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.

Prevalence of Asymptomatic Arterial Hypertension and Its Correlation with Inflammatory Activity in Early Rheumatoid Arthritis.

PubMed

Bajraktari, Ismet H; Rexhepi, Sylejman; Berisha, Idriz; Lahu, Ali; Kryeziu, Avni; Durmishi, Bastri; Bajraktari, Halit; Bahtiri, Elton

2017-08-15

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that worsens during the course of the disease and can cause disability. Early RA refers to the onset of symptoms within the past 3 months. In RA, increased levels of mediators of inflammation may cause arterial stiffness consequently leading to arterial hypertension. The aim of this cross-sectional study was to assess the prevalence of asymptomatic arterial hypertension in early RA patients as well as the correlation with parameters of inflammation. One hundred and seventy-nine early RA patients diagnosed in agreement with ACR/EULAR (American College of Rheumatology/ European League against Rheumatism) 2010 criteria were consecutively included in the study. CRP (C-reactive protein) and anti CCP (Antibodies to cyclic citrullinated peptides) serum levels, WBC (white blood cells) count and ESR (Erythrocyte sedimentation rate), likewise DAS-28 (28-joint disease activity score) were determined in all included patients. Parametric tests were used to compare the characteristics of the groups and to test the correlation of the variables. Statistical data analysis revealed that a majority of the patients were females (n = 141; 78.7%); the mean age at RA onset was 49.13 ± 12.13 years. Overall prevalence of hypertension was 44.13 % (n = 79). In comparison with the normotensive patients, the hypertensive patients were older and had significantly higher values of CRP, ESR, anti-CCP and DAS-28. A highly significant positive correlation between all the study parameters and systolic and diastolic blood pressure was observed. Presence of significantly higher values of CRP, ESR, anti-CCP and DAS-28 in hypertensive patients indicate that inflammation is associated with an increased risk of hypertension. In this context, early screening for arterial hypertension and adequate therapeutic measures should be considered in early RA patients.

Multicenter validation of the value of BASFI and BASDAI in Chinese ankylosing spondylitis and undifferentiated spondyloarthropathy patients

PubMed Central

Lin, Zhiming; He, Peigen; Gao, Jiesheng; Zuo, Xiaoxia; Ye, Zhizhong; Shao, Fengmin; Zhan, Feng; Lin, Jinying; Li, Li; Wei, Yanlin; Xu, Manlong; Liao, Zetao; Lin, Qu

2009-01-01

The objectives of this study were to evaluate the reliability of Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis disease activity index (BASDAI) in Chinese ankylosing spondylitis (AS) and undifferentiated spondyloarthropathy (USpA) patients. 664 AS patients by the revised New York criteria for AS and 252 USpA patients by the European Spondyloarthropathy Study Group criteria were enrolled. BASDAI and BASFI questionnaires were translated into Chinese. Participants were required to fill in BASFI and BASDAI questionnaires again after 24 h. Moreover, BASDAI and BASFI were compared in AS patients receiving Enbrel or infliximab before and after treatment. For AS group, BASDAI ICC: 0.9502 (95% CI: 0.9330–0.9502, α = 0.9702), BASFI ICC: 0.9587 (95% CI: 0.9521–0.9645, α = 0.9789). For USpA group, BASDAI ICC: 0.9530 (95% CI: 0.9402–0.9632, α = 0.9760), BASFI ICC: 0.9900 (95% CI: 0.9871–0.9922, α = 0.9950). In the AS group, disease duration, occipital wall distance, modified Schober test, chest expansion, ESR, and CRP showed significant correlation with BASDAI and BASFI (all P < 0.01). In the USpA group, onset age, ESR, and CRP were significantly correlated with BASDAI (all P < 0.05), while modified Schober test, ESR, and CRP were significantly associated with BASFI (all P < 0.05). The change in BASDAI and BASFI via Enbrel or infliximab treatment showed a significant positive correlation (P < 0.01). The two instruments have good reliability and reference value regarding the evaluation of patient’s condition and anti-TNF-α treatment response. PMID:20012866

The Diagnostic and Prognostic Value of Hematological and Chemical Abnormalities in Soft Tissue Sarcoma: A Comparative Study in Patients with Benign and Malignant Soft Tissue Tumors.

PubMed

Ariizumi, Takashi; Kawashima, Hiroyuki; Ogose, Akira; Sasaki, Taro; Hotta, Tetsuo; Hatano, Hiroshi; Morita, Tetsuro; Endo, Naoto

2018-01-01

The value of routine blood tests in malignant soft tissue tumors remains uncertain. To determine if these tests can be used for screening, the routine pretreatment blood test findings were retrospectively investigated in 359 patients with benign and malignant soft tissue tumors. Additionally, the prognostic potential of pretreatment blood abnormalities was evaluated in patients with soft tissue sarcomas. We compared clinical factors and blood tests findings between patients with benign and malignant soft tissue tumors using univariate and multivariate analysis. Subsequently, patients with malignant tumors were divided into two groups based on blood test reference values, and the prognostic significance of each parameter was evaluated. In the univariate analysis, age, tumor size, and tumor depth were significant clinical diagnostic factors. Significant increases in the granulocyte count, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and γ-glutamyl transpeptidase (γ-GTP) levels were found in patients with malignant soft tissue tumors. Multiple logistic regression showed that tumor size and ESR were independent factors that predicted malignant soft tissue tumors. The Kaplan-Meier survival analysis revealed that granulocyte counts, γ-GTP levels, and CRP levels correlated significantly with overall survival. Thus, pretreatment routine blood tests are useful diagnostic and prognostic markers for diagnosing soft tissue sarcoma. © 2018 by the Association of Clinical Scientists, Inc.

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.

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.

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

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.

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

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

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

Prevalence of Asymptomatic Arterial Hypertension and Its Correlation with Inflammatory Activity in Early Rheumatoid Arthritis

PubMed Central

Bajraktari, Ismet H.; Rexhepi, Sylejman; Berisha, Idriz; Lahu, Ali; Kryeziu, Avni; Durmishi, Bastri; Bajraktari, Halit; Bahtiri, Elton

2017-01-01

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that worsens during the course of the disease and can cause disability. Early RA refers to the onset of symptoms within the past 3 months. In RA, increased levels of mediators of inflammation may cause arterial stiffness consequently leading to arterial hypertension. AIM: The aim of this cross-sectional study was to assess the prevalence of asymptomatic arterial hypertension in early RA patients as well as the correlation with parameters of inflammation. METHODS: One hundred and seventy-nine early RA patients diagnosed in agreement with ACR/EULAR (American College of Rheumatology/ European League against Rheumatism) 2010 criteria were consecutively included in the study. CRP (C-reactive protein) and anti CCP (Antibodies to cyclic citrullinated peptides) serum levels, WBC (white blood cells) count and ESR (Erythrocyte sedimentation rate), likewise DAS-28 (28-joint disease activity score) were determined in all included patients. Parametric tests were used to compare the characteristics of the groups and to test the correlation of the variables. RESULTS: Statistical data analysis revealed that a majority of the patients were females (n = 141; 78.7%); the mean age at RA onset was 49.13 ± 12.13 years. Overall prevalence of hypertension was 44.13 % (n = 79). In comparison with the normotensive patients, the hypertensive patients were older and had significantly higher values of CRP, ESR, anti-CCP and DAS-28. A highly significant positive correlation between all the study parameters and systolic and diastolic blood pressure was observed. CONCLUSION: Presence of significantly higher values of CRP, ESR, anti-CCP and DAS-28 in hypertensive patients indicate that inflammation is associated with an increased risk of hypertension. In this context, early screening for arterial hypertension and adequate therapeutic measures should be considered in early RA patients. PMID:28932306

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.

Magnetic Resonance Characterization of Defects in Icosahedral and Cubic Boron Arsenide Bulk Crystals

NASA Astrophysics Data System (ADS)

Glaser, E. R.; Freitas, J. A., Jr.; Cress, C. D.; Perkins, F. K.; Prokes, S. M.; Ruppalt, L. B.; Culbertson, J. C.; Whiteley, C.; Edgar, J. H.; Tian, F.; Ren, Z.; Kim, J.; Shi, L.; Naval Research Lab Team; Kansas State U. Team; U. Houston Team; U. Texas Team

Low-temperature electron spin resonance (ESR) at 9.5 GHz and optically-detected magnetic resonance (ODMR) at 24 GHz were employed to investigate point defects in icosahedral and cubic Boron Arsenide bulk crystals. These semiconductors are of interest for use in high radiation and/or high temperature environments. ESR of the (001) B12As2 (Eg = 3.47 eV) mm-size platelets revealed two distinct features of unknown origin. The first signal is characterized by Zeeman splitting g-values of g|| = 2.017, g⊥ = 2.0183 while the second with g|| = 2.0182, g⊥ = 1.9997. Most notably, the second signal was also observed from ODMR on the broad 2.4 eV ``yellow/green'' photoluminescence band previously reported for these crystals and suggests its direct involvement in this likely defect-related radiative recombination process. Preliminary ESR obtained for the 100-300 micron-size cubic BAs crystals revealed a signal with g-value of 2.018 (very similar to that found for the B12As2 crystals) and broad FWHM value of 182 G. Possible origins of these defects will be discussed.

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.

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.

Differences in the effectiveness of serum biomarkers for the diagnosis of bacterial infections in adult and elderly patients admitted to the emergency department.

PubMed

Yilmaz, Hava; Duran, Latif; Yanik, Keramettin; Altuntaş, Mehmet; Sünbül, Mustafa

2015-01-01

This study aimed to evaluate the superiority of procalcitonin (PCT), C-reactive protein (CRP) levels, white blood cell (WBC) counts, and erythrocyte sedimentation rate (ESR) in discriminating among infection, systemic inflammatory response syndrome (SIRS), and sepsis, and their differences according to age groups. The patients were divided into an adult group and a geriatric group (over 65 years) and classified according to the presence of infection, SIRS, and sepsis. The patients' laboratory values (PCT, CRP, WBC, ESR), demographic characteristics, and vital signs were taken into consideration. When the laboratory parameters were evaluated, there were no significant differences in the PCT, WBC, and ESR values between the age groups (P > 0.05). CRP was significantly higher in the adult patient group compared to the geriatric group (P < 0.001). When the two groups were compared in terms of infection, there were no significant differences in the PCT levels and the WBC count (P > 0.05) in SIRS and sepsis. In addition, the CRP levels and the ESR were significantly higher in the adult sepsis patients when compared with the geriatric patients (P < 0.001). PCT levels do not distinguish among infection, SIRS, and sepsis in adult and geriatric age groups.

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.

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

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.

ON THE PROGNOSTIC SIGNIFICANCE OF THE ERYTHROCYTE SEDIMENTATION RATE, THE LEUKOCYTE COUNT, THE HEMOGLOBIN VALUE, AND BODY WEIGHT IN IRRADIATED AND NONIRRADIATED CANCER PATIENTS (in German)

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

Hofmann, D.

1962-06-01

Changes in these parameters were followed in 672 women with genital carcinoma during and after radiotherapy to determine whether any of them could be used to predict the eventual success of the treatment. All of these parameters were found to be of prognostic value in the 394 patients with carcinoma of the uterine cervix of grades I, II, and III. Erythrocyte sedimentation rate (ESR) was initially elevated in these patients, and in those without recurrence, irradiation caused a prompt and progressive drop in ESR. It continued to rise after radiotherapy in those who later showed tumor recurrence. Similar changes inmore » leukocyte count were seen in this group, the counts falling and staying down after successful treatment or rising when the treatment failed. An inverse relation with respect to the hemoglobin level and body wt was seen, both values progressively increasing in cases later shown to be cured and falling in those which were not. These relations did not hold or were of less prognostic value in patients with carcinomas of the body of the uterus, ovary, or vulva. However, in general, a gradual continual fall in ESR and a rapid fall in leukocyte count were favorable signs following irradiation. (BBB)« less

Origin and production process of eolian dust emitted from the Tarim Basin and their evolution through the Plio-Pleostocene based on ESR signal intensity and crystallinity of quartz

NASA Astrophysics Data System (ADS)

Tada, R.; Isozaki, Y.; Zheng, H.; Sun, Y.; Toyoda, S.; Hasegawa, H.; Yoshida, T.

2010-12-01

Tarim Basin (or Taklimakan Desert) is regarded as one of the major source area of eolian dust in the northern hemisphere. Although a previous study hypothesized that the detrital materials in the Tarim Basin were produced by glacial activity in the surrounding mountains, delivered by rivers, and homogenized by wind within the basin, not enough evidence has been presented to support this hypothesis. Here, we conducted provenance study of eolian dust in the Tarim Basin by examining fine silt fraction (< 20 μm) of the sediments collected from all over the Tarim Basin. We focused on quartz and measured its electron spin resonance [ESR] signal intensity and Crystallinity Index [CI] in the fine (<16μm) and coarse (> 64μm) fractions of various types of sediments including river sediments derived from the Kunlun and Tian Shan Mountains, dry lake sediments in the eastern part of the basin, and mountain loess on the northern slope of the Kunlun Mountains, to examine the process to produce eolian dust within the Tarim Basin. The result revealed that the coarse fractions of river sediments were derived from bedrocks exposed in the drainage area of each river, and that quartz in coarse fraction of the river sediment has ESR signal intensity and CI values unique to each river. ESR signal intensity and CI of quartz in fine fractions of river sediments discharged from the Tian Shan Mountains, which are located windward of the basin, and those discharged from mountainous rivers show values similar to the values for coarse fractions, suggesting that their sources are the same as those for the coarse fractions. On the other hand, ESR signal intensity and CI of quartz in fine fractions of river sediments discharged from the Kunlun Mountains show values different from those for the coarse fractions, and converged to the values close to the average values for the fine fractions of river sediments in the basin and also for the mountain loess, the latter represents the eolian dust emitted from the Tarim Basin. The converged values are considered as resulted from homogenization by the repeated recycling process within the basin. Analysis of the Quaternary mountain loess and Plio-Pleistocene loess-like siltstone intercalated in the alluvial sediments delivered from the Kunlun Mountains revealed that eolian dust source and production process essentially the same as the present has been established at ca. 3.5 Ma.

ESR concept paper on value-based radiology.

PubMed

2017-10-01

The European Society of Radiology (ESR) established a Working Group on Value-Based Imaging (VBI WG) in August 2016 in response to developments in European healthcare systems in general, and the trend within radiology to move from volume- to value-based practice in particular. The value-based healthcare (VBH) concept defines "value" as health outcomes achieved for patients relative to the costs of achieving them. Within this framework, value measurements start at the beginning of therapy; the whole diagnostic process is disregarded, and is considered only if it is the cause of errors or complications. Making the case for a new, multidisciplinary organisation of healthcare delivery centred on the patient, this paper establishes the diagnosis of disease as a first outcome in the interrelated activities of the healthcare chain. Metrics are proposed for measuring the quality of radiologists' diagnoses and the various ways in which radiologists provide value to patients, other medical specialists and healthcare systems at large. The ESR strongly believes value-based radiology (VBR) is a necessary complement to existing VBH concepts. The Society is determined to establish a holistic VBR programme to help European radiologists deal with changes in the evolution from volume- to value-based evaluation of radiological activities. Main Messages • Value-based healthcare defines value as patient's outcome over costs. • The VBH framework disregards the diagnosis as an outcome. • VBH considers diagnosis only if wrong or a cause of complications. • A correct diagnosis is the first outcome that matters to patients. • Metrics to measure radiologists' impacts on patient outcomes are key. • The value provided by radiology is multifaceted, going beyond exam volumes.

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.

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

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.

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.

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.

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.

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.

[Dynamic changes of inflammation-related indices in venous thromboembolism and the association between these indices and venous thromboembolism].

PubMed

Liu, Fang-fang; Zhai, Zhen-guo; Yang, Yuan-hua; Wang, Jun; Wang, Chen

2013-06-25

To evaluate the dynamic changes of inflammation-related indices in blood during the development of venous thromboembolism (VTE) and the association between these indices and VTE. A total of 95 VTE hospitalized patients(41 males,54 females) were recruited from Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital from January 2010 to December 2010. Comparisons of inflammation-related indices including white blood cell (WBC), neutrophil (NE), fibrinogen (FBG), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were conducted between VTE patients and normal ranges. And the dynamic changes of these indices during the development of VTE were evaluated. Then they were divided into subgroups according to disease stage, gender, age, VTE type, body mass index, smoking status and clinical manifestations. And statistical analyses were performed to elucidate the associations between these indices and VTE. The levels of NE and CRP in VTE patients (0.72, 15.0 mg/L) and ESR in male VTE patients (20.0 mm/1 h) were elevated compared with normal ranges; while WBC (male 7.27×10(9)/L, female 8.67×10(9)/L), FBG (male 3621 mg/L, female 3201 mg/L) and female ESR (19.5 mm/1 h) in VTE patients were within the normal ranges. The level of CRP was higher in acute (mean rank order value: 49.72) and sub-acute (mean rank order value: 44.80) VTE patients than chronic VTE patients (mean rank order value: 30.25). The level of FBG, CRP and ESR in patients ≥ 50 years old increased versus those <50 years old (mean rank order values 48.83 vs 34.53, 44.32 vs 28.90 and 45.95 vs 27.84 respectively), the patients whose body mass index (BMI) <25 kg/m(2) had higher WBC level than those whose BMI ≥ 25 kg/m(2) (mean rank order values 52.96 vs 36.46); smoking VTE patients had elevated FBG and CRP levels than non-smoking VTE patients (mean rank order values 57.75 vs 42.69 and 53.92 vs 37.75 respectively); compared with those without clinical manifestations of periphery pulmonary artery involved, the patients with clinical manifestations had higher levels of FBG, CRP and ESR (mean rank order values 59.24 vs 37.39, 52.68 vs 33.19 and 50.08 vs 36.55 respectively). The above differences had statistical significance (all P < 0.05). Some inflammation-related indices frequently used in clinical settings become elevated in VTE patients. Part of these indices show higher levels in VTE acute and sub-acute stages, and in older, non-obese, smoking and periphery pulmonary artery involved VTE patients.

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.

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

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.

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.

Absence of exchange interaction between localized magnetic moments and conduction-electrons in diluted Er{sup 3+} gold-nanoparticles

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

Lesseux, G. G., E-mail: lesseux@ifi.unicamp.br; Urbano, R. R.; Iwamoto, W.

2014-05-07

The Electron Spin Resonance (ESR) of diluted Er{sup 3+} magnetic ions in Au nanoparticles (NPs) is reported. The NPs were synthesized by reducing chloro triphenyl-phosphine gold(I) and erbium(III) trifluoroacetate. The Er{sup 3+} g-value along with the observed hyperfine splitting indicate that the Er{sup 3+} impurities are in a local cubic symmetry. Furthermore, the Er{sup 3+} ESR spectra show that the exchange interaction between the 4f and the conduction electrons (ce) is absent or negligible in Au{sub 1–x}Er{sub x} NPs, in contrast to the ESR results in bulk Au{sub 1–x}Er{sub x}. Therefore, the nature of this interaction needs to be reexaminedmore » at the nano scale range.« less

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.

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

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.

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.

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.

Magnetometry with Ensembles of Nitrogen Vacancy Centers in Bulk Diamond

DTIC Science & Technology

2015-10-23

the ESR curve. Any frequency components of the photodetector signal which are not close to the reference frequency, are filtered out. This mitigates ...indicating that we have not yet run up against thermal or flicker noise for these time scales. 5.3 Details of frequency modulation circuit In order

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.

Degradation of poly(2-hydroxyethyl methacrylate) by gamma irradiation

NASA Astrophysics Data System (ADS)

Hill, David J. T.; O'Donnell, James H.; Pomery, Peter J.; Saadat, Giti

1996-11-01

Electron Spin Resinance (ESR) spectroscopy has been utilised to examine the effect of high energy radiation on poly(2-hydroxyethyl methacrylate) PHEMA. Radiation chemical yields ( G-values) for radicals were 1.7 and 1.2 for γ-irradiation at 77 K and ambient temperature, respectively. The ESR spectra at 77 and 300 K were simulated. The ESR spectrum at 77 K is a combination of six types of radicals ·CH 3, ·CH 2CH 2OH, COOCHCH 2OH, ·COO-, -CH- and ·CHO. However, after room temperature irradiation, the spectrum is a combination of methacrylate main chain scission radical and -CH-. The high stability of this radical at room temperature indicates the system is very rigid as a result of hydrogen bonding from the inherent side chain structure and radiation induced crosslinking due to labile hydrogen atoms in the side chain.

Electron spin resonance study of CuGa1-xMnxSe2 magnetic semiconducting compounds

NASA Astrophysics Data System (ADS)

Fermin, José R.; Nava, Alexander; Durante-Rincón, C. A.; Castro, Jaime; Silva, Pedro J.

2013-02-01

We report on the magnetic properties of the diluted magnetic semiconductor CuGa1-xMnxSe2. For this, Electron spin resonance (ESR) experiments in the temperature range 70 K

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.

ESR and 230Th/234U dating of speleothems from Aladağlar Mountain Range (AMR) in Turkey

NASA Astrophysics Data System (ADS)

Ulusoy, Ülkü; Anbar, Gül; Bayarı, Serdar; Uysal, Tonguç

2014-03-01

Electron spin resonance (ESR) and 230Th/234U ages of speleothem samples collected from karstic caves located around 3000 m elevation in the Aladağlar Mountain Range (AMR), south-central Turkey, were determined in order to provide new insight and information regarding late Pleistocene climate. ESR ages were validated with the 230Th/234U ages of test samples. The ESR ages of 21 different layers of six speleothem samples were found to range mostly between about 59 and 4 ka, which cover the Marine Oxygen Isotope Stages (MIS) MIS 3 to MIS 1. Among all, only six layers appear to have deposited during MIS 8 and 5. Most of the samples dated were deposited during the late glacial stage (MIS 2). It appears that a cooler climate with a perennial and steady recharge was more conducive to speleothem development rather than a warmer climate with seasonal recharge in the AMR during the late Quaternary. This argument supports previous findings that suggest a two -fold increase in last glacial maximum mean precipitation in Turkey with respect to the present value.

