Phase II study of CC-486 (oral azacitidine) in previously treated patients with locally advanced or metastatic nasopharyngeal carcinoma

BACKGROUND: Treatment options are limited for recurrent nasopharyngeal carcinoma (NPC). We report results from a phase II study of CC-486 (oral azacitidine) in advanced NPC. PATIENTS AND METHODS: Patients with locally advanced or metastatic NPC and 1-2 prior treatment regimens received CC-486 300 mg daily on days 1-14 of 21-day cycles until disease progression or unacceptable toxicity. The first 6 patients of Asian-Pacific Islander (API) ethnicity received a reduced dose of 200 mg to preserve safety and tolerability; if well tolerated, subsequent API patients received CC-486 300 mg. The study could advance to stage 2 if > 4 patients achieved a response. Co-primary end-points were overall response rate (ORR) and progression-free survival (independent review). Key secondary end-points were overall survival and safety. RESULTS: Owing to faster-than-anticipated enrolment, 36 patients, including 13 of API ethnicity, were enrolled; the median age was 54.0 years. Most patients were male (81%) and had an Eastern Cooperative Oncology Group performance status 64 1 (97%). Among 25 efficacy-evaluable patients, the ORR was 12%; the median progression-free and overall survival were 4.7 and 18.0 months, respectively. The most common grade III/IV treatment-emergent adverse events were neutropenia (33%) and febrile neutropenia (11%). Twenty-one posttreatment deaths, primarily due to progressive disease or disease complications, and 1 on-treatment death (epistaxis, unrelated to study drug) occurred. The study did not advance to stage 2. CONCLUSION: CC-486 did not show sufficient clinical activity to support further development as monotherapy in this patient population. The safety profile of CC-486 in NPC was consistent with that in other solid tumours

Expression of mercuric reductase from Bacillus megaterium MB1 in eukaryotic microalga Chlorella sp DT: an approach for mercury phytoremediation

A eukaryotic microalga, Chlorella sp. DT, was transformed with the Bacillus megaterium strain MB1 merA gene, encoding mercuric reductase (MerA), which mediates the reduction of Hg2+ to volatile elemental Hg-0. The transformed Chlorella cells were selected first by hygromycin B and then by HgCl2. The existence of merA gene in the genomic DNA of transgenic strains was shown by polymerase chain reaction amplification, while the stable integration of merA into genomic DNA of transgenic strains was confirmed by Southern blot analysis. The ability to remove Hg2+ in merA transgenic strains was higher than that in the wild type. The merA transgenic strains showed higher growth rate and photosynthetic activity than the wild type did in the presence of a toxic concentration of Hg2+. Cultured with Hg2+, the expression level of superoxide dismutase in transgenic strains was lower than that in the wild type, suggesting that the transgenic strains faced a lower level of oxidative stress. All the results indicated that merA gene was successfully integrated into the genome of transgenic strains and functionally expressed to promote the removal of Hg2+

Effective d8 model: phase diagram

Wetensch. publicatieFaculteit der Wiskunde en Natuurwetenschappe

Expectation maximization (EM) algorithms using polar symmetriesfor computed tomography(CT) image reconstruction

We suggest a symmetric-polar pixellation scheme which makes possible a reduction of the computational cost for expectation maximization (EM) iterative algorithms. The proposed symmetric-polar pixellation allows us to deal with 3D images as a whole problem without dividing the 3D problem into 2D slices approach. Performance evaluation of each approach in terms of stability and image quality is presented. Exhaustive comparisons between all approaches were conducted in a 2D based image reconstruction model. From these 2D approaches, that showing the best performances were finally implemented and evaluated in a 3D based image reconstruction model. Comparison to 3D images reconstructed with FBP is also presented. Although the algorithm is presented in the context of computed tomography (CT) image reconstruction, it can be applied to any other tomographic technique as well, due to the fact that the only requirement is a scanning geometry involving measurements of an object under different projection angles. Real data have been acquired with a small animal (CT) scanner to verify the proposed mathematical description of the CT system.This work was supported by the Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+I) under Grant, FIS2010-21216-CO2-01, Valencian Local Government under Grant Nos. PROMETEO 2008/114 and APOSTD/2010/012. The authors would like to thank Brennan Holt for checking and correcting the text.Rodríguez Álvarez, MJ.; Soriano Asensi, A.; Iborra Carreres, A.; Sánchez Martínez, F.; González Martínez, AJ.; Conde, P.; Hernández Hernández, L.... (2013). Expectation maximization (EM) algorithms using polar symmetriesfor computed tomography(CT) image reconstruction. Computers in Biology and Medicine. 43(8):1053-1061. https://doi.org/10.1016/j.compbiomed.2013.04.015S1053106143

Isothermal and Cyclic Aging of 310S Austenitic Stainless Steel

Unusual damage and high creep strain rates have been observed on components made of 310S stainless steel subjected to thermal cycles between room temperature and 1143 K (870 °C). Microstructural characterization of such components after service evidenced high contents in sigma phase which formed first from δ-ferrite and then from γ-austenite. To get some insight into this microstructural evolution, isothermal and cyclic aging of 310S stainless steel has been studied experimentally and discussed on the basis of numerical simulations. The higher contents of sigma phase observed after cyclic agings than after isothermal treatments are clearly associated with nucleation triggered by thermal cycling

The Plasma Environment of Comets

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138863/1/rog199129s2976.pd

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap