety. To examine this issue, the effects of CP 55,940 at a moderate (50 �g/kg i.p.) and high (250 �g/kg i.p.) dose were observed on c-fos expression (a measure of neural activation) and behaviour in Lewis and Wistar rats. CP 55,940 dose-dependently inhibited locomotor activity and reduced body temperature with Lewis rats being significantly less affected than Wistar rats. The 250 �g/kg dose caused significant catalepsy in both strains with a significantly greater effect in Wistar rats. These strain differences in the effects of CP 55,940 on body temperature and motor behaviour clearly correlated with c-fos expression in various regions and subregions. In general, Lewis rats showed significantly less Fos-labeled cells in comparison to Wistar rats. These strain differences in the effects of CP 55,940 on c-fos expression appeared unique to cannabinoids, as cocaine (15 mg/kg i.p.) had equivalent effects on c-fos expression in Lewis and Wistar rats. CP 55,940 promoted c-fos expression in areas not previously assessed, such as the median preoptic nucleus (MnPO), medial preoptic nucleus (MPO), anterior hypothalamic area (AH), islands of Calleja (ICjM), periaqueductal gray (PAG) and the pedunculopontine tegmental nucleus (PPTg). The strain differences uncovered in Chapters 2 and 3 correlated well with strain differences in the effects of CP 55,940 on c-fos expression in areas implicated in cannabinoid-induced anxiety, such as the central nucleus of the amygdala, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus and PAG. However, the effects of CP 55,940 on c-fos expression in a neural circuit which may underlie reward, which includes the shell of the nucleus accumbens (NAS) and PPTg, were also less in Lewis rats in comparison to Wistar rats. Future investigations must address whether the reduced effects of CP 55,940 on the Lewis rat are due to pharmacokinetics or pharmacodynamics. In addition, future studies must reconcile the pattern of c-fos expression observed here with prior reports of the Lewis rat being a unique "cannabinoid-preferring" strain. In Chapter 4, CP 55,940 administration promoted c-fos expression in areas of the brain thought to play a critical role in behavioural sensitization such as the ventral tegmental area and NAS. This is interesting because it is possible that c-fos is involved in promoting neuroadaptations that underlie drug addiction. To examine this idea, Chapter 5 investigated a behavioural assay of the long-term neural adaptations that may occur with the chronic administration of cannabis, namely, behavioural sensitization. This chapter also examined an animal model of the "gateway hypothesis", that is, the hypothesis that prior exposure to cannabis increases an individuals vulnerability to using other drugs. This animal model is known as cross-sensitization. First it was shown that Lewis, but not Wistar rats, given cocaine (15 mg/kg i.p.) every second day over a two week period displayed a progressively greater locomotor response to the drug over days indicating behavioural sensitization. When CP 55,940 (0, 10, 25 or 50 �g/kg i.p.) was administered under a similar regime, no such sensitization was observed in either strain. Rather, the two highest doses of CP 55,940 (25 and 50 �g/kg) caused locomotor suppression that lasted throughout administration. When Lewis or Wistar rats pre-exposed ten times to CP 55,940 were challenged with cocaine (15 mg/kg), no exaggerated locomotor response to cocaine was evident relative to non pre-exposed rats. When these rats were subsequently re-tested with CP 55,940, it continued to produce a dose-dependent suppression of locomotor activity. Finally, when CP 55,940 (50 �g/kg) was co-administered with cocaine in Lewis rats, it significantly reduced the locomotor hyperactivity produced by the drug but did not block the development of behavioural sensitization to cocaine. These results show that CP 55,940 does not sensitize locomotor activity with repeated administration in the same way as cocaine, and that pre-exposure or concurrent exposure to CP 55,940 does not enhance sensitivity to the subsequent behavioural effects of cocaine. Therefore, unlike Chapters 2, 3 and 4 where strain differences were observed in CP 55,940?induced anxiety, hypothermia, catalepsy, c-fos expression and ataxia, there were no strain differences with respect to behavioural sensitization. Landmark studies by Gardner and colleagues showed that Lewis rats are particularly susceptible, in comparison to other rat strains, to the rewarding effects of delta 9-THC on: 1) medial forebrain bundle (MFB) self-stimulation behaviour and; 2) dopamine (DA) efflux in the NAS. However, in Chapter 4 Lewis rats were less susceptible than Wistar rats to CP 55,940-induced c-fos expression in the NAS. Further, Lewis rats showed no behavioural sensitization to the chronic administration of CP 55,940. In light of these findings, Chapter 6 assessed whether CP 55,940 does have a rewarding effect on MFB self-stimulation behaviour in Lewis rats. Lewis rats were trained to self-stimulate the MFB using a rate?frequency paradigm and then administered CP 55,940 (0, 10, 25 and 50 �g/kg i.p.). CP 55,940 had no effect on MFB self-stimulation behaviour as assessed by the M50, the stimulation frequency at which half-maximal response rates were obtained. This result calls into question previous assertions that Lewis rats are a "cannabis-preferring" strain of rat. Previous studies utilising the cannabinoid CB1 receptor antagonist, SR 141716, have shown that the endogenous cannabinoid system may have some involvement in the rewarding effects of cocaine, morphine, sucrose and alcohol. Thus, Chapter 6 also assessed the effects of SR 141716 (0, 1, 3, 10 and 20 mg/kg i.p.) on MFB stimulation in Lewis rats. The role of DA in MFB stimulation reward has already been established, so for comparison purposes the effects of the DA D1 receptor antagonist SCH 23390 (0.06 mg/kg i.p.) was also assessed. Only a very high dose of SR 141716 (20 mg/kg) caused a significant inhibition of the rewarding efficacy of the stimulation with all other doses (1, 3, and 10 mg/kg) being ineffective in modulating the rewarding impact of brain stimulation. This was seen as an increase in M50. By comparison, a relatively low dose (0.06 mg/kg) of SCH 23390 caused a large increase in M50. These results indicate a relatively modest influence of the endogenous cannabinoid system on reward-relevant neurotransmission in the self-stimulation paradigm. Chapter 7 concludes the thesis and discusses the implications of the results obtained. The main findings of the current thesis are: 1) that the suggested "addiction-prone" Lewis strain of rat is less susceptible to cannabinoid-induced anxiety in comparison to Wistar rats; 2) Lewis rats show less cannabinoid-induced c-fos expression in comparison to Wistar rats (including in brain regions implicated in cannabinoid-induced anxiety and reward); 3) cannabinoid-induced c-fos expression exists in a number of brain regions never previously assessed such as the MPO, ICjM and PPTg; 4) behavioural sensitization does not occur with the repeated administration of CP 55,940; 5) cannabinoid pre-exposure or co-administration does not increase the sensitivity of the locomotor-activating effects of cocaine; 6) the endogenous cannabinoid system, at most, only has a minor influence on the neural substrate of brain stimulation reward and; 7) that there are previously unreported strain differences in cannabinoid-induced hypothermia, catalepsy and ataxia. These results add to our understanding of the effects of the behavioural, emotional and neural effects of cannabinoids and the endogenous cannabinoid system

The dusty Nebula surrounding HR Car: a Spitzer view

We present mid-IR observations of the Galactic Luminous Blue Variable (LBV) HR Car and its associated nebula carried out with the Spitzer Space Telescope using both IRAC and IRS, as part of a GTO program aimed to study stellar ejecta from evolved stars. Our observations reveal a rich mid-IR spectrum of the inner nebula showing both solid state and atomic gas signatures. Strong low-excitation atomic fine structure lines such as $26.0 \mu$m [\ion{Fe}{2}] and $34.8 \mu$m [\ion{Si}{2}], indicate, for the first time, the presence of a PDR in this object class. While the physics and chemistry of the low-excitation gas appears to be dominated by photodissociation, a possible contribution due to shocks can be inferred from the evidence of gas phase Fe abundance enhancement. The presence of amorphous silicates, inferred from the observed characteristic broad feature at $10 \mu$m located in the inner nebula, suggests that dust has formed during the LBV outburst. This is in contrast with the detection of crystalline dust in other probably more evolved Galactic LBVs, which is similar to the crystalline dust observed in red supergiants. This has been considered to be evidence of dust production during evolutionary phases prior to the outburst.Comment: 27 pages, 6 figures. accepted by Ap

Gene-modified T cells for adoptive immunotherapy of renal cell cancer maintain transgene-specific immune functions in vivo

Abstract BACKGROUND: We have treated three patients with carboxy-anhydrase-IX (CAIX) positive metastatic renal cell cancer (RCC) by adoptive transfer of autologous T-cells that had been gene-transduced to express a single-chain antibody-G250 chimeric receptor [scFv(G250)], and encountered liver toxicity necessitating adaptation of the treatment protocol. Here, we investigate whether or not the in vivo activity of the infused scFv(G250)(+) T cells is reflected by changes of selected immune parameters measured in peripheral blood. METHODS: ScFv(G250)-chimeric receptor-mediated functions of peripheral blood mononuclear cells (PBMC) obtained from three patients during and after treatment were compared to the same functions of scFv(G250)(+) T lymphocytes prior to infusion, and were correlated with plasma cytokine levels. RESULTS: Prior to infusion, scFv(G250)(+) T lymphocytes showed in vitro high levels of scFv(G250)-chimeric receptor-mediated functions such as killing of CAIX(+) RCC cell lines and cytokine production upon exposure to these cells. High levels of IFN-gamma were produced, whilst production of TNF-alpha, interleukin-4 (IL-4), IL-5 and IL-10 was variable and to lower levels, and that of IL-2 virtually absent. PBMC taken from patients during therapy showed lower levels of in vitro scFv(G250)-receptor-mediated functions as compared to pre-infusion, whilst IFN-gamma was the only detectable cytokine upon in vitro PBMC exposure to CAIX. During treatment, plasma levels of IFN-gamma increased only in the patient with the most prominent liver toxicity. IL-5 plasma levels increased transiently during treatment in all patients, which may have been triggered by the co-administration of IL-2. CONCLUSION: ScFv(G250)-receptor-mediated functions of the scFv(G250)(+) T lymphocytes are, by and large, preserved in vivo upon administration, and may be reflected by fluctuations in plasma IFN-gamma levels

Disk winds of B[e] supergiants

The class of B[e] supergiants is characterized by a two-component stellar wind consisting of a normal hot star wind in the polar zone and a slow and dense disk-like wind in the equatorial region. The properties of the disk wind are discussed using satellite UV spectra of stars seen edge-on, i.e. through the equatorial disk. These observations show that the disk winds are extremely slow, 50-90 km/s, i.e. a factor of about 10 slower than expected from the spectral types. Optical emission lines provide a further means to study the disk wind. This is discussed for line profiles of forbidden lines formed in the disk.Comment: 7 pages, LaTeX, 3 ps figures, uses lamuphys.sty from Springer-Verlag, to be published in the proceedings of IAU Coll. 169 "Variable and Non-spherical Stellar Winds in Luminous Hot Stars" held in Heidelberg 199