21 CFR 582.1804 - Sodium potassium tartrate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium potassium tartrate. 582.1804 Section 582.1804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Additives § 582.1804 Sodium potassium tartrate. (a) Product. Sodium potassium tartrate. (b) Conditions of...

21 CFR 582.6804 - Sodium potassium tartrate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium potassium tartrate. 582.6804 Section 582.6804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....6804 Sodium potassium tartrate. (a) Product. Sodium potassium tartrate. (b) Conditions of use. This...

21 CFR 582.1804 - Sodium potassium tartrate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium potassium tartrate. 582.1804 Section 582.1804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Additives § 582.1804 Sodium potassium tartrate. (a) Product. Sodium potassium tartrate. (b) Conditions of...

21 CFR 582.6804 - Sodium potassium tartrate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium potassium tartrate. 582.6804 Section 582.6804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....6804 Sodium potassium tartrate. (a) Product. Sodium potassium tartrate. (b) Conditions of use. This...

21 CFR 582.1804 - Sodium potassium tartrate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium potassium tartrate. 582.1804 Section 582.1804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Additives § 582.1804 Sodium potassium tartrate. (a) Product. Sodium potassium tartrate. (b) Conditions of...

21 CFR 582.6804 - Sodium potassium tartrate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium potassium tartrate. 582.6804 Section 582.6804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....6804 Sodium potassium tartrate. (a) Product. Sodium potassium tartrate. (b) Conditions of use. This...

21 CFR 582.6804 - Sodium potassium tartrate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium potassium tartrate. 582.6804 Section 582.6804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....6804 Sodium potassium tartrate. (a) Product. Sodium potassium tartrate. (b) Conditions of use. This...

Zolpidem tartrate and somnambulism.

PubMed

Harazin, J; Berigan, T R

1999-09-01

A case is reported in which a patient experienced somnambulistic episodes only after taking zolpidem tartrate for insomnia. Previous to the patient's use of zolpidem tartrate he had never experienced sleepwalking, and once the medication was discontinued the sleepwalking stopped. A search of the literature revealed only two other cases of zolpidem-induced sleepwalking, both involving individuals with a previous history of somnambulism in their youth.

21 CFR 582.1077 - Potassium acid tartrate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium acid tartrate. 582.1077 Section 582.1077 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1077 Potassium acid tartrate. (a) Product. Potassium acid tartrate. (b) Conditions of use...

21 CFR 582.1077 - Potassium acid tartrate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium acid tartrate. 582.1077 Section 582.1077 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1077 Potassium acid tartrate. (a) Product. Potassium acid tartrate. (b) Conditions of use...

21 CFR 582.1077 - Potassium acid tartrate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium acid tartrate. 582.1077 Section 582.1077 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1077 Potassium acid tartrate. (a) Product. Potassium acid tartrate. (b) Conditions of use...

21 CFR 582.1077 - Potassium acid tartrate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium acid tartrate. 582.1077 Section 582.1077 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1077 Potassium acid tartrate. (a) Product. Potassium acid tartrate. (b) Conditions of use...

Section 9.1 new dosimeters. New dosimetry systems

NASA Astrophysics Data System (ADS)

McLaughlin, William L.

During the past two years there have been significant advances in several forms of radiation measurement systems for radiation processing, covering dose ranges of 1-10 6 Gy. Calorimeters as reference standards for both ionizing photon and electron fields have become well-established. In addition to the older ceric-cerous dosimetry solution analyzed potentiometrically, new liquid-phase dosimeters include those analyzed by spectrophotometry, e.g., improved forms of acidic aqueous solutions of K-Ag dichromate and organic radiochromic dye solutions. It has recently been demonstrated that by using certain refined sugars, e.g., D-(-) ribose, optical rotation response in aqueous solutions can be enhanced for dosimetry at doses > 10 4 Gy. There has been expanded development, use, and formulation (rods, tablets, and thin films) of the amino acid, alanine, as a solid-phase dosimeter analyzed by either ESR spectrometry or by glutamine or alanine spectrophotometry of complexes with ferric ion in the presence of a sulfonphthalein dye (xylenol orange). New commercial types of radiochromic plastic dosimeters, e.g., GafChromic TM, Riso B3 TM, GAMMACHROME YR TM, Radix TM, and Gammex TM, have been introduced and applied in practice. Improvements and broader use of optical waveguide dosimeters, e.g., Opti-Chromic TM, have also been reported, especially in food irradiation applications. Several novel dyed plastic dosimeters are available in large quantities and they lose color due to irradiation. An example is a dyed cellulosic thin film (ATC type DY-42 TM) which can be measured spectrophotometrically or densitometrically up to doses as high as 10 6 Gy.

21 CFR 184.1077 - Potassium acid tartrate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium acid tartrate. 184.1077 Section 184.1077... Listing of Specific Substances Affirmed as GRAS § 184.1077 Potassium acid tartrate. (a) Potassium acid tartrate (C4H5KO6, CAS Reg. No. 868-14-4) is the potassium acid salt of l−(+)−tartaric acid and is also...

21 CFR 184.1077 - Potassium acid tartrate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium acid tartrate. 184.1077 Section 184.1077... GRAS § 184.1077 Potassium acid tartrate. (a) Potassium acid tartrate (C4H5KO6, CAS Reg. No. 868-14-4) is the potassium acid salt of l−(+)−tartaric acid and is also called potassium bitartrate or cream of...

21 CFR 184.1077 - Potassium acid tartrate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium acid tartrate. 184.1077 Section 184.1077... Listing of Specific Substances Affirmed as GRAS § 184.1077 Potassium acid tartrate. (a) Potassium acid tartrate (C4H5KO6, CAS Reg. No. 868-14-4) is the potassium acid salt of l−(+)−tartaric acid and is also...

21 CFR 184.1804 - Sodium potassium tartrate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium potassium tartrate. 184.1804 Section 184... Listing of Specific Substances Affirmed as GRAS § 184.1804 Sodium potassium tartrate. (a) Sodium potassium tartrate (C4H4KNaO6·4H2O, CAS Reg. No. 304-59-6) is the sodium potassium salt of l−(+)−tartaric acid and is...

21 CFR 184.1804 - Sodium potassium tartrate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium potassium tartrate. 184.1804 Section 184... as GRAS § 184.1804 Sodium potassium tartrate. (a) Sodium potassium tartrate (C4H4KNaO6·4H2O, CAS Reg. No. 304-59-6) is the sodium potassium salt of l−(+)−tartaric acid and is also called the Rochelle...

21 CFR 184.1804 - Sodium potassium tartrate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium potassium tartrate. 184.1804 Section 184... Listing of Specific Substances Affirmed as GRAS § 184.1804 Sodium potassium tartrate. (a) Sodium potassium tartrate (C4H4KNaO6·4H2O, CAS Reg. No. 304-59-6) is the sodium potassium salt of l−(+)−tartaric acid and is...

21 CFR 184.1804 - Sodium potassium tartrate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium potassium tartrate. 184.1804 Section 184... Listing of Specific Substances Affirmed as GRAS § 184.1804 Sodium potassium tartrate. (a) Sodium potassium tartrate (C4H4KNaO6·4H2O, CAS Reg. No. 304-59-6) is the sodium potassium salt of l−(+)−tartaric acid and is...

21 CFR 582.1077 - Potassium acid tartrate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Additives § 582.1077 Potassium acid tartrate. (a) Product. Potassium acid tartrate. (b) Conditions of use. This substance is generally recognized as safe when used in accordance with good manufacturing or...

21 CFR 520.246 - Butorphanol tartrate tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Butorphanol tartrate tablets. 520.246 Section 520.246 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... tartrate tablets. (a) Specifications. Each tablet contains 1, 5, or 10 milligrams of butorphanol base...

Electron Spin Resonance (ESR) studies of returned comet nucleus samples

NASA Technical Reports Server (NTRS)

Tsay, Fun-Dow; Kim, Soon Sam; Liang, Ranty H.

1989-01-01

The most important objective of the Comet Nucleus Sample Returm Mission is to return samples which could reflect formation conditions and evolutionary processes in the early solar nebula. It is expected that the returned samples will consist of fine-grained silicate materials mixed with ices composed of simple molecules such as H2O, NH3, CH4 as well as organics and/or more complex compounds. Because of the exposure to ionizing radiation from cosmic-ray, gamma-ray, and solar wind protons at low temperature, free radicals are expected to be formed and trapped in the solid ice matrices. The kind of trapped radical species together with their concentration and thermal stability can be used as a dosimeter as well as a geothermometer to determine thermal and radiation histories as well as outgassing and other possible alternation effects since the nucleus material was formed. Since free radicals that are known to contain unpaired electrons are all paramagnetic in nature, they can be readily detected and characterized in their native form by the Electron Spin Resonance (ESR) method. In fact, ESR has been shown to be a non-destructive, highly sensitive tool for the detection and characterization of paramagnetic, ferromagnetic, and radiation damage centers in terrestrial and extraterrestrial geological samples. The potential use of ESR as an effective method in the study of returned comet nucleus samples, in particular, in the analysis of fine-grained solid state icy samples is discussed.

Radiation dosimeters

DOEpatents

Hoelsher, James W.; Hegland, Joel E.; Braunlich, Peter F.; Tetzlaff, Wolfgang

1992-01-01

Radiation dosimeters and dosimeter badges. The dosimeter badges include first and second parts which are connected to join using a securement to produce a sealed area in which at least one dosimeter is held and protected. The badge parts are separated to expose the dosimeters to a stimulating laser beam used to read dose exposure information therefrom. The badge is constructed to allow automated disassembly and reassembly in a uniquely fitting relationship. An electronic memory is included to provide calibration and identification information used during reading of the dosimeter. Dosimeter mounts which reduce thermal heating requirements are shown. Dosimeter constructions and production methods using thin substrates and phosphor binder-layers applied thereto are also taught.

Upregulation of the ESR1 Gene and ESR Ratio (ESR1/ESR2) is Associated with a Worse Prognosis in Papillary Thyroid Carcinoma: The Impact of the Estrogen Receptor α/β Expression on Clinical Outcomes in Papillary Thyroid Carcinoma Patients.

PubMed

Yi, Jin Wook; Kim, Su-Jin; Kim, Jong Kyu; Seong, Chan Yong; Yu, Hyeong Won; Chai, Young Jun; Choi, June Young; Lee, Kyu Eun

2017-11-01

A gender disparity exists with respect to the incidence of papillary thyroid cancer (PTC), suggesting that sex hormones such as estrogen play a role in PTC development and progression. In this study, we compared estrogen receptor gene expression patterns in PTCs to determine the clinical significance of estrogen gene expression in PTC. We analyzed ESR1 and ESR2 messenger RNA expression counts using data from The Cancer Genome Atlas (TCGA). To validate the results of TCGA analysis, we analyzed microarray data (GSE 54958) from the Gene Expression Omnibus. ESR1 gene expression and ESR ratio (ESR1/ESR2) were significantly higher in PTC tissues than in paired normal thyroid tissues (mean 659.427 vs. 264.045 for ESR1, 92.017 vs. 19.064 for ESR ratio). Among female patients, ESR1 expression and ESR ratio were negatively correlated with increased age. ESR1 expression and ESR ratio were higher in patients with classic PTC, lymphovascular invasion, BRAF V600E mutation, and radioiodine therapy. Classification analysis demonstrated that higher ESR1 expression and a higher ESR ratio faced a worse overall survival (hazard ratio 6.348 for ESR1, 4.031 for ESR ratio). Validation microarray analysis demonstrated that ESR1 expression and ESR ratio were higher in tumor tissues, classic PTC, and BRAF V600E . Higher ESR1 expression and a higher ESR ratio were associated with aggressive prognostic factors and worse overall survival in female PTC patients. Our results suggest that ESR1 and ESR ratio can be used as prognostic markers to predict female patient survival and have potential as a therapeutic target.

Molecular studies on di-sodium tartrate molecule

NASA Astrophysics Data System (ADS)

Divya, P.; Jayakumar, S.; George, Preethamary; Shubashree, N. S.; Ahmed. M, Anees

2015-06-01

Structural characterization is important for the development of new material. The acoustical parameters such as Free Length, Internal Pressure have been measured from ultrasonic velocity, density for di sodium tartrate an optically active molecule at different temperatures using ultrasonic interferometer of frequency (2MHZ). The ultrasonic velocity increases with increase in concentration there is an increase in solute-solvent interaction. The stability constant had been calculated. SEM with EDAX studies has been done for Di-sodium tartrate an optically active molecule.

Single crystal growth and characterization of pure and sodium-modified copper tartrate

NASA Astrophysics Data System (ADS)

Quasim, I.; Firdous, A.; Want, B.; Khosa, S. K.; Kotru, P. N.

2008-12-01

Single crystal growth of pure and modified copper tartrate crystals bearing composition (Cu) x(Na) yC 4H 4O 6· nH 2O (where x=1, 0.77, 0.65; y=0, 0.23, 0.35) is achieved using gel technique. The optimum conditions required for the growth of these crystals are worked out. The morphological development of these crystals is studied using optical and scanning electron microscopy. The dominant habit faces of the grown copper tartrate crystals are (0 0 1) and (1 1 1). Calculation of the cell parameters using CRYSFIRE software suggests that the pure copper tartrate crystal belongs to orthorhombic system with space group P2 1/c whereas the modified copper tartrate falls under tetragonal system with the space group P4 2/nbc. The external morphological development is shown to remain unaffected in the modified copper tartrate. The stoichiometric composition of the crystals is established by EDAX analysis, CH analysis, FTIR spectroscopy and thermoanalytical techniques. Thermal analysis of the grown crystals suggests that pure copper tartrate is thermally stable up to 42.84 °C whereas the modified copper tartrate crystals are stable only up to 33.11 and 25.11 °C. Calculation of the percentage weight loss from the thermogram supplemented by EDAX/CH analysis and FTIR spectroscopy suggest that the chemical formula of pure copper tartrate crystal is CuC 4H 4O 6·3H 2O whereas the chemical formula for the modified copper tartrate crystals is (Cu) 0.77(Na) 0.23C 4H 4O 6·3H 2O and (Cu) 0.65(Na) 0.35 C 4H 4O 6·H 2O.

Pocket radiation dosimeter: dosimeter charger assembly

DOEpatents

Manning, F.W.

1982-03-17

This invention is a novel pocket-type radiation dosimeter comprising an electrometric radiation dosimeter and a charging circuit therefor. The instrument is especially designed to be amenable to mass production, to have a long shelf life, and to be compact, lightweight, and usable by the layman. The dosimeter proper may be of conventional design. The charging circuit includes a shake-type electrostatic generator, a voltage doubler for integrating generator output voltages of one polarity, and a switch operated by an external permanent magnet.

Pocket radiation dosimeter--dosimeter charger assembly

DOEpatents

Manning, Frank W.

1984-01-01

This invention is a novel pocket-type radiation dosimeter comprising an electrometric radiation dosimeter and a charging circuit therefor. The instrument is especially designed to be amenable to mass production, to have a long shelf life, and to be compact, lightweight, and usable by the layman. The dosimeter proper may be of conventional design. The charging circuit includes a shake-type electrostatic generator, a voltage doubler for integrating generator output voltages of one polarity, and a switch operated by an external permanent magnet.

Composite material dosimeters

DOEpatents

Miller, Steven D.

1996-01-01

The present invention is a composite material containing a mix of dosimeter material powder and a polymer powder wherein the polymer is transparent to the photon emission of the dosimeter material powder. By mixing dosimeter material powder with polymer powder, less dosimeter material is needed compared to a monolithic dosimeter material chip. Interrogation is done with excitation by visible light.

Calcium Tartrate Tetrahydrate, Case Report of a Novel Human Kidney Stone.

PubMed

Kleinguetl, Colin; Williams, James C; Ibrahim, Samar A; Daudon, Michel; Bird, Erin T; El Tayeb, Marawan M

2017-01-01

Background: Calcium tartrate tetrahydrate has been reported as the main mineral in urinary stones in rats that have significant tartrate in their diet, but in humans, there has been only one mention of calcium tartrate stones in the form of bladder stone, and that case was in Africa. Case Presentation: Patient is a 34-year-old Caucasian male who presented with typical symptoms of nephrolithiasis. CT abd/pelvis (renal stone protocol) revealed a 2 cm nonobstructing stone of the right renal pelvis. Patient underwent an uncomplicated right percutaneous nephrolithotomy and was noted to be stone free after surgery. Stone analysis was difficult with regard to determining composition, but was finally identified as calcium tartrate tetrahydrate. Conclusion: This was an unusual case, as this is the first recorded case of a calcium tartrate tetrahydrate outside of Africa. This type of stone had only been mainly described in rat models with dl- bitartrate in their diet. Our patient was an otherwise healthy, relatively muscular individual with no obvious source for this stone other than a vitamin and amino acid supplement that he takes regularly that contains l-carnitine (as tartrate) and choline (as bitartrate and citrate). The prevalence of this stone type is presently unknown, as stone analysis laboratories have not had the ability to recognize it. Although a connection between the supplement and stone formation is conjecture at this time, we believe this necessitates further investigation.

Effect of molecular structure of tartrates on chiral recognition of tartrate-boric acid complex chiral selectors in chiral microemulsion electrokinetic chromatography.

PubMed

Hu, Shao-Qiang; Chen, Yong-Lei; Zhu, Hua-Dong; Shi, Hai-Jun; Yan, Na; Chen, Xing-Guo

2010-08-20

Eight l-tartrates and a d-tartrate with different alcohol moieties were used as chiral oils to prepare chiral microemulsions, which were utilized in conjunction with borate buffer to separate the enantiomers of beta-blockers or structurally related compounds by the chiral microemulsion electrokinetic chromatography (MEEKC) method. Among them, six were found to have a relatively good chiral separation performance and their chiral recognition effect in terms of both enantioselectivity and resolution increases linearly with the number of carbon atoms in the alkyl group of alcohol moiety. The tartrates containing alkyl groups of different structures but the same number of carbon atoms, i.e. one of straight chain and one of branched chain, provide similar enantioseparations. The trend was elucidated according to the changes in the difference of the steric matching between the molecules of two enantiomers and chiral selector. Furthermore, it was demonstrated for the first time that a water insoluble solid compound, di-i-butyl l-tartrate (mp. 73.5 degrees C), can be used as an oil to prepare a stable microemulsion to be used in the chiral MEEKC successfully. And a critical effect of the microemulsion for chiral separation, which has never been reported before, was found in this experiment, namely providing a hydrophobic environment to strengthen the interactions between the chiral selector and enantiomers. Copyright 2010 Elsevier B.V. All rights reserved.

Expression of oestrogen receptors (GPER, ESR1, ESR2) in human ductuli efferentes and proximal epididymis.

PubMed

Rago, V; Romeo, F; Giordano, F; Malivindi, R; Pezzi, V; Casaburi, I; Carpino, A

2018-01-01

Oestrogen targeting in the human genital ducts is still not well-known. In fact, to date, the localization of oestrogen receptors, ESR1 and ESR2, is controversial and the presence of the membrane oestrogen receptor GPER (G protein-coupled oestrogen receptor) is unexplored. This study has investigated the expression of GPER, ESR1, ESR2 in human ductuli efferentes and proximal caput epididymis by immunohistochemistry and Western blot analysis. Furthermore, the presence of PELP1 (proline-glutamic acid-leucine-rich protein 1), a co-regulator of the oestrogen receptors, was also evaluated. In ductuli efferentes, GPER and ESR1 were clearly localized in all epithelial cells, while ESR2 was evidenced only in ciliated cells. Conversely, the epithelial cells of proximal caput epididymis revealed moderate GPER immunoreactivity, the absence of ERS1 and the occasional presence of ESR2. Furthermore, PELP1 was observed in ciliated cells of ductuli efferentes and in principal cells of proximal caput epididymis. Therefore, this study firstly demonstrated the expression of GPER in human male genital ducts, revealing a new mediator of oestrogen action in these anatomical sites. ESR1 and ESR2 were differentially localized in the two genital tracts together with PELP1, but cell sites of ERs and their co-regulator were not homogeneous. So, a different regional/cellular association of GPER with the classical oestrogen receptors was highlighted, suggesting that oestrogen action could be mediated by GPER, ESR1, ESR2 in ductuli efferentes, while by GPER and, occasionally by ESR2, in proximal caput epididymis. This study suggests that the specific oestrogen-mediated functions in human genital ducts might result from the different local interactions of oestrogens with oestrogen receptors and their co-regulators. © 2017 American Society of Andrology and European Academy of Andrology.

Erythrocyte Sedimentation Rate (ESR)

MedlinePlus

... 3 screens]. Available from: https://labtestsonline.org/understanding/analytes/esr/tab/test/ Lab Tests Online [Internet]. Washington ... 2 screens]. Available from: https://labtestsonline.org/understanding/analytes/esr/tab/sample/ National Heart, Lung, and Blood ...

Powder XRD, TEM, FTIR and thermal studies of strontium tartrate nano particles

NASA Astrophysics Data System (ADS)

Lathiya, U. M.; Jethva, H. O.; Joshi, M. J.; Vyas, P. M.

2017-05-01

Strontium tartrate finds several applications, e.g., as non-linear optical and dielectric material, in tracer composition and ammunition unit, in treating structural integrity of bone. The growth of single crystals of strontium tartrate in silica gel has been widely reported. In the present study, strontium tartrate nano particles were synthesized by wet chemical method using strontium chloride, tartaric acid and sodium meta-silicate solutions in the presence of Triton X -100 surfactant. It was found that the presence of sodium meta-silicate facilitated the reaction for strontium tartrate product. The powder XRD study of strontium tartrate nano-particles suggested monoclinic crystal system and the average crystallite size was found to be 40 nm determined by applying Scherrer's formula. The TEM analysis indicated that the nano particles were spherical in nature. The FTIR spectrum confirmed the presence of various functional groups such as O-H,C-H, and C=O stretching mode. The thermal analysis was carried out by using TGA and DTA studies. The nano-particles were found to be stable up to 175°C and then decomposed through various stages. The results are compared with the bulk crystalline material available in the literature.

Persistent free radical ESR signals in marine bivalve tissues. [Electron Spin Resonance (ESR)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehlorn, R.J.; Mendez, A.T.; Higashi, R.

1992-08-01

Freeze-dried homogenates of the oyster Crassostrea rhizophorae collected from waters in Puerto Rico near urban and industrial sites as well as at relatively pristine locations yielded electron spin resonance (ESR) spectra characteristic of free radicals as well as spectral components of transition metal ions, dominated by manganese. The magnitudes of these ESR signals and the concentrations of trace elements (determined by X-ray fluorescence) varied considerably among oyster samples, masking any potential correlation with polluted waters. Laboratory studies were initiated to identify the factors controlling the magnitudes of the tissue free radical ESR signals. Another mollusc, Mytilus californianus collected at themore » Bodega Marine laboratory in northern California, was fractionated into goneds and remaining tissue. Freeze-dried homogenates of both fractions exhibited ESR signals that increased gradually with time. ESR signals were observed in freeze-dried perchloric acid (PCA) precipitates of the homogenates, delipidated PCA precipitates, and in chloroform extracts of these precipitates. Acid hydrolysis to degrade proteins to amino acids produced a residue, which yielded much larger ESR free radical signals after freeze-drying. Freshly thawed homogenates of Crassostrea rhizophorae also exhibited ESR signals. A laboratory model of copper stress in Crassostrea rhizophorae was developed to study the effect of this transition metal on dssue free radicals. Preliminary results suggested that sublethal copper exposure had little effect on tissue fire radicals, except possibly for a signal enhancement in an oyster fraction that was enriched in kidney granules. Since kidney granules are known to accumulate heavy metals in mussels and probably other marine bivalves, this signal enhancement may prove to be an indicator of free radical processes associated with heavy metal deposition in molluscs.« less

Association of polymorphisms in estrogen receptors (ESR1 and ESR2) with male infertility: a meta-analysis and systematic review.

PubMed

Ge, Yu-Zheng; Xu, Lu-Wei; Jia, Rui-Peng; Xu, Zheng; Li, Wen-Cheng; Wu, Ran; Liao, Sheng; Gao, Fei; Tan, Si-Jia; Song, Qun; Xin, Hui

2014-05-01

Estrogens play an important role in male reproduction via interacting with estrogen receptors (ERs), whose expression can be regulated by the polymorphisms in different regions of ESR1 and ESR2 genes. However, results from published studies on the association between four well-characterized polymorphisms (PvuII, XbaI, RsaI, and AluI) in the gene of ERs (ESR1 and ESR2) and male infertility risk are inconclusive. To investigate the strength of relationship of PvuII and XbaI in ESR1 and RsaI and AluI in ESR2 with male infertility, we conducted a meta-analysis of 12 eligible studies with odds ratio (OR) and its corresponding 95 % confidence intervals (95 % CI). Overall, ESR1 PvuII and ESR2 RsaI polymorphisms were significantly associated with male infertility risk. The subgroup analyses by ethnicities demonstrated that in Asians, ESR1 PvuII, XbaI and ESR2 RsaI polymorphisms were significantly associated with a decreased infertility risk, while in Caucasians both ESR1 PvuII and ESR2 RsaI polymorphisms increased the susceptibility to male infertility. As for ESR2 AluI polymorphism, no significant association was detected in either overall analysis or subgroup analyses by ethnicities/genotyping methods. This meta-analysis suggested that polymorphisms in the genes of ERs (ESR1 and ESR2) may have differential roles in the predisposition to male infertility according to the different ethnic backgrounds. Further well-designed and unbiased studies with larger sample size and diverse ethnic backgrounds should be conducted to verify our findings.

Genetic polymorphisms in ESR1 and ESR2 genes, and risk of hypospadias in a multiethnic study population.

PubMed

Choudhry, Shweta; Baskin, Laurence S; Lammer, Edward J; Witte, John S; Dasgupta, Sudeshna; Ma, Chen; Surampalli, Abhilasha; Shen, Joel; Shaw, Gary M; Carmichael, Suzan L

2015-05-01

Estrogenic endocrine disruptors acting via estrogen receptors α (ESR1) and β (ESR2) have been implicated in the etiology of hypospadias, a common congenital malformation of the male external genitalia. We determined the association of single nucleotide polymorphisms in ESR1 and ESR2 genes with hypospadias in a racially/ethnically diverse study population of California births. We investigated the relationship between hypospadias and 108 ESR1 and 36 ESR2 single nucleotide polymorphisms in 647 cases and 877 population based nonmalformed controls among infants born in selected California counties from 1990 to 2003. Subgroup analyses were performed by race/ethnicity (nonHispanic white and Hispanic subjects) and by hypospadias severity (mild to moderate and severe). Odds ratios for 33 of the 108 ESR1 single nucleotide polymorphisms had p values less than 0.05 (p = 0.05 to 0.007) for risk of hypospadias. However, none of the 36 ESR2 single nucleotide polymorphisms was significantly associated. In stratified analyses the association results were consistent by disease severity but different sets of single nucleotide polymorphisms were significantly associated with hypospadias in nonHispanic white and Hispanic subjects. Due to high linkage disequilibrium across the single nucleotide polymorphisms, haplotype analyses were conducted and identified 6 haplotype blocks in ESR1 gene that had haplotypes significantly associated with an increased risk of hypospadias (OR 1.3 to 1.8, p = 0.04 to 0.00001). Similar to single nucleotide polymorphism analysis, different ESR1 haplotypes were associated with risk of hypospadias in nonHispanic white and Hispanic subjects. No significant haplotype association was observed for ESR2. The data provide evidence that ESR1 single nucleotide polymorphisms and haplotypes influence the risk of hypospadias in white and Hispanic subjects, and warrant further examination in other study populations. Copyright © 2015 American Urological Association

21 CFR 556.560 - Pyrantel tartrate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.560 Pyrantel tartrate. Tolerances are established for...

21 CFR 556.560 - Pyrantel tartrate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.560 Pyrantel tartrate. Tolerances are established for...

21 CFR 556.560 - Pyrantel tartrate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.560 Pyrantel tartrate. Tolerances are established for...

21 CFR 556.560 - Pyrantel tartrate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.560 Pyrantel tartrate. Tolerances are established for...

21 CFR 556.560 - Pyrantel tartrate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.560 Pyrantel tartrate. Tolerances are established for...

AAS and spectrophotometric methods for the determination metoprolol tartrate in tablets

NASA Astrophysics Data System (ADS)

Alpdoğan, Güzin; Sungur, Sidika

1999-11-01

Sensitive and specific atomic adsorption spectroscopy (AAS) and spectrophotometric methods have been developed for the determination of beta adrenergic blocking drug, metoprolol tartrate.The method is based on the formation of Cu(II) dithiocarbamate complex by derivatization of the secondary amino group of metoprolol with CS 2 and CuCl 2 in the presence of ammonia.The copper-bis(dithiocarbamate) complex was extracted into chloroform and the concentration of metoprolol tartrate was determined directly by spectrophotometric and indirectly by AAS measurement of copper.The two methods developed were applied to the assay of metoprolol tartrate in commercial tablet formulations.The methods were compared statistically with each other and with the high performance liquid chromatography (HPLC) method of USPXXII using t- and F-tests.

Elevated serum tartrate-resistant acid phosphatase isoform 5a levels in metabolic syndrome.

PubMed

Huang, Yi-Jhih; Huang, Tsai-Wang; Chao, Tsu-Yi; Sun, Yu-Shan; Chen, Shyi-Jou; Chu, Der-Ming; Chen, Wei-Liang; Wu, Li-Wei

2017-09-29

Tartrate-resistant phosphatase isoform 5a is expressed in tumor-associated macrophages and is a biomarker of chronic inflammation. Herein, we correlated serum tartrate-resistant phosphatase isoform 5a levels with metabolic syndrome status and made comparisons with traditional markers of inflammation, including c-reactive protein and interleukin-6. One hundred healthy volunteers were randomly selected, and cut-off points for metabolic syndrome related inflammatory biomarkers were determined using receiver operating characteristic curves. Linear and logistic regression models were subsequently used to correlate inflammatory markers with the risk of metabolic syndrome. Twenty-two participants met the criteria for metabolic syndrome, and serum tartrate-resistant phosphatase isoform 5a levels of >5.8 μg/L were associated with metabolic syndrome (c-statistics, 0.730; p = 0.001; 95% confidence interval, 0.618-0.842). In addition, 1 μg/L increases in tartrate-resistant phosphatase isoform 5a levels were indicative of a 1.860 fold increase in the risk of metabolic syndrome (p = 0.012). Elevated serum tartrate-resistant phosphatase isoform 5a levels are associated with the risk of metabolic syndrome, with a cut-off level of 5.8 μg/L.

Establishment of estrogen receptor 1 (ESR1)-knockout medaka: ESR1 is dispensable for sexual development and reproduction in medaka, Oryzias latipes.

PubMed

Tohyama, Saki; Ogino, Yukiko; Lange, Anke; Myosho, Taijun; Kobayashi, Tohru; Hirano, Yu; Yamada, Gen; Sato, Tomomi; Tatarazako, Norihisa; Tyler, Charles R; Iguchi, Taisen; Miyagawa, Shinichi

2017-08-01

Estrogens play fundamental roles in regulating reproductive activities and they act through estrogen receptor (ESR) in all vertebrates. Most vertebrates have two ESR subtypes (ESR1 and ESR2), whereas teleost fish have at least three (Esr1, Esr2a and Esr2b). Intricate functionalization has been suggested among the Esr subtypes, but to date, distinct roles of Esr have been characterized in only a limited number of species. Study of loss-of-function in animal models is a powerful tool for application to understanding vertebrate reproductive biology. In the current study, we established esr1 knockout (KO) medaka using a TALEN approach and examined the effects of Esr1 ablation. Unexpectedly, esr1 KO medaka did not show any significant defects in their gonadal development or in their sexual characteristics. Neither male or female esr1 KO medaka exhibited any significant changes in sexual differentiation or reproductive activity compared with wild type controls. Interestingly, however, estrogen-induced vitellogenin gene expression, an estrogen-responsive biomarker in fish, was limited in the liver of esr1 KO males. Our findings, in contrast to mammals, indicate that Esr1 is dispensable for normal development and reproduction in medaka. We thus provide an evidence for estrogen receptor functionalization between mammals and fish. Our findings will also benefit interpretation of studies into the toxicological effects of estrogenic chemicals in fish. © 2017 Japanese Society of Developmental Biologists.

Differential association of ESR1 and ESR2 gene variants with the risk of breast cancer and associated features: A case-control study.

PubMed

Ghali, Rabeb M; Al-Mutawa, Maryam A; Al-Ansari, Abrar K; Zaied, Sonia; Bhiri, Hanen; Mahjoub, Touhami; Almawi, Wassim Y

2018-04-20

Estrogen is key to breast cancer pathogenesis, and acts by binding its receptor (ER), which exists as ERα and ERβ, encoded by ESR1 and ESR2 genes, respectively. Studies that investigated the association of ESR1 and ESR2 variants with breast cancer yielded mixed outcome, and ethnic contribution was proposed. We evaluated the association between ESR1 and ESR2 variants and breast cancer and associated features in Tunisian women. Retrospective case-control study involving 207 female breast cancer patients, and 284 control women. Genotyping was done by real-time PCR. Minor allele frequencies (MAF) of tagging SNPs rs2234693 and rs3798577 (ESR1) were significantly higher, while MAF of rs1256049 (ESR2) was significantly lower in breast cancer patients vs. Patients carrying rs3798577 genotypes had higher risk, while rs1256049 genotype carriers had reduced risk of breast cancer. The association of ESR1 and ESR2 gene variants with breast cancer depended on ER and Her-2 status. ESR1 rs3798577 and ESR2 rs1256049 were associated with breast cancer in ER-positive cases, and ESR1 rs2234693, and rs3798577 were associated with breast cancer in Her-2-negative cases, while the association of ESR2 rs1256049 with breast cancer was seen in Her-2 positive cases. Haploview analysis identified 4-locus ESR1 haplotypes that were positively (CGTT, TACC, and TACT), and negatively (CGTC) associated with breast cancer. No ESR2 haplotypes associated with breast cancer were identified. ESR1 alleles and genotypes, and specific 3-locus ESR1 haplotypes are related with increased breast cancer susceptibility in Tunisian women. However, ESR2 variant and specific 1-locus ESR1 haplotype have a protective effect. Copyright © 2018 Elsevier B.V. All rights reserved.

Wristwatch dosimeter

DOEpatents

Wolf, Michael A.; Waechter, David A.; Umbarger, C. John

1986-01-01

The disclosure is directed to a wristwatch dosimeter utilizing a CdTe detector, a microprocessor and an audio and/or visual alarm. The dosimeter is entirely housable with a conventional digital watch case having an additional aperture enabling the detector to receive radiation.

Wristwatch dosimeter

DOEpatents

Wolf, M.A.; Waechter, D.A.; Umbarger, C.J.

1986-08-26

The disclosure is directed to a wristwatch dosimeter utilizing a CdTe detector, a microprocessor and an audio and/or visual alarm. The dosimeter is entirely housable with a conventional digital watch case having an additional aperture enabling the detector to receive radiation. 10 figs.

Fundamentals of Polymer Gel Dosimeters

NASA Astrophysics Data System (ADS)

McAuley, Kim B.

2006-12-01

The recent literature on polymer gel dosimetry contains application papers and basic experimental studies involving polymethacrylic-acid-based and polyacrylamide-based gel dosimeters. The basic studies assess the relative merits of these two most commonly used dosimeters, and explore the effects of tetrakis hydroxymethyl phosphonium chloride (THPC) antioxidant on dosimeter performance. Polymer gel dosimeters that contain THPC or other oxygen scavengers are called normoxic dosimeters, because they can be prepared under normal atmospheric conditions, rather than in a glove box that excludes oxygen. In this review, an effort is made to explain some of the underlying chemical phenomena that affect dosimeter performance using THPC, and that lead to differences in behaviour between dosimeters made using the two types of monomer systems. Progress on the development of new more effective and less toxic dosimeters is also reported.

The discovery of novel tartrate-based TNF-[alpha] converting enzyme (TACE) inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosner, Kristin E.; Guo, Zhuyan; Orth, Peter

2010-09-17

A novel series of TNF-{alpha} convertase (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds are bis-amides of L-tartaric acid (tartrate) and coordinate to the active site zinc in a tridentate manner. They are selective for TACE over other MMP's. We report the first X-ray crystal structure for a tartrate-based TACE inhibitor.

Citizen's dosimeter

DOEpatents

Klemic, Gladys [Naperville, IL; Bailey, Paul [Chicago, IL; Breheny, Cecilia [Yonkers, NY

2008-09-02

The present invention relates to a citizen's dosimeter. More specifically, the invention relates to a small, portable, personal dosimetry device designed to be used in the wake of a event involving a Radiological Dispersal Device (RDD), Improvised Nuclear Device (IND), or other event resulting in the contamination of large area with radioactive material or where on site personal dosimetry is required. The card sized dosimeter generally comprises: a lower card layer, the lower card body having an inner and outer side; a upper card layer, the layer card having an inner and outer side; an optically stimulated luminescent material (OSLM), wherein the OSLM is sandwiched between the inner side of the lower card layer and the inner side of the upper card layer during dosimeter radiation recording, a shutter means for exposing at least one side of the OSLM for dosimeter readout; and an energy compensation filter attached to the outer sides of the lower and upper card layers.

21 CFR 556.425 - Morantel tartrate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.425 Morantel tartrate. A tolerance of 0.7 part per million is established for N-methyl-1,3-propanediamine (MAPA, marker residue) in the liver (target tissue) of...

21 CFR 556.425 - Morantel tartrate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.425 Morantel tartrate. A tolerance of 0.7 part per million is established for N-methyl-1,3-propanediamine (MAPA, marker residue) in the liver (target tissue) of...

21 CFR 556.425 - Morantel tartrate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.425 Morantel tartrate. A tolerance of 0.7 part per million is established for N-methyl-1,3-propanediamine (MAPA, marker residue) in the liver (target tissue) of...

21 CFR 556.425 - Morantel tartrate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.425 Morantel tartrate. A tolerance of 0.7 part per million is established for N-methyl-1,3-propanediamine (MAPA, marker residue) in the liver (target tissue) of...

21 CFR 556.425 - Morantel tartrate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.425 Morantel tartrate. A tolerance of 0.7 part per million is established for N-methyl-1,3-propanediamine (MAPA, marker residue) in the liver (target tissue) of...

Composite Resin Dosimeters: A New Concept and Design for a Fibrous Color Dosimeter.

PubMed

Kinashi, Kenji; Iwata, Takato; Tsuchida, Hayato; Sakai, Wataru; Tsutsumi, Naoto

2018-04-11

Polystyrene (PS)-based composite microfibers combined with a photochromic spiropyran dye, 1,3,3-trimethylindolino-6'-nitrobenzopyrylospiran (6-nitro BIPS), and a photostimulable phosphor, europium-doped barium fluorochloride (BaFCl:Eu 2+ ), were developed for the detection of X-ray exposure doses on the order of approximately 1 Gy. To produce the PS-based composite microfibers, we employed a forcespinning method that embeds a high concentration of phosphor in PS in a safe, inexpensive, and simple procedure. On the basis of the optimization of the forcespinning process, fibrous color dosimeters with a high radiation dose sensitivity of 1.2-4.4 Gy were fabricated. The color of the dosimeters was found to transition from white to blue in response to X-ray exposure. The optimized fibrous color dosimeter, made from a solution having a PS/6-nitro BIPS/BaFCl:Eu 2+ /C 2 Cl 4 ratio of 7.0/0.21/28.0/28.0 (wt %) and produced with a 290 mm distance between the needle and collectors, a 0.34 mm 23 G needle nozzle, and a spinneret rotational rate of 3000 rpm, exhibited sensitivity to a dose as low as 1.2 Gy. To realize practical applications, we manufactured the optimized fibrous color dosimeter into a clothlike color dosimeter. The clothlike color dosimeter was mounted on a stuffed bear, and its coloring behavior was demonstrated upon X-ray exposure. After exposure with X-ray, a blue colored and shaped in the form of the letter "[Formula: see text]" clearly appeared on the surface of the clothlike color dosimeter. The proposed fibrous color dosimeters having excellent workability will be an unprecedented dosimetry and contributed to all industries utilizing radiation dosimeters. This new fibrous "composite resin dosimeter" should be able to replace traditional, wearable, and individual radiation dose monitoring devices, such as film badges.

Targeting ESR1-Mutant Breast Cancer

DTIC Science & Technology

2015-09-01

AWARD NUMBER: W81XWH-14-1-0359 TITLE: Targeting ESR1 -Mutant Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Sarat Chandarlapaty CONTRACTING...31 Aug 2015 4. TITLE AND SUBTITLE Targeting ESR1 -Mutant Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0359 5c. PROGRAM ELEMENT...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The hypothesis of this proposal is that LBD mutations in ESR1 promote resistance to

Targeting ESR1-Mutant Breast Cancer

DTIC Science & Technology

2015-09-01

Award Number: W81XWH-14-1-0360 TITLE: Targeting ESR1 -Mutant Breast Cancer PRINCIPAL INVESTIGATOR: Geoffrey L. Greene, Ph.D. CONTRACTING...ADDRESS. 1. REPORT DATE September 2015 2. REPORT TYPE Annual 3. DATES COVERED 1 Sep 2014 - 31 Aug 2015 4. TITLE AND SUBTITLE Targeting ESR1 -Mutant...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The hypothesis of this proposal is that LBD mutations in ESR1 promote resistance to current FDA

High-field/high-pressure ESR

NASA Astrophysics Data System (ADS)

Sakurai, T.; Okubo, S.; Ohta, H.

2017-07-01

We present a historical review of high-pressure ESR systems with emphasis on our recent development of a high-pressure, high-field, multi-frequency ESR system. Until 2000, the X-band system was almost established using a resonator filled with dielectric materials or a combination of the anvil cell and dielectric resonators. Recent developments have shifted from that in the low-frequency region, such as X-band, to that in multi-frequency region. High-pressure, high-field, multi-frequency ESR systems are classified into two types. First are the systems that use a vector network analyzer or a quasi-optical bridge, which have high sensitivity but a limited frequency region; the second are like our system, which has a very broad frequency region covering the THz region, but lower sensitivity. We will demonstrate the usefulness of our high-pressure ESR system, in addition to its experimental limitations. We also discuss the recent progress of our system and future plans.

Crystal structure and tartrate inhibition of Legionella pneumophila histidine acid phosphatase.

PubMed

Dhatwalia, Richa; Singh, Harkewal; Reilly, Thomas J; Tanner, John J

2015-11-01

Histidine acid phosphatases (HAPs) utilize a nucleophilic histidine residue to catalyze the transfer of a phosphoryl group from phosphomonoesters to water. HAPs function as protein phosphatases and pain suppressors in mammals, are essential for Giardia lamblia excystation, and contribute to virulence of the category A pathogen Francisella tularensis. Herein we report the first crystal structure and steady-state kinetics measurements of the HAP from Legionella pneumophila (LpHAP), also known as Legionella major acid phosphatase. The structure of LpHAP complexed with the inhibitor l(+)-tartrate was determined at 2.0 Å resolution. Kinetics assays show that l(+)-tartrate is a 50-fold more potent inhibitor of LpHAP than of other HAPs. Electrostatic potential calculations provide insight into the basis for the enhanced tartrate potency: the tartrate pocket of LpHAP is more positive than other HAPs because of the absence of an ion pair partner for the second Arg of the conserved RHGXRXP HAP signature sequence. The structure also reveals that LpHAP has an atypically expansive active site entrance and lacks the nucleotide substrate base clamp found in other HAPs. These features imply that nucleoside monophosphates may not be preferred substrates. Kinetics measurements confirm that AMP is a relatively inefficient in vitro substrate of LpHAP. Copyright © 2015 Elsevier Inc. All rights reserved.

Investigation and Implementation of Commercially Available Optically Stimulated Luminescence Dosimeters for Use in Fixed Nuclear Accident Dosimeter Systems.

PubMed

Georgeson, David L; Christiansen, Byron H

2018-06-01

Idaho National Laboratory transitioned from an external dosimetry system reliant on thermoluminescent dosimeters to one that uses optically stimulated luminescence dosimeters in 2010. This change not only affected the dosimeters worn by personnel, but those found in the nuclear-accident dosimeters used across Idaho National Laboratory. The elimination of on-site use and processing of thermoluminescent dosimeters impacted Idaho National Laboratory's ability to process nuclear-accident dosimeters in a timely manner. This change in processes drove Idaho National Laboratory to develop an alternative method for fixed nuclear-accident dosimeter gamma-dose analyses. This new method was driven by the need to establish a simple, cost-effective, and rapid-turnaround alternative to the thermoluminescent-dosimeter-based fixed nuclear-accident dosimeter system. An adaptation of existing technologies proved to be the most efficient path to this end. The purpose of this article is to delineate the technical basis for replacing the thermoluminescent dosimeter contained within the Idaho National Laboratory fixed nuclear-accident dosimeter system with optically stimulated luminescence-based Landauer, Inc., nanoDot dosimeters.

ESR Dating Research of Glacial Tills in Tibetan Plateau

NASA Astrophysics Data System (ADS)

Bi, W.; Yi, C.

2016-12-01

In recent years, Quaternary Glacial-chronology has been made remarkable progress in the Tibetan Platean(TP) with the development of several numeric dating techniques, such as cosmogenic nuclides(NC), optically stimulated luminescence(OSL) and 14C. In constrast, the dating of Quaternary glacial tills in 100,000 years even more than million-year has been a challenge, just because the techniques has defects themselves and the sediments were stransformed during the geological and geomorphology progress later. Electron Spin Resonance(ESR) has been becoming one of the key methods of Quaternary Glacial-chronology with wide range of dating, expecially for the sample older than 100,000 years up to million-year scale. The accurate measurement of equivalent dose significantly impacts on accuracy and reliability of ESR dating method. Therefore, the study of the mechanisms of resetting processes is fundamental for accurate and reliable ESR dating. To understand the mechanism and characteristics of quartz ESR signal resetting of different samples, a series of laboratory simulation and field observation studies were carried out, which made lots of important breakthrough. But the research in quartz ESR signal of moraines is less and the test of ESR dating method is still in the qualitative investigation. Therefor, we use ESR dating and study on the mechanism and characteristics of quartz ESR signals in tills in the Tibetan Platean. In the adjust method of Modern, the quartz ESR signals in Modern glacial tills represent residual values which can be adjusted signals in the older glacial tills. As a consequence, ESR dating of the quartz in moraines needs to be explored in deep with building models to adjust ages which are measured by ESR dating. Therefore, ESR dating will become the trusted one of the cross dating methods in Quaternary Glacial-chronology with the adjust mothod improving the accuracy of ESR dating ages.

21 CFR 558.485 - Pyrantel tartrate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... containing 9.6, 19.2, 48, or 80 grams per pound pyrantel tartrate. (b) Approvals. See sponsors in § 510.600(c... grams per pound for use as in paragraph (e)(1) of this section. (2) [Reserved] (3) Nos. 010439, 011490, 011749, 012286, 016968, 017790, 043733, and 049685: 9.6 and 19.2 grams per pound for use as in paragraphs...

Manual for the Extrapyramidal Symptom Rating Scale (ESRS).

PubMed

Chouinard, Guy; Margolese, Howard C

2005-07-15

The Extrapyramidal Symptom Rating Scale (ESRS) was developed to assess four types of drug-induced movement disorders (DIMD): Parkinsonism, akathisia, dystonia, and tardive dyskinesia (TD). Comprehensive ESRS definitions and basic instructions are given. Factor analysis provided six ESRS factors: 1) hypokinetic Parkinsonism; 2) orofacial dyskinesia; 3) trunk/limb dyskinesia; 4) akathisia; 5) tremor; and 6) tardive dystonia. Two pivotal studies found high inter-rater reliability correlations in both antipsychotic-induced movement disorders and idiopathic Parkinson disease. For inter-rater reliability and certification of raters, >or=80% of item ratings of the complete scale should be +/-1 point of expert ratings and >or=70% of ratings on individual items of each ESRS subscale should be +/-1 point of expert ratings. During a cross-scale comparison, AIMS and ESRS were found to have a 96% (359/374) agreement between TD-defined cases by DSM-IV TD criteria. Two recent international studies using the ESRS included over 3000 patients worldwide and showed an incidence of TD ranging from 10.2% (2000) to 12% (1998). ESRS specificity was investigated through two different approaches, path analyses and ANCOVA PANSS factors changes, which found that ESRS measurement of drug-induced EPS is valid and discriminative from psychiatric symptoms.

Wrist-watch dosimeter

DOEpatents

Wolf, M.A.; Waechter, D.A.; Umbarger, C.J.

1982-04-16

The disclosure is directed to a wristwatch dosimeter utilizing a CdTe detector, a microprocessor and an audio and/or visual alarm. The dosimeter is entirely housable within a conventional digital watch case having an additional aperture enabling the detector to receive radiation.

21 CFR 184.1804 - Sodium potassium tartrate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium potassium tartrate. 184.1804 Section 184.1804 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... has a cooling saline taste. It is obtained as a byproduct of wine manufacture. (b) The ingredient...

Final product analysis in the e-beam and gamma radiolysis of aqueous solutions of metoprolol tartrate

NASA Astrophysics Data System (ADS)

Slegers, Catherine; Tilquin, Bernard

2006-09-01

The radiostability of metoprolol tartrate aqueous solutions and the influence of the absorbed dose (0-50 kGy), dose rate (e-beam (EB) vs. gamma ( γ)) and radioprotectors (pharmaceutical excipients) are investigated by HPLC-UV analyses and through computer simulations. The use of radioprotecting excipients is more promising than an increase in the dose rate to lower the degradation of metoprolol tartrate aqueous solutions for applications such as radiosterilization. The decontamination of metoprolol tartrate from waste waters by EB processing appears highly feasible.

[Identification of irradiated abalone by ESR spectroscopy].

PubMed

Song, Yeping; Wang, Chuanxian; Yang, Zhenyu; Zhong, Weike; Geng, Jinpei; Lu, Di; Ding, Zhuoping

2012-05-01

To establish an analytical method for the detection and identification of irradiated abalone by electron spin resonance spectroscopy. Electron spin resonance (ESR) was used to study the spectral characteristics of abalone and the characteristic peak for quantitation. There were obvious different ESR spectra between unirradiated and irradiated abalone. The g factor for unirradiated abalone was 2.0055-2.0060, the g1 and g2 factor for irradiated abalone were (2.0027 +/- 0.0001) and (1.9994 +/- 0.0001), respectively. The ESR signal intensity of characteristic peak was positively correlated with absorbed dose in the range of 0.5 - 10 kGy, left peak was the characteristic peak for quantitation and the detection limit was < or = 0.5 kGy. It was difficult to quantitate when the absorbed dose was over 10 kGy. ESR characteristic peak and g factor were able to qualitatively determine the irradiation of abalone. ESR spectroscopy is an effective method to determine whether the abalone being irradiated or not.

Status and outlook of the CRYRING@ESR project

NASA Astrophysics Data System (ADS)

Geithner, W.; Andelkovic, Z.; Beck, D.; Bräuning, H.; Bräuning-Demian, A.; Danared, H.; Dimopoulou, C.; Engström, M.; Fedotova, S.; Gorda, O.; Herfurth, F.; Hess, R.; Källberg, A.; Kleffner, C.; Kotovskiy, N.; Kraus, I.; Lestinsky, M.; Litvinov, S.; Nolden, F.; Reiter, A.; Sieber, T.; Steck, M.; Vorobyev, G.

2017-11-01

Once operational, CRYRING@ESR will store and decelerate ions delivered by the experimental storage ring ESR at energies well below those of ESR. In addition to that, CRYRING@ESR has an electron cooler operating with an ultracold electron beam, allowing to provide cooled ion beams for precision experiments. These ions will be delivered to a broad range of experiments presently in preparation; either in-ring or extracted to a dedicated beamline for experiments. An overview and status report of the installation and commissioning of the CRYRING-@ESR storage ring for highly charged ions at the GSI Helmholtzzentrum für Schwerionenforschung is presented. The installation of this storage ring started in 2014 and was completing end of 2016, when this publication was written.

Temporal dosimeter and method

DOEpatents

Warner, Benjamin P.; Lopez, Thomas A.

2003-09-30

The invention includes a temporal dosimeter. One dosimeter embodiment includes a housing that is opaque to visible light but transparent to ionizing radiation. The dosimeter also includes a sensor for recording dosages of ionizing radiation, a drive mechanism, a power source, and rotatable shields that work together to produce a compound aperture to unveil different portions of the sensor at different times to ionizing radiation. Another dosimeter embodiment includes a housing, a sensor, a shield with an aperture portion, and a linear actuator drive mechanism coupled to the sensor for moving the sensor past the aperture portion. The sensor turns as it moves past the aperture, tracing a timeline record of exposure to ionizing radiation along a helical path on the sensor.

Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits.

PubMed

Pinsonneault, Julia K; Frater, John T; Kompa, Benjamin; Mascarenhas, Roshan; Wang, Danxin; Sadee, Wolfgang

2017-01-01

Genetic variants of ESR1 have been implicated in multiple diseases, including behavioral disorders, but causative variants remain uncertain. We have searched for regulatory variants affecting ESR1 expression in human brain, measuring allelic ESR1 mRNA expression in human brain tissues with marker SNPs in exon4 representing ESR1-008 (or ESRα-36), and in the 3'UTR of ESR1-203, two main ESR1 isoforms in brain. In prefrontal cortex from subjects with bipolar disorder, schizophrenia, and controls (n = 35 each; Stanley Foundation brain bank), allelic ESR1 mRNA ratios deviated from unity up to tenfold at the exon4 marker SNP, with large allelic ratios observed primarily in bipolar and schizophrenic subjects. SNP scanning and targeted sequencing identified rs2144025, associated with large allelic mRNA ratios (p = 1.6E10-6). Moreover, rs2144025 was significantly associated with ESR1 mRNA levels in the Brain eQTL Almanac and in brain regions in the Genotype-Tissue Expression project. In four GWAS cohorts, rs2104425 was significantly associated with behavioral traits, including: hypomanic episodes in female bipolar disorder subjects (GAIN bipolar disorder study; p = 0.0004), comorbid psychological symptoms in both males and females with attention deficit hyperactivity disorder (GAIN ADHD, p = 0.00002), psychological diagnoses in female children (eMERGE study of childhood health, subject age ≥9, p = 0.0009), and traits in schizophrenia (e.g., grandiose delusions, GAIN schizophrenia, p = 0.0004). The first common ESR1 variant (MAF 12-33% across races) linked to regulatory functions, rs2144025 appears conditionally to affect ESR1 mRNA expression in the brain and modulate traits in behavioral disorders.

RADIATION DOSIMETER

DOEpatents

Balkwell, W.R. Jr.; Adams, G.D. Jr.

1960-05-10

An improvement was made in the determination of amounts of ionizing radiation, particularly low-energy beta particles of less than 1000 rad total dose by means of fluid-phase dosimeter employing a stabilized-- sensitized ferrous-ferric colorimetric system in a sulphuric acid medium. The improvement in the dosimeter consists of adding to the ferrous-ferric system in concentrations of 10/sub -2/ to 10/sup -4/M an organic compound having one or more carboxylic or equivalent groups, such compounds being capable of chelating or complexing the iron ions in the solution. Suitable sensitizing and stabilizing agents are benzoic, phthalic, salicylic, malonic, lactic, maleic, oxalic, citric, succinic, phenolic tartaric, acetic, and adipic acid, as well as other compounds which are added to the solution alone or in certain combinations. As in conventional fluid-phase dosimeters, the absorbed dosage is correlated with a corresponding change in optical density at particular wavelengths of the solution.

Evaluation of discrepancies between thermoluminescent dosimeter and direct-reading dosimeter results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaw, K.R.

1993-07-01

Currently at Oak Ridge National Laboratory (ORNL), the responses of thermoluminescent dosimeters (TLDs) and direct-reading dosimeters (DRDs) are not officially compared or the discrepancies investigated. However, both may soon be required due to the new US Department of Energy (DOE) Radiological Control Manual. In the past, unofficial comparisons of the two dosimeters have led to discrepancies of up to 200%. This work was conducted to determine the reasons behind such discrepancies. For tests conducted with the TLDs, the reported dose was most often lower than the delivered dose, while DRDs most often responded higher than the delivered dose. Trends weremore » identified in personnel DRD readings, and ft was concluded that more training and more control of the DRDs could improve their response. TLD responses have already begun to be improved; a new background subtraction method was implemented in April 1993, and a new dose algorithm is being considered. It was concluded that the DOE Radiological Control Manual requirements are reasonable for identifying discrepancies between dosimeter types, and more stringent administrative limits might even be considered.« less

Colorimetric detection of trivalent chromium in aqueous solution using tartrate-capped silver nanoparticles as probe.

PubMed

Xu, Yunbo; Dong, Yangjun; Jiang, Xue; Zhu, Ningning

2013-10-01

This study describes a simple and highly selective method for the colorimetric detection of trivalent chromium (Cr3+) using tartrate-capped silver nanoparticles (AgNPs) as probe. The addition of tartrate to the initially prepared AgNPs gives tartrate-stabilized AgNPs ascribing to the electrostatic repulsion of the highly negatively charged tartrate ions covered on the surface of AgNPs. It is found that, in the presence of Cr3+ in aqueous solution, the aggregation of tartrate-stabilized AgNPs occurs. The color of AgNPs suspension changes from yellow to pink and the surface plasmon absorption band broadens and red shifts, which could be applied for the colorimetric detection of Cr3+ in aqueous solution. The utilization of tartrate-stabilized AgNPs as probe substantially increases the selectivity and sensitivity for colorimetric detection of Cr3+. Control experiments with the addition of over 14 other metal ions, such as Pb2+, Zn2+, Cr2O7(2-), Cd2+, Co2+, Cu2+, Al3+, Ni2+, Mn2+, Ba2+, Fe3+, Ca2+, Mg2+, Sr+ do not result in a distinct change in the color or in the spectrum of the suspension, indicating that these metal ions do not interfere with the colorimetric detection of Cr3+. Under the conditions employed here, A502/A393 (ratio of absorption value at 502 nm to 393 nm) is linear with the concentration of Cr3+ within a concentration range from 0.1 to 1.17 microM with a detection limit of 0.06 microM. This study may offer a simple, rapid and sensitive approach to colorimetric detection of Cr3+ in aqueous solution.

[Polymer Gel Dosimeter].

PubMed

Hayashi, Shin-Ichiro

2017-01-01

With rapid advances being made in radiotherapy treatment, three-dimensional (3D) dose measurement techniques of great precision are required more than ever before. It is expected that 3D polymer gel dosimeters will satisfy clinical needs for an effective detector that can measure the complex 3D dose distributions. Polymer gel dosimeters are devices that utilize the radiation-induced polymerization reactions of vinyl monomers in a gel to store information about radiation dose. The 3D absorbed dose distribution can be deduced from the resulting polymer distribution using several imaging modalities, such as MRI, X-ray and optical CTs. In this article, the fundamental characteristics of polymer gel dosimeter are reviewed and some challenging keys are also suggested for the widely spread in clinical use.

Growth, structural, spectroscopic and optical characterization of barium doped calcium tartrate

NASA Astrophysics Data System (ADS)

Verma, Seema; Raina, Bindu; Gupta, Vandana; Bamzai, K. K.

2018-05-01

Barium doped calcium tartrates synthesized by controlled diffusion using silica gel technique at ambient temperature was characterized by single crystal X-ray diffraction which establishes monoclinic crystal system with volume of the unit cell 923.97(10) Ǻ3 and the space group being P21. UV - Vis characterization gives various linear optical constants like absorption, transmittance, reflectance, band gap, extinction coefficient, urbach energy, complex dielectric constant, optical and electrical conductivity. These constants are considered to be essential in characterizing materials that are used in various applications like fabrication of optoelectronic devices. FTIR spectrum establishes the presence of various bands of functional groups expected from metal tartrate with water of crystallization.

Kidney function and population-based outcomes of initiating oral atenolol versus metoprolol tartrate in older adults.

PubMed

Fleet, Jamie L; Weir, Matthew A; McArthur, Eric; Ozair, Sundus; Devereaux, Philip J; Roberts, Matthew A; Jain, Arsh K; Garg, Amit X

2014-12-01

Atenolol and metoprolol tartrate are commonly prescribed β-blockers. Atenolol elimination depends on kidney function, whereas metoprolol tartrate does not. We hypothesized that compared to metoprolol tartrate, initiating oral atenolol treatment would be associated with more adverse events in older adults, with the association most pronounced in patients with lower baseline estimated glomerular filtration rates (eGFRs). Population-based matched retrospective cohort study. Older adults (mean age, 75 years) in Ontario, Canada, prescribed oral atenolol versus metoprolol tartrate from April 2002 through December 2011. The 2 groups were well matched (n=75,257 in each group), with no difference in 31 measured baseline characteristics. Patients with end-stage renal disease were ineligible, and 4.6% of patients had chronic kidney disease (median eGFR, 38mL/min/1.73m(2) assessed through a database algorithm). β-Blocker type and eGFR. A composite outcome of hospitalization with bradycardia or hypotension and all-cause mortality were assessed in 90-day follow-up. Compared to metoprolol tartrate, initiating atenolol treatment was not associated with higher risk of hospitalization with bradycardia or hypotension (incidence, 0.71% vs 0.79%; relative risk, 0.90; 95%CI, 0.80-1.01). Atenolol treatment initiation was associated with lower 90-day risk of mortality than metoprolol tartrate (incidence, 0.97% vs 1.44%; relative risk, 0.68; 95%CI, 0.61-0.74). Lower eGFR did not modify either association (P for interaction=0.5 and 0.6, respectively). Heart rate and blood pressure were not available in our data sources, and effects ascertained from observational studies are subject to residual confounding. Contrary to our expectation, we found that atenolol versus metoprolol tartrate was associated with lower 90-day risk of mortality in patients regardless of eGFR, with no difference in risk of hospitalization with bradycardia or hypotension. Copyright © 2014 National Kidney Foundation

Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits

PubMed Central

Kompa, Benjamin; Mascarenhas, Roshan; Wang, Danxin; Sadee, Wolfgang

2017-01-01

Genetic variants of ESR1 have been implicated in multiple diseases, including behavioral disorders, but causative variants remain uncertain. We have searched for regulatory variants affecting ESR1 expression in human brain, measuring allelic ESR1 mRNA expression in human brain tissues with marker SNPs in exon4 representing ESR1-008 (or ESRα-36), and in the 3’UTR of ESR1-203, two main ESR1 isoforms in brain. In prefrontal cortex from subjects with bipolar disorder, schizophrenia, and controls (n = 35 each; Stanley Foundation brain bank), allelic ESR1 mRNA ratios deviated from unity up to tenfold at the exon4 marker SNP, with large allelic ratios observed primarily in bipolar and schizophrenic subjects. SNP scanning and targeted sequencing identified rs2144025, associated with large allelic mRNA ratios (p = 1.6E10-6). Moreover, rs2144025 was significantly associated with ESR1 mRNA levels in the Brain eQTL Almanac and in brain regions in the Genotype-Tissue Expression project. In four GWAS cohorts, rs2104425 was significantly associated with behavioral traits, including: hypomanic episodes in female bipolar disorder subjects (GAIN bipolar disorder study; p = 0.0004), comorbid psychological symptoms in both males and females with attention deficit hyperactivity disorder (GAIN ADHD, p = 0.00002), psychological diagnoses in female children (eMERGE study of childhood health, subject age ≥9, p = 0.0009), and traits in schizophrenia (e.g., grandiose delusions, GAIN schizophrenia, p = 0.0004). The first common ESR1 variant (MAF 12–33% across races) linked to regulatory functions, rs2144025 appears conditionally to affect ESR1 mRNA expression in the brain and modulate traits in behavioral disorders. PMID:28617822

Pistol-shaped dosimeter charger

DOEpatents

Maples, R.A.

A pistol-shaped charger assembly clamps a cylindrical radiation dosimeter against one edge thereof. A triggerlike lever on the handgrip of the assembly is manually pivoted to actuate a piezoelectric current generator held in the handgrip and thereby charge the dosimeter.

Pistol-shaped dosimeter charger

DOEpatents

Maples, Robert A.

1985-01-01

A pistol-shaped charger assembly clamps a cylindrical radiation dosimeter against one edge thereof. A triggerlike lever on the handgrip of the assembly is manually pivoted to actuate a piezoelectric current generator held in the handgrip and thereby charge the dosimeter.

Fast-neutron solid-state dosimeter

DOEpatents

Kecker, K.H.; Haywood, F.F.; Perdue, P.T.; Thorngate, J.H.

1975-07-22

This patent relates to an improved fast-neutron solid-state dosimeter that does not require separation of materials before it can be read out, that utilizes materials that do not melt or otherwise degrade at about 300$sup 0$C readout temperature, that provides a more efficient dosimeter, and that can be reused. The dosimeters are fabricated by intimately mixing a TL material, such as CaSO$sub 4$:Dy, with a powdered polyphenyl, such as p-sexiphenyl, and hot- pressing the mixture to form pellets, followed by out-gassing in a vacuum furnace at 150$sup 0$C prior to first use dosimeters. (auth)

A new radiochromic dosimeter film

NASA Astrophysics Data System (ADS)

Sidney, L. N.; Lynch, D. C.; Willet, P. S.

By employing acid-sensitive leuco dyes in a chlorine-containing polymer matrix, a new radiochromic dosimeter film has been developed for gamma, electron beam, and ultraviolet radiation. These dosimeter films undergo a color change from colorless to royal blue, red fuchsia, or black, depending on dye selection, and have been characterized using a visible spectrophotometer over an absorbed dose range of 1 to 100 kGy. The primary features of the film are improved color stability before and after irradiation, whether stored in the dark or under artificial lights, and improved moisture resistance. The effects of absorbed dose, dose rate, and storage conditions on dosimeter performance are discussed. The dosimeter material may be produced as a free film or coated onto a transparent substrate and optionally backed with adhesive. Potential applications for these materials include gamma sterilization indicator films for food and medical products, electron beam dosimeters, and in-line radiation monitors for electron beam and ultraviolet processing.

Length of stain dosimeter

NASA Astrophysics Data System (ADS)

Lueck, Dale E.

1994-04-01

Payload customers for the Space Shuttle have recently expressed concerns about the possibility of their payloads at an adjacent pad being contaminated by plume effluents from a shuttle at an active pad as they await launch on an inactive pad. As part of a study to satisfy such concerns a ring of inexpensive dosimeters was deployed around the active pad at the inter-pad distance. However, following a launch, dosimeters cannot be read for several hours after the exposure. As a consequence factors such as different substrates, solvent systems, and possible volatilization of HCl from the badges were studied. This observation led to the length of stain (LOS) dosimeters of this invention. Commercial passive LOS dosimeters are sensitive only to the extent of being capable of sensing 2 ppm to 20 ppm if the exposure is 8 hours. To map and quantitate the HCl generated by Shuttle launches, and in the atmosphere within a radius of 1.5 miles from the active pad, a sensitivity of 2 ppm HCl in the atmospheric gases on an exposure of 5 minutes is required. A passive length of stain dosimeter has been developed having a sensitivity rendering it capable of detecting a gas in a concentration as low as 2 ppm on an exposure of five minutes.

Length of stain dosimeter

NASA Technical Reports Server (NTRS)

Lueck, Dale E. (Inventor)

1994-01-01

Payload customers for the Space Shuttle have recently expressed concerns about the possibility of their payloads at an adjacent pad being contaminated by plume effluents from a shuttle at an active pad as they await launch on an inactive pad. As part of a study to satisfy such concerns a ring of inexpensive dosimeters was deployed around the active pad at the inter-pad distance. However, following a launch, dosimeters cannot be read for several hours after the exposure. As a consequence factors such as different substrates, solvent systems, and possible volatilization of HCl from the badges were studied. This observation led to the length of stain (LOS) dosimeters of this invention. Commercial passive LOS dosimeters are sensitive only to the extent of being capable of sensing 2 ppm to 20 ppm if the exposure is 8 hours. To map and quantitate the HCl generated by Shuttle launches, and in the atmosphere within a radius of 1.5 miles from the active pad, a sensitivity of 2 ppm HCl in the atmospheric gases on an exposure of 5 minutes is required. A passive length of stain dosimeter has been developed having a sensitivity rendering it capable of detecting a gas in a concentration as low as 2 ppm on an exposure of five minutes.

Ergotism related to a single dose of ergotamine tartrate in an AIDS patient treated with ritonavir

PubMed Central

Blanche, P; Rigolet, A; Gombert, B; Ginsburg, C; Salmon, D; Sicard, D

1999-01-01

We report a rare case of ergotism related to a single dose of ergotamine tartrate in a man with AIDS being treated with ritonavir. He was treated with a prostacyclin analogue and made a complete recovery.


Keywords: ergotism; ergotamine tartrate; AIDS; ritonavir; adverse drug reaction; HIV infection PMID:10616689

Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS

PubMed Central

Nesheim, Nils; Ellem, Stuart; Dansranjavin, Temuujin; Hagenkötter, Christina; Berg, Elena; Schambeck, Rupert; Schuppe, Hans-Christian; Pilatz, Adrian; Risbridger, Gail; Weidner, Wolfgang

2018-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III (n = 50; median age 39.8, range 23–65) and age-matched controls (n = 61; median age 36.8, range 20–69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes (ESR1 and ESR2) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation). We found elevated 17β-estradiol (E2) levels in seminal plasma, but not in blood plasma, that was significantly associated with CP/CPPS and impaired urinary tract symptoms. In ejaculated somatic cells of CP/CPPS patients we found that ESR1 and ESR2 were both significantly higher methylated in CpG-promoters and expressionally down-regulated in comparison to controls. Mast cells are reported to contribute to CP/CPPS and are estrogen responsive. Consistent with this, we found that E2 –treatment of human mast cell lines (HMC-1 and LAD2) resulted in altered cytokine and chemokine expression. Interestingly, in HMC-1 cells, possessing epigenetically inactivated ESR1 and ESR2, E2 –treatment led to a reduced transcription of a number of inflammatory genes. Overall, these data suggest that elevated local E2 levels associate with an epigenetic down-regulation of the estrogen receptors and have a prominent role in CP/CPPS. Investigating E2 levels in semen could therefore serve as a promising biomarker to select patients for estrogen targeted therapy. PMID:29731970

Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS.

PubMed

Nesheim, Nils; Ellem, Stuart; Dansranjavin, Temuujin; Hagenkötter, Christina; Berg, Elena; Schambeck, Rupert; Schuppe, Hans-Christian; Pilatz, Adrian; Risbridger, Gail; Weidner, Wolfgang; Wagenlehner, Florian; Schagdarsurengin, Undraga

2018-04-13

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III ( n = 50; median age 39.8, range 23-65) and age-matched controls ( n = 61; median age 36.8, range 20-69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes ( ESR1 and ESR2 ) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation). We found elevated 17β-estradiol (E 2 ) levels in seminal plasma, but not in blood plasma, that was significantly associated with CP/CPPS and impaired urinary tract symptoms. In ejaculated somatic cells of CP/CPPS patients we found that ESR1 and ESR2 were both significantly higher methylated in CpG-promoters and expressionally down-regulated in comparison to controls. Mast cells are reported to contribute to CP/CPPS and are estrogen responsive. Consistent with this, we found that E 2 -treatment of human mast cell lines (HMC-1 and LAD2) resulted in altered cytokine and chemokine expression. Interestingly, in HMC-1 cells, possessing epigenetically inactivated ESR1 and ESR2, E 2 -treatment led to a reduced transcription of a number of inflammatory genes. Overall, these data suggest that elevated local E 2 levels associate with an epigenetic down-regulation of the estrogen receptors and have a prominent role in CP/CPPS. Investigating E 2 levels in semen could therefore serve as a promising biomarker to select patients for estrogen targeted therapy.

ESR dosimetry for atomic bomb survivors and radiologic technologists

NASA Astrophysics Data System (ADS)

Tatsumi-Miyajima, Junko

1987-06-01

An individual absorbed dose for atomic bomb (A-bomb) survivors and radiologic technologists has been estimated using a new personal dosimetry. This dosimetry is based on the electron spin resonance (ESR) spectroscopy of the CO 33- radicals, which are produced in their teeth by radiation. Measurements were carried out to study the characteristics of the dosimetry; the ESR signals of the CO 33- radicals were stable and increased linearly with the radiation dose. In the evaluation of the absorbed dose, the ESR signals were considered to be a function of photon energy. The absorbed doses in ten cases of A-bomb victims and eight cases of radiologic technologists were determined. For A-bomb survivors, the adsorbed doses, which were estimated using the ESR dosimetry, were consistent with the ones obtained using the calculations of the tissue dose in air of A-bomb, and also with the ones obtained using the chromosome measurements. For radiologic technologists, the absorbed doses, which were estimated using the ESR dosimetry, agreed with the ones calculated using the information on the occupational history and conditions. The advantages of this method are that the absorbed dose can be directly estimated by measuring the ESR signals obtained from the teeth of persons, who are exposed to radiation. Therefore, the ESR dosimetry is useful to estimate the accidental exposure and the long term cumulative dose.

Development of modified-release tablets of zolpidem tartrate by biphasic quick/slow delivery system.

PubMed

Mahapatra, Anjan Kumar; Sameeraja, N H; Murthy, P N

2015-06-01

Zolpidem tartrate is a non-benzodiazepine analogue of imidazopyridine of sedative and hypnotic category. It has a short half-life with usual dosage regimen being 5 mg, two times a day, or 10 mg, once daily. The duration of action is considered too short in certain circumstances. Thus, it is desirable to lengthen the duration of action. The formulation design was implemented by preparing extended-release tablets of zolpidem tartrate using the biphasic delivery system technology, where sodium starch glycolate acts as a superdisintegrant in immediate-release part and hydroxypropyl methyl cellulose as a release retarding agent in extended-release core. Tablets were prepared by direct compression. Both the core and the coat contained the drug. The pre-compression blends were evaluated for angle of repose, bulk density, and compressibility index. The tablets were evaluated for thickness, hardness, weight variation test, friability, and in vitro release studies. No interaction was observed between zolpidem tartrate and excipients from the Fourier transform infrared spectroscopy and differential scanning calorimetry analysis. The results of all the formulations prepared were compared with reference product Stilnoct®. Optimized formulations showed release patterns that match the United States Pharmacopeia (USP) guidelines for zolpidem tartrate extended-release tablets. The mechanism of drug release was studied using different mathematical models, and the optimized formulation has shown Fickian diffusion. Accelerated stability studies were performed on the optimized formulation.

Electron spin resonance (ESR) dose measurement in bone of Hiroshima A-bomb victim.

PubMed

Kinoshita, Angela; Baffa, Oswaldo; Mascarenhas, Sérgio

2018-01-01

Explosion of the bombs in Hiroshima and Nagasaki corresponds to the only historical moment when atomic bombs were used against civilians. This event triggered countless investigations into the effects and dosimetry of ionizing radiation. However, none of the investigations has used the victims' bones as dosimeter. Here, we assess samples of bones obtained from fatal victims of the explosion by Electron Spin Resonance (ESR). In 1973, one of the authors of the present study (SM) traveled to Japan and conducted a preliminary experiment on the victims' bone samples. The idea was to use the paramagnetism induced in bone after irradiation to measure the radiation dose. Technological advances involved in the construction of spectrometers, better knowledge of the paramagnetic center, and improvement in signal processing techniques have allowed us to resume the investigation. We obtained a reconstructed dose of 9.46 ± 3.4 Gy from the jawbone, which was compatible with the dose distribution in different locations as measured in non-biological materials such as wall bricks and roof tiles.

Electron spin resonance (ESR) dose measurement in bone of Hiroshima A-bomb victim

PubMed Central

2018-01-01

Explosion of the bombs in Hiroshima and Nagasaki corresponds to the only historical moment when atomic bombs were used against civilians. This event triggered countless investigations into the effects and dosimetry of ionizing radiation. However, none of the investigations has used the victims’ bones as dosimeter. Here, we assess samples of bones obtained from fatal victims of the explosion by Electron Spin Resonance (ESR). In 1973, one of the authors of the present study (SM) traveled to Japan and conducted a preliminary experiment on the victims’ bone samples. The idea was to use the paramagnetism induced in bone after irradiation to measure the radiation dose. Technological advances involved in the construction of spectrometers, better knowledge of the paramagnetic center, and improvement in signal processing techniques have allowed us to resume the investigation. We obtained a reconstructed dose of 9.46 ± 3.4 Gy from the jawbone, which was compatible with the dose distribution in different locations as measured in non-biological materials such as wall bricks and roof tiles. PMID:29408890

Older adults with heart failure treated with carvedilol, bisoprolol, or metoprolol tartrate: risk of mortality.

PubMed

Perreault, Sylvie; de Denus, Simon; White, Michel; White-Guay, Brian; Bouvier, Michel; Dorais, Marc; Dubé, Marie-Pierre; Rouleau, Jean-Lucien; Tardif, Jean-Claude; Jenna, Sarah; Haibe-Kains, Benjamin; Leduc, Richard; Deblois, Denis

2017-01-01

The long-term use of β-blockers has been shown to improve clinical outcomes among patients with heart failure (HF). However, a lack of data persists in assessing whether carvedilol or bisoprolol are superior to metoprolol tartrate in clinical practice. We endeavored to compare the effectiveness of β-blockers among older adults following a primary hospital admission for HF. We conducted a cohort study using Quebec administrative databases to identify patients who were using β-blockers, carvedilol, bisoprolol, or metoprolol tartrate after the diagnosis of HF. We characterized the patients by the type of β-blocker prescribed at discharge of their first HF hospitalization. An adjusted multivariate Cox proportional hazards model was used to compare the primary outcome of all-cause mortality. We also conducted analyses by matching for a propensity score for initiation of β-blocker therapy and assessed the effect on primary outcome. Among 3197 patients with HF with a median follow-up of 2.8 years, the crude annual mortality rates (per 100 person-years) were at 16, 14.9, and 17.7 for metoprolol tartrate, carvedilol, and bisoprolol, respectively. Adjusted hazard ratios of carvedilol (hazard ratio 0.92; 0.78-1.09) and bisoprolol (hazard ratio 1.04; 0.93-1.16) were not significantly different from that of metoprolol tartrate in improving survival. After matching for propensity score, carvedilol and bisoprolol showed no additional benefit with respect to all-cause mortality compared with metoprolol tartrate. Our evidence suggests no differential effect of β-blockers on all-cause mortality among older adults with HF. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Study of Cleanliness of High Nitrogen Steel in ESR

NASA Astrophysics Data System (ADS)

Xuwei, Tang; Rong, Zhu

This paper compares inclusions in high nitrogen steel before and after ESR process, analyzes the influence of slag systems and total oxygen content in consumable ingots. The total oxygen content is reduced apparently during ESR process, which indicates good effects on removal of inclusions. In the experiment, it shows that different slag systems will affect the result of inclusions removal significantly; proper w(CaO/Al2O3) will reduce the level of inclusions and total oxygen content in ESR ingots. In ESR process, the type and chemical composition of inclusions have no difference when oxygen content in consumable ingots is different, which means O content in consumable ingots have no direct relationship with cleanliness of ESR ingots. In typical inclusions, w(MnO)/w(MnO+Al2O3)≈0.23 0.32. The total oxygen content of ESR ingots keeps between 20 30ppm when the oxygen contents in consumable ingots are diverse from 40 to 100ppm. Meanwhile, this paper studies desulfurization process of high nitrogen steel in ESR, analyzes the influence of slag systems a nd remelting rates on desulfurization efficiency. The results indicate that the average size and quant ity of sulfide inclusion decrease after ESR process. The typical inclusion after ESR process is MnS+Al2O3. Slag system with proper CaO content has higher sulfur partition ratio, which leads to better desulfurization effect. The desulfurization rate changes greatly with different remelting rates, which indicates the kinetic parameter has more influence in desulfurization. The reason of this phenomenon is that the process of desulfurization can be considered as a non-equilibrium reaction, which differs with thermodynamic equilibrium. In kinetic study, it is founded that the desulfurization efficiency increases with higher remelting area, sulfur partition and lower remelting rate, which is different from experiment. The desulfurization efficiency decreases firstly and then recovers when remelting rate drops. The

Dosimeter and method for using the same

DOEpatents

Warner, Benjamin P.; Johns, Deidre M.

2003-06-24

A very sensitive dosimeter that detects ionizing radiation is described. The dosimeter includes a breakable sealed container. A solution of a reducing agent is inside the container. The dosimeter has an air-tight dosimeter body with a transparent portion and an opaque portion. The transparent portion includes a transparent chamber that holds the breakable container with the reducing agent. The opaque portion includes an opaque chamber that holds an emulsion of silver salt (AgX) selected from silver chloride, silver bromide, silver iodide, and combinations of them. A passageway in the dosimeter provides fluid communication between the transparent chamber and the opaque chamber. The dosimeter may also include a chemical pH indicator in the breakable container that provides a detectable color change to the solution for a pH of about 3-10. The invention also includes a method of detecting ionizing radiation that involves producing the dosimeter, breaking the breakable container, allowing the solution to flow through the passageway and contact the emulsion, detecting any color change in the solution and using the color change to determine a radiation dosage.

NOTE: Cell-phone interference with pocket dosimeters

NASA Astrophysics Data System (ADS)

Djajaputra, David; Nehru, Ramasamy; Bruch, Philip M.; Ayyangar, Komanduri M.; Raman, Natarajan V.; Enke, Charles A.

2005-05-01

Accurate reporting of personal dose is required by regulation for hospital personnel that work with radioactive material. Pocket dosimeters are commonly used for monitoring this personal dose. We show that operating a cell phone in the vicinity of a pocket dosimeter can introduce large and erroneous readings of the dosimeter. This note reports a systematic study of this electromagnetic interference. We found that simple practical measures are enough to mitigate this problem, such as increasing the distance between the cell phone and the dosimeter or shielding the dosimeter, while maintaining its sensitivity to ionizing radiation, by placing it inside a common anti-static bag.

Degradation and ESR Failures in MnO2 Chip Tantalum Capacitors

NASA Technical Reports Server (NTRS)

Teverovsky, Alexander A.

2017-01-01

Equivalent series resistance (ESR) of chip tantalum capacitors determines the rate of energy delivery and power dissipation thus affecting temperature and reliability of the parts. Employment of advanced capacitors with reduced ESR decreases power losses and improves efficiency in power systems. Stability of ESR is essential for correct operations of power units and might cause malfunctioning and failures when ESR becomes too high or too low. Several cases with ESR values in CWR29 capacitors exceeding the specified limit that were observed recently raised concerns regarding environmental factors affecting ESR and the adequacy of the existing screening and qualification testing. In this work, results of stress testing of various types of military and commercial capacitors obtained over years by GSFC test lab and NEPP projects that involved ESR measurements are described. Environmental stress tests include testing in humidity and vacuum chambers, temperature cycling, long-term storage at high temperatures, and various soldering simulation tests. Note that in many cases parts failed due to excessive leakage currents or reduced breakdown voltages. However, only ESR-related degradation and failures are discussed. Mechanisms of moisture effect are discussed and recommendations to improve screening and qualification system are suggested.

Differential role of the estrogen receptors ESR1 and ESR2 on the regulation of proteins involved with proliferation and differentiation of Sertoli cells from 15-day-old rats.

PubMed

Lucas, Thaís F G; Lazari, Maria Fatima M; Porto, Catarina S

2014-01-25

The aim of the present study was to investigate the role of each estrogen receptors on the regulation of proteins involved with proliferation and differentiation of Sertoli cells from 15-day-old rats. Activation of ESR1 by 17β-estradiol (E2) and ESR1-selective agonist PPT increased CCND1 expression, and this effect was dependent on NF-kB activation. E2 and the ESR2-selective agonist DPN, but not PPT, increased, in a PI3K and CREB-dependent manner, the expression of CDKN1B and the transcription factors GATA-1 and DMRT1. Analyzing the expression of ESR1 and ESR2 in different stages of development of Sertoli cells, we observed that the ESR1/ESR2 ratio decreased with age, and this ratio seems to be important to determine the end of cell proliferation and the start of cell differentiation. In Sertoli cells from 15-day-old rats, the ESR1/ESR2 ratio favors the effect of ESR1 and the activation of this receptor increased [Methyl-(3)H]thymidine incorporation. We propose that in Sertoli cells from 15-day-old rats E2 modulates Sertoli cell proliferation through ESR1/NF-kB-mediated increase of CCND1, and cell cycle exit and differentiation through ESR2/CREB-mediated increase of CDKN1B, GATA-1 and DMRT1. The present study reinforces the important role of estrogen for normal testis development. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

ESR1 gene amplification in endometrial carcinomas: a clinicopathological analysis.

PubMed

Rahman, Mohammed Tanjimur; Nakayama, Kentaro; Rahman, Munmun; Ishikawa, Masako; Katagiri, Hiroshi; Katagiri, Atsuko; Ishibashi, Tomoka; Sato, Emi; Iida, Kouji; Ishikawa, Noriyuki; Nakayama, Naomi; Miyazaki, Kohji

2013-09-01

This study investigated the clinicopathological significance of estrogen receptor 1 (ESR1) gene amplification and its relationship to phosphatase and tensin homolog (PTEN), human epidermal growth factor receptor 2 (HER2), MutL homolog 1 (MLH1), p53, and AT rich interactive domain 1A (ARID1A) expression in endometrial carcinomas. ESR1 amplification and expression were assessed by fluorescence in situ hybridization and immunohistochemistry. Clinical data were collected by retrospective chart review. ESR1 amplification was identified in 13 out of 111 (11.7%) endometrial carcinomas. No significant association was observed between ESR1 amplification and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.17), histological grade (p=0.35), lymph node metastasis (p=0.51), or deep myometrial invasion (p=0.46). ESR1 amplification was independent of PTEN, p53, HER2, MLH1, and ARID1A protein expression. Patients without estrogen receptor (ER) or progesterone receptor (PR) expression had shorter progression-free and overall survival than those with ER or PR expression (p<0.01). ESR1 amplification is independent of known clinicopathological factors related to poor prognosis and PTEN, p53, HER2, MLH1, and ARID1A protein expression, suggesting ESR1 amplification may be an early event in endometrial carcinoma development.

Thermoluminescence dosimeter

DOEpatents

Zendle, R.

1983-11-03

A thermoluminescence dosimeter having a very small rate of decline of sensitivity during subsequent uses after heating is disclosed. The dosimeter includes a detector crystal and a glass enclosure in which the detector crystal is located. The glass enclosure is air tight and is filled with a super dry inert fill gas. The inert fill gas is nonreactive with the detector crystal when the detector crystal is heated to thermoluminescence. The fill gas is selected from the group consisting of air, nitrogen, and argon, suitable admixed with 5 to 25 percent helium. The detector crystal consists essentially of calcium fluoride. The fill gas is preferably contained at a subatmospheric pressure in the glass enclosure.

Thermoluminescence dosimeter

DOEpatents

Zendle, Robert

1985-01-01

A thermoluminescence dosimeter having a very small rate of decline of sensitivity during subsequent uses after heating is disclosed. The dosimeter includes a detector crystal and a glass enclosure in which the detector crystal is located. The glass enclosure is air tight and is filled with a super dry inert fill gas. The inert fill gas is nonreactive with the detector crystal when the detector crystal is heated to thermoluminescence. The fill gas is selected from the group consisting of air, nitrogen, and argon, suitable admixed with 5 to 25 percent helium. The detector crystal consists essentially of calcium fluoride. The fill gas is preferably contained at a subatmospheric pressure in the glass enclosure.

SOLID-STATE DOSIMETERS BASED ON OPTICAL THEORY (in Hungarian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patko, J.

1962-01-01

A comparison is made of applications of various dosimeters based on solid materials, and their comparative merits are described. Characteristics of the following types of dosimeters effective at various radiation intensities are discussed: condensation chambers for measurements over the range 10/sup -4/-10/ sup 2/ rad, film dosimeters 10/sup -1/-10/sup 5/ rad, thermoluminescent types 10/ sup -3/ - 10/sup 4/ rad, photoluminescent dosimeters 10/sup 1/-- 10/sup 4/ rad, crystal types 10/sup 1/- 10/sup 4/ rad, glass dosimeters 10/sup 3/- 10/sup 7/ rad, synthetic material types 10/sup 5/- 10/sup 9/ rad, and luminescent degradation dosimeters 10/sup 5/-10/sup 8/ rad. Special attention ismore » given to the thermoluminescent dosimeter, which utilizes Mn-activated Ca phosphate. This dosimeter utilizes a glass ampulla instead of a glass vacuum tube and polarography is used to determine the luminescence curve. Simple evaluation equipment is being developed to be used with this dosimeter. Such thermoluminescent dosimeters are generally small in size. Its high sensitivity makes it applicable to low intensity radiation aad after calibration it can again be utilized. Manganese-activated Ca phosphate dosimeters do not show any fading of response in the first hour after use. Use of solid dosimeters, for high- energy measurements« less

Formulation and in-vitro evaluation of floating bilayer tablet of lisinopril maleate and metoprolol tartrate.

PubMed

Ijaz, Hira; Qureshi, Junaid; Danish, Zeeshan; Zaman, Muhammad; Abdel-Daim, Mohamed; Hanif, Muhammad; Waheed, Imran; Mohammad, Imran Shair

2015-11-01

The purpose of this study was to introduce the technology for the development of rate-controlled oral drug delivery system to overcome various physiological problems. Several approaches are being used for the purpose of increasing the gastric retentive time, including floating drug delivery system. Gastric floating lisinopril maleate and metoprolol tartrate bilayer tablets were formulated by direct compression method using the sodium starch glycolate, crosscarmellose sodium for IR layer. Eudragit L100, pectin, acacia as sustained release polymers in different ratios for SR metoprolol tartrate layer and sodium bicarbonate, citric acid as gas generating agents for the floating extended release layer. The floating bilayer tablets of lisinopril maleate and metoprolol tartrate were designed to overcome the various problems associated with conventional oral dosage form. Floating tablets were evaluated for floating lag time, drug contents and in-vitro dissolution profile and different kinetic release models were applied. It was clear that the different ratios of polymers affected the drug release and floating time. L2 and M4 showed good drug release profile and floating behavior. The linear regression and model fitting showed that all formulation followed Higuchi model of drug release model except M4 that followed zero order kinetic. From the study it is evident that a promising controlled release by floating bilyer tablets of lisinopril maleate and metoprolol tartrate can be developed successfully.

ESR1 and ESR2 polymorphisms in the BIG 1-98 trial comparing adjuvant letrozole versus tamoxifen or their sequence for early breast cancer.

PubMed

Leyland-Jones, Brian; Gray, Kathryn P; Abramovitz, Mark; Bouzyk, Mark; Young, Brandon; Long, Bradley; Kammler, Roswitha; Dell'Orto, Patrizia; Biasi, Maria Olivia; Thürlimann, Beat; Harvey, Vernon; Neven, Patrick; Arnould, Laurent; Maibach, Rudolf; Price, Karen N; Coates, Alan S; Goldhirsch, Aron; Gelber, Richard D; Pagani, Olivia; Viale, Giuseppe; Rae, James M; Regan, Meredith M

2015-12-01

Estrogen receptor 1 (ESR1) and ESR2 gene polymorphisms have been associated with endocrine-mediated physiological mechanisms, and inconsistently with breast cancer risk and outcomes, bone mineral density changes, and hot flushes/night sweats. DNA was isolated and genotyped for six ESR1 and two ESR2 single-nucleotide polymorphisms (SNPs) from tumor specimens from 3691 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1-98 trial to receive tamoxifen and/or letrozole for 5 years. Associations with recurrence and adverse events (AEs) were assessed using Cox proportional hazards models. 3401 samples were successfully genotyped for five SNPs. ESR1 rs9340799(XbaI) (T>C) variants CC or TC were associated with reduced breast cancer risk (HR = 0.82,95% CI = 0.67-1.0), and ESR1 rs2077647 (T>C) variants CC or TC was associated with reduced distant recurrence risk (HR = 0.69, 95% CI = 0.53-0.90), both regardless of the treatments. No differential treatment effects (letrozole vs. tamoxifen) were observed for the association of outcome with any of the SNPs. Letrozole-treated patients with rs2077647 (T>C) variants CC and TC had a reduced risk of bone AE (HR = 0.75, 95% CI = 0.58-0.98, P interaction = 0.08), whereas patients with rs4986938 (G>A) genotype variants AA and AG had an increased risk of bone AE (HR = 1.37, 95% CI = 1.01-1.84, P interaction = 0.07). We observed that (1) rare ESR1 homozygous polymorphisms were associated with lower recurrence, and (2) ESR1 and ESR2 SNPs were associated with bone AEs in letrozole-treated patients. Genes that are involved in estrogen signaling and synthesis have the potential to affect both breast cancer recurrence and side effects, suggesting that individual treatment strategies can incorporate not only oncogenic drivers but also SNPs related to estrogen activity.

Persistent free radical ESR signals in marine bivalve tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehlorn, R.J.; Mendez, A.T.; Higashi, R.

1992-08-01

Freeze-dried homogenates of the oyster Crassostrea rhizophorae collected from waters in Puerto Rico near urban and industrial sites as well as at relatively pristine locations yielded electron spin resonance (ESR) spectra characteristic of free radicals as well as spectral components of transition metal ions, dominated by manganese. The magnitudes of these ESR signals and the concentrations of trace elements (determined by X-ray fluorescence) varied considerably among oyster samples, masking any potential correlation with polluted waters. Laboratory studies were initiated to identify the factors controlling the magnitudes of the tissue free radical ESR signals. Another mollusc, Mytilus californianus collected at themore » Bodega Marine laboratory in northern California, was fractionated into goneds and remaining tissue. Freeze-dried homogenates of both fractions exhibited ESR signals that increased gradually with time. ESR signals were observed in freeze-dried perchloric acid (PCA) precipitates of the homogenates, delipidated PCA precipitates, and in chloroform extracts of these precipitates. Acid hydrolysis to degrade proteins to amino acids produced a residue, which yielded much larger ESR free radical signals after freeze-drying. Freshly thawed homogenates of Crassostrea rhizophorae also exhibited ESR signals. A laboratory model of copper stress in Crassostrea rhizophorae was developed to study the effect of this transition metal on dssue free radicals. Preliminary results suggested that sublethal copper exposure had little effect on tissue fire radicals, except possibly for a signal enhancement in an oyster fraction that was enriched in kidney granules. Since kidney granules are known to accumulate heavy metals in mussels and probably other marine bivalves, this signal enhancement may prove to be an indicator of free radical processes associated with heavy metal deposition in molluscs.« less

HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR expression in infertile women with endometriosis.

PubMed

Osiński, Maciej; Wirstlein, Przemysław; Wender-Ożegowska, Ewa; Mikołajczyk, Mateusz; Jagodziński, Paweł Piotr; Szczepańska, Małgorzata

2018-01-01

The development of endometriosis is associated with changes in the expression of genes encoding the 3β-hydroxysteroid dehydrogenase type II (HSD3B2) and 17β-hydroxysteroid dehydrogenase type II (HSD17B2), estrogen receptors 1 (ESR1) and 2 (ESR2) and the androgen receptor (AR). However, little is known about the expression of HSD3B2, HSD17B1, HSD17B2, ESR1 ESR2 and AR during the endometrial phases in eutopic endometrium from infertile women with endometriosis. Using RT-qPCR analysis, we assessed the expression of the studied genes in the follicular and luteal phases in eutopic endometrium from fertile women (n = 17) and infertile women (n = 35) with endometriosis. In the mid-follicular eutopic endometrium, we observed a significant increase in HSD3B2 transcript levels in all infertile women with endometriosis (p = 0.003), in infertile women with stage I/II endometriosis (p = 0.008) and in infertile women with stage III/IV endometriosis (p = 0.009) compared to all fertile women. There was a significant increase in ESR1 tran-scripts in all infertile women with endometriosis (p = 0.008) and in infertile women with stage I/II endometriosis (p = 0.019) and in infertile women with stage III/IV endometriosis (p = 0.023) compared to all fertile women. In the mid-luteal eutopic endometrium, we did not observe significant differences in HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR transcripts between infertile women with endometriosis and fertile women. Observed significant increase in HSD3B2 and ESR1 transcripts in follicular eutopic endometrium from infer-tile women with endometriosis may be related to abnormal biological effect of E2 in endometrium, further affecting the development of human embryos.

Prognostic Significance of ESR1 Amplification and ESR1 PvuII, CYP2C19*2, UGT2B15*2 Polymorphisms in Breast Cancer Patients

PubMed Central

Markiewicz, Aleksandra; Wełnicka-Jaśkiewicz, Marzena; Skokowski, Jarosław; Jaśkiewicz, Janusz; Szade, Jolanta; Jassem, Jacek; Żaczek, Anna J.

2013-01-01

Introduction Amplification of the ESR1 gene, coding for estrogen receptor alpha, was shown to predict responsiveness to tamoxifen, however its prognostic impact in breast cancer patients has not been thoroughly investigated. Other factors that could contribute to responsiveness to tamoxifen treatment are polymorphisms in ESR1 gene and genes involved in tamoxifen metabolism. The aim of this study was to assess the prognostic role of ESR1 gene dosage in a consecutive group of breast cancer patients and to correlate this feature with clinico-pathological factors. Additionally, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphisms were analyzed in the tamoxifen-treated subgroup of patients. Materials and Methods Primary tumor samples from 281 stage I-III consecutive breast cancer patients were analyzed for ESR1 gene dosage using real-time PCR with locked nucleic acids hydrolysis probes. In the tamoxifen-treated subgroup of patients, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphism in leukocytes genomic DNA were analyzed. Results were correlated with clinico-pathological factors and with disease-free survival (DFS) and overall survival (OS). Results ESR1 amplification (with a cut-off level of 2.0) was found in 12% of the entire group of breast cancer patients, and in 18% of the ER-negative subgroup. This feature was associated with decreased DFS both in the entire group (P=0.007) and in the ER-negative subgroup (P=0.03), but not in the tamoxifen-treated patients. Patients with ESR1 PvuII wt/wt genotype and at least one UGT2B15 wt allele had a worse DFS (P=0.03) and showed a trend towards decreased Os (P=0.08) in comparison to patients with ESR1 PvuII wt/vt or vt/vt genotype and UGT2B15 *2/*2 genotype. Conclusions ESR1 amplification can occur in ER-negative tumors and may carry poor prognosis. In the tamoxifen-treated subgroup, poor prognosis was related to the combined presence of ESR1 PvuII wt/wt and UGT2B15wt/wt or wt/*2 genotype. PMID:23951298

Prognostic significance of ESR1 amplification and ESR1 PvuII, CYP2C19*2, UGT2B15*2 polymorphisms in breast cancer patients.

PubMed

Markiewicz, Aleksandra; Wełnicka-Jaśkiewicz, Marzena; Skokowski, Jarosław; Jaśkiewicz, Janusz; Szade, Jolanta; Jassem, Jacek; Zaczek, Anna J

2013-01-01

Amplification of the ESR1 gene, coding for estrogen receptor alpha, was shown to predict responsiveness to tamoxifen, however its prognostic impact in breast cancer patients has not been thoroughly investigated. Other factors that could contribute to responsiveness to tamoxifen treatment are polymorphisms in ESR1 gene and genes involved in tamoxifen metabolism. The aim of this study was to assess the prognostic role of ESR1 gene dosage in a consecutive group of breast cancer patients and to correlate this feature with clinico-pathological factors. Additionally, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphisms were analyzed in the tamoxifen-treated subgroup of patients. Primary tumor samples from 281 stage I-III consecutive breast cancer patients were analyzed for ESR1 gene dosage using real-time PCR with locked nucleic acids hydrolysis probes. In the tamoxifen-treated subgroup of patients, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphism in leukocytes genomic DNA were analyzed. Results were correlated with clinico-pathological factors and with disease-free survival (DFS) and overall survival (OS). ESR1 amplification (with a cut-off level of 2.0) was found in 12% of the entire group of breast cancer patients, and in 18% of the ER-negative subgroup. This feature was associated with decreased DFS both in the entire group (P=0.007) and in the ER-negative subgroup (P=0.03), but not in the tamoxifen-treated patients. Patients with ESR1 PvuII wt/wt genotype and at least one UGT2B15 wt allele had a worse DFS (P=0.03) and showed a trend towards decreased Os (P=0.08) in comparison to patients with ESR1 PvuII wt/vt or vt/vt genotype and UGT2B15 *2/*2 genotype. ESR1 amplification can occur in ER-negative tumors and may carry poor prognosis. In the tamoxifen-treated subgroup, poor prognosis was related to the combined presence of ESR1 PvuII wt/wt and UGT2B15wt/wt or wt/*2 genotype.

Functional analysis of the GmESR1 gene associated with soybean regeneration

PubMed Central

Chen, Qingshan; Liu, Ming; Xin, Dawei; Qi, Zhaoming; Li, Sinan; Ma, Yanlong; Wang, Lingshuang; Jin, Yangmei; Li, Wenbin; Wu, Xiaoxia; Su, An-yu

2017-01-01

Plant regeneration can occur via in vitro tissue culture through somatic embryogenesis or de novo shoot organogenesis. Transformation of soybean (Glycine max) is difficult, hence optimization of the transformation system for soybean regeneration is required. This study investigated ENHANCER OF SHOOT REGENERATION 1 (GmESR1), a soybean transcription factor that targets regeneration-associated genes. Sequence analysis showed that GmESR1 contained a conserved 57 amino acid APETALA 2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) DNA-binding domain. The relative expression level of GmESR1 was highest in young embryos, flowers and stems in the soybean cultivar ‘Dongnong 50’. To examine the function of GmESR1, transgenic Arabidopsis (Arabidopsis thaliana) and soybean plants overexpressing GmESR1 were generated. In Arabidopsis, overexpression of GmESR1 resulted in accelerated seed germination, and seedling shoot and root elongation. In soybean overexpression of GmESR1 also led to faster seed germination, and shoot and root elongation. GmESR1 specifically bound to the GCC-box. The results provide a foundation for the establishment of an efficient and stable transformation system for soybean. PMID:28403182

Generation of Esr1-Knockout Rats Using Zinc Finger Nuclease-Mediated Genome Editing

PubMed Central

Dhakal, Pramod; Kubota, Kaiyu; Chakraborty, Damayanti; Lei, Tianhua; Larson, Melissa A.; Wolfe, Michael W.; Roby, Katherine F.; Vivian, Jay L.

2014-01-01

Estrogens play pivotal roles in development and function of many organ systems, including the reproductive system. We have generated estrogen receptor 1 (Esr1)-knockout rats using zinc finger nuclease (ZFN) genome targeting. mRNAs encoding ZFNs targeted to exon 3 of Esr1 were microinjected into single-cell rat embryos and transferred to pseudopregnant recipients. Of 17 live births, 5 had biallelic and 1 had monoallelic Esr1 mutations. A founder with monoallelic mutations was backcrossed to a wild-type rat. Offspring possessed only wild-type Esr1 alleles or wild-type alleles and Esr1 alleles containing either 482 bp (Δ482) or 223 bp (Δ223) deletions, indicating mosaicism in the founder. These heterozygous mutants were bred for colony expansion, generation of homozygous mutants, and phenotypic characterization. The Δ482 Esr1 allele yielded altered transcript processing, including the absence of exon 3, aberrant splicing of exon 2 and 4, and a frameshift that generated premature stop codons located immediately after the codon for Thr157. ESR1 protein was not detected in homozygous Δ482 mutant uteri. ESR1 disruption affected sexually dimorphic postnatal growth patterns and serum levels of gonadotropins and sex steroid hormones. Both male and female Esr1-null rats were infertile. Esr1-null males had small testes with distended and dysplastic seminiferous tubules, whereas Esr1-null females possessed large polycystic ovaries, thread-like uteri, and poorly developed mammary glands. In addition, uteri of Esr1-null rats did not effectively respond to 17β-estradiol treatment, further demonstrating that the Δ482 Esr1 mutation created a null allele. This rat model provides a new experimental tool for investigating the pathophysiology of estrogen action. PMID:24506075

Generation of Esr1-knockout rats using zinc finger nuclease-mediated genome editing.

PubMed

Rumi, M A Karim; Dhakal, Pramod; Kubota, Kaiyu; Chakraborty, Damayanti; Lei, Tianhua; Larson, Melissa A; Wolfe, Michael W; Roby, Katherine F; Vivian, Jay L; Soares, Michael J

2014-05-01

Estrogens play pivotal roles in development and function of many organ systems, including the reproductive system. We have generated estrogen receptor 1 (Esr1)-knockout rats using zinc finger nuclease (ZFN) genome targeting. mRNAs encoding ZFNs targeted to exon 3 of Esr1 were microinjected into single-cell rat embryos and transferred to pseudopregnant recipients. Of 17 live births, 5 had biallelic and 1 had monoallelic Esr1 mutations. A founder with monoallelic mutations was backcrossed to a wild-type rat. Offspring possessed only wild-type Esr1 alleles or wild-type alleles and Esr1 alleles containing either 482 bp (Δ482) or 223 bp (Δ223) deletions, indicating mosaicism in the founder. These heterozygous mutants were bred for colony expansion, generation of homozygous mutants, and phenotypic characterization. The Δ482 Esr1 allele yielded altered transcript processing, including the absence of exon 3, aberrant splicing of exon 2 and 4, and a frameshift that generated premature stop codons located immediately after the codon for Thr157. ESR1 protein was not detected in homozygous Δ482 mutant uteri. ESR1 disruption affected sexually dimorphic postnatal growth patterns and serum levels of gonadotropins and sex steroid hormones. Both male and female Esr1-null rats were infertile. Esr1-null males had small testes with distended and dysplastic seminiferous tubules, whereas Esr1-null females possessed large polycystic ovaries, thread-like uteri, and poorly developed mammary glands. In addition, uteri of Esr1-null rats did not effectively respond to 17β-estradiol treatment, further demonstrating that the Δ482 Esr1 mutation created a null allele. This rat model provides a new experimental tool for investigating the pathophysiology of estrogen action.

The discrimination of d-tartrate positive and d-tartrate negative S. enterica subsp. enterica serovar Paratyphi B isolated in Malaysia by phenotypic and genotypic methods.

PubMed

Ahmad, Norazah; Hoon, Shirley Tang Gee; Ghani, Mohamed Kamel Abd; Tee, Koh Yin

2012-06-01

Serotyping is not sufficient to differentiate between Salmonella species that cause paratyphoid fever from the strains that cause milder gastroenteritis as these organisms share the same serotype Salmonella Paratyphi B (S. Paratyphi B). Strains causing paratyphoid fever do not ferment d-tartrate and this key feature was used in this study to determine the prevalence of these strains among the collection of S. Paratyphi B strains isolated from patients in Malaysia. A total of 105 isolates of S. Paratyphi B were discriminated into d-tartrate positive (dT+) and d-tartrate negative (dT) variants by two lead acetate test protocols and multiplex PCR. The lead acetate test protocol 1 differed from protocol 2 by a lower inoculum size and different incubation conditions while the multiplex PCR utilized 2 sets of primers targeting the ATG start codon of the gene STM3356. Lead acetate protocol 1 discriminated 97.1% of the isolates as S. Paratyphi B dT+ and 2.9% as dT while test protocol 2 discriminated all the isolates as S. Paratyphi B dT+. The multiplex PCR test identified all 105 isolates as S. Paratyphi B dT+ strains. The concordance of the lead acetate test relative to that of multiplex PCR was 97.7% and 100% for protocol 1 and 2 respectively. This study showed that S. Paratyphi B dT+ is a common causative agent of gastroenteritis in Malaysia while paratyphoid fever appears to be relatively uncommon. Multiplex PCR was shown to be a simpler, more rapid and reliable method to discriminate S. Paratyphi B than the phenotypic lead acetate test.

ESR1 Mutations in Circulating Plasma Tumor DNA from Metastatic Breast Cancer Patients.

PubMed

Chu, David; Paoletti, Costanza; Gersch, Christina; VanDenBerg, Dustin A; Zabransky, Daniel J; Cochran, Rory L; Wong, Hong Yuen; Toro, Patricia Valda; Cidado, Justin; Croessmann, Sarah; Erlanger, Bracha; Cravero, Karen; Kyker-Snowman, Kelly; Button, Berry; Parsons, Heather A; Dalton, W Brian; Gillani, Riaz; Medford, Arielle; Aung, Kimberly; Tokudome, Nahomi; Chinnaiyan, Arul M; Schott, Anne; Robinson, Dan; Jacks, Karen S; Lauring, Josh; Hurley, Paula J; Hayes, Daniel F; Rae, James M; Park, Ben Ho

2016-02-15

Mutations in the estrogen receptor (ER)α gene, ESR1, have been identified in breast cancer metastases after progression on endocrine therapies. Because of limitations of metastatic biopsies, the reported frequency of ESR1 mutations may be underestimated. Here, we show a high frequency of ESR1 mutations using circulating plasma tumor DNA (ptDNA) from patients with metastatic breast cancer. We retrospectively obtained plasma samples from eight patients with known ESR1 mutations and three patients with wild-type ESR1 identified by next-generation sequencing (NGS) of biopsied metastatic tissues. Three common ESR1 mutations were queried for using droplet digital PCR (ddPCR). In a prospective cohort, metastatic tissue and plasma were collected contemporaneously from eight ER-positive and four ER-negative patients. Tissue biopsies were sequenced by NGS, and ptDNA ESR1 mutations were analyzed by ddPCR. In the retrospective cohort, all corresponding mutations were detected in ptDNA, with two patients harboring additional ESR1 mutations not present in their metastatic tissues. In the prospective cohort, three ER-positive patients did not have adequate tissue for NGS, and no ESR1 mutations were identified in tissue biopsies from the other nine patients. In contrast, ddPCR detected seven ptDNA ESR1 mutations in 6 of 12 patients (50%). We show that ESR1 mutations can occur at a high frequency and suggest that blood can be used to identify additional mutations not found by sequencing of a single metastatic lesion. ©2015 American Association for Cancer Research.

[Relations between plasma-erythrocyte viscosity factors and ESR].

PubMed

Cortinovis, A; Crippa, A; Crippa, M; Bosoni, T; Moratti, R

1992-09-01

The ESR is usually put in relationship: to the real density of the RBCs (erythrocytes) (difference between the RBC specific gravity and the plasma one), and to the resistance that the RBCs meet moving in a medium, which is due to the plasma viscosity and to the total external RBC surface. When the RBCs take shape of aggregates, their external surface is decreased and ESR increases. The most important plasma factor causing changes in ESR is the fibrinogen level followed by the plasma globulins and by the products arising from the tissue damage. The resistance that the RBCs meet moving in the plasma is well expressed by the measurement of the plasma-RBC viscosity considering that is inclusive of both factors that are the plasma viscosity and the external RBC surface. The plasma-RBC viscosity is the resultant of several factors: Fa = Fb - Fe - Fs - Fm, were: Fa is the resultant, Fb the attracting forces due to the proteic macromolecules, Fe the repulsing forces due the negative charges. Fs the repulsing forces due to the shear-stress, Fm the force which opposes itself against the surface tension of the aggregation; it depends on the RBC morphology and on the RBC rigidity. The ESR has been recently used like an index of the RBC aggregation. The Authors study the relationship between several hemorheological parameters and the ESR in infective and inflammatory processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogen Receptor Alpha (ESR1)-Dependent Regulation of the Mouse Oviductal Transcriptome.

PubMed

Cerny, Katheryn L; Ribeiro, Rosanne A C; Jeoung, Myoungkun; Ko, CheMyong; Bridges, Phillip J

2016-01-01

Estrogen receptor-α (ESR1) is an important transcriptional regulator in the mammalian oviduct, however ESR1-dependent regulation of the transcriptome of this organ is not well defined, especially at the genomic level. The objective of this study was therefore to investigate estradiol- and ESR1-dependent regulation of the transcriptome of the oviduct using transgenic mice, both with (ESR1KO) and without (wild-type, WT) a global deletion of ESR1. Oviducts were collected from ESR1KO and WT littermates at 23 days of age, or ESR1KO and WT mice were treated with 5 IU PMSG to stimulate follicular development and the production of ovarian estradiol, and the oviducts collected 48 h later. RNA extracted from whole oviducts was hybridized to Affymetrix Genechip Mouse Genome 430-2.0 arrays (n = 3 arrays per genotype and treatment) or reverse transcribed to cDNA for analysis of the expression of selected mRNAs by real-time PCR. Following microarray analysis, a statistical two-way ANOVA and pairwise comparison (LSD test) revealed 2428 differentially expressed transcripts (DEG's, P < 0.01). Genotype affected the expression of 2215 genes, treatment (PMSG) affected the expression of 465 genes, and genotype x treatment affected the expression of 438 genes. With the goal of determining estradiol/ESR1-regulated function, gene ontology (GO) and bioinformatic pathway analyses were performed on DEG's in the oviducts of PMSG-treated ESR1KO versus PMSG-treated WT mice. Significantly enriched GO molecular function categories included binding and catalytic activity. Significantly enriched GO cellular component categories indicated the extracellular region. Significantly enriched GO biological process categories involved a single organism, modulation of a measurable attribute and developmental processes. Bioinformatic analysis revealed ESR1-regulation of the immune response within the oviduct as the primary canonical pathway. In summary, a transcriptomal profile of estradiol- and ESR1

Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer

PubMed Central

Trabucco, S E; Priedigkeit, N; Parachoniak, C A; Vanden Borre, P; Morley, S; Rosenzweig, M; Gay, L M; Goldberg, M E; Suh, J; Ali, S M; Ross, J; Leyland-Jones, B; Young, B; Williams, C; Park, B; Tsai, M; Haley, B; Peguero, J; Callahan, R D; Sachelarie, I; Cho, J; Atkinson, J M; Bahreini, A; Nagle, A M; Puhalla, S L; Watters, R J; Erdogan-Yildirim, Z; Cao, L; Oesterreich, S; Mathew, A; Lucas, P C; Davidson, N E; Brufsky, A M; Frampton, G M; Stephens, P J; Chmielecki, J; Lee, A V

2018-01-01

Abstract Background Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. Patients and methods To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287–395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. Results We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3′ partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations

Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast cancer.

PubMed

Hartmaier, R J; Trabucco, S E; Priedigkeit, N; Chung, J H; Parachoniak, C A; Vanden Borre, P; Morley, S; Rosenzweig, M; Gay, L M; Goldberg, M E; Suh, J; Ali, S M; Ross, J; Leyland-Jones, B; Young, B; Williams, C; Park, B; Tsai, M; Haley, B; Peguero, J; Callahan, R D; Sachelarie, I; Cho, J; Atkinson, J M; Bahreini, A; Nagle, A M; Puhalla, S L; Watters, R J; Erdogan-Yildirim, Z; Cao, L; Oesterreich, S; Mathew, A; Lucas, P C; Davidson, N E; Brufsky, A M; Frampton, G M; Stephens, P J; Chmielecki, J; Lee, A V

2018-04-01

Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287-395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3' partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Collectively, these data indicate that N-terminal ESR1

Personal noise dosimeters: accuracy and reliability in varied settings.

PubMed

Cook-Cunningham, Sheri Lynn

2014-01-01

This study investigated the accuracy, reliability, and characteristics of three brands of personal noise dosimeters (N = 7 units) in both pink noise (PN) environments and natural environments (NEs) through the acquisition of decibel readings, Leq readings and noise doses. Acquisition periods included repeated PN conditions, choir room rehearsals and participant (N = 3) Leq and noise dosages procured during a day in the life of a music student. Among primary results: (a) All dosimeters exhibited very strong positive correlations for PN measurements across all instruments; (b) all dosimeters were within the recommended American National Standard Institute (ANSI) SI.25-1991 standard of ±2 dB (A) of a reference measurement; and (c) all dosimeters were within the recommended ANSI SI.25-1991 standard of ±2 dB (A) when compared with each other. Results were discussed in terms of using personal noise dosimeters within hearing conservation and research contexts and recommendations for future research. Personal noise dosimeters were studied within the contexts of PN environments and NEs (choral classroom and the day in the life of collegiate music students). This quantitative study was a non-experimental correlation design. Three brands of personal noise dosimeters (Cirrus doseBadge, Quest Edge Eg5 and Etymotic ER200D) were tested in two environments, a PN setting and a natural setting. There were two conditions within each environment. In the PN environment condition one, each dosimeter was tested individually in comparison with two reference measuring devices (Ivie and Easera) while PN was generated by a Whites Instrument PN Tube. In condition two, the PN procedures were replicated for longer periods while all dosimeters measured the sound levels simultaneously. In the NE condition one, all dosimeters were placed side by side on a music stand and recorded sound levels of choir rehearsals over a 7-h rehearsal period. In NE, condition two noise levels were measured during

ESR detection of irradiated carob pods (Ceratoniasiliqua L) and its dosimetric feature

NASA Astrophysics Data System (ADS)

Tuner, Hasan; Polat, Mustafa

2017-12-01

Un-irradiated carob powder exhibited a weak ESR singlet at g = 2.0041 ± 0.0006 with peak-to-peak linewidth (ΔHpp) of 0.33 ± 0.01 mT. Irradiated carob powder exhibited an ESR spectrum consisting many resonance lines and similar to ESR spectrum of sugar in all aspects. A linear function of the absorbed radiation dose was found to describe best the dose-response curves of the ESR signal intensity Ipp. It is concluded that due to the similarity of carob powder ESR spectrum to the irradiated sugar and the fact that it is widely consumed, carob powder has the potential to be used as a retrospective and/or accidental dosimetric material.

Floating Gate CMOS Dosimeter With Frequency Output

NASA Astrophysics Data System (ADS)

Garcia-Moreno, E.; Isern, E.; Roca, M.; Picos, R.; Font, J.; Cesari, J.; Pineda, A.

2012-04-01

This paper presents a gamma radiation dosimeter based on a floating gate sensor. The sensor is coupled with a signal processing circuitry, which furnishes a square wave output signal, the frequency of which depends on the total dose. Like any other floating gate dosimeter, it exhibits zero bias operation and reprogramming capabilities. The dosimeter has been designed in a standard 0.6 m CMOS technology. The whole dosimeter occupies a silicon area of 450 m250 m. The initial sensitivity to a radiation dose is Hz/rad, and to temperature and supply voltage is kHz/°C and 0.067 kHz/mV, respectively. The lowest detectable dose is less than 1 rad.

Computer enhancement of ESR spectra of magnetite nanoparticles

NASA Astrophysics Data System (ADS)

Dobosz, B.; Krzyminiewski, R.; Koralewski, M.; Hałupka-Bryl, M.

2016-06-01

We present ESR measurements of non-interacting magnetic nanoparticle systems. Temperature and orientational dependence of ESR spectra were measured for Fe3O4 nanoparticle coated by dextran or oleic acid, frozen in different magnetic field. Several parameters describing magnetic properties such as g-factor, line width, the anisotropy constant were calculated and discussed. The ESR spectra of investigated nanoparticles were also subjected to Computer Resolution Enhancement Method (CREM). This procedure allows to separate a narrow line on the background of the broad line, which presence in this type of materials was recognized in the recent literature and have been further discussed in the paper. CREM is a valuable tool for monitoring of changes on the surface of magnetic core of nanoparticles.

[Tartrate-resistant acid phosphatase in free-living Amoeba proteus].

PubMed

Sopina, V A

2002-01-01

Tartrate-resistant acid phosphatase (TRAP) of Amoeba proteus (strain B) was represented by 3 of 6 bands (= electromorphs) revealed after disc-electrophoresis in polyacrylamide gels with the use of 2-naphthyl phosphate as a substrate at pH 4.0. The presence of MgCl2, CaCl2 or ZnCl2 (50 mM) in the incubation mixture used for gel staining stimulated activities of all 3 TRAP electromorphs or of two of them (in the case of ZnCl2). When gels were treated with MgCl2, CaCl2 or ZnCl2 (10 and 100 mM, 30 min) before their staining activity of TRAP electromorphs also increased. But unlike 1 M MgCl2 or 1 M CaCl2, 1 M ZnCl2 partly inactivated two of the three TRAP electromorphs. EDTA and EGTA (5 mM), and H2O2 (10 mM) completely inhibited TRAP electromorphs after gel treatment for 10, 20 and 30 min, resp. Of 5 tested ions (Mg2+, Ca2+, Fe2+, Fe3+ and Zn2+), only the latter reactivated the TRAP electromorphs previously inactivated by EDTA or EGTA treatment. In addition, after EDTA inactivation, TRAP electromorphs were reactivated better than after EGTA. The resistance of TRAP electromorphs to okadaic acid and phosphatase inhibitor cocktail 1 used in different concentrations is indicative of the absence of PP1 and PP2A among these electromorphs. Mg2+, Ca2+ and Zn2+ dependence of TRAP activity, and the resistance of its electromorphs to vanadate and phosphatase inhibitor cocktail 2 prevents these electromorphs from being classified as PTP. It is suggested that the active center of A. proteus TRAP contains zinc ion, which is essential for catalytic activity of the enzyme. Thus, TRAP of these amoebae is metallophosphatase showing phosphomonoesterase activity in acidic medium. This metalloenzyme differs from both mammalian tartrate-resistant PAPs and tartrate-resistant metallophosphatase of Rana esculenta.

Influence of photon beam energy on the dose enhancement factor caused by gold and silver nanoparticles: An experimental approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guidelli, Eder José, E-mail: ederguidelli@pg.ffclrp.usp.br; Baffa, Oswaldo

Purpose: Noble metal nanoparticles have found several medical applications in the areas of radiation detection; x-ray contrast agents and cancer radiation therapy. Based on computational methods, many papers have reported the nanoparticle effect on the dose deposition in the surrounding medium. Here the authors report experimental results on how silver and gold nanoparticles affect the dose deposition in alanine dosimeters containing several concentrations of silver and gold nanoparticles, for five different beam energies, using electron spin resonance spectroscopy (ESR). Methods: The authors produced alanine dosimeters containing several mass percentage of silver and gold nanoparticles. Nanoparticle sizes were measured by dynamicmore » light scattering and by transmission electron microscopy. The authors determined the dose enhancement factor (DEF) theoretically, using a widely accepted method, and experimentally, using ESR spectroscopy. Results: The DEF is governed by nanoparticle concentration, size, and position in the alanine matrix. Samples containing gold nanoparticles afford a DEF higher than 1.0, because gold nanoparticle size is homogeneous for all gold concentrations utilized. For samples containing silver particles, the silver mass percentage governs the nanoparticles size, which, in turns, modifies nanoparticle position in the alanine dosimeters. In this sense, DEF decreases for dosimeters containing large and segregated particles. The influence of nanoparticle size-position is more noticeable for dosimeters irradiated with higher beam energies, and dosimeters containing large and segregated particles become less sensitive than pure alanine (DEF < 1). Conclusions: ESR dosimetry gives the DEF in a medium containing metal nanoparticles, although particle concentration, size, and position are closely related in the system. Because this is also the case as in many real systems of materials containing inorganic nanoparticles, ESR is a valuable tool for

Implications of ESR1 Mutations in Hormone Receptor-Positive Breast Cancer.

PubMed

Reinert, Tomás; Gonçalves, Rodrigo; Bines, José

2018-04-17

Endocrine treatment resistance eventually develops during adjuvant and even more often during hormonal treatment for advanced breast cancer (ABC). An ESR1 gene mutation, which encodes for the estrogen receptor (ER) protein, is one of the potential mechanisms of therapy resistance. The ESR1 mutations result in conformational changes in the ER leading to subsequent estrogen-independent transcriptional activity. These mutations are found at a lower level in early stage when compared to metastatic BC, more often through selective pressure after aromatase inhibitor (AI) treatment. Recent studies have explored the role of ESR1 mutations as potential prognostic and predictive biomarkers and showed that ESR1 mutations are likely associated with a more aggressive disease. However, definitive associations with outcome in order to make a specific treatment recommendation are yet to be found. The development of targeted therapy directed to ESR1-mutated clones is an appealing concept, and preclinical and clinical works are in progress. ESR1 mutations represent an exciting field with a rapidly increasing number of recent publications that will likely advance the knowledge of treatment resistance mechanisms and pave the way into more individualized patient endocrine treatment.

GAMMA AND X-RAY DOSIMETER AND DOSIMETRIC METHOD

DOEpatents

Taplin, G.V.; Douglas, C.H.; Sigoloff, S.C.

1958-08-19

An improvement in colorimetric gamma and x-ray dosimeter systems and a self-contained. hand carried dostmeter of the afore-mentioned type ts described. A novel point of the invention ltes in the addition of specific quantities of certain normalizing agents to the two phase chlorinated hydro-carbon-aqueous dyc colortmetric dosimeter to eliminate the after reaction and thereby extend the utility of such systein. The structure of the two phase colorimetric dosimeter tubes and the carrying case for the tubes of the portable dosimeter are unique features.

Compton effect thermally activated depolarization dosimeter

DOEpatents

Moran, Paul R.

1978-01-01

A dosimetry technique for high-energy gamma radiation or X-radiation employs the Compton effect in conjunction with radiation-induced thermally activated depolarization phenomena. A dielectric material is disposed between two electrodes which are electrically short circuited to produce a dosimeter which is then exposed to the gamma or X radiation. The gamma or X-radiation impinging on the dosimeter interacts with the dielectric material directly or with the metal composing the electrode to produce Compton electrons which are emitted preferentially in the direction in which the radiation was traveling. A portion of these electrons becomes trapped in the dielectric material, consequently inducing a stable electrical polarization in the dielectric material. Subsequent heating of the exposed dosimeter to the point of onset of ionic conductivity with the electrodes still shorted through an ammeter causes the dielectric material to depolarize, and the depolarization signal so emitted can be measured and is proportional to the dose of radiation received by the dosimeter.

Deficiencies of active electronic radiation protection dosimeters in pulsed fields.

PubMed

Ankerhold, U; Hupe, O; Ambrosi, P

2009-07-01

Nowadays nearly all radiation fields used for X-ray diagnostics are pulsed. These fields are characterised by a high dose rate during the pulse and a short pulse duration in the range of a few milliseconds. The use of active electronic dosimeters has increased in the past few years, but these types of dosimeters might possibly not measure reliably in pulsed radiation fields. Not only personal dosimeters but also area dosimeters that are used mainly for dose rate measurements are concerned. These cannot be substituted by using passive dosimeter types. The characteristics of active electronic dosimeters determined in a continuous radiation field cannot be transferred to those in pulsed fields. Some provisional measurements with typical electronic dosimeters in pulsed radiation fields are presented to reveal this basic problem.

Dose-equivalent neutron dosimeter

DOEpatents

Griffith, R.V.; Hankins, D.E.; Tomasino, L.; Gomaa, M.A.M.

1981-01-07

A neutron dosimeter is disclosed which provides a single measurement indicating the amount of potential biological damage resulting from the neutron exposure of the wearer, for a wide range of neutron energies. The dosimeter includes a detecting sheet of track etch detecting material such as a carbonate plastic, for detecting higher energy neutrons, and a radiator layer contaning conversion material such as /sup 6/Li and /sup 10/B lying adjacent to the detecting sheet for converting moderate energy neutrons to alpha particles that produce tracks in the adjacent detecting sheet.

Increasing efficacy and reducing systemic absorption of brimonidine tartrate ophthalmic gels in rabbits.

PubMed

Pang, Xiaochen; Li, Jiawei; Pi, Jiaxin; Qi, Dongli; Guo, Pan; Li, Nan; Wu, Yumei; Liu, Zhidong

2018-03-01

Systemic absorption of ocularly administered Brimonidine Tartrate has been reported to give rise to several side-effects. Hence, it has become crucial to develop a delivery system that could increase efficacy and reduce systemic absorption. Therefore, the present work aims to develop Brimonidine Tartrate gels with different concentrations (0.05%, 0.1%, and 0.2% w/v, respectively) using Carbopol 974 P and HPMC E4M, and compare the therapeutic efficacy and systemic absorption with that of eye drop (0.2%, w/v) by UPLC-MS/MS. The result of histological analysis did not show any morphological or structural changes after the administration of formulations. In vitro residence time studies demonstrated that the gels exhibited a better precorneal residence time as compared with the eye drop. The gels with lower concentrations of the drug (0.05% and 0.1%, w/v) could significantly decrease intraocular pressure (IOP) in both normal and water-loaded rabbits as compared to the eye drop. Finally, the values of the ratio of AUC (0→∞) in comparison to eye drop showed the gels with lower concentrations of Brimonidine Tartrate could decrease the systemic absorption. From the result, it can be concluded the 0.1% ophthalmic gel has a potential to improve therapeutic efficacy and reduce the potential toxicity caused by systemic absorption.

ESR1 inhibits hCG-induced steroidogenesis and proliferation of progenitor Leydig cells in mice.

PubMed

Oh, Yeong Seok; Koh, Il Kyoo; Choi, Bomi; Gye, Myung Chan

2017-03-07

Oestrogen is an important regulator in reproduction. To understand the role of oestrogen receptor 1 (ESR1) in Leydig cells, we investigated the expression of ESR1 in mouse Leydig cells during postnatal development and the effects of oestrogen on steroidogenesis and proliferation of progenitor Leydig cells (PLCs). In Leydig cells, the ESR1 expression was low at birth, increased until postnatal day 14 at which PLCs were predominant, and then decreased until adulthood. In foetal Leydig cells, ESR1 immunoreactivity increased from birth to postnatal day 14. These suggest that ESR1 is a potential biomarker of Leydig cell development. In PLCs, 17β-estradiol and the ESR1-selective agonist propylpyrazoletriol suppressed human chorionic gonadotropin (hCG)-induced progesterone production and steroidogenic gene expression. The ESR2-selective agonist diarylpropionitrile did not affect steroidogenesis. In PLCs from Esr1 knockout mice, hCG-stimulated steroidogenesis was not suppressed by 17β-estradiol, suggesting that oestrogen inhibits PLC steroidogenesis via ESR1. 17β-estradiol, propylpyrazoletriol, and diarylpropionitrile decreased bromodeoxyuridine uptake in PLCs in the neonatal mice. In cultured PLCs, 17β-estradiol, propylpyrazoletriol, and diarylpropionitrile reduced hCG-stimulated Ki67 and Pcna mRNA expression and the number of KI67-positive PLCs, suggesting that oestrogen inhibits PLC proliferation via both ESR1 and ESR2. In PLCs, ESR1 mediates the oestrogen-induced negative regulation of steroidogenesis and proliferation.

ESR1 inhibits hCG-induced steroidogenesis and proliferation of progenitor Leydig cells in mice

PubMed Central

Oh, Yeong Seok; Koh, Il Kyoo; Choi, Bomi; Gye, Myung Chan

2017-01-01

Oestrogen is an important regulator in reproduction. To understand the role of oestrogen receptor 1 (ESR1) in Leydig cells, we investigated the expression of ESR1 in mouse Leydig cells during postnatal development and the effects of oestrogen on steroidogenesis and proliferation of progenitor Leydig cells (PLCs). In Leydig cells, the ESR1 expression was low at birth, increased until postnatal day 14 at which PLCs were predominant, and then decreased until adulthood. In foetal Leydig cells, ESR1 immunoreactivity increased from birth to postnatal day 14. These suggest that ESR1 is a potential biomarker of Leydig cell development. In PLCs, 17β-estradiol and the ESR1-selective agonist propylpyrazoletriol suppressed human chorionic gonadotropin (hCG)-induced progesterone production and steroidogenic gene expression. The ESR2-selective agonist diarylpropionitrile did not affect steroidogenesis. In PLCs from Esr1 knockout mice, hCG-stimulated steroidogenesis was not suppressed by 17β-estradiol, suggesting that oestrogen inhibits PLC steroidogenesis via ESR1. 17β-estradiol, propylpyrazoletriol, and diarylpropionitrile decreased bromodeoxyuridine uptake in PLCs in the neonatal mice. In cultured PLCs, 17β-estradiol, propylpyrazoletriol, and diarylpropionitrile reduced hCG-stimulated Ki67 and Pcna mRNA expression and the number of KI67-positive PLCs, suggesting that oestrogen inhibits PLC proliferation via both ESR1 and ESR2. In PLCs, ESR1 mediates the oestrogen-induced negative regulation of steroidogenesis and proliferation. PMID:28266530

Comparative analysis of radioecological monitoring dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sobolev, A.I.; Pol`skii, O.G.; Shanin, O.B.

