WorldWideScience

Sample records for mutation frequency response

  1. A threshold in the dose-response relationship for X-ray induced somatic mutation frequency in drosophila melanogaster

    International Nuclear Information System (INIS)

    Koana, Takao; Sakai, Kazuo; Okada, M.O.

    2004-01-01

    The dose-response relationship of ionizing radiation and its stochastic effects has been thought to be linear without any thresholds for a long time. The basic data for this model was obtained from mutational assays using germ cells of male fruit fly Drosophila melanogaster. However, cancer-causing activity should be examined more appropriately in somatic cells than in germ cells. In this paper, we examined the dose-response relationship of X-ray irradiation and somatic mutation in drosophila, and found a threshold at approximately 1 Gy in the DNA repair proficient flies. In the repair deficient siblings, the threshold was smaller and the inclination of the dose-response curve was five times steeper. These results suggest that the dose-response relationship between X-ray irradiation and somatic mutation has a threshold, and that the DNA repair function contributes to its formation. (author)

  2. BRCA Mutation Frequency and Patterns of Treatment Response in BRCA Mutation–Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group

    Science.gov (United States)

    Alsop, Kathryn; Fereday, Sian; Meldrum, Cliff; deFazio, Anna; Emmanuel, Catherine; George, Joshy; Dobrovic, Alexander; Birrer, Michael J.; Webb, Penelope M.; Stewart, Colin; Friedlander, Michael; Fox, Stephen; Bowtell, David; Mitchell, Gillian

    2012-01-01

    Purpose The frequency of BRCA1 and BRCA2 germ-line mutations in women with ovarian cancer is unclear; reports vary from 3% to 27%. The impact of germ-line mutation on response requires further investigation to understand its impact on treatment planning and clinical trial design. Patients and Methods Women with nonmucinous ovarian carcinoma (n = 1,001) enrolled onto a population-based, case-control study were screened for point mutations and large deletions in both genes. Survival outcomes and responses to multiple lines of chemotherapy were assessed. Results Germ-line mutations were found in 14.1% of patients overall, including 16.6% of serous cancer patients (high-grade serous, 22.6%); 44% had no reported family history of breast or ovarian cancer. Patients carrying germ-line mutations had improved rates of progression-free and overall survival. In the relapse setting, patients carrying mutations more frequently responded to both platin- and nonplatin-based regimens than mutation-negative patients, even in patients with early relapse after primary treatment. Mutation-negative patients who responded to multiple cycles of platin-based treatment were more likely to carry somatic BRCA1/2 mutations. Conclusion BRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials. Treatment outcomes in BRCA1/2 carriers challenge conventional definitions of platin resistance, and mutation status may be able to contribute to decision making and systemic therapy selection in the relapse setting. Our data, together with the advent of poly(ADP-ribose) polymerase inhibitor trials, supports the recommendation that germ-line BRCA1/2 testing should be offered to all women diagnosed with nonmucinous, ovarian carcinoma, regardless of family history. PMID:22711857

  3. Complexity of the ultraviolet mutation frequency response curve in Escherichia coli B/r: SOS induction, one-lesion and two-lesion mutagenesis

    International Nuclear Information System (INIS)

    Doudney, C.O.

    1976-01-01

    Three distinct sections of the ultraviolet mutation frequency response (MFR) curve toward tryptophan prototrophy have been demonstrated in Escherichia coli B/r WP2 trp thy and its uvrA derivative in log-phase growth in minimal medium. The initial section, which appears fluence-squared, may reflect the necessity, if mutation is to result, for induction of two lesions, one located within the potentially mutated genetic locus and the other damaging deoxyribonucleic acid replication and resulting in induction of the error-prone SOS repair function. A second linear section is ascribed to the continued induction, after exposure above that sufficient for complete SOS expression, of isolated lesions which lead to mutation in potentially mutated loci. The third section demonstrates an increased rate of mutagenesis and suggests the induction of two lesions in proximity which result in additional mutations. Split-exposure studies support the inducible nature of the SOS function and suggest that mutation frequency decline (MFD) is due to excision resulting from or related to the prevention of SOS induction by inhibition of protein synthesis. Preirradiation tryptophan starvation of the uvr + strain for 30 min decreases MFR in the first and second sections of the curve. Reduction of MFR in the third section requires more prestarvation time and is blocked by nalidixic acid. The decreased MFR of the first and second sections is ascribed to promotion of postirradiation MFD based on excision and that of the third section to completion of the chromosome during the prestarvation period

  4. EGFR mutation frequency and effectiveness of erlotinib

    DEFF Research Database (Denmark)

    Weber, Britta; Hager, Henrik; Sorensen, Boe S

    2014-01-01

    mutation (S768I), and two complex mutations. Seven percent of the patients were never smokers. The differences in median progression-free survival and overall survival between the mutated group and the wild-type group were 8.0 vs. 2.5 months, p...-1 vs. 2-3) and line of treatment (1st vs. 2nd and 3rd) had no influence on outcome in EGFR-mutated patients. CONCLUSION: We found a higher frequency of EGFR mutations than expected in a cohort with less than 10% never smokers. The outcome after treatment with erlotinib was much better in patients......OBJECTIVES: In 2008, we initiated a prospective study to explore the frequency and predictive value of epidermal growth factor receptor (EGFR) mutations in an unselected population of Danish patients with non-small cell lung cancer offered treatment with erlotinib, mainly in second-line. MATERIALS...

  5. Modification of mutation frequency in Saccharomyces Cerevisiae

    International Nuclear Information System (INIS)

    Vashishat, R.K.; Kakar, S.N.

    1976-01-01

    In a reverse mutation system, using haploid, histidine-requirinq strain of Saccharomyces cerevisiae, the frequency of uv-induced prototrophs increased if the post-irradiation minimal medium was supplemented with limited amounts of histidine. Addition of natural amino acids or RNA bases in the post-irradiation minimal medium, with or without histidine, also increased the uv-induced mutation frequency. Thus, post-irradiation conditions favouring protein and RNA synthesis, are effective in increasing uv-induced mutations in yeast. As compared to uv light, nitrous acid was more effective in inducing reversions in this strain and the frequency increased if the treated cells were plated on minimal medium supplemented with limited amounts of histidine. However, the addition of amino acids or RNA bases decreased the number of revertants. An additional inclusion of histidine reversed the suppressive effect of these metabolites. The mutation induction processes are thus different or differently modifiable in uv and nitrous acid. (author)

  6. Eastern Frequency Response Study

    Energy Technology Data Exchange (ETDEWEB)

    Miller, N.W.; Shao, M.; Pajic, S.; D' Aquila, R.

    2013-05-01

    This study was specifically designed to investigate the frequency response of the Eastern Interconnection that results from large loss-of-generation events of the type targeted by the North American Electric Reliability Corp. Standard BAL-003 Frequency Response and Frequency Bias Setting (NERC 2012a), under possible future system conditions with high levels of wind generation.

  7. Frequency Response Analysis Tool

    Energy Technology Data Exchange (ETDEWEB)

    Etingov, Pavel V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kosterev, Dmitry [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Dai, T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-12-01

    Frequency response has received a lot of attention in recent years at the national level, which culminated in the development and approval of North American Electricity Reliability Corporation (NERC) BAL-003-1 Frequency Response and Frequency Bias Setting Reliability Standard. This report is prepared to describe the details of the work conducted by Pacific Northwest National Laboratory (PNNL) in collaboration with the Bonneville Power Administration and Western Electricity Coordinating Council (WECC) Joint Synchronized Information Subcommittee (JSIS) to develop a frequency response analysis tool (FRAT). The document provides the details on the methodology and main features of the FRAT. The tool manages the database of under-frequency events and calculates the frequency response baseline. Frequency response calculations are consistent with frequency response measure (FRM) in NERC BAL-003-1 for an interconnection and balancing authority. The FRAT can use both phasor measurement unit (PMU) data, where available, and supervisory control and data acquisition (SCADA) data. The tool is also capable of automatically generating NERC Frequency Response Survey (FRS) forms required by BAL-003-1 Standard.

  8. A Threshold Exists in the Dose-response Relationship for Somatic Mutation Frequency Inducted by X-ray Irradiation of Drosophia

    International Nuclear Information System (INIS)

    Koana, T.; Takashima, Y.; Okada, M. O.; Ikehata, M.; Miyakoshi, J.; Sakai, K.

    2004-01-01

    The dose-response relationship of ionizing radiation and its stochastic effects has been thought to be linear without any thresholds. The basic data for this model was obtained from mutational assays in the male germ cells of fruits fly Drosophila melanogaster. However, carcinogenic activity should be examined more appropriately in somatic cells than in germ cells. Here, the dose-response relationship of X- ray irradiation and somatic mutation is examined in Drosophila. A threshold at approximately 1Gy was observed in the DNA repair proficient flies. In the repair deficient siblings, the threshold was smaller and the inclination of the dose-response curve was much steeper. These results suggest that the dose-response relationship between X-ray irradiation and somatic mutation has a threshold, and that the DNA repair function contributes to its formation. (Author) 35 refs

  9. Induced mutations in chickpea (Cicer arietinum L.) II. frequency and spectrum of chlorophyll mutations

    International Nuclear Information System (INIS)

    Kharkwal, M.C.

    1998-01-01

    A comparative study of frequency and spectrum of chlorophyll mutations induced by two physical (gamma rays, fast neutrons) and two chemical mutagens (NMU, EMS) in relation to the effects in M1 plants and induction of mutations in M2 was made in four chickpea (Cicer arietinum L.) varieties, two desi (G 130 & H 214) one Kabuli (C 104) and one green seeded (L 345). The treatments included three doses each of gamma rays (400, 500 & 600 Gy) and fast neutrons (5, 10 & 15 Gy) and two concentrations with two different durations of two chemical mutagens, NMU [0.01% (20h), & 0.02% (8h)] and EMS [0.1% (20h) & 0.2% (8h)]. The frequencies and spectrum of three different kinds of induced chlorophyll mutations in the order albina (43.5%), chlorina (27.3%) and xantha (24.2%) were recorded. Chemical mutagens were found to be efficient in inducing chlorophyll mutations in chickpea. Highest frequency of mutations was observed in green seeded var. L 345 (83% of M1 families and 19.9/1000 M2 plants). Kabuli var. C 104 was least responsive for chlorophyll mutations

  10. The spontaneous chlorophyll mutation frequency in barley

    DEFF Research Database (Denmark)

    Jørgensen, Jørgen Helms; Jensen, Hans Peter

    1986-01-01

    A total of 1866 barley plants were progeny tested in the greenhouse. Twenty-five plants segregated for newly arisen, spontaneous chlorophyll mutant genes. Among the total of 470,129 seedlings screened there were 79 mutants (1.7 .+-. 0.6 .times. 10-4). The data are added to data from three similar...... materials and the resulting estimate of the chlorophyll mutant frequency is 1.6 .times. 10-4 in about 1.43 million seedlings. The estimate of the chlorophyll mutation rate per generation is close to 67.3 .times. 10-4 per diploid genome or in the order of 6 .times. 10-7 per locus and haploid genome....

  11. The occurrence and frequency of genomic mutations that mediate ...

    African Journals Online (AJOL)

    The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi.

  12. Frequency and distribution of Notch mutations in tumor cell lines

    International Nuclear Information System (INIS)

    Mutvei, Anders Peter; Fredlund, Erik; Lendahl, Urban

    2015-01-01

    Deregulated Notch signaling is linked to a variety of tumors and it is therefore important to learn more about the frequency and distribution of Notch mutations in a tumor context. In this report, we use data from the recently developed Cancer Cell Line Encyclopedia to assess the frequency and distribution of Notch mutations in a large panel of cancer cell lines in silico. Our results show that the mutation frequency of Notch receptor and ligand genes is at par with that for established oncogenes and higher than for a set of house-keeping genes. Mutations were found across all four Notch receptor genes, but with notable differences between protein domains, mutations were for example more prevalent in the regions encoding the LNR and PEST domains in the Notch intracellular domain. Furthermore, an in silico estimation of functional impact showed that deleterious mutations cluster to the ligand-binding and the intracellular domains of NOTCH1. For most cell line groups, the mutation frequency of Notch genes is higher than in associated primary tumors. Our results shed new light on the spectrum of Notch mutations after in vitro culturing of tumor cells. The higher mutation frequency in tumor cell lines indicates that Notch mutations are associated with a growth advantage in vitro, and thus may be considered to be driver mutations in a tumor cell line context. The online version of this article (doi:10.1186/s12885-015-1278-x) contains supplementary material, which is available to authorized users

  13. Frequency of factor V Leiden mutation

    International Nuclear Information System (INIS)

    Nasiruddin; Ali, W.; Rehman, Z.; Anwar, M.; Ayyub, M.; Ali, W.; Ahmed, S.

    2005-01-01

    Objective: To determine the frequency of factor V Leiden mutation. Design: Observational study. Patients and Methods: Two hundred subjects each of apparently healthy and unrelated Punjabi and Pathan origins were included in the study. Peripheral blood samples were collected in EDTA and DNA extracted by phenol- chloroform extraction method. DNA analysis was done by PCR for restriction fragment length polymorphism. The product was digested overnight with Mn/1 and electrophoresed on acrylamide gel to detect 67 and 153 base pair fragments of factor V Leiden against 37, 67 and 116 base pair fragments of normal factor V. Results: In the 400 subjects studied, only 5 cases of heterozygotes for factor V Leiden were detected. The overall carrier rate was 1.3% (95% CI 0.2-2.2%). The carrier rate in Punjabis and Pathans was 1 % and 1.5% respectively. Conclusion: This study confirms that the prevalence of factor V Leiden is low in Asians and Africans as compared to the European population. (author)

  14. The Oenothera plastome mutator: effect of UV irradiation and nitroso-methyl urea on mutation frequencies

    International Nuclear Information System (INIS)

    Sears, B.B.; Sokalski, M.B.

    1991-01-01

    Oenothera plants homozygous for a recessive plastome mutator allele (pm) showed spontaneous mutation frequencies for plastome genes that are 200-fold higher than spontaneous levels. Mutations occurred at high frequencies in plants grown in the field, in a glasshouse, or as leaf tip cultures under fluorescent light, indicating that the plastome mutator activity is UV-independent. However, the chlorotic sectors became visible at an earlier stage of development when seedlings were irradiated, compared to seedlings that were not exposed to UV. These results imply that the rate of sorting-out was increased by the irradiation treatment, possibly due to a decrease in the effective number of multiplication-competent plastids, or a reduction in the extent of cytoplasmic mixing. Nitroso-methyl urea treatment of seeds had a dramatic effect on mutation frequency in both wild-type and plastome mutator samples. When the background mutation rates were low, the combination of the plastome mutator nucleus and the chemical mutagenesis treatment resulted in a synergistic effect, suggesting that the plastome mutator may involve a cpDNA repair pathway. (author)

  15. Frequencies of aneuploidy and dominant lethal mutations in young female mice induced by low dose γ-rays

    International Nuclear Information System (INIS)

    Yao Suyan; Zhang Chaoyang; Dai Lianlian; Gao Changwen

    1991-01-01

    Relationship between aneuploidy, dominant lethal mutations and doses in young feral mice induced by low dose γ-rays was examined. The results suggest that the frequencies of aneuploidy of embryos increased at 0.15 Gy, but increases at over 0.50 Gy after irradiation in groups. The frequencies of aneuploidy and dominant lethal mutations increased with increasing doses and fitted linear relationship. This dose-response relationship of trisomic was not significant. The frequency of dominant lethal mutations induced by 60 Co γ irradiation is 5.59%. The effect of dominant lethal mutation is higher than that of the aneuploidy

  16. Frequency response of electrochemical cells

    Science.gov (United States)

    Thomas, Daniel L.

    1990-01-01

    The main objective was to examine the feasibility of using frequency response techniques (1) as a tool in destructive physical analysis of batteries, particularly for estimating electrode structural parameters such as specific area, porosity, and tortuosity and (2) as a non-destructive testing technique for obtaining information such as state of charge and acceptability for space flight. The phenomena that contribute to the frequency response of an electrode include: (1) double layer capacitance; (2) Faradaic reaction resistance; (3) mass transfer of Warburg impedance; and (4) ohmic solution resistance. Nickel cadmium cells were investigated in solutions of KOH. A significant amount of data was acquired. Quantitative data analysis, using the developed software, is planned for the future.

  17. Identification of a novel mutation in WFS1 in a family affected by low-frequency hearing impairment

    Energy Technology Data Exchange (ETDEWEB)

    Kunz, Juergen; Marquez-Klaka, Ben; Uebe, Steffen; Volz-Peters, Anja; Berger, Roswitha; Rausch, Peter

    2003-04-09

    Previously we confirmed linkage of autosomal dominantly inherited low-frequency sensorineural hearing impairment (LFSNHI) in a German family to the genetic locus DFNA6/DFNA14 on chromosome 4p16.3 close to the markers D4S432 and D4S431. Analysis of data from the Human Genome Project, showed that WFS1 is located in this region. Mutations in WFS1 are known to be responsible for Wolfram syndrome (DIDMOAD, MIM no. 606201), which follows an autosomal recessive trait. Studies in low-frequency hearing loss families showed that mutations in WFS1 were responsible for the phenotype. In all affected family members analysed, we detected a missense mutation in WFS1 (K705N) and therefore confirm the finding that the majority of mutations responsible for LFSNHI are missense mutations which localise to the C-terminal domain of the protein.

  18. Identification of a novel mutation in WFS1 in a family affected by low-frequency hearing impairment

    International Nuclear Information System (INIS)

    Kunz, Juergen; Marquez-Klaka, Ben; Uebe, Steffen; Volz-Peters, Anja; Berger, Roswitha; Rausch, Peter

    2003-01-01

    Previously we confirmed linkage of autosomal dominantly inherited low-frequency sensorineural hearing impairment (LFSNHI) in a German family to the genetic locus DFNA6/DFNA14 on chromosome 4p16.3 close to the markers D4S432 and D4S431. Analysis of data from the Human Genome Project, showed that WFS1 is located in this region. Mutations in WFS1 are known to be responsible for Wolfram syndrome (DIDMOAD, MIM no. 606201), which follows an autosomal recessive trait. Studies in low-frequency hearing loss families showed that mutations in WFS1 were responsible for the phenotype. In all affected family members analysed, we detected a missense mutation in WFS1 (K705N) and therefore confirm the finding that the majority of mutations responsible for LFSNHI are missense mutations which localise to the C-terminal domain of the protein

  19. Frequency of common CFTR gene mutations in Venezuelan patients with cystic fibrosis

    OpenAIRE

    Sánchez, Karen; Arcia, Orlando; Matute, Xiorama; Mindiola, Luz; Chaustre, Ismenia; Takiff, Howard

    2014-01-01

    Mutations in the CFTR gene in Cystic Fibrosis (CF) patients have geographic differences and there is scant data on their prevalence in Venezuelan patients. This study determined the frequency of common CFTR gene mutations in these patients. We amplified and sequenced exons 7, 10, 11, 19, 20 and 21, which contain the most common CFTR mutations, from 105 Venezuelan patients in the National CF Program. Eleven different mutations were identified, four with frequencies greater than 1%: p.Phe508del...

  20. Mutation frequencies of the cytochrome CYP2D6 gene in Parkinson disease patients and in families

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; Turpin, J.C. [CHR, Reims (France); Gerard, N. [INSERM, Paris (France)] [and others

    1996-07-26

    The frequencies of five mutations of the debrisoquine 4-hydroxylase (CYP2D6) gene (mutations D6-A, B, C, D, and T), corresponding to poor metabolizer (PM) phenotypes, were determined by restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) in 47 patients with Parkinson disease, and compared with the findings in 47 healthy controls. These mutant alleles were about twice as frequent among patients as in controls, with an approximate relative risk ratio of 2.12 (95% confidence interval, 1.41-2.62). There seem to be no significant differences in frequencies of mutant genotypes in patients among gender and modalities of response with levodopa therapy; but frequency of the mutations was slightly enhanced after age-at-onset of 60 years. Mutations D6-B, D, and T were detected in 7 patients belonging to 10 Parkinson pedigrees. 25 refs., 1 fig., 2 tabs.

  1. Abiotic stress leads to somatic and heritable changes in homologous recombination frequency, point mutation frequency and microsatellite stability in Arabidopsis plants

    International Nuclear Information System (INIS)

    Yao Youli; Kovalchuk, Igor

    2011-01-01

    In earlier studies, we showed that abiotic stresses, such as ionizing radiation, heavy metals, temperature and water, trigger an increase in homologous recombination frequency (HRF). We also demonstrated that many of these stresses led to inheritance of high-frequency homologous recombination, HRF. Although an increase in recombination frequency is an important indicator of genome rearrangements, it only represents a minor portion of possible stress-induced mutations. Here, we analyzed the influence of heat, cold, drought, flood and UVC abiotic stresses on two major types of mutations in the genome, point mutations and small deletions/insertions. We used two transgenic lines of Arabidopsis thaliana, one allowing an analysis of reversions in a stop codon-containing inactivated β-glucuronidase transgene and another one allowing an analysis of repeat stability in a microsatellite-interrupted β-glucuronidase transgene. The transgenic Arabidopsis line carrying the β-glucuronidase-based homologous recombination substrate was used as a positive control. We showed that the majority of stresses increased the frequency of point mutations, homologous recombination and microsatellite instability in somatic cells, with the frequency of homologous recombination being affected the most. The analysis of transgenerational changes showed an increase in HRF to be the most prominent effect observed in progeny. Significant changes in recombination frequency were observed upon exposure to all types of stress except drought, whereas changes in microsatellite instability were observed upon exposure to UVC, heat and cold. The frequency of point mutations in the progeny of stress-exposed plants was the least affected; an increase in mutation frequency was observed only in the progeny of plants exposed to UVC. We thus conclude that transgenerational changes in genome stability in response to stress primarily involve an increase in recombination frequency.

  2. Comparison of somatic mutation frequencies at HGPRT locus induced by radiation and chemical pollutant from energy system

    International Nuclear Information System (INIS)

    Xu Honglan; Cao Yi; Duan Zhikai; Wu Qiqing; Chen Ying; Zhang Shuxian

    1998-12-01

    The somatic induction frequencies of mutation at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus induced by 60 Co γ-rays and Benzo-a-pyrene (B(a)P), which are representative of hazardous emission and pollutant from nuclear energy cycle and fossil-fuelled energy cycle respectively, were detected by using forward mutation assay and cloning technique in both V 79 Chinese hamster cells and human peripheral blood T-lymphocytes. Resistant mutants were selected with 6-thioguanine (6-TG). Dose-response curves and mathematical expressions were obtained for mutation frequencies and survival following γ-ray and B(a)P(+S 9 ) treatments. The dose ranges for the two mutagens were compared when they induced the same mutation frequencies. In V 79 /HGPRT assay system, when the mutation frequencies were 5∼35 mutants/10 6 cells the response of γ-rays in the dose range from 0.93∼4.96 Gy at dose rate of 1.16 Gy/min is nearly equivalent to that in the B(a)P dose range from 0.52∼4.27 μg/ml. By using cloning technique in T-lymphocytes, when the mutation frequencies were 1∼14 mutants/10 5 cells the response of γ-rays in the dose range from 0.05∼4.77 Gy at dose rate of 1.03 Gy/min is nearly equivalent to that in the B(a)P dose range from 0.15∼7.36 μg/ml. When the survival fraction is 37%, the mutation frequency induced by B(a)P is higher than that induced by 60 Co γ-rays

  3. Slot Machine Response Frequency Predicts Pathological Gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne

    2013-01-01

    . This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...... in individuals with exacerbated pathological gambling symptoms. These findings may have important implications for detecting behaviors underlying pathological gambling....

  4. The frequency pattern of dumpy mutations induced by x-rays in the successive stages of oocytes of Drosophila

    International Nuclear Information System (INIS)

    Miyamoto, Tomio; Nakao, Yoshio

    1978-01-01

    The frequency patterns of the different kinds of dumpy mutations induced by x-rays (1,500 and 3,000R) in the successive stages of oocyte development were investigated by transferring the inseminated females daily to fresh vials for 12 days. Under this transferring procedure, the first egg-laying period represents oocytes irradiated when they are at stage 14, and the subsequent ones represent progressively earlier stages of oocyte development at the time of irradiation. The results obtained indicate that (1) the overall yield of complete dumpy mutations recovered in the first six day egg-laying periods (1st-6th day) are relatively higher than that in the subsequent six day periods (7th-12th day), showing a response pattern with a higher mutation frequency in the early egg-laying periods and a lower frequency in the late egg-laying periods; (2) the frequency patterns for the exceptions of the ol and lv types and those of ov and olv types through the sampling periods are practically similar to those observed in the total dumpy mutations; (3) a somewhat peculiar frequency pattern, which seems to be variable by dose, is found in the yield of the o and v exceptions. At the exposure level of 1,500R, no definite difference in response pattern for these exceptions is found, though a response pattern which is practically similar to that observed in the total dumpy mutations is found at the exposure level of 3,000R. The foregoing findings seem to indicate that the different kinds of dumpy exceptions are affected at various degrees by the difference in the cell stages of oocyte. This may possibly suggest that these exceptions are different from each other in the nature of their mutations, that is to say, whether they are associated with chromosome breakage events or not. (auth.)

  5. Frequency and Prognostic Relevance of FLT3 Mutations in Saudi Acute Myeloid Leukemia Patients

    Directory of Open Access Journals (Sweden)

    Ghaleb Elyamany

    2014-01-01

    Full Text Available The Fms-like tyrosine kinase-3 (FLT3 is a receptor tyrosine kinase that plays a key role in cell survival, proliferation, and differentiation of hematopoietic stem cells. Mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia (AML. AML patients with FLT3 internal tandem duplication (ITD mutations have poor cure rates the prognostic significance of point mutations; tyrosine kinase domain (TKD is still unclear. We analyzed the frequency of FLT3 mutations (ITD and D835 in patients with AML at diagnosis; no sufficient data currently exist regarding FLT3 mutations in Saudi AML patients. This study was aimed at evaluating the frequency of FLT3 mutations in patients with AML and its significance for prognosis. The frequency of FLT3 mutations in our study (18.56% was lower than many of the reported studies, FLT3-ITD mutations were observed in 14.4%, and FLT3-TKD in 4.1%, of 97 newly diagnosed AML patients (82 adult and 15 pediatric. Our data show significant increase of FLT3 mutations in male more than female (13 male, 5 female. Our results support the view that FLT3-ITD mutation has strong prognostic factor in AML patients and is associated with high rate of relapse, and high leucocytes and blast count at diagnosis and relapse.

  6. Primary Frequency Response with Aggregated DERs: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Guggilam, Swaroop S.; Dhople, Sairaj V.; Zhao, Changhong; Dall' Anese, Emiliano; Chen, Yu Christine

    2017-03-03

    Power networks have to withstand a variety of disturbances that affect system frequency, and the problem is compounded with the increasing integration of intermittent renewable generation. Following a large-signal generation or load disturbance, system frequency is arrested leveraging primary frequency control provided by governor action in synchronous generators. In this work, we propose a framework for distributed energy resources (DERs) deployed in distribution networks to provide (supplemental) primary frequency response. Particularly, we demonstrate how power-frequency droop slopes for individual DERs can be designed so that the distribution feeder presents a guaranteed frequency-regulation characteristic at the feeder head. Furthermore, the droop slopes are engineered such that injections of individual DERs conform to a well-defined fairness objective that does not penalize them for their location on the distribution feeder. Time-domain simulations for an illustrative network composed of a combined transmission network and distribution network with frequency-responsive DERs are provided to validate the approach.

  7. Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations.

    Science.gov (United States)

    Verger, Emmanuelle; Cassinat, Bruno; Chauveau, Aurélie; Dosquet, Christine; Giraudier, Stephane; Schlageter, Marie-Hélène; Ianotto, Jean-Christophe; Yassin, Mohammed A; Al-Dewik, Nader; Carillo, Serge; Legouffe, Eric; Ugo, Valerie; Chomienne, Christine; Kiladjian, Jean-Jacques

    2015-12-10

    Myeloproliferative neoplasms are clonal disorders characterized by the presence of several gene mutations associated with particular hematologic parameters, clinical evolution, and prognosis. Few therapeutic options are available, among which interferon α (IFNα) presents interesting properties like the ability to induce hematologic responses (HRs) and molecular responses (MRs) in patients with JAK2 mutation. We report on the response to IFNα therapy in a cohort of 31 essential thrombocythemia (ET) patients with CALR mutations (mean follow-up of 11.8 years). HR was achieved in all patients. Median CALR mutant allelic burden (%CALR) significantly decreased from 41% at baseline to 26% after treatment, and 2 patients even achieved complete MR. In contrast, %CALR was not significantly modified in ET patients treated with hydroxyurea or aspirin only. Next-generation sequencing identified additional mutations in 6 patients (affecting TET2, ASXL1, IDH2, and TP53 genes). The presence of additional mutations was associated with poorer MR on CALR mutant clones, with only minor or no MRs in this subset of patients. Analysis of the evolution of the different variant allele frequencies showed that the mutated clones had a differential sensitivity to IFNα in a given patient, but no new mutation emerged during treatment. In all, this study shows that IFNα induces high rates of HRs and MRs in CALR-mutated ET, and that the presence of additional nondriver mutations may influence the MR to therapy. © 2015 by The American Society of Hematology.

  8. HPRT gene mutation frequency and the factor of influence in adult peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Zhao Jingyong; Zheng Siying; Cui Fengmei; Wang Liuyi; Lao Qinhua; Wu Hongliang

    2002-01-01

    Objective: To study the HPRT gene loci mutation frequencies and the factor of influence in peripheral blood lymphocytes of adult with ages ranging from 21-50. Methods: HPRT gene mutation frequency (GMf) were examined by the technique of multinuclear cell assay. Relation between GMf and years were fitted with a computer. Results: Relation could be described by the following equation: y = 0.7555 + 0.0440x, r = 0.9829. Smoking has influence on GMf and sex hasn't. Conclusion: HPRT gene mutation frequency increases with increasing of age. Increasing rate is 0.00440% per year

  9. Frequency response functions for nonlinear convergent systems

    NARCIS (Netherlands)

    Pavlov, A.V.; Wouw, van de N.; Nijmeijer, H.

    2007-01-01

    Convergent systems constitute a practically important class of nonlinear systems that extends the class of asymptotically stable linear time-invariant systems. In this note, we extend frequency response functions defined for linear systems to nonlinear convergent systems. Such nonlinear frequency

  10. Slot Machine Response Frequency Predicts Pathological Gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne

    2013-01-01

    Slot machines are among the most addictive forms of gambling, and pathological gambling slot machine players represent the largest group of treatment seekers, accounting for 35% to 93% of the population. Pathological gambling sufferers have significantly higher response frequency (games / time......) on slot machines compared with non-problem gamblers, which may suggest increased reinforcement of the gambling behavior in pathological gambling. However, to date it is unknown whether or not the increased response frequency in pathological gambling is associated with symptom severity of the disorder....... This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...

  11. Frequency response of slow beam extraction process

    International Nuclear Information System (INIS)

    Toyama, Takeshi; Sato, Hikaru; Marutsuka, Katsumi; Shirakata, Masashi.

    1994-01-01

    A servo control system has been incorporated into the practical slow extraction system in order to stabilize the spill structure less than a few kHz. Frequency responses of the components of the servo-spill control system and the open-loop frequency response were measured. The beam transfer function of the slow extraction process was derived from the measured data and approximated using a simple function. This is utilized to improve the performance of the servo-loop. (author)

  12. Understanding the role of p53 in adaptive response to radiation-induced germline mutations

    International Nuclear Information System (INIS)

    Langlois, N.L.; Quinn, J.S.; Somers, C.M.; Boreham, D.R.; Mitchel, R.E.J.

    2003-01-01

    Full text: Radiation-induced adaptive response is now a widely studied area of radiation biology. Studies have demonstrated reduced levels of radiation-induced biological damage when an 'adaptive dose' is given before a higher 'challenge dose' compared to when the challenge dose is given alone. It has been shown in some systems to be a result of inducible cellular repair systems. The adaptive response has been clearly demonstrated in many model systems, however its impact on heritable effects in the mammalian germline has never been studied. Expanded Simple Tandem Repeat (ESTR) loci have been used as markers demonstrating that induced heritable mutations in mice follow a dose-response relationship. Recent data in our laboratory show preliminary evidence of radiation-induced adaptive response suppressing germline mutations at ESTR loci in wild type mice. The frequency of heritable mutations was significantly reduced when a priming dose of 0.1 Gy was given 24 hours prior to a 1 Gy acute challenging dose. We are now conducting a follow-up study to attempt to understand the mechanism of this adaptive response. P53 is known to play a significant role in governing apoptosis, DNA repair and cancer induction. In order to determine what function p53 has in the adaptive response for heritable mutations, we have mated radiation treated Trp53+/- male mice (C57Bl) to untreated, normal females (C57Bl). Using DNA fingerprinting, we are investigating the rate of inherited radiation-induced mutations on pre- and post-meiotic radiation-treated gametocytes by examining mutation frequencies in offspring DNA. If p53 is integral in the mechanism of adaptive response, we should not see an adaptive response in radiation-induced heritable mutations in these mice. This research is significant in that it will provide insight to understanding the mechanism behind radiation-induced adaptive response in the mammalian germline

  13. The effects of extremely low frequency magnetic fields on mutation induction in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, James W. [Department of Genetics, University of Leicester, Leicester LE1 7RH (United Kingdom); Haines, Jackie; Sienkiewicz, Zenon [Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 0RQ (United Kingdom); Dubrova, Yuri E., E-mail: yed2@le.ac.uk [Department of Genetics, University of Leicester, Leicester LE1 7RH (United Kingdom)

    2015-03-15

    Highlights: • The effects of 50 Hz magnetic fields on mutation induction in mice were analyzed. • The frequency of ESTR mutation was established in sperm and blood. • Exposure to 10–300 μT for 2 and 15 h did not result in mutation induction. • Mutagenic effects of 50 Hz magnetic fields are likely to be negligible. - Abstract: The growing human exposure to extremely low frequency (ELF) magnetic fields has raised a considerable concern regarding their genotoxic effects. The aim of this study was to evaluate the in vivo effects of ELF magnetic fields irradiation on mutation induction in the germline and somatic tissues of male mice. Seven week old BALB/c × CBA/Ca F{sub 1} hybrid males were exposed to 10, 100 or 300 μT of 50 Hz magnetic fields for 2 or 15 h. Using single-molecule PCR, the frequency of mutation at the mouse Expanded Simple Tandem Repeat (ESTR) locus Ms6-hm was established in sperm and blood samples of exposed and matched sham-treated males. ESTR mutation frequency was also established in sperm and blood samples taken from male mice exposed to 1 Gy of acute X-rays. The frequency of ESTR mutation in DNA samples extracted from blood of mice exposed to magnetic fields did not significantly differ from that in sham-treated controls. However, there was a marginally significant increase in mutation frequency in sperm but this was not dose-dependent. In contrast, acute exposure X-rays led to significant increases in mutation frequency in sperm and blood of exposed males. The results of our study suggest that, within the range of doses analyzed here, the in vivo mutagenic effects of ELF magnetic fields are likely to be minor if not negligible.

  14. The effects of extremely low frequency magnetic fields on mutation induction in mice

    International Nuclear Information System (INIS)

    Wilson, James W.; Haines, Jackie; Sienkiewicz, Zenon; Dubrova, Yuri E.

    2015-01-01

    Highlights: • The effects of 50 Hz magnetic fields on mutation induction in mice were analyzed. • The frequency of ESTR mutation was established in sperm and blood. • Exposure to 10–300 μT for 2 and 15 h did not result in mutation induction. • Mutagenic effects of 50 Hz magnetic fields are likely to be negligible. - Abstract: The growing human exposure to extremely low frequency (ELF) magnetic fields has raised a considerable concern regarding their genotoxic effects. The aim of this study was to evaluate the in vivo effects of ELF magnetic fields irradiation on mutation induction in the germline and somatic tissues of male mice. Seven week old BALB/c × CBA/Ca F 1 hybrid males were exposed to 10, 100 or 300 μT of 50 Hz magnetic fields for 2 or 15 h. Using single-molecule PCR, the frequency of mutation at the mouse Expanded Simple Tandem Repeat (ESTR) locus Ms6-hm was established in sperm and blood samples of exposed and matched sham-treated males. ESTR mutation frequency was also established in sperm and blood samples taken from male mice exposed to 1 Gy of acute X-rays. The frequency of ESTR mutation in DNA samples extracted from blood of mice exposed to magnetic fields did not significantly differ from that in sham-treated controls. However, there was a marginally significant increase in mutation frequency in sperm but this was not dose-dependent. In contrast, acute exposure X-rays led to significant increases in mutation frequency in sperm and blood of exposed males. The results of our study suggest that, within the range of doses analyzed here, the in vivo mutagenic effects of ELF magnetic fields are likely to be minor if not negligible

  15. Estimating Exceptionally Rare Germline and Somatic Mutation Frequencies via Next Generation Sequencing.

    Directory of Open Access Journals (Sweden)

    Jordan Eboreime

    Full Text Available We used targeted next generation deep-sequencing (Safe Sequencing System to measure ultra-rare de novo mutation frequencies in the human male germline by attaching a unique identifier code to each target DNA molecule. Segments from three different human genes (FGFR3, MECP2 and PTPN11 were studied. Regardless of the gene segment, the particular testis donor or the 73 different testis pieces used, the frequencies for any one of the six different mutation types were consistent. Averaging over the C>T/G>A and G>T/C>A mutation types the background mutation frequency was 2.6x10-5 per base pair, while for the four other mutation types the average background frequency was lower at 1.5x10-6 per base pair. These rates far exceed the well documented human genome average frequency per base pair (~10-8 suggesting a non-biological explanation for our data. By computational modeling and a new experimental procedure to distinguish between pre-mutagenic lesion base mismatches and a fully mutated base pair in the original DNA molecule, we argue that most of the base-dependent variation in background frequency is due to a mixture of deamination and oxidation during the first two PCR cycles. Finally, we looked at a previously studied disease mutation in the PTPN11 gene and could easily distinguish true mutations from the SSS background. We also discuss the limits and possibilities of this and other methods to measure exceptionally rare mutation frequencies, and we present calculations for other scientists seeking to design their own such experiments.

  16. Loads as a Resource: Frequency Responsive Demand

    Energy Technology Data Exchange (ETDEWEB)

    Kalsi, Karanjit [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lian, Jianming [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Marinovici, Laurentiu D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Elizondo, Marcelo A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zhang, Wei [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Moya, Christian [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2014-10-08

    Frequency control plays an important role in preserving the power balance of a multi-machine power system. Generators modify their power output when a non-zero frequency deviation is presented in order to restore power balance across the network. However, with plans for large-scale penetration of renewable energy resources, performing primary frequency control using only supply-side resources becomes not only prohibitively expensive, but also technically difficult. Frequency control from the demand side or load control presents a novel and viable way for providing the desired frequency response. Loads can measure frequency locally and change their power consumption after a non-zero frequency deviation is presented in order to achieve power balance between generation and consumption. The specific objectives of this project are to: •Provide a framework to facilitate large-scale deployment of frequency responsive end-use devices •Systematically design decentralized frequency-based load control strategies for enhanced stability performance •Ensure applicability over wide range of operating conditions while accounting for unpredictable end-use behavior and physical device constraints •Test and validate control strategy using large-scale simulations and field demonstrations •Create a level-playing field for smart grid assets with conventional generators

  17. Frequency of BRAF V600E Mutation in the Mexican Population of Patients With Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Erika Ruiz-Garcia

    2017-06-01

    Full Text Available Purpose: The BRAF V600E mutation has been described in melanomas occurring in the Caucasian, European, and Asian populations. However, in the Mexican population, the status and clinical significance of BRAF mutation has not been researched on a large scale. Methods: Consecutive BRAF-tested Mexican patients with metastatic melanoma (n = 127 were analyzed for mutations in exon 15 of the BRAF gene in genomic DNA by real-time polymerase chain reaction technology for amplification and detection. The results were correlated with the clinical-pathologic features and the prognosis of the patients. Results: The frequency of somatic mutation V600E within the BRAF gene was 54.6% (43 of 127 patients. Nodular melanoma was the most prevalent subtype in our population, with BRAF mutations in 37.2% (16 of 55 patients. In contrast, superficial spread had a frequency of 18.6% BRAF mutation (eight of 24. Other clinicopathologic features were assessed to correlate with the mutation status. Conclusion: This study searched for the most prevalent BRAF V600E mutation type in melanoma in a heterogeneous population from Mexico. Nodular melanoma was found to be the most prevalent in metastatic presentation and the presence of BRAF V600E mutation, perhaps related to the mixed ancestry; in the north, ancestry is predominantly European and in the south, it is predominantly Asian. The outcomes of the mutation correlations were similar to those found in other populations.

  18. Terahertz-frequency dielectric response of liquids

    DEFF Research Database (Denmark)

    Jepsen, Peter Uhd; Møller, Uffe; Cooke, David

    The dielectric response of liquids spans many decades in frequency. The dielectric response of a polar liquid is typically determined by relaxational dynamics of the dipolar moments of the liquid. In contrast, the dielectric response of a nonpolar liquid is determined by much weaker collision......-induced dipole moments. In the polar liquid water the fastest relaxational dynamics is found at terahertz frequencies, just below the first intermolecular vibrational and librational modes. In this presentation we will discuss optical terahertz spectroscopic techniques for measurement of the full dielectric...... function of liquids at terahertz frequencies. We will review the current understanding of the high-frequency dielectric spectrum of water, and discuss the relation between the dielectric spectrum and the thermodynamic properties of certain aqueous solutions....

  19. The spectrum of HNF1A gene mutations in Greek patients with MODY3: relative frequency and identification of seven novel germline mutations.

