A local infrared perspective to deeper ISO surveys

We present new techniques to produce IRAS 12 micron samples of galaxies andstars. We show that previous IRAS 12 micron samples are incompatible fordetailed comparison with ISO surveys and review their problems. We provide astellar infrared diagnostic diagram to distinguish galaxies from stars withoutusing longer wavelength IRAS colour criteria and produce complete 12 micronsamples of galaxies and stars. This new technique allows us to estimate thecontribution of non-dusty galaxies to the IRAS 12 micron counts and produce atrue local mid-infrared extragalactic sample compatible with ISO surveys. Wepresent our initial analysis and results

Faster juvenile growth promotes earlier sex change in a protandrous hermaphrodite (barramundi Lates calcarifer)

The relationship between growth and sexual maturation is central to understanding the dynamics of animal populations which exhibit indeterminate growth. In sequential hermaphrodites, which undergo post-maturation sex change, the size and age at which sex change occurs directly affects reproductive output and hence population productivity. However, these traits are often labile, and may be strongly influenced by heterogenous growth and mortality rates. We analysed otolith microstructure of a protandrous (i.e., male-to-female) fish (barramundi Lates calcarifer) to examine growth in relation to individual variation in the timing of sex change. Growth trajectories of individuals with contrasting life histories were examined to elucidate the direction and extent to which growth rate influences the size and age individuals change sex. Then, the relationships between growth rate, maturation schedules and asymptotic maximum size were explored to identify potential trade-offs between age at female maturity and growth potential. Rapid growth was strongly associated with decreased age at sex change, but this was not accompanied by a decrease in size at sex change. Individuals that were caught as large females grew faster than those caught as males, suggesting that fast-growing individuals ultimately obtain higher fitness and therefore make a disproportionate contribution to population fecundity. These results indicate that individual-level variation in maturation schedules is not reflective of trade-offs between growth and reproduction. Rather, we suggest that conditions experienced during the juvenile phase are likely to be a key determinant of post-maturation fitness. These findings highlight the vulnerability of sex-changing species to future environmental change and harvest

Planck 2015 results. XXVII. The Second Planck Catalogue of Sunyaev-Zeldovich Sources

We present the all-sky Planck catalogue of Sunyaev-Zeldovich (SZ) sources detected from the 29 month full-mission data. The catalogue (PSZ2) is the largest SZ-selected sample of galaxy clusters yet produced and the deepest all-sky catalogue of galaxy clusters. It contains 1653 detections, of which 1203 are confirmed clusters with identified counterparts in external data-sets, and is the first SZ-selected cluster survey containing > $10^3$ confirmed clusters. We present a detailed analysis of the survey selection function in terms of its completeness and statistical reliability, placing a lower limit of 83% on the purity. Using simulations, we find that the Y5R500 estimates are robust to pressure-profile variation and beam systematics, but accurate conversion to Y500 requires. the use of prior information on the cluster extent. We describe the multi-wavelength search for counterparts in ancillary data, which makes use of radio, microwave, infra-red, optical and X-ray data-sets, and which places emphasis on the robustness of the counterpart match. We discuss the physical properties of the new sample and identify a population of low-redshift X-ray under- luminous clusters revealed by SZ selection. These objects appear in optical and SZ surveys with consistent properties for their mass, but are almost absent from ROSAT X-ray selected samples

Modelling ponatinib resistance in tyrosine kinase inhibitor-naive and dasatinib resistant BCR-ABL1+ cell lines

TKI resistance remains a major impediment to successful treatment of CML. In this study, we investigated the emerging modes of ponatinib resistance in TKI-naïve and dasatinib resistant BCR-ABL1+ cell lines. To investigate potential resistance mechanisms, ponatinib resistance was generated in BCR-ABL1+ cell-lines by long-term exposure to increasing concentrations of ponatinib. Two cell lines with prior dasatinib resistance demonstrated BCR-ABL1 kinase domain (KD) mutation(s) upon exposure to ponatinib. In one of these cell lines the T315I mutation had emerged during dasatinib exposure. When further cultured with ponatinib, the T315I mutation level and BCR-ABL1 mRNA expression level were increased. In the other cell line, compound mutations G250E/E255K developed with ponatinib exposure. In contrast, the ponatinib resistant cell lines that had no prior exposure to other TKIs (TKI-naïve) did not develop BCR-ABL1 KD mutations. Rather, both of these cell lines demonstrated Bcr-Abl-independent resistance via Axl overexpression. Axl, a receptor tyrosine kinase, has previously been associated with imatinib and nilotinib resistance. Ponatinib sensitivity was restored following Axl inhibition or shRNA-mediated-knockdown of Axl, suggesting that Axl was the primary driver of resistance and a potential target for therapy in this setting.Liu Lu, Chung Hoow Kok, Verity Ann Saunders, Jueqiong Wang, Jennifer Anne McLean, Timothy Peter Hughes, and Deborah Lee Whit