1995-03-01

This paper describes comparative estimates of radiation doses measured by two types of thermoluminescence dosimeters and two types of background radiation radiometers. The dosimetry systems were tested by simultaneously recording background radiation and standard radiation sources at a radioactive waste storage facility. Statistical analysis of the measurement results is summarized. The maximum recorded exposure dose rate for the experiment was 19 microrads per hour. The DTK-2 dosimeter overestimated dose rates by 6 to 43% and the DTU-2 dosimeter underestimated dose rates by 7 to 21%. Both devices are recommended for radioecological monitoring in populated areas. 4 refs., 3 figs., 5more » tabs.« less

Fiber-type dosimeter with improved illuminator

DOEpatents

Fox, Richard J.

1987-01-01

A single-piece, molded plastic, Cassigrainian-type condenser arrangement is incorporated in a tubular-shaped personal pocket dosimeter of the type which combines an ionization chamber with an optically-read fiber electrometer to provide improved illumination of the electrometer fiber. The condenser routes incoming light from one end of the dosimeter tubular housing around a central axis charging pin assembly and focuses the light at low angles to the axis so that it falls within the acceptance angle of the electrometer fiber objective lens viewed through an eyepiece lens disposed in the opposite end of the dosimeter. This results in improved fiber illumination and fiber image contrast.

The Development of a Beta-Gamma Personnel Dosimeter

NASA Astrophysics Data System (ADS)

Tsakeres, Frank Steven

The assessment of absorbed dose in mixed beta and gamma radiation fields is an extremely complex task. For many years, the assessment of the absorbed dose to tissue from the weakly penetrating components of a radiation field (i.e., beta particles, electrons) has been largely ignored. Beta radiation fields are encountered routinely in a nuclear facility and may represent the major radiation component under certain accident or emergency conditions. Many attempts have been made to develop an accurate mixed field personnel dosimeter. However, all of these dosimeters have exhibited numerous response problems which have limited their usefulness for personnel dose assessment. Consequently, the determination of the absorbed dose at the epidermal depth (i.e., 7 mg/cm('2)) has been difficult to measure accurately. The objective of this research project was to design, build, and test a sensitive and accurate personnel dosimeter for mixed field applications. The selection of the various dosimeter elements were determined by evaluating several types of phosphors, filters, and backscatter materials. After evaluating the various response characteristics of the badge components, a prototype dosimeter, the CHEMM (CaF(,2):Dy Highly Efficient Multiple Element Multiple Filter) personnel dosimeter, was developed and tested at Georgia Tech, Emory University and the National Bureau of Standards. This dosimeter was comprised of four large CaF(,2):Dy (TLD-200) TLD's and a standard LiF (TLD-100) chip. The weakly penetrating and penetrating components of a radiation field were separated using a series of TLD/filter combinations and a new dose assessment algorithm. The large TLD-200 chips, along with a series of tissue-equivalent filters, were used to determine the absorbed dose due to the weakly penetrating radiation while a LiF/filter combination was used to measure the penetrating component. In addition, a new backscatter material was included in the badge design to better simulate a

Deconnable self-reading pocket dosimeter containment with self-contained light

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevens, R.L.; Arnold, G.N.; McBride, R.G.

1995-12-31

A container for a self-reading pocket dosimeter includes a transparent tube for receiving the self-reading pocket dosimeter, a light source mounted at one end of the transparent tube, and an eyepiece mounted on an opposite end of the transparent tube for viewing a read-out of the self-reading pocket dosimeter. The container may further include an activation device for selectively supplying power to the light source. The container both protects the dosimeter from being contaminated and provides a light source for viewing the dosimeter.

Deconnable self-reading pocket dosimeter containment with self-contained light

DOEpatents

Stevens, Robyn L.; Arnold, Greg N.; McBride, Ryan G.

1996-01-01

A container for a self-reading pocket dosimeter includes a transparent tube for receiving the self-reading pocket dosimeter, a light source mounted at one end of the transparent tube, and an eyepiece mounted on an opposite end of the transparent tube for viewing a read-out of the self-reading pocket dosimeter. The container may further include an activation device for selectively supplying power to the light source. The container both protects the dosimeter from being contaminated and provides a light source for viewing the dosimeter.

The Evaluation of IL6 and ESR1 Gene Polymorphisms in Primary Dysmenorrhea.

PubMed

Ozsoy, Asker Zeki; Karakus, Nevin; Yigit, Serbulent; Cakmak, Bulent; Nacar, Mehmet Can; Yılmaz Dogru, Hatice

2016-01-01

Primary dysmenorrhea is the most common gynecological complaint with painful menstrual cramps in pelvis without any pathology. It affects about half of menstruating women, and it causes significant disruption in quality of life. We investigated the association between IL6 gene promoter and ESR1 gene XbaI and PvuII polymorphisms and primary dysmenorrhea. In this case-control study, 152 unrelated young women with primary dysmenorrhea and 150 unrelated healthy age-matched controls participated. Genomic DNA was isolated and IL6 and ESR1 gene polymorphisms were genotyped using PCR-based RFLP assay. The distribution of genotype and allele frequencies of IL6 gene promoter and ESR1 gene XbaI polymorphisms were not statistically different between patients and controls (p > 0.05). However, the genotype and allele frequencies of ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls (p = 0.009 and p = 0.021, respectively). Statistically significant associations were also observed between age and married status of primary dysmenorrhea patients and ESR1 gene PvuII polymorphism (p = 0.044 and p = 0.023, respectively). In combined genotype analyses, AG at ESR1 XbaI and TC at ESR1 PvuII loci encoded a p-value of 0.027. Thus, individuals who are heterozygote at both loci have a lower risk of developing primary dysmenorrhea. Our study suggests no strong association between IL6 gene promoter and ESR1 gene XbaI polymorphisms and primary dysmenorrhea in Turkish women. However, ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls. The potential association between ESR1 gene PvuII polymorphism and age and married status of dysmenorrhea patients deserves further consideration.

Enantioseparation of Racemic Flurbiprofen by Aqueous Two-Phase Extraction With Binary Chiral Selectors of L-dioctyl Tartrate and L-tryptophan.

PubMed

Chen, Zhi; Zhang, Wei; Wang, Liping; Fan, Huajun; Wan, Qiang; Wu, Xuehao; Tang, Xunyou; Tang, James Z

2015-09-01

A novel method for chiral separation of flurbiprofen enantiomers was developed using aqueous two-phase extraction (ATPE) coupled with biphasic recognition chiral extraction (BRCE). An aqueous two-phase system (ATPS) was used as an extracting solvent which was composed of ethanol (35.0% w/w) and ammonium sulfate (18.0% w/w). The chiral selectors in ATPS for BRCE consideration were L-dioctyl tartrate and L-tryptophan, which were screened from amino acids, β-cyclodextrin derivatives, and L-tartrate esters. Factors such as the amounts of L-dioctyl tartrate and L-tryptophan, pH, flurbiprofen concentration, and the operation temperature were investigated in terms of chiral separation of flurbiprofen enantiomers. The optimum conditions were as follows: L-dioctyl tartrate, 80 mg; L-tryptophan, 40 mg; pH, 4.0; flurbiprofen concentration, 0.10 mmol/L; and temperature, 25 °C. The maximum separation factor α for flurbiprofen enantiomers could reach 2.34. The mechanism of chiral separation of flurbiprofen enantiomers is discussed and studied. The results showed that synergistic extraction has been established by L-dioctyl tartrate and L-tryptophan, which enantioselectively recognized R- and S-enantiomers in top and bottom phases, respectively. Compared to conventional liquid-liquid extraction, ATPE coupled with BRCE possessed higher separation efficiency and enantioselectivity without the use of any other organic solvents. The proposed method is a potential and powerful alternative to conventional extraction for separation of various enantiomers. © 2015 Wiley Periodicals, Inc.

Crystal structure of rivastigmine hydrogen tartrate Form I (Exelon®), C 14H 23N 2O 2(C 4H 5O 6)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaduk, James A.; Zhong, Kai; Gindhart, Amy M.

2016-03-08

The crystal structure of rivastigmine hydrogen tartrate has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Rivastigmine hydrogen tartrate crystallizes in space groupP2 1(#4) witha= 17.538 34(5),b= 8.326 89(2),c= 7.261 11(2) Å,β= 98.7999(2)°,V= 1047.929(4) Å 3, andZ= 2. The un-ionized end of the hydrogen tartrate anions forms a very strong hydrogen bond with the ionized end of another anion to form a chain. The ammonium group of the rivastigmine cation forms a strong discrete hydrogen bond with the carbonyl oxygen atom of the un-ionized end of the tartrate anion. These hydrogen bondsmore » form a corrugated network in thebc-plane. Both hydroxyl groups of the tartrate anion form intramolecular O–H···O hydrogen bonds. Several C–H···O hydrogen bonds appear to contribute to the crystal energy. The powder pattern is included in the Powder Diffraction File ™as entry 00-064-1501.« less

The Impact of ESR1 Mutations on the Treatment of Metastatic Breast Cancer.

PubMed

Pejerrey, Sasha M; Dustin, Derek; Kim, Jin-Ah; Gu, Guowei; Rechoum, Yassine; Fuqua, Suzanne A W

2018-05-07

After nearly 20 years of research, it is now established that mutations within the estrogen receptor (ER) gene, ESR1, frequently occur in metastatic breast cancer and influence response to hormone therapy. Though early studies presented differing results, sensitive sequencing techniques now show that ESR1 mutations occur at a frequency between 20 and 40% depending on the assay method. Recent studies have focused on several "hot spot mutations," a cluster of mutations found in the hormone-binding domain of the ESR1 gene. Throughout the course of treatment, tumor evolution can occur, and ESR1 mutations emerge and become enriched in the metastatic setting. Sensitive techniques to continually monitor mutant burden in vivo are needed to effectively treat patients with mutant ESR1. The full impact of these mutations on tumor response to different therapies remains to be determined. However, recent studies indicate that mutant-bearing tumors may be less responsive to specific hormonal therapies, and suggest that aromatase inhibitor (AI) therapy may select for the emergence of ESR1 mutations. Additionally, different mutations may respond discretely to targeted therapies. The need for more preclinical mechanistic studies on ESR1 mutations and the development of better agents to target these mutations are urgently needed. In the future, sequential monitoring of ESR1 mutational status will likely direct personalized therapeutic regimens appropriate to each tumor's unique mutational landscape.

Fiber-optic dosimeters for radiation therapy

NASA Astrophysics Data System (ADS)

Li, Enbang; Archer, James

2017-10-01

According to the figures provided by the World Health Organization, cancer is a leading cause of death worldwide, accounting for 8.8 million deaths in 2015. Radiation therapy, which uses x-rays to destroy or injure cancer cells, has become one of the most important modalities to treat the primary cancer or advanced cancer. The newly developed microbeam radiation therapy (MRT), which uses highly collimated, quasi-parallel arrays of x-ray microbeams (typically 50 μm wide and separated by 400 μm) produced by synchrotron sources, represents a new paradigm in radiotherapy and has shown great promise in pre-clinical studies on different animal models. Measurements of the absorbed dose distribution of microbeams are vitally important for clinical acceptance of MRT and for developing quality assurance systems for MRT, hence are a challenging and important task for radiation dosimetry. On the other hand, during the traditional LINAC based radiotherapy and breast cancer brachytherapy, skin dose measurements and treatment planning also require a high spatial resolution, tissue equivalent, on-line dosimeter that is both economical and highly reliable. Such a dosimeter currently does not exist and remains a challenge in the development of radiation dosimetry. High resolution, water equivalent, optical and passive x-ray dosimeters have been developed and constructed by using plastic scintillators and optical fibers. The dosimeters have peak edge-on spatial resolutions ranging from 50 to 500 microns in one dimension, with a 10 micron resolution dosimeter under development. The developed fiber-optic dosimeters have been test with both LINAC and synchrotron x-ray beams. This work demonstrates that water-equivalent and high spatial resolution radiation detection can be achieved with scintillators and optical fiber systems. Among other advantages, the developed fiber-optic probes are also passive, energy independent, and radiation hard.

Response of personal noise dosimeters to continuous and impulse-like signals

NASA Astrophysics Data System (ADS)

Evans, D. J.; Flynn, D. R.; Nedzelnitsky, V.; Burnett, E. D.

1991-06-01

A study of the capabilities of noise dosimeters to measure personal exposure to time varying and impulse-like noises was carried out. Ten commercial noise dosimeters were obtained. A laboratory reference noise dosimeter was constructed to provide a demonstrably accurate basis with which to compare the commercial noise dosimeters. Each commercial dosimeter, when ordered from the manufacturer, was specified to have a threshold A-weighted sound level of 80 dB, a criterion sound level of 90 dB, and an exchange rate of 5 dB and/or 3 dB. The performance of the commercial dosimeters was compared with theory and with results obtained from the reference dosimeter. Except in a few isolated cases, the commercial dosimeters were in general agreement with the performance specification of the appropriate American National Standard and with the Occupational Safety and Health Administration (OSHA) regulations.

Deconnable self-reading pocket dosimeter containment with self-contained light

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevens, R.L.; Arnold, G.N.; McBride, R.G.

1996-10-22

A container for a self-reading pocket dosimeter includes a transparent tube for receiving the self-reading pocket dosimeter, a light source mounted at one end of the transparent tube, and an eyepiece mounted on an opposite end of the transparent tube for viewing a read-out of the self-reading pocket dosimeter. The container may further include an activation device for selectively supplying power to the light source. The container both protects the dosimeter from being contaminated and provides a light source for viewing the dosimeter. 4 figs.

ESR1 mutations: Moving towards guiding treatment decision-making in metastatic breast cancer patients.

PubMed

Angus, Lindsay; Beije, Nick; Jager, Agnes; Martens, John W M; Sleijfer, Stefan

2017-01-01

Mutations in the gene coding for the estrogen receptor (ER), ESR1, have been associated with acquired endocrine resistance in patients with ER-positive metastatic breast cancer (MBC). Functional studies revealed that these ESR1 mutations lead to constitutive activity of the ER, meaning that the receptor is active in absence of its ligand estrogen, conferring resistance against several endocrine agents. While recent clinical studies reported that the occurrence of ESR1 mutations is rare in primary breast cancer tumors, these mutations are more frequently observed in metastatic tissue and circulating cell-free DNA of MBC patients pretreated with endocrine therapy. Given the assumed impact that the presence of ESR1 mutations has on outcome to endocrine therapy, assessing ESR1 mutations in MBC patients is likely to be of significant interest to further individualize treatment for MBC patients. Here, ESR1 mutation detection methods and the most relevant pre-clinical and clinical studies on ESR1 mutations regarding endocrine resistance are reviewed, with particular interest in the ultimate goal of guiding treatment decision-making based on ESR1 mutations. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue.

PubMed

Fatima, L A; Campello, R S; Santos, R de Souza; Freitas, H S; Frank, A P; Machado, U F; Clegg, D J

2017-12-01

Vascular endothelial growth factor A (VEGFA) is a key factor in the regulation of angiogenesis in adipose tissue. Poor vascularization during adipose tissue proliferation causes fibrosis and local inflammation, and is associated with insulin resistance. It is known that 17-beta estradiol (E2) regulates adipose tissue function and VEGFA expression in other tissues; however, the ability of E2 to regulate VEGFA in adipose tissue is currently unknown. In this study, we showed that, in 3T3-L1 cells, E2 and the estrogen receptor 1 (ESR1) agonist PPT induced VEGFA expression, while ESR1 antagonist (MPP), and selective knockdown of ESR1 using siRNA decreased VEGFA and prevented the ability of E2 to modulate its expression. Additionally, we found that E2 and PPT induced the binding of hypoxia inducible factor 1 alpha subunit (HIF1A) in the VEGFA gene promoter. We further found that VEGFA expression was lower in inguinal and gonadal white adipose tissues of ESR1 total body knockout female mice compared to wild type mice. In conclusion, our data provide evidence of an important role for E2/ESR1 in modulating adipose tissue VEGFA, which is potentially important to enhance angiogenesis, reduce inflammation and improve adipose tissue function.

Estrogen receptor (ESR1) mutation in bone metastases from breast cancer.

PubMed

Bartels, Stephan; Christgen, Matthias; Luft, Angelina; Persing, Sascha; Jödecke, Kai; Lehmann, Ulrich; Kreipe, Hans

2018-01-01

Activating mutations of estrogen receptor α gene (ESR1) in breast cancer can cause endocrine resistance of metastatic tumor cells. The skeleton belongs to the metastatic sides frequently affected by breast cancer. The prevalence of ESR1 mutation in bone metastasis and the corresponding phenotype are not known. In this study bone metastases from breast cancer (n=231) were analyzed for ESR1 mutation. In 27 patients (12%) (median age 73 years, range: 55-82 years) activating mutations of ESR1 were detected. The most frequent mutation was p.D538G (53%), no mutations in exon 4 (K303) or 7 (S463) were found. Lobular breast cancer was present in 52% of mutated cases (n=14) and in 49% of all samples (n=231), respectively. Mutated cancers constantly displayed strong estrogen receptor expression. Progesterone receptor was positive in 78% of the mutated cases (n=21). From 194 estrogen receptor-positive samples, 14% had ESR1 mutated. Except for one mutated case, no concurrent HER2 overexpression was noted. Metastatic breast cancer with activating mutations of ESR1 had a higher Ki67 labeling index than primary luminal cancers (median 30%, ranging from 5 to 60% with 85% of cases revealing ≥20% Ki67-positive cells). From those patients from whom information on endocrine therapy was available (n=7), two had received tamoxifen only, 4 tamoxifen followed by aromatase inhibitors and one patient had been treated with aromatase inhibitors only. We conclude that ESR1 mutation is associated with estrogen receptor expression and high proliferative activity and affects about 14% of estrogen receptor-positive bone metastases from breast cancer.

Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer.

PubMed

Bailey, Swneke D; Desai, Kinjal; Kron, Ken J; Mazrooei, Parisa; Sinnott-Armstrong, Nicholas A; Treloar, Aislinn E; Dowar, Mark; Thu, Kelsie L; Cescon, David W; Silvester, Jennifer; Yang, S Y Cindy; Wu, Xue; Pezo, Rossanna C; Haibe-Kains, Benjamin; Mak, Tak W; Bedard, Philippe L; Pugh, Trevor J; Sallari, Richard C; Lupien, Mathieu

2016-10-01

Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers, suggesting that other mechanisms underlie the persistent expression of ESR1. We report significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by rs9383590, a functional inherited single-nucleotide variant (SNV) that accounts for several breast cancer risk-associated loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer.

Edge Stabilized Ribbon (ESR); Stress, Dislocation Density and Electronic Performance

NASA Technical Reports Server (NTRS)

Sachs, E. M.

1984-01-01

The edge stabilized ribbon (ESR) silicon ribbon was grown in widths of 1, 2.2 and 4.0 inches at speeds ranging from .6 to 7 in/min, which result in ribbon thicknesses of 5 to 400 microns. One of the primary problems remaining in ESR growth is that of thermally induced mechanical stresses. This problem is manifested as ribbon with a high degree of residual stress or as ribbon with buckled ribbon. Thermal stresses result in a high dislocation density in the grown material, resulting in compromised electronic performance. Improvements in ribbon flatness were accomplished by modification of the ribbon cooling profile. Ribbon flatness and other experimental observations of ESR ribbon are discussed. Laser scanner measurements show a good correlation between diffusion length and dislocation density which indicates that the high dislocation densities are the primary cause of the poor current performance of ESR materials. Dislocation densities were reduced and improved electronic performance resulted. Laser scanner data on new and old material are presented.

Environmental dosimeter of the thermoluminescent type

DOEpatents

Eichner, F.N.; Kocher, L.F.

1974-01-29

A dosimeter for accurately monitoring normally low-energy radiation including a thermoluminescent CaF phosphor enclosed within a tantalum capsule is described. The tantalum acts as a filter to weaken the measured dose due to photons having energies below about 0.2 MeV. Tantalum end caps are maintained on the capsule body by a polyolefin sheath formed from heat-contractable tubing. After exposing the dosimeter to environmental radiation, it is placed in a shielded chamber for about 24 h and subsequently annealed at about 80 deg C to release radiation energy accumulated in low-temperature traps. The dosimeter is then disassembled and the phosphors photometrically read at temperatures about 50 deg C to determine the absorbed radiation dose. (Official Gazette)

ULTRASONIC NEUTRON DOSIMETER

DOEpatents

Truell, R.; de Klerk, J.; Levy, P.W.

1960-02-23

A neutron dosimeter is described which utilizes ultrasonic waves in the megacycle region for determination of the extent of neutron damage in a borosilicate glass through ultrasonic wave velocity and attenuation measurements before and after damage.

Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance.

PubMed

Martin, Lesley-Ann; Ribas, Ricardo; Simigdala, Nikiana; Schuster, Eugene; Pancholi, Sunil; Tenev, Tencho; Gellert, Pascal; Buluwela, Laki; Harrod, Alison; Thornhill, Allan; Nikitorowicz-Buniak, Joanna; Bhamra, Amandeep; Turgeon, Marc-Olivier; Poulogiannis, George; Gao, Qiong; Martins, Vera; Hills, Margaret; Garcia-Murillas, Isaac; Fribbens, Charlotte; Patani, Neill; Li, Zheqi; Sikora, Matthew J; Turner, Nicholas; Zwart, Wilbert; Oesterreich, Steffi; Carroll, Jason; Ali, Simak; Dowsett, Mitch

2017-11-30

Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported in in vitro models of BC either before or after the acquisition of endocrine resistance making functional consequences difficult to study. We report the first discovery of naturally occurring ESR1 Y537C and ESR1 Y537S mutations in MCF7 and SUM44 ESR1-positive cell lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Mutations were enriched with time, impacted on ESR1 binding to the genome and altered the ESR1 interactome. The results highlight the importance and functional consequence of these mutations and provide an important resource for studying endocrine resistance.

Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer

PubMed Central

Bailey, Swneke D.; Desai, Kinjal; Kron, Ken J.; Mazrooei, Parisa; Sinnott-Armstrong, Nicholas A.; Treloar, Aislinn E.; Dowar, Mark; Thu, Kelsie L.; Cescon, David W.; Silvester, Jennifer; Yang, S. Y. Cindy; Wu, Xue; Pezo, Rossanna C.; Haibe-Kains, Benjamin; Mak, Tak W.; Bedard, Philippe L.; Pugh, Trevor J.; Sallari, Richard C.; Lupien, Mathieu

2016-01-01

Sustained expression of the oestrogen receptor alpha (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon oestrogen stimulation to establish an oncogenic expression program1. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers2–5, implying that other mechanisms underlie the persistent expression of ESR1. We report the significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by a functional inherited single nucleotide variant (SNV) rs9383590 that accounts for several breast cancer risk-loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer. PMID:27571262

Identification, synthesis, isolation and characterization of new impurity in metoprolol tartrate tablets.

PubMed

Reddy, R Buchi; More, Kishor R; Gupta, Leena; Jha, Mukesh S; Magar, Laki

2016-01-05

A new unknown impurity was observed in accelerated stability studies of Metoprolol tartrate tablets. This impurity has been identified, synthesized and characterized through different spectral studies and confirmed as an adduct of lactose and Metoprolol formed by Maillard reaction. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of sustained release capsules containing "coated matrix granules of metoprolol tartrate".

PubMed

Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

2010-09-01

The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet granulation method with subsequent coating. Optimized formulation of metoprolol tartrate was formed by using 30% HPMC K100M, 20% EC, and ratio of Eudragit® RS/RL as 97.5:2.5 at 25% coating level. Capsules were filled with free flowing optimized granules of uniform drug content. This extended the release period upto 12 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC and EC had been coupled satisfactorily with the controlled resistance offered by Eudragit® RS. The release mechanism of capsules followed Korsemeyer-Peppas model that indicated significant contribution of erosion effect of hydrophilic polymer. Biopharmaceutical study of this optimized dosage form in rabbit model showed 10 h prolonged drug release in vivo. A close correlation (R(2) = 0.9434) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with subsequent coating by fluidized bed technique, is a suitable method to formulate sustained release capsules of metoprolol tartrate and it can perform therapeutically better than conventional immediate release dosage form.

Polymer gel dosimeter based on itaconic acid.

PubMed

Mattea, Facundo; Chacón, David; Vedelago, José; Valente, Mauro; Strumia, Miriam C

2015-11-01

A new polymeric dosimeter based on itaconic acid and N, N'-methylenebisacrylamide was studied. The preparation method, compositions of monomer and crosslinking agent and the presence of oxygen in the dosimetric system were analyzed. The resulting materials were irradiated with an X-ray tube at 158cGy/min, 226cGymin and 298cGy/min with doses up to 1000Gy. The dosimeters presented a linear response in the dose range 75-1000Gy, sensitivities of 0.037 1/Gyat 298cGy/min and an increase in the sensitivity with lower dose rates. One of the most relevant outcomes in this study was obtaining different monomer to crosslinker inclusion in the formed gel for the dosimeters where oxygen was purged during the preparation method. This effect has not been reported in other typical dosimeters and could be attributed to the large differences in the reactivity among these species. Copyright © 2015 Elsevier Ltd. All rights reserved.

ESR identification of gamma-irradiated albendazole

NASA Astrophysics Data System (ADS)

Çolak, Seyda

2010-01-01

The use of ionizing radiation for sterilization of pharmaceuticals is a well-established technology. In the present work, the spectroscopic and kinetic features of the radicals induced in gamma-irradiated solid albendazole samples is investigated at different temperatures in the dose range of 3-34 kGy by electron spin resonance (ESR) spectroscopy. Irradiation with gamma radiation produced two different radical species in albendazole. They were fairly stable at room temperature but relatively unstable above room temperature, giving rise to an unresolved ESR spectrum consisting of three resonance peaks centered at g=2.0057. Decay activation energies of the contributing radical species were calculated to be 47.8 (±13.5) and 50.5 (±9.7) kJ/mol using the signal intensity decay data derived from annealing studies performed at high temperatures. A linear function of the applied dose was found to best describe the experimental dose-response data. Albendazole does not present the characteristics of good dosimetric materials. However, the discrimination of irradiated albendazole from its unirradiated form was possible even 6 months after storage in normal conditions. Based on these findings, it is concluded that albendazole and albendazole-containing drugs can be safely sterilized by gamma radiation and that ESR spectroscopy could be successfully used as a potential technique for monitoring their radiosterilization.

GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility.

PubMed

Theodorou, Vasiliki; Stark, Rory; Menon, Suraj; Carroll, Jason S

2013-01-01

Estrogen receptor (ESR1) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcription events that promote tumor growth. Differences in enhancer occupancy by ESR1 contribute to the diverse expression profiles and clinical outcome observed in breast cancer patients. GATA3 is an ESR1-cooperating transcription factor mutated in breast tumors; however, its genomic properties are not fully defined. In order to investigate the composition of enhancers involved in estrogen-induced transcription and the potential role of GATA3, we performed extensive ChIP-sequencing in unstimulated breast cancer cells and following estrogen treatment. We find that GATA3 is pivotal in mediating enhancer accessibility at regulatory regions involved in ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution of cofactors and active histone marks prior to estrogen stimulation. These global genomic changes altered the ESR1-binding profile that subsequently occurred following estrogen, with events exhibiting both loss and gain in binding affinity, implying a GATA3-mediated redistribution of ESR1 binding. The GATA3-mediated redistributed ESR1 profile correlated with changes in gene expression, suggestive of its functionality. Chromatin loops at the TFF locus involving ESR1-bound enhancers occurred independently of ESR1 when GATA3 was silenced, indicating that GATA3, when present on the chromatin, may serve as a licensing factor for estrogen-ESR1-mediated interactions between cis-regulatory elements. Together, these experiments suggest that GATA3 directly impacts ESR1 enhancer accessibility, and may potentially explain the contribution of mutant-GATA3 in the heterogeneity of ESR1+ breast cancer.

GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility

PubMed Central

Theodorou, Vasiliki; Stark, Rory; Menon, Suraj; Carroll, Jason S.

2013-01-01

Estrogen receptor (ESR1) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcription events that promote tumor growth. Differences in enhancer occupancy by ESR1 contribute to the diverse expression profiles and clinical outcome observed in breast cancer patients. GATA3 is an ESR1-cooperating transcription factor mutated in breast tumors; however, its genomic properties are not fully defined. In order to investigate the composition of enhancers involved in estrogen-induced transcription and the potential role of GATA3, we performed extensive ChIP-sequencing in unstimulated breast cancer cells and following estrogen treatment. We find that GATA3 is pivotal in mediating enhancer accessibility at regulatory regions involved in ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution of cofactors and active histone marks prior to estrogen stimulation. These global genomic changes altered the ESR1-binding profile that subsequently occurred following estrogen, with events exhibiting both loss and gain in binding affinity, implying a GATA3-mediated redistribution of ESR1 binding. The GATA3-mediated redistributed ESR1 profile correlated with changes in gene expression, suggestive of its functionality. Chromatin loops at the TFF locus involving ESR1-bound enhancers occurred independently of ESR1 when GATA3 was silenced, indicating that GATA3, when present on the chromatin, may serve as a licensing factor for estrogen–ESR1-mediated interactions between cis-regulatory elements. Together, these experiments suggest that GATA3 directly impacts ESR1 enhancer accessibility, and may potentially explain the contribution of mutant-GATA3 in the heterogeneity of ESR1+ breast cancer. PMID:23172872

A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation.

PubMed

Tomita, Saori; Abdalla, Mohamed Osama Ali; Fujiwara, Saori; Matsumori, Haruka; Maehara, Kazumitsu; Ohkawa, Yasuyuki; Iwase, Hirotaka; Saitoh, Noriko; Nakao, Mitsuyoshi

2015-04-29

Estrogen receptor-α (ER)-positive breast cancer cells undergo hormone-independent proliferation after deprivation of oestrogen, leading to endocrine therapy resistance. Up-regulation of the ER gene (ESR1) is critical for this process, but the underlying mechanisms remain unclear. Here we show that the combination of transcriptome and fluorescence in situ hybridization analyses revealed that oestrogen deprivation induced a cluster of noncoding RNAs that defined a large chromatin domain containing the ESR1 locus. We termed these RNAs as Eleanors (ESR1 locus enhancing and activating noncoding RNAs). Eleanors were present in ER-positive breast cancer tissues and localized at the transcriptionally active ESR1 locus to form RNA foci. Depletion of one Eleanor, upstream (u)-Eleanor, impaired cell growth and transcription of intragenic Eleanors and ESR1 mRNA, indicating that Eleanors cis-activate the ESR1 gene. Eleanor-mediated gene activation represents a new type of locus control mechanism and plays an essential role in the adaptation of breast cancer cells.

A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation

PubMed Central

Tomita, Saori; Abdalla, Mohamed Osama Ali; Fujiwara, Saori; Matsumori, Haruka; Maehara, Kazumitsu; Ohkawa, Yasuyuki; Iwase, Hirotaka; Saitoh, Noriko; Nakao, Mitsuyoshi

2015-01-01

Estrogen receptor-α (ER)-positive breast cancer cells undergo hormone-independent proliferation after deprivation of oestrogen, leading to endocrine therapy resistance. Up-regulation of the ER gene (ESR1) is critical for this process, but the underlying mechanisms remain unclear. Here we show that the combination of transcriptome and fluorescence in situ hybridization analyses revealed that oestrogen deprivation induced a cluster of noncoding RNAs that defined a large chromatin domain containing the ESR1 locus. We termed these RNAs as Eleanors (ESR1 locus enhancing and activating noncoding RNAs). Eleanors were present in ER-positive breast cancer tissues and localized at the transcriptionally active ESR1 locus to form RNA foci. Depletion of one Eleanor, upstream (u)-Eleanor, impaired cell growth and transcription of intragenic Eleanors and ESR1 mRNA, indicating that Eleanors cis-activate the ESR1 gene. Eleanor-mediated gene activation represents a new type of locus control mechanism and plays an essential role in the adaptation of breast cancer cells. PMID:25923108

A novel FOXA1/ESR1 interacting pathway: A study of Oncomine™ breast cancer microarrays

PubMed Central

Chaudhary, Sanjib; Krishna, B. Madhu; Mishra, Sandip K.

2017-01-01

Forkhead box protein A1 (FOXA1) is essential for the growth and differentiation of breast epithelium, and has a favorable outcome in breast cancer (BC). Elevated FOXA1 expression in BC also facilitates hormone responsiveness in estrogen receptor (ESR)-positive BC. However, the interaction between these two pathways is not fully understood. FOXA1 and GATA binding protein 3 (GATA3) along with ESR1 expression are responsible for maintaining a luminal phenotype, thus suggesting the existence of a strong association between them. The present study utilized the Oncomine™ microarray database to identify FOXA1:ESR1 and FOXA1:ESR1:GATA3 co-expression co-regulated genes. Oncomine™ analysis revealed 115 and 79 overlapping genes clusters in FOXA1:ESR1 and FOXA1:ESR1:GATA3 microarrays, respectively. Five ESR1 direct target genes [trefoil factor 1 (TFF1/PS2), B-cell lymphoma 2 (BCL2), seven in absentia homolog 2 (SIAH2), cellular myeloblastosis viral oncogene homolog (CMYB) and progesterone receptor (PGR)] were detected in the co-expression clusters. To further investigate the role of FOXA1 in ESR1-positive cells, MCF7 cells were transfected with a FOXA1 expression plasmid, and it was observed that the direct target genes of ESR1 (PS2, BCL2, SIAH2 and PGR) were significantly regulated upon transfection. Analysis of one of these target genes, PS2, revealed the presence of two FOXA1 binding sites in the vicinity of the estrogen response element (ERE), which was confirmed by binding assays. Under estrogen stimulation, FOXA1 protein was recruited to the FOXA1 site and could also bind to the ERE site (although in minimal amounts) in the PS2 promoter. Co-transfection of FOXA1/ESR1 expression plasmids demonstrated a significantly regulation of the target genes identified in the FOXA1/ESR1 multi-arrays compared with only FOXA1 transfection, which was suggestive of a synergistic effect of ESR1 and FOXA1 on the target genes. In summary, the present study identified novel FOXA1, ESR1

A novel FOXA1/ESR1 interacting pathway: A study of Oncomine™ breast cancer microarrays.

PubMed

Chaudhary, Sanjib; Krishna, B Madhu; Mishra, Sandip K

2017-08-01

Forkhead box protein A1 (FOXA1) is essential for the growth and differentiation of breast epithelium, and has a favorable outcome in breast cancer (BC). Elevated FOXA1 expression in BC also facilitates hormone responsiveness in estrogen receptor ( ESR )-positive BC. However, the interaction between these two pathways is not fully understood. FOXA1 and GATA binding protein 3 ( GATA3 ) along with ESR1 expression are responsible for maintaining a luminal phenotype, thus suggesting the existence of a strong association between them. The present study utilized the Oncomine™ microarray database to identify FOXA1:ESR1 and FOXA1:ESR1:GATA3 co-expression co-regulated genes. Oncomine™ analysis revealed 115 and 79 overlapping genes clusters in FOXA1:ESR1 and FOXA1:ESR1:GATA3 microarrays, respectively. Five ESR1 direct target genes [trefoil factor 1 ( TFF1/PS2 ), B-cell lymphoma 2 ( BCL2 ), seven in absentia homolog 2 ( SIAH2 ), cellular myeloblastosis viral oncogene homolog ( CMYB ) and progesterone receptor ( PGR )] were detected in the co-expression clusters. To further investigate the role of FOXA1 in ESR1-positive cells, MCF7 cells were transfected with a FOXA1 expression plasmid, and it was observed that the direct target genes of ESR1 ( PS2, BCL2, SIAH2 and PGR ) were significantly regulated upon transfection. Analysis of one of these target genes, PS2 , revealed the presence of two FOXA1 binding sites in the vicinity of the estrogen response element (ERE), which was confirmed by binding assays. Under estrogen stimulation, FOXA1 protein was recruited to the FOXA1 site and could also bind to the ERE site (although in minimal amounts) in the PS2 promoter. Co-transfection of FOXA1 / ESR1 expression plasmids demonstrated a significantly regulation of the target genes identified in the FOXA1 / ESR1 multi-arrays compared with only FOXA1 transfection, which was suggestive of a synergistic effect of ESR1 and FOXA1 on the target genes. In summary, the present study

SU-E-T-749: Thorough Calibration of MOSFET Dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plenkovich, D; Thomas, J

Purpose: To improve the accuracy of the MOSFET calibration procedure by performing the measurement several times and calculating the average value of the calibration factor for various photon and electron energies. Methods: The output of three photon and six electron beams of Varian Trilogy linear accelerator SN 5878 was calibrated. Five reinforced standard sensitivity MOSFET dosimeters were placed in the calibration jig and connected to the Reader Module. As the backscatter material was used 7 cm of Virtual Water. The MOSFET dosimeters were covered with 1.5 cm thick bolus for the regular and SRS 6 MV beams, 3 cm bolusmore » for 15 MV beam, 1.5 cm bolus for 6 MeV electron beam, and 2 cm bolus for the electron energies of 9, 12, 15, 18, and 22 MeV. The dosimeters were exposed to 100 MU, and the calibration factor was determined using the mobileMOSFET software. To improve the accuracy of calibration, this procedure was repeated ten times and the calibration factors were averaged. Results: As the number of calibrations was increasing the variability of calibration factors of different dosimeters was decreasing. After ten calibrations, the calibration factors for all five dosimeters were within 1% of one another for all energies, except 6 MV SRS photons and 6 MeV electrons, for which the variability was 2%. Conclusions: The described process results in calibration factors which are almost independent of modality or energy. Once calibrated, the dosimeters may be used for in-vivo dosimetry or for daily verification of the beam output. Measurement of the radiation dose under bolus and scatter to the eye are examples of frequent use of calibrated MOSFET dosimeters. The calibration factor determined for full build-up is used under these circumstances. To the best of our knowledge, such thorough procedure for calibrating MOSFET dosimeters has not been reported previously. Best Medical Canada provided MOSFET dosimeters for this project.« less

Light scattering in optical CT scanning of Presage dosimeters

NASA Astrophysics Data System (ADS)

Xu, Y.; Adamovics, J.; Cheeseborough, J. C.; Chao, K. S.; Wuu, C. S.

2010-11-01

The intensity of the scattered light from the Presage dosimeters was measured using a Thorlabs PM100D optical power meter (Thorlabs Inc, Newton, NJ) with an optical sensor of 1 mm diameter sensitive area. Five Presage dosimeters were made as cylinders of 15.2 cm, 10 cm, 4 cm diameters and irradiated with 6 MV photons using a Varian Clinac 2100EX. Each dosimeter was put into the scanning tank of an OCTOPUS" optical CT scanner (MGS Research Inc, Madison, CT) filled with a refractive index matching liquid. A laser diode was positioned at one side of the water tank to generate a stationary laser beam of 0.8 mm width. On the other side of the tank, an in-house manufactured positioning system was used to move the optical sensor in the direction perpendicular to the outgoing laser beam from the dosimeters at an increment of 1 mm. The amount of scattered photons was found to be more than 1% of the primary light signal within 2 mm from the laser beam but decreases sharply with increasing off-axis distance. The intensity of the scattered light increases with increasing light attenuations and/or absorptions in the dosimeters. The scattered light at the same off-axis distance was weaker for dosimeters of larger diameters and for larger detector-to-dosimeter distances. Methods for minimizing the effect of the light scattering in different types of optical CT scanners are discussed.

Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer.

PubMed

Fribbens, Charlotte; O'Leary, Ben; Kilburn, Lucy; Hrebien, Sarah; Garcia-Murillas, Isaac; Beaney, Matthew; Cristofanilli, Massimo; Andre, Fabrice; Loi, Sherene; Loibl, Sibylle; Jiang, John; Bartlett, Cynthia Huang; Koehler, Maria; Dowsett, Mitch; Bliss, Judith M; Johnston, Stephen R D; Turner, Nicholas C

2016-09-01

ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor-positive advanced breast cancer. In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). ESR1 mutation analysis in

Water-equivalent fiber radiation dosimeter with two scintillating materials

PubMed Central

Qin, Zhuang; Hu, Yaosheng; Ma, Yu; Lin, Wei; Luo, Xianping; Zhao, Wenhui; Sun, Weimin; Zhang, Daxin; Chen, Ziyin; Wang, Boran; Lewis, Elfed

2016-01-01

An inorganic scintillating material plastic optical fiber (POF) dosimeter for measuring ionizing radiation during radiotherapy applications is reported. It is necessary that an ideal dosimeter exhibits many desirable qualities, including water equivalence, energy independence, reproducibility, dose linearity. There has been much recent research concerning inorganic dosimeters. However, little reference has been made to date of the depth-dose characteristics of dosimeter materials. In the case of inorganic scintillating materials, they are predominantly non water-equivalent, with their effective atomic weight (Zeff) being typically much greater than that of water. This has been a barrier in preventing inorganic scintillating material dosimeter from being used in actual clinical applications. In this paper, we propose a parallel-paired fiber light guide structure to solve this problem. Two different inorganic scintillating materials are embedded separately in the parallel-paired fiber. It is shown that the information of water depth and absorbed dose at the point of measurement can be extracted by utilizing their different depth-dose properties. PMID:28018715

Portable battery-free charger for radiation dosimeters

DOEpatents

Manning, Frank W.

1984-01-01

This invention is a novel portable charger for dosimeters of the electrometer type. The charger does not require batteries or piezoelectric crystals and is of rugged construction. In a preferred embodiment, the charge includes a housing which carries means for mounting a dosimeter to be charged. The housing also includes contact means for impressing a charging voltage across the mounted dosimeter. Also, the housing carries a trigger for operating a charging system mounted in the housing. The charging system includes a magnetic loop including a permanent magnet for establishing a magnetic field through the loop. A segment of the loop is coupled to the trigger for movement thereby to positions opening and closing the loop. A coil inductively coupled with the loop generates coil-generated voltage pulses when the trigger is operated to open and close the loop. The charging system includes an electrical circuit for impressing voltage pulses from the coil across a capacitor for integrating the pulses and applying the resulting integrated voltage across the above-mentioned contact means for charging the dosimeter.

Are We Ready to Use ESR1 Mutations in Clinical Practice?

PubMed

Jeselsohn, Rinath

2017-10-01

The recurrent ligand-binding domain ESR1 mutations are an important mechanism of endocrine resistance in estrogen receptor-positive (ER+) metastatic breast cancer. These mutations evolve under the selective pressure of endocrine treatments and are rarely found in treatment-naïve ER+ breast cancers. Preclinical studies showed that these mutations lead to ligand-independent activity facilitating resistance to aromatase inhibitors and relative resistance to tamoxifen and fulvestrant. Retrospective analyses of ESR1 mutations in baseline plasma circulating tumor DNA from clinical trials suggest that these mutations are prognostic of poor overall survival and predictive of resistance to aromatase inhibitors in metastatic disease. Larger datasets and prospective studies to confirm these results are lacking. In addition, response to other standard treatments for metastatic breast cancer in the presence of the ESR1 mutations is unknown, and studies to determine the optimal treatment combinations for patients with ESR1 mutations are also needed.

Production of High Quality Die Steels from Large ESR Slab Ingots

NASA Astrophysics Data System (ADS)

Geng, Xin; Jiang, Zhou-hua; Li, Hua-bing; Liu, Fu-bin; Li, Xing

With the rapid development of manufacture industry in China, die steels are in great need of large slab ingot of high quality and large tonnage, such as P20, WSM718R and so on. Solidification structure and size of large slab ingots produced with conventional methods are not satisfied. However, large slab ingots manufactured by ESR process have a good solidification structure and enough section size. In the present research, the new slab ESR process was used to produce the die steels large slab ingots with the maximum size of 980×2000×3200mm. The compact and sound ingot can be manufactured by the slab ESR process. The ultra-heavy plates with the maximum thickness of 410 mm can be obtained after rolling the 49 tons ingots. Due to reducing the cogging and forging process, the ESR for large slab ingots process can increase greatly the yield and production efficiency, and evidently cut off product costs.

Genetic polymorphisms in the ESR1 gene and cerebral infarction risk: a meta-analysis.

PubMed

Gao, Hong-Hua; Gao, Lian-Bo; Wen, Jia-Mei

2014-09-01

A number of studies have documented that estrogen receptor α (ESR1) may play an important role in the development and progression of cerebral infarction, but many existing studies have yielded inconclusive results. This meta-analysis was performed to evaluate the relationships between ESR1 genetic polymorphisms and cerebral infarction risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1, 2013, without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Seven case-control studies were included with a total of 1471 patients with cerebral infarction and 4688 healthy control subjects. Two common single-nucleotide polymorphisms (SNPs) in the ESR1 gene (rs2234693 T>C and rs9340799 A>G) were assessed. Our meta-analysis results revealed that ESR1 genetic polymorphisms might increase the risk of cerebral infarction. Subgroup analysis by SNP type indicated that both rs2234693 and rs9340799 polymorphisms in the ESR1 gene were strongly associated with an increased risk of cerebral infarction. Further subgroup analysis by ethnicity showed significant associations between ESR1 genetic polymorphisms and increased risk of cerebral infarction among both Asians and Caucasians. In the stratified subgroup analysis by gender, the results suggested that ESR1 genetic polymorphisms were associated with an increased risk of cerebral infarction in the female population. However, there were no statistically significant associations between ESR1 genetic polymorphisms and cerebral infarction risk in the male population. Meta-regression analyses also confirmed that gender might be a main source of heterogeneity. Our findings indicate that ESR1 genetic polymorphisms may contribute to the development of cerebral infarction, especially in the female population.

ESR study of free radicals in mango

NASA Astrophysics Data System (ADS)

Kikuchi, Masahiro; Hussain, Mohammad S.; Morishita, Norio; Ukai, Mitsuko; Kobayashi, Yasuhiko; Shimoyama, Yuhei

2010-01-01

An electron spin resonance (ESR) spectroscopic study of radicals induced in irradiated fresh mangoes was performed. Mangoes in the fresh state were irradiated with γ-rays, lyophilized and then crushed into a powder. The ESR spectrum of the powder showed a strong main peak at g = 2.004 and a pair of peaks centered at the main peak. The main peak was detected from both flesh and skin specimens. This peak height gradually decreased during storage following irradiation. On the other hand, the side peaks showed a well-defined dose-response relationship even at 9 days post-irradiation. The side peaks therefore provide a useful means to define the irradiation of fresh mangoes.

Laser readable thermoluminescent radiation dosimeters and methods for producing thereof

DOEpatents

Braunlich, Peter F.; Tetzlaff, Wolfgang

1989-01-01

Thin layer thermoluminescent radiation dosimeters for use in laser readable dosimetry systems, and methods of fabricating such thin layer dosimeters. The thin layer thermoluminescent radiation dosimeters include a thin substrate made from glass or other inorganic materials capable of withstanding high temperatures and high heating rates. A thin layer of a thermoluminescent phoshphor material is heat bonded to the substrate using an inorganic binder such as glass. The dosimeters can be mounted in frames and cases for ease in handling. Methods of the invention include mixing a suitable phosphor composition and binder, both being in particulate or granular form. The mixture is then deposited onto a substrate such as by using mask printing techniques. The dosimeters are thereafter heated to fuse and bond the binder and phosphor to the substrate.

Laser readable thermoluminescent radiation dosimeters and methods for producing thereof

DOEpatents

Braunlich, P.F.; Tetzlaff, W.

1989-04-25

Thin layer thermoluminescent radiation dosimeters for use in laser readable dosimetry systems, and methods of fabricating such thin layer dosimeters are disclosed. The thin layer thermoluminescent radiation dosimeters include a thin substrate made from glass or other inorganic materials capable of withstanding high temperatures and high heating rates. A thin layer of a thermoluminescent phosphor material is heat bonded to the substrate using an inorganic binder such as glass. The dosimeters can be mounted in frames and cases for ease in handling. Methods of the invention include mixing a suitable phosphor composition and binder, both being in particulate or granular form. The mixture is then deposited onto a substrate such as by using mask printing techniques. The dosimeters are thereafter heated to fuse and bond the binder and phosphor to the substrate. 34 figs.

ESR1 and its antagonist fulvestrant in pituitary adenomas.

PubMed

Gao, Hua; Xue, Yake; Cao, Lei; Liu, Qian; Liu, Chunhui; Shan, Xiaosong; Wang, Hongyun; Gu, Yi; Zhang, Yazhuo

2017-03-05

Estrogen has a key role in the pathogenesis of pituitary adenomas (PAs). The study was to evaluate the estrogen receptor alpha (ESR1) level in 289 PAs cases, its association with clinicopathologic features and serving as a target of cancer treatment. In this study, the ESR1 level was evaluated by tissue microarray (TMA). The effect of fulvestrant was determined by an animal model of prolactinoma established by subcutaneous injection of 17β-estradiol in F344 rats. The volume and weight of the pituitary were assessed in the different groups. The effects of fulvestrant on cell proliferation and cell invasion were explored in the pituitary adenoma cell lines GH3 and JT1-1. The ESR1-positive cells rates of 191/289 cases were more than 50%. And ESR1 high level cases (age≥50) were 103/133, and 88/156 in cases (age<50) (X 2  = 14.17, p = 0.0001). The average weight of the pituitary gland in F344 rat tumor model induced by 17-β-estradiol was 38.6 ± 11.2 mg, almost 6 times higher than control group (6.2 ± 1.7 mg). Fulvestrant significantly reduced the weight of the pituitary and its inhibition rate was 68.4 ± 8.3%. TUNEL assay and Western blotting showed that fulvestrant induced apoptotic cell death in vivo and in vitro. PTEN/MAPK signaling pathways were activated in response to fulvestrant treatment in GH3 cells. U0126 partly rescued cell viability of GH3 cells after fulvestrant exposure. ESR1 can be a potential target for PAs, especially for elder GHomas and NFPAs. Fulvestrant may be a new choice for the treatment of PAs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Investigation of radiosterilization feasibility of sulfamethoxazole by ESR spectroscopy

NASA Astrophysics Data System (ADS)

Çolak, Şeyda

2017-12-01

In the present study, the spectroscopic features of the radiolytic intermediates that were produced in gamma-irradiated (5, 10, 25 and 50 kGy) sulfamethoxazole (SMX) have been investigated by electron spin resonance (ESR) spectroscopy and the radiation sterilization feasibility of SMX by ionizing radiation was examined. Gamma-irradiated SMX exhibited a complex ESR spectrum consisting of 13 resonance lines where spectral parameters for the central resonance line were found to be g = 2.0062 and ΔHpp = 0.6 mT. The radiation yield of SMX was calculated to be relatively low (G = 0.1) by ESR spectroscopy and no meaningful difference was observed in the comparison of unirradiated and 50 kGy gamma irradiated SMX by the Fourier transform infrared (FT-IR) technique, confirming that SMX is a radioresistive material. Although SMX could not be accepted to be a good dosimetric material, the identification of irradiated SMX from the unirradiated sample was possible even for the low absorbed radiation doses and for a relatively long time (three months) after the irradiation process. Decay activation energy of the radical species, which is mostly responsible for the central intense resonance line, is calculated to be 45.15 kJ/mol by using the signal intensity decay data derived from annealing studies. Four radical species with different spectroscopic properties were accepted to be responsible for the ESR spectra of gamma-irradiated SMX, by simulation calculations. It is concluded that SMX and SMX-containing drugs can be sterilized by gamma radiation and ESR spectroscopy is an appropriate technique for the characterization of these induced radical intermediates during the gamma irradiation process of SMX. Toxicology tests should also be done for its safe usage.

Identifying the Jaramillo Subchron in cave sediments using ESR

NASA Astrophysics Data System (ADS)

Pares, J. M.; Moreno, D.; Duval, M.

2017-12-01

The Jaramillo Subchron is represented by marine isotope stages 31 to 28, a period that embodies a fundamental shift in the Earth's climate known as the Early-Middle Pleistocene transition (EMPT). Also, this time interval is a critical period in human evolution and therefore identifying the Jaramillo provides an invaluable timeline. The correlation of magnetic chrons to the GPTS in sediments is typically hampered by the lack of a tie-point, as radiometric methods are rarely appropriate. In this study we combine Electron Spin Resonance (ESR) results from quartz grains, and paleomagnetism to identify the Jaramillo Subchron in cave sediments that include artifact-bearing layers. The ESR age estimate is basically derived from the determination of the equivalent dose, which is the laboratory estimate of the total dose absorbed by the sample since the ESR signal has been last reset to zero by sunlight exposure, and the dose rate, which is an estimation of the mean dose annually absorbed by the sample. The magnetostratigraphic study, based on more than 140 specimens over 20 meters-thick sedimentary sequence, results in three major reversals, which are interpreted from top to bottom as the Matuyama-Brunhes boundary and the Jaramillo Subchron. Both sediments and speleothems generally carry stable remanent magnetization directions mostly residing in magnetite, as supported by progressive alternating field (AF) demagnetization and rock magnetism. ESR dating on quartz grains from an 80 cm-thick stratigraphic layer that displays normal polarity gives an age of 0.84±0.12 Ma, consistent within the error with the current ages of the Jaramillo Subchron. Documenting the Jaramillo in fossiliferous sediments is important because it saw the EMPT and associated faunal turnover, as well as the expansion of hominins outside Africa. Also, this study highlights the potential of ESR dating on quartz grains from cave sediments to interpret magnetostratigraphic records.

Prevalence of ESR1 E380Q mutation in tumor tissue and plasma from Japanese breast cancer patients.

PubMed

Takeshita, Takashi; Yamamoto, Yutaka; Yamamoto-Ibusuki, Mutsuko; Sueta, Aiko; Tomiguchi, Mai; Murakami, Keiichi; Omoto, Yoko; Iwase, Hirotaka

2017-11-22

ESR1 mutations have attracted attention as a potentially important marker and treatment target in endocrine therapy-resistant breast cancer patients. The E380Q mutation, which is one of the ESR1 mutations, is associated with estradiol (E2) hypersensitivity, increased DNA binding to the estrogen response element, and E2-independent constitutive trans-activation activity, but its frequency in ESR1 mutations remains unknown. The present study aimed to investigate the E380Q mutation in comparison with the other representative ESR1 mutations. We screened a total of 62 patients (66 tumor tissues and 69 plasma cell-free DNA (cfDNA)) to detect ESR1 mutations (E380Q, Y537S, Y537N, Y537C, and D538G) using droplet-digital polymerase chain reaction. Plasma was collected at more than two points of the clinical course, in whom changes of ESR1 mutations under treatment were investigated. We detected ESR1 mutations in 21% (12/57) of MBCs. The E380Q ESR1 mutation was found in 16% (2/12) and the other ESR1 LBD mutations were five (41.6%) of Y537S, and four each (33.3%) of D538G, Y537N, and Y537C, in 12 ESR1 mutant breast cancer patients. Five tumors had multiple ESR1 mutations: three had double ESR1 mutations; Y537S/E380Q, Y37S/Y537C, and Y537S/D538G, and two had triple ESR1 mutations; Y537S/Y537N/D538G. In plasma cfDNA analysis, the E380Q mutation was not detected, but increases in other ESR1 mutations were detected in 46.2% (6/13) of MBC patients under treatment. We have shown that there are distinct populations of ESR1 mutations in metastatic tissue and plasma. Each ESR1 mutation may have different clinical significance, and it will be necessary to investigate them all.

LOW-COST PERSONNEL DOSIMETER.

DTIC Science & Technology

specification was achieved by simplifying and improving the basic Bendix dosimeter design, using plastics for component parts, minimizing direct labor, and making the instrument suitable for automated processing and assembly. (Author)

ESR and TL studies of irradiated Anatolian laurel leaf (Laurus nobilis L.)

NASA Astrophysics Data System (ADS)

Tepe Çam, Semra; Aydaş, Canan; Engin, Birol; Rabia Yüce, Ülkü; Aydın, Talat; Polat, Mustafa

2012-06-01

Laurel leaf (Laurus nobilis L.) samples that originated from Turkey were analyzed by electron spin resonance (ESR) and thermoluminescence (TL) techniques before and after γ-irradiation. Unirradiated (control) laurel leaf samples exhibit a weak ESR singlet centered at g=2.0020. Besides this central signal were two weak satellite signals situated about 3 mT left and right to it in radiation-induced spectra. The dose-response curve of the radiation-induced ESR signal at g=2.0187 (the left satellite signal) was found to be described well by a power function. Variation of the left satellite ESR signal intensity of irradiated samples at room temperature with time in a long term showed that cellulosic free radicals responsible for the ESR spectrum of laurel leaves were not stable but detectable even after 100 days. Annealing studies at four different temperatures were used to determine the kinetic behavior and activation energy of the radiation-induced cellulosic free radicals responsible from the left satellite signal (g=2.0187) in laurel leaves. TL measurements of the polymineral dust isolated from the laurel leaf samples allowed distinguishing between irradiated and unirradiated samples.

Angular dependence of the nanoDot OSL dosimeter.

PubMed

Kerns, James R; Kry, Stephen F; Sahoo, Narayan; Followill, David S; Ibbott, Geoffrey S

2011-07-01

Optically stimulated luminescent detectors (OSLDs) are quickly gaining popularity as passive dosimeters, with applications in medicine for linac output calibration verification, brachytherapy source verification, treatment plan quality assurance, and clinical dose measurements. With such wide applications, these dosimeters must be characterized for numerous factors affecting their response. The most abundant commercial OSLD is the InLight/OSL system from Landauer, Inc. The purpose of this study was to examine the angular dependence of the nanoDot dosimeter, which is part of the InLight system. Relative dosimeter response data were taken at several angles in 6 and 18 MV photon beams, as well as a clinical proton beam. These measurements were done within a phantom at a depth beyond the build-up region. To verify the observed angular dependence, additional measurements were conducted as well as Monte Carlo simulations in MCNPX. When irradiated with the incident photon beams parallel to the plane of the dosimeter, the nanoDot response was 4% lower at 6 MV and 3% lower at 18 MV than the response when irradiated with the incident beam normal to the plane of the dosimeter. Monte Carlo simulations at 6 MV showed similar results to the experimental values. Examination of the results in Monte Carlo suggests the cause as partial volume irradiation. In a clinical proton beam, no angular dependence was found. A nontrivial angular response of this OSLD was observed in photon beams. This factor may need to be accounted for when evaluating doses from photon beams incident from a variety of directions.

Angular dependence of the nanoDot OSL dosimeter

PubMed Central

Kerns, James R.; Kry, Stephen F.; Sahoo, Narayan; Followill, David S.; Ibbott, Geoffrey S.

2011-01-01

Purpose: Optically stimulated luminescent detectors (OSLDs) are quickly gaining popularity as passive dosimeters, with applications in medicine for linac output calibration verification, brachytherapy source verification, treatment plan quality assurance, and clinical dose measurements. With such wide applications, these dosimeters must be characterized for numerous factors affecting their response. The most abundant commercial OSLD is the InLight∕OSL system from Landauer, Inc. The purpose of this study was to examine the angular dependence of the nanoDot dosimeter, which is part of the InLight system.Methods: Relative dosimeter response data were taken at several angles in 6 and 18 MV photon beams, as well as a clinical proton beam. These measurements were done within a phantom at a depth beyond the build-up region. To verify the observed angular dependence, additional measurements were conducted as well as Monte Carlo simulations in MCNPX.Results: When irradiated with the incident photon beams parallel to the plane of the dosimeter, the nanoDot response was 4% lower at 6 MV and 3% lower at 18 MV than the response when irradiated with the incident beam normal to the plane of the dosimeter. Monte Carlo simulations at 6 MV showed similar results to the experimental values. Examination of the results in Monte Carlo suggests the cause as partial volume irradiation. In a clinical proton beam, no angular dependence was found.Conclusions: A nontrivial angular response of this OSLD was observed in photon beams. This factor may need to be accounted for when evaluating doses from photon beams incident from a variety of directions. PMID:21858992

In situ synthesis of di-n-butyl l-tartrate-boric acid complex chiral selector and its application in chiral microemulsion electrokinetic chromatography.

PubMed

Hu, Shaoqiang; Chen, Yonglei; Zhu, Huadong; Zhu, Jinhua; Yan, Na; Chen, Xingguo

2009-11-06

A novel procedure for in situ assembling a complex chiral selector, di-n-butyl l-tartrate-boric acid complex, by the reaction of di-n-butyl l-tartrate with boric acid in a running buffer was reported and its application in the enantioseparation of beta-blockers and structural related compounds by chiral microemulsion electrokinetic chromatography (MEEKC) has been demonstrated. In order to achieve a good enantioseparation, the effect of dibutyl l-tartrate and sodium tetraborate concentration, surfactant identity and concentration, cosurfactant, buffer pH and composition, organic modifiers, as well as applied voltage and capillary length were investigated. Ten pairs of enantiomers that could not be separated with only dibutyl l-tartrate, obtained good chiral separation using the complex chiral selector; among them, seven pairs could be baseline resolved under optimized experimental conditions. The fixation of chiral centers by the formation of five-membered rings, and being oppositely charged with basic analytes were thought to be the key factors giving the complex chiral selector a superior chiral recognition capability. The effect of the molecular structure of analytes on enantioseparation was discussed in terms of molecular interaction.

Polymer gel dosimeter with AQUAJOINT® as hydrogel matrix

NASA Astrophysics Data System (ADS)

Maeyama, Takuya; Ishida, Yasuhiro; Kudo, Yoshihiro; Fukasaku, Kazuaki; Ishikawa, Kenichi L.; Fukunishi, Nobuhisa

2018-05-01

We report a polymer gel dosimeter based on a new gel matrix (AQUAJOINT®) that is a thermo-irreversible hydrogel formed by mixing two types of water-based liquids at room temperature. Normoxic N-vinylpyrrolidone-based polymer gels were prepared with AQUAJOINT® instead of gelatin. This AQUAJOINT®-based gel dosimeter exhibits a 2.5-fold increase in sensitivity over a gelatin-based gel dosimeter and a linear dose-response in the dose range of 0-8 Gy. This gel has heat resistance in a jar and controlled gel properties such as viscoelastic and mechanical characters, which may be useful for deformable polymer gel dosimetry.

Probing Polymer-Segment Motions By ESR

NASA Technical Reports Server (NTRS)

Tsay, Fun-Dow; Gupta, Amitava

1988-01-01

Molecular origins of mechanical properties and aging processes studied. Rotational motions of segments of poly(methyl methacrylate) molecules studied theoretically and experimentally. Activation energies of these motions as determined from temperature dependencies of ESR spectra agree closely with predictions of theory.

Characterization of a Fiber Optic Coupled Dosimeter for Clinical Electron Beam Dosimetry

DTIC Science & Technology

2010-04-29

2010 2. REPORT TYPE 3. DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE Characterization of a Fiber Optic Coupled Dosimeter for...Fiber Optic Coupled Dosimeter for Clinical Electron Beam Dosimetry. Abstract approved: Camille J. Lodwick Fiber-optic-coupled dosimeters ...Rights Reserved CHARACTERIZATION OF A FIBER OPTIC COUPLED DOSIMETER FOR CLINICAL ELECTRON

Electron Spin Resonance (ESR) Studies of Returned Comet Nucleus Samples

NASA Technical Reports Server (NTRS)

Tsay, Fun-Dow; Kim, Soon Sam; Liang, Ranty H.

1997-01-01

Electron Spin Resonance (ESR) studies have been carried out on organic and inorganic free radicals generated by gamma-ray and/or UV-irradiation and trapped in ice matrices. It is suggested that the concentration of these free radicals together with their thermal stability can be used as an accurate built-in geothermometer and radiation probe for returned comet nucleus sample studies. ESR studies have also been carried out on paramagnetic (Mn(2+), Ti(3+), and Fe(3+)) and ferromagnetic (ferric oxide and metallic iron) centers known to be present in terrestrial and extraterrestrial samples. The presence or absence of these magnetic centers coupled with their characteristic ESR lineshape can be used to investigate the shock effects, quenching/cooling rate and oxidation-reduction conditions in the formation and subsequent evolution of returned comet nucleus samples.

Validation of an Innovative Satellite-Based UV Dosimeter

NASA Astrophysics Data System (ADS)

Morelli, Marco; Masini, Andrea; Simeone, Emilio; Khazova, Marina

2016-08-01

We present an innovative satellite-based UV (ultraviolet) radiation dosimeter with a mobile app interface that has been validated by exploiting both ground-based measurements and an in-vivo assessment of the erythemal effects on some volunteers having a controlled exposure to solar radiation.Both validations showed that the satellite-based UV dosimeter has a good accuracy and reliability needed for health-related applications.The app with this satellite-based UV dosimeter also includes other related functionalities such as the provision of safe sun exposure time updated in real-time and end exposure visual/sound alert. This app will be launched on the global market by siHealth Ltd in May 2016 under the name of "HappySun" and available both for Android and for iOS devices (more info on http://www.happysun.co.uk).Extensive R&D activities are on-going for further improvement of the satellite-based UV dosimeter's accuracy.

Improvements in opti-chromic dosimeters for radiation processing

NASA Astrophysics Data System (ADS)

Humpherys, K. C.; Kantz, A. D.

"Opti-Chromic" dosimeters consisting of radiachromic dye in flourinated polymer tubing have been introduced as a dosimetry system in the range from 10 1 to 5 × 10 4 Gy. Batches of "Opti-Chromic" dosimeters have been produced to evaluate performance under large scale industrial conditions. A systematic study was undertaken to determine the effect of various dosimeter parameters on radiation sensitivity, shelf life, and response characteristics at the higher absorbed doses. These parameters were (A) Type of flourinated polymer tubing; (B) Organic solvent used to activate the radiachromic dye; (C) Concentration of radiachromic dye; (D) Additives to provide proper viscosity, color stability, and high-dose response. Prototype batches were produced and experimental dosimeters exposed to a range of absorbed doses and the response measured as a function of shelf life and dose. The results of the study are presented, and an improved formulation recommended for application to Food Processing. Other formulations may be of value in specific requirements of sensitivity or temperature.

Thin thermoluminescent dosimeter and method of making same

DOEpatents

Simons, Gale G.; DeBey, Timothy M.

1987-01-01

An improved thermoluminescent ionizing radiation dosimeter of solid, extremely thin construction for more accurate low energy beta dosimetry is provided, along with a method of fabricating the dosimeter. In preferred forms, the dosimeter is a composite including a backing support (which may be tissue equivalent) and a self-sustaining body of solid thermoluminescent material such as LiF having a thickness of less than about 0.25 millimeters and a volume of at least about 0.0125 mm.sup.3. In preferred fabrication procedures, an initially thick (e.g., 0.89 millimeters) TLD body is wet sanded using 600 grit or less sandpaper to a thickness of less than about 0.25 millimeters, followed by adhesively attaching the sanded body to an appropriate backing. The sanding procedure permits routine production of extremely thin (about 0.05 millimeters) TLD bodies, and moreover serves to significantly reduce non-radiation-induced thermoluminescence. The composite dosimeters are rugged in use and can be subjected to annealing temperatures for increased accuracy.

Feasibility Study on Applying Radiophotoluminescent Glass Dosimeters for CyberKnife SRS Dose Verification

PubMed Central

Hsu, Shih-Ming; Hung, Chao-Hsiung; Liao, Yi-Jen; Fu, Hsiao-Mei; Tsai, Jo-Ting

2017-01-01

CyberKnife is one of multiple modalities for stereotactic radiosurgery (SRS). Due to the nature of CyberKnife and the characteristics of SRS, dose evaluation of the CyberKnife procedure is critical. A radiophotoluminescent glass dosimeter was used to verify the dose accuracy for the CyberKnife procedure and validate a viable dose verification system for CyberKnife treatment. A radiophotoluminescent glass dosimeter, thermoluminescent dosimeter, and Kodak EDR2 film were used to measure the lateral dose profile and percent depth dose of CyberKnife. A Monte Carlo simulation for dose verification was performed using BEAMnrc to verify the measured results. This study also used a radiophotoluminescent glass dosimeter coupled with an anthropomorphic phantom to evaluate the accuracy of the dose given by CyberKnife. Measurements from the radiophotoluminescent glass dosimeter were compared with the results of a thermoluminescent dosimeter and EDR2 film, and the differences found were less than 5%. The radiophotoluminescent glass dosimeter has some advantages in terms of dose measurements over CyberKnife, such as repeatability, stability, and small effective size. These advantages make radiophotoluminescent glass dosimeters a potential candidate dosimeter for the CyberKnife procedure. This study concludes that radiophotoluminescent glass dosimeters are a promising and reliable dosimeter for CyberKnife dose verification with clinically acceptable accuracy within 5%. PMID:28046056

RNA-based determination of ESR1 and HER2 expression and response to neoadjuvant chemotherapy.

PubMed

Denkert, C; Loibl, S; Kronenwett, R; Budczies, J; von Törne, C; Nekljudova, V; Darb-Esfahani, S; Solbach, C; Sinn, B V; Petry, C; Müller, B M; Hilfrich, J; Altmann, G; Staebler, A; Roth, C; Ataseven, B; Kirchner, T; Dietel, M; Untch, M; von Minckwitz, G

2013-03-01

Hormone and human epidermal growth factor receptor 2 (HER2) receptors are the most important breast cancer biomarkers, and additional objective and quantitative test methods such as messenger RNA (mRNA)-based quantitative analysis are urgently needed. In this study, we investigated the clinical validity of RT-PCR-based evaluation of estrogen receptor (ESR1) and HER2 mRNA expression. A total of 1050 core biopsies from two retrospective (GeparTrio, GeparQuattro) and one prospective (PREDICT) neoadjuvant studies were evaluated by quantitative RT-PCR for ESR1 and HER2. ESR1 mRNA was significantly predictive for reduced response to neoadjuvant chemotherapy in univariate and multivariate analysis in all three cohorts. The complete pathologically documented response (pathological complete response, pCR) rate for ESR1+/HER2- tumors was 7.3%, 8.0% and 8.6%; for ESR1-/HER2- tumors it was 34.4%, 33.7% and 37.3% in GeparTrio, GeparQuattro and PREDICT, respectively (P < 0.001 in each cohort). In the Kaplan-Meier analysis in GeparTrio patients with ESR1+/HER2- tumors had the best prognosis, compared with ESR1-/HER2- and ESR1-/HER2+ tumors [disease-free survival (DFS): P < 0.0005, overall survival (OS): P < 0.0005]. Our results suggest that mRNA levels of ESR1 and HER2 predict response to neoadjuvant chemotherapy and are significantly associated with long-term outcome. As an additional option to standard immunohistochemistry and gene-array-based analysis, quantitative RT-PCR analysis might be useful for determination of the receptor status in breast cancer.

Electron microscopy and computed microtomography studies of in vivo implanted mini-TL dosimeters.

PubMed

Strand, S E; Strandh, M; Spanne, P

1993-01-01

The need for direct methods of measuring the absorbed dose in vivo increases for systemic radiation therapy, and in more sophisticated methodologies developed for radioimmunotherapy. One method suggested is the use of mini-thermoluminescent dosimeters (TLD). Recent reports indicate a marked loss of signal when the dosimeters are used in vivo. We investigated the exterior surface of the dosimeters with scanning electron microscopy and the interior dosimeter volume with computed microtomography. The results show that the dosimeters initially have crystals uniformly embedded in the teflon matrix, with some of them directly exposed to the environment. After incubation in gel, holes appear in the dosimeter matrix where the crystals should have been. The computed microtomographic images show that crystals remain in the interior of the matrix, producing the remaining signal. We conclude that these dosimeters should be very carefully handled, and for practical use of mini-TLDs in vivo the dosimeters should be calibrated in equivalent milieus. An alternative solution to the problem of decreased TL efficiency, would be to coat the dosimeters with a thin layer, of Teflon, or other suitable material.

ESR analysis of natural and gamma irradiated coriander (Coriandrum sativum L.) seeds

NASA Astrophysics Data System (ADS)

Sezer, M. Özgür; Kaplan, Necati; Sayin, Ulku

2017-12-01

Electron spin resonance (ESR) is a powerful technique to detect radicals trapped in cellulosic food products and has been suggested as a useful method for identification of irradiated herbal foodstuffs. Coriander spice which has important medicinal properties was investigated using ESR spectroscopy. Radicals in natural and irradiated coriander samples were determined at room temperature. ESR spectra of natural sample were characterized by a single central signal with ? value and gamma irradiation produced satellite peaks attributed to cellulose-like radical which is used as a marker for detection of irradiated cellulosic plant products. The spectroscopic splitting values of radicals were determined. Dose dependency and stability of this center were analyzed by dose response and kinetic measurements. The reported results about activation energy, thermal life time and dose response relationship of the cellulose-like radical accurately prove that ESR can be used for identification of irradiated coriander spice seeds.

An ESR protocol based on relaxation phenomena of irradiated Japanese pepper

NASA Astrophysics Data System (ADS)

Ukai, Mitsuko; Nakamura, Hideo; Shimoyama, Yuhei

2006-03-01

We found various free radicals in a commercially available pepper in Japan before and after irradiation using electron spin resonance (ESR) spectroscopy. The typical ESR spectrum of the pepper consists of a sextet centered at g = 2.0, a singlet at the same g-value and a singlet at g = 4.0. Upon gamma ray irradiation, a new pair of signals appeared in the pepper. The progressive saturation behavior (PSB) at various microwave power levels indicated quite different relaxation behaviors of those radicals. Namely, the peak intensity of the organic free radical component decreases in a monotonic fashion, whereas the Mn 2+ and Fe 3+ ESR signals substantially keep constant. This reflects the evidence of three independent radicals in the pepper before irradiation. The PSB of the pair peaks as induced by irradiation possessed quite different PSB from that of the free radical located at g = 2.0. We proposed a new protocol for the ESR detection of irradiated foods by the PSB method at different microwave power levels. This would call for a major modification of the CEN protocol in European Union.

Clinical significance of ESR1 gene copy number changes in breast cancer as measured by fluorescence in situ hybridisation.

PubMed

Lin, Ching-Hung; Liu, Jacqueline M; Lu, Yen-Shen; Lan, Chieh; Lee, Wei-Chung; Kuo, Kuan-Ting; Wang, Chung-Chieh; Chang, Dwan-Ying; Huang, Chiun-Sheng; Cheng, Ann-Lii

2013-02-01

The ESR1 gene encodes for oestrogen receptor (ER) α, which plays a crucial role in mammary carcinogenesis and clinical outcome in patients with breast cancer. However, the clinical significance of the ESR1 gene copy number change for breast cancer has not been clarified. ESR1 gene copy number was determined by fluorescence in situ hybridisation (FISH) on tissue sections. A minimum of 20 tumour cells were counted per section, and a FISH ratio of ESR1 gene to CEP6 ≥ 2.0 was considered ESR1 amplification. A ratio >1.2 but <2.0 was considered ESR1 gain. The ESR1 copy number was further measured by quantitative real-time PCR (Q-PCR) with ASXL2 as a reference. FISH revealed ESR1 amplification in six cases (4.0%) and ESR1 gain in 13 cases (8.7%) from a total of 150 cases. ESR1 gain and amplification were more common in older patients (p<0.001), and correlated well with ER protein expression (p=0.03) measured by immunohistochemistry, and ESR1 copy number (p<0.001) measured by Q-PCR. Furthermore, the multivariate analysis revealed that ESR1 amplification was associated with a shorter disease-free survival (HR=5.56, p=0.03) and a shorter overall survival (HR=5.11, p=0.04). In general, the frequency of ESR1 amplification in breast cancer is low when measured by FISH in large sections. ESR1 gain and amplification in breast cancer may be associated with older age and poorer outcomes.

ESR dating pleistocene barnacles from BC and Maine: a new method for tracking sea level change.

PubMed

Blackwell, Bonnie A B; Gong, J J J; Skinner, Anne R; Blais-Stevens, Andrée; Nelson, Robert E; Blickstein, Joel I B

2010-02-01

Barnacles have never been successfully dated by electron spin resonance (ESR). Living mainly in the intertidal zone, barnacles die when sea level changes cause their permanent exposure. Thus, dating the barnacles dates past sea level changes. From this, we can measure apparent sea level changes that occur due to ocean volume changes, crustal isostasy, and tectonics. ESR can date aragonitic mollusc shells ranging in age from 5 ka to at least 500 ka. By modifying the standard ESR method for molluscs to chemically dissolve 20 microm from off the shells, six barnacle samples from Norridgewock, Maine, and Khyex River, British Columbia, were tested for suitability for ESR dating. Due to Mn2+ interference peaks, the four Maine barnacle samples were not datable by ESR. Two barnacles from BC, which lacked Mn2+ interference, yielded a mean ESR age of 15.1 +/- 1.0 ka. These ages agree well with 14C dates on the barnacles themselves and wood in the overlying glaciomarine sediment. Although stability tests to calculate the mean dating signal lifetime and more ESR calibration tests against other barnacles of known age are needed to ensure the method's accuracy, ESR can indeed date Balanus, and thus, sea level changes.

Applicability of Glass Dosimeters for In-vivo Dosimetry in Brachytherapy

NASA Astrophysics Data System (ADS)

Moon, Sun Young; Son, Jaeman; Yoon, Myonggeun; Jeang, EunHee; Lim, Young Kyung; Chung, Weon Kyu; Kim, Dong Wook

2018-06-01

During brachytherapy, confirming the dose delivered is very important in order to prevent radiation-associated side effects. Therefore, we aimed to confirm the accuracy of dose delivery near the source by inserting glass dosimeters within the applicator. We created an alternative pelvic phantom with the same shape and internal structures as the usual patient. In addition, we created a tandem for insertion of the glass dosimeters and measured the dose near the source by inserting the glass dosimeters into the tandem and evaluating the accuracy of the dwell position and time through the dose near the source. Errors between the values obtained from the five glass dosimeters and the values from the treatment planning system were -6.27, -2.1, -4.18, 6.31, and -0.39%, respectively. The mean error was 3.85%. This value was acceptable considering that the error of the glass dosimeter itself is approximately 3%. Even though a complement of the applicator and the error calibration is required in order to apply this technique clinically, we believe that radiation accidents and overdoses can be prevented through in-vivo dosimetry using a glass dosimeter for brachytherapy.

Electronic gating circuit and ultraviolet laser excitation permit improved dosimeter sensitivity

NASA Technical Reports Server (NTRS)

Eggenberger, D.; King, D.; Longnecker, A.; Schutt, D.

1968-01-01

Standard dosimeter reader, modified by adding an electronic gating circuit to trigger the intensity level photomultiplier, increases readout sensitivity of photoluminescent dosimeter systems. The gating circuit is controlled by a second photomultiplier which senses a short ultraviolet pulse from a laser used to excite the dosimeter.

Method and apparatus for reading free falling dosimeter punchcodes

DOEpatents

Langsted, J.M.

1992-12-22

A punchcode reader is provided for reading data encoded in a punchcode hole array on a dosimeter. The dosimeter falls through a passage in the reader containing photosensor detectors disposed along the passage which provide output signals to a microprocessor. The signals are processed to determine the orientation of the dosimeter in the reader, the location and state of punchcode holes in a two row array thereby decoding the encoded data. Multiple rate of fall calculations are made, and if appropriate matching of the punchcode array is not obtained in three tries, an error signal is output to the operator. The punchcode reader also provides for storage of data from multiple dosimeters passed through the reader, and for the output of decoded data to an external display or a computer for further processing. 8 figs.

Method and apparatus for reading free falling dosimeter punchcodes

DOEpatents

Langsted, James M.

1992-12-22

A punchcode reader is provided for reading data encoded in a punchcode hole array on a dosimeter. The dosimeter falls through a passage in the reader containing photosensor detectors disposed along the passage which provide output signals to a microprocessor. The signals are processed to determine the orientation of the dosimeter in the reader, the location and state of punchcode holes in a two row array thereby decoding the encoded data. Multiple rate of fall calculations are made, and if appropriate matching of the punchcode array is not obtained in three tries, an error signal is outputted to the operator. The punchcode reader also provides for storage of data from multiple dosimeters passed through the reader, and for the output of decoded data to an external display or a computer for further processing.

Angular dependence of the nanoDot OSL dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerns, James R.; Kry, Stephen F.; Sahoo, Narayan

Purpose: Optically stimulated luminescent detectors (OSLDs) are quickly gaining popularity as passive dosimeters, with applications in medicine for linac output calibration verification, brachytherapy source verification, treatment plan quality assurance, and clinical dose measurements. With such wide applications, these dosimeters must be characterized for numerous factors affecting their response. The most abundant commercial OSLD is the InLight/OSL system from Landauer, Inc. The purpose of this study was to examine the angular dependence of the nanoDot dosimeter, which is part of the InLight system. Methods: Relative dosimeter response data were taken at several angles in 6 and 18 MV photon beams, asmore » well as a clinical proton beam. These measurements were done within a phantom at a depth beyond the build-up region. To verify the observed angular dependence, additional measurements were conducted as well as Monte Carlo simulations in MCNPX. Results: When irradiated with the incident photon beams parallel to the plane of the dosimeter, the nanoDot response was 4% lower at 6 MV and 3% lower at 18 MV than the response when irradiated with the incident beam normal to the plane of the dosimeter. Monte Carlo simulations at 6 MV showed similar results to the experimental values. Examination of the results in Monte Carlo suggests the cause as partial volume irradiation. In a clinical proton beam, no angular dependence was found. Conclusions: A nontrivial angular response of this OSLD was observed in photon beams. This factor may need to be accounted for when evaluating doses from photon beams incident from a variety of directions.« less

Reflectivity quenching of ESR multilayer polymer film reflector in optically bonded scintillator arrays

NASA Astrophysics Data System (ADS)

Loignon-Houle, Francis; Pepin, Catherine M.; Charlebois, Serge A.; Lecomte, Roger

2017-04-01

The 3M-ESR multilayer polymer film is a widely used reflector in scintillation detector arrays. As specified in the datasheet and confirmed experimentally by measurements in air, it is highly reflective (> 98 %) over the entire visible spectrum (400-1000 nm) for all angles of incidence. Despite these outstanding characteristics, it was previously found that light crosstalk between pixels in a bonded LYSO scintillator array with ESR reflector can be as high as ∼30-35%. This unexplained light crosstalk motivated further investigation of ESR optical performance. Analytical simulation of a multilayer structure emulating the ESR reflector showed that the film becomes highly transparent to incident light at large angles when surrounded on both sides by materials of refractive index higher than air. Monte Carlo simulations indicate that a considerable fraction (∼25-35%) of scintillation photons are incident at these leaking angles in high aspect ratio LYSO scintillation crystals. The film transparency was investigated experimentally by measuring the scintillation light transmission through the ESR film sandwiched between a scintillation crystal and a photodetector with or without layers of silicone grease. Strong light leakage, up to nearly 30%, was measured through the reflector when coated on both sides with silicone, thus elucidating the major cause of light crosstalk in bonded arrays. The reflector transparency was confirmed experimentally for angles of incidence larger than 60 ° using a custom designed setup allowing illumination of the bonded ESR film at selected grazing angles. The unsuspected ESR film transparency can be beneficial for detector arrays exploiting light sharing schemes, but it is highly detrimental for scintillator arrays designed for individual pixel readout.

Dosimeter for monitoring vapors and aerosols of organic compounds

DOEpatents

Vo-Dinh, Tuan

1987-01-01

A dosimeter is provided for collecting and detecting vapors and aerosols of organic compounds. The dosimeter comprises a lightweight, passive device that can be conveniently worn by a person as a badge or placed at a stationary location. The dosimeter includes a sample collector comprising a porous web treated with a chemical for inducing molecular displacement and enhancing phosphorescence. Compounds are collected onto the web by molecular diffusion. The web also serves as the sample medium for detecting the compounds by a room temperature phosphorescence technique.

Characterization of Thymol blue Radiochromic dosimeters for high dose applications

NASA Astrophysics Data System (ADS)

Aldweri, Feras M.; Abuzayed, Manar H.; Al-Ajaleen, Musab S.; Rabaeh, Khalid A.

2018-03-01

Thymol blue (TB) solutions and Thymol blue Polyvinyl Alcohol (TB-PVA) films have been introduced as Radiochromic dosimeter for high dose applications. The dosimeters were irradiated with gamma ray (60Co source) from 5 to 30 kGy for film, and from 0.150 kGy to 4 kGy for solution. The optical density of unirradiated and irradiated TB solution as well as TB-PVA film dosimeters were studied in terms of absorbance at 434 nm using UV/VIS spectrophotometer. The effects of scan temperature, light pre-gamma irradiation, dose rate, relative humidity and stability of the absorbance of solutions and films after irradiation were investigated. We found the dose sensitivity of TB solution and TB-PVA film dosimeters increases significantly with increases of the absorbed dose as well as with the increases of TB dye concentrations. The useful dose range of developed TB solutions and TB-PVA films dosimeters is in the range 0.125-1 kGy and of 5-20 kGy, respectively.

Method and apparatus for reading free falling dosimeter punchcodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langsted, J.M.

1992-12-22

A punchcode reader is provided for reading data encoded in a punchcode hole array on a dosimeter. The dosimeter falls through a passage in the reader containing photosensor detectors disposed along the passage which provide output signals to a microprocessor. The signals are processed to determine the orientation of the dosimeter in the reader, the location and state of punchcode holes in a two row array thereby decoding the encoded data. Multiple rate of fall calculations are made, and if appropriate matching of the punchcode array is not obtained in three tries, an error signal is output to the operator.more » The punchcode reader also provides for storage of data from multiple dosimeters passed through the reader, and for the output of decoded data to an external display or a computer for further processing. 8 figs.« less

Dosimeter for monitoring vapors and aerosols of organic compounds

DOEpatents

Vo-Dinh, T.

1987-07-14

A dosimeter is provided for collecting and detecting vapors and aerosols of organic compounds. The dosimeter comprises a lightweight, passive device that can be conveniently worn by a person as a badge or placed at a stationary location. The dosimeter includes a sample collector comprising a porous web treated with a chemical for inducing molecular displacement and enhancing phosphorescence. Compounds are collected onto the web by molecular diffusion. The web also serves as the sample medium for detecting the compounds by a room temperature phosphorescence technique. 7 figs.

ESR response of phenol compounds for dosimetry of gamma photon beams

NASA Astrophysics Data System (ADS)

Marrale, M.; Longo, A.; Panzeca, S.; Gallo, S.; Principato, F.; Tomarchio, E.; Parlato, A.; Buttafava, A.; Dondi, D.; Zeffiro, A.

2014-11-01

In the present paper we investigate the features of IRGANOX® 1076 phenols as a material for electron spin resonance (ESR) dosimetry. We experimentally analyzed the ESR response of pellets of IRGANOX® 1076 phenols irradiated with 60Co photons. The best experimental parameters (modulation amplitude and microwave power) for dosimetric applications have been obtained. The dependence of ESR signal as function of γ dose is found to be linear in the dose range studied (12-60 Gy) and the lowest measurable dose is found to be of the order of 1 Gy. The signal after irradiation is very stable in the first thirty days. From the point of view of the tissue equivalence, these materials have mass energy absorption coefficient values comparable with those of soft tissue.

Low bioavailability of ergotamine tartrate after oral and rectal administration in migraine sufferers.

PubMed Central

Ibraheem, J J; Paalzow, L; Tfelt-Hansen, P

1983-01-01

Fifteen migraine patients were administered 2 mg ergotamine tartrate in a partial cross-over design as a single, oral tablet, rectal suppository and rectal solution. Eight of these patients were in a previous investigation given 0.5 mg ergotamine tartrate intravenously. The blood samples were taken up to 54 h after oral and suppository while it was followed for only 3 h after rectal solution. The chemical analysis was performed by applying h.p.l.c. method with a limit of sensitivity of 0.1 ng/ml ergotamine base in plasma. No ergotamine was detected in the blood samples after the oral route, whereas small and very variable quantities was found in blood after the rectal route. Regular calculation of bioavailability could therefore not be performed. An estimate of the maximal possible bioavailability was found to yield a mean value of 2% (tablets); 5% (suppositories) and 6% (rectal solution). Rectal solution elicited faster absorption and the extent of absorption was significantly higher (P less than 0.05) than for the suppository. PMID:6419759

Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer

PubMed Central

Schiavon, Gaia; Hrebien, Sarah; Garcia-Murillas, Isaac; Cutts, Rosalind J; Pearson, Alex; Tarazona, Noelia; Fenwick, Kerry; Kozarewa, Iwanka; Lopez-Knowles, Elena; Ribas, Ricardo; Nerurkar, Ashutosh; Osin, Peter; Chandarlapaty, Sarat; Martin, Lesley-Ann; Dowsett, Mitch; Smith, Ian E; Turner, Nicholas C.

2016-01-01

Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AI). We developed ultra-high sensitivity multiplexed digital PCR assays for ESR1 mutations in circulating tumor DNA (ctDNA) and used these to investigate the clinical relevance and origin of ESR1 mutations in a cohort of 171 women with advanced breast cancer. ESR1 mutation status in ctDNA showed high concordance with contemporaneous tumor biopsies, and could be assessed in samples shipped at room temperature in preservative tubes without loss of accuracy. ESR1 mutations were found exclusively in patients with estrogen receptor positive breast cancer previously exposed to AI. Patients with ESR1 mutations had a substantially shorter progression-free survival on subsequent AI-based therapy (HR 3.1, 95%CI 1.9-23.1, log rank p=0.0041). ESR1 mutation prevalence differed markedly between patients that were first exposed to AI during the adjuvant and metastatic settings (5.8% (3/52) vs 36.4% (16/44) respectively, p=0.0002). In an independent cohort, ESR1 mutations were identified in 0% (0/32, 95%CI 0-10.9%) tumor biopsies taken after progression on adjuvant AI. In a patient with serial samples taken during metastatic treatment, ESR1 mutation was selected during metastatic AI therapy, to become the dominant clone in the cancer. ESR1 mutations can be robustly identified with ctDNA analysis and predict for resistance to subsequent AI therapy. ESR1 mutations are rarely acquired during adjuvant AI therapy, but are commonly selected by therapy for metastatic disease, providing evidence that the mechanisms of resistance to targeted therapy may be substantially different between the treatment of micro-metastatic and overt metastatic cancer. PMID:26560360

Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer.

PubMed

Schiavon, Gaia; Hrebien, Sarah; Garcia-Murillas, Isaac; Cutts, Rosalind J; Pearson, Alex; Tarazona, Noelia; Fenwick, Kerry; Kozarewa, Iwanka; Lopez-Knowles, Elena; Ribas, Ricardo; Nerurkar, Ashutosh; Osin, Peter; Chandarlapaty, Sarat; Martin, Lesley-Ann; Dowsett, Mitch; Smith, Ian E; Turner, Nicholas C

2015-11-11

Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AIs). We developed ultra high-sensitivity multiplex digital polymerase chain reaction assays for ESR1 mutations in circulating tumor DNA (ctDNA) and investigated the clinical relevance and origin of ESR1 mutations in 171 women with advanced breast cancer. ESR1 mutation status in ctDNA showed high concordance with contemporaneous tumor biopsies and was accurately assessed in samples shipped at room temperature in preservative tubes. ESR1 mutations were found exclusively in estrogen receptor-positive breast cancer patients previously exposed to AI. Patients with ESR1 mutations had a substantially shorter progression-free survival on subsequent AI-based therapy [hazard ratio, 3.1; 95% confidence interval (CI), 1.9 to 23.1; P = 0.0041]. ESR1 mutation prevalence differed markedly between patients who were first exposed to AI during the adjuvant and metastatic settings [5.8% (3 of 52) versus 36.4% (16 of 44), respectively; P = 0.0002]. In an independent cohort, ESR1 mutations were identified in 0% (0 of 32; 95% CI, 0 to 10.9) tumor biopsies taken after progression on adjuvant AI. In a patient with serial sampling, ESR1 mutation was selected during metastatic AI therapy to become the dominant clone in the cancer. ESR1 mutations can be robustly identified with ctDNA analysis and predict for resistance to subsequent AI therapy. ESR1 mutations are rarely acquired during adjuvant AI but are commonly selected by therapy for metastatic disease, providing evidence that mechanisms of resistance to targeted therapy may be substantially different between the treatment of micrometastatic and overt metastatic cancer. Copyright © 2015, American Association for the Advancement of Science.

Neonatal uterine and vaginal cell proliferation and adenogenesis are independent of estrogen receptor 1 (ESR1) in the mouse.

PubMed

Nanjappa, Manjunatha K; Medrano, Theresa I; March, Amelia G; Cooke, Paul S

2015-03-01

Neonatal uterus and vagina express estrogen receptor 1 (ESR1) and respond mitogenically to exogenous estrogens. However, neonatal ovariectomy does not inhibit preweaning uterine cell proliferation, indicating that this process is estrogen independent. Extensive literature suggests that ESR1 can be activated by growth factors in a ligand-independent manner and drive uterine cell proliferation. Alternatively, neonatal uterine cell proliferation could be ESR1 independent despite its obligatory role in adult luminal epithelial proliferation. To determine ESR1's role in uterine and vaginal development, we analyzed cell proliferation, apoptosis, and uterine gland development (adenogenesis) in wild-type (WT) and Esr1 knockout (Esr1KO) mice from Postnatal Day 2 to Postnatal Day 60. Uterine and vaginal cell proliferation, apoptosis, and uterine adenogenesis were comparable in WT and Esr1KO mice before weaning. By Days 29-60, glands had regressed, and uterine cell proliferation was reduced in Esr1KO mice in contrast to continued adenogenesis and proliferation in WT. Apoptosis in Esr1KO uterine epithelium was not increased compared to WT at any age, indicating that differences in cell proliferation, rather than apoptosis, cause divergence of uterine size in these two groups at puberty. Similarly, vaginal epithelial proliferation was reduced, and the epithelium became atrophic in Esr1KO mice by 29 days of age and later in Esr1KO mice. These results indicate that preweaning uterine and vaginal development is ESR1 independent but becomes dependent on ESR1 by Day 29 on. It is not yet clear what mechanisms drive preweaning vaginal and uterine development, but ligand-independent activation of ESR1 is not involved. © 2015 by the Society for the Study of Reproduction, Inc.

Comparison of ESR1 Mutations in Tumor Tissue and Matched Plasma Samples from Metastatic Breast Cancer Patients.

PubMed

Takeshita, Takashi; Yamamoto, Yutaka; Yamamoto-Ibusuki, Mutsuko; Tomiguchi, Mai; Sueta, Aiko; Murakami, Keiichi; Omoto, Yoko; Iwase, Hirotaka

2017-10-01

ESR1 mutation in circulating cell-free DNA (cfDNA) is emerging as a noninvasive biomarker of acquired resistance to endocrine therapy, but there is a paucity of data comparing the status of ESR1 gene in cfDNA with that in its corresponding tumor tissue. The objective of this study is to validate the degree of concordance of ESR1 mutations between plasma and tumor tissue. ESR1 ligand-binding domain mutations Y537S, Y537N, Y537C, and D538G were analyzed using droplet digital PCR in 35 patients with metastatic breast cancer (MBC) (35 tumor tissue samples and 67 plasma samples). Of the 35 paired samples, 26 (74.3%) were concordant: one patient had detectable ESR1 mutations both plasma (ESR1 Y537S/Y537N) and tumor tissue (ESR1 Y537S/Y537C), and 25 had WT ESR1 alleles in both. Nine (25.7%) had discordance between the plasma and tissue results: five had mutations detected only in their tumor tissue (two Y537S, one Y537C, one D538G, and one Y537S/Y537N/D538G), and four had mutations detected only in their plasma (one Y537S, one Y537N, and two Y537S/Y537N/D538G). Furthermore, longitudinal plasma samples from 19 patients were used to assess changes in the presence of ESR1 mutations during treatment. Eleven patients had cfDNA ESR1 mutations over the course of treatment. A total of eight of 11 patients with MBC with cfDNA ESR1 mutations (72.7%) had the polyclonal mutations. We have shown the independent distribution of ESR1 mutations between plasma and tumor tissue in 35 patients with MBC. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

System for use with solid state dosimeter

DOEpatents

Miller, Steven D.; McDonald, Joseph C.; Eichner, Fred N.; Tomeraasen, Paul L.

1990-01-01

The present invention constitutes a system for determining the amounts of ionizing radiation to which dosimeters using thermoluminescent materials have been exposed. In accordance with this system, the thermoluminescent materials which comprise the dosimeters are first cooled by contact with a cryogenic substance such as liquified nitrogen. The thermoluminescent materials are then optically stimulated by exposure to ultraviolet light. Thereafter, the amounts of visible light emitted by the thermoluminescent materials are detected and counted as the materials are allowed to warm up to room temperature. The amounts of luminescence exhibited by the materials are related to radiation exposure and provide a sensitive measure of radiation dosage. It has been discovered that the above procedure is most effective when heavily doped thermoluminescent materials are used and that the procedure allows many useful plastic materials to now be employed in dosimeter constructions.

System for use with solid state dosimeter

DOEpatents

Miller, S.D.; McDonald, J.C.; Eichner, F.N.; Tomeraasen, P.L.

1990-09-04

The present invention constitutes a system for determining the amounts of ionizing radiation to which dosimeters using thermoluminescent materials have been exposed. In accordance with this system, the thermoluminescent materials which comprise the dosimeters are first cooled by contact with a cryogenic substance such as liquefied nitrogen. The thermoluminescent materials are then optically stimulated by exposure to ultraviolet light. Thereafter, the amounts of visible light emitted by the thermoluminescent materials are detected and counted as the materials are allowed to warm up to room temperature. The amounts of luminescence exhibited by the materials are related to radiation exposure and provide a sensitive measure of radiation dosage. It has been discovered that the above procedure is most effective when heavily doped thermoluminescent materials are used and that the procedure allows many useful plastic materials to now be employed in dosimeter constructions. 3 figs.

Dosimetric characteristics of PASSAG as a new polymer gel dosimeter with negligible toxicity

NASA Astrophysics Data System (ADS)

Farhood, Bagher; Abtahi, Seyed Mohammad Mahdi; Geraily, Ghazale; Ghorbani, Mehdi; Mahdavi, Seied Rabi; Zahmatkesh, Mohammad Hasan

2018-06-01

Despite many advantages of polymer gel dosimeters, their clinical use is only not realized now. Toxicity of polymer gel dosimeters can be considered as one of their main limitations for use in routine clinical applications. In the current study, a new polymer gel dosimeter is introduced with negligible toxicity. For this purpose, 2-Acrylamido-2-Methy-1-PropaneSulfonic acid (AMPS) sodium salt monomer was replaced instead of acrylamide monomer used in PAGAT gel dosimeter by using %6 T and %50 C to the gel formula and the new formulation is called PASSAG (Poly AMPS Sodium Salt and Gelatin) polymer gel dosimeter. The irradiation of gel dosimeters was carried out using a Co-60 therapy machine. MRI technique was used to quantify the dose responses of the PASSAG gel dosimeter. Then, the MRI responses (R2) of the gel dosimeter was analyzed at different dose values, post-irradiation times, and scanning temperatures. The results showed that the new gel formulation has a negligible toxicity and it is also eco-friendly. In addition, carcinogenicity and genetic toxicity tests are negative for the monomer used in PASSAG. The radiological properties of PASSAG gel dosimeter showed that this substance can be considered as a soft tissue/water equivalent material. Furthermore, dosimetric evaluation of the new polymer gel dosimeter revealed an excellent linear R2-dose response in the evaluated dose range (0-15 Gy). The R2-dose sensitivity and dose resolution of PASSAG gel dosimeter were 0.081 s-1Gy-1 (in 0-15 Gy dose range) and 1 Gy (in 0-10 Gy dose range), respectively. Moreover, it was shown that the R2-dose sensitivity and dose resolution of the new gel dosimeter improves over time after irradiation. It was also found that the R2 response of the PASSAG gel dosimeter has less dependency to the 18, 20, and 24 °C scanning temperature in comparison to that of room temperature (22 °C).

Antioxidant effect of green tea on polymer gel dosimeter

NASA Astrophysics Data System (ADS)

Samuel, E. J. J.; Sathiyaraj, P.; Deena, T.; Kumar, D. S.

2015-01-01

Extract from Green Tea (GTE) acts as an antioxidant in acrylamide based polymer gel dosimeter. In this work, PAGAT gel was used for investigation of antioxidant effect of GTE.PAGAT was called PAGTEG (Polyacrylamide green tea extract gel dosimeter) after adding GTE. Free radicals in water cause pre polymerization of polymer gel before irradiation. Polyphenols from GTE are highly effective to absorb the free radicals in water. THPC is used as an antioxidant in polymer gel dosimeter but here we were replaced it by GTE and investigated its effect by spectrophotometer. GTE added PAGAT samples response was lower compared to THPC added sample. To increase the sensitivity of the PAGTEG, sugar was added. This study confirmed that THPC was a good antioxidant for polymer gel dosimeter. However, GTE also can be used as an antioxidant in polymer gel if use less quantity (GTE) and add sugar as sensitivity enhancer.

Activating ESR1 Mutations Differentially Affect the Efficacy of ER Antagonists.

PubMed

Toy, Weiyi; Weir, Hazel; Razavi, Pedram; Lawson, Mandy; Goeppert, Anne U; Mazzola, Anne Marie; Smith, Aaron; Wilson, Joanne; Morrow, Christopher; Wong, Wai Lin; De Stanchina, Elisa; Carlson, Kathryn E; Martin, Teresa S; Uddin, Sharmeen; Li, Zhiqiang; Fanning, Sean; Katzenellenbogen, John A; Greene, Geoffrey; Baselga, José; Chandarlapaty, Sarat

2017-03-01

Recent studies have identified somatic ESR1 mutations in patients with metastatic breast cancer and found some of them to promote estrogen-independent activation of the receptor. The degree to which all recurrent mutants can drive estrogen-independent activities and reduced sensitivity to ER antagonists like fulvestrant is not established. In this report, we characterize the spectrum of ESR1 mutations from more than 900 patients. ESR1 mutations were detected in 10%, with D538G being the most frequent (36%), followed by Y537S (14%). Several novel, activating mutations were also detected (e.g., L469V, V422del, and Y537D). Although many mutations lead to constitutive activity and reduced sensitivity to ER antagonists, only select mutants such as Y537S caused a magnitude of change associated with fulvestrant resistance in vivo Correspondingly, tumors driven by Y537S, but not D5358G, E380Q, or S463P, were less effectively inhibited by fulvestrant than more potent and bioavailable antagonists, including AZD9496. These data point to a need for antagonists with optimal pharmacokinetic properties to realize clinical efficacy against certain ESR1 mutants. Significance: A diversity of activating ESR1 mutations exist, only some of which confer resistance to existing ER antagonists that might be overcome by next-generation inhibitors such as AZD9496. Cancer Discov; 7(3); 277-87. ©2016 AACR. This article is highlighted in the In This Issue feature, p. 235 . ©2016 American Association for Cancer Research.

Applying Costs, Risks and Values Evaluation (CRAVE) methodology to Engineering Support Request (ESR) prioritization

NASA Technical Reports Server (NTRS)

Joglekar, Prafulla N.

1994-01-01

Given limited budget, the problem of prioritization among Engineering Support Requests (ESR's) with varied sizes, shapes, and colors is a difficult one. At the Kennedy Space Center (KSC), the recently developed 4-Matrix (4-M) method represents a step in the right direction as it attempts to combine the traditional criteria of technical merits only with the new concern for cost-effectiveness. However, the 4-M method was not adequately successful in the actual prioritization of ESRs for the fiscal year 1995 (FY95). This research identifies a number of design issues that should help us to develop better methods. It emphasizes that given the variety and diversity of ESR's one should not expect that a single method could help in the assessment of all ESR's. One conclusion is that a methodology such as Costs, Risks, and Values Evaluation (CRAVE) should be adopted. It also is clear that the development of methods such as 4-M requires input not only from engineers with technical expertise in ESR's but also from personnel with adequate background in the theory and practice of cost-effectiveness analysis. At KSC, ESR prioritization is one part of the Ground Support Working Teams (GSWT) Integration Process. It was discovered that the more important barriers to the incorporation of cost-effectiveness considerations in ESR prioritization lie in this process. The culture of integration, and the corresponding structure of review by a committee of peers, is not conducive to the analysis and confrontation necessary in the assessment and prioritization of ESR's. Without assistance from appropriately trained analysts charged with the responsibility to analyze and be confrontational about each ESR, the GSWT steering committee will continue to make its decisions based on incomplete understanding, inconsistent numbers, and at times, colored facts. The current organizational separation of the prioritization and the funding processes is also identified as an important barrier to the

Development and evaluation of polycrystalline cadmium telluride dosimeters for accurate quality assurance in radiation therapy

NASA Astrophysics Data System (ADS)

Oh, K.; Han, M.; Kim, K.; Heo, Y.; Moon, C.; Park, S.; Nam, S.

2016-02-01

For quality assurance in radiation therapy, several types of dosimeters are used such as ionization chambers, radiographic films, thermo-luminescent dosimeter (TLD), and semiconductor dosimeters. Among them, semiconductor dosimeters are particularly useful for in vivo dosimeters or high dose gradient area such as the penumbra region because they are more sensitive and smaller in size compared to typical dosimeters. In this study, we developed and evaluated Cadmium Telluride (CdTe) dosimeters, one of the most promising semiconductor dosimeters due to their high quantum efficiency and charge collection efficiency. Such CdTe dosimeters include single crystal form and polycrystalline form depending upon the fabrication process. Both types of CdTe dosimeters are commercially available, but only the polycrystalline form is suitable for radiation dosimeters, since it is less affected by volumetric effect and energy dependence. To develop and evaluate polycrystalline CdTe dosimeters, polycrystalline CdTe films were prepared by thermal evaporation. After that, CdTeO3 layer, thin oxide layer, was deposited on top of the CdTe film by RF sputtering to improve charge carrier transport properties and to reduce leakage current. Also, the CdTeO3 layer which acts as a passivation layer help the dosimeter to reduce their sensitivity changes with repeated use due to radiation damage. Finally, the top and bottom electrodes, In/Ti and Pt, were used to have Schottky contact. Subsequently, the electrical properties under high energy photon beams from linear accelerator (LINAC), such as response coincidence, dose linearity, dose rate dependence, reproducibility, and percentage depth dose, were measured to evaluate polycrystalline CdTe dosimeters. In addition, we compared the experimental data of the dosimeter fabricated in this study with those of the silicon diode dosimeter and Thimble ionization chamber which widely used in routine dosimetry system and dose measurements for radiation

Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant

PubMed Central

Spoerke, Jill M.; Gendreau, Steven; Walter, Kimberly; Qiu, Jiaheng; Wilson, Timothy R.; Savage, Heidi; Aimi, Junko; Derynck, Mika K.; Chen, Meng; Chan, Iris T.; Amler, Lukas C.; Hampton, Garret M.; Johnston, Stephen; Krop, Ian; Schmid, Peter; Lackner, Mark R.

2016-01-01

Mutations in ESR1 have been associated with resistance to aromatase inhibitor (AI) therapy in patients with ER+ metastatic breast cancer. Little is known of the impact of these mutations in patients receiving selective oestrogen receptor degrader (SERD) therapy. In this study, hotspot mutations in ESR1 and PIK3CA from ctDNA were assayed in clinical trial samples from ER+ metastatic breast cancer patients randomized either to the SERD fulvestrant or fulvestrant plus a pan-PI3K inhibitor. ESR1 mutations are present in 37% of baseline samples and are enriched in patients with luminal A and PIK3CA-mutated tumours. ESR1 mutations are often polyclonal and longitudinal analysis shows distinct clones exhibiting divergent behaviour over time. ESR1 mutation allele frequency does not show a consistent pattern of increases during fulvestrant treatment, and progression-free survival is not different in patients with ESR1 mutations compared with wild-type patients. ESR1 mutations are not associated with clinical resistance to fulvestrant in this study. PMID:27174596

Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant.

PubMed

Spoerke, Jill M; Gendreau, Steven; Walter, Kimberly; Qiu, Jiaheng; Wilson, Timothy R; Savage, Heidi; Aimi, Junko; Derynck, Mika K; Chen, Meng; Chan, Iris T; Amler, Lukas C; Hampton, Garret M; Johnston, Stephen; Krop, Ian; Schmid, Peter; Lackner, Mark R

2016-05-13

Mutations in ESR1 have been associated with resistance to aromatase inhibitor (AI) therapy in patients with ER+ metastatic breast cancer. Little is known of the impact of these mutations in patients receiving selective oestrogen receptor degrader (SERD) therapy. In this study, hotspot mutations in ESR1 and PIK3CA from ctDNA were assayed in clinical trial samples from ER+ metastatic breast cancer patients randomized either to the SERD fulvestrant or fulvestrant plus a pan-PI3K inhibitor. ESR1 mutations are present in 37% of baseline samples and are enriched in patients with luminal A and PIK3CA-mutated tumours. ESR1 mutations are often polyclonal and longitudinal analysis shows distinct clones exhibiting divergent behaviour over time. ESR1 mutation allele frequency does not show a consistent pattern of increases during fulvestrant treatment, and progression-free survival is not different in patients with ESR1 mutations compared with wild-type patients. ESR1 mutations are not associated with clinical resistance to fulvestrant in this study.

An NMR relaxometry and gravimetric study of gelatin-free aqueous polyacrylamide dosimeters.

PubMed

Babic, Steven; Schreiner, L John

2006-09-07

In conformal radiation therapy, a high dose of radiation is given to a target volume to increase the probability of cure, and care is taken to minimize the dose to surrounding healthy tissue. The techniques used to achieve this are very complicated and the precise verification of the resulting three-dimensional (3D) dose distribution is required. Polyacrylamide gelatin (PAG) dosimeters with magnetic resonance imaging and optical computed tomography scanning provide the required 3D dosimetry with high spatial resolution. Many basic studies have characterized these chemical dosimeters that polymerize under irradiation. However, the investigation of the fundamental properties of the radiation-induced polymerization in PAG dosimeters is complicated by the presence of the background gelatin matrix. In this work, a gelatin-free model system for the study of the basic radiation-induced polymerization in PAG dosimeters has been developed. Experiments were performed on gelatin-free dosimeters, named aqueous polyacrylamide (APA) dosimeters, containing equal amounts of acrylamide and N,N'-methylene-bisacrylamide. The APA dosimeters were prepared with four different total monomer concentrations (2, 4, 6 and 8% by weight). Nuclear magnetic resonance (NMR) spin-spin and spin-lattice proton relaxation measurements at 20 MHz, and gravimetric analyses performed on all four dosimeters, show a continuous degree of polymerization over the dose range of 0-25 Gy. The developed NMR model explains the relationship observed between the relaxation data and the amount of crosslinked polymer formed at each dose. This model can be extended with gelatin relaxation data to provide a fundamental understanding of radiation-induced polymerization in the conventional PAG dosimeters.

An NMR relaxometry and gravimetric study of gelatin-free aqueous polyacrylamide dosimeters

NASA Astrophysics Data System (ADS)

Babic, Steven; Schreiner, L. John

2006-09-01

In conformal radiation therapy, a high dose of radiation is given to a target volume to increase the probability of cure, and care is taken to minimize the dose to surrounding healthy tissue. The techniques used to achieve this are very complicated and the precise verification of the resulting three-dimensional (3D) dose distribution is required. Polyacrylamide gelatin (PAG) dosimeters with magnetic resonance imaging and optical computed tomography scanning provide the required 3D dosimetry with high spatial resolution. Many basic studies have characterized these chemical dosimeters that polymerize under irradiation. However, the investigation of the fundamental properties of the radiation-induced polymerization in PAG dosimeters is complicated by the presence of the background gelatin matrix. In this work, a gelatin-free model system for the study of the basic radiation-induced polymerization in PAG dosimeters has been developed. Experiments were performed on gelatin-free dosimeters, named aqueous polyacrylamide (APA) dosimeters, containing equal amounts of acrylamide and N,N'-methylene-bisacrylamide. The APA dosimeters were prepared with four different total monomer concentrations (2, 4, 6 and 8% by weight). Nuclear magnetic resonance (NMR) spin-spin and spin-lattice proton relaxation measurements at 20 MHz, and gravimetric analyses performed on all four dosimeters, show a continuous degree of polymerization over the dose range of 0-25 Gy. The developed NMR model explains the relationship observed between the relaxation data and the amount of crosslinked polymer formed at each dose. This model can be extended with gelatin relaxation data to provide a fundamental understanding of radiation-induced polymerization in the conventional PAG dosimeters.

Thermal Properties of the ESR Centres in Speleothem Samples

NASA Astrophysics Data System (ADS)

Ulusoy, Ü.; Anbar, Gül

2007-04-01

The paramagnetic centres used for ESR (Electron Spin Resonance) dating method should be thermally stable which is the main factor limiting the range of this method. In this work, thermal stabilities of the ESR centres in the cave deposites from the Aladaǧlar Massive and Alanya in Turkey has been investigated. The life times of the dating signal were calculated as about 4.0 and 3.7 years for G06 and G08 samples at the 10 °C depositing temperature. The activation energies of the centres are obtained the same, 0.7eV for both samples.

Enantioselective toxicities of chiral ionic liquids 1-alkyl-3-methyl imidazolium tartrate on Scenedesmus obliquus.

PubMed

Liu, Huijun; Zhang, Xiaoqiang; Dong, Ying; Chen, Caidong; Zhu, Shimin; Ma, Xiangjuan

2015-12-01

Ionic liquids (ILs) are being used in various industries during the last few decades, while the good solubility and high stability of ILs may pose a potential threat to the aquatic environment. Effect of chiral ionic liquids (CILs) 1-alkyl-3-methyl imidazolium tartrate (RMIM T) on Scenedesmus obliquus (S.obliquus) was studied. The growth rate inhibition and cell membrane permeability increased with increasing RMIM T concentration and increasing alkyl chain lengths. The IC50 values of D-(-)-tartrate 1-hexyl-3-methyl imidazolium (D-(-)-HMIM T) were 28.30, 12.23,10.15 and 14.41 mg/L, respectively, at 24, 48, 72 and 96h. While that of L-(+)-tartrate 1-hexyl-3-methyl imidazolium (L-(+)-HMIM T) were 15.97, 7.91, 9.43 and 12.04 mg/L respectively. The concentration of chl a, chl b and chl (a+b) decreased with increasing RMIM T concentration. The chlorophyll fluorescence parameters (F0, Fv/Fm, Fv/F0, Y(II), ETR and NPQ) were affected by RMIM T, indicating that the RMIM T will damage the PSII, inhibit the transmission of excitation energy, decrease the efficiency of photosynthesis. The results showed that there were enantioselective toxicity of RMIM T to algae, and the toxicity of L-(+)-RMIM T was greater than that of D-(-)-RMIM T, but the enantioselective difference becomes smaller with increasing exposure time, and with the increasing carbon chain length of cation, indicating that cation properties may have a larger effect on toxicity than anion properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Experimental evaluation of a MOSFET dosimeter for proton dose measurements.

PubMed

Kohno, Ryosuke; Nishio, Teiji; Miyagishi, Tomoko; Hirano, Eriko; Hotta, Kenji; Kawashima, Mitsuhiko; Ogino, Takashi

2006-12-07

The metal oxide semiconductor field-effect transistor (MOSFET) dosimeter has been widely studied for use as a dosimeter for patient dose verification. The major advantage of this detector is its size, which acts as a point dosimeter, and also its ease of use. The commercially available TN502RD MOSFET dosimeter manufactured by Thomson and Nielsen has never been used for proton dosimetry. Therefore we used the MOSFET dosimeter for the first time in proton dose measurements. In this study, the MOSFET dosimeter was irradiated with 190 MeV therapeutic proton beams. We experimentally evaluated dose reproducibility, linearity, fading effect, beam intensity dependence and angular dependence for the proton beam. Furthermore, the Bragg curve and spread-out Bragg peak were also measured and the linear-energy transfer (LET) dependence of the MOSFET response was investigated. Many characteristics of the MOSFET response for proton beams were the same as those for photon beams reported in previous papers. However, the angular MOSFET responses at 45, 90, 135, 225, 270 and 315 degrees for proton beams were over-responses of about 15%, and moreover the MOSFET response depended strongly on the LET of the proton beam. This study showed that the angular dependence and LET dependence of the MOSFET response must be considered very carefully for quantitative proton dose evaluations.

ESR spectroscopy for detecting gamma-irradiated dried vegetables and estimating absorbed doses

NASA Astrophysics Data System (ADS)

Kwon, Joong-Ho; Chung, Hyung-Wook; Byun, Myung-Woo

2000-03-01

In view of an increasing demand for food irradiation technology, the development of a reliable means of detection for the control of irradiated foods has become necessary. Various vegetable food materials (dried cabbage, carrot, chunggyungchae, garlic, onion, and green onion), which can be legally irradiated in Korea, were subjected to a detection study using ESR spectroscopy. Correlation coefficients ( R2) between absorbed doses (2.5-15 kGy) and their corresponding ESR signals were identified from ESR signals. Pre-established threshold values were successfully applied to the detection of 54 coded unknown samples of dried clean vegetables ( chunggyungchae, Brassica camestris var. chinensis), both non-irradiated and irradiated. The ESR signals of irradiated chunggyungchae decreased over a longer storage time, however, even after 6 months of ambient storage, these signals were still distinguishable from those of non-irradiated samples. The most successful estimates of absorbed dose (5 and 8 kGy) were obtained immediately after irradiation using a quadratic fit with average values of 4.85 and 8.65 kGy being calculated.

Rapid screening for anthocyanins in cane sugars using ESR spectroscopy.

PubMed

Thamaphat, Kheamrutai; Goodman, Bernard A; Limsuwan, Pichet; Smith, Siwaporn Meejoo

2015-03-15

Anthocyanin, which is soluble in water and released into sugar steam during extraction, was investigated in this study. The anthocyanin content in refined sugar, plantation white sugar, soft brown sugar and raw sugar was determined using electron spin resonance (ESR) spectroscopy, which was operated at room temperature, and compared with spectra from standard anthocyanin. The ESR spectra of red and violet anthocyanins was predominantly g ≈ 2.0055, which corresponded to an unpaired electron located in the pyrylium ring. Signals for Fe(III) and Mn(II), which naturally occur in plants, were found in raw sugar, soft brown sugar and standard anthocyanin but were absent from refined sugar and plantation white sugar due to the refining process. In addition, the ESR results were correlated with the apparent colour of the sugar, which was determined using the method of the International Commission for Uniform Methods of Sugar Analysis and inductively coupled plasma optical emission spectroscopy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Early development and characterization of a DNA-based radiation dosimeter

NASA Astrophysics Data System (ADS)

Avarmaa, Kirsten A.

It is the priority of first responders to minimize damage to persons and infrastructure in the case of a nuclear emergency due to an accident or deliberate terrorist attack -- if this emergency includes a radioactive hazard, first responders require a simple-to-use, accurate and complete dosimeter for radiation protection purposes in order to minimize the health risk to these individuals and the general population at large. This work consists of the early evaluation of the design and performance of a biologically relevant dosimeter which uses DNA material that can respond to the radiation of any particle type. The construct consists of fluorescently tagged strands of DNA. The signalling components of this dosimeter are also investigated for their sensitivity to radiation damage and light exposure. The dual-labelled dosimeter that is evaluated in this work gave a measurable response to gamma radiation at dose levels of 10 Gy for the given detector design and experimental setup. Further testing outside of this work confirmed this finding and indicated a working range of 100 mGy to 10 Gy using a custom-built fluorimeter as part of a larger CRTI initiative. Characterization of the chromatic components of the dosimeter showed that photobleaching is not expected to have an effect on dosimeter performance, but that radiation can damage the non-DNA signalling components at higher dose levels, although this damage is minimal at lower doses over the expected operating ranges. This work therefore describes the early steps in the quantification of the behaviour of the DNA dosimeter as a potential biologically-based device to measure radiation dose.

[Measurement of the air kerma using dosimeters embedded in an acrylic phantom in interventional radiology.].

PubMed

Kawabe, Atsushi; Shibuya, Koichi; Takeda, Yoshihiro

2006-01-01

Interventional radiology procedure guidelines and a measurement manual (IVR guidelines) have been published for the maintenance of interventional equipment with an objective of avoiding serious radiation-induced skin injuries. In the IVR guidelines, the positioning of a dosimeter at the interventional reference point is determined, whereas placement of a phantom is not specified. Therefore, the phantom is placed at any convenient location between the dosimeter and image intensifier. The space around the dosimeter reduces detection of scattered radiation. In this study, dosimeters (consisting of a parallel plate ionization chamber, glass dosimeter and OSL dosimeter) were embedded in the phantom surface to detected scattered radiation accurately. As a result, when dosimeters were embedded in the phantom surface, the air kerma was increased compared with that when dosimeters were placed on the phantom. This suggested that embedded dosimeters were able to detect scattered radiation from the phantom.

Droplet digital polymerase chain reaction assay for screening of ESR1 mutations in 325 breast cancer specimens.

PubMed

Takeshita, Takashi; Yamamoto, Yutaka; Yamamoto-Ibusuki, Mutsuko; Inao, Toko; Sueta, Aiko; Fujiwara, Saori; Omoto, Yoko; Iwase, Hirotaka

2015-12-01

Droplet digital polymerase chain reaction (ddPCR), which could perform thousands of PCRs on a nanoliter scale simultaneously, would be an attractive method to massive parallel sequencing for identifying and studying the significance of low-frequency rare mutations. Recent evidence has shown that the key potential mechanisms of the failure of aromatase inhibitors-based therapy involve identifying activating mutations affecting the ligand-binding domain of the ESR1 gene. Therefore, the detection of ESR1 mutations may be useful as a biomarker predicting an effect of the treatment. We aimed to develop a ddPCR-based method for the sensitive detection of ESR1 mutations in 325 breast cancer specimens, in which 270 primary and 55 estrogen receptor-positive (ER+) metastatic breast cancer (MBC) specimens. Our ddPCR assay could detect the ESR1 mutant molecules with low concentration of 0.25 copies/μL. According to the selected cutoff, ESR1 mutations occurred in 7 (2.5%) of 270 primary breast cancer specimens and in 11 (20%) of 55 ER+ MBC specimens. Among the 11 MBC specimens, 5 specimens (45.5%) had the most common ESR1 mutation, Y537S, 4 specimens (36.3%) each had D538G, Y537N, and Y537C. Interestingly, 2 patients had 2 ESR1 mutations, Y537N/D538G and Y537S/Y537C, and 2 patients had 3 ESR1 mutations, Y537S/Y537N/D538G. Biopsy was performed in heterochrony in 8 women twice. In 8 women, 4 women had primary breast cancer and MBC specimens and 4 women had 2 specimens when treatment was failure. Four of these 8 women acquired ESR1 mutation, whereas no ESR1 mutation could be identified at first biopsy. ddPCR technique could be a promising tool for the next-generation sequencing-free precise detection of ESR1 mutations in endocrine therapy resistant cases and may assist in determining the treatment strategy. Copyright © 2015 Elsevier Inc. All rights reserved.

ESR1 and PGR polymorphisms are associated with estrogen and progesterone receptor expression in breast tumors.

PubMed

Hertz, Daniel L; Henry, N Lynn; Kidwell, Kelley M; Thomas, Dafydd; Goddard, Audrey; Azzouz, Faouzi; Speth, Kelly; Li, Lang; Banerjee, Mousumi; Thibert, Jacklyn N; Kleer, Celina G; Stearns, Vered; Hayes, Daniel F; Skaar, Todd C; Rae, James M

2016-09-01

Hormone receptor-positive (HR+) breast cancers express the estrogen (ERα) and/or progesterone (PgR) receptors. Inherited single nucleotide polymorphisms (SNPs) in ESR1, the gene encoding ERα, have been reported to predict tamoxifen effectiveness. We hypothesized that these associations could be attributed to altered tumor gene/protein expression of ESR1/ERα and that SNPs in the PGR gene predict tumor PGR/PgR expression. Formalin-fixed paraffin-embedded breast cancer tumor specimens were analyzed for ESR1 and PGR gene transcript expression by the reverse transcription polymerase chain reaction based Oncotype DX assay and for ERα and PgR protein expression by immunohistochemistry (IHC) and an automated quantitative immunofluorescence assay (AQUA). Germline genotypes for SNPs in ESR1 (n = 41) and PGR (n = 8) were determined by allele-specific TaqMan assays. One SNP in ESR1 (rs9322336) was significantly associated with ESR1 gene transcript expression (P = 0.006) but not ERα protein expression (P > 0.05). A PGR SNP (rs518162) was associated with decreased PGR gene transcript expression (P = 0.003) and PgR protein expression measured by IHC (P = 0.016), but not AQUA (P = 0.054). There were modest, but statistically significant correlations between gene and protein expression for ESR1/ERα and PGR/PgR and for protein expression measured by IHC and AQUA (Pearson correlation = 0.32-0.64, all P < 0.001). Inherited ESR1 and PGR genotypes may affect tumor ESR1/ERα and PGR/PgR expression, respectively, which are moderately correlated. This work supports further research into germline predictors of tumor characteristics and treatment effectiveness, which may someday inform selection of hormonal treatments for patients with HR+ breast cancer. Copyright © 2016 the American Physiological Society.

Absence of estrogen receptor alpha (ESR1) gene amplification in a series of breast cancers in Taiwan.

PubMed

Chen, Jim-Ray; Hsieh, Tsan-Yu; Chen, Huang-Yang; Yeh, Kun-Yan; Chen, Kuo-Su; ChangChien, Yi-Che; Pintye, Mariann; Chang, Liang-Che; Hwang, Cheng-Cheng; Chien, Hui-Ping; Hsu, Yuan-Chun

2014-06-01

Immunohistochemical expression of ERα, encoded by the ESR1 (estrogen receptor 1) gene located at 6q25.1, is the most important determinant of responsiveness to endocrine therapy in breast cancer. The prevalence and significance of ESR1 amplification in breast cancer remain controversial. We set out to assess ESR1 status and its relevance in breast cancer in Taiwan. We tested tissue samples from 311 invasive carcinomas in a tissue microarray for ESR1 status by fluorescent in situ hybridization (FISH) and chromogenic in situ hybridization (CISH). In order to examine its association with ERα and ESR1 status, HER2 status was determined by FISH. Of the carcinomas, 58.8 % (183/311) was ERα positive. None of the carcinomas showed amplification of ESR1 by either method, whereas 24.1 % (75/311) of the carcinomas harbored HER2 amplification. Of the carcinomas, 9.6 % (26/301) showed ESR1 gain (1.3 ≤ ratio ESR1/chromosome 6 < 2) by FISH and 10 % (24/299) by CISH. FISH and CISH results showed a good correlation (κ-coefficient = 0.786). ESR1 gain by FISH and CISH was significantly associated with high-grade (P = 0.0294 and 0.0417, respectively) but not with ERα expression, HER2 status, or overall survival. ERα positivity was significantly associated with better overall survival (P = 0.039). HER2 amplification was significantly related with poor overall survival (P = 0.002). Our data confirm that in breast cancer, HER2 amplification is a frequent genetic aberration and a negative prognostic factor, and show that ESR1 amplification is not a key genetic abnormality in the tumorigenesis of breast cancer in Taiwan.

[Fabrication of annealing equipment for optically stimulated luminescence (OSL) dosimeter].

PubMed

Nakagawa, Kohei; Hayashi, Hiroaki; Okino, Hiroki; Takegami, Kazuki; Okazaki, Tohru; Kobayashi, Ikuo

2014-10-01

The optically stimulated luminescence (OSL) dosimeter is a useful detector for measuring absorbed doses of X-rays. A small-type OSL dosimeter, "nanoDot", has recently been developed by Landauer, Inc., who also manufacture "microStar" reading equipment. However, additional annealing equipment is needed if the nanoDot OSL dosimeter is used repeatedly. The aim of this study was to fabricate suitable annealing equipment using commonly available products. Our device positions four fluorescent light tubes in a close configuration. The heat from the fluorescent light tubes is dissipated using fans. Experiments using diagnostic X-ray equipment were carried out to evaluate the capability of our annealing equipment. The results indicated that our equipment can fully anneal the nanoDot OSL dosimeter with annealing times of approximately 20 hours.

Improvement of the ESR detection of irradiated food containing cellulose employing a simple extraction method

NASA Astrophysics Data System (ADS)

Delincée, Henry; Soika, Christiane

2002-03-01

Fruit may be irradiated at rather low doses, below 1 kGy in combination treatments or for quarantine purposes. To improve the ESR detection sensitivity of irradiated fruit de Jesus et al. (Int. J. Food Sci. Technol. 34 (1999) 173.) proposed extracting the fruit pulp with 80% ethanol and measuring the residue with ESR using low power (0.25 mW) for detection of 'cellulosic' radicals. An improvement in ESR sensitivity using the extraction procedure could be confirmed in this paper for strawberries and papayas. In most cases, a radiation dose of 0.5 kGy could be detected in both fruits even after 2-3 weeks storage. In addition, some herbs and spices were also tested, but only for a few of them the ESR detection of the 'cellulosic' signal was improved by previous alcoholic extraction. As an alternative to ESR measurements, other detection methods like DNA Comet Assay and thermoluminescence were also tested.

Development of a Dosimeter System for Unsymmetrical Dimethylhydrazine, Monomethylhydrazine and Hydrazine

DTIC Science & Technology

1994-06-27

the amount of dilution air . Conditioned house- compressed air was used as the diluent. The conditioning procedure consisted of passing the house air ...unsymmetrical dlmethylhydrazine (UDMI-) in air has been developed. The dosimeter consists of a replaceable dosimeter card and a reusable...Department of Defense and NASA require air monitoring for hydrazines in areas where they are handled and/or stored. A real-time dosimeter using vanillin

SU-F-T-159: Monte Carlo Simulation Studies of Three-Dimensional Dose Distribution for Polymer Gel Dosimeter and Radiochromic Gel Dosimeter in a Proton Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, M; Kim, G; Jung, H

Purpose: The purpose of this simulation study is to evaluate the proton detectability of gel dosimeters, and estimate the three-dimensional dose distribution of protons in the radiochromic gel and polymer gel dosimeter compared with the dose distribution in water. Methods: The commercial composition ratios of normoxic polymer gel and LCV micelle radiochromic gel were included in this simulation study. The densities of polymer and radiochromic gel were 1.024 and 1.005 g/cm3, respectively. The 50, 80 and 140 MeV proton beam energies were selected. The dose distributions of protons in the polymer and radiochromic gel were simulated using Monte Carlo radiationmore » transport code (MCNPX 2.7.0, Los Alamos Laboratory). The water equivalent depth profiles and the dose distributions of two gel dosimeters were compared for the water. Results: In case of irradiating 50, 80 and 140 MeV proton beam to water phantom, the reference Bragg-peak depths are represented at 2.22, 5.18 and 13.98 cm, respectively. The difference in the water equivalent depth is represented to about 0.17 and 0.37 cm in the radiochromic gel and polymer gel dosimeter, respectively. The proton absorbed doses in the radiochromic gel dosimeter are calculated to 2.41, 3.92 and 6.90 Gy with increment of incident proton energies. In the polymer gel dosimeter, the absorbed doses are calculated to 2.37, 3.85 and 6.78 Gy with increment of incident proton energies. The relative absorbed dose in radiochromic gel (about 0.47 %) is similar to that of water than the relative absorbed dose of polymer gel (about 2.26 %). In evaluating the proton dose distribution, we found that the dose distribution of both gel dosimeters matched that of water in most cases. Conclusion: As the dosimetry device, the radiochromic gel dosimeter has the potential particle detectability and is feasible to use for quality assurance of proton beam therapy beam.« less

Surface-enhanced Raman scattering (SERS) dosimeter and probe

DOEpatents

Vo-Dinh, Tuan

1995-01-01

A dosimeter and probe for measuring exposure to chemical and biological compounds is disclosed. The dosimeter or probe includes a collector which may be analyzed by surface-enhanced Raman spectroscopy. The collector comprises a surface-enhanced Raman scattering-active material having a coating applied thereto to improve the adsorption properties of the collector. The collector may also be used in automated sequential devises, in probe array devices.

Assessing doses to interventional radiologists using a personal dosimeter worn over a protective apron.

PubMed

Stranden, E; Widmark, A; Sekse, T

2008-05-01

Interventional radiologists receive significant radiation doses, and it is important to have simple methods for routine monitoring of their exposure. To evaluate the usefulness of a dosimeter worn outside the protective apron for assessments of dose to interventional radiologists. Assessments of effective dose versus dose to dosimeters worn outside the protective apron were achieved by phantom measurements. Doses outside and under the apron were assessed by phantom measurements and measurements on eight radiologists wearing two routine dosimeters for a 2-month period during ordinary working conditions. Finger doses for the same radiologists were recorded using thermoluminescent dosimeters (TLD; DXT-RAD Extremity dosimeters). Typical values for the ratio between effective dose and dosimeter dose were found to be about 0.02 when the radiologist used a thyroid shield and about 0.03 without. The ratio between the dose to the dosimeter under and outside a protective apron was found to be less than 0.04. There was very good correlation between finger dose and dosimeter dose. A personal dosimeter worn outside a protective apron is a good screening device for dose to the eyes and fingers as well as for effective dose, even though the effective dose is grossly overestimated. Relatively high dose to the fingers and eyes remains undetected by a dosimeter worn under the apron.

Evaluation of a Colorimetric Personal Dosimeter for Nitrogen Oxide.

ERIC Educational Resources Information Center

Diamond, Philip

A personal colorimetric dosimeter for nitrogen dioxide was developed. Tests were performed to determine the response of these strips to various concentrations of NO2. The dosimeter strips were satisfactory for approximate determinations of total exposure (concentration + time) of nitrogen dioxide. The total exposure was calculated in terms of time…

ESR1 methylation in primary tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer.

PubMed

Giannopoulou, Lydia; Mastoraki, Sophia; Buderath, Paul; Strati, Areti; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

2018-05-25

Estrogen receptor, coded by the ESR1 gene, is highly expressed in epithelial ovarian cancer. ESR1 gene is frequently methylated in many types of gynecological malignancies. However, only a few studies attempted to investigate the role of ESR1 methylation and its clinical significance in ovarian cancer so far. The aim of our study was to examine ESR1 methylation status in primary tumors and corresponding circulating tumor DNA of patients with high-grade serous ovarian cancer (HGSC). ESR1 methylation was detected by a highly specific and sensitive real-time methylation-specific PCR assay. Two groups of HGSC samples were analyzed: group A (n = 66 primary tumors) and group B (n = 53 primary tumors and 50 corresponding plasma samples). ESR1 was found methylated in both groups of primary tumors: in 32/66 (48.5%) of group A and in 15/53 (28.3%) of group B. 19/50 (38.0%) corresponding plasma samples of group B were also methylated for ESR1. A significant agreement for ESR1 methylation was observed between primary tumors and paired plasma ctDNA samples (P = 0.004). Interestingly, the presence of ESR1 methylation in primary tumor samples of group B was significantly correlated with a better overall survival (P = 0.027) and progression-free survival (P = 0.041). We report for the first time the presence of ESR1 methylation in plasma ctDNA of patients with HGSC. The agreement between ESR1 methylation in primary tumors and paired ctDNA is statistically significant. Our results indicate a correlation between the presence of ESR1 methylation and a better clinical outcome in HGSC patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Measurement of Absorbed Dose from Radionuclide Solutions Mixed Intimately with the Fbx Dosimeter.

NASA Astrophysics Data System (ADS)

Benedetto, Anthony Richard

Chemical dosimeters are used widely for accurate measurement of large radiation doses due to external beam irradiation from radioisotope sources and from particle accelerators. Their use for measurement of absorbed doses from radioactive solutions mixed in the dosimeter solution was reported as early as 1952, but the large activities needed to produce suitable absorbance values in the relatively insensitive dosimeters of that time discouraged further work. This manuscript reports the results of an investigation into the suitability of the ferrous sulfate-benzoic acid -xylenol orange (FBX) dosimeter for measurement of small absorbed doses caused by radionuclide solutions dissolved in the dosimeter solution. The FBX dosimeter exhibited a linear dose response as a function of activity for two common radiopharmaceuticals, technetium-99m sodium pertechnetate and iodine-131 sodium iodide. Conditions under which the FBX dosimeter may be used with radionuclide solutions were studied and were found to be amenable to routine use by laboratories possessing relatively unsophisticated instrumentation. It appears likely that any radionuclide could be studied using this dosimeter. Finally, potential applications and future research work are suggested, including measurement of absorbed dose from radiopharmaceuticals using realistic human-like phantoms to assess the risk from clinical nuclear medicine studies.

Dose equivalent neutron dosimeter

DOEpatents

Griffith, Richard V.; Hankins, Dale E.; Tomasino, Luigi; Gomaa, Mohamed A. M.

1983-01-01

A neutron dosimeter is disclosed which provides a single measurements indicating the amount of potential biological damage resulting from the neutron exposure of the wearer, for a wide range of neutron energies. The dosimeter includes a detecting sheet of track etch detecting material such as a carbonate plastic, for detecting higher energy neutrons, and a radiator layer containing conversion material such as .sup.6 Li and .sup.10 B lying adjacent to the detecting sheet for converting moderate energy neutrons to alpha particles that produce tracks in the adjacent detecting sheet. The density of conversion material in the radiator layer is of an amount which is chosen so that the density of tracks produced in the detecting sheet is proportional to the biological damage done by neutrons, regardless of whether the tracks are produced as the result of moderate energy neutrons striking the radiator layer or as the result of higher energy neutrons striking the sheet of track etch material.

Expression of estrogen receptor α 36 (ESR36) in the hamster ovary throughout the estrous cycle: effects of gonadotropins.

PubMed

Chakraborty, Prabuddha; Roy, Shyamal K

2013-01-01

Estradiol-17β (E) plays an important role in ovarian follicular development. Evidence indicates that some of the effect of E is mediated by the transmembrane estrogen receptor. In this study, we examined the spatio-temporal expression of recently discovered ERα36 (ESR36), a splice variant of Esr1 and a receptor for non-genomic E signaling, in the hamster ovary during the estrous cycle and the role of gonadotropins and ovarian steroid hormones in ESR36 expression. ESR36 expression was high on estrus (D1:0900 h) and declined precipitously by proestrus (D4:0900 h) and remained low up to D4:1600 h. Immunofluorescence findings corroborated immunoblot findings and revealed that ESR36 was expressed only in the cell membrane of both follicular and non-follicular cells, except the oocytes. Ovarian ESR36 was capable of binding to the E-affinity matrix, and have different molecular weight than that of the ESR1 or GPER. Hypophysectomy (Hx) resulted in a marked decline in ESR36 protein levels. FSH and LH, alone or combined, markedly upregulated ESR36 protein in Hx hamsters to the levels observed in D1 hamsters, but neither E nor P had any effect. Inhibition of the gonadotropin surge by phenobarbital treatment on D4:1100 h attenuated ESR36 expression in D1:0900 h ovaries, but the decline was restored by either FSH or LH replacement on D4 afternoon. This is the first report to show that ESR36, which is distinct from ESR1 or GPER is expressed in the plasma membrane of ovarian follicular and non-follicular cells, binds to E and its expression is regulated directly by the gonadotropins. In light of our previous findings, the results suggest that ovarian cells contain at least two distinct membrane estrogen receptors, such as GPER and ESR36, and strongly suggest for a non-genomic action of E regulating ovarian follicular functions.

ESR teleradiology survey: results.

PubMed

2016-08-01

With recent developments of teleradiology technology and services, it has become necessary to better evaluate its extent and use among different countries in Europe. With this goal in mind, the ESR launched two specific surveys intended to gather the current state of adoption and implementation of teleradiology in clinical practice. A special focus on differentiating between insourcing teleradiology services among partners of the same organisation and outsourcing to external services was an essential part of the design of these surveys. The first survey was addressed to 44 national societies of different countries in Europe, while the second survey was intended for all practicing radiologist ESR members. While the results of these surveys reported here may provide a wealth of information to better understand the trends in adoption of teleradiology in Europe, they only represent a snapshot at a certain point in time. The rapid development of telecommunication tools as well as a fundamental change in practice and healthcare economics will certainly influence these observations in the upcoming years. These data, however, will provide objective and relevant parameters for supporting the efforts of experts and policy makers in promoting appropriate criteria and guidelines for adequate use of teleradiology in clinical practice. Main Messages • Understand concepts and challenges of teleradiology • Provide insight into current trends and solutions for teleradiology • Compare differences in teleradiolgy strategies between countries in Europe • Establish a reference on statistical data of usage of teleradiology in Europe.

Comprehensive Angular Response Study of LLNL Panasonic Dosimeter Configurations and Artificial Intelligence Algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stone, D. K.

In April of 2016, the Lawrence Livermore National Laboratory External Dosimetry Program underwent a Department of Energy Laboratory Accreditation Program (DOELAP) on-site assessment. The assessment reported a concern that the study performed in 2013 Angular Dependence Study Panasonic UD-802 and UD-810 Dosimeters LLNL Artificial Intelligence Algorithm was incomplete. Only the responses at ±60° and 0° were evaluated and independent data from dosimeters was not used to evaluate the algorithm. Additionally, other configurations of LLNL dosimeters were not considered in this study. This includes nuclear accident dosimeters (NAD) which are placed in the wells surrounding the TLD in the dosimeter holder.

New evidence for involvement of ESR1 gene in susceptibility to Chinese migraine.

PubMed

An, Xingkai; Fang, Jie; Lin, Qing; Lu, Congxia; Ma, Qilin; Qu, Hongli

2017-01-01

Migraine is a common and disabling nervous system disease with a significant genetic predisposition. The sex hormones play an important role in the pathogenesis of migraine. However, the conclusions of the previous genetic relation studies are conflicting. The aim of this study is to determine whether variants in genes involved in estrogen receptor and estrogen hormone metabolism are related to Chinese migraine. By employing a case-control approach, 8 SNPs in the ESR1, ESR2, and CYP19A1 genes are studied in a cohort of 494 migraine cases and 533 controls. In addition, genotyping is performed using Sequenom MALDI-TOF mass spectrometry iPLEX platform. Univariate and multivariate analyses are carried out by logistic regression. The corresponding haplotypes are studied with the Haploview software and gene-gene interaction is assessed using the Generalized Multifactor Dimensionality Reduction (GMDR) analysis. There are significant differences in allelic distributions for rs2234693 and rs9340799 in ESR1 gene between patients with migraine and control subjects. Univariate logistic analysis shows that rs2234693 and rs9340799 are risk factors for migraine, but multivariate analysis reveals that only rs2234693 is significant associated with migraine. In the subgroup analysis, rs2234693 in ESR1 gene is found associated with menstrually related migraine. Further haplotypic analysis shows that rs2234693-rs9340799 TA haplotype serves as risk haplotype for migraine. The GMDR analysis identifies rs2234693 in ESR1 alone to be a crucial candidate in migraine susceptibility. This study is in agreement with the previous studies that variants in the ESR1 gene are associated with migraine suggesting that it plays a role in the migraine process.

The thermoluminescence study of epoxy based LiF:Mg,Cu,P dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahangdale, S. R., E-mail: sachin.rahangdale1@gmail.com; Palikundwar, U. A.; Moharil, S. V.

The LiF:Mg,Cu,P phosphor is the most investigated phosphor in radiation dosimetry. Results on thermoluminescence of the epoxy based LiF:Mg,Cu,P dosimeters irradiated with gamma radiations are presented and compared with results of LiF:Mg,Cu,P powder. The glow curve structure of both LiF powder and dosimeter are same and only difference is found in the glow curve peak temperature. The LiF dosimeters were made from the 5012A and 5012B epoxy. The dosimeters had a mass of about 18 mg, 5.0 mm diameter and 0.5 mm thickness. The sensitivity variation of the dosimeters for exposure to {sup 60}Co gamma rays at different angles of incidence of themore » radiation is found to be within 4%. Its minimum detectable dose is about 3020 µGy. The epoxy based dosimeters withstand different environment and it can be used with general TL reader without need of any special design due to its small size and plane surface.« less

ESR dating of submarine hydrothermal activities using barite in sulfide deposition

NASA Astrophysics Data System (ADS)

Toyoda, S.; Fujiwara, T.; Ishibashi, J.; Isono, Y.; Uchida, A.; Takamasa, A.; Nakai, S.

2012-12-01

The temporal change of submarine hydrothermal activities has been an important issue in the aspect of the evolution of hydrothermal systems which is related with ore formation (Urabe, 1995) and biological systems sustained by the chemical species arising from hydrothermal activities (Macdonald et al., 1980). Determining the ages of the hydrothermal deposit will provide essential information on such studies. Dating methods using disequilibrium between radioisotopes such as U-Th method (e.g. You and Bickle, 1998), 226}Ra-{210Pb and 228}Ra-{228Th method (e.g. Noguchi et al., 2011) have been applied to date submarine hydrothermal deposits. ESR (electron spin resonance) dating method is commonly applied to fossil teeth, shells, and quartz of Quaternay period where the natural accumulated dose is obtained from the intensities of the ESR signals which are created by natural radiation. The natural dose is divided by the dose rate to the mineral/sample to deduce the age. Okumura et al., (2010) made the first practical application of ESR (electron spin resonance) dating technique to a sample of submarine hydrothermal barite (BaSO4) to obtain preliminary ages, where Kasuya et al. (1991) first pointed out that barite can be used for ESR dating. Knowing that ESR dating of barite is promising, in this paper, we will present how we have investigated each factor that contributes ESR dating of barite in submarine hydrothermal sulfide deposition. (1) The best ESR condition for measuring the SO3- signal in barite is with the microwave power of 1mW and modulation amplitude of 0.1mT. (2) As results of heating experiments, the signal was found to be stable for the dating age range of several thousands. (3) 226Ra replacing Ba in barite is the source of the radiation. The amount of radioactive elements in sulfide mineral surrounding barite is negligible. (4) The external radiation from the sea water is negligible even in the submarine hydrothermal area where the radiation level is much

Surface-enhanced Raman scattering (SERS) dosimeter and probe

DOEpatents

Vo-Dinh, T.

1995-03-21

A dosimeter and probe for measuring exposure to chemical and biological compounds is disclosed. The dosimeter or probe includes a collector which may be analyzed by surface-enhanced Raman spectroscopy. The collector comprises a surface-enhanced Raman scattering-active material having a coating applied thereto to improve the adsorption properties of the collector. The collector may also be used in automated sequential devices, in probe array devices. 10 figures.

Performance of KCl:Eu2+ storage phosphor dosimeters for low dose measurements

PubMed Central

Li, H. Harold; Hansel, Rachael; Knutson, Nels; Yang, Deshan

2013-01-01

Recent research has demonstrated that europium doped potassium chloride (KCl:Eu2+) storage phosphor material has the potential to become the physical foundation of a novel and reusable dosimetry system using either film-like devices or devices similar to thermoluminescent dosimeter (TLD) chips. The purposes of this work are to quantify the performance of KCl:Eu2+ prototype dosimeters for low dose measurements and to demonstrate how it can be incorporated into clinical application for in vivo peripheral dose measurements. Pellet-style KCl:Eu2+ dosimeters, 6 mm in diameter, and 1 mm thick, were fabricated in-house for this study. The dosimeters were read using a laboratory photostimulated luminescence detection system. KCl:Eu2+ prototype storage phosphor dosimeter was capable of measuring a dose-to-water as low as 0.01 cGy from a 6 MV photon beam with a signal-to-noise ratio greater than 6. A pre-readout thermal annealing procedure enabled the dosimeter to be read within an hour post irradiation. After receiving large accumulated doses (~10 kGy), the dosimeters retained linear response in the low dose region with only a 20 percent loss of sensitivity comparing to a fresh sample (zero Gy history). The energy-dependence encountered during low dose peripheral measurements could be accounted for via a single point outside-field calibration per each beam quality. With further development the KCl:Eu2+− based dosimeter could become a versatile and durable dosimetry tool with large dynamic range (sub-cGy to 100 Gy). PMID:23735856

Microstructure Characterization and Corrosion Resistance Behavior of New Cobalt-Free Maraging Steel Produced Through ESR Techniques

NASA Astrophysics Data System (ADS)

Seikh, Asiful H.; Halfa, Hossam; Baig, Muneer; Khan, Sohail M. A.

2017-04-01

In this study, two different grades (M23 and M29) of cobalt-free low nickel maraging steel have been produced through electroslag remelting (ESR) process. The corrosion resistance of these ESR steels was investigated in 1 M H2SO4 solution using linear potentiodynamic polarization (LPP) and electrochemical impedance spectroscopy (EIS) techniques. The experiments were performed for different immersion time and solution temperature. To evaluate the corrosion resistance of the ESR steels, some significant characterization parameters from LPP and EIS curves were analyzed and compared with that of conventional C250 maraging steel. Irrespective of measurement techniques used, the results show that the corrosion resistance of the ESR steels was higher than the C250 steel. The microstructure of ESR steels was composed of uniform and well-distributed martensite accompanied with little amount of retained austenite in comparison with C250 steel.

Lack of association between ESR1 gene polymorphisms and premature ovarian failure in Serbian women.

PubMed

Li, J; Vujovic, S; Dalgleish, R; Thompson, J; Dragojevic-Dikic, S; Al-Azzawi, F

2014-06-01

It has previously been reported that estrogen receptor-alpha (ERα) gene (ESR1: estrogen receptor 1) polymorphisms are associated with premature ovarian failure (POF). The aim of this study was to investigate whether these genetic polymorphisms of ESR1 are associated with POF in Serbian women. A series of 197 POF cases matched with 547 fertile controls was recruited by the Institute for Endocrinology, Diabetes and Metabolic Disorders of Serbia between 2007 and 2010. Genomic DNA was extracted from saliva using Oragene® DNA sample collection kits. Two single-nucleotide polymorphisms (SNPs), PvuII and XbaI, in ESR1 were genotyped by dynamic allele-specific hybridization. Haplotype analyses were performed with the restriction fragment length polymorphism method. SNP and haplotype effects were analyzed by logistic regression models. No significant difference was found in the distribution of ESR1 PvuII and XbaI polymorphisms or haplotypes between the POF and control groups. The two ESR1 SNPs, PvuII and XbaI, are not commonly associated with POF in Serbian women and may not contribute to the genetic basis of the condition.

Development of multi-frequency ESR system for high-pressure measurements up to 2.5 GPa.

PubMed

Sakurai, T; Fujimoto, K; Matsui, R; Kawasaki, K; Okubo, S; Ohta, H; Matsubayashi, K; Uwatoko, Y; Tanaka, H

2015-10-01

A new piston-cylinder pressure cell for electron spin resonance (ESR) has been developed. The pressure cell consists of a double-layer hybrid-type cylinder with internal components made of the ZrO2-based ceramics. It can generate a pressure of 2 GPa repeatedly and reaches a maximum pressure of around 2.5 GPa. A high-pressure ESR system using a cryogen-free superconducting magnet up 10T has also been developed for this hybrid-type pressure cell. The frequency region is from 50 GHz to 400 GHz. This is the first time a pressure above 2 GPa has been achieved in multi-frequency ESR system using a piston-cylinder pressure cell. We demonstrate its potential by showing the results of the high-pressure ESR of the S=1 system with the single ion anisotropy NiSnCl6·6H2O and the S=1/2 quantum spin system CsCuCl3. We performed ESR measurements of these systems above 2 GPa successfully. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of multi-frequency ESR system for high-pressure measurements up to 2.5 GPa

NASA Astrophysics Data System (ADS)

Sakurai, T.; Fujimoto, K.; Matsui, R.; Kawasaki, K.; Okubo, S.; Ohta, H.; Matsubayashi, K.; Uwatoko, Y.; Tanaka, H.

2015-10-01

A new piston-cylinder pressure cell for electron spin resonance (ESR) has been developed. The pressure cell consists of a double-layer hybrid-type cylinder with internal components made of the ZrO2-based ceramics. It can generate a pressure of 2 GPa repeatedly and reaches a maximum pressure of around 2.5 GPa. A high-pressure ESR system using a cryogen-free superconducting magnet up 10 T has also been developed for this hybrid-type pressure cell. The frequency region is from 50 GHz to 400 GHz. This is the first time a pressure above 2 GPa has been achieved in multi-frequency ESR system using a piston-cylinder pressure cell. We demonstrate its potential by showing the results of the high-pressure ESR of the S = 1 system with the single ion anisotropy NiSnCl6 · 6H2O and the S = 1 / 2 quantum spin system CsCuCl3. We performed ESR measurements of these systems above 2 GPa successfully.

Noninvasive detection of activating estrogen receptor 1 (ESR1) mutations in estrogen receptor-positive metastatic breast cancer.

PubMed

Guttery, David S; Page, Karen; Hills, Allison; Woodley, Laura; Marchese, Stephanie D; Rghebi, Basma; Hastings, Robert K; Luo, Jinli; Pringle, J Howard; Stebbing, Justin; Coombes, R Charles; Ali, Simak; Shaw, Jacqueline A

2015-07-01

Activating mutations in the estrogen receptor 1 (ESR1) gene are acquired on treatment and can drive resistance to endocrine therapy. Because of the spatial and temporal limitations of needle core biopsies, our goal was to develop a highly sensitive, less invasive method of detecting activating ESR1 mutations via circulating cell-free DNA (cfDNA) and tumor cells as a "liquid biopsy." We developed a targeted 23-amplicon next-generation sequencing (NGS) panel for detection of hot-spot mutations in ESR1, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), tumor protein p53 (TP53), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 2 (FGFR2) in 48 patients with estrogen receptor-α-positive metastatic breast cancer who were receiving systemic therapy. Selected mutations were validated using droplet digital PCR (ddPCR). Nine baseline cfDNA samples had an ESR1 mutation. NGS detected 3 activating mutations in ESR1, and 3 hot-spot mutations in PIK3CA, and 3 in TP53 in baseline cfDNA, and the ESR1 p.D538G mutation in 1 matched circulating tumor cell sample. ddPCR analysis was more sensitive than NGS and identified 6 additional baseline cfDNA samples with the ESR1 p.D538G mutation at a frequency of <1%. In serial blood samples from 11 patients, 4 showed changes in cfDNA, 2 with emergence of a mutation in ESR1. We also detected a low frequency ESR1 mutation (1.3%) in cfDNA of 1 primary patient who was thought to have metastatic disease but was clear by scans. Early identification of ESR1 mutations by liquid biopsy might allow for cessation of ineffective endocrine therapies and switching to other treatments, without the need for tissue biopsy and before the emergence of metastatic disease. © 2015 American Association for Clinical Chemistry.

Structure of dysprosium(111) dl-tartrate dimer in aqueous solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chevela, V.V.; Vulfson, S.G.; Salnikov, Y.I.

1994-10-01

The paramagnetic birefringence method was supplemented by numerical simulation to determine the molar paramagnetic-birefringence constant of the dysprosium dl-tartrate dimer Dy{sub 2}(d-L)(l-L){sup 2-} (I), where d-L{sup 4-} and l-L{sup 4-} are the deprotonated d- and l-tartaric acid molecules, respectively. The structure of the ligand and hydration surroundings of I was modeled by molecular mechanic calculations (the Dashevskii-Pylamovatyi model). It is shown that adequate results can be obtained only if one takes into account the coordination of I to the Na{sup +} ion.

Chemical Dosimeter Tube With Coaxial Sensing Rod

NASA Technical Reports Server (NTRS)

Lueck, Dale E.

1993-01-01

Improved length-of-stain (LOS) chemical dosimeter indicates total dose of chemical vapor in air. Made with rods and tubes of various diameters to obtain various sensitivities and dynamic ranges. Sensitivity larger and dose range smaller when more room for diffusion in gap between tube and rod. Offers greater resistance to changing of color of exposed dye back to color of unexposed condition, greater sensitivity, and higher degree of repeatability. Developed to measure doses of gaseous HCI, dosimeter modified by use of other dyes to indicate doses of other chemical vapors.

SU-E-T-753: Three-Dimensional Dose Distributions of Incident Proton Particle in the Polymer Gel Dosimeter and the Radiochromic Gel Dosimeter: A Simulation Study with MCNP Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, M; Kim, G; Ji, Y

Purpose: The purpose of this study is to estimate the three-dimensional dose distributions in the polymer and the radiochromic gel dosimeter, and to identify the detectability of both gel dosimeters by comparing with the water phantom in case of irradiating the proton particles. Methods: The normoxic polymer gel and the LCV micelle radiochromic gel were used in this study. The densities of polymer and the radiochromic gel dosimeter were 1.024 and 1.005 g/cm{sup 3}, respectively. The dose distributions of protons in the polymer and radiochromic gel were simulated using Monte Carlo radiation transport code (MCNPX, Los Alamos National Laboratory). Themore » shape of phantom irradiated by proton particles was a hexahedron with the dimension of 12.4 × 12.4 × 15.0 cm{sup 3}. The energies of proton beam were 50, 80, and 140 MeV energies were directed to top of the surface of phantom. The cross-sectional view of proton dose distribution in both gel dosimeters was estimated with the water phantom and evaluated by the gamma evaluation method. In addition, the absorbed dose(Gy) was also calculated for evaluating the proton detectability. Results: The evaluation results show that dose distributions in both gel dosimeters at intermediated section and Bragg-peak region are similar with that of the water phantom. At entrance section, however, inconsistencies of dose distribution are represented, compared with water. The relative absorbed doses in radiochromic and polymer gel dosimeter were represented to be 0.47 % and 2.26 % difference, respectively. These results show that the radiochromic gel dosimeter was better matched than the water phantom in the absorbed dose evaluation. Conclusion: The polymer and the radiochromic gel dosimeter show similar characteristics in dose distributions for the proton beams at intermediate section and Bragg-peak region. Moreover the calculated absorbed dose in both gel dosimeters represents similar tendency by comparing with that in water

ESR1 single nucleotide polymorphisms predict breast cancer susceptibility in the central European Caucasian population.

PubMed

Lipphardt, Mark F; Deryal, Mustafa; Ong, Mei Fang; Schmidt, Werner; Mahlknecht, Ulrich

2013-01-01

Estrogen and progesterone hormones are key regulators of a wide variety of biological processes. In addition to their influence on reproduction, cell differentiation and apoptosis, they affect inflammatory response, cell metabolism and most importantly, they regulate physiological breast tissue proliferation and differentiation as well as the development and progression of breast cancer. In order to assess whether genetic variants in the steroid hormone receptor gene ESR1 (estrogen receptor alpha) had an effect on sporadic breast cancer susceptibility, we assessed 7 ESR1 single nucleotide polymorphisms (SNPs) for associations with breast cancer susceptibility and clinical parameters in 221 breast cancer patients and 221 controls, respectively. We identified ESR1 intron SNP +2464 C/T (rs3020314) and ESR1 intron SNP -4576 A/C (rs1514348) to correlate with breast cancer susceptibility and progesterone receptor expression status. Patients genotyped CT for ESR1 intron SNP +2464 (rs3020314) (p ≤ 0.045) or genotyped AC for ESR1 intron SNP -4576 (rs1514348) (p ≤ 0.000026) were identified to carry a significant risk as to the development of breast cancer in the Central European Caucasian population (both together: p ≤ 0.000488). Our study could confirm previous associations and revealed new associations of SNP rs1514348 with susceptibility to breast cancer and clinical outcome, which might be used as new additional SNP markers.

The vacuolar channel VvALMT9 mediates malate and tartrate accumulation in berries of Vitis vinifera.

PubMed

De Angeli, Alexis; Baetz, Ulrike; Francisco, Rita; Zhang, Jingbo; Chaves, Maria Manuela; Regalado, Ana

2013-08-01

Vitis vinifera L. represents an economically important fruit species. Grape and wine flavour is made from a complex set of compounds. The acidity of berries is a major parameter in determining grape berry quality for wine making and fruit consumption. Despite the importance of malic and tartaric acid (TA) storage and transport for grape berry acidity, no vacuolar transporter for malate or tartrate has been identified so far. Some members of the aluminium-activated malate transporter (ALMT) anion channel family from Arabidopsis thaliana have been shown to be involved in mediating malate fluxes across the tonoplast. Therefore, we hypothesised that a homologue of these channels could have a similar role in V. vinifera grape berries. We identified homologues of the Arabidopsis vacuolar anion channel AtALMT9 through a TBLASTX search on the V. vinifera genome database. We cloned the closest homologue of AtALMT9 from grape berry cDNA and designated it VvALMT9. The expression profile revealed that VvALMT9 is constitutively expressed in berry mesocarp tissue and that its transcription level increases during fruit maturation. Moreover, we found that VvALMT9 is targeted to the vacuolar membrane. Using patch-clamp analysis, we could show that, besides malate, VvALMT9 mediates tartrate currents which are higher than in its Arabidopsis homologue. In summary, in the present study we provide evidence that VvALMT9 is a vacuolar malate channel expressed in grape berries. Interestingly, in V. vinifera, a tartrate-producing plant, the permeability of the channel is apparently adjusted to TA.

a Thermally Desorbable Miniature Passive Dosimeter for Organic Vapors

NASA Astrophysics Data System (ADS)

Gonzalez, Jesus Antonio

A thermally desorbable miniature passive dosimeter (MPD) for organic vapors has been developed in conformity with theoretical and practical aspects of passive dosimeter design. The device was optimized for low sample loadings resulting from short-term and/or low concentration level exposure. This was accomplished by the use of thermal desorption rather than solvent elution, which provided the GC method with significantly higher sensitivity. Laboratory evaluation of this device for factors critical to the performance of passive dosimeters using benzene as the test vapor included: desorption efficiency (97.2%), capacity (1400 ppm-min), sensitivity (7ng/sample or 0.06 ppmv for 15 minutes sampling) accuracy and precision, concentration level, environmental conditions (i.e., air face velocity, relative humidity) and sample stability during short (15 minutes) and long periods of time (15 days). This device has demonstrated that its overall accuracy meets NIOSH and OSHA requirements for a sampling and analytical method for the exposure concentration range of 0.1 to 50 ppm (v/v) and 15 minutes exposures. It was demonstrated that the MPD operates in accordance with theoretically predicted performance and should be adequate for short-term and/or low concentration exposure monitoring of organic vapors in the workplace. In addition a dynamic vapor exposure evaluation system for passive dosimeters have been validated using benzene as the test vapor. The system is capable of generating well defined short-square wave concentration profiles suitable for the evaluation of passive dosimeters for ceiling exposure monitoring.

Estrogen Receptor 1 ( ESR1) Gene Polymorphisms and Obesity Phenotypes in a Population of Young Adults.

PubMed

Correa-Rodríguez, María; Schmidt-RioValle, Jacqueline; González-Jiménez, Emilio; Rueda-Medina, Blanca

2017-06-01

Obesity is considered an increasingly serious health problem determined by multiple genetic and environmental factors. Estrogens have been found to play a major role in body weight and adiposity regulation through estrogen receptor 1 ( ESR1). The aim of this study was to determine whether genotype and haplotype frequencies of ESR1 polymorphisms are associated with body composition measures in a population of 572 young adults. A lack of significant association between genotypes of ESR1 gene polymorphisms and obesity phenotypes was seen after adjustment for confounding factors. Linkage disequilibrium (LD) analysis identified a single LD block for the ESR1 gene including PvuII and XbaI single-nucleotide polymorphisms (SNPs) (pairwise r 2 = .66). None of the haplotypes identified revealed statistically significant associations with any of the obesity phenotypes. Our results suggest that polymorphisms of the ESR1 gene do not contribute significantly to the genetic risk for obesity phenotypes in a population of young Caucasian adults.

ESR statement on radiation protection: globalisation, personalised medicine and safety (the GPS approach).

PubMed

2013-12-01

In keeping with its responsibility for the radiation protection of patients undergoing radiological examinations and procedures, as well as of staff who are getting exposed, and with due regard to requirements under European Directives, the European Society of Radiology (ESR) issues this statement. It provides a holistic approach, termed as Globalisation (indicating all the steps and involving all stakeholders), Personalisation (referring to patient-centric) and Safety-thus called GPS. While being conscious that there is need to increase access of radiological imaging, ESR is aware about the increasing inappropriate medical exposures to ionising radiation and wide variation in patient doses for the same examination. The ESR is convinced that the different components of radiation protection are often interrelated and cannot be considered in isolation The ESR's GPS approach stands for: Globalisation (indicating all the steps and involving all stakeholders), Personalisation (referring to patient-centric) and Safety-thus called GPS It can be anticipated that enhanced protection of patients in Europe will result through the GPS approach. Although the focus is on patient safety, staff safety issues will find a place wherever pertinent.

Development and characterization of a three-dimensional radiochromic film stack dosimeter for megavoltage photon beam dosimetry.

PubMed

McCaw, Travis J; Micka, John A; DeWerd, Larry A

2014-05-01

Three-dimensional (3D) dosimeters are particularly useful for verifying the commissioning of treatment planning and delivery systems, especially with the ever-increasing implementation of complex and conformal radiotherapy techniques such as volumetric modulated arc therapy. However, currently available 3D dosimeters require extensive experience to prepare and analyze, and are subject to large measurement uncertainties. This work aims to provide a more readily implementable 3D dosimeter with the development and characterization of a radiochromic film stack dosimeter for megavoltage photon beam dosimetry. A film stack dosimeter was developed using Gafchromic(®) EBT2 films. The dosimeter consists of 22 films separated by 1 mm-thick spacers. A Virtual Water™ phantom was created that maintains the radial film alignment within a maximum uncertainty of 0.3 mm. The film stack dosimeter was characterized using simulations and measurements of 6 MV fields. The absorbed-dose energy dependence and orientation dependence of the film stack dosimeter were investigated using Monte Carlo simulations. The water equivalence of the dosimeter was determined by comparing percentage-depth-dose (PDD) profiles measured with the film stack dosimeter and simulated using Monte Carlo methods. Film stack dosimeter measurements were verified with thermoluminescent dosimeter (TLD) microcube measurements. The film stack dosimeter was also used to verify the delivery of an intensity-modulated radiation therapy (IMRT) procedure. The absorbed-dose energy response of EBT2 film differs less than 1.5% between the calibration and film stack dosimeter geometries for a 6 MV spectrum. Over a series of beam angles ranging from normal incidence to parallel incidence, the overall variation in the response of the film stack dosimeter is within a range of 2.5%. Relative to the response to a normally incident beam, the film stack dosimeter exhibits a 1% under-response when the beam axis is parallel to the film

Development and characterization of a three-dimensional radiochromic film stack dosimeter for megavoltage photon beam dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCaw, Travis J., E-mail: mccaw@wisc.edu; Micka, John A.; DeWerd, Larry A.

Purpose: Three-dimensional (3D) dosimeters are particularly useful for verifying the commissioning of treatment planning and delivery systems, especially with the ever-increasing implementation of complex and conformal radiotherapy techniques such as volumetric modulated arc therapy. However, currently available 3D dosimeters require extensive experience to prepare and analyze, and are subject to large measurement uncertainties. This work aims to provide a more readily implementable 3D dosimeter with the development and characterization of a radiochromic film stack dosimeter for megavoltage photon beam dosimetry. Methods: A film stack dosimeter was developed using Gafchromic{sup ®} EBT2 films. The dosimeter consists of 22 films separated bymore » 1 mm-thick spacers. A Virtual Water™ phantom was created that maintains the radial film alignment within a maximum uncertainty of 0.3 mm. The film stack dosimeter was characterized using simulations and measurements of 6 MV fields. The absorbed-dose energy dependence and orientation dependence of the film stack dosimeter were investigated using Monte Carlo simulations. The water equivalence of the dosimeter was determined by comparing percentage-depth-dose (PDD) profiles measured with the film stack dosimeter and simulated using Monte Carlo methods. Film stack dosimeter measurements were verified with thermoluminescent dosimeter (TLD) microcube measurements. The film stack dosimeter was also used to verify the delivery of an intensity-modulated radiation therapy (IMRT) procedure. Results: The absorbed-dose energy response of EBT2 film differs less than 1.5% between the calibration and film stack dosimeter geometries for a 6 MV spectrum. Over a series of beam angles ranging from normal incidence to parallel incidence, the overall variation in the response of the film stack dosimeter is within a range of 2.5%. Relative to the response to a normally incident beam, the film stack dosimeter exhibits a 1% under

[Accuracy Check of Monte Carlo Simulation in Particle Therapy Using Gel Dosimeters].

PubMed

Furuta, Takuya

2017-01-01

Gel dosimeters are a three-dimensional imaging tool for dose distribution induced by radiations. They can be used for accuracy check of Monte Carlo simulation in particle therapy. An application was reviewed in this article. An inhomogeneous biological sample placing a gel dosimeter behind it was irradiated by carbon beam. The recorded dose distribution in the gel dosimeter reflected the inhomogeneity of the biological sample. Monte Carlo simulation was conducted by reconstructing the biological sample from its CT image. The accuracy of the particle transport by Monte Carlo simulation was checked by comparing the dose distribution in the gel dosimeter between simulation and experiment.

European Community Respiratory Health Survey calibration project of dosimeter driving pressures.

PubMed

Ward, R J; Ward, C; Johns, D P; Skoric, B; Abramson, M; Walters, E H

2002-02-01

Two potential sources of systematic variation in output from Mefar dosimeters, the system used in the European Community Respiratory Health Survey (ECRHS) study have been evaluated: individual nebulizer characteristics and dosimeter driving pressure. Output variation from 366 new nebulizers produced in two batches for the second ECRHS were evaluated, using a solute tracer method, at a fixed driving pressure. The relationship between dosimeter driving pressure was then characterized and between-centre variation in dosimeter driving pressure was evaluated in an Internet-based survey. A systematic difference between nebulizers manufactured in the two batches was identified. Batch one had a mean+/-SD output of 7.0+/-0.8 mg x s(-1) and batch two, 6.3+/-0.7 mg x s(-1) (p<0.005). There was a wide range of driving pressures generated by Mefar dosimeters as set, ranging between 70-245 kPa, with most outside the quoted manufacturer's specification of 180+/-5%. Nebulizer output was confirmed as linearly related to dosimeter driving pressure (coefficient of determination (R2)=0.99, output=0.0377 x driving pressure-0.4151). The range in driving pressures observed was estimated as consistent with a variation of about one doubling in the provocative dose causing a 20% fall in forced expiratory volume in one second. Systematic variation has been identified that constitutes potentially significant confounders for between-centre comparisons of airway responsiveness in the European Community Respiratory Health Survey, with the dosimeter driving pressure representing the most serious issue. This work confirms the need for appropriate quality control of both nebulizer output and dosimeter driving pressure, in laboratories undertaking field measurements of airway responsiveness. In particular, appropriate data on driving pressures need to be collected and factored into between-centre comparisons. Comprehensive collection of such data to optimize quality control is practicable and has

TH-CD-201-08: Flexible Dosimeter Bands for Whole-Body Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, T; Fahimian, B; Pratx, G

Purpose: The two commonly used radiotherapy techniques are total body irradiation (TBI) and the total skin irradiation (TSI). In order to ensure the accuracy of the prescription beams, the dose received throughout the entire body must be checked using dosimetry. However, the available number of data points is limited as the dosimeters are manually placed on the patient. We developed a flexible and wearable dosimeter that can collect 1D continuous dose information around the peripheral of the patients’ body, including areas obscured from the beam path. Methods: The flexible dosimeter bands are fabricated by embedding storage phosphor powders in amore » thin layer of non-toxic silicone based elastomer (PDMS). An additional elastomer layer is formed on top of the phosphor layer to provide additional mechanical support for the dosimeter. Once the curing process is complete, the dosimeter is cut into multiple bands and rolled into spools prior to use. Results: The dose responses are tested using a preclinical cabinet X-ray system, where the readout is performed with a storage phosphor reader. Results show that the dose calibration factor is ∼1400 (A.U./Gy) from the beam center. Also, 1-D dose distribution experiment was performed in water phantoms, where preliminary results demonstrate that the dose in water is indeed attenuated compared to in air. Conclusion: Dose response and high-resolution 1-D dosimetry is demonstrated using the flexible dosimeters. By providing a detailed spatial description of the beam dose profile, we expect that the dosimeter bands may aid in enhancing the current existing modality in dosimetry. Since the dosimeter is flexible (can retract back to its original length), they can be comfortably worn around the patient. Potentially, multiple 1-D dose information can be stitched together and extrapolated to provide a coarse 3-D image of the dose distribution. This work was supported by funding from the Cutaneous Lymphoma Foundation under the

Diffusion studies on permeable nitroxyl spin probes through bilayer lipid membranes: A low frequency ESR study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meenakumari, V.; Benial, A. Milton Franklin, E-mail: miltonfranklin@yahoo.com; Utsumi, Hideo

2015-06-24

Electron spin resonance (ESR) studies were carried out for permeable 2mM {sup 14}N-labeled deutrated 3 Methoxy carbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL) in pure water and 1mM, 2mM, 3mM, 4mM concentration of 14N-labeled deutrated MC-PROXYL in 400mM concentration of liposomal solution by using a 300 MHz ESR spectrometer. The ESR parameters such as linewidth, hyperfine coupling constant, g-factor, partition parameter and permeability were reported for these samples. The line broadening was observed for the nitroxyl spin probe in the liposomal solution. The line broadening indicates that the high viscous nature of the liposomal solution. The partition parameter and permeability values indicate the maximum diffusion ofmore » nitroxyl spin probes in the bilayer lipid membranes at 2 mM concentration of nitroxyl radical. This study illustrates that ESR can be used to differentiate between the intra and extra- membrane water by loading the liposome vesicles with a lipid-permeable nitroxyl spin probe. From the ESR results, the spin probe concentration was optimized as 2mM in liposomal solution for ESR phantom studies/imaging, invivo and invitro experiments.« less

Educating for Social Responsibility. The ESR Journal.

ERIC Educational Resources Information Center

Pittman, Susan Peters, Ed.

1990-01-01

Dedicated to Seth Kreisberg, this document is the first journal issue of the Educators for Social Responsibility (ESR). It begins with "The Real Ropes Course: The Development of Social Consciousness" (Shelley Berman). The other articles are presented in five sections. The first section, "Our Relationship to Society," contains:…

Radiation dose enhancement of gold nanoparticle on different polymer gel dosimeters

NASA Astrophysics Data System (ADS)

Jabaseelan Samuel, E. James; Srinivasan, K.; Poopathi, V.

2017-05-01

In this work, we evaluated the dose enhancement produced by gold nanoparticle on ten different polymer gel dosimeters with a concentration of 7mgAu /g over a wide photon energy range of 15KeV to 20MeV and the results were compared with Soft tissue ICRU-44 produced. Our result showed that maximum DEF was observed at 40KeV, while it was almost negligible at higher energy range. Dose enhancement produced by AuNP on the gel dosimeter medium was varied compared to the reference ICRU-44 tissue, it was ± <1% for PAGAT, NIPAM, nPAG and ± <5% for PABIG, VIPAR, HEAG, BANG1, nMAG & ± <10% for MAGIC, ABAGIC gel dosimeters. Hence, we conclude that choosing the proper gel dosimeter is essential in dose enhancement study.

Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor.

PubMed

Clatot, Florian; Perdrix, Anne; Augusto, Laetitia; Beaussire, Ludivine; Delacour, Julien; Calbrix, Céline; Sefrioui, David; Viailly, Pierre-Julien; Bubenheim, Michael; Moldovan, Cristian; Alexandru, Cristina; Tennevet, Isabelle; Rigal, Olivier; Guillemet, Cécile; Leheurteur, Marianne; Gouérant, Sophie; Petrau, Camille; Théry, Jean-Christophe; Picquenot, Jean-Michel; Veyret, Corinne; Frébourg, Thierry; Jardin, Fabrice; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric

2016-11-15

To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment. ESR1 circulating D538G and Y537S/N/C mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas. Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome. ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted.

Monitoring of environmental UV radiation by biological dosimeters

NASA Astrophysics Data System (ADS)

Rontó, Gy.; Bérces, A.; Gróf, P.; Fekete, A.; Kerékgyártó, T.; Gáspár, S.; Stick, C.

As a consequence of the stratospheric ozone layer depletion biological systems can be damaged due to increased UV-B radiation. The aim of biological dosimetry is to establish a quantitative basis for the risk assessment of the biosphere. DNA is the most important target molecule of biological systems having special sensitivity against short wavelength components of the environmental radiation. Biological dosimeters are usually simple organisms, or components of them, modeling the cellular DNA. Phage T7 and polycrystalline uracil biological dosimeters have been developed and used in our laboratory for monitoring the environmental radiation in different radiation conditions (from the polar to equatorial regions). Comparisons with Robertson-Berger (RB) meter data, as well as with model calculation data weighted by the corresponding spectral sensitivities of the dosimeters are presented. Suggestion is given how to determine the trend of the increase in the biological risk due to ozone depletion.

Radiological properties of normoxic polymer gel dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Venning, A.J.; Nitschke, K.N.; Keall, P.J.

2005-04-01

The radiological properties of the normoxic polymer gel dosimeters MAGIC, MAGAS, and MAGAT [methacrylic and ascorbic acid in gelatin initiated by copper; methacrylic acid gelatine gel with ascorbic acid; and methacrylic acid gelatine and tetrakis (hydroxymethyl) phosphonium chloride, respectively] have been investigated. The radiological water equivalence was determined by comparing the polymer gel macroscopic photon and electron interaction cross sections over the energy range from 10 keV to 20 MeV and by Monte Carlo modeling of depth doses. Normoxic polymer gel dosimeters have a high gelatine and monomer concentration and therefore mass density (kg m{sup -3}) up to 3.8% highermore » than water. This results in differences between the cross-section ratios of the normoxic polymer gels and water of up to 3% for the attenuation, energy absorption, and collision stopping power coefficient ratios through the Compton dominant energy range. The mass cross-section ratios were within 2% of water except for the mass attenuation and energy absorption coefficients ratios, which showed differences with water of up to 6% for energies less than 100 keV. Monte Carlo modeling was undertaken for the polymer gel dosimeters to model the electron and photon transport resulting from a 6 MV photon beam. The absolute percentage differences between gel and water were within 1% and the relative percentage differences were within 3.5%. The results show that the MAGAT gel formulation is the most radiological water equivalent of the normoxic polymer gel dosimeters investigated due to its lower mass density measurement compared with MAGAS and MAGIC gels.« less

Synchronous delivery of felodipine and metoprolol tartrate using monolithic osmotic pump technology.

PubMed

Zhao, Shiqing; Yu, Fanglin; Liu, Nan; Di, Zhong; Yan, Kun; Liu, Yan; Li, Ying; Zhang, Hui; Yang, Yang; Yang, Zhenbo; Li, Zhiping; Mei, Xingguo

2016-11-01

The synchronous sustained-release of two drugs was desired urgently for patients needing combination therapy in long term. However, sophisticated technologies were used generally to realize the simultaneous delivery of two drugs especially those with different physico-chemical properties. The purpose of this study was to obtain the concurrent release of felodipine and metoprolol tartrate, two drugs with completely different solubilities, in a simple monolithic osmotic pump system (FMOP). Two types of blocking agents were used in monolithic osmotic pump tablets and the synchronous sustained-release of FMOP was acquired in vitro. The tablets were also administered to beagle dogs and the plasma levels of FMOP were determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated using a non-compartmental model. Cmax of both felodipine and metoprolol from the osmotic pump tablets were lower, tmax and mean residence time of both felodipine and metoprolol from the osmotic pump tablets were longer significantly than those from immediate release tablets. These results verified prolonged release of felodipine and metoprolol tartrate from osmotic pump formulations. The similar absorption rate between felodipine and metoprolol in beagles was also obtained by this osmotic pump formulation. Therefore, it could be supposed that the accordant release of two drugs with completely different solubilities may be realized just by using monolithic osmotic pump technology.

Development of force-detected THz-ESR measurement system and its application to metal porphyrin complexes

NASA Astrophysics Data System (ADS)

Takahashi, Hideyuki; Okamoto, Tsubasa; Ohmichi, Eiji; Ohta, Hitoshi

Electron spin resonance spectroscopy in the terahertz region (THz-ESR) is a promising technique to study biological materials such as metalloproteins because it directly probes the metal ion sites that play an important role in the emergence of functionality. By combining THz-ESR with force detection, the samples mass is reduced to the order of ng. This feature is of great advantage because the sample preparation process of biological materials is time-consuming. We developed a force-detected THz-ESR system utilizing optical interferometry for precise cantilever displacement measurement. In order to suppress the sensitivity fluctuation and instability of cantilever dynamics under high magnetic field, the tuning of interferometer is feedback-controlled during a measurement. By using this system, we successfully observed the ESR signal of hemin, which is a model substance of hemoglobin and myoglobin, in THz region.

The ESR1 and GPX1 gene expression level in human malignant and non-malignant breast tissues.

PubMed

Król, Magdalena B; Galicki, Michał; Grešner, Peter; Wieczorek, Edyta; Jabłońska, Ewa; Reszka, Edyta; Morawiec, Zbigniew; Wąsowicz, Wojciech; Gromadzińska, Jolanta

2018-01-01

The aim of this study was to establish whether the gene expression of estrogen receptor alpha (encoded by ESR1) correlates with the expression of glutathione peroxidase 1 (encoded by GPX1) in the tumor and adjacent tumor-free breast tissue, and whether this correlation is affected by breast cancer. Such relationships may give further insights into breast cancer pathology with respect to the status of estrogen receptor. We used the quantitative real-time PCR technique to analyze differences in the expression levels of the ESR1 and GPX1 genes in paired malignant and non-malignant tissues from breast cancer patients. ESR1 and GPX1 expression levels were found to be significantly down-regulated by 14.7% and 7.4% (respectively) in the tumorous breast tissue when compared to the non-malignant one. Down-regulation of these genes was independent of the tumor histopathology classification and clinicopathological factors, while the ESR1 mRNA level was reduced with increasing tumor grade (G1: 103% vs. G2: 85.8% vs. G3: 84.5%; p<0.05). In the non-malignant and malignant breast tissues, the expression levels of ESR1 and GPX1 were significantly correlated with each other (Rs=0.450 and Rs=0.360; respectively). Our data suggest that down-regulation of ESR1 and GPX1 was independent of clinicopathological factors. Down-regulation of ESR1 gene expression was enhanced by the development of the disease. Moreover, GPX1 and ESR1 gene expression was interdependent in the malignant breast tissue and further work is needed to determine the mechanism underlying this relationship.

Water equivalence of NIPAM based polymer gel dosimeters with enhanced sensitivity for x-ray CT

NASA Astrophysics Data System (ADS)

Gorjiara, Tina; Hill, Robin; Bosi, Stephen; Kuncic, Zdenka; Baldock, Clive

2013-10-01

Two new formulations of N-isopropylacrylamide (NIPAM) based three dimensional (3D) gel dosimeters have recently been developed with improved sensitivity to x-ray CT readout, one without any co-solvent and the other one with isopropanol co-solvent. The water equivalence of the NIPAM gel dosimeters was investigated using different methods to calculate their radiological properties including: density, electron density, number of electrons per grams, effective atomic number, photon interaction probabilities, mass attenuation and energy absorption coefficients, electron collisional, radiative and total mass stopping powers and electron mass scattering power. Monte Carlo modelling was also used to compare the dose response of these gel dosimeters with water for kilovoltage and megavoltage x-ray beams and for megavoltage electron beams. We found that the density and electron density of the co-solvent free gel dosimeter are more water equivalent with less than a 2.6% difference compared to a 5.7% difference for the isopropanol gel dosimeter. Both the co-solvent free and isopropanol solvent gel dosimeters have lower effective atomic numbers than water, differing by 2.2% and 6.5%, respectively. As a result, their photoelectric absorption interaction probabilities are up to 6% and 19% different from water, respectively. Compton scattering and pair production interaction probabilities of NIPAM gel with isopropanol differ by up to 10% from water while for the co-solvent free gel, the differences are 3%. Mass attenuation and energy absorption coefficients of the co-solvent free gel dosimeter and the isopropanol gel dosimeter are up to 7% and 19% lower than water, respectively. Collisional and total mass stopping powers of both gel dosimeters differ by less than 2% from those of water. The dose response of the co-solvent free gel dosimeter is water equivalent (with <1% discrepancy) for dosimetry of x-rays with energies <100 keV while the discrepancy increases (up to 5%) for the

Short report: Monitoring ESR1 mutations by circulating tumor DNA in aromatase inhibitor resistant metastatic breast cancer.

PubMed

Sefrioui, David; Perdrix, Anne; Sarafan-Vasseur, Nasrin; Dolfus, Claire; Dujon, Antoine; Picquenot, Jean-Michel; Delacour, Julien; Cornic, Marie; Bohers, Elodie; Leheurteur, Marianne; Rigal, Olivier; Tennevet, Isabelle; Thery, Jean-Christophe; Alexandru, Cristina; Guillemet, Cécile; Moldovan, Cristian; Veyret, Corinne; Frebourg, Thierry; Di Fiore, Frédéric; Clatot, Florian

2015-11-15

Acquired estrogen receptor gene (ESR1) mutations have been recently reported as a marker of resistance to aromatase inhibitors in hormone receptor positive metastatic breast cancer. We retrospectively considered seven patients treated for metastatic breast cancer with available samples from the primary tumor before any treatment, cryopreserved metastasis removed during progression and concomitant plasmas. All these seven patients were in disease progression after previous exposure to aromatase inhibitors for at least 6 months, and were assessed for ESR1 mutations detection in tumor and circulating DNA. For these patients, Sanger sequencing identified four metastases with clear ESR1 mutation and one possible, whereas digital PCR identified six mutated metastases. Then, under blind conditions and using digital PCR, corresponding circulating ESR1 mutations were successfully detected in four of these six metastatic breast cancer patients. Moreover, in two patients with serial blood samples following treatments exposure, the monitoring of circulating ESR1 mutations clearly predicted disease evolution. In the context of high interest for ESR1 mutations, our results highlight that these acquired recurrent mutations may be tracked in circulating tumor DNA and may be of clinical relevance for metastatic breast cancer patient monitoring. © 2015 UICC.

A Black Phosphate Conversion Coating on Steel Surface Using Antimony(III)-Tartrate as an Additive

NASA Astrophysics Data System (ADS)

Li, Feng; Wang, Guiping

2016-05-01

A novel black phosphate conversion coating was formed on steel surface through a Zn-Mn phosphating bath containing mainly ZnO, H3PO4, Mn(H2PO4)2, and Ca(NO3)2, where antimony(III)-tartrate was used as the blackening agent of phosphatization. The surface morphology and composition of the coating were characterized by scanning electron microscopy, energy dispersion spectroscopy, and x-ray photoelectron spectroscopy. Corrosion resistance of the coating was studied by potentiodynamic polarization curves and electrochemical impedance spectroscopy. The pH value of the solution had significant influence on the formation and corrosion resistance of the coating. The experimental results indicated that the Sb plays a vital role in the blackening of phosphate conversion coating. The optimal concentration of antimony(III)-tartrate in the phosphating bath used in this experiment was 1.0 g L-1, as higher values reduced the corrosion resistance of the coating. In addition, by saponification and oil seals, the corrosion duration of the black phosphate coating in a copper sulfate spot test can be as long as 20 min.

Cerium nanoparticle effect on sensitivity of Fricke gel dosimeter: Initial investigation

NASA Astrophysics Data System (ADS)

Ebenezer Suman Babu, S.; Peace Balasingh, S. Timothy; Benedicta Pearlin, R.; Rabi Raja Singh, I.; Ravindran, B. Paul

2017-05-01

Fricke gel dosimeters (FXGs) have been the preferred dosimeters because of its ease in preparation and water and tissue equivalency. Visible changes happen three dimensionally in the dosimeter as the ferrous (Fe2+) ions change into ferric (Fe3+) ions upon irradiation and the measure of this change can be correlated to the dose absorbed. Nanoparticles are promising entities that can improve the sensitivity of the gel dosimeter. Cerium Oxide nanoparticle was investigated for possible enhancement of absorbed dose in the FXG. Various concentrations of the nanoparticle based gel dosimeters were prepared and irradiated for a clinical dose range of 0-3 Gy in a telegamma unit. The optimal concentration of 0.1 mM nanoparticle incorporated in the FXG enhances the radiation sensitivity of the unmodified FXG taken as reference without modifying the background absorbance prior to irradiation. The gel recipe consisted of 5% (wt) gelatin, 50 mM Sulphuric acid, 0.05 mM Xylenol Orange, 0.5 mM Ferrous Ammonium Sulphate and 0.1 mM Cerium (IV) Oxide nanoparticle (< 25 nm particle size) and triple distilled water. The FXGs with nanoparticle showed linear dose response in the dose range tested.

A critical assessment of two types of personal UV dosimeters.

PubMed

Seckmeyer, Gunther; Klingebiel, Marcus; Riechelmann, Stefan; Lohse, Insa; McKenzie, Richard L; Liley, J Ben; Allen, Martin W; Siani, Anna-Maria; Casale, Giuseppe R

2012-01-01

Doses of erythemally weighted irradiances derived from polysulphone (PS) and electronic ultraviolet (EUV) dosimeters have been compared with measurements obtained using a reference spectroradiometer. PS dosimeters showed mean absolute deviations of 26% with a maximum deviation of 44%, the calibrated EUV dosimeters showed mean absolute deviations of 15% (maximum 33%) around noon during several test days in the northern hemisphere autumn. In the case of EUV dosimeters, measurements with various cut-off filters showed that part of the deviation from the CIE erythema action spectrum was due to a small, but significant sensitivity to visible radiation that varies between devices and which may be avoided by careful preselection. Usually the method of calibrating UV sensors by direct comparison to a reference instrument leads to reliable results. However, in some circumstances the quality of measurements made with simple sensors may be over-estimated. In the extreme case, a simple pyranometer can be used as a UV instrument, providing acceptable results for cloudless skies, but very poor results under cloudy conditions. It is concluded that while UV dosimeters are useful for their design purpose, namely to estimate personal UV exposures, they should not be regarded as an inexpensive replacement for meteorological grade instruments. © 2011 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor

PubMed Central

Clatot, Florian; Perdrix, Anne; Augusto, Laetitia; Beaussire, Ludivine; Delacour, Julien; Calbrix, Céline; Sefrioui, David; Viailly, Pierre-Julien; Bubenheim, Michael; Moldovan, Cristian; Alexandru, Cristina; Tennevet, Isabelle; Rigal, Olivier; Guillemet, Cécile; Leheurteur, Marianne; Gouérant, Sophie; Petrau, Camille; Théry, Jean-Christophe; Picquenot, Jean-Michel; Veyret, Corinne; Frébourg, Thierry; Jardin, Fabrice

2016-01-01

Purpose To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment. Patients and methods ESR1 circulating D538G and Y537S/N/C mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas. Results Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome. Conclusion ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted. PMID:27801670

Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients.

PubMed

Allouchery, Violette; Beaussire, Ludivine; Perdrix, Anne; Sefrioui, David; Augusto, Laetitia; Guillemet, Cécile; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric; Clatot, Florian

2018-05-16

Detection of circulating ESR1 mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of circulating ESR1 mutations at the end of adjuvant treatment by AI in early breast cancer had never been clearly established. In this context, the aim of the present study was to evaluate the circulating ESR1 mutation frequency at the end of adjuvant treatment and after relapse. This monocentric retrospective study was based on available stored plasmas and included all early breast cancer patients who completed at least 2 years of AI adjuvant treatment and experienced a documented relapse after the end of their treatment. Circulating ESR1 mutations (D538G, Y537S/N/C) were assessed by droplet digital PCR in plasma samples taken at the end of adjuvant treatment, at time of relapse and at time of progression under first line metastatic treatment. A total of 42 patients were included, with a median adjuvant AI exposure of 60 months (range 41-85). No circulating ESR1 mutation was detectable at the end of AI adjuvant therapy. At first relapse, 5.3% of the patients (2/38) had a detectable circulating ESR1 mutation. At time of progression on first-line metastatic treatment, 33% of the patients (7/21) under AI had a detectable circulating ESR1 mutation compared to none of the patients under chemotherapy (0/10). The two patients with a detectable ESR1 mutation at relapse were treated by AI and had an increase of their variant allele fraction at time of progression on first-line metastatic treatment. Circulating ESR1 mutation detection at the end of AI-based adjuvant treatment is not clinically useful. Circulating ESR1 mutation could be assessed as soon as first relapse to guide interventional studies.

Method for preparing dosimeter for measuring skin dose

DOEpatents

Jones, Donald E.; Parker, DeRay; Boren, Paul R.

1982-01-01

A personnel dosimeter includes a plurality of compartments containing thermoluminescent dosimeter phosphors for registering radiation dose absorbed in the wearer's sensitive skin layer and for registering more deeply penetrating radiation. Two of the phosphor compartments communicate with thin windows of different thicknesses to obtain a ratio of shallowly penetrating radiation, e.g. beta. A third phosphor is disposed within a compartment communicating with a window of substantially greater thickness than the windows of the first two compartments for estimating the more deeply penetrating radiation dose. By selecting certain phosphors that are insensitive to neutrons and by loading the holder material with neutron-absorbing elements, energetic neutron dose can be estimated separately from other radiation dose. This invention also involves a method of injection molding of dosimeter holders with thin windows of consistent thickness at the corresponding compartments of different holders. This is achieved through use of a die insert having the thin window of precision thickness in place prior to the injection molding step.

Status of estrogen receptor 1 (ESR1) gene in mastopathy predicts subsequent development of breast cancer.

PubMed

Soysal, Savas D; Kilic, Incken B; Regenbrecht, Christian R A; Schneider, Sandra; Muenst, Simone; Kilic, Nerbil; Güth, Uwe; Dietel, Manfred; Terracciano, Luigi M; Kilic, Ergin

2015-06-01

Mastopathy is a common disease of the breast likely associated with elevated estrogen levels and a putative risk factor for breast cancer. The role of estrogen receptor alpha (ESR1) in mastopathy has not been investigated previously. Here, we investigated the prevalence of ESR1 gene amplification in mastopathy and its prediction for breast cancer. Paraffin-embedded tissues from 58 women with invasive breast cancer were analyzed. For all women, tissues with mastopathy taken at least 1.5 years before first diagnosis of breast cancer were available. Tissue from 46 women with mastopathy without a diagnosis of breast carcinoma in the observed time frame (12-18 years) was used as control. Fluorescence in situ hybridization analysis revealed that ESR1 was amplified in nine of 58 (15.5 %) breast cancers. All ESR1-amplified breast cancers were strongly positive for estrogen receptor with ER immunohistochemistry. Interestingly, in women with ESR1 amplification in breast cancer, the amplification was detectable in mastopathic tissues prior to the first diagnosis of breast cancer but was absent in tissues from women with mastopathy who did not develop breast cancer. Our study suggests that ESR1 gene amplification is an early event in breast pathology and might be a helpful predictive marker to identify patients at high risk of developing breast cancer.

Association of oestrogen-receptor gene (ESR1) polymorphisms with migraine in the large Norfolk Island pedigree.

PubMed

Rodriguez-Acevedo, Astrid J; Maher, Bridget H; Lea, Rodney A; Benton, Miles; Griffiths, Lyn R

2013-10-01

Oestrogen receptor 1 ( ESR1) is located in region 6q25.1 and encodes a ligand-activated transcription factor composed of several domains important for hormone binding and transcription activation. Progesterone receptor ( PGR) is located in 11q22-23 and mediates the role of progesterone interacting with different transcriptional co-regulators. ESR1 and PGR have previously been implicated in migraine susceptibility. Here, we report the results of an association study of these genes in a migraine pedigree from the genetic isolate of Norfolk Island, a population descended from a small number of Isle of Man "Bounty Mutineer" and Tahitian founders. A significant number of molecular markers in the ESR1 (143) and PGR (43) genes were evaluated in a sample of 285 related individuals (135 males; 150 females). A pedigree-based analysis in the GenABEL package was used to analyse the results. A total of 10 markers in the ESR1 gene showed association with migraine ( P  < 0.05) in the Norfolk Island population. No association was detected with PGR . Three haplotypes in ESR1 were found to be associated with migraine ( P  = 0.004, 0.03, 0.005). Future genetic studies in larger populations and expression analysis are required to clarify the role of ESR1 in migraine susceptibility.

TH-CD-201-11: Optimizing the Response and Cost of a DNA Double-Strand Break Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Obeidat, M; Cline, K; Stathakis, S

Purpose: A DNA double-strand break (DSB) dosimeter was developed to measure the biological effect of radiation. The goal here is to refine the fabrication method of this dosimeter to reproducibly create a low coefficient of variation (CoV) and reduce the cost for the dosimeter. Methods: Our dosimeter consists of 4 kilo-base pair DNA strands (labeled on one end with biotin and on the other with fluorescein) attached to streptavidin magnetic beads. The final step of the DNA dosimeter fabrication is to suspend these attached beads in phosphate-buffered saline (PBS). The amount of PBS used to suspend the attached beads andmore » the relative volume of the DNA strands to the beads both affect the CoV and dosimeter cost. We diluted the beads attached with DNA in different volumes of PBS (100, 200, and 400 µL) to create different concentrations of the DNA dosimeter. Then we irradiated these dosimeters (50 µL samples) in a water-equivalent plastic phantom at 25 and 50 Gy (three samples per dose) and calculated the CoV for each dosimeter concentration. Also, we used different masses of DNA strands (1, 2, 8, 16, 24, and 32 µg) to attach to the same volume of magnetic beads (100 µL) to explore how this affects the cost of the dosimeter. Results: The lowest CoV was produced for the highest concentration of dosimeter (100 µL of PBS), which created CoV of 2.0 and 1.0% for 25 and 50 Gy, respectively. We found that the lowest production cost for the dosimeter occurs by attaching 16 µg of DNA strands with 100 µL of beads. Conclusion: : We optimized the fabrication of the DNA dosimeter to produce low CoV and cost, but we still need to explore ways to further improve the dosimeter for use at lower doses. This work was supported in part by Yarmouk University (Irbid, Jordan) and CPRIT (RP140105)« less

Hidden negative linear compressibility in lithium l-tartrate.

PubMed

Yeung, Hamish H-M; Kilmurray, Rebecca; Hobday, Claire L; McKellar, Scott C; Cheetham, Anthony K; Allan, David R; Moggach, Stephen A

2017-02-01

By decoupling the mechanical behaviour of building units for the first time in a wine-rack framework containing two different strut types, we show that lithium l-tartrate exhibits NLC with a maximum value, K max = -21 TPa -1 , and an overall NLC capacity, χ NLC = 5.1%, that are comparable to the most exceptional materials to date. Furthermore, the contributions from molecular strut compression and angle opening interplay to give rise to so-called "hidden" negative linear compressibility, in which NLC is absent at ambient pressure, switched on at 2 GPa and sustained up to the limit of our experiment, 5.5 GPa. Analysis of the changes in crystal structure using variable-pressure synchrotron X-ray diffraction reveals new chemical and geometrical design rules to assist the discovery of other materials with exciting hidden anomalous mechanical properties.

ESR1 Mutations Affect Anti-proliferative Responses to Tamoxifen through Enhanced Cross-Talk with IGF Signaling

PubMed Central

Gelsomino, Luca; Gu, Guowei; Rechoum, Yassine; Beyer, Amanda R; Pejerrey, Sasha M; Tsimelzon, Anna; Wang, Tao; Huffman, Kenneth; Ludlow, Andrew; Ando’, Sebastiano; Fuqua, Suzanne AW

2017-01-01

It is now generally accepted that estrogen receptor (ESR1) mutations occur frequently in metastatic breast cancers, however we do not yet know how to best treat these patients. We have modeled the three most frequent hormone binding ESR1 (HBD-ESR1) mutations (Y537N, Y537S, and D538G) using stable lentiviral transduction in human breast cancer cell lines. Effects on growth were examined in response to hormonal and targeted agents, and mutation-specific changes were studied using microarray and western blot analysis. We determined that the HBD-ESR1 mutations alter anti-proliferative effects to tamoxifen (Tam), due to cell-intrinsic changes in activation of the insulin-like growth factor receptor (IGF1R) signaling pathway and levels of PIK3R1/PIK3R3. The selective estrogen receptor degrader, fulvestrant, significantly reduced the anchorage-independent growth of ESR1 mutant-expressing cells, while combination treatments with the mTOR inhibitor everolimus, or an inhibitor blocking IGF1R and the insulin receptor significantly enhanced anti-proliferative responses. Using digital drop (dd) PCR we identified mutations at high frequencies ranging from 12% for Y537N, 5% for Y537S, and 2% for D538G in archived primary breast tumors from women treated with adjuvant mono-tamoxifen therapy. The HBD-ESR1 mutations were not associated with recurrence-free or overall survival in response in this patient cohort, and suggest that knowledge of other cell-intrinsic factors in combination with ESR1 mutation status will be needed determine anti-proliferative responses to Tam. PMID:27178332

ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling.

PubMed

Gelsomino, Luca; Gu, Guowei; Rechoum, Yassine; Beyer, Amanda R; Pejerrey, Sasha M; Tsimelzon, Anna; Wang, Tao; Huffman, Kenneth; Ludlow, Andrew; Andò, Sebastiano; Fuqua, Suzanne A W

2016-06-01

The purpose of this study was to address the role of ESR1 hormone-binding mutations in breast cancer. Soft agar anchorage-independent growth assay, Western blot, ERE reporter transactivation assay, proximity ligation assay (PLA), coimmunoprecipitation assay, silencing assay, digital droplet PCR (ddPCR), Kaplan-Meier analysis, and statistical analysis. It is now generally accepted that estrogen receptor (ESR1) mutations occur frequently in metastatic breast cancers; however, we do not yet know how to best treat these patients. We have modeled the three most frequent hormone-binding ESR1 (HBD-ESR1) mutations (Y537N, Y537S, and D538G) using stable lentiviral transduction in human breast cancer cell lines. Effects on growth were examined in response to hormonal and targeted agents, and mutation-specific changes were studied using microarray and Western blot analysis. We determined that the HBD-ESR1 mutations alter anti-proliferative effects to tamoxifen (Tam), due to cell-intrinsic changes in activation of the insulin-like growth factor receptor (IGF1R) signaling pathway and levels of PIK3R1/PIK3R3. The selective estrogen receptor degrader, fulvestrant, significantly reduced the anchorage-independent growth of ESR1 mutant-expressing cells, while combination treatments with the mTOR inhibitor everolimus, or an inhibitor blocking IGF1R, and the insulin receptor significantly enhanced anti-proliferative responses. Using digital drop (dd) PCR, we identified mutations at high frequencies ranging from 12 % for Y537N, 5 % for Y537S, and 2 % for D538G in archived primary breast tumors from women treated with adjuvant mono-tamoxifen therapy. The HBD-ESR1 mutations were not associated with recurrence-free or overall survival in response in this patient cohort and suggest that knowledge of other cell-intrinsic factors in combination with ESR1 mutation status will be needed determine anti-proliferative responses to Tam.

Morphological Analysis of the Axonal Projections of EGFP-Labeled Esr1-Expressing Neurons in Transgenic Female Medaka.

PubMed

Zempo, Buntaro; Karigo, Tomomi; Kanda, Shinji; Akazome, Yasuhisa; Oka, Yoshitaka

2018-02-01

Some hypothalamic neurons expressing estrogen receptor α (Esr1) are thought to transmit a gonadal estrogen feedback signal to gonadotropin-releasing hormone 1 (GnRH1) neurons, which is the final common pathway for feedback regulation of reproductive functions. Moreover, estrogen-sensitive neurons are suggested to control sexual behaviors in coordination with reproduction. In mammals, hypothalamic estrogen-sensitive neurons release the peptide kisspeptin and regulate GnRH1 neurons. However, a growing body of evidence in nonmammalian species casts doubt on the regulation of GnRH1 neurons by kisspeptin neurons. As a step toward understanding how estrogen regulates neuronal circuits for reproduction and sex behavior in vertebrates in general, we generated a transgenic (Tg) medaka that expresses enhanced green fluorescent protein (EGFP) specifically in esr1-expressing neurons (esr1 neurons) and analyzed their axonal projections. We found that esr1 neurons in the preoptic area (POA) project to the gnrh1 neurons. We also demonstrated by transcriptome and histological analyses that these esr1 neurons are glutamatergic or γ-aminobutyric acidergic (GABAergic) but not kisspeptinergic. We therefore suggest that glutamatergic and GABAergic esr1 neurons in the POA regulate gnrh1 neurons. This hypothesis is consistent with previous studies in mice that found that glutamatergic and GABAergic transmission is critical for estrogen-dependent changes in GnRH1 neuron firing. Thus, we propose that this neuronal circuit may provide an evolutionarily conserved mechanism for regulation of reproduction. In addition, we showed that telencephalic esr1 neurons project to medulla, which may control sexual behavior. Moreover, we found that some POA-esr1 neurons coexpress progesterone receptors. These neurons may form the neuronal circuits that regulate reproduction and sex behavior in response to the serum estrogen/progesterone. Copyright © 2018 Endocrine Society.

Investigations of interference between electromagnetic transponders and wireless MOSFET dosimeters: a phantom study.

PubMed

Su, Zhong; Zhang, Lisha; Ramakrishnan, V; Hagan, Michael; Anscher, Mitchell

2011-05-01

To evaluate both the Calypso Systems' (Calypso Medical Technologies, Inc., Seattle, WA) localization accuracy in the presence of wireless metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters of dose verification system (DVS, Sicel Technologies, Inc., Morrisville, NC) and the dosimeters' reading accuracy in the presence of wireless electromagnetic transponders inside a phantom. A custom-made, solid-water phantom was fabricated with space for transponders and dosimeters. Two inserts were machined with positioning grooves precisely matching the dimensions of the transponders and dosimeters and were arranged in orthogonal and parallel orientations, respectively. To test the transponder localization accuracy with/without presence of dosimeters (hypothesis 1), multivariate analyses were performed on transponder-derived localization data with and without dosimeters at each preset distance to detect statistically significant localization differences between the control and test sets. To test dosimeter dose-reading accuracy with/without presence of transponders (hypothesis 2), an approach of alternating the transponder presence in seven identical fraction dose (100 cGy) deliveries and measurements was implemented. Two-way analysis of variance was performed to examine statistically significant dose-reading differences between the two groups and the different fractions. A relative-dose analysis method was also used to evaluate transponder impact on dose-reading accuracy after dose-fading effect was removed by a second-order polynomial fit. Multivariate analysis indicated that hypothesis 1 was false; there was a statistically significant difference between the localization data from the control and test sets. However, the upper and lower bounds of the 95% confidence intervals of the localized positional differences between the control and test sets were less than 0.1 mm, which was significantly smaller than the minimum clinical localization resolution of 0

Detection of Activating Estrogen Receptor Gene (ESR1) Mutations in Single Circulating Tumor Cells.

PubMed

Paolillo, Carmela; Mu, Zhaomei; Rossi, Giovanna; Schiewer, Matthew J; Nguyen, Thomas; Austin, Laura; Capoluongo, Ettore; Knudsen, Karen; Cristofanilli, Massimo; Fortina, Paolo

2017-10-15

Purpose: Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 ( ESR1 ) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hotspot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch and DEPArray technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were subjected to whole genome amplification by MALBAC and Sanger sequencing. Results: Among 3 selected patients, 2 had an ESR1 mutation (Y537). One showed two different ESR1 variants in a single CTC and another showed loss of heterozygosity. All mutations were detected in matched cell-free DNA (cfDNA). Furthermore, one had 2 serial blood samples analyzed and showed changes in both cfDNA and CTCs with emergence of mutations in ESR1 (Y537S and T570I), which has not been reported previously. Conclusions: CTCs are easily accessible biomarkers to monitor and better personalize management of patients with previously demonstrated ER-MBC who are progressing on endocrine therapy. We showed that single CTC analysis can yield important information on clonal heterogeneity and can be a source of discovery of novel and potential driver mutations. Finally, we also validate a workflow for liquid biopsy that will facilitate early detection of ESR1 mutations, the emergence of endocrine resistance and the choice of further target therapy. Clin Cancer Res; 23(20); 6086-93. ©2017 AACR . ©2017 American Association for Cancer Research.

ON THE RELATIVE STABILITY OF ALUMINUM, TITANIUM, VANADIUM, IRON, AND COPPER TARTRATE COMPLEXES IN ALKALI MEDIA (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pyatnitskii, I.V.; Kostyshina, A.P.

1959-06-01

The stability of aluminum, copper, iron, titunium, and vanadium tartrate complexes was determined using bond magnitudes as criteria (the ratio between the concentrations of complexed and free ions at a certain standard acid condition). A method is suggested for determining the ratio of the bonds combining the complexes of two metals. The partition constaats of aluminum, copper, iron(III), and vanadium hydroxyquinolinates between the aqueous solution and chloroform were 2.6 x 10/sup -33/, 7.3 x 10/sup -23/, 1.5 x 10/sup -37/, and 4.2 x 10/sup -23/, respectively. The relative stability of copper and iron turtrate complexes in alkali solution (pH 13)more » and aluminum, iron(III), titunium, and vanadium(IV) tartrate complexes in ammonium solution (pH 9.5) was determined. (R.V.J.)« less

High-sensitivity assay for monitoring ESR1 mutations in circulating cell-free DNA of breast cancer patients receiving endocrine therapy.

PubMed

Lupini, Laura; Moretti, Anna; Bassi, Cristian; Schirone, Alessio; Pedriali, Massimo; Querzoli, Patrizia; Roncarati, Roberta; Frassoldati, Antonio; Negrini, Massimo

2018-03-12

Approximately 70% of breast cancers (BCs) express estrogen receptor alpha (ERα) and are treated with endocrine therapy. However, the effectiveness of this therapy is limited by innate or acquired resistance in approximately one-third of patients. Activating mutations in the ESR1 gene that encodes ERα promote critical resistance mechanisms. Here, we developed a high sensitivity approach based on enhanced-ice-COLD-PCR for detecting ESR1 mutations. The method produced an enrichment up to 100-fold and allowed the unambiguous detection of ESR1 mutations even when they consisted of only 0.01% of the total ESR1 allelic fraction. After COLD-PCR enrichment, methods based on next-generation sequencing or droplet-digital PCR were employed to detect and quantify ESR1 mutations. We applied the method to detect ESR1 mutations in circulating free DNA from the plasma of 56 patients with metastatic ER-positive BC. Fifteen of these patients were found to have ESR1 mutations at codons 536-538. This study demonstrates the utility of the enhanced-ice-COLD-PCR approach for simplifying and improving the detection of ESR1 tumor mutations in liquid biopsies. Because of its high sensitivity, the approach may potentially be applicable to patients with non-metastatic disease.

MO-AB-BRA-04: Radiation Measurements with a DNA Double-Strand-Break Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Obeidat, M; Cline, K; Stathakis, S

Purpose: Many types of dosimeters are used to measure radiation, but none of them directly measures the biological effect of this dose. The purpose here is to create a dosimeter that can measure the probability of double-strand breaks (DSB) for DNA, which is directly related to the biological effect of radiation. Methods: The dosimeter has DNA strands, which are labeled on one end with biotin and on the other with fluorescein. The biotin attaches these strands to magnetic beads. We suspended the DNA dosimeter in phosphate-buffered saline (PBS) as it matches the internal environment of the body. We placed smallmore » volumes (50µL) of the DNA dosimeter into tubes and irradiated these samples in a water-equivalent plastic phantom with several doses (three samples per dose). After irradiating the samples, a magnet was placed against the tubes. The fluorescein attached to broken DNA strands was extracted (called the supernatant) and placed into a different tube. The fluorescein on the unbroken strands remained attached to the beads in the tube and was re-suspended with 50µL of PBS. A fluorescence reader was used to measure the fluorescence for both the re-suspended beads and supernatant. To prove that we are measuring DSB, we tested dosimeter response with two different lengths of attached DNA strands (1 and 4 kilo-base pair). Results: The probability of DSB at the dose levels of 5, 10, 25, and 50 Gy were 0.05, 0.08, 0.12, and 0.19, respectively, while the coefficients of variation were 0.14, 0.07, 0.02, and 0.01, respectively. The 4 kilo-base-pair dosimeter produced 5.3 times the response of the 1 kilo-base-pair dosimeter. Conclusion: The DNA dosimeter yields a measurable response to dose that scales with the DNA strand length. The goal now is to refine the dosimeter fabrication to reproducibly create a low coefficient of variation for the lower doses. This work was supported in part by Yarmouk University (Irbid, Jordan) and CPRIT (RP140105)« less

Development of Eye Dosimeter Using Additive Manufacturing Techniques to Monitor Occupational Eye Lens Exposures to Interventional Radiologists

NASA Astrophysics Data System (ADS)

Choi, JungHwan

In this project, an eye dosimeter was designed for monitoring occupational lens of the eye exposures targeted to interventional radiologists who are often indirectly exposed to scattered radiation from the patient while performing image-guided procedures. The dosimeter was designed with a computer-aided design software to facilitate additive manufacturing techniques to make the dosimeter. The dosimeter consisted of three separate components that are attached to the hinges and the bridge of the occupational worker's protective eyewear. The produced dosimeter was radiologically calibrated to measure the lens dose on an anthropomorphic phantom of the human head. To supplement the physical design, an algorithm was written that prompts the user to input the element responses of the dosimeter, then estimates the average angle, energy, and resulting lens dose of the exposure by comparing the input with the data acquired during the dosimeter calibration procedure. The performance of the calibrated dosimeter (and the algorithm) was evaluated according to guidelines of the American National Standards Institute, and the dosimeter demonstrated a performance that was in compliance with the standard's performance criteria which suggests that the design of the eye dosimeter is feasible.

Clinical significance of monitoring ESR1 mutations in circulating cell-free DNA in estrogen receptor positive breast cancer patients.

PubMed

Takeshita, Takashi; Yamamoto, Yutaka; Yamamoto-Ibusuki, Mutsuko; Inao, Toko; Sueta, Aiko; Fujiwara, Saori; Omoto, Yoko; Iwase, Hirotaka

2016-05-31

The measurement of circulating cell-free DNA (cfDNA) may transform the management of breast cancer patients. We aimed to investigate the clinical significance of sequential measurements of ESR1 mutations in primary breast cancer (PBC) and metastatic breast cancer (MBC) patients. ESR1 mutations ratio in the PBC groups was used as the minimum cutoff for determining increases in cfDNA ESR1 mutation ratio. An increase in cfDNA ESR1 mutations was found in 13 samples of cfDNA from 12 (28.6%) out of 42 MBC patients. A total of 10 (83.3%) out of 12 MBC patients with increase cfDNA ESR1 mutations showed a poor response to treatment. In survival analysis, increase cfDNA ESR1 mutations may predict a shorter duration of post-endocrine-therapy effectiveness (P = 0.0033). A total of 119 patients (253 plasma samples) with breast carcinoma were enrolled in this study. Cases were selected if archival plasma samples were available from PBC before and after treatment and from MBC gathered more than twice at the time of progression. cfDNA was isolated from the 77 PBC patients (154 plasma samples) and from the 42 MBC patients (99 plasma samples). To investigate any changes in each cfDNA ESR1 mutation before and after treatment, we analyzed the difference with cfDNA ESR1 mutations ratio in the first blood sample using droplet digital polymerase chain reaction (ddPCR). We demonstrate that ddPCR monitoring of the recurrent ESR1 mutation in cfDNA of MBC patients is a feasible and useful method of providing relevant predictive information.

Clinical significance of monitoring ESR1 mutations in circulating cell-free DNA in estrogen receptor positive breast cancer patients

PubMed Central

Takeshita, Takashi; Yamamoto, Yutaka; Yamamoto-Ibusuki, Mutsuko; Inao, Toko; Sueta, Aiko; Fujiwara, Saori; Omoto, Yoko; Iwase, Hirotaka

2016-01-01

Background The measurement of circulating cell-free DNA (cfDNA) may transform the management of breast cancer patients. We aimed to investigate the clinical significance of sequential measurements of ESR1 mutations in primary breast cancer (PBC) and metastatic breast cancer (MBC) patients. Results ESR1 mutations ratio in the PBC groups was used as the minimum cutoff for determining increases in cfDNA ESR1 mutation ratio. An increase in cfDNA ESR1 mutations was found in 13 samples of cfDNA from 12 (28.6%) out of 42 MBC patients. A total of 10 (83.3%) out of 12 MBC patients with increase cfDNA ESR1 mutations showed a poor response to treatment. In survival analysis, increase cfDNA ESR1 mutations may predict a shorter duration of post-endocrine-therapy effectiveness (P = 0.0033). Methods A total of 119 patients (253 plasma samples) with breast carcinoma were enrolled in this study. Cases were selected if archival plasma samples were available from PBC before and after treatment and from MBC gathered more than twice at the time of progression. cfDNA was isolated from the 77 PBC patients (154 plasma samples) and from the 42 MBC patients (99 plasma samples). To investigate any changes in each cfDNA ESR1 mutation before and after treatment, we analyzed the difference with cfDNA ESR1 mutations ratio in the first blood sample using droplet digital polymerase chain reaction (ddPCR). Conclusions We demonstrate that ddPCR monitoring of the recurrent ESR1 mutation in cfDNA of MBC patients is a feasible and useful method of providing relevant predictive information. PMID:27102299

Design of Interrogation Protocols for Radiation Dose Measurements Using Optically-Stimulated Luminescent Dosimeters.

PubMed

Abraham, Sara A; Kearfott, Kimberlee J; Jawad, Ali H; Boria, Andrew J; Buth, Tobias J; Dawson, Alexander S; Eng, Sheldon C; Frank, Samuel J; Green, Crystal A; Jacobs, Mitchell L; Liu, Kevin; Miklos, Joseph A; Nguyen, Hien; Rafique, Muhammad; Rucinski, Blake D; Smith, Travis; Tan, Yanliang

2017-03-01

Optically-stimulated luminescent dosimeters are capable of being interrogated multiple times post-irradiation. Each interrogation removes a fraction of the signal stored within the optically-stimulated luminescent dosimeter. This signal loss must be corrected to avoid systematic errors in estimating the average signal of a series of optically-stimulated luminescent dosimeter interrogations and requires a minimum number of consecutive readings to determine an average signal that is within a desired accuracy of the true signal with a desired statistical confidence. This paper establishes a technical basis for determining the required number of readings for a particular application of these dosimeters when using certain OSL dosimetry systems.

PNNL Results from 2010 CALIBAN Criticality Accident Dosimeter Intercomparison Exercise

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hill, Robin L.; Conrady, Matthew M.

2011-10-28

This document reports the results of the Hanford personnel nuclear accident dosimeter (PNAD) and fixed nuclear accident dosimeter (FNAD) during a criticality accident dosimeter intercomparison exercise at the CEA Valduc Center on September 20-23, 2010. Pacific Northwest National Laboratory (PNNL) participated in a criticality accident dosimeter intercomparison exercise at the Commissariat a Energie Atomique (CEA) Valduc Center near Dijon, France on September 20-23, 2010. The intercomparison exercise was funded by the U.S. Department of Energy, Nuclear Criticality Safety Program, with Lawrence Livermore National Laboratory as the lead Laboratory. PNNL was one of six invited DOE Laboratory participants. The other participatingmore » Laboratories were: Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Savannah River Site (SRS), the Y-12 National Security Complex at Oak Ridge, and Sandia National Laboratory (SNL). The goals of PNNL's participation in the intercomparison exercise were to test and validate the procedures and algorithm currently used for the Hanford personnel nuclear accident dosimeters (PNADs) on the metallic reactor, CALIBAN, to test exposures to PNADs from the side and from behind a phantom, and to test PNADs that were taken from a historical batch of Hanford PNADs that had varying degrees of degradation of the bare indium foil. Similar testing of the PNADs was done on the Valduc SILENE test reactor in 2009 (Hill and Conrady, 2010). The CALIBAN results are reported here.« less

Characterization of MOSFET dosimeters for low‐dose measurements in maxillofacial anthropomorphic phantoms

PubMed Central

Wolff, Jan E.; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-01-01

The aims of this study were to characterize reinforced metal‐oxide‐semiconductor field‐effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low‐dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50–90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point‐dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k=2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low‐dose limit. The sensitivity was 3.09±0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was −8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD‐comparable low‐dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However

Characterization of MOSFET dosimeters for low-dose measurements in maxillofacial anthropomorphic phantoms.

PubMed

Koivisto, Juha H; Wolff, Jan E; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-07-08

The aims of this study were to characterize reinforced metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low-dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50-90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point-dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k = 2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low-dose limit. The sensitivity was 3.09 ± 0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was -8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD-comparable low-dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However, for single in

Detection of irradiated chicken by ESR spectroscopy of bone

NASA Astrophysics Data System (ADS)

Duarte, C. L.; Villavicencio, A. L. C. H.; Del Mastro, N. L.; Wiendl, F. M.

1995-02-01

Ionizing radiation has been used to treat poultry to remove harmful microorganisms, mainly Salmonella, which contaminates chicken, goose and other fresh and frozen poultry. This microorganism is sensitive to low dose radiation. Thus, irradiating these foods with doses between 1 to 7 kGy results in a large reduction of bacteria. Since it is necessary to determine whether irradiation has occurred and to what extend, this work studied the signal produced by ionizing radiation within the hard crystalline matrix of chicken's bone to establish a control method. Chicken's drumsticks were irradiated and bones separated from flesh were lyophilized and milled. ESR spectrum was then obtained. The ESR signal increased linearly with dose over the range 0.25 to 8.0 kGy. Free radicals evaluated during 30 days after irradiation showed stable in this period.

ESR and dielectric studies on superparamagnetic LaFeO3 nanoparticles

NASA Astrophysics Data System (ADS)

Kumar, A. Sendil; Bhatnagar, Anil K.

2017-05-01

Superparamagnetic LaFeO3 nanoparticles are synthesized through sol gel method. Structural, magnetic and dielectric studies are carried out. Temperature dependent ESR studies show that the intensity of the ESR spectra increases at higher temperatures. The line shape at low temperature has inhomogeneous broadening and at higher temperature more symmetry is developed and it fits better with the Lorentzian. Resonance field decreases when temperature is lowered due to dipolar interactions and there are no extrema in linewidth are observed. Single semi-circular arc in the Cole-Cole plot shows that the AC conductivity is from grains only.

PRESAGE® as a solid 3-D radiation dosimeter: A review article

NASA Astrophysics Data System (ADS)

Khezerloo, Davood; Nedaie, Hassan Ali; Takavar, Abbas; Zirak, Alireza; Farhood, Bagher; Movahedinejhad, Hadi; Banaee, Nooshin; Ahmadalidokht, Isa; Knuap, Courtney

2017-12-01

Radiation oncology has been rapidly improved by the application of new equipment and techniques. With the advent of new complex and precise radiotherapy techniques such as intensity modulated radiotherapy, stereotactic radiosurgery, and volumetric modulated arc therapy, the demand for an accurate and feasible three-dimensional (3-D) dosimetry system has increased. The most important features of a 3-D dosimeter, apart from being precise, accurate and reproducible, include also its low cost, feasibility, and availability. In 2004 a new generation of solid plastic dosimeters which demonstrate a radiochromic response to ionizing radiation was introduced. PRESAGE® plastic dosimeter lacks the limitations of previous Ferric and polymer plastic 3-D dosimeters such as diffusion, sensitivity to oxygen, fabrication problems, scanning and read out challenges. In this decade, a large number of efforts have been carried out to enhance PRESAGE® structure and scanning methods. This article attempts to review and reflect on the results of these investigations.

Expression of ESR1 in Glutamatergic and GABAergic Neurons Is Essential for Normal Puberty Onset, Estrogen Feedback, and Fertility in Female Mice.

PubMed

Cheong, Rachel Y; Czieselsky, Katja; Porteous, Robert; Herbison, Allan E

2015-10-28

Circulating estradiol exerts a profound influence on the activity of the gonadotropin-releasing hormone (GnRH) neuronal network controlling fertility. Using genetic strategies enabling neuron-specific deletion of estrogen receptor α (Esr1), we examine here whether estradiol-modulated GABA and glutamate transmission are critical for the functioning of the GnRH neuron network in the female mouse. Using Vgat- and Vglut2-ires-Cre knock-in mice and ESR1 immunohistochemistry, we demonstrate that subpopulations of GABA and glutamate neurons throughout the limbic forebrain express ESR1, with ESR1-GABAergic neurons being more widespread and numerous than ESR1-glutamatergic neurons. We crossed Vgat- and Vglut2-ires-Cre mice with an Esr1(lox/lox) line to generate animals with GABA-neuron-specific or glutamate-neuron-specific deletion of Esr1. Vgat-ires-Cre;Esr1(lox/lox) mice were infertile, with abnormal estrous cycles, and exhibited a complete failure of the estrogen positive feedback mechanism responsible for the preovulatory GnRH surge. However, puberty onset and estrogen negative feedback were normal. Vglut2-ires-Cre;Esr1(lox/lox) mice were also infertile but displayed a wider range of deficits, including advanced puberty onset, abnormal negative feedback, and abolished positive feedback. Whereas <25% of preoptic kisspeptin neurons expressed Cre in Vgat- and Vglut2-ires-Cre lines, ∼70% of arcuate kisspeptin neurons were targeted in Vglut2-ires-Cre;Esr1(lox/lox) mice, possibly contributing to their advanced puberty phenotype. These observations show that, unexpectedly, ESR1-GABA neurons are only essential for the positive feedback mechanism. In contrast, we reveal the key importance of ESR1 in glutamatergic neurons for multiple estrogen feedback loops within the GnRH neuronal network required for fertility in the female mouse. Copyright © 2015 the authors 0270-6474/15/3514533-11$15.00/0.

ESR1 mutations as a mechanism for acquired endocrine resistance in breast cancer

PubMed Central

Jeselsohn, Rinath; Buchwalter, Gilles; De Angelis, Carmine; Brown, Myles; Schiff, Rachel

2016-01-01

Most breast cancers are estrogen receptor α (ER)-positive (+) and are treated with endocrine therapies targeting ER activity. Despite efforts, the mechanisms of the frequent clinical resistance to these therapies remain largely unknown. Several recent parallel studies unveiled gain-of-function recurrent ESR1 mutations in up to 20% of patients with metastatic ER+ disease who all received endocrine therapies, which for more cases included an aromatase inhibitor. These mutations, clustered in a hotspot within the ligand-binding domain (LBD), lead to ligand independent ER activity and tumor growth, partial resistance to tamoxifen and fulvestrant, and potentially increased metastatic capacity. Together, these findings suggest that the ESR1 LBD mutations account for acquired endocrine resistance in a substantial fraction of patients with metastatic disease. The absence of detectable ESR1 mutations in treatment-naïve disease and the correlation with the number of endocrine treatments indicate a clonal expansion of rare mutant clones, selected under the pressure of treatment. New technologies to detect low/ultra rare ESR1 mutations together with tissue and liquid biopsies are required to fully expose their clinical relevance in prognosis and treatment. Pre-clinical and clinical development of rationale-based novel therapeutic strategies to inhibit these mutants has the potential to substantially improve treatment outcomes. PMID:26122181

EsrE-A yigP Locus-Encoded Transcript-Is a 3′ UTR sRNA Involved in the Respiratory Chain of E. coli

PubMed Central

Xia, Hui; Yang, Xichen; Tang, Qiongwei; Ye, Jiang; Wu, Haizhen; Zhang, Huizhan

2017-01-01

The yigP locus is widely conserved among γ-proteobacteria. Mutation of the yigP locus impacts aerobic growth of Gram-negative bacteria. However, the underlying mechanism of how the yigP locus influences aerobic growth remains largely unknown. Here, we demonstrated that the yigP locus in Escherichia coli encodes two transcripts; the mRNA of ubiquinone biosynthesis protein, UbiJ, and the 3′ untranslated region small regulatory RNA (sRNA), EsrE. EsrE is an independent transcript that is transcribed using an internal promoter of the yigP locus. Surprisingly, we found that both the EsrE sRNA and UbiJ protein were required for Q8 biosynthesis, and were sufficient to rescue the growth defect ascribed to deletion of the yigP locus. Moreover, our data showed that EsrE targeted multiple mRNAs involved in several cellular processes including murein biosynthesis and the tricarboxylic acid cycle. Among these targets, sdhD mRNA that encodes one subunit of succinate dehydrogenase (SDH), was significantly activated. Our findings provided an insight into the important function of EsrE in bacterial adaptation to various environments, as well as coordinating different aspects of bacterial physiology. PMID:28900423

Measurement of a 200 MeV proton beam using a polyurethane dosimeter

NASA Astrophysics Data System (ADS)

Heard, Malcolm; Adamovics, John; Ibbott, Geoffrey

2006-12-01

PRESAGETM (Heuris Pharma LLC, Skillman, NJ) is a three-dimensional polyurethane dosimeter containing a leuco dye that generates a color change when irradiated. The dosimeter is solid and does not require a container to maintain its shape. The dosimeter is transparent before irradiation and the maximum absorbance of the leuco dye occurs at 633 nm which is compatible with the OCT-OPUSTM laser CT scanner (MGS Research, Inc., Madison, CT). The purpose of this study was to investigate the response of PRESAGETM to proton beam radiotherapy.

SU-D-213-07: Initial Characterization of a Gel Patch Dosimeter for in Vivo Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matrosic, C; Culberson, W; Rosen, B

Purpose: In vivo dosimetry, despite being the most direct method for monitoring the dose delivered during radiation therapy and being recommended by several national and international organizations (AAPM, ICRU, NACP), is underutilized in the clinic due to issues associated with dose sensitivity, feasibility, and cost. Given the increasing complexity of radiation therapy modern treatments, there is a compelling need for a robust, affordable in vivo dosimetry option. In this work we present the initial characterization of a novel gel patch in vivo dosimeter. Methods: DEFGEL (6%T) was used to make 1-cm thick small cylindrical patch dosimeters. The optical density ofmore » each dosimeter was read before and after irradiation by an in-house laser densitometer. The dosimeters were irradiated using a Varian Clinac EX linac. Three separate batches of gel patches were used to create dose response curves and evaluate repeatability. The development time of the dosimeter was also evaluated. Results: The dose response of the dosimeter was found to be linear from a range of approximately 1-Gy to 20-Gy, which is a larger window of linearity compared to other in vivo dosimeters. At doses below 1-Gy, the cumulative uncertainties were on the order of the measured data. When compared, the three batches demonstrated repeatability from 1-Gy to approximately 13-Gy, with some variation at higher doses. For doses of >8-Gy, the dosimeter reached full optical density after 4-hours, whereas low doses developed within an hour. Conclusion: Initial results indicate that the gel patch dosimeter is a reliable and simple way to measure a large range of doses, including high doses such as those delivered during hypofractionated treatments (e.g. SBRT or MR-guided radiotherapy). The simple fabrication method for the dosimeter and the use of a laser densitometer would allow for the dosimeter to used and read in-house, cheaply and easily.« less

Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer.

PubMed

O'Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Dennis, Joe; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Shah, Mitul; Ahmed, Shahana; Healey, Catherine S; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dürst, Matthias; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Lambrechts, Diether; Depreeuw, Jeroen; Annibali, Daniela; Amant, Frederic; Zhao, Hui; Goode, Ellen L; Dowdy, Sean C; Fridley, Brooke L; Winham, Stacey J; Salvesen, Helga B; Njølstad, Tormund S; Trovik, Jone; Werner, Henrica M J; Tham, Emma; Liu, Tao; Mints, Miriam; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

2015-10-01

Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86×10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76×10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types. © 2015 Society for Endocrinology.

Initial Characterization of a Gel Patch Dosimeter for In Vivo Dosimetry

PubMed Central

Matrosic, C; Culberson, W; Rosen, B; Madsen, E; Frank, G; Bednarz, B

2016-01-01

In vivo dosimetry is a greatly underutilized tool for patient safety in clinical external beam radiotherapy treatments, despite being recommended by several national and international organizations (AAPM, ICRU, IAEA, NACP). The reasons for this underutilization mostly relate to the feasibility and cost of in vivo dosimetry methods. Due to the increase in the number of beam angles and dose per fraction in modern treatments, there is a compelling need for a novel dosimeter that is robust and affordable while able to operate properly in these complex conditions. This work presents a gel patch dosimeter as a novel method of in vivo dosimetry. DEFGEL, a 6%T normoxic polyacrylamide gel, was injected into 1-cm thick acrylic molds to create 1-cm thick small cylindrical patch dosimeters. To evaluate the change in optical density due to radiation induced polymerization, dosimeters were scanned before and after irradiation using an in-house developed laser densitometer. The dose-responses of three separate batches of gel were evaluated and compared to check for linearity and repeatability. The response development time was evaluated to ensure that the patch dosimeter could be high throughput. Additionally, the potential of this system to be used as an in vivo dosimeter was tested with a clinically relevant end-to-end in vivo phantom test. All irradiations were performed with a Varian Clinac 21EX at the University of Wisconsin Medical Radiation Research Center (UWMRRC). The dose response of all three batches of gel was found to be linear within the range of 2–20 Gy. At doses below 0.5 Gy the statistical uncertainties were prohibitively large to make quantitative assessments of the results. The three batches demonstrated good repeatability in the range of 2 Gy to up to 10 Gy, with only slight variations in response at higher doses. For low doses the dosimeter fully developed within an hour while at higher doses they fully developed within four hours. During the in vivo

Initial characterization of a gel patch dosimeter for in vivo dosimetry

NASA Astrophysics Data System (ADS)

Matrosic, C.; Culberson, W.; Rosen, B.; Madsen, E.; Frank, G.; Bednarz, B.

2016-05-01

In vivo dosimetry is a greatly underutilized tool for patient safety in clinical external beam radiotherapy treatments, despite being recommended by several national and international organizations (AAPM, ICRU, IAEA, NACP). The reasons for this underutilization mostly relate to the feasibility and cost of in vivo dosimetry methods. Due to the increase in the number of beam angles and dose per fraction in modern treatments, there is a compelling need for a novel dosimeter that is robust and affordable while able to operate properly in these complex conditions. This work presents a gel patch dosimeter as a novel method of in vivo dosimetry. DEFGEL, a 6% T normoxic polyacrylamide gel, was injected into 1 cm thick acrylic molds to create 1 cm thick small cylindrical patch dosimeters. To evaluate the change in optical density due to radiation induced polymerization, dosimeters were scanned before and after irradiation using an in-house developed laser densitometer. The dose-responses of three separate batches of gel were evaluated and compared to check for linearity and repeatability. The response development time was evaluated to ensure that the patch dosimeter could be high throughput. Additionally, the potential of this system to be used as an in vivo dosimeter was tested with a clinically relevant end-to-end in vivo phantom test. All irradiations were performed with a Varian Clinac 21EX at the University of Wisconsin Medical Radiation Research Center (UWMRRC). The dose-response of all three batches of gel was found to be linear within the range of 2-20 Gy. At doses below 0.5 Gy the statistical uncertainties were prohibitively large to make quantitative assessments of the results. The three batches demonstrated good repeatability in the range of 2 Gy to up to 10 Gy, with only slight variations in response at higher doses. For low doses the dosimeter fully developed within an hour while at higher doses they fully developed within four hours. During the in vivo

Feasibility Study of Glass Dosimeter for In Vivo Measurement: Dosimetric Characterization and Clinical Application in Proton Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rah, Jeong-Eun; Oh, Do Hoon; Kim, Jong Won

Purpose: To evaluate the suitability of the GD-301 glass dosimeter for in vivo dose verification in proton therapy. Methods and Materials: The glass dosimeter was analyzed for its dosimetrics characteristic in proton beam. Dosimeters were calibrated in a water phantom using a stairlike holder specially designed for this study. To determine the accuracy of the glass dosimeter in proton dose measurements, we compared the glass dosimeter and thermoluminescent dosimeter (TLD) dose measurements using a cylindrical phantom. We investigated the feasibility of the glass dosimeter for the measurement of dose distributions near the superficial region for proton therapy plans with amore » varying separation between the target volume and the surface of 6 patients. Results and Discussion: Uniformity was within 1.5%. The dose-response has good linearity. Dose-rate, fading, and energy dependence were found to be within 3%. The beam profile measured using the glass dosimeter was in good agreement with the profile obtained from the ionization chamber. Depth-dose distributions in nonmodulated and modulated proton beams obtained with the glass dosimeter were estimated to be within 3%, which was lower than those with the ionization chamber. In the phantom study, the difference of isocenter dose between the delivery dose calculated by the treatment planning system and that measured by the glass dosimeter was within 5%. With in vivo dosimetry, the calculated surface doses overestimated measurements by 4%-16% using glass dosimeter and TLD. Conclusion: It is recommended that bolus be added for these clinical cases. We also believe that the glass dosimeter has considerable potential for use with in vivo patient proton dosimetry.« less

Feasibility study of glass dosimeter for in vivo measurement: dosimetric characterization and clinical application in proton beams.

PubMed

Rah, Jeong-Eun; Oh, Do Hoon; Kim, Jong Won; Kim, Dae-Hyun; Suh, Tae-Suk; Ji, Young Hoon; Shin, Dongho; Lee, Se Byeong; Kim, Dae Yong; Park, Sung Yong

2012-10-01

To evaluate the suitability of the GD-301 glass dosimeter for in vivo dose verification in proton therapy. The glass dosimeter was analyzed for its dosimetrics characteristic in proton beam. Dosimeters were calibrated in a water phantom using a stairlike holder specially designed for this study. To determine the accuracy of the glass dosimeter in proton dose measurements, we compared the glass dosimeter and thermoluminescent dosimeter (TLD) dose measurements using a cylindrical phantom. We investigated the feasibility of the glass dosimeter for the measurement of dose distributions near the superficial region for proton therapy plans with a varying separation between the target volume and the surface of 6 patients. Uniformity was within 1.5%. The dose-response has good linearity. Dose-rate, fading, and energy dependence were found to be within 3%. The beam profile measured using the glass dosimeter was in good agreement with the profile obtained from the ionization chamber. Depth-dose distributions in nonmodulated and modulated proton beams obtained with the glass dosimeter were estimated to be within 3%, which was lower than those with the ionization chamber. In the phantom study, the difference of isocenter dose between the delivery dose calculated by the treatment planning system and that measured by the glass dosimeter was within 5%. With in vivo dosimetry, the calculated surface doses overestimated measurements by 4%-16% using glass dosimeter and TLD. It is recommended that bolus be added for these clinical cases. We also believe that the glass dosimeter has considerable potential for use with in vivo patient proton dosimetry. Copyright © 2012 Elsevier Inc. All rights reserved.

Conceptual design of the SMART dosimeter

NASA Astrophysics Data System (ADS)

Johnson, Erik B.; Vogel, Sam; Frank, Rebecca; Stoddard, Graham; Vera, Alonzo; Alexander, David; Christian, James

2017-08-01

Active dosimeters for astronauts and space weather monitors are critical tools for mitigating radiation induced health issues or system failure on capital equipment. Commercial spaceflight, deep space flight, and satellites require smarter, smaller, and lower power dosimeters. There are a number of instruments with flight heritage, yet as identified in NASA's roadmaps, these technologies do not lend themselves to a viable solution for active dosimetry for an astronaut, particularly for deep space missions. For future missions, nano- and micro-satellites will require compact instruments that will accurately assess the radiation hazard without consuming major resources on the spacecraft. RMD has developed the methods for growing an advanced scintillation material called phenylcarbazole, which provides pulse shape discrimination between protons and electrons. When used in combination with an anti-coincidence detector system, an assessment of the dose from charged ions and neutral particles can be determined. This is valuable as damage on a system (such as silicon or tissue) is dependent on the particle species. Using this crystal with readout electronics developed in partnership with COSMIAC at the University of New Mexico, the design of the Small Mixed field Autonomous Radiation Tracker (SMART) Dosimeter consists of a low-power analog to digital conversion scheme with low-power digital signal processing algorithms, which are to be implemented within a compact system on a chip, such as the Xilinx Zynq series. A review of the conceptual design is presented.

Investigations of interference between electromagnetic transponders and wireless MOSFET dosimeters: A phantom study

PubMed Central

Su, Zhong; Zhang, Lisha; Ramakrishnan, V.; Hagan, Michael; Anscher, Mitchell

2011-01-01

Purpose: To evaluate both the Calypso Systems’ (Calypso Medical Technologies, Inc., Seattle, WA) localization accuracy in the presence of wireless metal–oxide–semiconductor field-effect transistor (MOSFET) dosimeters of dose verification system (DVS, Sicel Technologies, Inc., Morrisville, NC) and the dosimeters’ reading accuracy in the presence of wireless electromagnetic transponders inside a phantom.Methods: A custom-made, solid-water phantom was fabricated with space for transponders and dosimeters. Two inserts were machined with positioning grooves precisely matching the dimensions of the transponders and dosimeters and were arranged in orthogonal and parallel orientations, respectively. To test the transponder localization accuracy with∕without presence of dosimeters (hypothesis 1), multivariate analyses were performed on transponder-derived localization data with and without dosimeters at each preset distance to detect statistically significant localization differences between the control and test sets. To test dosimeter dose-reading accuracy with∕without presence of transponders (hypothesis 2), an approach of alternating the transponder presence in seven identical fraction dose (100 cGy) deliveries and measurements was implemented. Two-way analysis of variance was performed to examine statistically significant dose-reading differences between the two groups and the different fractions. A relative-dose analysis method was also used to evaluate transponder impact on dose-reading accuracy after dose-fading effect was removed by a second-order polynomial fit.Results: Multivariate analysis indicated that hypothesis 1 was false; there was a statistically significant difference between the localization data from the control and test sets. However, the upper and lower bounds of the 95% confidence intervals of the localized positional differences between the control and test sets were less than 0.1 mm, which was significantly smaller than the minimum

Ceric and ferrous dosimeters show precision for 50-5000 rad range

NASA Technical Reports Server (NTRS)

Frigerio, N. A.; Henry, V. D.

1968-01-01

Ammonium thiocyanate, added to the usual ferrous sulfate dosimeter solution, yielded a very stable, precise and temperature-independent system eight times as sensitive as the classical Fricke system in the 50 to 5000 rad range. The ceric dosimeters, promising for use in mixed radiation fields, respond nearly independently of LET.

A diffusion-free and linear-energy-transfer-independent nanocomposite Fricke gel dosimeter

NASA Astrophysics Data System (ADS)

Maeyama, T.; Fukunishi, N.; Ishikawa, K. L.; Furuta, T.; Fukasaku, K.; Takagi, S.; Noda, S.; Himeno, R.; Fukuda, S.

2014-03-01

We report a new magnetic-resonance-imaging (MRI) based nanocomposite Fricke gel (NC-FG) dosimeter system, which is free from two main drawbacks of conventional Fricke gel dosimeters, namely, the diffusion of the radiation products and the linear-energy-transfer (LET) dependence of the radiation sensitivity when used for ion beams. The NC-FG dosimeter was prepared by incorporating 1% (w/w) clay nanoparticles into deaerated Fricke gel. We have dosimetrically characterized the NC-FG by using MRI measurements after irradiation with a monoenergetic 290 MeV/nucleon carbon beam. No diffusion of the radiation products was observed during nine days after the irradiation. Moreover, its response faithfully reproduced the depth-dose distribution measured by an ionization chamber, which indicates the absence of the LET dependence. Also, the NC-FG dosimeter exhibited a good linearity up to 800 Gy.

ESR Measurement Of Crystallinity In Semicrystalline Polymers

NASA Technical Reports Server (NTRS)

Kim, Soon Sam; Tsay, Fun-Dow

1989-01-01

Photogenerated free radicals decay at different rates in crystalline and amorphous phases. Degree of crystallinity in polymer having both crystalline and amorphous phases measured indirectly by technique based in part on electron-spin-resonance (ESR) spectroscopy. Accuracy of crystallinity determined by new technique equals or exceeds similar determinations by differential scanning calorimetry, wide-angle x-ray scattering, or measurement of density.

Growth, structural, optical and surface analysis of piperazinium tartrate: A NLO single crystal

NASA Astrophysics Data System (ADS)

Gupta, Apurva; Raseel Rahman M., K.; Nair, Lekha

2018-05-01

Single crystal of piperazinium tartrate (PPZT) was grown by the slow evaporation solution growth technique at room temperature. Crystallinity of grown crystal was examined by powder X-ray diffraction. High transparency and wide band gap were observed in the UV-Visible spectroscopic studies. Intense and broad emissions were observed in the blue region, as that is indicated by photoluminescence spectroscopy. The quality of the grown PPZT single crystals were analyzed by the etching studies using the water as the etchant.

Analysis of ESR1 and PIK3CA mutations in plasma cell-free DNA from ER-positive breast cancer patients.

PubMed

Takeshita, Takashi; Yamamoto, Yutaka; Yamamoto-Ibusuki, Mutsuko; Tomiguchi, Mai; Sueta, Aiko; Murakami, Keiichi; Omoto, Yoko; Iwase, Hirotaka

2017-08-08

The measurement of ESR1 and PIK3CA mutations in plasma cell-free DNA (cfDNA) has been studied as a non-invasive method to quickly assess and monitor endocrine therapy (ET) resistant metastatic breast cancer (MBC) patients. The subjects of this retrospective study were a total of 185 plasma samples from 86 estrogen receptor-positive BC patients, of which 151 plasma samples were from 69 MBC patients and 34 plasma samples were from 17 primary BC (PBC) patients. We developed multiplex droplet digital PCR assays to verify the clinical significance of ESR1 and PIK3CA mutations both in a snapshot and serially in these patients. cfDNA ESR1 and PIK3CA mutations were found in 28.9% and 24.6 % of MBC patients, respectively. The relation between ESR1 or PIK3CA mutations and clinical features showed that ESR1 mutations occurred mostly in patients previously treated by ET, which was not the case for PIK3CA mutations. The analysis of the clinical impact of those mutations on subsequent lines of treatment for the 69 MBC patients revealed that both ESR1 and PIK3CA mutations detection were related to a shorter duration of ET effectiveness in univariate analysis but only for ESR1 mutations in multivariate analysis. The monitoring of cfDNA in a subset of 52 patients showed that loss of ESR1 mutations was related to a longer duration of response, which was not the case for PIK3CA mutations. We have demonstrated the clinical significance of on-treatment ESR1 mutations both in a snapshot and serially in comparison with PIK3CA mutations.

Incidence and clinical significance of ESR1 mutations in heavily pretreated metastatic breast cancer patients.

PubMed

Niu, Jiaxin; Andres, Grant; Kramer, Kim; Kundranda, Madappa N; Alvarez, Ricardo H; Klimant, Eiko; Parikh, Ankur R; Tan, Bradford; Staren, Edgar D; Markman, Maurie

2015-01-01

ESR1 mutation has recently emerged as one of the important mechanisms involved in endocrine resistance. The incidence and clinical implication of ESR1 mutation has not been well evaluated in heavily pretreated breast cancer patients. We conducted a retrospective review of advanced breast cancer patients with tumors who underwent next-generation sequencing genomic profiling using Foundation One test at Cancer Treatment Centers of America(®) regional hospitals between November 2012 and November 2014. We identified a total of 341 patients including 217 (59%) estrogen receptor (ER)+, 177 (48%) progesterone receptor (PR)+, 30 (8%) hormone receptor+/HER2 positive, and 119 (32%) triple negative patients. ESR1 mutation was noted in 27/222 (12.1%) ER+ or PR+ breast cancer patients. All ER+ patients received at least one line of an aromatase inhibitor. All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). In this cohort, 19 (67.9%) patients carried three or more, seven (25%) patients had one or two additional genomic alterations and one (3.6%) patient had an ESR1 mutation only. Of 28 patients, three patients were treated with fulvestrant immediately before and two patients were treated after next-generation sequencing testing; only one patient achieved stable disease for 8 months and the other four patients had progression of disease. In all, 3/3 (100%) patients before testing and 2/4 (50%) after testing treated with exemestane and everolimus achieved stable disease for at least 6 months. ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings.

TH-C-19A-05: Evaluation of a New Reusable 3D Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juang, T; Adamovics, J; Oldham, M

Purpose: PRESAGE is a radiochromic plastic which has demonstrated strong potential for high resolution single-use 3D dosimetry. This study evaluates a new PRESAGE formulation (Presage-RU) in which the radiochromic response is reversible (the dosimeter optically clears after irradiation), enabling the potential for reusability. Methods: Presage-RU dose response and optical-clearing rates were evaluated in both small volume dosimeters (1×1×4.5cm) and a larger cylindrical dosimeter (8cm diameter, 4.5cm length). All dosimeters were allowed to fully optically clear in dark, room temperature conditions between irradiations. Dose response was determined by irradiating small volume samples from 0–8.0Gy and measuring change in optical density. Themore » cylindrical dosimeter was irradiated with a simple 4-field box plan (parallel opposed pairs of 4cm×4cm AP-PA beams and 2cm×4cm lateral beams) to 20Gy. High resolution 3D dosimetry was achieved utilizing optical-CT readout. Readings were tracked up to 14 days to characterize optical clearing. Results: Initial irradiation yielded a response of 0.0119△OD/(Gy*cm) while two subsequent reirradiations yielded a lower but consistent response of 0.0087△OD/(Gy*cm). Strong linearity of dose response was observed for all irradiations. In the large cylindrical dosimeter, the integral dose within the high dose region exhibited an exponential decay in signal over time (halflife= 23.9 hours), with the dosimeter effectively cleared (0.04% of the initial signal) after 10 days. Subsequent irradiation resulted in 19.5% lower initial signal but demonstrated that the exponential clearing rate remained consistent. Results of additional subsequent irradiations will also be presented. Conclusion: This work introduces a new re-usable radiochromic dosimeter (Presage-RU) compatible with high resolution (sub-millimeter) 3D dosimetry. Sensitivity of the initial radiation was observed to be slightly higher than subsequent irradiations, but the

Beam profiles measured with thermoluminescent dosimeters

NASA Technical Reports Server (NTRS)

Lucks, H.; Marcowitz, S. M.; Wheeler, R. W.

1969-01-01

Beam profilometer, using thermoluminescent dosimeters, gives a quantitative and qualitative representation of the focus of an external protron beam of a synchrotron. The total number of particles in the beam, particle distribution, and the shape of the beam are determined.

[Clinical relevance of ESR1 circulating mutations detection in hormone receptor positive metastatic breast cancer].

PubMed

Clatot, Florian; Perdrix, Anne; Sefrioui, David; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric

2018-01-01

If hormone therapy is a key treatment for hormone receptor positive advanced breast cancers, secondary resistance occurs as a rule. Recently, acquired alterations of the ESR1 gene have been identified as a mechanism of resistance on aromatase inhibitor (AI) treatment. The selective pressure by AI exposure during the metastatic setting triggers the emergence of ESR1 activating mutations. In that context, the "liquid biopsy" concept has been used to detect this molecular resistance before progression. Thus, the ESR1 circulating mutation detection will soon be used in daily practice to help monitoring patients on AI treatment and provide an early change for specific therapies that still have to be determined in prospective clinical trials. This review will present the acquired ESR1 mutations, as well as the methods used for their detection in blood and the potential clinical impact of this approach for hormone receptor positive breast cancer management. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Randomized, double-blind, placebo-controlled trial of the 5-HT1A receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate) in patients with irritable bowel syndrome.

PubMed

Drossman, Douglas A; Danilewitz, Mervyn; Naesdal, Jørgen; Hwang, Clara; Adler, John; Silberg, Debra G

2008-10-01

To investigate the efficacy and safety of the 5-hydroxytrypamine 1A (5-HT(1A)) receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate), termed AZD7371 here, in patients with irritable bowel syndrome (IBS). Patients meeting the Rome II criteria for IBS (N = 402) were randomized to treatment with AZD7371 20 mg or 5 mg or matching placebo tablets twice daily for 12 wk. The patients completed daily and weekly diary assessments, reporting abdominal discomfort or pain and description of bowel movements. They also completed validated symptom and quality-of-life questionnaires. Neither AZD7371 regimen was significantly more effective than placebo in providing adequate relief from IBS symptoms in at least 2 out of 4 wk per month over the 12 wk of treatment. There was also no significant difference between the treatment groups and placebo in the change in score in the validated symptom and quality-of-life questionnaires. Overall, 22.1% of patients experienced adverse events (AEs) attributed to the study medication: 44 of 133 (33.1%) in the 20 mg AZD7371 group, 27 of 131 (20.6%) in the 5 mg AZD7371 group, and 17 of 134 (12.7%) in the placebo group. Also, 31 of 57 (54%) of AEs leading to discontinuation were central nervous system-related. Hallucinations or hallucination-like AEs were reported by eight patients taking AZD7371, and by none of the patients in the placebo group. After these events led to discontinuation in six patients, the study was prematurely terminated. In view of the AE profile and lack of efficacy in IBS, the clinical development of AZD7371 has been stopped.

ESR dating of barite in sulphide deposits formed by the sea-floor hydrothermal activities.

PubMed

Toyoda, Shin; Fujiwara, Taisei; Uchida, Ai; Ishibashi, Jun-ichiro; Nakai, Shun'ichi; Takamasa, Asako

2014-06-01

Barite is a mineral newly found to be practically useful for electron spin resonance (ESR) dating of sulphide deposits formed by the sea-floor hydrothermal activities. The recent studies for the properties of the ESR dating signal in barite are summarised in the present paper as well as the formulas for corrections for accurate dose-rate estimation are developed including the dose-rate conversion factors, shape correction for gamma-ray dose and decay of (226)Ra. Although development of the techniques for ESR dating of barite has been completed, further comparative studies with other dating techniques such as U-Th and (226)Ra-(210)Pb dating are necessary for the technique to be widely used. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Passive radon/thoron personal dosimeter using an electrostatic collector and a diffused-junction detector

NASA Astrophysics Data System (ADS)

Bigu, J.; Raz, R.

1985-01-01

A solid-state alpha dosimeter has been designed and tested suitable for personal and environmental radon/thoron monitoring. The dosimeter basically consists of an electrostatic collector and an alpha-particle counting system with spectroscopy capabilities. The sensitive volume (˜20 cm3) of the electrostatic collector consists of a cylindrically shaped metal wire screen and a diffused-junction silicon alpha-detector covered with a thin aluminized Mylar sheet. A dc voltage (˜500 V) is applied between the wire screen and the Mylar sheet, with the latter held at negative potential relative to the former. Data can be retrieved during or after sampling by means of a microcomputer (Epson HX20) via a RS-232 communication interface unit. The dosimeter has been calibrated in a large (26 m3) radon/thoron test facility. A linear relationship was found between the dosimeter's alpha-count and both radon gas concentration and radon daughter working level. The dosimeter is mounted on top of an ordinary miner's cap lamp battery and is ideally suited for personal monitoring in underground uranium mines and other working areas. The dosimeter presented here is a considerably improved version of an earlier prototype.

Feasibility study of glass dosimeter postal dosimetry audit of high-energy radiotherapy photon beams.

PubMed

Mizuno, Hideyuki; Kanai, Tatsuaki; Kusano, Yohsuke; Ko, Susumu; Ono, Mari; Fukumura, Akifumi; Abe, Kyoko; Nishizawa, Kanae; Shimbo, Munefumi; Sakata, Suoh; Ishikura, Satoshi; Ikeda, Hiroshi

2008-02-01

The characteristics of a glass dosimeter were investigated for its potential use as a tool for postal dose audits. Reproducibility, energy dependence, field size and depth dependence were compared to those of a thermoluminescence dosimeter (TLD), which has been the major tool for postal dose audits worldwide. A glass dosimeter, GD-302M (Asahi Techno Glass Co.) and a TLD, TLD-100 chip (Harshaw Co.) were irradiated with gamma-rays from a (60)Co unit and X-rays from a medical linear accelerator (4, 6, 10 and 20 MV). The dosimetric characteristics of the glass dosimeter were almost equivalent to those of the TLD, in terms of utility for dosimetry under the reference condition, which is a 10 x 10 cm(2) field and 10 cm depth. Because of its reduced fading, compared to the TLD, and easy quality control with the ID number, the glass dosimeter proved to be a suitable tool for postal dose audits. Then, we conducted postal dose surveys of over 100 facilities and got good agreement, with a standard deviation of about 1.3%. Based on this study, postal dose audits throughout Japan will be carried out using a glass dosimeter.

SU-E-T-274: Does Atmospheric Oxygen Affect the PRESAGE Dosimeter?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alqathami, M; Ibbott, G; Blencowe, A

Purpose: To experimentally determine the influence of atmospheric oxygen on the efficiency of the PRESAGE dosimeter and its reporting system. Methods: Batches of the reporting system – a mixture of chloroform and leuchomalachite green dye – and PRESAGE were prepared in aerobic and anaerobic conditions. For anaerobic batches, samples were deoxygenated by bubbling nitrogen through the dosimeter precursors or reporting system for 10 min. The dosimeters and reporting systems were prepared in spectrophotometric cuvettes and glass vials, respectively, and were irradiated with 6 MV photons to various radiation doses using a clinical linear accelerator. Changes in optical density of themore » dosimeters and reporting system before and after irradiation were measured using a spectrophotometer. In addition, the concentrations of dissolved oxygen were measured using a dissolved oxygen meter. Results: The experiments revealed that oxygen has little influence on the characteristics of PRESAGE, with the radical initiator oxidizing the leucomalachite green even in the presence of oxygen. However, deoxygenation of the reporting system leads to an increase in sensitivity to radiation dose by ∼ 30% when compared to the non-deoxygenated system. A slight improvement in sensitivity (∼ 5%) was also achieved by deoxygenating the PRESAGE precursor prior to casting. Measurement of the dissolved oxygen revealed low levels (0.4 ppm) in the polyurethane precursor used to fabricate the dosimeters, as compared to water (8.6 ppm). In addition, deoxygenation had no effect on the retention of the post-response absorption value of the PRESAGE dosimeter. Conclusion: The results suggest that the presence of oxygen does not inhibit the radiochromic properties of the PRESAGE system. In addition, there were no observed changes in the dose linearity, absorption spectrum and post-response photofading characteristics of the PRESAGE under the conditions investigated.« less

Ionization chamber dosimeter

DOEpatents

Renner, Tim R.; Nyman, Mark A.; Stradtner, Ronald

1991-01-01

A method for fabricating an ion chamber dosimeter collecting array of the type utilizing plural discrete elements formed on a uniform collecting surface which includes forming a thin insulating layer over an aperture in a frame having surfaces, forming a predetermined pattern of through holes in the layer, plating both surfaces of the layer and simultaneously tilting and rotating the frame for uniform plate-through of the holes between surfaces. Aligned masking and patterned etching of the surfaces provides interconnects between the through holes and copper leads provided to external circuitry.

Estradiol-induced regulation of GLUT4 in 3T3-L1 cells: involvement of ESR1 and AKT activation.

PubMed

Campello, Raquel S; Fátima, Luciana A; Barreto-Andrade, João Nilton; Lucas, Thais F; Mori, Rosana C; Porto, Catarina S; Machado, Ubiratan F

2017-10-01

Impaired insulin-stimulated glucose uptake involves reduced expression of the GLUT4 (solute carrier family 2 facilitated glucose transporter member 4, SLC2A4 gene). 17β-estradiol (E 2 ) modulates SLC2A4 /GLUT4 expression, but the involved mechanisms are unclear. Although E 2 exerts biological effects by binding to estrogen receptors 1/2 (ESR1/2), which are nuclear transcriptional factors; extranuclear effects have also been proposed. We hypothesize that E 2 regulates GLUT4 through an extranuclear ESR1 mechanism. Thus, we investigated the effects of E 2 upon (1) subcellular distribution of ESRs and the proto-oncogene tyrosine-protein kinases (SRC) involvement; (2) serine/threonine-protein kinase (AKT) activation; (3) Slc2a4 /GLUT4 expression and (4) GLUT4 subcellular distribution and glucose uptake in 3T3-L1 adipocytes. Differentiated 3T3-L1 adipocytes were cultivated or not with E 2 for 24 h, and additionally treated or not with ESR1-selective agonist (PPT), ESR1-selective antagonist (MPP) or selective SRC inhibitor (PP2). Subcellular distribution of ESR1, ESR2 and GLUT4 was analyzed by immunocytochemistry; Slc2a4 mRNA and GLUT4 were quantified by qPCR and Western blotting, respectively; plasma membrane GLUT4 translocation and glucose uptake were analyzed under insulin stimulus for 20 min or not. E 2 induced (1) translocation of ESR1, but not of ESR2, from nucleus to plasma membrane and AKT phosphorylation, effects mimicked by PPT and blocked by MPP and PP2; (2) increased Slc2a4 /GLUT4 expression and (3) increased insulin-stimulated GLUT4 translocation and glucose uptake. In conclusion, E 2 treatment promoted a SRC-mediated nucleus-plasma membrane shuttle of ESR1, and increased AKT phosphorylation, Slc2a4 /GLUT4 expression and plasma membrane GLUT4 translocation; consequently, improving insulin-stimulated glucose uptake. These results unravel mechanisms through which estrogen improves insulin sensitivity. © 2017 Society for Endocrinology.

Feasibility of reading LiF thermoluminescent dosimeters by electron spin resonance

NASA Astrophysics Data System (ADS)

Breen, S. L.; Battista, J. J.

1999-08-01

Lithium fluoride is a commonly used solid state dosimeter. During irradiation, electrons and holes become trapped in crystal imperfections; thermoluminescence dosimetry measures their thermally induced recombination. Electron paramagnetic resonance (EPR) spectroscopy can be used to measure the resonant absorption of microwaves by the unpaired electrons trapped in LiF. In an effort to extend the use of LiF dosimeters to smaller sizes and to the harsh environments encountered in internal dosimetry, EPR was evaluated as an alternative technique to read the radiation dose delivered to TLD-100 dosimeters. TLD-100 rods were irradiated with a 60Co source to doses of 10 Gy to 100 Gy. A radiation-induced signal (with a g-value of 2.002) could be detected only at liquid nitrogen temperatures at doses above 20 Gy. The EPR spectrum of irradiated LiF contains three components, one of which correlates positively with dose. However, the low sensitivity of the technique, and difficulty in interpreting the EPR spectrum from polycrystalline dosimeters, preclude its use as a dosimetry technique.

Feasibility of reading LiF thermoluminescent dosimeters by electron spin resonance.

PubMed

Breen, S L; Battista, J J

1999-08-01

Lithium fluoride is a commonly used solid state dosimeter. During irradiation, electrons and holes become trapped in crystal imperfections; thermoluminescence dosimetry measures their thermally induced recombination. Electron paramagnetic resonance (EPR) spectroscopy can be used to measure the resonant absorption of microwaves by the unpaired electrons trapped in LiF. In an effort to extend the use of LiF dosimeters to smaller sizes and to the harsh environments encountered in internal dosimetry, EPR was evaluated as an alternative technique to read the radiation dose delivered to TLD-100 dosimeters. TLD-100 rods were irradiated with a 60Co source to doses of 10 Gy to 100 Gy. A radiation-induced signal (with a g-value of 2.002) could be detected only at liquid nitrogen temperatures at doses above 20 Gy. The EPR spectrum of irradiated LiF contains three components, one of which correlates positively with dose. However, the low sensitivity of the technique, and difficulty in interpreting the EPR spectrum from polycrystalline dosimeters, preclude its use as a dosimetry technique.

The responses of three kinds of passive dosimeters to secondary cosmic rays in the lower atmosphere.

PubMed

Yang, Zhen; Chen, Bo; Zhuo, Weihai; Fan, Dunhuang; Zhao, Chao; Zhang, Yu

2015-12-01

For accurate measurements of the secondary cosmic rays by using passive dosimeters, the relative responses of the thermoluminescence dosimeter (TLD), optically stimulated luminescence (OSL) dosimeter, and radiophotoluminescent glass dosimeter (RPLGD) were studied. The cosmic-ray shower generator was used to simulate the secondary cosmic rays at the sea level. Monte Carlo simulations were performed to calculate the air kerma and absorbed doses in each kind of dosimeter. The results showed that compared with their responses to gamma rays of (137)Cs, the relative responses of the TLD, OSL, and RPLGD were 0.786, 0.707, and 0.735 to the hard component of cosmic rays, respectively, and the values were 0.904, 0.838, and 0.857 to the soft component of cosmic rays, respectively. To verify the simulations results, an in situ measurement with the three kinds of dosimeters was performed at the same place. The results indicated that the secondary cosmic rays monitored with the three kinds of dosimeters were well consistent with each other provided their relative responses were taken into account.

The responses of three kinds of passive dosimeters to secondary cosmic rays in the lower atmosphere

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Zhen; Chen, Bo, E-mail: bochenfys@fudan.edu.cn; Zhuo, Weihai

For accurate measurements of the secondary cosmic rays by using passive dosimeters, the relative responses of the thermoluminescence dosimeter (TLD), optically stimulated luminescence (OSL) dosimeter, and radiophotoluminescent glass dosimeter (RPLGD) were studied. The cosmic-ray shower generator was used to simulate the secondary cosmic rays at the sea level. Monte Carlo simulations were performed to calculate the air kerma and absorbed doses in each kind of dosimeter. The results showed that compared with their responses to gamma rays of {sup 137}Cs, the relative responses of the TLD, OSL, and RPLGD were 0.786, 0.707, and 0.735 to the hard component of cosmicmore » rays, respectively, and the values were 0.904, 0.838, and 0.857 to the soft component of cosmic rays, respectively. To verify the simulations results, an in situ measurement with the three kinds of dosimeters was performed at the same place. The results indicated that the secondary cosmic rays monitored with the three kinds of dosimeters were well consistent with each other provided their relative responses were taken into account.« less

The responses of three kinds of passive dosimeters to secondary cosmic rays in the lower atmosphere

NASA Astrophysics Data System (ADS)

Yang, Zhen; Chen, Bo; Zhuo, Weihai; Fan, Dunhuang; Zhao, Chao; Zhang, Yu

2015-12-01

For accurate measurements of the secondary cosmic rays by using passive dosimeters, the relative responses of the thermoluminescence dosimeter (TLD), optically stimulated luminescence (OSL) dosimeter, and radiophotoluminescent glass dosimeter (RPLGD) were studied. The cosmic-ray shower generator was used to simulate the secondary cosmic rays at the sea level. Monte Carlo simulations were performed to calculate the air kerma and absorbed doses in each kind of dosimeter. The results showed that compared with their responses to gamma rays of 137Cs, the relative responses of the TLD, OSL, and RPLGD were 0.786, 0.707, and 0.735 to the hard component of cosmic rays, respectively, and the values were 0.904, 0.838, and 0.857 to the soft component of cosmic rays, respectively. To verify the simulations results, an in situ measurement with the three kinds of dosimeters was performed at the same place. The results indicated that the secondary cosmic rays monitored with the three kinds of dosimeters were well consistent with each other provided their relative responses were taken into account.

