Weight Management Program for Fire Fighters: Feasibility Pilot

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The peritoneal tumour microenvironment of high-grade serous ovarian cancer

High-grade serous ovarian cancer (HGSC) disseminates early and extensively throughout the peritoneal space, causing multiple lesions that are a major clinical problem. The aim of this study was to investigate the cellular composition of peritoneal tumour deposits in patient biopsies and their evolution in mouse models using immunohistochemistry, intravital microscopy, confocal microscopy, and 3D modelling. Tumour deposits from the omentum of HGSC patients contained a prominent leukocyte infiltrate of CD3(+) T cells and CD68(+) macrophages, with occasional neutrophils. Alpha-smooth muscle actin(+) (α-SMA(+) ) pericytes and/or fibroblasts surrounded these well-vascularized tumour deposits. Using the murine bowel mesentery as an accessible mouse peritoneal tissue that could be easily imaged, and two different transplantable models, we found multiple microscopic tumour deposits after i.p. injection of malignant cells. Attachment to the peritoneal surface was rapid (6-48 h) with an extensive CD45(+) leukocyte infiltrate visible by 48 h. This infiltrate persisted until end point and in the syngeneic murine ID8 model, it primarily consisted of CD3(+) T lymphocytes and CD68(+) macrophages with α-SMA(+) cells also involved from the earliest stages. A majority of tumour deposits developed above existing mesenteric blood vessels, but in avascular spaces new blood vessels tracked towards the tumour deposits by 2-3 weeks in the IGROV-1 xenografts and 6 weeks in the ID8 syngeneic model; a vigorous convoluted blood supply was established by end point. Inhibition of tumour cell cytokine production by stable expression of shRNA to CXCR4 in IGROV-1 cells did not influence the attachment of cells to the mesentery but delayed neovascularization and reduced tumour deposit size. We conclude that the multiple peritoneal tumour deposits found in HGSC patients can be modelled in the mouse. The techniques described here may be useful for assessing treatments that target the disseminated stage of this disease

Freshly Formed Dust in the Cassiopeia A Supernova Remnant as Revealed by the Spitzer Space Telescope

We performed Spitzer Infrared Spectrograph mapping observations covering nearly the entire extent of the Cassiopeia A supernova remnant (SNR), producing mid-infrared (5.5-35 micron) spectra every 5-10". Gas lines of Ar, Ne, O, Si, S and Fe, and dust continua were strong for most positions. We identify three distinct ejecta dust populations based on their continuum shapes. The dominant dust continuum shape exhibits a strong peak at 21 micron. A line-free map of 21 micron-peak dust made from the 19-23 micron range closely resembles the [Ar II], [O IV], and [Ne II] ejecta-line maps implying that dust is freshly formed in the ejecta. Spectral fitting implies the presence of SiO2, Mg protosilicates, and FeO grains in these regions. The second dust type exhibits a rising continuum up to 21 micron and then flattens thereafter. This ``weak 21 micron'' dust is likely composed of Al2O3 and C grains. The third dust continuum shape is featureless with a gently rising spectrum and is likely composed of MgSiO3 and either Al2O3 or Fe grains. Using the least massive composition for each of the three dust classes yields a total mass of 0.02 Msun. Using the most-massive composition yields a total mass of 0.054 Msun. The primary uncertainty in the total dust mass stems from the selection of the dust composition necessary for fitting the featureless dust as well as 70 micron flux. The freshly formed dust mass derived from Cas A is sufficient from SNe to explain the lower limit on the dust masses in high redshift galaxies.Comment: 8 figures: Accepted for the publication in Ap

Threats to the validity of the Collegiate Learning Assessment (CLA+) as a measure of critical thinking skills and implications for Learning Gain

The University of Reading Learning Gain project is a three-year longitudinal project to test and evaluate a range of available methodologies and to draw conclusions on what might be the right combination of instruments for the measurement of Learning Gain in higher education. This paper analyses the validity of a measure of critical thinking skills, the Collegiate Learning Assessment (CLA+) and the implications of using this standardised test as a proxy for Learning Gain. The paper reviews five inferences regarding the interpretations and use of test scores: construct representation, scoring, generalisation, extrapolation and decision-making. Each section reviews some of the available evidence in support of the claims the CLA+ makes and the threats to their validity. The possible impact of these issues on Learning Gain in the UK is considered

The Middle Way: East Asian masters students’ perceptions of critical argumentation in U.K. universities.