Solute Carrier Family 29A1 Mediates In Vitro Resistance to Azacitidine in Acute Myeloid Leukemia Cell Lines

Azacitidine (AZA) is commonly used hypomethylating agent for higher risk myelodysplastic syndromes and acute myeloid leukemia (AML). Although some patients achieve remission, eventually most patients fail AZA therapy. Comprehensive analysis of intracellular uptake and retention (IUR) of carbon-labeled AZA (14C-AZA), gene expression, transporter pump activity with or without inhibitors, and cytotoxicity in naïve and resistant cell lines provided insight into the mechanism of AZA resistance. AML cell lines were exposed to increasing concentrations of AZA to create resistant clones. 14C-AZA IUR was significantly lower in MOLM-13- (1.65 ± 0.08 ng vs. 5.79 ± 0.18 ng; p < 0.0001) and SKM-1- (1.10 ± 0.08 vs. 5.08 ± 0.26 ng; p < 0.0001) resistant cells compared to respective parental cells. Importantly, 14C-AZA IUR progressively reduced with downregulation of SLC29A1 expression in MOLM-13- and SKM-1-resistant cells. Furthermore, nitrobenzyl mercaptopurine riboside, an SLC29A inhibitor, reduced 14C-AZA IUR in MOLM-13 (5.79 ± 0.18 vs. 2.07 ± 0.23, p < 0.0001) and SKM-1-naive cells (5.08 ± 2.59 vs. 1.39 ± 0.19, p = 0.0002) and reduced efficacy of AZA. As the expression of cellular efflux pumps such as ABCB1 and ABCG2 did not change in AZA-resistant cells, they are unlikely contribute to AZA resistance. Therefore, the current study provides a causal link between in vitro AZA resistance and downregulation of cellular influx transporter SLC29A1.Monika M. Kutyna, Sophie Loone, Verity A. Saunders, Deborah L. White, Chung H. Kok, and Devendra K. Hiwas

Polyurethane Elastomers as Maxillofacial Prosthetic Materials

A series of polyurethane elastomers based on an aliphatic diisocyanate and a polyether macroglycol was polymerized with various crosslink densities and OH/NCO ratios. Stoichiometries yielding between 8,600 and 12,900 gm/ mole/crosslink and an OH/NCO ratio of 1.1 resulted in polymers with the low modulus, yet high strength and elongation necessary for maxillofacial applications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68299/2/10.1177_00220345780570040501.pd

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

BCR-ABL1 genomic DNA PCR response kinetics during first-line imatinib treatment of chronic myeloid leukemia

Accurate quantification of minimal residual disease during treatment of chronic myeloid leukaemia guides clinical decisions. The conventional minimal residual disease method, RQ-PCR for BCR-ABL1 mRNA, reflects a composite of the number of circulating leukemic cells and the BCR-ABL1 transcripts per cell. BCR-ABL1 genomic DNA only reflects leukemic cell number. We used both methods in parallel to determine the relative contribution of the leukemic cell number to molecular response. BCR-ABL1 DNA PCR and RQ-PCR were monitored up to 24 months in 516 paired samples from 59 newly-diagnosed patients treated with first-line imatinib in the TIDEL-II study. In the first 3 months of treatment BCR-ABL1 mRNA values declined more rapidly than DNA. By 6 months the two measures aligned closely. The expression of BCR-ABL1 mRNA was normalized to cell number to generate an expression ratio. The expression of e13a2 BCR-ABL1 was lower than that of e14a2 transcripts at multiple time points during treatment. BCR-ABL1 DNA was quantifiable in 48% of samples with undetectable BCR-ABL1 mRNA, resulting in minimal residual disease being quantifiable for an additional 5-18 months (median 12 months). These parallel studies show for the first time that the rapid decline in BCR-ABL1 mRNA over the first 3 months of treatment is due to a reduction in both cell number and transcript level per cell, whereas beyond 3 months falling levels of BCR-ABL1 mRNA are predominantly due to depletion of leukaemic cells.Ilaria S. Pagani, Phuong Dang, Ivar O. Kommers, Jarrad M. Goyne, Mario Nicola, Verity A. Saunders, Jodi Braley, Deborah L. White, David T. Yeung, Susan Branford, Timothy P. Hughes, and David M. Ros