Direct access to dithiobenzoate RAFT agent fragmentation rate coefficients by ESR spin-trapping.

PubMed

Ranieri, Kayte; Delaittre, Guillaume; Barner-Kowollik, Christopher; Junkers, Thomas

2014-12-01

The β-scission rate coefficient of tert-butyl radicals fragmenting off the intermediate resulting from their addition to tert-butyl dithiobenzoate-a reversible addition-fragmentation chain transfer (RAFT) agent-is estimated via the recently introduced electron spin resonance (ESR)-trapping methodology as a function of temperature. The newly introduced ESR-trapping methodology is critically evaluated and found to be reliable. At 20 °C, a fragmentation rate coefficient of close to 0.042 s(-1) is observed, whereas the activation parameters for the fragmentation reaction-determined for the first time-read EA = 82 ± 13.3 kJ mol(-1) and A = (1.4 ± 0.25) × 10(13) s(-1) . The ESR spin-trapping methodology thus efficiently probes the stability of the RAFT adduct radical under conditions relevant for the pre-equilibrium of the RAFT process. It particularly indicates that stable RAFT adduct radicals are indeed formed in early stages of the RAFT poly-merization, at least when dithiobenzoates are employed as controlling agents as stipulated by the so-called slow fragmentation theory. By design of the methodology, the obtained fragmentation rate coefficients represent an upper limit. The ESR spin-trapping methodology is thus seen as a suitable tool for evaluating the fragmentation rate coefficients of a wide range of RAFT adduct radicals. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Small-Field Measurements of 3D Polymer Gel Dosimeters through Optical Computed Tomography.

PubMed

Shih, Tian-Yu; Wu, Jay; Shih, Cheng-Ting; Lee, Yao-Ting; Wu, Shin-Hua; Yao, Chun-Hsu; Hsieh, Bor-Tsung

2016-01-01

With advances in therapeutic instruments and techniques, three-dimensional dose delivery has been widely used in radiotherapy. The verification of dose distribution in a small field becomes critical because of the obvious dose gradient within the field. The study investigates the dose distributions of various field sizes by using NIPAM polymer gel dosimeter. The dosimeter consists of 5% gelatin, 5% monomers, 3% cross linkers, and 5 mM THPC. After irradiation, a 24 to 96 hour delay was applied, and the gel dosimeters were read by a cone beam optical computed tomography (optical CT) scanner. The dose distributions measured by the NIPAM gel dosimeter were compared to the outputs of the treatment planning system using gamma evaluation. For the criteria of 3%/3 mm, the pass rates for 5 × 5, 3 × 3, 2 × 2, 1 × 1, and 0.5 × 0.5 cm2 were as high as 91.7%, 90.7%, 88.2%, 74.8%, and 37.3%, respectively. For the criteria of 5%/5 mm, the gamma pass rates of the 5 × 5, 3 × 3, and 2 × 2 cm2 fields were over 99%. The NIPAM gel dosimeter provides high chemical stability. With cone-beam optical CT readouts, the NIPAM polymer gel dosimeter has potential for clinical dose verification of small-field irradiation.

Direct and pulsed current annealing of p-MOSFET based dosimeter: the "MOSkin".

PubMed

Alshaikh, Sami; Carolan, Martin; Petasecca, Marco; Lerch, Michael; Metcalfe, Peter; Rosenfeld, Anatoly

2014-06-01

Contemporary radiation therapy (RT) is complicated and requires sophisticated real-time quality assurance (QA). While 3D real-time dosimetry is most preferable in RT, it is currently not fully realised. A small, easy to use and inexpensive point dosimeter with real-time and in vivo capabilities is an option for routine QA. Such a dosimeter is essential for skin, in vivo or interface dosimetry in phantoms for treatment plan verification. The metal-oxide-semiconductor-field-effect-transistor (MOSFET) detector is one of the best choices for these purposes, however, the MOSFETs sensitivity and its signal stability degrade after essential irradiation which limits its lifespan. The accumulation of positive charge on the gate oxide and the creation of interface traps near the silicon-silicon dioxide layer is the primary physical phenomena responsible for this degradation. The aim of this study is to investigate MOSFET dosimeter recovery using two proposed annealing techniques: direct current (DC) and pulsed current (PC), both based on hot charged carrier injection into the gate oxide of the p-MOSFET dosimeter. The investigated MOSFETs were reused multiple times using an irradiation-annealing cycle. The effect of the current-annealing parameters was investigated for the dosimetric characteristics of the recovered MOSFET dosimeters such as linearity, sensitivity and initial threshold voltage. Both annealing techniques demonstrated excellent results in terms of maintaining a stable response, linearity and sensitivity of the MOSFET dosimeter. However, PC annealing is more preferable than DC annealing as it offers better dose response linearity of the reused MOSFET and has a very short annealing time.

Method for correcting for isotope burn-in effects in fission neutron dosimeters

DOEpatents

Gold, Raymond; McElroy, William N.

1988-01-01

A method is described for correcting for effect of isotope burn-in in fission neutron dosimeters. Two quantities are measured in order to quantify the "burn-in" contribution, namely P.sub.Z',A', the amount of (Z', A') isotope that is burned-in, and F.sub.Z', A', the fissions per unit volume produced in the (Z', A') isotope. To measure P.sub.Z', A', two solid state track recorder fission deposits are prepared from the very same material that comprises the fission neutron dosimeter, and the mass and mass density are measured. One of these deposits is exposed along with the fission neutron dosimeter, whereas the second deposit is subsequently used for observation of background. P.sub.Z', A' is then determined by conducting a second irradiation, wherein both the irradiated and unirradiated fission deposits are used in solid state track recorder dosimeters for observation of the absolute number of fissions per unit volume. The difference between the latter determines P.sub.Z', A' since the thermal neutron cross section is known. F.sub.Z', A' is obtained by using a fission neutron dosimeter for this specific isotope, which is exposed along with the original threshold fission neutron dosimeter to experience the same neutron flux-time history at the same location. In order to determine the fissions per unit volume produced in the isotope (Z', A') as it ingrows during the irradiation, B.sub.Z', A', from these observations, the neutron field must generally be either time independent or a separable function of time t and neutron energy E.

Analysis of ESR1 and PIK3CA mutations in plasma cell-free DNA from ER-positive breast cancer patients

PubMed Central

Takeshita, Takashi; Yamamoto, Yutaka; Yamamoto-Ibusuki, Mutsuko; Tomiguchi, Mai; Sueta, Aiko; Murakami, Keiichi; Omoto, Yoko; Iwase, Hirotaka

2017-01-01

Background The measurement of ESR1 and PIK3CA mutations in plasma cell-free DNA (cfDNA) has been studied as a non-invasive method to quickly assess and monitor endocrine therapy (ET) resistant metastatic breast cancer (MBC) patients. Methods The subjects of this retrospective study were a total of 185 plasma samples from 86 estrogen receptor-positive BC patients, of which 151 plasma samples were from 69 MBC patients and 34 plasma samples were from 17 primary BC (PBC) patients. We developed multiplex droplet digital PCR assays to verify the clinical significance of ESR1 and PIK3CA mutations both in a snapshot and serially in these patients. Results cfDNA ESR1 and PIK3CA mutations were found in 28.9% and 24.6 % of MBC patients, respectively. The relation between ESR1 or PIK3CA mutations and clinical features showed that ESR1 mutations occurred mostly in patients previously treated by ET, which was not the case for PIK3CA mutations. The analysis of the clinical impact of those mutations on subsequent lines of treatment for the 69 MBC patients revealed that both ESR1 and PIK3CA mutations detection were related to a shorter duration of ET effectiveness in univariate analysis but only for ESR1 mutations in multivariate analysis. The monitoring of cfDNA in a subset of 52 patients showed that loss of ESR1 mutations was related to a longer duration of response, which was not the case for PIK3CA mutations. Conclusions We have demonstrated the clinical significance of on-treatment ESR1 mutations both in a snapshot and serially in comparison with PIK3CA mutations. PMID:28881720

Electron Spin Resonance (ESR) detection of active oxygen species and organic phases in Martian soils

NASA Technical Reports Server (NTRS)

Tsay, Fun-Dow; Kim, Soon Sam; Liang, Ranty H.

1989-01-01

The presence of active oxygen species (O(-), O2(-), O3(-)) and other strong oxidants (Fe2O3 and Fe3O4) was invoked in interpretations of the Viking biological experiments and a model was also suggested for Martian surface chemistry. The non-biological interpretations of the biological results gain futher support as no organic compounds were detected in the Viking pyrolysis-gas chromatography mass spectrometer (GCSM) experiments at concentrations as low as 10 ppb. Electron spin resonance (ESR) measures the absorption of microwaves by a paramagnetic and/or ferromagnetic center in the presence of an external field. In many instances, ESR has the advantage of detailed submicroscopic identification of the transient species and/or unstable reaction intermediates in their environments. Since the higly active oxygen species (O(-), O2(-), O3(-), and R-O-O(-)) are all paramagnetic in nature, they can be readily detected in native form by the ESR method. Active oxygen species likely to occur in the Martian surface samples were detected by ESR in UV-irradiated samples containing MgO. A miniaturized ESR spectrometer system can be developed for the Mars Rover Sample Return Mission. The instrument can perform the following in situ Martian samples analyses: detection of active oxygen species; characterization of Martian surface chemistry and photooxidation processes; and searching for organic compounds in the form of free radicals preserved in subsoils, and detection of microfossils with Martian carbonate sediments.

Acceptance Testing of Thermoluminescent Dosimeter Holders.

PubMed

Romanyukha, Alexander; Grypp, Matthew D; Sharp, Thad J; DiRito, John N; Nelson, Martin E; Mavrogianis, Stanley T; Torres, Jeancarlo; Benevides, Luis A

2018-05-01

The U.S. Navy uses the Harshaw 8840/8841 dosimetric (DT-702/PD) system, which employs LiF:Mg,Cu,P thermoluminescent dosimeters (TLDs), developed and produced by Thermo Fisher Scientific (TFS). The dosimeter consists of four LiF:Mg,Cu,P elements, mounted in Teflon® on an aluminum card and placed in a plastic holder. The holder contains a unique filter for each chip made of copper, acrylonitrile butadiene styrene (ABS), Mylar®, and tin. For accredited dosimetry labs, the ISO/IEC 17025:2005(E) requires an acceptance procedure for all new equipment. The Naval Dosimetry Center (NDC) has developed and tested a new non-destructive procedure, which enables the verification and the evaluation of embedded filters in the holders. Testing is based on attenuation measurements of low-energy radiation transmitted through each filter in a representative sample group of holders to verify that the correct filter type and thickness are present. The measured response ratios are then compared with the expected response ratios. In addition, each element's measured response is compared to the mean response of the group. The test was designed and tested to identify significant nonconformities, such as missing copper or tin filters, double copper or double tin filters, or other nonconformities that may impact TLD response ratios. During the implementation of the developed procedure, testing revealed a holder with a double copper filter. To complete the evaluation, the impact of the nonconformities on proficiency testing was examined. The evaluation revealed failures in proficiency testing categories III and IV when these dosimeters were irradiated to high-energy betas.

ESR modes in a Strong-Leg Ladder in the Tomonaga-Luttinger Liquid Phase

NASA Astrophysics Data System (ADS)

Zvyagin, S.; Ozerov, M.; Maksymenko, M.; Wosnitza, J.; Honecker, A.; Landee, C. P.; Turnbull, M.; Furuya, S. C.; Giamarchi, T.

Magnetic excitations in the strong-leg quantum spin ladder compound (C7H10N)2CuBr4 (known as DIMPY) in the field-induced Tomonaga-Luttinger spin liquid phase are studied by means of high-field electron spin resonance (ESR) spectroscopy. The presence of a gapped ESR mode with unusual non-linear frequency-field dependence is revealed experimentally. Using a combination of analytic and exact diagonalization methods, we compute the dynamical structure factor and identify this mode with longitudinal excitations in the antisymmetric channel. We argue that these excitations constitute a fingerprint of the spin dynamics in a strong-leg spin-1/2 Heisenberg antiferromagnetic ladder and owe its ESR observability to the uniform Dzyaloshinskii-Moriya interaction. This work was partially supported by the DFG and Helmholtz Gemeinschaft (Germany), Swiss SNF under Division II, and ERC synergy UQUAM project. We acknowledge the support of the HLD at HZDR, member of the European Magnetic Field Laboratory (EMFL).

A multiplex allele-specific real-time PCR assay for screening of ESR1 mutations in metastatic breast cancer.

PubMed

Wang, Ting; Liu, Jin-Hui; Zhang, Jie; Wang, Le; Chen, Chao; Dai, Peng-Gao

2015-04-01

Acquired resistance to endocrine-based therapies occurs in virtually all estrogen receptor-α (ERα, encoded by ESR1) positive breast cancer patients. The underlying molecular mechanism is attributed to the activating mutations in ESR1. These mutations provide an exciting opportunity for the development of new antagonists that specifically inhibit the mutant proteins. Therefore, accurate detection of ESR1 mutations is of critical importance in clinical practice. We carried out a single tube, multiplex allele-specific real-time PCR assay for the detection of four ESR1 mutations (Y537S, Y537C, Y537N, and D538G). The assay was found to be highly specific and sensitive. With this assay, as low as 1% mutant DNA template in wild type DNA could be detected. Fifteen DNA samples were prepared from archived formalin-fixed paraffin-embedded metastatic breast cancer biopsies. They were further screened with this assay, and three samples were identified as ESR1 mutant. The results were validated with pyrosequencing and complete concordance was observed between the two assays. The multiplex allele-specific real-time PCR assay provides a rapid and reliable diagnostic tool for accurate detection of ESR1 mutations. This procedure may be used in the clinical treatment of breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Determination of dosimetric and kinetic features of gamma irradiated solid calcium ascorbate dihydrate using ESR spectroscopy

NASA Astrophysics Data System (ADS)

Tuner, H.

2013-01-01

Effects of gamma radiation on solid calcium ascorbate dihydrate were studied using electron spin resonance (ESR) spectroscopy. Irradiated samples were found to present two specific ESR lines with shoulder at low and high magnetic field sides. Structural and kinetic features of the radicalic species responsible for experimental ESR spectrum were explored through the variations of the signal intensities with applied microwave power, variable temperature, high-temperature annealing and room temperature storage time studies. Dosimetric potential of the sample was also determined using spectrum area and measured signal intensity measurements. It was concluded that three radicals with different spectroscopic and kinetic features were produced upon gamma irradiation.

Effects of daily pyrantel tartrate on strongylid population dynamics and performance parameters of young horses repeatedly infected with cyathostomins and Strongylus vulgaris.

PubMed

Reinemeyer, C R; Prado, J C; Andersen, U V; Nielsen, M K; Schricker, B; Kennedy, T

2014-08-29

Strongylid infections are ubiquitous in grazing horse populations. Infections with cyathostomin (small strongyle) and strongylin (large strongyle) nematodes have long been associated with clinical disease in horses, but little is known about their subclinical impact. A masked, randomized, controlled study was conducted to evaluate the effects of daily administration of pyrantel tartrate on body condition scores, weight gain, fecal egg counts, and total worm counts of young horses repeatedly inoculated with strongylid larvae. Twenty eight immature horses were treated with larvicidal anthelmintic regimens and randomly allocated to two groups. Group 1 horses were given a pelleted placebo product once daily, and those in Group 2 received pyrantel tartrate once daily at ∼ 2.64 mg/kg body weight. On five days during each week, ∼ 5000 infective cyathostomin larvae were administered to each horse. In addition, horses received ∼ 25 infective Strongylus vulgaris larvae once weekly. Horses were maintained on pasture for 154 days and had ad libitum access to grass hay throughout. At approximate, 14-day intervals, body weights were measured, body condition scores were assigned, fecal samples were collected for egg counts, and blood samples were collected for measurement of S. vulgaris antibodies and various physiologic parameters. After 22 weeks at pasture and 14-17 days in confinement, horses were euthanatized and necropsied. Nematodes were recovered and counted from aliquots of organ contents, representative samples of large intestinal mucosa, and the root of the cranial mesenteric artery. Daily treatment with pyrantel tartrate at the recommended dosage significantly reduced numbers of adult cyathostomins in the gut lumen and early third-stage larvae in the cecal mucosa, increased the proportions of fourth-stage larvae in the gut contents, and was accompanied by significant improvements in body condition scores. Fecal egg counts of horses receiving daily pyrantel

Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus.

PubMed

Lee, Hyosang; Kim, Dong-Wook; Remedios, Ryan; Anthony, Todd E; Chang, Angela; Madisen, Linda; Zeng, Hongkui; Anderson, David J

2014-05-29

Social behaviours, such as aggression or mating, proceed through a series of appetitive and consummatory phases that are associated with increasing levels of arousal. How such escalation is encoded in the brain, and linked to behavioural action selection, remains an unsolved problem in neuroscience. The ventrolateral subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons whose activity increases during male-male and male-female social encounters. Non-cell-type-specific optogenetic activation of this region elicited attack behaviour, but not mounting. We have identified a subset of VMHvl neurons marked by the oestrogen receptor 1 (Esr1), and investigated their role in male social behaviour. Optogenetic manipulations indicated that Esr1(+) (but not Esr1(-)) neurons are sufficient to initiate attack, and that their activity is continuously required during ongoing agonistic behaviour. Surprisingly, weaker optogenetic activation of these neurons promoted mounting behaviour, rather than attack, towards both males and females, as well as sniffing and close investigation. Increasing photostimulation intensity could promote a transition from close investigation and mounting to attack, within a single social encounter. Importantly, time-resolved optogenetic inhibition experiments revealed requirements for Esr1(+) neurons in both the appetitive (investigative) and the consummatory phases of social interactions. Combined optogenetic activation and calcium imaging experiments in vitro, as well as c-Fos analysis in vivo, indicated that increasing photostimulation intensity increases both the number of active neurons and the average level of activity per neuron. These data suggest that Esr1(+) neurons in VMHvl control the progression of a social encounter from its appetitive through its consummatory phases, in a scalable manner that reflects the number or type of active neurons in the population.

The use of ESR spectroscopy for the identification and dose assessment of irradiated pink shrimp (Parapenaeus longirostris) from Turkey

NASA Astrophysics Data System (ADS)

Aydaş, Canan; Tepe Çam, Semra; Engin, Birol; Aydın, Talat; Polat, Mustafa

2013-03-01

Turkish pink shrimp (Parapenaeus longirostris) samples were studied by electron spin resonance (ESR) spectroscopy for identification and dose assessment purposes. In this work, the calcified shells of shrimps were used as a sample material. Before irradiation, all shrimp shell samples exhibit one weak ESR singlet with a g-factor of 2.0047. After irradiation, all samples exhibit two asymmetric ESR signal components centered at g-values of 2.0013 and 1.9959. The dose-response curves of the samples exposed to gamma radiations were found to be described well by a single saturation exponential function. Variation of ESR signal intensity of irradiated samples at room and-20 °C temperatures with time in a long-term showed that free radicals responsible from the ESR spectrum of shrimp shells were not stable but still detectable after 87 days. Also, the kinetic behavior of signal at g=2.0013 was studied and the additive dose method was used to evaluate the dose in the product.

Radiotherapy Measurements with a Deoxyribonucleic Acid Doublestrand-Break Dosimeter

NASA Astrophysics Data System (ADS)

Obeidat, Mohammad Ali

Many types of dosimeters are used in the clinic to measure radiation dose for therapy but none of them directly measures the biological effect of this dose. The overall purpose of this work was to develop a dosimeter that measures biological damage in the form of double-strand breaks to deoxyribonucleic acid. This dosimeter could provide a more biologically relevant measure of radiation damage than the currently utilized dosimeters. A pair of oligonucleotides was designed to fabricate this dosimeter. One is labeled with a 5'-end biotin and the other with a 5'-end 6 Fluorescein amidite (fluorescent dye excited at 495?nanometer, with a peak emission at 520 nanometer). These were designed to adhere to certain locations on the pRS316 vector and serve as the primers for polymerase chain reactions. The end product of this reaction is a 4 kilo-base pair double strands deoxyribonucleic acid fragment with biotin on one end and 6 Fluorescein amidite oligonucleotide on the other attached to streptavidin beads. The biotin end connects the double strands deoxyribonucleic acid to the streptavidin bead. These bead-connected double strands deoxyribonucleic acid were suspended in 50 microliter of phosphate-buffered saline and placed into a tube for irradiation. Following irradiation of the deoxyribonucleic acid dosimeter, we take advantage of the magnetic properties of the streptavidin bead by placing our sample microtube against a magnet. The magnetic field pulls the streptavidin beads against the side of the tube. If a double-strand-break has occurred for a double strands deoxyribonucleic acid, the fluorescein end of the double strands deoxyribonucleic acid becomes free and is no longer attached to the bead or held against the side of the microtube. The free fluorescein following a double-strand-break in double strands deoxyribonucleic acid is referred to here as supernatant. The supernatant is extracted and placed in another microtube, while the unbroken double strands

Characteristics of optically stimulated luminescence dosimeters in the spread-out Bragg peak region of clinical proton beams.

PubMed

Kerns, James R; Kry, Stephen F; Sahoo, Narayan

2012-04-01

Optically stimulated luminescent detectors (OSLDs) have a number of advantages in radiation dosimetry making them excellent dosimeters for quality assurance and patient dose verification. Although the dosimeters have been investigated in several modalities, relatively little work has been done in examining the dosimeters for use in clinical proton beams. This study examined a number of characteristics of the response of the dosimeters in the spread-out Bragg peak (SOBP) region of clinical proton beams. Optically stimulated luminescence (OSL) dosimeters from Landauer, Inc., specifically the nanoDot dosimeter, were investigated. These dosimeters were placed in a special phantom with a recess to fit the dosimeters without an air gap. Beams with nominal energies of 160, 200, and 250 MeV were used in the passively-scattered proton beam at the MD Anderson Cancer Center Proton Therapy Center. Dosimetric properties including linearity, field size dependence, energy dependence, residual signal as a function of cumulative dose, and postirradiation fading were investigated by taking measurements at the center of SOBPs. The dosimeters showed 1% supralinearity at 200 cGy and 5% supralinearity at 1000 cGy. No noticeable field size dependence of the detector was found for field sizes from 2 × 2 cm(2) to 18 × 18 cm(2). Residual signal as a function of cumulative dose showed a small increase for measurements up to 1000 cGy. Readout signal depletion of the dosimeters after consecutive readings showed a slightly larger depletion in protons for doses up to 500 cGy but not by a clinically significant amount. Within the center of various SOBP widths and proton energies the variation in response was less than 2%. An average beam quality factor of 1.089 with experimental standard deviation of 0.007 was determined and applied to the data such that the results were within 1.2% of ion chamber data. The nanoDot OSL dosimeter characteristics were studied in the SOBP region of

Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole.

PubMed

Gyanchandani, Rekha; Kota, Karthik J; Jonnalagadda, Amruth R; Minteer, Tanya; Knapick, Beth A; Oesterreich, Steffi; Brufsky, Adam M; Lee, Adrian V; Puhalla, Shannon L

2017-09-15

ESR1 mutations are frequently acquired in hormone-resistant metastatic breast cancer (MBC). CDK4/6 inhibition along with endocrine therapy is a promising strategy in hormone receptor-positive MBC. However, the incidence and impact of ESR1 mutations on clinical outcome in patients treated with CDK4/6 inhibitors have not been defined. In this study, we evaluated the frequency of ESR1 mutations in cfDNA from 16 patients with MBC undergoing palbociclib and letrozole therapy. Four common ESR1 mutations (D538G, Y537C, Y537N, and Y537S) were analyzed in serial blood draws using ddPCR. Mutation rate was 31.3% (5/16) (n=3; de novo , n=2; acquired). D538G was the most frequent mutation (n=3), followed by Y537N and Y537S (n=2). One patient showed multiple ESR1 mutations. Mutations were enriched during therapy. Progression-free survival (PFS) and overall survival (OS) were similar in patients with and without mutation detected at any given time during treatment. However, PFS was significantly shorter in patients with ESR1 mutation at initial blood draw (3.3 versus 9.0 months, P-value=0.038). In conclusion, ESR1 mutation prevalence is consistent with recent studies in hormone-refractory breast cancer. Further, treatment with palbociclib and letrozole does not prevent selection of ESR1 mutations in later lines of therapy. Larger studies are warranted to validate these findings.

Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole

PubMed Central

Gyanchandani, Rekha; Kota, Karthik J.; Jonnalagadda, Amruth R.; Minteer, Tanya; Knapick, Beth A.; Oesterreich, Steffi; Brufsky, Adam M.; Lee, Adrian V.; Puhalla, Shannon L.

2017-01-01

ESR1 mutations are frequently acquired in hormone-resistant metastatic breast cancer (MBC). CDK4/6 inhibition along with endocrine therapy is a promising strategy in hormone receptor-positive MBC. However, the incidence and impact of ESR1 mutations on clinical outcome in patients treated with CDK4/6 inhibitors have not been defined. In this study, we evaluated the frequency of ESR1 mutations in cfDNA from 16 patients with MBC undergoing palbociclib and letrozole therapy. Four common ESR1 mutations (D538G, Y537C, Y537N, and Y537S) were analyzed in serial blood draws using ddPCR. Mutation rate was 31.3% (5/16) (n=3; de novo, n=2; acquired). D538G was the most frequent mutation (n=3), followed by Y537N and Y537S (n=2). One patient showed multiple ESR1 mutations. Mutations were enriched during therapy. Progression-free survival (PFS) and overall survival (OS) were similar in patients with and without mutation detected at any given time during treatment. However, PFS was significantly shorter in patients with ESR1 mutation at initial blood draw (3.3 versus 9.0 months, P-value=0.038). In conclusion, ESR1 mutation prevalence is consistent with recent studies in hormone-refractory breast cancer. Further, treatment with palbociclib and letrozole does not prevent selection of ESR1 mutations in later lines of therapy. Larger studies are warranted to validate these findings. PMID:28978004

FlexyDos3D: a deformable anthropomorphic 3D radiation dosimeter: radiation properties

NASA Astrophysics Data System (ADS)

De Deene, Y.; Skyt, P. S.; Hil, R.; Booth, J. T.

2015-02-01

Three dimensional radiation dosimetry has received growing interest with the implementation of highly conformal radiotherapy treatments. The radiotherapy community faces new challenges with the commissioning of image guided and image gated radiotherapy treatments (IGRT) and deformable image registration software. A new three dimensional anthropomorphically shaped flexible dosimeter, further called ‘FlexyDos3D’, has been constructed and a new fast optical scanning method has been implemented that enables scanning of irregular shaped dosimeters. The FlexyDos3D phantom can be actuated and deformed during the actual treatment. FlexyDos3D offers the additional advantage that it is easy to fabricate, is non-toxic and can be molded in an arbitrary shape with high geometrical precision. The dosimeter formulation has been optimized in terms of dose sensitivity. The influence of the casting material and oxygen concentration has also been investigated. The radiophysical properties of this new dosimeter are discussed including stability, spatial integrity, temperature dependence of the dosimeter during radiation, readout and storage, dose rate dependence and tissue equivalence. The first authors Y De Deene and P S Skyt made an equivalent contribution to the experimental work presented in this paper.

ESR1 Methylation: A Liquid Biopsy-Based Epigenetic Assay for the Follow-up of Patients with Metastatic Breast Cancer Receiving Endocrine Treatment.

PubMed

Mastoraki, Sophia; Strati, Areti; Tzanikou, Eleni; Chimonidou, Maria; Politaki, Eleni; Voutsina, Alexandra; Psyrri, Amanda; Georgoulias, Vassilis; Lianidou, Evi

2018-03-15

Purpose: Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of circulating tumor cells (CTCs) and plasma-circulating tumor DNA (ctDNA). ESR1 epigenetic silencing potentially affects response to endocrine treatment. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA as a potential biomarker for response to everolimus/exemestane treatment. Experimental Design: A highly sensitive and specific real-time MSP assay for ESR1 methylation was developed and validated in (i) 65 primary breast tumors formalin-fixed paraffin-embedded (FFPE), (ii) EpCAM + CTC fractions (122 patients and 30 healthy donors; HD), (iii) plasma ctDNA (108 patients and 30HD), and (iv) in CTCs (CellSearch) and in paired plasma ctDNA for 58 patients with breast cancer. ESR1 methylation status was investigated in CTCs isolated from serial peripheral blood samples of 19 patients with ER + /HER2 - advanced breast cancer receiving everolimus/exemestane. Results: ESR1 methylation was detected in: (i) 25/65 (38.5%) FFPEs, (ii) EpCAM + CTC fractions : 26/112 (23.3%) patients and 1/30 (3.3%) HD, and (iii) plasma ctDNA: 8/108 (7.4%) patients and 1/30 (3.3%) HD. ESR1 methylation was highly concordant in 58 paired DNA samples, isolated from CTCs (CellSearch) and corresponding plasma. In serial peripheral blood samples of patients treated with everolimus/exemestane, ESR1 methylation was observed in 10/36 (27.8%) CTC-positive samples, and was associated with lack of response to treatment ( P = 0.023, Fisher exact test). Conclusions: We report for the first time the detection of ESR1 methylation in CTCs and a high concordance with paired plasma ctDNA. ESR1 methylation in CTCs was associated with lack of response to everolimus/exemestane regimen. ESR1 methylation should be further evaluated as a potential liquid biopsy-based biomarker. Clin Cancer Res; 24(6); 1500-10. ©2017 AACR . ©2017

In situ ion-beam-induced luminescence analysis for evaluating a micrometer-scale radio-photoluminescence glass dosimeter

NASA Astrophysics Data System (ADS)

Kawabata, Shunsuke; Kada, Wataru; Parajuli, Raj Kumar; Matsubara, Yoshinori; Sakai, Makoto; Miura, Kenta; Satoh, Takahiro; Koka, Masashi; Yamada, Naoto; Kamiya, Tomihiro; Hanaizumi, Osamu

2016-06-01

Micrometer-scale responses of radio-photoluminescence (RPL) glass dosimeters to focused ionized particle radiation were evaluated by combining ion-beam-induced luminescence (IBIL) and proton beam writing (PBW) using a 3 MeV focused proton microbeam. RPL phosphate glass dosimeters doped with ionic Ag or Cu activators at concentrations of 0.2 and 0.1% were fabricated, and their scintillation intensities were evaluated by IBIL spectroscopy under a PBW micropatterning condition. Compared with the Ag-doped dosimeter, the Cu-doped dosimeter was more tolerant of the radiation, while the peak intensity of its luminescence was lower, under the precise dose control of the proton microprobe. Proton-irradiated areas were successfully recorded using these dosimeters and their RPL centers were visualized under 375 nm ultraviolet light. The reproduction of the irradiated region by post-RPL imaging suggests that precise estimation of irradiation dose using microdosimeters can be accomplished by optimizing RPL glass dosimeters for various proton microprobe applications in organic material analysis and in micrometer-scale material modifications.

Evaluating the Potential of Q-Band ESR Spectroscopy for Dose Reconstruction of Fossil Tooth Enamel

PubMed Central

Guilarte, Verónica; Trompier, François; Duval, Mathieu

2016-01-01

The potential of Q-band Electron Spin Resonance (ESR) for quantitative measurements has been scarcely evaluated in the literature and its application for dose reconstruction of fossil tooth enamel with dating purposes remains still quite unknown. Hence, we have performed a comparative study based on several Early to Middle Pleistocene fossil tooth samples using both X- and Q-band spectroscopies. Our results show that Q-band offers a significant improvement in terms of sensitivity and signal resolution: it allows not only to work with reduced amounts of valuable samples (< 4 mg), but also to identify different components of the main composite ESR signal. However, inherent precision of the ESR intensity measurements at Q-band is clearly lower than that achieved at X-band, highlighting the necessity to carry out repeated measurements. All dose values derived from X- and Q-band are nevertheless systematically consistent at either 1 or 2 sigma. In summary, our results indicate that Q-band could now be considered as a reliable tool for ESR dosimetry/dating of fossil teeth although further work is required to improve the repeatability of the measurements. PMID:26930398

Reconstruction of nuclear receptor network reveals that NR2E3 is a novel upstream regulator of ESR1 in breast cancer

PubMed Central

Park, Yun-Yong; Kim, Kyounghyun; Kim, Sang-Bae; Hennessy, Bryan T; Kim, Soo Mi; Park, Eun Sung; Lim, Jae Yun; Li, Jane; Lu, Yiling; Gonzalez-Angulo, Ana Maria; Jeong, Woojin; Mills, Gordon B; Safe, Stephen; Lee, Ju-Seog

2012-01-01

ESR1 is one of the most important transcription factors and therapeutic targets in breast cancer. By applying systems-level re-analysis of publicly available gene expression data, we uncovered a potential regulator of ESR1. We demonstrated that orphan nuclear receptor NR2E3 regulates ESR1 via direct binding to the ESR1 promoter with concomitant recruitment of PIAS3 to the promoter in breast cancer cells, and is essential for physiological cellular activity of ESR1 in estrogen receptor (ER)-positive breast cancer cells. Moreover, expression of NR2E3 was significantly associated with recurrence-free survival and a favourable response to tamoxifen treatment in women with ER-positive breast cancer. Our results provide mechanistic insights on the regulation of ESR1 by NR2E3 and the clinical relevance of NR2E3 in breast cancer. PMID:22174013

Upregulation of IRS1 Enhances IGF1 Response in Y537S and D538G ESR1 Mutant Breast Cancer Cells.

PubMed

Li, Zheqi; Levine, Kevin M; Bahreini, Amir; Wang, Peilu; Chu, David; Park, Ben Ho; Oesterreich, Steffi; Lee, Adrian V

2018-01-01

Increased evidence suggests that somatic mutations in the ligand-binding domain of estrogen receptor [ER (ERα/ESR1)] are critical mediators of endocrine-resistant breast cancer progression. Insulinlike growth factor-1 (IGF1) is an essential regulator of breast development and tumorigenesis and also has a role in endocrine resistance. A recent study showed enhanced crosstalk between IGF1 and ERα in ESR1 mutant cells, but detailed mechanisms are incompletely understood. Using genome-edited MCF-7 and T47D cell lines harboring Y537S and D538G ESR1 mutations, we characterized altered IGF1 signaling. RNA sequencing revealed upregulation of multiple genes in the IGF1 pathway, including insulin receptor substrate-1 (IRS1), consistent in both Y537S and D538G ESR1 mutant cell line models. Higher IRS1 expression was confirmed by quantitative reverse transcription polymerase chain reaction and immunoblotting. ESR1 mutant cells also showed increased levels of IGF-regulated genes, reflected by activation of an IGF signature. IGF1 showed increased sensitivity and potency in growth stimulation of ESR1 mutant cells. Analysis of downstream signaling revealed the phosphoinositide 3-kinase (PI3K)-Akt axis as a major pathway mediating the enhanced IGF1 response in ESR1 mutant cells. Decreasing IRS1 expression by small interfering RNA diminished the increased sensitivity to IGF1. Combination treatment with inhibitors against IGF1 receptor (IGF1R; OSI-906) and ER (fulvestrant) showed synergistic growth inhibition in ESR1 mutant cells, particularly at lower effective concentrations. Our study supports a critical role of enhanced IGF1 signaling in ESR1 mutant cell lines, pointing toward a potential for cotargeting IGF1R and ERα in endocrine-resistant breast tumors with mutant ESR1. Copyright © 2018 Endocrine Society.

Dosimeter Badge Detects Hydrazines

NASA Technical Reports Server (NTRS)

Young, Rebecca C.; Travis, Joshua C.; Moore, Gerald; Rose-Pehrsson, Susan; Carver, Patricia; Brenner, Karen

1993-01-01

Disposable dosimeter badge indicates approximate cumulative exposure to hydrazine or monomethyl hydrazine in air. Indication is change in colors of both paper tapes; one coated with para-N, N-dimethylaminobenzaldehyde. Colors of exposed tapes compared with colors on two preprinted color wheels to obtain estimate of exposure. Badges help minimize risks associated with exposure of personnel to hydrazine or monomethyl hydrazine, or suspected carcinogens. Also used as stationary monitors by taping them on walls or equipment at strategic locations.

ESR signals in a core from the lake Baikal: implications for climate change

NASA Astrophysics Data System (ADS)

Toyoda, S.; Hidaka, K.; Takamatsu, N.

2002-12-01

Electron spin resonance dating method has been used for obtaining ages of Quaternary events using speleothem, corals, shells, hydroxyapatite in tooth enamel, gypsum, and quartz (Ikeya, 1993). Recently, it was also found that an ESR signal in quartz of loess is useful to discuss the variation of its origin (e. g. Ono et al., 1998). The method is based on the signal intensity of the heat treated (gamma ray irradiation and heating, Toyoda and Ikeya, 1991) E 1_f center (an unpaired electron at an oxygen vacancy) correlates the original (crystallization) age of quartz (e.g. Toyoda and Hattori, 2000). If there is variation in ages of basement rocks (origin of loess), ESR signal intensity may differentiate the origins. We applied the present method to sediments taken from the core of the lake Baikal with the length of 600m. The ESR intensity of the heat treated E1_f center was determined by an ESR measurement at room temperature for about 100 mg of the bulk samples, with a microwave power of 0.01 mW, field modulation amplitude of 0.1 mT, and with a scan range of 5 mT around g=2.001 after gamma ray irradiation to 1 kGy and subsequent heating at 300C. The ESR signal of the E1_f center was clearly observed although other minerals are also included in the bulk sample. The peak to peak height was taken as the signal intensity after normalizing the height with the gain (the instrumental setting at the time of measurement), mass, and the intensity of the standard simultaneously measured with the sample. The concentrations of the quartz in the bulk samples were obtained by the X ray diffraction study, normalizing the peak intensity with a standard CeO sample. The variation of the ESR signal intensity with depth of the core will be presented together with the possible climate change which may have caused the variation. References M. Ikeya (1993) New applications of electron spin resonance, dating, dosimetry and imaging, World Scientific. Y. Ono, T. Naruse, M. Ikeya, H. Kohno, and

[Chiral separation of five beta-blockers using di-n-hexyl L-tartrate-boric acid complex as mobile phase additive by reversed-phase liquid chromatography].

PubMed

Yang, Juan; Wang, Lijuan; Guo, Qiaoling; Yang, Gengliang

2012-03-01

A reversed-phase high performance liquid chromatographic (HPLC) method using the di-n-hexyl L-tartrate-boric acid complex as a chiral mobile phase additive was developed for the enantioseparation of five beta-blockers including propranolol, esmolol, metoprolol, bisoprolol and sotalol. In order to obtain a better enantioseparation, the influences of concentrations of di-n-butyl L-tartrate and boric acid, the type, concentration and pH of the buffer, methanol content as well as the molecular structure of analytes were extensively investigated. The separation of the analytes was performed on a Venusil MP-C18 column (250 mm x 4.6 mm, 5 microm). The mobile phase was 15 mmol/L ammonium acetate-methanol containing 60 mmol/L boric acid, 70 mmol/L di-n-hexyl L-tartrate (pH 6.00). The volume ratios of 15 mmol/L ammonium acetate to methanol were 20: 80 for propranolol, esmolol, metoprolol, bisoprolol and 30: 70 for sotalol. The flow rate was 0.5 mL/min and the detection wavelength was set at 214 nm. Under the optimized conditions, baseline enantioseparation was obtained separately for the five pairs of analytes.

Miniature personal UV solar dosimeter

NASA Technical Reports Server (NTRS)

Adams, R. R.; Macconochie, I. O.; Poole, B. D., Jr.

1981-01-01

Small light-powered meter measures accumulated radiation in ultraviolet or other selected regions. Practical advantages are device's low cost, small size, accuracy, and adaptability to specific wave-band measurements. Medical applications include detection of skin cancer, vitamin D production, and jaundice. Dosimeter also measures sunlight for solar energy designs, agriculture and meteorology, and monitors stability of materials and environmental and occupational lighting.

Water equivalency evaluation of PRESAGE® dosimeters for dosimetry of Cs-137 and Ir-192 brachytherapy sources

NASA Astrophysics Data System (ADS)

Gorjiara, Tina; Hill, Robin; Kuncic, Zdenka; Baldock, Clive

2010-11-01

A major challenge in brachytherapy dosimetry is the measurement of steep dose gradients. This can be achieved with a high spatial resolution three dimensional (3D) dosimeter. PRESAGE® is a polyurethane based dosimeter which is suitable for 3D dosimetry. Since an ideal dosimeter is radiologically water equivalent, we have investigated the relative dose response of three different PRESAGE® formulations, two with a lower chloride and bromide content than original one, for Cs-137 and Ir-192 brachytherapy sources. Doses were calculated using the EGSnrc Monte Carlo package. Our results indicate that PRESAGE® dosimeters are suitable for relative dose measurement of Cs-137 and Ir-192 brachytherapy sources and the lower halogen content PRESAGE® dosimeters are more water equivalent than the original formulation.

Association between VDR and ESR1 gene polymorphisms with bone and obesity phenotypes in Chinese male nuclear families.

PubMed

Gu, Jie-mei; Xiao, Wen-jin; He, Jin-wei; Zhang, Hao; Hu, Wei-wei; Hu, Yun-qiu; Li, Miao; Liu, Yu-juan; Fu, Wen-zhen; Yu, Jin-bo; Gao, Gao; Yue, Hua; Ke, Yao-hua; Zhang, Zhen-lin

2009-12-01

The goal of this study was to determine whether polymorphisms in the vitamin D receptor (VDR) and estrogen receptor alpha (ESR1) genes are associated with variations of peak bone mineral density (BMD) and obesity phenotypes in young Chinese men. A total of 1215 subjects from 400 Chinese nuclear families were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific multiple PCR (ASM-PCR) analysis at the ApaI, FokI, and CDX2 sites in the VDR gene and the PvuII and XbaI sites in the ESR1 gene. BMD at the lumbar spine and hip, total fat mass, and total lean mass were measured using dual energy X-ray absorptiometry. The associations between VDR and ESR1 gene polymorphisms with peak BMD, body mass index (BMI), total fat mass, total lean mass, and percentage fat mass (PFM) were determined using quantitative transmission disequilibrium tests (QTDTs). Using QTDTs, no significant within-family associations were obtained between genotypes or haplotypes of the VDR and ESR1 genes and peak BMD. For the obesity phenotypes, the within-family associations were significant between CDX2 genotypes and BMI (P=0.046), fat mass (P=0.004), and PFM (P=0.020). Further, PvuII was significantly associated with the variation of fat mass and PFM (P=0.002 and P=0.039, respectively). A subsequent 1000 permutations were in agreement with these within-family association results. Our findings showed that VDR and ESR1 polymorphisms were associated with total fat mass in young Chinese men, but we failed to find a significant association between VDR and ESR1 genotypes and peak BMD. These findings suggested that the VDR and ESR1 genes are quantitative trait loci (QTL) underlying fat mass variation in young Chinese men.

Scalable Control of Mounting and Attack by ESR1+ Neurons in the Ventromedial Hypothalamus

PubMed Central

Lee, Hyosang; Kim, Dong-Wook; Remedios, Ryan; Anthony, Todd E.; Chang, Angela; Madisen, Linda; Zeng, Hongkui; Anderson, David J.

2014-01-01

Social behaviors, such as aggression or mating, proceed through a series of appetitive and consummatory phases1 that are associated with increasing levels of arousal2. How such escalation is encoded in the brain, and linked to behavioral action selection, remains an important unsolved problem in neuroscience. The ventrolateral subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons whose activity increases during male-male and male-female social encounters. Non-cell type-specific optogenetic activation of this region elicited attack behavior, but not mounting3. We have identified a subset of VMHvl neurons marked by the estrogen receptor 1 (Esr1), and investigated their role in male social behavior. Optogenetic manipulations indicated that Esr1+ (but not Esr1-) neurons are sufficient to initiate attack, and that their activity is continuously required during ongoing agonistic behavior. Surprisingly, weaker optogenetic activation of these neurons promoted mounting behavior, rather than attack, towards both males and females, as well as sniffing and close investigation (CI). Increasing photostimulation intensity could promote a transition from CI and mounting to attack, within a single social encounter. Importantly, time-resolved optogenetic inhibition experiments revealed requirements for Esr1+ neurons in both the appetitive (investigative) and the consummatory phases of social interactions. Combined optogenetic activation and calcium imaging experiments in vitro, as well as c-Fos analysis in vivo, indicated that increasing photostimulation intensity increases both the number of active neurons and the average level of activity per neuron. These data suggest that Esr1+ neurons in VMHvl control the progression of a social encounter from its appetitive through its consummatory phases, in a scalable manner that reflects the number or type of active neurons in the population. PMID:24739975

The radiation dosimeter on-board the FY-4 Satellite

NASA Astrophysics Data System (ADS)

Zhang, B.; Sun, Y.; Zhang, S.; Zhang, X.; Sun, Y.; Jing, T.

2017-12-01

The total radiation dose effect can lead to a decrease in the performance of satellite devices or materials. Accurately obtaining the total radiation dose during satellite operation could help to analyze the abnormality of payloads in orbit and optimize the design of radiation shielding. The radiation dosimeter is one of the space environmental monitoring devices on the "FY-4" satellite, which is a new generation of geostationary meteorological satellite. The dosimeter consists of 8 detectors, which are installed in different locations of the satellite, to obtain the total radiation dose with different shielding thickness and different orientations. To measure a total radiation dose up to 2000krad(Si), 100nm ion implantation RADFET was used. To improve the sensitivity of the dosimeter, the bias voltage of RADFET is set to 15V, and a 10V, 15-bit A/D is adopted to digitalize the RADFET's threshold voltage, which is increased as the total radiation dose grows. In addition, the temperature effect of RADFET is corrected from the measured temperature on orbit. The preliminary monitoring results show that the radiation dose is less than 35rad (Si) per day at 0.87 mm shielding thickness of equivalent aluminum in the geostationary orbit, and the dose in Y direction of the satellite is less than those in the X and Z directions. The radiation dose at the thickness of 3.87 mm equivalent aluminum is less than 1rad(Si)/day. It is found that the daily total dose measured by the dosimeter has a strong correlation with the flux of high energy electrons.

The study of N-isopropylacrylamide gel dosimeter doped iodinated contrast agents

NASA Astrophysics Data System (ADS)

Chang, Y. J.; Hsieh, L. L.; Liu, M. H.; Liu, J. S.; Hsieh, B. T.

2013-06-01

Low toxicity of N-isopropylacrylamide (NIPAM) dosimeter was doped with clinical iodinated contrast medium agents(Iobitridol (Xenetix® 350) and organically bound iodine (Conray® 60) as radiation sensitizers; The suitable gel dosimeter preparation formula in this research was 5 w/w% gelatin, 5 w/w% N-isopropylacrylamide, 3 w/w% N,N-methylene-bis-acrylamide, and 5 mM Tetrakis phosphonium chloride. The spiral CT was irradiator, and 120 kVp was the operating tube voltage. The maximum radiation dose was 0.6 Gy, and optical CT was the gel measurement device used. The results showed SERs with the addition of radiosensitizers were 10.70 (Xenetix® 350) and 9.67 (Conray® 60), respectively. Thus, the polymerized gel dosimeter could be used in the efficacy evaluation of low-energy and low-radiation dose.

Determination of the depth dose distribution of proton beam using PRESAGE TM dosimeter

NASA Astrophysics Data System (ADS)

Zhao, L.; Das, I. J.; Zhao, Q.; Thomas, A.; Adamovics, J.; Oldman, M.

2010-11-01

PRESAGETM dosimeter dosimeter has been proved useful for 3D dosimetry in conventional photon therapy and IMRT [1-5]. Our objective is to examine the use of PRESAGETM dosimeter for verification of depth dose distribution in proton beam therapy. Three PRESAGETM samples were irradiated with a 79 MeV un-modulated proton beam. Percent depth dose profile measured from the PRESAGETM dosimeter is compared with data obtained in a water phantom using a parallel plate Advanced Markus chamber. The Bragg-peak position determined from the PRESAGETM is within 2 mm compared to measurements in water. PRESAGETM shows a highly linear response to proton dose. However, PRESAGETM also reveals an underdosage around the Bragg peak position due to LET effects. Depth scaling factor and quenching correction factor need further investigation. Our initial result shows that PRESAGETM has promising dosimetric characteristics that could be suitable for proton beam dosimetry.

Relative performance of different types of passive dosimeters employing solid state nuclear track detectors.

PubMed

Jamil, K; Al-Ahmady, K K; Fazal-ur-Rehman; Ali, S; Qureshi, A A; Khan, H A

1997-10-01

Radon and its progeny, known to be carcinogenic, are a matter of great concern in underground mines and energy conserved air-tight houses. Different shapes of dosimeters using solid state nuclear track detectors (SSNTDs) have been devised to measure radon concentrations in mines and dwellings. Sometimes intercomparison of results is required by various laboratories working with solid state nuclear track detector-based passive dosimeters. The present work includes the determination of various parameters for a set of dosimeters consisting of (1) box-type, (2) pen-type, (3) tube-type, (4) Karlsruhe Diffusion Chamber, and (5) bare-type dosimeters. In this research two types of plastics, allyl-diglycol-carbonate (C12H18O7) and cellulose nitrate (C6H8O8N2) known as CR-39 and CN-85, respectively, have been employed. The detection efficiency for alpha particles from radon and its progeny for CR-39 and CN-85 have been compared. All experiments have been carried out in a custom-designed exposure chamber connected to a radon source. The calibration factors, in terms of Bq m(-3) per unit track density (1.0 cm(-2)) with respect to box-type dosimeter, have been determined for intercomparison and standardization of measured radon concentrations by a set of passive radon dosimeters used in various laboratories of the world.

Characteristics of optically stimulated luminescence dosimeters in the spread-out Bragg peak region of clinical proton beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerns, James R.; Kry, Stephen F.; Sahoo, Narayan

Purpose: Optically stimulated luminescent detectors (OSLDs) have a number of advantages in radiation dosimetry making them excellent dosimeters for quality assurance and patient dose verification. Although the dosimeters have been investigated in several modalities, relatively little work has been done in examining the dosimeters for use in clinical proton beams. This study examined a number of characteristics of the response of the dosimeters in the spread-out Bragg peak (SOBP) region of clinical proton beams. Methods: Optically stimulated luminescence (OSL) dosimeters from Landauer, Inc., specifically the nanoDot dosimeter, were investigated. These dosimeters were placed in a special phantom with a recessmore » to fit the dosimeters without an air gap. Beams with nominal energies of 160, 200, and 250 MeV were used in the passively-scattered proton beam at the MD Anderson Cancer Center Proton Therapy Center. Dosimetric properties including linearity, field size dependence, energy dependence, residual signal as a function of cumulative dose, and postirradiation fading were investigated by taking measurements at the center of SOBPs. Results: The dosimeters showed 1% supralinearity at 200 cGy and 5% supralinearity at 1000 cGy. No noticeable field size dependence of the detector was found for field sizes from 2 x 2 cm{sup 2} to 18 x 18 cm{sup 2}. Residual signal as a function of cumulative dose showed a small increase for measurements up to 1000 cGy. Readout signal depletion of the dosimeters after consecutive readings showed a slightly larger depletion in protons for doses up to 500 cGy but not by a clinically significant amount. Within the center of various SOBP widths and proton energies the variation in response was less than 2%. An average beam quality factor of 1.089 with experimental standard deviation of 0.007 was determined and applied to the data such that the results were within 1.2% of ion chamber data. Conclusions: The nanoDot OSL dosimeter

Study of a non-diffusing radiochromic gel dosimeter for 3D radiation dose imaging

NASA Astrophysics Data System (ADS)

Marsden, Craig Michael

2000-12-01

This thesis investigates the potential of a new radiation gel dosimeter, based on nitro-blue tetrazolium (NBTZ) suspended in a gelatin mold. Unlike all Fricke based gel dosimeters this dosimeter does not suffer from diffusive loss of image stability. Images are obtained by an optical tomography method. Nitro blue tetrazolium is a common biological indicator that when irradiated in an aqueous medium undergoes reduction to a highly colored formazan, which has an absorbance maximum at 525nm. Tetrazolium is water soluble while the formazan product is insoluble. The formazan product sticks to the gelatin matrix and the dose image is maintained for three months. Methods to maximize the sensitivity of the system were evaluated. It was found that a chemical detergent, Triton X-100, in combination with sodium formate, increased the dosimeter sensitivity significantly. An initial G-value of formazan production for a dosimeter composed of 1mM NBTZ, gelatin, and water was on the order of 0.2. The addition of Triton and formate produced a G-value in excess of 5.0. The effects of NBTZ, triton, formate, and gel concentration were all investigated. All the gels provided linear dose vs. absorbance plots for doses from 0 to >100 Gy. It was determined that gel concentration had minimal if any effect on sensitivity. Sensitivity increased slightly with increasing NBTZ concentration. Triton and formate individually and together provided moderate to large increases in dosimeter sensitivity. The dosimeter described in this work can provide stable 3D radiation dose images for all modalities of radiation therapy equipment. Methods to increase sensitivity are developed and discussed.

The Arabidopsis KH-Domain RNA-Binding Protein ESR1 Functions in Components of Jasmonate Signalling, Unlinking Growth Restraint and Resistance to Stress

PubMed Central

Thatcher, Louise F.; Kamphuis, Lars G.; Hane, James K.; Oñate-Sánchez, Luis; Singh, Karam B.

2015-01-01

Glutathione S-transferases (GSTs) play important roles in the protection of cells against toxins and oxidative damage where one Arabidopsis member, GSTF8, has become a commonly used marker gene for early stress and defense responses. A GSTF8 promoter fragment fused to the luciferase reporter gene was used in a forward genetic screen for Arabidopsis mutants with up-regulated GSTF8 promoter activity. This identified the esr1-1 (enhanced stress response 1) mutant which also conferred increased resistance to the fungal pathogen Fusarium oxysporum. Through positional cloning, the ESR1 gene was found to encode a KH-domain containing RNA-binding protein (At5g53060). Whole transcriptome sequencing of esr1-1 identified altered expression of genes involved in responses to biotic and abiotic stimuli, hormone signaling pathways and developmental processes. In particular was an overall significant enrichment for jasmonic acid (JA) mediated processes in the esr1-1 down-regulated dataset. A subset of these genes were tested for MeJA inducibility and we found the expression of some but not all were reduced in esr1-1. The esr1-1 mutant was not impaired in other aspects of JA-signalling such as JA- sensitivity or development, suggesting ESR1 functions in specific components of the JA-signaling pathway. Examination of salicylic acid (SA) regulated marker genes in esr1-1 showed no increase in basal or SA induced expression suggesting repression of JA-regulated genes is not due to antagonistic SA-JA crosstalk. These results define new roles for KH-domain containing proteins with ESR1 unlinking JA-mediated growth and defense responses. PMID:25985302

The Arabidopsis KH-Domain RNA-Binding Protein ESR1 Functions in Components of Jasmonate Signalling, Unlinking Growth Restraint and Resistance to Stress.

PubMed

Thatcher, Louise F; Kamphuis, Lars G; Hane, James K; Oñate-Sánchez, Luis; Singh, Karam B

2015-01-01

Glutathione S-transferases (GSTs) play important roles in the protection of cells against toxins and oxidative damage where one Arabidopsis member, GSTF8, has become a commonly used marker gene for early stress and defense responses. A GSTF8 promoter fragment fused to the luciferase reporter gene was used in a forward genetic screen for Arabidopsis mutants with up-regulated GSTF8 promoter activity. This identified the esr1-1 (enhanced stress response 1) mutant which also conferred increased resistance to the fungal pathogen Fusarium oxysporum. Through positional cloning, the ESR1 gene was found to encode a KH-domain containing RNA-binding protein (At5g53060). Whole transcriptome sequencing of esr1-1 identified altered expression of genes involved in responses to biotic and abiotic stimuli, hormone signaling pathways and developmental processes. In particular was an overall significant enrichment for jasmonic acid (JA) mediated processes in the esr1-1 down-regulated dataset. A subset of these genes were tested for MeJA inducibility and we found the expression of some but not all were reduced in esr1-1. The esr1-1 mutant was not impaired in other aspects of JA-signalling such as JA- sensitivity or development, suggesting ESR1 functions in specific components of the JA-signaling pathway. Examination of salicylic acid (SA) regulated marker genes in esr1-1 showed no increase in basal or SA induced expression suggesting repression of JA-regulated genes is not due to antagonistic SA-JA crosstalk. These results define new roles for KH-domain containing proteins with ESR1 unlinking JA-mediated growth and defense responses.

Performance improvement of pentacosa-diynoic acid label dosimeter for radiation processing technology

NASA Astrophysics Data System (ADS)

Abdel-Fattah, A. A.; Soliman, Y. S.

2017-12-01

A radiation sensitive material, 10,12-pentacosa-diynoic acid (PCDA), was incorporated into polyvinyl butyral (PVB) films to develop indicators/dosimeters for blood and food irradiation. The present study aims to improve the dosimetric performance of these previously prepared dosimeters and to extend their shelf life by the combination of a radical scavenger, propyl gallate (PG), and a UV absorber, tinuvin-p (TP). The X-ray diffraction (XRD) patterns of the dosimeters were analysed and their dosimetric characteristics were investigated by specular reflectance in the visible spectrum range of 400-700 nm. Upon irradiation, the films turn blue exhibiting two main bands around 670 and 620 nm. Their dose-response functions were fitted by a double exponential growth, 5 parameters, equation. Irradiation temperature influences the dosimeter response at 670 nm without causing thermochromic transition up to 50 °C in poly-PCDA. The useful dose range is 5-4000 Gy depending on the wavelengths of analysis and PCDA content in the films. The overall uncertainty of dose measurement is less than 6% at 2σ.

Dosimeter for measuring skin dose and more deeply penetrating radiation

DOEpatents

Jones, Donald E.; Parker, DeRay; Boren, Paul R.

1981-01-01

A personnel dosimeter includes a plurality of compartments containing thermoluminescent dosimeter phosphors for registering radiation dose absorbed in the wearer's sensitive skin layer and for registering more deeply penetrating radiation. Two of the phosphor compartments communicate with thin windows of different thicknesses to obtain a ratio of shallowly penetrating radiation, e.g. beta. A third phosphor is disposed within a compartment communicating with a window of substantially greater thickness than the windows of the first two compartments for estimating the more deeply penetrating radiation dose. By selecting certain phosphors that are insensitive to neutrons and by loading the holder material with netruon-absorbing elements, energetic neutron dose can be estimated separately from other radiation dose. This invention also involves a method of injection molding of dosimeter holders with thin windows of consistent thickness at the corresponding compartments of different holders. This is achieved through use of a die insert having the thin window of precision thickness in place prior to the injection molding step.

Dose control in electron beam processing: Comparison of results from a graphite charge collector, routine dosimeters and the ISS alanine-based dosimeter

NASA Astrophysics Data System (ADS)

Fuochi, P. G.; Onori, S.; Casali, F.; Chirco, P.

1993-10-01

A 12 MeV linear accelerator is currently used for electron beam processing of power semiconductor devices for lifetime control and, on an experimental basis, for food irradiation, sludge treatment etc. In order to control the irradiation process a simple, quick and reliable method for a direct evaluation of dose and fluence in a broad electron beam has been developed. This paper presents the results obtained using a "charge collector" which measures the charge absorbed in a graphite target exposed in air. Calibration of the system with super-Fricke dosimeter and comparison of absorbed dose results obtained with plastic dosimeters and alanine pellets are discussed.

Characteristics of a normoxic polymethacrylic acid gel dosimeter for a 72-MeV proton beam

NASA Astrophysics Data System (ADS)

Bong, Jihye; Shin, Dongho; Kwon, Soo-Il

2014-01-01

The characteristics of a normoxic polymethacrylic acid gel dosimeter for a 72-MeV proton beam were evaluated. A polymer gel dosimeter was synthesized using gelatin, methacrylic acid, hydroquinone, tetrakis(hydroxymethyl) phosphonium chloride, and highly purified distilled water. The dosimeter was manufactured by placement in a polyethylene (PE) container. Irradiated dosimeters were analyzed to determine the transverse relaxation time (T2) using a 1.5-T MRI. A calibration curve was obtained as a function of the absorbed dose. A Bragg curve made by irradiating the gel with mono-energy was compared with the results for a parallel plate ionization chamber. The spread-out Bragg peak (SOBP) range and distal dose fall-off (DDF) were comparatively analyzed by comparing the irradiated gel with a spread-out Bragg peak against with the ion chamber. Lastly, the gel's usefulness as a dosimeter for therapeutic radiation quality assurance was evaluated by obtaining its practical field size, flatness, and symmetry, through comparison of the profiles of the gel and ion chamber.

Adaptation of a Pocket PC for Use as a Wearable Voice Dosimeter

ERIC Educational Resources Information Center

Popolo, Peter S.; Svec, Jan G.; Titze, Ingo R.

2005-01-01

This article deals with the adaptation of a commercially available Pocket PC for use as a voice dosimeter, a wearable device that measures the vocal dose of teachers or other individuals on the job, at home, and elsewhere during the course of an entire day. An engineering approach for designing a voice dosimeter is described, and design data are…

A New Rapid and Sensitive Stability-Indicating UPLC Assay Method for Tolterodine Tartrate: Application in Pharmaceuticals, Human Plasma and Urine Samples.

PubMed

Yanamandra, Ramesh; Vadla, Chandra Sekhar; Puppala, Umamaheshwar; Patro, Balaram; Murthy, Yellajyosula L N; Ramaiah, Parimi Atchuta

2012-01-01

A new rapid, simple, sensitive, selective and accurate reversed-phase stability-indicating Ultra Performance Liquid Chromatography (RP-UPLC) technique was developed for the assay of Tolterodine Tartrate in pharmaceutical dosage form, human plasma and urine samples. The developed UPLC method is superior in technology to conventional HPLC with respect to speed, solvent consumption, resolution and cost of analysis. Chromatographic run time was 6 min in reversed-phase mode and ultraviolet detection was carried out at 220 nm for quantification. Efficient separation was achieved for all the degradants of Tolterodine Tartrate on BEH C18 sub-2-μm Acquity UPLC column using Trifluoroacetic acid and acetonitrile as organic solvent in a linear gradient program. The active pharmaceutical ingredient was extracted from tablet dosage form using a mixture of acetonitrile and water as diluent. The calibration graphs were linear and the method showed excellent recoveries for bulk and tablet dosage form. The test solution was found to be stable for 40 days when stored in the refrigerator between 2 and 8 °C. The developed UPLC method was validated and meets the requirements delineated by the International Conference on Harmonization (ICH) guidelines with respect to linearity, accuracy, precision, specificity and robustness. The intra-day and inter-day variation was found be less than 1%. The method was reproducible and selective for the estimation of Tolterodine Tartrate. Because the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one.

Hepatic reduction of carbamoyl-PROXYL in ferric nitrilotriacetate induced iron overloaded mice: an in vivo ESR study.

PubMed

Morales, Noppawan Phumala; Yamaguchi, Yumiko; Murakami, Kimiyo; Kosem, Nuttavut; Utsumi, Hideo

2012-01-01

Reduction of a nitroxyl radical, carbamoyl-PROXYL in association of free radical production and hepatic glutathione (GSH) was investigated in iron overloaded mice using an in vivo L-band electron spin resonance (ESR) spectrometer. Significant increases in hepatic iron, lipid peroxidation and decrease in hepatic GSH were observed in mice intraperitoneally (i.p.) administrated with ferric nitrilotriacetate (Fe(III)-NTA, a total 45 µmol/mouse over a period of 3 weeks). Free radical production in iron overloaded mice was evidenced by significantly enhanced rate constant of ESR signal decay of carbamoyl-PROXYL, which was slightly reduced by treatment with iron chelator, deferoxamine. Moreover, the rate constant of ESR signal decay was negatively correlated with hepatic GSH level (r=-0.586, p<0.001). On the other hand, hepatic GSH-depletion (>80%) in mice through daily i.p. injection and drinking water supplementation of L-buthionine-[S,R]-sulfoximine (BSO) significantly retarded ESR signal decay, while there were no changes in serum aspartate aminotransferase and liver thiobarbituric acid-reactive substances levels. In conclusion, GSH plays two distinguish roles on ESR signal decay of carbamoyl-PROXYL, as an antioxidant and as a reducing agent, dependently on its concentration. Therefore, it should be taken into account in the interpretation of free radical production in each specific experimental setting.

Diagnostic applications of an optoelectronic device for high temporal resolution of erythrocyte sedimentation (ESR-graphy)

NASA Astrophysics Data System (ADS)

Voeikov, Vladimir L.; Buravleva, Ekaterina; Bulargina, Yulia; Gurfinkel, Youri I.

2001-10-01

An automatic device for high-temporal resolution of the process of erythrocytes sedimentation in blood was designed. The position of the boundary between red blood and plasma is registered each 30 sec in several pipettes simultaneously with +/- 10 mkm precision. Data are processed by a PC and presented as velocity-time curves (ESR-grams) and the curves describing time evolution of the boundary position. ESR-grams demonstrate non-monotonous character of erythrocytes sedimentation in blood. Blood of particular donor being in a stable physiological state taken on different days is characterized by similar ESR-grams. Pathological deviations from a normal physiological state are reflected in the shortening of duration of each process stage and increasing of average sedimentation rate. Intravenous infusion of some medical preparations may lead either to improving (prolonging of macrokinetic stages, decreasing of sedimentation rate), or to worsening of studied parameters depending on an individual. The low extent of blood dilution with saline in vitro lead as a rule to decreasing of sedimentation rate and improving of microkinetic parameters of the process. Adding of highly diluted hydrogen peroxide to blood samples of patients resulted in the improving of sedimentation kinetics. ESR-graphy may widen opportunities of practical medicine in diagnostics, prognostics and drug therapy.

