ESR/Alanine gamma-dosimetry in the 10-30 Gy range.

PubMed

Fainstein, C; Winkler, E; Saravi, M

2000-05-01

We report Alanine Dosimeter preparation, procedures for using the ESR/Dosimetry method, and the resulting calibration curve for gamma-irradiation in the range from 10-30 Gy. We use calibration curve to measure the irradiation dose in gamma-irradiation of human blood, as required in Blood Transfusion Therapy. The ESR/Alanine results are compared against those obtained using the thermoluminescent dosimetry (TLD) method.

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.

[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.

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.

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 pursuit of cost-effectiveness. Perhaps the greatest barrier is that, at the working level, KSC's culture is so preoccupied with technical concerns that it seems almost oblivious to any cost concerns, let alone cost-effectiveness concerns. It is recommended that we must urgently begin to change that culture and seek a better balance between these two concerns.

Changes in estrogen receptor signaling alters the timekeeping system in male mice.

PubMed

Blattner, Margaret S; Mahoney, Megan M

2015-11-01

Circadian rhythms are modulated by steroid hormones; however, the mechanisms of this action are not fully understood, particularly in males. In females estradiol regulates activity level, pattern of expression, and free running period (tau). We tested the hypothesis that activity level and distribution in male mice includes both classical and "non-classical" actions of estrogens at the estrogen receptor subtype 1 (ESR1). We used transgenic mice with mutations in their estrogen response pathways: ESR1 knock-out (ERKO) mice lack the ability to respond to estrogens via ESR1. "Non-classical" estrogen receptor knock-in (NERKI) mice have an inserted ESR1 receptor with a mutation in the estrogen-response-element binding domain, allowing activation via non-genomic and second messenger pathways. Gonadectomized male NERKI, ERKO, and wildtype (WT) littermates were given oil, or low or high dose estradiol and daily activity parameters were quantified. Estradiol shortened the ratio of activity in the light relative to dark (LD ratio), shortened tau, advanced the time of activity onset, and altered responsiveness to light cues administered in the late subjective night, suggesting modulation by an ESR1-independent mechanism. Estradiol treatment in NERKI but not WT males altered the timing of activity onset, LD ratio, and the behavioral response to light cues. These results may represent disruptions in the balance of genomic/nongenomic or ESR1/ESR2 signaling pathways. We also found a significant genotype effect on total activity, LD ratio, tau, and activity duration. These data provide new information about the role of ESR1-dependent and independent signaling pathways on the timekeeping system in male mice. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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

Early Life Exposure to Endocrine-Disrupting Chemicals Causes Lifelong Molecular Reprogramming of the Hypothalamus and Premature Reproductive Aging

PubMed Central

Walker, Deena M.; Zama, Aparna M.; Armenti, AnnMarie E.; Uzumcu, Mehmet

2011-01-01

Gestational exposure to the estrogenic endocrine disruptor methoxychlor (MXC) disrupts the female reproductive system at the molecular, physiological, and behavioral levels in adulthood. The current study addressed whether perinatal exposure to endocrine disruptors reprograms expression of a suite of genes expressed in the hypothalamus that control reproductive function and related these molecular changes to premature reproductive aging. Fischer rats were exposed daily for 12 consecutive days to vehicle (dimethylsulfoxide), estradiol benzoate (EB) (1 mg/kg), and MXC (low dose, 20 μg/kg or high dose, 100 mg/kg), beginning on embryonic d 19 through postnatal d 7. The perinatally exposed females were aged to 16–17 months and monitored for reproductive senescence. After euthanasia, hypothalamic regions [preoptic area (POA) and medial basal hypothalamus] were dissected for real-time PCR of gene expression or pyrosequencing to assess DNA methylation of the Esr1 gene. Using a 48-gene PCR platform, two genes (Kiss1 and Esr1) were significantly different in the POA of endocrine-disrupting chemical-exposed rats compared with vehicle-exposed rats after Bonferroni correction. Fifteen POA genes were up-regulated by at least 50% in EB or high-dose MXC compared with vehicle. To understand the epigenetic basis of the increased Esr1 gene expression, we performed bisulfite conversion and pyrosequencing of the Esr1 promoter. EB-treated rats had significantly higher percentage of methylation at three CpG sites in the Esr1 promoter compared with control rats. Together with these molecular effects, perinatal MXC and EB altered estrous cyclicity and advanced reproductive senescence. Thus, early life exposure to endocrine disruptors has lifelong effects on neuroendocrine gene expression and DNA methylation, together with causing the advancement of reproductive senescence. PMID:22016562

Effects of Aggregation on Blood Sedimentation and Conductivity

PubMed Central

Zhbanov, Alexander; Yang, Sung

2015-01-01

The erythrocyte sedimentation rate (ESR) test has been used for over a century. The Westergren method is routinely used in a variety of clinics. However, the mechanism of erythrocyte sedimentation remains unclear, and the 60 min required for the test seems excessive. We investigated the effects of cell aggregation during blood sedimentation and electrical conductivity at different hematocrits. A sample of blood was drop cast into a small chamber with two planar electrodes placed on the bottom. The measured blood conductivity increased slightly during the first minute and decreased thereafter. We explored various methods of enhancing or retarding the erythrocyte aggregation. Using experimental measurements and theoretical calculations, we show that the initial increase in blood conductivity was indeed caused by aggregation, while the subsequent decrease in conductivity resulted from the deposition of erythrocytes. We present a method for calculating blood conductivity based on effective medium theory. Erythrocytes are modeled as conducting spheroids surrounded by a thin insulating membrane. A digital camera was used to investigate the erythrocyte sedimentation behavior and the distribution of the cell volume fraction in a capillary tube. Experimental observations and theoretical estimations of the settling velocity are provided. We experimentally demonstrate that the disaggregated cells settle much slower than the aggregated cells. We show that our method of measuring the electrical conductivity credibly reflected the ESR. The method was very sensitive to the initial stage of aggregation and sedimentation, while the sedimentation curve for the Westergren ESR test has a very mild slope in the initial time. We tested our method for rapid estimation of the Westergren ESR. We show a correlation between our method of measuring changes in blood conductivity and standard Westergren ESR method. In the future, our method could be examined as a potential means of accelerating ESR tests in clinical practice. PMID:26047511

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.

ROS evaluation for a series of CNTs and their derivatives using an ESR method with DMPO.

PubMed

Tsuruoka, S; Takeuchi, K; Koyama, K; Noguchi, T; Endo, M; Tristan, F; Terrones, M; Matsumoto, H; Saito, N; Usui, Y; Porter, D W; Castranova, V

Carbon nanotubes (CNTs) are important materials in advanced industries. It is a concern that pulmonary exposure to CNTs may induce carcinogenic responses. It has been recently reported that CNTs scavenge ROS though non-carbon fibers generate ROS. A comprehensive evaluation of ROS scavenging using various kinds of CNTs has not been demonstrated well. The present work specifically investigates ROS scavenging capabilities with a series of CNTs and their derivatives that were physically treated, and with the number of commercially available CNTs. CNT concentrations were controlled at 0.2 through 0.6 wt%. The ROS scavenging rate was measured by ESR with DMPO. Interestingly, the ROS scavenging rate was not only influenced by physical treatments, but was also dependent on individual manufacturing methods. Ratio of CNTs to DMPO/ hydrogen peroxide is a key parameter to obtain appropriate ROS quenching results for comparison of CNTs. The present results suggest that dangling bonds are not a sole factor for scavenging, and electron transfer on the CNT surface is not clearly determined to be the sole mechanism to explain ROS scavenging.

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.

Incorporating geographical factors with artificial neural networks to predict reference values of erythrocyte sedimentation rate.

PubMed

Yang, Qingsheng; Mwenda, Kevin M; Ge, Miao

2013-03-12

The measurement of the Erythrocyte Sedimentation Rate (ESR) value is a standard procedure performed during a typical blood test. In order to formulate a unified standard of establishing reference ESR values, this paper presents a novel prediction model in which local normal ESR values and corresponding geographical factors are used to predict reference ESR values using multi-layer feed-forward artificial neural networks (ANN). Local normal ESR values were obtained from hospital data, while geographical factors that include altitude, sunshine hours, relative humidity, temperature and precipitation were obtained from the National Geographical Data Information Centre in China.The results show that predicted values are statistically in agreement with measured values. Model results exhibit significant agreement between training data and test data. Consequently, the model is used to predict the unseen local reference ESR values. Reference ESR values can be established with geographical factors by using artificial intelligence techniques. ANN is an effective method for simulating and predicting reference ESR values because of its ability to model nonlinear and complex relationships.

Development of an Efficient Binaural Simulation for the Analysis of Structural Acoustic Data

NASA Technical Reports Server (NTRS)

Lalime, Aimee L.; Johnson, Marty E.; Rizzi, Stephen A. (Technical Monitor)

2002-01-01

Binaural or "virtual acoustic" representation has been proposed as a method of analyzing acoustic and vibroacoustic data. Unfortunately, this binaural representation can require extensive computer power to apply the Head Related Transfer Functions (HRTFs) to a large number of sources, as with a vibrating structure. This work focuses on reducing the number of real-time computations required in this binaural analysis through the use of Singular Value Decomposition (SVD) and Equivalent Source Reduction (ESR). The SVD method reduces the complexity of the HRTF computations by breaking the HRTFs into dominant singular values (and vectors). The ESR method reduces the number of sources to be analyzed in real-time computation by replacing sources on the scale of a structural wavelength with sources on the scale of an acoustic wavelength. It is shown that the effectiveness of the SVD and ESR methods improves as the complexity of the source increases. In addition, preliminary auralization tests have shown that the results from both the SVD and ESR methods are indistinguishable from the results found with the exhaustive method.

Magnetic defects in chemically converted graphene nanoribbons: electron spin resonance investigation

NASA Astrophysics Data System (ADS)

Singamaneni, Srinivasa Rao; Stesmans, Andre; van Tol, Johan; Kosynkin, D. V.; Tour, James M.

2014-04-01

Electronic spin transport properties of graphene nanoribbons (GNRs) are influenced by the presence of adatoms, adsorbates and edge functionalization. To improve the understanding of the factors that influence the spin properties of GNRs, local (element) spin-sensitive techniques such as electron spin resonance (ESR) spectroscopy are important for spintronics applications. Here, we present results of multi-frequency continuous wave (CW), pulse and hyperfine sublevel correlation (HYSCORE) ESR spectroscopy measurements performed on oxidatively unzipped graphene nanoribbons (GNRs), which were subsequently chemically converted (CCGNRs) with hydrazine. ESR spectra at 336 GHz reveal an isotropic ESR signal from the CCGNRs, of which the temperature dependence of its line width indicates the presence of localized unpaired electronic states. Upon functionalization of CCGNRs with 4-nitrobenzene diazonium tetrafluoroborate, the ESR signal is found to be 2 times narrower than that of pristine ribbons. NH3 adsorption/desorption on CCGNRs is shown to narrow the signal, while retaining the signal intensity and g value. The electron spin-spin relaxation process at 10 K is found to be characterized by slow (163 ns) and fast (39 ns) components. HYSCORE ESR data demonstrate the explicit presence of protons and 13C atoms. With the provided identification of intrinsic point magnetic defects such as proton and 13C has been reported, which are roadblocks to spin travel in graphene-based materials, this work could help in advancing the present fundamental understanding on the edge-spin (or magnetic)-based transport properties of CCGNRs.

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

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 source of error lies in the difficulty in modelling the external γ dose. Only U leaching, not incorrectly modelled U uptake, would cause the underestimation. Diagenetic alteration may also cause anomalous fading, thermal instability, variation in k, or ESR signal suppression. More study into the effects of diagenesis alteration on enamel ESR signals is needed, as is a reevaluation of the mean signal life and α efficiency for several more enamel samples.

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

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

Development of a Hot Working Steel Based on a Controlled Gas-Metal-Reaction

NASA Astrophysics Data System (ADS)

Ritzenhoff, Roman; Gharbi, Mohammad Malekipour

As a result of cost sensitiveness, the demand on hot working steels with advanced characteristics and properties are ascending. We have used a controlled gas-metal-reaction in a P-ESR furnace to produce high quality hot working steel. These types of materials are also known as High Nitrogen Steels (HNS). An overview of the development in a pressurized induction furnace to the final industrial scale using P-ESR will be provided. Different heat treatment strategies are conducted and their effect on mechanical properties is investigated.

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.

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.

Estrogen receptor 1 modulates circadian rhythms in adult female mice.

PubMed

Blattner, Margaret S; Mahoney, Megan M

2014-06-01

Estradiol influences the level and distribution of daily activity, the duration of the free-running period, and the behavioral phase response to light pulses. However, the mechanisms by which estradiol regulates daily and circadian rhythms are not fully understood. We tested the hypothesis that estrogens modulate daily activity patterns via both classical and "non-classical" actions at the estrogen receptor subtype 1 (ESR1). We used female transgenic mice with mutations in their estrogen response pathways; ESR1 knock-out (ERKO) mice and "non-classical" estrogen receptor knock-in (NERKI) mice. NERKI mice have an ESR1 receptor with a mutation in the estrogen-response-element binding domain, allowing only actions via "non-classical" genomic and second messenger pathways. Ovariectomized female NERKI, ERKO, and wildtype (WT) mice were given a subcutaneous capsule with low- or high-dose estradiol and compared with counterparts with no hormone replacement. We measured wheel-running activity in a light:dark cycle and constant darkness, and the behavioral phase response to light pulses given at different points during the subjective day and night. Estradiol increased average daily wheel-running, consolidated activity to the dark phase, and shortened the endogenous period in WT, but not NERKI and ERKO mice. The timing of activity onset during entrainment was advanced in all estradiol-treated animals regardless of genotype suggesting an ESR1-independent mechanism. We propose that estradiol modifies period, activity level, and distribution of activity via classical actions of ESR1 whereas an ESR1 independent mechanism regulates the phase of rhythms.

Assessment of Diesse Ves-matic automated system for measuring erythrocyte sedimentation rate.

PubMed Central

Caswell, M; Stuart, J

1991-01-01

Measurement of the erythrocyte sedimentation rate (ESR) using a closed tube system reduces the biohazard risk to laboratory staff. The Diesse Ves-matic system offers manual or vacuum collection of blood into plastic tubes, automated mixing of the sample, and automated reading of the end point after 20 minutes of sedimentation. This system was compared with the 1977 Westergren ESR method of the International Council for Standardization in Haematology (ICSH) and with the 1988 ICSH undiluted ESR method. Manually collected Ves-matic samples showed good agreement with ICSH values, although there was a tendency to false low results at low ESR values which may represent dilution of plasma protein with excess citrate. Vacuum collected Ves-matic samples also showed good agreement with ICSH values, although there was a tendency to false high results which may reflect a change in the blood: citrate ratio caused by loss of anticoagulant diluent or vacuum from plastic tubes during storage. The Diesse Ves-matic system incorporates several improvements over previous technology and offers a safer, quicker, and more standardised ESR. PMID:1752986

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

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.

On the temporal development of erythrocyte sedimentation rate using sealed vacuum tubes.

PubMed

Kallner, A

1991-07-01

The temporal development of the erythrocyte sedimentation rate (ESR) was studied in wide, short vacuum tubes. It was found that in about 3% of the specimens arriving in the laboratory the ESR developed in three different phases during 60 min, whereas the other showed only two. The specimens with three phases behaved similarly in the Westergren method. It was shown that the Westergren ESR can be estimated with an acceptable accuracy already from measurements obtained after 30 min. Reproducibility and precision were improved by using a special instrument. Several advantages by this procedure were recognized, e.g., quicker results, identification of several otherwise missed rapid ESR. Accurate timing of the readings further improves accuracy and precision, and permits estimation of ESR (Westergren) up to 100 mm. In view of the obvious phases in the development of the ESR, it is proposed that this abbreviation is interpreted as erythrocyte sedimentation reaction and that the kind of quantity that is length is expressed in mm.

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.

Age-specific effects of estrogen receptors' polymorphisms on the bone traits in healthy fertile women: the BONTURNO study

PubMed Central

Massart, Francesco; Marini, Francesca; Bianchi, Gerolamo; Minisola, Salvatore; Luisetto, Giovanni; Pirazzoli, Antonella; Salvi, Sara; Micheli, Dino; Masi, Laura; Brandi, Maria Luisa

2009-01-01

Background Skeletal characteristics such as height (Ht), bone mineral density (BMD) or bone turnover markers are strongly inherited. Common variants in the genes encoding for estrogen receptor alpha (ESR1) and beta (ESR2) are proposed as candidates for influencing bone phenotypes at the population level. Methods We studied 641 healthy premenopausal women aged 20–50 years (yrs) participating into the BONTURNO study. Exclusion criteria were irregular cyclic menses, low trauma fracture, metabolic bone or chronic diseases. Serum C-telopeptide of type I collagen (CTX), osteocalcin (OC), and N-terminal propeptide of type I procollagen (P1NP) were measured in all enrolled subjects, who underwent to lumbar spine (LS), total hip (TH) and femoral neck (FN) BMD evaluation by DXA. Five hundred seventy Caucasian women were genotyped for ESR1 rs2234693 and rs9340799 and ESR2 rs4986938 polymorphisms. Results Although no genotype differences were found in body parameters, subjects with combined ESR1 CCGG plus ESR2 AA-AG genotype were taller than those with opposite genotype (P = 0.044). Moreover, ESR1 rs2234693 genotypes correlated with family history of osteoporosis (FHO) and hip fracture (FHF) (P < 0.01), while ESR2 AA-AC genotypes were strongly associated with FHF (OR 2.387, 95% CI 1.432–3.977; P < 0.001). When clustered by age, 20–30 yrs old subjects, having at least one ESR1 rs2234693 C allele presented lower LS- (P = 0.008) and TH-BMD (P = 0.047) than TT genotypes. In 41–50 yrs age, lower FN-BMD was associated with ESR2 AA (P = 0.0180) subjects than in those with the opposite genotype. ESR1 rs2234693 and rs9340799 and ESR2 rs4986938 polymorphisms did not correlate with age-adjusted values of OC, CTX and P1NP. Conclusion These findings support the presence of age-specific effects of ESR1 and ESR2 polymorphisms on various skeletal traits in healthy fertile women. PMID:19386104

Electron spin resonance spectral study of PVC and XLPE insulation materials and their life time analysis.

PubMed

Morsy, M A; Shwehdi, M H

2006-03-01

Electron spin resonance (ESR) study is carried out to characterize thermal endurance of insulating materials used in power cable industry. The presented work provides ESR investigation and evaluation of widely used cable insulation materials, namely polyvinyl chloride (PVC) and cross-linked polyethylene (XLPE). The results confirm the fact that PVC is rapidly degrades than XLPE. The study also indicates that colorants and cable's manufacturing processes enhance the thermal resistance of the PVC. It also verifies the powerfulness and the importance of the ESR-testing of insulation materials compared to other tests assumed by International Electrotechnical Commission (IEC) Standard 216-procedure, e.g. weight loss (WL), electric strength (ES) or tensile strength (TS). The estimated thermal endurance parameters by ESR-method show that the other standard methods overestimate these parameters and produce less accurate thermal life time curves of cable insulation materials.

[Status of the development of electron spin resonance measurement for the detection of irradiated food].

PubMed

Helle, N; Linke, B; Mager, M; Schreiber, G; Bögl, K W

1992-09-01

Electron spin resonance spectroscopy can be used for the detection of irradiation of various groups of foodstuffs. The results of ESR-measurements on irradiated meat and fish and fresh fruit, as well as dried fruit, spices and nuts as performed by the food irradiation laboratory of the German Federal Health Office are summarized in this report. For the detection of irradiated meat and fish, we examined the bones. Using the results from 10 different animal bones, we were able to develop an official method according to the German law section 35 LMBG. A similar routine method for fish will be established in 1992 (at the moment, an intercomparison with German food control laboratories is in progress). Irradiated dried fruit can be identified easily, because unirradiated samples give no ESR-spectra, while irradiated fruit show a partially resolved spectrum, which is caused by radiation induced sugar radicals. Interestingly, the structure of the resulting spectra is not identical for all irradiated species of fruit. We found three different types of ESR-spectra for irradiated dried fruit. Irradiated nutshells show an ESR-spectrum which reveals two additional lines (from cellulose-radicals) beside the main signal, while unirradiated samples show only the main signal. An official method for identifying irradiated nuts will be proposed in 1992. Irradiation specific ESR-signals of the cellulose radical were not only found for nutshells but also for fresh fruit and some spices, while most of the irradiated spices and herbs could not be identified by ESR-measurements.

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.

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.

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.

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.

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.

N-VSi-related center in non-irradiated 6H SiC nanostructure

NASA Astrophysics Data System (ADS)

Bagraev, Nikolay; Danilovskii, Eduard; Gets, Dmitrii; Kalabukhova, Ekaterina; Klyachkin, Leonid; Malyarenko, Anna; Savchenko, Dariya; Shanina, Bella

2014-02-01

We present the first findings of the vacancy-related centers identified by the electron spin resonance (ESR) and electrically-detected (ED) ESR method in the non-irradiated 6H-SiC nanostructure. This planar 6H-SiC nanostructure represents the ultra-narrow p-type quantum well confined by the δ-barriers heavily doped with boron on the surface of the n-type 6H-SiC (0001) wafer. The EDESR method by measuring the only magnetoresistance of the 6H SiC nanostructure under the high frequency generation from the δ-barriers appears to allow the identification of the silicon vacancy centers as well as the triplet center with spin state S=1. The same triplet center that is characterized by the larger value of the zero-field splitting constant D and anisotropic g-factor is revealed by the ESR (X-band) method. The hyperfine (hf) lines in the ESR and EDESR spectra originating from the hf interaction with the 14N nucleus allow us to attribute this triplet center to the N-VSi defect.

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.

Microwave absorption studies on high-T sub c superconductors and related materials 7--ESR of DPPH coated on a thin BiSrCaCuO film fabricated on MgO(100) substrate

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

Sugawara, K.; Sugimoto, T.; Shiohara, Y.

1992-05-10

In this paper, ESR of DPPH coated on a Bi-Sr-Ca-Cu-O (BSCCO) film (350 {Angstrom} thick) fabricated on MgO(100) substrate by MOCVD is studied. Temperature dependence of the ESR peak-to-peak linewidth, {Delta}H{sub pp}, and the effect of applied magnetic field on {Delta}H{sub pp} are below about 100 K. The results are compared with those of ESR of DPPH coated on ceramic Y-Ba-Cu-O samples (powder and bulk) made by the MPMG method. The DPPH ESR for the BSCCO film reveals that {Delta}H{sub pp} was independent of applied magnetic field up to about 9 kG. In addition, no similarity between the temperature dependencemore » of the excess ESR linewidth of the DPPH and that of critical current density was found for the BSCCO film. These results for the BSCCO film are different from those for the MPMG YBCO samples.« less

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.

CROSS: A GDSS for the Evaluation and Prioritization of Engineering Support Requests and Advanced Technology Projects at NASA

NASA Technical Reports Server (NTRS)

Tavana, Madjid; Lee, Seunghee

1996-01-01

Objective evaluation and prioritization of engineering support requests (ESRs) is a difficult task at the Kennedy Space Center (KSC) Shuttle Project Engineering Office. The difficulty arises from the complexities inherent in the evaluation process and the lack of structured information. The purpose of this project is to implement the consensus ranking organizational support system (CROSS), a multiple criteria decision support system (DSS) developed at KSC that captures the decision maker's beliefs through a series of sequential, rational, and analytical processes. CROSS utilizes the analytic hierarchy process (AHP), subjective probabilities, entropy concept, and maximize agreement heuristic (MAH) to enhance the decision maker's intuition in evaluation ESRs. Some of the preliminary goals of the project are to: (1) revisit the structure of the ground systems working team (GWST) steering committee, (2) develop a template for ESR originators to provide more comple and consistent information to the GSWT steering committee members to eliminate the need for a facilitator, (3) develop an objective and structured process for the initial screening of ESRs, (4) extensive training of the stakeholders and the GWST steering committee to eliminate the need for a facilitator, (5) automate the process as much as possible, (6) create an environment to compile project success factor data on ESRs and move towards a disciplined system that could be used to address supportability threshold issues at the KSC, and (7) investigate the possibility of an organization-wide implementation of CROSS.

TL and ESR based identification of gamma-irradiated frozen fish using different hydrolysis techniques

NASA Astrophysics Data System (ADS)

Ahn, Jae-Jun; Akram, Kashif; Shahbaz, Hafiz Muhammad; Kwon, Joong-Ho

2014-12-01

Frozen fish fillets (walleye Pollack and Japanese Spanish mackerel) were selected as samples for irradiation (0-10 kGy) detection trials using different hydrolysis methods. Photostimulated luminescence (PSL)-based screening analysis for gamma-irradiated frozen fillets showed low sensitivity due to limited silicate mineral contents on the samples. Same limitations were found in the thermoluminescence (TL) analysis on mineral samples isolated by density separation method. However, acid (HCl) and alkali (KOH) hydrolysis methods were effective in getting enough minerals to carry out TL analysis, which was reconfirmed through the normalization step by calculating the TL ratios (TL1/TL2). For improved electron spin resonance (ESR) analysis, alkali and enzyme (alcalase) hydrolysis methods were compared in separating minute-bone fractions. The enzymatic method provided more clear radiation-specific hydroxyapatite radicals than that of the alkaline method. Different hydrolysis methods could extend the application of TL and ESR techniques in identifying the irradiation history of frozen fish fillets.

Microwave-assisted synthesis and critical analysis for YBa2Cu3O6+δ nanoparticles

NASA Astrophysics Data System (ADS)

Chhaganlal Gandhi, Ashish; Lin, Jauyn Grace

2018-05-01

A new cost effective scheme of a microwave-assisted sol–gel route followed by a short annealing time is proposed to synthesize YBCO nanoparticles (NPs) of various sizes. The advanced techniques of synchrotron radiation x-ray diffraction (SRXRD) and electron spin resonance (ESR) are used to analyze the size effects on their magnetic/superconducting properties. The major interesting finding is that the size of YBCO NPs could confine the amount of oxygen content and consequently change the superconducting transition temperature (T C ) of YBCO NPs. The ESR result demonstrates a sensitive probe to characterize surface defects in the oxygen-deficient YBCO NPs.

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.

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.

Electron spin resonance. Part two: a diagnostic method in the environmental sciences.

PubMed

Rhodes, Christopher J

2011-01-01

A review is presented of some of the ways in which electron spin resonance (ESR) spectroscopy may be useful to investigate systems of relevance to the environmental sciences. Specifically considered are: quantititave ESR, photocatalysis for pollution control; sorption and mobility of molecules in zeolites; free radicals produced by mechanical action and by shock waves from explosives; measurement of peroxyl radicals and nitrate radicals in air; determination of particulate matter polyaromatic hydrocarbons (PAH), soot and black carbon in air; estimation of nitrate and nitrite in vegetables and fruit; lipid-peroxidation by solid particles (silica, asbestos, coal dust); ESR of soils and other biogenic substances: formation of soil organic matter carbon capture and sequestration (CCS) and no-till farming; detection of reactive oxygen species in the photosynthetic apparatus of higher plants under light stress; molecular mobility and intracellular glasses in seeds and pollen; molecular mobility in dry cotton; characterisation of the surface of carbon black used for chromatography; ESR dating for archaeology and determining seawater levels; measurement of the quality of tea-leaves by ESR; green-catalysts and catalytic media; studies of petroleum (crude oil); fuels; methane hydrate; fuel cells; photovoltaics; source rocks; kerogen; carbonaceous chondrites to find an ESR-based marker for extraterrestrial origin; samples from the Moon taken on the Apollo 11 and Apollo 12 missions to understand space-weathering; ESR studies of organic matter in regard to oil and gas formation in the North Sea; solvation by ionic liquids as green solvents, ESR in food and nutraceutical research.

sedimentation rate in patients with diabetes

PubMed

Kaya, Tezcan; Akçay, Emine Ülkü; Ertürk, Zeynep; Ergenç, Hasan; Tamer, Ali

2018-04-30

Background/aim: Vitamin D deficiency in diabetic patients has been shown to be associated with some inflammatory markers. However, its relationship with erythrocyte sedimentation rate (ESR) is still unknown. The aim of this study was to investigate the relationship between vitamin D deficiency and ESR in patients with type 2 diabetes mellitus (T2DM). Materials and methods: This cross-sectional study was conducted with 294 consecutive patients with T2DM. Serum levels of 25-hydroxyvitamin D, glycemic parameters, lipids, ESR, and C-reactive protein were measured. Patients were evaluated according to 25-hydroxyvitamin D levels as having vitamin D deficiency, vitamin D insufficiency, and vitamin D sufficiency. Results: ESR was found to be higher in patients with vitamin D deficiency than in patients who were vitamin D-sufficient (P < 0.001), and ESR was negatively correlated with 25-hydroxyvitamin D level (r = –0.265, P < 0.001). HbA1c and postprandial glucose levels were higher in patients with vitamin D deficiency than vitamin D-sufficient patients (P = 0.005 and P = 0.019, respectively). In receiver operating curve analysis, an ESR value of 14.5 mm/h had 70.1% sensitivity and 50.3% specificity for the prediction of vitamin D deficiency. Conclusion: The present study revealed that ESR is higher in T2DM patients with vitamin D deficiency than patients with sufficient vitamin D. There was an inverse association between ESR and vitamin D levels. Furthermore, vitamin D deficiency was related to poor glycemic control.

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.

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

ESR dating of barite in sea-floor hydrothermal sulfide deposits at Okinawa Trough

NASA Astrophysics Data System (ADS)

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

2013-12-01

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 and biological systems sustained by the chemical species arising from hydrothermal activities (Macdonald et al., 1980). With this aspect, Okumura et al. (2010) made the first practical application of ESR (electron spin resonance) dating technique to a sample of submarine hydrothermal barite to obtain preliminary ages, while Kasuya et al. (1991) first pointed out that barite can be used for ESR dating. ESR is a method to observe radicals having unpaired electrons. As natural radiation creates unpaired electrons in minerals, the age is deduced by dividing the natural radiation dose (obtained from the amount of unpaired electrons) by the dose rate which is estimated by the amount of environmental radioactive elements. The samples were taken by the research cruises, NT12-10 and NT11-20 and NT12-06 operated by JAMSTEC from Hatoma, Yoron, Izena, North Iheya, and Yonaguni IV Knolls of Okinawa Trough. The blocks of sulfide deposits were cut into pieces, and about 2.0g was crushed. The samples were soaked in 12M hydrochloric acid, left for approximately 24 hours. Then, 13M nitric acid was added. Finally, after rinsing in distilled water, the sample was filtered and dried. Impurities were removed by handpicking. A X-ray diffraction study was made to confirm that the grains are pure barite. After γ-ray irradiation at Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency, they were measured at room temperature with an ESR spectrometer (JES-PX2300) with a microwave power of 1mW, and the magnetic field modulation amplitude of 0.1mT. The equivalent natural radiation doses were obtained from the increase of ESR signal intensity of SO3- by irradiation. The bulk Ra concentration was measured by the low background pure Ge gamma ray spectrometer. Assuming that Ra is populated only in barite, the dose rate was calculated with the alpha effectiveness of 0.043 (Toyoda et al., 2012), where the decay of Ra (a half life of 1600 years) was also taken into account. The dating results indicate that the ages are, Yron Knoll < Hatoma Knoll ≒ North Iheya Knoll < Izena Knoll. This order of ages is consistent with the development of the hydrothermal vent ecosystem estimated by observed landscape.. The results of U-Th dating for these samples will also be presented.

Prioritization of engineering support requests and advanced technology projects using decision support and industrial engineering models

NASA Technical Reports Server (NTRS)

Tavana, Madjid

1995-01-01

The evaluation and prioritization of Engineering Support Requests (ESR's) is a particularly difficult task at the Kennedy Space Center (KSC) -- Shuttle Project Engineering Office. This difficulty is due to the complexities inherent in the evaluation process and the lack of structured information. The evaluation process must consider a multitude of relevant pieces of information concerning Safety, Supportability, O&M Cost Savings, Process Enhancement, Reliability, and Implementation. Various analytical and normative models developed over the past have helped decision makers at KSC utilize large volumes of information in the evaluation of ESR's. The purpose of this project is to build on the existing methodologies and develop a multiple criteria decision support system that captures the decision maker's beliefs through a series of sequential, rational, and analytical processes. The model utilizes the Analytic Hierarchy Process (AHP), subjective probabilities, the entropy concept, and Maximize Agreement Heuristic (MAH) to enhance the decision maker's intuition in evaluating a set of ESR's.

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.

Electron Spin Resonance (ESR) for the study of Reactive Oxygen Species (ROS) on the isolated frog skin (Pelophylax bergeri): A non-invasive method for environmental monitoring.

PubMed

D'Errico, Gerardino; Vitiello, Giuseppe; De Tommaso, Gaetano; Abdel-Gawad, Fagr Kh; Brundo, Maria Violetta; Ferrante, Margherita; De Maio, Anna; Trocchia, Samantha; Bianchi, Anna Rita; Ciarcia, Gaetano; Guerriero, Giulia

2018-04-11

Reactive oxygen species (ROS) in biological tissues of elected biosentinels represent an optimal biomarker for eco-monitoring of polluted areas. Electron spin resonance (ESR) is the most definitive method for detecting, quantifying and possibly identifying radicals in complex systems. A non-invasive method for monitoring polluted areas by the quantitative determination of ROS in frog skin biopsy is presented. We assessed by ESR spectroscopy the ROS level in adult male of Pelophylax bergeri, specie not a risk of extinction, collected from the polluted Sarno River (SA, Italy) basin. The spin-trap ESR method was validated by immunohistochemical analysis of the well-assessed pollution biomarkers cytochrome P450 aromatase 1A (CYP1A) and glutathione S-transferase (GST), and by determining the poly(ADPribose) polymerase (PARP) and GST enzymatic activity. ROS concentration in skin samples from frogs collected in the polluted area is significantly higher than that determined for the unpolluted reference area. Immunohistochemical analysis of CYP1A and GST supported the reliability of our approach, even in the absence of evident morphological and ultrastructural differences. PARP activity assay, connected to possible oxidative DNA damage, and the detoxification index by GST enzymatic assay give statistically significant evidence that higher levels of ROS are associated to alterations of the different biomarkers. ROS concentration, measured by ESR on isolated frog skin, through the presented non-lethal method, is a reliable biomarker for toxicity screening and represents a useful basic datum for future modelling studies on environmental monitoring and biodiversity loss prevention. Copyright © 2018 Elsevier Inc. All rights reserved.

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 higher than usual sea water. (5) The decay of 226Ra has to be considered. (6) Major terms of dose rate are the internal alpha dose rate and the external beta and gamma dose rates. (7) The alpha effectiveness, the ratio of forming the radical by internal alpha particles to by beta and gamma rays, was obtained to be 0.043±0.018. (8) The shape of the chimney sample should be considered for gamma ray dose. Examples of dating results for submarine hydrothermal deposits from South Mariana and Okinawa Trough will be presented.

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.

l-Tryptophan Radical Cation Electron Spin Resonance Studies: Connecting Solution-derived Hyperfine Coupling Constants with Protein Spectral Interpretations

PubMed Central

Connor, Henry D.; Sturgeon, Bradley E.; Mottley, Carolyn; Sipe, Herbert J.; Mason, Ronald P.

2009-01-01

Fast-flow electron spin resonance (ESR) spectroscopy has been used to detect a free radical formed from the reaction of l-tryptophan with Ce4+ in an acidic aqueous environment. Computer simulations of the ESR spectra from l-tryptophan and several isotopically modified forms strongly support the conclusion that the l-tryptophan radical cation has been detected by ESR for the first time. The hyperfine coupling constants (HFCs) determined from the well-resolved isotropic ESR spectra support experimental and computational efforts to understand l-tryptophan's role in protein catalysis of oxidation-reduction processes. l-tryptophan HFCs facilitated the simulation of fast-flow ESR spectra of free radicals from two related compounds, tryptamine and 3-methylindole. Analysis of these three compounds' β-methylene hydrogen HFC data along with equivalent l-tyrosine data has led to a new computational method that can distinguish between these two amino acid free radicals in proteins without dependence on isotope labeling, electron nuclear double resonance or high-field ESR. This approach also produces geometric parameters (dihedral angles for the β-methylene hydrogens) which should facilitate protein site assignment of observed l-tryptophan radicals as has been done for l-tyrosine radicals. PMID:18433127

A portable microfluidic system for rapid measurement of the erythrocyte sedimentation rate.

PubMed

Isiksacan, Ziya; Erel, Ozcan; Elbuken, Caglar

2016-11-29

The erythrocyte sedimentation rate (ESR) is a frequently used 30 min or 60 min clinical test for screening of several inflammatory conditions, infections, trauma, and malignant diseases, as well as non-inflammatory conditions including prostate cancer and stroke. Erythrocyte aggregation (EA) is a physiological process where erythrocytes form face-to-face linear structures, called rouleaux, at stasis or low shear rates. In this work, we proposed a method for ESR measurement from EA. We developed a microfluidic opto-electro-mechanical system, using which we experimentally showed a significant correlation (R 2 = 0.86) between ESR and EA. The microfluidic system was shown to measure ESR from EA using fingerprick blood in 2 min. 40 μl of whole blood is filled in a disposable polycarbonate cartridge which is illuminated with a near infrared emitting diode. Erythrocytes were disaggregated under the effect of a mechanical shear force using a solenoid pinch valve. Following complete disaggregation, transmitted light through the cartridge was measured using a photodetector for 1.5 min. The intensity level is at its lowest at complete disaggregation and highest at complete aggregation. We calculated ESR from the transmitted signal profile. We also developed another microfluidic cartridge specifically for monitoring the EA process in real-time during ESR measurement. The presented system is suitable for ultrafast, low-cost, and low-sample volume measurement of ESR at the point-of-care.

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, suggesting a mutation-specific effect. Taken together, ESR1 mutations in genome-edited breast cancer cell lines confer ligand-independent growth and endocrine resistance. These biologically relevant models can be used for further mechanistic and translational studies, including context-specific and mutation site-specific analysis of the ESR1 mutations.

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.

Mating changes the subcellular distribution and the functionality of estrogen receptors in the rat oviduct

PubMed Central

2009-01-01

Background Mating changes the mode of action of 17beta-estradiol (E2) to accelerate oviductal egg transport from a nongenomic to a genomic mode, although in both pathways estrogen receptors (ER) are required. This change was designated as intracellular path shifting (IPS). Methods Herein, we examined the subcellular distribution of ESR1 and ESR2 (formerly known as ER-alpha and ER-beta) in oviductal epithelial cells of rats on day 1 of cycle (C1) or pregnancy (P1) using immunoelectron microscopy for ESR1 and ESR2. The effect of mating on intraoviductal ESR1 or ESR2 signaling was then explored comparing the expression of E2-target genes c-fos, brain creatine kinase (Ckb) and calbindin 9 kDa (s100g) in rats on C1 or P1 treated with selective agonists for ESR1 (PPT) or ESR2 (DPN). The effect of ER agonists on egg transport was also evaluated on C1 or P1 rats. Results Receptor immunoreactivity was associated with the nucleus, cytoplasm and plasma membrane of the epithelial cells. Mating affected the subcellular distribution of both receptors as well as the response to E2. In C1 and P1 rats, PPT increased Ckb while both agonists increased c-fos. DPN increased Ckb and s100g only in C1 and P1 rats, respectively. PPT accelerated egg transport in both groups and DPN accelerated egg transport only in C1 rats. Conclusion Estrogen receptors present a subcellular distribution compatible with E2 genomic and nongenomic signaling in the oviductal epithelial cells of C1 and P1 although IPS occurs independently of changes in the distribution of ESR1 and ESR2 in the oviductal epithelial cells. Mating affected intraoviductal ER-signaling and induced loss of functional involvement of ESR2 on E2-induced accelerated egg transport. These findings reveal a profound influence on the ER signaling pathways exerted by mating in the oviduct. PMID:19948032

Induction-detection electron spin resonance with spin sensitivity of a few tens of spins

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

Artzi, Yaron; Twig, Ygal; Blank, Aharon

2015-02-23

Electron spin resonance (ESR) is a spectroscopic method that addresses electrons in paramagnetic materials directly through their spin properties. ESR has many applications, ranging from semiconductor characterization to structural biology and even quantum computing. Although it is very powerful and informative, ESR traditionally suffers from low sensitivity, requiring many millions of spins to get a measureable signal with commercial systems using the Faraday induction-detection principle. In view of this disadvantage, significant efforts were made recently to develop alternative detection schemes based, for example, on force, optical, or electrical detection of spins, all of which can reach single electron spin sensitivity.more » This sensitivity, however, comes at the price of limited applicability and usefulness with regard to real scientific and technological issues facing modern ESR which are currently dealt with conventional induction-detection ESR on a daily basis. Here, we present the most sensitive experimental induction-detection ESR setup and results ever recorded that can detect the signal from just a few tens of spins. They were achieved thanks to the development of an ultra-miniature micrometer-sized microwave resonator that was operated at ∼34 GHz at cryogenic temperatures in conjunction with a unique cryogenically cooled low noise amplifier. The test sample used was isotopically enriched phosphorus-doped silicon, which is of significant relevance to spin-based quantum computing. The sensitivity was experimentally verified with the aid of a unique high-resolution ESR imaging approach. These results represent a paradigm shift with respect to the capabilities and possible applications of induction-detection-based ESR spectroscopy and imaging.« less

Bone Metastasis in Advanced Breast Cancer: Analysis of Gene Expression Microarray.

PubMed

Cosphiadi, Irawan; Atmakusumah, Tubagus D; Siregar, Nurjati C; Muthalib, Abdul; Harahap, Alida; Mansyur, Muchtarruddin

2018-03-08

Approximately 30% to 40% of breast cancer recurrences involve bone metastasis (BM). Certain genes have been linked to BM; however, none have been able to predict bone involvement. In this study, we analyzed gene expression profiles in advanced breast cancer patients to elucidate genes that can be used to predict BM. A total of 92 advanced breast cancer patients, including 46 patients with BM and 46 patients without BM, were identified for this study. Immunohistochemistry and gene expression analysis was performed on 81 formalin-fixed paraffin-embedded samples. Data were collected through medical records, and gene expression of 200 selected genes compiled from 6 previous studies was performed using NanoString nCounter. Genetic expression profiles showed that 22 genes were significantly differentially expressed between breast cancer patients with metastasis in bone and other organs (BM+) and non-BM, whereas subjects with only BM showed 17 significantly differentially expressed genes. The following genes were associated with an increasing incidence of BM in the BM+ group: estrogen receptor 1 (ESR1), GATA binding protein 3 (GATA3), and melanophilin with an area under the curve (AUC) of 0.804. In the BM group, the following genes were associated with an increasing incidence of BM: ESR1, progesterone receptor, B-cell lymphoma 2, Rab escort protein, N-acetyltransferase 1, GATA3, annexin A9, and chromosome 9 open reading frame 116. ESR1 and GATA3 showed an increased strength of association with an AUC of 0.928. A combination of the identified 3 genes in BM+ and 8 genes in BM showed better prediction than did each individual gene, and this combination can be used as a training set. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Microfluidic-Based Measurement Method of Red Blood Cell Aggregation under Hematocrit Variations

PubMed Central

2017-01-01

Red blood cell (RBC) aggregation and erythrocyte sedimentation rate (ESR) are considered to be promising biomarkers for effectively monitoring blood rheology at extremely low shear rates. In this study, a microfluidic-based measurement technique is suggested to evaluate RBC aggregation under hematocrit variations due to the continuous ESR. After the pipette tip is tightly fitted into an inlet port, a disposable suction pump is connected to the outlet port through a polyethylene tube. After dropping blood (approximately 0.2 mL) into the pipette tip, the blood flow can be started and stopped by periodically operating a pinch valve. To evaluate variations in RBC aggregation due to the continuous ESR, an EAI (Erythrocyte-sedimentation-rate Aggregation Index) is newly suggested, which uses temporal variations of image intensity. To demonstrate the proposed method, the dynamic characterization of the disposable suction pump is first quantitatively measured by varying the hematocrit levels and cavity volume of the suction pump. Next, variations in RBC aggregation and ESR are quantified by varying the hematocrit levels. The conventional aggregation index (AI) is maintained constant, unrelated to the hematocrit values. However, the EAI significantly decreased with respect to the hematocrit values. Thus, the EAI is more effective than the AI for monitoring variations in RBC aggregation due to the ESR. Lastly, the proposed method is employed to detect aggregated blood and thermally-induced blood. The EAI gradually increased as the concentration of a dextran solution increased. In addition, the EAI significantly decreased for thermally-induced blood. From this experimental demonstration, the proposed method is able to effectively measure variations in RBC aggregation due to continuous hematocrit variations, especially by quantifying the EAI. PMID:28878199

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.

Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.

PubMed

O'Leary, Ben; Hrebien, Sarah; Morden, James P; Beaney, Matthew; Fribbens, Charlotte; Huang, Xin; Liu, Yuan; Bartlett, Cynthia Huang; Koehler, Maria; Cristofanilli, Massimo; Garcia-Murillas, Isaac; Bliss, Judith M; Turner, Nicholas C

2018-03-01

CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.

A Study of Ziegler–Natta Propylene Polymerization Catalysts by Spectroscopic Methods

PubMed Central

Tkachenko, Olga P.; Kucherov, Alexey V.; Kustov, Leonid M.; Virkkunen, Ville; Leinonen, Timo; Denifl, Peter

2017-01-01

Ziegler–Natta polymerization catalysts were characterized by a complex of surface- and bulk-sensitive methods (DRIFTS, XPS, ESR, and XAS = XANES + EXAFS). A diffuse-reflectance Fourier-transform IR spectroscopy (DRIFTS) study showed the presence of strong Lewis acid sites in different concentrations and absence of strong basic sites in the polymerization catalysts. X-ray photoelectron spectroscopy (XPS), electron-spin resonance (ESR), and (X-ray absorption near-edge structure (XANES) analysis revealed the presence of Ti4+, Ti3+, Ti2+, and Ti1+ species in the surface layers and in the bulk of catalysts. The samples under study differ drastically in terms of the number of ESR-visible paramagnetic sites. The EXAFS study shows the presence of a Cl atom as a nearest neighbor of the absorbing Ti atom. PMID:28772850

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.

Dating of barite and anhydrite in sea-floor hydrothermal deposits in the Okinawa Trough

NASA Astrophysics Data System (ADS)

Taisei, F.; Toyoda, S.; Uchida, A.; Ishibashi, J. I.; Totsuka, S.; Shimada, K.; Nakai, S.

2016-12-01

Dating of submarine hydrothermal activities has been an important issue in the aspect of the ore formation (Urabe, 1995) and biological systems sustained by the chemical species arising from hydrothermal activities (Macdonald et al., 1980). For this purpose, dating methods using radioactive disequilibrium such as U-Th method (e.g. You and Bickle, 1998) for sulfide, 226Ra-210Pb and 228Ra-228Th (e.g. Noguchi et al., 2011), Ra/Ba, and ESR (Electron Spin Resonance) methods for barite (Okumura et al., 2010) have been employed. In this study, firstly, we will report the first successful dating results on anhydrite using 226Ra-210Pb and 228Ra-228Th methods. The anhydrite samples were taken from the Daiyon-Yonaguni knoll field and the Hatoma knoll field and the Iheya North Knoll field of the Okinawa Trough by research cruises operated by JAMSTEC. The anhydrite crystals were physically scratched out of the samples. 226Ra, 228Ra and daughter nuclei were measured in the same samples for the ESR method by the low background gamma ray spectrometry. From the activity ratios, disequilibrium ages were obtained to be about 7.3 years by 226Ra-210Pb method, and to be 0.6-2.5 years by 228Ra-228Th method. Secondly, the ESR ages of barite taken from hydrothermal areas in the Okinawa trough range from 4.1 to 16000 years, filling the age gap of the maximum age, 150 years, of 226Ra-210Pb method and the minimum age, several thousand years of U-Th method, being the most appropriate age range to discuss the evolution of the hydrothermal systems. Interestingly, the 226Ra-210Pb and 228Ra-228Th ages for the same samples are the same or younger than the ESR ages. As for the latter samples, the reason has already been discussed (Uchida et al., 2015) as the deposits had been formed by two or more hydrothermal events. In the present paper, the disequilibrium and ESR ages will be simulated with these multiple hydrothermal events so that the differences in the ages are explained.

Characterization of lipid oxidation process of beef during repeated freeze-thaw by electron spin resonance technology and Raman spectroscopy.

PubMed

Chen, Qingmin; Xie, Yunfei; Xi, Jinzhong; Guo, Yahui; Qian, He; Cheng, Yuliang; Chen, Yi; Yao, Weirong

2018-03-15

In this study, electron spin resonance (ESR) and Raman spectroscopy were applied to characterize lipid oxidation of beef during repeated freeze-thaw (RFT). Besides the conventional indexes including peroxide values (PV), thiobarbituric acid-reactive substances (TBARS) and acid values (AV) were evaluated, the radical and molecular structure changes were also measured by ESR and Raman spectroscopy. The results showed that PV, TBARS and AV were increased (P<0.05) after RFT. This suggested that lipid oxidation was occurred during RFT. With the increase of radical signal intensity, lower oxidation stability was presented by ESR. Raman intensity of ν(CC) stretching region (1655cm -1 ) was decreased during RFT. Furthermore, lower Raman intensity ratio of I 1655 /I 1442 , I 1655 /I 1745 that determine total unsaturation was also observed. Significant correlations (p<0.01) were obtained among conventional methods, ESR and Raman spectroscopy. Our result has proved that ESR and Raman spectroscopy showed great potential in characterizing lipid oxidation process of beef during RFT. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Prognostic grouping of metastatic prostate cancer using conventional pretreatment prognostic factors.

PubMed

Mikkola, Arto; Aro, Jussi; Rannikko, Sakari; Ruutu, Mirja

2009-01-01

To develop three prognostic groups for disease specific mortality based on the binary classified pretreatment variables age, haemoglobin concentration (Hb), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), prostate-specific antigen (PSA), plasma testosterone and estradiol level in hormonally treated patients with metastatic prostate cancer (PCa). The present study comprised 200 Finnprostate 6 study patients, but data on all variables were not known for every patient. The patients were divided into three prognostic risk groups (Rgs) using the prognostically best set of pretreatment variables. The best set was found by backward stepwise selection and the effect of every excluded variable on the binary classification cut-off points of the remaining variables was checked and corrected when needed. The best group of variables was ALP, PSA, ESR and age. All data were known in 142 patients. Patients were given one risk point each for ALP > 180 U/l (normal value 60-275 U/l), PSA > 35 microg/l, ESR > 80 mm/h and age < 60 years. Three risk groups were formed: Rg-a (0-1 risk points), Rg-b (2 risk points) and Rg-c (3-4 risk points). The risk of death from PCa increased statistically significantly with advancing prognostic group. Patients with metastatic PCa can be divided into three statistically significantly different prognostic risk groups for PCa-specific mortality by using the binary classified pretreatment variables ALP, PSA, ESR and age.

Erythrocyte sedimentation rate and fibrinogen concentration of whole blood influences the cellular composition of platelet-rich plasma obtained from centrifugation methods.

PubMed

Yin, Wenjing; Xu, Zhengliang; Sheng, Jiagen; Xie, Xuetao; Zhang, Changqing

2017-09-01

Erythrocyte sedimentation rate (ESR), which reflects the sedimentation rate of platelets, leukocytes and erythrocytes in response to centrifugal force, may influence the cellular composition of platelet-rich plasma (PRP) obtained via centrifugation methods. However, no relevant studies have substantiated this. In the present study, blood was collected from 40 healthy volunteers and used to prepare PRP with two plasma-based preparation systems [YinPRP and Plasma Rich in Growth Factor (PRGF) systems] and two buffy coat-based systems (RegenPRP and WEGOPRP systems) in a single-donor model. Volumes of PRP and platelet-poor plasma (PPP) that were removed in the preparation process were recorded. Analyses of ESR, haematocrit, C-reaction protein, coagulation, serum glucose and serum lipid of the whole blood used for PRP preparation were performed to evaluate the levels of ESR and the factors known to influence it. Whole blood analysis was performed to evaluate the cellular composition of PRP. Results demonstrated that there were marked positive correlations between the ESR of the whole blood used for PRP preparation and PPP removal efficiencies, platelet concentrations, platelet capture efficiencies and platelet enrichment factors of PRP formulations obtained from plasma-based systems, and PRP yield efficiency of RegenPRP and PPP removal efficiency of WEGOPRP. Furthermore, there were marked negative correlations between ESR and concentrations and enrichment factors of platelets, leukocytes and erythrocytes of RegenPRP. Fibrinogen concentration of the whole blood, which had a marked positive correlation with ESR, also influenced the cellular composition of PRP. These findings may increase the understanding of PRP preparation and provide substantial evidence for the individualised optimisation of PRP preparation systems used in clinical practice.

Monitoring post-fire vegetation rehabilitation projects: A common approach for non-forested ecosystems

USGS Publications Warehouse

Wirth, Troy A.; Pyke, David A.

2007-01-01

Emergency Stabilization and Rehabilitation (ES&R) and Burned Area Emergency Response (BAER) treatments are short-term, high-intensity treatments designed to mitigate the adverse effects of wildfire on public lands. The federal government expends significant resources implementing ES&R and BAER treatments after wildfires; however, recent reviews have found that existing data from monitoring and research are insufficient to evaluate the effects of these activities. The purpose of this report is to: (1) document what monitoring methods are generally used by personnel in the field; (2) describe approaches and methods for post-fire vegetation and soil monitoring documented in agency manuals; (3) determine the common elements of monitoring programs recommended in these manuals; and (4) describe a common monitoring approach to determine the effectiveness of future ES&R and BAER treatments in non-forested regions. Both qualitative and quantitative methods to measure effectiveness of ES&R treatments are used by federal land management agencies. Quantitative methods are used in the field depending on factors such as funding, personnel, and time constraints. There are seven vegetation monitoring manuals produced by the federal government that address monitoring methods for (primarily) vegetation and soil attributes. These methods vary in their objectivity and repeatability. The most repeatable methods are point-intercept, quadrat-based density measurements, gap intercepts, and direct measurement of soil erosion. Additionally, these manuals recommend approaches for designing monitoring programs for the state of ecosystems or the effect of management actions. The elements of a defensible monitoring program applicable to ES&R and BAER projects that most of these manuals have in common are objectives, stratification, control areas, random sampling, data quality, and statistical analysis. The effectiveness of treatments can be determined more accurately if data are gathered using an approach that incorporates these six monitoring program design elements and objectives, as well as repeatable procedures to measure cover, density, gap intercept, and soil erosion within each ecoregion and plant community. Additionally, using a common monitoring program design with comparable methods, consistently documenting results, and creating and maintaining a central database for query and reporting, will ultimately allow a determination of the effectiveness of post-fire rehabilitation activities region-wide.

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.

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 S. Toyoda (1998) Global Planet. Change, 18, 129-135. S. Toyoda and M. Ikeya (1991) Geochem. J. 25, 437-445. S. Toyoda and W. Hattori (2000) Appl. Radiat. Isot., 52, 1351-1356.

Electron spin resonance (ESR/EPR) of free radicals observed in human red hair: a new, simple empirical method of determination of pheomelanin/eumelanin ratio in hair.

PubMed

Chikvaidze, Eduard N; Partskhaladze, Tamar M; Gogoladze, Temur V

2014-07-01

The definition of the concentration of pheomelanin in the skin is an issue of great interest because in the case of being influenced by UV radiation, it manifests itself as a prooxidant, causing various skin disorders including melanoma that might help to explain the relatively high incidence of skin cancer among individuals with red hair. The ESR spectra of red hair samples were investigated. It was found that at low microwave power, they are characterized by two types of spectra. Red hair ESR signals result from a superposition of two spectral shapes, a singlet spectrum as a result of the existence of eumelanin and a triplet spectrum as a result of the existence of pheomelanin. At high microwave power, only triplet spectra shape was detected, caused by saturation of the eumelanin singlet. Using different concentration ratios of black to red hair, we measured ESR spectra and plotted the ratio values in each sample against a measured 'g-factor' (experimental). We found that there is a linear relationship between these two parameters. So, it is evident that using these results, the concentration ratio of pheomelanin to eumelanin in a sample of hair can be easily determined by an almost noninvasive method. This can be considered a potential advantage for many practical activities compared with other invasive methods. The concentration dependence curve of pheomelanin (µg/mg) on gexp-factor in an ESR spectrum of hair has been designed, which allows the determination of the amount of pheomelanin in hair of any color. Copyright © 2014 John Wiley & Sons, Ltd.

Expression of Estrogen Receptor Coactivator Proline-, Glutamic Acid- and Leucine-Rich Protein 1 within Paraspinal Muscles in Adolescents with Idiopathic Scoliosis

PubMed Central

Skibinska, Izabela; Tomaszewski, Marek; Andrusiewicz, Miroslaw; Urbaniak, Paulina; Czarnecka-Klos, Roza; Shadi, Milud; Kotwicki, Tomasz; Kotwicka, Malgorzata

2016-01-01

Purpose The aim of this study was to detect and assess the estrogen receptor (ESR) coactivator PELP1 expression within human paraspinal skeletal muscles in patients suffering from idiopathic scoliosis. Methods During surgical correction of scoliosis the muscle biopsies harvested in 29 females. Presence of PELP1, ESR1 and ESR2 genes transcripts was studied using RT-qPCR technique while immunohistochemistry and western blot methods were used to detect the PEPL1 protein presence. Results PELP1 expression in deep paraspinal muscles revealed higher than in superficial back muscles (p = 0.005). Positive immunohistochemical staining for PELP1 was observed in the nuclei of the paraspinal muscle cells. Western blot revealed PELP1 protein in all samples. No significant difference in PELP1 expression between the convex and the concave scoliosis side (p>0.05) was found. In deep paraspinal back muscles, a significant correlation between the PELP1 expression level on the concave side and the Cobb angle (r = 0.4; p<0.05) was noted as well as between the PELP1 and ESR1 expression level (r = 0.7; p<0.05) while no correlation between PELP1 and ESR2 expression level was found. Conclusion To our knowledge, three techniques for the first time demonstrated the presence of the PELP1 in paraspinal muscles of patients with idiopathic scoliosis. The PELP1 potential regulatory impact on back muscle function is to be further investigated. PMID:27045366

A rapid method to estimate Westergren sedimentation rates.

PubMed

Alexy, Tamas; Pais, Eszter; Meiselman, Herbert J

2009-09-01

The erythrocyte sedimentation rate (ESR) is a nonspecific but simple and inexpensive test that was introduced into medical practice in 1897. Although it is commonly utilized in the diagnosis and follow-up of various clinical conditions, ESR has several limitations including the required 60 min settling time for the test. Herein we introduce a novel use for a commercially available computerized tube viscometer that allows the accurate prediction of human Westergren ESR rates in as little as 4 min. Owing to an initial pressure gradient, blood moves between two vertical tubes through a horizontal small-bore tube and the top of the red blood cell (RBC) column in each vertical tube is monitored continuously with an accuracy of 0.083 mm. Using data from the final minute of a blood viscosity measurement, a sedimentation index (SI) was calculated and correlated with results from the conventional Westergren ESR test. To date, samples from 119 human subjects have been studied and our results indicate a strong correlation between SI and ESR values (R(2)=0.92). In addition, we found a close association between SI and RBC aggregation indices as determined by an automated RBC aggregometer (R(2)=0.71). Determining SI on human blood is rapid, requires no special training and has minimal biohazard risk, thus allowing physicians to rapidly screen for individuals with elevated ESR and to monitor therapeutic responses.

Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXIX. Elevation of erythrocyte sedimentation rate is associated with disease activity and damage accrual.

PubMed

Vilá, Luis M; Alarcón, Graciela S; McGwin, Gerald; Bastian, Holly M; Fessler, Barri J; Reveille, John D

2005-11-01

To determine if different categories of erythrocyte sedimentation rate (ESR) elevation are associated with disease activity and/or damage in systemic lupus erythematosus (SLE). We studied 2317 study visits in 553 SLE patients (> or = 4 American College of Rheumatology criteria, < or = 5 years' disease duration at enrollment) from a multiethnic (Hispanic, African American, and Caucasian) longitudinal study of outcome. A study visit was done every 6 months for the first year and annually thereafter. Erythrocyte sedimentation rate (ESR) was measured using the Westergren method; results were expressed in 4 categories: < 25 (normal), 25-50 (mild elevation), 51-75 (moderate elevation), and > 75 (marked elevation) mm/h. Anti-dsDNA antibodies were measured at enrollment with the Crithidia luciliae assay. Disease activity was assessed with the Systemic Lupus Activity Measure (SLAM) and the Physician's Global Assessment (PGA). Because ESR is one of the measures evaluated in the SLAM, it was excluded from the total SLAM score. Disease damage was assessed with the Systemic Lupus International Collaborating Clinics damage index (SDI). The relationship between the SLAM (total and PGA) and SDI scores (at baseline and for all visits) and anti-dsDNA antibodies (at enrollment) with ESR was examined by univariable and generalized estimating equation (GEE) regression analyses. Ethnicity, age, and sex were entered in all regression models. The cohort consisted of 89.7% women with mean age 36.8 (SD 12.6) years and disease duration 4.6 (SD 3.2) years. GEE analyses showed that increasing levels of ESR and anti-dsDNA antibody positivity were independently associated with SLAM and PGA scores, at enrollment and for all visits. Overall, the associations of ESR with SLAM and PGA scores were stronger than for the presence of anti-dsDNA antibodies. At baseline, there was no relationship of ESR elevation or anti-dsDNA positivity with SDI scores. However, when all visits were studied, moderate and marked elevations of ESR were independently associated with SDI scores. Mild, moderate, and marked ESR elevations are strongly associated with disease activity in SLE. Moderate and marked ESR elevations are also associated with damage accrual. These associations are stronger than those for the presence of anti-dsDNA antibodies. Our data suggest that ESR could be used to assess disease activity and predict organ/system damage in a relatively rapid and inexpensive manner in SLE.

Construction of imaging system for wide-field-range ESR spectra using localized microwave field and its case study of crystal orientation in suspension of copper sulfate pentahydrate (CuSO4 . 5H2O).

PubMed

Tani, Atsushi; Ueno, Takehiro; Yamanaka, Chihiro; Katsura, Makoto; Ikeya, Motoji

2005-02-01

A scanning electron spin resonance (ESR) microscope using a localized microwave field was redesigned to measure ESR spectra from 0 to 400 mT using electromagnets. Divalent copper ion (Cu2+) in copper sulfate pentahydrate (CuSO4 . 5H2O) was imaged, after the powdered samples were cemented in silicone rubber under a magnetic field. The ratio of the two signal intensities at g=2.27 and 2.08 clearly indicates the orientation of the particles. This method can be used for mapping the local magnetic field and its direction.

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.

Prediagnostic Smoking Is Associated with Binary and Quantitative Measures of ER Protein and ESR1 mRNA Expression in Breast Tumors.

PubMed

Butler, Eboneé N; Bensen, Jeannette T; Chen, Mengjie; Conway, Kathleen; Richardson, David B; Sun, Xuezheng; Geradts, Joseph; Olshan, Andrew F; Troester, Melissa A

2018-01-01

Background: Smoking is a possible risk factor for breast cancer and has been linked to increased risk of estrogen receptor-positive (ER + ) disease in some epidemiologic studies. It is unknown whether smoking has quantitative effects on ER expression. Methods: We examined relationships between smoking and ER expression from tumors of 1,888 women diagnosed with invasive breast cancer from a population-based study in North Carolina. ER expression was characterized using binary (±) and continuous measures for ER protein, ESR1 mRNA, and a multigene luminal score (LS) that serves as a measure of estrogen signaling in breast tumors. We used logistic and linear regression models to estimate temporal and dose-dependent associations between smoking and ER measures. Results: The odds of ER + , ESR1 + , and LS + tumors among current smokers (at the time of diagnosis), those who smoked 20 or more years, and those who smoked within 5 years of diagnosis were nearly double those of nonsmokers. Quantitative levels of ESR1 were highest among current smokers compared with never smokers overall [mean (log 2 ) = 9.2 vs. 8.7, P < 0.05] and among ER + cases; however, we did not observe associations between smoking measures and continuous ER protein expression. Conclusions: In relationship to breast cancer diagnosis, recent smoking was associated with higher odds of the ER + , ESR1 + , and LS + subtype. Current smoking was associated with elevated ESR1 mRNA levels and an elevated LS, but not with altered ER protein. Impact: A multigene LS and single-gene ESR1 mRNA may capture tumor changes associated with smoking. Cancer Epidemiol Biomarkers Prev; 27(1); 67-74. ©2017 AACR . ©2017 American Association for Cancer Research.

ESR study of photoinduced free radicals by visible light in hair and the effects of ascorbic acid (vitamin C).

PubMed

Chikvaidze, E; Khachatryan, I

2011-08-01

The ESR spectra of melanin's free radicals in natural black and red hair have been investigated. It is shown that the ESR spectrum of black hair is slightly asymmetric singlet with g=2.0037 and ΔH=0.5 mTl. The ESR spectrum of red hair with g=2.0053 differs from the spectrum of black hair. Using the method of saturation was shown that ESR spectrum of red hair represents a superposition of two signals: a singlet, relating to the black hair, and a triplet from red hair's pheomelanin. Under the influence of visible light (blue with λ(max) =450 nm, green with λ(max) =510 nm and red with λ(max) =650 nm) in both types of hair (black and red), the photoinduced free radicals appear, which indicates an increase in the intensity of already existing ESR spectrum of hair. It should be noted that the ESR spectra of red hair from various donors are different. The antioxidant ascorbic acid (vitamin C) has the different effect on the photoinduced free radicals. In particular, in the case of black hair, the concentration of photoinduced free radicals is slightly reduced, whereas in red hair, the disappearance of the triplet in the spectrum is observed, and at the same time, the spectrum becomes a singlet, the intensity of which increases sharply. It is assumed that the antioxidants, effective for black hair, may be ineffective for red hair and vice versa. Therefore, in each, specific case is necessary to investigate the effectiveness of an antioxidant separately. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Dating of fossil human teeth and shells from Toca do Enoque site at Serra das Confusões National Park, Brazil.

PubMed

Kinoshita, Angela; Sullasi, Henry L; Asfora, Viviane K; Azevedo, Renata L; Guzzo, Pedro; Guidon, Niede; Figueiredo, Ana Maria G; Khoury, Helen; Pessis, Anne-Marie; Baffa, Oswaldo

2016-06-07

This work reports the dating of a fossil human tooth and shell found at the archaeological site Toca do Enoque located in Serra das Confusões National Park (Piauí, Brazil). Many prehistoric paintings have been found at this site. An archaeological excavation unearthed three sepulchers with human skeletons and some shells. Two Brazilian laboratories, in Ribeirão Preto (USP) and Recife (UFPE), independently performed Electron Spin Resonance (ESR) measurements to date the tooth and the shell and obtain the equivalent dose received by each sample. The laboratories determined similar ages for the tooth and the shell (~4.8 kyBP). The results agreed with C-14 dating of the shell and other samples (charcoal) collected in the same sepulcher. Therefore, this work provides a valid inter-comparison of results by two independent ESR-dating laboratories and between two dating methods; i.e., C-14 and ESR, showing the validity of ESR dating for this range of ages.

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).

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.

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.

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.

Expression of Genomic Functional Estrogen Receptor 1 in Mouse Sertoli Cells

PubMed Central

Lin, Jing; Zhu, Jia; Li, Xian; Li, Shengqiang; Lan, Zijian; Ko, Jay

2014-01-01

There is no consensus whether Sertoli cells express estrogen receptor 1 (Esr1). Reverse transcription-polymerase chain reaction, Western blot, and immunofluorescence demonstrated that mouse Sertoli cell lines, TM4, MSC-1, and 15P-1, and purified primary mouse Sertoli cells (PSCs) contained Esr1 messenger RNA and proteins. Incubation of Sertoli cells with 17β-estradiol (E2) or ESR1 agonist stimulated the expression of an estrogen responsive gene Greb1, which was prevented by ESR inhibitor or ESR1 antagonist. Overexpression of Esr1 in MSC-1 enhanced E2-induced Greb1 expression, while knockdown of Esr1 by small interfering RNA in TM4 attenuated the response. Furthermore, E2-induced Greb1 expression was abolished in the PSCs isolated from Amh-Cre/Esr1-floxed mice in which Esr1 in Sertoli cells were selectively deleted. Chromatin immunoprecipitation assays indicated that E2-induced Greb1 expression in Sertoli cells was mediated by binding of ESR1 to estrogen responsive elements. In summary, ligand-dependent nuclear ESR1 was present in mouse Sertoli cells and mediates a classical genomic action of estrogens. PMID:24615934

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

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.

A Parametric Study of Slag Skin Formation in Electroslag Remelting

NASA Astrophysics Data System (ADS)

Yanke, Jeff; Krane, Matthew John M.

In electroslag remelting (ESR), the slag generates heat, chemically refines the melting electrode material, and forms frozen skin on the mold. An axisymmetric model is used to simulate fluid flow, heat transfer, solidification, and electromagnetics and their interaction with slag skin formation in ESR. A volume of fluid (VOF) method is used to track the slag/metal interface, allowing simulation of slag freezing to the mold. Mold diameter and applied current are varied to determine how these parameters affect melt rate and formation of slag skin during ESR. Variations in the slag skin thickness within the slag cap are found to have a significant impact on melt rate and depth of metal sump. Changes in slag cap volume resulted in small changes in melt rate.

Electron spin resonance modes in a strong-leg ladder in the Tomonaga-Luttinger liquid phase

NASA Astrophysics Data System (ADS)

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

2015-12-01

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 nonlinear 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 their ESR observability to the uniform Dzyaloshinskii-Moriya interaction.

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.

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.

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

PAM50 Breast Cancer Subtyping by RT-qPCR and Concordance with Standard Clinical Molecular Markers

PubMed Central

2012-01-01

Background Many methodologies have been used in research to identify the “intrinsic” subtypes of breast cancer commonly known as Luminal A, Luminal B, HER2-Enriched (HER2-E) and Basal-like. The PAM50 gene set is often used for gene expression-based subtyping; however, surrogate subtyping using panels of immunohistochemical (IHC) markers are still widely used clinically. Discrepancies between these methods may lead to different treatment decisions. Methods We used the PAM50 RT-qPCR assay to expression profile 814 tumors from the GEICAM/9906 phase III clinical trial that enrolled women with locally advanced primary invasive breast cancer. All samples were scored at a single site by IHC for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu (HER2) protein expression. Equivocal HER2 cases were confirmed by chromogenic in situ hybridization (CISH). Single gene scores by IHC/CISH were compared with RT-qPCR continuous gene expression values and “intrinsic” subtype assignment by the PAM50. High, medium, and low expression for ESR1, PGR, ERBB2, and proliferation were selected using quartile cut-points from the continuous RT-qPCR data across the PAM50 subtype assignments. Results ESR1, PGR, and ERBB2 gene expression had high agreement with established binary IHC cut-points (area under the curve (AUC) ≥ 0.9). Estrogen receptor positivity by IHC was strongly associated with Luminal (A and B) subtypes (92%), but only 75% of ER negative tumors were classified into the HER2-E and Basal-like subtypes. Luminal A tumors more frequently expressed PR than Luminal B (94% vs 74%) and Luminal A tumors were less likely to have high proliferation (11% vs 77%). Seventy-seven percent (30/39) of ER-/HER2+ tumors by IHC were classified as the HER2-E subtype. Triple negative tumors were mainly comprised of Basal-like (57%) and HER2-E (30%) subtypes. Single gene scoring for ESR1, PGR, and ERBB2 was more prognostic than the corresponding IHC markers as shown in a multivariate analysis. Conclusions The standard immunohistochemical panel for breast cancer (ER, PR, and HER2) does not adequately identify the PAM50 gene expression subtypes. Although there is high agreement between biomarker scoring by protein immunohistochemistry and gene expression, the gene expression determinations for ESR1 and ERBB2 status was more prognostic. PMID:23035882

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

Antioxidant activities of two sericin proteins extracted from cocoon of silkworm (Bombyx mori) measured by DPPH, chemiluminescence, ORAC and ESR methods.

PubMed

Takechi, Tayori; Wada, Ritsuko; Fukuda, Tsubasa; Harada, Kazuki; Takamura, Hitoshi

2014-05-01

Recent efforts have focused on the use of sericin proteins extracted from cocoons of silkworm as a healthy food source for human consumption. In this study, we focused on the antioxidative properties of sericin proteins. The antioxidative properties were measured in sericin proteins extracted from the shell of the cocoon, designated hereafter as white sericin protein and yellow-green sericin protein, as well as bread without sericin protein and bread to which white sericin powder had been added using four measurement methods: 1,1-Diphenyl-2-picrylhydrazyl (DPPH), chemiluminescence, oxygen radical absorbance capacity (ORAC) and electron spin resonance (ESR). High antioxidative properties of sericin proteins were indicated by all four methods. A comparison of the two types of sericin proteins revealed that yellow-green sericin protein exhibited high antioxidative properties as indicated by the DPPH, chemiluminescence and ORAC methods. By contrast, a higher antioxidative property was determined in white sericin protein by the ESR method. Consequently, our findings confirmed that sericin proteins have antioxidative properties against multiple radicals. In addition, the antioxidative property of bread was enhanced by the addition of sericin powder to the bread. Therefore, findings of this study suggest that sericin proteins may be efficiently used as beneficial food for human health.

Antioxidant activities of two sericin proteins extracted from cocoon of silkworm (Bombyx mori) measured by DPPH, chemiluminescence, ORAC and ESR methods

PubMed Central

TAKECHI, TAYORI; WADA, RITSUKO; FUKUDA, TSUBASA; HARADA, KAZUKI; TAKAMURA, HITOSHI

2014-01-01

Recent efforts have focused on the use of sericin proteins extracted from cocoons of silkworm as a healthy food source for human consumption. In this study, we focused on the antioxidative properties of sericin proteins. The antioxidative properties were measured in sericin proteins extracted from the shell of the cocoon, designated hereafter as white sericin protein and yellow-green sericin protein, as well as bread without sericin protein and bread to which white sericin powder had been added using four measurement methods: 1,1-Diphenyl-2-picrylhydrazyl (DPPH), chemiluminescence, oxygen radical absorbance capacity (ORAC) and electron spin resonance (ESR). High antioxidative properties of sericin proteins were indicated by all four methods. A comparison of the two types of sericin proteins revealed that yellow-green sericin protein exhibited high antioxidative properties as indicated by the DPPH, chemiluminescence and ORAC methods. By contrast, a higher antioxidative property was determined in white sericin protein by the ESR method. Consequently, our findings confirmed that sericin proteins have antioxidative properties against multiple radicals. In addition, the antioxidative property of bread was enhanced by the addition of sericin powder to the bread. Therefore, findings of this study suggest that sericin proteins may be efficiently used as beneficial food for human health. PMID:24748975

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.

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.

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

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.

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 Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Increased Sensitivity of Estrogen Receptor Alpha Overexpressing Antral Follicles to Methoxychlor and Its Metabolites

PubMed Central

Paulose, Tessie; Hernández-Ochoa, Isabel; Basavarajappa, Mallikarjuna S.; Peretz, Jackye; Flaws, Jodi A.

2011-01-01

Methoxychlor (MXC), an organochlorine pesticide, and its metabolites, mono-hydroxy MXC (MOH) and bis-hydroxy MXC (HPTE) are known ovarian toxicants and can cause inhibition of antral follicle growth. Since these chemicals bind to estrogen receptor alpha (ESR1), we hypothesized that ovaries overexpressing ESR1 (ESR1 OE) would be more susceptible to toxicity induced by MXC and its metabolites because the chemicals can bind to more ESR1 in the antral follicles. We cultured antral follicles from controls and ESR1 OE mouse ovaries with either the vehicle dimethylsulfoxide (DMSO), MXC, MOH, or HPTE. The data show that at 96 h, the cultured antral follicles from ESR1 OE antral follicles are more susceptible to toxicity induced by MXC, MOH, and HPTE because low doses of these chemicals cause follicle growth inhibition in ESR1 OE mice but not in control mice. On comparing gene expression levels of nuclear receptors in the cultured antral follicles of ESR1 OE and control follicles, we found differential messenger RNA (mRNA) expression of Esr1, estrogen receptor beta (Esr2), androgen receptor (Ar), progesterone receptor (Pr), and aryl hydrocarbon receptor (Ahr) between the genotypes. We also analyzed mRNA levels of Cyp3a41a, the enzyme metabolizing MOH and HPTE, in the cultured follicles and found that Cyp3a41a was significantly lower in DMSO-treated ESR1 OE follicles compared with controls. In ESR1 OE livers, we found that Cyp3a41a levels were significantly lower compared with control livers. Collectively, these data suggest that MXC and its metabolites cause differential gene expression in ESR1 OE mice compared with controls. The results also suggest that the increased sensitivity of ESR1 OE mouse ovaries to toxicity induced by MXC and its metabolites is due to low clearance of the metabolites by the liver and ovary. PMID:21252393

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.

Silicon vacancy-related centers in non-irradiated 6H-SiC nanostructure

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

Bagraev, N. T., E-mail: Impurity.Dipole@mail.ioffe.ru; Danilovskii, E. Yu.; Gets, D. S.

2015-05-15

We present the first findings of the silicon vacancy related centers identified in the non-irradiated 6H-SiC nanostructure using the electron spin resonance (ESR) and electrically-detected (ED) ESR technique. This planar 6H-SiC nanostructure represents the ultra-narrow p-type quantum well confined by the δ-barriers heavily doped with boron on the surface of the n-type 6H-SiC(0001) wafer. The new EDESR technique by measuring the only magnetoresistance of the 6H-SiC nanostructure under the high frequency generation from the δ-barriers appears to allow the identification of the isolated silicon vacancy centers as well as the triplet center with spin state S = 1. The samemore » triplet center that is characterized by the large value of the zero-field splitting constant D and anisotropic g-factor is revealed by the ESR (X-band) method. The hyperfine (HF) lines in the ESR and EDESR spectra originating from the HF interaction with the {sup 14}N nucleus seem to attribute this triplet center to the N-V{sub Si} defect.« less

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.

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.

Radical production from the interaction of ozone and PUFA as demonstrated by electron spin resonance spin-trapping techniques

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

Pryor, W.A.; Prier, D.G.; Church, D.F.

1981-02-01

There is considerable evidence that indicates that a fraction of the damage caused by ozone to cellular systems involves radical-mediated reactions. The most direct method for probing the mechanism by which ozone reacts with target molecules such as polyunsaturated fatty acids involves the use of electron spin resonance. In 1968, Goldstein et al. reported that ESR signals were observed when 40 ppM ozone in air is bubbled through linoleic acid. We have repeated this experiment and have performed several experiments modified from this design; in none of these do we observe ESR signals. We have studied the reaction of ozonemore » with PUFA at -78/sup 0/C using spin traps. Spin traps themselves react with ozone, but the following protocol avoids that reaction. (1) Ozone in air or oxygen-free ozone is allowed to bubble through the sample in Freon-11 in an ESR tube at -78/sup 0/C; no ESR absorption is observed. (2) Unreacted ozone is flushed out with argon or nitrogen. (3) The spin trap in Freon-11 is added to give a 0.1 M solution, still at -78/sup 0/C; no ESR signal is observed. (4) The tube is allowed to warm slowly. At about -45/sup 0/C, the ESR spectra of spin adducts appear. Using this method with methyl linoleate we observe spin adducts of alkoxy radicals and also a signal that is consistent with a carbon radical with one ..cap alpha..-H. We hypothesize that an intermediate is formed from the reaction of ozone with PUFA that is stable at -78/sup 0/Cbut decomposes to form radicals at about -45/sup 0/C. We tentatively identify the intermediate as a trioxide on the basis of analogies and its temperature profile for decomposition to radicals. It appears reasonable to suggest that the reaction(s) responsible for the production of radicals under these low-temperature conditions also occurs at room temperature. Although the low-temperature intermediate cannot be observed at ambient temperatures, radicals from it could be responsible for the effects on autoxidation that are induced by ozone.« less

The ESR age of Portlandia arctica shells from glacial deposits of Central Latvia . an answer to a controversy on the age and genesis of their enclosing sediments

NASA Astrophysics Data System (ADS)

Molodkov, Anatoly; Dreimanis, Aleksis; ĀBoltiņš, Ojars; Raukas, Anto

The occurrence of Portlandia arctica shells in glacigenic sediments of Central Latvia had created a controversy in many publications about (1) their age ranging from the Holsteinian to the Late Weichselian and (2) the genesis of their enclosing sediments: glacial, glaciomarine or marine. Our reinvestigation of the main object of controversy, the Lı¯čupe site, leads to a conclusion that the sedimentary package of diamictons, clays and sands containing Portlandia arctica shells and marine microfossils is a large glacial raft that had been transported and deposited by the Riga lobe during the Weichselian. The electron spin resonance (ESR) ages on five sets of Portlandia arctica shells from the Lı¯čupe and Daugmales Tomēni sites range from 86.0±6.8 to 105.0±9.2 ka BP. These ESR age determinations and the cool climate indicators of the associated microflora and microfauna suggest that their source sediments, probably in the Gulf of Riga, are marine clays of Early Weichselian age, probably correlative to the Brørup Interstadial. In Central Latvia Portlandia arctica shells and their enclosing clay occur resedimented or translocated in glacial deposits during Weichselian glacial advances.

Estrogen Receptor (ESR1) mRNA Expression and Benefit From Tamoxifen in the Treatment and Prevention of Estrogen Receptor–Positive Breast Cancer

PubMed Central

Kim, Chungyeul; Tang, Gong; Pogue-Geile, Katherine L.; Costantino, Joseph P.; Baehner, Frederick L.; Baker, Joffre; Cronin, Maureen T.; Watson, Drew; Shak, Steven; Bohn, Olga L.; Fumagalli, Debora; Taniyama, Yusuke; Lee, Ahwon; Reilly, Megan L.; Vogel, Victor G.; McCaskill-Stevens, Worta; Ford, Leslie G.; Geyer, Charles E.; Wickerham, D. Lawrence; Wolmark, Norman; Paik, Soonmyung

2011-01-01

Purpose Several mechanisms have been proposed to explain tamoxifen resistance of estrogen receptor (ER) –positive tumors, but a clinically useful explanation for such resistance has not been described. Because the ER is the treatment target for tamoxifen, a linear association between ER expression levels and the degree of benefit from tamoxifen might be expected. However, such an association has never been demonstrated with conventional clinical ER assays, and the ER is currently used clinically as a dichotomous marker. We used gene expression profiling and ER protein assays to help elucidate molecular mechanism(s) responsible for tamoxifen resistance in breast tumors. Patients and Methods We performed gene expression profiling of paraffin-embedded tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) trials that tested the worth of tamoxifen as an adjuvant systemic therapy (B-14) and as a preventive agent (P-1). This was a retrospective subset analysis based on available materials. Results In B-14, ESR1 was the strongest linear predictor of tamoxifen benefit among 16 genes examined, including PGR and ERBB2. On the basis of these data, we hypothesized that, in the P-1 trial, a lower level of ESR1 mRNA in the tamoxifen arm was the main difference between the two study arms. Only ESR1 was downregulated by more than two-fold in ER-positive cancer events in the tamoxifen arm (P < .001). Tamoxifen did not prevent ER-positive tumors with low levels of ESR1 expression. Conclusion These data suggest that low-level expression of ESR1 is a determinant of tamoxifen resistance in ER-positive breast cancer. Strategies should be developed to identify, treat, and prevent such tumors. PMID:21947828

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.

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

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.

International Conference on Quantum Chemical Calculations of NMR and EPR Parameters Held in Castle Smolenice, Slovak Republic on September 14-18 1998

DTIC Science & Technology

1998-10-21

site. The electric-field- induced linear shift is also observed in the hyperfine splitting of nuclear quadrupole resonance ( NQR ) spectrum of a nucleus...located at a noncentrosymmetric site in a molecule or in crystal lattice. Thus, the linear electric field effect on the ESR and NQR hyperfine splitting...the electric field effects on ESR and NQR hyperfine couplings. Theoretical methods to calculate the electric field effects within Hartree-Fock

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.

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

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.

Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor–Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14

PubMed Central

Wolmark, Norman; Baehner, Frederick L.; Butler, Steven M.; Tang, Gong; Jamshidian, Farid; Sing, Amy P.; Shak, Steven; Paik, Soonmyung

2016-01-01

Purpose We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1–expressing groups. Patients and Methods RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) –positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Results Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14 patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). Conclusion For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. PMID:27217450

Evaluation of absorbed dose in irradiated sugar-containing plant material (peony roots) by an ESR method

NASA Astrophysics Data System (ADS)

Yamaoki, Rumi; Kimura, Shojiro; Ohta, Masatoshi

2015-12-01

The relationship between electron spin resonance (ESR) signal intensity of irradiated plant materials and sugar content was investigated by spectral analysis using peony roots. A weak background signal near g=2.005 was observed in the roots. After a 10 kGy irradiation, the ESR line broadened and the intensity increased, and the spectral characteristics were similar to a typical spectrum of irradiated food containing crystalline sugars. The free radical concentration was nearly stable 30 days after irradiation. The spectrum of peony root 30 days after irradiation was simulated using the summation of the intensities of six assumed components: radical signals derived from (a) sucrose, (b) glucose, (c) fructose, (d) cellulose, (e) the background signal near g=2.005 and (f) unidentified component. The simulated spectra using the six components were in agreement with the observed sample spectra. The intensity of sucrose radical signal in irradiated samples increased proportionally up to 20 kGy. In addition, the intensity of sucrose radical signals was strongly correlated with the sucrose contents of the samples. The results showed that the radiation sensitivity of sucrose in peony roots was influenced little by other plant constituents. There was also a good correlation between the total area of the spectra and the sucrose content, because the sucrose content was higher than that of other sugars in the samples. In peony roots, estimation of the absorbed dose from the ESR signal intensity may be possible by a calibration method based on the sucrose content.

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.

Association study of estrogen receptor alpha gene polymorphisms with spontaneous abortion: is this a possible reason for unexplained spontaneous abortion?

PubMed

Anousha, Negin; Hossein-Nezhad, Arash; Biramijamal, Firouzeh; Rahmani, Ali; Maghbooli, Zhila; Aghababaei, Elahe; Nemati, Shahram

2013-01-01

Estrogen plays a crucial role in fetal and placental development through estrogen receptors. Association of estrogen receptor alpha gene (ESR1) polymorphisms with spontaneous abortion has been shown in some studies. Our main goal was to study the potential association of spontaneous abortion with the ESR1 gene variations (PvuII and XbaI) in fetal tissue. Totally, 161 samples were recruited including 80 samples of formalin-fixed paraffin-embedded fetal tissue from spontaneous abortion and 81 samples of normal term placental tissue. The restriction fragment length polymorphism (RFLP) method was performed for genotyping the rs2234693 (A/G XbaI) and rs9340799 (T/C PvuII) single nucleotide polymorphisms located in intron 1 of ESR1. The results have been confirmed by DNA sequencing analysis. The different genotypes distribution was detected in two study groups. Haplotype analysis indicated that ppxx is protective genotype against spontaneous abortion (P = 0.01). In conclusion, the potential role of ESR1 genetic variation in spontaneous abortion might be valuable in high-risk subjects, and that needs to be confirmed with future studies.

Association Study of Estrogen Receptor Alpha Gene Polymorphisms with Spontaneous Abortion: Is This a Possible Reason for Unexplained Spontaneous Abortion?

PubMed Central

Anousha, Negin; Hossein-Nezhad, Arash; Biramijamal, Firouzeh; Rahmani, Ali; Maghbooli, Zhila; Aghababaei, Elahe; Nemati, Shahram

2013-01-01

Estrogen plays a crucial role in fetal and placental development through estrogen receptors. Association of estrogen receptor alpha gene (ESR1) polymorphisms with spontaneous abortion has been shown in some studies. Our main goal was to study the potential association of spontaneous abortion with the ESR1 gene variations (PvuII and XbaI) in fetal tissue. Totally, 161 samples were recruited including 80 samples of formalin-fixed paraffin-embedded fetal tissue from spontaneous abortion and 81 samples of normal term placental tissue. The restriction fragment length polymorphism (RFLP) method was performed for genotyping the rs2234693 (A/G XbaI) and rs9340799 (T/C PvuII) single nucleotide polymorphisms located in intron 1 of ESR1. The results have been confirmed by DNA sequencing analysis. The different genotypes distribution was detected in two study groups. Haplotype analysis indicated that ppxx is protective genotype against spontaneous abortion (P = 0.01). In conclusion, the potential role of ESR1 genetic variation in spontaneous abortion might be valuable in high-risk subjects, and that needs to be confirmed with future studies. PMID:24228243

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.

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.

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.

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.

Comparison of the disease activity score using erythrocyte sedimentation rate and C-reactive protein in African Americans with rheumatoid arthritis.

PubMed

Tamhane, Ashutosh; Redden, David T; McGwin, Gerald; Brown, Elizabeth E; Westfall, Andrew O; Reynolds, Richard J; Hughes, Laura B; Conn, Doyt L; Callahan, Leigh F; Jonas, Beth L; Smith, Edwin A; Brasington, Richard D; Moreland, Larry W; Bridges, S Louis

2013-11-01

The Disease Activity Score based on 28 joints (DAS28) has been increasingly used in clinical practice and research studies of rheumatoid arthritis (RA). Studies have reported discordance between DAS28 based on erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) in patients with RA. However, such comparison is lacking in African Americans with RA. This analysis included participants from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) registry, which enrolls self-declared African Americans with RA. Using tender and swollen joint counts, separate ESR-based and CRP-based DAS28 scores (DAS28-ESR3 and DAS28-CRP3) were calculated, as were DAS28-ESR4 and DAS28-CRP4, which included the patient's assessment of disease activity. The scores were compared using paired t-test, simple agreement and κ, correlation coefficient, and Bland-Altman plots. Of the 233 included participants, 85% were women, mean age at enrollment was 52.6 years, and median disease duration at enrollment was 21 months. Mean DAS28-ESR3 was significantly higher than DAS28-CRP3 (4.8 vs 3.9; p < 0.001). Similarly, mean DAS28-ESR4 was significantly higher than DAS28-CRP4 (4.7 vs 3.9; p < 0.001). ESR-based DAS28 remained higher than CRP-based DAS28 even when stratified by age, sex, and disease duration. Overall agreement was not high between DAS28-ESR3 and DAS28-CRP3 (50%) or between DAS28-ESR4 and DAS28-CRP4 (59%). DAS28-CRP3 underestimated disease activity in 47% of the participants relative to DAS28-ESR3 and DAS28-CRP4 in 40% of the participants relative to DAS28-ESR4. There was significant discordance between the ESR-based and CRP-based DAS28, a situation that could affect clinical treatment decisions for African Americans with RA.

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-regulated gene expression and related bioinformatic analysis is presented to increase our understanding of how estradiol/ESR1 affects function of the oviduct, and to identify genes that may be proven as important regulators of fertility in the future.

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 and GATA3 co-expressed genes that may be involved in breast tumorigenesis. PMID:28789340

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 identified novel FOXA1 , ESR1 and GATA 3 co-expressed genes that may be involved in breast tumorigenesis.

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.

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.

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

CIDEP study on the flash photolysis of benzoin included in β-cyclodextrin

NASA Astrophysics Data System (ADS)

Kitahama, Yasutaka; Murai, Hisao

1996-10-01

The photodissociation reaction of benzoin (Norrish type I) included in a β-cyclodextrin (CD) cavity in the aqueous phase was studied by using time-resolved ESR and Fourier transform ESR methods. The CIDEP (chemically induced dynamic electron polarization) spectra of α-hydroxybenzyl radical and benzoyl radical were carefully investigated in β-CD, in ethanol, in an ethanol/water mixture, and in saturated aqueous solutions. According to these data and the calculations due to an extended Bloch equation, the spin-lattice relaxation time observed in the β-CD system was compared to those in homogeneous solutions. It is concluded that dissociation takes place from the excited triplet state of benzoin and the fragment radicals are easily ejected from the cavity of β-CD to the aqueous phase much faster than the time-resolution (˜ 20 ns) of the present FT-ESR measurement.

Sensitivity of Erythrocyte Sedimentation Rate and C-reactive Protein in Childhood Bone and Joint Infections

PubMed Central

Kallio, Markku J. T.; Kallio, Pentti E.; Peltola, Heikki

2009-01-01

In addition to the examination of clinical signs, several laboratory markers have been measured for diagnostics and monitoring of pediatric septic bone and joint infections. Traditionally erythrocyte sedimentation rate (ESR) and leukocyte cell count have been used, whereas C-reactive protein (CRP) has gained in popularity. We monitored 265 children at ages 3 months to 15 years with culture-positive osteoarticular infections with a predetermined series of ESR, CRP, and leukocyte count measurements. On admission, ESR exceeded 20 mm/hour in 94% and CRP exceeded 20 mg/L in 95% of the cases, the mean (± standard error of the mean) being 51 ± 2 mm/hour and 87 ± 4 mg/L, respectively. ESR normalized in 24 days and CRP in 10 days. Elevated CRP gave a slightly better sensitivity in diagnostics than ESR, but best sensitivity was gained with the combined use of ESR and CRP (98%). Elevated ESR or CRP was seen in all cases during the first 3 days. Measuring ESR and CRP on admission can help the clinician rule out an acute osteoarticular infection. CRP normalizes faster than ESR, providing a clear advantage in monitoring recovery. Level of Evidence: Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence. PMID:19533263

Upregulation of estrogen receptor subtypes and vitellogenin mRNA in cinnamon clownfish Amphiprion melanopus during the sex change process: profiles on effects of 17beta-estradiol.

PubMed

Kim, Na Na; Jin, Deuk-Hee; Lee, Jehee; Kil, Gyung-Suk; Choi, Cheol Young

2010-10-01

In the present study, we investigated the expression pattern of estrogen receptors (esr) and vitellogenin (vtg) mRNA in the gonads and liver during sex change in cinnamon clownfish by using quantitative polymerase chain reaction. We divided gonadal development during the sex change from male to female into 3 stages (mature male, male at 90days after removing female, and mature female) and investigated esr and vtg mRNA expressions during the sex change. With female, the esr and vtg mRNA expressions increased. In western blot analysis, Esr1 protein was detected only in the ovaries of female cinnamon clownfish. Also, to understand the effect of 17beta-estradiol (E(2)), we investigated the esr and vtg mRNA expression patterns in the gonads and liver, and the changes in plasma E(2) level after E(2) injection. E(2) treatment increased both mRNA expression levels of esr and vtg and plasma E(2) levels. The present study describes the molecular characterization of esr subtypes and the interactions between esr and vtg after E(2) treatment in cinnamon clownfish. 2010 Elsevier Inc. All rights reserved.

Epithelial estrogen receptor 1 intrinsically mediates squamous differentiation in the mouse vagina.

PubMed

Miyagawa, Shinichi; Iguchi, Taisen

2015-10-20

Estrogen-mediated actions in female reproductive organs are tightly regulated, mainly through estrogen receptor 1 (ESR1). The mouse vaginal epithelium cyclically exhibits cell proliferation and differentiation in response to estrogen and provides a unique model for analyzing the homeostasis of stratified squamous epithelia. To address the role of ESR1-mediated tissue events during homeostasis, we analyzed mice with a vaginal epithelium-specific knockout of Esr1 driven by keratin 5-Cre (K5-Esr1KO). We show here that loss of epithelial ESR1 in the vagina resulted in aberrant epithelial cell proliferation in the suprabasal cell layers and led to failure of keratinized differentiation. Gene expression analysis showed that several known estrogen target genes, including erbB growth factor ligands, were not induced by estrogen in the K5-Esr1KO mouse vagina. Organ culture experiments revealed that the addition of erbB growth factor ligands, such as amphiregulin, could activate keratinized differentiation in the absence of epithelial ESR1. Thus, epithelial ESR1 integrates estrogen and growth factor signaling to mediate regulation of cell proliferation in squamous differentiation, and our results provide new insights into estrogen-mediated homeostasis in female reproductive organs.

Epithelial estrogen receptor 1 intrinsically mediates squamous differentiation in the mouse vagina

PubMed Central

Miyagawa, Shinichi; Iguchi, Taisen

2015-01-01

Estrogen-mediated actions in female reproductive organs are tightly regulated, mainly through estrogen receptor 1 (ESR1). The mouse vaginal epithelium cyclically exhibits cell proliferation and differentiation in response to estrogen and provides a unique model for analyzing the homeostasis of stratified squamous epithelia. To address the role of ESR1-mediated tissue events during homeostasis, we analyzed mice with a vaginal epithelium-specific knockout of Esr1 driven by keratin 5-Cre (K5-Esr1KO). We show here that loss of epithelial ESR1 in the vagina resulted in aberrant epithelial cell proliferation in the suprabasal cell layers and led to failure of keratinized differentiation. Gene expression analysis showed that several known estrogen target genes, including erbB growth factor ligands, were not induced by estrogen in the K5-Esr1KO mouse vagina. Organ culture experiments revealed that the addition of erbB growth factor ligands, such as amphiregulin, could activate keratinized differentiation in the absence of epithelial ESR1. Thus, epithelial ESR1 integrates estrogen and growth factor signaling to mediate regulation of cell proliferation in squamous differentiation, and our results provide new insights into estrogen-mediated homeostasis in female reproductive organs. PMID:26438838

Substituted Quaternary Ammonium Salts Improve Low-Temperature Performance of Double-Layer Capacitors

NASA Technical Reports Server (NTRS)

Brandon, Erik J.; Smart, Marshall C.; West, William C.

2011-01-01

Double-layer capacitors are unique energy storage devices, capable of supporting large current pulses as well as a very high number of charging and discharging cycles. The performance of doublelayer capacitors is highly dependent on the nature of the electrolyte system used. Many applications, including for electric and fuel cell vehicles, back-up diesel generators, wind generator pitch control back-up power systems, environmental and structural distributed sensors, and spacecraft avionics, can potentially benefit from the use of double-layer capacitors with lower equivalent series resistances (ESRs) over wider temperature limits. Higher ESRs result in decreased power output, which is a particular problem at lower temperatures. Commercially available cells are typically rated for operation down to only 40 C. Previous briefs [for example, Low Temperature Supercapacitors (NPO-44386), NASA Tech Briefs, Vol. 32, No. 7 (July 2008), p. 32, and Supercapacitor Electrolyte Solvents With Liquid Range Below 80 C (NPO-44855), NASA Tech Briefs, Vol. 34, No. 1 (January 2010), p. 44] discussed the use of electrolytes that employed low-melting-point co-solvents to depress the freezing point of traditional acetonitrile-based electrolytes. Using these modified electrolyte formulations can extend the low-temperature operational limit of double-layer capacitors beyond that of commercially available cells. This previous work has shown that although the measured capacitance is relatively insensitive to temperature, the ESR can rise rapidly at low temperatures, due to decreased electrolyte conductance within the pores of the high surface- area carbon electrodes. Most of these advanced electrolyte systems featured tetraethylammonium tetrafluoroborate (TEATFB) as the salt. More recent work at JPL indicates the use of the asymmetric quaternary ammonium salt triethylmethylammonium tetrafluoroborate (TEMATFB) or spiro-(l,l')-bipyrrolidium tetrafluoroborate (SBPBF4) in a 1:1 by volume solvent mixture of acetonitrile (AN) and methyl formate (MF) enables double-layer capacitor cells to operate well below -40 C with a relatively low ESR. Typically, a less than twofold increase in ESR is observed at -65 C relative to room-temperature values, when these modified electrolyte blends are used in prototype cells. Double-layer capacitor coin cells filled with these electrolytes have displayed the lowest measured ESR for an organic electrolyte to date at low temperature (based on a wide range of electrolyte screening studies at JPL). The cells featured high-surface-area (approximately equal to 2,500 m/g) carbon electrodes that were 0.50 mm thick and 1.6 cm in diameter, and coated with a thin layer of platinum to reduce cell resistance. A polyethylene separator was used to electrically isolate the electrodes.

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

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

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.

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 ...

Optimization, evaluation and calibration of a cross-strip DOI detector

NASA Astrophysics Data System (ADS)

Schmidt, F. P.; Kolb, A.; Pichler, B. J.

2018-02-01

This study depicts the evaluation of a SiPM detector with depth of interaction (DOI) capability via a dual-sided readout that is suitable for high-resolution positron emission tomography and magnetic resonance (PET/MR) imaging. Two different 12  ×  12 pixelated LSO scintillator arrays with a crystal pitch of 1.60 mm are examined. One array is 20 mm-long with a crystal separation by the specular reflector Vikuiti enhanced specular reflector (ESR), and the other one is 18 mm-long and separated by the diffuse reflector Lumirror E60 (E60). An improvement in energy resolution from 22.6% to 15.5% for the scintillator array with the E60 reflector is achieved by taking a nonlinear light collection correction into account. The results are FWHM energy resolutions of 14.0% and 15.5%, average FWHM DOI resolutions of 2.96 mm and 1.83 mm, and FWHM coincidence resolving times of 1.09 ns and 1.48 ns for the scintillator array with the ESR and that with the E60 reflector, respectively. The measured DOI signal ratios need to be assigned to an interaction depth inside the scintillator crystal. A linear and a nonlinear method, using the intrinsic scintillator radiation from lutetium, are implemented for an easy to apply calibration and are compared to the conventional method, which exploits a setup with an externally collimated radiation beam. The deviation between the DOI functions of the linear or nonlinear method and the conventional method is determined. The resulting average of differences in DOI positions is 0.67 mm and 0.45 mm for the nonlinear calibration method for the scintillator array with the ESR and with the E60 reflector, respectively; Whereas the linear calibration method results in 0.51 mm and 0.32 mm for the scintillator array with the ESR and the E60 reflector, respectively; and is, due to its simplicity, also applicable in assembled detector systems.

Optimization, evaluation and calibration of a cross-strip DOI detector.

PubMed

Schmidt, F P; Kolb, A; Pichler, B J

2018-02-20

This study depicts the evaluation of a SiPM detector with depth of interaction (DOI) capability via a dual-sided readout that is suitable for high-resolution positron emission tomography and magnetic resonance (PET/MR) imaging. Two different 12  ×  12 pixelated LSO scintillator arrays with a crystal pitch of 1.60 mm are examined. One array is 20 mm-long with a crystal separation by the specular reflector Vikuiti enhanced specular reflector (ESR), and the other one is 18 mm-long and separated by the diffuse reflector Lumirror E60 (E60). An improvement in energy resolution from 22.6% to 15.5% for the scintillator array with the E60 reflector is achieved by taking a nonlinear light collection correction into account. The results are FWHM energy resolutions of 14.0% and 15.5%, average FWHM DOI resolutions of 2.96 mm and 1.83 mm, and FWHM coincidence resolving times of 1.09 ns and 1.48 ns for the scintillator array with the ESR and that with the E60 reflector, respectively. The measured DOI signal ratios need to be assigned to an interaction depth inside the scintillator crystal. A linear and a nonlinear method, using the intrinsic scintillator radiation from lutetium, are implemented for an easy to apply calibration and are compared to the conventional method, which exploits a setup with an externally collimated radiation beam. The deviation between the DOI functions of the linear or nonlinear method and the conventional method is determined. The resulting average of differences in DOI positions is 0.67 mm and 0.45 mm for the nonlinear calibration method for the scintillator array with the ESR and with the E60 reflector, respectively; Whereas the linear calibration method results in 0.51 mm and 0.32 mm for the scintillator array with the ESR and the E60 reflector, respectively; and is, due to its simplicity, also applicable in assembled detector systems.

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.

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.

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.

Molecular cloning, characterization, tissue distribution and mRNA expression changes during the hibernation and reproductive periods of estrogen receptor alpha (ESR1) in Chinese alligator, Alligator sinensis.

PubMed

Zhang, Ruidong; Hu, Yuehong; Wang, Huan; Yan, Peng; Zhou, Yongkang; Wu, Rong; Wu, Xiaobing

2016-10-01

Chinese alligator, Alligator sinensis, is a critically endangered reptile species unique to China. Little is known about the mechanism of growth- and reproduction-related hormones gene expression in Chinese alligator. Estrogens play important roles in regulating multiple reproduction- and non-reproduction-related functions by binding to their corresponding receptors. Here, the full-length cDNA of estrogen receptor alpha (ERα/ESR1) was cloned and sequenced from Chinese alligator for the first time, which comprises 1764bp nucleotides and encodes a predicted protein of 587 amino acids. Phylogenetic analysis of ESR1 showed that crocodilians and turtles were the sister-group of birds. The results of real-time quantitative PCR indicated that the ESR1 mRNA was widely expressed in the brain and peripheral tissues. In the brain and pituitary gland, ESR1 was most highly transcribed in the cerebellum. But in other peripheral tissues, ESR1 mRNA expression level was the highest in the ovary. Compared with hibernation period, ESR1 mRNA expression levels were increased significantly in the reproductive period (P<0.05) in cerebellum, pituitary gland, liver, spleen, lung, kidney and ovary, while no significant change in other examined tissues (P>0.05). The ESR1 mRNA expression levels changes during the two periods of different tissues suggested that ESR1 might play an important role in mediation of estrogenic multiple reproductive effects in Chinese alligator. Furthermore, it was the first time to quantify ESR1 mRNA level in the brain of crocodilians, and the distribution and expression of ESR1 mRNA in the midbrain, cerebellum and medulla oblongata was also reported for the first time in reptiles. Copyright © 2016 Elsevier Inc. All rights reserved.

Mating changes the subcellular distribution and the functionality of estrogen receptors in the rat oviduct.

PubMed

Orihuela, Pedro A; Zuñiga, Lidia M; Rios, Mariana; Parada-Bustamante, Alexis; Sierralta, Walter D; Velásquez, Luis A; Croxatto, Horacio B

2009-11-30

Mating changes the mode of action of 17beta-estradiol (E2) to accelerate oviductal egg transport from a nongenomic to a genomic mode, although in both pathways estrogen receptors (ER) are required. This change was designated as intracellular path shifting (IPS). Herein, we examined the subcellular distribution of ESR1 and ESR2 (formerly known as ER-alpha and ER-beta) in oviductal epithelial cells of rats on day 1 of cycle (C1) or pregnancy (P1) using immunoelectron microscopy for ESR1 and ESR2. The effect of mating on intraoviductal ESR1 or ESR2 signaling was then explored comparing the expression of E2-target genes c-fos, brain creatine kinase (Ckb) and calbindin 9 kDa (s100g) in rats on C1 or P1 treated with selective agonists for ESR1 (PPT) or ESR2 (DPN). The effect of ER agonists on egg transport was also evaluated on C1 or P1 rats. Receptor immunoreactivity was associated with the nucleus, cytoplasm and plasma membrane of the epithelial cells. Mating affected the subcellular distribution of both receptors as well as the response to E2. In C1 and P1 rats, PPT increased Ckb while both agonists increased c-fos. DPN increased Ckb and s100g only in C1 and P1 rats, respectively. PPT accelerated egg transport in both groups and DPN accelerated egg transport only in C1 rats. Estrogen receptors present a subcellular distribution compatible with E2 genomic and nongenomic signaling in the oviductal epithelial cells of C1 and P1 although IPS occurs independently of changes in the distribution of ESR1 and ESR2 in the oviductal epithelial cells. Mating affected intraoviductal ER-signaling and induced loss of functional involvement of ESR2 on E2-induced accelerated egg transport. These findings reveal a profound influence on the ER signaling pathways exerted by mating in the oviduct.

Comparison of the disease activity score using the erythrocyte sedimentation rate and C-reactive protein levels in Koreans with rheumatoid arthritis.

PubMed

Son, Kyeong Min; Kim, Suk Yeon; Lee, Sun Ho; Yang, Chung Mi; Seo, Young Il; Kim, Hyun Ah

2016-12-01

The Disease Activity Score based on 28 joints (DAS28) has been widely used in clinical practice and research studies of rheumatoid arthritis (RA). The objective of this study was to evaluate the discordance in the DAS28 based on the erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) levels in Korean patients with RA. From August to December 2011, 540 patients with RA who visited two rheumatology clinics affiliated with Hallym University (Korea) and had at least one DAS28 evaluation were examined. The mean age of the included patients was 53 years, and 82% were female. The mean duration of disease was 32.9 ± 41.2 months. The mean DAS28-ESR was higher than the DAS28-CRP (3.65 vs. 3.44; P < 0.001). In the DAS28-ESR group, 126 patients (23.3%) satisfied the criteria for remission versus 134 (24.8%) in the DAS28-CRP group. High disease activity was determined in 80 (14.8%) patients in the DAS28-ESR group and in 43 (8.0%) in the DAS28-CRP group. A comparison of the two groups with respect to four DAS28 disease activity categories showed agreement in 344 patients (63.7%; κ = 0.45). In classifying patients as European League Against Rheumatism (EULAR) responders, agreement between the two methods was shown in 56 patients (71.8%; κ = 0.76). When disagreements between the two scores occurred, more patients had a better EULAR response based on the DAS28-ESR than on the DAS28-CRP (19.2% vs. 8.9%, respectively). The discordance between the ESR-based and CRP-based DAS28 could affect clinical treatment decisions for patients with RA. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

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.

Magnetic and electron spin resonance studies of W doped CoFe2O4 polycrystalline materials

NASA Astrophysics Data System (ADS)

Singamaneni, S. R.; Martinez, L. M.; Swadipta, R.; Ramana, C. V.

2018-05-01

We report the magnetic and electron spin resonance (ESR) properties of W doped CoFe2O4 polycrystalline materials, prepared by standard solid-state reaction method. W was doped (0-15%) in CFO lattice on Fe site. Isothermal magnetization measurements reveal that the coercive field (Hc) (1300-2200 Oe) and saturation magnetization MS (35-82 emu/g) vary strongly as a function of W doping at all the temperatures (4-300 K) measured. We believe that a strong decrease in magnetic anisotropy in CFO after doping with W could cause a decrease in Hc. Up on doping CFO with W in place of Fe, the process transforms part of Fe3+ into Fe2+ due to the creation of more oxygen vacancies. This hinders the super-exchange interaction between Fe3+ and Fe2+, which causes a decrease in MS. Zero-field cooled (ZFC) and field cooled (FC, 1000 Oe) magnetization responses measured at 4 K on 1% W doped CFO show no indication of exchange bias, inferring that there are no other microscopic secondary magnetic phases (no segregation). This observation is corroborated by ESR (9.398 GHz) measurements collected as a function of temperature (10-150 K) and W doping (0-15%). We find that ESR spectra did not change after doping with W above 0.5%. However, ESR spectra collected from 0.5% W doped CFO sample showed a strong temperature dependence. We observed several ESR signals from 0.5% W doped CFO sample that could be due to phase separation.

Highly sensitive detection of ESR1 mutations in cell-free DNA from patients with metastatic breast cancer using molecular barcode sequencing.

PubMed

Masunaga, Nanae; Kagara, Naofumi; Motooka, Daisuke; Nakamura, Shota; Miyake, Tomohiro; Tanei, Tomonori; Naoi, Yasuto; Shimoda, Masafumi; Shimazu, Kenzo; Kim, Seung Jin; Noguchi, Shinzaburo

2018-01-01

We aimed to develop a highly sensitive method to detect ESR1 mutations in cell-free DNA (cfDNA) using next-generation sequencing with molecular barcode (MB-NGS) targeting the hotspot segment (c.1600-1713). The sensitivity of MB-NGS was tested using serially diluted ESR1 mutant DNA and then cfDNA samples from 34 patients with metastatic breast cancer were analyzed with MB-NGS. The results of MB-NGS were validated in comparison with conventional NGS and droplet digital PCR (ddPCR). MB-NGS showed a higher sensitivity (0.1%) than NGS without barcode (1%) by reducing background errors. Of the cfDNA samples from 34 patients with metastatic breast cancer, NGS without barcode revealed seven mutations in six patients (17.6%) and MB-NGS revealed six additional mutations including three mutations not reported in the COSMIC database of breast cancer, resulting in total 13 ESR1 mutations in ten patients (29.4%). Regarding the three hotspot mutations, all the patients with mutations detected by MB-NGS had identical mutations detected by droplet digital PCR (ddPCR), and mutant allele frequency correlated very well between both (r = 0.850, p < 0.01). Moreover, all the patients without these mutations by MB-NGS were found to have no mutations by ddPCR. In conclusion, MB-NGS could successfully detect ESR1 mutations in cfDNA with a higher sensitivity of 0.1% than conventional NGS and was considered as clinically useful as ddPCR.

Preoperative Erythrocyte Sedimentation Rate Independently Predicts Overall Survival in Localized Renal Cell Carcinoma following Radical Nephrectomy

PubMed Central

Cross, Brian W.; Johnson, Timothy V.; DeRosa, Austin B.; Ogan, Kenneth; Pattaras, John G.; Nieh, Peter T.; Kucuk, Omer; Harris, Wayne B.; Master, Viraj A.

2012-01-01

Objectives. To determine the relationship between preoperative erythrocyte sedimentation rate (ESR) and overall survival in localized renal cell carcinoma (RCC) following nephrectomy. Methods. 167 patients undergoing nephrectomy for localized RCC had ESR levels measured preoperatively. Receiver Operating Characteristics curves were used to determine Area Under the Curve and relative sensitivity and specificity of preoperative ESR in predicting overall survival. Cut-offs for low (0.0–20.0 mm/hr), intermediate (20.1–50.0 mm/hr), and high risk (>50.0 mm/hr) groups were created. Kaplan-Meier analysis was conducted to assess the univariate impact of these ESR-based groups on overall survival. Univariate and multivariate Cox regression analysis was conducted to assess the potential of these groups to predict overall survival, adjusting for other patient and tumor characteristics. Results. Overall, 55.2% were low risk, while 27.0% and 17.8% were intermediate and high risk, respectively. Median (95% CI) survival was 44.1 (42.6–45.5) months, 35.5 (32.3–38.8) months, and 32.1 (25.5–38.6) months, respectively. After controlling for other patient and tumor characteristics, intermediate and high risk groups experienced a 4.5-fold (HR: 4.509, 95% CI: 0.735–27.649) and 18.5-fold (HR: 18.531, 95% CI: 2.117–162.228) increased risk of overall mortality, respectively. Conclusion. Preoperative ESR values represent a robust predictor of overall survival following nephrectomy in localized RCC. PMID:22900160

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

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.

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.

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.

Systemic inflammation and intelligence in early adulthood and subsequent risk of schizophrenia and other non-affective psychoses: a longitudinal cohort and co-relative study.

PubMed

Kappelmann, Nils; Khandaker, Golam M; Dal, Henrik; Stochl, Jan; Kosidou, Kyriaki; Jones, Peter B; Dalman, Christina; Karlsson, Håkan

2018-04-06

Schizophrenia is associated with impaired neurodevelopment as indexed by lower premorbid IQ. We examined associations between erythrocyte sedimentation rate (ESR), a marker of low-grade systemic inflammation, IQ, and subsequent schizophrenia and other non-affective psychoses (ONAP) to elucidate the role of neurodevelopment and inflammation in the pathogenesis of psychosis. Population-based data on ESR and IQ from 638 213 Swedish men assessed during military conscription between 1969 and 1983 were linked to National Hospital Discharge Register for hospitalisation with schizophrenia and ONAP. The associations of ESR with IQ (cross-sectional) and psychoses (longitudinal) were investigated using linear and Cox-regression. The co-relative analysis was used to examine effects of shared familial confounding. We examined mediation and moderation of effect between ESR and IQ on psychosis risk. Baseline IQ was associated with subsequent risk of schizophrenia (adjusted HR per 1-point increase in IQ = 0.961; 95% confidence interval (CI) 0.960-0.963) and ONAP (adjusted HR = 0.973; 95% CI 0.971-0.975). Higher ESR was associated with lower IQ in a dose-response fashion. High ESR was associated with increased risk for schizophrenia (adjusted HR = 1.14; 95% CI 1.01-1.28) and decreased risk for ONAP (adjusted HR = 0.85; 95% CI 0.74-0.96), although these effects were specific to one ESR band (7-10 mm/hr). Familial confounding explained ESR-IQ but not ESR-psychoses associations. IQ partly mediated the ESR-psychosis relationships. Lower IQ is associated with low-grade systemic inflammation and with an increased risk of schizophrenia and ONAP in adulthood. Low-grade inflammation may influence schizophrenia risk by affecting neurodevelopment. Future studies should explore the differential effects of inflammation on different types of psychosis.

Inferring sex-specific demographic history from SNP data

PubMed Central

Gautier, Mathieu

2018-01-01

The relative female and male contributions to demography are of great importance to better understand the history and dynamics of populations. While earlier studies relied on uniparental markers to investigate sex-specific questions, the increasing amount of sequence data now enables us to take advantage of tens to hundreds of thousands of independent loci from autosomes and the X chromosome. Here, we develop a novel method to estimate effective sex ratios or ESR (defined as the female proportion of the effective population) from allele count data for each branch of a rooted tree topology that summarizes the history of the populations of interest. Our method relies on Kimura’s time-dependent diffusion approximation for genetic drift, and is based on a hierarchical Bayesian model to integrate over the allele frequencies along the branches. We show via simulations that parameters are inferred robustly, even under scenarios that violate some of the model assumptions. Analyzing bovine SNP data, we infer a strongly female-biased ESR in both dairy and beef cattle, as expected from the underlying breeding scheme. Conversely, we observe a strongly male-biased ESR in early domestication times, consistent with an easier taming and management of cows, and/or introgression from wild auroch males, that would both cause a relative increase in male effective population size. In humans, analyzing a subsample of non-African populations, we find a male-biased ESR in Oceanians that may reflect complex marriage patterns in Aboriginal Australians. Because our approach relies on allele count data, it may be applied on a wide range of species. PMID:29385127

Investigation of irradiated 1H-Benzo[b]pyrrole by ESR, thermal methods and learning algorithm

NASA Astrophysics Data System (ADS)

Algul, Gulay; Ceylan, Yusuf; Usta, Keziban; Yumurtaci Aydogmus, Hacer; Usta, Ayhan; Asik, Biray

2016-05-01

1H-Benzo[b]pyrrole samples were irradiated in the air with gamma source at 0.969 kGy per hour at room temperature for 24, 48 and 72 h. After irradiation, electron spin resonance, thermogravimetry analysis (TGA) and differential thermal analysis (DTA) measurements were immediately carried out on the irradiated and unirradiated samples. The ESR measurements were performed between 320 and 400 K. ESR spectra were recorded from the samples irradiated for 48 and 72 h. The obtained spectra were observed to be dependent on temperature. Two radical-type centres were detected on the sample. Detected radiation-induced radicals were attributed to R-+•NH and R=•CC2H2. The g-values and hyperfine constants were calculated by means of the experimental spectra. It was also determined from TGA spectrum that both the unirradiated and irradiated samples were decomposed at one step with the rising temperature. Moreover, a theoretical study was presented. Success of the machine learning methods was tested. It was found that bagging techniques, which are widely used in the machine learning literature, could optimise prediction accuracy noticeably.

An improved method of measuring tropospheric NO2, NO3, HO2, and RO2 by Matrix Isolation and Electronic Spin Resonance (MIESR)

NASA Technical Reports Server (NTRS)

1994-01-01

The MIESR method consists of two steps (1) collection of the radicals present in the ambient air at 77K in a polycrystalline D2O matrix and (2) identification and quantification of the different radicals in the laboratory by Electron Spin Resonance spectroscopy. In step (1), the sampling efficiency for sampling NO2 and RO2 was determined to be greater than or equal to 95 percent, with a measured accuracy of plus or minus 5 percent. In step (2), after collection, the samples are maintained at 77 K and spectra are recorded in the laboratory using a standard 9.5 GHz ESR system (Varian E-line). About 50 individual scans of each spectrum are recorded and digitally averaged in order to improve the signal-to-noise ratio. The ESR-spectra are analyzed with a recently developed numerical procedure which was demonstrated to allow speciation of NO2, NO3, HO2, CH3C(O)O2, and the sum of the alkylperoxy radicals. The detection limit is 5ppt for HO2, RO2, and NO2 and 3ppt for NO3 due to its narrower ESR-linewidth.

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

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.

ECOLOGICAL AND EVOLUTIONARY APPLICATIONS FOR ENVIRONMENTAL SEX REVERSAL OF FISH.

PubMed

Mcnair, Alistair; Lokman, P Mark; Closs, Gerard P; Nakagawa, Shinichi

2015-03-01

Environmental sex reversal (ESR), which results in a mismatch between genotypic and phenotypic sex, is well documented in numerous fish species and may be induced by chemical exposure. Historically, research involving piscine ESR has been carried out with a view to improving profitability in aquaculture or to elucidate the processes governing sex determination and sexual differentiation. However, recent studies in evolution and ecology suggest research on ESR now has much wider applications and ramifications. We begin with an overview of ESR in fish and a brief review of the traditional applications thereof. We then discuss ESR and its potential demographic consequences in wild populations. Theory even suggests sex-reversed fish may be purposefully released to manipulate population dynamics. We suggest new research directions that may prove fruitful in understanding how ESR at the individual level translates to population-level processes. In the latter portion of the review we focus on evolutionary applications of ESR. Sex-reversal studies from the aquaculture literature provide insight in to the evolvability of determinants of sexual phenotype. Additionally, induced sex reversal can provide information about the evolution of sex chromosomes and sex-linked traits. Recently, naturally occurring ESR has been implicated as a mechanism contributing to the evolution of sex chromosomes.

An electron spin resonance study for real-time detection of ascorbyl free radicals after addition of dimethyl sulfoxide in murine hippocampus or plasma during kainic acid-induced seizures.

PubMed

Matsumoto, Shigekiyo; Shingu, Chihiro; Koga, Hironori; Hagiwara, Satoshi; Iwasaka, Hideo; Noguchi, Takayuki; Yokoi, Isao

2010-07-01

Electron spin resonance (ESR)-silent ascorbate solutions generate a detectable, likely concentration-dependent signal of ascorbyl free radicals (AFR) immediately upon addition of a molar excess of dimethyl sulfoxide (DMSO). We aimed to perform quantitative ESR analysis of AFR in real time after addition of DMSO (AFR/DMSO) to evaluate ascorbate concentrations in fresh hippocampus or plasma following systemic administration of kainate in mice. Use of a special tissue-type quartz cell allowed immediate detection of AFR/DMSO ESR spectra in fresh tissues from mice. AFR/DMSO content was increased significantly in fresh hippocampus or plasma obtained during kainate-induced seizures of mice, reaching maximum levels at 90 min after intraperitoneal administration of 50 mg/kg kainic acid. This suggests that oxidative injury of the hippocampus resulted from the accumulation of large amounts of ascorbic acid in the brain after kainic acid administration. AFR/DMSO content measured on an ESR spectrometer can be used for real-time evaluation of ascorbate content in fresh tissue. Due to the simplicity, good performance, low cost and real-time monitoring of ascorbate, this method may be applied to clinical research and treatment in the future.

Identification of irradiated peppers by electron spin resonance, thermoluminescence and viscosity

NASA Astrophysics Data System (ADS)

Polónia, Isabel; Esteves, M. P.; Andrade, M. E.; Empis, J.

1995-02-01

White and black pepper purchased in local retailers were analysed by electron spin resonance (ESR), thermoluminescence (TL) and viscosimetry (VISC) in order to establish a viable method for identifying possibly irradiated peppers. Samples studied were non irradiated or irradiated in a cobalt-60 plant with the absorbed doses of 3, 5, 7 and 10 kGy. Confirming the data found in the literature TL was revealed by our results the best method to identify irradiated peppers. Nevertheless, the dose received by the samples could not be estimated. The ESR signal of irradiated peppers is similar to the spectrum of cellulose radical but very short lived at ambient temperature. The study on the alteration of viscosity of heat-treated alkaline pepper suspensions indicate that VISC is a very promising method for detection of irradiated peppers.

Inorganic Halogen Oxidizer Research

DTIC Science & Technology

1975-02-26

K. 0. Christe and C. J. Schack, Advances Inorg. Chem. Radiochem. 15. "The NF * Radical Cation. Esr Studies of Radiation Effects in NF„+ Salts...and 25°) in a wide variety of polar and nonpolar solvents, such as aqueous solutions, alcohols, ketones , esters, ethers , and aromatic and halogenated... Studies of Radiation Effects in NF, Salts = 4 S. P. Mishra, M. C R. Symons, K. 0. Christe, R. D. Wilson and R. I. Wagner Received. . . August .9

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

Tumor Genomic Profiling in Breast Cancer Patients Using Targeted Massively Parallel Sequencing

DTIC Science & Technology

2014-01-01

binding domain mutations in ESR1 ) were identified. Analysis is currently underway to further elucidate causes of resistance in those cases where the... ESR1 , the gene that encodes the estrogen receptor (Wagle, Garraway, and Arteaga, unpublished results). Given the potential importance of ESR...translocations in ER+ breast cancer, we have further modified our bait design to include genomic coordinates across select introns in ESR1 . In addition, two

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.

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.

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

Estrogen receptor alpha gene amplification in breast cancer: 25 years of debate

PubMed Central

Holst, Frederik

2016-01-01

Twenty-five years ago, Nembrot and colleagues reported amplification of the estrogen receptor alpha gene (ESR1) in breast cancer, initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration, which affects one of the most important genes in breast cancer. Since then, a multitude of studies on this topic has been published, covering a wide range of divergent results and arguments. The reported prevalence of this alteration in breast cancer ranges from 0% to 75%, suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues. To date, two major issues related to ESR1 amplification remain to be conclusively addressed: (1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1, and (2) the clinical relevance of ESR1 amplification: Such relevance is strongly disputed, with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies, or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1. This review provides a comprehensive summary of the various views on ESR1 amplification, and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research. PMID:27081639

Erythrocyte Sedimentation Rate and C-reactive Protein Measurements and Their Relevance in Clinical Medicine.

PubMed

Bray, Christopher; Bell, Lauren N; Liang, Hong; Haykal, Rasha; Kaiksow, Farah; Mazza, Joseph J; Yale, Steven H

2016-12-01

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are widely used laboratory markers of systemic inflammation. A thorough understanding of the similarities and differences between these two serological markers, including factors that affect measurements, is necessary for the proper utilization and interpretation of ESR and CRP. This review summarizes the current published literature (searched on MEDLINE through February 2016) surrounding the history and utilization of ESR and CRP, and examines factors that affect ESR and CRP measurements and discordance amongst these two inflammatory markers. As ESR and CRP lack sensitivity or specificity, these tests should be used only in combination with clinical history and physical exam for diagnosis and monitoring of pathological conditions. The clinical application of these tests in diagnosis is best applied to conditions in which there is high or low clinical probability of disease. Importantly, discrepancies between ESR and CRP measurements commonly have been reported in both inpatient and outpatient settings and this problem may be particularly prevalent in chronic inflammatory diseases. Numerous physiological factors, including noninfectious conditions and resolution of inflammation can contribute to abnormally high ESR/low CRP readings or vice versa. Although discordance may be encountered in certain settings, proper utilization of ESR and CRP measurements continues to play an important role in clinical management of many inflammatory and other conditions.

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.

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.

Pubertal Escape From Estradiol Negative Feedback in Ewe Lambs Is Not Accounted for by Decreased ESR1 mRNA or Protein in Kisspeptin Neurons.

PubMed

Bedenbaugh, Michelle N; D'Oliveira, Marcella; Cardoso, Rodolfo C; Hileman, Stanley M; Williams, Gary L; Amstalden, Marcel

2018-01-01

In this study, we investigated whether decreased sensitivity to estradiol negative feedback is associated with reduced estrogen receptor α (ESR1) expression in kisspeptin neurons as ewe lambs approach puberty. Lambs were ovariectomized and received no implant (OVX) or an implant containing estradiol (OVX+E). In the middle arcuate nucleus (mARC), ESR1 messenger RNA (mRNA) was greater in OVX than OVX+E lambs but did not differ elsewhere. Post hoc analysis of luteinizing hormone (LH) secretion from OVX+E lambs revealed three patterns of LH pulsatility: low [1 to 2 pulses per 12 hours; low frequency (LF), n = 3], moderate [6 to 7 pulses per 12 hours; moderate frequency (MF), n = 6], and high [>10 pulses per 12 hours; high frequency (HF), n = 5]. The percentage of kisspeptin neurons containing ESR1 mRNA in the preoptic area did not differ among HF, MF, or LF groups. However, the percentage of kisspeptin neurons containing ESR1 mRNA in the mARC was greater in HF (57%) than in MF (36%) or LF (27%) lambs and did not differ from OVX (50%) lambs. A higher percentage of kisspeptin neurons contained ESR1 protein in all regions of the arcuate nucleus (ARC) in OVX compared with OVX+E lambs. There were no differences in ESR1 protein among the HF, MF, or LF groups in the preoptic area or ARC. Contrary to our hypothesis, increases in LH pulsatility were associated with enhanced ESR1 mRNA abundance in kisspeptin neurons in the ARC, and absence of estradiol increased the percentage of kisspeptin neurons containing ESR1 protein in the ARC. Therefore, changes in the expression of ESR1, particularly in kisspeptin neurons in the ARC, do not explain the pubertal escape from estradiol negative feedback in ewe lambs. Copyright © 2018 Endocrine Society.

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 enrichment of sulfide in slag results in resulfurization in steel, which leads to lower desulfurization efficiency.

DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with ulcerative colitis (UC).

PubMed

Arasaradnam, Ramesh P; Khoo, Kevin; Bradburn, Mike; Mathers, John C; Kelly, Seamus B

2010-07-01

Epigenetic marking such as DNA methylation influence gene transcription and chromosomal stability and may also be affected by environmental exposures. Few studies exist on alteration in DNA methylation profiles (genomic and gene specific methylation) in patients with Ulcerative Colitis (UC) and no studies exist that assess its relationship with lifestyle exposures. The methylation level of both ESR-1 and N-33 genes were significantly higher in UC subjects compared with controls (7.9% vs. 5.9%; p = 0.015 and 66% vs. 9.3%; p < 0.001 respectively). There was no detectable difference in global DNA methylation between patients with UC and age and sex matched controls. No associations between indices of DNA methylation and anthropometric measures or smoking patterns were detected. To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor-1) and N-33 (tumor suppressor candidate-3) genes in the macroscopically normal mucosa of UC patients as well as to investigate effects of anthropometric and lifestyle exposures on DNA methylation. Sixty eight subjects were recruited (24 UC and 44 age and sex matched controls). Colorectal mucosal biopsies were obtained and DNA was extracted. Genomic DNA methylation was quantified using the tritium-labelled cytosine extension assay (3[H] dCTP) while gene specific methylation was quantified using the COBRA method. For the first time, we have shown increased methylation in the promoter regions of the putative tumor suppressor gene N-33 in macroscopically normal mucosa of patients with UC. In addition, we have confirmed that methylation of ESR-1 promoter is higher in UC patients compared with age and sex matched controls. These findings suggest that inactivation through methylation of the putative tumor suppressor genes N-33 and ESR-1 may not be associated with colorectal carcinogenesis in UC.

Sex steroid metabolism polymorphisms and mammographic density in pre- and early perimenopausal women

PubMed Central

Crandall, Carolyn J; Sehl, Mary E; Crawford, Sybil L; Gold, Ellen B; Habel, Laurel A; Butler, Lesley M; Sowers, MaryFran R; Greendale, Gail A; Sinsheimer, Janet S

2009-01-01

Introduction We examined the association between mammographic density and single-nucleotide polymorphisms (SNPs) in genes encoding CYP1A1, CYP1B1, aromatase, 17β-HSD, ESR1, and ESR2 in pre- and early perimenopausal white, African-American, Chinese, and Japanese women. Methods The Study of Women's Health Across the Nation is a longitudinal community-based cohort study. We analyzed data from 451 pre- and early perimenopausal participants of the ancillary SWAN Mammographic Density study for whom we had complete information regarding mammographic density, genotypes, and covariates. With multivariate linear regression, we examined the relation between percentage mammographic breast density (outcome) and each SNP (primary predictor), adjusting for age, race/ethnicity, parity, cigarette smoking, and body mass index (BMI). Results After multivariate adjustment, the CYP1B1 rs162555 CC genotype was associated with a 9.4% higher mammographic density than the TC/TT genotype (P = 0.04). The CYP19A1 rs936306 TT genotype was associated with 6.2% lower mammographic density than the TC/CC genotype (P = 0.02). The positive association between CYP1A1 rs2606345 and mammographic density was significantly stronger among participants with BMI greater than 30 kg/m2 than among those with BMI less than 25 kg/m2 (Pinteraction = 0.05). Among white participants, the ESR1 rs2234693 CC genotype was associated with a 7.0% higher mammographic density than the CT/TT genotype (P = 0.01). Conclusions SNPs in certain genes encoding sex steroid metabolism enzymes and ESRs were associated with mammographic density. Because the encoded enzymes and ESR1 are expressed in breast tissue, these SNPs may influence breast cancer risk by altering mammographic density. PMID:19630952

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.

Development of direct dating methods of fault gouges: Deep drilling into Nojima Fault, Japan

NASA Astrophysics Data System (ADS)

Miyawaki, M.; Uchida, J. I.; Satsukawa, T.

2017-12-01

It is crucial to develop a direct dating method of fault gouges for the assessment of recent fault activity in terms of site evaluation for nuclear power plants. This method would be useful in regions without Late Pleistocene overlying sediments. In order to estimate the age of the latest fault slip event, it is necessary to use fault gouges which have experienced high frictional heating sufficient for age resetting. It is said that frictional heating is higher in deeper depths, because frictional heating generated by fault movement is determined depending on the shear stress. Therefore, we should determine the reliable depth of age resetting, as it is likely that fault gouges from the ground surface have been dated to be older than the actual age of the latest fault movement due to incomplete resetting. In this project, we target the Nojima fault which triggered the 1995 Kobe earthquake in Japan. Samples are collected from various depths (300-1,500m) by trenching and drilling to investigate age resetting conditions and depth using several methods including electron spin resonance (ESR) and optical stimulated luminescence (OSL), which are applicable to ages later than the Late Pleistocene. The preliminary results by the ESR method show approx. 1.1 Ma1) at the ground surface and 0.15-0.28 Ma2) at 388 m depth, respectively. These results indicate that samples from deeper depths preserve a younger age. In contrast, the OSL method dated approx. 2,200 yr1) at the ground surface. Although further consideration is still needed as there is a large margin of error, this result indicates that the age resetting depth of OSL is relatively shallow due to the high thermosensitivity of OSL compare to ESR. In the future, we plan to carry out further investigation for dating fault gouges from various depths up to approx. 1,500 m to verify the use of these direct dating methods.1) Kyoto University, 2017. FY27 Commissioned for the disaster presentation on nuclear facilities (Drilling borehole survey at the Nojima fault), Technical Report. (in Japanese)2) T. Fukuchi, 2001, Assessment of fault activity by ESR dating of fault gouge; an example of the 500m core samples drilled into the Nojima Earthquake Fault in Japan. Quaternary Science Reviews, 20, 1005-1008.

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 investigating DEF. Moreover, these results alert to the importance of controlling the size-position of nanoparticles to enhance DEF.« less

Roles of Estrogen Receptor-α and the Coactivator MED1 During Human Endometrial Decidualization

PubMed Central

Kaya Okur, Hatice S.; Das, Amrita; Taylor, Robert N.; Bagchi, Indrani C.

2016-01-01

The steroid hormones 17β-estradiol and progesterone are critical regulators of endometrial stromal cell differentiation, known as decidualization, which is a prerequisite for successful establishment of pregnancy. The present study using primary human endometrial stromal cells (HESCs) addressed the role of estrogen receptor-α (ESR1) in decidualization. Knockdown of ESR1 transcripts by RNA interference led to a marked reduction in decidualization of HESCs. Gene expression profiling at an early stage of decidualization indicated that ESR1 negatively regulates several cell cycle regulatory factors, thereby suppressing the proliferation of HESCs as these cells enter the differentiation program. ESR1 also controls the expression of WNT4, FOXO1, and progesterone receptor (PGR), well-known mediators of decidualization. Whereas ESR1 knockdown strongly inhibited the expression of FOXO1 and WNT4 transcripts within 24 hours of the initiation of decidualization, PGR expression remained unaffected at this early time point. Our study also revealed a major role of cAMP signaling in influencing the function of ESR1 during decidualization. Using a proteomic approach, we discovered that the cAMP-dependent protein kinase A (PKA) phosphorylates Mediator 1 (MED1), a subunit of the mediator coactivator complex, during HESC differentiation. Using immunoprecipitation, we demonstrated that PKA-phosphorylated MED1 interacts with ESR1. The PKA-dependent phosphorylation of MED1 was also correlated with its enhanced recruitment to estrogen-responsive elements in the WNT4 gene. Knockdown of MED1 transcripts impaired the expression of ESR1-induced WNT4 and FOXO1 transcripts and blocked decidualization. Based on these findings, we conclude that modulation of ESR1-MED1 interactions by cAMP signaling plays a critical role in human decidualization. PMID:26849466

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.

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.

Developmental programming: Impact of fetal exposure to endocrine disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus

PubMed Central

Mahoney, Megan M.; Padmanabhan, Vasantha

2010-01-01

Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine disrupting chemicals (EDCs) with estrogenic and anti-androgenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude and MXC on LH surge timing in sheep. The neural mechanisms involved in differential disruption of the LH surge by these two EDCs remains to be elucidated. We tested the hypothesis that differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2 mRNA expression. Pregnant sheep were given daily injections of cottonseed oil (controls), MXC or BPA (5 mg/kg/day) from day 30 to 90 of gestation (term 147 d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F2α, just prior to the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female. PMID:20621667

Developmental programming: Impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus

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

Mahoney, Megan M.; Padmanabhan, Vasantha, E-mail: vasantha@umich.ed

Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine-disrupting chemicals (EDCs) with estrogenic and antiandrogenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude, and MXC has profound effects on on LH surge timing in sheep. The neural mechanisms involved in the differential disruption of the LH surge by these two EDCs remain to be elucidated. We tested the hypothesis that the differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin-releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2, mRNA expression. Pregnant sheep were given daily injections of cottonseedmore » oil (controls), MXC, or BPA (5 mg/kg/day) from day 30 to 90 of gestation (term 147 d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F{sub 2{alpha}}, just before the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast, ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female.« less

Developmental programming: impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus.

PubMed

Mahoney, Megan M; Padmanabhan, Vasantha

2010-09-01

Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine-disrupting chemicals (EDCs) with estrogenic and antiandrogenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude, and MXC has profound effects on on LH surge timing in sheep. The neural mechanisms involved in the differential disruption of the LH surge by these two EDCs remain to be elucidated. We tested the hypothesis that the differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin-releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2, mRNA expression. Pregnant sheep were given daily injections of cottonseed oil (controls), MXC, or BPA (5mg/kg/day) from day 30 to 90 of gestation (term 147d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F(2alpha), just before the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast, ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female. 2010 Elsevier Inc. All rights reserved.

Functional Analysis of Nuclear Estrogen Receptors in Zebrafish Reproduction by Genome Editing Approach.

PubMed

Lu, Huijie; Cui, Yong; Jiang, Liwen; Ge, Wei

2017-07-01

Estrogens signal through both nuclear and membrane receptors with most reported effects being mediated via the nuclear estrogen receptors (nERs). Although much work has been reported on nERs in the zebrafish, there is a lack of direct genetic evidence for their functional roles and importance in reproduction. To address this issue, we undertook this study to disrupt all three nERs in the zebrafish, namely esr1 (ERα), esr2a (ERβII), and esr2b (ERβI), by the genome-editing technology clustered regularly interspaced short palindromic repeats and its associated nuclease (CRISPR/Cas9). Using this loss-of-function genetic approach, we successfully created three mutant zebrafish lines with each nER knocked out. In addition, we also generated all possible double and triple knockouts of the three nERs. The phenotypes of these mutants in reproduction were analyzed in all single, double, and triple nER knockouts in both females and males. Surprisingly, all three single nER mutant fish lines display normal reproductive development and function in both females and males, suggesting functional redundancy among these nERs. Further analysis of double and triple knockouts showed that nERs, especially Esr2a and Esr2b, were essential for female reproduction, and loss of these two nERs led to an arrest of folliculogenesis at previtellogenic stage II followed by sex reversal from female to male. In addition, the current study also revealed a unique role for Esr2a in follicle cell proliferation and transdifferentiation, follicle growth, and chorion formation. Taken together, this study provides the most comprehensive genetic analysis for differential functions of esr1, esr2a, and esr2b in fish reproduction. Copyright © 2017 Endocrine Society.

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

Effects of equivalent series resistance on the noise mitigation performance of piezoelectric shunt damping

NASA Astrophysics Data System (ADS)

Lai, Szu Cheng; Sharifzadeh Mirshekarloo, Meysam; Yao, Kui

2017-05-01

Piezoelectric shunt damping (PSD) utilizes an electrically-shunted piezoelectric damper attached on a panel structure to suppress the transmission of acoustic noise. The paper develops an understanding on the effects of equivalent series resistance (ESR) of the piezoelectric damper in a PSD system on noise mitigation performance, and demonstrates that an increased ESR leads to a significant rise in the noise transmissibility due to reduction in the system’s mechanical damping. It is further demonstrated with experimental results that ESR effects can be compensated in the shunt circuit to significantly improve the noise mitigation performance. A theoretical electrical equivalent model of the PSD incorporating the ESR is established for quantitative analysis of ESR effects on noise mitigation.

SDSL-ESR-based protein structure characterization.

PubMed

Strancar, Janez; Kavalenka, Aleh; Urbancic, Iztok; Ljubetic, Ajasja; Hemminga, Marcus A

2010-03-01

As proteins are key molecules in living cells, knowledge about their structure can provide important insights and applications in science, biotechnology, and medicine. However, many protein structures are still a big challenge for existing high-resolution structure-determination methods, as can be seen in the number of protein structures published in the Protein Data Bank. This is especially the case for less-ordered, more hydrophobic and more flexible protein systems. The lack of efficient methods for structure determination calls for urgent development of a new class of biophysical techniques. This work attempts to address this problem with a novel combination of site-directed spin labelling electron spin resonance spectroscopy (SDSL-ESR) and protein structure modelling, which is coupled by restriction of the conformational spaces of the amino acid side chains. Comparison of the application to four different protein systems enables us to generalize the new method and to establish a general procedure for determination of protein structure.

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.

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.

Diffusion studies on permeable nitroxyl spin probe through lipid bilayer membrane

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

Benial, A. Milton Franklin; Meenakumari, V.; Ichikawa, Kazuhiro

2014-04-24

Electron spin resonance (ESR) studies were carried out for 2mM {sup 14}N labeled deutrated permeable 3- methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL) in pure water, 1 mM, 2 mM, 3 mM and 4 mM concentration of MC-PROXYL in 300 mM concentration of liposomal solution by using a L-band ESR spectrometer. The ESR parameters such as linewidth, hyperfine coupling constant, g-factor, partition parameter and permeability were reported. The partition parameter and permeability values indicate the maximum spin distribution in the lipid phase at 2 mM concentration. This study illustrates that ESR can be used to differentiate between the intra and extra-membrane water by loading themore » liposome vesicles with a lipid-permeable nitroxyl spin probe. From the ESR results, the radical concentration was optimized as 2 mM in liposomal solution for ESR phantom studies and experiments.« 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 the ClO2 radical. This result indicates that an unpaired electron of the ClO2 radical is localized on oxygen atom, because nitroso spin-traps cannot form the stable spin adduct with oxygen-centered radical.

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.

Validity and Agreement between the 28-Joint Disease Activity Score Based on C-Reactive Protein and Erythrocyte Sedimentation Rate in Patients with Rheumatoid Arthritis

PubMed Central

Nielung, Louise; Christensen, Robin; Danneskiold-Samsøe, Bente; Bliddal, Henning; Holm, Christian Cato; Ellegaard, Karen; Slott Jensen, Hanne; Bartels, Else Marie

2015-01-01

Objective. To validate the agreement between the 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) and the 28-joint disease activity score based on C-reactive protein (DAS28-CRP) in a group of Danish patients with rheumatoid arthritis (RA). Methods. Data from 109 Danish RA patients initiating biologic treatment were analysed at baseline and following one year of treatment. Participants were retrospectively enrolled from a previous cohort study and were considered eligible for this project if CRP and ESR were measured at baseline and at the follow-up visit. To assess the extent of agreement between the two DAS28 definitions, the “European League Against Rheumatism” (EULAR) response criteria based on each definition were calculated with cross-classification. Weighted Kappa (κ) coefficients were calculated, and Bland-Altman plots were used to illustrate degree of agreement between DAS28 definitions. Results. The 75 eligible patients were classified as EULAR good, moderate, and nonresponders with good agreement (61/75; 81%) between DAS28-CRP and DAS28-ESR (κ = 0.75 (95% CI: 0.63 to 0.88)). Conclusions. According to our findings, DAS28-CRP and DAS28-ESR are interchangeable when assessing RA patients and the two versions of DAS28 are comparable between studies. PMID:25632353

Free-radical reactions induced by OH-radical attack on cytosine-related compounds: a study by a method combining ESR, spin trapping and HPLC.

PubMed Central

Hiraoka, W; Kuwabara, M; Sato, F; Matsuda, A; Ueda, T

1990-01-01

Free-radical reactions induced by OH-radical attack on cytosine-related compounds were investigated by a method combining ESR, spin trapping with 2-methyl-2-nitrosopropane and high-performance liquid chromatography (HPLC). Cytidine, 2'-deoxycytidine, cytidine 3'-monophosphate, cytidine 5'-monophosphate, 2'-deoxycytidine 5'-monophosphate and their derivatives, of which 5,6-protons at the base moiety were replaced by deuterons, and polycytidylic acid (poly(C] were employed as samples. OH radicals were generated by X-irradiating an N2O-saturated aqueous solution. Five spin adducts were separated by HPLC. Examination of them by ESR spectroscopy and UV photospectrometry showed that spin adducts assigned to C5 and C6 radicals due to OH addition to the 5,6 double-bond, a deaminated form of the spin adduct derived from a C5 radical due to the cyclization reaction between C5' of the sugar and C6 of the base, and a spin adduct assigned to the C4' radical due to H abstraction by OH radicals were produced. From these results the sites of OH-radical attack and the subsequent radical reactions in cytosine-related compounds were clarified. PMID:2157193

Measurement of electron paramagnetic resonance using terahertz time-domain spectroscopy.

PubMed

Kozuki, Kohei; Nagashima, Takeshi; Hangyo, Masanori

2011-12-05

We present a frequency-domain electron spin resonance (ESR) measurement system using terahertz time-domain spectroscopy. A crossed polarizer technique is utilized to increase the sensitivity in detecting weak ESR signals of paramagnets caused by magnetic dipole transitions between magnetic sublevels. We demonstrate the measurements of ESR signal of paramagnetic copper(II) sulfate pentahydrate with uniaxial anisotropy of the g-factor under magnetic fields up to 10 T. The lineshape of the obtained ESR signals agrees well with the theoretical predictions for a powder sample with the uniaxial anisotropy.

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

Some dinophycean red tide plankton species generate a superoxide scavenging substance.

PubMed

Sato, Emiko; Niwano, Yoshimi; Matsuyama, Yukihiko; Kim, Daekyung; Nakashima, Takuji; Oda, Tatsuya; Kohno, Masahiro

2007-03-01

Recent studies indicate that some raphidophycean red tide flagellates produce substances able to scavenge superoxide, whereas there have been no reports on superoxide scavenger production by dinophycean red tide flagellates. In this study, we examined the superoxide-scavenging activity of aqueous extracts from dinophycean red tide flagellates, Gymnodinium spp., Scrippsiella trochoidea, and Karenia sp., by a luminol analog L-012-dependent chemiluminescence (CL) method and an electron spin resonance (ESR)-spin trapping method, and compared the activity to that of raphidophycean red tide flagellates, Chattonella spp., Heterosigma akashiwo, and Fibrocapsa japonica. In the experiment applying the L-012-dependent CL method, only the aqueous extracts from raphidophycean red tide flagellates showed superoxide-scavenging activity. On the other hand, applying the ESR-spin trapping method, we found that the aqueous extracts from dinophycean red tide flagellates also showed superoxide-scavenging activity. This is the first report on the production of a superoxide-scavenger by dinophycean red tide flagellates.

Prognostic significance of ESR1 gene amplification, mRNA/protein expression and functional profiles in high-risk early breast cancer: a translational study of the Hellenic Cooperative Oncology Group (HeCOG).

PubMed

Pentheroudakis, George; Kotoula, Vassiliki; Eleftheraki, Anastasia G; Tsolaki, Eleftheria; Wirtz, Ralph M; Kalogeras, Konstantine T; Batistatou, Anna; Bobos, Mattheos; Dimopoulos, Meletios A; Timotheadou, Eleni; Gogas, Helen; Christodoulou, Christos; Papadopoulou, Kyriaki; Efstratiou, Ioannis; Scopa, Chrisoula D; Papaspyrou, Irene; Vlachodimitropoulos, Dimitrios; Linardou, Helena; Samantas, Epaminontas; Pectasides, Dimitrios; Pavlidis, Nicholas; Fountzilas, George

2013-01-01

Discrepant data have been published on the incidence and prognostic significance of ESR1 gene amplification in early breast cancer. Formalin-fixed paraffin-embedded tumor blocks were collected from women with early breast cancer participating in two HeCOG adjuvant trials. Messenger RNA was studied by quantitative PCR, ER protein expression was centrally assessed using immunohistochemistry (IHC) and ESR1 gene copy number by dual fluorescent in situ hybridization probes. In a total of 1010 women with resected node-positive early breast adenocarcinoma, the tumoral ESR1/CEP6 gene ratio was suggestive of deletion in 159 (15.7%), gene gain in 551 (54.6%) and amplification in 42 cases (4.2%), with only 30 tumors (3%) harboring five or more ESR1 copies. Gene copy number ratio showed a significant, though weak correlation to mRNA and protein expression (Spearman's Rho <0.23, p = 0.01). ESR1 clusters were observed in 9.5% (57 gain, 38 amplification) of cases. In contrast to mRNA and protein expression, which were favorable prognosticators, gene copy number changes did not obtain prognostic significance. When ESR1/CEP6 gene ratio was combined with function (as defined by ER protein and mRNA expression) in a molecular classifier, the Gene Functional profile, it was functional status that impacted on prognosis. In univariate analysis, patients with functional tumors (positive ER protein expression and gene ratio normal or gain/amplification) fared better than those with non-functional tumors with ESR1 gain (HR for relapse or death 0.49-0.64, p = 0.003). Significant interactions were observed between gene gain/amplification and paclitaxel therapy (trend for DFS benefit from paclitaxel only in patients with ESR1 gain/amplification, p = 0.066) and Gene Functional profile with HER2 amplification (Gene Functional profile prognostic only in HER2-normal cases, p = 0.029). ESR1 gene deletion and amplification do not constitute per se prognostic markers, instead they can be classified to distinct prognostic groups according to their protein-mediated functional status.

The anti-oestrogen fulvestrant (ICI 182,780) reduces the androgen receptor expression, ERK1/2 phosphorylation and cell proliferation in the rat ventral prostate.

PubMed

Fernandes, S A F; Gomes, G R O; Siu, E R; Damas-Souza, D M; Bruni-Cardoso, A; Augusto, T M; Lazari, M F M; Carvalho, H F; Porto, C S

2011-10-01

This study proposed to investigate further the role of oestrogens during pubertal growth of rat ventral prostate, by analysing the effect of anti-oestrogen fulvestrant (ICI 182,780) on the expression of androgen (AR) and oestrogen receptors (ESR1 and ESR2), mitogen-activated protein kinase (ERK1/2) phosphorylation, and expression of Ki-67, a biomarker for cell proliferation. Ventral prostates were obtained from 90-day-old rats treated once a week for 2 months with vehicle (control) or ICI 182,780 (10 mg/rat, s.c.). Transcripts for AR, ESR1 and ESR2 were evaluated by quantitative real-time polymerase chain reaction. Expression of AR, ESR1, ESR2, total and phospho-ERK1/2 was analysed by Western blot or immunofluorescence. Ki-67-positive cells and myosin heavy chain were detected by immunohistochemistry. Cylindrical epithelial cells slightly taller, epithelial dysplasia and an increase in smooth muscle layer were observed in the ventral prostate from ICI 182,780-treated rats. ICI 182,780 did not change the mRNA, but decreased the protein levels for AR in the ventral prostate. The expression of ESR1 (mRNA and protein) was upregulated by ICI 182,780, but no changes were observed on ESR2 expression (mRNA and protein). ICI 182,780 decreased the phosphorylation state of ERK1/2, with no changes in total ERK1/2 levels. Ki-67-positive cells in the ventral prostate were also decreased by ICI 182,780. In conclusion, ICI 182,780 induces downregulation of AR expression and may block the translocation of ESR1 and ESR2 from the nucleus to the plasma membrane, decreasing ERK1/2 phosphorylation and prostatic epithelial cell proliferation. These findings provide a basis for physiological roles of oestrogen in the ventral prostate. Further studies with fulvestrant are necessary in benign prostate hyperplasia and prostatic cancer models. © 2010 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

Around Semipalatinsk nuclear test site: progress of dose estimations relevant to the consequences of nuclear tests (a summary of 3rd Dosimetry Workshop on the Semipalatinsk nuclear test site area, RIRBM, Hiroshima University, Hiroshima, 9-11 of March, 2005).

PubMed

Stepanenko, Valeriy F; Hoshi, Masaharu; Bailiff, Ian K; Ivannikov, Alexander I; Toyoda, Shin; Yamamoto, Masayoshi; Simon, Steven L; Matsuo, Masatsugu; Kawano, Noriyuki; Zhumadilov, Zhaxybay; Sasaki, Masao S; Rosenson, Rafail I; Apsalikov, Kazbek N

2006-02-01

The paper is an analytical overview of the main results presented at the 3rd Dosimetry Workshop in Hiroshima(9-11 of March 2005), where different aspects of the dose reconstruction around the Semipalatinsk nuclear test site(SNTS) were discussed and summarized. The results of the international intercomparison of the retrospective luminescence dosimetry(RLD) method for Dolon' village(Kazakhstan) were presented at the Workshop and good concurrence between dose estimations by different laboratories from 6 countries (Japan, Russia, USA, Germany, Finland and UK) was pointed out. The accumulated dose values in brick for a common depth of 10mm depth obtained independently by all participating laboratories were in good agreement for all four brick samples from Dolon' village, Kazakhstan, with the average value of the local gamma dose due to fallout (near the sampling locations) being about 220 mGy(background dose has been subtracted).Furthermore, using a conversion factor of about 2 to obtain the free-in-air dose, a value of local dose approximately 440 mGy is obtained, which supports the results of external dose calculations for Dolon': recently published soil contamination data, archive information and new models were used for refining dose calculations and the external dose in air for Dolon village was estimated to be about 500 mGy. The results of electron spin resonance(ESR) dosimetry with tooth enamel have demonstrated the notable progress in application of ESR dosimetry to the problems of dose reconstruction around the Semipalatinsk nuclear test site. At the present moment, dose estimates by the ESR method have become more consistent with calculated values and with retrospective luminescence dosimetry data, but differences between ESR dose estimates and RLD/calculation data were noted. For example mean ESR dose for eligible tooth samples from Dolon' village was estimated to be about 140 mGy(above background dose), which is less than dose values obtained by RLD and calculations. A possible explanation of the differences between ESR and RLD/calculations doses is the following: for interpretation of ESR data the "shielding and behaviour" factors for investigated persons should be taken into account. The "upper level" of the combination of "shielding and behaviour" factors of dose reduction for inhabitants of Dolon' village of about 0.28 was obtained by comparing the individual ESR tooth enamel dose estimates with the calculated mean dose for this settlement. The biological dosimetry data related to the settlements near SNTS were presented at the Workshop. A higher incidence of unstable chromosome aberrations, micronucleus in lymphocytes, nuclear abnormalities of thyroid follicular cells, T-cell receptor mutations in peripheral blood were found for exposed areas (Dolon', Sarjal) in comparison with unexposed ones(Kokpekty). The significant greater frequency of stable translocations (results of analyses of chromosome aberrations in lymphocytes by the FISH technique) was demonstrated for Dolon' village in comparison with Chekoman(unexposed village). The elevated level of stable translocations in Dolon' corresponds to a dose of about 180 mSv, which is close to the results of ESR dosimetry for this village. The importance of investigating specific morphological types of thyroid nodules for thyroid dosimetry studies was pointed out. In general the 3rd Dosimetry Workshop has demonstrated remarkable progress in developing an international level of common approaches for retrospective dose estimations around the SNTS and in understanding the tasks for the future joint work in this direction. In the framework of a special session the problems of developing a database and registry in order to support epidemiological studies around SNTS were discussed. The results of investigation of psychological consequences of nuclear tests, which are expressed in the form of verbal behaviour, were presented at this session as well.

Prenatal Bisphenol A Exposure Alters Sex-Specific Estrogen Receptor Expression in the Neonatal Rat Hypothalamus and Amygdala

PubMed Central

Patisaul, Heather B.

2013-01-01

Bisphenol A (BPA) exposure is ubiquitous, and in laboratory animals, early-life BPA exposure has been shown to alter sex-specific neural organization, neuroendocrine physiology, and behavior. The specific mechanisms underlying these brain-related outcomes, however, remain largely unknown, constraining the capacity to ascertain the potential human relevance of neural effects observed in animal models. In the perinatal rat brain, estrogen is masculinizing, suggesting that BPA-induced perturbation of estrogen receptor (ESR) expression may underpin later in-life neuroendocrine effects. We hypothesized that prenatal BPA exposure alters sex-specific ESR1 (ERα) and ESR2 (ERβ) expression in postnatal limbic nuclei. Sprague Dawley rats were mated and gavaged on gestational days (GDs) 6–21 with vehicle, 2.5 or 25 μg/kg bw/day BPA, or 5 or 10 μg/kg bw/day ethinyl estradiol. An additional group was restrained but not gavaged (naïve control). Offspring were sacrificed the day after birth to quantify ESR gene expression throughout the hypothalamus and amygdala by in situ hybridization. Relative to the vehicle group, significant effects of BPA were observed on ESR1 and ESR2 expression throughout the mediobasal hypothalamus and amygdala in both sexes. Significant differences in ESR expression were also observed in the mediobasal hypothalamus and amygdala of the naïve control group compared with the vehicle group, highlighting the potential for gavage to influence gene expression in the developing brain. These results indicate that ESR expression in the neonatal brain of both sexes can be altered by low-dose prenatal BPA exposure. PMID:23457122

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

Numerical dating of a Late Quaternary spit-shoreline complex at the northern end of Silver Lake playa, Mojave Desert, California: A comparison of the applicability of radiocarbon, luminescence, terrestrial cosmogenic nuclide, electron spin resonance, U-series and amino acid racemization methods

USGS Publications Warehouse

Owen, L.A.; Bright, Jordon; Finkel, R.C.; Jaiswal, M.K.; Kaufman, D.S.; Mahan, S.; Radtke, U.; Schneider, J.S.; Sharp, W.; Singhvi, A.K.; Warren, C.N.

2007-01-01

A Late Quaternary spit-shoreline complex on the northern shore of Pleistocene Lake Mojave of southeastern California, USA was studied with the goal of comparing accelerator mass spectrometry (AMS) radiocarbon, luminescence, electron spin resonance (ESR), terrestrial cosmogenic radionuclide (TCN) surface exposure, amino acid racemization (AAR) and U-series dating methods. The pattern of ages obtained by the different methods illustrates the complexity of processes acting in the lakeshore environment and highlights the utility of a multi-method approach. TCN surface exposure ages (mostly ???20-30 ka) record the initial erosion of shoreline benches, whereas radiocarbon ages on shells (determined in this and previous studies) within the spit, supported by AAR data, record its construction at fluctuating lake levels from ???16 to 10 ka. Luminescence ages on spit sediment (???6-7 ka) and ESR ages on spit shells (???4 ka) are anomalously young relative to radiocarbon ages of shells within the same deposits. The significance of the surprisingly young luminescence ages is not clear. The younger ESR ages could be a consequence of post-mortem enrichment of U in the shells. High concentrations of detrital thorium in tufa coating spit gravels inhibited the use of single-sample U-series dating. Detailed comparisons such as this provide one of the few means of assessing the accuracy of Quaternary dating techniques. More such comparisons are needed. ?? 2007 Elsevier Ltd and INQUA.

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.

The ground state of metallic nano-structures in heavily irradiated NaCl-KBF4

NASA Astrophysics Data System (ADS)

Cherkasov, F. G.; L'Vov, S. G.; Tikhonov, D. A.; den Hartog, H. W.; Vainshtein, D. I.

ESR, NMR and static magnetic susceptibility measurements of heavily irradiated NaCl-K and NaCl-KBF4 are reported. Up to 10% of the NaCl-molecules are transformed into metallic Na nanoparticles and Cl-2 precipitates. In addition, there are paramagnetic F- and F-aggregates, which are coupled by exchange interactions to the conduction electrons in the nanoparticles. Above 160 K the NMR and ESR signals of NaCl-K and NaCl-KBF4 show Pauli paramagnetism and the properties of the Na nanoparticles are similar to bulk sodium. A single ESR line is observed revealing exchange interaction between conduction electrons in the nano-particles and F-aggregates. The observed decrease of the ESR susceptibility with decreasing temperature is due to a metal-insulator transition. The conduction electrons are localized below 40 K and the above mentioned F-aggregate centers contribute significantly to the overall ESR signal. For NaCl-KBF4 we observed that with decreasing temperature the ESR line shifts towards lower fields due to antiferromagnetic ordering and internal magnetic fields.

Complementary deoxyribonucleic acid cloning of spermatogonial stem cell renewal factor.

PubMed

Miura, Takeshi; Ohta, Takashi; Miura, Chiemi I; Yamauchi, Kohei

2003-12-01

Spermatogonial mitosis can be subdivided into two processes: spermatogonial stem cell renewal and spermatogonial proliferation toward meiosis. Recently it has been indicated that estrogen, estradiol-17beta, is involved in regulating the renewal of spermatogonial stem cells in eel. To determine the genes that directly regulate this process, we used expression screening to identify genes whose expression is regulated by estradiol-17beta in testes. We detected a previously unidentified cDNA clone that is up-regulated by estradiol-17beta stimulation and named it eel spermatogenesis-related substances 34 (eSRS34) cDNA. Homology searching showed that eSRS34 shares amino acid sequence similarity with human platelet-derived endothelial cell growth factor. We examined the function of eSRS34 using several in vitro systems. Recombinant eSRS34 produced by a baculovirus system induced spermatogonial mitosis in testicular organ culture. Furthermore, the addition of an antibody specific for eSRS34 prevented spermatogonial mitosis induced by estradiol-17beta stimulation in a germ cell/somatic cell coculture system. We therefore conclude that eSRS34 is a "spermatogonial stem cell renewal factor."

The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

PubMed Central

Shor, Erika; Fox, Catherine A.; Broach, James R.

2013-01-01

Conditions of chronic stress are associated with genetic instability in many organisms, but the roles of stress responses in mutagenesis have so far been elucidated only in bacteria. Here, we present data demonstrating that the environmental stress response (ESR) in yeast functions in mutagenesis induced by proteotoxic stress. We show that the drug canavanine causes proteotoxic stress, activates the ESR, and induces mutagenesis at several loci in an ESR-dependent manner. Canavanine-induced mutagenesis also involves translesion DNA polymerases Rev1 and Polζ and non-homologous end joining factor Ku. Furthermore, under conditions of chronic sub-lethal canavanine stress, deletions of Rev1, Polζ, and Ku-encoding genes exhibit genetic interactions with ESR mutants indicative of ESR regulating these mutagenic DNA repair processes. Analyses of mutagenesis induced by several different stresses showed that the ESR specifically modulates mutagenesis induced by proteotoxic stress. Together, these results document the first known example of an involvement of a eukaryotic stress response pathway in mutagenesis and have important implications for mechanisms of evolution, carcinogenesis, and emergence of drug-resistant pathogens and chemotherapy-resistant tumors. PMID:23935537

Mechanical detection of electron spin resonance beyond 1 THz

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

Takahashi, Hideyuki; Ohmichi, Eiji; Ohta, Hitoshi

2015-11-02

We report the cantilever detection of electron spin resonance (ESR) in the terahertz (THz) region. This technique mechanically detects ESR as a change in magnetic torque that acts on the cantilever. The ESR absorption of a tiny single crystal of Co Tutton salt, Co(NH{sub 4}){sub 2}(SO{sub 4}){sub 2}⋅6H{sub 2}O, was observed in frequencies of up to 1.1 THz using a backward travelling wave oscillator as a THz-wave source. This is the highest frequency of mechanical detection of ESR till date. The spectral resolution was evaluated with the ratio of the peak separation to the sum of the half-width at halfmore » maximum of two absorption peaks. The highest resolution value of 8.59 ± 0.53 was achieved at 685 GHz, while 2.47 ± 0.01 at 80 GHz. This technique will not only broaden the scope of ESR spectroscopy application but also lead to high-spectral-resolution ESR imaging.« less

Effect of electroslag remelting on carbides in 8Cr13MoV martensitic stainless steel

NASA Astrophysics Data System (ADS)

Zhu, Qin-tian; Li, Jing; Shi, Cheng-bin; Yu, Wen-tao

2015-11-01

The effect of electroslag remelting (ESR) on carbides in 8Cr13MoV martensitic stainless steel was experimentally studied. Phases precipitated from liquid steel during solidification were calculated using the Thermo-Calc software. The carbon segregation was analyzed by original position analysis (OPA), and the carbides were analyzed by optical microscopy (OM), scanning electron microscopy (SEM), energy- dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). The results indicated that more uniform carbon distribution and less segregation were obtained in the case of samples subjected to the ESR process. After ESR, the amount of netty carbides decreased significantly, and the chromium and vanadium contents in the grain-boundary carbides was reduced. The total area and average size of carbides were obviously smaller after the ESR process. In the sample subjected to ESR, the morphology of carbides changed from lamellar and angular to globular or lump, whereas the types of carbides did not change; both M23C6 and M7C3 were present before and after the ESR process.

Accident investigation practices in Europe--main responses from a recent study of accidents in industry and transport.

PubMed

Roed-Larsen, Sverre; Valvisto, T; Harms-Ringdahl, L; Kirchsteiger, C

2004-07-26

Europe has during recent years been shocked by disasters from natural events and technical breakdowns. The consequences have been comprehensive, measured by lost lives, injuries, and material and environmental damage. ESReDA wanted in 2000--by setting up a special expert group on accident investigation--to clarify the state of art of accident investigation practices and to map the use of thoroughly accident investigation in order to learn lessons from past disasters and prevent new ones. The scope was to cover three sectors in the society: transport, production processes and storage of hazardous materials, and energy production. The main method used was a questionnaire, which was sent in 2001 to about 150 organisations. About 50 replies were analysed. The replies showed great variations but also similarities, among others in definition of accident and incident, the objectives of the investigation team, criteria used to start an investigation, the status of the investigation organisation, the flow of information, the composition of the investigation team, and the use of internal or international procedures or rules. Several methods (in total 14 different methods were mentioned) were used for carrying out accident /incident investigations. Most of the respondents were willing to co-operate in one or another way with ESReDA. Although there are important biases in the material, the results from questionnaire are important inputs to the future work of ESReDA Expert group in this field. 3 safety approaches have been identified.

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.

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.

Molecular characterization of five steroid receptors from pengze crucian carp and their expression profiles of juveniles in response to 17α-ethinylestradiol and 17α-methyltestosterone.

PubMed

Zheng, Yao; Wang, Lihong; Li, Meng; Liang, Hongwei; Qin, Fang; Liu, Shaozhen; Wang, Houpeng; Wu, Tingting; Zhang, Yingying; Wang, Zaizhao

2013-09-15

Pengze crucian carp (Carassius auratus var. pengze, Pcc), a triploid gynogenetic fish, was used in this study to investigate the cross-talk between EDCs and steroid receptors. The full-length cDNAs of five steroid receptors (esr1, er alpha2, esr2a, esr2b, ar) and partial cDNA of vtg B were isolated. The tissue distributions of these genes were analyzed in adult fish by qRT-PCR. Then the expression profiles of five steroid receptors (esrs and ar) and vtg B were detected in the juveniles exposed to 17α-ethinylestradiol (EE2, 0.1, 1 and 10ng/L) and 17α-methyltestosterone (MT, 50μg/L) for 4weeks. The results demonstrated that esrs, ar, and vtg B were predominantly expressed in liver of adult fish. However, among these detected genes, esr1 and er alpha2 mRNAs are sensitive biomarkers in response to EE2 at 0.1, 1, and 10ng/L for 1 and 2weeks compared to esr2a, esr2b, ar, and vtg B in the juveniles of mono-female gynogenetic fish. Totally, the subtypes of esrs show biphasic responses to EE2 exposures for 4weeks, and most of the EE2 exposures at 0.1, 1, and 10ng/L for 1, 2, 3 and 4weeks did not induce the mRNA expressions of vtg B. However, 1-, 2-, and 4-week 50μg/L MT all significantly stimulated vtg B transcripts. Further investigations are needed to elucidate the mechanism underlying the insensitivity or down-regulation of vtg B mRNA in response to EE2 in juvenile Pcc. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

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.

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.

WIND1 Promotes Shoot Regeneration through Transcriptional Activation of ENHANCER OF SHOOT REGENERATION1 in Arabidopsis[OPEN

PubMed Central

Ohnuma, Mariko; Kurata, Tetsuya; Nakata, Masaru; Ohme-Takagi, Masaru

2017-01-01

Many plant species display remarkable developmental plasticity and regenerate new organs after injury. Local signals produced by wounding are thought to trigger organ regeneration but molecular mechanisms underlying this control remain largely unknown. We previously identified an AP2/ERF transcription factor WOUND INDUCED DEDIFFERENTIATION1 (WIND1) as a central regulator of wound-induced cellular reprogramming in plants. In this study, we demonstrate that WIND1 promotes callus formation and shoot regeneration by upregulating the expression of the ENHANCER OF SHOOT REGENERATION1 (ESR1) gene, which encodes another AP2/ERF transcription factor in Arabidopsis thaliana. The esr1 mutants are defective in callus formation and shoot regeneration; conversely, its overexpression promotes both of these processes, indicating that ESR1 functions as a critical driver of cellular reprogramming. Our data show that WIND1 directly binds the vascular system-specific and wound-responsive cis-element-like motifs within the ESR1 promoter and activates its expression. The expression of ESR1 is strongly reduced in WIND1-SRDX dominant repressors, and ectopic overexpression of ESR1 bypasses defects in callus formation and shoot regeneration in WIND1-SRDX plants, supporting the notion that ESR1 acts downstream of WIND1. Together, our findings uncover a key molecular pathway that links wound signaling to shoot regeneration in plants. PMID:28011694

Electron spin resonance of particulate soot samples from automobiles to help environmental studies.

PubMed

Yamanaka, C; Matsuda, T; Ikeya, M

2005-02-01

The application of electron spin resonance (ESR) was studied for diesel soot samples and suspended particulate matter (SPM) from automobile engines. Soot samples or diesel exhaust particles (DEP) were recovered at various points: in the exhaust pipe of a diesel engine, at the dust sampler of a highway tunnel (standard DEP), on the soundproofing wall alongside a heavy traffic road, and on the filters of a dust sampler for SPM. The diesel soot samples apparently showed two ESR spectra: one was a broad spectrum at g=2.1 with a line width of ca. 80-120 mT and the other was a sharp signal of a carbon radical at g=2.003 with a line width of 0.4 mT. Annealing experiments with a DEP sample at 250 degrees C revealed drastic enhancement of the sharp ESR signal, which suggested a thermal process of carbonization of remnant organics. An oximetric study by ESR showed an enhancement of the broad signal in the diesel soot sample as well as in the sharp ESR signal. Therefore, the main part of the broad ESR signal would be attributed to carbon radicals, which form a different configuration, probably closely interacting aggregates. Enhancement of the sharp ESR signal was not observed in the standard DEP sample under vacuum condition, which suggested less adsorption sites on the surface of DEP samples.

Detection and original dose assessment of egg powders subjected to gamma irradiation by using ESR technique

NASA Astrophysics Data System (ADS)

Aydın, Talat

2015-09-01

ESR (electron spin resonance) techniques were applied for detection and original dose estimation to radiation-processed egg powders. The un-irradiated (control) egg powders showed a single resonance line centered at g=2.0086±0.0005, 2.0081±0.0005, 2.0082±0.0005 (native signal) for yolk, white and whole egg, respectively. Irradiation induced at least one additional intense singlet overlapping to the control signal and caused a significant increase in signal intensity without any changes in spectral patterns. Responses of egg powders to different gamma radiation doses in the range 0-10 kGy were examined. The stability of the radiation-induced ESR signal of irradiated egg powders were investigated over a storage period of about 5 months. Additive reirradiation of the egg powders produces a reproducible dose response function, which can be used to assess the initial dose by back-extrapolation. The additive dose method gives an estimation of the original dose within ±12% at the end of the 720 h storage period.

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

17Beta-estradiol signaling and regulation of proliferation and apoptosis of rat Sertoli cells.

PubMed

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

2012-04-01

The aim of the present study was to investigate the intracellular signaling events downstream of the classical estrogen receptors (ESRs) and G protein-coupled estrogen receptor 1 (GPER) involved in regulation of proliferation and apoptosis of rat Sertoli cells, in which we have previously described ESR1, ESR2, and GPER. ESRs play a role in Sertoli cell proliferation, and GPER, but not ESRs, plays a role modulating gene expression involved with apoptosis. The present study shows that 17beta-estradiol (E2) and the GPER-selective agonist G-1 rapidly activate phosphatidylinositol 3-kinase (PIK3)/serine threonine protein kinase (AKT) and cyclic AMP response element-binding (CREB) phosphorylation. E2 and the ESR1-selective agonist 4,4',4″-(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol (PPT) increase the expression of cyclin D1 (CCND1), whereas the ESR2-selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and G-1 do not change the expression of this protein, suggesting that ESR1 is the upstream receptor regulating Sertoli cell proliferation. E2- or PPT-ESR1, through activation of epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase 3/1 (MAPK3/1) and PIK3 pathways, induces upregulation of CCND1. KG-501, the compound that disrupts the phospho-CREB/CREB binding protein (CBP) complex, does not change E2- or PPT-ESR1-mediated CCND1 expression, suggesting that phospho-CREB/cyclic AMP response element/CBP is not involved in the expression of this protein. E2- or G-1-GPER, through activation of EGFR/MAPK3/1 and PIK3 pathways, may be involved in the upregulation of antiapoptotic proteins BCL2 and BCL2L2. E2- or G-1-GPER/EGFR/MAPK3/1/phospho-CREB decreases BAX expression. Taken together, these results show a differential effect of E2-GPER on the CREB-mediated transcription of proapoptotic and antiapoptotic genes of the same BCL2 gene family. ESR1 and GPER can mediate the rapid E2 actions in the Sertoli cells, which in turn can modulate nuclear transcriptional events important for Sertoli cell function and maintenance of normal testis development and homeostasis. Our findings are important to clarify the role of estrogen in a critical period of testicular development, and to direct further studies, which may contribute to better understanding of the causes of male infertility.

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.

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

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.

Raloxifene increases prefrontal activity during emotional inhibition in schizophrenia based on estrogen receptor genotype.

PubMed

Kindler, Jochen; Weickert, Cynthia Shannon; Schofield, Peter R; Lenroot, Rhoshel; Weickert, Thomas W

2016-12-01

People with schizophrenia show decreased prefrontal cortex (PFC) activity during emotional response inhibition, a cognitive process sensitive to hormonal influences. Raloxifene, a selective estrogen receptor modulator, binds estrogen receptor alpha (ESR-α), improves memory, attention and normalizes cortical and hippocampal activity during learning and emotional face recognition in schizophrenia. Here, we tested the extent to which raloxifene restores neuronal activity during emotional response inhibition in schizophrenia. Since genetic variation in estrogen receptor alpha (ESR-1) determines cortical ESR-α production and correlates with cognition, we also predicted that genetic ESR-1 variation would differentially relate to increased cortical activity by raloxifene administration. Thirty people with schizophrenia participated in a thirteen-week randomized, double-blind, placebo-controlled, cross-over adjunctive treatment trial of raloxifene administered at 120mg/day. Effects of raloxifene on brain activation were assessed based on ESR-1 genotype using functional magnetic resonance imaging during emotional word inhibition. Raloxifene increased PFC activity during inhibition of response to negative words and the raloxifene related increased PFC activity was greater in patients homozygous for ESR-1 rs9340799 AA relative to G carriers. Comparison to 23 healthy controls demonstrated that PFC activity of people with schizophrenia receiving raloxifene was more similar to controls than to their own brain activity during placebo. Estrogen receptor modulation by raloxifene restores PFC activity during emotional response inhibition in schizophrenia and ESR-1 genotype predicts degree of increased neural activity in response to raloxifene. While these preliminary results require replication, they suggest the potential for personalized pharmacotherapy using ESR-1 and estrogen receptor targeting compounds in schizophrenia. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

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.

The DAS28-ESR cutoff value necessary to achieve remission under the new Boolean-based remission criteria in patients receiving tocilizumab.

PubMed

Hirabayashi, Yasuhiko; Ishii, Tomonori

2013-01-01

To seek the cutoff value of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) that is necessary to achieve remission under the new Boolean-based criteria, we analyzed the data for 285 patients with rheumatoid arthritis registered between May 2008 and November 2009 by the Michinoku Tocilizumab Study Group and observed for 1 year after receiving tocilizumab (TCZ) in real clinical practice. Remission rates under the DAS28-ESR criteria and the Boolean criteria were assessed every 6 months after the first TCZ dose. The DAS28-ESR cutoff value necessary to achieve remission under the new criteria was analyzed by receiver operating characteristic (ROC) analysis. Data were analyzed using last observation carried forward. After 12 months of TCZ use, remission was achieved in 164 patients (57.5 %) by DAS28-ESR and 71 patients (24.9 %) under the new criteria for clinical trials. CRP levels scarcely affected remission rates, and the difference between remission rates defined by DAS28-ESR and by the new criteria was mainly due to patient global assessment (PGA). Improvement of PGA was inversely related to disease duration. ROC analysis revealed that the DAS28-ESR cutoff value necessary to predict remission under the new criteria for clinical trials was 1.54, with a sensitivity of 88.7 %, specificity of 85.5 %, positive predictive value of 67.0 %, and negative predictive value of 95.8 %. A DAS28-ESR cutoff value of 1.54 may be reasonable to predict achievement of remission under the new Boolean-based criteria for clinical trials in patients receiving TCZ.

Human Endometriosis Tissue Microarray Reveals Site-specific Expression of Estrogen Receptors, Progesterone Receptor, and Ki67.

PubMed

Colón-Caraballo, Mariano; García, Miosotis; Mendoza, Adalberto; Flores, Idhaliz

2018-04-07

Most available therapies for endometriosis are hormone-based and generally broadly used without taking into consideration the ovarian hormone receptor expression status. This contrasts strikingly with the standard of care for other hormone-based conditions such as breast cancer. We therefore aimed to characterize the expression of ovarian steroid hormone receptors for estrogen alpha (ESR1), estrogen beta (ESR2), and progesterone (PGR) in different types of endometriotic lesions and eutopic endometrium from women with endometriosis and controls using a tissue microarray (TMA). Nuclear expression levels of the receptors were analyzed by tissue (ie, ectopic vs. eutopic endometrium) and cell type (ie, glands vs. stroma). Ovarian lesions showed the lowest expression of ESR1 and PGR, and the highest expression of ESR2, whereas the fallopian tube lesions showed high expression of the 3 receptors. Differences among endometria included lower expression of ESR1 and higher expression of ESR2 in stroma of proliferative endometrium from patients versus patients, and a trend towards loss of PGR nuclear positivity in proliferative endometrium from patients. The largest ESR2:ESR1 ratios were observed in ovarian lesions and secretory endometrium. The highest proportion of samples with >10% Ki67 positive nuclei was in glands of fallopian tube (54%) and extrapelvic lesions (75%); 60% of glands of secretory endometrium from patients had >10% Ki67 positivity compared with only 15% in controls. Our results provide a better understanding of endometriosis heterogeneity by revealing lesion type-specific differences and case-by-case variability in the expression of ovarian hormone receptors. This knowledge could potentially predict individual responses to hormone therapies, and set the basis for the application of personalized medicine approaches for women with endometriosis.

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

Screening to Identify Commonly Used Chinese Herbs That Affect ERBB2 and ESR1 Gene Expression Using the Human Breast Cancer MCF-7 Cell Line.

PubMed

Chiu, Jen-Hwey; Chang, Chun-Ju; Wu, Jing-Chong; Liu, Hui-Ju; Wen, Che-Sheng; Hsu, Chung-Hua; Chen, Jiun-Liang; Tseng, Ling-Ming; Chen, Wei-Shone; Shyr, Yi-Ming

2014-01-01

Aim. Our aim the was to screen the commonly used Chinese herbs in order to detect changes in ERBB2 and ESR1 gene expression using MCF-7 cells. Methods. Using the MCF-7 human breast cancer cell line, cell cytotoxicity and proliferation were evaluated by MTT and trypan blue exclusion assays, respectively. A luciferase reporter assay was established by transient transfecting MCF-7 cells with plasmids containing either the ERBB2 or the ESR1 promoter region linked to the luciferase gene. Chinese herbal extracts were used to treat the cells at 24 h after transfection, followed by measurement of their luciferase activity. The screening results were verified by Western blotting to measure HER2 and ER α protein expression. Results. At concentrations that induced little cytotoxicity, thirteen single herbal extracts and five compound recipes were found to increase either ERBB2 or ESR1 luciferase activity. By Western blotting, Si-Wu-Tang, Kuan-Shin-Yin, and Suan-Tsao-Ren-Tang were found to increase either HER2 or ER α protein expression. In addition, Ligusticum chuanxiong was shown to have a great effect on ERBB2 gene expression and synergistically with estrogen to stimulate MCF-7 cell growth. Conclusion. Our results provide important information that should affect clinical treatment strategies among breast cancer patients who are receiving hormonal or targeted therapies.

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.

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.

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.

g-Tensor determination from single-crystal ESR data

NASA Astrophysics Data System (ADS)

Byrn, Marianne P.; Strouse, Charles E.

A general method is presented for extraction of the g tensor from single-crystal electron spin resonance data. This method does not depend on knowledge of crystal morphology or on the presence of crystallographic symmetry. The g values are obtained from rotations around three arbitrarily chosen but accurately known axes.

Study into the identification of irradiation ground paprika

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

Beczner, J.; Farkas, J.; Kiss, I.

From international colloquium: the identification of irradiated foodstuffs; Karlsruhe, Germany (24 Oct 1973). Several methods for the demonstration of irradiation in ground paprika were tested. In carbonyl compounds extracted by steam distillation unambiguous changes, which might have served as a basis for detecting irradiation, were not observed. Derivatography did not prove suitable either. On the basis of the size of ESR signal, the control sample and the irradiated one could be distinguished 2 to 3 weeks after irradiation. After a longer storage period, the size of the signal is irrelevant. Further study of the shape of the ESR signals maymore » yield valuable information in experiments on the demonstration of irradiation. (GE)« less

Development of Emotion Self-Regulation among Young Children with Autism Spectrum Disorders: The Role of Parents

ERIC Educational Resources Information Center

Laurent, Amy C.; Gorman, Kathleen

2018-01-01

Emotional self-regulation (ESR) challenges are well-documented in the diagnostic profiles of children with Autism; however, less is known about the development of ESR and the role of parents in ESR development for this population. Thirty-seven young children with autism and one of their parents participated in a home-based, observational study…

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.

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.

Association between estrogen receptora gene (ESR1) PvuII (T/C) and XbaI (A/G) polymorphisms and premature ovarian failure risk: evidence from a meta-analysis.

PubMed

He, Meirong; Shu, Jingcheng; Huang, Xing; Tang, Hui

2015-02-01

Genetic factors are important in the pathogenesis of Premature ovarian failure (POF). Notably, estrogen receptor-a (ESR1) has been suggested as a possible candidate gene for POF; however, published studies of ESR1 gene polymorphisms have been hampered by small sample sizes and inconclusive or ambiguous results. The aim of this meta analysis is to investigate the associations between two novel common ESR1 polymorphisms (intron 1 polymorphisms PvuII-rs2234693: T.C and XbaI-rs9340799: A.G) and POF. A comprehensive search was conducted to identify all studies on the association of ESR1 gene polymorphisms with POF up to August 2014. Pooled odds ratio (OR) and corresponding 95 % confidence interval (CI) were calculated using fixed-or random-effects model in the meta-analysis. Three studies covering 1396 subjects were identified. Pooled data showed significant association between ESR1 gene PvuII polymorphism and risk of POF: [allele model: Cvs. T, OR = 0.735, 95%CI: 0.624 ~ 0.865, p = 0.001; co-dominant models: CCvs.TT, OR = 0.540, 95%CI: 0.382 ~ 0.764, p = 0.001, CTvs.TT, OR = 0.735, 95%CI: 0.555 ~ 0.972, p = 0.031; dominant model: CT + CCvs.TT, OR = 0.618, 95%CI: 0.396 ~ 0.966, p = 0.035; recessive model: CCvs.TT + CT, OR = 0.659, 95%CI: 0.502 ~ 0.864, p = 0.003]. Subgroup analyses showed a significant association in all models in Asian population, but no significant association in any model in European population. For the XbaI polymorphism, overall, no significant association was observed under any genetic models. However, under dominant model, ESR1 gene XbaI polymorphism is significantly association with risk of POF in Asian population. The present meta-analysis suggests that ESR1gene PvuII polymorphism is significantly associated with an increased risk of POF. And ESR1gene XbaI polymorphism is not association with risk of POF overall. However, under dominant model, ESR1gene XbaI polymorphism is significantly association with risk of POF in Asian population. Further large and well-designed studies are needed to confirm the association.

Iron-chelating agents never suppress Fenton reaction but participate in quenching spin-trapped radicals.

PubMed

Li, Linxiang; Abe, Yoshihiro; Kanagawa, Kiyotada; Shoji, Tomoko; Mashino, Tadahiko; Mochizuki, Masataka; Tanaka, Miho; Miyata, Naoki

2007-09-19

Hydroxyl radical formation by Fenton reaction in the presence of an iron-chelating agent such as EDTA was traced by two different assay methods; an electron spin resonance (ESR) spin-trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and high Performance liquid chromatography (HPLC)-fluorescence detection with terephthalic acid (TPA), a fluorescent probe for hydroxyl radicals. From the ESR spin-trapping measurement, it was observed that EDTA seemed to suppress hydroxyl radical formation with the increase of its concentration. On the other hand, hydroxyl radical formation by Fenton reaction was not affected by EDTA monitored by HPLC assay. Similar inconsistent effects of other iron-chelating agents such as nitrylotriacetic acid (NTA), diethylenetriamine penta acetic acid (DTPA), oxalate and citrate were also observed. On the addition of EDTA solution to the reaction mixture 10 min after the Fenton reaction started, when hydroxyl radical formation should have almost ceased but the ESR signal of DMPO-OH radicals could be detected, it was observed that the DMPO-OH* signal disappeared rapidly. With the simultaneous addition of Fe(II) solution and EDTA after the Fenton reaction ceased, the DMPO-OH* signal disappeared more rapidly. The results indicated that these chelating agents should enhance the quenching of [DMPO-OH]* radicals by Fe(II), but they did not suppress Fenton reaction by forming chelates with iron ions.

Inhibitory effect of naturally occurring flavonoids on the formation of advanced glycation endproducts.

PubMed

Wu, Chi-Hao; Yen, Gow-Chin

2005-04-20

The objective of this study was to investigate the inhibitory effect of naturally occurring flavonoids on individual stage of protein glycation in vitro using the model systems of delta-Gluconolactone assay (early stage), BSA-methylglyoxal assay (middle stage), BSA-glucose assay, and G.K. peptide-ribose assay (last stage). In the early stage of protein glycation, luteolin, qucertin, and rutin exhibited significant inhibitory activity on HbA1C formation (p < 0.01), which were more effective than that of aminoguanidine (AG, 10 mM), a well-known inhibitor for advanced glycation endproducts (AGEs). For the middle stage, luteolin and rutin developed more significant inhibitory effect on methylglyoxal-medicated protein modification, and the IC50's were 66.1 and 71.8 microM, respectively. In the last stage of glycation, luteolin was found to be potent inhibitors of both the AGEs formation and the subsequent cross-linking of proteins. In addition, phenyl-tert-butyl-nitron served as a spin-trapping agent, and electron spin resonance (ESR) was used to explore the possible mechanism of the inhibitory effect of flavonoids on glycation. The results indicated that protein glycation was accompanied by oxidative reactions, as the ESR spectra showed a clear-cut radical signal. Statistical analysis showed that inhibitory capability of flavonoids against protein glycation was remarkably related to the scavenging free radicals derived from glycoxidation process (r = 0.79, p < 0.01). Consequently, the inhibitory mechanism of flavonoids against glycation was, at least partly, due to their antioxidant properties.

Combined ESR/U-series chronology of Acheulian hominid-bearing layers at Trinchera Galería site, Atapuerca, Spain.

PubMed

Falguères, Christophe; Bahain, Jean-Jacques; Bischoff, James L; Pérez-González, Alfredo; Ortega, Ana Isabel; Ollé, Andreu; Quiles, Anita; Ghaleb, Bassam; Moreno, Davinia; Dolo, Jean-Michel; Shao, Qingfeng; Vallverdú, Josep; Carbonell, Eudald; Bermúdez de Castro, Jose María; Arsuaga, Juan Luis

2013-08-01

The Sierra de Atapuerca, northern Spain, is known from many prehistoric and palaeontological sites documenting human prehistory in Europe. Three major sites, Gran Dolina, Galería and Sima del Elefante, range in age from the oldest hominin of Western Europe dated to 1.1 to 1.3 Ma (millions of years ago) at Sima del Elefante to c.a. 0.2 Ma on the top of the Galería archaeological sequence. Recently, a chronology based on luminescence methods (Thermoluminescence [TL] and Infrared Stimulated Luminescence [IRSL]) applied to cave sediments was published for the Gran Dolina and Galería sites. The authors proposed for Galería an age of 450 ka (thousands of years ago) for the units lower GIII and GII, suggesting that the human occupation there is younger than the hominid remains of Sima de los Huesos (>530 ka) around 1 km away. In this paper, we present new results obtained by combined Electron Spin Resonance/Uranium-series (ESR/U-series) dating on 20 herbivorous teeth from different levels at the Galería site. They are in agreement with the TL results for the upper part of the stratigraphic sequence (GIV and GIIIb), in the range of between 200 and 250 ka. But for the GIIIa to GIIb levels, the TL ages become abruptly older by 200 ka while ESR ages remain relatively constant. Finally, the TL and ESR data agree in the lowest part of the section (GIIa); both fall in the range of around 350-450 ka. Our results suggest a different interpretation for the GII, GIII and GIV units of Galería and the upper part of Gran Dolina (TD10 and TD11) than obtained by TL. The ESR/U-series results are supported by a Bayesian analysis, which allows a better integration between stratigraphic information and radiometric data. Copyright © 2013 Elsevier Ltd. All rights reserved.

Numerical modeling of materials processes with fluid-fluid interfaces

NASA Astrophysics Data System (ADS)

Yanke, Jeffrey Michael

A numerical model has been developed to study material processes that depend on the interaction between fluids with a large discontinuity in thermophysical properties. A base model capable of solving equations of mass, momentum, energy conservation, and solidification has been altered to enable tracking of the interface between two immiscible fluids and correctly predict the interface deformation using a volume of fluid (VOF) method. Two materials processes investigated using this technique are Electroslag Remelting (ESR) and plasma spray deposition. ESR is a secondary melting technique that passes an AC current through an electrically resistive slag to provide the heat necessary to melt the alloy. The simulation tracks the interface between the slag and metal. The model was validated against industrial scale ESR ingots and was able to predict trends in melt rate, sump depth, macrosegregation, and liquid sump depth. In order to better understand the underlying physics of the process, several constant current ESR runs simulated the effects of freezing slag in the model. Including the solidifying slag in the imulations was found to have an effect on the melt rate and sump shape but there is too much uncertainty in ESR slag property data at this time for quantitative predictions. The second process investigated in this work is the deposition of ceramic coatings via plasma spray deposition. In plasma spray deposition, powderized coating material is injected into a plasma that melts and carries the powder towards the substrate were it impacts, flattening out and freezing. The impacting droplets pile up to form a porous coating. The model is used to simulate this rain of liquid ceramic particles impacting the substrate and forming a coating. Trends in local solidification time and porosity are calculated for various particle sizes and velocities. The predictions of decreasing porosity with increasing particle velocity matches previous experimental results. Also, a preliminary study was conducted to investigate the effects of substrate surface defects and droplet impact angle on the propensity to form columnar porosity.

Combined ESR/U-series chronology of Acheulian hominid-bearing layers at Trinchera Galería site, Atapuerca, Spain

USGS Publications Warehouse

Falguères, Christophe; Bahain, Jean-Jacques; Bischoff, James L.; Pérez-González, Alfredo; Ortega, Ana Isabel; Ollé, Andreu; Quilles, Anita; Ghaleb, Bassam; Moreno, Davinia; Dolo, Jean-Michel; Shao, Qingfeng; Vallverdú, Josep; Carbonell, Eudald; María Bermúdez de Castro, Jose; Arsuaga, Juan Luis

2013-01-01

The Sierra de Atapuerca, northern Spain, is known from many prehistoric and palaeontological sites documenting human prehistory in Europe. Three major sites, Gran Dolina, Galería and Sima del Elefante, range in age from the oldest hominin of Western Europe dated to 1.1 to 1.3 Ma (millions of years ago) at Sima del Elefante to c.a. 0.2 Ma on the top of the Galería archaeological sequence. Recently, a chronology based on luminescence methods (Thermoluminescence [TL] and Infrared Stimulated Luminescence [IRSL]) applied to cave sediments was published for the Gran Dolina and Galería sites. The authors proposed for Galería an age of 450 ka (thousands of years ago) for the units lower GIII and GII, suggesting that the human occupation there is younger than the hominid remains of Sima de los Huesos (>530 ka) around 1 km away. In this paper, we present new results obtained by combined Electron Spin Resonance/Uranium-series (ESR/U-series) dating on 20 herbivorous teeth from different levels at the Galería site. They are in agreement with the TL results for the upper part of the stratigraphic sequence (GIV and GIIIb), in the range of between 200 and 250 ka. But for the GIIIa to GIIb levels, the TL ages become abruptly older by 200 ka while ESR ages remain relatively constant. Finally, the TL and ESR data agree in the lowest part of the section (GIIa); both fall in the range of around 350–450 ka. Our results suggest a different interpretation for the GII, GIII and GIV units of Galería and the upper part of Gran Dolina (TD10 and TD11) than obtained by TL. The ESR/U-series results are supported by a Bayesian analysis, which allows a better integration between stratigraphic information and radiometric data.

Analysis of estrogen receptor β gene methylation in autistic males in a Chinese Han population.

PubMed

Wang, Xuelai; Liang, Shuang; Sun, Yi; Li, Haixin; Endo, Fumio; Nakao, Mitsuyoshi; Saitoh, Noriko; Wu, Lijie

2017-08-01

Autism spectrum disorder (ASD) is a neurodevelopment disorder with abnormalities of social interaction, communication and repetitive behaviors. The higher prevalence of ASD in men implies a potential relationship between sex hormones and ASD etiology. The ESR2 gene encodes estrogen receptor beta (ESR2) and plays an important role during brain development. A relationship between ESR2 and ASD has been suggested by studies on single nucleotide polymorphisms and mRNA and protein expression levels in ASD patients. Here, we explored the possible epigenetic regulation of the ESR2 gene in autism. We collected genomic DNA from the peripheral blood of Chinese Han males with autism and age-matched normal males and measured DNA methylation of CpG islands in the ESR2 gene, which consisted of 41 CpG sites among the proximal promoter region and an untranslated exon, by bisulfite sequencing. We also investigated a relationship between DNA methylation and phenotypic features of autism, as assessed by the Children Autism Rating Scale. We found little overall difference in the DNA methylation of the ESR2 5'-flanking region in individuals with autism compared with normal individuals. However, detailed analyses revealed that eight specific CpG sites were hypermethylated in autistic individuals and that four specific CpG sites were positively associated with the severity of autistic symptoms. Our study indicates that the epigenetic dysregulation of ESR2 may govern the development of autism.

Ovarian steroids, oxytocin, and tumor necrosis factor modulate equine oviduct function.

PubMed

Pinto-Bravo, P; Galvão, A; Rebordão, M R; Amaral, A; Ramilo, D; Silva, E; Szóstek-Mioduchowska, A; Alexandre-Pires, G; Roberto da Costa, R; Skarzynski, D J; Ferreira-Dias, G

2017-10-01

The oviduct plays important roles in the early reproductive process. The aim of this study was to evaluate gene transcription and protein expression of progesterone receptor (PGR), estrogen receptors 1 (ESR1) and 2 (ESR2); oxytocin receptor (OXTR); prostaglandin F2α synthase (AKR1C3), and prostaglandin E2 synthase (Ptges) in mare oviduct in different estrous cycle stages. Estradiol (E 2 ), progesterone (P 4 ), oxytocin (OXT), and tumor necrosis factor α (TNF) effect on in vitro PGE 2 and prostaglandin F2α (PGF 2α ) secretion by equine oviduct explants or by oviductal epithelial cells (OECs) were also assessed. During the breeding season, oviduct tissue was obtained post mortem from cyclic mares. Protein of ESR1, ESR2, PGR, AKR1C3, and Ptges was present in OECs, whereas OXTR was shown in oviduct stroma. In follicular phase, protein expression of ESR1, ESR2, PGR, and OXTR increased in oviduct explants (P < 0.05), whereas no estrous cycle effect was noted for AKR1C3 or Ptges. In follicular phase, mRNA transcription was upregulated for Pgr but downregulated for Oxtr, Ptges, and Akr1c3 (P < 0.05). Nevertheless, Esr1 and Esr2 mRNA levels did not change with the estrous cycle. In the ampulla, Esr1, Esr2, and Oxtr mRNA transcription increased, but not for Pgr or Ptges. In contrast, Akr1c3 mRNA level was upregulated in the infundibulum (P < 0.05). In follicular phase, E 2 , P 4 , and OXT downregulated PGE 2 production by OEC (P < 0.05), but no difference was observed in mid-luteal phase. Explants production of PGE 2 rose when treated with OXT in follicular phase; with TNF or OXT in early luteal phase; or with TNF, OXT, or P 4 in mid-luteal phase. PGF 2α production by OEC was downregulated by all treatments in follicular phase but upregulated in mid-luteal phase (P < 0.05). Oviduct explants PGF 2α production was stimulated by TNF or OXT in all estrous cycle phases. In conclusion, this work has shown that ESR1, ESR2, OXTR, Ptges, and AKRLC3 gene transcription and/or translation is estrous cycle dependent and varies with oviduct portion (infundibulum vs ampulla) and cell type. Ovarian steroid hormones, OXT and TNF stimulation of PGF 2α and/or PGE 2 production is also estrous cycle dependent and varies in the different portions of mare oviduct. Differential transcription level and protein localization in various portions of the oviduct throughout the estrous cycle, as well as PG production, suggest coordinated physiologic actions and mechanisms of steroid hormones, OXT, and TNF in the equine oviduct. Copyright © 2017 Elsevier Inc. All rights reserved.

Cytogenetic Reconstruction of Gamma-Ray Doses Delivered to Atomic Bomb Survivors: Dealing with Wide Distributions of Photon Energies and Contributions from Hematopoietic Stem/Progenitor Cells.

PubMed

Nakamura, Nori; Hirai, Yuko; Kodama, Yoshiaki; Hamasaki, Kanya; Cullings, Harry M; Cordova, Kismet A; Awa, Akio

2017-10-01

Retrospective estimation of the doses received by atomic bomb (A-bomb) survivors by cytogenetic methods has been hindered by two factors: One is that the photon energies released from the bomb were widely distributed, and since the aberration yield varies depending on the energy, the use of monoenergetic 60 Co gamma radiation to construct a calibration curve may bias the estimate. The second problem is the increasing proportion of newly formed lymphocytes entering into the lymphocyte pool with increasing time intervals since the exposures. These new cells are derived from irradiated precursor/stem cells whose radiosensitivity may differ from that of blood lymphocytes. To overcome these problems, radiation doses to tooth enamel were estimated using the electron spin resonance (ESR; or EPR, electron paramagnetic resonance) method and compared with the cytogenetically estimated doses from the same survivors. The ESR method is only weakly dependent on the photon energy and independent of the years elapsed since an exposure. Both ESR and cytogenetic doses were estimated from 107 survivors. The latter estimates were made by assuming that although a part of the cells examined could be lymphoid stem or precursor cells at the time of exposure, all the cells had the same radiosensitivity as blood lymphocytes, and that the A-bomb gamma-ray spectrum was the same as that of the 60 Co gamma rays. Subsequently, ESR and cytogenetic endpoints were used to estimate the kerma doses using individual DS02R1 information on shielding conditions. The results showed that the two sets of kerma doses were in close agreement, indicating that perhaps no correction is needed in estimating atomic bomb gamma-ray doses from the cytogenetically estimated 60 Co gamma-ray equivalent doses. The present results will make it possible to directly compare cytogenetic doses with the physically estimated doses of the survivors, which would pave the way for testing whether or not there are any systematic trends or factors affecting physically estimated doses.

Crucial role of estrogen for the mammalian female in regulating semen coagulation and liquefaction in vivo

PubMed Central

2017-01-01

Semen liquefaction changes semen from a gel-like to watery consistency and is required for sperm to gain mobility and swim to the fertilization site in the Fallopian tubes. Kallikrein-related peptidases 3 (KLK3) and other kallikrein-related peptidases from male prostate glands are responsible for semen liquefaction by cleaving gel-forming proteins (semenogelin and collagen). In a physiological context, the liquefaction process occurs within the female reproductive tract. How seminal proteins interact with the female reproductive environment is still largely unexplored. We previously reported that conditional genetic ablation of Esr1 (estrogen receptor α) in the epithelial cells of the female reproductive tract (Wnt7aCre/+;Esr1f/f) causes female infertility, partly due to a drastic reduction in the number of motile sperm entering the oviduct. In this study, we found that post-ejaculated semen from fertile wild-type males was solidified and the sperm were entrapped in Wnt7aCre/+;Esr1f/f uteri, compared to the watery semen (liquefied) found in Esr1f/f controls. In addition, semenogelin and collagen were not degraded in Wnt7aCre/+;Esr1f/f uteri. Amongst multiple gene families aberrantly expressed in the absence of epithelial ESR1, we have identified that a lack of Klks in the uterus is a potential cause for the liquefaction defect. Pharmacological inhibition of KLKs in the uterus replicated the phenotype observed in Wnt7aCre/+;Esr1f/f uteri, suggesting that loss of uterine and seminal KLK function causes this liquefaction defect. In human cervical cell culture, expression of several KLKs and their inhibitors (SPINKs) was regulated by estrogen in an ESR1-dependent manner. Our study demonstrates that estrogen/ESR1 signaling in the female reproductive tract plays an indispensable role in normal semen liquefaction, providing fundamental evidence that exposure of post-ejaculated semen to the suboptimal microenvironment in the female reproductive tract leads to faulty liquefaction and subsequently causes a fertility defect. PMID:28414719

Effects of thyroid endocrine manipulation on sex-related gene expression and population sex ratios in Zebrafish.

PubMed

Sharma, Prakash; Tang, Song; Mayer, Gregory D; Patiño, Reynaldo

2016-09-01

Thyroid hormone reportedly induces masculinization of genetic females and goitrogen treatment delays testicular differentiation (ovary-to-testis transformation) in genetic males of Zebrafish. This study explored potential molecular mechanisms of these phenomena. Zebrafish were treated with thyroxine (T4, 2nM), goitrogen [methimazole (MZ), 0.15mM], MZ (0.15mM) and T4 (2nM) (rescue treatment), or reconstituted water (control) from 3 to 33days postfertilization (dpf) and maintained in control water until 45dpf. Whole fish were collected during early (25dpf) and late (45dpf) testicular differentiation for transcript abundance analysis of selected male (dmrt1, amh, ar) and female (cyp19a1a, esr1, esr2a, esr2b) sex-related genes by quantitative RT-PCR, and fold-changes relative to control values were determined. Additional fish were sampled at 45dpf for histological assessment of gonadal sex. The T4 and rescue treatments caused male-biased populations, and T4 alone induced precocious puberty in ∼50% of males. Male-biased sex ratios were accompanied by increased expression of amh and ar and reduced expression of cyp19a1a, esr1, esr2a, and esr2b at 25 and 45dpf and, unexpectedly, reduced expression of dmrt1 at 45dpf. Goitrogen exposure increased the proportion of individuals with ovaries (per previous studies interpreted as delay in testicular differentiation of genetic males), and at 25 and 45dpf reduced the expression of amh and ar and increased the expression of esr1 (only at 25dpf), esr2a, and esr2b. Notably, cyp19a1a transcript was reduced but via non-thyroidal pathways (not restored by rescue treatment). In conclusion, the masculinizing activity of T4 at the population level may be due to its ability to inhibit female and stimulate male sex-related genes in larvae, while the inability of MZ to induce cyp19a1a, which is necessary for ovarian differentiation, may explain why its "feminizing" activity on gonadal sex is not permanent. Published by Elsevier Inc.

Sex-steroid receptors, prostaglandin E2 receptors, and cyclooxygenase in the equine cervix during estrus, diestrus and pregnancy: Gene expression and cellular localization.

PubMed

Fernandes, Claudia B; Loux, Shavahn C; Scoggin, Kirsten E; Squires, Edward L; Troedsson, Mats H; Esteller-Vico, Alejandro; Ball, Barry A

2017-12-01

The cervix is a dynamic structure that undergoes dramatic changes during the estrous cycle, pregnancy and parturition. It is well established that hormonal changes, including estrogens, progestogens and prostaglandins, regulate the expression of key proteins involved in cervical function. The arachidonic acid cascade is important in the remodeling and relaxation of the cervix in the days preceding parturition. Despite the complexity of this mechanism, regulation of cervical function has received little study in the mare. Therefore, the objective of this study was to compare the expression of estrogen receptor α (ESR1) and β (ESR2), progesterone receptor (PGR), prostaglandin E2 type 2 (PTGER2) and type 4 (PTGER4) receptors as well as cyclooxygenase-1 (PTGS1) and -2 (PTGS2) in the equine cervical mucosa and stroma during estrus, diestrus and late pregnancy using qPCR. Immunohistochemistry was used to localize ESR1, ESR2, PGR, PTGER2 and PTGER4 receptors in these regions of the cervix. Relative mRNA expression of ESR1 and PGR was greater during estrus and diestrus than in late pregnancy in both the mucosa and stroma of the cervix. Expression of PTGER2 was highest in the cervical stroma during late pregnancy compared to either estrus or diestrus. Moreover, PTGS1 expression in mucosa and PTGS2 in stroma was greater during late pregnancy compared with estrus, but not diestrus. Immunostaining for ESR1, ESR2, PGR, PTGER2 and PTGER4 was consistently detected in the nucleus and cytoplasm of epithelium of the endocervix as well as the smooth muscle cytoplasm of the cervix in all stages evaluated. Immunolabeling in smooth muscle nuclei was detected for ESR1 and PGR in estrus, diestrus and late pregnancy, and for ESR2 in estrus and late pregnancy stages. The changes noted in late gestation likely reflect preparation of the equine cervix for subsequent parturition. Copyright © 2017 Elsevier B.V. All rights reserved.

ESR1, ERBB2, and Ki67 mRNA expression predicts stage and grade of non-muscle-invasive bladder carcinoma (NMIBC).

PubMed

Breyer, Johannes; Wirtz, Ralph M; Laible, Mark; Schlombs, Kornelia; Erben, Philipp; Kriegmair, Maximilian Christian; Stoehr, Robert; Eidt, Sebastian; Denzinger, Stefan; Burger, Maximilian; Hartmann, Arndt; Otto, Wolfgang

2016-11-01

Pathological staging and grading are crucial for risk assessment in non-muscle-invasive bladder cancer (NMIBC). Molecular grading might support pathological evaluation and minimize interobserver variability. In this study, the well-established breast cancer markers ESR1, PGR, ERBB2, and MKI67 were evaluated as potential molecular markers to support grading and staging in NMIBC. We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with NMIBC. Messenger RNA (mRNA) expression of the aforementioned markers was measured by single-step reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) using RNA-specific TaqMan assays. Relative gene expression was determined by normalization to two reference genes (CALM2 and B2M) using the 40 -ΔΔCT method and correlated to histopathological stage and grade. Pathological assessment was performed by an experienced uropathologist. Statistical analysis was performed using the SAS software JMP 9.0.0 version and GraphPad Prism 5.04. Of 381 cases of NMIBC, samples of 100 pTa and 255 pT1 cases were included in the final study. Spearman rank correlation revealed significant correlations between grade and expression of MKI67 (r = 0.52, p < 0.0001), ESR1 (r = 0.25, p < 0.0001), and ERBB2 (r = 0.18, p = 0.0008). In Mann-Whitney tests, MKI67 was significantly different between all grades (p < 0.0001), while ESR1 (p = 0.0006) and ERBB2 (p = 0.027) were significantly different between G2 and G3. Higher expression of MKI67 (r = 0.49; p < 0.0001), ERBB2 (r = 0.22; p < 0.0001), and ESR1 (r = 0.18; p = 0.0009) mRNA was positively correlated with higher stage. MKI67 (p < 0.0001), ERBB2 (p = 0.0058), and PGR (p = 0.0007) were significantly different between pTa and pT1. In NMIBC expression of ESR1, ERBB2 and MKI67 are significantly different between stage and grade. This potentially provides objective parameters for pathological evaluation.

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.

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.

An electron spin resonance study of gamma-ray irradiated ginseng.

PubMed

Nakamura, Hideo; Ukai, Mitsuko; Shimoyama, Yuhei

2006-03-13

Using electron spin resonance (ESR) spectroscopy, we revealed the presence of four radical species in gamma-ray irradiated ginseng (Agaliaceae). Before irradiation, the representative ESR spectrum of ginseng is composed of a sextet centered at g = 2.0, a sharp singlet at the same g-value, and a singlet at about g = 4.0. The first one is attributable to a hyperfine (hf) signal of Mn2+ ion (hf constant: 7.4 mT). The second one is due to an organic free radical. The third one is originated from Fe3+. Upon gamma-ray irradiation, a new ESR (the fourth) signal was detectable in the vicinity of g = 2.0 region. The progressive saturation behaviors of the ESR signals at various microwave power levels were indicative of different relaxation time for those radicals. The anisotropic ESR spectra were detected by the angular rotation of the sample tube. This is due to the existence of anisotropic microcrystalline in the ginseng powder sample.

An electron spin resonance study of γ-ray irradiated ginseng

NASA Astrophysics Data System (ADS)

Nakamura, Hideo; Ukai, Mitsuko; Shimoyama, Yuhei

2006-03-01

Using electron spin resonance (ESR) spectroscopy, we revealed the presence of four radical species in γ-ray irradiated ginseng ( Agaliaceae). Before irradiation, the representative ESR spectrum of ginseng is composed of a sextet centered at g = 2.0, a sharp singlet at the same g-value, and a singlet at about g = 4.0. The first one is attributable to a hyperfine (hf) signal of Mn 2+ ion (hf constant: 7.4 mT). The second one is due to an organic free radical. The third one is originated from Fe 3+. Upon γ-ray irradiation, a new ESR (the fourth) signal was detectable in the vicinity of g = 2.0 region. The progressive saturation behaviors of the ESR signals at various microwave power levels were indicative of different relaxation time for those radicals. The anisotropic ESR spectra were detected by the angular rotation of the sample tube. This is due to the existence of anisotropic microcrystalline in the ginseng powder sample.

Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity

DTIC Science & Technology

2011-07-01

Betty Diamond – DOD FINAL REPORT 9 Figure 3: (A) expression of estrogen receptors ERalpha( Esr1 ) and ERbeta (Esr2) in splenic B cells and (B...Urinary 16 OH-Estradiol metabolite in BALB/c and C57BL6 mice. Esr1 0 0.05 0.1 0.15 0.2 Transit. Mature Transit. Mature Transit. Mature Transit. mature P E2

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.

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.

Estrogens in Male Physiology.

PubMed

Cooke, Paul S; Nanjappa, Manjunatha K; Ko, CheMyong; Prins, Gail S; Hess, Rex A

2017-07-01

Estrogens have historically been associated with female reproduction, but work over the last two decades established that estrogens and their main nuclear receptors (ESR1 and ESR2) and G protein-coupled estrogen receptor (GPER) also regulate male reproductive and nonreproductive organs. 17β-Estradiol (E2) is measureable in blood of men and males of other species, but in rete testis fluids, E2 reaches concentrations normally found only in females and in some species nanomolar concentrations of estrone sulfate are found in semen. Aromatase, which converts androgens to estrogens, is expressed in Leydig cells, seminiferous epithelium, and other male organs. Early studies showed E2 binding in numerous male tissues, and ESR1 and ESR2 each show unique distributions and actions in males. Exogenous estrogen treatment produced male reproductive pathologies in laboratory animals and men, especially during development, and studies with transgenic mice with compromised estrogen signaling demonstrated an E2 role in normal male physiology. Efferent ductules and epididymal functions are dependent on estrogen signaling through ESR1, whose loss impaired ion transport and water reabsorption, resulting in abnormal sperm. Loss of ESR1 or aromatase also produces effects on nonreproductive targets such as brain, adipose, skeletal muscle, bone, cardiovascular, and immune tissues. Expression of GPER is extensive in male tracts, suggesting a possible role for E2 signaling through this receptor in male reproduction. Recent evidence also indicates that membrane ESR1 has critical roles in male reproduction. Thus estrogens are important physiological regulators in males, and future studies may reveal additional roles for estrogen signaling in various target tissues. Copyright © 2017 the American Physiological Society.

Elderly suicide trends in the context of transforming China, 1987–2014

PubMed Central

Zhong, Bao-Liang; Chiu, Helen F. K.; Conwell, Yeates

2016-01-01

In the context of rapid ageing, understanding the time-trend of elderly suicide (ES) could inform China’s efforts on suicide prevention. We examined time-trends in Chinese ES rates (ESRs) from 1987 to 2014, a period of profound social changes. Suicide rates by residence (rural/urban), gender, and 5-year age-group (65+) in 1987–2014 were provided by the Chinese Ministry of Health. Time-trends were analyzed with joinpoint analysis. The time-trend of national ESRs was downward (average annual percent change [AAPC] = −3.7, P < 0.001): 76.6/100000 in 1987 and 30.2/100000 in 2014. However, the time-trend of corresponding percentages of ESs among the total suicides was monotonically increasing (AAPC = 3.4, P < 0.001): 16.9% in 1987 to 41.2% in 2014. The time-trends in ESRs of both rural and urban men and women were decreasing, but only the rural trends were significant (P < 0.001). Rural-urban and male-female differences in ESRs were decreasing over time (slope = −4.2 and −3.0, P ≤ 0.006), but the rural-urban and male-female ESR differences in 2014 remained large (16.3/100000 and 9.8/100000, P < 0.001). While national ESRs decreased significantly during the past three decades, the current ESR remains high in China. Further, the age-pattern of Chinese suicide is transitioning to elderly predominance. ES, particularly rural ES, should be a public health priority in China. PMID:27886219

Does erythrocyte sedimentation rate reflect and discriminate flare from infection in systemic lupus erythematosus? Correlation with clinical and laboratory parameters of disease activity.

PubMed

Schäfer, Valentin Sebastian; Weiß, Katharina; Krause, Andreas; Schmidt, Wolfgang Andreas

2018-07-01

To examine disease activity parameters in patients with systemic lupus erythematosus (SLE) experiencing flare, infection, both, or neither condition, focusing on erythrocyte sedimentation rate (ESR). This study is a retrospective analysis of 371 consecutive inpatient SLE cases from 2006 to 2015. Cases were classified as flare (n = 147), infection (n = 48), both (n = 23), or neither (n = 135). ESR levels were correlated to C-reactive protein (CRP), ferritin, anti-dsDNA antibodies, complement C3 reduction, serositis, and erythrocyturia with proteinuria (Pearson's correlation). ESR levels were related to an age- and gender-adapted cut-off value (ESRp). We analyzed mean values of age, ESR, ESRp, CRP, ferritin and distribution of anti-dsDNA antibodies, C3 reduction, serositis, and erythrocyturia with proteinuria. Sensitivity and specificity were calculated via receiver operating characteristic or two-by-two table. Association of parameters with disease activity and infection was tested via two-sided chi square test. ESR correlated moderately with CRP in cases with flare and/or infection (r = 0.505-0.586). While ESR and CRP were normal in remission, mean values overlapped in cases with flare, infection, or both. ESRp was higher in flare than in infection (p = 0.048). ESR lost association to activity in infected cases, CRP to infection in flaring cases. ESRp, serositis, and anti-dsDNA antibodies were related to disease activity regardless of infections. Anti-dsDNA antibodies were most sensitive for detecting flares (74%), while serositis, proteinuria with erythrocyturia, anti-dsDNA antibodies, C3 reduction, and ESRp values ≥ 2 were most specific. ESR levels were raised by flares, infections, and age; adapting them to age and gender increased their diagnostic value. Obtaining several parameters remains necessary to differentiate flare from infection.

Sex and seasonal differences in mRNA expression of estrogen receptor α (ESR1) in red-sided garter snakes (Thamnophis sirtalis parietalis).

PubMed

Ashton, Sydney E; Vernasco, Ben J; Moore, Ignacio T; Parker, M Rockwell

2018-05-25

Estrogens are important regulators of reproductive physiology including sexual signal expression and vitellogenesis. For the regulation to occur, the hormone must bind and activate receptors in target tissues, and expression of the receptors can vary by sex and/or season. By simultaneously comparing circulating hormone levels with receptor expression, a more complete understanding of hormone action can be gained. Our study species, the red-sided garter snake (Thamnophis sirtalis parietalis), provides an excellent opportunity to study the interaction between sex steroid hormones and receptor expression in addition to sexual dimorphism and seasonality. During the spring mating season, male garter snakes rely exclusively on the female's skin-based, estrogen-dependent sex pheromone to direct courtship. Males can be stimulated to produce this sexual attractiveness pheromone by treatment with estradiol (E 2 ), which also induces male vitellogenesis. Estrogen receptors (ESRs) are required to transduce the effects of estrogens, thus we used quantitative RT-PCR to analyze expression of ESR alpha (ERα; gene ESR1) mRNA in the skin and liver of wild caught male and female garter snakes across simulated spring and fall conditions in the laboratory. While ESR1 was present in the skin of both sexes, there were no sex or seasonal differences in expression levels. Liver expression of ESR1, however, was sexually dimorphic, with females showing greatest expression in fall when circulating E 2 concentrations were lowest. There were no statistically significant correlations between E 2 and ESR1 expression. Our data suggest that the skin of both sexes is sensitive to estrogen signaling and thus the production of sex pheromone is dependent on bioavailable levels of E 2 . Female expression of ESR1 in the liver may increase in the fall to prime energy storage mechanisms required for vitellogenesis the following year. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Extent and timing of paleoglaciation in the Kanas Valley, Altai Mountains, China, based on remote sensing, field investigations and multiple dating methods

NASA Astrophysics Data System (ADS)

Zhang, Wei; Harbor, Jon; Cui, Zhijiu; Liu, Liang; Liu, Beibei; Fu, Yanjing; Shi, Yuanhuang; Gribenski, Natacha; Blomdin, Robin; Stroeven, Arjen; Caffee, Marc; Jansson, Krister

2014-05-01

Reconstructions of the timing and extent of past glaciation provide key constraints for paleoclimate and numerical modeling of past glacier behavior. As part of the multinational Central Asian Paleoglaciology Project we are reconstructing the timing and extent of past glaciation along and across a series of mountain ranges in central Asia using consistent methods for mapping, field investigations and numerical dating. Here we report on new findings for the Kanas Valley in northwest China, a large glaciated valley system on the south side of the Altai Mountains. Previous studies have concluded that the Kanas Valley has been shaped by a series of major glacial advances that produced overdeepened basins, a U-shaped valley cross profile, and extensive glacial and glaciofluvial deposits. Existing Optically Stimulated Luminescence (OSL) and Electron Spin Resonance (ESR) dating results suggest major glaciation in the Kanas Valley during Marine Oxygen Isotope Stages (MIS) 3, 5, and 6, but very limited MIS 2 glaciation. Limited MIS 2 glaciation has also been suggested for other parts of central Asia, and this contrasts with extensive MIS 2 glaciation in Europe and North America. Field studies in 2013 provided new evidence for the highest elevation extent of glaciation in the Kanas Valley in the vicinity of the 20-km long Lake Kanas, with the upper limit of distinct erratics on the valley sidewalls indicating past ice thicknesses here up to 1000 m. Upper limits of erratics extending from Lake Kanas to the mapped maximum down-valley extent of glaciation suggest an ice surface slope of 1.8 degrees for the lower half of the paleoglacier in the Kanas Valley, assuming that all the erratics were deposited at the same time. Systematic sampling of glacial erratics, basal till, terminal moraines, glacially eroded bedrock, and glaciofluvial deposits provided material that is being used for cosmogenic radionuclide, OSL and ESR dating of the glacial chronology, and for dating intercomparisons.

Picosecond Pulsed Laser Ablation for the Surface Preparation of Epoxy Composites

NASA Technical Reports Server (NTRS)

Palmieri, Frank; Ledesma, Rodolfo; Fulton, Tayler; Arthur, Alexandria; Eldridge, Keishara; Thibeault, Sheila; Lin, Yi; Wohl, Chris; Connell, John

2017-01-01

As part of a technical challenge under the Advanced Composites Program, methods for improving pre-bond process control for aerospace composite surface treatments and inspections, in conjunction with Federal Aviation Administration guidelines, are under investigation. The overall goal is to demonstrate high fidelity, rapid and reproducible surface treatment and surface characterization methods to reduce uncertainty associated with the bonding process. The desired outcomes are reliable bonded airframe structure, and reduced timeline to certification. In this work, laser ablation was conducted using a q-switched Nd:YVO4 laser capable of nominal pulse durations of 8 picoseconds (ps). Aerospace structural carbon fiber reinforced composites with an epoxy resin matrix were laser treated, characterized, processed into bonded assemblies and mechanically tested. The characterization of ablated surfaces were conducted using scanning electron microscopy (SEM), water contact angle (WCA) goniometry, micro laser induced breakdown spectroscopy (uLIBS), and electron spin resonance (ESR). The bond performance was assessed using a double cantilever beam (DCB) test with an epoxy adhesive. The surface characteristics and bond performance obtained from picosecond ablated carbon fiber reinforced plastics (CFRPs) are presented herein.

Analysis of current assessments and perspectives of ESR tooth dosimetry for radiation dose reconstruction of the population residing near the Semipalatinsk nuclear test site.

PubMed

Romanyukha, Alex; Schauer, David A; Malikov, Yurii K

2006-02-01

Between 1949 and 1989 the Semipalatinsk nuclear test site (SNTS), an area of 19,000 square km in northeastern Kazakhstan, was the location of over 400 nuclear test explosions with a total explosive energy of 6.6 Mt TNT (trinitrotoluene or trotyl) equivalent. It is estimated that the bulk of the radiation exposure to the population resulted from three tests, conducted in 1949, 1951, and 1953 although estimations of radiation doses received by the local population have varied significantly. Analysis of the published ESR dose reconstruction results for residents of the villages near the SNTS show that they do not correlate well with other methods of dose assessment (e.g. model dose calculation and thermo luminescence dosimetry (TLD) in bricks). The most significant difference in dose estimations was found for the population of Dolon, which was exposed as result of the first Soviet nuclear test in 1949. Published results of ESR measurements in tooth enamel are considerably lower than other dose estimations. Detailed analysis of these results is provided and a possible explanation for this discrepancy and ways to eliminate it are suggested.

Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin-6 dependent.

PubMed

Reddel, C J; Allen, J D; Ehteda, A; Taylor, R; Chen, V M Y; Curnow, J L; Kritharides, L; Robertson, G

2017-03-01

Essentials Cancer cachexia and cancer-associated thrombosis have not previously been mechanistically linked. We assessed thrombin generation and coagulation parameters in cachectic C26 tumor-bearing mice. C26 mice are hypercoagulable, partially corrected by blocking tumor derived interleukin-6. Coagulability and anti-inflammatory interventions may be clinically important in cancer cachexia. Background Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer, which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. Objectives To assess if cancer cachexia altered the coagulation state and if this was attributable to tumor IL-6 production. Methods In male BALB/c*DBA2 (F1 hybrid) mice with a C26 tumor we used modified calibrated automated thrombogram and fibrin generation (based on overall hemostatic potential) assays to assess the functional coagulation state, and also examined fibrinogen, erythrocyte sedimentation rate (ESR), platelet count, tissue factor pathway inhibitor (TFPI) and hepatic expression of coagulation factors by microarray. C26 mice were compared with non-cachectic NC26, pair-fed and sham control mice. IL-6 expression in C26 cells was knocked down by lentiviral shRNA constructs. Results C26 mice with significant weight loss and highly elevated IL-6 had elevated thrombin generation, fibrinogen, ESR, platelets and TFPI compared with all control groups. Fibrin generation was elevated compared with pair-fed and sham controls but not compared with NC26 tumor mice. Hepatic expression of coagulation factors and fibrinolytic inhibitors was increased. Silencing IL-6 in the tumor significantly, but incompletely, attenuated the increased thrombin generation, fibrinogen and TFPI. Conclusions Cachectic C26 tumor-bearing mice are in a hypercoagulable state, which is partly attributable to IL-6 release by the tumor. The findings support the importance of the coagulation state in cancer cachexia and the clinical utility of anti-inflammatory interventions. © 2017 International Society on Thrombosis and Haemostasis.

Integration of Dust Prediction Systems and Vegetation Phenology to Track Pollen for Asthma Alerts in Public Health

NASA Technical Reports Server (NTRS)

Luvall, Jeffrey; Sprigg, William; Huete, Alfredo; Levetin, Estelle; VandeWater, Peter; Nickovic, Slobodan; Pejanovic, Goran; Budge, Amelia; Heidi Krapfl; Myers, Orrin;

Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B cell Autoreactivity. Addendum

DTIC Science & Technology

2012-07-01

Betty Diamond – DOD FINAL REPORT 9 Figure 3: (A) expression of estrogen receptors ERalpha( Esr1 ) and ERbeta (Esr2) in splenic B cells and (B)Urinary...16 OH-Estradiol metabolite in BALB/c and C57BL6 mice. Esr1 0 0.05 0.1 0.15 0.2 Transit. Mature Transit. Mature Transit. Mature Transit. mature P E2 P

Overcoming Endocrine Resistance by Targeting ER/FoxA1/IL-8 Axis

DTIC Science & Technology

2015-10-01

residual disease after 6-month neoadjuvant endocrine therapy 45 . Recent studies unveiled gain-of- function mutations in ESR1 , the gene encoding ER...described previously 61 . SYBR dye (Life Technologies) was used in real- time PCR and the target primer sequences are as follows: ESR1 forward...Breast Cancer Symposium (ed^(eds). Cancer Res (2013). 46. Li S, et al. Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of

Is ESR Important for Predicting Post-ERCP Pancreatitis?

PubMed Central

Mohammad Alizadeh, Amir Houshang; Afzali, Esmaeil Shamsi; Behzad, Catherine; Mousavi, Mirhadi; Mirsattari, Dariush; Doagoo, Siavash Zafar; Zali, Mohammad Reza

2015-01-01

BACKGROUND Pancreatitis remains the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), resulting in substantial morbidity and occasional mortality. There are notable controversies and conflicting reports about risk factors of post-ERCP pancreatitis (PEP). AIM To evaluate the potential risk factors for PEP at a referral tertiary center, as a sample of the Iranian population. MATERIALS AND METHODS Baseline characteristics and clinical as well as paraclinical information of 780 patients undergoing diagnostic and therapeutic ERCP at Taleghani hospital in Tehran between 2008 and 2012 were reviewed. Data were collected prior to the ERCP, at the time of the procedure, and 24–72 hours after discharge. PEP was diagnosed according to consensus criteria. RESULTS Of the 780 patients who underwent diagnostic ERCP, pancreatitis developed in 26 patients (3.3%). In the multivariable risk model, significant risk factors with adjusted odds ratios (ORs) were age <65 years (OR = 10.647, P = 0.023) and erythrocyte sedimentation rate (ESR) >30 (OR = 6.414, P < 0.001). Female gender, history of recurrent pancreatitis, pre-ERCP hyperamylasemia, and difficult or failed cannulation could not predict PEP. There was no significant difference in the rate of PEP in wire-guided cannulation versus biliary cannulation using a sphincterotome and contrast injection as the conventional method. CONCLUSIONS Performing ERCP may be safer in the elderly. Patients with high ESR may be at greater risk of PEP, which warrants close observation of these patients for signs of pancreatitis after ERCP. PMID:26005364

Effects of thyroid endocrine manipulation on sex-related gene expression and population sex ratios in Zebrafish

USGS Publications Warehouse

Sharma, Prakash; Tang, Song; Mayer, Gregory D.; Patino, Reynaldo

2016-01-01

Thyroid hormone reportedly induces masculinization of genetic females and goitrogen treatment delays testicular differentiation (ovary-to-testis transformation) in genetic males of Zebrafish. This study explored potential molecular mechanisms of these phenomena. Zebrafish were treated with thyroxine (T4, 2 nM), goitrogen [methimazole (MZ), 0.15 mM], MZ (0.15 mM) and T4 (2 nM) (rescue treatment), or reconstituted water (control) from 3 to 33 days postfertilization (dpf) and maintained in control water until 45 dpf. Whole fish were collected during early (25 dpf) and late (45 dpf) testicular differentiation for transcript abundance analysis of selected male (dmrt1, amh, ar) and female (cyp19a1a, esr1, esr2a, esr2b) sex-related genes by quantitative RT-PCR, and fold-changes relative to control values were determined. Additional fish were sampled at 45 dpf for histological assessment of gonadal sex. The T4 and rescue treatments caused male-biased populations, and T4 alone induced precocious puberty in ∼50% of males. Male-biased sex ratios were accompanied by increased expression of amh and ar and reduced expression of cyp19a1a, esr1, esr2a, and esr2b at 25 and 45 dpf and, unexpectedly, reduced expression of dmrt1 at 45 dpf. Goitrogen exposure increased the proportion of individuals with ovaries (per previous studies interpreted as delay in testicular differentiation of genetic males), and at 25 and 45 dpf reduced the expression of amh and ar and increased the expression of esr1 (only at 25 dpf), esr2a, and esr2b. Notably, cyp19a1a transcript was reduced but via non-thyroidal pathways (not restored by rescue treatment). In conclusion, the masculinizing activity of T4 at the population level may be due to its ability to inhibit female and stimulate male sex-related genes in larvae, while the inability of MZ to induce cyp19a1a, which is necessary for ovarian differentiation, may explain why its “feminizing” activity on gonadal sex is not permanent.

Selective sequential separation of ABS/HIPS and PVC from automobile and electronic waste shredder residue by hybrid nano-Fe/Ca/CaO assisted ozonisation process.

PubMed

Mallampati, Srinivasa Reddy; Lee, Byoung Ho; Mitoma, Yoshiharu; Simion, Cristian

2017-02-01

The separation of plastics containing brominated flame retardants (BFR) like (acrylonitrile-butadiene-styrene (ABS), high-impact polystyrene (HIPS), and polyvinyl chloride (PVC)) from automobile and electronic waste shredder residue (ASR/ESR) are a major concern for thermal recycling. In laboratory scale tests using a hybrid nano-Fe/Ca/CaO assisted ozonation treatment has been found to selectively hydrophilize the surface of ABS/HIPS and PVC plastics, enhancing ABS wettability and thereby promoting its separation from ASR/ESR by means of froth flotation. The water contact angles, of ABS/HIPS and PVC decreased, about 18.7°, 18.3°, and 17.9° in ASR and about 21.2°, 20.7°, and 20.0° in ESR respectively. SEM-EDS, FT-IR, and XPS analyses demonstrated a marked decrease in [Cl] and a significant increase in the number of hydrophilic groups, such as CO, CO, and (CO)O, on the PVC or ABS surface. Under froth flotation conditions at 50rpm, about 99.1% of combined fraction of ABS/HIPS in ASR samples and 99.6% of ABS/HIPS in ESR samples were separated as settled fraction. After separation, the purity of the recovered combined ABS/HIPS fraction was 96.5% and 97.6% in ASR and ESR samples respectively. Furthermore, at 150rpm a 100% PVC separation in the settled fraction, with 98% and 99% purity in ASR and ESR plastics, respectively. Total recovery of non-ABS/HIPS and PVC plastics reached nearly 100% in the floating fraction. Further, this process improved the quality of recycled ASR/ESR plastics by removing surface contaminants or impurities. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

Takotsubo syndrome and estrogen receptor genes: partners in crime?

PubMed

Pizzino, Gabriele; Bitto, Alessandra; Crea, Pasquale; Khandheria, Bijoy; Vriz, Olga; Carerj, Scipione; Squadrito, Francesco; Minisini, Rosalba; Citro, Rodolfo; Cusmà-Piccione, Maurizio; Madaffari, Antonio; Andò, Giuseppe; Altavilla, Domenica; Zito, Concetta

2017-04-01

We aimed to analyze genetic polymorphism of estrogen receptor (ESR) 1 and ESR2 in a series of postmenopausal women with Takotsubo syndrome (TS). In total, 81 consecutive white women were prospectively enrolled: 22 with TS (TS group; mean age 71.2 ± 9.8 years), 22 with acute myocardial infarction (MI group; mean age 73.2 ± 8 years), and 37 asymptomatic healthy controls (CTRL group; mean age 69 ± 4.2 years). Genotyping of ESR1 -397C>T (rs2234693) and -351A>G (rs9340799) and ESR2 -1839G>T (rs 1271572) and 1082G>A (rs1256049) genetic variants was performed. We estimated the odds ratio (OR) between the genotype of each examined locus with the occurrence of TS or MI. The risk of experiencing TS was higher for those study participants carrying the T allele at the rs2234693 locus of the ESR1 gene [OR: 2.0, 95% confidence interval (CI): 0.973-4.11, P = 0.04, TS vs. MI + CTRL; OR: 2.79, 95% CI: 1.17-6.64, P = 0.016, TS vs. MI alone]. Women carrying a T allele at the rs1271572 locus of the ESR2 gene demonstrated an even higher risk (OR: 3.23, 95% CI: 1.55-6.73, P = 0.0019, TS vs. MI + CTRL; OR: 9.13, 95% CI: 2.78-29.9, P = 0.0001, TS vs. MI alone). The study reports preliminary findings suggesting a possible link between ESR polymorphisms and the occurrence of TS. Larger studies are needed to confirm our results.

Tumor Genomic Profiling in Breast Cancer Patients Using Targeted Massively Parallel Sequencing

DTIC Science & Technology

2016-03-01

recently, we identified several novel alterations in in ER+ breast tumors, including translocations in ESR1 , the gene that encodes the estrogen receptor...modified our bait design to include genomic coordinates across select introns in ESR1 . In addition, two papers from the Broad Institute published in...with PIK3CA mutations, 23% with ESR1 ligand-binding domain mutations, 9% with ERBB2 mutations, 9% with FGFR1/2 amplifications, and 1% with

Multidisciplinary Biomarkers of Early Mammary Carcinogenesis

DTIC Science & Technology

2011-04-01

cDNA prepared. Quantitative real-time PCR (qRT-PCR) was then performed on the cDNA. All qRT-PCR reactions were performed in triplicate. ESR1 ...in Figure 4, all ER(+) cells express ESR1 at high levels (at least 4 fold higher than ER(-) cell lines). A Pearson correlation coefficient was...calculated to determine the linear relationship between the optical redox ratio and ESR1 expression levels and found to be significant (p = 0.0024, r

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.

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.

[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)

Procalcitonin for the early prediction of renal parenchymal involvement in children with UTI: preliminary results.

PubMed

Kotoula, Aggeliki; Gardikis, Stefanos; Tsalkidis, Aggelos; Mantadakis, Elpis; Zissimopoulos, Athanassios; Kambouri, Katerina; Deftereos, Savvas; Tripsianis, Gregorios; Manolas, Konstantinos; Chatzimichael, Athanassios; Vaos, George

2009-01-01

In order to establish the most reliable marker for distinguishing urinary tract infections (UTI) with and without renal parenchymal involvement (RPI), we recorded the clinical features and admission leukocyte count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum procalcitonin (PCT) in 57 children (including 43 girls) aged 2-108 months admitted with a first episode of UTI. RPI was evaluated by Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy within 7 days of admission. To establish cut-off points for ESR, CRP, and PCT, we used receiver operating characteristics curves and compared the area under the curve for ESR, CRP, and PCT. Twenty-seven children were diagnosed as having RPI based on positive renal scintigraphy. A body temperature of >38 degrees C, a history of diarrhea, and poor oral intake were more common in patients with RPI. ESR, CRP, and PCT, but not leukocyte count, were significantly higher in patients with RPI (P < 0.001). PCT was more sensitive and specific for the diagnosis of upper versus lower UTI than ESR and CRP. Using a cut-off value of 0.85 ng/ml, PCT had the best performance, with sensitivity, specificity, and positive and negative predictive values of 89%, 97%, 96%, and 91% respectively. Serum PCT is a better marker than ESR, CRP, and leukocyte count for the early prediction of RPI in children with a first episode of UTI.

ESR Analysis of Polymer Photo-Oxidation

NASA Technical Reports Server (NTRS)

Kim, Soon Sam; Liang, Ranty Hing; Tsay, Fun-Dow; Gupta, Amitave

1987-01-01

Electron-spin resonance identifies polymer-degradation reactions and their kinetics. New technique enables derivation of kinetic model of specific chemical reactions involved in degradation of particular polymer. Detailed information provided by new method enables prediction of aging characteristics long before manifestation of macroscopic mechanical properties.

Microwave absorption studies of high T sub c superconductors and related materials 8; ESR of DPPH coated on BiSrCaCuO films fabricated on MgO (100) substrates

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

Sugawara, K.; Tanaka, S.

1992-06-20

This paper reports that ESR of DPPH coated on Bi-Sr-Ca-Cu-O films fabricated on MgO (100) substrates by MOCVD have been studied for samples with different thicknesses, 1000 {Angstrom} and 100 {Angstrom}. Temperature dependence of the ESR peak-to-peak linewidth, {Delta}H{sub pp}, revealed that {Delta}H{sub pp} increases with film thickness. The Excess ESR linewidth, {delta}({Delta}H{sub pp}) was also analyzed in terms of (1 {minus} t{sup alpha}, with t = T/T{sub c}, giving for example {alpha} = 4 ={minus}1 for the 1000 {Angstrom} thick sample. The ESR lineshapes were distorted by rotating the samples in applied magnetic fields. Severe distortion was found formore » the 1000 {Angstrom} sample below about 30 K, but the distortion almost disappears at temperatures above 30 K. The applied magnetic field effects were also examined in both field-cooled and zero-field-cooled cases.« less

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.

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.

Selective electron spin resonance measurements of micrometer-scale thin samples on a substrate

NASA Astrophysics Data System (ADS)

Dikarov, Ekaterina; Fehr, Matthias; Schnegg, Alexander; Lips, Klaus; Blank, Aharon

2013-11-01

An approach to the selective observation of paramagnetic centers in thin samples or surfaces with electron spin resonance (ESR) is presented. The methodology is based on the use of a surface microresonator that enables the selective obtention of ESR data from thin layers with minimal background signals from the supporting substrate. An experimental example is provided, which measures the ESR signal from a 1.2 µm polycrystalline silicon layer on a glass substrate used in modern solar-cell technology. The ESR results obtained with the surface microresonator show the effective elimination of background signals, especially at low cryogenic temperatures, compared to the use of a conventional resonator. The surface microresonator also facilitates much higher absolute spin sensitivity, requiring much smaller surfaces for the measurement.

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

PubMed

Dunning, Alison M; Michailidou, Kyriaki; Kuchenbaecker, Karoline B; Thompson, Deborah; French, Juliet D; Beesley, Jonathan; Healey, Catherine S; Kar, Siddhartha; Pooley, Karen A; Lopez-Knowles, Elena; Dicks, Ed; Barrowdale, Daniel; Sinnott-Armstrong, Nicholas A; Sallari, Richard C; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; Moradi Marjaneh, Mahdi; Lee, Jason S; Hills, Margaret; Jarosz, Monika; Drury, Suzie; Canisius, Sander; Bolla, Manjeet K; Dennis, Joe; Wang, Qin; Hopper, John L; Southey, Melissa C; Broeks, Annegien; Schmidt, Marjanka K; Lophatananon, Artitaya; Muir, Kenneth; Beckmann, Matthias W; Fasching, Peter A; Dos-Santos-Silva, Isabel; Peto, Julian; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; González-Neira, Anna; Perez, Jose I A; Anton-Culver, Hoda; Eunjung, Lee; Arndt, Volker; Brenner, Hermann; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Aittomäki, Kristiina; Blomqvist, Carl; Ito, Hidemi; Matsuo, Keitaro; Bogdanova, Natasha; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Kosma, Veli-Matti; Mannermaa, Arto; Tseng, Chiu-Chen; Wu, Anna H; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Rudolph, Anja; Peterlongo, Paolo; Radice, Paolo; Olson, Janet E; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Henderson, Brian E; Goldberg, Mark S; Teo, Soo H; Yip, Cheng Har; Nord, Silje; Borresen-Dale, Anne-Lise; Kristensen, Vessela; Long, Jirong; Zheng, Wei; Pylkäs, Katri; Winqvist, Robert; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; Figueroa, Jonine; Sherman, Mark E; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; van den Ouweland, Ans M W; Humphreys, Keith; Gao, Yu-Tang; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S; Blot, William; Cai, Qiuyin; Ghoussaini, Maya; Perkins, Barbara J; Shah, Mitul; Choi, Ji-Yeob; Kang, Daehee; Lee, Soo Chin; Hartman, Mikael; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Brennan, Paul; Sangrajrang, Suleeporn; Ambrosone, Christine B; Toland, Amanda E; Shen, Chen-Yang; Wu, Pei-Ei; Orr, Nick; Swerdlow, Anthony; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Kapuscinski, Miroslav; John, Esther M; Terry, Mary Beth; Daly, Mary B; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ejlertsen, Bent; Hansen, Thomas V O; Osorio, Ana; Benitez, Javier; Rando, Rachel; Weitzel, Jeffrey N; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Papi, Laura; Ottini, Laura; Konstantopoulou, Irene; Apostolou, Paraskevi; Garber, Judy; Rashid, Muhammad Usman; Frost, Debra; Izatt, Louise; Ellis, Steve; Godwin, Andrew K; Arnold, Norbert; Niederacher, Dieter; Rhiem, Kerstin; Bogdanova-Markov, Nadja; Sagne, Charlotte; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Sinilnikova, Olga M; Mazoyer, Sylvie; Isaacs, Claudine; Claes, Kathleen B M; De Leeneer, Kim; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Khan, Sofia; Mensenkamp, Arjen R; Hooning, Maartje J; Rookus, Matti A; Kwong, Ava; Olah, Edith; Diez, Orland; Brunet, Joan; Pujana, Miquel Angel; Gronwald, Jacek; Huzarski, Tomasz; Barkardottir, Rosa B; Laframboise, Rachel; Soucy, Penny; Montagna, Marco; Agata, Simona; Teixeira, Manuel R; Park, Sue Kyung; Lindor, Noralane; Couch, Fergus J; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Singer, Christian F; Rappaport, Christine; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Imyanitov, Evgeny N; Hulick, Peter J; Phillips, Kelly-Anne; Piedmonte, Marion; Mulligan, Anna Marie; Glendon, Gord; Bojesen, Anders; Thomassen, Mads; Caligo, Maria A; Yoon, Sook-Yee; Friedman, Eitan; Laitman, Yael; Borg, Ake; von Wachenfeldt, Anna; Ehrencrona, Hans; Rantala, Johanna; Olopade, Olufunmilayo I; Ganz, Patricia A; Nussbaum, Robert L; Gayther, Simon A; Nathanson, Katherine L; Domchek, Susan M; Arun, Banu K; Mitchell, Gillian; Karlan, Beth Y; Lester, Jenny; Maskarinec, Gertraud; Woolcott, Christy; Scott, Christopher; Stone, Jennifer; Apicella, Carmel; Tamimi, Rulla; Luben, Robert; Khaw, Kay-Tee; Helland, Åslaug; Haakensen, Vilde; Dowsett, Mitch; Pharoah, Paul D P; Simard, Jacques; Hall, Per; García-Closas, Montserrat; Vachon, Celine; Chenevix-Trench, Georgia; Antoniou, Antonis C; Easton, Douglas F; Edwards, Stacey L

2016-04-01

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

PubMed Central

Dunning, Alison M; Michailidou, Kyriaki; Kuchenbaecker, Karoline B; Thompson, Deborah; French, Juliet D; Beesley, Jonathan; Healey, Catherine S; Kar, Siddhartha; Pooley, Karen A; Lopez-Knowles, Elena; Dicks, Ed; Barrowdale, Daniel; Sinnott-Armstrong, Nicholas A; Sallari, Richard C; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; Marjaneh, Mahdi Moradi; Lee, Jason S; Hills, Margaret; Jarosz, Monika; Drury, Suzie; Canisius, Sander; Bolla, Manjeet K; Dennis, Joe; Wang, Qin; Hopper, John L; Southey, Melissa C; Broeks, Annegien; Schmidt, Marjanka K; Lophatananon, Artitaya; Muir, Kenneth; Beckmann, Matthias W; Fasching, Peter A; dos-Santos-Silva, Isabel; Peto, Julian; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; González-Neira, Anna; Perez, Jose I A; Anton-Culver, Hoda; Eunjung, Lee; Arndt, Volker; Brenner, Hermann; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Aittomäki, Kristiina; Blomqvist, Carl; Ito, Hidemi; Matsuo, Keitaro; Bogdanova, Natasha; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Kosma, Veli-Matti; Mannermaa, Arto; Tseng, Chiu-chen; Wu, Anna H; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Rudolph, Anja; Peterlongo, Paolo; Radice, Paolo; Olson, Janet E; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Henderson, Brian E; Goldberg, Mark S; Teo, Soo H; Yip, Cheng Har; Nord, Silje; Borresen-Dale, Anne-Lise; Kristensen, Vessela; Long, Jirong; Zheng, Wei; Pylkäs, Katri; Winqvist, Robert; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; Figueroa, Jonine; Sherman, Mark E; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; van den Ouweland, Ans M W; Humphreys, Keith; Gao, Yu-Tang; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S; Blot, William; Cai, Qiuyin; Ghoussaini, Maya; Perkins, Barbara J; Shah, Mitul; Choi, Ji-Yeob; Kang, Daehee; Lee, Soo Chin; Hartman, Mikael; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Brennan, Paul; Sangrajrang, Suleeporn; Ambrosone, Christine B; Toland, Amanda E; Shen, Chen-Yang; Wu, Pei-Ei; Orr, Nick; Swerdlow, Anthony; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Kapuscinski, Miroslav; John, Esther M; Terry, Mary Beth; Daly, Mary B; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ejlertsen, Bent; Hansen, Thomas V O; Osorio, Ana; Benitez, Javier; Rando, Rachel; Weitzel, Jeffrey N; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Papi, Laura; Ottini, Laura; Konstantopoulou, Irene; Apostolou, Paraskevi; Garber, Judy; Rashid, Muhammad Usman; Frost, Debra; Izatt, Louise; Ellis, Steve; Godwin, Andrew K; Arnold, Norbert; Niederacher, Dieter; Rhiem, Kerstin; Bogdanova-Markov, Nadja; Sagne, Charlotte; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Sinilnikova, Olga M; Mazoyer, Sylvie; Isaacs, Claudine; Claes, Kathleen B M; De Leeneer, Kim; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Khan, Sofia; Mensenkamp, Arjen R; Hooning, Maartje J; Rookus, Matti A; Kwong, Ava; Olah, Edith; Diez, Orland; Brunet, Joan; Pujana, Miquel Angel; Gronwald, Jacek; Huzarski, Tomasz; Barkardottir, Rosa B; Laframboise, Rachel; Soucy, Penny; Montagna, Marco; Agata, Simona; Teixeira, Manuel R; Park, Sue Kyung; Lindor, Noralane; Couch, Fergus J; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Singer, Christian F; Rappaport, Christine; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Imyanitov, Evgeny N; Hulick, Peter J; Phillips, Kelly-Anne; Piedmonte, Marion; Mulligan, Anna Marie; Glendon, Gord; Bojesen, Anders; Thomassen, Mads; Caligo, Maria A; Yoon, Sook-Yee; Friedman, Eitan; Laitman, Yael; Borg, Ake; von Wachenfeldt, Anna; Ehrencrona, Hans; Rantala, Johanna; Olopade, Olufunmilayo I; Ganz, Patricia A; Nussbaum, Robert L; Gayther, Simon A; Nathanson, Katherine L; Domchek, Susan M; Arun, Banu K; Mitchell, Gillian; Karlan, Beth Y; Lester, Jenny; Maskarinec, Gertraud; Woolcott, Christy; Scott, Christopher; Stone, Jennifer; Apicella, Carmel; Tamimi, Rulla; Luben, Robert; Khaw, Kay-Tee; Helland, Åslaug; Haakensen, Vilde; Dowsett, Mitch; Pharoah, Paul D P; Simard, Jacques; Hall, Per; García-Closas, Montserrat; Vachon, Celine; Chenevix-Trench, Georgia; Antoniou, Antonis C; Easton, Douglas F; Edwards, Stacey L

2016-01-01

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER+ or ER−) and human ERBB2 (HER2+ or HER2−) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER− tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression. PMID:26928228

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.

Vision Loss, Sudden

MedlinePlus

... present. CT = computed tomography; ECG = electrocardiography; ESR = erythrocyte sedimentation rate; MRI = magnetic resonance imaging. Spotlight on Aging: ... swelling is seen during the eye examination. Erythrocyte sedimentation rate (ESR) and C-reactive protein level (blood ...

Analysis of Sex Hormone Genes Reveals Gender Differences in the Genetic Etiology of Blood Pressure Salt Sensitivity: The GenSalt Study

PubMed Central

2013-01-01

BACKGROUND We examined the association between 799 single-nucleotide polymorphisms in 39 sex hormone genes and blood pressure (BP) responses to a dietary-sodium intervention. METHODS A 7-day low-sodium feeding study (51.3 mmol sodium/day) followed by a 7-day high-sodium feeding study (307.8 mmol sodium/day) was conducted among 1,906 Han Chinese participants. Nine BP measurements were obtained at baseline and the end of each intervention period using a random-zero sphygmomanometer. RESULTS Among men, absolute BP responses to sodium interventions decreased with the number of minor alleles of estrogen receptor 1 (ESR1) markers rs9340844, rs9397453, rs9371562, rs9397459, and rs9383951. For example, mean diastolic blood pressure (DBP) responses to low-sodium intervention (95% confidence interval) were –2.67 (–3.13, –2.22) mm Hg among those with the rs9397453 C/C genotype, –1.23 (–1.98, –0.48) mm Hg among those with the C/T genotype, and 0.08 (–2.31, 2.47) mm Hg among those with the T/T genotype (P = 1×10–4; false discovery rate (FDR)-q = 0.04). Mean DBP responses to high sodium according to the rs9397453 genotypes were 1.46 (1.03, 1.89) mm Hg among those with C/C, 0.19 (–0.54, 0.91) mm Hg among those with C/T, and –1.10 (–2.82, 0.61) mm Hg among those with T/T (P = 2×10–4; FDR-q = 0.04). Similar trends were noted for the association between these ESR1 variants and SBP responses to the dietary intervention. There were no significant associations between sex hormone gene variants and salt sensitivity in women, with genotype-gender interactions noted for the ESR1 markers that achieved significance in men. CONCLUSIONS We identified strong, consistent associations between ESR1 gene variants and salt sensitivity in men. Our results support a gender-specific role for ESR1 in the etiology of this complex trait. PMID:23382403

ESR1 Is Co-Expressed with Closely Adjacent Uncharacterised Genes Spanning a Breast Cancer Susceptibility Locus at 6q25.1

PubMed Central

Dunbier, Anita K.; Anderson, Helen; Ghazoui, Zara; Lopez-Knowles, Elena; Pancholi, Sunil; Ribas, Ricardo; Drury, Suzanne; Sidhu, Kally; Leary, Alexandra; Martin, Lesley-Ann; Dowsett, Mitch

2011-01-01

Approximately 80% of human breast carcinomas present as oestrogen receptor α-positive (ER+ve) disease, and ER status is a critical factor in treatment decision-making. Recently, single nucleotide polymorphisms (SNPs) in the region immediately upstream of the ER gene (ESR1) on 6q25.1 have been associated with breast cancer risk. Our investigation of factors associated with the level of expression of ESR1 in ER+ve tumours has revealed unexpected associations between genes in this region and ESR1 expression that are important to consider in studies of the genetic causes of breast cancer risk. RNA from tumour biopsies taken from 104 postmenopausal women before and after 2 weeks treatment with an aromatase (oestrogen synthase) inhibitor was analyzed on Illumina 48K microarrays. Multiple-testing corrected Spearman correlation revealed that three previously uncharacterized open reading frames (ORFs) located immediately upstream of ESR1, C6ORF96, C6ORF97, and C6ORF211 were highly correlated with ESR1 (Rs = 0.67, 0.64, and 0.55 respectively, FDR<1×10−7). Publicly available datasets confirmed this relationship in other groups of ER+ve tumours. DNA copy number changes did not account for the correlations. The correlations were maintained in cultured cells. An ERα antagonist did not affect the ORFs' expression or their correlation with ESR1, suggesting their transcriptional co-activation is not directly mediated by ERα. siRNA inhibition of C6ORF211 suppressed proliferation in MCF7 cells, and C6ORF211 positively correlated with a proliferation metagene in tumours. In contrast, C6ORF97 expression correlated negatively with the metagene and predicted for improved disease-free survival in a tamoxifen-treated published dataset, independently of ESR1. Our observations suggest that some of the biological effects previously attributed to ER could be mediated and/or modified by these co-expressed genes. The co-expression and function of these genes may be important influences on the recently identified relationship between SNPs in this region and breast cancer risk. PMID:21552322

Electron spin resonance measurement of radical scavenging activity of Aronia melanocarpa fruit juice

PubMed Central

Valcheva-Kuzmanova, Stefka; Blagović, Branka; Valić, Srećko

2012-01-01

Background: The fruits of Aronia melanocarpa (Michx.) Elliot contain large amounts of phenolic substances, mainly procyanidins, anthocyanins and other flavonoids, and phenolic acids. The ability of phenolic substances to act as antioxidants has been well established. Objective: In this study, we investigated the radical scavenging activity of A. melanocarpa fruit juice (AMFJ). Materials and Methods: The method used was electron spin resonance (ESR) spectroscopy. The galvinoxyl free radical was used as a scavenging object. AMFJ was added to the galvinoxyl free radical solution. The measure of the radical scavenging activity was the decrease of signal intensity. Results: AMFJ showed a potent antiradical activity causing a strong and rapid decrease of signal intensity as a function of time and juice concentration. This effect of AMFJ was probably due to the activity of its phenolic constituents. Conclusion: The ESR measurements in this study showed a pronounced radical scavenging effect of AMFJ, an important mechanism of its antioxidant activity. PMID:22701293

Electron spin resonance spectroscopy for immunoassay using iron oxide nanoparticles as probe.

PubMed

Jiang, Jia; Tian, Sizhu; Wang, Kun; Wang, Yang; Zang, Shuang; Yu, Aimin; Zhang, Ziwei

2018-02-01

With the help of iron oxide nanoparticles, electron spin resonance spectroscopy (ESR) was applied to immunoassay. Iron oxide nanoparticles were used as the ESR probe in order to achieve an amplification of the signal resulting from the large amount of Fe 3+ ion enclosed in each nanoparticle. Rabbit IgG was used as antigen to test this method. Polyclonal antibody of rabbit IgG was used as antibody to detect the antigen. Iron oxide nanoparticle with a diameter of either 10 or 30 nm was labeled to the antibody, and Fe 3+ in the nanoparticle was probed for ESR signal. The sepharose beads were used as solid phase to which rabbit IgG was conjugated. The nanoparticle-labeled antibody was first added in the sample containing antigen, and the antigen-conjugated sepharose beads were then added into the sample. The nanoparticle-labeled antibody bound to the antigen on sepharose beads was separated from the sample by centrifugation and measured. We found that the detection ranges of the antigen obtained with nanoparticles of different sizes were different because the amount of antibody on nanoparticles of 10 nm was about one order of magnitude higher than that on nanoparticles of 30 nm. When 10 nm nanoparticle was used as probe, the upper limit of detection was 40.00 μg mL -1 , and the analytical sensitivity was 1.81 μg mL -1 . When 30 nm nanoparticle was used, the upper limit of detection was 3.00 μg mL -1 , and the sensitivity was 0.014 and 0.13 μg mL -1 depending on the ratio of nanoparticle to antibody. Graphical abstract Schematic diagram of procedure and ESR spectra.

Preliminary Criteria for Global Flares in Childhood-Onset Systemic Lupus Erythematosus

PubMed Central

Brunner, Hermine I.; Mina, Rina; Pilkington, Clarissa; Beresford, Michael W.; Reiff, Andreas; Levy, Deborah M.; Tucker, Lori B.; Eberhard, B. Anne; Ravelli, Angelo; Schanberg, Laura E.; Saad-Magalhaes, Claudia; Higgins, Gloria C.; Onel, Karen; Singer, Nora G.; von Scheven, Emily; Itert, Lukasz; Klein-Gitelman, Marisa S.; Punaro, Marilynn; Ying, Jun; Giannini, Edward H.

2011-01-01

Objectives To develop widely acceptable preliminary criteria of global flare for childhood-onset SLE (cSLE). Methods Pediatric rheumatologists (n=138) rated a total of 358 unique patient profiles (PP) with information about the cSLE flare descriptors (cSLE-FD) from two consecutive visits: patient global assessment of well-being, physician global assessment of disease activity (MD-global), health-related quality of life, anti-dsDNA antibodies, disease activity index score, protein/creatinine (P/C) ratio, complement levels and ESR. Based on 2996 rater responses about the course of cSLE (baseline vs. follow-up) the accuracy (sensitivity, specificity, area under the receiver operating characteristic curve) of candidate flare criteria was assessed. An international consensus conference was held to rank these candidate flare criteria as per the ACR-recommendations for the development and validation of criteria sets. Results The highest ranked candidate criteria considered absolute changes (Δ) of the SLEDAI or BILAG, MD-global, P/C ratio, and ESR; Flare scores can be calculated [0.5 × ΔSLEDAI + 0.45 × ΔP/C ratio + 0.5 × ΔMD-global + 0.02 × ΔESR], where values ≥ 1.04 are reflective of a flare. Similarly, BILAG-based flare scores [0.4 × ΔBILAG + 0.65 × ΔP/C ratio + 0.5 × ΔMD-global + 0.02 × ΔESR] of ≥ 1.15 were diagnostic of a flare. Flare scores increase with flare severity. Conclusions Consensus has been reached on preliminary criteria for global flares in cSLE. Further validation studies are needed to confirm the usefulness of the cSLE flare criteria in research and for clinical care. PMID:21618452

In Vivo Genome-Wide Expression Study on Human Circulating B Cells Suggests a Novel ESR1 and MAPK3 Network for Postmenopausal Osteoporosis

PubMed Central

Xiao, Peng; Chen, Yuan; Jiang, Hui; Liu, Yao-Zhong; Pan, Feng; Yang, Tie-Lin; Tang, Zi-Hui; Larsen, Jennifer A; Lappe, Joan M; Recker, Robert R; Deng, Hong-Wen

2008-01-01

Introduction Osteoporosis is characterized by low BMD. Studies have shown that B cells may participate in osteoclastogenesis through expression of osteoclast-related factors, such as RANKL, transforming growth factor β (TGFB), and osteoprotegerin (OPG). However, the in vivo significance of B cells in human bone metabolism and osteoporosis is still largely unknown, particularly at the systematic gene expression level. Materials and Methods In this study, Affymetrix HG-U133A GeneChip arrays were used to identify genes differentially expressed in B cells between 10 low and 10 high BMD postmenopausal women. Significance of differential expression was tested by t-test and adjusted for multiple testing with the Benjamini and Hochberg (BH) procedure (adjusted p ≤ 0.05). Results Twenty-nine genes were downregulated in the low versus high BMD group. These genes were further analyzed using Ingenuity Pathways Analysis (Ingenuity Systems). A network involving estrogen receptor 1 (ESR1) and mitogen activated protein kinase 3 (MAPK3) was identified. Real-time RT-PCR confirmed differential expression of eight genes, including ESR1, MAPK3, methyl CpG binding protein 2 (MECP2), proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), Scr-like-adaptor (SLA), serine/threonine kinase 11 (STK11), WNK lysine-deficient protein kinase 1 (WNK1), and zinc finger protein 446 (ZNF446). Conclusions This is the first in vivo genome-wide expression study on human B cells in relation to osteoporosis. Our results highlight the significance of B cells in the etiology of osteoporosis and suggest a novel mechanism for postmenopausal osteoporosis (i.e., that downregulation of ESR1 and MAPK3 in B cells regulates secretion of factors, leading to increased osteoclastogenesis or decreased osteoblastogenesis). PMID:18433299

ESR dosimeter material properties of phenols compound exposed to radiotherapeutic electron beams

NASA Astrophysics Data System (ADS)

Gallo, Salvatore; Iacoviello, Giuseppina; Bartolotta, Antonio; Dondi, Daniele; Panzeca, Salvatore; Marrale, Maurizio

2017-09-01

There is a need for a sensitive dosimeter using Electron Spin Resonance spectroscopy for use in medical applications, since non-destructive read-out and dose archival could be achieved with this method. This work reports a systematic ESR investigation of IRGANOX ® 1076 exposed to clinical electron beams produced by a LINAC used for radiation therapy treatments. Recently, dosimetric features of this material were investigated for irradiation with 60Co γ -photons and neutrons in both pellet and film shape and have been found promising thanks to their high efficiency of radiation-matter energy transfer and radical stability at room temperature. Here the analysis of the dosimetric features of these ESR dosimeters exposed to clinical electron beams at energies of 7, 10 and 14 MeV, is described in terms of dependence on microwave power and modulation amplitude, response on dose, dependence on beam type, detection limits, and signal stability after irradiation. The analysis of the ESR signal as function of absorbed dose highlights that the response of this material is linear in the dose range investigated (1-13 Gy) and is independent of the beam energy. The minimum detectable dose is found to be smaller than 1 Gy. Comparison of electron stopping power values of these dosimeters with those of water and soft tissue highlights equivalence of the response to electron beams in the energy range considered. The signal intensity was monitored for 40 days after irradiation and for all energies considered and it shows negligible variations in the first 500 h after irradiation whereas after 1100 h the signal decay is only of about 4%. In conclusion, it is found that phenolic compounds possess good dosimetric features which make it useful as a sensitive dosimeter for medical applications.

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

Serum Hydroxyl Radical Scavenging Capacity as Quantified with Iron-Free Hydroxyl Radical Source

PubMed Central

Endo, Nobuyuki; Oowada, Shigeru; Sueishi, Yoshimi; Shimmei, Masashi; Makino, Keisuke; Fujii, Hirotada; Kotake, Yashige

2009-01-01

We have developed a simple ESR spin trapping based method for hydroxyl (OH) radical scavenging-capacity determination, using iron-free OH radical source. Instead of the widely used Fenton reaction, a short (typically 5 seconds) in situ UV-photolysis of a dilute hydrogen peroxide aqueous solution was employed to generate reproducible amounts of OH radicals. ESR spin trapping was applied to quantify OH radicals; the decrease in the OH radical level due to the specimen’s scavenging activity was converted into the OH radical scavenging capacity (rate). The validity of the method was confirmed in pure antioxidants, and the agreement with the previous data was satisfactory. In the second half of this work, the new method was applied to the sera of chronic renal failure (CRF) patients. We show for the first time that after hemodialysis, OH radical scavenging capacity of the CRF serum was restored to the level of healthy control. This method is simple and rapid, and the low concentration hydrogen peroxide is the only chemical added to the system, that could eliminate the complexity of iron-involved Fenton reactions or the use of the pulse-radiolysis system. PMID:19794928

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.

Interpretation of cw-ESR spectra of p-methyl-thio-phenyl-nitronyl nitroxide in a nematic liquid crystalline phase.

PubMed

Collauto, Alberto; Zerbetto, Mirco; Brustolon, Marina; Polimeno, Antonino; Caneschi, Andrea; Gatteschi, Dante

2012-03-07

In this paper we report on the characterization by continuous wave electron spin resonance spectroscopy (cw-ESR) of a nitronyl nitroxide radical in a nematic phase. A detailed analysis is performed by exploiting an innovative modeling strategy alternative to the usual spectral simulation approach: most of the molecular parameters needed to calculate the spectrum are evaluated a priori and the ESR spectrum is obtained by direct application of the stochastic Liouville equation. Allowing a limited set of fitting parameters it is possible to reproduce satisfactorily ESR spectra in the temperature range 260 K-340 K including the nematic-to-isotropic phase transition (325.1 K). Our results open the way to a more quantitative understanding of the ordering and mobility of nitronyl nitroxide radicals in nanostructured environments.

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.

Angle-dependent electron spin resonance of YbRh2Si2 measured with planar microwave resonators and in-situ rotation

NASA Astrophysics Data System (ADS)

Bondorf, Linda; Beutel, Manfred; Thiemann, Markus; Dressel, Martin; Bothner, Daniel; Sichelschmidt, Jörg; Kliemt, Kristin; Krellner, Cornelius; Scheffler, Marc

2018-05-01

We present a new experimental approach to investigate the magnetic properties of the anisotropic heavy-fermion system YbRh2Si2 as a function of crystallographic orientation. Angle-dependent electron spin resonance (ESR) measurements are performed at a low temperature of 1.6 K and at an ESR frequency of 4.4 GHz utilizing a superconducting planar microwave resonator in a 4He-cryostat in combination with in-situ sample rotation. The obtained ESR g-factor of YbRh2Si2 as a function of the crystallographic angle is consistent with results of previous measurements using conventional ESR spectrometers at higher frequencies and fields. Perspectives to implement this experimental approach into a dilution refrigerator and to reach the magnetically ordered phase of YbRh2Si2 are discussed.

Electron spin resonance of nitrogen-vacancy centers in optically trapped nanodiamonds

PubMed Central

Horowitz, Viva R.; Alemán, Benjamín J.; Christle, David J.; Cleland, Andrew N.; Awschalom, David D.

2012-01-01

Using an optical tweezers apparatus, we demonstrate three-dimensional control of nanodiamonds in solution with simultaneous readout of ground-state electron-spin resonance (ESR) transitions in an ensemble of diamond nitrogen-vacancy color centers. Despite the motion and random orientation of nitrogen-vacancy centers suspended in the optical trap, we observe distinct peaks in the measured ESR spectra qualitatively similar to the same measurement in bulk. Accounting for the random dynamics, we model the ESR spectra observed in an externally applied magnetic field to enable dc magnetometry in solution. We estimate the dc magnetic field sensitivity based on variations in ESR line shapes to be approximately . This technique may provide a pathway for spin-based magnetic, electric, and thermal sensing in fluidic environments and biophysical systems inaccessible to existing scanning probe techniques. PMID:22869706

ESR1 and PIK3CA mutational status in serum and plasma from metastatic breast cancer patients: A comparative study.

PubMed

Takeshita, Takashi; Yamamoto, Yutaka; Yamamoto-Ibusuki, Mutsuko; Tomiguchi, Mai; Sueta, Aiko; Iwase, Hirotaka

2018-04-07

Plasma and serum cell-free DNA (cfDNA) are useful sources of tumor DNA, but comparative investigations of the tumor mutational status between them are rare. we performed droplet digital PCR assay for representative hotspot mutations in metastatic breast cancer (MBC) (ESR1 and PIK3CA) in serum and plasma cfDNA concurrently extracted from the blood of 33 estrogen receptor-positive MBC patients. ESR1 mutations in plasma cfDNA were found in 7 of the 33 patients; ESR1 mutations in serum cfDNA were detected in only one out of 7 patients with ESR1 mutations in plasma cfDNA. PIK3CA exon 9 and exon 20 mutations in plasma cfDNA were found in 3 and 7 out of the 33 patients, respectively; PIK3CA exon 9 mutations in serum cfDNA were detected in 2 out of 3 patients with PIK3CA exon 9 mutations in plasma cfDNA; PIK3CA exon 20 mutations in serum cfDNA were detected in 2 out of 7 patients with PIK3CA exon 20 mutations in plasma cfDNA. Here we show the higher frequency of ESR1 and PIK3CA mutations in the plasma than in the serum in 33 MBC patients; therefore, serum samples should not be considered the preferred source of cfDNA.

Sera DNA Methylation of CDH1, DNMT3b and ESR1 Promoters as Biomarker for the Early Diagnosis of Hepatitis B Virus-Related Hepatocellular Carcinoma.

PubMed

Dou, Cheng-Yun; Fan, Yu-Chen; Cao, Chuang-Jie; Yang, Yang; Wang, Kai

2016-04-01

DNA methylation mainly affects tumor suppressor genes in the development of hepatocellular carcinoma (HCC). However, sera methylation of specific genes in hepatitis B virus (HBV)-related HCC remains unknown. The purpose of this study was to identify methylation frequencies of sera E-cadherin (CDH1), DNA methyltransferase 3b (DNMT3b) and estrogen receptor 1 (ESR1) promoter in HBV-related HCC and analyze the associated clinical significance. Methylation-specific PCR was used to determine the frequencies of DNA methylation for CDH1, DNMT3b and ESR1 genes in sera from 183 patients with HCC, 47 liver cirrhosis (LC), 126 chronic hepatitis B (CHB), and 50 normal controls (NCs). Significantly higher frequencies of methylation of CDH1, DNMT3b and ESR1 were found in HBV-related HCC compared with LC, CHB and NCs. Nodule numbers, tumor size and the presence of liver cirrhosis were significantly associated with gene methylation status in HBV-related HCC. Moreover, HBV may have a strong and enhanced effect on the concurrent methylation of CDH1, DNMT3b and ESR1 in HBV-related HCC. More importantly, combined methylation as a biomarker displayed significantly higher diagnostic value than AFP to discriminate HCC from CHB and LC. Aberrant sera DNA methylation of CDH1, DNMT3b and ESR1 gene promoters could be a biomarker in the early diagnosis of HBV-related HCC.

Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico.

PubMed

Cahua-Pablo, José Ángel; Cruz, Miguel; Méndez-Palacios, Abigail; Antúnez-Ortiz, Diana Lizzete; Vences-Velázquez, Amalia; del Carmen Alarcón-Romero, Luz; Parra, Esteban Juan; Tello-Flores, Vianet Argelia; Leyva-Vázquez, Marco Antonio; Valladares-Salgado, Adán; Pérez-Macedonio, Claudia Paola; Flores-Alfaro, Eugenia

2015-09-08

Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

Genetically-induced Estrogen Receptor Alpha mRNA (Esr1) Overexpression Does Not Adversely Affect Fertility or Penile Development in Male Mice

PubMed Central

Heath, John; Abdelmageed, Yazeed; Braden, Tim D.; Williams, Carol S.; Williams, John W.; Paulose, Tessie; Hernandez-Ochoa, Isabel; Gupta, Rupesh; Flaws, Jodi A.; Goyal, Hari O.

2011-01-01

Previously, we reported that estrogen receptor alpha mRNA (Esr1) or protein (ESR1) overexpression resulting from neonatal exposure to estrogens in rats was associated with infertility and mal-developed penis characterized by reduced length and weight and abnormal accumulation of fat cells. The objective of this study was to determine if mutant male mice overexpressing Esr1 are naturally infertile or have reduced fertility and/or develop abnormal penis. The fertility parameters, including fertility and fecundity indices, numbers of days from the day of cohabitation to the day of delivery, and numbers of pups per female, were not altered from controls, as a result of Esr1 overexpression. Likewise, penile morphology, including the length, weight, and diameter and os penis development, was not altered from controls. Conversely, weights of the seminal vesicles and bulbospongiosus and levator ani (BS/LA) muscles were significantly (P < 0.05) lower as compared to controls; however, the weight of the testis, the morphology of the testis and epididymis, and the plasma and testicular testosterone concentration were not different from controls. Hence, the genetically-induced Esr1 overexpression alone, without an exogenous estrogen exposure during the neonatal period, is unable to adversely affect the development of the penis as well as other male reproductive organs, except limited, but significant, reductions in weights of the seminal vesicles and BS/LA muscles. PMID:20930192

Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico

PubMed Central

Cahua-Pablo, José Ángel; Cruz, Miguel; Méndez-Palacios, Abigail; Antúnez-Ortiz, Diana Lizzete; Vences-Velázquez, Amalia; del Carmen Alarcón-Romero, Luz; Parra, Esteban Juan; Tello-Flores, Vianet Argelia; Leyva-Vázquez, Marco Antonio; Valladares-Salgado, Adán; Pérez-Macedonio, Claudia Paola; Flores-Alfaro, Eugenia

2015-01-01

Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features. PMID:26370976

Association of estrogen receptor gene polymorphisms with human precocious puberty: a systematic review and meta-analysis.

PubMed

Luo, Yan; Liu, Qin; Lei, Xun; Wen, Yi; Yang, Ya-Lan; Zhang, Rui; Hu, Meng-Yao

2015-07-01

This study aims to estimate the association between ESR1 polymorphisms (PvuII and XbaI) and ESR2 polymorphisms (RsaI and AluI) with precocious puberty. Relevant studies published before March 2014 were retrieved by a electronic search among nine databases. Meta-analysis of the pooled odds ratios (ORs) with 95% confidence intervals (CIs) was calculated. Four eligible case-control studies including 491 precocious puberty patients and 370 healthy controls were identified. Three studies reported ESR1 PvuII and XbaI polymorphism and one study reported ESR2 RsaI and AluI polymorphism. Increment of precocious puberty risk was associated with PvuII polymorphism in the heterosis model ((CT) versus TT: OR 1.42, 95% CI: 1.05-1.91, p = 0.02). Risk of precocious puberty was associated with XbaI polymorphism in the dominant model (GG + GA versus AA: OR 1.48, 95% CI: 1.11-1.97, p = 0.007) and the heterosis model (GA versus AA: OR 1.68, 95% CI: 1.23-2.29, p = 0.001). This meta-analysis suggests that ESR1 XbaI and PvuII polymorphisms are associated with precocious puberty susceptibility, and the relationship between ESR2 RsaI and AluI polymorphism with precocious puberty remains to be further investigated. Well-designed studies with large sample size among different polymorphisms and ethnicities are in urgent need to provide and update reliable data for comprehensive and definite conclusion.

Epigenetic Changes of the ESR1 Gene in Breast Tissue of Healthy Women: A Missing Link with Breast Cancer Risk Factors?

PubMed

Daraei, Abdolreza; Izadi, Pantea; Khorasani, Ghasemali; Nafissi, Nahid; Naghizadeh, Mohammad Mehdi; Younosi, Nasim; Meysamie, Alipasha; Mansoori, Yaser; Bastami, Milad; Tavakkoly-Bazzaz, Javad

2017-08-01

Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of the estrogen receptor 1 (ESR1) gene hypermethylation is reportedly important in the development of breast cancer. Thus, it is speculated that such ESR1 epigenetic changes may be influenced or shaped by obesity and reproductive history-related factors before and during breast carcinogenesis. Breast samples were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. DNA was extracted from the breast tissues and, then, the methylation levels at the promoter and exon 1 regions of the ESR1 gene CpG island were determined by using the methylated DNA immunoprecipitation-quantitative PCR assay. The methylation level of the ESR1 promoter observed in women with a body mass index (BMI) ≥30 kg/m 2 (p ≤ 0.001) was higher than in the subgroups of women of BMI <25 kg/m 2 (p < 0.001) and BMI 25-29 kg/m 2 (p < 0.001) and was also higher in postmenopausal women compared with that in premenopausal women (p = 0.046). Pearson correlation coefficient analyses also showed that the high methylation of the ESR1 promoter was correlated with increasing age (r = -0.246, p = 0.007) and BMI (r = -0.331, p ≤ 0.001). Finally, linear multivariate regression revealed a significant association between high methylation rates in the ESR1 gene promoter and increased BMI (β = -0.285, 95% CI = -0.457 to -0.113, p = 0.001). Furthermore, a higher methylation level at the ESR1 gene exon 1 was found in the BMI ≥ 30 kg/m 2 subgroup compared to the BMI 25-29 kg/m 2 subgroup (p = 0.023). These findings provide new hints about the relationship between epigenetic changes within the ESR1 gene CpG island and postmenopausal obesity and aging in cancer-free women. In terms of lifestyle intervention opportunities, this study also highlights the significance and feasibility of such interventions for BMI as a modifiable risk factor.

Temperature dependent behavior of localized and delocalized electrons in nitrogen-doped 6H SiC crystals as studied by electron spin resonance

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

Savchenko, D., E-mail: dariyasavchenko@gmail.com; National Technical University of Ukraine “Kyiv Polytechnic Institute”, Kyiv 03056; Kalabukhova, E.

2016-01-28

We have studied the temperature behavior of the electron spin resonance (ESR) spectra of nitrogen (N) donors in n-type 6H SiC crystals grown by Lely and sublimation sandwich methods (SSM) with donor concentration of 10{sup 17 }cm{sup −3} at T = 60–150 K. A broad signal in the ESR spectrum was observed at T ≥ 80 K with Lorentzian lineshape and g{sub ||} = 2.0043(3), g{sub ⊥} = 2.0030(3), which was previously assigned in the literature to the N donors in the 1s(E) excited state. Based on the analysis of the ESR lineshape, linewidth and g-tensor we attribute this signal to the conduction electrons (CE). The emergence of the CE ESRmore » signal at T > 80 K was explained by the ionization of electrons from the 1s(A{sub 1}) ground and 1s(E) excited states of N donors to the conduction band while the observed reduction of the hyperfine (hf) splitting for the N{sub k1,k2} donors with the temperature increase is attributed to the motional narrowing effect of the hf splitting. The temperature dependence of CE ESR linewidth is described by an exponential law (Orbach process) with the activation energy corresponding to the energy separation between 1s(A{sub 1}) and 1s(E) energy levels for N residing at quasi-cubic sites (N{sub k1,k2}). The theoretical analysis of the temperature dependence of microwave conductivity measured by the contact-free method shows that due to the different position of the Fermi level in two samples the ionization of free electrons occurs from the energy levels of N{sub k1,k2} donors in Lely grown samples and from the energy level of N{sub h} residing at hexagonal position in 6H SiC grown by SSM.« less

Significant role of serum CRP in differentiating inflammatory from non-inflammatory causes of thyrotoxicosis

PubMed Central

Baruah, Manash P.; Bhattacharya, Bhaskar

2012-01-01

Background: C-reactive protein (CRP), which is a marker of inflammation, has not been widely studied in inflammatory thyroid disorders particularly in sub-acute thyroiditis (SAT). Aim: This study was aimed to find the significance of CRP level rise in patients with SAT and compare that to the rise in erythrocyte sedimentation rate (ESR), a gold standard laboratory parameter in establishing the diagnosis of SAT. Materials and Methods: Serum CRP levels were measured at initial presentation in 28 subjects with SAT(12 male, 16 female, age (Mean +SD) 37.96 ±8.5 years),and 19 patients with Graves’ disease (2 male, 17 female, age [Mean +SD] 36.8 ±16.5 years) as controls. Erythrocyte sedimentation rate (ESR) was measured in all 28 patients with SAT by Westergrens’ method. Either Tc99 nucleotide thyroid scan or high resolution ultrasonography (HR-USG) was performed to differentiate SAT from Graves’ disease.Fine needle aspiration cytology (FNAC) of thyroid was performed selected patients. Results: Serum CRP level was high in 61% of SAT patients but in none of the Graves′patients. Mean (SEM) (90%CI) serum CRP level (mg/L) was also significantly higher (P <0.0004) in the SAT group [27.55 (5.76) (15.72-39.38)], than in the Graves’ group [4.09 (0.12) (3.81-4.36)]. The sensitivity of serum CRP was 73.33%, specificity 53.85%, positive predictive value (PPV) 64.71%, and negative predictive value (NPV) 63.64% as compared to the sensitivity (53.57%), specificity (15.38%), PPV (57.69 %), and NPV (13.33%) of ESR. Conclusion: There is significantly higher rise in serum CRP level in patients with SAT is compared to patients with Graves’ disease. It correlates well with the rise in ESR. Such findings of this pilot study highlight the scope of using serum CRP as a diagnostic marker of SAT specially in situations when it may be confused with Graves’ disease, another common cause of thyrotoxicosis. It is logical to carry out studies to find a particular cut-off for serum CRP which can serve as an objective parameter for grading the inflammation in patients with SAT. PMID:23226645

Product yield-detected ESR on magnetic field-dependent photoreduction of quinones in SDS micellar solution

NASA Astrophysics Data System (ADS)

Okazaki, M.; Sakata, S.; Konaka, R.; Shiga, T.

1987-06-01

Transient free radicals in the magnetic field-dependent photoreduction of quinones (menadione or anthraquinone) in a sodium dodecyl sulfate (SDS) micellar solution, were converted to stable nitroxide radicals by the ``spin trapping'' technique with or without the microwave irradiation. Upon irradiating the microwave at 160 mW, the product yield (``spin adduct'' of the alkyl radical generated from SDS molecule) decreased by up to 14% at certain magnetic fields in a resonant manner. Although only one component of the postulated radical pair was converted to the spin adduct, the decrease in the yield as a function of external magnetic field revealed the ESR spectra of both component radicals of the radical pair, i.e., the semiquinone radical and the alkyl radical from SDS. This experiment not only gives the direct evidence for the radical pair model, but also suggests the possibility for this method to be applied in controlling the chemical reactions by the microwave. A simple calculation was made to simulate the observed ``product yield-detected ESR.'' Agreements were achieved semiquantitatively between the observed reductions in the spin adduct yields and those calculated. The estimated exchange interaction between the component radicals in the radical pair of the present systems was lower than 0.3 mT.

Annealing shallow traps in electron beam irradiated high mobility metal-oxide-silicon transistors

NASA Astrophysics Data System (ADS)

Kim, Jin-Sung; Tyryshkin, Alexei; Lyon, Stephen

In metal-oxide-silicon (MOS) quantum devices, electron beam lithography (EBL) is known to create defects at the Si/SiO2 interface which can be catastrophic for single electron control. Shallow traps ( meV), which only manifest themselves at low temperature ( 4 K), are especially detrimental to quantum devices but little is known about annealing them. In this work, we use electron spin resonance (ESR) to measure the density of shallow traps in two sets of high mobility (μ) MOS transistors. One set (μ=14,000 cm2/Vs) was irradiated with an EBL dose (10 kV, 40 μC/cm2) and was subsequently annealed in forming gas while the other remained unexposed (μ=23,000 cm2/Vs). Our ESR data show that the forming gas anneal is sufficient to remove shallow traps generated by the EBL dose over the measured shallow trap energy range (0.3-4 meV). We additionally fit these devices' conductivity data to a percolation transition model and extract a zero temperature percolation threshold density, n0 ( 9 ×1010 cm-2 for both devices). We find that the extracted n0 agrees within 15 % with our lowest temperature (360 mK) ESR measurements, demonstrating agreement between two independent methods of evaluating the interface.

Lithospheric flexure revealed by Pleistocene emerged marine terraces on the southern Hawaiian Islands

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

Jones, A.T.

1992-01-01

New field and geochronological data from emerged marine deposits in the southern Hawaiian Islands suggest uplift of the islands of Molokai, Lanai and Oahu. Corals from these islands were dated by ESR. The accumulated dose for aragonitic coral at ESR signal, g = 2.0007, was determined by the additive dose method. The environmental dose rate was estimated from the Uranium concentration in corals and by using an estimate of 2.5 rad/a for the cosmic ray dose. The ESR ages of the highest terraces on Molokai are 290 [+-] 31 ka (30 m), on Lanai 217 [+-] 19 ka (50 m)more » and on Oahu 468 [+-] 36 ka (28 m). The age and elevation of the marine terraces are interpreted to imply uplift during the Late Quaternary. Lithospheric flexure combined with horizontal plate motion is proposed as a mechanism to describe the pattern of uplifted terraces on these islands. Using two-dimensional elastic plate models, the height of maximum bulge is approximately 4% to 7% of the maximum deflection for a continuous or broken plate model. Drowned reefs off Hawaii indicate subsidence of 1 km since 340 ka. Thus, the magnitude of observed uplift (30--50 m) is consistent with theoretical maximum bulge heights derived from numerical results.« less

ESR, spectroscopic, and quantum-chemical studies on the electronic structures of complexes formed by Cu(I) with radicals (in Russian)

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

Gritsan, N.P.; Usov, O.M.; Shokhirev, N.V.

1986-07-01

The optical and ESR spectra have been examined for complexes of Cu(I) with various radicals, which contain various numbers of Cl/sup -/ ions in the central-atom coordination sphere. The spin-Hamiltonian parameters have been determined for all these radical complexes, and the observed ESR spectra have been compared with those calculated with allowance for second-order effects. The observed values for the isotropic and anisotropic components of the HFI constant from the central ion have been used to estimate the contributions from the 4s and 3d/sup 2//sub z/ orbitals of the copper ion to the unpaired-electron MO. Quantum-chemical calculations have been performedmore » by the INDO method on the electronic structures and geometries of complexes formed by CH/sub 2/OH with Cu(I) for various Cl/sup -/ contents in the coordination sphere. The radical is coordinated by the ..pi.. orbital on the carbon atom, and the stabilities of the radical complexes decrease as the number of Cl/sup -/ ions in the coordination sphere increases. A geometry close to planar for the CuCl/sub 4//sup 3 -/ fragment in a complex containing four Cl/sup -/ ions.« less

High-frequency electron-spin-resonance measurements on Mn x Mg1-x O (x = 1.0×10-4) and DPPH at very low temperatures

NASA Astrophysics Data System (ADS)

Ishikawa, Y.; Ohya, K.; Miura, S.; Fujii, Y.; Mitsudo, S.; Mizusaki, T.; Fukuda, A.; Matsubara, A.; Kikuchi, H.; Asano, T.; Yamamori, H.; Lee, S.; Vasiliev, S.

2018-03-01

We have developed a millimeter-wave electron-spin-resonance (ESR) system for very low temperatures (T < 1 K) that can be employed for nuclear-magnetic-resonance measurements by using dynamic nuclear polarization. The system uses a Fabry-Pérot resonator that works in the frequency range of 125 – 130 GHz and covers the temperature range of 0.09 – 6.5 K. We have performed ESR measurements in the frequency around 128 GHz by using Mn x Mg1-x O (x = 1.0 × 10-4) and free-radical samples of 1, 1-diphenyl-2-picrylhydrazyl (DPPH), because these samples have been proposed as field and sensitivity markers. Temperature dependence of the ESR signal intensity for Mn x Mg1-x O shows anomalies originating from magnetic order are found around 3.5 – 4 K. We estimate the sensitivity of the system for ESR detections to be 6 × 1013 spins/G at 5.8 K. Because DPPH shows no observable shift in the magnetic field, we propose it as a useful standard marker for ESR measurements at very low temperatures.

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

ESR and nonresonant microwave absorption of ErBa2Cu3O(7-delta) and HoBa2Cu3O(7-delta) single crystals

NASA Astrophysics Data System (ADS)

Tagaya, Kimihito; Fukuoka, Nobuo; Nakanishi, Shigemitsu

1990-12-01

ESR measurements were performed for ErBa2Cu3O(7-delta) and HoBa2Cu3O(7-delta) single crystals from 77 K to room temperature. The ESR signals of Er2BaCuO5 and Ho2BaCuO5 were observed, and their temperature variations were investigated. Nonresonant microwave absorption was also observed below the superconducting critical temperature of 93 K. The principal values of lower critical field were determined.

Electron spin resonance from NV centers in diamonds levitating in an ion trap

NASA Astrophysics Data System (ADS)

Delord, T.; Nicolas, L.; Schwab, L.; Hétet, G.

2017-03-01

We report observations of the electron spin resonance (ESR) of nitrogen vacancy centers in diamonds that are levitating in an ion trap. Using a needle Paul trap operating under ambient conditions, we demonstrate efficient microwave driving of the electronic spin and show that the spin properties of deposited diamond particles measured by the ESR are retained in the Paul trap. We also exploit the ESR signal to show angle stability of single trapped mono-crystals, a necessary step towards spin-controlled levitating macroscopic objects.

Repeat polymorphisms in ESR2 and AR and colorectal cancer risk and prognosis: results from a German population-based case-control study.

PubMed

Rudolph, Anja; Shi, Hong; Försti, Asta; Hoffmeister, Michael; Sainz, Juan; Jansen, Lina; Hemminki, Kari; Brenner, Hermann; Chang-Claude, Jenny

2014-11-07

Evidence has accumulated which suggests that sex steroids influence colorectal cancer development and progression. We therefore assessed the association of repeat polymorphisms in the estrogen receptor β gene (ESR2) and the androgen receptor gene (AR) with colorectal cancer risk and prognosis. The ESR2 CA and AR CAG repeat polymorphisms were genotyped in 1798 cases (746 female, 1052 male) and 1810 controls (732 female, 1078 male), matched for sex, age and county of residence. Colorectal cancer risk associations overall and specific for gender were evaluated using multivariate logistic regression models adjusted for sex, county of residence and age. Associations with overall and disease-specific survival were evaluated using Cox proportional hazard models adjusted for established prognostic factors (diagnosis of other cancer after colorectal cancer diagnosis, detection by screening, treatment with adjuvant chemotherapy, tumour extent, nodal status, distant metastasis, body mass index, age at diagnosis and year of diagnosis) and stratified for grade of differentiation. Heterogeneity in gender specific associations was assessed by comparing models with and without a multiplicative interaction term by means of a likelihood ratio test. The average number of ESR2 CA repeats was associated with a small 5% increase in colorectal cancer risk (OR = 1.05, 95% CI 1.01-1.10) without significant heterogeneity according to gender or tumoural ESR2 expression. We found no indication for an association between the AR CAG repeat polymorphisms and risk of colorectal cancer. The ESR2 CA and AR CAG repeat polymorphisms were not associated with overall survival or disease specific survival after colorectal cancer diagnosis. Higher numbers of ESR2 CA repeats are potentially associated with a small increase in colorectal cancer risk. Our study does not support an association between colorectal cancer prognosis and the investigated repeat polymorphisms.

Expression and signaling of G protein-coupled estrogen receptor 1 (GPER) in rat sertoli cells.

PubMed

Lucas, Thaís F G; Royer, Carine; Siu, Erica R; Lazari, Maria Fatima M; Porto, Catarina S

2010-08-01

The aim of the present study was to investigate the expression and signaling of the G protein-coupled estrogen receptor 1 (GPER) in cultured immature rat Sertoli cells--in which we have previously described the classical estrogen receptors (ESR1 and ESR2). Expression of GPER in cultured Sertoli cells from 15-day-old rats was detected by RT-PCR and immunoassays. Gper transcripts also were present in testes from 5-, 15-, and 120-day-old rats. Short-term treatment of Sertoli cells with 17beta-estradiol (E2), the GPER agonist G-1, or the ESR antagonist ICI 182,780 (ICI) rapidly activated MAPK3/1 (ERK1/2), even after down-regulation of ESR1 and ESR2, suggesting a role for GPER in the rapid E2 action in these cells. MAPK3/1 phosphorylation induced by ICI or G-1 was blocked by pertussis toxin, selective inhibitor of the SRC family of protein tyrosine kinases, metalloprotease inhibitor, MAP2K1/2 inhibitor, and epidermal growth factor receptor (EGFR) kinase inhibitor. Furthermore, E2, but not G-1, induced up-regulation of cyclin D1 in the Sertoli cells. This effect was blocked by ICI. E2 and G-1 decreased BAX and increased BCL2 expression and these effects were blocked by MAP2K1/2 inhibitor and EGFR kinase inhibitor. The pretreatment with ICI did not block the effect of E2. Taken together, these results indicate that in Sertoli cells 1) GPER-mediated MAPK3/1 activation occurs via EGFR transactivation through G protein beta gamma subunits that promote SRC-mediated metalloprotease-dependent release of EGFR ligands, which bind to EGFR and lead to MAPK3/1 phosphorylation; 2) E2-ESRs play a role in Sertoli cell proliferation; and 3) E2-GPER may regulate gene expression involved with apoptosis. ESR and GPER may mediate actions important for Sertoli cell function and maintenance of normal testis development and homeostasis.

ESR studies on the influence of physiological dissolution and digestion media on the lipid phase characteristics of SEDDS and SEDDS pellets.

PubMed

Abdalla, Ahmed; Mäder, Karsten

2009-02-09

The aim of the current study is the evaluation of a recently optimized SEDDS, composed of Solutol HS15 and medium chain glycerides, and self-emulsifying pellets by means of ESR. Tempol-benzoate (TB)-loaded SEDDS were produced and electron spin resonance (ESR) spectroscopy was used to evaluate the diluted self-emulsifying mixtures. Moreover, ESR in vitro digestion experiments were carried out to have an insight on the characteristics of the different phases formed during the digestion process and to evaluate the distribution and the localization of TB in these phases. In addition, self-emulsifying pellets were produced using nitroxide-loaded SEDDS and the microenvironment within the pellets during release process was monitored in an online process using ESR spectroscopy. After dilution of nitroxide-loaded SEDDS, the percent of TB localized in the lipophilic compartment was decreasing with increasing the surfactant fraction in the mixture. Moreover, it was found that different phases with variable viscosity and polarity were produced as a result of the enzymatic digestion of SEDDS in physiologically relevant media. This change in lipid composition has largely affected the distribution and the localization of the spin probe during the digestion process. A rapid increase in the mobility of the spin probe inside the pellets was noticed after exposure to the release media. Additionally, TB was localized within the self-emulsifying mixture environment for the time of the experiment. ESR is considered a powerful non-invasive tool to assess the microenvironment of the diluted SEDDS and to monitor in vitro digestion process. Digestion induces a change in lipid composition which can affect the solubilization capacity of the administered drug. Therefore, monitoring in vitro digestion process using ESR spectroscopy will help in providing greater understanding of the interaction between the administered drug and the digested lipid vehicles.

ESR lineshape and {sup 1}H spin-lattice relaxation dispersion in propylene glycol solutions of nitroxide radicals – Joint analysis

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

Kruk, D., E-mail: danuta.kruk@matman.uwm.edu.pl; Hoffmann, S. K.; Goslar, J.

2013-12-28

Electron Spin Resonance (ESR) spectroscopy and Nuclear Magnetic Relaxation Dispersion (NMRD) experiments are reported for propylene glycol solutions of the nitroxide radical: 4-oxo-TEMPO-d{sub 16} containing {sup 15}N and {sup 14}N isotopes. The NMRD experiments refer to {sup 1}H spin-lattice relaxation measurements in a broad frequency range (10 kHz–20 MHz). A joint analysis of the ESR and NMRD data is performed. The ESR lineshapes give access to the nitrogen hyperfine tensor components and the rotational correlation time of the paramagnetic molecule. The NMRD data are interpreted in terms of the theory of paramagnetic relaxation enhancement in solutions of nitroxide radicals, recentlymore » presented by Kruk et al. [J. Chem. Phys. 138, 124506 (2013)]. The theory includes the effect of the electron spin relaxation on the {sup 1}H relaxation of the solvent. The {sup 1}H relaxation is caused by dipole-dipole interactions between the electron spin of the radical and the proton spins of the solvent molecules. These interactions are modulated by three dynamic processes: relative translational dynamics of the involved molecules, molecular rotation, and electron spin relaxation. The sensitivity to rotation originates from the non-central positions of the interacting spin in the molecules. The electronic relaxation is assumed to stem from the electron spin–nitrogen spin hyperfine coupling, modulated by rotation of the radical molecule. For the interpretation of the NMRD data, we use the nitrogen hyperfine coupling tensor obtained from ESR and fit the other relevant parameters. The consistency of the unified analysis of ESR and NMRD, evaluated by the agreement between the rotational correlation times obtained from ESR and NMRD, respectively, and the agreement of the translation diffusion coefficients with literature values obtained for pure propylene glycol, is demonstrated to be satisfactory.« less

Salient Ecological Sensitive Regions of Central Western Ghats, India

NASA Astrophysics Data System (ADS)

Ramachandra, T. V.; Bharath, Setturu; Subash Chandran, M. D.; Joshi, N. V.

2018-05-01

Ecologically sensitive regions (ESRs) are the `ecological units' with the exceptional biotic and abiotic elements. Identification of ESRs considering spatially both ecological and social dimensions of environmental variables helps in ecological and conservation planning as per Biodiversity Act, 2002, Government of India. The current research attempts to integrate ecological and environmental considerations into administration, and prioritizes regions at Panchayat levels (local administrative unit) in Uttara Kannada district, Central Western Ghats, Karnataka state considering attributes (biological, Geo-climatic, Social, etc.) as ESR (1-4) through weightage score metrics. The region has the distinction of having highest forest area (80.48%) in Karnataka State, India and has been undergoing severe anthropogenic pressures impacting biogeochemistry, hydrology, food security, climate and socio-economic systems. Prioritisation of ESRs helps in the implementation of the sustainable developmental framework with the appropriate conservation strategies through the involvement of local stakeholders.

Salient Ecological Sensitive Regions of Central Western Ghats, India

NASA Astrophysics Data System (ADS)

Ramachandra, T. V.; Bharath, Setturu; Subash Chandran, M. D.; Joshi, N. V.

2018-02-01

Ecologically sensitive regions (ESRs) are the `ecological units' with the exceptional biotic and abiotic elements. Identification of ESRs considering spatially both ecological and social dimensions of environmental variables helps in ecological and conservation planning as per Biodiversity Act, 2002, Government of India. The current research attempts to integrate ecological and environmental considerations into administration, and prioritizes regions at Panchayat levels (local administrative unit) in Uttara Kannada district, Central Western Ghats, Karnataka state considering attributes (biological, Geo-climatic, Social, etc.) as ESR (1-4) through weightage score metrics. The region has the distinction of having highest forest area (80.48%) in Karnataka State, India and has been undergoing severe anthropogenic pressures impacting biogeochemistry, hydrology, food security, climate and socio-economic systems. Prioritisation of ESRs helps in the implementation of the sustainable developmental framework with the appropriate conservation strategies through the involvement of local stakeholders.

Electron Spin Relaxation: The Role of Spin-Orbit Coupling in Organic Semiconductors

NASA Astrophysics Data System (ADS)

Willis, M.; Nuccio, L.; Schulz, L.; Gillin, W.; Kreouzis, T.; Pratt, F.; Lord, J.; Heeney, M.; Fratini, S.; Bernhard, C.; Drew, A.

2012-02-01

Rapid development of organic materials has lead to their availability in commercial products. Until now, the spin degree of freedom has not generally been used in organic materials. As well as engineering difficulties, there are fundamental questions with respect to the electron spin relaxation (eSR) mechanisms in organic molecules. Muons used as a microscopic spin probe, localized to a single molecule, can access information needed to identify the relevant model for eSR. In this presentation I will introduce the ALC-MuSR technique describing how eSR can be extracted and the expected effects. I will show how the technique has been applied to small organic molecules such as the group III Quinolate series and functionalized molecules with a pentacene-like backbone. Lastly I will present the Z-number and temperature dependence in these organic molecules and show strong evidence for a spin-orbit based eSR mechanism.

Broadband electron spin resonance from 500 MHz to 40 GHz using superconducting coplanar waveguides

NASA Astrophysics Data System (ADS)

Clauss, Conrad; Bothner, Daniel; Koelle, Dieter; Kleiner, Reinhold; Bogani, Lapo; Scheffler, Marc; Dressel, Martin

2013-04-01

We present non-conventional electron spin resonance (ESR) experiments based on microfabricated superconducting Nb thin film waveguides. A very broad frequency range, from 0.5 to 40 GHz, becomes accessible at low temperatures down to 1.6 K and in magnetic fields up to 1.4 T. This allows for an accurate inspection of the ESR absorption position in the frequency domain, in contrast to the more common observation as a function of magnetic field. We demonstrate the applicability of frequency-swept ESR on Cr3+ atoms in ruby as well as on organic radicals of the nitronyl-nitroxide family. Measurements between 1.6 and 30 K reveal a small frequency shift of the ESR and a resonance broadening below the critical temperature of Nb, which we both attribute to a modification of the magnetic field configuration due to the appearance of shielding supercurrents in the waveguide.

Observing electron spin resonance between 0.1 and 67 GHz at temperatures between 50 mK and 300 K using broadband metallic coplanar waveguides

NASA Astrophysics Data System (ADS)

Wiemann, Yvonne; Simmendinger, Julian; Clauss, Conrad; Bogani, Lapo; Bothner, Daniel; Koelle, Dieter; Kleiner, Reinhold; Dressel, Martin; Scheffler, Marc

2015-05-01

We describe a fully broadband approach for electron spin resonance (ESR) experiments, where it is possible to tune not only the magnetic field but also the frequency continuously over wide ranges. Here, a metallic coplanar transmission line acts as compact and versatile microwave probe that can easily be implemented in different cryogenic setups. We perform ESR measurements at frequencies between 0.1 and 67 GHz and at temperatures between 50 mK and room temperature. Three different types of samples (Cr3+ ions in ruby, organic radicals of the nitronyl-nitroxide family, and the doped semiconductor Si:P) represent different possible fields of application for the technique. We demonstrate that an extremely large phase space in temperature, magnetic field, and frequency for ESR measurements, substantially exceeding the range of conventional ESR setups, is accessible with metallic coplanar lines.

Spin-labelling study of interactions of ovalbumin with multilamellar liposomes and specific anti-ovalbumin antibodies.

PubMed

Brgles, Marija; Mirosavljević, Krunoslav; Noethig-Laslo, Vesna; Frkanec, Ruza; Tomasić, Jelka

2007-03-10

Ovalbumin (OVA) has been used continuously as the model antigen in numerous studies of immune reactions and antigen processing, very often encapsulated into liposomes. The purpose of this work was to study the possible interactions of spin-labelled OVA and lipids in liposomal membranes using electron spin resonance (ESR) spectroscopy. OVA was covalently spin-labelled with 4-maleimido-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO-maleimide), characterized and encapsulated into multilamellar, negatively charged liposomes. ESR spectra of this liposomal preparation gave evidence for the interaction of OVA with the lipid bilayers. Such an interaction was also evidenced by the ESR spectra of liposomal preparation containing OVA, where liposomes were spin-labelled with n-doxyl stearic acids. The spin-labelled OVA retains its property to bind specific anti-OVA antibodies, as shown by ESR spectroscopy, but also in ELISA for specific anti-OVA IgG.

Prevalence of hypothyroidism in rheumatoid arthritis and its correlation with disease activity.

PubMed

Joshi, Prakash; Agarwal, Abhishek; Vyas, Sony; Kumar, Ravindra

2017-01-01

To analyse the prevalence of hypothyroidism in rheumatoid arthritis (RA) patients and to elucidate its correlation with disease activity. A total of 52 RA patients were enrolled in this study. All patients were assessed fully clinically and underwent routine laboratory investigation including thyroid function testing. Hypothyroidism (defined as having a TSH level >4.20 μIU/mL) was observed in 20/52 (38.4%). Erythrocyte sedimentation rates (ESR) were found significantly elevated in patients with hypothyroidism compared to those without (36.3 ± 24.2 vs. 24.6 ± 9.0 mm/h). Disease activity parameters such as DAS-28-ESR, tender joint count; VAS scores were also significantly higher in the former. A significant correlation with serum TSH levels was observed with ESR and DAS-28-ESR. Thyroid function test should be included in clinical evaluation of RA patients. © The Author(s) 2016.

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.

Association between polymorphisms of estrogen receptor 2 and benign prostatic hyperplasia

PubMed Central

KIM, SU KANG; CHUNG, JOO-HO; PARK, HYUN CHUL; KIM, JUN HO; ANN, JAE HONG; PARK, HUN KUK; LEE, SANG HYUP; YOO, KOO HAN; LEE, BYUNG-CHEOL; KIM, YOUNG OCK

2015-01-01

Estrogens and estrogen receptors (ESRs) have been implicated in the stimulation of aberrant prostate growth and the development of prostate diseases. The aim of the present study was to investigate four single nucleotide polymorphisms (SNPs) of the ESR2 gene in order to examine whether ESR2 is a susceptibility gene for benign prostatic hyperplasia (BPH). In order to evaluate whether an association exists between ESR2 and BPH risk, four polymorphisms [rs4986938 (intron), rs17766755 (intron), rs12435857 (intron) and rs1256049 (Val328Val)] of the ESR2 gene were genotyped by direct sequencing. A total of 94 patients with BPH and 79 control subjects were examined. SNPStats and Haploview version 4.2 we used for the genetic analysis. Multiple logistic regression models (codominant1, codominant2, dominant, recessive and log-additive) were produced in order to obtain the odds ratio, 95% confidence interval and P-value. Three SNPs (rs4986938, rs17766755 and rs12435857) showed significant associations with BPH (rs4986938, P=0.015 in log-additive model; rs17766755, P=0.033 in codominant1 model, P=0.019 in dominant model and P=0.020 in log-additive model; rs12435857, P=0.023 in dominant model and P=0.011 in log-additive model). The minor alleles of these SNPs increased the risk of BPH, and the AAC haplotype showed significant association with BPH (χ2=6.34, P=0.0118). These data suggest that the ESR2 gene may be associated with susceptibility to BPH. PMID:26640585

Association between polymorphisms of estrogen receptor 2 and benign prostatic hyperplasia.

PubMed

Kim, Su Kang; Chung, Joo-Ho; Park, Hyun Chul; Kim, Jun Ho; Ann, Jae Hong; Park, Hun Kuk; Lee, Sang Hyup; Yoo, Koo Han; Lee, Byung-Cheol; Kim, Young Ock

2015-11-01

Estrogens and estrogen receptors (ESRs) have been implicated in the stimulation of aberrant prostate growth and the development of prostate diseases. The aim of the present study was to investigate four single nucleotide polymorphisms (SNPs) of the ESR2 gene in order to examine whether ESR2 is a susceptibility gene for benign prostatic hyperplasia (BPH). In order to evaluate whether an association exists between ESR2 and BPH risk, four polymorphisms [rs4986938 (intron), rs17766755 (intron), rs12435857 (intron) and rs1256049 (Val328Val)] of the ESR2 gene were genotyped by direct sequencing. A total of 94 patients with BPH and 79 control subjects were examined. SNPStats and Haploview version 4.2 we used for the genetic analysis. Multiple logistic regression models (codominant1, codominant2, dominant, recessive and log-additive) were produced in order to obtain the odds ratio, 95% confidence interval and P-value. Three SNPs (rs4986938, rs17766755 and rs12435857) showed significant associations with BPH (rs4986938, P=0.015 in log-additive model; rs17766755, P=0.033 in codominant1 model, P=0.019 in dominant model and P=0.020 in log-additive model; rs12435857, P=0.023 in dominant model and P=0.011 in log-additive model). The minor alleles of these SNPs increased the risk of BPH, and the AAC haplotype showed significant association with BPH (χ 2 =6.34, P=0.0118). These data suggest that the ESR2 gene may be associated with susceptibility to BPH.

The importance of pre-annealing treatment for ESR dating of mollusc shells: A key study for İsmil in Konya closed Basin/Turkey

NASA Astrophysics Data System (ADS)

Ekici, Gamze; Sayin, Ulku; Aydin, Hulya; Isik, Mesut; Kapan, Sevinc; Demir, Ahmet; Engin, Birol; Delikan, Arif; Orhan, Hukmu; Biyik, Recep; Ozmen, Ayhan

2018-02-01

In this study, Electron Spin Resonance (ESR) spectroscopy is used to determine the geological ages of fossil mollusc shells systematically collected from two different geological splitting at İsmil Location (37.72769° N, 33.17781° E) in eastern part of Konya. According to the assessment of obtained ESR ages, the importance of pre-annealing treatment emphasize in the case of g=2.0007 dating signal is overlapped with the other signals arisen from short lived radicals that cause the wrong age calculation. To overcome this problem, the samples are pre-annealed at 180°C for 16 minutes and, in this case ESR ages are re-calculated for g=1.9973 dating signal. Dose response curves are obtained using 1.9973 signals after pre-annealing treatments for each samples. ESR ages of samples are obtained in the range of 138 ± 38 ka and 132 ± 30 ka (Upper Pleistocene) according to the Early Uranium Uptake model and the results are in good agreement with the estimated ages from stratigraphic and paleontological correlation by geologists. Thus, it is suggested that especially in the case of 2.0007 dating signal cannot been used due to superimposition case, the signal with 1.9973 g value can be used for dating after pre-annealing treatment. The results reports the first ESR ages on shells collected from İsmil Location and highlight the importance of pre-annealing treatment. This study is supported by TUBITAK 114Y237 research project.

DNA Methylation Status of the Estrogen Receptor α Gene in Canine Mammary Tumors.

PubMed

Brandão, Yara de Oliveira; Toledo, Mariana Busato; Chequin, Andressa; Cristo, Thierry Grima; Sousa, Renato Silva; Ramos, Edneia Amancio Souza; Klassen, Giseli

2018-01-01

Estrogen receptor α (ERα) has an important role in mammary carcinogenesis, prognosis, and treatment. In human and canine mammary cancer, the most aggressive tumors show loss of ERα expression, which in human breast cancer has been attributed to methylation of the cytosine followed by guanine (CpG) island within the estrogen receptor α gene ( ESR1) promoter. This study aimed to investigate the role of ESR1 CpG island (CGI) methylation in ERα expression in canine mammary tumors. Twenty-one canine mammary samples were sorted into three groups: malignant tumor (n = 9), benign tumor (n = 8), and normal gland (n = 4). Immunohistochemical analysis and reverse-transcription quantitative real-time PCR were performed to assess ERα expression and ESR1 mRNA levels. The methylation status was determined using sodium-bisulfite-treated DNA sequencing. All normal mammary glands and benign tumors showed high ERα expression (score range, 5-8). Six of the nine malignant tumors did not show ERα expression (score 0), two had score 2, and one had score 4. Lower ERα ( P < .005) and ESR1 mRNA levels ( P < .005) were found in malignant mammary tumors than in the other two groups. Canine ESR1 has an intragenic and non-promoter-associated CGI, different from humans. No significant variation in methylation percentage was observed among the groups, suggesting that ESR1 is not regulated by DNA methylation, unlike that in humans. This difference should be considered in further research using ERα as a biomarker for mammary tumors in canine studies on ERα-targeting therapy.

17β-Estradiol activates GPER- and ESR1-dependent pathways inducing apoptosis in GC-2 cells, a mouse spermatocyte-derived cell line.

PubMed

Chimento, Adele; Sirianni, Rosa; Casaburi, Ivan; Ruggiero, Carmen; Maggiolini, Marcello; Andò, Sebastiano; Pezzi, Vincenzo

2012-05-15

In mammals, spontaneous apoptosis is observed particularly in differentiating spermatogonia and in spermatocytes. 17β-Estradiol (E2) in primary rat pachytene spermatocytes (PS) binds estrogen receptor α (ESR1) and GPER to activate EGFR/ERK/c-Jun pathway leading to up regulation of proapoptotic factor bax. Aim of this study was to clarify the effector pathway(s) controlling spermatocytes apoptosis using as model GC-2 cells, an immortalized mouse pachytene spermatocyte-derived cell line, which reproduces primary cells responses to E2. In fact, in GC-2 cells we observed that ESR1 and GPER activation caused rapid ERK and c-Jun phosphorylation, bax up-regulation, events associated with apoptosis. We further investigated the apoptotic mechanism demonstrating that E2, as well as ESR1 and GPER specific agonists, induced sustained ERK, c-Jun and p38 phosphorylation, Cytochrome c release, caspase 3 and endogenous substrate Poly (ADP-ribose) polymerase (PARP) activation and increased expression of cell cycle inhibitor p21. When ESR1 or GPER expression was silenced, E2 was still able to decrease cell proliferation, only the concomitant silencing abolished E2 effect. These results indicate that GC-2 cells are a valid cell model to study E2-dependent apoptosis in spermatocytes and show that E2, activating both ESR1 and GPER, is able to induce an ERK1/2, c-Jun and p38-dependent mitochondrion apoptotic pathway in this cell type. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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.

Prognostic role of methylated GSTP1, p16, ESR1 and PITX2 in patients with breast cancer: A systematic meta-analysis under the guideline of PRISMA.

PubMed

Sheng, Xianneng; Guo, Yu; Lu, Yang

2017-07-01

BRCA1 and RASSF1A promoter methylation has been reported to be correlated with a worse survival in patients with breast cancer. However, the prognostic values of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer remain to be determined. Here, we performed this study to evaluate the prognostic significance of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer. A range of online databases was systematically searched to identify available studies based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. The pooled hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were applied to estimate the prognostic effect of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer for multivariate regression analysis. 13 eligible articles involving 3915 patients with breast cancer were analyzed in this meta-analysis. In a large patient population, GSTP1 showed a trend toward a worse prognosis in overall survival (OS) (HR = 1.64, 95% CI = 0.93-2.87, P = .085). PITX2 promoter methylation was significantly correlated with a worse prognosis in OS (HR = 1.57, 95% CI = 1.15-2.14, P = .004), but no association between p16 promoter methylation and OS (HR = 0.92, 95% CI = 0.31-2.71, P = .884). PITX2 promoter methylation was significantly correlated with an unfavorable prognosis of patients with breast cancer in metastasis-free survival (MFS) (HR = 1.73, 95% CI = 1.33-2.26, P < .001). The result from 3 studies with 227 cases showed that ESR1 promoter methylation was linked to a worse prognosis in OS (HR = 1.55, 95% CI = 1.06-2.28, P = .025). Our findings suggest ESR1 and PITX2 promoter methylation may be correlated with a worse survival of patients with breast cancer (ESR1: OS, PITX2: OS and MFS). The clinical utility of aberrantly methylated ESR1 and PITX2 could be a promising factor for the prognosis of breast cancer.

Clinical significance of plasma cell-free DNA mutations in PIK3CA, AKT1, and ESR1 gene according to treatment lines in ER-positive breast cancer.

PubMed

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

2018-02-26

The somatic activation of PI3K/AKT pathway mutations, PIK3CA and AKT1, and ESR1 mutations in plasma cell-free DNA (cfDNA) has been studied as a non-invasive procedure to quickly assess and monitor disease progression or therapeutic effect in breast cancer (BC) patients, but the clinical significance of these mutations in late treatment lines (TLs) remains unclear. The subjects of this study were a total of 251 plasma samples from 128 estrogen receptor-positive (ER+) BC patients. Of these plasma samples, 133 were from 73 primary BC (PBC) patients, and 118 plasma samples were from 68 metastatic BC (MBC) patients. We developed droplet digital PCR (ddPCR) assays to verify the clinical significance of PIK3CA, AKT1, and ESR1 mutations in these patients. cfDNA PIK3CA mutations were observed in 15.1% of the PBC patients, while a cfDNA AKT1 mutation was observed in 1.4% of patients, and cfDNA ESR1 mutations were observed in 2.7% of patients. Patients with detectable cfDNA PIK3CA mutations were not associated with clinical outcomes. According to the TL, the prevalence of the PIK3CA and ESR1 mutations in cfDNA were lower in early TLs compared with late TLs. In the early TL group, patients with cfDNA PIK3CA mutations had a shorter time to treatment failure (TTF) than patients without mutations (P = 0.035). However, there was no statistically significant difference between patients with or without cfDNA ESR1 mutations. However, in the late TL group, patients with cfDNA ESR1 mutations had a shorter TTF than patients without mutations (P = 0.048). However, there was no statistically significant difference between patients with or without cfDNA PIK3CA mutations. Since the prevalence of cfDNA AKT1 mutation is low in both PBC and MBC patients, the impact of AKT1 mutations on the prognosis remains unclear. We have demonstrated the difference in the clinical significance of the hotspot PIK3CA, AKT1, and ESR1 mutations in cfDNA for each TL in ER+ BC patients.

Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor-Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14.

PubMed

Wolmark, Norman; Mamounas, Eleftherios P; Baehner, Frederick L; Butler, Steven M; Tang, Gong; Jamshidian, Farid; Sing, Amy P; Shak, Steven; Paik, Soonmyung

2016-07-10

We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1-expressing groups. RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) -positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14 patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. © 2016 by American Society of Clinical Oncology.

Oligothiophene bipyridine alternate copolymers and their ruthenium metalated analogues: in situ ESR and UV-vis investigations of metal-chain interactions.

PubMed

Lafolet, F; Genoud, F; Divisia-Blohorn, B; Aronica, C; Guillerez, S

2005-07-07

In situ electron spin resonance (ESR) and UV-vis spectro-electrochemical studies have been performed on two copolymers consisting of alternating subunits of regioregular head to tail (HT) coupled 3-octylthiophene tetramer and 2,2'-bipyridine subunits (P4) or 3-octylthiophene hexamer subunits of the same regioregularity and 2,2'-bipyridine subunits (P6). Both P4 and P6 have been investigated in their metal-free form as well as in the ruthenium(II) metalated form (P4-Ru and P6-Ru). P4 and P6 in the p-doped state exhibit a clear ESR signal characteristic of the presence of polarons in the oligothienylene subunits. In the case of P4, no recombination of polarons into bipolarons is observed, whereas the recombination process takes place in P6. The formation of bipolarons is well-rationalized in terms of the conjugation length, and it seems clear that the higher length of the oligothiophene subunit in P6( )()stabilizes bipolarons(.)() The same effect, is induced by the coordination of -Ru(bpy)(2)(2+) to the bipyridine unit in the metalated form of both polymers, which results in an increase of the conjugation length. Important information is gained from the analysis of the ESR spectra of both nonmetalated and metalated in the oxidized (p-doped) and reduced (n-doped) forms. In the p-doped state both nonmetalated and metalated polymers reveal the presence of a narrow ESR line characteristic of the mobile spin carriers in the polymer matrix. The oxidation of the metal center occurs at higher potentials and leads to an irreversible destruction of the system. To the contrary, in the reduced (n-doped) state the ESR lines of the nonmetalated and metalated polymers markedly differ. A significant line broadening with simultaneous change of the g-value is caused by spin-orbit coupling phenomenon induced by the presence of the coordinating metal. Finally, the observation of a clear polaronic band in the UV-vis spectrum of p-doped P4 and its strong dependence on the applied potential can be clearly correlated with the potential induced changes in the ESR spin density. The same applies to P4-Ru, where the changes in the polaronic and bipolaronic bands can also be correlated with the ESR spin density changes.

Gper and ESRs are expressed in rat round spermatids and mediate oestrogen-dependent rapid pathways modulating expression of cyclin B1 and Bax.

PubMed

Chimento, A; Sirianni, R; Zolea, F; Bois, C; Delalande, C; Andò, S; Maggiolini, M; Aquila, S; Carreau, S; Pezzi, V

2011-10-01

Spermatogenesis is a precisely controlled and timed process, comprising mitotic divisions of spermatogonia, meiotic divisions of spermatocytes, maturation and differentiation of haploid spermatids giving rise to spermatozoa. It is well known that the maintenance of spermatogenesis is controlled by gonadotrophins and testosterone, the effects of which are modulated by a complex network of locally produced factors, including oestrogens. However, it remains uncertain whether oestrogens are able to activate rapid signalling pathways directly in male germ cells. Classically, oestrogens act by binding to oestrogen receptors (ESRs) 1 and 2. Recently, it has been demonstrated that rapid oestrogen action can also be mediated by the G-protein-coupled oestrogen receptor 1 (Gper). The aim of the present study was to investigate ESRs and Gper expression in primary cultures of adult rat round spermatids (RS) and define if oestradiol (E2) is able to activate, through these receptors, pathways involved in the regulation of genes controlling rat RS apoptosis and/or maturation. In this study, we demonstrated that rat RS express ESR1, ESR2 and Gper. Short-time treatment of RS with E2, the selective Gper agonist G1 and the selective ESR1 and ERβ agonists, 4,4',4"-(4-propyl-[1H]pyrazole-1,3,5-triyl) trisphenol (PPT) and 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), respectively, determined activation of Extra-cellular signal-regulated kinase (ERK1/2) through the involvement of epidermal growth factor receptor transactivation. In addition, we investigated the effects of ESRs and Gper pathway activation on factors involved in RS maturation. Expression of cyclin B1 mRNA was downregulated by E2, G1 and PPT, but not by DPN. A concomitant and inverse regulation of the pro-apoptotic factor Bax mRNA expression was observed in the same conditions, with DPN being the only one determining an increase in this factor expression. Collectively, these data demonstrate that E2 activates, through ESRs and Gper, pathways involved in the regulation of genes controlling rat RS apoptosis and differentiation such as cyclin B1 and Bax. © 2010 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

The clinical usefulness of ESR, CRP, and disease duration in ankylosing spondylitis: the product of these acute-phase reactants and disease duration is associated with patient's poor physical mobility.

PubMed

Chen, Chun-Hsiung; Chen, Hung-An; Liao, Hsien-Tzung; Liu, Chin-Hsiu; Tsai, Chang-Youh; Chou, Chung-Tei

2015-07-01

We evaluated the clinical usefulness of ESR, CRP, and disease duration in ankylosing spondylitis (AS) disease severity. There were 156 Chinese AS patients included in Taiwan. Patients completed the questionnaires, containing demographic data, disease activity (BASDAI), functional status (BASFI), and patient's global assessment (BASG). Meanwhile, patient's physical mobility (BASMI) and acute-phase reactants, including ESR and CRP levels were measured. Receiver operating characteristic (ROC) plot analysis was used to evaluate the performance of ESR, CRP, and disease duration in the AS patients. ESR mildly correlated with BASFI (r = 0.176, p = 0.028) and disease duration (r = 0.214, p = 0.008), and moderately correlated with BASMI (r = 0.427, p < 0.001). CRP moderately correlated with BASMI (r = 0.410, p < 0.001). By using ROC plot analysis, ESR, CRP, and disease duration showed the best and significant "area under the curve (AUC)", in distinguishing the AS patients with poor physical mobility (BASMI ≥ 3.6, the Median) (AUC = 0.748, 0.751 and 0.738, respectively, all p < 0.001), as compared to BASDAI, BASFI, and BASG. ESR × disease duration (AUC = 0.801, p < 0.001) and CRP × disease duration (AUC = 0.821, p < 0.001) showed higher AUC values than ESR or CRP alone in indicating poor physical mobility. For detecting poor physical mobility (BASMI ≥ 3.6) in the AS patients: ESR × disease duration (≥60.0 mm/h × year): sensitivity = 72.7 % and specificity = 72.8 %; CRP × disease duration (≥8.3 mg/dl × year): sensitivity = 72.7 % and specificity = 74.6 %. ESR, CRP, and disease duration are particularly related to AS patient's poor physical mobility. Combining the usefulness of acute-phase reactants and disease duration, the values of ESR × disease duration and CRP × disease duration demonstrate better association with poor physical mobility in AS patients.

Development of an open source package for the processing of sun-sky photometric data in the European Skyrad Users network (ESR)

NASA Astrophysics Data System (ADS)

Estelles, V.; Smyth, T.; Campanelli, M.; Utrillas, M. P.

2009-04-01

The European SkyRad users network (ESR) is a joint initiative from the Institute of Atmospheric and Climate Sciences (ISAC) at the National Research Council (CNR) in Italy, the Group of Solar Radiation (GRSV) at the University of Valencia (UV) in Spain, and the Plymouth Marine Laboratory (PML) in the United Kingdom. It was started as a Protocol of Agreement between the three institutions, in 2003. The main objective was to collaborate on the improvement of some technical aspects of the Skyrad.pack algorithm. Currently the network is addressed at European research groups that are users of sun - sky photometers and mainly focus their research on the study of atmospheric aerosols and their application to remote sensing or climatological studies. There exist well known international networks such as AERONET (Aerosol Robotic Network) or SKYNET (SKYrad NETwork, in Asia) but they have some characteristics that actually prevent many European research groups to get involved with them. These limitations mean that a number of European groups are working independently, with no coordination. The resultant databases are not made public or the employed methodology is not homogeneous. In turn, it means that a great amount of data is being lost for critical regional studies in Europe. One of these limitations is related to the supported instrumentation. International networks usually adopt a given model of sun photometer as a standard. The ESR is a multi instrumental network using both Prede POM and Cimel CE318 sun - sky photometers. Another limitation is related to the calibration. In the case of AERONET, a centralized and stringent calibration protocol is adopted. This protocol is designed in order to offer a well tracked and quality assured calibration and data elaboration; it is in fact the key stone for the homogeneity of the network results. But centralization raises other problems. The instruments must be periodically sent every 6 - 12 months to United States or France; therefore, 1) the instrument absence generates considerable data gaps, 2) it is also a chance for equipment damage during the transport, and 3) the proprietary group must cope with the economical cost of these international insured deliveries. Moreover, the protocol constrains the network capability to handle a large amount of instruments. In fact, AERONET is very reluctant at the moment to accept new sites in Europe. ESR has developed an improved version of the Langley plot technique (SKYIL) that allows the users to perform a continuous in situ calibration. Previous results show that the obtained uncertainties in the calibration factors (1.0 - 2.5%) are very similar to the uncertainty values for field instruments in AERONET (1.0 - 2.0%). A third difference that could make ESR more appealing to some European research groups is related to the algorithms itself. The core inversion code (Skyrad.pack), the calibration codes and all the automatization scripts are free open source codes that can be further customized by the users. Therefore, an advanced user could easily access and modify the algorithms for new improvements. As a conclusion, the ESR users network has been conceived as a flexible network and collaborative platform for European groups whose main research is focused on atmospheric aerosols characterization and model development. The package we have developed for the network is an open source product that is available for public use, both for Cimel CE318 and Prede POM instruments.

Electron spin polarization (CIDEP) investigation of the interaction of reactive free radicals with polynitroxyl stable free radicals

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

Turro, N.J.; Khudyakov, I.V.; Dwyer, D.W.

1993-10-14

Time-resolved electron spin resonance (TR ESR) was employed to investigate the polarized ESR (CIDEP) spectra produced by interaction of mono- and polynitroxyls with reactive free radicals (r[sup [number sign

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.

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

Erythrocyte sedimentation rate as baseline predictor for the development of uveitis in children with juvenile idiopathic arthritis.

PubMed

Haasnoot, Arenda J W; van Tent-Hoeve, Maretta; Wulffraat, Nico M; Schalij-Delfos, Nicoline E; Los, Leonoor I; Armbrust, Wineke; Zuithoff, Nicolaas P A; de Boer, Joke H

2015-02-01

To analyze inflammatory parameters as possible predictors for the development of uveitis in juvenile idiopathic arthritis (JIA) patients. Further, to analyze the predictive value of demographic and clinical factors at the onset of arthritis. Retrospective cohort study. In 358 children with oligoarthritis and rheumatoid factor-negative polyarthritis, erythrocyte sedimentation rate (ESR), C-reactive protein, leukocyte count, presence of antinuclear antibodies (ANA), presence of human leukocyte antigen (HLA-)B27, age of onset of JIA, and sex were analyzed for their predictive value for the onset of uveitis. One hundred forty-seven patients (41%) were diagnosed with chronic anterior uveitis. Young age of onset, presence of ANA, and elevated ESR appeared to be predictive factors according to univariate analyses (P = .029, P = .007, and P = 5E(-4), respectively). According to multivariate analysis, young age of onset and elevated ESR appeared to be predictive after adjusting for the other relevant factors (P = .004 and P = .001, respectively). A prediction model was developed. Elevated ESR appears to be a predictor for the occurrence of uveitis in patients with JIA. Since ESR is already routinely tested in patients with recently diagnosed arthritis, its use as a biomarker can easily be implemented in daily practice. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Percolation effects in supercapacitors with thin, transparent carbon nanotube electrodes.

PubMed

King, Paul J; Higgins, Thomas M; De, Sukanta; Nicoloso, Norbert; Coleman, Jonathan N

2012-02-28

We have explored the effects of percolation on the properties of supercapacitors with thin nanotube networks as electrodes. We find the equivalent series resistance, R(ESR), and volumetric capacitance, C(V), to be thickness independent for relatively thick electrodes. However, once the electrode thickness falls below a threshold thickness (∼100 nm for R(ESR) and ∼20 nm for C(V)), the properties of the electrode become thickness dependent. We show the thickness dependence of both R(ESR) and C(V) to be consistent with percolation theory. While this is expected for R(ESR), that the capacitance follows a percolation scaling law is not. This occurs because, for sparse networks, the capacitance is proportional to the fraction of nanotubes connected to the main network. This fraction, in turn, follows a percolation scaling law. This allows us to understand and quantify the limitations on the achievable capacitance for transparent supercapacitors. We find that supercapacitors with thickness independent R(ESR) and C(V) occupy a well-defined region of the Ragone plot. However, supercapacitors whose electrodes are limited by percolation occupy a long tail to lower values of energy and power density. For example, replacing electrodes with transparency of T = 80% with thinner networks displaying T = 97% will result in a 20-fold reduction of both power and energy density.

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.

Free radical reaction characteristics of coal low-temperature oxidation and its inhibition method.

PubMed

Li, Zenghua; Kong, Biao; Wei, Aizhu; Yang, Yongliang; Zhou, Yinbo; Zhang, Lanzhun

2016-12-01

Study on the mechanism of coal spontaneous combustion is significant for controlling fire disasters due to coal spontaneous combustion. The free radical reactions can explain the chemical process of coal at low-temperature oxidation. Electron spin resonance (ESR) spectroscopy was used to measure the change rules of the different sorts and different granularity of coal directly; ESR spectroscopy chart of free radicals following the changes of temperatures was compared by the coal samples applying air and blowing nitrogen, original coal samples, dry coal samples, and demineralized coal samples. The fragmentation process was the key factor of producing and initiating free radical reactions. Oxygen, moisture, and mineral accelerated the free radical reactions. Combination of the free radical reaction mechanism, the mechanical fragmentation leaded to the elevated CO concentration, fracturing of coal pillar was more prone to spontaneous combustion, and spontaneous combustion in goaf accounted for a large proportion of the fire in the mine were explained. The method of added diphenylamine can inhibit the self-oxidation of coal effectively, the action mechanism of diphenylamine was analyzed by free radical chain reaction, and this research can offer new method for the development of new flame retardant.

Development of an Efficient Binaural Simulation for the Analysis of Structural Acoustic Data

NASA Technical Reports Server (NTRS)

Johnson, Marty E.; Lalime, Aimee L.; Grosveld, Ferdinand W.; Rizzi, Stephen A.; Sullivan, Brenda M.

2003-01-01

Applying binaural simulation techniques to structural acoustic data can be very computationally intensive as the number of discrete noise sources can be very large. Typically, Head Related Transfer Functions (HRTFs) are used to individually filter the signals from each of the sources in the acoustic field. Therefore, creating a binaural simulation implies the use of potentially hundreds of real time filters. This paper details two methods of reducing the number of real-time computations required by: (i) using the singular value decomposition (SVD) to reduce the complexity of the HRTFs by breaking them into dominant singular values and vectors and (ii) by using equivalent source reduction (ESR) to reduce the number of sources to be analyzed in real-time by replacing sources on the scale of a structural wavelength with sources on the scale of an acoustic wavelength. The ESR and SVD reduction methods can be combined to provide an estimated computation time reduction of 99.4% for the structural acoustic data tested. In addition, preliminary tests have shown that there is a 97% correlation between the results of the combined reduction methods and the results found with the current binaural simulation techniques

Detection of ESR1 mutations in plasma and tumors from metastatic breast cancer patients using next-generation sequencing.

PubMed

Yanagawa, Takehiro; Kagara, Naofumi; Miyake, Tomohiro; Tanei, Tomonori; Naoi, Yasuto; Shimoda, Masafumi; Shimazu, Kenzo; Kim, Seung Jin; Noguchi, Shinzaburo

2017-06-01

Liquid biopsy using digital PCR (dPCR) has been widely used for the screening of ESR1 mutations, since they are frequently identified in the hotspot. However, dPCR is limited to the known mutations. Therefore, we aimed to analyze the utility of next-generation sequencing (NGS) to discover novel ESR1 mutations. Whole exon sequencing of the ESR1 gene using NGS was performed in 16 primary and 47 recurrent tumor samples and 38 plasma samples from hormone receptor-positive metastatic breast cancer patients. Functional analyses were then performed for the novel mutations we detected. We identified no mutations in primary tumors and six mutations in five recurrent tumors, including three types of known mutations (Y537C, Y537N, and D538G) and two novel mutations (E279V and G557R). We also identified seven mutations in five plasma samples, including three types of known mutations (S463P, Y537S, and D538G) and one mutation not reported in COSMIC database (L536H). All nine patients with ESR1 mutations were treated with aromatase inhibitors (AIs) prior to sampling, and the mutations were frequently detected in patients who received AI treatments in the metastatic setting. Among the three novel mutations (E279V, L536H, and G557R), L536H, but not E279V and G557R, showed ligand-independent activity. All three mutant proteins showed nuclear localization and had no relation with non-genomic ER pathways. Although the molecular mechanisms of the E279V and G557R mutations remain unclear, our data suggest the utility of NGS as a liquid biopsy for metastatic breast cancer patients and the potential to identify novel ESR1 mutations.

Sex and ESR1 genotype may influence the response to treatment with donepezil and rivastigmine in patients with Alzheimer's disease.

PubMed

Scacchi, Renato; Gambina, Giuseppe; Broggio, Elisabetta; Corbo, Rosa Maria

2014-06-01

Many factors could be responsible for the different response to treatment with the cholinesterase inhibitors (ChEIs) donepezil and rivastigmine in Alzheimer's disease (AD) patients. Sex and the variants of the estrogen receptor α (ESR1) gene are reported to modulate AD susceptibility or the course of the disease. The aim of the present study was to verify whether patient's sex and ESR1 genotype could influence the response to ChEI treatment, as there is evidence that estrogens affect cholinergic system functioning. Two ESR1 intronic polymorphisms (PvuII, rs2234693; XbaI, rs9340799) were examined in 184 AD patients: 157 were receiving treatment with donepezil or rivastigmine and 27 were receiving no treatment. Cognitive status was assessed using the mini mental state examination at four time points (1, 3, 9, and 15 months into therapy). Among the patients under treatment with either ChEI, the women responded more markedly than the men. As compared with the untreated patients, the effects of treatment were statistically significant for both donepezil and rivastigmine. A significant effect of ESR1 genotypes was observed for the donepezil-treated patients, among which those carrying at least one copy of P and X alleles showed a significantly lower cognitive decline than the noncarriers. The present data seem to confirm a sex-related influence on treatment, as the women seemed to be more sensitive to therapy and to have experienced less cognitive decline. ESR1 may be another gene contributing to interindividual variability in response to treatment with ChEIs. Copyright © 2013 John Wiley & Sons, Ltd.

Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner

PubMed Central

Gertz, Jason; Reddy, Timothy E.; Varley, Katherine E.; Garabedian, Michael J.; Myers, Richard M.

2012-01-01

Endogenous estrogens that are synthesized in the body impact gene regulation by activating estrogen receptors in diverse cell types. Exogenous compounds that have estrogenic properties can also be found circulating in the blood in both children and adults. The genome-wide impact of these environmental estrogens on gene regulation is unclear. To obtain an integrated view of gene regulation in response to environmental and endogenous estrogens on a genome-wide scale, we performed ChIP-seq to identify estrogen receptor 1 (ESR1; previously estrogen receptor α) binding sites, and RNA-seq in endometrial cancer cells exposed to bisphenol A (BPA; found in plastics), genistein (GEN; found in soybean), or 17β-estradiol (E2; an endogenous estrogen). GEN and BPA treatment induces thousands of ESR1 binding sites and >50 gene expression changes, representing a subset of E2-induced gene regulation changes. Genes affected by E2 were highly enriched for ribosome-associated proteins; however, GEN and BPA failed to regulate most ribosome-associated proteins and instead enriched for transporters of carboxylic acids. Treatment-dependent changes in gene expression were associated with treatment-dependent ESR1 binding sites, with the exception that many genes up-regulated by E2 harbored a BPA-induced ESR1 binding site but failed to show any expression change after BPA treatment. GEN and BPA exhibited a similar relationship to E2 in the breast cancer line T-47D, where cell type specificity played a much larger role than treatment specificity. Overall, both environmental estrogens clearly regulate gene expression through ESR1 on a genome-wide scale, although with lower potency resulting in less ESR1 binding sites and less gene expression changes compared to the endogenous estrogen, E2. PMID:23019147

Bisphenol A causes malformation of the head region in embryos of Xenopus laevis and decreases the expression of the ESR-1 gene mediated by Notch signaling.

PubMed

Imaoka, Susumu; Mori, Tomohiro; Kinoshita, Tsutomu

2007-02-01

Bisphenol A (BpA) is widely used in industry and dentistry. Its effects on the embryonic development of Xenopus laevis were investigated. Xenopus embryos at stage 10.5 were treated with BpA. Developmental abnormalities were observed at stage 35; malformation of the head region including eyes and scoliosis. The expression of several markers of embryonic development was investigated by reverse transcription-polymerase chain reaction (RT-PCR). The pan-neural marker SOX-2, the neural stem cell marker nrp-1, the mesodermal marker MyoD, and the endodermal marker sox17alpha, were used. Although the expression of marker genes was not changed by treatment with BpA, that of Pax-6, a key regulator of the morphogenesis of the eyes, was decreased by BpA. Pax-6 is a downstream factor of Notch signaling. So, the expression of a typical Notch-dependent factor, ESR-1, was investigated in the presence of BpA. The expression of ESR-1 was efficiently suppressed by BpA. In whole mount in situ hybridization (WISH), Pax-6 was expressed in the central nervous system and eyes. The expression was lost completely on treatment with BpA. The expression of ESR-1 in the central nervous system and eyes also disappeared with BpA treatment. Injection of the intracellular domain of Notch efficiently recovered ESR-1 expression in the presence of BpA although injection of a ligand for notch, Delta, did not. These results suggest that BpA decreased the expression of ESR-1 by disrupting the Notch signal.

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.

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 expression of genes involved in myometrial contractility changes during ex situ culture of pregnant human uterine smooth muscle tissue.

PubMed

Ilicic, Marina; Butler, Trent; Zakar, Tamas; Paul, Jonathan W

2017-01-01

Ex situ analyses of human myometrial tissue has been used to investigate the regulation of uterine quiescence and transition to a contractile phenotype. Following concerns about the validity of cultured primary cells, we examined whether myometrial tissue undergoes culture-induced changes ex situ that may affect the validity of in vitro models. To determine whether human myometrial tissue undergoes culture-induced changes ex situ in Estrogen receptor 1 (ESR1), Prostaglandin-endoperoxide synthase 2 (PTGS2) and Oxytocin receptor (OXTR) expression. Additionally, to determine whether culture conditions approaching the in vivo environment influence the expression of these key genes. Term non-laboring human myometrial tissues were cultured in the presence of specific treatments, including; serum supplementation, progesterone and estrogen, cAMP, PMA, stretch or NF-κB inhibitors. ESR1, PTGS2 and OXTR mRNA abundance after 48 h culture was determined using quantitative RT-PCR. Myometrial tissue in culture exhibited culture-induced up-regulation of ESR1 and PTGS2 and down-regulation of OXTR mRNA expression. Progesterone prevented culture-induced increase in ESR1 expression. Estrogen further up-regulated PTGS2 expression. Stretch had no direct effect, but blocked the effects of progesterone and estrogen on ESR1 and PTGS2 expression. cAMP had no effect whereas PMA further up-regulated PTGS2 expression and prevented decline of OXTR expression. Human myometrial tissue in culture undergoes culture-induced gene expression changes consistent with transition toward a laboring phenotype. Changes in ESR1, PTGS2 and OXTR expression could not be controlled simultaneously. Until optimal culture conditions are determined, results of in vitro experiments with myometrial tissues should be interpreted with caution.

Preventing the forgotten ureteral stent: implementation of a web-based stent registry with automatic recall application.

PubMed

Lynch, Mark F; Ghani, Khurshid R; Frost, Ian; Anson, Ken M

2007-09-01

To describe and analyze a unique computerized system that tracks ureteral stents and automatically sends a notice by e-mail to clinical staff if a stent becomes overdue for removal. We have developed an electronic stent register (ESR) and stent extraction reminder facility (SERF) located within our hospital computer network. After stent insertion, a stent "episode" is created in the ESR with a mandatory maximal stent life (MSL). The SERF interrogates the ESR on a daily basis and identifies stents that have breached its MSL, generating daily e-mail notices to personnel until the stent is removed and the ESR updated. The episode data capture initially employing manual entry was changed to barcode technology acquisition. We analyzed the success of patient recall and conducted a prospective, blinded review to determine the success of the data acquisition. A total of 293 episodes were created within 2.4 years. Of the 241 (86%) episodes that were closed, 123 (51%) went beyond the MSL. The mean delay from designated MSL to stent removal was 20.89 days (SD 19.71). In the 7 months before barcode data acquisition, 43 of 71 stents were entered into the ESR (data capture rate 61%). In the 7 months after barcode data acquisition, 52 of 60 stents were entered (data capture rate 87%; P = 0.0009). The results of our study have shown the ESR and SERF to be robust and valuable tools for the treatment of patients with ureteral stents. Barcode acquisition significantly improved the stent insertion capture rate. This system ensures improved patient safety with an element of protection from potential litigation.

Lean body mass and creatine kinase are associated with reduced inflammation in obesity.

PubMed

Bekkelund, Svein I; Jorde, Rolf

2017-11-01

Obesity is associated with inflammation, but the role of lean mass and creatine kinase (CK) on the inflammatory process is less known. We investigated the associations between lean mass, CK and fat mass upon inflammatory parameters in an overweight and obese adult population. Body composition examined by dual-energy X-ray absorptiometry, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), CK and supplementary clinical parameters were measured in 454 overweight and obese individuals. This is a secondary analysis from a cohort of obese individuals treated with Vitamin D. Mean age was 47·6 ± 11·4 years and mean body mass index 34·6 ± 3·9 kg/m 2 . Lean mass correlated negatively with hs-CRP (r = -0·127, P = 0·042) and ESR (r = -0·381, P < 0·001). Median lean mass in the lower ESR quartile was significantly higher than in the upper quartile (P < 0·001) but not between lower and upper hs-CRP quartiles (P = 0·114). CK was negatively correlated with hs-CRP (r = -0·151, P < 0·001) and ESR (r = -0·240, P < 0·001). Median CK in the lower hs-CRP and ESR quartiles were significantly higher than in the upper quartiles (P < 0·001 for both). Conversely, fat mass was positively associated with hs-CRP and ESR. Inflammatory parameters were related to reduced lean mass and CK in an overweight and obese population. Hypothetically, lean mass has a favourable effect on obesity-related inflammation, and CK may play a role as an inhibitor of inflammation in obesity. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

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.

Neonatal over-expression of estrogen receptor-α alters midbrain dopamine neuron development and reverses the effects of low maternal care in female offspring

PubMed Central

Peña, Catherine Jensen; Champagne, Frances A

2014-01-01

Maternal behavior is dependent on estrogen receptor-alpha (ERα; Esr1) and oxytocin receptor (OTR) signaling in the medial preoptic area (MPOA) of the hypothalamus, as well as dopamine signaling from the ventral tegmental area (VTA) to forebrain regions. Previous studies in rats indicate that low levels of maternal care, particularly licking/grooming (LG), lead to reduced levels of MPOA ERα and VTA dopamine neurons in female offspring and predict lower levels of postpartum maternal behavior by these offspring. The aim of the current study was to determine the functional impact on maternal behavior of neonatal manipulation of ERα in females that had experienced low vs. high levels of postnatal maternal LG. Adenovirus expressing ESR1 was targeted to the MPOA in female pups from low and high LG litters on postnatal day 2–3. Over-expression of ESR1 in low LG offspring elevated the level of ERα-immunoreactive cells in the MPOA and of tyrosine hydroxylase cells in the VTA to that observed in high LG females. Amongst juvenile female low LG offspring, ESR1 over-expression also decreased the latency to engage in maternal behavior toward donor pups. These results show that virally-mediated expression of ESR1 in the neonatal rat hypothalamus results in lasting changes in ESR1 expression through the juvenile period, and can “rescue” hormone receptor levels and behavior of offspring reared by low LG dams, potentially mediated by downstream alterations within reward circuitry. Thus, the transmission of maternal behavior from one generation to the next can be augmented by neonatal ERα in the MPOA. PMID:25044746

Estrogen receptor (ESR1) mRNA expression and benefit from tamoxifen in the treatment and prevention of estrogen receptor-positive breast cancer.

PubMed

Kim, Chungyeul; Tang, Gong; Pogue-Geile, Katherine L; Costantino, Joseph P; Baehner, Frederick L; Baker, Joffre; Cronin, Maureen T; Watson, Drew; Shak, Steven; Bohn, Olga L; Fumagalli, Debora; Taniyama, Yusuke; Lee, Ahwon; Reilly, Megan L; Vogel, Victor G; McCaskill-Stevens, Worta; Ford, Leslie G; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman; Paik, Soonmyung

2011-11-01

Several mechanisms have been proposed to explain tamoxifen resistance of estrogen receptor (ER) -positive tumors, but a clinically useful explanation for such resistance has not been described. Because the ER is the treatment target for tamoxifen, a linear association between ER expression levels and the degree of benefit from tamoxifen might be expected. However, such an association has never been demonstrated with conventional clinical ER assays, and the ER is currently used clinically as a dichotomous marker. We used gene expression profiling and ER protein assays to help elucidate molecular mechanism(s) responsible for tamoxifen resistance in breast tumors. We performed gene expression profiling of paraffin-embedded tumors from National Surgical Adjuvant Breast and Bowel Project (NSABP) trials that tested the worth of tamoxifen as an adjuvant systemic therapy (B-14) and as a preventive agent (P-1). This was a retrospective subset analysis based on available materials. In B-14, ESR1 was the strongest linear predictor of tamoxifen benefit among 16 genes examined, including PGR and ERBB2. On the basis of these data, we hypothesized that, in the P-1 trial, a lower level of ESR1 mRNA in the tamoxifen arm was the main difference between the two study arms. Only ESR1 was downregulated by more than two-fold in ER-positive cancer events in the tamoxifen arm (P < .001). Tamoxifen did not prevent ER-positive tumors with low levels of ESR1 expression. These data suggest that low-level expression of ESR1 is a determinant of tamoxifen resistance in ER-positive breast cancer. Strategies should be developed to identify, treat, and prevent such tumors.

Characteristics of the spin-trapping reaction of a free radical derived from AAPH: further development of the ORAC-ESR assay.

PubMed

Nakajima, A; Matsuda, E; Masuda, Y; Sameshima, H; Ikenoue, T

2012-06-01

The characteristics of the spin-trapping reaction in the oxygen radical absorbance capacity (ORAC)-electron spin resonance (ESR) assay were examined, focusing on the kind of spin traps. 2,2-Azobis(2-amidinopropane) dihydrochloride (AAPH) was used as a free radical initiator. The spin adducts of the AAPH-derived free radical were assigned as those of the alkoxyl radical, RO· (R=H(2)N(HN)C-C(CH(3))(2)). Among the spin traps tested, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), 5,5-dimethyl-4-phenyl-1-pyrroline N-oxide (4PDMPO), 5-(2,2-dimethyl-1,3-propoxycyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO), and 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO) were applicable to the ORAC-ESR assay. Optimal formation of spin-trapped radical adduct was observed with 1 mM AAPH, 10 mM spin trap, and 5 s UV irradiation. The calibration curve (the Stern-Volmer's plot) for each spin trap showed good linearity, and their slopes, k (SB)/k (ST), were estimated to be 87.7±2.3, 267±15, 228±9, and 213±16 for DMPO, 4PDMPO, CYPMPO, and DEPMPO, respectively. Though the k (SB)/k (ST) values for selected biosubstances varied with various spin traps, their ratios to Trolox (the relative ORAC values) were almost the same for all spin traps tested. The ORAC-ESR assay also had a very good reproducibility. The ORAC-ESR assay was conducted under stoichiometric experimental conditions. The present results demonstrate the superiority of the ORAC-ESR assay.

Effects of Reoxidation of Liquid Steel and Slag Composition on the Chemistry Evolution of Inclusions During Electroslag Remelting

NASA Astrophysics Data System (ADS)

Shi, Chengbin; Wang, Hui; Li, Jing

2018-06-01

Electroslag remelting (ESR) is increasingly used to produce some varieties of special steels and alloys, mainly because of its ability to provide extreme cleanliness and an excellent solidification structure simultaneously. In the present study, the combined effects of varying SiO2 contents in slag and reoxidation of liquid steel on the chemistry evolution of inclusions and the alloying element content in steel during ESR were investigated. The inclusions in the steel before ESR refining were found to be oxysulfides of patch-type (Ca,Mn)S adhering to a CaO-Al2O3-SiO2-MgO inclusion. The oxide inclusions in both the liquid metal pool and remelted ingots are CaO-Al2O3-MgO and MgAl2O4 together with CaO-Al2O3-SiO2-MgO inclusions (slightly less than 30 pct of the total inclusions), which were confirmed to originate from the reduction of SiO2 from the original oxide inclusions by dissolved Al in liquid steel during ESR. CaO-Al2O3-MgO and MgAl2O4 are newly formed inclusions resulting from the reactions taking place inside liquid steel in the liquid metal pool caused by reoxidation of liquid steel during ESR. Increasing the SiO2 content in slag not only considerably reduced aluminum pickup in parallel with silicon loss during ESR, but also suppressed the decrease in SiO2 content in oxide inclusions. (Ca,Mn)S inclusions were fully removed before liquid metal droplets collected in the liquid metal pool.

Emotion Self-Regulation Moderates the Association Between Symptoms of ADHD and Weight Loss After Bariatric Surgery.

PubMed

Williamson, Tamara M; Campbell, Tavis S; Telfer, Jo Ann; Rash, Joshua A

2018-06-01

This study aimed to examine the combined effect of pre-surgical emotion self-regulation (ESR) and symptoms of attention deficit hyperactivity disorder (sADHD, i.e., inattention, impulsivity, and hyperactivity) on weight loss 12 months following bariatric surgery independent of psychological distress and eating pathology. Adults with obesity were recruited from a bariatric surgery specialty clinic in Canada. Patients completed measures of psychological distress (i.e., Beck Depression Inventory II and Beck Anxiety Inventory), eating pathology (i.e., Eating Disorder Examination Questionnaire), ESR (i.e., "Managing Own Emotions" subscale of the Schutte Emotional Intelligence Test), and sADHD (i.e., Adult ADHD Self-Report Scale) prior to surgery. Measures of height and weight were obtained and used to calculate percent excess weight loss (%EWL) of body mass index (BMI) pre- and 12 months post-surgery. Thirty-seven patients were recruited. The final sample consisted of 30 patients (80% female; mean age = 48 years; mean BMI = 49.32). Patients experienced significant weight loss and reported significant improvement in anxiety, depressed mood, and eating pathology from pre- to 12 months post-surgery. A significant sADHD by ESR interaction on %EWL (F(1, 21) = 6.43, p = .019) was observed and accounted for 13% of unique variance after adjusting for relevant covariates. Probing the interaction with the Johnson-Neyman technique indicated that there was a significant inverse association between sADHD and %EWL among individuals who scored ≤ 0.15 SD below the mean on ESR. ESR moderated the association between sADHD and %EWL, suggesting that sADHD may attenuate weight loss following bariatric surgery among individuals deficient in ESR. This finding has implications for bariatric surgery pre-surgical psychological assessment.

Paternal exposure to environmental 17-alpha-ethinylestradiol concentrations modifies testicular transcription, affecting the sperm transcript content and the offspring performance in zebrafish.

PubMed

Valcarce, David G; Vuelta, Elena; Robles, Vanesa; Herráez, Maria Paz

2017-12-01

The synthetic estrogen 17-α-ethinylestradiol (EE2), a major constituent in contraceptive pills, is an endocrine disrupting chemical (EDC) present in the aquatic environment at concentrations of ng/L. Developmental exposure to these low concentrations in fish can induce several disorders. Zebrafish (Danio rerio) is a perfect organism for monitoring the effects of environmental contaminants. Our hypothesis is that changes promoted by EE2 in the germ line of male adults could be transmitted to the unexposed progeny. We exposed male zebrafish to 2.5, 5 and 10ng/L of EE2 during spermatogenesis and mated them with untreated females. Detailed progeny development was studied concentrating to survival, hatching and malformations. Due to the high incidence of lymphedemas within larvae, we performed qPCR analysis of genes involved in lymphatic development (vegfc and vegfr3) and endothelial cell migration guidance (cxcr4a and cxcl12b). Estrogen receptor (ER) transcript presence was also evaluated in sperm, testis and embryos. Progenies showed a range of disorders although at a low incidence: skeletal distortions, uninflated swimbladder, lymphedema formation, cartilage deformities and otolith tethering. Swimming evaluation revealed less active locomotion. All these processes are related to pathways involving ERs (esr1, esr2a and esr2b). mRNA analysis revealed that environmental EE2 causes the up-regulation of esr1 an esr2b in testis and the increase of esr2b transcripts in sperm pointing to a link between lymphedema in embryos and ER expression impairment. We demonstrate that the effects induced by environmental toxicants can be paternally inherited and point to the changes on the sperm transcriptome as the responsible mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

The Guanine Cation Radical: Investigation of Deprotonation States by ESR and DFT

PubMed Central

Adhikary, Amitava; Kumar, Anil; Becker, David; Sevilla, Michael D.

2008-01-01

This work reports ESR studies that identify the favored site of deprotonation of the guanine cation radical (G•+) in an aqueous medium at 77 K. Using ESR and UV-visible spectroscopy, one-electron oxidized guanine is investigated in frozen aqueous D2O solutions of 2′-deoxyguanosine (dGuo) at low temperatures at various pHs at which the guanine cation, G•+ (pH 3–5), singly deprotonated species, G(-H)• (pH 7–9) and doubly deprotonated species, G(-2H)•− (pH>11) are found. C-8-deuteration of dGuo to give 8-D-dGuo removes the major proton hyperfine coupling at C-8. This isolates the anisotropic nitrogen couplings for each of the three species and aids our analyses. These anisotropic nitrogen couplings were assigned to specific nitrogen sites by use of 15N substituted derivatives at N1, N2 N3 atoms in dGuo. Both ESR and UV-visible spectra are reported for each of the species: G•+, G(-H)•, and G(-2H)•−. The experimental anisotropic ESR hyperfine couplings are compared to those obtained from DFT calculations for the various tautomers of G(-H)•. Using the B3LYP/6–31G(d) method, the geometries and energies of G•+ and its singly deprotonated state in its two tautomeric forms, G(N1-H)• and G(N2-H)•, were investigated. In a non-hydrated state G(N2-H)• is found to be more stable than G(N1-H)• but on hydration with 7 water molecules G(N1-H)• is found to be more stable than G(N2-H)•. The theoretically calculated hyperfine coupling constants (HFCC) of G•+, G(N1-H)• and G(-2H)•− match the experimentally observed HFCCs best on hydration with 7 or more waters. For G(-2H)•−, the hyperfine coupling constant (HFCC) at the exocyclic nitrogen atom (N2) is especially sensitive to the number of hydrating water molecules; good agreement with experiment is not obtained until 9 or 10 waters of hydration are included. PMID:17125389

Polymorphisms in the estrogen receptor alpha gene (ESR1), daily cycling estrogen and mammographic density phenotypes.

PubMed

Fjeldheim, F N; Frydenberg, H; Flote, V G; McTiernan, A; Furberg, A-S; Ellison, P T; Barrett, E S; Wilsgaard, T; Jasienska, G; Ursin, G; Wist, E A; Thune, I

2016-10-07

Single nucleotide polymorphisms (SNPs) involved in the estrogen pathway and SNPs in the estrogen receptor alpha gene (ESR1 6q25) have been linked to breast cancer development, and mammographic density is an established breast cancer risk factor. Whether there is an association between daily estradiol levels, SNPs in ESR1 and premenopausal mammographic density phenotypes is unknown. We assessed estradiol in daily saliva samples throughout an entire menstrual cycle in 202 healthy premenopausal women in the Norwegian Energy Balance and Breast Cancer Aspects I study. DNA was genotyped using the Illumina Golden Gate platform. Mammograms were taken between days 7 and 12 of the menstrual cycle, and digitized mammographic density was assessed using a computer-assisted method (Madena). Multivariable regression models were used to study the association between SNPs in ESR1, premenopausal mammographic density phenotypes and daily cycling estradiol. We observed inverse linear associations between the minor alleles of eight measured SNPs (rs3020364, rs2474148, rs12154178, rs2347867, rs6927072, rs2982712, rs3020407, rs9322335) and percent mammographic density (p-values: 0.002-0.026), these associations were strongest in lean women (BMI, ≤23.6 kg/m 2. ). The odds of above-median percent mammographic density (>28.5 %) among women with major homozygous genotypes were 3-6 times higher than those of women with minor homozygous genotypes in seven SNPs. Women with rs3020364 major homozygous genotype had an OR of 6.46 for above-median percent mammographic density (OR: 6.46; 95 % Confidence Interval 1.61, 25.94) when compared to women with the minor homozygous genotype. These associations were not observed in relation to absolute mammographic density. No associations between SNPs and daily cycling estradiol were observed. However, we suggest, based on results of borderline significance (p values: 0.025-0.079) that the level of 17β-estradiol for women with the minor genotype for rs3020364, rs24744148 and rs2982712 were lower throughout the cycle in women with low (<28.5 %) percent mammographic density and higher in women with high (>28.5 %) percent mammographic density, when compared to women with the major genotype. Our results support an association between eight selected SNPs in the ESR1 gene and percent mammographic density. The results need to be confirmed in larger studies.

[Clinical efficacy of posterior intervertebral surgery for treating single-segment thoracolumbar spinal tuberculosis].

PubMed

Yang, Zongqiang; He, Jinwen; Shi, Jiandang; Niu, Ningkui; Ding, Huiqiang; Wang, Zili

2018-05-28

To determine the clinical efficacy of posterior intervertebral surgery for single-segment thoracolumbar spinal tuberculosis.
 Methods: Clinical data were retrospectively analyzed in 62 patients with thoracolumbar spinal tuberculosis who underwent posterior intervertebral surgery (A group) or posterior and anterior combined intervertebral surgery (B group) from January 2010 to January 2015 in Department of Spinal Surgery, General Hospital, Ningxia Medical University. The operative time, blood loss, length of hospital stay, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, neurological function, VAS score, vertebral Cobb angle, bone healing, and postoperative complications were compared between the 2 groups.
 Results: All patients were followed up for 10 to 30 (average 22) months after the operation. In the A group, operative time, blood loss, and hospital stay were less than those in the B group (P<0.05). In the follow-up, the pain of patients was alleviated and nervous function was improved obviously in the 2 groups compared with pre-operation. The ESR and CRP at the 6 months after operation returned to the normal range in patients of the 2 groups. There were significant differences in the ESR and CRP among the pre-operation, the 6 months after operation, and the end of follow-up within the group (P<0.05), while there were no significant differences in ESR and CRP between the 6 months after operation and the end of follow-up (P>0.05). There were no significant differences in the ESR and CRP among the pre-operation, the 6 months after operation, and the end of follow-up in the 2 group (P>0.05). The Cobb angles after the operation and the end of follow-up were significanthy smaller than those before the operation (P<0.01), while there were no significant differences in Cobb angle before operation, after the operation, and the end of follow-up between the 2 groups (P>0.05). There were no significant differences in the bone healing rate at 6 months or 1 year after operation between the A group and B group (P>0.05) and the complication rate of the A group was lower than the B group (P<0.01).
 Conclusion: Clinical efficacy of posterior intervertebral surgery is satisfatory in treating single-segment thoracolumbar spinal tuberculosis with less complications.

The ESR signals in silk fibroin and wool keratin under both the effect of UV-irradiation and without any external effects and the formation of free radicals.

PubMed

Mamedov, Sh V; Aktas, B; Cantürk, M; Aksakal, B; Alekperov, V; Bülbül, F; Yilgin, R; Aslanov, R B

2002-08-01

ESR studies have been done on natural and UV-irradiated silk fibroins and wool keratins at the temperature range of -196 degrees C to 20 C. The intensities of ESR signals obtained from the irradiated samples at -196 C remarkably increase with respect to those of natural samples. While the signals mainly consist of triplet peaks at -196 C. a doublet arises around the room temperatures. For the first time, at room temperature without any external effect the complicated ESR spectra of fibrous proteins (wool keratin and silk fibroin) whose components are as follows have been observed: (1) (for white wool keratin) a central doublet with deltaHm = 1.1 mT and g = 2.0075; deltaHm = 5mT and g = 2.1911; (2) a wide peak with deltaHm approximately 66 mT and g approximately 2.1575; (3) the 'sulfur' peak given in the literature with deltaHm = 2.2 mT and g = 2.0218; (4) the signal with deltaHm = 0.6 mT and g = 2.0065, and for silk fibroin, (a) a very wide signal with deltaHm approximately 70 mT and g approximately 2.084; (b) a very sharp signal with deltaHm approximately 1.1 mT and g approximately 2.01; and (c) relatively narrower signal with deltaHm approximately 5 mT and g approximately 2.336. It has been shown by recombination kinetic method that 30-50% of the free radicals formed by UV-irradiation do not undergo recombination up to 220 degrees C and 15 degrees C for silk libroin and wool keratin, respectively, even they keep their concentration constant for long period of time (weeks, months, even longer). In this article, considering above-mentioned results, the mechanism of signals observed in natural wool keratin and silk fibroin without any external effects is examined. We can briefly explain the role of the subject of the article, by considering fibrous proteins and some applications of the reactions by free radical occurring in these proteins tinder the effects of different factors in medicine and biology and the important role of oxidation and the other kinds of degradations on these processes. as well as the significant applications of ESR investigations on comprehending the processes by free radical.

Expression of receptors for ovarian steroids and prostaglandin E2 in the endometrium and myometrium of mares during estrus, diestrus and early pregnancy.

PubMed

Silva, E S M; Scoggin, K E; Canisso, I F; Troedsson, M H T; Squires, E L; Ball, B A

2014-12-30

The objective of this study was to compare expression of estrogen receptor alpha (ER-α), β (ER-β), progesterone receptor (PR), as well as prostaglandin E2 type 2 (EP2) and 4 (EP4) receptors in the equine myometrium and endometrium during estrus, diestrus and early pregnancy. Tissues were collected during estrus, diestrus, and early pregnancy. Transcripts for ER-α (ESR1), ER-β (ESR2), PR (PGR), EP2 (PTGER2) and EP4 (PTGER4) were quantified by qPCR. Immunohistochemistry was used to localize ER-α, ER-β, PR, EP2 and EP4. Differences in transcript in endometrium and myometrium were compared by the ΔΔCT method. Expression for ESR1 (P<0.05) tended to be higher during estrus than diestrus in the endometrium (P=0.1) and myometrium (P=0.06). In addition, ESR1 expression was greater during estrus than pregnancy (P<0.05) in the endometrium and tended to be higher in estrus compared to pregnancy in the myometrium (P=0.1). Expression for PGR was greater (P<0.05) in the endometrium during estrus and diestrus than during pregnancy. In the myometrium, PGR expression was greater in estrus than pregnancy (P=0.05) and tended to be higher during diestrus in relation to pregnancy (P=0.07). There were no differences among reproductive stages in ESR2, PTGER2 and PTGER4 mRNA expression (P>0.05). Immunolabeling in the endometrium appeared to be more intense for ER-α during estrus than diestrus and pregnancy. In addition, immunostaining for PR during pregnancy appeared to be more intense in the stroma and less intense in glands and epithelium compared to estrus and diestrus. EP2 immunoreactivity appeared to be more intense during early pregnancy in both endometrium and myometrium, whereas weak immunolabeling for EP4 was noted across reproductive stages. This study demonstrates differential regulation of estrogen receptor (ER) and PR in the myometrium and endometrium during the reproductive cycle and pregnancy as well as abundant protein expression of EP2 in the endometrium and myometrium during early pregnancy in mares. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural and electronic studies of metal carbide clusterfullerene Sc2C2@Cs-C72

NASA Astrophysics Data System (ADS)

Feng, Yongqiang; Wang, Taishan; Wu, Jingyi; Feng, Lai; Xiang, Junfeng; Ma, Yihan; Zhang, Zhuxia; Jiang, Li; Shu, Chunying; Wang, Chunru

2013-07-01

We present a metal carbide clusterfullerene Sc2C2@Cs(10528)-C72, whose structure has been baffling for many years. A motional endohedral Sc2C2 cluster, special molecule geometry and electronic structure were found in Sc2C2@Cs(10528)-C72. The paramagnetic Sc2C2@Cs-C72 anion radical was successfully prepared by a chemical reduction method and hyperfine couplings in the ESR spectrum were observed.We present a metal carbide clusterfullerene Sc2C2@Cs(10528)-C72, whose structure has been baffling for many years. A motional endohedral Sc2C2 cluster, special molecule geometry and electronic structure were found in Sc2C2@Cs(10528)-C72. The paramagnetic Sc2C2@Cs-C72 anion radical was successfully prepared by a chemical reduction method and hyperfine couplings in the ESR spectrum were observed. Electronic supplementary information (ESI) available: Experimental details, HPLC chromatogram, and DFT calculations. CCDC 917712. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3nr01739g

ESR spectroscopy as a tool for identifying joining fragments of antique marbles: the example of a pulpit by Donatello and Michelozzo.

PubMed

Attanasio, D; Platania, R

2000-06-01

ESR spectroscopy is one of the physicochemical techniques used to characterize archaeological white marbles and obtain information about their quarries of provenance. This is done by measuring selected spectral features of the Mn(2+) impurity ubiquitously present in marbles and developing a statistical classification rule from the variable vectors measured for a significant number of samples of known provenance (the quarry database). Now we show that the overall variability exhibited by the same spectroscopic features decreases rapidly with the linear dimensions of the sampled block and can be used to distinguish fragments belonging to the same piece of stone from those simply originating from the same quarry. Application of the method to the seven marble panels of the Donatello pulpit in Prato (Tuscany) shows that they have all been cut from the same single block and their different degradation must be ascribed to differential weathering and to the different conservation treatments undergone in the past. The limits and possible drawbacks of the method are also discussed. Copyright 2000 Academic Press.

Is ESR Important for Predicting Post-ERCP Pancreatitis?

PubMed

Mohammad Alizadeh, Amir Houshang; Afzali, Esmaeil Shamsi; Behzad, Catherine; Mousavi, Mirhadi; Mirsattari, Dariush; Doagoo, Siavash Zafar; Zali, Mohammad Reza

2015-01-01

Pancreatitis remains the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), resulting in substantial morbidity and occasional mortality. There are notable controversies and conflicting reports about risk factors of post-ERCP pancreatitis (PEP). To evaluate the potential risk factors for PEP at a referral tertiary center, as a sample of the Iranian population. Baseline characteristics and clinical as well as paraclinical information of 780 patients undergoing diagnostic and therapeutic ERCP at Taleghani hospital in Tehran between 2008 and 2012 were reviewed. Data were collected prior to the ERCP, at the time of the procedure, and 24-72 hours after discharge. PEP was diagnosed according to consensus criteria. Of the 780 patients who underwent diagnostic ERCP, pancreatitis developed in 26 patients (3.3%). In the multivariable risk model, significant risk factors with adjusted odds ratios (ORs) were age <65 years (OR = 10.647, P = 0.023) and erythrocyte sedimentation rate (ESR) >30 (OR = 6.414, P < 0.001). Female gender, history of recurrent pancreatitis, pre-ERCP hyperamylasemia, and difficult or failed cannulation could not predict PEP. There was no significant difference in the rate of PEP in wire-guided cannulation versus biliary cannulation using a sphincterotome and contrast injection as the conventional method. Performing ERCP may be safer in the elderly. Patients with high ESR may be at greater risk of PEP, which warrants close observation of these patients for signs of pancreatitis after ERCP.

Diagnostics of plasma-biological surface interactions in low pressure and atmospheric pressure plasmas

NASA Astrophysics Data System (ADS)

Ishikawa, Kenji; Hori, Masaru

2014-08-01

Mechanisms of plasma-surface interaction are required to understand in order to control the reactions precisely. Recent progress in atmospheric pressure plasma provides to apply as a tool of sterilization of contaminated foodstuffs. To use the plasma with safety and optimization, the real time in situ detection of free radicals - in particular dangling bonds by using the electron-spin-resonance (ESR) technique has been developed because the free radical plays important roles for dominantly biological reactions. First, the kinetic analysis of free radicals on biological specimens such as fungal spores of Penicillium digitatum interacted with atomic oxygen generated plasma electric discharge. We have obtained information that the in situ real time ESR signal from the spores was observed and assignable to semiquinone radical with a g-value of around 2.004 and a line width of approximately 5G. The decay of the signal was correlated with a link to the inactivation of the fungal spore. Second, we have studied to detect chemical modification of edible meat after the irradiation. Using matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF-MS) and ESR, signals give qualification results for chemical changes on edible liver meat. The in situ real-time measurements have proven to be a useful method to elucidate plasma-induced surface reactions on biological specimens.

Establishing an Operational Data System for Surface Currents Derived from Satellite Altimeters and Scatterometers; Pilot Study for the Tropical Pacific

NASA Astrophysics Data System (ADS)

Lagerloef, G. S.; Cheney, R.; Mitchum, G. T.

2001-12-01

We are initiating a pilot processing system and data center to provide operational ocean surface velocity fields from satellite altimeter and vector wind data. The team includes the above authors plus M. Bourassa (FSU), V.Kousky (NOAA/NCEP), J.Polovina (NOAA/NMFS/Hawaii CoastWatch), R.Legeckis (NOAA/NESDIS), G. Jacobs (NRL), F. Bonjean (ESR), E.Johnson (ESR) and J.Gunn (ESR). Methods to derive surface currents are the outcome of several years of NASA sponsored research and the pilot project will transition that capability to operational oceanographic applications. The regional focus will be the tropical Pacific. Data applications include large scale climate diagnostics and prediction, fisheries management and recruitment, monitoring debris drift, larvae drift, oil spills, fronts and eddies. Additional uses for search and rescue, naval and maritime operations will be investigated. The pilot study will produce velocity maps to be updated on a weekly basis initially, with a goal for eventual 2-day maximum delay from time of satellite measurement. Grid resolution will be 100 km for the basin scale, and finer resolution in the vicinity of the Pacific Islands. Various illustrations of the velocity maps and their applications will be presented. The project's goal is to leave in place an automated system running at NOAA/NESDIS, with an established user clientele and open Internet data access.

Surface modification of layered perovskite Sr2TiO4 for improved CO2 photoreduction with H2O to CH4.

PubMed

Kwak, Byeong Sub; Do, Jeong Yeon; Park, No-Kuk; Kang, Misook

2017-11-27

Layered perovskite Sr 2 TiO 4 photocatalyst was synthesized by using sol-gel method with citric acid. In order to increase the surface area of layered perovskite Sr 2 TiO 4 , and thus to improve its photocatalytic activity for CO 2 reduction, its surface was modified via hydrogen treatment or exfoliation. The physical and chemical properties of the prepared catalysts were characterized by X-ray diffraction, high-resolution transmission electron microscopy, elemental mapping analysis, energy-dispersive X-ray spectroscopy, N 2 adsorption-desorption, UV-Vis spectroscopy, X-ray photoelectron spectroscopy, photoluminescence, and electrophoretic light scattering. CO 2 photoreduction was performed in a closed reactor under 6 W/cm 2 UV irradiation. The gaseous products were analyzed using a gas chromatograph equipped with flame ionization and thermal conductivity detectors. The exfoliated Sr 2 TiO 4 catalyst (E-Sr 2 TiO 4 ) exhibited a narrow band gap, a large surface area, and high dispersion. Owing to these advantageous properties, E-Sr 2 TiO 4 photocatalyst showed an excellent catalytic performance for CO 2 photoreduction reaction. The rate of CH 4 production from the photoreduction of CO 2 with H 2 O using E-Sr 2 TiO 4 was about 3431.77 μmol/g cat after 8 h.

Estimation of background radiation doses for the Peninsular Malaysia's population by ESR dosimetry of tooth enamel.

PubMed

Rodzi, Mohd; Zhumadilov, Kassym; Ohtaki, Megu; Ivannikov, Alexander; Bhattacharjee, Deborshi; Fukumura, Akifumi; Hoshi, Masaharu

2011-08-01

Background radiation dose is used in dosimetry for estimating occupational doses of radiation workers or determining radiation dose of an individual following accidental exposure. In the present study, the absorbed dose and the background radiation level are determined using the electron spin resonance (ESR) method on tooth samples. The effect of using different tooth surfaces and teeth exposed with single medical X-rays on the absorbed dose are also evaluated. A total of 48 molars of position 6-8 were collected from 13 district hospitals in Peninsular Malaysia. Thirty-six teeth had not been exposed to any excessive radiation, and 12 teeth had been directly exposed to a single X-ray dose during medical treatment prior to extraction. There was no significant effect of tooth surfaces and exposure with single X-rays on the measured absorbed dose of an individual. The mean measured absorbed dose of the population is 34 ± 6.2 mGy, with an average tooth enamel age of 39 years. From the slope of a regression line, the estimated annual background dose for Peninsular Malaysia is 0.6 ± 0.3 mGy y(-1). This value is slightly lower than the yearly background dose for Malaysia, and the radiation background dose is established by ESR tooth measurements on samples from India and Russia.

Entropic stochastic resonance without external force in oscillatory confined space.

PubMed

Ding, Huai; Jiang, Huijun; Hou, Zhonghuai

2015-05-21

We have studied the dynamics of Brownian particles in a confined geometry of dumbbell-shape with periodically oscillating walls. Entropic stochastic resonance (ESR) behavior, characterizing by a maximum value of the coherent factor Q at some optimal level of noise, is observed even without external periodic force in the horizontal direction, which is necessary for conventional ESR where the wall is static and the particle is subjected to the force. Interestingly, the ESR can be remarkably enhanced by the particle gravity G, in contrast to the conventional case. In addition, Q decreases (increases) with G in the small (large) noise limit, respectively, while it non-monotonically changes with G for moderate noise levels. We have applied an effective 1D coarsening description to illustrate such a nontrivial dependence on G, by investigating the property of the 1D effective potential of entropic nature and paying special attention to the excess part resulting from the boundary oscillation. Dependences of the ESR strength with other related parameters are also discussed.

Trace element control in binary Ni-25Cr and ternary Ni-30Co-30Cr master alloy castings

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

Detrois, Martin; Jablonski, Paul D.

Electro-slag remelting (ESR) is used for control of unwanted elements in commercial alloys. This study focuses on master alloys of Ni-25Cr and Ni-30Co-30Cr, processed through a combination of vacuum induction melting (VIM) and electro-slag remelting (ESR). Minor additions were made to control tramp element levels and modify the melting characteristics. Nitrogen and sulfur levels below 10 ppm and oxygen levels below 100 ppm were obtained in the final products. The role of the alloy additions in lowering the tramp element content, the resulting residual inclusions and the melting characteristics were determined computationally and confirmed experimentally. Additions of titanium were beneficialmore » to the control of oxygen levels during VIM and nitrogen levels during ESR. Aluminum additions helped to control oxygen levels during remelting, however, aluminum pickup occurred when excess titanium was present during ESR. The usefulness of these master alloys for use as experimental remelt stock will also be discussed.« less

Observing electron spin resonance between 0.1 and 67 GHz at temperatures between 50 mK and 300 K using broadband metallic coplanar waveguides

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

Wiemann, Yvonne; Simmendinger, Julian; Clauss, Conrad

2015-05-11

We describe a fully broadband approach for electron spin resonance (ESR) experiments, where it is possible to tune not only the magnetic field but also the frequency continuously over wide ranges. Here, a metallic coplanar transmission line acts as compact and versatile microwave probe that can easily be implemented in different cryogenic setups. We perform ESR measurements at frequencies between 0.1 and 67 GHz and at temperatures between 50 mK and room temperature. Three different types of samples (Cr{sup 3+} ions in ruby, organic radicals of the nitronyl-nitroxide family, and the doped semiconductor Si:P) represent different possible fields of application formore » the technique. We demonstrate that an extremely large phase space in temperature, magnetic field, and frequency for ESR measurements, substantially exceeding the range of conventional ESR setups, is accessible with metallic coplanar lines.« less

Ab initio modeling of CW-ESR spectra of the double spin labeled peptide Fmoc-(Aib-Aib-TOAC)2-Aib-OMe in acetonitrile.

PubMed

Zerbetto, Mirco; Carlotto, Silvia; Polimeno, Antonino; Corvaja, Carlo; Franco, Lorenzo; Toniolo, Claudio; Formaggio, Fernando; Barone, Vincenzo; Cimino, Paola

2007-03-15

In this work we address the interpretation, via an ab initio integrated computational approach, of the CW-ESR spectra of the double spin labeled, 310-helical, peptide Fmoc-(Aib-Aib-TOAC)2-Aib-OMe dissolved in acetonitrile. Our approach is based on the determination of geometric and local magnetic parameters of the heptapeptide by quantum mechanical density functional calculations taking into account solvent and, when needed, vibrational averaging contributions. The system is then described by a stochastic Liouville equation for the two electron spins interacting with each other and with two 14N nuclear spins, in the presence of diffusive rotational dynamics. Parametrization of the diffusion rotational tensor is provided by a hydrodynamic model. CW-ESR spectra are simulated with minimal resorting to fitting procedures, proving that the combination of sensitive ESR spectroscopy and sophisticated modeling can be highly helpful in providing 3D structural and dynamic information on molecular systems.

Structural, optical and magnetic properties of Co doped ZnO DMS nanoparticles by microwave irradiation method

NASA Astrophysics Data System (ADS)

Guruvammal, D.; Selvaraj, S.; Meenakshi Sundar, S.

2018-04-01

Microwave irradiation method is employed to synthesis of Zn1-xCoxO (x = 0.001-0.004) nanoparticles and investigate their structural, optical and magnetic properties using various characterization techniques. Structural studies reveal single phase hexagonal structure with average crystallite size 18-28 nm. FTIR study identifies the functional group present in the samples. The incorporation of Co2+ ions into the ZnO lattice is confirmed through XRD and UV-Vis studies. PL spectra exhibit a strong emission peak in UV region and a defect related visible emission peak in orange red region. These peaks are attributed to near band edge emission and the presence of oxygen related defects in the samples respectively. The blue shift observed in the UV emission peak shows an increase in the carrier concentration caused by the interstitial incorporation of ions into the ZnO lattice. The oxygen related defect is also confirmed through a peak obtained around g factor 1.9933 in ESR studies. Further, the number of spin contributing the ESR signal demonstrates the dependence of the strength of ferromagnetism on the concentration of oxygen ion vacancies. The VSM, ESR and PL measurements confirm the origin of RTFM of Co doped ZnO nanoparticles from the exchange interaction between the localized spin moments resulting from oxygen vacancies. The reason for the obtained super paramagnetic nature for x = 0.002 and x = 0.003 may be either due to some of nanoparticles or due to the weakly coupled Co ions in the Zn2+ site in the ZnO lattice. Further, the ferromagnetic behavior arises again for x = 0.004 due to the incorporation of Co2+ ions in the interstitial positions.

The Cu2+-nitrilotriacetic acid complex improves loading of α-helical double histidine site for precise distance measurements by pulsed ESR

NASA Astrophysics Data System (ADS)

Ghosh, Shreya; Lawless, Matthew J.; Rule, Gordon S.; Saxena, Sunil

2018-01-01

Site-directed spin labeling using two strategically placed natural histidine residues allows for the rigid attachment of paramagnetic Cu2+. This double histidine (dHis) motif enables extremely precise, narrow distance distributions resolved by Cu2+-based pulsed ESR. Furthermore, the distance measurements are easily relatable to the protein backbone-structure. The Cu2+ ion has, till now, been introduced as a complex with the chelating agent iminodiacetic acid (IDA) to prevent unspecific binding. Recently, this method was found to have two limiting concerns that include poor selectivity towards α-helices and incomplete Cu2+-IDA complexation. Herein, we introduce an alternative method of dHis-Cu2+ loading using the nitrilotriacetic acid (NTA)-Cu2+ complex. We find that the Cu2+-NTA complex shows a four-fold increase in selectivity toward α-helical dHis sites. Furthermore, we show that 100% Cu2+-NTA complexation is achievable, enabling precise dHis loading and resulting in no free Cu2+ in solution. We analyze the optimum dHis loading conditions using both continuous wave and pulsed ESR. We implement these findings to show increased sensitivity of the Double Electron-Electron Resonance (DEER) experiment in two different protein systems. The DEER signal is increased within the immunoglobulin binding domain of protein G (called GB1). We measure distances between a dHis site on an α-helix and dHis site either on a mid-strand or a non-hydrogen bonded edge-strand β-sheet. Finally, the DEER signal is increased twofold within two α-helix dHis sites in the enzymatic dimer glutathione S-transferase exemplifying the enhanced α-helical selectivity of Cu2+-NTA.

Effect of silane coupling agents on the chemical and physical properties of photocrosslinked poly(dimethylsiloxane) dimethacrylate/poly(ethylene glycol) diacrylate hydrogel

NASA Astrophysics Data System (ADS)

Lim, K. W.; Hamid, Z. A. A.

2017-07-01

Inorganic-organic hydrogels based on dimethacrylated polydimethylsiloxane (PDMSMA) and diacrylated poly(ethylene glycol) (PEGDA) macromers were prepared via photocrosslinking method. Silane coupling agent was incorporated into the hydrogel formulations to overcome the phase incompatibility. Pure PEGDA (0:100) hydrogels showed the highest value of ESR %, while pure PDMSMA (100:0) hydrogels showed no swelling as we expected. Inclusion of more hydrophobic domains resulted in a lower value of ESR %, i.e. in 75:25 hybrid hydrogels. Beside, we had noticed 50:50 and 75:25 hybrid hydrogels disintegrate during swelling period. However, their integrity was improved and sustained after the coupling agent was added. Similarly, the value of E* for the hybrid hydrogels showed an increment after the coupling agent was incorporated, and this is in a good agreement with the SEM micrograph which display an improved interfacial adhesion.

Molecular organization and dynamics of micellar phase of polyelectrolyte-surfactant complexes: ESR spin probe study

NASA Astrophysics Data System (ADS)

Wasserman, A. M.; Kasaikin, V. A.; Zakharova, Yu. A.; Aliev, I. I.; Baranovsky, V. Yu.; Doseva, V.; Yasina, L. L.

2002-04-01

Molecular dynamics and organization of the micellar phase of complexes of linear polyelectrolytes with ionogenic and non-ionogenic surfactants was studied by the ESR spin probe method. Complexes of polyacrylic acid (PAA) and sodium polystyrenesulfonate (PSS) with alkyltrimethylammonium bromides (ATAB), as well as complexes of poly- N, N'-dimethyldiallylammonium chloride (PDACL) with sodium dodecylsulfate (SDS) were studied. The micellar phase of such complexes is highly organized molecular system, molecular ordering of which near the polymeric chain is much higher than in the 'center' of the micelle, it depends on the polymer-detergent interaction, flexibility of polymeric chain and length of carbonic part of the detergent molecule. Complexes of polymethacrylic acid (PMAA) with non-ionic detergent (dodecyl-substituted polyethyleneglycol), show that the local mobility of surfactant in such complexes is significantly lower than in 'free' micelles and depends on the number of micellar particles participating in formation of complexes.

Cooking processes increase bioactive compounds in organic and conventional green beans.

PubMed

Lima, Giuseppina Pace Pereira; Costa, Sergio Marques; Monaco, Kamila de Almeida; Uliana, Maira Rodrigues; Fernandez, Roberto Morato; Correa, Camila Renata; Vianello, Fabio; Cisneros-Zevallos, Luis; Minatel, Igor Otavio

2017-12-01

The influence of cooking methods on chlorophyl, carotenoids, polyamines, polyphenols contents and antioxidant capacity were analyzed in organic and conventional green beans. The initial raw material had a higher content of chlorophyl and total phenolics in conventional green beans, whereas organic cultive favored flavonoid content and antioxidant capacity. Polyamines and carotenoids were similar for the two crop systems. After the cooking process, carotenoids (β-carotene, lutein and zeaxanthin) increased. Microwave heating favored the enhancement of some polar compounds, whereas pressure cooking favored carotenoids. When we used the estimation of the radical scavenging activity by electron spin resonance (ESR) spectroscopy, a reduction of the DPPH radical signal in the presence of green bean extracts was observed, regardless of the mode of cultivation. The highest reduction of the ESR signal ocurred for microwave cooking in organic and conventional green beans, indicating a higher availability of antioxidants with this type of heat treatment.

[Detection of the lethal process in plankton noctiluca by means of a forbidden transition of ESR of Mn2+ ion].

PubMed

Kamenev, S E; Kopvillem, U Kh; Pasynkov, A S; Sharipov, R Z

1981-01-01

A forbidden ESR line of Mn2+ that is connected with the penetration of Mn into the plancton organism and binding it to a marcomolecule is selected from the experiment. A method for saturating the plancton organism with paramagnetic ions is proposed. It is shown that the constant of the axial electric field in the spin hamiltonian of Mn2+ ion described the dynamics of a selforganizing system. It is tested that the lethal process in the plancton with paramagnetic ion enrichment originated from boson avalanche. Experiments are performed with plancton noctiluca which illustrate the occurrence of avalancheline lethal process in the case of paramagnetic ion enrichment with limiting concentration. The meaning of these results for the problems of oceanology and pollution-ocean inhabitants interaction in the case of paramagnetic ions is discussed.

Electron spin resonance measurement of radical scavenging activity of Aronia melanocarpa fruit juice.

PubMed

Valcheva-Kuzmanova, Stefka; Blagović, Branka; Valić, Srećko

2012-04-01

The fruits of Aronia melanocarpa (Michx.) Elliot contain large amounts of phenolic substances, mainly procyanidins, anthocyanins and other flavonoids, and phenolic acids. The ability of phenolic substances to act as antioxidants has been well established. In this study, we investigated the radical scavenging activity of A. melanocarpa fruit juice (AMFJ). The method used was electron spin resonance (ESR) spectroscopy. The galvinoxyl free radical was used as a scavenging object. AMFJ was added to the galvinoxyl free radical solution. The measure of the radical scavenging activity was the decrease of signal intensity. AMFJ showed a potent antiradical activity causing a strong and rapid decrease of signal intensity as a function of time and juice concentration. This effect of AMFJ was probably due to the activity of its phenolic constituents. The ESR measurements in this study showed a pronounced radical scavenging effect of AMFJ, an important mechanism of its antioxidant activity.

[Correlation study between interleukin-17 and ESR and CRP in serum and the synovial fluid of rheumatoid arthritis patients of accumulated dampness-heat obstruction in joints syndrome].

PubMed

Liu, De-Fang; Yan, Jiao; Guo, Ming-Yang; Wang, Chao; Hu, Yong-He; Yang, Min; Yun, Ming-Dong; Luo, Yong; Zhang, Jun; Li, Hua

2014-03-01

To probe the function of interleukin-17 (IL-17) in rheumatoid arthritis (RA) patients of accumulated dampness-heat obstruction in joints syndrome (ADOJS) by detecting levels of IL-17 in serum and the synovial fluid and analyzing its correlation with erythrocyte sedimentation rate (ESR) and C reactive protein (CRP). From January 2011 to January 2013, recruited were 90 RA inpatients of ADOJS at Department of Integrative Medical Rheumatism, General Hospital of Chengdu Military Region, of which 28 patients had knee joint effusion. Besides, 30 healthy volunteers who received physical examination at our hospital were recruited as the normal control group, and 30 patients with osteoarthritis (OA) who had knee joint effusion were recruited as the synovial fluid control group. The expression levels of IL-17 in serum and the synovial fluid were detected by enzyme linked immunosorbent assay (ELISA), and contents of ESR and CRP were detected in RA patients. Then correlation analyses were performed between levels of IL-17 and contents of ESR and CRP. Compared with the normal serum control group, the expression levels of IL-17 in serum of RA patients significantly increased (P < 0.05). Compared with the serum of RA patients and the synovial fluid of OA patients, the expression levels of IL-17 in the synovial fluid of RA patients significantly increased (P < 0.05). The expression levels of IL-17 in serum of RA patients were not correlated with ESR or CRP (r = 0.092, -0.082; P > 0.05), and the expressional levels of IL-17 in the synovial fluid of RA patients were not correlated with ESR or CRP (r = 0.113, -0.034; P > 0.05). IL-17 was the main effector cytokine of Th17 cells. The expressional levels of IL-17 significantly increased in serum and the synovial fluid of RA patients of ADOJS, but with no correlation to ESR or CRP. It indicated that IL-17 participated in the occurrence and development of RA. Concrete mechanisms needed to be further proved in larger samples.

The Role of Skp1-Cul1-F-box Ubiquitin Ligases in Src-Stimulated Estrogen Receptor Proteolysis and Estrogen Receptor Target Gene Expression

DTIC Science & Technology

2014-03-01

encoded by ESR1 , is a steroid hormone receptor superfamily member1,2 that mediates oestrogen-stimulated proliferation in hormone-responsive cancers. ERα...cancer. Deletions, rearrangements and point mutations in ESR1 are too uncommon to account for ER– breast cancer20,21. MicroRNA 22 (miR-22)22, miR...222 (REF. 23), miR-221 (REF. 23), miR-206 (REF. 24) and miR-18a25 have been shown to target ESR1 . Increased miR-18a levels were observed more

Role of IKK-alpha in EGFR Signaling Regulation

DTIC Science & Technology

2013-09-01

correlated with IKKα expression using CCLE. Nonsupervised hierarchical clustering analysis was performed based on Erbb2, ERα ( ESR1 ), PR (PgR...signature (ERBB2, ESR1 , and PGR) genes. A subset of 4 genes showing distinct expression pattern in TNBC versus non-TNBC cell lines is shown in the...AKT2 AKT3 CDH1 MYB CDH2 VIM ERBB2 ESR1 PGR H C C 11 87 C A L- 85 -1 H C C 11 43 H D Q -P 1 C A L- 51 H C C 38 H C C 21 57 C A L- 12 0 B T- 54 9 H C C

Investigating electron spin resonance spectroscopy of a spin-½ compound in a home-built spectrometer

NASA Astrophysics Data System (ADS)

Sarkar, Jit; Roy, Subhadip; Singh, Jitendra Kumar; Singh, Sourabh; Chakraborty, Tanmoy; Mitra, Chiranjib

2018-05-01

In this work we report electron spin resonance (ESR) measurements performed on NH4CuPO4.H2O, a Heisenberg spin ½ dimer compound. We carried out the experiments both at room temperature and at 78 K, which are well above the antiferromagnetic ordering temperature of the system where the paramagnetic spins have a dominant role in determining its magnetic behavior. We performed the measurements in a home built custom designed continuous wave electron spin resonance (CW-ESR) spectrometer. By analyzing the experimental data, we were able to quantify the Landé g-factor and the ESR line-width of the sample.

The comparative impact of the market penetration of energy-efficient measures: A sensitivity analysis of its impact on minority households

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

Bozinovich, L.V.; Poyer, D.A.; Anderson, J.L.

1993-12-01

A sensitivity study was made of the potential market penetration of residential energy efficiency as energy service ratio (ESR) improvements occurred in minority households, by age of house. The study followed a Minority Energy Assessment Model analysis of the National Energy Strategy projections of household energy consumption and prices, with majority, black, and Hispanic subgroup divisions. Electricity and total energy consumption and expenditure patterns were evaluated when the households` ESR improvement followed a logistic negative growth (i.e., market penetration) path. Earlier occurrence of ESR improvements meant greater discounted savings over the 22-year period.

Successful combination of electron spin resonance, luminescence and palaeomagnetic dating methods allows reconstruction of the Pleistocene evolution of the lower Moulouya river (NE Morocco)

NASA Astrophysics Data System (ADS)

Bartz, Melanie; Rixhon, Gilles; Duval, Mathieu; King, Georgina E.; Álvarez Posada, Claudia; Parés, Josep M.; Brückner, Helmut

2018-04-01

Based on a combination of Electron Spin Resonance (ESR) dating of quartz, luminescence dating of K-feldspar and palaeomagnetism, this study presents the first chronostratigraphic framework for the Pleistocene fluvial deposits of the lower Moulouya river in the Triffa basin (NE Morocco). K-feldspar pIRIR225 and pIRIR290 signals of all samples are saturated, suggesting fluvial deposition at least as early as the Middle Pleistocene (∼0.39-0.80 Ma). Consequently, further chronological information was obtained with ESR dating of quartz grains from the ancient Pleistocene fluvial deposits. As for ESR, the multiple centres approach provides equivalent dose values derived from the Al and Ti centres that mostly agree within 1σ-error, suggesting complete signal resetting from the former during fluvial transport. ESR dating results yield Calabrian deposition ages for all river profiles from ∼1.1 to ∼1.5 Ma. These ages are remarkably consistent with the palaeomagnetic results: the occurrence of mostly reversed polarity in the deposits indicates a Matuyama age (>0.78 Ma). While low incision rates in the Triffa basin (0.025 ± 0.003 mm/a) related to thrusting activity during the Calabrian could be inferred, the fluvial record points to an acyclic and discontinuous sedimentation pattern over the last ∼1.3 Ma. It thereby probably rules out climate as the main driver for fluvial aggradation in the lowermost sedimentary basin. At a regional scale, several indicators point to transient fluvial response resulting from major Quaternary tectonic activity along the Beni Snassen gorge, located directly upstream of the investigated basin. We suggest that a capture event at the margin of the uplifting Beni Snassen massif occurred between 1.04 and 1.36 Ma at the latest and subsequently led to the creation of the gorge.

ESR study of molecular orientation and dynamics of nitronyl nitroxide radicals in CLPOT 1D nanochannels.

PubMed

Kobayashi, Hirokazu; Morinaga, Yuka; Fujimori, Etsuko; Asaji, Tetsuo

2014-07-10

New inclusion compounds (ICs) were prepared using the organic 1D nanochannels of 2,4,6-tris(4-chlorophenoxy)-1,3,5-triazine (CLPOT) as a nanosized template and nitronyl nitroxide (NN) radicals such as phenylnitronylnitroxide (PhNN) and p-nitrophenylnitronylnitroxide (p-NPNN). ESR measurements below 255 K for the CLPOT ICs diluted with spacer molecules gave rigid limit spectra similar to that for PhNN molecules in a glassy ethanol matrix at low temperature, which suggests isolation of the radical molecules. ESR measurements for them in the range of 290-400 K gave a modulated quintet ESR signal, which suggested uniaxial rotational diffusion of NN radicals in the nanochannels approximately around the principal y-axis of the g-tensors. In the ESR measurements to 430 K for the [(CLPOT)2-(p-NPNN)0.07] IC without spacers, the broader line width than the case in dilution was observed by inter-radical dipolar interaction. In every case, the rotational diffusion activation energies of NN radicals in the CLPOT nanochannels were several times larger than those of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) radical derivatives (4-X-TEMPO) in CLPOT nanochannels. This is expected due to the larger molecular size of NN radicals than 4-X-TEMPO or stronger interaction between NN radicals and the surrounding host or guest molecules.

Promoting language and social communication development in babies through an early storybook reading intervention.

PubMed

Brown, Michelle I; Westerveld, Marleen F; Trembath, David; Gillon, Gail T

2017-12-15

This study examined the effectiveness of low- and high-intensity early storybook reading (ESR) intervention workshops delivered to parents for promoting their babies language and social communication development. These workshops educated parents on how to provide a stimulating home reading environment and engage in parent-child interactions during ESR. Parent-child dyads (n = 32); child age: 3-12 months, were assigned into two intervention conditions: low and high intensity (LI versus HI) groups. Both groups received the same ESR strategies; however, the HI group received additional intervention time, demonstrations and support. Outcome measures were assessed pre-intervention, one and three months post-intervention and when the child turned 2 years of age. A significant time-group interaction with increased performance in the HI group was observed for language scores immediately post-intervention (p = 0.007) and at 2-years-of-age (p = 0.022). Significantly higher broader social communication scores were associated with the HI group at each of the time points (p = 0.018, p = 0.001 and p = 0.021, respectively). Simple main effect revealed that both groups demonstrated a significant improvement in language, broader social communication and home reading practices scores. ESR intervention workshops may promote language and broader social communication skills. The HI ESR intervention workshop was associated with significantly higher language and broader social communication scores.

Development of Millimeter Wave Fabry-Pérot Resonator for Simultaneous Electron-Spin and Nuclear Magnetic Resonance Measurement

NASA Astrophysics Data System (ADS)

Ishikawa, Yuya; Ohya, Kenta; Fujii, Yutaka; Fukuda, Akira; Miura, Shunsuke; Mitsudo, Seitaro; Yamamori, Hidetomo; Kikuchi, Hikomitsu

2018-04-01

We report a Fabry-Pérot resonator with spherical and flat mirrors to allow simultaneous electron-spin resonance (ESR) and nuclear magnetic resonance (NMR) measurements that could be used for double magnetic resonance (DoMR). In order to perform simultaneous ESR and NMR measurements, the flat mirror must reflect millimeter wavelength electromagnetic waves and the resonator must have a high Q value ( Q > 3000) for ESR frequencies, while the mirror must simultaneously let NMR frequencies pass through. This requirement can be achieved by exploiting the difference of skin depth for the two frequencies, since skin depth is inversely proportional to the square root of the frequency. In consideration of the skin depth, the optimum conditions for conducting ESR and NMR using a gold thin film are explored by examining the relation between the Q value and the film thickness. A flat mirror with a gold thin film was fabricated by sputtering gold on an epoxy plate. We also installed a Helmholtz radio frequency coil for NMR and tested the system both at room and low temperatures with an optimally thick gold film. As a result, signals were obtained at 0.18 K for ESR and at 1.3 K for NMR. A flat-mirrored resonator with a thin gold film surface is an effective way to locate NMR coils closer to the sample being examined with DoMR.

Reaching the quantum limit of sensitivity in electron spin resonance

DOE PAGES

Bienfait, A.; Pla, J. J.; Kubo, Y.; ...

2015-12-14

The detection and characterization of paramagnetic species by electron spin resonance (ESR) spectroscopy is widely used throughout chemistry, biology and materials science, from in vivo imaging to distance measurements in spin-labelled proteins. ESR relies on the inductive detection of microwave signals emitted by the spins into a coupled microwave resonator during their Larmor precession. However, such signals can be very small, prohibiting the application of ESR at the nanoscale (for example, at the single-cell level or on individual nanoparticles). Here in this work, using a Josephson parametric microwave amplifier combined with high-quality-factor superconducting microresonators cooled at millikelvin temperatures, we improvemore » the state-of-the-art sensitivity of inductive ESR detection by nearly four orders of magnitude. We demonstrate the detection of 1,700 bismuth donor spins in silicon within a single Hahn echo with unit signal-to-noise ratio, reduced to 150 spins by averaging a single Carr-Purcell-Meiboom-Gill sequence. This unprecedented sensitivity reaches the limit set by quantum fluctuations of the electromagnetic field instead of thermal or technical noise, which constitutes a novel regime for magnetic resonance. In conclusion, the detection volume of our resonator is ~0.02nl, and our approach can be readily scaled down further to improve sensitivity, providing a new versatile toolbox for ESR at the nanoscale.« less

Lack of Association of Estrogen Receptor Alpha Gene Polymorphisms with Cardiorespiratory and Metabolic Variables in Young Women

PubMed Central

Rebelo, Ana Cristina; Verlengia, Rozangela; Kunz, Vandeni; Tamburus, Nayara; Cerda, Alvaro; Hirata, Rosario; Hirata, Mario; Silva, Ester

2012-01-01

This study examined the association of estrogen receptor alpha gene (ESR1) polymorphisms with cardiorespiratory and metabolic parameters in young women. In total, 354 healthy women were selected for cardiopulmonary exercise testing and short-term heart rate (HR) variability (HRV) evaluation. The HRV analysis was determined by the temporal indices rMSSD (square root of the mean squared differences of successive R–R intervals (RRi) divided by the number of RRi minus one), SDNN (root mean square of differences from mean RRi, divided by the number of RRi) and power spectrum components by low frequency (LF), high frequency (HF) and LF/HF ratio. Blood samples were obtained for serum lipids, estradiol and DNA extraction. ESR1 rs2234693 and rs9340799 polymorphisms were analyzed by PCR and fragment restriction analysis. HR and oxygen uptake (VO2) values did not differ between the ESR1 polymorphisms with respect to autonomic modulation. We not find a relationship between ESR1 T–A, T–G, C–A and C–G haplotypes and cardiorespiratory and metabolic variables. Multiple linear regression analysis demonstrated that VO2, total cholesterol and triglycerides influence HRV (p < 0.05). The results suggest that ESR1 variants have no effect on cardiorespiratory and metabolic variables, while HRV indices are influenced by aerobic capacity and lipids in healthy women. PMID:23202974

Soluble triggering receptor expressed on myeloid cells 1 and the diagnosis of sepsis.

PubMed

Barati, Mitra; Bashar, Farshid Rahimi; Shahrami, Reza; Zadeh, Mohammad Hossein Jarrah; Taher, Mahshid Talebi; Nojomi, Marzieh

2010-06-01

Early diagnosis and assessment of the systemic inflammatory response to infection are difficult with usual markers (fever, leukocytosis, C-reactive protein [CRP]). Triggering receptor expressed on myeloid cells-1 (TREM-1) expression on phagocytes is up-regulated by microbial products. We studied the ability of soluble TREM-1 (sTREM-1) to identify patients with sepsis. Plasma samples were obtained on intensive care unit admission from patients with systemic inflammatory response syndrome for sTREM-1 measurement. Soluble TREM-1, CRP concentrations and erythrocyte sedimentation rate (ESR) were higher in the sepsis group (n = 52) than in the non-infectious systemic inflammatory response syndrome group (n = 43; P = .00, .02, and .001, respectively). Soluble TREM-1, CRP concentrations, white blood cell count and ESR were higher in the sepsis group than in the non SIRS group (n = 37; P = .04, .00, .01, and .00, respectively). In a receiver-operating characteristic curve analysis, ESR, CRP and sTREM-1 had an area under the curve larger than 0.65 (P = .00), in distinguishing between septic and non-infectious SIRS patients. CRP, ESR, sTREM-1 had a sensitivity of 60%, 70% and 70% and a specificity of 60%, 69% and, 60% respectively in diagnosing infection in SIRS. C-reactive protein and ESR performed better than sTREM-1 and white blood cell count in diagnosing infection. Copyright (c) 2010. Published by Elsevier Inc.

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.

Tumor Genomic Profiling in Breast Cancer Patients Using Targeted Massively Parallel Sequencing

DTIC Science & Technology

2015-04-30

recently, we identified several novel alterations in in ER+ breast tumors, including translocations in ESR1 , the gene that encodes the estrogen receptor...modified our bait design to include genomic coordinates across select introns in ESR1 . In addition, two recent papers from the Broad Institute published

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:…

Measurement Of Molecular Mobilities Of Polymers

NASA Technical Reports Server (NTRS)

Kim, Soon Sam; Tsay, Fun-Dow

1989-01-01

New molecular-probe technique used to measure molecular mobility of polymer. Method based on use of time-resolved electron-spin resonance (ESR) spectroscopy to monitor decay of transient nutation amplitudes from photoexcited triplet states of probe molecules with which polymer is doped. The higher molecular mobility of polymer matrix, the faster nutation amplitudes of the probe molecules decay.

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.

IN VIVO EVIDENCE OF FREE RADICAL FORMATION AFTER ASBESTOS INSTILLATION: AN ESR SPIN TRAPPING INVESTIGATION

EPA Science Inventory

It has been postulated that the in vivo toxicity of asbestos results from its catalysis of free radical generation. We examined in vivo radical production using electron spin resonance (ESR) coupled with the spin trap alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (4-POBN); 180 d...

Beneficial use of off-specification fly ashes to increase the shear strength and stiffness of expansive soil-rubber (ESR) mixtures.

DOT National Transportation Integrated Search

2011-07-01

The use of off-specification fly ashes to increase the shear strength and stiffness of an expansive soil-rubber (ESR) mixture is investigated systematically in this study. The off-specification fly ashes used include a high-sulfur content and a high-...

Recurrent ESR1-CCDC170 rearrangements in an aggressive subset of estrogen-receptor positive breast cancers

PubMed Central

Veeraraghavan, Jamunarani; Tan, Ying; Cao, Xi-Xi; Kim, Jin-Ah; Wang, Xian; Chamness, Gary C.; Maiti, Sourindra N.; Cooper, Laurence J. N.; Edwards, Dean P.; Contreras, Alejandro; Hilsenbeck, Susan G.; Chang, Eric C.; Schiff, Rachel; Wang, Xiao-Song

2014-01-01

Characterizing the genetic alterations leading to the more aggressive forms of estrogen receptor positive (ER+) breast cancers are of critical significance in breast cancer management. Here we identify recurrent rearrangements between estrogen receptor gene ESR1 and its neighbor CCDC170, which are enriched in the more aggressive and endocrine-resistant luminal-B tumors, through large-scale analyses of breast cancer transcriptome and copy number alterations. Further screening of 200 ER+ breast cancers identifies eight ESR1-CCDC170 positive tumors. These fusions encode N-terminally truncated CCDC170 proteins (ΔCCDC170). When introduced into ER+ breast cancer cells, ΔCCDC170 leads to markedly increased cell motility and anchorage-independent growth, reduced endocrine sensitivity, and enhanced xenograft tumor formation. Mechanistic studies suggest that ΔCCDC170 engages Gab1 signalosome to potentiate growth factor signaling and enhance cell motility. Together, this study identifies neoplastic ESR1-CCDC170 fusions in a more aggressive subset of ER+ breast cancer, which suggests a new concept of ER pathobiology in breast cancer. PMID:25099679

Electron diffusion deduced from eiscat

NASA Astrophysics Data System (ADS)

Roettger, J.; Fukao, S.

The EISCAT Svalbard Radar (ESR) operates on 500 MHz; collocated with it is the SOUSY Svalbard Radar (SSR), which operates on 53.5 MHz. We have used both radars during Polar Mesosphere Summer Echoes (PMSE) coherent scatter conditions, where the ESR can also detect incoherent scatter and thus allows to estimate the electron density. We describe obser-vations during two observing periods in summer 1999 and 2000. Well calibrated sig-nal power was obtained with both radars, from which we deduced the radar reflec-tivity. Estimating the turbulence dissipation rate from the narrow beam observations of PMSE with the ESR, using the estimate of the electron density and the radar reflec-tivity on both frequencies we can obtain estimates of the Schmidt number by compar-ing our observational results with the model of Cho and Kelley (1993). Schmidt num-bers of at least 100 are necessary to obtain the measured radar reflectivities, which ba-sically support the model of Cho and Kelley claiming that the inertial-viscous subrange in the electron gas can extend down to small scales of some ten centimeters (namely, the Bragg scale of the ESR).

ESR1 Promoter Hypermethylation Does Not Predict Atypia in RPFNA nor Persistent Atypia after 12 Months Tamoxifen Chemoprevention

PubMed Central

Baker, Joseph C.; Ostrander, Julie H.; Lem, Siya; Broadwater, Gloria; Bean, Gregory R.; D'Amato, Nicholas C.; Goldenberg, Vanessa K.; Rowell, Craig; Ibarra-Drendall, Catherine; Grant, Tracey; Pilie, Patrick G.; Vasilatos, Shauna N.; Troch, Michelle M.; Scott, Victoria; Wilke, Lee G.; Paisie, Carolyn; Rabiner, Sarah M.; Torres-Hernandez, Alejandro; Zalles, Carola M.; Seewaldt, Victoria L.

2009-01-01

Purpose Currently, we lack biomarkers to predict whether high-risk women with mammary atypia will respond to tamoxifen chemoprevention. Experimental Design Thirty-four women with cytologic mammary atypia from the Duke University High-Risk clinic were offered tamoxifen chemoprevention. We tested whether ESR1 promoter hypermethylation and/or estrogen receptor (ER) protein expression by immunohistochemistry predicted persistent atypia in 18 women who were treated with tamoxifen for 12 months and in 16 untreated controls. Results We observed a statistically significant decrease in the Masood score of women on tamoxifen chemoprevention for 12 months compared with control women. This was a significant interaction effect of time (0, 6, and 12 months) and treatment group (tamoxifen versus control) P = 0.0007. However, neither ESR1 promoter hypermethylation nor low ER expression predicted persistent atypia in Random Periareolar Fine Needle Aspiration after 12 months tamoxifen prevention. Conclusions Results from this single institution pilot study provide evidence that, unlike for invasive breast cancer, ESR1 promoter hypermethylation and/or low ER expression is not a reliable marker of tamoxifen-resistant atypia. PMID:18708376

Applicability of ASST-A helium refrigeration system for JLab End Station Refrigerator

NASA Astrophysics Data System (ADS)

Hasan, N.; Knudsen, P.; Ganni, V.

2017-12-01

The MØLLER experiment at Jefferson Lab (JLab) is a high power (5 kW) liquid hydrogen target scheduled to be operational in the 12 GeV-era. At present, cryogenic loads and targets at three of JLab’s four experimental halls are supported by the End Station Refrigerator (ESR) - a CTI/Helix 1.5 kW 4.5 K refrigerator. It is not capable of supporting the high power target load and a capacity upgrade of the ESR cryogenic system is essential. The ASST-A helium refrigeration system is a 4 kW 4.5 K refrigerator. It was designed and used for the Superconducting Super Collider Lab (SSCL) magnet string test and later obtained by JLab after the cancellation of that project. The modified ASST-A refrigeration system, which will be called ESR-II along with a support flow from JLab’s Central Helium Liquefier (CHL) is considered as an option for the End Station Refrigerator capacity upgrade. The applicability of this system for ESR-II under varying load conditions is investigated. The present paper outlines the findings of this process study.

Distribution of localized states from fine analysis of electron spin resonance spectra of organic semiconductors: Physical meaning and methodology

NASA Astrophysics Data System (ADS)

Mishchenko, Andrey S.; Matsui, Hiroyuki; Hasegawa, Tatsuo

2012-02-01

We develop an analytical method for the processing of electron spin resonance (ESR) spectra. The goal is to obtain the distributions of trapped carriers over both their degree of localization and their binding energy in semiconductor crystals or films composed of regularly aligned organic molecules [Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.104.056602 104, 056602 (2010)]. Our method has two steps. We first carry out a fine analysis of the shape of the ESR spectra due to the trapped carriers; this reveals the distribution of the trap density of the states over the degree of localization. This analysis is based on the reasonable assumption that the linewidth of the trapped carriers is predetermined by their degree of localization because of the hyperfine mechanism. We then transform the distribution over the degree of localization into a distribution over the binding energies. The transformation uses the relationships between the binding energies and the localization parameters of the trapped carriers. The particular relation for the system under study is obtained by the Holstein model for trapped polarons using a diagrammatic Monte Carlo analysis. We illustrate the application of the method to pentacene organic thin-film transistors.

Purity analyses of high-purity organic compounds with nitroxyl radicals based on the Curie–Weiss law

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

Matsumoto, Nobuhiro, E-mail: nobu-matsumoto@aist.go.jp; Shimosaka, Takuya

2015-05-07

This work reports an attempt to quantify the purities of powders of high-purity organic compounds with stable nitroxyl radicals (namely, 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (TEMPOL), and 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl benzoate (4-hydroxy-TEMPO benzoate)) in terms of mass fractions by using our “effective magnetic moment method,” which is based on both the Curie–Weiss law and a fundamental equation of electron paramagnetic resonance (ESR). The temperature dependence of the magnetic moment resulting from the radicals was measured with a superconducting quantum interference device magnetometer. The g value for each compound was measured with an X-band ESR spectrometer. The results of the purities were (0.998 ± 0.064) kg kg{supmore » −1} for TEMPO, (1.019 ± 0.040) kg kg{sup −1} for TEMPOL, and (1.001 ± 0.048) kg kg{sup −1} for 4-hydroxy-TEMPO benzoate. These results demonstrate that this analytical method as a future candidate of potential primary direct method can measure the purities with expanded uncertainties of approximately 5%.« less

CVD-graphene for low equivalent series resistance in rGO/CVD-graphene/Ni-based supercapacitors.

PubMed

Kwon, Young Hwi; Kumar, Sunil; Bae, Joonho; Seo, Yongho

2018-05-11

Reduced equivalent series resistance (ESR) is necessary, particularly at a high current density, for high performance supercapacitors, and the interface resistance between the current collector and electrode material is one of the main components of ESR. In this report, we have optimized chemical vapor deposition-grown graphene (CVD-G) on a current collector (Ni-foil) using reduced graphene oxide as an active electrode material to fabricate an electric double layer capacitor with reduced ESR. The CVD-G was grown at different cooling rates-20 °C min -1 , 40 °C min -1 and 100 °C min -1 -to determine the optimum conditions. The lowest ESR, 0.38 Ω, was obtained for a cell with a 100 °C min -1 cooling rate, while the sample without a CVD-G interlayer exhibited 0.80 Ω. The CVD-G interlayer-based supercapacitors exhibited fast CD characteristics with high scan rates up to 10 Vs -1 due to low ESR. The specific capacitances deposited with CVD-G were in the range of 145.6 F g -1 -213.8 F g -1 at a voltage scan rate of 0.05 V s -1 . A quasi-rectangular behavior was observed in the cyclic voltammetry curves, even at very high scan rates of 50 and 100 V s -1 , for the cell with optimized CVD-G at higher cooling rates, i.e. 100 °C min -1 .

Developmental Effects and Estrogenicity of Bisphenol A Alternatives in a Zebrafish Embryo Model.

PubMed

Mu, Xiyan; Huang, Ying; Li, Xuxing; Lei, Yunlei; Teng, Miaomiao; Li, Xuefeng; Wang, Chengju; Li, Yingren

2018-03-06

In order to understand the negative effects of bisphenol A (BPA) alternatives comprehensively, zebrafish embryos were used to assess the lethality, developmental effects, and estrogenic activity of bisphenol analogues. The in silico estrogenic activities of bisphenol analogues were assayed by binding simulation. According to our results, the lethality of bisphenol analogues decreased in order of bisphenol AF (BPAF) > BPA > bisphenol F (BPF) > bisphenol S (BPS). BPAF and BPF induced significant effects on zebrafish embryos, including decreased heart rate, hatching inhibition, and teratogenic effects. The binding potentials of bisphenol analogues toward zebrafish ERs (zfERS) decreased in the following order: BPAF > BPA > BPF > BPS. Among the three subtypes of zfERs, zfERβ2 showed the highest binding activity toward the bisphenols, followed by zfERα and zfERβ1. In vivo estrogenic activity tests showed that BPAF, BPA, and BPF significantly enhanced the protein levels of ERα along with the mRNA levels of esr1, esr2a, esr2b, and vtg1 in zebrafish embryos. Esr2b showed the strongest response to BPAF and BPA exposure among the three esrs. In contrast, BPS did not significantly regulate ER protein level or ER transcription. In conclusion, BPAF showed the highest lethality, developmental effects, and estrogenic activity (both in silico and in vivo) followed by BPA and BPF. BPS showed the weakest toxicity and estrogenic activity. zfERβ2 might act as the main target among the three ER subtypes of zebrafish after exposure to BPAF and BPA.

CVD-graphene for low equivalent series resistance in rGO/CVD-graphene/Ni-based supercapacitors

NASA Astrophysics Data System (ADS)

Kwon, Young Hwi; Kumar, Sunil; Bae, Joonho; Seo, Yongho

2018-05-01

Reduced equivalent series resistance (ESR) is necessary, particularly at a high current density, for high performance supercapacitors, and the interface resistance between the current collector and electrode material is one of the main components of ESR. In this report, we have optimized chemical vapor deposition-grown graphene (CVD-G) on a current collector (Ni-foil) using reduced graphene oxide as an active electrode material to fabricate an electric double layer capacitor with reduced ESR. The CVD-G was grown at different cooling rates—20 °C min‑1, 40 °C min‑1 and 100 °C min‑1—to determine the optimum conditions. The lowest ESR, 0.38 Ω, was obtained for a cell with a 100 °C min‑1 cooling rate, while the sample without a CVD-G interlayer exhibited 0.80 Ω. The CVD-G interlayer-based supercapacitors exhibited fast CD characteristics with high scan rates up to 10 Vs‑1 due to low ESR. The specific capacitances deposited with CVD-G were in the range of 145.6 F g‑1–213.8 F g‑1 at a voltage scan rate of 0.05 V s‑1. A quasi-rectangular behavior was observed in the cyclic voltammetry curves, even at very high scan rates of 50 and 100 V s‑1, for the cell with optimized CVD-G at higher cooling rates, i.e. 100 °C min‑1.

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.

Electron spin resonance as a high sensitivity technique for environmental magnetism: determination of contamination in carbonate sediments

NASA Astrophysics Data System (ADS)

Crook, Nigel P.; Hoon, Stephen R.; Taylor, Kevin G.; Perry, Chris T.

2002-05-01

This study investigates the application of high sensitivity electron spin resonance (ESR) to environmental magnetism in conjunction with the more conventional techniques of magnetic susceptibility, vibrating sample magnetometry (VSM) and chemical compositional analysis. Using these techniques we have studied carbonate sediment samples from Discovery Bay, Jamaica, which has been impacted to varying degrees by a bauxite loading facility. The carbonate sediment samples contain magnetic minerals ranging from moderate to low concentrations. The ESR spectra for all sites essentially contain three components. First, a six-line spectra centred around g = 2 resulting from Mn2+ ions within a carbonate matrix; second a g = 4.3 signal from isolated Fe3+ ions incorporated as impurities within minerals such as gibbsite, kaolinite or quartz; third a ferrimagnetic resonance with a maxima at 230 mT resulting from the ferrimagnetic minerals present within the bauxite contamination. Depending upon the location of the sites within the embayment these signals vary in their relative amplitude in a systematic manner related to the degree of bauxite input. Analysis of the ESR spectral components reveals linear relationships between the amplitude of the Mn2+ and ferrimagnetic signals and total Mn and Fe concentrations. To assist in determining the origin of the ESR signals coral and bauxite reference samples were employed. Coral representative of the matrix of the sediment was taken remote from the bauxite loading facility whilst pure bauxite was collected from nearby mining facilities. We find ESR to be a very sensitive technique particularly appropriate to magnetic analysis of ferri- and para-magnetic components within environmental samples otherwise dominated by diamagnetic (carbonate) minerals. When employing typical sample masses of 200 mg the practical detection limit of ESR to ferri- and para-magnetic minerals within a diamagnetic carbonate matrix is of the order of 1 ppm and 1 ppb respectively, approximately 102 and 105 times the sensitivity achievable employing the VSM in our laboratory.

Thermally assisted OSL application for equivalent dose estimation; comparison of multiple equivalent dose values as well as saturation levels determined by luminescence and ESR techniques for a sedimentary sample collected from a fault gouge

NASA Astrophysics Data System (ADS)

Şahiner, Eren; Meriç, Niyazi; Polymeris, George S.

2017-02-01

Equivalent dose estimation (De) constitutes the most important part of either trap-charge dating techniques or dosimetry applications. In the present work, multiple, independent equivalent dose estimation approaches were adopted, using both luminescence and ESR techniques; two different minerals were studied, namely quartz as well as feldspathic polymineral samples. The work is divided into three independent parts, depending on the type of signal employed. Firstly, different De estimation approaches were carried out on both polymineral and contaminated quartz, using single aliquot regenerative dose protocols employing conventional OSL and IRSL signals, acquired at different temperatures. Secondly, ESR equivalent dose estimations using the additive dose procedure both at room temperature and at 90 K were discussed. Lastly, for the first time in the literature, a single aliquot regenerative protocol employing a thermally assisted OSL signal originating from Very Deep Traps was applied for natural minerals. Rejection criteria such as recycling and recovery ratios are also presented. The SAR protocol, whenever applied, provided with compatible De estimations with great accuracy, independent on either the type of mineral or the stimulation temperature. Low temperature ESR signals resulting from Al and Ti centers indicate very large De values due to bleaching in-ability, associated with large uncertainty values. Additionally, dose saturation of different approaches was investigated. For the signal arising from Very Deep Traps in quartz saturation is extended almost by one order of magnitude. It is interesting that most of De values yielded using different luminescence signals agree with each other and ESR Ge center has very large D0 values. The results presented above highly support the argument that the stability and the initial ESR signal of the Ge center is highly sample-dependent, without any instability problems for the cases of quartz resulting from fault gouge.

On the interpretation of continuous wave electron spin resonance spectra of tempo-palmitate in 5-cyanobiphenyl.

PubMed

Zerbetto, Mirco; Polimeno, Antonino; Cimino, Paola; Barone, Vincenzo

2008-01-14

Electron spin resonance (ESR) measurements are highly informative on the dynamic behavior of molecules, which is of fundamental importance to understand their stability, biological functions and activities, and catalytic action. The wealth of dynamic information which can be extracted from a continuous wave electron spin resonance (cw-ESR) spectrum can be inferred by a basic theoretical approach defined within the stochastic Liouville equation formalism, i.e., the direct inclusion of motional dynamics in the form of stochastic (Fokker-Planck/diffusive) operators in the super Hamiltonian H governing the time evolution of the system. Modeling requires the characterization of magnetic parameters (e.g., hyperfine and Zeeman tensors) and the calculation of ESR observables in terms of spectral densities. The magnetic observables can be pursued by the employment of density functional theory which is apt, provided that hybrid functionals are employed, for the accurate computation of structural properties of molecular systems. Recently, an ab initio integrated computational approach to the in silico interpretation of cw-ESR spectra of multilabeled systems in isotropic fluids has been discussed. In this work we present the extension to the case of nematic liquid crystalline environments by performing simulations of the ESR spectra of the prototypical nitroxide probe 4-(hexadecanoyloxy)-2,2,6,6-tetramethylpiperidine-1-oxy in isotropic and nematic phases of 5-cyanobiphenyl. We first discuss the basic ingredients of the integrated approach, i.e., (1) determination of geometric and local magnetic parameters by quantum-mechanical calculations, taking into account the solvent and, when needed, the vibrational averaging contributions; (2) numerical solution of a stochastic Liouville equation in the presence of diffusive rotational dynamics, based on (3) parameterization of diffusion rotational tensor provided by a hydrodynamic model. Next we present simulated spectra with minimal resorting to fitting procedures, proving that the combination of sensitive ESR spectroscopy and sophisticated modeling can be highly helpful in providing three-dimensional structural and dynamic information on molecular systems in anisotropic environments.

ESR and mass-spectrometric uranium-series dating studies of a mammoth tooth from stanton harcourt, Oxfordshire, England

NASA Astrophysics Data System (ADS)

Zhou, L. P.; McDermott, F.; Rhodes, E. J.; Marseglia, E. A.; Mellars, P. A.

The age of the Channel Deposits at Stanton Harcourt, Oxfordshire, England, has been a topic of debate with important implications for British Pleistocene stratigraphy. Recent excavations led by K. Scott reveal ample evidence for ancient environmental conditions characteristic of an interglacial. However, the question remains on the assignment of its age. At present it is thought to represent an interglacial corresponding to either marine OI Stage 7 or 5e. In an attempt to constrain the chronology of the site, and to assess the techniques' reliability, we have made electron spin resonance (ESR) measurements on enamel and mass-spectrometric U-series measurements on both enamel and dentine from a mammoth tooth buried in the Channel Deposits at Stanton Harcourt. Four dentine samples gave U-series dates between 65.4±0.4 and 146.5±1.0 ka and two enamel samples between these dentine layers were dated to 53.3±0.2 and 61.1±0.6 ka. The corresponding ESR age estimates for the enamel samples are 59±6 and 62±4 ka (early U-uptake, EU) and 95±11 and 98±7 ka (linear U-uptake, LU). The recent U-uptake (RU) dates are 245±38 and 238±31 ka, but in light of the U-series data we would not expect these to represent realistic age estimates. Similar ESR results were obtained from two other adjacent enamel samples. The effect of the large size of the mammoth tooth on the external gamma dose, and the internal gamma contribution from the high U content of the dentine, are considered. While the recent uptake ESR dates appear to coincide with OI Stage 7, all the early and linear uptake ESR and mass-spectrometric U-series dates are younger than the expected age estimation based on recent geological interpretation and amino acid racemisation measurements (>200 ka) and optical dating studies (200-450 ka). Possible causes of the unexpected dating results are discussed. We conclude that our mass-spectrometric U-series and EU and LU ESR measurements represent minimum age estimates for the tooth analysed. Our results seem to suggest that the tooth and hence the Channel Deposits are at least 147 ka in age. i.e. predating the last interglacial.

Correlation between erythropoietin receptor(s) and estrogen and progesterone receptor expression in different breast cancer cell lines.

PubMed

Trošt, Nina; Hevir, Neli; Rižner, Tea Lanišnik; Debeljak, Nataša

2013-03-01

Erythropoietin (EPO) receptor (EPOR) expression in breast cancer has been shown to correlate with the expression of estrogen receptor (ESR) and progesterone receptor (PGR) and to be associated with the response to tamoxifen in ESR+/PGR+ tumors but not in ESR- tumors. In addition, the correlation between EPOR and G protein-coupled estrogen receptor 1 [GPER; also known as G protein-coupled receptor 30 (GPR30)] has been reported, suggesting the prognostic potential of EPOR expression. Moreover, the involvement of colony stimulating factor 2 receptor, β, low‑affinity (CSF2RB) and ephrin type-B receptor 4 (EPHB4) as EPOR potential receptor partners in cancer has been indicated. This study analyzed the correlation between the expression of genes for EPO, EPOR, CSF2RB, EPHB4, ESR, PGR and GPER in the MCF-7, MDA-MB-361, T-47D, MDA-MB-231, Hs578Bst, SKBR3, MCF-10A and Hs578T cell lines. The cell lines were also treated with recombinant human EPO (rHuEPO) in order to determine its ability to activate the Jak/STAT5, MAPK and PI3K signaling pathways and modify cell growth characteristics. Expression analysis stratified the cell lines in 2 main clusters, hormone-dependent cell lines expressing ESR and PGR and a hormone-independent cluster. A significant correlation was observed between the expression levels of ESR and PGR and their expression was also associated with that of GPER. Furthermore, the expression of GPER was associated with that of EPOR, suggesting the connection between this orphan G protein and EPO signaling. A negative correlation between EPOR and CSF2RB expression was observed, questioning the involvement of these two receptors in the hetero-receptor formation. rHuEPO treatment only influenced the hormone-independent cell lines, since only the MDA-MB-231, SKBR3 and Hs578T cells responded to the treatment. The correlation between the expression of the analyzed receptors suggests that the receptors may interact in order to activate signaling pathways or to evade their inhibition. Therefore, breast cancer classification upon ESR, PGR and human epidermal growth factor receptor 2 (HER2) may not be sufficient for the selection of suitable treatment protocol. The expression of EPOR, GPER and EPHB4 may be considered as additional classification factors.

Coamplification of miR-4728 protects HER2-amplified breast cancers from targeted therapy

PubMed Central

Floros, Konstantinos V.; Hu, Bin; Monterrubio, Carles; Hughes, Mark T.; Wells, Jason D.; Morales, Cristina Bernadó; Ghotra, Maninderjit S.; Costa, Carlotta; Souers, Andrew J.; Boikos, Sosipatros A.; Leverson, Joel D.; Tan, Ming; Serra, Violeta; Koblinski, Jennifer E.; Arribas, Joaquin; Prat, Aleix; Paré, Laia; Miller, Todd W.; Harada, Hisashi; Windle, Brad E.; Scaltriti, Maurizio; Faber, Anthony C.

2018-01-01

HER2 (ERBB2) amplification is a driving oncogenic event in breast cancer. Clinical trials have consistently shown the benefit of HER2 inhibitors (HER2i) in treating patients with both local and advanced HER2+ breast cancer. Despite this benefit, their efficacy as single agents is limited, unlike the robust responses to other receptor tyrosine kinase inhibitors like EGFR inhibitors in EGFR-mutant lung cancer. Interestingly, the lack of HER2i efficacy occurs despite sufficient intracellular signaling shutdown following HER2i treatment. Exploring possible intrinsic causes for this lack of response, we uncovered remarkably depressed levels of NOXA, an endogenous inhibitor of the antiapoptotic MCL-1, in HER2-amplified breast cancer. Upon investigation of the mechanism leading to low NOXA, we identified a micro-RNA encoded in an intron of HER2, termed miR-4728, that targets the mRNA of the Estrogen Receptor α (ESR1). Reduced ESR1 expression in turn prevents ERα-mediated transcription of NOXA, mitigating apoptosis following treatment with the HER2i lapatinib. Importantly, resistance can be overcome with pharmacological inhibition of MCL-1. More generally, while many cancers like EGFR-mutant lung cancer are driven by activated kinases that when drugged lead to robust monotherapeutic responses, we demonstrate that the efficacy of targeted therapies directed against oncogenes active through focal amplification may be mitigated by coamplified genes. PMID:29476008

Do classic blood biomarkers of JSLE identify active lupus nephritis? Evidence from the UK JSLE Cohort Study.

PubMed

Smith, E M D; Jorgensen, A L; Beresford, M W

2017-10-01

Background Lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus (JSLE) patients. The value of commonly available biomarkers, such as anti-dsDNA antibodies, complement (C3/C4), ESR and full blood count parameters in the identification of active LN remains uncertain. Methods Participants from the UK JSLE Cohort Study, aged <16 years at diagnosis, were categorized as having active or inactive LN according to the renal domain of the British Isles Lupus Assessment Group score. Classic biomarkers: anti-dsDNA, C3, C4, ESR, CRP, haemoglobin, total white cells, neutrophils, lymphocytes, platelets and immunoglobulins were assessed for their ability to identify active LN using binary logistic regression modeling, with stepAIC function applied to select a final model. Receiver-operating curve analysis was used to assess diagnostic accuracy. Results A total of 370 patients were recruited; 191 (52%) had active LN and 179 (48%) had inactive LN. Binary logistic regression modeling demonstrated a combination of ESR, C3, white cell count, neutrophils, lymphocytes and IgG to be best for the identification of active LN (area under the curve 0.724). Conclusions At best, combining common classic blood biomarkers of lupus activity using multivariate analysis provides a 'fair' ability to identify active LN. Urine biomarkers were not included in these analyses. These results add to the concern that classic blood biomarkers are limited in monitoring discrete JSLE manifestations such as LN.

The Parameters Affecting the Success of Irrigation and Debridement with Component Retention in the Treatment of Acutely Infected Total Knee Arthroplasty

PubMed Central

Kim, Jae Gyoon; Bae, Ji Hoon; Lee, Seung Yup; Cho, Won Tae

2015-01-01

Background The aims of our study were to evaluate the success rate of irrigation and debridement with component retention (IDCR) for acutely infected total knee arthroplasty (TKA) (< 4 weeks of symptom duration) and to analyze the factors affecting prognosis of IDCR. Methods We retrospectively reviewed 28 knees treated by IDCR for acutely infected TKA from 2003 to 2012. We evaluated the success rate of IDCR. All variables were compared between the success and failure groups. Multivariable logistic regression analysis was also used to examine the relative contribution of these parameters to the success of IDCR. Results Seventeen knees (60.7%) were successfully treated. Between the success and failure groups, there were significant differences in the time from primary TKA to IDCR (p = 0.021), the preoperative erythrocyte sedimentation rate (ESR; p = 0.021), microorganism (p = 0.006), and polyethylene liner exchange (p = 0.017). Multivariable logistic regression analysis of parameters affecting the success of IDCR demonstrated that preoperative ESR (odds ratio [OR], 1.02; p = 0.041), microorganism (OR, 12.4; p = 0.006), and polyethylene liner exchange (OR, 0.07; p = 0.021) were significant parameters. Conclusions The results show that 60.7% of the cases were successfully treated by IDCR for acutely infected TKA. The preoperative ESR, microorganism, and polyethylene liner exchange were factors that affected the success of IDCR in acutely infected TKA. PMID:25729521

Electron spin resonance observation of charge carrier concentration in organic field-effect transistors during device operation

NASA Astrophysics Data System (ADS)

Tanaka, Hisaaki; Hirate, Masataka; Watanabe, Shun-ichiro; Kaneko, Kazuaki; Marumoto, Kazuhiro; Takenobu, Taishi; Iwasa, Yoshihiro; Kuroda, Shin-ichi

2013-01-01

Charge carrier concentration in operating organic field-effect transistors (OFETs) reflects the electric potential within the channel, acting as a key quantity to clarify the operation mechanism of the device. Here, we demonstrate a direct determination of charge carrier concentration in the operating devices of pentacene and poly(3-hexylthiophene) (P3HT) by field-induced electron spin resonance (FI-ESR) spectroscopy. This method sensitively detects polarons induced by applying gate voltage, giving a clear FI-ESR signal around g=2.003 in both devices. Upon applying drain-source voltage, carrier concentration decreases monotonically in the FET linear region, reaching about 70% of the initial value at the pinch-off point, and stayed constant in the saturation region. The observed results are reproduced well from the theoretical potential profile based on the gradual channel model. In particular, the carrier concentration at the pinch-off point is calculated to be β/(β+1) of the initial value, where β is the power exponent in the gate voltage (Vgs) dependence of the mobility (μ), expressed as μ∝Vgsβ-2, providing detailed information of charge transport. The present devices show β=2.6 for the pentacene and β=2.3 for the P3HT cases, consistent with those determined by transfer characteristics. The gate voltage dependence of the mobility, originating from the charge trapping at the device interface, is confirmed microscopically by the motional narrowing of the FI-ESR spectra.

An alternative estimation of the RF-enhanced plasma temperature during SPEAR artificial heating experiments: Early results

NASA Astrophysics Data System (ADS)

Vickers, H.; Baddeley, L.

2011-11-01

RF heating of the F region plasma at high latitudes has long been known to produce electron temperature increases that can vary from tens to hundreds of percent above the background, unperturbed level. In contrast, artificial ionospheric modification experiments conducted using the Space Plasma Exploration by Active Radar (SPEAR) heating facility on Svalbard have often failed to produce obvious enhancements in the electron temperatures when measured using the European Incoherent Scatter Svalbard radar (ESR), colocated with the heater. Contamination of the ESR ion line spectra by the zero-frequency purely growing mode (PGM) feature is known to persist at varying amplitudes throughout SPEAR heating, and such spectral features can lead to significant temperature underestimations when the incoherent scatter spectra are analyzed using conventional methods. In this study, we present the first results of applying a recently developed technique to correct the PGM-contaminated spectra to SPEAR-enhanced ESR spectra and derive an alternative estimate of the SPEAR-heated electron temperature. We discuss how the effectiveness of the spectrum corrections can be affected by the data variance, estimated over the integration period. The subsequent electron temperatures, inferred from corrected spectra, range from a few tens to a few hundred Kelvin above the average background temperature. These temperatures are found to be in reasonable agreement with the theoretical “enhanced” temperature, calculated for the peak of the stationary temperature perturbation profile, when realistic absorption effects are accounted for.

Investigating Ductal Carcinoma in Situ Using Noninvasive Imaging of Genetically Engineered Mouse Models

DTIC Science & Technology

2013-08-01

cancers that are ‘‘triple-negative’’ for the clinical markers ESR1 , PGR, and HER2 typically belong to the Basal-like molecular subtype. Defective Rb, p53...triple- negative’’ by clinical diagnostic markers ( ESR1 , PGR, and HER2 negative) are heterogeneous in their clinical behavior, morphology, and

48 CFR 52.219-9 - Small business subcontracting plan.

Code of Federal Regulations, 2011 CFR

2011-10-01

... subcontracting program reporting. The eSRS is located at http://www.esrs.gov. Indian tribe means any Indian tribe... Bureau of Indian Affairs in accordance with 25 U.S.C. 1452(c). This definition also includes Indian-owned... awarded to an ANC or Indian tribe shall be counted towards the subcontracting goals for small business and...

48 CFR 52.219-9 - Small business subcontracting plan.

Code of Federal Regulations, 2013 CFR

2013-10-01

... subcontracting program reporting. The eSRS is located at http://www.esrs.gov. Indian tribe means any Indian tribe... Bureau of Indian Affairs in accordance with 25 U.S.C. 1452(c). This definition also includes Indian-owned... awarded to an ANC or Indian tribe shall be counted towards the subcontracting goals for small business and...

48 CFR 52.219-9 - Small business subcontracting plan.

Code of Federal Regulations, 2014 CFR

2014-10-01

... subcontracting program reporting. The eSRS is located at http://www.esrs.gov. Indian tribe means any Indian tribe... Bureau of Indian Affairs in accordance with 25 U.S.C. 1452(c). This definition also includes Indian-owned... awarded to an ANC or Indian tribe shall be counted towards the subcontracting goals for small business and...

48 CFR 52.219-9 - Small business subcontracting plan.

Code of Federal Regulations, 2012 CFR

2012-10-01

... subcontracting program reporting. The eSRS is located at http://www.esrs.gov. Indian tribe means any Indian tribe... Bureau of Indian Affairs in accordance with 25 U.S.C. 1452(c). This definition also includes Indian-owned... awarded to an ANC or Indian tribe shall be counted towards the subcontracting goals for small business and...

Cryogenic radiometers and intensity-stabilized lasers for Eos radiometric calibrations

NASA Technical Reports Server (NTRS)

Foukal, P.; Hoyt, C.; Jauniskis, L.

1991-01-01

Liquid helium-cooled electrical substitution radiometers (ESRs) provide irradiance standards with demonstrated absolute accuracy at the 0.01 percent level, spectrally flat response between the UV and IR, and sensitivity down to 0.1 nW/sq cm. We describe an automated system developed for NASA - Goddard Space Flight Center, consisting of a cryogenic ESR illuminated by servocontrolled laser beams. This system is designed to provide calibration of single-element and array detectors over the spectral range between 257nm in the UV to 10.6 microns in the IR. We also describe a cryogenic ESR optimized for black body calibrations that has been installed at NIST, and another that is under construction for calibrations of the CERES scanners planned for Eos.

Evaluation of the Mechanical Properties of Electroslag Refined Fe-12Ni Alloys

NASA Technical Reports Server (NTRS)

Bhat, G. K.

1978-01-01

Three Fe-12Ni alloys, individually alloyed with small amounts of V, Ti, and Al, were manufactured through different melting techniques, with special emphasis on electroslag remelting, in order to achieve different levels of metal purity and associated costs. The relative effectiveness of these melting techniques was evaluated from tensile and slow bend fracture toughness behavior at 25 C and -196 C after tempering the test specimens at various temperatures. The best melting procedure was vacuum induction melting (VIM) with or without electroslag remelting (ESR). VIM+ESR is the recommended procedure since ESR provides increased yield of plate product, a reduction of overall manufacturing costs and, depending on the alloy composition, improved tensile and fracture toughness properties.

Measuring sunscreen protection against solar-simulated radiation-induced structural radical damage to skin using ESR/spin trapping: development of an ex vivo test method.

PubMed

Haywood, Rachel; Volkov, Arsen; Andrady, Carima; Sayer, Robert

2012-03-01

The in vitro star system used for sunscreen UVA-testing is not an absolute measure of skin protection being a ratio of the total integrated UVA/UVB absorption. The in vivo persistent-pigment-darkening method requires human volunteers. We investigated the use of the ESR-detectable DMPO protein radical-adduct in solar-simulator-irradiated skin substitutes for sunscreen testing. Sunscreens SPF rated 20+ with UVA protection, reduced this adduct by 40-65% when applied at 2 mg/cm(2). SPF 15 Organic UVA-UVB (BMDBM-OMC) and TiO(2)-UVB filters and a novel UVA-TiO(2) filter reduced it by 21, 31 and 70% respectively. Conventional broad-spectrum sunscreens do not fully protect against protein radical-damage in skin due to possible visible-light contributions to damage or UVA-filter degradation. Anisotropic spectra of DMPO-trapped oxygen-centred radicals, proposed intermediates of lipid-oxidation, were detected in irradiated sunscreen and DMPO. Sunscreen protection might be improved by the consideration of visible-light protection and the design of filters to minimise radical leakage and lipid-oxidation.

Primary gastric mucosa associated lymphoid tissue lymphoma: Clinical data predicted treatment outcome

PubMed Central

Todorovic, Milena; Balint, Bela; Jevtic, Miodrag; Suvajdzic, Nada; Ceric, Amela; Stamatovic, Dragana; Markovic, Olivera; Perunicic, Maja; Marjanovic, Slobodan; Krstic, Miodrag

2008-01-01

AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy. METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MALT) lymphoma (Ann Arbor stages I to IV) were enrolled. All had upper gastric endoscopy, abdominal ultrasonography, CT and H pylori status assessment (histology and serology). After anti-H pylori treatment and initial chemotherapy, patients were re-examined every 4 mo. RESULTS: Histological regression of the lymphoma was complete in 22/34 (64.7%) and partial in 9 (26.5%) patients. Median follow up time for these 31 responders was 60 mo (range 48-120). No regression was noted in 3 patients. Among the 25 (73.5%) H pylori positive patients, the eradication rate was 100%. CONCLUSION: Using univariate analysis, predictive factors for overall survival were international prognostic index (IPI) score, hemoglobin level, erythrocyte sedimentation rate (ESR), and platelet numbers (P < 0.005). In addition to this, Cox proportion hazard model differentiate IPI score, ESR, and platelets as predictors of survival. PMID:18416467

The effect of gamma irradiation on curcumin component of Curcuma domestica

NASA Astrophysics Data System (ADS)

Chosdu, R.; Erizal; Iriawan, T.; Hilmy, N.

1995-02-01

The effect of gamma irradiation on curcumin component of Curcuma domestica rhizome were investigated. Pure curcumin, sliced and powdered rhizome with 10% of moisture content were irradiated at 0, 10, 30 and 50 kGy (dose rate of 6 kGy/h). Curcumin content was analysed using HPLC method and ESR spectra. Results show that free radicals are already present in unirradiated rhizome. Gamma irradiation at the doses of 10, 30 and 50 kGy induced the free radicals formation of pure curcumin and Curcuma domestica rhizome. The ESR spectra of irradiated rhizome gave a very similar spectra to the signal of irradiated pure curcumin. The percentage of free radicals intensity from pure curcumin was very stable at room temperature up to 670 hours of storage. However, the percentage intensity of free radicals in the irradiated rhizome were decay during storage. Irradiation treatment and storage time did not give a significant change on curcumin content, water activity, pH and moisture content of rhizome investigated.

Marine Terrace Deposits along the Mediterranean Coast on the Southeastern Turkey and Their Implications for Tectonic Uplift and Sea Level Change

NASA Astrophysics Data System (ADS)

Tari, U.; Tüysüz, O.; Blackwell, B. A. B.; Genç, Ş. C.; Florentin, J. A.; Mahmud, Z.; Li, G. L.; Blickstein, J. I. B.; Skinner, A. R.

2016-12-01

Tectonic movements among the African, Arabian and Anatolian Plates have deformed the eastern Mediterranean. These movements caused transtensional opening of the NE-trending Antakya Graben since the late Pliocene. Tectonic uplift coupled with Quaternary sealevel fluctuations has produced several stacked marine terraces along the Mediterranean coasts on the graben. Here, marine terrace deposits that sit on both flanks of the graben at elevations between 3 and 175 m were dated using electron spin resonance (ESR) method in order to calculate uplift rates. The ESR ages range from 12 ka in late MIS 2 to 457 ka in MIS 9-11, but most of the terraces contain molluscs reworked from several earlier deposits due to successive tectonic movements and sealevel fluctuations. By dating in situ fossils, along the basal contacts of the marine terraces, uplift rates were calculated on both sides of the Antakya Graben. Results indicate that these deposits were mainly uplifted by local active faults rather than regional movements.

Epidemiological and Clinical Characteristics of Kawasaki Disease and Factors Associated with Coronary Artery Abnormalities in East China: Nine Years Experience

PubMed Central

Tang, Yunjia; Gao, Xiang; Shen, Jie; Sun, Ling

2016-01-01

Background: Because of the different genetic backgrounds, living environments and economic conditions, the epidemiologic, clinical characteristics and risk factors for coronary artery abnormalities (CAAs) in the Chinese population may differ among different parts of China. Methods: We did a retrospective study to explore the clinical characteristics and risk factors for CAAs in east China between 2006 and 2014. Results: There were 1016 patients during the study period. Of the 1004 patients who completed echocardiographic studies, 23.9% had CAAs. Sex, serum albumin, erythrocyte sedimentation rate (ESR), Mycoplasma pneumoniae (MP) infection, intravenous immunoglobulin (IVIG) started after the 10th day of illness and IVIG non-responders were independent risk factors associated with CAA. Conclusions: East China has a lower incidence of CAAs compared with southwest and northeast China, while similar to north China. Male gender, serum albumin, ESR, MP infection, IVIG started after the 10th day of illness and IVIG non-responders were predictive of CAA. PMID:26884440

Mechanism of the coupling of diazonium to single-walled carbon nanotubes and its consequences.

PubMed

Schmidt, Grégory; Gallon, Salomé; Esnouf, Stéphane; Bourgoin, Jean-Philippe; Chenevier, Pascale

2009-01-01

On the tube: The coupling of diazonium ions onto single-walled carbon nanotubes is shown to proceed through a radical chain reaction by kinetic analysis of the absorption peak drop (see picture). Radical species are also revealed by ESR. Metallic (m) nanotubes play a special catalytic role in the functionalization of semiconducting (sc) nanotubes.Due to its simplicity and versatility, diazonium coupling is the most widely used method for carbon nanotube (CNT) functionalization to increase CNT processability and add new functionalities. Yet, its mechanism is so far mostly unknown. Herein, we use kinetic analysis to shed light on this complex mechanism. A free-radical chain reaction is revealed by absorption spectroscopy and ESR. Metallic CNTs are shown to play an unexpected catalytic role. The step determining the selectivity towards metallic CNTs is identified by a Hammett correlation. A mechanistic model is proposed that predicts reactivity and selectivity as a function of diazonium electrophilicity and metallic-to-semiconducting CNT ratio, thus opening perspectives of controlled high-yield functionalization and purification.

Vasohibin 2 promotes epithelial-mesenchymal transition in human breast cancer via activation of transforming growth factor β 1 and hypoxia dependent repression of GATA-binding factor 3.

PubMed

Tu, Min; Li, Zhanjun; Liu, Xian; Lv, Nan; Xi, Chunhua; Lu, Zipeng; Wei, Jishu; Song, Guoxin; Chen, Jianmin; Guo, Feng; Jiang, Kuirong; Wang, Shui; Gao, Wentao; Miao, Yi

2017-03-01

Vasohibin 2 (VASH2) is identified as an angiogenic factor, and has been implicated in tumor angiogenesis, proliferation and epithelial-mesenchymal transition (EMT). To investigate the EMT role of VASH2 in breast cancer, we overexpressed or knocked down expression of VASH2 in human breast cancer cell lines. We observed that VASH2 induced EMT in vitro and in vivo. The transforming growth factor β1 (TGFβ1) pathway was activated by VASH2, and expression of a dominant negative TGFβ type II receptor could block VASH2-mediated EMT. In clinical breast cancer tissues VASH2 positively correlated with TGFβ1 expression, but negatively correlated with E-cadherin (a marker of EMT) expression. Under hypoxic conditions in vitro or in vivo, we found that down-regulation of estrogen receptor 1 (ESR1) in VASH2 overexpressing ESR1 positive cells suppressed E-cadherin. Correlation coefficient analysis indicated that VASH2 and ESR1 expression were negatively correlated in clinical human breast cancer tissues. Further study revealed that a transcription factor of ESR1, GATA-binding factor 3 (GATA3), was down-regulated by VASH2 under hypoxia or in vivo. These findings suggest that VASH2 drives breast cancer cells to undergo EMT by activation of the TGFβ1 pathway and hypoxia dependent repression GATA3-ESR1 pathway, leading to cancer metastasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluating intra- and inter- sample variability in Electron Spin Resonance dating of fossil teeth: an example from Cuesta de la Bajada site (Spain).

NASA Astrophysics Data System (ADS)

Duval, Mathieu; Grün, Rainer; Shao, Qingfeng; Martin, Loïc; Arnold, Lee J.

2017-04-01

Over the last decades, technological improvements have progressively enabled to significantly decrease the amount of material required for dating analyses. In particular, the combined use of laser ablation (LA) with ICP-MS opened new possibilities for high resolution in situ U-series analyses of fossil teeth. With this technique it is now possible to directly visualise the spatial distribution of U and Th isotopes in dental tissues. Moreover, the combination of LA-ICP-MS with Electron Spin Resonance (ESR) enables an increased sampling resolution, and offers the possibility to produce several ages for different areas within a given fossil tooth. To test the potential of this new approach, several fossil teeth were collected from the Middle Palaeolithic site of Cuesta de la Bajada (Teruel, Spain). Each tooth was divided into several subsamples, providing thus several combined US-ESR age results per tooth. For each subsample, ESR, high-resolution laser ablation and solution ICP-MS U-series analyses were systematically performed. Relative beta dose rate contributions from the different tissues and the sediment were also adjusted using DosiVox software and compared with those derived from the standard approach. The results of this work give some interesting insight into the intra- and inter- sample variability that may exist at a given site. The consistency of the final US-ESR age estimates obtained on teeth are also evaluated by comparison with the (semi)-independent results derived from ESR and Luminescence dating of optically bleached quartz grains collected from the same excavation area.

Investigation of the estrogen receptor-alpha gene with type 2 diabetes and/or nephropathy in African-American and European-American populations.

PubMed

Gallagher, Carla J; Keene, Keith L; Mychaleckyj, Josyf C; Langefeld, Carl D; Hirschhorn, Joel N; Henderson, Brian E; Gordon, Candace J; Freedman, Barry I; Rich, Stephen S; Bowden, Donald W; Sale, Michèle M

2007-03-01

The estrogen receptor-alpha gene (ESR1) was selected as a positional candidate under a type 2 diabetes linkage peak at 6q24-27. A total of 42 ESR1 single nucleotide polymorphisms (SNPs) were genotyped in 380 African-American type 2 diabetic case subjects with end-stage renal disease (ESRD) and 276 African-American control subjects. A total of 22 ancestry informative markers were also genotyped, and the program Admixmap was used to adjust allelic and haplotypic association tests for individual estimates of admixture. The most significant association with type 2 diabetes-ESRD was with rs1033182 in intron 2 (P = 0.013, admixture-adjusted P(a) = 0.021). Genotyping 17 SNPs across a region of ESR1 intron 1-intron 2 in an expanded population of 851 case and 635 control subjects supported association with rs1033182 (P = 0.004, P(a) = 0.027) and with an independent six-SNP haplotype of high linkage disequilibrium spanning 6.4 kb (P < 0.0001, P(a) < 0.0001). The same 17 ESR1 SNPs were genotyped in 300 European-American type 2 diabetes-ESRD case subjects and 310 European-American control subjects. Two intron 2 SNPs, rs2431260 (P = 0.015) and rs1709183 (P = 0.019), and a four-SNP haplotype containing these SNPs (P = 0.033) were associated with type 2 diabetes and/or ESRD. Results suggest that intron 1 and intron 2 of the ESR1 gene may contain functionally important regions related to type 2 diabetes or ESRD risk.

In-situ Measurement of Reversed Flow Event in the Cusp Ionosphere

NASA Astrophysics Data System (ADS)

Jin, Y.; Moen, J.; Miloch, W. J.; Spicher, A.; Clausen, L. B. N.

2017-12-01

The Reversed Flow Events (RFEs) are a new category of flow channel that frequently occur in the cusp ionosphere. The RFEs are 100-200 km wide and east-west elongated flow channels, in which plasma flow opposes to the background convection direction. The RFEs are thought to be an important source for the rapid development of the ionospheric irregularities. We present an overview of the ionospheric conditions during the launch of the Investigation of Cusp Irregularities 3 (ICI-3) sounding rockets. The ICI-3 was launched from Ny-Ålesund, Svalbard at 7:21.31 UT on December 3, 2011. The objective of the ICI-3 was to target a RFE. The IMF was characterized by strongly negative Bz and weakly negative By during the time period of interest. The EISCAT Svalbard Radar (ESR) 32m beam was operating in a fast azimuth sweep mode between 180° (south) and 300° (northwest) at an elevation angle of 30°. The ESR observed a series of RFEs as westward flow channels opposing to the eastward normal plasma flow in the prenoon sector. The ICI-3 was shot to cross the first observed RFE in the ESR field of view. The ICI-3 observed flow structures that were consistent with the ESR. Furthermore, the ICI-3 reveals fine-scale of the flow structures inside the RFE observed by the ESR. The high resolution electron density data show intense fluctuations at all scales throughout the RFE region. The GPS TEC and scintillation data inside the same RFE region are used to compare with the in-situ measurements.

Control of Transcriptional Repression of the Vitellogenin Receptor Gene in Largemouth Bass (Micropterus Salmoides) by Select Estrogen Receptors Isotypes

PubMed Central

Dominguez, Gustavo A.; Bisesi, Joseph H.; Kroll, Kevin J.; Denslow, Nancy D.; Sabo-Attwood, Tara

2014-01-01

The vitellogenin receptor (Vtgr) plays an important role in fish reproduction. This receptor functions to incorporate vitellogenin (Vtg), a macromolecule synthesized and released from the liver in the bloodstream, into oocytes where it is processed into yolk. Although studies have focused on the functional role of Vtgr in fish, the mechanistic control of this gene is still unexplored. Here we report the identification and analysis of the first piscine 5′ regulatory region of the vtgr gene which was cloned from largemouth bass (Micropterus salmoides). Using this putative promoter sequence, we investigated a role for hormones, including insulin and 17β-estradiol (E2), in transcriptional regulation through cell-based reporter assays. No effect of insulin was observed, however, E2 was able to repress transcriptional activity of the vtgr promoter through select estrogen receptor subtypes, Esr1 and Esr2a but not Esr2b. Electrophoretic mobility shift assay demonstrated that Esr1 likely interacts with the vtgr promoter region through half ERE and/or SP1 sites, in part. Finally we also show that ethinylestradiol (EE2), but not bisphenol-A (BPA), represses promoter activity similarly to E2. These results reveal for the first time that the Esr1 isoform may play an inhibitory role in the expression of LMB vtgr mRNA under the influence of E2, and potent estrogens such as EE2. In addition, this new evidence suggests that vtgr may be a target of select endocrine disrupting compounds through environmental exposures. PMID:25061109

T Lymphocytes Do Not Directly Mediate the Protective Effect of Estrogen on Experimental Autoimmune Encephalomyelitis

PubMed Central

Polanczyk, Magdalena J.; Jones, Richard E.; Subramanian, Sandhya; Afentoulis, Michael; Rich, Cathleen; Zakroczymski, Melissa; Cooke, Paul; Vandenbark, Arthur A.; Offner, Halina

2004-01-01

Gender influences mediated by 17β-estradiol (E2) have been associated with susceptibility to and severity of autoimmune diseases such as diabetes, arthritis, and multiple sclerosis. In this regard, we have shown that estrogen receptor-α (Esr1) is crucial for the protective effect of 17β-estradiol (E2) in murine experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis. The expression of estrogen receptors among various immune cells (eg, T and B lymphocytes, antigen-presenting cells) suggests that the therapeutic effect of E2 is likely mediated directly through specific receptor binding. However, the target immune cell populations responsive to E2 treatment have not been identified. In the current study, we induced EAE in T-cell-deficient, severe combined immunodeficient mice or in immunocompetent mice with encephalitogenic T cells from wild-type Esr1+/+ or Esr1 knockout (Esr1−/−) donors and compared the protective E2 responses. The results showed that E2-responsive, Esr1+/+ disease-inducing encephalitogenic T cells were neither necessary nor sufficient for E2-mediated protection from EAE. Instead, the therapeutic response appeared to be mediated through direct effects on nonlymphocytic, E2-responsive cells and down-regulation of the inflammatory response in the central nervous system. These results provide the first demonstration that the protective effect of E2 on EAE is not mediated directly through E2-responsive T cells and raise the alternative possibility that nonlymphocytic cells such as macrophages, dendritic cells, or other nonlymphocytic cells are primarily responsive to E2 treatment in EAE. PMID:15579449

Defining a Role for the Oncogene Beta-Catenin in Prostate Epithelial Growth and Invasion

DTIC Science & Technology

2011-07-01

receptor function. To determine in increased or decreased Wnt signaling can affect androgen receptor function, we harvested E15.5 UGSs from Esr1 -Cre x...beta-cateninfl/fl and Esr1 -Cre APCfl/fl embryos and treated them with 2 uM tamoxifen and zero, low, normal, or high androgen to determine if high

Developmental expression and estrogen responses of endocrine genes in juvenile yellow perch (Perca flavescens)

USDA-ARS?s Scientific Manuscript database

The present study examines the expression of growth-regulating genes (gh, prl, smtl and igf1b), the estrogen receptors (esr1 and esr2a) and aromatase (cyp19a1a) in developing yellow perch. To gain an initial understanding into the endocrine control of growth preceding and involved with sexual size d...

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.

Hertz's special relativity and physical reality.

NASA Astrophysics Data System (ADS)

Mocanu, C. I.

Maxwell-Hertz electrodynamics (MHE), valid for nonuniform motions as they occur in physical reality and which holds for the noninertial reference frame of our laboratory at small velocities only, is extended to relativistic velocities. The new theory, called Hertz's relativistic electrodynamics (HRE), is completely independent and built-up in a completely different way than Einstein's special relativity (ESR). HRE, a coordinate-free formulation, does not need postulates, but confirms the constancy principle of the speed of light in a vacuum. All experiments of first and second order in v2/c2 are correctly interpreted. To this theory a Hertzian kinematics and dynamics are associated. HRE with its corresponding mechanics form Hertz's special relativity (HSR) as a theory complementary to ESR. According to the principle of complementarity and neglecting gravitational effects, extended special relativity (ExSR) is a double-faced theory which becomes either ESR when the motion is inertial or HSR when the motion is noninertial. The complementarity of both theories assumes that the two descriptions cannot be employed for the same motion, being mutually exclusive. Consequently, to every statement of ExSR, a complementary statement of the other ExSR corresponds. The completeness of ESR with HSR ensures an extended view over relativity in our physical world.

The knocked-out erythrocyte sedimentation rate: periodontal abscess.

PubMed

Sevinc, Alper; Bayindir, Yasar; But, Ayse

2008-01-01

The erythrocyte sedimentation rate (ESR) is a common but nonspecific test that is often used as an indicator of active disease. Infection of dental origin may be responsible for a number of cases in unresolved elevated ESR and fever etiology. Dental sepsis is the one of the potential causes of persistent fever that can escape detection. An 18-year-old female patient was admitted to the emergency room with complaints of headache, fever, nausea, and vomiting for the past four days. Erythrocyte sedimentation rate was 110 mm/h. She was started empirically on antibiotic treatment as no etiology was found. Four days later, while searching for the etiology of the fever, the patient experienced an acute pain in association with localizing symptoms in two decayed teeth. Oral examination revealed abscess formation in both teeth. Teeth were extracted and ESR was decreased to 95 mm/h on the day of the second extraction and to 60, 35, and 10 mm/h taken weekly. During the follow-up, she was in good health with no fever seen 3 months after treatment and her ESR was 15 mm/h. Dental infection should be considered as an unusual but very treatable cause of pyrexia of unknown origin.

Electron Spin Resonance Studies of Carbonic Anhydrase: Transition Metal Ions and Spin-Labeled Sulfonamides*

PubMed Central

Taylor, June S.; Mushak, Paul; Coleman, Joseph E.

1970-01-01

Electron spin resonance (esr) spectra of Cu(II) and Co(II) carbonic anhydrase, and a spin-labeled sulfonamide complex of the Zn(II) enzyme, are reported. The coordination geometry of Cu(II) bound in the enzyme appears to have approximately axial symmetry. Esr spectra of enzyme complexes with metal-binding anions also show axial symmetry and greater covalency, in the order ethoxzolamide < SH- < N3- ≤ CN-. Well-resolved superhyperfine structure in the spectrum of the cyanide complex suggests the presence of two, and probably three, equivalent nitrogen ligands from the protein. Esr spectra of the Co(II) enzyme and its complexes show two types of Co(II) environment, one typical of the native enzyme and the 1:1 CN- complex, and one typical of a 2:1 CN- complex. Co(II) in the 2:1 complex appears to be low-spin and probably has a coordination number of 5. Binding of a spin-labeled sulfonamide to the active center immobilizes the free radical. The similarity of the esr spectra of spin-labeled Zn(II) and Co(II) carbonic anhydrases suggests that the conformation at the active center is similar in the two metal derivatives. PMID:4320976

ESR studies on the thermal decomposition of trimethylamine oxide to formaldehyde and dimethylamine in jumbo squid (Dosidicus gigas) extract.

PubMed

Zhu, Junli; Jia, Jia; Li, Xuepeng; Dong, Liangliang; Li, Jianrong

2013-12-15

The effects of ferrous iron, heating temperature and different additives on the decomposition of trimethylamine oxide (TMAO) to formaldehyde (FA) and dimethylamine (DMA) and generation of free radicals in jumbo squid (Dosidicus gigas) extract during heating were evaluated by electron spin resonance (ESR). The thermal decomposition of TMAO to TMA, DMA and FA and free radical signals was observed in squid extract, whereas no DMA, FA and free radical signals were detected in cod extract or in aqueous TMAO solution in vitro at high temperatures. Significant increase in levels of DMA, FA and radicals intensity were observed in squid extract and TMAO solution in the presence of ferrous iron with increasing temperature. Hydrogen peroxide stimulated the production of DMA, FA and ESR signals in squid extract, while citric acid, trisodium citrate, calcium chloride, tea polyphenols and resveratrol had the opposite effect. Similar ESR spectra of six peaks regarded as amminium radical were detected in the squid extract and TMAO-iron(II) solution, suggesting that the amminium radical was involved in the decomposition of TMAO. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of hydrogen pressure on free radicals in direct coal liquefaction/coprocessing

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

Seehra, M.S.; Ibrahim, M.M.

1995-12-31

The objective of this study was to investigate the coprocessing of coal with waste tires and commingled plastics and to characterize the relevant catalysts, using high pressure/high temperature in-situ ESR (Electron Spin Resonance) spectroscopy. The recent results from high pressure ESR spectroscopy are emphasized. During this period, considerable progress was made in developing the high pressure capabilities in in-situ ESR spectroscopy and new results carried out in 1000 psi of H{sub 2}gas are presented. In these experiments, sapphire tubes were used to contain the high pressures at temperatures up to 500{degrees}C. Results of the experiments carried out under 1000 psimore » of H{sub 2} are compared with those under 1000 psi of non-interacting argon and with the earlier experiments in flowing H{sub 2} gas where the volatiles are removed by the flowing gas. In these experiments, the free radical density N of the Blind Canyon coal was measured at each temperature and pressure by double integration of the ESR signal and calibrating it against a standard. The details of the experimental apparatus and procedures have been described in earlier publications.« less