Electron Spin Resonance and optical absorption spectroscopic studies of manganese centers in aluminium lead borate glasses.

PubMed

SivaRamaiah, G; LakshmanaRao, J

2012-12-01

Electron Spin Resonance (ESR) and optical absorption studies of 5Al(2)O(3)+75H(3)BO(3)+(20-x)PbO+xMnSO(4) (where x=0.5, 1,1.5 and 2 mol% of MnSO(4)) glasses at room temperature have been studied. The ESR spectrum of all the glasses exhibits resonance signals with effective isotropic g values at ≈2.0, 3.3 and 4.3. The ESR resonance signal at isotropic g≈2.0 has been attributed to Mn(2+) centers in an octahedral symmetry. The ESR resonance signals at isotropic g≈3.3 and 4.3 have been attributed to the rhombic symmetry of the Mn(2+) ions. The zero-field splitting parameter (zfs) has been calculated from the intensities of the allowed hyperfine lines. The optical absorption spectrum exhibits an intense band in the visible region and it has been attributed to (5)E(g)→(5)T(2g) transition of Mn(3+)centers in an octahedral environment. The optical band gap and the Urbach energies have been calculated from the ultraviolet absorption edges. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Calculating the ankylosing spondylitis disease activity score if the conventional c-reactive protein level is below the limit of detection or if high-sensitivity c-reactive protein is used: an analysis in the DESIR cohort.

PubMed

Machado, Pedro; Navarro-Compán, Victoria; Landewé, Robert; van Gaalen, Floris A; Roux, Christian; van der Heijde, Désirée

2015-02-01

The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite measure of disease activity in axial spondyloarthritis. The aims of this study were to determine the most appropriate method for calculating the ASDAS using the C-reactive protein (CRP) level when the conventional CRP level was below the limit of detection, to determine how low CRP values obtained by high-sensitivity CRP (hsCRP) measurement influence ASDAS-CRP results, and to test agreement between different ASDAS formulae. Patients with axial spondyloarthritis who had a conventional CRP level below the limit of detection (5 mg/liter) were selected (n = 257). The ASDAS–conventional CRP with 11 different imputations for the conventional CRP value (range 0–5 mg/liter, at 0.5-mg/liter intervals) was calculated. The ASDAS-hsCRP and ASDAS using the erythrocyte sedimentation rate (ESR) were also calculated. Agreement between the ASDAS formulae was tested. The ASDAS-hsCRP showed better agreement with the ASDAS-CRP calculated using the conventional CRP imputation values of 1.5 and 2.0 mg/liter and with the ASDAS-ESR than with other imputed formulae. Disagreement occurred mainly in lower disease activity states (inactive/moderate disease activity). When the CRP value was <2 mg/liter, the resulting ASDAS-CRP scores may have been inappropriately low. When the conventional CRP level is below the limit of detection or when the hsCRP level is <2 mg/liter, the constant value of 2 mg/liter should be used to calculate the ASDAS-CRP score. There is good agreement between the ASDAS-hsCRP and ASDAS-ESR; however, formulae are not interchangeable.

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.

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

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.

Microfluidic channel flow cell for simultaneous cryoelectrochemical electron spin resonance.

PubMed

Wain, Andrew J; Compton, Richard G; Le Roux, Rudolph; Matthews, Sinead; Fisher, Adrian C

2007-03-01

A novel microfluidic electrochemical channel flow cell has been constructed for in situ operation in a cylindrical TE011 resonant ESR cavity under variable temperature conditions. The cell has a U-tube configuration, consisting of an inlet and outlet channel which run parallel and contain evaporated gold film working, pseudo-reference, and counter electrodes. This geometry was employed to permit use in conjunction with variable temperature apparatus which does not allow a flow-through approach. The cell is characterized qualitatively and quantitatively using the one-electron reduction of p-bromonitrobenzene in acetonitrile at room temperature as a model system, and the ESR signal-flow rate response is validated by use of three-dimensional digital simulation of the concentration profile for a stable electrogenerated radical species under hydrodynamic conditions. The cell is then used to obtain ESR spectra for a number of radical species in acetonitrile at 233 K, including the radical anions of m- and p-iodonitrobenzene, o-bromonitrobenzene, and m-nitrobenzyl chloride, the latter three being unstable at room temperature. Spectra are also presented for the radical anion of 2-chloranthraquinone and the crystal violet radical, which display improved resolution at low temperatures.

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.

The polymyalgia rheumatica activity score in daily use: proposal for a definition of remission.

PubMed

Leeb, Burkhard F; Rintelen, Bernhard; Sautner, Judith; Fassl, Christian; Bird, Howard A

2007-06-15

To confirm the reliability and applicability of the Polymyalgia Rheumatica Disease Activity Score (PMR-AS), and to establish a threshold for remission. First, 78 patients with PMR (50 women/28 men, mean age 65.97 years) were enrolled in a cross-sectional evaluation. The PMR-AS, patient's satisfaction with disease status (PATSAT; range 1-5), erythrocyte sedimentation rate (ESR; first hour), and a visual analog scale of patients' general health assessment (VAS patient global; range 0-100) were recorded. Subsequently, another 39 PMR patients (24 women/15 men, mean age 68.12 years) were followed longitudinally. Relationships between the PMR-AS, PATSAT, ESR, and VAS patient global were analyzed by the Kruskal-Wallis test, Spearman's rank correlation, and kappa statistics. PMR-AS values in patients with a PATSAT score of 1 and a VAS patient global <10 formed the basis to establish a remission threshold. PMR-AS values were significantly related to PATSAT (P < 0.001), VAS patient global (P < 0.001), and ESR (P < 0.01). PATSAT and VAS patient global were reasonably different (kappa = 0.226). The median PMR-AS score in patients with PATSAT score 1 and VAS patient global <10 was 0.7 (range 0-3.3), and the respective 75th percentile was 1.3. To enhance applicability, a range from 0 to 1.5 was proposed to define remission in PMR. The median ESR in these patients was 10 mm/hour (range 3-28), indicating external validity. We demonstrated the reliability, validity, and applicability of the PMR-AS in daily routine. Moreover, we proposed a remission threshold (0-1.5) founded on patient-dependent parameters.

Serum inflammatory markers in the elderly: are they useful in differentiating sepsis from SIRS?

PubMed

Talebi-Taher, Mahshid; Babazadeh, Shahin; Barati, Mitra; Latifnia, Maryam

2014-01-01

Differentiating sepsis from other noninfectious causes of systemic inflammation is often difficult in the elderly. The aim of this study was to evaluate the ability of C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), procalcitonin (PCT), and Interleukin-6 (IL-6) to identify elderly patients with sepsis. In this single center prospective observational study, we included all consecutive elderly patients admitted with suspected sepsis and systemic inflammatory response syndrome (SIRS) in an emergency department. Blood samples for measuring CRP, PCT, IL-6, ESR and white blood cells (WBC) count were taken at first day of admission. Sensitivity, specificity, positive and negative predictive values were calculated for each inflammatory markers being studied. A total of 150 elderly patients aged 65 and older, 50 with sepsis and 50 with SIRS, and fifty individuals in a normal health status were included. CRP exhibited the greatest sensitivity (98%) and negative predictive value (98.6%) and performed best in differentiating patients with sepsis from those with SIRS. In a receiver operating characteristic curve analysis, IL-6 performed best in distinguishing between SIRS and the control group (AUC 0.75, 95% CI). On the other hand, both CRP and ESR appeared to be a more accurate diagnostic parameter for differentiating sepsis from SIRS among elderly patients.

Evaluation of a Powered Ankle-Foot Prosthesis during Slope Ascent Gait

PubMed Central

2016-01-01

Passive prosthetic feet lack active plantarflexion and push-off power resulting in gait deviations and compensations by individuals with transtibial amputation (TTA) during slope ascent. We sought to determine the effect of active ankle plantarflexion and push-off power provided by a powered prosthetic ankle-foot (PWR) on lower extremity compensations in individuals with unilateral TTA as they walked up a slope. We hypothesized that increased ankle plantarflexion and push-off power would reduce compensations commonly observed with a passive, energy-storing-returning prosthetic ankle-foot (ESR). We compared the temporal spatial, kinematic, and kinetic measures of ten individuals with TTA (age: 30.2 ± 5.3 yrs) to matched abled-bodied (AB) individuals during 5° slope ascent. The TTA group walked with an ESR and separately with a PWR. The PWR produced significantly greater prosthetic ankle plantarflexion and push-off power generation compared to an ESR and more closely matched AB values. The PWR functioned similar to a passive ESR device when transitioning onto the prosthetic limb due to limited prosthetic dorsiflexion, which resulted in similar deviations and compensations. In contrast, when transitioning off the prosthetic limb, increased ankle plantarflexion and push-off power provided by the PWR contributed to decreased intact limb knee extensor power production, lessening demand on the intact limb knee. PMID:27977681

Investigation of defects in In–Ga–Zn oxide thin film using electron spin resonance signals

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

Nonaka, Yusuke; Kurosawa, Yoichi; Komatsu, Yoshihiro

In–Ga–Zn oxide (IGZO) is a next-generation semiconductor material seen as an alternative to silicon. Despite the importance of the controllability of characteristics and the reliability of devices, defects in IGZO have not been fully understood. We investigated defects in IGZO thin films using electron spin resonance (ESR) spectroscopy. In as-sputtered IGZO thin films, we observed an ESR signal which had a g-value of g = 2.010, and the signal was found to disappear under thermal treatment. Annealing in a reductive atmosphere, such as N{sub 2} atmosphere, generated an ESR signal with g = 1.932 in IGZO thin films. The temperature dependence of the lattermore » signal suggests that the signal is induced by delocalized unpaired electrons (i.e., conduction electrons). In fact, a comparison between the conductivity and ESR signal intensity revealed that the signal's intensity is related to the number of conduction electrons in the IGZO thin film. The signal's intensity did not increase with oxygen vacancy alone but also with increases in both oxygen vacancy and hydrogen concentration. In addition, first-principle calculation suggests that the conduction electrons in IGZO may be generated by defects that occur when hydrogen atoms are inserted into oxygen vacancies.« less

Evaluation of a Powered Ankle-Foot Prosthesis during Slope Ascent Gait.

PubMed

Rábago, Christopher A; Aldridge Whitehead, Jennifer; Wilken, Jason M

2016-01-01

Passive prosthetic feet lack active plantarflexion and push-off power resulting in gait deviations and compensations by individuals with transtibial amputation (TTA) during slope ascent. We sought to determine the effect of active ankle plantarflexion and push-off power provided by a powered prosthetic ankle-foot (PWR) on lower extremity compensations in individuals with unilateral TTA as they walked up a slope. We hypothesized that increased ankle plantarflexion and push-off power would reduce compensations commonly observed with a passive, energy-storing-returning prosthetic ankle-foot (ESR). We compared the temporal spatial, kinematic, and kinetic measures of ten individuals with TTA (age: 30.2 ± 5.3 yrs) to matched abled-bodied (AB) individuals during 5° slope ascent. The TTA group walked with an ESR and separately with a PWR. The PWR produced significantly greater prosthetic ankle plantarflexion and push-off power generation compared to an ESR and more closely matched AB values. The PWR functioned similar to a passive ESR device when transitioning onto the prosthetic limb due to limited prosthetic dorsiflexion, which resulted in similar deviations and compensations. In contrast, when transitioning off the prosthetic limb, increased ankle plantarflexion and push-off power provided by the PWR contributed to decreased intact limb knee extensor power production, lessening demand on the intact limb knee.

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.

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

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.

Investigation of radiation-induced free radicals and luminescence properties in fresh pomegranate fruits.

PubMed

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

2013-05-01

Radiation-induced free radicals and luminescence properties were investigated in γ-irradiated (0-3 kGy) pomegranate ( Punica granatum L.) fruits. Photostimulated luminescence (PSL) analysis showed limited applicability, and only 3 kGy-irradiated pomegranates showed positive PSL values (>5000 PCs). Thermoluminescence (TL) glow curve features, such as intensity and the presence of maximum glow peak in radiation-specific temperature range (150-250 °C), provided definite proof of irradiation, and the TL ratios (TL1/TL2) also confirmed the reliability of TL results. Scanning electron microscopy energy dispersive X-ray (SEM-EDX) analysis of the separated minerals showed that feldspar and quartz minerals were responsible for the luminescence properties. Radiation-induced cellulose radicals were detected in the seeds and rinds by ESR analysis. The ESR results were better in freeze-dried samples than in alcohol-extracted ones. A positive correlation was found between the ESR and TL signal intensities and irradiation doses; however, the most promising detection of the irradiation status was possible through TL analysis.

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

Analysis of the Role of Carriership of Polymorphic Genotypes of ESR1, eNOS, and APOE4 Genes in the Development of Arterial Hypertension in Men.

PubMed

Dolgikh, O V; Zaitseva, N V; Nosov, A E; Krivtsov, A V; Dianova, D G; Kazakova, O A; Otavina, E A; Alikina, I N

2018-04-01

We studied the role of the carrier status for polymorphic loci of genes encoding estrogen receptors (ESR1), endothelial NO synthase (eNOS), and apolipoprotein E (APOE4) and products of their expression nitrogen oxide (NO) and apolipoprotein (ApoE) in the development of arterial hypertension in men. Conventionally healthy volunteers and 149 men with clinical manifestations of stage I-II arterial hypertension were examined. In men with arterial hypertension, the frequency of minor allele A of ESR1 gene was higher (27.5 vs. 9.5% in the reference group; χ 2 =4.43, p=0.04). The level of NO in the peripheral blood was also higher in the main group (χ 2 =3.93, p=0.047). The increase in NO concentration did not depend on the presence of polymorphic genotypes (GG and GT) of eNOS gene, but the decrease in ApoE level in blood serum was associated with TC genotype of APOE4 gene (p=0.04). Our results suggest that minor allele A of ESR1 gene is associated with the development of arterial hypertension in men. Reduced content of ApoE in blood serum of men with arterial hypertension was associated with APOE4 gene polymorphism. However, increased level of NO did not depend on polymorphic genotypes GG and GT of eNOS gene. These polymorphisms are of specific interest as additional markers of genetic predisposition to the development of arterial hypertension in middle-age men.

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

Multiferroicity of CuCrO2 tested by electron spin resonance

NASA Astrophysics Data System (ADS)

Gotovko, S. K.; Soldatov, T. A.; Svistov, L. E.; Zhou, H. D.

2018-03-01

We have carried out the electron spin resonance (ESR) study of the multiferroic triangular antiferromagnet CuCrO2 in the presence of an electric field. The shift of ESR spectra by the electric field was observed; the value of the shift exceeds that in materials with linear magnetoelectric coupling. It was shown that the low-frequency dynamics of magnetically ordered CuCrO2 is defined by joint oscillations of the spin plane and electric polarization. The results demonstrate an agreement with theoretical expectations of a phenomenological model [V. I. Marchenko, J. Exp. Theor. Phys. 119, 1084 (2014), 10.1134/S1063776114120073].

ESR/spin probe study of ice cream.

PubMed

Gillies, Duncan G; Greenley, Katherine R; Sutcliffe, Leslie H

2006-07-12

Spin probes based on the 1,1,3,3-tetramethylisoindolin-2-yl structure have been used, in conjunction with electron spin resonance spectroscopy (ESR), to study the physical changes occurring in ice cream during freezing and melting. The ESR measurements allowed the rotational correlation times, tau(B), of the spin probes to be determined. Two probes were used together in a given sample of ice cream, namely, 1,1,3,3-tetramethylisoindolin-2-yl (TMIO), which samples the fat phase, and the sodium salt of 1,1,3,3-tetramethylisoindolin-2-yloxyl-5-sulfonate (NaTMIOS), which samples the aqueous phase. Data from the TMIO probe showed that when ice cream is cooled, the fat phase is a mixture of solid and liquid fat until a temperature of approximately -60 degrees C is reached. The water-soluble probe NaTMIOS showed that the aqueous phase changes completely from liquid to solid within 1 degrees C of -18 degrees C. On cooling further to -24.7 degrees C and then allowing it to warm to +25.0 degrees C, the rotational correlation times of the NaTMIOS were slow to recover to their previous values. For the lipid phase, tau(B)(298) was found to be 65.7 +/- 2.0 ps and the corresponding activation enthalpy, DeltaH, was 32.5 +/- 0.9 kJ mol(-)(1): These values are typical of those expected to be found in the type of fat used to make ice cream. The water phase gave corresponding values of 32.2 +/- 0.5 ps and 24.5 +/- 0.4 kJ mol(-)(1) values, which are those expected for a sucrose concentration of 24%.

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.

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.

Free radical scavenging activities measured by electron spin resonance spectroscopy and B16 cell antiproliferative behaviors of seven plants.

PubMed

Calliste, C A; Trouillas, P; Allais, D P; Simon, A; Duroux, J L

2001-07-01

In an effort to discover new antioxidant natural compounds, seven plants that grow in France (most of them in the Limousin countryside) were screened. Among these plants, was the extensively studied Vitis vinifera as reference. For each plant, sequential percolation was realized with five solvents of increasing polarities (hexane, chloroform, ethyl acetate, methanol, and water). Free radical scavenging activities were examined in different systems using electron spin resonance (ESR) spectroscopy. These assays were based on the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), the hydroxyl radicals generated by a Fenton reaction, and the superoxide radicals generated by the X/XO system. Antiproliferative behavior was studied on B16 melanoma cells. ESR results showed that three plants (Castanea sativa, Filipendula ulmaria, and Betula pendula) possessed, for the most polar fractions (presence of phenolic compounds), high antioxidant activities in comparison with the Vitis vinifera reference. Gentiana lutea was the only one that presented a hydroxyl scavenging activity for the ethyl acetate and chloroform fractions. The antiproliferative test results showed that the same three plants are the most effective, but for the apolar fractions (chloroform and hexane).

Laboratory Tests for Diagnosis of Chronic Periprosthetic Joint Infection Can Help Predict Outcomes of Two-Stage Exchange.

PubMed

Dwyer, Maureen K; Damsgaard, Christopher; Wadibia, Jason; Wong, Gordon; Lazar, Damien; Smith, Eric; Talmo, Carl; Bedair, Hany

2018-06-20

Although 2-stage exchange arthroplasty is the most effective treatment among available strategies for managing chronic periprosthetic joint infection (PJI), rates of its success vary greatly. The purpose of our study was to examine whether objective measurements collected at the time of the diagnosis of PJI could be used to identify patients at risk of failure of 2-stage exchange. We identified 205 patients across 4 institutions who underwent 2-stage exchange arthroplasty for the treatment of PJI following total hip or total knee arthroplasty. Demographic, surgical, and laboratory data were obtained for each patient from their medical chart. Laboratory values included serum erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, synovial fluid white blood-cell (WBC) count and neutrophil percentage, synovial fluid and/or tissue culture, and Gram stain. Patients who underwent revision surgery for recurrent infection were considered to have failed the 2-stage procedure. Demographic, surgical, and laboratory variables were compared between the 2 groups. Receiver operating characteristic (ROC) curves were constructed to determine threshold cutoffs for significant laboratory values. Risk ratios and 95% confidence intervals were calculated. Overall, 2-stage exchange was unsuccessful for 27.3% of the patients. Preoperative serum ESR (p = 0.035) and synovial fluid WBC count (p = 0.008) and neutrophil percentage (p = 0.041) were greater in patients with recurrent infection. ROC curve analysis revealed a threshold of >60,000 cells/μL for synovial fluid WBC count, >92% for synovial fluid WBC neutrophil percentage, and >99 mm/hr for serum ESR. Failure of 2-stage exchange was 2.5 times more likely for patients with an elevated preoperative synovial fluid WBC count, 2.0 times more likely for those with an elevated preoperative synovial fluid WBC neutrophil percentage, and 1.8 times more likely for those with an elevated preoperative serum ESR. Our results demonstrated that a greater number of patients in whom 2-stage exchange arthroplasty ultimately failed had a preoperative synovial fluid WBC count of >60,000 cells/μL, a synovial fluid WBC neutrophil percentage of >92%, or a serum ESR of >99 mm/hr. Patients with elevated laboratory values had 1.8 to 2.5 times the risk of treatment failure. These data can serve as a clinical guideline to identify patients most at risk for failure of 2-stage exchange. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

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, 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.

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.

Correlation of rheumatoid arthritis activity indexes (Disease Activity Score 28 measured with ESR and CRP, Simplified Disease Activity Index and Clinical Disease Activity Index) and agreement of disease activity states with various cut-off points in a Northeastern Brazilian population.

PubMed

Medeiros, Marta Maria das Chagas; de Oliveira, Brenda Maria Gurgel Barreto; de Cerqueira, João Victor Medeiros; Quixadá, Raquel Telles de Souza; de Oliveira, Ídila Mont'Alverne Xavier

2015-01-01

The Disease Activity Score 28 (DAS28) and its versions have been used to measure rheumatoid arthritis (RA) activity, but there is no consensus about which one is the best. Determine the correlation among indexes (DAS28 ESR, DAS28 CRP, SDAI and CDAI) and evaluate agreement of activity strata using different cutoff points. Rheumatoid arthritis patients were cross-sectionally evaluated with data collection to calculate the DAS28 (ESR and CRP), SDAI and CDAI, using different cut-offs for defining remission, mild, moderate and high activity. Pearson correlations were calculated for continuous measures and agreement (kappa test) for the strata (remission, mild, moderate and high activity). Of 111 patients included, 108 were women, age 55.6 years, 11-year disease duration. DAS28 (ESR) was significantly higher than DAS28 (CRP) (4.0 vs. 3.5; p<0.001) and the values remained higher after stratification by age, gender, disease duration, rheumatoid factor and HAQ. Correlations among indexes ranged from 0.84 to 0.99, with better correlation between SDAI and CDAI. Agreements among activity strata ranged from 46.8% to 95.8%. DAS28 (CRP) with cut-off point for the remission of 2.3 underestimated disease activity by 45.8% compared with DAS28 (ESR). SDAI and CDAI showed agreement of 95.8%. The four indexes were associated with disease duration and HAQ. Although the activity indexes show good correlation, they show discrepancies in activity strata, thus requiring more researches to define a better index and better cutoff points. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Anisotropic magnetic interactions and spin dynamics in the spin-chain compound Cu (py) 2Br2 : An experimental and theoretical study

NASA Astrophysics Data System (ADS)

Zeisner, J.; Brockmann, M.; Zimmermann, S.; Weiße, A.; Thede, M.; Ressouche, E.; Povarov, K. Yu.; Zheludev, A.; Klümper, A.; Büchner, B.; Kataev, V.; Göhmann, F.

2017-07-01

We compare theoretical results for electron spin resonance (ESR) properties of the Heisenberg-Ising Hamiltonian with ESR experiments on the quasi-one-dimensional magnet Cu (py) 2Br2 (CPB). Our measurements were performed over a wide frequency and temperature range giving insight into the spin dynamics, spin structure, and magnetic anisotropy of this compound. By analyzing the angular dependence of ESR parameters (resonance shift and linewidth) at room temperature, we show that the two weakly coupled inequivalent spin-chain types inside the compound are well described by Heisenberg-Ising chains with their magnetic anisotropy axes perpendicular to the chain direction and almost perpendicular to each other. We further determine the full g tensor from these data. In addition, the angular dependence of the linewidth at high temperatures gives us access to the exponent of the algebraic decay of a dynamical correlation function of the isotropic Heisenberg chain. From the temperature dependence of static susceptibilities, we extract the strength of the exchange coupling (J /kB=52.0 K ) and the anisotropy parameter (δ ≈-0.02 ) of the model Hamiltonian. An independent compatible value of δ is obtained by comparing the exact prediction for the resonance shift at low temperatures with high-frequency ESR data recorded at 4 K . The spin structure in the ordered state implied by the two (almost) perpendicular anisotropy axes is in accordance with the propagation vector determined from neutron scattering experiments. In addition to undoped samples, we study the impact of partial substitution of Br by Cl ions on spin dynamics. From the dependence of the ESR linewidth on the doping level, we infer an effective decoupling of the anisotropic component J δ from the isotropic exchange J in these systems.

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.

Factors associated with sustained remission in patients with rheumatoid arthritis.

PubMed

Martire, María Victoria; Marino Claverie, Lucila; Duarte, Vanesa; Secco, Anastasia; Mammani, Marta

2015-01-01

To find out the factors that are associated with sustained remission measured by DAS28 and boolean ACR EULAR 2011 criteria at the time of diagnosis of rheumatoid arthritis. Medical records of patients with rheumatoid arthritis in sustained remission according to DAS28 were reviewed. They were compared with patients who did not achieved values of DAS28<2.6 in any visit during the first 3 years after diagnosis. We also evaluated if patients achieved the boolean ACR/EULAR criteria. Variables analyzed: sex, age, smoking, comorbidities, rheumatoid factor, anti-CCP, ESR, CRP, erosions, HAQ, DAS28, extra-articular manifestations, time to initiation of treatment, involvement of large joints, number of tender joints, number of swollen joints, pharmacological treatment. Forty five patients that achieved sustained remission were compared with 44 controls. The variables present at diagnosis that significantly were associated with remission by DAS28 were: lower values of DAS28, HAQ, ESR, NTJ, NSJ, negative CRP, absence of erosions, male sex and absence of involvement of large joints. Only 24.71% achieved the boolean criteria. The variables associated with sustained remission by these criteria were: lower values of DAS28, HAQ, ESR, number of tender joints and number of swollen joints, negative CRP and absence of erosions. The factors associated with sustained remission were the lower baseline disease activity, the low degree of functional disability and lower joint involvement. We consider it important to recognize these factors to optimize treatment. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

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.

Electron spin relaxation of synthetic melanin and melanin-containing human tissues as studied by electron spin echo and electron spin resonance.

PubMed

Okazaki, M; Kuwata, K; Miki, Y; Shiga, S; Shiga, T

1985-10-01

Electron spin lattice relaxation times (T1) and the phase memory times (Tm) were obtained for the synthetic melanin system from 3-hydroxytyrosine (dopa) by means of electron spin echo spectroscopy at 77 degrees K. Saturation behavior of the ESR spectra of melanins in melanin-containing tissue and of the synthetic melanin was also determined at the same temperature. The spin lattice relaxation time and the spectral diffusion time of the synthetic melanin are very long (4.3 ms and 101 microseconds, respectively, in the solid state), and the ESR signal saturates readily at low microwave powers. On the other hand, ESR spectra of natural melanins from the tissues chosen for this study, as well as those of synthetic melanins which contain Fe3+ of g = 4.3 and Mn2+ of g = 2, are relatively difficult to saturate compared with samples without such metal ions. These results show clearly that a large part of those two metal ions in sites responsible for the ESR spectral components with these particular g values are coordinated to melanin in melanin-containing tissue, and modify the magnetic relaxation behavior of the melanin. Accumulations of these metal ions in melanins are different from system to system, and they increase in the order: hair (black), retina and choroid (brown), malignant melanoma of eye and skin, and lentigo and nevus of skin.

Fingerprints of single nuclear spin energy levels using STM - ENDOR

NASA Astrophysics Data System (ADS)

Manassen, Yishay; Averbukh, Michael; Jbara, Moamen; Siebenhofer, Bernhard; Shnirman, Alexander; Horovitz, Baruch

2018-04-01

We performed STM-ENDOR experiments where the intensity of one of the hyperfine components detected in ESR-STM is recorded while an rf power is irradiated into the tunneling junction and its frequency is swept. When the latter frequency is near a nuclear transition a dip in ESR-STM signal is observed. This experiment was performed in three different systems: near surface SiC vacancies where the electron spin is coupled to a next nearest neighbor 29Si nucleus; Cu deposited on Si(111)7x7 surface, where the unpaired electron of the Cu atom is coupled to the Cu nucleus (63Cu, 65Cu) and on Tempo molecules adsorbed on Au(111), where the unpaired electron is coupled to a Nitrogen nucleus (14N). While some of the hyperfine values are unresolved in the ESR-STM data due to linewidth we find that they are accurately determined in the STM-ENDOR data including those from remote nuclei, which are not detected in the ESR-STM spectrum. Furthermore, STM-ENDOR can measure single nuclear Zeeman frequencies, distinguish between isotopes through their different nuclear magnetic moments and detect quadrupole spectra. We also develop and solve a Bloch type equation for the coupled electron-nuclear system that facilitates interpretation of the data. The improved spectral resolution of STM - ENDOR opens many possibilities for nanometric scale chemical analysis.

Fingerprints of single nuclear spin energy levels using STM - ENDOR.

PubMed

Manassen, Yishay; Averbukh, Michael; Jbara, Moamen; Siebenhofer, Bernhard; Shnirman, Alexander; Horovitz, Baruch

2018-04-01

We performed STM-ENDOR experiments where the intensity of one of the hyperfine components detected in ESR-STM is recorded while an rf power is irradiated into the tunneling junction and its frequency is swept. When the latter frequency is near a nuclear transition a dip in ESR-STM signal is observed. This experiment was performed in three different systems: near surface SiC vacancies where the electron spin is coupled to a next nearest neighbor 29 Si nucleus; Cu deposited on Si(111)7x7 surface, where the unpaired electron of the Cu atom is coupled to the Cu nucleus ( 63 Cu, 65 Cu) and on Tempo molecules adsorbed on Au(111), where the unpaired electron is coupled to a Nitrogen nucleus ( 14 N). While some of the hyperfine values are unresolved in the ESR-STM data due to linewidth we find that they are accurately determined in the STM-ENDOR data including those from remote nuclei, which are not detected in the ESR-STM spectrum. Furthermore, STM-ENDOR can measure single nuclear Zeeman frequencies, distinguish between isotopes through their different nuclear magnetic moments and detect quadrupole spectra. We also develop and solve a Bloch type equation for the coupled electron-nuclear system that facilitates interpretation of the data. The improved spectral resolution of STM - ENDOR opens many possibilities for nanometric scale chemical analysis. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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

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

PubMed Central

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

2016-01-01

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

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

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

PubMed

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

2015-11-11

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

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

PubMed

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

2015-10-28

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

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.

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.

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

24/7 Solar Minimum Polar Cap and Auroral Ion Temperature Observations

NASA Technical Reports Server (NTRS)

Sojka, Jan J.; Nicolls, Michael; van Eyken, Anthony; Heinselman, Craig; Bilitza, Dieter

2011-01-01

During the International Polar Year (IPY) two Incoherent Scatter Radars (ISRs) achieved close to 24/7 continuous observations. This presentation describes their data sets and specifically how they can provide the International Reference Ionosphere (IRI) a fiduciary E- and F-region ionosphere description for solar minimum conditions in both the auroral and polar cap regions. The ionospheric description being electron density, ion temperature and electron temperature profiles from as low as 90 km extending to several scale heights above the F-layer peak. The auroral location is Poker Flat in Alaska at 65.1 N latitude, 212.5 E longitude where the NSF s new Poker Flat Incoherent Scatter Radar (PFISR) is located. This location during solar minimum conditions is in the auroral region for most of the day but is at midlatitudes, equator ward of the cusp, for about 4-8 h per day dependent upon geomagnetic activity. In contrast the polar location is Svalbard, at 78.2 N latitude, 16.0 E longitude where the EISCAT Svalbard Radar (ESR) is located. For most of the day the ESR is in the Northern Polar Cap with a noon sector passage often through the dayside cusp. Of unique relevance to IRI is that these extended observations have enabled the ionospheric morphology to be distinguished between quiet and disturbed geomagnetic conditions. During the IPY year, 1 March 2007 - 29 February 2008, about 50 solar wind Corotating Interaction Regions (CIRs) impacted geospace. Each CIR has a two to five day geomagnetic disturbance that is observed in the ESR and PFISR observations. Hence, this data set also enables the quiet-background ionospheric climatology to be established as a function of season and local time. These two separate climatologies for the ion temperature at an altitude of 300 km are presented and compared with IRI ion temperatures. The IRI ion temperatures are about 200-300 K hotter than the observed values. However, the MSIS neutral temperature at 300 km compares favorably with the quiet-background in temperature, both in magnitude and climatology.

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.

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.

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

PubMed

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

2018-03-12

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

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

PubMed

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

2010-02-01

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

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.

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

PubMed

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

2018-04-01

Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287-395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3' partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6-7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies.

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.

Unusual diffusive effects on the ESR of Nd 3+ ions in the tunable topologically nontrivial semimetal YBiPt

DOE PAGES

Lesseux, G. G.; Garitezi, T. M.; Rosa, P. F. S.; ...

2016-02-24

Electron spin resonance (ESR) of diluted Nd 3+ ions in the topologically nontrivial semimetallic (TNSM) YBiPt compound is reported. The cubic YBiPt compound is a non-centrosymmetric half Heusler material which crystallizes in the F43m space group. The low temperature Nd 3+ ESR spectra showed a g-value of 2.66(4) corresponding to amore » $${{\\Gamma}_{6}}$$ cubic crystal field Kramers' doublet ground state. Remarkably, the observed metallic and diffusive (Dysonian) Nd 3+ lineshape presented an unusual dependence with grain size, microwave power, Nd 3+ concentration and temperature. Furthermore, the spin dynamic of the localized Nd 3+ ions in YBiPt was found to be characteristic of a phonon-bottleneck regime. It is claimed that, in this regime for YBiPt, phonons are responsible for mediating the diffusion of the microwave energy absorbed at resonance by the Nd 3+ ions to the thermal bath throughout the skin depth ($$\\delta \\simeq 15$$ μm). We argue that this is only possible because of the existence of highly mobile conduction electrons inside the skin depth of YBiPt that are strongly coupled to the phonons by spin–orbit coupling. Thus, our unexpected ESR results point to a coexistence of metallic and insulating behaviors within the skin depth of YBiPt. This scenario is discussed in the light of the TNSM properties of this compound.« less

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.

ESR teleradiology survey: results.

PubMed

2016-08-01

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

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.

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

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 Central

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

2013-01-01

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

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

PubMed

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

2013-01-01

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

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 ...

ESR1 Methylation: A Liquid Biopsy-Based Epigenetic Assay for the Follow-up of Patients with Metastatic Breast Cancer Receiving Endocrine Treatment.

PubMed

Mastoraki, Sophia; Strati, Areti; Tzanikou, Eleni; Chimonidou, Maria; Politaki, Eleni; Voutsina, Alexandra; Psyrri, Amanda; Georgoulias, Vassilis; Lianidou, Evi

2018-03-15

Purpose: Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of circulating tumor cells (CTCs) and plasma-circulating tumor DNA (ctDNA). ESR1 epigenetic silencing potentially affects response to endocrine treatment. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA as a potential biomarker for response to everolimus/exemestane treatment. Experimental Design: A highly sensitive and specific real-time MSP assay for ESR1 methylation was developed and validated in (i) 65 primary breast tumors formalin-fixed paraffin-embedded (FFPE), (ii) EpCAM + CTC fractions (122 patients and 30 healthy donors; HD), (iii) plasma ctDNA (108 patients and 30HD), and (iv) in CTCs (CellSearch) and in paired plasma ctDNA for 58 patients with breast cancer. ESR1 methylation status was investigated in CTCs isolated from serial peripheral blood samples of 19 patients with ER + /HER2 - advanced breast cancer receiving everolimus/exemestane. Results: ESR1 methylation was detected in: (i) 25/65 (38.5%) FFPEs, (ii) EpCAM + CTC fractions : 26/112 (23.3%) patients and 1/30 (3.3%) HD, and (iii) plasma ctDNA: 8/108 (7.4%) patients and 1/30 (3.3%) HD. ESR1 methylation was highly concordant in 58 paired DNA samples, isolated from CTCs (CellSearch) and corresponding plasma. In serial peripheral blood samples of patients treated with everolimus/exemestane, ESR1 methylation was observed in 10/36 (27.8%) CTC-positive samples, and was associated with lack of response to treatment ( P = 0.023, Fisher exact test). Conclusions: We report for the first time the detection of ESR1 methylation in CTCs and a high concordance with paired plasma ctDNA. ESR1 methylation in CTCs was associated with lack of response to everolimus/exemestane regimen. ESR1 methylation should be further evaluated as a potential liquid biopsy-based biomarker. Clin Cancer Res; 24(6); 1500-10. ©2017 AACR . ©2017 American Association for Cancer Research.

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

PubMed Central

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

2018-01-01

Abstract Background Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. Patients and methods To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287–395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. Results We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 3′ partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Conclusions Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6–7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies. PMID:29360925

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.

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.

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.

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.

Spin and charge ordering in organic conductors investigated by electron spin resonance

NASA Astrophysics Data System (ADS)

Tokumoto, Takahisa D.

This dissertation presents systematic studies on ordered states of organic conductors investigated mainly by Electron Spin Resonance (ESR). First, we describe an introduction to organic conductors. Organic conductors are based on conducting layers of highly planar donor molecules, separated by insulating layers of acceptors. The donor arrangements in the conducting layers determine the three simple parameters, transfer integral t between the donor molecules, onsite Coulomb interaction U and next neighboring Coulomb interaction V. Depending on the values of the above three parameters, a variety of ground states is realized and hence the organic conductors has become a main stream of condensed matter physics. Among many ground states, the main focus is on magnetic orders in this dissertation. Therefore we have employed ESR to probe local magnetic structures. And we cover a basic theory of ESR in paramagnetic/antiferromagnetically ordered states and the experimental realizations. Next, after an introduction to a system with an exchange interaction between d magnetic moments embedded at acceptor sites and pi spins at donor molecules is given, we discuss the effectiveness of systematic studies on isostructural magnetic and non-magnetic acceptor based organic conductors. Then, we go over one of the "exchange coupled" materials, beta-(BDA-TTP)2MCl 4 (M=Fe3+,Ga3+). We examine the origins of the Metal-Insulator transition and the long range antiferromangetic order in the magnetic acceptor based material, where we found the critical importance of the quantum fluctuations of pi spins. Finally, we delineate the magnetic order of alternating easy axes of a class of an organic conductor, tau-(P-(S,S)-DMEDT)2(AuBr2) 1+y, at low temperature/field by ESR. We briefly discuss the origin of this unprecedented magnetic structure in terms of the unstoichiometric ratio of donors to acceptors and the tetragonal symmetry of the unit cell. Then, we report the results of the ultra high field ESR to probe the magnetic structure changes around a hysteretic field induced metal insulator transition.

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

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.

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.

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.

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.

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

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.

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.

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.

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.

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

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.

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

PubMed

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

2016-09-01

ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor-positive advanced breast cancer. In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required. © 2016 by American Society of Clinical Oncology.

Mean platelet volume as an indicator of disease activity in juvenile SLE.

PubMed

Yavuz, Sevgi; Ece, Aydin

2014-05-01

The aim of the study was to assess mean platelet volume (MPV) in children with systemic lupus erythematosus (SLE) at the active and inactive stages. Twenty children with SLE and 30 age- and gender-matched controls were enrolled. Demographic data, SLE disease activity index (SLEDAI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), MPV, complement 3 (C3), complement 4 (C4), urine protein (Up), and urine creatinine (Ucr) values upon reactivation and remission phases were recorded. MPV was statistically higher in patients than in controls and significantly increased in active phase compared to inactive phase (p = 0.001). A MPV level of 8.4 fL was determined as predictive cutoff value of activation of SLE (sensitivity 75 %, specificity 90 %). MPV was positively correlated with SLEDAI (p = 0.01, r = 0.55), ESR (p = 0.01, r = 0.45), CRP (p = 0.04, r = 0.24), and Up/Ucr (p = 0.01, r = 0.45) and negatively correlated with C3 (p = 0.02, r = -0.36), albumin (p = 0.01, r = -0.63), and Hb (p = 0.01, r = -0.48). There was not any significant association between MPV and the histological classification of lupus nephritis (p = 0.65). MPV might be used as an early indicator of reactivation in children with SLE. MPV seemed to be more accurate than ESR, CRP, and C3 for monitoring the disease activity in SLE.

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.

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.

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

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.

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.

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

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer.

PubMed

Kukulj, Suzana; Jaganjac, Morana; Boranic, Milivoj; Krizanac, Simun; Santic, Zarko; Poljak-Blazi, Marija

2010-06-01

The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12 months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), alpha-1 globulin, and alpha-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.

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.

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

PubMed

Reinert, Tomás; Gonçalves, Rodrigo; Bines, José

2018-04-17

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

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.

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

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

PubMed

Baruah, Manash P; Bhattacharya, Bhaskar

2012-11-01

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). 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. 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 Tc(99) 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. 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. 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.

ESR signals in quartz for the studies of earth surface processes

NASA Astrophysics Data System (ADS)

Toyoda, S.; Shimada, A., , Dr; Takada, M.

2017-12-01

Various ESR (electron spin resonance) signals are observed in quartz. As they are formed by natural radiation, the signals are useful in dating of geological events, such as volcanic eruption, faulting and sedimentation. It was also found that those paramagnetic defects can be fingerprints of sediments, to be used for studies in sediment provenance. The signal of the E1' center, unpaired electron at an oxygen vacancy, was first used for such studies. A method was proposed to estimate the number of the precursors (oxygen vacancies) from the E1' center intensity. The number of oxygen vacancies in quartz was found to have positive correlation with the crystallization age. Using this feature, studies were quite successful in aeolian dust. It was shown that the sources of aeolian dust deposited in northern part of Japanese Islands were different between in MIS1 and MIS 2. In combination with crystallinity index, the contributions of the dust components from three origins were quantitatively obtained. After these, the provenance studies on river sediments have started where the impurity centers in quartz were employed, which are the Al center, the Ti centers, and the Ge centers. Sediments of Kizu River, Mie to Nara prefectures in Central Japan are most extensively studied. Firstly, it was shown that each of possible sources of granitic quartz around the reaches has respective characteristics in the number of oxygen vacancies and the signal intensities of impurity centers. Secondary, by the artificial mixing experiments, the impurity signal intensities have the values consistent with the mixing ratio of the two samples of quartz with different intensities. At river junctions, the mixing ratios were calculated from the ESR signals. At some locations, the mixing ratio values obtained from one signal were consistent with the ones from another signal while at some locations they were not. The latter inconsistent results would indicate that the river sediments are inhomogeneous and complicated. Several results will be presented showing the source to sink changes in the ESR signal intensities along with the river. The signals are basically consistent with the possible sources in the river beds having the variation due to the inflow of the tributaries.

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.

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.

[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.

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.

ENDOR/ESR of Mn atoms and MnH molecules in solid argon

NASA Astrophysics Data System (ADS)

van Zee, R. J.; Garland, D. A.; Weltner, W., Jr.

1986-09-01

Mn atoms and MnH molecules, the latter formed by reaction between metal and hydrogen atoms, were trapped in solid argon and their ESR/ENDOR spectra measured at 4 K. At each pumping magnetic field two ENDOR lines were observed for 55Mn(I=5/2) atoms, corresponding to hyperfine transitions within the MS =±1/2 levels. Values of the hyperfine interaction constant and nuclear moment of 55Mn were derived from the six sets of data. For MnH, three sets of signals were detected: a proton ``matrix ENDOR'' line, transitions in the MS =0,±1 levels involving MI (55Mn)=1/2, 3/2, 5/2 levels, and proton transitions corresponding to νH and νH±aH. Analysis yielded the hyperfine constant aH =6.8(1) MHz and the nuclear quadrupole coupling constant Q'(55Mn)=-11.81(2) MHz. The latter compared favorably with a theoretical value derived earlier by Bagus and Schaefer. A higher term in the spin Hamiltonian appeared to be necessary to fit the proton hyperfine data.

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.

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.

Value of supervised learning events in predicting doctors in difficulty.

PubMed

Patel, Mumtaz; Agius, Steven; Wilkinson, Jack; Patel, Leena; Baker, Paul

2016-07-01

In the UK, supervised learning events (SLE) replaced traditional workplace-based assessments for foundation-year trainees in 2012. A key element of SLEs was to incorporate trainee reflection and assessor feedback in order to drive learning and identify training issues early. Few studies, however, have investigated the value of SLEs in predicting doctors in difficulty. This study aimed to identify principles that would inform understanding about how and why SLEs work or not in identifying doctors in difficulty (DiD). A retrospective case-control study of North West Foundation School trainees' electronic portfolios was conducted. Cases comprised all known DiD. Controls were randomly selected from the same cohort. Free-text supervisor comments from each SLE were assessed for the four domains defined in the General Medical Council's Good Medical Practice Guidelines and each scored blindly for level of concern using a three-point ordinal scale. Cumulative scores for each SLE were then analysed quantitatively for their predictive value of actual DiD. A qualitative thematic analysis was also conducted. The prevalence of DiD in this sample was 6.5%. Receiver operator characteristic curve analysis showed that Team Assessment of Behaviour (TAB) was the only SLE strongly predictive of actual DiD status. The Educational Supervisor Report (ESR) was also strongly predictive of DiD status. Fisher's test showed significant associations of TAB and ESR for both predicted and actual DiD status and also the health and performance subtypes. None of the other SLEs showed significant associations. Qualitative data analysis revealed inadequate completion and lack of constructive, particularly negative, feedback. This indicated that SLEs were not used to their full potential. TAB and the ESR are strongly predictive of DiD. However, SLEs are not being used to their full potential, and the quality of completion of reports on SLEs and feedback needs to be improved in order to better identify and manage DiD. © 2016 John Wiley & Sons Ltd.

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.

Preliminary criteria for global flares in childhood-onset systemic lupus erythematosus.

PubMed

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

2011-09-01

To develop widely acceptable preliminary criteria of global flare for childhood-onset systemic lupus erythematosus (cSLE). Pediatric rheumatologists (n = 138) rated a total of 358 unique patient profiles with information about the cSLE flare descriptors from 2 consecutive visits: patient global assessment of well-being, physician global assessment of disease activity (MD-global), health-related quality of life, anti-double-stranded DNA antibodies, disease activity index scores, protein:creatinine (P:C) ratio, complement levels, and erythrocyte sedimentation rate (ESR). Based on 2,996 rater responses about the course of cSLE (baseline versus followup), the accuracy (sensitivity, specificity, and 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 American College of Rheumatology recommendations for the development and validation of criteria sets. The highest-ranked candidate criteria considered absolute changes (Δ) of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) or British Isles Lupus Assessment Group (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 of ≥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 increased with flare severity. 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. Copyright © 2011 by the American College of Rheumatology.

Comprehensive evaluation of the Estrogen Receptor Alpha gene reveals further evidence for association with type 2 diabetes enriched for nephropathy in an African American population

PubMed Central

Keene, Keith L.; Mychaleckyj, Josyf C.; Smith, Shelly G.; Leak, Tennille S.; Perlegas, Peter S.; Langefeld, Carl D.; Herrington, David M.; Freedman, Barry I.; Rich, Stephen S.; Bowden, Donald W.; Sale, Michèle M.

2009-01-01

We previously investigated the estrogen receptor α gene (ESR1) as a positional candidate for type 2 diabetes (T2DM), and found evidence for association between the intron 1-intron 2 region of this gene and type 2 diabetes and/or nephropathy in an African American (AA) population. Our objective was to comprehensively evaluate variants across the entire ESR1 gene for association in AA with T2DM and End Stage Renal Disease (T2DM-ESRD). One hundred fifty SNPs in ESR1, spanning 476 kb, were genotyped in 577 AA individuals with T2DM-ESRD and 596 AA controls. Genotypic association tests for dominant, additive, and recessive models, and haplotypic association, were calculated using a χ2 statistic and corresponding P value. Thirty-one SNPs showed nominal evidence for association (P< 0.05) with T2DM-ESRD in one or more genotypic model. After correcting for multiple tests, promoter SNP rs11964281 (nominal P=0.000291, adjusted P=0.0289), and intron 4 SNPs rs1569788 (nominal P=0.000754, adjusted P=0.0278) and rs9340969 (nominal P=0.00109, adjusted P=0.0467) remained significant at experimentwise error rate (EER) P<0.05 for the dominant class of tests. Twenty-three of the thirty-one associated SNPs cluster within the intron 4-intron 6 region. Gender stratification revealed nominal evidence for association with 35 SNPs in females (352 cases; 306 controls) and seven SNPs in males (225 cases; 290 controls). We have identified a novel region of the ESR1 gene that may contain important functional polymorphisms in relation to susceptibility to T2DM and/or diabetic nephropathy. PMID:18305958

Comprehensive evaluation of the estrogen receptor alpha gene reveals further evidence for association with type 2 diabetes enriched for nephropathy in an African American population.

PubMed

Keene, Keith L; Mychaleckyj, Josyf C; Smith, Shelly G; Leak, Tennille S; Perlegas, Peter S; Langefeld, Carl D; Herrington, David M; Freedman, Barry I; Rich, Stephen S; Bowden, Donald W; Sale, Michèle M

2008-05-01

We previously investigated the estrogen receptor alpha gene (ESR1) as a positional candidate for type 2 diabetes (T2DM), and found evidence for association between the intron 1-intron 2 region of this gene and T2DM and/or nephropathy in an African American (AA) population. Our objective was to comprehensively evaluate variants across the entire ESR1 gene for association in AA with T2DM and end stage renal disease (T2DM-ESRD). One hundred fifty SNPs in ESR1, spanning 476 kb, were genotyped in 577 AA individuals with T2DM-ESRD and 596 AA controls. Genotypic association tests for dominant, additive, and recessive models, and haplotypic association, were calculated using a chi(2) statistic and corresponding P value. Thirty-one SNPs showed nominal evidence for association (P < 0.05) with T2DM-ESRD in one or more genotypic model. After correcting for multiple tests, promoter SNP rs11964281 (nominal P = 0.000291, adjusted P = 0.0289), and intron 4 SNPs rs1569788 (nominal P = 0.000754, adjusted P = 0.0278) and rs9340969 (nominal P = 0.00109, adjusted P = 0.0467) remained significant at experimentwise error rate (EER) P

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

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.

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

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.

META-ANALYSIS OF GENOME-WIDE STUDIES IDENTIFIES WNT16 AND ESR1 SNPS ASSOCIATED WITH BONE MINERAL DENSITY IN PREMENOPAUSAL WOMEN

PubMed Central

Koller, Daniel L.; Zheng, Hou-Feng; Karasik, David; Yerges-Armstrong, Laura; Liu, Ching-Ti; McGuigan, Fiona; Kemp, John P.; Giroux, Sylvie; Lai, Dongbing; Edenberg, Howard J.; Peacock, Munro; Czerwinski, Stefan A.; Choh, Audrey C.; McMahon, George; St Pourcain, Beate; Timpson, Nicholas J.; Lawlor, Debbie A; Evans, David M; Towne, Bradford; Blangero, John; Carless, Melanie A.; Kammerer, Candace; Goltzman, David; Kovacs, Christopher S.; Prior, Jerilynn C.; Spector, Tim D.; Rousseau, Francois; Tobias, Jon H.; Akesson, Kristina; Econs, Michael J.; Mitchell, Braxton D.; Richards, J. Brent; Kiel, Douglas P.; Foroud, Tatiana

2013-01-01

Previous genome-wide association studies (GWAS) have identified common variants in genes associated with variation in bone mineral density (BMD), although most have been carried out in combined samples of older women and men. Meta-analyses of these results have identified numerous SNPs of modest effect at genome-wide significance levels in genes involved in both bone formation and resorption, as well as other pathways. We performed a meta-analysis restricted to premenopausal white women from four cohorts (n= 4,061 women, ages 20 to 45) to identify genes influencing peak bone mass at the lumbar spine and femoral neck. Following imputation, age- and weight-adjusted BMD values were tested for association with each SNP. Association of a SNP in the WNT16 gene (rs3801387; p=1.7 × 10−9) and multiple SNPs in the ESR1/C6orf97 (rs4870044; p=1.3 × 10−8) achieved genome-wide significance levels for lumbar spine BMD. These SNPs, along with others demonstrating suggestive evidence of association, were then tested for association in seven Replication cohorts that included premenopausal women of European, Hispanic-American, and African-American descent (combined n=5,597 for femoral neck; 4,744 for lumbar spine). When the data from the Discovery and Replication cohorts were analyzed jointly, the evidence was more significant (WNT16 joint p=1.3 × 10−11; ESR1/C6orf97 joint p= 1.4 × 10−10). Multiple independent association signals were observed with spine BMD at the ESR1 region after conditioning on the primary signal. Analyses of femoral neck BMD also supported association with SNPs in WNT16 and ESR1/C6orf97 (p< 1 × 10−5). Our results confirm that several of the genes contributing to BMD variation across a broad age range in both sexes have effects of similar magnitude on BMD of the spine in premenopausal women. These data support the hypothesis that variants in these genes of known skeletal function also affect BMD during the premenopausal period. PMID:23074152

Insufficient sensitivity of joint aspiration during the two-stage exchange of the hip with spacers.

PubMed

Boelch, Sebastian Philipp; Weissenberger, Manuel; Spohn, Frederik; Rudert, Maximilian; Luedemann, Martin

2018-01-10

Evaluation of infection persistence during the two-stage exchange of the hip is challenging. Joint aspiration before reconstruction is supposed to rule out infection persistence. Sensitivity and specificity of synovial fluid culture and synovial leucocyte count for detecting infection persistence during the two-stage exchange of the hip were evaluated. Ninety-two aspirations before planned joint reconstruction during the two-stage exchange with spacers of the hip were retrospectively analyzed. The sensitivity and specificity of synovial fluid culture was 4.6 and 94.3%. The sensitivity and specificity of synovial leucocyte count at a cut-off value of 2000 cells/μl was 25.0 and 96.9%. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were significantly higher before prosthesis removal and reconstruction or spacer exchange (p = 0.00; p = 0.013 and p = 0.039; p = 0.002) in the infection persistence group. Receiver operating characteristic area under the curve values before prosthesis removal and reconstruction or spacer exchange for ESR were lower (0.516 and 0.635) than for CRP (0.720 and 0.671). Synovial fluid culture and leucocyte count cannot rule out infection persistence during the two-stage exchange of the hip.

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

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

Steroid signaling system responds differently to temperature and hormone manipulation in the red-eared slider turtle (Trachemys scripta elegans), a reptile with temperature-dependent sex determination.

PubMed

Ramsey, M; Crews, D

2007-01-01

Many reptiles, including the red-eared slider turtle (Trachemys scripta elegans), exhibit temperature-dependent sex determination (TSD). Temperature determines gonadal sex during the middle of embryogenesis, or the temperature-sensitive period (TSP), when gonadal sex is labile to both temperature and hormones--particularly estrogen. The biological actions of steroid hormones are mediated by their receptors as defined here as the classic transcriptional regulation of target genes. To elucidate estrogen action during sex determination, we examined estrogen receptor alpha (Esr1, hereafter referred to as ERalpha), estrogen receptor beta (Esr2, hereafter referred to as ERbeta), and androgen receptor (Ar, hereafter referred to as AR) expression in slider turtle gonads before, during and after the TSP, as well as following sex reversal via temperature or steroid hormone manipulation. ERalpha and AR levels spike at the female-producing temperature while ovarian sex is determined, but none of the receptors exhibited sexually dimorphic localization within the gonad prior to morphological differentiation. All three receptors respond differentially to sex-reversing treatments. When shifted to female-producing temperatures, embryos maintain ERalpha and AR expression while ERbeta is reduced. When shifted to male-producing temperatures, medullary expression of all three receptors is reduced. Feminization via estradiol (E(2)) treatment at a male-producing temperature profoundly changed the expression patterns for all three receptors. ERalpha and ERbeta redirected to the cortex in E(2)-created ovaries, while AR medullary expression was transiently reduced. Although warmer incubation temperature and estrogen result in the same endpoint (ovarian development), our results indicate different steroid signaling patterns between temperature- and estrogen-induced feminization. 2007 S. Karger AG, Basel

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

PubMed

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

2014-06-01

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

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

PubMed

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

2015-10-01

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

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.

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

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

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.

Serum HDL-C levels, log (TG/HDL-C) values and serum total cholesterol/HDL-C ratios significantly correlate with radiological extent of disease in patients with community-acquired pneumonia.

PubMed

Deniz, Omer; Tozkoparan, Ergun; Yaman, Halil; Cakir, Erdinc; Gumus, Seyfettin; Ozcan, Omer; Bozlar, Ugur; Bilgi, Cumhur; Bilgic, Hayati; Ekiz, Kudret

2006-03-01

In several studies, it was shown that there was a marked decrease in serum levels of HDL-C during infection and inflammation in general. In particular, a decrease in the level of serum HDL-C was also shown in pneumonia. Correlations between inflammatory markers such as acute phase proteins, cytokines and serum HDL-C levels were shown. However, there are no studies indicating a correlation between serum HDL-C levels and the radiological extent of the disease (RED) in community-acquired pneumonia (CAP). We hypothesized that there could be a relationship between serum HDL-C levels and RED in CAP. A case-controlled study, including 97 patients with CAP and 45 healthy subjects, was performed. Chest X-rays of CAP patients were scored for RED, and correlations were investigated between RED scores, serum lipid parameters, the erythrocyte sedimentation rate (ESR) and serum albumin levels. The mean serum HDL-C level was lower in CAP patients than in controls. A significant and negative correlation between RED scores (REDS) and serum HDL-C levels was detected (r = -0.64, P = 0.0001). There were also significant correlations between REDS and other lipid parameters. Significant correlations between ESR and serum HDL-C levels and between ESR and other serum lipid parameters were also found. It appears that serum HDL-C levels are generally lower in CAP cases than in healthy controls. Serum HDL-C levels and serum albumin levels might decrease and serum total cholesterol/HDL-C ratios and log (TG/HDL-C) values might increase proportionally with RED in CAP patients. These results might have some significance for individuals having long-standing and/or recurrent pneumonia and other cardiovascular risk factors.

Added value of 18F-FDG PET/CT in diagnosing infected hip prosthesis.

PubMed

Kwee, Robert M; Broos, Wouter Am; Brans, Boudewijn; Walenkamp, Geert Him; Geurts, Jan; Weijers, René E

2018-05-01

Background The diagnosis of infected hip prosthesis is frequently not straightforward yet very important as it changes treatment. Purpose To retrospectively investigate the added value of 18F-FDG PET/CT to conventional tests including radiography, erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) testing, and joint aspiration, in diagnosing infected hip prosthesis. Material and Methods Seventy-eight hip prostheses of 78 patients (55% men; mean age = 66.5 years; age range = 30-85 years) with non-specific clinical presentation, i.e. no abscess or sinus tract communicating with the joint space at clinical examination, were analyzed. Cultures of intra-articular fluid and peri-implant tissues after revision surgery or clinical follow-up ≥6 months served as gold standard. Areas under the receiver operating characteristic curves (AUCs) of radiography, ESR/CRP testing, aspiration culture, and white blood cell (WBC) count without and with the addition of 18F-FDG PET/CT were compared. Results The addition of 18F-FDG PET/CT increased AUCs: for radiography with 0.212, P = 0.001; for ESR/CRP testing with 0.076, P = 0.072; for aspiration culture with 0.126, P = 0.032; and for aspiration WBC count with 0.191, P = 0.035. Conclusion This study shows that 18F-FDG PET/CT adds to individual conventional tests in diagnosing infected hip prosthesis. It may improve the preoperative planning and should therefore be considered in the diagnostic work-up. Future studies should define the exact place of 18F-FDG PET/CT in the diagnostic work-up of periprosthetic joint infection.

Erythrocyte Sedimentation Rate Levels among a Sample of Pregnant Women Attending Health Centers in Erbil-Iraq

ERIC Educational Resources Information Center

Khazal, Suhad Ali; Zangana, Jwan M. Sabir

2016-01-01

There are so many significant hematological changes occurring in pregnancy, erythrocyte sedimentation rate (ESR) is one of them. The objectives of this study were to determine the range of erythrocyte sedimentation rate values obtained in healthy pregnant women and to examine the effect of gestational age and hemoglobin concentration on…

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.

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.

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.

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.

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.

IntelliCable Interface Specification

DTIC Science & Technology

2016-07-14

address to configure itself for. NiMH/NiCAD: The checking of this bit means that this particular battery is not a Lithium - ion but is a NiCAD or a NiMH...value of 0, Lithium , should be used for all class of Lithium batteries , including Lithium - Ion and Lithium -Polymer. These all function much the same...2590 is Lithium - Ion but the 390 is NiMH, which have incompatible charging schemes. Offset 48 – ESR Value This field is the Equivalent Series

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.

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.

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.

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.

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

Effect of Sidaguri (Sidarhombifolia L) on C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in osteoarthritis patients

NASA Astrophysics Data System (ADS)

Marpaung, B.; Siregar, J.

2018-03-01

Osteoarthritis (OA) is degenerative and inflammatory joint diseases. Management of OA, until now limited only to overcome the pain, inflammation, and improvement of joint function with medication in the form of NSAIDs that have many side effects. Damage to cells due to the stimulus will free various mediators or substances inflammation such as prostaglandin, IL-6, TNF-α and nitric oxide. Sidaguri plant (Sidarhombifolia L) has anti-inflammatory activity by inhibition of nitric oxide. The mechanism of action Meloxicam, like other NSAIDs, may be associated with the inhibition of prostaglandin synthetase (cyclo-oxygenase). One of the markers of the inflammatory process is CRP and ESR. We tested 50 patients divided into two groups, patients who get Meloxicam and Sidaguri (n = 25) and patients who get Meloxicam and placebo (n = 25). There were significant changes before and after therapy with p-value<0.0001.

Chemical analysis applied to the radiation sterilization of solid ketoprofen

NASA Astrophysics Data System (ADS)

Colak, S.; Maquille, A.; Tilquin, B.

2006-01-01

The aim of this work is to investigate the feasibility of radiation sterilization of ketoprofen from a chemical point of view. Although irradiated ketoprofen has already been studied in the literature [Katusin-Razem et al., Radiat. Phys. Chem. 73 111-116 (2005)], new results, on the basis of electron spin resonance (ESR) measurements and the use of hyphenated techniques (GC-MS and LC-MS), are obtained. The ESR spectra of irradiated ketoprofen consists of four unresolved resonance peaks and the mean G-value of ketoprofen is found to be 4 +/- 0.9 nmoles/J, which is very small. HPLC-UV analyses indicate that no significant loss of ketoprofen is detected after irradiation. LC-MS-MS analyses show that the structures of the non-volatile final products are similar to ketoprofen. Benzaldehyde is detected in the irradiated samples after dynamic-extraction GC-MS. The analyses show that ketoprofen is radioresistant and therefore might be radiosterilized.

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.

Acute rhinosinusitis (ARS). Diagnosis and treatment of adults in general practice.

PubMed

Hansen, Jens Georg

2014-02-01

The idea behind this thesis is to present how ARS and especially acute maxillary sinusitis in adults is diagnosed and treated in general practice. The study extends over many years, beginning with the first survey in 1991. Based on doctors' answers, we then investigated the diagnostic values ​​of the symptoms, signs and examinations which the doctors reported using. All patients over 18 years suspected of acute maxillary sinusitis were included consecutively and only once and, after a clinical examination with the GP, they were offered the opportunity to enter into the prospective study referred to acute CT scan and by changes in the CT, immediately referred to sinus puncture. Both examinations were conducted at Aalborg Hospital. The disease was found most frequently in younger and 2/3 were women. The reason for this gender difference is unknown. We have assessed the diagnostic values of the symptoms, objective findings and investigations ​​using 3 different reference standards: sinus puncture, microbiological diagnosis and CT scan described in three articles. In all examinations, it appeared that the usual signs and symptoms of acute maxillary sinusitis occur almost equally often and with a few exceptions in patients, with and without pus in the sinus cavities. Pain in the sinus cavities occurring in 95% of patients, and only elevated levels of CRP and ESR are significantly and independently associated with pus in the sinus cavities. This finding is surprising, because they are two nonspecific markers. CRP tested by near-patient testing has, within the investigations period, been introduced in general practice, and from 1999 the doctors also get reimbursed for performing the test. We have on this background originally defined a clinical criterion with pain over the sinuses accompanied by elevated values ​​of CRP and/or ESR giving a sensitivity of 0.82, specificity 0.57, ppv 0.68 and npv 0.74. But looking at the ROC curve we suggest that a more clinical relevant diagnose will be based on use of CRP alone, as the test can be made easily and fast while the patient is in the clinic compared to the use of ESR. The disease is over-diagnosed in general practice. In only 53% of patients, who the GP suspected of having acute sinusitis, was there detected pus or mucopus at the sinus puncture, furthermore the patients' statements that they had had sinusitis was significantly negatively associated with current acute maxillary sinusitis. Almost all patients are prescribed topical treatment to the nose in the form of vasoconstrictor, and 50-70% also antibiotics. The most common bacteria that can be isolated are S. pneumoniae and H. influenzae. For many years the first drug of choice has been penicillin V, and treatment with penicillin V has followed Scandinavian recommendations. However, the resistance patterns in respect of H. influenzae have changed over the years and if the dominant flora is H. influenzae, then oral penicillin is not sufficient anymore, and should be replaced by amoxicillin with or without clavulanate. It is reported that the MIC of penicillin V is too high, such that oral dosage cannot provide sufficiently high concentrations. However, in daily clinical practice the doctor does not have the possibility to decide whether the infection is caused by either S. pneumoniae or H. influenzae, unless a sinus puncture is performed and it is not considered as a standard procedure. The recommended treatment is therefore starting with penicillin V, and at treatment failure switching to amoxicillin with or without clavulanate. It is well known that URTI's can exacerbate a chronic pulmonary disease - like asthma - in allergic patients, but this influence is also demonstrated as described in article 6 where ARS in adults without any sign of chronic lung disease or allergy is accompanied by a temporary reduction lung function. Future research should focus on the use of CRP in general practice, analysing cost-effectiveness of the use of CRP patient outcome in relation to antibiotic treatment, clarification of ARS as a female disease, and a detailed exploration of the relationship between URTI's and impaired lung function in lung-healthy patients.