Selected variants of the steroid-5-alpha-reductase isoforms SRD5A1 and SRD5A2 and the sex steroid hormone receptors ESR1, ESR2 and PGR: no association with female pattern hair loss identified.

PubMed

Redler, Silke; Tazi-Ahnini, Rachid; Drichel, Dmitriy; Birch, Mary P; Brockschmidt, Felix F; Dobson, Kathy; Giehl, Kathrin A; Refke, Melanie; Kluck, Nadine; Kruse, Roland; Lutz, Gerhard; Wolff, Hans; Böhm, Markus; Becker, Tim; Nöthen, Markus M; Betz, Regina C; Messenger, Andrew

2012-05-01

Female pattern hair loss (FPHL) is a common disorder with a complex mode of inheritance. Although understanding of its etiopathogenesis is incomplete, an interaction between genetic and hormonal factors is assumed to be important. The involvement of an androgen-dependent pathway and sex steroid hormones is the most likely hypothesis. We therefore selected a total of 21 variants from the steroid-5-alpha-reductase isoforms SRD5A1 and SRD5A2, the sex steroid hormone receptors ESR1, ESR2 (oestrogen receptor) and PGR (progesterone receptor) and genotyped these in a case-control sample of 198 patients (145 UK; 53 German patients) and 329 controls (179 UK; 150 German). None of these variants showed any significant association, either in the overall UK and German samples or in the subgroup analyses. In summary, the present results, while based on a limited selection of gene variants, do not point to the involvement of SRD5A1, SRD5A2, ESR1, ESR2 or PGR in FPHL. © 2012 John Wiley & Sons A/S.

Reliability of an x-ray system for calibrating and testing personal radiation dosimeters

NASA Astrophysics Data System (ADS)

Guimarães, M. C.; Silva, C. R. E.; Rosado, P. H. G.; Cunha, P. G.; Da Silva, T. A.

2018-03-01

Metrology laboratories are expected to maintain standardized radiation beams and traceable standard dosimeters to provide reliable calibrations or testing of detectors. Results of the characterization of an x-ray system for performing calibration and testing of radiation dosimeters used for individual monitoring are shown in this work.

FSensitive detection of mono- and polyclonal ESR1 mutations in primary tumors, metastatic lesions and cell free DNA of breast cancer patients

PubMed Central

Wang, Peilu; Bahreini, Amir; Gyanchandani, Rekha; Lucas, Peter C.; Hartmaier, Ryan J.; Watters, Rebecca J.; Jonnalagadda, Amruth R.; Trejo Bittar, Humberto E.; Berg, Aaron; Hamilton, Ronald L.; Kurland, Brenda F.; Weiss, Kurt R.; Mathew, Aju; Leone, Jose Pablo; Davidson, Nancy E; Nikiforova, Marina N.; Brufsky, Adam M.; Ambros, Tadeu F.; Stern, Andrew M.; Puhalla, Shannon L.; Lee, Adrian V.; Oesterreich, Steffi

2015-01-01

Purpose Given the clinical relevance of ESR1 mutations as potential drivers of resistance to endocrine therapy, this study used sensitive detection methods to determine the frequency of ESR1 mutations in primary and metastatic breast cancer, and in cell free DNA (cfDNA). Patients and Methods Six ESR1 mutations (K303R, S463P, Y537C, Y537N, Y537S, D538G) were assessed by digital droplet PCR (ddPCR), with lower limits of detection of 0.05% to 0.16%, in primary tumors (n=43), bone (n=12) and brain metastases (n=38), and cfDNA (n=29). Correlations between ESR1 mutations in metastatic lesions and single (1 patient) or serial blood draws (4 patients) were assessed. Results ESR1 mutations were detected for D538G (n=13), Y537S (n=3) and Y537C (n=1), and not for K303R, S463P or Y537N. Mutation rates were 7.0% (3/43 primary tumors), 9.1% (1/11 bone metastases), 12.5% (3/24 brain metastases), and 24.1% (7/29 cfDNA). Two patients showed polyclonal disease with more than one ESR1 mutation. Mutation allele frequencies were 0.07% to 0.2% in primary tumors, 1.4% in bone metastases, 34.3 to 44.9% in brain metastases, and 0.2% to 13.7% in cfDNA. In cases with both cfDNA and metastatic samples (n=5), mutations were detected in both (n=3) or in cfDNA only (n=2). Treatment was associated with changes in ESR1 mutation detection and allele frequency. Conclusions ESR1 mutations were detected at very low allele frequencies in some primary breast cancers, and at high allele frequency in metastases, suggesting that in some tumors rare ESR1 mutant clones are enriched by endocrine therapy. Further studies should address if sensitive detection of ESR1 mutations in primary breast cancer and in serial blood draws may be predictive for development of resistant disease. PMID:26500237

Radiant energy dosimeter for field use

Treesearch

A. Broido; A.W. McMasters

1967-01-01

Thermal radiation measurements in Project Flambeau fires involved a limited number of conventional radiometers located outside the fire periphery. A simple, cheap, easily-fabricated, light-weight, self-contained, rugged dosimeter was desired to withstand a hot fire environment, including a specific energy input of 5,000 cal cm -2, and to record...

Study of EPR/ESR Dosimetry in Fingernails as a Method for Assessing Dose of Victims of Radiological Accidents/Incidents

DTIC Science & Technology

2008-06-17

dosimeters . .............................................................................................. 117 Figure 4-2. Flow chart illustrating...alanine, various sugars, quartz in rocks and sulfates, as EPR dosimeters [15]. Alternatively, radiation-induced EPR signals have been detected using...the medical response to radiological accidents, as a method for estimating radiation dose without the use of physical dosimeters and using exposed

Effects of refractive index mismatch in optical CT imaging of polymer gel dosimeters.

PubMed

Manjappa, Rakesh; Makki S, Sharath; Kumar, Rajesh; Kanhirodan, Rajan

2015-02-01

Proposing an image reconstruction technique, algebraic reconstruction technique-refraction correction (ART-rc). The proposed method takes care of refractive index mismatches present in gel dosimeter scanner at the boundary, and also corrects for the interior ray refraction. Polymer gel dosimeters with high dose regions have higher refractive index and optical density compared to the background medium, these changes in refractive index at high dose results in interior ray bending. The inclusion of the effects of refraction is an important step in reconstruction of optical density in gel dosimeters. The proposed ray tracing algorithm models the interior multiple refraction at the inhomogeneities. Jacob's ray tracing algorithm has been modified to calculate the pathlengths of the ray that traverses through the higher dose regions. The algorithm computes the length of the ray in each pixel along its path and is used as the weight matrix. Algebraic reconstruction technique and pixel based reconstruction algorithms are used for solving the reconstruction problem. The proposed method is tested with numerical phantoms for various noise levels. The experimental dosimetric results are also presented. The results show that the proposed scheme ART-rc is able to reconstruct optical density inside the dosimeter better than the results obtained using filtered backprojection and conventional algebraic reconstruction approaches. The quantitative improvement using ART-rc is evaluated using gamma-index. The refraction errors due to regions of different refractive indices are discussed. The effects of modeling of interior refraction in the dose region are presented. The errors propagated due to multiple refraction effects have been modeled and the improvements in reconstruction using proposed model is presented. The refractive index of the dosimeter has a mismatch with the surrounding medium (for dry air or water scanning). The algorithm reconstructs the dose profiles by estimating

Polymorphisms in the Estrogen Receptor β (ESR2) Gene Are Associated with Bone Mineral Density in Caucasian Men and Women

PubMed Central

Ichikawa, Shoji; Koller, Daniel L.; Peacock, Munro; Johnson, Michelle L.; Lai, Dongbing; Hui, Siu L.; Johnston, C. Conrad; Foroud, Tatiana M.; Econs, Michael J.

2007-01-01

Context A major determinant of osteoporotic fractures is peak bone mineral density (BMD), which is a highly heritable trait. Recently, we identified significant linkage for hip BMD in premenopausal sister pairs at chromosome 14q (LOD score = 3.5), where the estrogen receptor β gene (ESR2) is located. Objective The objective of the study was to determine whether ESR2 polymorphisms are associated with normal BMD variation. Design This was a population‐based genetic association study, using 11 single nucleotide polymorphisms (SNPs) distributed across the ESR2 gene. Setting The study was conducted at an academic research laboratory and medical center. Patients and Other Participants A total of 411 healthy men (aged 18–61 yr) and 1291 healthy premenopausal women (aged 20–50 yr) living in Indiana participated in the study. Intervention(s) There were no interventions. Main Outcome Measure(s) The main outcome measures were SNP genotype distributions and their association with BMD at the femoral neck and lumbar spine. Results Significant association of spine BMD was found with three SNPs in men and one SNP in women (P ≤ 0.05). The conditional linkage analysis using the ESR2 haplotypes showed that the ESR2 gene accounts for, at most, 18% of the original linkage. Conclusions ESR2 polymorphisms are significantly associated with bone mass in both men and women. However, the ESR2 gene is not entirely responsible for our original linkage, and an additional gene(s) in chromosome 14q contributes to the determination of BMD. PMID:16118344

PERSONNEL NEUTRON DOSIMETER

DOEpatents

Fitzgerald, J.J.; Detwiler, C.G. Jr.

1960-05-24

A description is given of a personnel neutron dosimeter capable of indicating the complete spectrum of the neutron dose received as well as the dose for each neutron energy range therein. The device consists of three sets of indium foils supported in an aluminum case. The first set consists of three foils of indium, the second set consists of a similar set of indium foils sandwiched between layers of cadmium, whereas the third set is similar to the second set but is sandwiched between layers of polyethylene. By analysis of all the foils the neutron spectrum and the total dose from neutrons of all energy levels can be ascertained.

Activation of Dosimeters Used in qa of Medical Linear Accelerators

NASA Astrophysics Data System (ADS)

Polaczek-Grelik, Kinga; Nowacka, Magdalena; Raczkowski, Maciej

2017-09-01

This paper presents the first results of a project intended to investigate γ-radiation activity induced in dosimeters used in clinical practice during routine quality assurance of high-energy photon beams emitted by electron linear accelerators. Two aspects of the activation via photonuclear reactions (X, n) of therapeutic beam and subsequent capture of secondary neutrons (n,γ) are under considerations: the influence of activation on intrinsic background of the dosimeters and exposure of dosimetrists who operate this equipment. The activation of several types of ionization chambers as well as the silicon diodes was studied after long-time exposure (10 000 MUs) of the 15 MV photon beam (Elekta Synergy). Photon fluxes obtained from spectra of γ-rays registered by HPGe spectrometer were subsequently converted to equivalent doses using appropriate coefficients. The main contribution to the induced activity comes from the neutron capture process on Al, Mn and Cu, therefore it decays quite fast with the half-lives of the order of 15 minutes. Nevertheless, the activation of chlorine was also observed. The estimated equivalent doses to skin and eye lens were in the range 0.19 - 0.62 μSv/min. However, no influence on intrinsic background signal of all studied dosimeters was observed. The preliminary results indicate that induced radioactivity of dosimeters is strongly influenced by therapeutic beam quality and neutron source strength of particular linac. This dependence will be studied deeper in order to quantify it more precisely.

Lack of Association between ESR1 and CYP1A1 Gene Polymorphisms and Susceptibility to Uterine Leiomyoma in Female Patients of Iranian Descent.

PubMed

Taghizade Mortezaee, Fatemeh; Tabatabaiefar, Mohammad Amin; Hashemzadeh Chaleshtori, Morteza; Miraj, Sepideh

2014-01-01

Uterine leiomyoma (UL) is the most common benign smooth muscle cell tumor with as yet unknown etiology and pathogenesis. This study was carried out to investigate the association of ESR1-351 A>G, ESR1 -397 T>C and CYP1A1 (Ile462Val) polymorphisms with UL in female patients of Iranian origin. In this case-control study, 276 patients with UL and 156 healthy women were recruited. The genetic polymorphisms ESR1-351 A>G, ESR1-397 T>C and CYP1A1 (Ile462Val) were genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). No significant difference were found in frequencies of both genotypes and alleles of ESR1-351 A>G, ESR1-397 T>C and CYP1A1 (Ile462Val) polymorphisms between the two groups (p>0.05). Our findings indicated that these ESR1 and CYP1A1 polymorphisms were not associated with the development of UL in the cases reported here.

ESR (electron spin resonance)-determined osmotic behavior of bull spermatozoa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, J.; Kleinhans, F.W.; Spitzer, V.J.

1990-01-01

Our laboratories are pursuing a fundamental approach to the problems of semen cryopreservation. For many cell types (human red cells, yeast, HeLa) it has been demonstrated that there is an optimum cooling rate for cryopreservation. Faster rates allow insufficient time for cell dehydration and result in intracellular ice formation and cell death. It is possible to predict this optimal rate provided that the cell acts as an ideal osmometer and several other cell parameters are known such as the membrane hydraulic conductivity. It is the purpose of this work to examine the osmotic response of bull sperm to sucrose andmore » NaCl utilizing electron spin resonance (ESR) to measure cell volume. For calibration purposes we also measured the ESR response of human red cells (RBC), the osmotic response of which is well documented with other methods. 15 refs., 1 fig.« less

Pen Ink as an Ultraviolet Dosimeter

ERIC Educational Resources Information Center

Downs, Nathan; Turner, Joanna; Parisi, Alfio; Spence, Jenny

2008-01-01

A technique for using highlighter ink as an ultraviolet dosimeter has been developed for use by secondary school students. The technique requires the students to measure the percentage of colour fading in ink drawn onto strips of paper that have been exposed to sunlight, which can be calibrated to measurements of the ultraviolet irradiance using…

Study of a Single-Power Two-Circuit ESR Process with Current-Carrying Mold: Mathematical Simulation of the Process and Experimental Verification

NASA Astrophysics Data System (ADS)

Dong, Yanwu; Hou, Zhiwen; Jiang, Zhouhua; Cao, Haibo; Feng, Qianlong; Cao, Yulong

2018-02-01

A novel single-power two-circuit ESR process (ESR-STCCM) with current-carrying mold has been investigated via numerical simulation and experimental research in this paper. A 2D quasi-steady-state mathematical model is developed to describe ESR-STCCM. The electromagnetic field, flow field, slag pool temperature distribution, and the shape of a molten steel pool in ESR-STCCM have been investigated by FLUENT software as well as user-defined functions (UDF). The results indicate that ESR-STCCM is different from the conventional ESR process. The maximum electromagnetic force, current density, Joule heat, and slag pool flow velocity are located in the lower part of the conductor in the ESR-STCCM process. The direction of the maximum electromagnetic force inclines upward. There are two distinct vortices in the slag pool. The larger swirl rotates counterclockwise near the conductor, with a value of 0.0263 m s-1 due to the interaction of the electromagnetic force and gravity. The maximum temperature of the slag pool is 2070 K (1797 °C) and is located in the center of the swirl with a filling ratio of 0.6 and a 20 mm electrode immersion depth. The depth of a molten steel pool is shallower, which is conducive to improving solidification quality. In addition, the filling ratio of 0.6 is conducive to controlling steel solidification quality. Some experiments have been done, and the numerical model is confirmed by experimental results.

SU-F-BRF-13: Investigating the Feasibility of Accurate Dose Measurement in a Deforming Radiochromic Dosimeter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juang, T; Adamovics, J; Oldham, M

Purpose: Presage-Def, a deformable radiochromic 3D dosimeter, has been previously shown to have potential for validating deformable image registration algorithms. This work extends this effort to investigate the feasibility of using Presage-Def to validate dose-accumulation algorithms in deforming structures. Methods: Two cylindrical Presage-Def dosimeters (8cm diameter, 4.5cm length) were irradiated in a water-bath with a simple 4-field box treatment. Isocentric dose was 20Gy. One dosimeter served as control (no deformation) while the other was laterally compressed during irradiation by 21%. Both dosimeters were imaged before and after irradiation with a fast (∼10 minutes for 1mm isotropic resolution), broad beam, highmore » resolution optical-CT scanner. Measured dose distributions were compared to corresponding distributions calculated by a commissioned Eclipse planning system. Accuracy in the control was evaluated with 3D gamma (3%/3mm). The dose distribution calculated for the compressed dosimeter in the irradiation geometry cannot be directly compared via profiles or 3D gamma to the measured distribution, which deforms with release from compression. Thus, accuracy under deformation was determined by comparing integral dose within the high dose region of the deformed dosimeter distribution versus calculated dose. Dose profiles were used to study temporal stability of measured dose distributions. Results: Good dose agreement was demonstrated in the control with a 3D gamma passing rate of 96.6%. For the dosimeter irradiated under compression, the measured integral dose in the high dose region (518.0Gy*cm3) was within 6% of the Eclipse-calculated integral dose (549.4Gy*cm3). Elevated signal was noted on the dosimeter edge in the direction of compression. Change in dosimeter signal over 1.5 hours was ≤2.7%, and the relative dose distribution remained stable over this period of time. Conclusion: Presage-Def is promising as a 3D dosimeter capable of accurately

SU-E-T-171: Characterization of the New Xoft Axxent Electronic Brachytherapy Source Using PRESAGE Dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinmann, A; Followill, D; Ibbott, G

Purpose: To characterize the Xoft Axxent electronic brachytherapy source using PRESAGE™ dosimeters to obtain independent confirmation of TG-43U1 dosimetry values from previous studies and ascertain its reproducibility in HDR brachytherapy. Methods: PRESAGE™ dosimeters are solid, polyurethane-based dosimeters doped with radiochromic leucodyes that produce a linear optical-density response when exposed to radiation. Eight 1-kg dosimeters were scanned prior to irradiation on an optical-CT scanner to eliminate background signal and any optical imperfections from each dosimeter. To quantify potential imaging artifacts due to oversaturated responses in the immediate range of the source, half of the eight dosimeters were cast with a smallermore » channel diameter of 5.4 mm, and the other half were cast with a larger channel diameter of 15mm. During irradiation, the catheters were placed in the center of each channel. Catheters fit the 5.4mm diameters channels whereas polyurethane plugs were inserted into the larger channels to create a sturdy, immobile catheter which allowed uniform dose distributions. Two dosimeters of each 5.4mm and 15mm were irradiated at either 1517.3 cGy or 2017.5 cGy. Post-irradiation scans were performed within 48 hours of irradiation. A 3D reconstruction based on subtraction of these two images and the relative dose measurements were made using in-house software. Results: Comparing measured radial dose rates with previous results revealed smaller percent errors when PRESAGE™ irradiations were at lower maximum dose. The dosimeters showed small deviations in radial dose function, g{sub p} (r), from previous studies. Among the dosimeters irradiated at 1517.3 cGy, the g{sub p}(r) compared to previous studies fluctuated from 0.0043 to 0.3922. This suggests small fluctuations can drastically change radial dose calculations. Conclusion: The subtraction of pre-irradiation and post-irradiation scans of PRESAGE™ dosimeters using an optical

Mutation site and context dependent effects of ESR1 mutation in genome-edited breast cancer cell models.

PubMed

Bahreini, Amir; Li, Zheqi; Wang, Peilu; Levine, Kevin M; Tasdemir, Nilgun; Cao, Lan; Weir, Hazel M; Puhalla, Shannon L; Davidson, Nancy E; Stern, Andrew M; Chu, David; Park, Ben Ho; Lee, Adrian V; Oesterreich, Steffi

2017-05-23

Mutations in the estrogen receptor alpha (ERα) 1 gene (ESR1) are frequently detected in ER+ metastatic breast cancer, and there is increasing evidence that these mutations confer endocrine resistance in breast cancer patients with advanced disease. However, their functional role is not well-understood, at least in part due to a lack of ESR1 mutant models. Here, we describe the generation and characterization of genome-edited T47D and MCF7 breast cancer cell lines with the two most common ESR1 mutations, Y537S and D538G. Genome editing was performed using CRISPR and adeno-associated virus (AAV) technologies to knock-in ESR1 mutations into T47D and MCF7 cell lines, respectively. Various techniques were utilized to assess the activity of mutant ER, including transactivation, growth and chromatin-immunoprecipitation (ChIP) assays. The level of endocrine resistance was tested in mutant cells using a number of selective estrogen receptor modulators (SERMs) and degraders (SERDs). RNA sequencing (RNA-seq) was employed to study gene targets of mutant ER. Cells with ESR1 mutations displayed ligand-independent ER activity, and were resistant to several SERMs and SERDs, with cell line and mutation-specific differences with respect to magnitude of effect. The SERD AZ9496 showed increased efficacy compared to other drugs tested. Wild-type and mutant cell co-cultures demonstrated a unique evolution of mutant cells under estrogen deprivation and tamoxifen treatment. Transcriptome analysis confirmed ligand-independent regulation of ERα target genes by mutant ERα, but also identified novel target genes, some of which are involved in metastasis-associated phenotypes. Despite significant overlap in the ligand-independent genes between Y537S and D538G, the number of mutant ERα-target genes shared between the two cell lines was limited, suggesting context-dependent activity of the mutant receptor. Some genes and phenotypes were unique to one mutation within a given cell line

A Hilbert Space Representation of Generalized Observables and Measurement Processes in the ESR Model

NASA Astrophysics Data System (ADS)

Sozzo, Sandro; Garola, Claudio

2010-12-01

The extended semantic realism ( ESR) model recently worked out by one of the authors embodies the mathematical formalism of standard (Hilbert space) quantum mechanics in a noncontextual framework, reinterpreting quantum probabilities as conditional instead of absolute. We provide here a Hilbert space representation of the generalized observables introduced by the ESR model that satisfy a simple physical condition, propose a generalization of the projection postulate, and suggest a possible mathematical description of the measurement process in terms of evolution of the compound system made up of the measured system and the measuring apparatus.

Dose evaluation of an NIPAM polymer gel dosimeter using gamma index

NASA Astrophysics Data System (ADS)

Chang, Yuan-Jen; Lin, Jing-Quan; Hsieh, Bor-Tsung; Yao, Chun-Hsu; Chen, Chin-Hsing

2014-11-01

An N-isopropylacrylamide (NIPAM) polymer gel dosimeter has great potential in clinical applications. However, its three-dimensional dose distribution must be assessed. In this work, a quantitative evaluation of dose distributions was performed to evaluate the NIPAM polymer gel dosimeter using gamma analysis. A cylindrical acrylic phantom filled with NIPAM gel measuring 10 cm (diameter) by 10 cm (height) by 3 mm (thickness) was irradiated by a 4×4 cm2 square light field. The irradiated gel phantom was scanned using an optical computed tomography (optical CT) scanner (OCTOPUS™, MGS Research, Inc., Madison, CT, USA) at 1 mm resolution. The projection data were transferred to an image reconstruction program, which was written using MATLAB (The MathWorks, Natick, MA, USA). The program reconstructed the image of the optical density distribution using the algorithm of a filter back-projection. Three batches of replicated gel phantoms were independently measured. The average uncertainty of the measurements was less than 1%. The gel was found to have a high degree of spatial uniformity throughout the dosimeter and good temporal stability. A comparison of the line profiles of the treatment planning system and of the data measured by optical CT showed that the dose was overestimated in the penumbra region because of two factors. The first is light scattering due to changes in the refractive index at the edge of the irradiated field. The second is the edge enhancement caused by free radical diffusion. However, the effect of edge enhancement on the NIPAM gel dosimeter is not as significant as that on the BANG gel dosimeter. Moreover, the dose uncertainty is affected by the inaccuracy of the gel container positioning process. To reduce the uncertainty of 3D dose distribution, improvements in the gel container holder must be developed.

Commissioning optically stimulated luminescence in vivo dosimeters for fast neutron therapy.

PubMed

Young, Lori A; Yang, Fei; Woodworth, Davis; McCormick, Zephyr; Sandison, George

2016-01-01

Clinical in vivo dosimeters intended for use with photon and electron therapies have not been utilized for fast neutron therapy because they are highly susceptible to neutron damage. The objective of this work was to determine if a commercial optically stimulated luminescence (OSL) in vivo dosimetry system could be adapted for use in fast neutron therapy. A 50.5 MeV fast neutron beam generated by a clinical neutron therapy cyclotron was used to irradiate carbon doped aluminum oxide (Al2O3:C) optically simulated luminescence dosimeters (OSLDs) in a solid water phantom under standard calibration conditions, 150 cm SAD, 1.7 cm depth, and 10.3 × 10.0 cm field size. OSLD fading and electron trap depletion studies were performed with the OSLDs irradiated with 20 and 50 cGy and monitored over a 24-h period to determine the optimal time for reading the dosimeters during calibration. Four OSLDs per group were calibrated over a clinical dose range of 0-150 cGy. OSLD measurement uncertainties were lowered to within ±2%-3% of the expected dose by minimizing the effect of transient fading that occurs with neutron irradiation and maintaining individual calibration factors for each dosimeter. Dose dependent luminescence fading extended beyond the manufacturer's recommended 10 min period for irradiation with photon or electron beams. To minimize OSL variances caused by inconsistent fading among dosimeters, the observed optimal time for reading the OSLDs postirradiation was between 30 and 90 min. No field size, wedge factor, or gantry angle dependencies were observed in the OSLDs irradiated by the studied fast neutron beam. Measurements demonstrated that uncertainties less than ±3% were attainable in OSLDs irradiated with fast neutrons under clinical conditions. Accuracy and precision comparable to clinical OSL measurements observed with photons can be achieved by maintaining individual OSLD calibration factors and minimizing transient fading effects.

Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose response using different monomers

NASA Astrophysics Data System (ADS)

Senden, R. J.; DeJean, P.; McAuley, K. B.; Schreiner, L. J.

2006-07-01

In this work, three new polymer gel dosimeter recipes were investigated that may be more suitable for widespread applications than polyacrylamide gel dosimeters, since the extremely toxic acrylamide has been replaced with the less harmful monomers N-isopropylacrylamide (NIPAM), diacetone acrylamide and N-vinylformamide. The new gel dosimeters studied contained gelatin (5 wt%), monomer (3 wt%), N,N'-methylene-bis-acrylamide crosslinker (3 wt%) and tetrakis (hydroxymethyl) phosphonium chloride antioxidant (10 mM). The NMR response (R2) of the dosimeters was analysed for conditions of varying dose, dose rate, time post-irradiation, and temperature during irradiation and scanning. It was shown that the dose-response behaviour of the NIPAM/Bis gel dosimeter is comparable to that of normoxic polyacrylamide gel (PAGAT) in terms of high dose-sensitivity and low dependence on dose rate and irradiation temperature, within the ranges considered. The dose-response (R2) of NIPAM/Bis appears to be linear over a greater dose range than the PAGAT gel dosimeter. The effects of time post-irradiation (temporal instability) and temperature during NMR scanning on the R2 response were more significant for NIPAM/Bis dosimeters. Diacetone acrylamide and N-vinylformamide gel dosimeters possessed considerably lower dose-sensitivities. The optical dose-response, measured in terms of the attenuation coefficient for each polymer gel dosimeter, showed potential for the use of optical imaging techniques in future studies.

Estrogen receptor ESR1 mediates activation of ERK1/2, CREB, and ELK1 in the corpus of the epididymis.

PubMed

Cavalcanti, Fernanda N; Lucas, Thais F G; Lazari, Maria Fatima M; Porto, Catarina S

2015-06-01

Expression of the estrogen receptor ESR1 is higher in the corpus than it is in the initial segment/caput and cauda of the epididymis. ESR1 immunostaining in the corpus has been localized not only in the nuclei but also in the cytoplasm and apical membrane, which indicates that ESR1 plays a role in membrane-initiated signaling. The present study investigated whether ESR1 mediates the activation of rapid signaling pathways by estradiol (E2) in the epididymis. We investigated the effect of E2 and the ESR1-selective agonist (4,4',4''-(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol (PPT) on the activation of extracellular signal-regulated protein kinases (ERK1/2), CREB protein, and ETS oncogene-related protein (ELK1). Treatment with PPT did not affect ERK1/2 phosphorylation in the cauda, but it rapidly increased ERK1/2 phosphorylation in the initial segment/caput and corpus of the epididymis. PPT also activated CREB and ELK1 in the corpus of the epididymis. The PPT-induced phosphorylation of ERK1/2, CREB, and ELK1 was blocked by the ESR1-selective antagonist MPP and by pretreatment with a non-receptor tyrosine kinase SRC inhibitor, an EGFR kinase inhibitor, an MEK1/2 inhibitor, and a phosphatidylinositol-3-kinase inhibitor. In conclusion, these results indicate that the corpus, which is a region with high expression of the estrogen receptor ESR1, is a major target in the epididymis for the activation of rapid signaling by E2. The sequence of events that follow E2 interaction with ESR1 includes the SRC-mediated transactivation of EGFR and the phosphorylation of ERK1/2, CREB, and ELK1. This rapid estrogen signaling may modulate gene expression in the corpus of the epididymis, and it may play a role in the dynamic microenvironment of the epididymal lumen. © 2015 Society for Endocrinology.

An ion-pair principle for enantioseparations of basic analytes by nonaqueous capillary electrophoresis using the di-n-butyl L-tartrate-boric acid complex as chiral selector.

PubMed

Wang, Li-Juan; Liu, Xiu-Feng; Lu, Qie-Nan; Yang, Geng-Liang; Chen, Xing-Guo

2013-04-05

A chiral recognition mechanism of ion-pair principle has been proposed in this study. It rationalized the enantioseparations of some basic analytes using the complex of di-n-butyl l-tartrate and boric acid as the chiral selector in methanolic background electrolytes (BGEs) by nonaqueous capillary electrophoresis (NACE). An approach of mass spectrometer (MS) directly confirmed that triethylamine promoted the formation of negatively charged di-n-butyl l-tartrate-boric acid complex chiral counter ion with a complex ratio of 2:1. And the negatively charged counter ion was the real chiral selector in the ion-pair principle enantioseparations. It was assumed that triethylamine should play its role by adjusting the apparent acidity (pH*) of the running buffer to a higher value. Consequently, the effects of various basic electrolytes including inorganic and organic ones on the enantioseparations in NACE were investigated. The results showed that most of the basic electrolytes tested were favorable for the enantioseparations of basic analytes using di-n-butyl l-tartrate-boric acid complex as the chiral ion-pair selector. Copyright © 2013 Elsevier B.V. All rights reserved.

SU-E-T-643: Pure Alanine Dosimeter for Verification Dosimetry in IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Karmi, Anan M.; Zraiqat, Fadi

Purpose: The objective of this study was evaluation of accuracy of pure alanine dosimeters measuring intensity-modulated radiation therapy (IMRT) dose distributions in a thorax phantom. Methods: Alanine dosimeters were prepared in the form of 110 mg pure L-α-alanine powder filled into clear tissue-equivalent polymethylmethacrylate (PMMA) plastic tubes with the dimensions 25 mm length, 3 mm inner diameter, and 1 mm wall thickness. A dose-response calibration curve was established for the alanine by placing the dosimeters at 1.5 cm depth in a 30×30×30 cm{sup 3} solid water phantom and then irradiating on a linac with 6 MV photon beam at 10×10more » cm{sup 2} field size to doses ranging from 1 to 5 Gy. Electron paramagnetic resonance (EPR) spectroscopy was used to determine the absorbed dose in alanine. An IMRT treatment plan was designed for a commercial heterogeneous CIRS thorax phantom and the dose values were calculated at three different points located in tissue, lung, and bone equivalent materials. A set of dose measurements was carried out to compare measured and calculated dose values by placing the alanine dosimeters at those selected locations inside the thorax phantom and delivering the IMRT to the phantom. Results: The alanine dose measurements and the IMRT plan dose calculations were found to be in agreement within ±2%. Specifically, the deviations were −0.5%, 1.3%, and −1.7% for tissue, lung, and bone; respectively. The slightly large deviations observed for lung and bone may be attributed to tissue inhomogeneity, steep dose gradients in these regions, and uncontrollable changes in spectrometer conditions. Conclusion: The results described herein confirmed that pure alanine dosimeter was suitable for in-phantom dosimetry of IMRT beams because of its high sensitivity and acceptable accuracy. This makes the dosimeter a promising option for quality control of the therapeutic beams, complementing the commonly used ionization chambers, TLDs, and

Simple method for quantification of gadolinium magnetic resonance imaging contrast agents using ESR spectroscopy.

PubMed

Takeshita, Keizo; Kinoshita, Shota; Okazaki, Shoko

2012-01-01

To develop an estimation method of gadolinium magnetic resonance imaging (MRI) contrast agents, the effect of concentration of Gd compounds on the ESR spectrum of nitroxyl radical was examined. A solution of either 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPONE) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) was mixed with a solution of Gd compound and the ESR spectrum was recorded. Increased concentration of gadolinium-diethylenetriamine pentaacetic acid chelate (Gd-DTPA), an MRI contrast agent, increased the peak-to-peak line widths of ESR spectra of the nitroxyl radicals, in accordance with a decrease of their signal heights. A linear relationship was observed between concentration of Gd-DTPA and line width of ESR signal, up to approximately 50 mmol/L Gd-DTPA, with a high correlation coefficient. Response of TEMPONE was 1.4-times higher than that of TEMPOL as evaluated from the slopes of the lines. The response was slightly different among Gd compounds; the slopes of calibration curves for acua[N,N-bis[2-[(carboxymethyl)[(methylcarbamoyl)methyl]amino]ethyl]glycinato(3-)]gadolinium hydrate (Gd-DTPA-BMA) (6.22 μT·L/mmol) and gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelate (Gd-DOTA) (6.62 μT·L/mmol) were steeper than the slope for Gd-DTPA (5.45 μT·L/mmol), whereas the slope for gadolinium chloride (4.94 μT·L/mmol) was less steep than that for Gd-DTPA. This method is simple to apply. The results indicate that this method is useful for rough estimation of the concentration of Gd contrast agents if calibration is carried out with each standard compound. It was also found that the plot of the reciprocal square root of signal height against concentrations of contrast agents could be useful for the estimation if a constant volume of sample solution is taken and measured at the same position in the ESR cavity every time.

Comparative stability of repackaged metoprolol tartrate tablets.

PubMed

Yang, Yongsheng; Gupta, Abhay; Carlin, Alan S; Faustino, Patrick J; Lyon, Robbe C; Ellison, Christopher D; Rothman, Barry; Khan, Mansoor A

2010-01-29

The stability of metoprolol tartrate tablets packaged in original high density polyethylene containers and repackaged in USP Class A unit-dose blister packs was investigated. Studies were conducted at 25 degrees C/60% relative humidity (RH) for 52 weeks and at 40 degrees C/75% RH for 13 weeks. The potency, dissolution, water content, loss on drying and hardness of the drug products were analyzed. Results indicated no differences in the stability between the tablets in both packages stored under 25 degrees C/60% RH. No difference in potency was found in both packages under either condition. However, a significant weight increase due to moisture uptake was observed for the repackaged tablets stored under 40 degrees C/75% RH. The weight increase was accompanied by a decrease in tablet hardness (6.5-0 kp) and a increase in dissolution rate (51-92%) in 5 min. Near-infrared (NIR) chemical imaging also monitored moisture uptake of the tablet non-invasively through the package. The observed changes in product stability may adversely affect the products bioavailability profile, even though the potency of the active drug remained within USP specification range of 90-110%. Study results suggest product quality can be negatively impacted even when using USP Class A repackaging materials. Published by Elsevier B.V.

RADIATION DOSIMETER AND DOSIMETRIC METHODS

DOEpatents

Taplin, G.V.

1958-10-28

The determination of ionizing radiation by means of single fluid phase chemical dosimeters of the colorimetric type is presented. A single fluid composition is used consisting of a chlorinated hydrocarbon, an acidimetric dye, a normalizer and water. Suitable chlorinated hydrocarbons are carbon tetrachloride, chloroform, trichloroethylene, trichlorethane, ethylene dichioride and tetracbloroethylene. Suitable acidimetric indicator dyes are phenol red, bromcresol purple, and creosol red. Suitable normallzers are resorcinol, geraniol, meta cresol, alpha -tocopberol, and alpha -naphthol.

Dynamic nuclear polarization-magnetic resonance imaging at low ESR irradiation frequency for ascorbyl free radicals.

PubMed

Ito, Shinji; Hyodo, Fuminori

2016-02-19

Highly water-soluble ubiquinone-0 (CoQ0) reacts with ascorbate monoanion (Asc) to mediate the production of ascorbyl free radicals (AFR). Using aqueous reaction mixture of CoQ0 and Asc, we obtained positively enhanced dynamic nuclear polarization (DNP)-magnetic resonance (MR) images of the AFR at low frequency (ranging from 515 to 530 MHz) of electron spin resonance (ESR) irradiation. The shape of the determined DNP spectrum was similar to ESR absorption spectra with doublet spectral peaks. The relative locational relationship of spectral peaks in the DNP spectra between the AFR (520 and 525 MHz), (14)N-labeled carbamoyl-PROXYL ((14)N-CmP) (526.5 MHz), and Oxo63 (522 MHz) was different from that in the X-band ESR spectra, but were similar to that in the 300-MHz ESR spectra. The ratio of DNP enhancement to radical concentration for the AFR was higher than those for (14)N-CmP, Oxo63, and flavin semiquinone radicals. The spectroscopic DNP properties observed for the AFR were essentially the same as those for AFR mediated by pyrroloquinoline quinone. Moreover, we made a success of in vivo DNP-MR imaging of the CoQ0-mediated AFR which was administered by the subcutaneous and oral injections as an imaging probe.

Sensitive Detection of Mono- and Polyclonal ESR1 Mutations in Primary Tumors, Metastatic Lesions, and Cell-Free DNA of Breast Cancer Patients.

PubMed

Wang, Peilu; Bahreini, Amir; Gyanchandani, Rekha; Lucas, Peter C; Hartmaier, Ryan J; Watters, Rebecca J; Jonnalagadda, Amruth R; Trejo Bittar, Humberto E; Berg, Aaron; Hamilton, Ronald L; Kurland, Brenda F; Weiss, Kurt R; Mathew, Aju; Leone, Jose Pablo; Davidson, Nancy E; Nikiforova, Marina N; Brufsky, Adam M; Ambros, Tadeu F; Stern, Andrew M; Puhalla, Shannon L; Lee, Adrian V; Oesterreich, Steffi

2016-03-01

Given the clinical relevance of ESR1 mutations as potential drivers of resistance to endocrine therapy, this study used sensitive detection methods to determine the frequency of ESR1 mutations in primary and metastatic breast cancer, and in cell-free DNA (cfDNA). Six ESR1 mutations (K303R, S463P, Y537C, Y537N, Y537S, D538G) were assessed by digital droplet PCR (ddPCR), with lower limits of detection of 0.05% to 0.16%, in primary tumors (n = 43), bone (n = 12) and brain metastases (n = 38), and cfDNA (n = 29). Correlations between ESR1 mutations in metastatic lesions and single (1 patient) or serial blood draws (4 patients) were assessed. ESR1 mutations were detected for D538G (n = 13), Y537S (n = 3), and Y537C (n = 1), and not for K303R, S463P, or Y537N. Mutation rates were 7.0% (3/43 primary tumors), 9.1% (1/11 bone metastases), 12.5% (3/24 brain metastases), and 24.1% (7/29 cfDNA). Two patients showed polyclonal disease with more than one ESR1 mutation. Mutation allele frequencies were 0.07% to 0.2% in primary tumors, 1.4% in bone metastases, 34.3% to 44.9% in brain metastases, and 0.2% to 13.7% in cfDNA. In cases with both cfDNA and metastatic samples (n = 5), mutations were detected in both (n = 3) or in cfDNA only (n = 2). Treatment was associated with changes in ESR1 mutation detection and allele frequency. ESR1 mutations were detected at very low allele frequencies in some primary breast cancers, and at high allele frequency in metastases, suggesting that in some tumors rare ESR1-mutant clones are enriched by endocrine therapy. Further studies should address whether sensitive detection of ESR1 mutations in primary breast cancer and in serial blood draws may be predictive for development of resistant disease. See related commentary by Gu and Fuqua, p. 1034. ©2015 American Association for Cancer Research.

Clinical Implications of ESR1 Mutations in Hormone Receptor-Positive Advanced Breast Cancer

PubMed Central

Reinert, Tomas; Saad, Everardo D.; Barrios, Carlos H.; Bines, José

2017-01-01

Hormone receptor-positive breast cancer is the most frequent breast cancer subtype. Endocrine therapy (ET) targeting the estrogen receptor (ER) pathway represents the main initial therapeutic approach. The major strategies include estrogen deprivation and the use of selective estrogen modulators or degraders, which show efficacy in the management of metastatic and early-stage disease. However, clinical resistance associated with progression of disease remains a significant therapeutic challenge. Mutations of the ESR1 gene, which encodes the ER, have been increasingly recognized as an important mechanism of ET resistance, with a prevalence that ranges from 11 to 39%. The majority of these mutations are located within the ligand-binding domain and result in an estrogen-independent constitutive activation of the ER and, therefore, resistance to estrogen deprivation therapy such as aromatase inhibition. ESR1 mutations, most often detected from liquid biopsies, have been consistently associated with a worse outcome and are being currently evaluated as a potential biomarker to guide therapeutic decisions. At the same time, targeted therapy directed to ESR1-mutated clones is an appealing concept with preclinical and clinical work in progress. PMID:28361033

[Measurement of scatter radiation on MDCT equipment using an OSL dosimeter].

PubMed

Tomita, Hironobu; Morozumi, Kunihiko

2004-11-01

The recent introduction of multi-detector row computed tomography (MDCT) has made it possible to scan the entire abdomen within approximately 10 sec in procedures such as interventional radiology computed tomography (IVRCT), which are associated with operator exposure. Therefore, anxious patients and patients who are not able to remain still can be examined with an assistant. In the present study, radiation exposure to the assistant was estimated, and the distribution of scattered radiation near the gantry was measured using an optically stimulated luminescence (OSL) dosimeter. Simultaneous measurements were obtained using a direction storage (DIS) dosimeter for reference. The maximum value of 1.47 mSv per examination was obtained at the point closest to the gantry's center (50 cm from the center at a height of 150 cm above the floor) . In addition, scattered radiation decreased as the measurement point was moved further from the gantry's center, falling below the limit of detection (0.1 mSv or less) at 200 cm and at the sides of the gantry. OSL dosimeters are also employed as personal dosimeters, permitting reliable values to be obtained easily. They were found to be an effective tool for the measurement of scattered radiation, as in the present study, helping to provide better understanding of the distribution of scattered radiation within the CT room.

Characterization of ferrous-methylthymol blue-polyvinyl alcohol gel dosimeters using nuclear magnetic resonance and optical techniques

NASA Astrophysics Data System (ADS)

Rabaeh, Khalid A.; Eyadeh, Molham M.; Hailat, Tariq F.; Aldweri, Feras M.; Alheet, Samer M.; Eid, Rania M.

2018-07-01

A new composition of Ferrous sulphate-Metheylthymol blue (MTB)-Polyvinyl alcohol (PVA) dosimeter is introduced in this work and evaluated using nuclear magnetic resonance (NMR) and absorbance spectrophotometry techniques. The Fricke-MTB-PVA dosimeters were irradiated using a medical linear accelerator in a cubic water phantom. The dose response of the dosimeters was investigated using NMR in terms of spin-spin relaxation rate (R2), and ultraviolet and visible regions (UV-Vis) spectrophotometry in terms of absorbance. The dosimeter presents a linear dose response for doses up to 20 Gy with UV-Vis and 40 Gy with NMR method. The sample with 0.1 mM MTB, 5% PVA by weight showed highest dose sensitivity for both techniques. The Fricke-MTB-PVA dosimeter developed in this work has a significant advance over the Fricke-MTB-gelatin system: the NMR sensitivity was remarkably improved; the auto-oxidation rate was seven times lower, and no significant dose rate or photon energy effects were observed.

Feasibility study of a photoconductor based dosimeter for quality assurance in radiotherapy

NASA Astrophysics Data System (ADS)

Lee, Y. K.; Kim, S. W.; Kim, J. N.; Kang, Y. N.; Kim, J. Y.; Lee, D. S.; Kim, K. T.; Han, M. J.; Ahn, K. J.; Park, S. K.

2017-09-01

With the recent market entries of new types of linear accelerators (LINACs) with a multi leaf collimator (MLC) mounted on them, high-precision radiosurgery applying a LINAC to measure high-dose radiation on the target region has been gaining popularity. Systematic and accurate quality assurance (QA) is of vital important for high-precision radiosurgery because of its increased risk of side effects including life-threatening ones such as overexposure of healthy tissues to high-dose radiation beams concentrated on small areas. Therefore, accurate dose and dose-distribution measurements are crucial in the treatment procedure. The accurate measurement of the properties of beams concentrated on small areas requires high-precision dosimeters capable of high-resolution output and dose mapping as well as accurate dosimetry in penumbra regions. In general, the properties of beams concentrated on small areas are measured using thermos luminescent dosimeters (TLD), diode detectors, ion chambers, diamond detectors, or films, and many papers have presented the advantages and disadvantages of each of these detectors for dosimetry. In this study, a solid-state photoconductor dosimeter was developed, and its clinical usability was tested by comparing its relative dosimetric performance with that of a conventional ion chamber. As materials best-suited for radiation dosimeters, four candidates namely lead (II) iodide (PbI2), lead (II) oxide (PbO), mercury (II) iodide (HgI2), and HgI2/ titanium dioxide (TiO2) composite, the performances of which were proved in previous studies, were used. The electrical properties of each candidate material were examined using the sedimentation method, one of the particle-in-binder (PIB) methods, and unit-cell-type prototypes were fabricated. The unit-cell samples thus prepared were cut into specimens of area 1 × 1 cm2 with 400-μ m thickness. The electrical properties of each sample, such as sensitivity, dark current, output current, rising time

A New Rapid and Sensitive Stability-Indicating UPLC Assay Method for Tolterodine Tartrate: Application in Pharmaceuticals, Human Plasma and Urine Samples

PubMed Central

Yanamandra, Ramesh; Vadla, Chandra Sekhar; Puppala, Umamaheshwar; Patro, Balaram; Murthy, Yellajyosula. L. N.; Ramaiah, Parimi Atchuta

2012-01-01

A new rapid, simple, sensitive, selective and accurate reversed-phase stability-indicating Ultra Performance Liquid Chromatography (RP-UPLC) technique was developed for the assay of Tolterodine Tartrate in pharmaceutical dosage form, human plasma and urine samples. The developed UPLC method is superior in technology to conventional HPLC with respect to speed, solvent consumption, resolution and cost of analysis. Chromatographic run time was 6 min in reversed-phase mode and ultraviolet detection was carried out at 220 nm for quantification. Efficient separation was achieved for all the degradants of Tolterodine Tartrate on BEH C18 sub-2-μm Acquity UPLC column using Trifluoroacetic acid and acetonitrile as organic solvent in a linear gradient program. The active pharmaceutical ingredient was extracted from tablet dosage form using a mixture of acetonitrile and water as diluent. The calibration graphs were linear and the method showed excellent recoveries for bulk and tablet dosage form. The test solution was found to be stable for 40 days when stored in the refrigerator between 2 and 8 °C. The developed UPLC method was validated and meets the requirements delineated by the International Conference on Harmonization (ICH) guidelines with respect to linearity, accuracy, precision, specificity and robustness. The intra-day and inter-day variation was found be less than 1%. The method was reproducible and selective for the estimation of Tolterodine Tartrate. Because the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one. PMID:22396907

Prognostic and predictive role of ESR1 status for postmenopausal patients with endocrine-responsive early breast cancer in the Danish cohort of the BIG 1-98 trial

PubMed Central

Ejlertsen, B.; Aldridge, J.; Nielsen, K. V.; Regan, M. M.; Henriksen, K. L.; Lykkesfeldt, A. E.; Müller, S.; Gelber, R. D.; Price, K. N.; Rasmussen, B. B.; Viale, G.; Mouridsen, H.

2012-01-01

Background: Estrogen Receptor 1 (ESR1) aberrations may be associated with expression of estrogen receptor (ER) or progesterone receptor (PgR), human epidermal growth factor receptor-2 (HER2) or Ki-67 labeling index and prognosis. Patients and methods: ESR1 was assessed in 1129 (81%) of 1396 postmenopausal Danish women with early breast cancer randomly assigned to receive 5 years of letrozole, tamoxifen or a sequence of these agents in the Breast International Group 1-98 trial and who had ER ≥1% after central review. Results: By FISH, 13.6% of patients had an ESR1-to-Centromere-6 (CEN-6) ratio ≥2 (amplified), and 4.2% had ESR1-to-CEN-6 ratio <0.8 (deleted). Deletion of ESR1 was associated with significantly lower levels of ER (P < 0.0001) and PgR (P = 0.02) and more frequent HER2 amplification. ESR1 deletion or amplification was associated with higher-Ki-67 than ESR1-normal tumors. Overall, there was no evidence of heterogeneity of disease-free survival (DFS) or in treatment effect according to ESR1 status. However, significant differences in DFS were observed for subsets based on a combination of ESR1 and HER2 status (P = 0.02). Conclusions: ESR1 aberrations were associated with HER2 status, Ki-67 labeling index and ER and PgR levels. When combined with HER2, ESR1 may be prognostic but should not be used for endocrine treatment selection in postmenopausal women with endocrine-responsive early breast cancer. PMID:21986093

Significance of estrogen receptor 1 (ESR-1) gene imbalances in colon and hepatocellular carcinomas based on tissue microarrays analysis.

PubMed

Tsiambas, Evangelos; Georgiannos, Stavros N; Salemis, Nikolaos; Alexopoulou, Despoina; Lambropoulou, Sofia; Dimo, Blerta; Ioannidis, Ioannis; Kravvaritis, Christos; Karameris, Andreas; Patsouris, Efstratios; Dourakis, Spyridon

2011-12-01

Estrogen receptor alpha-encoded by ESR1 gene-overexpression correlates with prognosis and response to specific chemotherapy in breast adenocarcinoma cases. Mechanisms of ESR-1 deregulation in carcinomas remain under investigation. To analyze ESR1 in carcinomas of different histogenesis. Using tissue microarray technology, 172 primary carcinomas including breast ductal adenocarcinomas (n=60), hepatocellular carcinomas (n=52), and colon adenocarcinomas (n=60) were cored and re-embedded in three paraffin blocks. Initial diagnosis was based on liquid based cytology (LiquiPrep/ThinPrep). Immunohistochemistry and fluorescence in situ hybridization were performed. Quantitative evaluation of ER-a protein levels was assessed by applying digital image analysis. ER-a overexpression was observed in 41/60 (68.3%), 23/52 (44.2%) and 4/60 (6.6%) cases, respectively. ESR1 gene multiple copies were confirmed in 13/60 (21.6%) breast adenocarcinomas, but high amplification only in 8/13 (62.8%). Allelic absence was identified in 3/52 (5.7%) hepatocellular carcinomas, whereas colon adenocarcinomas demonstrated gene gains in 5/60 (8.3%) cases referred to chr 6 aneuploidy and not to amplification. ER-a overall expression was associated strongly to ESR1 gene copies only in breast carcinoma (P=0.036). ESR-1 gene overexpression happens frequently in breast cancer, but only a subset of them are high amplified cases correlated to increased response rates in hormonal therapy (tamoxifen). Absence of this mechanism in hepatocellular and colon carcinomas maybe is a negative factor for applying this therapy. This is a pattern of histo-genetic depended targeted therapeutic strategy.

NASA Crew Personal Active Dosimeters (CPADs): Leveraging Novel Terrestrial Personal Radiation Monitoring Capabilities for Space Exploration

NASA Technical Reports Server (NTRS)

Leitgab, Martin; Semones, Edward; Lee, Kerry

2016-01-01

The NASA Space Radiation Analysis Group (SRAG) is developing novel Crew Personal Active Dosimeters (CAPDs) for upcoming crewed space exploration missions and beyond. To reduce the resource footprint of the project a COTS dosimeter base is used for the development of CPADs. This base was identified from evaluations of existing COTS personal dosimeters against the concept of operations of future crewed missions and tests against detection requirements for radiation characteristic of the space environment. CPADs exploit operations efficiencies from novel features for space flight personal dosimeters such as real-time dose feedback, and autonomous measuring and data transmission capabilities. Preliminary CPAD design, results of radiation testing and aspects of operational integration will be presented.

Effects of refractive index mismatch in optical CT imaging of polymer gel dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manjappa, Rakesh; Makki S, Sharath; Kanhirodan, Rajan, E-mail: rajan@physics.iisc.ernet.in

2015-02-15

Purpose: Proposing an image reconstruction technique, algebraic reconstruction technique-refraction correction (ART-rc). The proposed method takes care of refractive index mismatches present in gel dosimeter scanner at the boundary, and also corrects for the interior ray refraction. Polymer gel dosimeters with high dose regions have higher refractive index and optical density compared to the background medium, these changes in refractive index at high dose results in interior ray bending. Methods: The inclusion of the effects of refraction is an important step in reconstruction of optical density in gel dosimeters. The proposed ray tracing algorithm models the interior multiple refraction at themore » inhomogeneities. Jacob’s ray tracing algorithm has been modified to calculate the pathlengths of the ray that traverses through the higher dose regions. The algorithm computes the length of the ray in each pixel along its path and is used as the weight matrix. Algebraic reconstruction technique and pixel based reconstruction algorithms are used for solving the reconstruction problem. The proposed method is tested with numerical phantoms for various noise levels. The experimental dosimetric results are also presented. Results: The results show that the proposed scheme ART-rc is able to reconstruct optical density inside the dosimeter better than the results obtained using filtered backprojection and conventional algebraic reconstruction approaches. The quantitative improvement using ART-rc is evaluated using gamma-index. The refraction errors due to regions of different refractive indices are discussed. The effects of modeling of interior refraction in the dose region are presented. Conclusions: The errors propagated due to multiple refraction effects have been modeled and the improvements in reconstruction using proposed model is presented. The refractive index of the dosimeter has a mismatch with the surrounding medium (for dry air or water scanning). The

Entrance surface dose measurements using a small OSL dosimeter with a computed tomography scanner having 320 rows of detectors.

PubMed

Takegami, Kazuki; Hayashi, Hiroaki; Yamada, Kenji; Mihara, Yoshiki; Kimoto, Natsumi; Kanazawa, Yuki; Higashino, Kousaku; Yamashita, Kazuta; Hayashi, Fumio; Okazaki, Tohru; Hashizume, Takuya; Kobayashi, Ikuo

2017-03-01

Entrance surface dose (ESD) measurements are important in X-ray computed tomography (CT) for examination, but in clinical settings it is difficult to measure ESDs because of a lack of suitable dosimeters. We focus on the capability of a small optically stimulated luminescence (OSL) dosimeter. The aim of this study is to propose a practical method for using an OSL dosimeter to measure the ESD when performing a CT examination. The small OSL dosimeter has an outer width of 10 mm; it is assumed that a partial dose may be measured because the slice thickness and helical pitch can be set to various values. To verify our method, we used a CT scanner having 320 rows of detectors and checked the consistencies of the ESDs measured using OSL dosimeters by comparing them with those measured using Gafchromic™ films. The films were calibrated using an ionization chamber on the basis of half-value layer estimation. On the other hand, the OSL dosimeter was appropriately calibrated using a practical calibration curve previously proposed by our group. The ESDs measured using the OSL dosimeters were in good agreement with the reference ESDs from the Gafchromic™ films. Using these data, we also estimated the uncertainty of ESDs measured with small OSL dosimeters. We concluded that a small OSL dosimeter can be considered suitable for measuring the ESD with an uncertainty of 30 % during CT examinations in which pitch factors below 1.000 are applied.

ESR dating of tooth enamel: comparison with {230Th }/{234U } speleothem dates at La Chaise-de-Vouthon (Charente), France

NASA Astrophysics Data System (ADS)

Blackwell, Bonnie; Porat, N.; Schwarcz, H. P.; Debénath, A.

One way to assess a new dating method's reliability is by comparing its results with those from well established, independent techniques. A controlled test of the electron spin resonance (ESR) dating method as it is currently being applied to teeth was attempted for the time range 100-250 ka, beyond that of 14C, at the archaeological site of La Chaise-de-Vouthon (Charente, France). Although absent in modern enamel, a single ESR signal with g = 2.0018 in fossil tooth enamel hydroxyapatite increases in amplitude with increasing irradiation doses. ESR ages are derived from the ratio of the AD, the radiation dose needed to produce the observed ESR signal, relative to the natural, environmental dose rate (ED) experienced by the tooth after deposition. Since the age depends on the uranium (U) uptake history assumed, three ages are calculated assuming: (1) early U uptake (EU); (2) continuous (linear) uptake (LU); (3) recent uptake (RU). Generally, the LU age agrees best with known ages determined by other methods, although the RU model is better for some teeth. ESR dating assumes that the fossil has not suffered recrystallization or significant diagenetic alteration. In the preliminary test, three teeth were dated. In Bourgeois-Delaunay, a bovid molar associated with Palaeolithic artefacts was collected from layers dated at 101 ± 12 to 114 ± 7 ka by {230Th }/{234U } dating of the over- and underlying stalagmitic floors. From Suard, two Equus teeth were collected from beneath a stalagmitic floor dating 112 ± 12 ka. ESR dating teeth significantly underestimated the true age for the teeth: the mean ESR ages range from 37 to 94 ka with standard errors of 2-6 ka, and good replicability. Although more teeth at La Chaise need to be tested to ascertain that the underestimation does not result from random variation commonly seen among teeth within one unit, the consistent underestimation suggests a fault in one of the assumptions underlying the dating method. The most obvious

SU-E-T-368: Effect of a Strong Magnetic Field On Select Radiation Dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathis, M; Wen, Z; Tailor, R

Purpose: To determine the effect of a strong magnetic field on TLD-100, OSLD (Al{sub 2}O{sub 2}:C), and PRESAGE dosimetry devices. This study will help to determine which types of dosimeters can be used for quality assurance and in-vivo dosimetry measurements in a magnetic resonance imaginglinear accelerator (MRI-linac) system. Methods: The dosimeters were separated into two categories which were either exposed or not exposed to a strong magnetic field. In each category a set of dosimeters was irradiated with 0, 2, or 6 Gy. To expose the dosimeters to a magnetic field the samples in that category were place in amore » Bruker small animal magnetic resonance scanner at a field strength slightly greater than 2.5 T for at least 1 hour preirradiation and at least 1 hour post-irradiation. Irradiations were performed with a 6 MV x-ray beam from a Varian TrueBeam linac with 10×10 cm{sup 2} field at a 600 MU/min dose rate. The samples that received no radiation dose were used as control detectors. Results: The readouts of the dosimeters which were not exposed to a strong magnetic field were compared with the measurements of the dosimetry devices which were exposed to a magnetic field. No significant differences (less than 2% difference) in the performance of TLD, OSLD, or PRESAGE dosimeters due to exposure to a strong magnetic field were observed. Conclusion: Exposure to a strong magnetic field before and after irradiation does not appear to change the dosimetric properties of TLD, OSLD, or PRESAGE which indicates that these dosimeters have potential for use in quality assurance and in-vivo dosimetry in a MRI-linac. We plan to further test the effect of magnetic fields on these devices by irradiating them in the presence of a magnetic fields similar to those produced by a MRI-linac system. Elekta-MD Anderson Cancer Center Research Agreement.« less

Oxidation of spin-traps by chlorine dioxide (ClO2) radical in aqueous solutions: first ESR evidence of formation of new nitroxide radicals.

PubMed

Ozawa, T; Miura, Y; Ueda, J

1996-01-01

The reactivities of the chlorine dioxide (ClO2), which is a stable free radical towards some water-soluble spin-traps were investigated in aqueous solutions by an electron spin resonance (ESR) spectroscopy. The ClO2 radical was generated from the redox reaction of Ti3+ with potassium chlorate (KClO3) in aqueous solutions. When one of the spin-traps, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), was included in the Ti3+-KClO3 reaction system, ESR spectrum due to the ClO2 radical completely disappeared and a new ESR spectrum [aN(1) = 0.72 mT, aH(2) = 0.41 mT], which is different from that of DMPO-ClO2 adduct, was observed. The ESR parameters of this new ESR signal was identical to those of 5,5-dimethylpyrrolidone-(2)-oxyl-(1) (DMPOX), suggesting the radical species giving the new ESR spectrum is assignable to DMPOX. The similar ESR spectrum consisting of a triplet [aN(1) = 0.69 mT] was observed when the derivative of DMPO, 3,3,5,5-tetramethyl-1-pyrroline N-oxide (M4PO) was included in the Ti3+-KClO3 reaction system. This radical species is attributed to the oxidation product of M4PO, 3,3,5,5-tetramethylpyrrolidone-(2)-oxyl-(1) (M4POX). When another nitrone spin-trap, alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN) was used as a spin-trap, the ESR signal intensity due to the ClO2 radical decreased and a new ESR signal consisting of a triplet [aN(1) = 0.76 mT] was observed. The similar ESR spectrum was observed when N-t-butyl-alpha- nitrone (PBN) was used as a spin-trap. This ESR parameter [a(N)(1) = 0.85 mT] was identical to the oxidation product of PBN, PBNX. Thus, the new ESR signal observed from POBN may be assigned to the oxidation product of POBN, POBNX. These results suggest that the ClO2, radical does not form the stable spin adducts with nitrone spin-traps, but oxidizes these spin-traps to give the corresponding nitroxyl radicals. On the other hand, nitroso spin-traps, 5,5-dibromo-4-nitrosobenzenesulfonate (DBNBS), and 2-methyl-2-nitrosopropane (MNP) did not trap

Radiation dosimeter utilizing the thermoluminescence of lithium fluoride.

PubMed

CAMERON, J R; DANIELS, F; JOHNSON, N; KENNEY, G

1961-08-04

A dosimeter, with little wavelength dependence and large useful energy range for electromagnetic radiation, which is simple to use and read, has been developed. It appears to have applications in personnel monitoring as well as radiation research.

Development of a high efficiency personal/environmental radon dosimeter using polycarbonate detectors.

PubMed

Taheri, M; Jafarizadeh, M; Baradaran, S; Zainali, Gh

2006-12-01

Passive radon dosimeters, based on alpha particle etched track detectors, are widely used for the assessment of radon exposure. These methods are often applied in radon dosimetry for long periods of time. In this research work, we have developed a highly efficient method of personal/environmental radon dosimetry that is based upon the detection of alpha particles from radon daughters, (218)Po and (214)Po, using a polycarbonate detector (PC). The radon daughters are collected on the filter surface by passing a fixed flow of air through it and the PC detector, placed at a specified distance from the filter, is simultaneously exposed to alpha particles. After exposure, the latent tracks on the detector are made to appear by means of an electrochemical etching process; these are proportional to the radon dose. The air flow rate and the detector-filter distance are the major factors that can affect the performance of the dosimeter. The results obtained in our experimental investigations have shown that a distance of 1.5 cm between the detector and the filter, an absorber layer of Al with a thickness of 12 microm and an air flow rate of 4 l min(-1) offer the best design parameters for a high efficiency radon dosimeter. Then, the designed dosimeter was calibrated against different values of radon exposures and the obtained sensitivity was found to be 2.1 (tracks cm(-2)) (kBq h m(-3))(-1). The most important advantages of this method are that it is reliable, fast and convenient when used for radon dose assessment. In this paper, the optimized parameters of the dosimeter structure and its calibration procedure are presented and discussed.

Optically stimulated Al2O3:C luminescence dosimeters for teletherapy: Hp(10) performance evaluation.

PubMed

Hashim, S; Musa, Y; Ghoshal, S K; Ahmad, N E; Hashim, I H; Yusop, M; Bradley, D A; Kadir, A B A

2018-05-01

The performance of optically stimulated luminescence dosimeters (OSLDs, Al 2 O 3 :C) was evaluated in terms of the operational quantity of H P (10) in Co-60 external beam teletherapy unit. The reproducibility, signal depletion, and dose linearity of each dosimeter was investigated. For ten repeated readouts, each dosimeter exposed to 50mSv was found to be reproducible below 1.9 ± 3% from the mean value, indicating good reader stability. Meanwhile, an average signal reduction of 0.5% per readout was found. The dose response revealed a good linearity within the dose range of 5-50mSv having nearly perfect regression line with R 2 equals 0.9992. The accuracy of the measured doses were evaluated in terms of operational quantity H P (10), wherein the trumpet curve method was used respecting the 1990 International Commission on Radiological Protection (ICRP) standard. The accuracy of the overall measurements from all dosimeters was discerned to be within the trumpet curve and devoid of outlier. It is established that the achieved OSL Al 2 O 3 :C dosimeters are greatly reliable for equivalent dose assessment. Copyright © 2018 Elsevier Ltd. All rights reserved.

X-ray microbeam measurements with a high resolution scintillator fibre-optic dosimeter.

PubMed

Archer, James; Li, Enbang; Petasecca, Marco; Dipuglia, Andrew; Cameron, Matthew; Stevenson, Andrew; Hall, Chris; Hausermann, Daniel; Rosenfeld, Anatoly; Lerch, Michael

2017-09-29

Synchrotron microbeam radiation therapy is a novel external beam therapy under investigation, that uses highly brilliant synchrotron x-rays in microbeams 50 μm width, with separation of 400 μm, as implemented here. Due to the fine spatial fractionation dosimetry of these beams is a challenging and complicated problem. In this proof-of-concept work, we present a fibre optic dosimeter that uses plastic scintillator as the radiation conversion material. We claim an ideal one-dimensional resolution of 50 μm. Using plastic scintillator and fibre optic makes this dosimeter water-equivalent, a very desirable dosimetric property. The dosimeter was tested at the Australian Synchrotron, on the Imaging and Medical Beam-Line. The individual microbeams were able to be resolved and the peak-to-valley dose ratio and the full width at half maximum of the microbeams was measured. These results are compared to a semiconductor strip detector of the same spatial resolution. A percent depth dose was measured and compared to data acquired by an ionisation chamber. The results presented demonstrate significant steps towards the development of an optical dosimeter with the potential to be applied in quality assurance of microbeam radiation therapy, which is vital if clinical trials are to be performed on human patients.

Unfolding neutron spectra from simulated response of thermoluminescence dosimeters inside a polyethylene sphere using GRNN neural network