    Science.gov (United States)

    Tatsi, Christina; Kanaka-Gantenbein, Christina; Vazeou-Gerassimidi, Adriani; Chrysis, Dionysios; Delis, Dimitrios; Tentolouris, Nikolaos; Dacou-Voutetakis, Catherine; Chrousos, George P; Sertedaki, Amalia

    2013-11-01

    Maturity-Onset Diabetes of the Young (MODY) is the most common type of monogenic diabetes accounting for 1-2% of the population with diabetes. The relative incidence of HNF1A-MODY (MODY3) is high in European countries; however, data are not available for the Greek population. The aims of this study were to determine the relative frequency of MODY3 in Greece, the type of the mutations observed, and their relation to the phenotype of the patients. Three hundred ninety-five patients were referred to our center because of suspected MODY during a period of 15 yr. The use of Denaturing Gradient Gel Electrophoresis of polymerase chain reaction amplified DNA revealed 72 patients carrying Glucokinase gene mutations (MODY2) and 8 patients carrying HNF1A gene mutations (MODY3). After using strict criteria, 54 patients were selected to be further evaluated by direct sequencing or by multiplex ligation probe amplification (MLPA) for the presence of HNF1A gene mutations. In 16 unrelated patients and 13 of their relatives, 15 mutations were identified in the HNF1A gene. Eight of these mutations were previously reported, whereas seven were novel. Clinical features, such as age of diabetes at diagnosis or severity of hyperglycemia, were not related to the mutation type or location. In our cohort of patients fulfilling strict clinical criteria for MODY, 12% carried an HNF1A gene mutation, suggesting that defects of this gene are responsible for a significant proportion of monogenic diabetes in the Greek population. No clear phenotype-genotype correlations were identified. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Prevalence of common MEFV mutations and carrier frequencies in a ...

    Indian Academy of Sciences (India)

    Christian Oberkanins, oberkanins@viennalab.com. 1967; Pras et al. ... affected populations with spreading very diverse mutational patterns, especially ..... Arabs, mainly living in Syria, Lebanon, Palestine, Jordan and Iraq, and North .... Mediterranean fever suspected patients and gender correlation: a retrospective study.

  1. X-ray-induced bystander response reduce spontaneous mutations in V79 cells

    International Nuclear Information System (INIS)

    Maeda, Munetoshi; Kobayashi, Katsumi; Matsumoto, Hideki; Usami, Noriko; Tomiya, Masanori

    2013-01-01

    The potential for carcinogenic risks is increased by radiation-induced bystander responses; these responses are the biological effects in unirradiated cells that receive signals from the neighboring irradiated cells. Bystander responses have attracted attention in modern radiobiology because they are characterized by non-linear responses to low-dose radiation. We used a synchrotron X-ray microbeam irradiation system developed at the Photon Factory, High Energy Accelerator Research Organization, KEK, and showed that nitric oxide (NO)-mediated bystander cell death increased biphasically in a dose-dependent manner. Here, we irradiated five cell nuclei using 10 × 10 µm 2 5.35 keV X-ray beams and then measured the mutation frequency at the hypoxanthine-guanosine phosphoribosyl transferase (HPRT) locus in bystander cells. The mutation frequency with the null radiation dose was 2.6 × 10 -5 (background level), and the frequency decreased to 5.3 × 10 -6 with a dose of approximately 1 Gy (absorbed dose in the nucleus of irradiated cells). At high doses, the mutation frequency returned to the background level. A similar biphasic dose-response effect was observed for bystander cell death. Furthermore, we found that incubation with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a specific scavenger of NO, suppressed not only the biphasic increase in bystander cell death but also the biphasic reduction in mutation frequency of bystander cells. These results indicate that the increase in bystander cell death involves mechanisms that suppress mutagenesis. This study has thus shown that radiation-induced bystander responses could affect processes that protect the cell against naturally occurring alterations such as mutations. (author)

  2. Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans.

    Directory of Open Access Journals (Sweden)

    Arbel Harpak

    2016-12-01

    Full Text Available The site frequency spectrum (SFS has long been used to study demographic history and natural selection. Here, we extend this summary by examining the SFS conditional on the alleles found at the same site in other species. We refer to this extension as the "phylogenetically-conditioned SFS" or cSFS. Using recent large-sample data from the Exome Aggregation Consortium (ExAC, combined with primate genome sequences, we find that human variants that occurred independently in closely related primate lineages are at higher frequencies in humans than variants with parallel substitutions in more distant primates. We show that this effect is largely due to sites with elevated mutation rates causing significant departures from the widely-used infinite sites mutation model. Our analysis also suggests substantial variation in mutation rates even among mutations involving the same nucleotide changes. In summary, we show that variable mutation rates are key determinants of the SFS in humans.

  3. High frequency oscillations in brain hemodynamic response

    Science.gov (United States)

    Akin, Ata; Bolay, Hayrunnisa

    2007-07-01

    Tight autoregulation of vessel tone guarantees proper delivery of nutrients to the tissues. This regulation is maintained at a more delicate level in the brain since any decrease in the supply of glucose and oxygen to neuronal tissues might lead to unrecoverable injury. Functional near infrared spectroscopy has been proposed as a new tool to monitor the cerebrovascular response during cognitive activity. We have observed that during a Stroop task three distinct oscillatory patterns govern the control of the cerebrovascular reactivity: very low frequency (0.02-0.05 Hz), low frequency (0.08-0.12 Hz) and high frequency (0.12-0.18 Hz). High frequency oscillations have been shown to be related to stress level of the subjects. Our findings indicate that as the stress level is increased so does the energy of the high frequency component indicating a higher stimulation from the autonomic nervous system.

  4. High Frequency of Alkaptonuria in Slovakia: Evidence for the Appearance of Multiple Mutations in HGO Involving Different Mutational Hot Spots

    Science.gov (United States)

    Zatková, Andrea; de Bernabé, Daniel Beltrán Valero; Poláková, Helena; Zvarík, Marek; Feráková, Eva; Bošák, Vladimir; Ferák, Vladimír; Kádasi, L'udovít; de Córdoba , Santiago Rodríguez

    2000-01-01

    Alkaptonuria (AKU) is an autosomal recessive disorder caused by the deficiency of homogentisate 1,2 dioxygenase (HGO) activity. AKU shows a very low prevalence (1:100,000–250,000) in most ethnic groups. One notable exception is in Slovakia, where the incidence of AKU rises to 1:19,000. This high incidence is difficult to explain by a classical founder effect, because as many as 10 different AKU mutations have been identified in this relatively small country. We have determined the allelic associations of 11 HGO intragenic polymorphisms for 44 AKU chromosomes from 20 Slovak pedigrees. These data were compared to the HGO haplotype data available in our laboratory for >80 AKU chromosomes from different European and non-European countries. The results show that common European AKU chromosomes have had only a marginal contribution to the Slovak AKU gene pool. Six of the ten Slovak AKU mutations, including the prevalent G152fs, G161R, G270R, and P370fs mutations, most likely originated in Slovakia. Data available for 17 Slovak AKU pedigrees indicate that most of the AKU chromosomes have their origins in a single very small region in the Carpathian mountains, in the northwestern part of the country. Since all six Slovak AKU mutations are associated with HGO mutational hot spots, we suggest that an increased mutation rate at the HGO gene is responsible for the clustering of AKU mutations in such a small geographical region. PMID:11017803

  5. Somatic mutation frequencies in the stamen hairs of stable and mutable clones of Tradescantia after acute gamma-ray treatments with small doses

    International Nuclear Information System (INIS)

    Ichikawa, Sadao; Takahashi, C.S.

    1977-01-01

    Young inflorescences of two different Tradescantia clones heterozygous for flower and stamen-hair color, one stable (KU 9) and the other spontaneously mutable (KU 20), were irradiated acutely with small doses (approx. 3 to 50 R) of 60 Co gamma-rays. Somatic mutation frequencies from blue to pink in the stamen hairs scored on post-irradiation days 10 to 16 increased essentially linearly with increasing gamma-ray dose in both clones. Despite about a 5-fold difference in spontaneous mutation frequency per hair found between the two clones, the dose-response curves of pink mutations determined were similar to each other, giving average mutation frequencies of 1.51 and 1.41 pink-mutant events per 1000 hairs per R for KU 9 and KU 20, respectively. These frequencies are comparable to earlier results obtained from acute irradiation treatments of other clones with higher doses. The doubling dose of pink mutation (the radiation dose making the mutation frequency double the spontaneous level) was calculated to be 2.09 R for KU 9, and this low doubling dose must be given full attention. On the other hand, the doubling dose for KU 20 (calculated to be 10.4 R) is of questionable value, being greatly subject to change because of the diversely variable spontaneous mutation frequency of this clone

  6. Combination of the mutation process with the sensitization and repair processes leading to increased frequencies of mutations in algal populations

    International Nuclear Information System (INIS)

    Necas, J.

    1977-01-01

    The possibility of combining the mutation process with the induction of the repair processes was studied to increase the mutation frequencies in algal populations after UV treatment. The repair process induced by visible light was found to be much more effective than the dark repair processes in the chlorococcal algae used. In these algae, visible light possibly does not induce only those repair processes which affect their DNA, but probably also certain recovery processes which affect their damaged structures and physiological functions. A suitable combination of the sensitization of algae cells by a DNA-base analogue before UV treatment and the induction of the light repair and recovery processes resulted in a rather high increase of viable mutations in chlorococcal algae. These findings may be useful in breeding chlorococcal algae, which have no possibility of hybridization other than somatic. (author)

  7. Effect of combined mutagenic treatments on sensitivity and mutation frequency in rice

    International Nuclear Information System (INIS)

    Gopinathan Nair, V.

    1977-01-01

    Rice seeds were subjected to two sets of combination treatments of radiations and NMH. The effects of mutagenic treatments in the M 1 and M 2 generations were recorded and discussed. Mutation frequencies estimated as number of mutations per 100 M 1 years were not higher than the values expected on the basis of additive effects. When estimated as number of mutants per 100 M 2 plants, the frequencies revealed more than additive effects. The synergistic effect on mutant frequencies was due to increase in the segregation ratio of mutants. This effect was more pronounced at the higher dose combinations of fast neutrons and NMH. (author)

  8. Loads as a Resource: Frequency Responsive Demand

    Energy Technology Data Exchange (ETDEWEB)

    Kalsi, Karanjit [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Williams, Tess L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Marinovici, Laurentiu D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Elizondo, Marcelo A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lian, Jianming [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-11-30

    Demand-side frequency control can complement traditional generator controls to maintain the stability of large electric systems in the face of rising uncertainty and variability associated with renewable energy resources. This report presents a hierarchical frequency-based load control strategy that uses a supervisor to flexibly adjust control gains that a population of end-use loads respond to in a decentralized manner to help meet the NERC BAL-003-1 frequency response standard at both the area level and interconnection level. The load model is calibrated and used to model populations of frequency-responsive water heaters in a PowerWorld simulation of the U.S. Western Interconnection (WECC). The proposed design is implemented and demonstrated on physical water heaters in a laboratory setting. A significant fraction of the required frequency response in the WECC could be supplied by electric water heaters alone at penetration levels of less than 15%, while contributing to NERC requirements at the interconnection and area levels.

  9. Modeling the frequency response of photovoltaic inverters

    NARCIS (Netherlands)

    Ernauli Christine Aprilia, A.; Cuk, V.; Cobben, J.F.G.; Ribeiro, P.F.; Kling, W.L.

    2012-01-01

    The increased presence of photovoltaic (PV) systems inevitably affects the power quality in the grid. This new reality demands grid power quality studies involving PV inverters. This paper proposes several frequency response models in the form of equivalent circuits. Models are based on laboratory

  10. The Mutation Frequency in Different Spike Categories in Barley

    DEFF Research Database (Denmark)

    Frydenberg, O.; Doll, Hans; Sandfær, J.

    1964-01-01

    After gamma irradiation of barley seeds, a comparison has been made between the chlorophyll-mutant frequencies in X1 spikes that had multicellular bud meristems in the seeds at the time of treatment (denoted as pre-formed spikes) and X1 spikes having no recognizable meristems at the time...

  11. Frequency and spectrum of mutations induced by gamma irradiation in single, double and triple dwarf wheats

    International Nuclear Information System (INIS)

    Dhonukshe, B.L.

    1981-01-01

    Induced mutation studies were carried with three dwarf wheat varieties viz., ''Sonalika'', ''Chhoti Lerma'' and ''Hira'', considered to be single, double and trible dwarfs, respectively. Gamma-rays were used as a source of irradiation. Frequency of chlorophyll mutations were comparatively low and the spectrum was narrow. Chlorophyll mutations were altogether absent in the variety ''Sonalika''. A very wide spectrum of viable mutations affecting stem, leaf, ear growth habit, maturity and fertility characteristics was observed in the M 2 . The cumulative frequency of all the mutants together was quite high, which varied with the varieties. There were varietal differences in the composition and width of the spectrum induced by gamma-rays. The dwarf mutants having desirable leaf and spike characters were isolated in all the three varieties. (author)

  12. Mutation frequencies in male mice and the estimation of genetic hazards of radiation in men

    International Nuclear Information System (INIS)

    Russell, W.L.; Kelly, E.M.

    1982-01-01

    Estimation of the genetic hazards of ionizing radiation in men is based largely on the frequency of transmitted specific-locus mutations induced in mouse spermatogonial stem cells at low radiation dose rates. The publication of new data on this subject has permitted a fresh review of all the information available. The data continue to show no discrepancy from the interpretation that, although mutation frequency decreases markedly as dose rate is decreased from 90 to 0.8 R/min (1 R = 2.6 x 10/sup -4/ coulombs/kg) there seems to be no further change below 0.8 R/min over the range from that dose rate to 0.0007 R/min. Simple mathematical models are used to compute: (a) a maximum likelihood estimate of the induced mutation frequency at the low dose rates, and (b) a maximum likelihood estimate of the ratio of this to the mutation frequency at high dose rates in the range of 72 to 90 R/min. In the application of these results to the estimation of genetic hazards of radiation in man, the former value can be used to calcualte a doubling dose - i.e., the dose of radiation that induces a mutation frequency equal to the spontaneous frequency. The doubling dose based on the low-dose-rate data compiled here is 110 R. The ratio of the mutation frequency at low dose rate to to that at high dose rate is useful when it becomes necessary to extrapolate from experimental determinations, or from human data, at high dose rates to the expected risk at low dose rates. The ratio derived from the present analysis is 0.33

  13. Diversity and frequency of kdr mutations within Anopheles sinensis populations from Guangxi, China.

    Science.gov (United States)

    Yang, Chan; Feng, Xiangyang; Huang, Zushi; Li, Mei; Qiu, Xinghui

    2016-08-15

    Anopheles sinensis is a major vector of malaria in China and its control is under great threat as the development of insecticide resistance. Voltage-gated sodium channel (VGSC) is the target of several classes of insecticides. Genetic mutations of VGSC have been documented to confer knockdown resistance (kdr) to dichlorodiphenyltrichloroethane (DDT) and pyrethroids in mosquitoes. To control this vector efficiently, it is important to know the resistance-associated genetic mutations, their distribution frequencies and genealogical relations. Three hundreds and thirteen (313) adults of An. sinensis collected from nine locations across Guangxi Zhuang Autonomous Region were used. The partial sequence of the An. sinensis voltage gated sodium channel gene (AS-VGSC) containing codon 1014 was sequenced. PHASE2.1 was used to construct the haplotypes of each individual, and the accuracy of haplotypes was further confirmed by clone sequencing. The genealogical relations of kdr mutations in AS-VGSC was analysed using TCS 2.1 and Network 5.0. Sixteen AS-VGSC haplotypes including seven haplotypes carrying non-synonymous mutations at codon 1014, and fifty-five AS-VGSC genotypes were identified from 313 mosquitoes collected from nine geographical locations across Guangxi. The number of haplotypes in each of the nine populations ranged from 5 to 13. The frequency of haplotypes carrying kdr mutations ranged from 2.7 to 80.0 % within the nine populations, of which 1014C was unexpectedly high in the northeast of Guangxi. Genealogical analysis suggested multiple origins of kdr mutations in An. sinensis. Diverse haplotypes of AS-VGSC are distributed in Guangxi. The presence of haplotypes carrying mutations at codon 1014 indicates a risk of pyrethroid and DDT resistance. The kdr mutations show differential distribution geographically, with high frequencies occurred in the northeast of Guangxi. Genealogical analysis suggests multiple origins of kdr mutations in An. sinensis populations

  14. Modification of radiation-induced sex-linked recessive lethal mutation frequency by tocopherol

    International Nuclear Information System (INIS)

    Beckman, C.; Roy, R.M.; Sproule, A.

    1982-01-01

    The present study evaluates the effect of supplementing culture medium with α-tocopherol acetate on the yield of sex-linked recessive lethal mutants induced by X-irradiation in mature sperm of Drosophila. Although tocopherol treatment of males had no impact on the yield of mutations, a drastic reduction in mutation frequency was observed when irradiated males were mated to females raised and subsequently maintained on tocopherol-enriched diet. (orig./MG)

  15. Mutational jackpot events generate effective frequency-dependent selection in adapting populations

    Science.gov (United States)

    Hallatschek, Oskar

    The site-frequency spectrum is one the most easily measurable quantities that characterize the genetic diversity of a population. While most neutral models predict that site frequency spectra should decay with increasing frequency, a high-frequency uptick has been reported in many populations. Anomalies in the high-frequency tail are particularly unsettling because the highest frequencies can be measured with greatest accuracy. Here, we show that an uptick in the spectrum of neutral mutations generally arises when mutant frequencies are dominated by rare jackpot events, mutational events with large descendant numbers. This leads to an effective pattern of frequency-dependent selection (or unstable internal equilibrium at one half frequency) that causes an accumulation of high-frequency polymorphic sites. We reproduce the known uptick occurring for recurrent hitchhiking (genetic draft) as well as rapid adaptation, and (in the future) generalize the shape of the high-frequency tail to other scenarios that are dominated by jackpot events, such as frequent range expansions. We also tackle (in the future) the inverse approach to use the high-frequency uptick for learning about the tail of the offspring number distribution. Positively selected alleles need to surpass, typically, an u NSF Career Award (PoLS), NIH NIGMS R01, Simons Foundation.

  16. The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect

    Science.gov (United States)

    Tiemann-Boege, Irene; Navidi, William; Grewal, Raji; Cohn, Dan; Eskenazi, Brenda; Wyrobek, Andrew J.; Arnheim, Norman

    2002-01-01

    The lifelong spermatogonial stem cell divisions unique to male germ cell production are thought to contribute to a higher mutation frequency in males. The fact that certain de novo human genetic conditions (e.g., achondroplasia) increase in incidence with the age of the father is consistent with this idea. Although it is assumed that the paternal age effect is the result of an increasing frequency of mutant sperm as a man grows older, no direct molecular measurement of the germ-line mutation frequency has been made to confirm this hypothesis. Using sperm DNA from donors of different ages, we determined the frequency of the nucleotide substitution in the fibroblast growth factor receptor 3 (FGFR3) gene that causes achondroplasia. Surprisingly, the magnitude of the increase in mutation frequency with age appears insufficient to explain why older fathers have a greater chance of having a child with this condition. A number of alternatives may explain this discrepancy, including selection for sperm that carry the mutation or an age-dependent increase in premutagenic lesions that remain unrepaired in sperm and are inefficiently detected by the PCR assay. PMID:12397172

  17. Survey on the frequency of somatic mutations in A-bomb survivors

    International Nuclear Information System (INIS)

    Akiyama, Mitoshi

    1992-01-01

    Several methods have recently been established for quantitatively detecting somatic cell mutations on a specific locus using human blood cells. These methods have enabled the biological estimation of A-bomb radiation doses in surveys on somatic cell mutations. This paper outlines HPRT, GPA, and TCR assays used to measure somatic cell mutations, focusing on the outcome in A-bomb survivors. HPRT assay is based on colony formation with interleukin-2. The frequency of HPRT mutant cells was significantly increased with advancing age in A-bomb survivors and was positively correlated with the frequency of chromosomal aberrations in lymphocytes. There was also a significantly positive correlation between HPRT mutant cell frequencies and DS86 estimated doses, although the slope was slow. In GPA assay, flow cytometric measurements of fluorescence-labeled erythrocytes are used to detect somatic cell mutations. There was a positive correlation between GPA mutant cell frequencies and age in A-bomb survivors. The GPA mutant cell frequencies showed much more positive correlation with lymphocyte chromosomal aberration frequencies than the HPRT mutant cell frequencies. When anti-CD3 antibody and anti-CD4 antibody are labeled with different fluorescences and are analyzed by using flow cytometry, TCR mutant cells having CD3 - 4 + can be detected. When the frequency of TCR mutant cells was examined in 342 A-bomb survivors, it did not correlate with radiation doses. This implies that TCR assay may be unadequate for biological estimation of A-bomb radiation doses throughout a lifetime of A-bomb survivors, because TCR mutant cells seems to be unable to live for a long time due to national selection. (N.K.)

  18. High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients

    Directory of Open Access Journals (Sweden)

    R. Rozenberg

    2006-09-01

    Full Text Available Gaucher disease (GD, the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47% of all the alleles, but N370S/N370S homozygosity was found in only 10% of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44% of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25% of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42% type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation.

  19. Inherited and environmentally induced differences in mutation frequencies between wild strains of Sordaria fimicola from "Evolution Canyon".

    Science.gov (United States)

    Lamb, B C; Saleem, M; Scott, W; Thapa, N; Nevo, E

    1998-05-01

    We have studied whether there is natural genetic variation for mutation frequencies, and whether any such variation is environment-related. Mutation frequencies differed significantly between wild strains of the fungus Sordaria fimicola isolated from a harsher or a milder microscale environment in "Evolution Canyon," Israel. Strains from the harsher, drier, south-facing slope had higher frequencies of new spontaneous mutations and of accumulated mutations than strains from the milder, lusher, north-facing slope. Collective total mutation frequencies over many loci for ascospore pigmentation were 2.3, 3.5 and 4.4% for three strains from the south-facing slope, and 0.9, 1.1, 1.2, 1.3 and 1.3% for five strains from the north-facing slope. Some of this between-slope difference was inherited through two generations of selfing, with average spontaneous mutation frequencies of 1.9% for south-facing slope strains and 0.8% for north-facing slope strains. The remainder was caused by different frequencies of mutations arising in the original environments. There was also significant heritable genetic variation in mutation frequencies within slopes. Similar between-slope differences were found for ascospore germination-resistance to acriflavine, with much higher frequencies in strains from the south-facing slope. Such inherited variation provides a basis for natural selection for optimum mutation rates in each environment.

  20. Effects of diurnal temperature difference and gamma radiation on the frequency of somatic cell mutations in the stamen hairs

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Kim, Won Rok; Kim, Jae Sung; Shin, Hae Shick; Lee, Jeong Joo

    1998-01-01

    This study deals with the effects of diurnal temperature difference (DTD) on somatic cell mutation frequencies in Tradescantia stamen hairs irradiated with radiation. Potted plants of Tradescantia 4430 were irradiated with 0.3, 0.5, 1.0 and 2.0 Gy of gamma radiation. The irradiated plants were maintained under two different experimental conditions; at constant temperature of 20 degree C (DTD0) and at 28 degree C for 14-h day and 8 degree C for 10-h night (DTD20). The somatic cell mutation rate in 0.5 Gy irradiated group showed a big increase on the 6th day and reached a maximum value on the 10th day after irradiation while the rate in the experimental group under the condition of DTD20 started to increase on the 8th day and got to a maximal value on the 14th day postirradiation. In both of the two experiments, the dose-response relationships were clearly linear. The slope of the DTD20 dose-response curve was much steeper than that of the DTD0 one. In conclusion, a great DTD, as one of environmental stresses, enhanced the effectiveness of radiation in the induction of somatic cell mutations and caused a shift of the peak interval of radiation-induced mutations in Tradescantia stamen hairs

  1. C282Y and H63D Mutation Frequencies in a Population from Central Spain

    Directory of Open Access Journals (Sweden)

    S. Alvarez

    2001-01-01

    Full Text Available Objectives: To determine the frequency of hereditary hemochromatosis gene mutations, C282Y and H63D, from 125 autochthonous blood donors originating from a Central region of Spain, to provide epidemiological data about HFE gene in the Iberian Peninsula.

  2. Pre-thymic somatic mutation leads to high mutant frequency at hypoxanthine-guanine phosphoribosyltransferase gene

    Energy Technology Data Exchange (ETDEWEB)

    Jett, J. [Lawrence Livermore National Lab., CA (United States)

    1994-12-01

    While characterizing the background mutation spectrum of the Hypoxathine-guanine phosphoribosyltransferase (HPRT) gene in a healthy population, an outlier with a high mutant frequency of thioguanine resistant lymphocytes was found. When studied at the age of 46, this individual had been smoking 60 cigarettes per day for 38 years. His mutant frequency was calculated at 3.6 and 4.2x10{sup {minus}4} for two sampling periods eight months apart. Sequencing analysis of the HPRT gene in his mutant thioguanine resistant T lymphocytes was done to find whether the cells had a high rate of mutation, or if the mutation was due to a single occurrence of mutation and, if so, when in the T lymphocyte development the mutation occurred. By T-cell receptor analysis it has been found that out of 35 thioguanine resistant clones there was no dominant gamma T cell receptor gene rearrangement. During my appointment in the Science & Engineering Research Semester, I found that 34 of those clones have the same base substitution of G{yields}T at cDNA position 197. Due to the consistent mutant frequency from both sampling periods and the varying T cell receptors, the high mutant frequency cannot be due to recent proliferation of a mature mutant T lymphocyte. From the TCR and DNA sequence analysis we conclude that the G{yields}T mutation must have occurred in a T lymphocyte precursor before thymic differentiation so that the thioguanine resistant clones share the same base substitution but not the same gamma T cell receptor gene.

  3. Deficiency of the DNA repair protein nibrin increases the basal but not the radiation induced mutation frequency in vivo

    International Nuclear Information System (INIS)

    Wessendorf, Petra; Vijg, Jan; Nussenzweig, André; Digweed, Martin

    2014-01-01

    Highlights: • lacZ mutant frequencies measured in vivo in mouse models of radiosensitive Nijmegen Breakage Syndrome. • Spontaneous mutation frequencies are increased in lymphatic tissue due to Nbn mutation. • Single base transitions, not deletions, dominate the mutation spectrum. • Radiation induced mutation frequencies are not increased due to Nbn mutation. - Abstract: Nibrin (NBN) is a member of a DNA repair complex together with MRE11 and RAD50. The complex is associated particularly with the repair of DNA double strand breaks and with the regulation of cell cycle check points. Hypomorphic mutation of components of the complex leads to human disorders characterised by radiosensitivity and increased tumour occurrence, particularly of the lymphatic system. We have examined here the relationship between DNA damage, mutation frequency and mutation spectrum in vitro and in vivo in mouse models carrying NBN mutations and a lacZ reporter plasmid. We find that NBN mutation leads to increased spontaneous DNA damage in fibroblasts in vitro and high basal mutation rates in lymphatic tissue of mice in vivo. The characteristic mutation spectrum is dominated by single base transitions rather than the deletions and complex rearrangements expected after abortive repair of DNA double strand breaks. We conclude that in the absence of wild type nibrin, the repair of spontaneous errors, presumably arising during DNA replication, makes a major contribution to the basal mutation rate. This applies also to cells heterozygous for an NBN null mutation. Mutation frequencies after irradiation in vivo were not increased in mice with nibrin mutations as might have been expected considering the radiosensitivity of NBS patient cells in vitro. Evidently apoptosis is efficient, even in the absence of wild type nibrin

  4. Deficiency of the DNA repair protein nibrin increases the basal but not the radiation induced mutation frequency in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wessendorf, Petra [Institute of Medical and Human Genetics, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin (Germany); Vijg, Jan [Albert Einstein College of Medicine, Michael F. Price Center, 1301 Morris Park Avenue, Bronx, NY 10461 (United States); Nussenzweig, André [Laboratory of Genome Integrity, National Cancer Institute, National Institute of Health, 37 Convent Drive, Room 1106, Bethesda, MD 20892 (United States); Digweed, Martin, E-mail: martin.digweed@charite.de [Institute of Medical and Human Genetics, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin (Germany)

    2014-11-15

    Highlights: • lacZ mutant frequencies measured in vivo in mouse models of radiosensitive Nijmegen Breakage Syndrome. • Spontaneous mutation frequencies are increased in lymphatic tissue due to Nbn mutation. • Single base transitions, not deletions, dominate the mutation spectrum. • Radiation induced mutation frequencies are not increased due to Nbn mutation. - Abstract: Nibrin (NBN) is a member of a DNA repair complex together with MRE11 and RAD50. The complex is associated particularly with the repair of DNA double strand breaks and with the regulation of cell cycle check points. Hypomorphic mutation of components of the complex leads to human disorders characterised by radiosensitivity and increased tumour occurrence, particularly of the lymphatic system. We have examined here the relationship between DNA damage, mutation frequency and mutation spectrum in vitro and in vivo in mouse models carrying NBN mutations and a lacZ reporter plasmid. We find that NBN mutation leads to increased spontaneous DNA damage in fibroblasts in vitro and high basal mutation rates in lymphatic tissue of mice in vivo. The characteristic mutation spectrum is dominated by single base transitions rather than the deletions and complex rearrangements expected after abortive repair of DNA double strand breaks. We conclude that in the absence of wild type nibrin, the repair of spontaneous errors, presumably arising during DNA replication, makes a major contribution to the basal mutation rate. This applies also to cells heterozygous for an NBN null mutation. Mutation frequencies after irradiation in vivo were not increased in mice with nibrin mutations as might have been expected considering the radiosensitivity of NBS patient cells in vitro. Evidently apoptosis is efficient, even in the absence of wild type nibrin.

  5. Step response and frequency response of an air conditioning system

    NARCIS (Netherlands)

    Crommelin, R.D.; Jackman, P.J.

    1978-01-01

    A system of induction units of an existing air conditioning system has been analyzed with respect to its dynamic properties. Time constants were calculated and measured by analogue models. Comparison with measurements at the installation itself showed a reasonable agreement. Frequency responses were

  6. Frequencies, Laboratory Features, and Granulocyte Activation in Chinese Patients with CALR-Mutated Myeloproliferative Neoplasms.

    Directory of Open Access Journals (Sweden)

    Haixiu Guo

    Full Text Available Somatic mutations in the CALR gene have been recently identified as acquired alterations in myeloproliferative neoplasms (MPNs. In this study, we evaluated mutation frequencies, laboratory features, and granulocyte activation in Chinese patients with MPNs. A combination of qualitative allele-specific polymerase chain reaction and Sanger sequencing was used to detect three driver mutations (i.e., CALR, JAK2V617F, and MPL. CALR mutations were identified in 8.4% of cases with essential thrombocythemia (ET and 5.3% of cases with primary myelofibrosis (PMF. Moreover, 25% of polycythemia vera, 29.5% of ET, and 48.1% of PMF were negative for all three mutations (JAK2V617F, MPL, and CALR. Compared with those patients with JAK2V617F mutation, CALR-mutated ET patients displayed unique hematological phenotypes, including higher platelet counts, and lower leukocyte counts and hemoglobin levels. Significant differences were not found between Chinese PMF patients with mutants CALR and JAK2V617F in terms of laboratory features. Interestingly, patients with CALR mutations showed markedly decreased levels of leukocyte alkaline phosphatase (LAP expression, whereas those with JAK2V617F mutation presented with elevated levels. Overall, a lower mutant rate of CALR gene and a higher triple-negative rate were identified in the cohort of Chinese patients with MPNs. This result indicates that an undiscovered mutant gene may have a significant role in these patients. Moreover, these pathological features further imply that the disease biology varies considerably between mutants CALR and JAK2V617F.

  7. Empirical evaluation of cell critical volume dose vs. cell response function for pink mutations in tradescantia

    International Nuclear Information System (INIS)

    Varma, M.N.; Bond, V.P.

    1982-01-01

    Microdosimetric spectra for 0.43, 1.8, and 14.7 MeV neutrons, and for 215 kVp x rays and 1250 keV gammas were used in conjunction with relative biological effectiveness (RBE) values for pink mutations in Tradescantia to obtain an effectiveness function (i.e., a cell critical volume dose vs. cell response function). This effectiveness function (or hit size weighting function) provides the probability of inducing a biological effect of interest (in the present study, pink mutations in Tradescantia) as a function of lineal energy density y. In a preliminary analysis the critical value of y above which pink mutations are seen was 4.5 keV/μm, and the value of y at which the probability reaches unity was 115 keV/μm. Idealized but approximate event size distributions for mono-LET particles ranging from 10 to 5000 keV/μm were generated, and these distributions were weighted by the effectiveness function to determine the pink mutation frequencies. Results are compared with measured pink mutation frequencies for 11 keV/μm ( 12 C) and 31 keV/μm ( 20 Ne) ions

  8. Dynamic Frequency Response of Wind Power Plants

    DEFF Research Database (Denmark)

    Altin, Müfit

    according to their grid codes. In these scenarios particularly with high wind power penetration cases, conventional power plants (CPPs) such as old thermal power plants are planned to be replaced with wind power plants (WPPs). Consequently, the power system stability will be affected and the control...... to maintain sustainable and reliable operation of the power system for these targets, transmission system operators (TSOs) have revised the grid code requirements. Also, the TSOs are planning the future development of the power system with various wind penetration scenarios to integrate more wind power...... capability of WPPs would be investigated. The objective of this project is to analyze and identify the power system requirements for the synchronizing power support and inertial response control of WPPs in high wind power penetration scenarios. The dynamic frequency response of WPPs is realized...

  9. Frequency of CNKSR2 mutation in the X-linked epilepsy-aphasia spectrum.

    Science.gov (United States)

    Damiano, John A; Burgess, Rosemary; Kivity, Sara; Lerman-Sagie, Tally; Afawi, Zaid; Scheffer, Ingrid E; Berkovic, Samuel F; Hildebrand, Michael S

    2017-03-01

    Synaptic proteins are critical to neuronal function in the brain, and their deficiency can lead to seizures and cognitive impairments. CNKSR2 (connector enhancer of KSR2) is a synaptic protein involved in Ras signaling-mediated neuronal proliferation, migration and differentiation. Mutations in the X-linked gene CNKSR2 have been described in patients with seizures and neurodevelopmental deficits, especially those affecting language. In this study, we sequenced 112 patients with phenotypes within the epilepsy-aphasia spectrum (EAS) to determine the frequency of CNKSR2 mutation within this complex set of disorders. We detected a novel nonsense mutation (c.2314 C>T; p.Arg712*) in one Ashkenazi Jewish family, the male proband of which had a severe epileptic encephalopathy with continuous spike-waves in sleep (ECSWS). His affected brother also had ECSWS with better outcome, whereas the sister had childhood epilepsy with centrotemporal spikes. This mutation segregated in the three affected siblings in an X-linked manner, inherited from their mother who had febrile seizures. Although the frequency of point mutation is low, CNKSR2 sequencing should be considered in families with suspected X-linked EAS because of the specific genetic counseling implications. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  10. High frequency of PTEN mutations in nevi and melanomas from xeroderma pigmentosum patients.

    Science.gov (United States)

    Masaki, Taro; Wang, Yun; DiGiovanna, John J; Khan, Sikandar G; Raffeld, Mark; Beltaifa, Senda; Hornyak, Thomas J; Darling, Thomas N; Lee, Chyi-Chia R; Kraemer, Kenneth H

    2014-05-01

    We examined nevi and melanomas in 10 xeroderma pigmentosum (XP) patients with defective DNA repair. The lesions had a lentiginous appearance with markedly increased numbers of melanocytes. Using laser capture microdissection, we performed DNA sequencing of 18 benign and atypical nevi and 75 melanomas (melanoma in situ and invasive melanomas). The nevi had a similar high frequency of PTEN mutations as melanomas [61% (11/18) versus 53% (39/73)]. Both had a very high proportion of UV-type mutations (occurring at adjacent pyrimidines) [91% (10/11) versus 92% (36/39)]. In contrast to melanomas in the general population, the frequency of BRAF mutations (11%, 7/61), NRAS mutations (21%, 13/62), and KIT mutations (21%, 6/28) in XP melanomas was lower than for PTEN. Phospho-S6 immunostaining indicated activation of the mTOR pathway in the atypical nevi and melanomas. Thus, the clinical and histological appearances and the molecular pathology of these UV-related XP nevi and melanomas were different from nevi and melanomas in the general population. © 2014 Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  11. Studies on induced mutation frequency in Catharanthus roseus (L.) G. Don by gamma rays and EMS individually and in combination

    International Nuclear Information System (INIS)

    Venkateswarlu, M.; Susheelamma, B.N.; Kumar, P.; Subhash, K.

    1988-01-01

    Seeds of pink flowered (PF) and white flowered (WF) Catharanthus roseus were soaked in distilled water for 24 h and treated with gamma rays and 0.1% EMS separately and in combination. Six types of chlorophyll mutations, viz., xantha, albina, chlorina, viridis, maculata and tigrina were recovered to M 2 generation of both forms. The frequency of chlorophyll mutations was found to be dependent on the dose, of gamma rays and duration of treatment with EMS. Higher frequency of chlorophyll mutations was noticed in PF, which is mutagenically more sensitive than WF. It was also noticed that the combination treatments of gamma rays and EMS enhanced the frequency of chlorophyll mutations

  12. Loads as a Resource: Frequency Responsive Demand

    Energy Technology Data Exchange (ETDEWEB)

    Kalsi, Karanjit [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hansen, Jacob [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Fuller, Jason C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Marinovici, Laurentiu D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Elizondo, Marcelo A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Williams, Tess L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lian, Jianming [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sun, Yannan [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-12-01

    Current power grid operation predominantly relies on scheduling and regulating generation resources to supply loads and balance load changes. Due to the inherent intermittency of renewable energy, more flexible and fast ramping capacity is required to compensate for the uncertainty and variability introduced by renewable energy resources. With the advancement of information technologies, power system end-use loads are becoming more agile and can participate in provision of balancing energy and other grid services. The use of demand response can greatly reduce the required generation reserve in a clean and environmentally friendly way. In this report, a new frequency responsive load (FRL) controller was proposed based on the GFA controller, which can respond to both over and under-frequency events. A supervisory control was introduced to coordinate the autonomous response from FRLs in order to overcome the issues of excessive system response due to high penetration of FRLs. The effectiveness of the proposed FRL controller was demonstrated by large-scale simulation studies on the WECC system. Specifically, the FRLs were deployed in the WECC system at different penetration levels to analyze the performance of the proposed strategy both with and without supervisory level control. While both methods have their own advantages, the case without supervisory control could lead to system-wide instability depending on the size of the contingency and the number of FRLs deployed in the system. In addition, the voltage impacts of this controller on distribution system were also carefully investigated. Finally, a preliminary measurement and verification approach was also developed.

  13. A novel mutation in the WFS1 gene identified in a Taiwanese family with low-frequency hearing impairment

    Directory of Open Access Journals (Sweden)

    Chung Shing-Fang

    2007-05-01

    Full Text Available Abstract Background Wolfram syndrome gene 1 (WFS1 accounts for most of the familial nonsyndromic low-frequency sensorineural hearing loss (LFSNHL which is characterized by sensorineural hearing losses equal to and below 2000 Hz. The current study aimed to contribute to our understanding of the molecular basis of LFSNHL in an affected Taiwanese family. Methods The Taiwanese family with LFSNHL was phenotypically characterized using audiologic examination and pedigree analysis. Genetic characterization was performed by direct sequencing of WFS1 and mutation analysis. Results Pure tone audiometry confirmed that the family members affected with LFSNHL had a bilateral sensorineural hearing loss equal to or below 2000 Hz. The hearing loss threshold of the affected members showed no progression, a characteristic that was consistent with a mutation in the WFS1 gene located in the DFNA6/14/38 locus. Pedigree analysis showed a hereditarily autosomal dominant pattern characterized by a full penetrance. Among several polymorphisms, a missense mutation Y669H (2005T>C in exon 8 of WFS1 was identified in members of a Taiwanese family diagnosed with LFSNHL but not in any of the control subjects. Conclusion We discovered a novel heterozygous missense mutation in exon 8 of WFS1 (i.e., Y669H which is likely responsible for the LFSNHL phenotype in this particular Taiwanese family.

  14. Mutation frequencies in female mice and the estimation of genetic hazards of radiation in women

    International Nuclear Information System (INIS)

    Russell, W.L.

    1977-01-01

    The female germ cell stage of primary importance in radiation genetic hazards is the immature, arrested oocyte. In the mouse, this stage has a near zero or zero sensitivity to mutation induction by radiation. However, the application of these mouse results to women has been questioned on the ground that the mouse arrested oocytes are highly sensitive to killing by radiation, while the human cells are not; and, furthermore, that the mature and maturing oocytes in the mouse, which are resistant to killing, are sensitive to mutation induction. The present results have a 2-fold bearing on this problem. First, a more detailed analysis of oocyte-stage sensitivity to killing and mutation induction shows that there is no consistent correlation, either negative or positive, between the two. This indicates that the sensitivity to cell killing of the mouse immature oocyte may not be sufficient reason to prevent its use in predicting the mutational response of the human immature oocyte. Second, if the much more cautious assumption is made that the human arrested oocyte might be as mutationally sensitive as the most sensitive of all oocyte stages in the mouse, namely the maturing and mature ones, then the present data on the duration of these stages permit more accurate estimates than were heretofore possible on the mutational response of these stages to chronic irradiation

  15. Frequency of ABL gene mutations in chronic myeloid leukemia patients resistant to imatinib and results of treatment switch to second-generation tyrosine kinase inhibitors.

    Science.gov (United States)

    Marcé, Silvia; Zamora, Lurdes; Cabezón, Marta; Xicoy, Blanca; Boqué, Concha; Fernández, Cristalina; Grau, Javier; Navarro, José-Tomás; Fernández de Sevilla, Alberto; Ribera, Josep-Maria; Feliu, Evarist; Millá, Fuensanta

    2013-08-04

    Tyrosine kinase inhibitors (TKI) have improved the management of patients with chronic myeloid leukemia (CML). However, a significant proportion of patients do not achieve the optimal response or are resistant to TKI. ABL kinase domain mutations have been extensively implicated in the pathogenesis of TKI resistance. Treatment with second-generation TKI has produced high rates of hematologic and cytogenetic responses in mutated ABL patients. The aim of this study was to determine the type and frequency of ABL mutations in patients who were resistant to imatinib or had lost the response, and to analyze the effect of second-generation TKI on their outcome. The presence of ABL mutations in 45 CML patients resistant to imatinib was evaluated by direct sequencing and was correlated with the results of the cytogenetic study (performed in 39 cases). The outcome of these patients after therapy with nilotinib or dasatinib was analyzed. ABL mutations were detected in 14 out of 45 resistant patients. Patients with clonal cytogenetic evolution tended to develop mutations more frequently than those without clonal evolution. Nine out of the 15 patients with ABL mutation responded to a treatment switch to nilotinib (n=4), dasatinib (n=2), interferon (n=1) or hematopoietic stem cell transplantation (n=2). The frequency of ABL mutations in CML patients resistant to imatinib is high and is more frequent among those with clonal cytogenetic evolution. The change to second-generation TKI can overcome imatinib resistance in most of the mutated patients. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  16. The influence of large deletions on the mutation frequency induced by tritiated water and X-radiation in male Drosophila melanogaster post-meiotic germ cells

    International Nuclear Information System (INIS)

    Fossett, N.G.; Byrne, B.J.; Kelley, S.J.; Tucker, A.B.; Arbour-Reily, P.; Lee, W.R.

    1994-01-01

    Tritium beta radiation ( 3 H β-radiation) in the form of tritiated water was used to induce mutations at the alcohol dehydrogenase (Adh) locus in male Drosophila melanogaster post-meiotic germ cells. All 23 Adh null mutations were large deletions (>20 kb), determined by genetic complementation and Southern blot analyses. 27 Adh null mutations have been induced by 100-kVp X-rays and have been genetically and molecularly characterized. In contrast to 3 H β-radiation, 100-kVp X-rays induced a bimodal distribution of Adh null mutations, intragenic mutations, ≤250 bp, and large deletions, >100 kb. A statistically significant difference was observed between the frequency of large deletions (23/23 or 1.0) induced by 3 H β-radiation and the frequency of large deletions (19/27 or 0.7) induced by 100-kVp X-rays. However, a statistical difference was not observed between the size distribution of the large deletions induced by 3 H β-radiation and X-rays. The relative deletion frequency (RDF) induced by 3 H β-radiation and 100-kVp X-rays was (1.0/0.7=1.4). The relative biological effectiveness (RBE) of these two radiation sources was 1.4, determined from the ratio of the regression coefficients of the respective 3 H β-radiation and X-ray sex-linked recessive lethal (SLRL) dose-response data. The large difference in size between the two classes of X-ray-induced Adh null mutations and the increase in mutation frequency and deletion frequency for 3 H β-radiation with respect to X-rays may indicate that the relative deletion frequency (RDF) is the molecular biological basis for the increase in the RBE for radiation sources with a mean LET value ≤10 keV/μm

  17. Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: Family studies indicate a mutation type-dependent sex ratio of mutation frequencies

    Energy Technology Data Exchange (ETDEWEB)

    Becker, J.; Schmidt, W.; Olek, K. [Univ. of Bonn (Germany)] [and others

    1996-04-01

    The clinical manifestation of hemophilia A is caused by a wide range of different mutations. In this study the factor VIII genes of 147 severe hemophilia A patients-all exclusively from sporadic families-were screened for mutations by use of the complete panel of modern DNA techniques. The pathogenous defect could be characterized in 126 patients (85.7%). Fifty-five patients (37.4%) showed a F8A-gene inversion, 47 (32.0%) a point mutation, 14 (9.5%) a small deletion, 8 (5.4%) a large deletion, and 2 (1.4%) a small insertion. Further, four (2.7%) mutations were localized but could not be sequenced yet. No mutation could be identified in 17 patients (11.6%). Sixteen (10.9%) of the P identified mutations occurred in the B domain. Four of these were located in an adenosine nucleotide stretch at codon 1192, indicating a mutation hotspot. Somatic mosaicisms were detected in 3 (3.9%) of 76 patients` mothers, comprising 3 of 16 de novo mutations in the patients` mothers. Investigation of family relatives allowed detection of a de novo mutation in 16 of 76 two-generation and 28 of 34 three-generation families. On the basis of these data, the male:female ratio of mutation frequencies (k) was estimated as k = 3.6. By use of the quotients of mutation origin in maternal grandfather to patient`s mother or to maternal grandmother, k was directly estimated as k = 15 and k = 7.5, respectively. Considering each mutation type separately, we revealed a mutation type-specific sex ratio of mutation frequencies. Point mutations showed a 5-to-10-fold-higher and inversions a >10-fold- higher mutation rate in male germ cells, whereas deletions showed a >5-fold-higher mutation rate in female germ cells. Consequently, and in accordance with the data of other diseases like Duchenne muscular dystrophy, our results indicate that at least for X-chromosomal disorders the male:female mutation rate of a disease is determined by its proportion of the different mutation types. 68 refs., 1 fig., 5 tabs.

  18. A Hardware transverse beam frequency response simulator

    International Nuclear Information System (INIS)

    Ning, J.; Tan, C.Y.

    2005-01-01

    We built an electronic instrument that can mimic the transverse beam frequency response. The instrument consists of (1) a time delay circuit with an analog-to-digital converter (ADC) which contains a first-in-first-out random assess memory (FIFO RAM) and a digital-to-analog converter (DAC); (2) a variable phase shifter circuit which is based on an all pass filter with a bandwidth of 25kHz to 30kHz and (3) a commutating filter which is a nonlinear band pass filter. With this instrument, we can dynamically adjust the betatron tune, the synchrotron tune, and the chromaticity. Using this instrument, we are able to test other beam systems without using actual beam

  19. HFE H63D mutation frequency shows an increase in Turkish women with breast cancer

    Directory of Open Access Journals (Sweden)

    Guler Emine

    2006-02-01

    Full Text Available Abstract Background The hereditary hemochromatosis gene HFE plays a pivotal role in iron homeostasis. The association between cancer and HFE hetero- or homozygosity has previously been shown including hepatocellular and nonhepatocellular malignancies. This study was performed to compare frequencies of HFE C282Y and H63D variants in Turkish women with breast cancer and healthy controls. Methods Archived DNA samples of Hacettepe University Oncology Institute were used in this study. The HFE gene was investigated by PCR-RFLP. Results All subjects studied were free from C282Y mutation. Thirty-nine patients had H63D mutation and were all heterozygous. H63D allele frequency was 22.2% (39/176 in the breast cancer patients, and 14% (28/200 in the healthy volunteers. Statistical analysis of cases with HFE H63D phenotype showed significant difference between breast cancer and healthy volunteers (P = 0.02. Conclusion Our results suggest that HFE H63D mutation frequencies were increased in the breast cancer patients in comparison to those in the general population. Also, odds ratios (odds ratio = 2.05 computed in this study suggest that H63D has a positive association with breast cancer.

  20. Spectrum and frequency of chlorophyll mutations in urdbean (Vigna mungo L. Hepper) induced by EMS and gamma rays

    International Nuclear Information System (INIS)

    Sharma, A.K.; Singh, V.P.; Sarma, M.K.

    2006-01-01

    In mutation breeding experiment, plants with altered characteristics such as chlorophyll changes, sterility, plant lethality etc. could be the marker of the mutability of a variety. In fact, spectrum and frequency of chlorophyll mutations have been studied in the great detail. The chlorophyll mutation is the clear-cut indication of non-directional nature of mutation and possibility of induction of useful mutations. The spectrum and frequency of chlorophyll mutation was estimated by using gamma rays (100, 200, 300 and 400 Gy doses), EMS (0.2, 0.4, 0.6 and 0.8%) and combination of gamma rays (100, 200, 300 400 Gy) with 0.2 % concentration EMS on two cultivars, namely, Pant Urd-19 and Pant Urd-30 of urdbean ( Vigna mungo L. Hepper). Five different types of chlorophyll mutations viz., albina, xantha, viridis, chlorina and maculata were identified in both the cultivars. Almost all the combination treatments produced maximum frequency and wider spectrum of chlorophyll mutations followed by single treatment of gamma rays or EMS. The frequency of chlorophyll mutation increased with higher doses of mutagens but decreased at highest dose. Proc. Nat. Acad. Sci. India. 76(8), I, 2006. 64-68. (author)

  1. Adaptation responses to increasing drought frequency

    Science.gov (United States)

    Loch, A. J.; Adamson, D. C.; Schwabe, K.

    2016-12-01

    Using state contingent analysis we discuss how and why irrigators adapt to alternative water supply signals. This analysis approach helps to illustrate how and why producers currently use state-general and state-allocable inputs to adapt and respond to known and possible future climatic alternative natures. Focusing on the timing of water allocations, we explore inherent differences in the demand for water by two key irrigation sectors: annual and perennial producers which in Australia have allowed a significant degree of risk-minimisation during droughts. In the absence of land constraints, producers also had a capacity to respond to positive state outcomes and achieve super-normal profits. In the future, however, the probability of positive state outcomes is uncertain; production systems may need to adapt to minimise losses and/or achieve positive returns under altered water supply conditions that may arise as a consequence of more frequent drought states. As such, producers must assess whether altering current input/output choice sets in response to possible future climate states will enhance their long-run competitive advantage for both expected new normal and extreme water supply outcomes. Further, policy supporting agricultural sector climate change resilience must avoid poorly-designed strategies that increase producer vulnerability in the face of drought. Our analysis explores the reliability of alternative water property right bundles and how reduced allocations across time influence alternative responses by producers. We then extend our analysis to explore how management strategies could adapt to two possible future drier state types: i) where an average reduction in water supply is experienced; and ii) where the frequency of droughts increase. The combination of these findings are subsequently used to discuss the role water reform policy has to deal with current and future climate scenarios. We argue current policy strategies could drive producers to

  2. Frequency of p53 Gene Mutation and Protein Expression in Oral Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Ara, N.; Atique, M.; Ahmed, S.; Bukhari, S. G. A.

    2014-01-01

    Objective: To determine the frequency of p53 gene mutation and protein expression in Oral Squamous Cell Carcinoma (OSCC) and to establish correlation between the two. Study Design: Analytical study. Place and Duration of Study: Histopathology Department and Molecular Biology Laboratory, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from May 2010 to May 2011. Methodology: Thirty diagnosed cases of OSCC were selected by consecutive sampling. Seventeen were retrieved from the record files of the AFIP, and 13 fresh/frozen sections were selected from patients reporting to the Oral Surgery Department, Armed Forces Institute of Dentistry (AFID). Gene p53 mutation was analyzed in all the cases using PCRSSCP analysis. DNA was extracted from the formalin-fixed and paraffin-embedded tissue sections and fresh/frozen sections. DNA thus extracted was amplified by polymerase chain reaction. The amplified products were denatured and finally analyzed by gel electrophoresis. Gene mutation was detected as electrophoretic mobility shift. The immunohistochemical marker p53 was applied to the same 30 cases and overexpression of protein p53 was recorded. Results: Immunohistochemical expression of marker p53 was positive in 67% (95% Confidence Interval (CI) 48.7 - 80.9) of the cases. Mutations of the p53 gene were detected in 23% (95% CI 11.5 - 41.2) of the OSCC. No statistically significant correlation was found between p53 gene mutation and protein p53 expression (rs = - 0.057, p = 0.765). Conclusion: A substantial number of patients have p53 gene mutation (23%) and protein p53 expression (67%) in oral squamous cell carcinoma (OSCC). (author)

  3. High frequency response of open quantum dots

    International Nuclear Information System (INIS)

    Brunner, R.; Meisels, R.; Kuchar, F.; Ferry, D.; Elhassan, M.; Ishibashi, K.

    2002-01-01

    Full text: We investigate the response of the transport through open quantum dots to millimeterwave radiation (up to 55 GHz). In the low-field region ( 11 cm -2 and a mobility of 1.2 10 6 cm 2 /Vs. By applying a sufficiently negative voltage to the gates the 2DES is split into two regions connected only by a dot-like region (about 350 nm diameter) between them. The DC data exhibit backscattering peaks at fields of a few tenth of a Tesla. Shubnikovde- Haas (SdH) oscillations appear above 0.5 T. While the SdH oscillations show the usual temperature dependence, the backscattering peaks are temperature independent up to 2.5 K. The backscattering peak shows a reduction of 10 percent due to the millimeterwave irradiation. However, due to the temperature independence of this peak, this reduction cannot simply be attributed to electron heating. This conclusion is supported by the observation of a strong frequency dependence of the reduction of the peak height. (author)

  4. Frequency of Epidermal Growth Factor Receptor Mutation in Smokers with Lung Cancer Without Pulmonary Emphysema.

    Science.gov (United States)

    Takeda, Kenichi; Yamasaki, Akira; Igishi, Tadashi; Kawasaki, Yuji; Ito-Nishii, Shizuka; Izumi, Hiroki; Sakamoto, Tomohiro; Touge, Hirokazu; Kodani, Masahiro; Makino, Haruhiko; Yanai, Masaaki; Tanaka, Natsumi; Matsumoto, Shingo; Araki, Kunio; Nakamura, Hiroshige; Shimizu, Eiji

    2017-02-01

    Chronic obstructive pulmonary disease is a smoking-related disease, and is categorized into the emphysema and airway dominant phenotypes. We examined the relationship between emphysematous changes and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma. The medical records for 250 patients with lung adenocarcinoma were retrospectively reviewed. All patients were categorized into the emphysema or non-emphysema group. Wild-type EGFR was detected in 136 (54%) and mutant EGFR in 48 (19%). Emphysematous changes were observed in 87 (36%) patients. EGFR mutation was highly frequent in the non-emphysema group (p=0.0014). Multivariate logistic regression analysis showed that emphysema was an independent risk factor for reduced frequency of EGFR mutation (Odds Ratio=3.47, p=0.005). Our data showed a relationship between emphysematous changes and EGFR mutation status. There might be mutually exclusive genetic risk factors for carcinogenesis and development of emphysematous changes. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Low frequency of c-MPL gene mutations in Iranian patients with Philadelphia-negative myeloproliferative disorders.

    Science.gov (United States)

    Ghotaslou, A; Nadali, F; Chahardouli, B; Alizad Ghandforosh, N; Rostami, S H; Alimoghaddam, K; Ghavamzadeh, A

    2015-01-01

    Myeloproliferative disorders are a group of diseases characterized by increased proliferation of myeloid lineage. In addition to JAK2V617F mutation, several mutations in the c-MPL gene have been reported in patients with philadelphia-negative chronic myeloproliferative disorders that could be important in the pathogenesis of diseases. The aim of the present study was to investigate the frequency of c-MPL and JAK2V617F mutations in Iranian patients with Philadelphia-negativemyeloproliferative disorders. Peripheral blood samples were collected from 60 patients with Philadelphia-negative MPD) Subgroups ET and PMF) and 25 healthy subjects as control group. The mutation status of c-MPL and Jak2V617F were investigated by using Amplification-refractory mutation system (ARMS) and Allele-Specific PCR (AS-PCR), respectively. The results were confirmed by sequencing. Among 60 patients, 34 (56.6%) and 1(1.7%) had Jak2V617F and c-MPL mutation, respectively. Patients with Jak2V617F mutation had higher WBC counts and hemoglobin concentration than those without the mutation (p= 0.005, p=0.003). In addition, for all healthy subjects in control group, mutations were negative. The present study revealed that the c-MPL mutations unlike the Jak2V617F mutations are rare in Iranian patients with Ph-negative MPNs and the low mutation rate should be considered in the design of screening strategies of MPD patients.

  6. HFE gene C282Y, H63D and S65C mutations frequency in the Transylvania region, Romania.

    Science.gov (United States)

    Trifa, Adrian P; Popp, Radu A; Militaru, Mariela S; Farcaş, Marius F; Crişan, Tania O; Gana, Ionuţ; Cucuianu, Andrei; Pop, Ioan V

    2012-06-01

    HFE-associated haemochromatosis is one of the most frequent autosomal recessive disorders in the Caucasian population. Although most of the cases are homozygous individuals for the C282Y mutation, another two mutations, H63D and S65C, have been reported to be associated with milder forms of the disease. This study was a first attempt to evaluate the distribution of these HFE gene mutations in the Transylvania region. Two-hundred and twenty-five healthy, unrelated volunteers originating from the Transylvania region, Romania, were screened for the HFE gene C282Y, H63D and S65C mutations, using molecular genetics assays (Polymerase Chain Reaction-Restriction Fragments Length Polymorphism). For the C282Y mutation, 7 heterozygotes (3.1%) were found, but no homozygous individual. In the case of the H63D mutation, 40 heterozygotes (17.8%) and 4 homozygotes (1.75%) for the mutant allele were evidenced. We found a compound heterozygous genotype (C282Y/H63D) in one individual (0.45%). Thus, the allele frequencies of the C282Y and H63D were 1.75% and 10.9%, respectively. Three individuals (1.3%) were found to harbour the S65C mutation in a heterozygous state, but none in a homozygous state: the allele frequency of the mutant allele was 0.75%. The distribution of the HFE gene C282Y, H63D and S65C mutations found in our group matches the tendencies observed in other European countries: a decreasing gradient from Northern to Southern Europe for the C282Y mutation; high frequency for the H63D mutation, and low frequency for the S65C mutation in most of the countries.

  7. Frequency and spectrum of hemoglobinopathy mutations in a Uruguayan pediatric population

    Directory of Open Access Journals (Sweden)

    Julio Da Luz

    2013-01-01

    Full Text Available Hemoglobinopathies are the most common recessive diseases worldwide but their prevalence in Uruguay has not been investigated. In this study, 397 unrelated outpatient children from the Pereira Rosell Hospital Center (CHPR, as well as 31 selected patients with microcytic anemia and 28 β-thalassemia carriers were analyzed for hemoglobinopathies by using biochemical and molecular biology methods. Parametric and non-parametric methods were used to compare the hematological indices between groups of genotypes. Of the 397 patients in the first group, approximately 1% (0.76% HbS and 0.25% β-thalassemia had a mutation in the HBB gene and 3.3% had α-thalassemia. These mutations had a heterogeneous distribution that varied according to individual ancestry. HbS was found exclusively in individuals with declared African ancestry and had a carrier frequency of 2.2%. The frequency of α-thalassemia carriers in outpatients of European and African ancestry was 1.2% and 6.5%, respectively. In contrast, the frequency of α-thalassemia carriers in patients with microcytic anemia was 25.8%, significantly higher (p < 0.01 than that observed in the sample as a whole and in Afro-descendants and Euro-descendants. Significant differences were observed in the hematological parameters between individuals with thalassemia genotypes and those with a normal genotype. These results indicate that hemoglobinopathies are a relevant health problem in Uruguay.

  8. The Frequency and Type of K-RAS Mutations in Mexican Patients With Colorectal Cancer: A National Study.

    Science.gov (United States)

    Cárdenas-Ramos, Susana G; Alcázar-González, Gregorio; Reyes-Cortés, Luisa M; Torres-Grimaldo, Abdiel A; Calderón-Garcidueñas, Ana L; Morales-Casas, José; Flores-Sánchez, Patricia; De León-Escobedo, Raúl; Gómez-Díaz, Antonio; Moreno-Bringas, Carmen; Sánchez-Guillén, Jorge; Ramos-Salazar, Pedro; González-de León, César; Barrera-Saldaña, Hugo A

    2017-06-01

    Current metastatic colorectal cancer (mCRC) therapy uses monoclonal antibodies against the epidermal growth factor receptor. This treatment is only useful in the absence of K-RAS gene mutations; therefore the study of such mutations is part of a personalized treatment. The aim of this work is to determine the frequency and type of the most common K-RAS mutations in Mexican patients with metastatic disease by nucleotide sequencing. We studied 888 patients with mCRC from different regions of Mexico. The presence of mutations in exon 2, codons 12 and 13, of the K-RAS gene was determined by nucleotide sequencing. Patients exhibited K-RAS gene mutations in 35% (310/888) of cases. Mutation frequency of codons 12 and 13 was 71% (221/310) and 29% (89/310), respectively. The most common mutation (45.7%) in codon 12 was c.35G>A (p.G12D), whereas the one in codon 13 was c.38G>A (p.G13D) (78.7%). Given the frequency of K-RAS mutations in Mexicans, making a genetic study before deciding to treat mCRC patients with monoclonal antibodies is indispensable.