The paper explores the learning experiences of East Asian masters students in dealing with Western academic norms of critical thinking in classroom debate and assignment writing. The research takes a cultural approach, and employs grounded theory and case study methodology, the aims being for students to explain their perceptions of their personal learning journeys. The data suggest that the majority of students interviewed rejected full academic acculturation into Western norms of argumentation. They instead opted for a ‘Middle Way’ that synergizes the traditional cultural academic values held by many East Asian students with those elements of Western academic norms that are perceived to be aligned with these. This is a relatively new area of research which represents a challenge for British lecturers and students

Influence of Carburisation on the Room Temperature Tensile Properties of High Temperature Alloys

A series of doctoral and diploma investigations which have been carries out at the Institute of Reactor Materials of the KFA are reported. The influence of both thermal exposure and carburisation at 800 $^{°}$C and above on the room temperature tensile properties of INCOLOY 800 H, INCONEL 617, HASTELLOY X and NIMONIC 86 has been studied and the results have been compared with literature data. It is shown that the room temperature ductility of INCOLOY 800 H is much less sinsitive to carburisation than that of the nickel-base alloys. This is attributed to the greater volume fraction of carbide formed in the nickel-base alloys for a particular bulk carbon content. In the nickel-base alloys carbide volume fractions are higher than in iron-base alloys due to the lower solubility of carbon and to the formation of M$_{6}$C carbides. The ductility of reformer and intermediate heat exchanger (IHX) tubes after long service times in a process heat high temperature reactor has been estimated using carburisation rates found in corrosion experiments. The data indicate that a reformer tube of INCOLOY 800 H should retain a room temperature ductility equivalent to 5 % tensile elongation - a normal minimum requirement in conventional engineering design over the anticipated service life of 140000 h. For the IHX tubes, the impurity concentrations in the primary coolant must be carefully controlled in order to avoid embrittlement by carburisation. Alternatively, a design concept to allow the use of low ductility tubes will be required. Suggestions are given for future work, in particular for alloy development to produce alloys which are less severely embrittled by carburisation

Effective index of refraction, optical rotation, and circular dichroism in isotropic chiral liquid crystals

This paper concerns optical properties of the isotropic phase above the isotropic-cholesteric transition and of the blue phase BP III. We introduce an effective index, which describes spatial dispersion effects such as optical rotation, circular dichroism, and the modification of the average index due to the fluctuations. We derive the wavelength dependance of these spatial dispersion effects quite generally without relying on an expansion in powers of the chirality and without assuming that the pitch of the cholesteric $P$ is much shorter than the wavelength of the light $\lambda$, an approximation which has been made in previous studies of this problem. The theoretical predictions are supported by comparing them with experimental spectra of the optical activity in the BP III phase.Comment: 15 pages and 7 figures. Submitted to PR

Dual G9A/EZH2 inhibition stimulates anti-tumour immune response in ovarian high-grade serous carcinoma

Ovarian high-grade serous carcinoma (HGSC) prognosis correlates directly with presence of intratumoral lymphocytes. However, cancer immunotherapy has yet to achieve meaningful survival benefit in patients with HGSC. Epigenetic silencing of immunostimulatory genes is implicated in immune evasion in HGSC and re-expression of these genes could promote tumour immune clearance. We discovered that simultaneous inhibition of the histone methyltransferases G9A and EZH2 activates the CXCL10-CXCR3 axis and increases homing of intratumoral effector lymphocytes and natural killer cells whilst suppressing tumour-promoting FoxP3+ CD4 T cells. The dual G9A/EZH2 inhibitor HKMTI-1-005 induced chromatin changes that resulted in the transcriptional activation of immunostimulatory gene networks, including the re-expression of elements of the ERV-K endogenous retroviral family. Importantly, treatment with HKMTI-1-005 improved the survival of mice bearing Trp53-/- null ID8 ovarian tumours and resulted in tumour burden reduction. These results indicate that inhibiting G9A and EZH2 in ovarian cancer alters the immune microenvironment and reduces tumour growth and therefore positions dual inhibition of G9A/EZH2 as a strategy for clinical development

AKARI and BLAST Observations of the Cassiopeia A Supernova Remnant and Surrounding Interstellar Medium

We use new large area far infrared maps ranging from 65 - 500 microns obtained with the AKARI and the Balloon-borne Large Aperture Submillimeter Telescope (BLAST) missions to characterize the dust emission toward the Cassiopeia A supernova remnant (SNR). Using the AKARI high resolution data we find a new "tepid" dust grain population at a temperature of ~35K and with an estimated mass of 0.06 solar masses. This component is confined to the central area of the SNR and may represent newly-formed dust in the unshocked supernova ejecta. While the mass of tepid dust that we measure is insufficient by itself to account for the dust observed at high redshift, it does constitute an additional dust population to contribute to those previously reported. We fit our maps at 65, 90, 140, 250, 350, and 500 microns to obtain maps of the column density and temperature of "cold" dust (near 16 K) distributed throughout the region. The large column density of cold dust associated with clouds seen in molecular emission extends continuously from the surrounding interstellar medium to project on the SNR, where the foreground component of the clouds is also detectable through optical, X-ray, and molecular extinction. At the resolution available here, there is no morphological signature to isolate any cold dust associated only with the SNR from this confusing interstellar emission. Our fit also recovers the previously detected "hot" dust in the remnant, with characteristic temperature 100 K.Comment: Accepted for publication in the Astrophysical Journal. Maps and related data are available at http://blastexperiment.info