925 research outputs found
Luminescence of Apollo 11 and 12 lunar samples
Luminescence of Apollo 11 and 12 rocks measured with UV, X ray, and proton radiatio
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LOSS OF HETEROZYGOSITY OF THE ESTROGEN-RECEPTOR GENE IN BREAST-CANCER
Feasibility study of the ultraviolet spectral analysis of the lunar surface
Ultraviolet spectral analysis of granite, gabbro, and serpentinite samples to determine feasibility of mapping surface composition of moo
Luminescence analysis of lunar samples returned by Apollo: Luminescence of Apollo 14 and Apollo 15 lunar samples
Luminescence measurements were made of Apollo 14 lunar samples with far UV X-ray, and proton irradiation and of Apollo 15 lunar samples with X-ray irradiation. Preliminary efficiencies with the far UV are in the range 0.001 to 0.01; efficiencies with X-rays and protons are in the range 10 to the -8th to 10 to the -6th powers. The crystalline igneous rocks show higher efficiencies, in general, than the breccias and glasses, and the ratio of intensity of the green to the blue luminescence peak tends to be higher for the crystalline igneous rocks than for breccias and glasses. Therefore, both the efficiency and the spectral character appear to have a systematic relationship to lithologic type (granitic versus gabbroic versus fragmental) and to geologic history and processes on the moon (shocked versus unshocked or only mildly shocked material)
Breast cancer adjuvant chemotherapy dosing in obese patients
BACKGROUND Substantial variation in adjuvant breast cancer chemotherapy dosing in obese women suggests that there is uncertainty about optimal practices. The purpose of this study was to investigate variations in dose determinations in clinical trial protocols and publications over the last 3 decades as potential sources of this uncertainty. METHODS The National Cancer Institute database was used to identify protocols of breast cancer adjuvant chemotherapy conducted by cooperative groups between 1970–2000, and these protocols were then obtained directly from the cooperative groups. Dose determinations were categorized in each protocol and in published reports from each clinical trial. Fisher exact tests were used to compare the proportions of protocols that used full weight-based doses over time. RESULTS Protocol-specified chemotherapy dosing was obtained for all of 44 eligible trials. A significant increase was identified in the use of full weight-based doses in the later time period compared with the earlier ( P = .004; 2-sided Fisher exact test). A notable exception was 1 cooperative group that continues to require dose limitations for doxorubicin and cyclophosphamide in patients with a body surface area of more than 2.0 m 2 . Regardless of publication date, published reports of clinical trials rarely provide information on use of full or limited weight-based doses. CONCLUSIONS Variations in dose determinations among clinical trial protocols and lack of information on use of full weight-based doses in most publications are 2 likely sources of variation in chemotherapy dosing in obese women. Developing consensus and disseminating information on optimal chemotherapy dosing will likely reduce such variation and may improve survival among obese patients with breast cancer. Cancer 2008. © 2008 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58590/1/23416_ftp.pd
Molecular Mechanics Simulations and Improved Tight-binding Hamiltonians for Artificial Light Harvesting Systems: Predicting Geometric Distributions, Disorder, and Spectroscopy of Chromophores in a Protein Environment
We present molecular mechanics {and spectroscopic} calculations on prototype
artificial light harvesting systems consisting of chromophores attached to a
tobacco mosaic virus (TMV) protein scaffold. These systems have been
synthesized and characterized spectroscopically, but information about the
microscopic configurations and geometry of these TMV-templated chromophore
assemblies is largely unknown. We use a Monte Carlo conformational search
algorithm to determine the preferred positions and orientations of two
chromophores, Coumarin 343 together with its linker, and Oregon Green 488, when
these are attached at two different sites (104 and 123) on the TMV protein. The
resulting geometric information shows that the extent of disorder and
aggregation properties, and therefore the optical properties of the
TMV-templated chromophore assembly, are highly dependent on the choice of
chromophores and protein site to which they are bound. We used the results of
the conformational search as geometric parameters together with an improved
tight-binding Hamiltonian to simulate the linear absorption spectra and compare
with experimental spectral measurements. The ideal dipole approximation to the
Hamiltonian is not valid since the distance between chromophores can be very
small. We found that using the geometries from the conformational search is
necessary to reproduce the features of the experimental spectral peaks
A microfluidic chip based model for the study of full thickness human intestinal tissue using dual flow
© 2016 Author(s). The study of inflammatory bowel disease, including Ulcerative Colitis and Crohn's Disease, has relied largely upon the use of animal or cell culture models; neither of which can represent all aspects of the human pathophysiology. Presented herein is a dual flow microfluidic device which holds full thickness human intestinal tissue in a known orientation. The luminal and serosal sides are independently perfused ex vivo with nutrients with simultaneous waste removal for up to 72 h. The microfluidic device maintains the viability and integrity of the tissue as demonstrated through Haematoxylin & Eosin staining, immunohistochemistry and release of lactate dehydrogenase. In addition, the inflammatory state remains in the tissue after perfusion on the device as determined by measuring calprotectin levels. It is anticipated that this human model will be extremely useful for studying the biology and tes ting novel interventions in diseased tissue
MoKCa database - mutations of kinases in cancer
Members of the protein kinase family are amongst the most commonly mutated genes in human cancer, and both mutated and activated protein kinases have proved to be tractable targets for the development of new anticancer therapies The MoKCa database (Mutations of Kinases in Cancer, http://strubiol.icr.ac.uk/extra/mokca) has been developed to structurally and functionally annotate, and where possible predict, the phenotypic consequences of mutations in protein kinases implicated in cancer. Somatic mutation data from tumours and tumour cell lines have been mapped onto the crystal structures of the affected protein domains. Positions of the mutated amino-acids are highlighted on a sequence-based domain pictogram, as well as a 3D-image of the protein structure, and in a molecular graphics package, integrated for interactive viewing. The data associated with each mutation is presented in the Web interface, along with expert annotation of the detailed molecular functional implications of the mutation. Proteins are linked to functional annotation resources and are annotated with structural and functional features such as domains and phosphorylation sites. MoKCa aims to provide assessments available from multiple sources and algorithms for each potential cancer-associated mutation, and present these together in a consistent and coherent fashion to facilitate authoritative annotation by cancer biologists and structural biologists, directly involved in the generation and analysis of new mutational data
De-palmitoylation of tissue factor regulates its activity, phosphorylation and cellular functions
In this study, the role of de-palmitoylation of tissue factor (TF) in the decryption of its activity was explored. TF-tGFP constructs were prepared by mutagenesis-substitution at Cys245 to prevent or mimic palmitolyation. Additionally, to reduce TF de-palmitoylation, the expression of palmitoyl-protein thioesterases (PPT) was suppressed. Other TF mutants were prepared with altered flexibility, hydrophobicity or length of the transmembrane domain. The outcome of these alterations on fXa-generation, fVIIa binding, Ser253 phosphorylation and TF-microvesicle release were assessed in endothelial cells, and the influence on endothelial and MCF-7 cell proliferation and apoptosis was analysed. Preventing TF palmitoylation (TFSer245-tGFP), increasing the hydropho-bicity (TFPhe241-tGFP) or lengthening (TFLongTM-tGFP) of the transmembrane domain enhanced fXa-generation in resting cells compared to cells expressing TFWt-tGFP, but fXa-generation was not further increased following PAR2 activation. Extending the available length of the transmembrane domain enhanced the TF-tGFP release within microvesicles and Ser253 phosphorylation and increased cell proliferation. Moreover, prevention of PKCα-mediated Ser253 phosphorylation with Gö6976 did not preclude fXa-generation. Conversely, reducing the hydrophobicity (TFSer242-tGFP), shortening (TFShortTM-tGFP) or reducing the flexibility (TFVal225-tGFP) of the transmembrane domain suppressed fXa-generation, fVIIa-HRP binding and Ser253 phosphorylation following PAR2 activa-tion. PPT knock-down or mimicking palmitoylation (TFPhe245-tGFP) reduced fXa-generation without affecting fVIIa binding. This study has for the first time shown that TF procoagulant activity is regulated through de-palmitoylation, which alters the orientation of its transmembrane domain and is independent of TF phosphorylation. However, Ser253 phosphorylation is facilitated by changes in the orientation of the transmembrane domain and can induce TF-cellular signalling that influences cellular proliferation/apoptosis
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