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…

Resonant polarization transfer from electron spins to nuclear spins-or to muon spins-in semiconductors

NASA Astrophysics Data System (ADS)

Henstra, A.; Wenckebach, W. Th.

1991-02-01

A review is given of newly developed pulsed Electron Spin Resonance (ESR) methods for dynamic polarization of nuclear spins. The application of two of these methods, Nuclear Orientation Via Electron spin Locking (NOVEL) and the Integrated Solid Effect (ISE), for the polarization of nuclear spins in semiconductors is discussed in more detail. It is proposed to use these methods to study the ESR spectrum of unpaired electrons in the vicinity of muons that are bound in a solid. Thus, ESR would be observed with a sensitivity which is enhanced by about ten orders of magnitude compared to conventional ESR.

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

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.

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.

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

Agreement of central site measurements and land use regression modeled oxidative potential of PM{sub 2.5} with personal exposure

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

Yang, Aileen, E-mail: Yang@uu.nl; Institute for Risk Assessment Sciences, Division Environmental Epidemiology, Utrecht University, P.O. Box 80.178, 3508TD Utrecht; Hoek, Gerard

Oxidative potential (OP) of ambient particulate matter (PM) has been suggested as a health-relevant exposure metric. In order to use OP for exposure assessment, information is needed about how well central site OP measurements and modeled average OP at the home address reflect temporal and spatial variation of personal OP. We collected 96-hour personal, home outdoor and indoor PM{sub 2.5} samples from 15 volunteers living either at traffic, urban or regional background locations in Utrecht, the Netherlands. OP was also measured at one central reference site to account for temporal variations. OP was assessed using electron spin resonance (OP{sup ESR})more » and dithiothreitol (OP{sup DTT}). Spatial variation of average OP at the home address was modeled using land use regression (LUR) models. For both OP{sup ESR} and OP{sup DTT}, temporal correlations of central site measurements with home outdoor measurements were high (R>0.75), and moderate to high (R=0.49–0.70) with personal measurements. The LUR model predictions for OP correlated significantly with the home outdoor concentrations for OP{sup DTT} and OP{sup ESR} (R=0.65 and 0.62, respectively). LUR model predictions were moderately correlated with personal OP{sup DTT} measurements (R=0.50). Adjustment for indoor sources, such as vacuum cleaning and absence of fume-hood, improved the temporal and spatial agreement with measured personal exposure for OP{sup ESR}. OP{sup DTT} was not associated with any indoor sources. Our study results support the use of central site OP for exposure assessment of epidemiological studies focusing on short-term health effects. - Highlights: • Oxidative potential (OP) of PM was proposed as a health-relevant exposure metric. • We evaluated the relationship between measured and modeled outdoor and personal OP. • Temporal correlations of central site with personal OP are moderate to high. • Adjusting for indoor sources improved the agreement with personal OP. • Our results support the use of central site OP for short-term health effect studies.« less

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.

The effect of simulated low earth orbit radiation on polyimides (UV degradation study)

NASA Technical Reports Server (NTRS)

Forsythe, John S.; George, Graeme A.; Hill, David J. T.; Odonnell, James H.; Pomery, Peter J.; Rasoul, Firas A.

1995-01-01

UV degradation of polyimide films in air and vacuum were studied using UV-visible, ESR, FTIR, and XPS spectroscopies. The UV-visible spectra of polyimide films showed a blue shift in the absorption compared to Kapton. This behavior was attributed to the presence of bulky groups and kinks along the polymer chains which disrupt the formation of a charge transfer complex. The UV-visible spectra showed also that UV irradiation of polyimides result extensively in surface degradation, leaving the bulk of the polymer intact. ESR spectra of polyimides irradiated in vacuum revealed the formation of stable carbon-centered radicals which give a singlet ESR spectrum, while polyimides irradiated in air produced an asymmetric signal shifted to a lower magnetic field, with a higher g value and line width. This signal was attributed to oxygen-cenetered radicals of peroxy and/or alkoxy type. The rate of radical formation in air was two fold higher than for vacuum irradiation, and reached a plateau after a short time. This suggests a continuous depletion of radicals on the surface via an ablative degradation process. FTIR, XPS, and weight loss studies supported this postulate. An XPS study of the surface indicated a substantial increase in the surface oxidation after irradiation in air. The sharp increase in the C-O binding energy peak relative to the C-C peak was believed to be associated with an aromatic ring opening reaction.

Moving towards high-power, high-frequency and low-resistance CNT supercapacitors by tuning the CNT length, axial deformation and contact resistance

NASA Astrophysics Data System (ADS)

Basiricò, L.; Lanzara, G.

2012-08-01

In this paper it is shown that the electrochemical behaviour of vertically aligned multi-walled carbon nanotube (VANT) supercapacitors is influenced by the VANTs’ length (electrode thickness), by their axial compression and by their interface with the current collector. It is found that the VANTs, which can be interpreted as a dense array of nanochannels, have an active area available to ions that is strongly affected by the electrode’s thickness and compressional state. Consequently, the tested thinner electrodes, compressed electrodes or a combination of the two were found to be characterized by a significant improvement in terms of power density (up to 1246%), knee frequency (58 822% working up to 10 kHz), equivalent series resistance (ESR, up to 67%) and capacitance (up to 21%) when compared with thicker and/or uncompressed electrodes. These values are significantly higher than those reported in the literature where long VANTs with no control on compression are typically used. It is also shown that the ESR can be reduced not only by using shorter and compressed VANTs that have a higher conductance or by improving the electrode/collector electrical contact by changing the contact morphology at the nanoscale through compression, but also by depositing a thin platinum layer on the VANT tips in contact with the current collector (73% ESR decrease).

Moving towards high-power, high-frequency and low-resistance CNT supercapacitors by tuning the CNT length, axial deformation and contact resistance.

PubMed

Basiricò, L; Lanzara, G

2012-08-03

In this paper it is shown that the electrochemical behaviour of vertically aligned multi-walled carbon nanotube (VANT) supercapacitors is influenced by the VANTs' length (electrode thickness), by their axial compression and by their interface with the current collector. It is found that the VANTs, which can be interpreted as a dense array of nanochannels, have an active area available to ions that is strongly affected by the electrode's thickness and compressional state. Consequently, the tested thinner electrodes, compressed electrodes or a combination of the two were found to be characterized by a significant improvement in terms of power density (up to 1246%), knee frequency (58,822% working up to 10 kHz), equivalent series resistance (ESR, up to 67%) and capacitance (up to 21%) when compared with thicker and/or uncompressed electrodes. These values are significantly higher than those reported in the literature where long VANTs with no control on compression are typically used. It is also shown that the ESR can be reduced not only by using shorter and compressed VANTs that have a higher conductance or by improving the electrode/collector electrical contact by changing the contact morphology at the nanoscale through compression, but also by depositing a thin platinum layer on the VANT tips in contact with the current collector (73% ESR decrease).

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.

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.

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

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.

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.

LCR circuit: new simple methods for measuring the equivalent series resistance of a capacitor and inductance of a coil

NASA Astrophysics Data System (ADS)

Ivković, Saša S.; Marković, Marija Z.; Ivković, Dragica Ž.; Cvetanović, Nikola

2017-09-01

Equivalent series resistance (ESR) represents the measurement of total energy loss in a capacitor. In this paper a simple method for measuring the ESR of ceramic capacitors based on the analysis of the oscillations of an LCR circuit is proposed. It is shown that at frequencies under 3300 Hz, the ESR is directly proportional to the period of oscillations. Based on the determined dependence of the ESR on the period, a method is devised and tested for measuring coil inductance. All measurements were performed using the standard equipment found in student laboratories, which makes both methods very suitable for implementation at high school and university levels.

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.

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.

PLUME and research sotware

NASA Astrophysics Data System (ADS)

Baudin, Veronique; Gomez-Diaz, Teresa

2013-04-01

The PLUME open platform (https://www.projet-plume.org) has as first goal to share competences and to value the knowledge of software experts within the French higher education and research communities. The project proposes in its platform the access to more than 380 index cards describing useful and economic software for this community, with open access to everybody. The second goal of PLUME focuses on to improve the visibility of software produced by research laboratories within the higher education and research communities. The "development-ESR" index cards briefly describe the main features of the software, including references to research publications associated to it. The platform counts more than 300 cards describing research software, where 89 cards have an English version. In this talk we describe the theme classification and the taxonomy of the index cards and the evolution with new themes added to the project. We will also focus on the organisation of PLUME as an open project and its interests in the promotion of free/open source software from and for research, contributing to the creation of a community of shared knowledge.

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

A Short Study of Large Rotary Forged Cylinders

DTIC Science & Technology

1979-06-01

ESR Steel Hollow ESR Steel Rotary Forge Vacuum Degassed Steel 20. ABSTRACT (Continue on reverse aide It necessary and identity by block number...treatment rging Line was used to produce steel for the Advanced ocram. Cylinders were rotary forged from cast hollow ESR ssed steel . Anomalies in the data...prompted a more detailed The results are presented. Satisfactory properties were cuum degassed steel . However, the very light forging th the very

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.

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

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.

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.

Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women.

PubMed

Koller, Daniel L; Zheng, Hou-Feng; Karasik, David; Yerges-Armstrong, Laura; Liu, Ching-Ti; McGuigan, Fiona; Kemp, John P; Giroux, Sylvie; Lai, Dongbing; Edenberg, Howard J; Peacock, Munro; Czerwinski, Stefan A; Choh, Audrey C; McMahon, George; St Pourcain, Beate; Timpson, Nicholas J; Lawlor, Debbie A; Evans, David M; Towne, Bradford; Blangero, John; Carless, Melanie A; Kammerer, Candace; Goltzman, David; Kovacs, Christopher S; Prior, Jerilynn C; Spector, Tim D; Rousseau, Francois; Tobias, Jon H; Akesson, Kristina; Econs, Michael J; Mitchell, Braxton D; Richards, J Brent; Kiel, Douglas P; Foroud, Tatiana

2013-03-01

Previous genome-wide association studies (GWAS) have identified common variants in genes associated with variation in bone mineral density (BMD), although most have been carried out in combined samples of older women and men. Meta-analyses of these results have identified numerous single-nucleotide polymorphisms (SNPs) of modest effect at genome-wide significance levels in genes involved in both bone formation and resorption, as well as other pathways. We performed a meta-analysis restricted to premenopausal white women from four cohorts (n = 4061 women, aged 20 to 45 years) to identify genes influencing peak bone mass at the lumbar spine and femoral neck. After imputation, age- and weight-adjusted bone-mineral density (BMD) values were tested for association with each SNP. Association of an SNP in the WNT16 gene (rs3801387; p = 1.7 × 10(-9) ) and multiple SNPs in the ESR1/C6orf97 region (rs4870044; p = 1.3 × 10(-8) ) achieved genome-wide significance levels for lumbar spine BMD. These SNPs, along with others demonstrating suggestive evidence of association, were then tested for association in seven replication cohorts that included premenopausal women of European, Hispanic-American, and African-American descent (combined n = 5597 for femoral neck; n = 4744 for lumbar spine). When the data from the discovery and replication cohorts were analyzed jointly, the evidence was more significant (WNT16 joint p = 1.3 × 10(-11) ; ESR1/C6orf97 joint p = 1.4 × 10(-10) ). Multiple independent association signals were observed with spine BMD at the ESR1 region after conditioning on the primary signal. Analyses of femoral neck BMD also supported association with SNPs in WNT16 and ESR1/C6orf97 (p < 1 × 10(-5) ). Our results confirm that several of the genes contributing to BMD variation across a broad age range in both sexes have effects of similar magnitude on BMD of the spine in premenopausal women. These data support the hypothesis that variants in these genes of known skeletal function also affect BMD during the premenopausal period. Copyright © 2013 American Society for Bone and Mineral Research.

Routinely detected indicators in plasma have a predictive effect on the identification of HIV-infected patients with non-tuberculous mycobacterial and tuberculous infections.

PubMed

Cai, Ren-Tian; Yu, Feng-Xue; Tao, Zhen; Qian, Xue-Qin; Chen, Jun; Lu, Hong-Zhou

2017-11-02

It is difficult to quickly distinguish non-tuberculous mycobacterial (NTM) infection from tuberculosis (TB) infection in human immunodeficiency virus (HIV)-infected patients because of many similarities between these diseases. A simple and effective way to determine the differences using routine blood tests is necessary in developing countries. A retrospective cohort study was conducted to recruit HIV-infected patients with either NTM infection or TB infection diagnosed for the first time according to mycobacterial culture and microscopic identification from May 2010 to March 2016. These data included the analysis of blood cells, liver function, renal function, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), and were compared between the HIV/TB and HIV/NTM groups. A total of 240 patients were enrolled. The number of HIV/TB and HIV/NTM patients was 113 and 127, respectively. There were no significant differences in the CD4 T-cell count, age, sex, percentage of patients initiating antiretroviral therapy (ART) before the explicit diagnosis of TB or NTM infection. NTM infection was more likely to be restricted in the pulmonary while TB infection also involves extra-pulmonary sites. Both the leukocyte count(5.60 × 10 9 /L) and the proportion of neutrophils in the leukocyte count (76.70%) in the HIV/TB group were significantly higher than those in the HIV/NTM group (4.40 × 10 9 /L [P = 0.0014] and 69.30% [P < 0.001]. The analysis of liver function markers indicated that the concentration of albumin but not ALT and AST was significantly lower in the HIV/TB group than in the HIV/NTM group (P < 0.001). The creatinine and urea levels were not significantly different between the two groups. The ESR (84.00 mm/h) and the concentration of CRP (59.60 mg/L) were significantly higher in the HIV/TB group than in the HIV/NTM group (52.00 mm/h and 19.60 mg/L, respectively) (P < 0.001). To distinguish TB infection from NTM infection, the best cut-off value was 69.5 mm/h for ESR, with a positive predictive value (PPV) of 0.740 and negative predictive value (NPV) of 0.721, and 48.8 mg/L for CRP, with a PPV of 0.676 and NPV of 0.697. The dissemination character as well as stronger immune response characterized by higher inflammation markers (e.g. WBC, ESR, CRP) can help distinguish TB from NTM infection in HIV-infected patients who need empirical therapy or diagnostic therapy immediately in low-income areas.

Feasibility study of entrance and exit dose measurements at the contra lateral breast with alanine/electron spin resonance dosimetry in volumetric modulated radiotherapy of breast cancer

NASA Astrophysics Data System (ADS)

Wagner, Daniela M.; Hüttenrauch, Petra; Anton, Mathias; von Voigts-Rhetz, Philip; Zink, Klemens; Wolff, Hendrik A.

2017-07-01

The Physikalisch-Technische Bundesanstalt has established a secondary standard measurement system for the dose to water, D W, based on alanine/ESR (Anton et al 2013 Phys. Med. Biol. 58 3259-82). The aim of this study was to test the established measurement system for the out-of-field measurements of inpatients with breast cancer. A set of five alanine pellets were affixed to the skin of each patient at the contra lateral breast beginning at the sternum and extending over the mammilla to the distal surface. During 28 fractions with 2.2 Gy per fraction, the accumulated dose was measured in four patients. A cone beam computer tomography (CBCT) scan was generated for setup purposes before every treatment. The reference CT dataset was registered rigidly and deformably to the CBCT dataset for 28 fractions. To take the actual alanine pellet position into account, the dose distribution was calculated for every fraction using the Acuros XB algorithm. The results of the ESR measurements were compared to the calculated doses. The maximum dose measured at the sternum was 19.9 Gy  ±  0.4 Gy, decreasing to 6.8 Gy  ±  0.2 Gy at the mammilla and 4.5 Gy  ±  0.1 Gy at the distal surface of the contra lateral breast. The absolute differences between the calculated and measured doses ranged from  -1.9 Gy to 0.9 Gy. No systematic error could be seen. It was possible to achieve a combined standard uncertainty of 1.63% for D W  =  5 Gy for the measured dose. The alanine/ESR method is feasible for in vivo measurements.

Comparison of Photo Optical Imaging with Musculoskeletal Ultrasound and Clinical Examination in the Assessment of Inflammatory Activity in Proximal Interphalangeal Joints in Rheumatoid Arthritis and Osteoarthritis.

PubMed

Amitai, Isabella; Werner, Stephanie; Schicke, Bernd; Burmester, Gerd-Rüdiger; Minet, Olaf; Zabaryło, Urszula; Backhaus, Marina; Ohrndorf, Sarah

2015-09-01

Lightscan is a novel, rapid, low-cost, easily operated and noninvasive imaging technology used to assess inflammatory activity in proximal interphalangeal (PIP) joints. The results are calculated automatically. To our knowledge, this is the first comparative study of photo optical imaging (POI), with clinical examination (CE), disease activity score at 28 joints (DAS28)-erythrocyte sedimentation rate (ESR), and musculoskeletal ultrasonography (US) in healthy subjects and patients with rheumatoid arthritis (RA) or osteoarthritis (OA). There were 688 PIP joints of both hands examined in 87 subjects (38 RA, 21 OA, 28 healthy) by Lightscan and compared with CE for clinically swollen and tender joints, DAS28-ESR (only RA), and US. With US as reference, POI had a sensitivity of 74% and a specificity of 93%. In the receiver-operating curve (ROC) analysis, the Lightscan showed a higher sensitivity and specificity [area under the curve (AUC) 0.879] for the distinction of healthy subjects versus patients (OA, RA) than US in greyscale (GSUS; AUC 0.797) and power Doppler (PDUS; AUC 0.67). POI correlated significantly with GSUS (r 0.473, p < 0.01) and PDUS (r 0.486, p < 0.01). The agreement rates between POI and GSUS were up to 79%, between POI and PDUS up to 92%, and between POI and CE up to 66%. POI did not correlate with DAS28-ESR. The Lightscan is a new technology offering sensitive imaging detection of inflammatory changes in subjects with RA and OA with PIP arthritis. POI was more sensitive than CE and correlated significantly to GSUS and PDUS, while presenting a higher sensitivity and specificity for the detection of healthy subjects versus patients (RA, OA) based on the ROC analysis.

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.

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

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.

Immune function in Amazonian horticulturalists

PubMed Central

Blackwell, Aaron D.; Trumble, Benjamin C.; Suarez, Ivan Maldonado; Stieglitz, Jonathan; Beheim, Bret; Snodgrass, J. Josh; Kaplan, Hillard; Gurven, Michael

2016-01-01

Background Amazonian populations are exposed to diverse parasites and pathogens, including protozoal, bacterial, fungal, and helminthic infections. Yet much of our understanding of the immune system is based on industrialised populations where these infections are relatively rare. Aim We examine distributions and age-related differences in 22 measures of immune function for Bolivian forager-horticulturalists and US and European populations. Subjects and Methods Subjects were 6,338 Tsimane aged 0–90 years. Blood samples collected between 2004–2014 were analysed for 5-part blood differentials, C-reactive protein, erythrocyte sedimentation rate (ESR), and total immunoglobulins E, G, A, and M. Flow cytometry was used to quantify naive and non-naïve CD4 and CD8 T cells, natural killer cells, and B cells. Results Compared to reference populations, Tsimane have elevated levels of most immunological parameters, particularly immunoglobulins, eosinophils, ESR, B cells, and natural killer cells. However, monocytes and basophils are reduced and naïve CD4 cells depleted in older age groups. Conclusion Tsimane ecology leads to lymphocyte repertoires and immunoglobulin profiles that differ from those observed in industrialised populations. These differences have consequences for disease susceptibility and co-vary with patterns of other life history traits, such as growth and reproduction. PMID:27174705

A multiple dating approach (luminescence and electron spin resonance) to assess rates of crustal deformation using Quaternary fluvial terraces of the lower Moulouya River (NE Morocco)

NASA Astrophysics Data System (ADS)

Bartz, Melanie; Rixhon, Gilles; Duval, Mathieu; King, Georgina; Brückner, Helmut

2017-04-01

The Moulouya River, the largest catchment in Morocco, drains an area characterized by active crustal deformation during the Late Cenozoic due to the convergence between the African and Eurasian plates. Our study focuses on the lowermost reach of the river in NE Morocco, where a thrust zone associated with N-S compressive shortening in this region was identified (Barcos et al., 2014; Rixhon et al., 2017). New geomorphological results demonstrate contrasting fluvial environments on each side of the thrust: long-lasting fluvial aggradation, materialized by >37 m-thick stacked fill terraces, and the development of a well-preserved terrace staircase, with three Pleistocene terrace levels, occurred in the footwall and the hanging wall, respectively (Rixhon et al., 2017). Here, we present a preliminary geochronological background for these contrasting terrace systems based on a multiple dating approach. Samples for (i) luminescence (pIRIR225 and pIRIR290 dating of coarse-grained K-feldspars) and (ii) electron spin resonance (ESR dating of coarse-grained quartz) from four different profiles were collected. (i) Due to the application of the athermal detrapping model by Huntley (2006) (modified after Kars et al., 2008), it appears that the feldspar signals are in sample specific field saturation. Our results yielded minimum ages of 0.9 Ma and 0.7 Ma for the footwall and hanging wall, respectively. (ii) Using the multiple centre approach with ESR dating (Duval et al., 2015), we measured both the aluminium (Al) and the titanium (Ti) centres in order to evaluate whether they would provide consistent results. Results indicate that De values of the Al centre are either slightly higher compared to those of the Ti centre or they agree within a 1σ-error range, which may simply be due to the slower bleaching kinetics of the Al centre. Thus, the ESR ages were inferred from the Ti centre. Ages between 1.35±0.10 and 1.17±0.10 Ma in the footwall show sediment aggradation between MIS 40 and MIS 32, whilst the last terrace formation in the hanging wall is dated between 1.19±0.11 and 1.61±0.15 Ma, indicating even older fluvial deposition. This study shows the high potential of the multiple centre approach in ESR dating, especially when dealing with samples beyond the dating range of luminescence techniques. Nevertheless, independent age control is still required to evaluate the reliability of the ESR dating results; this will be achieved in the near future using palaeomagnetism (CENIEH, Burgos) and isochron burial dating (26Al/10Be) on the same deposits. The acquisition of a reliable chronological framework based on different techniques will eventually give new insights into the rate of Quaternary crustal deformation in this region of Morocco. References: Barcos, L., Jabaloy, A., Azdimousa, A., Asebriy, L., Gómez-Ortiz, D., Rodríguez-Peces, M.J., Tejero, R., Pérez-Peña, J.V., 2014. Study of relief changes related to active doming in the eastern Moroccan Rif (Morocco) using geomorphological indices. J. African Earth Sci. 100, 493-509. Duval, M., Sancho, C., Calle, M., Guilarte, V., Penna-Monné, J.L., 2015. On the interest of using the multiple centre approach in ESR dating of optically bleached quartz grains: Some examples from the Early Pleistocene terraces of the Alcanadre River (Ebro basin, Spain). Quat. Geochr. 29, 58-69. Huntley, 2006. An explanation of the power-law decay of luminescence. Journal of Physics: Condensed Matter 18, 1359-1365. Kars, R.H., Wallinga, J., Cohen, K.M., 2008. A new approach towards anomalous fading correction for feldspar IRSL dating - tests on samples in field saturation. Radiation Measurements 43, 786-790. Rixhon, G., Bartz, M., El Ouahabi, M., Szemkus, N., Brückner, H., 2017, Contrasting terrace systems of the lower Moulouya river as indicator of crustal deformation in NE Morocco. J. African Earth Sci. 126, 45-47.

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.

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.

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.

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.

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)

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

PubMed

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

2018-01-01

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

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

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

H-modulated microwave absorption and resistive transition in the high- Tc superconductor YBa 2Cu 3O 7

NASA Astrophysics Data System (ADS)

Buluggiu, E.; Vera, A.; Amoretti, G.

1990-11-01

The derivative microwave absorption near Tc in presence of a sufficiently high field ( H⩾1 kOe) is related to the temperature variation of resistivity. This idea, originally proposed by Kim et al. (1988), is extended to take into account the effects of the anomalous resistive tail by using the thermoactivated flux-creep model proposed by Tinkham (1988). This gives a simple explanation for some relevant features observed in the temperature behaviour of the ESR absorption, as the asymmetry of the peak at Tc, with the long tail extending toward low temperatures, and the field dependence of height and linewidth, for which the model provides H-1 and H2/3 behaviour, respectively, ESR data on YBa 2Cu 3O 7 powder are in satisfactory agreement with this picture, when the role of the intrinsic 2D-character of this compound is properly taken into account. This allows us to deduce consistent values for the parameters a‖ and a⊥ of the anisotropic resistivity.

ESR study of aqueous dispersions of beta-lactoglobulin and spin-labelled glyceryl monostearate.

PubMed

Van Gorkom, M; Van der Molen, M H; Korver, O

1975-05-05

From the ESR spectra of aqueous dispersions of synthetic glyceryl monostearate (spin labelled at C-12) a critical micelle concentration of 30 mumol/l at room temperature was obtained, which agrees with that deduced from surface tension measurements. At monoglyceride concentrations smaller or larger than the critical micelle concentration, the monomers show increased motional restriction with increasing molar ratio of beta-lactoglobulin to monoglyceride up to a value of 10, as determined from calculated rotational correlation times; A similar progressive interaction was deduced from spectral changes observed on equimolar dispersions of beta-lactoglobulin and monoglyceride on raising the temperature to 55 degrees C at which the protein and monoglyceride coprecipitate. The relevance of these finding for non-labelled monoglyceride dispersions is indicated by the similarity of the pH-dependent flocculation behaviour of labelled and non-labelled monoglycerides, both in the absence and presence of beta-lactoglobulin; In addition, proton magnetic resonance and mechanical stability measurements suggest that spin-labelled glyceryl monosterate behaves analogously to non-labelled glyceryl monooleate.

An investigation of the iron-sulphur proteins of benzene dioxygenase from Pseudomonas putida by electron-spin-resonance spectroscopy.

PubMed Central

Geary, P J; Saboowalla, F; Patil, D; Cammack, R

1984-01-01

Benzene dioxygenase from Pseudomonas putida comprises three components, namely a flavoprotein (NADH:ferredoxin oxidoreductase; Mr 81000), an intermediate electron-transfer protein, or ferredoxin (Mr 12000) with a [2Fe-2S] cluster, and a terminal dioxygenase containing two [2Fe-2S] iron-sulphur clusters (Mr 215000), which requires two additional Fe2+ atoms/molecule for oxygenase activity. The ferredoxin and the dioxygenase give e.s.r. signals in the reduced state with rhombic symmetry and average g values of 1.92 and 1.896 respectively. The mid-point redox potentials were determined by e.s.r. titration at pH 7.0 to be -155 mV and -112 mV respectively. The signal from the dioxygenase shows pronounced g anisotropy and most closely resembles those of 4-methoxybenzoate mono-oxygenase from Pseudomonas putida and the [2Fe-2S] 'Rieske' proteins of the quinone-cytochrome c region of electron-transport chains of respiration and photosynthesis. PMID:6324743

A Novel Highly Bioavailable Curcumin Formulation Improves Symptoms and Diagnostic Indicators in Rheumatoid Arthritis Patients: A Randomized, Double-Blind, Placebo-Controlled, Two-Dose, Three-Arm, and Parallel-Group Study.

PubMed

Amalraj, Augustine; Varma, Karthik; Jacob, Joby; Divya, Chandradhara; Kunnumakkara, Ajaikumar B; Stohs, Sidney J; Gopi, Sreeraj

2017-10-01

Rheumatoid arthritis (RA) is an autoimmune, chronic systemic inflammatory disorder. The long-term use of currently available drugs for the treatment of RA has many potential side effects. Natural phytonutrients may serve as alternative strategies for the safe and effective treatment of RA, and curcuminoids have been used in Ayurvedic medicine for the treatment of inflammatory conditions for centuries. In this study, a novel, highly bioavailable form of curcumin in a completely natural turmeric matrix was evaluated for its ability to improve the clinical symptoms of RA. A randomized, double-blind, placebo-controlled, three-arm, parallel-group study was conducted to evaluate the comparative efficacy of two different doses of curcumin with that of a placebo in active RA patients. Twelve patients in each group received placebo, 250 or 500 mg of the curcumin product twice daily for 90 days. The responses of the patients were assessed using the American College of Rheumatology (ACR) response, visual analog scale (VAS), C-reactive protein (CRP), Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) values. RA patients who received the curcumin product at both low and high doses reported statistically significant changes in their clinical symptoms at the end of the study. These observations were confirmed by significant changes in ESR, CPR, and RF values in patients receiving the study product compared to baseline and placebo. The results indicate that this novel curcumin in a turmeric matrix acts as an analgesic and anti-inflammatory agent for the management of RA at a dose as low as 250 mg twice daily as evidenced by significant improvement in the ESR, CRP, VAS, RF, DAS28, and ACR responses compared to placebo. Both doses of the study product were well tolerated and without side effects.

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.

Associations among body composition, inflammatory profile and disease extent in ulcerative colitis patients.

PubMed

Urbano, Ana Paula Signori; Sassaki, Ligia Yukie; Dorna, Mariana de Souza; Presti, Paula Torres; Carvalhaes, Maria Antonieta de Barros Leite; Martini, Ligia Araújo; Ferreira, Ana Lucia Anjos

2018-02-01

The aim of our study was to assess body composition status and its association with inflammatory profile and extent of intestinal damage in ulcerative colitis patients during clinical remission. This is a cross-sectional study in which body composition data (phase angle [PhA], fat mass [FM], triceps skin fold thickness [TSFt], mid-arm circumference [MAC], mid-arm muscle circumference [MAMC], adductor pollicis muscle thickness [APMt]), inflammatory profile (C-reactive protein [CRP], a1-acid glycoprotein, erythrocyte sedimentation rate [ESR]) and disease extent were recorded. The mean age of the 59 patients was 48.1 years; 53.3% were women. Most patients were in clinical remission (94.9%) and 3.4% was malnourished according to body mass index. PhA was inversely correlated with inflammatory markers such as CRP (R=-0.59; p<0.001) and ESR (R=-0.46; p<0.001) and directly correlated with lean mass: MAMC (R=0.31; p=0.01) and APMt (R=0.47; p<0.001). Lean mass was inversely correlated with non-specific inflammation marker (APMt vs. ESR) and directly correlated with hemoglobin values (MAMC vs. hemoglobin). Logistic regression analysis revealed that body cell mass was associated with disease extent (OR 0.92; 95CI 0.87-0.97; p<0.01). PhA was inversely correlated with inflammatory markers and directly correlated with lean mass. Acute inflammatory markers were correlated with disease extent. Body cell mass was associated with disease extent.

The formation of post-spreading volcanic ridges in the South China Sea

NASA Astrophysics Data System (ADS)

Zhao, Minghui; Sibuet, Jean-Claude; He, Enyuan; Tan, Pingchuan; Wang, Jian; Qiu, Xuelin

2016-04-01

In the South China Sea (SCS), the post-spreading magmatism (˜8-13 Ma) largely masks the previous spreading fabric. The resulting post-spreading seamounts are more numerous in the northern part than in the southern part of the East sub-basin. In the eastern part of the East sub-basin, the post-spreading volcanic ridge (PSVR) is approximately N055° oriented and follows the extinct spreading ridge (ESR). In the western part of the East sub-basin, the PSVR, called the Zhenbei-Huangyan seamounts chain, is E-W oriented and hides the ESR. Based on swath bathymetric and magnetic data, the ESR in the eastern part of the East basin is also N055° oriented and thus is oblique the E-W Zhenbei-Huangyan seamounts chain (Sibuet et al., 2016). We conducted a seismic refraction survey covering both the Zhenbei-Huangyan seamounts chain and the adjacent ESR, providing new constraints for understanding the relationship between the PSVR and the ESR. The detailed velocity structure shows that the Zhenbei-Huangyan seamounts chain was emplaced through a typical oceanic crust. The thicknesses of Zhenbei (14 km) and Huangyan seamounts (8 km) are larger than the ones of the normal oceanic crust. The correlation between crustal thicknesses and mean lower-crustal seismic velocities suggest that an asymmetric generation of seamounts in the East sub-basin where active upwelling mantle (Holbrook et al., 2001), the presence of a fertile mantle component (Korenaga et al., 2002), or buoyancy-driven decompression melting may happened (Castillo et al., 2010). Below the seamounts, the thickened lower crust is probably due to secondary magmatic intrusions and the large thickness of upper crust is possibly due to volcanic extrusions. The crustal thicknesses as well as the mean lower-crustal velocities of the Zhenbei and Huangyan seamounts are different, suggesting an independent origin for magmatic feeding. This research was granted by the Natural Science Foundation of China (91028002, 91428204, 41176053). References Sibuet J.-C., Yeh Y.-C. and Lee C.-S., 2016 revised. Geodynamics of the South China Sea. Tectonophysics. Holbrook, W. S., H. C. Larsen, J. Korenaga, et al., 2001. Mantle thermal structure and active upwelling during continental breakup in the North Atlantic, Earth Planet. Sci. Lett., 190, 251-266. Korenaga, J., P.B.Kelemen, W.S. Holbrook., 2002. Methods for resolving the origin of large igneous provinces from crustal seismology. Journal of Geophysical research: Solid Earth (1978-2012), 107(B9), 2178,doi:10.1029/2001JB001030. Castillo, P. R., Clague, D. A., Davis, A. S., et al., 2010. Petrogenesis of Davidson Seamount lavas and its implications for fossil spreading center and intraplate magmatism in the eastern Pacific. Geochemistry, Geophysics, Geosystems, 11, Q02005, doi:10.1029/2009GC002992.

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 ...

Delocalized and localized states of eg electrons in half-doped manganites.

PubMed

Winkler, E L; Tovar, M; Causa, M T

2013-07-24

We have studied the magnetic behaviour of half-doped manganite Y0.5Ca0.5MnO3 in an extended range of temperatures by means of magnetic susceptibility, χ(T), and electron spin resonance (ESR) experiments. At high temperature the system crystallizes in an orthorhombic structure. The resistivity value, ρ ≃ 0.05 Ω cm at 500 K, indicates a metallic behaviour, while the Curie-Weiss dependence of χ(T) and the thermal evolution of the ESR parameters are very well described by a model that considers a system conformed by localized Mn(4+) cores, [Formula: see text], and itinerant, eg, electrons. The strong coupling between t2g and eg electrons results in an enhanced Curie constant and an FM Curie-Weiss temperature that overcomes the AFM interactions between the [Formula: see text] cores. A transition to a more distorted phase is observed at T ≈ 500 K and signatures of localization of the eg electrons appear in the χ(T) behaviour below 300 K. A new Curie-Weiss regime is observed, where the Curie-constant value is consistent with dimer formation. Based on mean-field calculations, the dimer formation is predicted as a function of the interaction strength between the t2g and eg electrons.

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

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.

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

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.

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.

The 2013 Frank Stinchfield Award: Diagnosis of infection in the early postoperative period after total hip arthroplasty.

PubMed

Yi, Paul H; Cross, Michael B; Moric, Mario; Sporer, Scott M; Berger, Richard A; Della Valle, Craig J

2014-02-01

Diagnosis of periprosthetic joint infection (PJI) can be difficult in the early postoperative period after total hip arthroplasty (THA) because normal cues from the physical examination often are unreliable, and serological markers commonly used for diagnosis are elevated from the recent surgery. The purposes of this study were to determine the optimal cutoff values for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), synovial fluid white blood cell (WBC) count, and differential for diagnosing PJI in the early postoperative period after primary THA. We reviewed 6033 consecutive primary THAs and identified 73 patients (1.2%) who underwent reoperation for any reason within the first 6 weeks postoperatively. Thirty-six of these patients were infected according to modified Musculoskeletal Infection Society criteria. Mean values for the diagnostic tests were compared between groups and receiver operating characteristic curves generated along with an area under the curve (AUC) to determine test performance and optimal cutoff values to diagnose infection. The best test for the diagnosis of PJI was the synovial fluid WBC count (AUC = 98%; optimal cutoff value 12,800 cells/μL) followed by the CRP (AUC = 93%; optimal cutoff value 93 mg/L), and synovial fluid differential (AUC = 91%; optimal cutoff value 89% PMN). The mean ESR (infected = 69 mm/hr, not infected = 46 mm/hr), CRP (infected = 192 mg/L, not infected = 30 mg/L), synovial fluid WBC count (infected = 84,954 cells/μL, not infected = 2391 cells/μL), and differential (infected = 91% polymorphonuclear cells [PMN], not infected = 63% PMN) all were significantly higher in the infected group. Optimal cutoff values for the diagnosis of PJI in the acute postoperative period were higher than those traditionally used for the diagnosis of chronic PJI. The serum CRP is an excellent screening test, whereas the synovial fluid WBC count is more specific.

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.

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.

ESR, SIMS and TEMF of an Y-Ba-Cu-O superconductor

NASA Technical Reports Server (NTRS)

Kirschner, I.; Giber, J.; Halasz, I.

1995-01-01

Superconducting transition comes into being between 92 K and 82 K in the samples having a Meissner's state value of 68 vol. percent. The main material content has an orthorhombic unit cell of Y1Ba2Cu408 accompanied by low quantity CuO and a sporadic phase. A proof of anisotropic superconductivity, an unusually high Cu ion concentration and a temperature dependent transition of charge carriers have been observed.

Physical and Electrical Characterization of Aluminum Polymer Capacitors

NASA Technical Reports Server (NTRS)

Liu, David; Sampson, Michael J.

2010-01-01

Polymer aluminum capacitors from several manufacturers with various combinations of capacitance, rated voltage, and ESR values were physically examined and electrically characterized. The physical construction analysis of the capacitors revealed three different capacitor structures, i.e., traditional wound, stacked, and laminated. Electrical characterization results of polymer aluminum capacitors are reported for frequency-domain dielectric response at various temperatures, surge breakdown voltage, and other dielectric properties. The structure-property relations in polymer aluminum capacitors are discussed.

Physical and Electrical Characterization of Polymer Aluminum Capacitors

NASA Technical Reports Server (NTRS)

Liu, David; Sampson, Michael J.

2010-01-01

Polymer aluminum capacitors from several manufacturers with various combinations of capacitance, rated voltage, and ESR values were physically examined and electrically characterized. The physical construction analysis of the capacitors revealed three different capacitor structures, i.e., traditional wound, stacked, and laminated. Electrical characterization results of polymer aluminum capacitors are reported for frequency-domain dielectric response at various temperatures, surge breakdown voltage, and other dielectric properties. The structure-property relations in polymer aluminum capacitors are discussed.

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

PubMed

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

2015-01-01

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

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.

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.

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.

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.

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.

[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.

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.

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.

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.

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.

Interaction of lipids with the neurotensin receptor 1.

PubMed

Bolivar, Juan H; Muñoz-García, Juan C; Castro-Dopico, Tomas; Dijkman, Patricia M; Stansfeld, Phillip J; Watts, Anthony

2016-06-01

Information about lipid-protein interactions for G protein-coupled receptors (GPCRs) is scarce. Here, we use electron spin resonance (ESR) and spin-labelled lipids to study lipid interactions with the rat neurotensin receptor 1 (NTS1). A fusion protein containing rat NTS1 fully able to bind its ligand neurotensin was reconstituted into phosphatidylcholine (PC) bilayers at specific lipid:protein molar ratios. The fraction of motionally restricted lipids in the range of 40:1 to 80:1 lipids per receptor suggested an oligomeric state of the protein, and the result was unaffected by increasing the hydrophobic thickness of the lipid bilayer from C-18 to C-20 or C-22 chain length PC membranes. Comparison of the ESR spectra of different spin-labelled lipids allowed direct measurement of lipid binding constants relative to PC (Kr), with spin-labelled phosphatidylethanolamine (PESL), phosphatidylserine (PSSL), stearic acid (SASL), and a spin labelled cholesterol analogue (CSL) Kr values of 1.05±0.05, 1.92±0.08, 5.20±0.51 and 0.91±0.19, respectively. The results contrast with those from rhodopsin, the only other GPCR studied this way, which has no selectivity for the lipids analysed here. Molecular dynamics simulations of NTS1 in bilayers are in agreement with the ESR data, and point to sites in the receptor where PS could interact with higher affinity. Lipid selectivity could be necessary for regulation of ligand binding, oligomerisation and/or G protein activation processes. Our results provide insight into the potential modulatory mechanisms that lipids can exert on GPCRs. Copyright © 2016 Elsevier B.V. All rights reserved.

Treatment of Spinal Epidural Abscess and Predisposing Factors of Motor Weakness: Experience with 48 Patients

PubMed Central

Ju, Min-Wook; Kwon, Hyon-Jo; Kim, Seon-Hwan; Koh, Hyeon-Song; Youm, Jin-Young; Song, Shi-Hun

2015-01-01

Objective Spinal epidural abscess (SEA) can be fatal if untreated, so early diagnosis and treatment are essential. We conducted a retrospective study to define its clinical features and evaluate the risk factors of motor weakness. Methods We retrospectively analyzed the medical records and images of patients with SEA who had been hospitalized in our institute from January 2005 to June 2012. Pyogenic SEA patients were categorized as patients without motor weakness (Group A) and with motor weakness (Group B). Abscess volume was measured using the Gamma-Plan program. Intervertebral foramen height and posterior disc height were measured to evaluate degree of spinal stenosis. Results Of 48 patients with pyogenic SEA, 33 (68%) were treated surgically, and 15 (32%) were treated with antibiotics. Eleven patients had weakness and abscess volume was unrelated to motor weakness. Old age, 'spare room' (abscess volume subtracted from spinal volume) and intervertebral foramen height and posterior disc height were statistically significant. Among the 48 patients, 43 (85%) had good outcome and erythrocyte sedimentation rate (ESR) was the only meaningful prognostic factor (p=0.014). The cut-off value of ESR was 112mm/h with 80% sensitivity and 79% specificity and had borderline significance (p=0.062). Conclusion SEA needs emergent diagnosis and treatment. Motor weakness is the most important factor in treatment decision. By careful image reading, early surgical treatment can be an option for selected patients with severe spinal stenosis for prevent motor weakness. Inflammatory markers, especially ESR, are valuable to identify worsening of SEA. PMID:26512265

Evaluation of systemic markers of inflammation in atomic-bomb survivors with special reference to radiation and age effects.

PubMed

Hayashi, Tomonori; Morishita, Yukari; Khattree, Ravindra; Misumi, Munechika; Sasaki, Keiko; Hayashi, Ikue; Yoshida, Kengo; Kajimura, Junko; Kyoizumi, Seishi; Imai, Kazue; Kusunoki, Yoichiro; Nakachi, Kei

2012-11-01

Past exposure to atomic bomb (A-bomb) radiation has exerted various long-lasting deleterious effects on the health of survivors. Some of these effects are seen even after >60 yr. In this study, we evaluated the subclinical inflammatory status of 442 A-bomb survivors, in terms of 8 inflammation-related cytokines or markers, comprised of plasma levels of reactive oxygen species (ROS), interleukin (IL)-6, tumor necrosis factor α (TNF-α), C-reactive protein (CRP), IL-4, IL-10, and immunoglobulins, and erythrocyte sedimentation rate (ESR). The effects of past radiation exposure and natural aging on these markers were individually assessed and compared. Next, to assess the biologically significant relationship between inflammation and radiation exposure or aging, which was masked by the interrelationship of those cytokines/markers, we used multivariate statistical analyses and evaluated the systemic markers of inflammation as scores being calculated by linear combinations of selected cytokines and markers. Our results indicate that a linear combination of ROS, IL-6, CRP, and ESR generated a score that was the most indicative of inflammation and revealed clear dependences on radiation dose and aging that were found to be statistically significant. The results suggest that collectively, radiation exposure, in conjunction with natural aging, may enhance the persistent inflammatory status of A-bomb survivors.

π to σ Radical Tautomerization in One-Electron Oxidized 1-Methylcytosine and its Analogs

PubMed Central

Adhikary, Amitava; Kumar, Anil; Bishop, Casandra T.; Wiegand, Tyler J.; Hindi, Ragda M.; Adhikary, Ananya; Sevilla, Michael D.

2015-01-01

In this work iminyl σ-radical formation in several one-electron oxidized cytosine analogs including 1-MeC, cidofovir, 2′-deoxycytidine (dCyd), and 2′-deoxycytidine 5′-monophosphate (5′-dCMP) were investigated in homogeneous aqueous (D2O or H2O) glassy solutions at low temperatures employing electron spin resonance (ESR) spectroscopy. Employing density functional theory (DFT) (DFT/B3LYP/6-31G* method), the calculated hyperfine coupling constant (HFCC) values of iminyl σ-radical agree quite well with the experimentally observed ones thus confirming its assignment. ESR and DFT studies show that the cytosine-iminyl σ-radical is a tautomer of the deprotonated cytosine π-cation radical (cytosine π-aminyl radical, C(N4-H)•). Employing 1-MeC samples at various pHs ranging ca. 8 to ca. 11, ESR studies show that the tautomeric equilibrium between C(N4-H)• and the iminyl σ-radical at low temperature is too slow to be established without added base. ESR and DFT studies agree that in the iminyl-σ radical, the unpaired spin is localized to the exocyclic nitrogen (N4) in an in-plane pure p-orbital. This gives rise to an anisotropic nitrogen hyperfine coupling (Azz = 40 G) from N4 and a near isotropic β-nitrogen coupling of 9.7 G from the cytosine ring nitrogen at N3. Iminyl σ-radical should exist in its N3-protonated form as the N3-protonated iminyl σ-radical is stabilized in solution by over 30 kcal/mol (ΔG= −32 kcal/mol) over its conjugate base, the N3-deprotonated form. This is the first observation of an isotropic β-hyperfine ring nitrogen coupling in an N-centered DNA-radical. Our theoretical calculations predict that the cytosine iminyl σ-radical can be formed in dsDNA by a radiation-induced ionization–deprotonation process that is only 10 kcal/mol above the lowest energy path. PMID:26237072

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

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.

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.

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.

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

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.

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.

Effect of nano-scale characteristics of graphene on electrochemical performance of activated carbon supercapacitor electrodes

NASA Astrophysics Data System (ADS)

Jasni, M. R. M.; Deraman, M.; Suleman, M.; Hamdan, E.; Sazali, N. E. S.; Nor, N. S. M.; Shamsudin, S. A.

2016-02-01

Graphene with its typical nano-scale characteristic properties has been widely used as an additive in activated carbon electrodes in order to enhance the performance of the electrodes for their use in high performance supercapacitors. Activated carbon monoliths (ACMs) electrodes have been prepared by carbonization and activation of green monoliths (GMs) of pre-carbonized fibers of oil palm empty fruit bunches or self-adhesive carbon grains (SACGs) and SACGs added with 6 wt% of KOH-treated multi-layer graphene. ACMs electrodes have been assembled in symmetrical supercapacitor cells that employed aqueous KOH electrolyte (6 M). The cells have been tested with cyclic voltammetry, electrochemical impedance spectroscopy and galvanostatic charge discharge methods to investigate the effect of graphene addition on the specific capacitance (Csp), specific energy (E), specific power (P), equivalent series resistance (ESR) and response time (τo) of the supercapacitor cells. The results show that the addition of graphene in the GMs change the values of Csp, Emax, Pmax, ESR and τo from (61-96) F/g, 2 Wh/kg, 104 W/kg, 2.6 Ω and 38 s, to the respective values of (110-124) F/g, 3 Wh/kg, 156 W/kg, 3.4 Ω and 63 s. This study demonstrates that the graphene addition in the GMs has a significant effect on the electrochemical behavior of the electrodes.

Interpretation of ESR results for some semimagnetic semiconductor alloys

NASA Astrophysics Data System (ADS)

Woolley, J. C.; Chehab, S. F.; Donofrio, T.; Manhas, S.; Manoogian, A.; Lamarche, G.

1987-03-01

Previously reported values of the ESR linewidth variation with temperature for the alloys (i) Cd xZn yMn zSe (ii) Cd xZn yMn zTe and (iii) Cd 1- zMn zTe 1- ySe y have been analyzed in terms of the relation, δ H = Γ exp (- T/ T0) + B{1 - exp(- T/ T0)}(1-θ/ T), where the first term is attributed to spatial inhomogeneity effects and the second to paramagnetic behaviour. Values of the parameters, Γ, T0 and B have been determined as a function of composition in each alloy system. The parameter T0, which measures the potential barrier separating two neighbouring ground states of the disordered spin system, is found to satisfy the relation T0 = (α + β f) z, where f = y/( x + y) for (i) and (ii) and f = y for (iii). β is positive for (i) and (ii) and negative for (iii), consistent with previous suggestions of Kremer and Furdyna, and may be correlated with the exchange constants Jsp-d discussed by Hass et al. The parameter Γ, which measures the width of the distribution of the local field seen by manganese ions in the lattice, is found to satisfy the relation Γ = Dz2(1 - z), where D appears to be characteristic of the crystal structure. The parameter B which measures the linewidth δ H at high temperatures due to paramagnetic effects is found to vary as B = B0 + γ z and the values of the coefficient γ appear to be related to the exchange parameters of the materials.

Some effects of sarcoptic mange on dogs.

PubMed

Arlian, L G; Morgan, M S; Rapp, C M; Vyszenski-Moher, D L

1995-10-01

Sequential changes in pathology were examined for scabies-infested dogs to determine the effects of infestation with Sarcoptes scabiei var. canis. During 8 wk of infestation with S. scabiei, the progression of the disease was evaluated weekly by skin scrape, clinical examination, and blood analyses. At 8 wk, selected organs were microscopically examined for histopathology. All infested dogs developed an advanced level of scabies infestation by 8 wk. Of the 36 blood parameters evaluated, only values for erythrocyte sedimentation rate (ESR) deviated significantly from the normal ranges for dogs. However, infested dogs had significantly (P < 0.01) lower average hemoglobin and hematocrit concentrations after 8 wk of infestation compared to their values prior to infestation or to the values for the control dogs. Red blood cell levels for infested dogs dropped significantly (P < 0.01) from preinfestation concentrations by week 8. Conversely, by 8 wk total white blood cell and neutrophil concentrations were significantly (P < 0.01) greater than uninfested controls. Also, whereas average eosinophil concentrations were not statistically different for infested dogs compared to controls, some individual infested dogs exhibited eosinophilia at 4-8 wk of infestation. The ESRs for infested dogs were significantly (P < 0.01) greater at week 6 and 8 than for experimental dogs prior to infestation or control dogs. All parameters except neutrophils had returned to preinfestation levels by 2 wk after treatment for scabies. Neutrophil concentrations were no longer significantly different by 4 wk posttreatment. There were no significant differences in serum enzyme, biochemical and electrolyte concentrations between infested and control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic value of lactate, procalcitonin, ferritin, serum-C-reactive protein, and other biomarkers in bacterial and viral meningitis: A cross-sectional study.

PubMed

Sanaei Dashti, Anahita; Alizadeh, Shekoofan; Karimi, Abdullah; Khalifeh, Masoomeh; Shoja, Seyed Abdolmajid

2017-09-01

There are many difficulties distinguishing bacterial from viral meningitis that could be reasonably solved using biomarkers. The aim of this study was to evaluate lactate, procalcitonin (PCT), ferritin, serum-CRP (C-reactive protein), and other known biomarkers in differentiating bacterial meningitis from viral meningitis in children.All children aged 28 days to 14 years with suspected meningitis who were admitted to Mofid Children's Hospital, Tehran, between October 2012 and November 2013, were enrolled in this prospective cross-sectional study. Children were divided into 2 groups of bacterial and viral meningitis, based on the results of cerebrospinal fluid (CSF) culture, polymerase chain reaction, and cytochemical profile. Diagnostic values of CSF parameters (ferritin, PCT, absolute neutrophil count [ANC], white blood cell count, and lactate) and serum parameters (PCT, ferritin, CRP, and erythrocyte sedimentation rate [ESR]) were evaluated.Among 50 patients with meningitis, 12 were diagnosed with bacterial meningitis. Concentrations of all markers were significantly different between bacterial and viral meningitis, except for serum (P = .389) and CSF (P = .136) PCT. The best rates of area under the receiver operating characteristic (ROC) curve (AUC) were achieved by lactate (AUC = 0.923) and serum-CRP (AUC = 0.889). The best negative predictive values (NPV) for bacterial meningitis were attained by ANC (100%) and lactate (97.1%).The results of our study suggest that ferritin and PCT are not strong predictive biomarkers. A combination of low CSF lactate, ANC, ESR, and serum-CRP could reasonably rule out the bacterial meningitis.

Diagnostic value of lactate, procalcitonin, ferritin, serum-C-reactive protein, and other biomarkers in bacterial and viral meningitis

PubMed Central

Sanaei Dashti, Anahita; Alizadeh, Shekoofan; Karimi, Abdullah; Khalifeh, Masoomeh; Shoja, Seyed Abdolmajid

2017-01-01

Abstract There are many difficulties distinguishing bacterial from viral meningitis that could be reasonably solved using biomarkers. The aim of this study was to evaluate lactate, procalcitonin (PCT), ferritin, serum-CRP (C-reactive protein), and other known biomarkers in differentiating bacterial meningitis from viral meningitis in children. All children aged 28 days to 14 years with suspected meningitis who were admitted to Mofid Children's Hospital, Tehran, between October 2012 and November 2013, were enrolled in this prospective cross-sectional study. Children were divided into 2 groups of bacterial and viral meningitis, based on the results of cerebrospinal fluid (CSF) culture, polymerase chain reaction, and cytochemical profile. Diagnostic values of CSF parameters (ferritin, PCT, absolute neutrophil count [ANC], white blood cell count, and lactate) and serum parameters (PCT, ferritin, CRP, and erythrocyte sedimentation rate [ESR]) were evaluated. Among 50 patients with meningitis, 12 were diagnosed with bacterial meningitis. Concentrations of all markers were significantly different between bacterial and viral meningitis, except for serum (P = .389) and CSF (P = .136) PCT. The best rates of area under the receiver operating characteristic (ROC) curve (AUC) were achieved by lactate (AUC = 0.923) and serum-CRP (AUC = 0.889). The best negative predictive values (NPV) for bacterial meningitis were attained by ANC (100%) and lactate (97.1%). The results of our study suggest that ferritin and PCT are not strong predictive biomarkers. A combination of low CSF lactate, ANC, ESR, and serum-CRP could reasonably rule out the bacterial meningitis. PMID:28858084

Thermodynamic properties of a layered S = 7/2 Heisenberg magnet Gd(OH)CO3

NASA Astrophysics Data System (ADS)

Orendac, Martin; Ulicny, Martin; Cizmar, Erik; Orendacova, Alzbeta; Chen, Yan-Cong; Meng, Zhao-Sha; Tong, Ming-Liang

2015-03-01

Thermodynamic quantities and ESR spectra of Gd(OH)CO3 (I) are reported. The material may be considered to consist of weakly coupled layers with potentially triangular arrangement of exchange paths within each layer. Different bridging groups and distances among Gd3+ ions may be responsible for spatial anisotropy of magnetic coupling. Preliminary analysis of magnetic susceptibility using Curie-Weiss law yielded θ = -1.05 K indicating weak antiferromagnetic coupling and consequently, spin frustration in (I). More detailed simultaneous analysis of specific heat, susceptibility and magnetization studied down to nominally 0.45 K revealed non-negligible role of single-ion anisotropy. Using the model of weakly interacting S =7/2 trimers, the gross features of measured data may be explained while assuming single-ion anisotropy D /kB ~ 0.6 K and effective intratrimer magnetic coupling | J /kB | ~0.3 K. The obtained D value reasonably reproduces the position and shape of ESR line. The performed analysis suggests that magnetism in (I) is governed predominantly by crystal field effects and frustration plays a minor role. Supported by ITMS26220120005 and VEGA 1/0143/13.

Electron spin resonance identification di-carbon-related centers in irradiated silicon

NASA Astrophysics Data System (ADS)

Hayashi, S.; Saito, H.; Itoh, K. M.; Vlasenko, M. P.; Vlasenko, L. S.

2018-04-01

A previously unreported electron spin resonance (ESR) spectrum was found in γ-ray irradiated silicon by the detection of the change in microwave photoconductivity arising from spin-dependent recombination (SDR). In the specially prepared silicon crystals doped by 13C isotope, a well resolved hyperfine structure of SDR-ESR lines due to the interaction between electrons and two equivalent carbon atoms having nuclear spin I = 1/2 was observed. The Si-KU4 spectrum is described by spin Hamiltonian for spin S = 1 and of g and D tensors of orthorhombic symmetry with principal values g1 = 2.008, g2 = 2.002, and g3 =2.007; and D1 = ± 103 MHz, D2 = ∓170 MHz, and D3 = ± 67 MHz where axes 1, 2, and 3 are parallel to the [1 1 ¯ 0 ], [110], and [001] crystal axes, respectively. The hyperfine splitting arising from 13C nuclei is about 0.35 mT. A possible microstructure of the detect leading to the Si-KU4 spectrum is discussed.

ESR, electrochemical and cyclodextrin-inclusion studies of triazolopyridyl pyridyl ketones and dipyridyl ketones derivatives

NASA Astrophysics Data System (ADS)

Olea-Azar, C.; Abarca, B.; Norambuena, E.; Opazo, L.; Jullian, C.; Valencia, S.; Ballesteros, R.; Chadlaoui, M.

2008-11-01

The electron spin resonance (ESR) spectra of free radicals obtained by electrolytic reduction of triazolopyridyl pyridyl ketones and dipyridyl ketones derivatives were measured in dimethylsulfoxide (DMSO). The hyperfine patterns indicate that the spin density delocalization is dependent of the rings presented in the molecule. The electrochemistry of these compounds was characterized using cyclic voltammetry, in DMSO as solvent. When one carbonyl is present in the molecule one step in the reduction mechanism was observed while two carbonyl are present two steps were detected. The first wave was assigned to the generation of the correspondent free radical species, and the second wave was assigned to the dianion derivatives. The phase-solubility measurements indicated an interaction between molecules selected and cyclodextrins in water. These inclusion complexes are 1:1 with βCD, and HP-βCD. The values of Ks showed a different kind of complexes depending on which rings are included. AM1 and DFT calculations were performed to obtain the optimized geometries, theoretical hyperfine constants, and spin distributions, respectively. The theoretical results are in complete agreement with the experimental ones.

Epigenetic Alteration by DNA Methylation of ESR1, MYOD1 and hTERT Gene Promoters is Useful for Prediction of Response in Patients of Locally Advanced Invasive Cervical Carcinoma Treated by Chemoradiation.

PubMed

Sood, S; Patel, F D; Ghosh, S; Arora, A; Dhaliwal, L K; Srinivasan, R

2015-12-01

Locally advanced invasive cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) IIB/III] is treated by chemoradiation. The response to treatment is variable within a given FIGO stage. Therefore, the aim of the present study was to evaluate the gene promoter methylation profile and corresponding transcript expression of a panel of six genes to identify genes which could predict the response of patients treated by chemoradiation. In total, 100 patients with invasive cervical cancer in FIGO stage IIB/III who underwent chemoradiation treatment were evaluated. Ten patients developed systemic metastases during therapy and were excluded. On the basis of patient follow-up, 69 patients were chemoradiation-sensitive, whereas 21 were chemoradiation-resistant. Gene promoter methylation and gene expression was determined by TaqMan assay and quantitative real-time PCR, respectively, in tissue samples. The methylation frequency of ESR1, BRCA1, RASSF1A, MLH1, MYOD1 and hTERT genes ranged from 40 to 70%. Univariate and hierarchical cluster analysis revealed that gene promoter methylation of MYOD1, ESR1 and hTERT could predict for chemoradiation response. A pattern of unmethylated MYOD1, unmethylated ESR1 and methylated hTERT promoter as well as lower ESR1 transcript levels predicted for chemoradiation resistance. Methylation profiling of a panel of three genes that includes MYOD1, ESR1 and hTERT may be useful to predict the response of invasive cervical carcinoma patients treated with standard chemoradiation therapy. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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

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

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.

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

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.

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.

Reference dosimeter system of the iaea

NASA Astrophysics Data System (ADS)

Mehta, Kishor; Girzikowsky, Reinhard

1995-09-01

Quality assurance programmes must be in operation at radiation processing facilities to satisfy national and international Standards. Since dosimetry has a vital function in these QA programmes, it is imperative that the dosimetry systems in use at these facilities are well calibrated with a traceability to a Primary Standard Dosimetry Laboratory. As a service to the Member States, the International Atomic Energy Agency operates the International Dose Assurance Service (IDAS) to assist in this process. The transfer standard dosimetry system that is used for this service is based on ESR spectrometry. The paper describes the activities undertaken at the IAEA Dosimetry Laboratory to establish the QA programme for its reference dosimetry system. There are four key elements of such a programme: quality assurance manual; calibration that is traceable to a Primary Standard Dosimetry Laboratory; a clear and detailed statement of uncertainty in the dose measurement; and, periodic quality audit.

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

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.

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.

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).

[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.

Understanding and controlling spin-systems using electron spin resonance techniques

NASA Astrophysics Data System (ADS)

Martens, Mathew

Single molecule magnets (SMMs) posses multi-level energy structures with properties that make them attractive candidates for implementation into quantum information technologies. However there are some major hurdles that need to be overcome if these systems are to be used as the fundamental components of an eventual quantum computer. One such hurdle is the relatively short coherence times these systems display which severely limits the amount of time quantum information can remain encoded within them. In this dissertation, recent experiments conducted with the intent of bringing this technology closer to realization are presented. The detailed knowledge of the spin Hamiltonian and mechanisms of decoherence in SMMs are absolutely essential if these systems are to be used in technologies. To that effect, experiments were done on a particularly promising SMM, the complex K6[VIV15AsIII 6O42(H2O)] · 8H2O, known as V15. High-field electron spin resonance (ESR) measurements were performed on this system at the National High Magnetic Field Laboratory. The resulting spectra allowed for detailed analysis of the V15 spin Hamiltonian which will be presented as well as the most precise values yet reported for the g-factors of this system. Additionally, the line widths of the ESR spectra are studied in depth and found to reveal that fluctuations within the spin-orbit interaction are a mechanism for decoherence in V15. A new model for decoherence is presented that describes very well both the temperature and field orientation dependences of the measured ESR line widths. Also essential is the ability to control spin-states of SMMs. Presented in this dissertation as well is the demonstration of the coherent manipulation of the multi-state spin system Mn2+ diluted in MgO by means of a two-tone pulse drive. Through the detuning between the excitation and readout radio frequency pulses it is possible to select the number of photons involved in a Rabi oscillation as well as increase the frequency of this nutation. Experimental findings fit well the analytical model developed. This process could lead to the use of multi-level spin systems as tunable solid state qubits. Finally, if quantum computing technologies are to be commercially realized, an on-chip method to address qubits must be developed. One way to incorporate SMMs to an on-chip device is by way of a coplanar waveguide (CPW) resonator. Efforts to create a resonator of this type to be used to perform low-temperature ESR on-chip will be described. Our work is focused on implementing such on-chip techniques in high magnetic fields, which is desirable for ESR-type of experiments in (quasi-)isotropic spin systems. Considerable attention is given to the coupling of these devices and a geometry is presented for a superconducting CPW resonator that is critically coupled. The effect of the magnetic field on the resonance position and its quality factor is addressed as well. Our devices show robust performance in field upwards of 1 Tesla and their use in performing on-chip ESR measurements seem promising.

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.

[Laboratory findings in patients with hemorrhagic fever with renal syndrome].

PubMed

Puljiz, Ivan; Kuzman, Ilija; Turcinov, Drago; Makek, Nikola; Markotić, Alemka

2005-01-01

To examine the frequency and distribution of hematologic and biochemical laboratory findings in 94 patients with hemorrhagic fever with renal syndrome (HFRS) in the epidemic year 2002. The following laboratory findings were retrospectively analyzed: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin, hematocrit, leukocyte count and differential percentage (segmented neutrophils, band neutrophils, atypical lymphocytes), platelet count, coagulation tests, blood urea nitrogen (BUN), creatinine, urine, potassium, bilirubin (BIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GT), alkaline phosphatase (ALP), and serum protein electrophoresis. The study included 94 HFRS patients treated at the Dr Fran Mihaljević University Hospital for Infectious Diseases in Zagreb during 2002. ESR increase, mostly mild to moderate, was found in 86.2% of study patients. Increased CRP was recorded in 98.9% of study patients, however, one-fourth had CRP higher than 100 mg/L. Leukocytosis was recorded in 38.3% (10.1 +/- 4.2 x 10(9)/L), thrombocytopenia in 89.4% patients (68.2 +/- 48.3 x 10(9)/L), and severe thrombocytopenia (x 10(9)/L) in six patients. Three patients had abnormal coagulation tests. Increased values of BUN and creatinine were recorded in more than a half of patients, while only four patients had mild hyperkalemia. Only three patinets required hemodialysis. Mildly to moderately increased values of aminotransferases (AST, ALT, GT) were observed in more than 2/3; hypoalbuminaemia in nearly 1/3, and elevated alpha-2 fraction in more than 2/3 of patients. The majority of patients had pathologic urine findings. First laboratory abnormalities were usually found between day 5 and 7 of the disease (increased CRP level, thrombocytopenia, leukocytosis, and elevation of hemoglobin and hematocrit). Biochemical abnormalities(elevation of cratinine and urea, increased levels of aminotransferases) usually occurred at the beginning of the second week, and ESR increase in the second week of disease. The majority of our patients had laboratory findings characteristic of HFRS. Thrombocytopenia and increased level of CRP were the most common laboratory findings during the first week of the disease. Renal and liver impairment occurred at the beginning of the second week of the disease.

