Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo.

Spores of some species of the strictly anaerobic bacteria Clostridium naturally target and partially lyse the hypoxic cores of tumors, which tend to be refractory to conventional therapies. The anti-tumor effect can be augmented by engineering strains to convert a non-toxic prodrug into a cytotoxic drug specifically at the tumor site by expressing a prodrug-converting enzyme (PCE). Safe doses of the favored prodrug CB1954 lead to peak concentrations of 6.3 μM in patient sera, but at these concentration(s) known nitroreductase (NTR) PCEs for this prodrug show low activity. Furthermore, efficacious and safe Clostridium strains that stably express a PCE have not been reported. Here we identify a novel nitroreductase from Neisseria meningitidis, NmeNTR, which is able to activate CB1954 at clinically-achievable serum concentrations. An NmeNTR expression cassette, which does not contain an antibiotic resistance marker, was stably localized to the chromosome of Clostridium sporogenes using a new integration method, and the strain was disabled for safety and containment by making it a uracil auxotroph. The efficacy of Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) using this system was demonstrated in a mouse xenograft model of human colon carcinoma. Substantial tumor suppression was achieved, and several animals were cured. These encouraging data suggest that the novel enzyme and strain engineering approach represent a promising platform for the clinical development of CDEPT

All-Sky spectrally matched UBVRI-ZY and u'g'r'i'z' magnitudes for stars in the Tycho2 catalog

We present fitted UBVRI-ZY and u'g'r'i'z' magnitudes, spectral types and distances for 2.4M stars, derived from synthetic photometry of a library spectrum that best matches the Tycho2 BtVt, NOMAD Rn and 2MASS JHK_{2/S} catalog magnitudes. We present similarly synthesized multi-filter magnitudes, types and distances for 4.8M stars with 2MASS and SDSS photometry to g<16 within the Sloan survey region, for Landolt and Sloan primary standards, and for Sloan Northern (PT) and Southern secondary standards. The synthetic magnitude zeropoints for BtVt, UBVRI, ZvYv, JHK_{2/S}, JHK_{MKO}, Stromgren uvby, Sloan u'g'r'i'z' and ugriz are calibrated on 20 calspec spectrophotometric standards. The UBVRI and ugriz zeropoints have dispersions of 1--3%, for standards covering a range of color from -0.3 < V-I < 4.6; those for other filters are in the range 2--5%. The spectrally matched fits to Tycho2 stars provide estimated 1-sigma errors per star of ~0.2, 0.15, 0.12, 0.10 and 0.08 mags respectively in either UBVRI or u'g'r'i'z'; those for at least 70% of the SDSS survey region to g<16 have estimated 1-sigma errors per star of ~0.2, 0.06, 0.04, 0.04, 0.05 in u'g'r'i'z' or UBVRI. The density of Tycho2 stars, averaging about 60 stars per square degree, provides sufficient stars to enable automatic flux calibrations for most digital images with fields of view of 0.5 degree or more. Using several such standards per field, automatic flux calibration can be achieved to a few percent in any filter, at any airmass, in most workable observing conditions, to facilitate inter-comparison of data from different sites, telescopes and instruments.Comment: 36 pages, 30 figures, 3 printed tables, several electronic tables, accepted PASP Dec 201

What makes for prize-winning television?

We investigate the determinants of success in four international television awards festivals between 1994 and 2012. We find that countries with larger markets and greater expenditure on public broadcasting tend to win more awards, but that the degree of concentration in the market for television and rates of penetration of pay-per-view television are unrelated to success. These findings are consistent with general industrial organisation literature on quality and market size, and with media policy literature on public service broadcasting acting as a force for quality. However, we also find that ‘home countries’ enjoy a strong advantage in these festivals, which is not consistent with festival success acting as a pure proxy for television quality

Land resource survey of Rottnest Island - an aid to land use planning

This report provides a description of the landforms, soils and vegetation of Rottnest Island. In addition, it provides a discussion of the relative capability of each of the landforms of the island to sustain various forms of development. The primary objective of this work is to direct development into areas of high capability (low risk of land degradation) in preference to areas of lower capability (higher risk of land degradation). Rottnest Island is located approximately 30 km west of Perth. The proximity of the island to the capital city of Western Australia, its warm Mediterranean climate and the subsequent likelihood of further development, mean that there will be increasing pressure on the natural resources of the island. This report details the nature and inherent stability of those natural resources, and provides a guide for their management.https://researchlibrary.agric.wa.gov.au/bulletins/1062/thumbnail.jp

Terminal velocities of luminous, early-type SMC stars

Ultraviolet spectra from the Space Telescope Imaging Spectrograph (STIS) are used to determine terminal velocities for 11 O and B-type giants and supergiants in the Small Magellanic Cloud (SMC) from the Si IV and C IV resonance lines. Using archival data from observations with the Goddard High-Resolution Spectrograph and the International Ultraviolet Explorer telescope, terminal velocities are obtained for a further five B-type supergiants. We discuss the metallicity dependence of stellar terminal velocities, finding no evidence for a significant scaling between Galactic and SMC metallicities for Teff < 30,000 K, consistent with the predictions of radiation driven wind theory for supergiant stars. A comparison of the $v_\infty / v_{esc}$ ratio between the SMC and Galactic samples, while consistent with the above statement, emphasizes that the uncertainties in the distances to galactic O-stars are a serious obstacle to a detailed comparison with theory. For the SMC sample there is considerable scatter in this ratio at a given effective temperature, perhaps indicative of uncertainties in stellar masses.Comment: 28 pages, 8 figures, accepted by ApJ; minor revisions prior to acceptanc

Emission Line Galaxies in the STIS Parallel Survey I: Observations and Data Analysis

In the first three years of operation STIS obtained slitless spectra of approximately 2500 fields in parallel to prime HST observations as part of the STIS Parallel Survey (SPS). The archive contains almost 300 fields at high galactic latitude (|b|>30) with spectroscopic exposure times greater than 3000 seconds. This sample contains 220 fields (excluding special regions and requiring a consistent grating angle) observed between 6 June 1997 and 21 September 2000, with a total survey area of about 160 square arcminutes. At this depth, the SPS detects an average of one emission line galaxy per three fields. We present the analysis of these data, and the identification of 131 low to intermediate redshift galaxies detected by optical emission lines. The sample contains 78 objects with emission lines that we infer to be redshifted [OII]3727 emission at 0.43<z<1.7. The comoving number density of these objects is comparable to that of H-alpha emitting galaxies in the NICMOS parallel observations. One quasar and three probable Seyfert galaxies are detected. Many of the emission-line objects show morphologies suggestive of mergers or interactions. The reduced data are available upon request from the authors.Comment: 58 preprint pages, including 26 figures; accepted for publication in ApJ

Fundamental Properties of O-Type Stars

We present a comprehensive analysis of high-resolution, far-UV HST/STIS, FUSE, and optical spectra of 17 O stars in the SMC. Our analysis is based on NLTE metal line-blanketed model atmospheres calculated with our NLTE code TLUSTY. We systematically explore the sensitivity of various UV and optical lines to different stellar parameters. We have obtained consistent fits of the UV and the optical spectrum to derive the effective temperature, surface gravity, surface composition, and microturbulent velocity of each star. Stellar radii, masses, luminosities and ages then follow. Similarly to more limited recent studies, we derive cooler temperatures than the standard Teff calibration of O stars. We propose a new calibration between the spectral type and effective temperature based on our results from UV metal lines as well as optical hydrogen and helium lines. For stars of the same spectral subtype, we find a general good agreement between Teff determinations obtained with TLUSTY, CMFGEN, and FASTWIND models. We derive ionizing luminosities that are smaller by a factor of 3 compared to luminosities inferred from previous standard calibrations. The chemical composition analysis reveals that the surface of about 3/4 of the program stars is moderately to strongly enriched in nitrogen, while showing the original helium, carbon, and oxygen abundances. Our results support the new stellar evolution models that predict that the surface of fast rotating stars becomes N-rich during the main sequence phase because of rotationally-induced mixing. Most stars exhibit the ``mass discrepancy'' problem. This discrepancy too is a result of fast rotation which lowers the measured effective gravity. Our study thus emphasizes the importance of rotation in our understanding of the properties of massive stars. (abridged)Comment: Submitted to Astrophysical Journal; 69 page

Paraphrases and summaries: A means of clarification or a vehicle for articulating a preferred version of student accounts?

The use of group discussions as a means to facilitate learning from experiences is well documented in adventure education literature. Priest and Naismith (1993) assert that the use of the circular discussion method, where the leader poses questions to the participants, is the most common form of facilitation in adventure education. This paper draws on transcripts of facilitation sessions to argue that the widely advocated practice of leader summaries or paraphrases of student responses in these sessions functions as a potential mechanism to control and sponsor particular knowledge(s). Using transcripts from recorded facilitation sessions the analysis focuses on how the leader paraphrases the students’ responses and how these paraphrases or ‘formulations’ function to modify or exclude particular aspects of the students’ responses. I assert that paraphrasing is not simply a neutral activity that merely functions to clarify a student response, it is a subtle means by which the leader of the session can, often inadvertently or unknowingly, alter the student’s reply with the consequence of favouring particular knowledge(s). Revealing the subtle work that leader paraphrases perform is of importance for educators who claim to provide genuine opportunities for students to learn from their experience

Postcolonial town planning in Commonwealth nations: A case study of the Solomon Islands - an agenda for change

This is the author's PDF version of an article published in The Round Table: The Commonwealth Journal of International Affairs© 2007. The definitive version is available at www.informaworld.comThe principal argument advanced in this paper is that spatial planning in the Solomon Islands has failed to deliver any substantive benefits and is therefore in urgent need of reform. The present model of planning, derived from a combination of colonial practice and legislation originating in the UK, does not add much, if any, value to the development process. The poor quality of planning in the Solomons cannot be seen in isolation. There are similar systems in use throughout much of the Commonwealth and anecdotal evidence suggests that the failings are widely duplicated. The Solomon Islands only appear exceptional in the extent to which other government systems have demonstrably broken down, following the 'Ethnic Tension' of 2000 - 03. The Regional Assistance Mission to the Solomon Islands (RAMSI) provides a unique opportunity for a review of the way in which planning operates. A number of issues are identified which any reformed system must address