Conceptual design proposal: HUGO global range/mobility transport aircraft

With the collapse of the former Soviet Union and the emergence of the United Nations actively pursuing a peace keeping role in world affairs, the United States has been forced into a position as the world's leading peace enforcer. It is still a very dangerous world with seemingly never ending ideological, territorial, and economic disputes requiring the U.S. to maintain a credible deterrent posture in this uncertain environment. This has created an urgent need to rapidly transport large numbers of troops and equipment from the continental United States (CONUS) to any potential world trouble spot by means of a global range/mobility transport aircraft. The most recent examples being Operation Desert Shield/Storm and Operation Restore Hope. To meet this challenge head-on, a request for proposal (RFP) was developed and incorporated into the 1992/1993 AIAA/McDonnell Douglas Corporation Graduate Team Aircraft Design Competition. The RFP calls for the conceptual design and justification of a large aircraft capable of power projecting a significant military force without surface transportation reliance

Played in England, made around the world: the origins of Badminton through the Commonwealth

Kimberley Hibbert-Mayne is the coordinator of the University of Worcester PGCE secondary professional studies programme and a member of the PGCE secondary physical education tutor team. She has worked in education for the last 16 years as a physical education teacher in secondary schools before embarking on a career in teacher education in 2015. Charlotte Ross is a member of the University of Worcester PGCE secondary physical education tutor team. She spent over 16 years in secondary education, before moving into a career in ITTE in 2020. Charlotte’s leads the PSHE and Citizenship enhancement activity. Dave Woodward is the University of Worcester PGCE secondary subject lead for physical education. He spent over 10 years in secondary teaching. He is an examiner and moderator for Edexcel/Pearson GCSE PE. Dave has presented at TEAN conferences and had several articles published in AfPE journal

Gasoline: An adaptable implementation of TreeSPH

The key algorithms and features of the Gasoline code for parallel hydrodynamics with self-gravity are described. Gasoline is an extension of the efficient Pkdgrav parallel N-body code using smoothed particle hydrodynamics. Accuracy measurements, performance analysis and tests of the code are presented. Recent successful Gasoline applications are summarized. These cover a diverse set of areas in astrophysics including galaxy clusters, galaxy formation and gas-giant planets. Future directions for gasdynamical simulations in astrophysics and code development strategies for tackling cutting edge problems are discussed.Comment: 30 pages, 11 figures, submitted to New Astronomy. Movies and high resolution images are available at http://imp.mcmaster.ca/image

The Phenotypic Radiation Resistance of CD44+/CD24−or low Breast Cancer Cells Is Mediated through the Enhanced Activation of ATM Signaling

Cancer initiating cells (CIC) are stem-like cells. CIC may contribute not only to the initiation of cancer but also to cancer recurrence because of the resistance of CIC both to chemotherapy and radiation therapy. From the MCF-7 and MDA-MB231 breast cancer cell lines and primary culture of patient breast cancer cells, we isolated by flow cytometry a CIC subset of cells with the CD44+/CD24−or low phenotype. The CD44+/CD24−or low subset showed increased sphere formation and resistance to radiation compared to the non- CD44+/CD24−or low subset. The increased radiation resistance was not dependent on the result of altered non-homologous end joining (NHEJ) DNA repair activity as both NHEJ activity and expression of the various proteins involved in NHEJ were not significantly different between the CD44+/CD24−or low and non- CD44+/CD24−or low subsets. However, activation of ATM signaling was significantly increased in CD44+/CD24−or low cells compared to non- CD44+/CD24−or low cells in both from breast cancer cell lines and primary human breast cancer cells. Application of an ATM inhibitor effectively decreased the radiation resistance of CD44+/CD24−or low subset, suggesting that targeting ATM signaling may provide a new tool to eradicate stem-like CIC and abolish the radiation resistance of breast cancer

CfA4: Light Curves for 94 Type Ia Supernovae

We present multi-band optical photometry of 94 spectroscopically-confirmed Type Ia supernovae (SN Ia) in the redshift range 0.0055 to 0.073, obtained between 2006 and 2011. There are a total of 5522 light curve points. We show that our natural system SN photometry has a precision of roughly 0.03 mag or better in BVr'i', 0.06 mag in u', and 0.07 mag in U for points brighter than 17.5 mag and estimate that it has a systematic uncertainty of 0.014, 0.010, 0.012, 0.014, 0.046, and 0.073 mag in BVr'i'u'U, respectively. Comparisons of our standard system photometry with published SN Ia light curves and comparison stars reveal mean agreement across samples in the range of ~0.00-0.03 mag. We discuss the recent measurements of our telescope-plus-detector throughput by direct monochromatic illumination by Cramer et al (in prep.). This technique measures the whole optical path through the telescope, auxiliary optics, filters, and detector under the same conditions used to make SN measurements. Extremely well-characterized natural-system passbands (both in wavelength and over time) are crucial for the next generation of SN Ia photometry to reach the 0.01 mag accuracy level. The current sample of low-z SN Ia is now sufficiently large to remove most of the statistical sampling error from the dark energy error budget. But pursuing the dark-energy systematic errors by determining highly-accurate detector passbands, combining optical and near-infrared (NIR) photometry and spectra, using the nearby sample to illuminate the population properties of SN Ia, and measuring the local departures from the Hubble flow will benefit from larger, carefully measured nearby samples.Comment: 43 page

Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

<p>Abstract</p> <p>Background</p> <p>Breast cancer stem cells (BCSCs) are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs).</p> <p>Methods</p> <p>We isolated a breast cancer cell population (CD44⁺CD24^-cells) from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44⁺CD24^-phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs.</p> <p>Results</p> <p>Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs.</p> <p>Conclusions</p> <p>Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.</p

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome