3,112 research outputs found
CYP2D6 polymorphisms and the impact on tamoxifen therapy
No full textThe cytochrome P450 2D6 (CYP2D6) is an enzyme known to metabolize a variety of xenobiotics and drugs. Inter-individual variation in the metabolic capacity of this enzyme has been extensively studied and associations with genotype have been established. Genetic polymorphisms have been grouped as nonfunctional, reduced function, functional, and multiplication alleles phenotypically. Individuals carrying these alleles are presumed to correspond to poor, intermediate, extensive, and ultrarapid metabolizers (UM), respectively. Tamoxifen has been shown to be metabolized by CYP2D6 to the more potent metabolite endoxifen. Poor metabolizers (PM) of tamoxifen have lower levels of endoxifen and poorer clinical outcomes as compared to extensive metabolizers (EM). Here, we will provide an overview of the history and application of CYP2D6 pharmacogenetics, and will discuss the clinical implications of recent developments relating to the involvement of CYP2D6 in tamoxifen treatment
The role of vascular endothelial growth factor SNPs as predictive and prognostic markers for major solid tumors
No full textAngiogenesis is crucial for development and metastasis of tumors, and vascular endothelial growth factor (VEGF) is a key mediator of this process. The importance of VEGF in tumorigenesis and tumor progression makes it an attractive target for the development of anticancer therapies. Inhibition of angiogenesis has shown promising clinical efficacy; however, not all patients treated with antiangiogenic agents derive benefit from them. Some patients are predisposed to refractory disease, whereas others develop resistance after initial response. Patients may also have different severity of drug-related adverse events. Optimization of drug administration based on disease status and individual responsiveness is important in limiting the treatment failure and minimization of side-effects. Single nucleotide polymorphisms (SNP) in VEGF may alter VEGF protein concentrations, influence the process of angiogenesis, and may relate to interindividual variation in the risk and progression of selected tumors, and their resistance to treatments. This review examines the role of SNPs in the VEGF gene as predictive and prognostic markers for major solid tumors, including the breast, non-small cell lung, colorectal, and prostate cancers. Selected VEGF SNPs seem to be associated with risk of these cancers; however, there is lack of unanimity in findings, in part influenced by differences in study design and analysis
Estrogen receptor alpha and aromatase polymorphisms affect risk, prognosis, and therapeutic outcome in men with castration-resistant prostate cancer treated with docetaxel-based therapy
No full textContext: Reactive estrogen species cause genotoxicity and interfere with docetaxel-mediated tubulin polymerization resulting in shortened survival in men with castrate-resistant prostate cancer (CRPC).
Objective: We hypothesized that polymorphisms in estrogen synthesis and estrogen targets (i.e., CYP19 and ER alpha) would be linked to interindividual variation in CRPC risk, docetaxel response, and overall survival in men with CRPC.
Materials and Methods: Patients with CRPC (n=115) treated with docetaxel, single-agent thalidomide (n=42), or healthy controls (n=289) were genotyped for the CYP19 R264C (rs700519) and the ER alpha PvuII T>C (rs2234693) and XbaI A>G (rs9340799) polymorphisms.
Results: Patients carrying two copies of ER alpha polymorphisms had shorter progression-free survival on docetaxel than other patients (median survival difference >= 3.1 months; P G polymorphism and PFS improved (median survival difference = 3.5 months; P = 0.0078). The CYP19 R264C variant was related to the duration of survival after docetaxel in patients who were >70 years old (median survival difference = 10.6 months; P=0.041). Both ER alpha polymorphisms were also associated with increases in CRPC risk [P = 2.6], and the association with the ER alpha PvuII T>C also improved in those men who were <70 years old (P = 0.0073; odds ratio = 3.0).