  9. The frequency of CCR5 promoter polymorphisms and CCR5 32 mutation in Iranian populations

    Directory of Open Access Journals (Sweden)

    Mohammad Zare-Bidaki

    2015-04-01

    Full Text Available Evidence showed that chemokines serve as pro-migratory factors for immune cells. CCL3, CCL4 and CCL5, as the main CC  chemokines subfamily members, activate immune cells through binding to CC chemokine receptor 5 or CCR5. Macrophages, NK cells and T lymphocytes express CCR5 and thus, affected CCR5 expression or functions could be associated with altered immune responses. Deletion of 32 base pairs (D 32 in the exon 1 of the CCR5 gene, which is known as CCR5 D 32 mutation causes down regulation and malfunction of the molecule. Furthermore, it has been evidenced that three polymorphisms in the promoter region of CCR5 modulate its expression. Altered CCR5 expression in microbial infection and immune related diseases have been reported by several researchers but the role of CCR5 promoter polymorphisms and CCR5 D 32 mutation in Iranian patients suffering from these diseases are controversial. Due to the fact that Iranian people have different genetic backgrounds compared to other ethnics, hence, CCR5 promoter polymorphisms and CCR5 D 32 mutation association with the diseases may be different in Iranian patients. Therefore, this review addresses the most recent information regarding the prevalence as well as association of the mutation and polymorphisms in Iranian patients with microbial infection and immune related diseases as along with normal population.

  10. Mutation frequency and genotype/phenotype correlation among phenylketonuria patients from Georgia

    Energy Technology Data Exchange (ETDEWEB)

    Woo, S.L.C.; Martinez, D.; Kuozmine, A. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). To determine the molecular basis of PKU in the state of Georgia, thirty-five Georgian PKU patients representing sixty independent alleles were examined by a combination of DGGE and direct sequence analysis. At present, this approach has led to the identification of 55/60 or about 92% of all mutant alleles. The relatively high frequencies of mutations common to the British Isles (R408W, I65T and L348V) are compatible with 1990 census data showing that 34% of the general Georgian population claim Irish, English or Scottish ancestors. Three new mutations, E76A (1/60), R241L (2/60), and R400R (2/60), were also detected in this study. Although the nucleotide substitution in codon 400 (AGG{r_arrow}CGG) did not change the amino acid sequence, it was the only base change detected in a scan of all 13 exons of two independent alleles. Since codon 400 is split between exons 11 and 12, this change may exert some effect on splicing, as has previously been seen in the PAH gene for the silent mutation Q304Q and the nonsense mutation Y356X, each of which effect codons immediately adjacent to splicing signals. This hypothesis remains to be tested by expression analysis or studies of ectopic transcripts. The remaining 19 characterized alleles contained one of 15 previously identified mutations. Twenty-five of the thirty non-related patients examined in this study were completely genotyped, and there was a strong correlation between mutant PAH genotype, PAH activity predicted from in vitro expression studies where known, and PKU or HPA phenotype. For mutations not yet studied by expression analysis, this correlation suggests that L213P, R241L, Y277D may drastically reduce residual PAH activity while F39L and E76A may retain significant amounts of PAH activity.

  11. Frequency and clinical features of the JAK2 V617F mutation in pediatric patients with sporadic essential thrombocythemia.

    Science.gov (United States)

    Nakatani, Takuya; Imamura, Toshihiko; Ishida, Hiroyuki; Wakaizumi, Katsuji; Yamamoto, Tohru; Otabe, Osamu; Ishigami, Tsuyoshi; Adachi, Souichi; Morimoto, Akira

    2008-12-01

    Pediatric essential thrombocythemia (ET) is a rare and heterogenous disease entity. While several recent studies have focused on the role of the JAK2 V617F mutation in pediatric ET, the frequency of pediatric ET cases with this mutation and the associated clinical features remain unclear. We examined six childhood cases who had been diagnosed with ET according to WHO criteria (onset age: 0.2-14 years) for the presence of the JAK2 V617F mutation, MPLW515L mutation and JAK2 exon 12 mutations. Two sensitive PCR-based methods were used for the JAK2 V617F genotyping. We also examined the expression of polycythemia rubra vera-1 (PRV-1), which is a diagnostic marker for clonal ET. We found that three of the six cases had the JAK2 V617F mutation and that all six cases expressed PRV-1 in their peripheral granulocytes. Neither MPL W515L mutation nor JAK2 exon 12 mutations was detected in the patients without JAK2 V617F mutation. The two patients who developed thrombocythemia during infancy were JAK2 V617F-negative. These findings suggest that the JAK2 V617F mutation is not rare in childhood sporadic ET cases, and that these cases might be older and myeloproliferative features.

  12. Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor

    DEFF Research Database (Denmark)

    Jönsson, Mats; Ekstrand, Anna; Edekling, Thomas

    2009-01-01

    . METHODS: We used a real-time PCR based method to determine KRAS mutations in 136 colorectal cancers with mutations identified in 53 (39%) tumors. RESULTS: KRAS mutations were significantly more often found in rectal cancer (21/38, 55%) than in colon cancer (32/98, 33%) (P = 0.02). This finding...... was explained by marked differences mutation rates in female patients who showed mutations in 33% of the colon cancers and in 67% of the rectal cancers (P = 0.01). Concurrent KRAS mutations were identified in three tumors; two colorectal cancers harbored Gly12Asp/Gly13Asp and Gly12Cys/Gly13Asp and a third tumor...... carried Gly12Cys/Gly12Asp in an adenomatous component and additionally acquired Gly12Val in the invasive component. CONCLUSION: The demonstration of a particularly high KRAS mutation frequency among female rectal cancer patients suggests that this subset is the least likely to respond to anti...

  13. Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay.

    Science.gov (United States)

    Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

    2014-01-01

    A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner.

  14. Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay.

    Directory of Open Access Journals (Sweden)

    Hiraku Takei

    Full Text Available A gain-of-function mutation in the myeloproliferative leukemia virus (MPL gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs. The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5% of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner.

  15. Characterization of a mutant of Escherichia coli B/R defective in mutation frequency decline

    International Nuclear Information System (INIS)

    George, D.L.

    1974-01-01

    A mutant of Escherichia coli B/r designated mfd is very deficient in the ability to exhibit mutation frequency decline (MFD), the characteristic loss of potential suppressor mutations which occurs when protein synthesis is briefly inhibited after irradiation with ultraviolet light (uv). This mutant is known to excise pyrimidine dimers very slowly, although it is as uv-resistant as its mfd + B/r parent strain. We have found that the mfd mutant performs the initial incision step of excision repair normally, but repairs the resulting single-strand breaks much more slowly than the mfd + strain. In spite of the slow dimer excision in the mfd mutant, single-strand DNA breaks do not accumulate during postirradiation incubation, implying that incision and excision are well corrdinated. the prolonged postirradiation lag in cell division and DNA synthesis which accompany slow excision in the mfd strain indicates that resumption of these processes of optimal rates is linked to the timing of excision repair. The normal uv-resistance of the mfd mutant also suggests such coordination and shows that the rate of excision repair is independent of its ultimate efficiency in the removal of potentially lethal uv-induced damage. (U.S.)

  16. Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort.

    Science.gov (United States)

    Davidson, G L; Murphy, S M; Polke, J M; Laura, M; Salih, M A M; Muntoni, F; Blake, J; Brandner, S; Davies, N; Horvath, R; Price, S; Donaghy, M; Roberts, M; Foulds, N; Ramdharry, G; Soler, D; Lunn, M P; Manji, H; Davis, M B; Houlden, H; Reilly, M M

    2012-08-01

    The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.

  17. Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort.

    LENUS (Irish Health Repository)

    Davidson, G L

    2012-08-01

    The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1\\/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1\\/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.

  18. Microsatellite frequencies vary with body mass and body temperature in mammals, suggesting correlated variation in mutation rate

    Directory of Open Access Journals (Sweden)

    William Amos

    2014-11-01

    Full Text Available Substitution rate is often found to correlate with life history traits such as body mass, a predictor of population size and longevity, and body temperature. The underlying mechanism is unclear but most models invoke either natural selection or factors such as generation length that change the number of mutation opportunities per unit time. Here we use published genome sequences from 69 mammals to ask whether life history traits impact another form of genetic mutation, the high rates of predominantly neutral slippage in microsatellites. We find that the length-frequency distributions of three common dinucleotide motifs differ greatly between even closely related species. These frequency differences correlate with body mass and body temperature and can be used to predict the phenotype of an unknown species. Importantly, different length microsatellites show complicated patterns of excess and deficit that cannot be explained by a simple model where species with short generation lengths have experienced more mutations. Instead, the patterns probably require changes in mutation rate that impact alleles of different length to different extents. Body temperature plausibly influences mutation rate by modulating the propensity for slippage. Existing hypotheses struggle to account for a link between body mass and mutation rate. However, body mass correlates inversely with population size, which in turn predicts heterozygosity. We suggest that heterozygote instability, HI, the idea that heterozygous sites show increased mutability, could provide a plausible link between body mass and mutation rate.

  19. Transformation Algorithm of Dielectric Response in Time-Frequency Domain

    Directory of Open Access Journals (Sweden)

    Ji Liu

    2014-01-01

    Full Text Available A transformation algorithm of dielectric response from time domain to frequency domain is presented. In order to shorten measuring time of low or ultralow frequency dielectric response characteristics, the transformation algorithm is used in this paper to transform the time domain relaxation current to frequency domain current for calculating the low frequency dielectric dissipation factor. In addition, it is shown from comparing the calculation results with actual test data that there is a coincidence for both results over a wide range of low frequencies. Meanwhile, the time domain test data of depolarization currents in dry and moist pressboards are converted into frequency domain results on the basis of the transformation. The frequency domain curves of complex capacitance and dielectric dissipation factor at the low frequency range are obtained. Test results of polarization and depolarization current (PDC in pressboards are also given at the different voltage and polarization time. It is demonstrated from the experimental results that polarization and depolarization current are affected significantly by moisture contents of the test pressboards, and the transformation algorithm is effective in ultralow frequency of 10−3 Hz. Data analysis and interpretation of the test results conclude that analysis of time-frequency domain dielectric response can be used for assessing insulation system in power transformer.

  20. The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.

    LENUS (Irish Health Repository)

    Flanagan, J M

    2010-02-01

    Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa.

  1. Biological responses of mobile phone frequency exposure.

    Science.gov (United States)

    Behari, Jitendra

    2010-10-01

    Existence of low level electromagnetic fields in the environment has been known since antiquity and their biological implications are noted for several decades. As such dosimetry of such field parameters and their emissions from various sources of mass utilization has been a subject of constant concern. Recent advancement in mobile communications has also drawn attention to their biological effects. Hand held children and adults alike generally use mobile sources as cordless phones in various positions with respect to the body. Further, an increasing number of mobile communication base stations have led to wide ranging concern about possible health effects of radiofrequency emissions. There are two distinct possibilities by which health could be affected as a result of radio frequency field exposure. These are thermal effects caused by holding mobile phones close to the body and extended conversations over a long period of time. Secondly, there could be possibly non thermal effects from both phones and base stations whereby the affects could also be cumulative. Some people may be adversely affected by the environmental impact of mobile phone base stations situated near their homes, schools or any other place. In addition to mobile phones, appliances like microwave oven etc are also in increasing use. Apart from the controversy over the possible health effects due to the non-thermal effect of electromagnetic fields the electromagnetic interaction of portable radio waves with human head needs to be quantitatively evaluated. Relating to this is the criteria of safe exposure to the population at large. While a lot of efforts have gone into resolving the issue, a clear picture has yet to emerge. Recent advances and the problems relating to the safety criteria are discussed.

  2. Studies of adaptive response and mutation induction in MCF-10A cells following exposure to chronic or acute ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Manesh, Sara Shakeri; Sangsuwan, Traimate; Wojcik, Andrzej; Haghdoost, Siamak, E-mail: Siamak.haghdoost@su.se

    2015-10-15

    Highlights: • 50 mGy at 1.4 mGy/h induces adaptive response in MCF-10A at mutation level. • Low dose rate γ-radiation does not induce adaptive response at survival level. • Overall, a dose rate effect is absent at the level of mutation in MCF-10A cells. - Abstract: A phenomenon in which exposure to a low adapting dose of radiation makes cells more resistant to the effects of a subsequent high dose exposure is termed radio-adaptive response. Adaptive response could hypothetically reduce the risk of late adverse effects of chronic or acute radiation exposures in humans. Understanding the underlying mechanisms of such responses is of relevance for radiation protection as well as for the clinical applications of radiation in medicine. However, due to the variability of responses depending on the model system and radiation condition, there is a need to further study under what conditions adaptive response can be induced. In this study, we analyzed if there is a dose rate dependence for the adapting dose, assuming that the adapting dose induces DNA response/repair pathways that are dose rate dependent. MCF-10A cells were exposed to a 50 mGy adapting dose administered acutely (0.40 Gy/min) or chronically (1.4 mGy/h or 4.1 mGy/h) and then irradiated by high acute challenging doses. The endpoints of study include clonogenic cell survival and mutation frequency at X-linked hprt locus. In another series of experiment, cells were exposed to 100 mGy and 1 Gy at different dose rates (acutely and chronically) and then the mutation frequencies were studied. Adaptive response was absent at the level of clonogenic survival. The mutation frequencies were significantly decreased in the cells pre-exposed to 50 mGy at 1.4 mGy/h followed by 1 Gy acute exposure as challenging dose. Importantly, at single dose exposures (1 Gy or 100 mGy), no differences at the level of mutation were found comparing different dose rates.

  3. The allele-frequency spectrum in a decoupled Moran model with mutation, drift, and directional selection, assuming small mutation rates.

    Science.gov (United States)

    Vogl, Claus; Clemente, Florian

    2012-05-01

    We analyze a decoupled Moran model with haploid population size N, a biallelic locus under mutation and drift with scaled forward and backward mutation rates θ(1)=μ(1)N and θ(0)=μ(0)N, and directional selection with scaled strength γ=sN. With small scaled mutation rates θ(0) and θ(1), which is appropriate for single nucleotide polymorphism data in highly recombining regions, we derive a simple approximate equilibrium distribution for polymorphic alleles with a constant of proportionality. We also put forth an even simpler model, where all mutations originate from monomorphic states. Using this model we derive the sojourn times, conditional on the ancestral and fixed allele, and under equilibrium the distributions of fixed and polymorphic alleles and fixation rates. Furthermore, we also derive the distribution of small samples in the diffusion limit and provide convenient recurrence relations for calculating this distribution. This enables us to give formulas analogous to the Ewens-Watterson estimator of θ for biased mutation rates and selection. We apply this theory to a polymorphism dataset of fourfold degenerate sites in Drosophila melanogaster. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Low-frequency versus high-frequency synchronisation in chirp-evoked auditory brainstem responses

    DEFF Research Database (Denmark)

    Rønne, Filip Munch; Gøtsche-Rasmussen, Kristian

    2011-01-01

    This study investigates the frequency specific contribution to the auditory brainstem response (ABR) of chirp stimuli. Frequency rising chirps were designed to compensate for the cochlear traveling wave delay, and lead to larger wave-V amplitudes than for click stimuli as more auditory nerve fibr...

  5. Method of detecting system function by measuring frequency response

    Science.gov (United States)

    Morrison, John L [Butte, MT; Morrison, William H [Manchester, CT; Christophersen, Jon P [Idaho Falls, ID

    2012-04-03

    Real-time battery impedance spectrum is acquired using a one-time record. Fast Summation Transformation (FST) is a parallel method of acquiring a real-time battery impedance spectrum using a one-time record that enables battery diagnostics. An excitation current to a battery is a sum of equal amplitude sine waves of frequencies that are octave harmonics spread over a range of interest. A sample frequency is also octave and harmonically related to all frequencies in the sum. The time profile of this signal has a duration that is a few periods of the lowest frequency. The voltage response of the battery, average deleted, is the impedance of the battery in the time domain. Since the excitation frequencies are known and octave and harmonically related, a simple algorithm, FST, processes the time record by rectifying relative to the sine and cosine of each frequency. Another algorithm yields real and imaginary components for each frequency.

  6. Method of detecting system function by measuring frequency response

    Science.gov (United States)

    Morrison, John L.; Morrison, William H.; Christophersen, Jon P.; Motloch, Chester G.

    2013-01-08

    Methods of rapidly measuring an impedance spectrum of an energy storage device in-situ over a limited number of logarithmically distributed frequencies are described. An energy storage device is excited with a known input signal, and a response is measured to ascertain the impedance spectrum. An excitation signal is a limited time duration sum-of-sines consisting of a select number of frequencies. In one embodiment, magnitude and phase of each frequency of interest within the sum-of-sines is identified when the selected frequencies and sample rate are logarithmic integer steps greater than two. This technique requires a measurement with a duration of one period of the lowest frequency. In another embodiment, where selected frequencies are distributed in octave steps, the impedance spectrum can be determined using a captured time record that is reduced to a half-period of the lowest frequency.

  7. IHH Gene Mutations Causing Short Stature With Nonspecific Skeletal Abnormalities and Response to Growth Hormone Therapy.

    Science.gov (United States)

    Vasques, Gabriela A; Funari, Mariana F A; Ferreira, Frederico M; Aza-Carmona, Miriam; Sentchordi-Montané, Lucia; Barraza-García, Jimena; Lerario, Antonio M; Yamamoto, Guilherme L; Naslavsky, Michel S; Duarte, Yeda A O; Bertola, Debora R; Heath, Karen E; Jorge, Alexander A L

    2018-02-01

    Genetic evaluation has been recognized as an important tool to elucidate the causes of growth disorders. To investigate the cause of short stature and to determine the phenotype of patients with IHH mutations, including the response to recombinant human growth hormone (rhGH) therapy. We studied 17 families with autosomal-dominant short stature by using whole exome sequencing and screened IHH defects in 290 patients with growth disorders. Molecular analyses were performed to evaluate the potential impact of N-terminal IHH variants. We identified 10 pathogenic or possibly pathogenic variants in IHH, an important regulator of endochondral ossification. Molecular analyses revealed a smaller potential energy of mutated IHH molecules. The allele frequency of rare, predicted to be deleterious IHH variants found in short-stature samples (1.6%) was higher than that observed in two control cohorts (0.017% and 0.08%; P IHH variants segregate with short stature in a dominant inheritance pattern. Affected individuals typically manifest mild disproportional short stature with a frequent finding of shortening of the middle phalanx of the fifth finger. None of them have classic features of brachydactyly type A1, which was previously associated with IHH mutations. Five patients heterozygous for IHH variants had a good response to rhGH therapy. The mean change in height standard deviation score in 1 year was 0.6. Our study demonstrated the association of pathogenic variants in IHH with short stature with nonspecific skeletal abnormalities and established a frequent cause of growth disorder, with a preliminary good response to rhGH. Copyright © 2017 Endocrine Society

  8. Effect of Ku80 deficiency on mutation frequencies and spectra at a LacZ reporter locus in mouse tissues and cells.

    Directory of Open Access Journals (Sweden)

    Rita A Busuttil

    Full Text Available Non-homologous end joining (NHEJ is thought to be an important mechanism for preventing the adverse effects of DNA double strand breaks (DSBs and its absence has been associated with premature aging. To investigate the effect of inactivated NHEJ on spontaneous mutation frequencies and spectra in vivo and in cultured cells, we crossed a Ku80-deficient mouse with mice harboring a lacZ-plasmid-based mutation reporter. We analyzed various organs and tissues, as well as cultured embryonic fibroblasts, for mutations at the lacZ locus. When comparing mutant with wild-type mice, we observed a significantly higher number of genome rearrangements in liver and spleen and a significantly lower number of point mutations in liver and brain. The reduced point mutation frequency was not due to a decrease in small deletion mutations thought to be a hallmark of NHEJ, but could be a consequence of increased cellular responses to unrepaired DSBs. Indeed, we found a substantial increase in persistent 53BP1 and gammaH2AX DNA damage foci in Ku80-/- as compared to wild-type liver. Treatment of cultured Ku80-deficient or wild-type embryonic fibroblasts, either proliferating or quiescent, with hydrogen peroxide or bleomycin showed no differences in the number or type of induced genome rearrangements. However, after such treatment, Ku80-deficient cells did show an increased number of persistent DNA damage foci. These results indicate that Ku80-dependent repair of DNA damage is predominantly error-free with the effect of alternative more error-prone pathways creating genome rearrangements only detectable after extended periods of time, i.e., in young adult animals. The observed premature aging likely results from a combination of increased cellular senescence and an increased load of stable, genome rearrangements.

  9. Dynamic Response to Pedestrian Loads with Statistical Frequency Distribution

    DEFF Research Database (Denmark)

    Krenk, Steen

    2012-01-01

    on the magnitude of the resulting response. A frequency representation of vertical pedestrian load is developed, and a compact explicit formula is developed for the magnitude of the resulting response, in terms of the damping ratio of the structure, the bandwidth of the pedestrian load, and the mean footfall...... frequency. The accuracy of the formula is verified by a statistical moment analysis using the Lyapunov equations....

  10. Elastic-plastic response characteristics during frequency nonstationary waves

    International Nuclear Information System (INIS)

    Miyama, T.; Kanda, J.; Iwasaki, R.; Sunohara, H.

