Effect of clinical levels of misonidazole on the response of tumour and normal tissues in the mouse to alkylating agents.

Experiments were carried out to determine whether the enhancement of alkylating-agent cytotoxicity seen after large single doses of misonidazole (MISO) in mouse tumours can also be achieved by prolonged exposure to low MISO levels similar to those which can be tolerated clinically. The level in mouse blood plasma could be maintained at about 100 micrograms/ml for 7 h by injecting small doses of MISO every 1/2 h. The effect of this treatment in combination with cyclophosphamide (CY) or melphalan (L-PAM) was studied in the RIF-1 tumour, using regrowth delay and cell-survival cloning assays. In each case, prolonged exposure to low levels of MISO gave enhancement ratios very close to those obtained with a large single dose. ERs of 1.6-2.0 were obtained with CY and 1.8-2.2 with L-PAM over the range of alkylating-agent doses used. In experiments with CY the response of 2 normal-tissue systems, marrow and WBC count, was also studied. No significant enhancement of CY damage occurred in either case. In the L-PAM experiments the LD50/30 and WBC counts were determined as normal-tissue end points. Multiple MISO had no effect. Our results show that levels of MISO which can be achieved safely in man yield good enhancement of the tumour cytotoxicity of 2 widely used chemotherapeutic agents without increasing the damage to normal tissues

Developing sexual competence? Exploring strategies for the provision of effective sexualities and relationships education

School-based sexualities and relationships education (SRE) offers one of the most promising means of improving young people's sexual health through developing 'sexual competence'. In the absence of evidence on whether the term holds the same meanings for young people and adults (e.g. teachers, researchers, policy-makers), the paper explores 'adult' notions of sexual competence as construed in research data and alluded to in UK Government guidance on SRE, then draws on empirical research with young people on factors that affect the contexts, motivations and outcomes of sexual encounters, and therefore have implications for sexual competence. These data from young people also challenge more traditional approaches to sexualities education in highlighting disjunctions between the content of school-based input and their reported sexual experience. The paper concludes by considering the implications of these insights for developing a shared notion of what SRE is trying to achieve and suggestions for recognition in the content and approaches to SRE.</p

A Near-Infrared Spectroscopic Study of the Accreting Magnetic White Dwarf SDSS J121209.31+013627.7 and its Substellar Companion

The nature of the excess near-infrared emission associated with the magnetic white dwarf commonly known as SDSS 1212 is investigated primarily through spectroscopy, and also via photometry. The inferred low mass secondary in this system has been previously detected by the emission and variation of H$\alpha$, and the $1-2.5$ $\mu$m spectral data presented here are consistent with the presence of a late L or early T dwarf. The excess flux seen beyond 1.5 $\mu$m in the phase-averaged spectrum is adequately modeled with an L8 dwarf substellar companion and cyclotron emission in a 7 MG magnetic field. This interesting system manifests several observational properties typical of polars, and is most likely an old interacting binary with a magnetic white dwarf and a substellar donor in an extended low state.Comment: 28 pages, 5 figures, Accepted to Ap

A Constant Bar Fraction out to Redshift z~1 in the Advanced Camera for Surveys Field of the Tadpole Galaxy

Bar-like structures were investigated in a sample of 186 disk galaxies larger than 0.5 arcsec that are in the I-band image of the Tadpole galaxy taken with the HST ACS. We found 22 clear cases of barred galaxies, 21 galaxies with small bars that appear primarily as isophotal twists in a contour plot, and 11 cases of peculiar bars in clump-cluster galaxies, which are face-on versions of chain galaxies. The latter bars are probably young, as the galaxies contain only weak interclump emission. Four of the clearly barred galaxies at z~0.8-1.2 have grand design spirals. The bar fraction was determined as a function of galaxy inclination and compared with the analogous distribution in the local Universe. The bar fraction was also determined as a function of galaxy angular size. These distributions suggest that inclination and resolution effects obscure nearly half of the bars in our sample. The bar fraction was also determined as a function of redshift. We found a nearly constant bar fraction of 0.23+-0.03 from z~0 to z=1.1. When corrected for inclination and size effects, this fraction is comparable to the bar fraction in the local Universe, ~0.4, as tabulated for all bar and Hubble types in the Third Reference Catalogue of Galaxies. The average major axis of a barred galaxy in our sample is ~10 kpc after correcting for redshift with a LambdaCDM cosmology. Galaxy bars were present in normal abundance at least ~8 Gy ago (z~1); bar dissolution cannot be common during a Hubble time unless the bar formation rate is comparable to the dissolution rate.Comment: to appear in ApJ, Sept 1, 2004, Vol 612, 18 pg, 12 figure

Gold nanoparticles as novel agents for cancer therapy

Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed

Interpretable correlation descriptors for quantitative structure-activity relationships

<p>Abstract</p> <p>Background</p> <p>The topological maximum cross correlation (TMACC) descriptors are alignment-independent 2D descriptors for the derivation of QSARs. TMACC descriptors are generated using atomic properties determined by molecular topology. Previous validation (<it>J Chem Inf Model </it>2007, <b>47</b>: 626-634) of the TMACC descriptor suggests it is competitive with the current state of the art.</p> <p>Results</p> <p>Here, we illustrate the interpretability of the TMACC descriptors, through the analysis of the QSARs of inhibitors of angiotensin converting enzyme (ACE) and dihydrofolate reductase (DHFR). In the case of the ACE inhibitors, the TMACC interpretation shows features specific to C-domain inhibition, which have not been explicitly identified in previous QSAR studies.</p> <p>Conclusions</p> <p>The TMACC interpretation can provide new insight into the structure-activity relationships studied. Freely available, open source software for generating the TMACC descriptors can be downloaded from <url>http://comp.chem.nottingham.ac.uk</url>.</p

Quasi-Moessbauer effect in two dimensions

Expressions for the absorption spectrum of a nucleus in a three- and a two-dimensional crystal respectively are obtained analytically at zero and at finite temperature respectively. It is found that for finite temperature in two dimensions the Moessbauer effect vanishes but is replaced by what we call a Quasi-Moessbauer effect. Possibilities to identify two-dimensional elastic behavior are discussed.Comment: 18 pages, 5 figures, notation simplifie