Conclusions: This study demonstrates that estrogen-related genetic variation affects docetaxel clinical response and that this relationship is dependent on age and body-type in men with CRPC. Moreover, this study suggests ER alpha polymorphisms confer risk of developing prostate cancer, especially in men under 70 years of age
Genetic variation: effect on prostate cancer
No full textThe crucial role of androgens in the development of prostate cancer is well established. The aim of this review is to examine the role of constitutional (germline) and tumor-specific (somatic) polymorphisms within important regulatory genes of prostate cancer. These include genes encoding enzymes of the androgen biosynthetic pathway, the androgen receptor gene, genes that encode proteins of the signal transduction pathways that may have a role in disease progression and survival, and genes involved in prostate cancer angiogenesis. Characterization of deregulated pathways critical to cancer cell growth have lead to the development of new treatments, including the CYP17 inhibitor abiraterone and clinical trials using novel drugs that are ongoing or recently completed [1]. The pharmacogenetics of the drugs used to treat prostate cancer will also be addressed. This review will define how germline polymorphisms are known affect a multitude of pathways, and therefore phenotypes, in prostate cancer etiology, progression, and treatment
Synthesis optimization and charge carrier transfer mechanism in LiLuSiO<sub>4</sub>:Ce, Tm storage phosphor
No full textLiLuSiO4:Ce and LiLuSiO4:Ce, Tm show very efficient charge carrier storage properties upon beta irradiation after samples have received treatment in vacuum. They outperform the commercial storage phosphor BaFBr(I):Eu2+ in many aspects. The influence of the synthesis conditions, Ce and Tm concentration, nonstoichiometry and codoping with Ca, Hf, Al and Ge are reported. Based on the results of the synthesis optimization, thermoluminescence (TL) emission and TL excitation spectra a mechanism of charge carrier transfer, storage, and recombination during irradiation and thermal or optical readout is proposed.Accepted Author ManuscriptRST/Fundamental Aspects of Materials and EnergyRST/Luminescence Material
GA Landsat 5 TM Analysis Ready Data Collection 3
No full textMaintenance and Update Frequency: asNeededStatement: This product is derived from the USGS Landsat Collection 1 archive.
The Moderate Resolution Imaging Spectroradiometer (MODIS) MCD43A1 Version 6 Bidirectional Reflectance Distribution Function and Albedo (BRDF/Albedo) Model Parameters dataset was provided by the National Aeronautics and Space Administration (NASA). It was produced daily using 16 days of Terra and Aqua MODIS data at 500 m resolution.
The ozone data was provided by Environment Canada.
The Aerosol Optical Thickness data was provided by the Commonwealth Scientific and Industrial Research Organisation (CSIRO).
The Precipitable Water for Entire Atmosphere data was provided by the National Oceanic and Atmospheric Administration (NOAA) / Earth System Research Laboratory (ESRL) / Physical Sciences Division (PSD).
The baseline Digital Surface Model (DSM) data produced from the Shuttle Radar Topography Mission (SRTM) was provided by the National Geospatial-Intelligence Agency (NGA).
Level 1 Collection 1 data was provided by the United States Geological Survey (USGS)'s Earth Resources Observation and Science (EROS) Center.<b>BACKGROUND</b><br/><p><br/><p>The United States Geological Survey's (USGS) Landsat satellite program has been capturing images of the Australian continent for more than 30 years. This data is highly useful for land and coastal mapping studies. <br/><p>In particular, the light reflected from the Earth’s surface (surface reflectance) is important for monitoring environmental resources – such as agricultural production and mining activities – over time. <br/><p>We need to make accurate comparisons of imagery acquired at different times, seasons and geographic locations. However, inconsistencies can arise due to variations in atmospheric conditions, sun position, sensor view angle, surface slope and surface aspect. These need to be reduced or removed to ensure the data is consistent and can be compared over time. <br/><p> </p><br/><b>WHAT THIS PRODUCT OFFERS</b><br/><p><br/><p>GA Landsat 5 TM Analysis Ready Data Collection 3 takes Landsat 5 Thematic Mapper (TM) imagery captured over the Australian continent and corrects for inconsistencies across land and coastal fringes. The result is accurate and standardised surface reflectance data, which is instrumental in identifying and quantifying environmental change. <br/><p><br/><p>The TM instrument is an advanced, multispectral scanning, Earth resources sensor which is designed to categorise the Earth's surface. It is particularly useful for agricultural applications and identification of land use. <br/><p><br/><p>This product is a single, cohesive Analysis Ready Data (ARD) package, which allows you to analyse surface reflectance data as is, without the need to apply additional corrections. <br/><p><br/><p>It contains three sub-products that provide corrections or attribution information:<br/><p><br/><p> 1) GA Landsat 5 TM NBAR Collection 3 <br/><p> 2) GA Landsat 5 TM NBART Collection 3<br/><p> 3) GA Landsat 5 TM OA Collection 3<br/><p><br/><p>The resolution is a 30 m grid based on the USGS Landsat Collection 1 archive
The dependence of light extraction improvement on optimized surface microstructure for AlGaN-based UVC-LEDs considering TM-polarized emission
No full textIn order to improve the light extraction of AlGaN-based short wavelength ultraviolet light emitting diodes (DUC-LEDs), a type of microstructure with high aspect ratio is introduced and optimized on the AlN substrate surface. And, particle swarm optimization (PSO) algorithm is used to inverse design of the surface microstructure to maximize the light extraction efficiency (LEE). Considering that the propagation characteristics of TM-polarized light are different from that of TE-polarized light, the optical field distribution and LEE is analyzed for the UVC-LEDs with different TE-polarized component when the optimized surface microstructure is applied. Furthermore, the preparation process tolerance of the high aspect ratio structure is discussed by calculating the LED's LEE when the structural deviation occurs or morphology changes. Simulation results show that, by using the optimized surface microstructure based on parabola cone array, the LEDs' LEE is increased from 4.4% to 8.7% and from 0.4% to 3.7% for TE-polarized and TM-polarized emission, respectively. In addition, it is demonstrated that the light extraction improvement by the surface microstructure has a good tolerance to the structural deviation and morphology. The results are significant for improving light extraction and realizing high efficient short wavelength AlGaN-based UVC-LEDs by designing surface microstructures.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.ImPhys/Esmaeil Zadeh grou
Rigor and relevance in empirical TM research: Key issues and challenges Author links open overlay panel
No full textThis paper aims to offer a critical reflection on the way Talent Management (TM) is investigated in practice, by addressing the key issues regarding the quality (in terms of rigor and relevance) of academic empirical TM research and therefore the critical scrutiny of TM scholars’ work. We will argue that despite the growth in the quantity, the quality of many empirical TM papers is lagging behind and hindering the progress of the academic field of TM. Based on a content analysis of 174 peer-reviewed articles published between 2006 and 2017, the paper outlines nine critical issues regarding the quality of the existent empirical TM research. In order to improve the positioning of the field as well as the impact of TM research on practice itis absolutely necessary for TM scholars to secure the quality of academic empirical TM research. Also, the collaboration between practitioners and scholars should increase.Peer ReviewedPostprint (author's final draft
Rigor and relevance in empirical TM research: Key issues and challenges Author links open overlay panel
No full textThis paper aims to offer a critical reflection on the way Talent Management (TM) is investigated in practice, by addressing the key issues regarding the quality (in terms of rigor and relevance) of academic empirical TM research and therefore the critical scrutiny of TM scholars’ work. We will argue that despite the growth in the quantity, the quality of many empirical TM papers is lagging behind and hindering the progress of the academic field of TM. Based on a content analysis of 174 peer-reviewed articles published between 2006 and 2017, the paper outlines nine critical issues regarding the quality of the existent empirical TM research. In order to improve the positioning of the field as well as the impact of TM research on practice itis absolutely necessary for TM scholars to secure the quality of academic empirical TM research. Also, the collaboration between practitioners and scholars should increase.Peer Reviewe
Dalla Biblioteca Comunale di Urbania: due raccolte musicali per un interprete
No full textIn the Library of Urbania (Marche, Italy) six musical manuscripts containing seventeenth century arias and cantatas are preserved. They belonged to an aristocratic family of Apecchio, (Marche), the Ubaldini. This article investigates two of them containing cantatas by Cossoni, Giovanni Bonaventura Viviani, Legrenzi Bassani and others, and in which there is the note “ex libris Antonij Barbarini”. This article reconstructs the origin of these two manuscripts, for whom the author individuated the probable owner, the singer Ippolito Fusai, by means the repertory identified in it. A thorough investigation of this hitherto little-known manuscripts may shed new light on the diffusion and transmission of music in Italy during the Seventeenth and early-Eighteenth centurie
- …