    1987-01-01

    The purpose of this paper is to study fundamental effects of the frequency nonstationarity on the inelastic responses. First, the inelastic response characteristics are examined by applying stationary waves. Then simple representation of nonstationary characteristics is considered to general nonstationary input. The effects for frequency nonstationary response are summarized for inelastic systems. The inelastic response characteristics under white noise and simple frequency nonstationary wave were investigated, and conclusions can be summarized as follows. 1) The maximum response values for both BL model and OO model corresponds fairly well with those estimated from the energy constant law, even when R is small. For the OO model, the maximum displacement response forms a unique curve except for very small R. 2) The plastic deformation for the BL model is affected by wide frequency components, as R decreases. The plastic deformation for the OO model can be determined from the last stiffness. 3). The inelastic response of the BL model is considerably affected by the frequency nonstationarity of the input motion, while the response is less affected by the nonstationarity for OO model. (orig./HP)

  11. [Mutational frequencies in usherin(USH2A gene) in 26 Colombian individuals with Usher syndrome type II].

    Science.gov (United States)

    López, Greizy; Gelvez, Nancy Yaneth; Tamayo, Martalucía

    2011-03-01

    Usher syndrome is a disorder characterized by progressive retinitis pigmentosa, prelingual sensory hearing loss and vestibular dysfunction. It is the most frequent cause of deaf-blindness in humans. Three clinical types and twelve genetic subtypes have been characterized. Type II is the most common, and among these cases, nearly 80% have mutations in the USH2A gene. The aim of the study was to establish the mutational frequencies for the short isoform of USH2A gene in Usher syndrome type II. Twenty-six Colombian individuals with Usher syndrome type II were included. SSCP analysis for 20 exons of the short isoform was performed and abnormal patterns were sequenced. Sequencing of exon 13 of the USH2A gene was performed for all the individuals because the most frequent mutation is located in this exon. The most frequent mutation was c.2299delG, identified in the 27% (n=8) of the sample. The second mutation, p.R334W, showed a frequency of 15%. A new variant identified in the 5’UTR region, g.129G>T, was present in 1 individual (4%). Four polymorphisms were identified; one of them is a new deletion in exon 20, first reported in this study. Mutations in the usherin short isoform were identified in 38% of a sample of 26 USH2 cases. Molecular diagnosis was established in 7 of the 26.

  12. An Extended System Frequency Response Model Considering Wind Power Participation in Frequency Regulation

    Directory of Open Access Journals (Sweden)

    Yi Tang

    2017-11-01

    Full Text Available With increasing penetration of wind power into the power system, wind power participation in frequency regulation is regarded as a beneficial strategy to improve the dynamic frequency response characteristics of power systems. The traditional power system frequency response (SFR model, which only includes synchronous generators, is no longer suitable for power systems with high penetrated wind power. An extended SFR model, based on the reduced-order model of wind turbine generator (WTG and the traditional SFR model, is presented in this paper. In the extended SFR model, the reduced-order model of WTG with combined frequency control is deduced by employing small signal analysis theory. Afterwards, the stability analysis of a closed-loop control system for the extended SFR model is carried out. Time-domain simulations using a test system are performed to validate the effectiveness of the extended SFR model; this model can provide a simpler, clearer and faster way to analyze the dynamic frequency response characteristic for a high-wind integrated power systems. The impact of additional frequency control parameters and wind speed disturbances on the system dynamic frequency response characteristics are investigated.

  13. Responses of an isolation system with distinct multiple frequencies

    International Nuclear Information System (INIS)

    Wu, Ting-shu; Seidensticker, R.W.

    1991-01-01

    Base isolation systems are generally designed with a single natural frequency. A major concern for these isolation systems is that, if the dominant frequency of a future earthquake is equal or close to the system's natural frequency, the ground motion will be greatly amplified because of resonance,and the superstructure would suffer severe damages. This paper present an isolation system designed with two distinct frequencies. Its responses to different ground motions, including a harmonic motion, show that no excessive amplification will occur. Adoption of this isolation system would greatly enhance the safety of an isolated superstructure against future strong earthquakes. 3 refs., 4 figs., 2 tabs

  14. Investigation of the Relationship Between Electrical Stimulation Frequency and Muscle Frequency Response Under Submaximal Contractions.

    Science.gov (United States)

    Papcke, Caluê; Krueger, Eddy; Olandoski, Marcia; Nogueira-Neto, Guilherme Nunes; Nohama, Percy; Scheeren, Eduardo Mendonça

    2018-03-25

    Neuromuscular electrical stimulation (NMES) is a common tool that is used in clinical and laboratory experiments and can be combined with mechanomyography (MMG) for biofeedback in neuroprostheses. However, it is not clear if the electrical current applied to neuromuscular tissues influences the MMG signal in submaximal contractions. The objective of this study is to investigate whether the electrical stimulation frequency influences the mechanomyographic frequency response of the rectus femoris muscle during submaximal contractions. Thirteen male participants performed three maximal voluntary isometric contractions (MVIC) recorded in isometric conditions to determine the maximal force of knee extensors. This was followed by the application of nine modulated NMES frequencies (20, 25, 30, 35, 40, 45, 50, 75, and 100 Hz) to evoke 5% MVIC. Muscle behavior was monitored by the analysis of MMG signals, which were decomposed into frequency bands by using a Cauchy wavelet transform. For each applied electrical stimulus frequency, the mean MMG spectral/frequency response was estimated for each axis (X, Y, and Z axes) of the MMG sensor with the values of the frequency bands used as weights (weighted mean). Only with respect to the Z (perpendicular) axis of the MMG signal, the stimulus frequency of 20 Hz did not exhibit any difference with the weighted mean (P = 0.666). For the frequencies of 20 and 25 Hz, the MMG signal displayed the bands between 12 and 16 Hz in the three axes (P frequencies from 30 to 100 Hz, the muscle presented a higher concentration of the MMG signal between the 22 and 29 Hz bands for the X and Z axes, and between 16 and 34 Hz bands for the Y axis (P frequency, because their frequency contents tend to mainly remain between the 20- and 25-Hz bands. Hence, NMES does not interfere with the use of MMG in neuroprosthesis. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  15. Specificity of the Human Frequency Following Response for Carrier and Modulation Frequency Assessed Using Adaptation.

    Science.gov (United States)

    Gockel, Hedwig E; Krugliak, Alexandra; Plack, Christopher J; Carlyon, Robert P

    2015-12-01

    The frequency following response (FFR) is a scalp-recorded measure of phase-locked brainstem activity to stimulus-related periodicities. Three experiments investigated the specificity of the FFR for carrier and modulation frequency using adaptation. FFR waveforms evoked by alternating-polarity stimuli were averaged for each polarity and added, to enhance envelope, or subtracted, to enhance temporal fine structure information. The first experiment investigated peristimulus adaptation of the FFR for pure and complex tones as a function of stimulus frequency and fundamental frequency (F0). It showed more adaptation of the FFR in response to sounds with higher frequencies or F0s than to sounds with lower frequency or F0s. The second experiment investigated tuning to modulation rate in the FFR. The FFR to a complex tone with a modulation rate of 213 Hz was not reduced more by an adaptor that had the same modulation rate than by an adaptor with a different modulation rate (90 or 504 Hz), thus providing no evidence that the FFR originates mainly from neurons that respond selectively to the modulation rate of the stimulus. The third experiment investigated tuning to audio frequency in the FFR using pure tones. An adaptor that had the same frequency as the target (213 or 504 Hz) did not generally reduce the FFR to the target more than an adaptor that differed in frequency (by 1.24 octaves). Thus, there was no evidence that the FFR originated mainly from neurons tuned to the frequency of the target. Instead, the results are consistent with the suggestion that the FFR for low-frequency pure tones at medium to high levels mainly originates from neurons tuned to higher frequencies. Implications for the use and interpretation of the FFR are discussed.

  16. Frequency and spectrum of chlorophyll-deficient mutations in rice after treatment with radiation and alkylating agents

    International Nuclear Information System (INIS)

    Bhan, A.K.; Kaul, M.L.H.

    1976-01-01

    Three varieties of rice were treated with gamma rays and two alkylating agents EMS and DES, separately and in combinations, with a view to finding out the frequency and spectrum of chlorophyll mutations in relation to the genotype and the nature of the mutagen. Chlorophyll mutation frequency was enhanced with increasing dose but dropped at very high doses (doses that induced over 90% seeding lethality in M 1 ). The fall was attributed to either the increased mutated sector and diplontic selection after exposure to very high doses or relatively high resistance of some of the seeds. Among chlorophyll mutants in M 2 induced by radiations as well as alkylating agents, the albina type formed the majority class. EMS induced a significantly higher proportion of albinas than did gamma rays

  17. Modifying effect of 5-fluoro-2-deoxiuridine on the frequency of x-ray-induced visible mutations in wheat

    International Nuclear Information System (INIS)

    Azatyan, R.A.; Avakyan, V.A.

    1985-01-01

    A modifying effect of FUDR on the output of visible mutations induced by X-ray radiation has been studied at soft fall wheat (Tr. aestivum var. turcicum). It is shown that at X-ray radiation of dry seeds with subsequent treatment of FUDR increased is the mutant percent in M 3 which has constituted 0.61% at irradiation in dose of 100 Gy ad 1.03% at irradiation by the same dose and FUDR influence during 10 hours. In analogous variants at irradiation by 150 Gi dose the mutation frequency reached 1.47 and 2.07% respectively. It is shown that FUDR postradiation treatment promotes not only the increase of frequency but consderablly widens the spectrum of induced mutations. A supposition is made that FUDR modyfying effect is caused by DNA synthesis inhibition. A problem is discussed on a possible realization of potential DNA changes caused by irradiation, at additional influence of inhibitor

  18. Rectennas at optical frequencies: How to analyze the response

    International Nuclear Information System (INIS)

    Joshi, Saumil; Moddel, Garret

    2015-01-01

    Optical rectennas, antenna-coupled diode rectifiers that receive optical-frequency electromagnetic radiation and convert it to DC output, have been proposed for use in harvesting electromagnetic radiation from a blackbody source. The operation of these devices is qualitatively different from that of lower-frequency rectennas, and their design requires a new approach. To that end, we present a method to determine the rectenna response to high frequency illumination. It combines classical circuit analysis with classical and quantum-based photon-assisted tunneling response of a high-speed diode. We demonstrate the method by calculating the rectenna response for low and high frequency monochromatic illumination, and for radiation from a blackbody source. Such a blackbody source can be a hot body generating waste heat, or radiation from the sun

  19. Rectennas at optical frequencies: How to analyze the response

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Saumil; Moddel, Garret, E-mail: moddel@colorado.edu [Department of Electrical, Computer, and Energy Engineering, University of Colorado, Boulder, Colorado 80309-0425 (United States)

    2015-08-28

    Optical rectennas, antenna-coupled diode rectifiers that receive optical-frequency electromagnetic radiation and convert it to DC output, have been proposed for use in harvesting electromagnetic radiation from a blackbody source. The operation of these devices is qualitatively different from that of lower-frequency rectennas, and their design requires a new approach. To that end, we present a method to determine the rectenna response to high frequency illumination. It combines classical circuit analysis with classical and quantum-based photon-assisted tunneling response of a high-speed diode. We demonstrate the method by calculating the rectenna response for low and high frequency monochromatic illumination, and for radiation from a blackbody source. Such a blackbody source can be a hot body generating waste heat, or radiation from the sun.

  20. Rectennas at optical frequencies: How to analyze the response

    Science.gov (United States)

    Joshi, Saumil; Moddel, Garret

    2015-08-01

    Optical rectennas, antenna-coupled diode rectifiers that receive optical-frequency electromagnetic radiation and convert it to DC output, have been proposed for use in harvesting electromagnetic radiation from a blackbody source. The operation of these devices is qualitatively different from that of lower-frequency rectennas, and their design requires a new approach. To that end, we present a method to determine the rectenna response to high frequency illumination. It combines classical circuit analysis with classical and quantum-based photon-assisted tunneling response of a high-speed diode. We demonstrate the method by calculating the rectenna response for low and high frequency monochromatic illumination, and for radiation from a blackbody source. Such a blackbody source can be a hot body generating waste heat, or radiation from the sun.

  1. Activation of the SOS response increases the frequency of small colony variants

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm Erik Axel; Ingmer, Hanne

    2015-01-01

    BACKGROUND: In Staphylococcus aureus sub-populations of slow-growing cells forming small colony variants (SCVs) are associated with persistent and recurrent infections that are difficult to eradicate with antibiotic therapies. In SCVs that are resistant towards aminoglycosides, mutations have been...... with different mechanism of action influence the formation of SCVs that are resistant to otherwise lethal concentrations of the aminoglycoside, gentamicin. We found that exposure of S. aureus to fluoroquinolones and mitomycin C increased the frequency of gentamicin resistant SCVs, while other antibiotic classes...... failed to do so. The higher proportion of SCVs in cultures exposed to fluoroquinolones and mitomycin C compared to un-exposed cultures correlate with an increased mutation rate monitored by rifampicin resistance and followed induction of the SOS DNA damage response. CONCLUSION: Our observations suggest...

  2. Providing frequency regulation reserve services using demand response scheduling

    International Nuclear Information System (INIS)

    Motalleb, Mahdi; Thornton, Matsu; Reihani, Ehsan; Ghorbani, Reza

    2016-01-01

    Highlights: • Proposing a market model for contingency reserve services using demand response. • Considering transient limitations of grid frequency for inverter-based generations. • Price-sensitive scheduling of residential batteries and water heaters using dynamic programming. • Calculating the profits of both generation companies and demand response aggregators. - Abstract: During power grid contingencies, frequency regulation is a primary concern. Historically, frequency regulation during contingency events has been the sole responsibility of the power utility. We present a practical method of using distributed demand response scheduling to provide frequency regulation during contingency events. This paper discusses the implementation of a control system model for the use of distributed energy storage systems such as battery banks and electric water heaters as a source of ancillary services. We present an algorithm which handles the optimization of demand response scheduling for normal operation and during contingency events. We use dynamic programming as an optimization tool. A price signal is developed using optimal power flow calculations to determine the locational marginal price of electricity, while sensor data for water usage is also collected. Using these inputs to dynamic programming, the optimal control signals are given as output. We assume a market model in which distributed demand response resources are sold as a commodity on the open market and profits from demand response aggregators as brokers of distributed demand response resources can be calculated. In considering control decisions for regulation of transient changes in frequency, we focus on IEEE standard 1547 in order to prevent the safety shut-off of inverter-based generation and further exacerbation of frequency droop. This method is applied to IEEE case 118 as a demonstration of the method in practice.

  3. Mutagenic effects of gamma rays and EMS on frequency and spectrum of chlorophyll mutations in urdbean (Vigna mungo (L.) Hepper)

    International Nuclear Information System (INIS)

    Usharani, K.S.; Ananda Kumar, C.R.

    2015-01-01

    Chlorophyll mutations act as a significant index in the judgment of induced genetic variations in mutagen treated populations. Different types of chlorophyll mutation have been observed in various crop plants. In the current study, the effect of different concentrations (40 kR, 50 kR and 60 kR) of gamma rays, Ethyl Methane Sulphonate (50 mM, 60 mM and 70 mM) in single and combination dose/concentration on the frequency and spectrum of chlorophyll mutation and the effect of VBN 4 urdbean variety to such irradiation dose was observed. Results showed induction of broad spectrum of chlorophyll mutations which included albina, xantha, chlorina and viridis. Among these chlorina type was predominant in all the mutagenic treatments. The albina type of chlorophyll mutants occurred very rarely and was found only at 60 mM of EMS treatment and at 40 kR + 50 mM, 60 kR + 70 mM of combination treatments. Based on the chlorophyll mutation frequency, gamma rays were most effective followed by EMS and combination of treatments. (author)

  4. Different mosaicism frequencies for proximal and distal Duchenne muscular dystrophy (DMD) mutations indicate difference in etiology and recurrence risk

    Energy Technology Data Exchange (ETDEWEB)

    Passos-Bueno, M.R.; Takata, R.I.; Rapaport, D.; Bakker, E.; Kneppers, A.L.J.; Dunnen, J.T. den; Ommen, J.B. van

    1992-11-01

    In about 65% of the cases of Duchenne muscular dystrophy (DMD) a partial gene deletion or duplication in the dystrophin gene can be detected. These mutations are clustered at two hot spots: 30% at the hot spot in the proximal part of the gene and about 70% at a more distal hot spot. Unexpectedly the authors observed a higher frequency of proximal gene rearrangements among proved germ line' mosaic cases. Of the 24 mosaic cases they are aware of, 19 (79%) have a proximal mutation, while only 5 (21%) have a distal mutation. This finding indicates that the mutations at the two hot spots in the dystrophin gene differ in origin. Independent support for the different mosaicism frequency was found by comparing the mutation spectra observed in isolated cases of DMD and familial cases (ratio 1:1). The authors conclude from these data that proximal deletions most likely occur early in embryonic development, causing them to have a higher chance of becoming familial, while distal deletions occur later and have a higher chance of causing only isolated cases. Finally, the findings have important consequences for the calculation of recurrence-risk estimates according to the site of the deletion: a [open quote]proximal[close quote] new mutant has an increased recurrence risk of approximately 30%, and a [open quote]distal[close quote] new mutant has a decreased recurrence risk of approximately 4%. 28 refs., 2 figs., 2 tabs.

  5. Effect of dose-rate on the frequency of X-linked lethal mutation in the nematode Panagrellus redivivus

    International Nuclear Information System (INIS)

    Ager, D.

    1984-01-01

    A total X-ray dose of 50 Gy was applied to the nematode Panagrellus redivivus using dose-rates ranging from 0.23 Gy/min to 10.49 Gy/min, and the frequency of lethal X-chromosomes was determined. This frequency ranged from approximately 1.6% at the lower dose-rate to 4.3% at the highest dose-rate, indicating a dose-rate dependency of mutation frequency in the spermatogonia and oogonia of this organism. (orig.)

  6. WFS1 and non-syndromic low-frequency sensorineural hearing loss: a novel mutation in a Portuguese case.

    Science.gov (United States)

    Gonçalves, A C; Matos, T D; Simões-Teixeira, H R; Pimenta Machado, M; Simão, M; Dias, O P; Andrea, M; Fialho, G; Caria, H

    2014-04-01

    Low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of HL in which frequencies at 2,000 Hz and below are predominantly affected. Most of the families with LFSNHL carry missense mutations in WFS1 gene, coding for wolframin. A Portuguese patient aged 49, reporting HL since her third decade of life, and also referring tinnitus, was shown to display bilateral moderate LFSNHL after audiological evaluation. Molecular analysis led to the identification of a novel mutation, c.511G>A (p.Asp171Asn), found in heterozygosity in the exon 5 of the WFS1 gene, and changing the aspartic acid at position 171 to an asparagine, in the extracellular N-terminus domain of the wolframin protein. This novel mutation wasn't present either in 200 control chromosomes analyzed or in the hearing proband's half-brother, and it had not been reported in 1000 Genomes, Exome Variant Server, HGMD or dbSNP databases. No mutations were found in GJB2 and GJB6 genes. Multi-alignment of 27 wolframin sequences from mammalian species, against the human wolframin sequence in ConSurf, indicated a conservation score corresponding to 7 in a 1-9 color scale where 9 is conserved and 1 is variable. In addition, the mutation p.Asp171Asn was predicted to be damaging and possibly damaging by SIFT and Polyphen-2, respectively. The auditory phenotype of this patient could thus be due to the novel mutation p.Asp171Asn. Further functional characterization might enable to elucidate in which way the change in the residue 171, as other changes introduced by LFSNHL-associated mutations previously described, leads to this type of HL. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Frequency of JAK2 V617F mutation in patients with Philadelphia positive Chronic Myeloid Leukemia in Pakistan.

    Science.gov (United States)

    Tabassum, Najia; Saboor, Mohammed; Ghani, Rubina; Moinuddin, Moinuddin

    2014-01-01

    Co-existence of myeloproliferative disorders (MPD) and Janus associated kinase 2 mutation (JAK2 V617F) is a well-established fact. Only few case reports are available showing presence of JAK2 V617F mutation in chronic myeloid leukemia (CML). Purpose of this study was to determine the frequency of JAK2 V617F mutation in Philadelphia Chromosome positive (Ph (+)) CML patients in Pakistan. The study was conducted from August 2009 to July 2010 at Civil Hospital and Baqai Institute of Hematology (BIH) Karachi. Blood samples from 25 patients with CML were collected. Multiplex reverse transcription polymerase chain reaction (RT-PCR) was performed for Breakpoint Cluster Region - Abelson (BCR-ABL) rearrangement. Conventional PCR was performed for JAK2 V617F mutation on BCR-ABL positive samples. All 25 samples showed BCR-ABL rearrangement. Out of these 11 samples (44%) had JAK2 V617F mutation; the remaining 14 (56%) cases showed JAK2 617V wild type. It is concluded that the co-existence of Ph (+)CML and JAK2 V617F mutation is possible.

  8. Frequency- and amplitude-transitioned waveforms mitigate the onset response in high-frequency nerve block

    Science.gov (United States)

    Gerges, Meana; Foldes, Emily L.; Ackermann, D. Michael; Bhadra, Narendra; Bhadra, Niloy; Kilgore, Kevin L.