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.

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.

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

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:…

Pulse-based electron spin transient nutation measurement of BaTiO3 fine particle: Identification of controversial signal around g = 2.00

NASA Astrophysics Data System (ADS)

Sawai, Takatoshi; Yamaguchi, Yoji; Kitamura, Noriko; Date, Tomotsugu; Konishi, Shinya; Taga, Kazuya; Tanaka, Katsuhisa

2018-05-01

Two dimensional pulse-based electron spin transient nutation (2D-ESTN) spectroscopy is a powerful tool for determining the spin quantum number and has been applied to BaTiO3 fine powder in order to identify the origin of the continuous wave electron spin resonance (CW-ESR) signal around g = 2.00. The signal is frequently observed in BaTiO3 ceramics, and the correlation between the signal intensity and positive temperature coefficient of resistivity (PTCR) properties has been reported to date. The CW-ESR spectrum of BaTiO3 fine particles synthesized by the sol-gel method shows a typical asymmetric signal at g = 2.004. The 2D-ESTN measurements of the sample clearly reveal that the signal belongs to the S = 5/2 high spin state, indicating that the signal is not due to a point defect as suggested by a number of researchers but rather to a transition metal ion. Our elemental analysis, as well as previous studies, indicates that the origin of the g = 2.004 signal is due to the presence of an Fe3+ impurity. The D value (second-order fine structure parameter) reveals that the origin of the signal is an Fe3+ center with distant charge compensation. In addition, we show a peculiar temperature dependence of the CW-ESR spectrum, suggesting that the phase transition behavior of a BaTiO3 fine particle is quite different from that of a bulk single crystal. Our identification does not contradict a vacancy-mediated mechanism for PTCR. However, it is incorrect to use the signal at g = 2.00 as evidence to support the vacancy-mediated mechanism.

SU-E-I-78: Neuromelanin in the Subthalamic Nucleus of Patients with Parkinson's Disease: An Electron Spin Resonance Spectroscopy Study.

PubMed

Gomez, J; Salmon, C Garrido; Filho, O Baffa; Santos, J Peixoto; Pitella, J

2012-06-01

Parkinson disease and related syndromes are associated directly with the concentrations of neuromelanin, iron and other heavy metals, and nowadays it is discussed the possible protective role of neuromelanin by the sequester redox active iron ions, reducing the formation of free hydroxyl radicals and therefore inactivating the iron ions that induce oxidative stress. The aim of this work is to study the concentration ratios between iron ions and neuromelanin in subthalamic nucleus of patients with Parkinson's disease (PD) using Electron Spin Resonance (ESR). Necropsy samples of subthalamic nucleus from eight human brains were studied: three non-affected by any neurodegenerative disease and five with Parkinson's disease. The samples were stored in formaldehyde and washed with a solution of 0.01 molar of ethylenediaminetetraacetic acid. ESR experiments were development in a JEOL FA-200 X-Band spectrometer at different temperatures between -170° C to room temperature. The relative concentrations of each species were estimated from the double integral values of the fitted spectra. For all samples, ESR spectra showed to be composed of three different signals following the Curie's law. One signal was attributed to high-spin ferric ions (g∼ 4.3) in rhomboedric symmetry, Cu(II) ions (close to g=2.0) and neuromelanin (g∼ 2.01). The ferric ions concentration ratio between patients and controls was 3.0±0.2. The same ratio for neuromelanine was 0.24±0.06. Our preliminary results indicated a significant increment of iron concentration in PD samples which agrees with previous histochemical and biochemical reports. This finding and the clear reduction of neuromelanin concentration in PD samples suggest the possible role of neuromelanin as iron ions storage. © 2012 American Association of Physicists in Medicine.

A Study of Carbon Nanofibers and Active Carbon as Symmetric Supercapacitor in Aqueous Electrolyte: A Comparative Study

NASA Astrophysics Data System (ADS)

Daraghmeh, Allan; Hussain, Shahzad; Saadeddin, Iyad; Servera, Llorenç; Xuriguera, Elena; Cornet, Albert; Cirera, Albert

2017-12-01

Symmetric supercapacitors are fabricated by carbon nanofibers (CNF) and activated carbon (AC) using similar proportions of 7 wt% polyvinylidene fluoride (PVDF) polymer binder in an aqueous electrolyte. In this study, a comparison of porous texture and electrochemical performances between CNFs and AC based supercapacitors was carried out. Electrodes were assembled in the cell without a current collector. The prepared electrodes of CNFs and AC present Brunauer-Emmett-Teller (BET) surface area of 83 and 1042 m2/g, respectively. The dominant pore structure for CNFs is mesoporous while for AC is micropore. The results showed that AC provided higher specific capacitance retention up to very fast scan rate of 500 mV/s. AC carbon had a specific capacitance of 334 F/g, and CNFs had 52 F/g at scan rate 5 mV/s in aqueous solution. Also, the results indicate the superior conductivity of CNFs in contrast to AC counterparts. The measured equivalent series resistance (ESR) showed a very small value for CNFs (0.28 Ω) in comparison to AC that has an ESR resistance of (3.72 Ω). Moreover, CNF delivered higher specific power (1860 W/kg) than that for AC (450 W/kg). On the other hand, AC gave higher specific energy (18.1 Wh/kg) than that for CNFs (2 Wh/kg).This indicates that the AC is good for energy applications. Whereas, CNF is good for power application. Indeed, the higher surface area will lead to higher specific capacitance and hence higher energy density for AC. For CNF, lower ESR is responsible for having higher power density. Both CNF and AC supercapacitor exhibit an excellent charge-discharge stability up to 2500 cycles.

Middle Pleistocene volcanic activity dated by red thermoluminescence (RTL) - a case study from Lanzarote (Canary Islands)

NASA Astrophysics Data System (ADS)

von Suchodoletz, H.; Blanchard, H.; Rittner, S.; Radtke, U.; Fuchs, M.; Dietze, M.; Zöller, L.

2009-04-01

On Lanzarote (Canary Islands) soils were baked by Quaternary lava flows. This offers the possibility to date phases of eruptive activity by red thermoluminescence (RTL). We dated soil material baked by two different lava flows originating from the "Las Calderetas de Guatiza" volcanic chain in the northeast of the island by RTL. Furthermore, three samples of Helicidae-mollusk shells overlying one of the lava flows (site Mála) were dated using electron spin resonance (ESR). RTL datings were carried out using quartz grains 63-200 µm from baked material that were originally brought by eolian transport from the nearby Saharan desert. It appears that in spite of a baking temperature < 550°C the RTL-signal was sufficiently annealed and thus dating by RTL was possible. RTL ages of ca. 170 ka show good agreement with each other, however, ESR ages are up to 40 % higher than the corresponding RTL age of the lava flow in Mála. Despite this disagreement these results demonstrate that eruptive activity of the volcanic chain occurred during the Middle Pleistocene rather than during the Early Holocene/Late Pleistocene as supposed based on geomorphologic features. Furthermore, they show that 14C-ages of mollusk shells originating from Mála are underestimating volcanic activity up to a factor of 10, a problem often recorded in arid areas. These results demonstrate the value of luminescence and ESR datings on the semi arid Eastern Canary Islands. The successful dating of lava-baked soils on Lanzarote by RTL thus offers the possibility to further investigate the yet fragmentary Middle and Late Quaternary eruptive history of these islands.

Photon correlation spectroscopy applied to tear analysis.

PubMed

Picarazzi, S; Lecchi, M; Pastori, V; D'Arienzo, M; Scotti, R; Tavazzi, S

2017-09-01

This study aims to deepen the knowledge on tear film properties by the development of a protocol for analyses of Photon Correlation Spectroscopy (PCS) on human tears and by the comparison between PCS results obtained on tears of contact lens wearers and non-wearers. Tears (5μL) were collected by a glass capillary. The analyses provide the hydrodynamic diameter of tear components by analyzing intensity fluctuations in time of scattered light. PCS appears a promising technique for studying tear features and for shedding light on specific eye conditions, such as on the clinical effects of CL wear. In fact, statistical difference (p<0.001) was found between the measured mean hydrodynamic diameter of tear components of wearers and non-wearers, the resulting value significantly higher for CL wearers. The scenario does not substantially change after (25±5)min from the CL removal. The difference is attributed to changes in the interactions between tear constituents due to CL wear. In order to get deeper insights on the influence of CL wear on aggregation and structure of tear components, a preliminary Electron Spin Resonance (ESR) investigation was performed, monitoring Fe 3+ species. ESR spectra on tears of both CL wearers and non-wearers showed the presence of intense signals, probably associated to iron (III) centers in proteins such as lactoferrin, and a weaker resonance attributable to Fe 3+ species interacting with S-S bridges of lysozyme. Differences in ESR spectra between CL wearers and non-wearers were detected and tentatively ascribed to changes in coordination or in local environment of Fe 3+ centers connected to aggregation phenomena induced by CL wear, which promote their interaction with other neighboring iron species. Copyright © 2017. Published by Elsevier B.V.

Could Neutrophil CD64 Expression Be Used as a Diagnostic Parameter of Bacteremia in Patients with Febrile Neutropenia?

PubMed

Efe İris, Nur; Yıldırmak, Taner; Gedik, Habip; Şimşek, Funda; Aydın, Demet; Demirel, Naciye; Yokuş, Osman

2017-06-05

The aim of this study is to investigate if neutrophil CD64 expression in febrile neutropenia patients could be used as an early indicator of bacteremia. All consecutive patients older than 18 years of age who had developed febrile neutropenia episodes due to hematological malignancies were included in the study. Those patients who had significant growth in their blood cultures constituted the case group, while those who had febrile neutropenia without any growth in their cultures and who did not have any documented infections formed the control group. Blood culture bottles were incubated in the Bact ALERT 3D system (bioMerieux, France), identification and susceptibility testing were performed using an automated broth microdilution method (VITEK 2, bioMerieux), and CD64 expression analysis was performed by the flow cytometry method. C-reactive protein (CRP) was measured by turbidimetric methods (Biosystems, Spain) and erythrocyte sedimentation rate (ESR) was measured by the Wintrobe method. In total, we prospectively evaluated 31 febrile episodes. The case group consisted of 17 patients while the control group included 14 patients. CD64 was found on neutrophils of the case group patients with a mean count of 8006 molecules/cell and of control group with a mean count of 2786 molecules/cell. CD64 levels of the case group were significantly higher than those of the control group (p=0.005). In the differentiation of the case group from the control group, a 2500 cut-off value for CD64 had significant [AUC=0.792 (0.619-0.965)] predictive value (p=0.001). In the prediction of patients with a 2500 cut-off value for CD64, sensitivity was 94.1%, positive predictive value was 76.2%, specificity was 64.3%, and negative predictive value was 90.0%. CRP levels and ESR values did not differ significantly between the groups (p=0.005). Neutrophil CD64 expression could be a good predictor as an immune parameter with high sensitivity and a negative predictive value for bacteremia in febrile neutropenic patients.

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.

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.

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-...

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

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.

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 .

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

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.

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.

Electrochemical impedance spectroscopy study of carbon electrodes prepared from date pits and fibers of oil palm empty fruit bunches

NASA Astrophysics Data System (ADS)

Hamdan, E.; Deraman, M.; Suleman, M.; Nor, N. S. M.; Basri, N. H.; Hanappi, M. F. Y. M.; Sazali, N. E. S.; Tajuddin, N. S. M.; Omar, R.; Othman, M. A. R.; Shamsudin, S. A.

2016-11-01

In this study, we produced pre-carbonized date pits (PDP) and self-adhesive carbon grains (SACGs) from oil palm empty fruit bunches (EFB) by a low temperature (200°C for DP and 280°C for SACGs, respectively) carbonization method followed by KOH treatment to obtain KOH treated PDP (T-PDP) and KOH treated SACGs (T-SACGs). Four sets of green monolith (GMs) denoted as GM-A, GM-B, GM-C and GM-D were prepared respectively from SACGs (100 wt. %), mixture of PDP and SACGs (50:50 wt. %), T-SACGs (100 wt. %), and mixture of T-SACGs and T-PDP (50:50 wt. %), respectively. From these GMs the respective activated carbon monolith (ACMs) electrodes namely ACM-A, ACM-B, ACM-C and ACM-D were prepared via carbonization (N2 carbonization) and activation (CO2 environment). These ACMs electrodes were used to fabricate the corresponding EDLC cells: Cell-A, Cell-B, Cell-C and Cell-D, respectively. The electrochemical impedance spectroscopy tests conducted on the cells found that the Cell-D showed the maximum value of specific capacitance, Csp (˜ 135 F g-1) whereas the Cell-A showed the minimum values of ESR and characteristic response time, respectively, ˜ 2.14 Ω and ˜ 46 s. Therefore, it can be concluded that the KOH treatment can improve the capacitance but caused the increase in the ESR and response time.

Characterization of the activity of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-be nzopyran-6-yl-hydrogen phosphate] potassium salt in hydroxyl radical elimination.

PubMed

Tomita, T; Kashima, M; Tsujimoto, Y

2000-03-01

The effect of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1-benzopyran-6-yl-hydrogen phosphate] potassium salt (EPC-K1) on hydroxyl radical (*OH) elimination was studied using electron spin resonance (ESR) and spectrophotometric experiments. The addition of EPC-K, and *OH scavengers eliminated the *OH generated from Cu2+/H2O2, Fe2+/H2O2 and H2O2/UV-irradiation reaction systems. However, in competitive reactions using different concentrations of a spin-trap agent, the addition of the *OH scavenger altered the IC50 values, whereas the addition of EPC-K1 and a metal chelater did not change the value in the Cu2+/H2O2 and Fe2+/H2O2 reaction systems. The addition of EPC-K1 and metal chelater changed the ESR signal for free Cu2+. The spectrophotometric experiments confirmed that the addition of EPC-K1 and metal chelater altered the absorption spectra due to CuCl2 and FeSO4, whereas the *OH scavenger did not alter the spectra. Therefore, it was demonstrated that EPC-K, has the ability both to scavenge *OH directly and to inhibit the generation of *OH by the chelation of Cu2+ and Fe2+.

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.

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.

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.

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.

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.

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.

Effect of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitor on Disease Activity in Patients With Rheumatoid Arthritis

PubMed Central

Xing, Bin; Yin, Yu-Feng; Zhao, Li-Dan; Wang, Li; Zheng, Wen-Jie; Chen, Hua; Wu, Qing-Jun; Tang, Fu-Lin; Zhang, Feng-Chun; Shan, Guangliang; Zhang, Xuan

2015-01-01

Abstract HMG-CoA reductase inhibitors (also known as statins) are widely used as lipid-lowering agents in patients with rheumatoid arthritis (RA) to reduce their cardiovascular risk. However, whether they have an effect on RA disease activity is controversial. This study aimed to investigate the effect of statins on disease activity in RA patients. A systematic literature review was performed using the MEDLINE, EMBASE, Cochrane Library, ISI WEB of Knowledge, Scopus, and Clinical Trials Register databases. Only prospective randomized controlled trials or controlled clinical trials comparing the efficacy of statins with placebo on adult RA patients were included. The efficacy was measured according to the ACR criteria, EULAR criteria, DAS28, HAQ score, ESR, or CRP. The Jadad score was used for quality assessment. The inverse variance method was used to analyze continuous outcomes. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was used. For stability of results, we performed leave-one-study-out sensitivity analysis by omitting individual studies one at a time from the meta-analysis. Publication bias was assessed using Egger test. A total 13 studies involving 737 patients were included in the meta-analysis; 11 studies were included in the meta-analysis based on DAS28, while the other 2 studies were only included in the meta-analysis based on ESR or CRP. The standardized mean difference (SMD) in DAS28 between the statin group and the placebo group was −0.55 (95% CI [−0.83, −0.26], P = 0.0002), with an I2 value of 68%. Subgroup analysis showed that patients with more active disease tended to benefit more from statin therapy (SMD −0.73, P = 0.01) than patients with moderate or low disease activity (SMD −0.38, P = 0.03). Statin therapy also significantly reduced tender joint counts, swollen joint counts, ESR, and CRP compared with placebo, but the reduction in HAQ score and VAS was not significant (P > 0.05). This meta-analysis suggested that statin therapy might be effective in the reduction of RA disease activity measured by DAS28, TJC, SJC, as well as ESR and CRP. PMID:25715256

Efficacy of noninvasive evaluations in monitoring inflammatory bowel disease activity: A prospective study in China

PubMed Central

Chen, Jin-Min; Liu, Tao; Gao, Shan; Tong, Xu-Dong; Deng, Fei-Hong; Nie, Biao

2017-01-01

AIM To optimize the efficacy of noninvasive evaluations in monitoring the endoscopic activity of inflammatory bowel disease (IBD). METHODS Fecal calprotectin (FC), clinical activity index (CDAI or CAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) were measured for 136 IBD patients. Also, FC was measured in 25 irritable bowel syndrome (IBS) patients that served as controls. Then, endoscopic activity was determined by other two endoscopists for colonic or ileo-colonic Crohn’s disease (CICD) with the “simple endoscopic score for Crohn’s disease” (SES-CD), CD-related surgery patients with the Rutgeerts score, and ulcerative colitis (UC) with the Mayo score. The efficacies of these evaluations to predict the endoscopic disease activity were assessed by Mann-Whitney test, χ2 test, Spearman’s correlation, and multiple linear regression analysis. RESULTS The median FC levels in CD, UC, and IBS patients were 449.6 (IQR, 137.9-1344.8), 497.9 (IQR, 131.7-118.0), and 9.9 (IQR, 049.7) μg/g, respectively (P < 0.001). For FC, CDAI or CAI, CRP, and ESR differed significantly between endoscopic active and remission in CICD and UC patients, but not in CD-related surgery patients. The SES-CD correlated closely with levels of FC (r = 0.802), followed by CDAI (r = 0.734), CRP (r = 0.658), and ESR (r = 0.557). The Mayo score also correlated significantly with FC (r = 0.837), CAI (r = 0.776), ESR (r = 0.644), and CRP (r = 0.634). For FC, a cut-off value of 250 μg/g indicated endoscopic active inflammation with accuracies of 87.5%, 60%, and 91.1%, respectively, for CICD, CD-related surgery, and UC patients. Moreover, clinical FC activity (CFA) calculated as 0.8 × FC + 4.6 × CDAI showed higher area under the curve (AUC) of 0.962 for CICD and CFA calculated as 0.2 × FC + 50 × CAI showed higher AUC (0.980) for UC patients than the FC. Also, the diagnostic accuracy of FC in identifying patients with mucosal inflammation in clinical remission was reflected by an AUC of 0.91 for CICD and 0.96 for UC patients. CONCLUSION FC is the most promising noninvasive evaluation for monitoring the endoscopic activity of CICD and UC. CFA might be more accurate for IBD activity evaluation. PMID:29290660

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.

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.

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.

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.

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.

Effect of surfactant and mineralizer on the dielectric properties of zirconia nanocrsytals

NASA Astrophysics Data System (ADS)

Maheswari, A. Uma; Mohan, Sreedevi R.; Sivakumar, M.

2018-01-01

The combined effect of surfactants (PVP/CTAB) and alkaline mineralizers (NaOH/NH4OH) on dielectric properties of zirconia nanocrystals is analyzed. It is found that, the stabilization of zirconia tetramers by surfactants and the rate of hydroxyl ions released by alkaline mineralizers have significant impact on the dielectric properties of nanocrystals. The PVP capped tetramers form highly conducting grains with insulating boundaries, whereas the grains of CTAB capped tetramers are highly insulating with conducting grain boundaries, as revealed by Nyquist plots. Consequently, the space charge polarization would be quite large in highly conducting grains resulting in higher dielectric constant values at lower frequencies. The higher dielectric constant of PVP capped nanocrystals is due to greater tetragonal coordination of 3d5/2 and 3d3/2 electrons of Zr4+ ions than that of CTAB capped nanocrystals. Further, the surface oxygen vacancies of PVP samples are higher, resulting in a high space charge polarization. The ESR signal corresponding to F+ centers appears stronger for PVP/NH4OH nanocrystals. Moreover, the larger ESR line width of PVP/NH4OH nanocrystals corresponding to more oxygen vacancies is in accordance with the inference attained from the XPS analysis.

Predictive factors of clinical response in steroid-refractory ulcerative colitis treated with granulocyte-monocyte apheresis

PubMed Central

D'Ovidio, Valeria; Meo, Donatella; Viscido, Angelo; Bresci, Giampaolo; Vernia, Piero; Caprilli, Renzo

2011-01-01

AIM: To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA). METHODS: Sixty-nine ulcerative colitis patients (39 F, 30 M) dependent upon/refractory to steroids were treated with GMA. Steroid dependency, clinical activity index (CAI), C reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), values at baseline, use of immunosuppressant, duration of disease, and age and extent of disease were considered for statistical analysis as predictive factors of clinical response. Univariate and multivariate logistic regression models were used. RESULTS: In the univariate analysis, CAI (P = 0.039) and ESR (P = 0.017) levels at baseline were singled out as predictive of clinical remission. In the multivariate analysis steroid dependency [Odds ratio (OR) = 0.390, 95% Confidence interval (CI): 0.176-0.865, Wald 5.361, P = 0.0160] and low CAI levels at baseline (4 < CAI < 7) (OR = 0.770, 95% CI: 0.425-1.394, Wald 3.747, P = 0.028) proved to be effective as factors predicting clinical response. CONCLUSION: GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 mo. PMID:21528055

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.

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.