419 research outputs found
Immune microenvironment dysfunctions enable malignification at the onset of myelodysplastic syndromes
View full abstracthttps://openworks.mdanderson.org/leading-edge/1002/thumbnail.jp
Photoinduced 3D orientational order in side chain liquid crystalline azopolymers
We apply experimental technique based on the combination of methods dealing
with principal refractive indices and absorption coefficients to study the
photoinduced 3D orientational order in the films of liquid crystalline (LC)
azopolymers. The technique is used to identify 3D orientational configurations
of trans azobenzene chromophores and to characterize the degree of ordering in
terms of order parameters. We study two types of LC azopolymers which form
structures with preferred in-plane and out-of-plane alignment of
azochromophores, correspondingly. Using irradiation with the polarized light of
two different wavelengths we find that the kinetics of photoinduced anisotropy
can be dominated by either photo-reorientation or photoselection mechanisms
depending on the wavelength. We formulate the phenomenological model describing
the kinetics of photoinduced anisotropy in terms of the isomer concentrations
and the order parameter tensor. We present the numerical results for absorption
coefficients that are found to be in good agreement with the experimental data.
The model is also used to interpret the effect of changing the mechanism with
the wavelength of the pumping light.Comment: uses revtex4 28 pages, 10 figure
L-Edge Spectroscopy of Dilute, Radiation-Sensitive Systems Using a Transition-Edge-Sensor Array
We present X-ray absorption spectroscopy and resonant inelastic X-ray
scattering (RIXS) measurements on the iron L-edge of 0.5 mM aqueous
ferricyanide. These measurements demonstrate the ability of high-throughput
transition-edge-sensor (TES) spectrometers to access the rich soft X-ray
(100-2000eV) spectroscopy regime for dilute and radiation-sensitive samples.
Our low-concentration data are in agreement with high-concentration
measurements recorded by conventional grating-based spectrometers. These
results show that soft X-ray RIXS spectroscopy acquired by high-throughput TES
spectrometers can be used to study the local electronic structure of dilute
metal-centered complexes relevant to biology, chemistry and catalysis. In
particular, TES spectrometers have a unique ability to characterize frozen
solutions of radiation- and temperature-sensitive samples.Comment: 19 pages, 4 figure
Genomic context and TP53 allele frequency define clinical outcomes in TP53-mutated myelodysplastic syndromes
TP53 mutations are associated with adverse outcomes and shorter response to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS). Limited data have evaluated the impact of the type, number, and patterns of TP53 mutations in response outcomes and prognosis of MDS. We evaluated the clinicopathologic characteristics, outcomes, and response to therapy of 261 patients with MDS and TP53 mutations. Median age was 68 years (range, 18-80 years). A total of 217 patients (83%) had a complex karyotype. TP53 mutations were detected at a median variant allele frequency (VAF) of 0.39 (range, 0.01-0.94). TP53 deletion was associated with lower overall response rate (ORR) (odds ratio, 0.3; P = .021), and lower TP53 VAF correlated with higher ORR to HMAs. Increase in TP53 VAF at the time of transformation was observed in 13 patients (61%), and previously undetectable mutations were observed in 15 patients (65%). TP53 VAF was associated with worse prognosis (hazard ratio, 1.02 per 1% VAF increase; 95% confidence interval, 1.01-1.03; P \u3c .001). Integration of TP53 VAF and karyotypic complexity identified prognostic subgroups within TP53-mutant MDS. We developed a multivariable model for overall survival that included the revised International Prognostic Scoring System (IPSS-R) categories and TP53 VAF. Total score for each patient was calculated as follows: VAF TP53 + 13 Ă IPSS-R blast score + 16 Ă IPSS-R cytogenetic score + 28 Ă IPSS-R hemoglobin score + 46 Ă IPSS-R platelet score. Use of this model identified 4 prognostic subgroups with median survival times of not reached, 42.2, 21.9, and 9.2 months. These data suggest that outcomes of patients with TP53-mutated MDS are heterogeneous and that transformation may be driven not only by TP53 but also by other factors
Manipulating charge transfer excited state relaxation and spin crossover in iron coordination complexes with ligand substitution
Developing light-harvesting and photocatalytic molecules made with iron could provide a cost effective, scalable, and environmentally benign path for solar energy conversion. To date these developments have been limited by the sub-picosecond metal-to-ligand charge transfer (MLCT) electronic excited state lifetime of iron based complexes due to spin crossover-the extremely fast intersystem crossing and internal conversion to high spin metal-centered excited states. We revitalize a 30 year old synthetic strategy for extending the MLCT excited state lifetimes of iron complexes by making mixed ligand iron complexes with four cyanide (CN-;) ligands and one 2,2â˛-bipyridine (bpy) ligand. This enables MLCT excited state and metal-centered excited state energies to be manipulated with partial independence and provides a path to suppressing spin crossover. We have combined X-ray Free-Electron Laser (XFEL) Kβ hard X-ray fluorescence spectroscopy with femtosecond time-resolved UV-visible absorption spectroscopy to characterize the electronic excited state dynamics initiated by MLCT excitation of [Fe(CN)4(bpy)]2-. The two experimental techniques are highly complementary; the time-resolved UV-visible measurement probes allowed electronic transitions between valence states making it sensitive to ligand-centered electronic states such as MLCT states, whereas the Kβ fluorescence spectroscopy provides a sensitive measure of changes in the Fe spin state characteristic of metal-centered excited states. We conclude that the MLCT excited state of [Fe(CN)4(bpy)]2- decays with roughly a 20 ps lifetime without undergoing spin crossover, exceeding the MLCT excited state lifetime of [Fe(2,2â˛-bipyridine)3]2+ by more than two orders of magnitude
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Mesenchymal-epithelial signalling in tumour microenvironment: role of high-mobility group Box 1.
Glucose deprivation, hypoxia and acidosis are characteristic features of the central core of most solid tumours. Myofibroblasts are stromal cells present in many such solid tumours, including those of the colon, and are known to be involved in all stages of tumour progression. HMGB1 is a nuclear protein with an important role in nucleosome stabilisation and gene transcription; it is also released from immune cells and is involved in the inflammatory process. We report that the microenvironmental condition of glucose deprivation is responsible for the active release of HMGB1 from various types of cancer cell lines (HT-29, MCF-7 and A549) under normoxic conditions. Recombinant HMGB1 (10Â ng/ml) triggered proliferation in myofibroblast cells via activation of PI3K and MEK1/2. Conditioned medium collected from glucose-deprived HT-29 colon cancer cells stimulated the migration and invasion of colonic myofibroblasts, and these processes were significantly inhibited by immunoneutralising antibodies to HMGB1, RAGE and TLR4, together with specific inhibitors of PI3K and MEK1/2. Our data suggest that HMGB1 released from cancer cells under glucose deprivation is involved in stimulating colonic myofibroblast migration and invasion and that this occurs through the activation of RAGE and TLR4, resulting in the activation of the MAPK and PI3K signalling pathways. Thus, HMGB1 might be released by cancer cells in areas of low glucose in solid tumours with the resulting activation of myofibroblasts and is a potential therapeutic target to inhibit solid tumour growth
A population-based case-control study of Selective Serotonin Reuptake Inhibitors (SSRIs) and breast cancer: The impact of duration of use, cumulative dose and latency
Performance and Operation of the CMS Electromagnetic Calorimeter
The operation and general performance of the CMS electromagnetic calorimeter
using cosmic-ray muons are described. These muons were recorded after the
closure of the CMS detector in late 2008. The calorimeter is made of lead
tungstate crystals and the overall status of the 75848 channels corresponding
to the barrel and endcap detectors is reported. The stability of crucial
operational parameters, such as high voltage, temperature and electronic noise,
is summarised and the performance of the light monitoring system is presented
Demonstrating a superconducting dual-rail cavity qubit with erasure-detected logical measurements
A critical challenge in developing scalable error-corrected quantum systems
is the accumulation of errors while performing operations and measurements. One
promising approach is to design a system where errors can be detected and
converted into erasures. A recent proposal aims to do this using a dual-rail
encoding with superconducting cavities. In this work, we implement such a
dual-rail cavity qubit and use it to demonstrate a projective logical
measurement with erasure detection. We measure logical state preparation and
measurement errors at the -level and detect over of cavity decay
events as erasures. We use the precision of this new measurement protocol to
distinguish different types of errors in this system, finding that while decay
errors occur with probability per microsecond, phase errors occur
6 times less frequently and bit flips occur at least 170 times less frequently.
These findings represent the first confirmation of the expected error hierarchy
necessary to concatenate dual-rail erasure qubits into a highly efficient
erasure code
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