Spectroscopic investigation of PF-1000 discharges under different experimental conditions

The emission from free-propagating plasma streams was studied in experiments with a 1-MJ plasma-focus PF-1000 facility operated at the IPPLM in Warsaw, Poland. The machine was filled up with a pure deuterium or a mixture of deuterium and argon. Optical spectra were recorded at a distance of 30 cm from the electrodes, at different experimental conditions, i.e. initial pressures, charging voltages and acquisition times, in the wavelength range of 350…1000 nm. The most intense lines originated from the applied working gases. In some cases distinct CuI and FeI lines resulted from the electrodes and the insulator were observed. From the Balmer lines, Dβ and Dγ, an electron density as a function of time was estimated. The application of this finding made it possible to perform some experiments concerning spectroscopic research on the interaction of free-propagating plasma streams with tungsten targets. In the recorded spectra some WI and WII lines were identified, but the resolution of the spectrometer was not good enough for their quantitative analysis.Исследовано излучение свободно распространяющихся плазменных потоков, генерируемых мегаджоульным плазменным фокусом ПФ-1000 (ИФПЛМ, Варшава, Польша). В качестве рабочего газа использовался чистый дейтерий и смесь дейтерия с аргоном. Оптические спектры в диапазоне 350...1000 нм регистрировались на расстоянии 30 см от электродов при вариации экспериментальных условий (начального давления, напряжения и времени обработки). Наиболее интенсивными спектральными линиями, зарегистрированными в экспериментальных спектрах, являются линии рабочего газа. В некоторых случаях наблюдались также линии примесных элементов: CuI – материала электродов и FeI – изолятора. Временная зависимость электронной плотности плазмы оценивалась из уширения бальмеровских линий Dβ и Dγ. Представлены также результаты спектрального анализа процесса взаимодействия плазменных потоков с вольфрамом. Идентифицированы спектральные линии WI и WII, однако разрешение спектрометра не позволило провести количественный анализ.Досліджено випромінювання плазмових потоків, що генеруються мегаджоульним плазмовим фокусом ПФ-1000 (ІФПЛМ, Варшава, Польща). В якості робочого газу використовувався чистий дейтерій і суміш дейтерію з аргоном. Оптичні спектри в діапазоні 350...1000 нм реєструвалися на відстані 30 см від електродів при варіації експериментальних умов (початкового тиску, напруги і часу обробки). Найбільш інтенсивними спектральними лініями, зареєстрованими в експериментальних спектрах, є лінії робочого газу. У деяких випадках спостерігались також лінії домішкових елементів: CuI – матеріалу електродів і FeI – ізолятора. Часова залежність електронної густини плазми оцінювалась з розширення бальмерівських ліній Dβ та Dγ. Представлено також результати спектрального аналізу процесу взаємодії плазмових потоків з вольфрамом. Ідентифіковано спектральні лінії WI і WII, проте роздільність спектрометра не дозволила провести кількісний аналіз

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers

Purpose To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers. Methods Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up. Results Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC d

Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03-6.30, P = 3.1 × 10-9). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics

Prediction and clinical utility of a contralateral breast cancer risk model

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Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts

PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1

Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.Peer reviewe