    2010-12-01

    High-frequency alternating currents (HFAC) have proven to be a reversible and rapid method of blocking peripheral nerve conduction, holding promise for treatment of disorders associated with undesirable neuronal activity. The delivery of HFAC is characterized by a transient period of neural firing at its inception, termed the 'onset response'. The onset response is minimized for higher frequencies and higher amplitudes, but requires larger currents. However, the complete block can be maintained at lower frequencies and amplitudes, using lower currents. In this in vivo study on whole mammalian peripheral nerves, we demonstrate a method to minimize the onset response by initiating the block using a stimulation paradigm with a high frequency and large amplitude, and then transitioning to a low-frequency and low-amplitude waveform, reducing the currents required to maintain the conduction block. In five of six animals, it was possible to transition from a 30 kHz to a 10 kHz waveform without inducing any transient neural firing. The minimum transition time was 0.03 s. Transition activity was minimized or eliminated with longer transition times. The results of this study show that this method is feasible for achieving a nerve block with minimal onset responses and current amplitude requirements.

  9. The shapes of the radiation dose-mutation response curves in drosophila: Mechanisms and implications

    International Nuclear Information System (INIS)

    Abrahamson, S.; DeJongh, C.; Meyer, H.U.

    1981-01-01

    This chapter proposes that radiation induced mutations, namely sex-linked recessive lethals in Drosophila and forward mutations at specific loci in Drosophila, mammals and lower eucaryotes, are the result of two sub-lesions or hits, induced by either single ionization tracks or by the interaction of two independent tracks for low LET radiations, when the dose is delivered in an acute fashion. Utilizes the well recognized linear quadratic expression Y=C+αD+βD 2 , where C is the spontaneous frequency of events scored and α and β represent the coefficients of the dose. Concludes that for low LET radiations, X or gamma rays, the linear-quadratic model can be used to predict the genetic response of germ cells and somatic cells to a variety of radiation regimes. Points out that the point of inflection in the curve, α/β value, can be determined specifically by target dimensions which vary with respect to DNA content. Considers the difference in RBE values observed for different species to be a reflection of their different target sizes

  10. Evaluation of random temperature fluctuation problems with frequency response approach

    International Nuclear Information System (INIS)

    Lejeail, Yves; Kasahara, Naoto

    2000-01-01

    Since thermal striping is a coupled thermohydraulic and thermomechanical phenomenon, sodium mock-up tests were usually required to confirm structural integrity. Authors have developed the frequency response function to establish design-by-analysis methodology for this phenomenon. Applicability of this method to sinusoidal fluctuation was validated through two benchmark problems with FAENA and TIFFSS facilities under EJCC contract. This report describes the extension of the frequency response method to random fluctuations. As an example of application, fatigue strength of a Tee junction of PHENIX secondary piping system was investigated. (author)

  11. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL response.

    Directory of Open Access Journals (Sweden)

    Ryan M Troyer

    2009-04-01

    Full Text Available Human lymphocyte antigen (HLA-restricted CD8(+ cytotoxic T lymphocytes (CTL target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish viral replication fitness. Here, we assess the fitness impact of escape mutations emerging in seven CTL epitopes in the gp120 Env and p24 Gag coding regions of an individual followed longitudinally from the time of acute HIV-1 infection, as well as some of these same epitopes recognized in other HIV-1-infected individuals. Nine dominant mutations appeared in five gp120 epitopes within the first year of infection, whereas all four mutations found in two p24 epitopes emerged after nearly two years of infection. These mutations were introduced individually into the autologous gene found in acute infection and then placed into a full-length, infectious viral genome. When competed against virus expressing the parental protein, fitness loss was observed with only one of the nine gp120 mutations, whereas four had no effect and three conferred a slight increase in fitness. In contrast, mutations conferring CTL escape in the p24 epitopes significantly decreased viral fitness. One particular escape mutation within a p24 epitope was associated with reduced peptide recognition and high viral fitness costs but was replaced by a fitness-neutral mutation. This mutation appeared to alter epitope processing concomitant with a reduced CTL response. In conclusion, CTL escape mutations in HIV-1 Gag p24 were associated with significant fitness costs, whereas most escape mutations in the Env gene were fitness neutral, suggesting a balance between immunologic escape and replicative fitness costs.

  12. DC response of dust to low frequency AC signals

    Science.gov (United States)

    McKinlay, Michael; Konopka, Uwe; Thomas, Edward

    2017-10-01

    Macroscopic changes in the shape and equilibrium position of clouds of charged microparticles suspended in a plasma have been observed in response to low frequency AC signals. In these experiments, dusty plasmas consisting of 2-micron diameter silica microspheres suspended between an anode and cathode in an argon, DC glow discharge plasma are produced in a grounded, 6-way cross vacuum chamber. An AC signal, produced by a function generator and amplified by a bipolar op-amp, is superimposed onto the potential from the cathode. The frequencies of the applied AC signals, ranging from tens to hundreds of kHz, are comparable to the ion-neutral collision frequency; well below the ion/electron plasma frequencies, but also considerably higher than the dust plasma frequency. This presentation will detail the experimental setup, present documentation and categorization of observations of the dust response, and present an initial model of the response. This work is supported by funding from the US Dept. of Energy, Grant Number DE-SC0016330, and by the National Science Foundation, Grant Number PHY-1613087.

  13. Control and Coordination of Frequency Responsive Residential Water Heaters

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Tess L.; Kalsi, Karanjit; Elizondo, Marcelo A.; Marinovici, Laurentiu D.; Pratt, Richard M.

    2016-07-31

    Demand-side frequency control can complement traditional generator controls to maintain the stability of large electric systems in the face of rising uncertainty and variability associated with renewable energy resources. This paper presents a hierarchical frequency-based load control strategy that uses a supervisor to flexibly adjust control gains that a population of end-use loads respond to in a decentralized manner to help meet the NERC BAL-003-1 frequency response standard at both the area level and interconnection level. The load model is calibrated and used to model populations of frequency-responsive water heaters in a PowerWorld simulation of the U.S. Western Interconnection (WECC). The proposed design is implemented and demonstrated on physical water heaters in a laboratory setting. A significant fraction of the required frequency response in the WECC could be supplied by electric water heaters alone at penetration levels of less than 15%, while contributing to NERC requirements at the interconnection and area levels.

  14. Tumor-specific mutations in low-frequency genes affect their functional properties

    NARCIS (Netherlands)

    L. Erdem-Eraslan (Lale); D. Heijsman (Daphne); M. De Wit (Maurice); A.E. Kremer (Andreas); A. Sacchetti (Andrea); P.J. van der Spek (Peter); P.A.E. Sillevis Smitt (Peter); P.J. French (Pim)

    2015-01-01

    textabstractCausal genetic changes in oligodendrogliomas (OD) with 1p/19q co-deletion include mutations in IDH1, IDH2, CIC, FUBP1, TERT promoter and NOTCH1. However, it is generally assumed that more somatic mutations are required for tumorigenesis. This study aimed to establish whether genes

  15. Frequency of rare mutations and common genetic variations in severe hypertriglyceridemia in the general population of Spain.

    Science.gov (United States)

    Lamiquiz-Moneo, Itziar; Blanco-Torrecilla, Cristian; Bea, Ana M; Mateo-Gallego, Rocío; Pérez-Calahorra, Sofía; Baila-Rueda, Lucía; Cenarro, Ana; Civeira, Fernando; de Castro-Orós, Isabel

    2016-04-23

    Hypertriglyceridemia (HTG) is a common complex metabolic trait that results of the accumulation of relatively common genetic variants in combination with other modifier genes and environmental factors resulting in increased plasma triglyceride (TG) levels. The majority of severe primary hypertriglyceridemias is diagnosed in adulthood and their molecular bases have not been fully defined yet. The prevalence of HTG is highly variable among populations, possibly caused by differences in environmental factors and genetic background. However, the prevalence of very high TG and the frequency of rare mutations causing HTG in a whole non-selected population have not been previously studied. The total of 23,310 subjects over 18 years from a primary care-district in a middle-class area of Zaragoza (Spain) with TG >500 mg/dL were selected to establish HTG prevalence. Those affected of primary HTG were considered for further genetic analysis. The promoters, coding regions and exon-intron boundaries of LPL, LMF1, APOC2, APOA5, APOE and GPIHBP1 genes were sequenced. The frequency of rare variants identified was studied in 90 controls. One hundred ninety-four subjects (1.04%) had HTG and 90 subjects (46.4%) met the inclusion criteria for primary HTG. In this subgroup, nine patients (12.3%) were carriers of 7 rare variants in LPL, LMF1, APOA5, GPIHBP1 or APOE genes. Three of these mutations are described for the first time in this work. The presence of a rare pathogenic mutation did not confer a differential phenotype or a higher family history of HTG. The prevalence of rare mutations in candidate genes in subjects with primary HTG is low. The low frequency of rare mutations, the absence of a more severe phenotype or the dominant transmission of the HTG would not suggest the use of genetic analysis in the clinical practice in this population.

  16. Effect of bimodularity on frequency response of cylindrical panels ...

    Indian Academy of Sciences (India)

    M. Senthilkumar (Newgen Imaging) 1461 1996 Oct 15 13:05:22

    The actual stress strain behaviour ... The work on frequency response of bimodular structures is scarce in open literature (Khan .... Analysis is carried out using a C0 eight-noded serendipity quadrilateral shear flexible shell ..... specified convergence tolerance (each incremental displacement becomes less than equal to. 10.

  17. Frequency response as a surrogate eigenvalue problem in topology optimization

    DEFF Research Database (Denmark)

    Andreassen, Erik; Ferrari, Federico; Sigmund, Ole

    2018-01-01

    This article discusses the use of frequency response surrogates for eigenvalue optimization problems in topology optimization that may be used to avoid solving the eigenvalue problem. The motivation is to avoid complications that arise from multiple eigenvalues and the computational complexity as...

  18. Estimating low-bias frequency response using random decrement

    DEFF Research Database (Denmark)

    Brincker, Rune; Brandt, Anders

    2011-01-01

    It is well known that in order to minimize the influence of leakage bias in frequency response function (FRF) estimates, smooth windows should be applied in the FFT processing. It is also normal practice to use self windowing excitation signals whenever possible. However, in many cases FRFs have...

  19. Modal Identification from Ambient Responses using Frequency Domain Decomposition

    DEFF Research Database (Denmark)

    Brincker, Rune; Zhang, L.; Andersen, P.

    2000-01-01

    In this paper a new frequency domain technique is introduced for the modal identification from ambient responses, ie. in the case where the modal parameters must be estimated without knowing the input exciting the system. By its user friendliness the technique is closely related to the classical ...

  20. Modal Identification from Ambient Responses Using Frequency Domain Decomposition

    DEFF Research Database (Denmark)

    Brincker, Rune; Zhang, Lingmi; Andersen, Palle

    2000-01-01

    In this paper a new frequency domain technique is introduced for the modal identification from ambient responses, i.e. in the case where the modal parameters must be estimated without knowing the input exciting the system. By its user friendliness the technique is closely related to the classical...

  1. Transducer frequency response variations investigated by time reversal calibration

    Czech Academy of Sciences Publication Activity Database

    Kober, Jan; Převorovský, Zdeněk

    2016-01-01

    Roč. 26, č. 2 (2016), A16-A16 ISSN 1213-3825. [Europen Conference on Acoustic Emission Testing /32./. 07.09.2016-09.09.2016, Praha] Institutional support: RVO:61388998 Keywords : calibration * time reversal * transducer * frequency response Subject RIV: BI - Acoustics

  2. Fitting of transfer functions to frequency response measurements

    International Nuclear Information System (INIS)

    Moret, J.M.

    1994-12-01

    An algorithm for approximating a given complex frequency response with a rational function of two polynomials with real coefficients is presented, together with its extension to distributed parameter systems, the corresponding error analysis and its application to a real case. (author) 5 figs., 4 refs

  3. Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature

    International Nuclear Information System (INIS)

    Corso, Giovanni; Marrelli, Daniele; Pascale, Valeria; Vindigni, Carla; Roviello, Franco

    2012-01-01

    The frequency of E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has not been well established. The goal of this study was to assess the worldwide frequency of CDH1 germline mutations in gastric cancers coming from low- and high-risk areas. English articles using MEDLINE access (from 1998 to 2011). Search terms included CDH1, E-cadherin, germline mutation, gastric cancer, hereditary, familial and diffuse histotype. The study included all E-cadherin germline mutations identified in gastric cancer patients; somatic mutations and germline mutations reported in other tumors were excluded. The method of this study was scheduled in accordance with the 'PRISMA statement for reporting systematic reviews and meta-analyses'. Countries were classified as low- or middle/high risk-areas for gastric carcinoma incidence. Statistical analysis was performed to correlate the CDH1 mutation frequency with gastric cancer incidence areas. A total of 122 E-cadherin germline mutations have been identified; the majority (87.5%) occurred in gastric cancers coming from low-risk areas. In high-risk areas, we identified 16 mutations in which missense mutations were predominant. (68.8%). We verified a significant association between the mutation frequency and the gastric cancer risk area (p < 0.001: overall identified mutations in low- vs. middle/high-risk areas). E-cadherin genetic screenings performed in low-risk areas for gastric cancer identified a higher frequency of CDH1 germline mutations. This data could open new approaches in the gastric cancer prevention test; before proposing a proband candidate for the CDH1 genetic screening, geographic variability, alongside the family history should be considered

  4. Human frequency-following response to speech-like sounds: correlates of off-frequency masking.

    Science.gov (United States)

    Krishnan, Ananthanarayan; Agrawal, Smita

    2010-01-01

    Off-frequency masking of the second formant by energy at the first formant has been shown to influence both identification and discrimination of the second formant in normal-hearing and hearing-impaired listeners. While both excitatory spread and two-tone suppression have been implicated in this simultaneous masking, their relative contribution has been shown to depend on both the level of the masker and the frequency separation between the probe and the masker. Off-frequency masking effects were evaluated in 10 normal-hearing human adults using the frequency-following response (FFR) to two two-tone approximations of vowel stimuli (/a/ and /u/). In the first experiment, the masking effect of F(1) on F(2) was evaluated by attenuating the level of F(1) relative to a fixed F(2) level. In the second experiment, the masking effect was evaluated by increasing the frequency separation between F(1) and F(2) using F(2) frequency as the variable. Results revealed that both attenuation of the F(1) level, and increasing the frequency separation between F(1) and F(2) increased the magnitude of the FFR component at F(2). These results are consistent with a release from off-frequency masking. Given that the results presented here are for high signal and masker levels and for relatively smaller frequency separation between the masker and the probe, it is possible that both suppression and excitatory spread contributed to the masking effects observed in our data. Copyright2009 S. Karger AG, Basel.

  5. Frequency of janus associated kinase 2 (jak2) mutation in patients of bcr-abl negative myeloproliferative neoplasms

    International Nuclear Information System (INIS)

    Sadiq, M.A.; Ahmed, S.; Ali, N.

    2013-01-01

    To determine the frequency of Janus associated kinase 2 mutation in the patients of BCR-ABL negative classical myeloproliferative neoplasms. Study Design: Cross-sectional descriptive study Place and Duration of Study: Molecular Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi from Jul 2011 to Jul 2012. Patients and Methods: Ninety three consecutive patients of Polycythaemia vera (PV), Essential thrombocythaemia (ET) and Idiopathic myelofibrosis (IMF) diagnosed by the conventional haematological criteria were included in the study. All patients were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific PCR. Results: Out of the 93 myeloproliferative neoplasm (MPN) patients, 33(35%) had polycythaemia vera, 36(39%) had essential thrombocythaemia and 24(26%) had idiopathic myelofibrosis. JAK2 mutation was seen in 64/93 (69%) patients including 33/33(100%) in PV, 19/36(52.6%) in ET and 12/24(50%) in IMF. Conclusion: Classical myeloproliferative neoplasms are an important group of heamatological disorder in our country. JAK2 gene mutation is seen in significant proportion of these disorders (69%). JAK2 mutation analysis can be used to differentiate between polycythemia vera and secondary polycythemia in most cases with near certainty, where it was found in 100% of the cases. (author)

  6. Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing

    Directory of Open Access Journals (Sweden)

    Uta Francke

    2013-02-01

    Full Text Available Background. Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. Benefits and risks of providing this information directly to consumers are unknown.Methods. To assess and quantify emotional and behavioral reactions of consumers to their 23andMe Personal Genome Service® report of three BRCA mutations that are common in Ashkenazi Jews, we invited all 136 BRCA1 and BRCA2 mutation-positive individuals in the 23andMe customer database who had chosen to view their BRCA reports to participate in this IRB-approved study. We also invited 160 mutation-negative customers who were matched for age, sex and ancestry. Semi-structured phone interviews were completed for 32 mutation carriers, 16 women and 16 men, and 31 non-carriers. Questions addressed personal and family history of cancer, decision and timing of viewing the BRCA report, recollection of the result, emotional responses, perception of personal cancer risk, information sharing, and actions taken or planned.Results. Eleven women and 14 men had received the unexpected result that they are carriers of a BRCA1 185delAG or 5382insC, or BRCA2 6174delT mutation. None of them reported extreme anxiety and four experienced moderate anxiety that was transitory. Remarkably, five women and six men described their response as neutral. Most carrier women sought medical advice and four underwent risk-reducing procedures after confirmatory mutation testing. Male carriers realized that their test results implied genetic risk for female relatives, and several of them felt considerably burdened by this fact. Sharing mutation information with family members led to screening of at least 30 relatives and identification of 13 additional carriers. Non-carriers did not report inappropriate actions, such as foregoing cancer screening. All but one of the 32 mutation

  7. Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing.

    Science.gov (United States)

    Francke, Uta; Dijamco, Cheri; Kiefer, Amy K; Eriksson, Nicholas; Moiseff, Bianca; Tung, Joyce Y; Mountain, Joanna L

    2013-01-01

    Background. Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. Benefits and risks of providing this information directly to consumers are unknown. Methods. To assess and quantify emotional and behavioral reactions of consumers to their 23andMe Personal Genome Service(®) report of three BRCA mutations that are common in Ashkenazi Jews, we invited all 136 BRCA1 and BRCA2 mutation-positive individuals in the 23andMe customer database who had chosen to view their BRCA reports to participate in this IRB-approved study. We also invited 160 mutation-negative customers who were matched for age, sex and ancestry. Semi-structured phone interviews were completed for 32 mutation carriers, 16 women and 16 men, and 31 non-carriers. Questions addressed personal and family history of cancer, decision and timing of viewing the BRCA report, recollection of the result, emotional responses, perception of personal cancer risk, information sharing, and actions taken or planned. Results. Eleven women and 14 men had received the unexpected result that they are carriers of a BRCA1 185delAG or 5382insC, or BRCA2 6174delT mutation. None of them reported extreme anxiety and four experienced moderate anxiety that was transitory. Remarkably, five women and six men described their response as neutral. Most carrier women sought medical advice and four underwent risk-reducing procedures after confirmatory mutation testing. Male carriers realized that their test results implied genetic risk for female relatives, and several of them felt considerably burdened by this fact. Sharing mutation information with family members led to screening of at least 30 relatives and identification of 13 additional carriers. Non-carriers did not report inappropriate actions, such as foregoing cancer screening. All but one of the 32 mutation-positive participants

  8. Electiveness of photorepair, influence of dark-repair on shape of dose-response curves, and high-dose decline, in UV-induced colour mutations of Serratia

    International Nuclear Information System (INIS)

    Kaplan, R.W.

    1978-01-01

    Strain CV of Serratia marcescens mutates by UV with high frequency to 3 groups of mutants (w, h, s) differing in colour from the red wild-type. The mutational dose-response curve has a curvature corresponding to about 3 hits. It reaches a peak and declines at high doses. Inactivation curves have a broad shoulder and mostly, but not always, a break to a lesser slope at UV doses near the peak of mutations. Photo reactivation (PR) gives a dose reduction of about 2 for both inactivation and mutation including the break and peak. The dose curve with PR for w-mutations shows 1 hit-, the other types 2-hit curvature leading to a change of mutation spectrum with dose due to PR. The UV-sensitive mutant uvs21 of CV has a survival curve with a small shoulder and a long upward concavity without a break, and the mutation curve is of the one-hit type without a peak and decline. PR gives a dose reduction of 12 for inactivation and of 7.5 for mutation. The 3-hit mutation curve of CV is interpreted by assuming that 2 further hits are required to protect the 1-hit pre-mutations from being abolished by the repair lacking in uvs21. UV induction of SOS repair cannot be responsible for the 3-hit curvature because UVR of phages and induction of prophage are already saturated at rather low doses. As high-dose decline is not observed in uvs21, possibly the non-mutagenic repair lacking from uvs21 interferes with the mutation finishing processes at high doses in the repair-proficient strain CV. However, UV induction of this interference cannot be a one-hit process but requires a very large number of hits. (Auth.)

  9. Benefits of Demand Side Response in Providing Frequency Response Service in the Future GB Power System

    Directory of Open Access Journals (Sweden)

    Fei eTeng

    2015-08-01

    Full Text Available The demand for ancillary service is expected to increase significantly in the future GB electricity system due to high penetration of wind. In particular, the need for frequency response, required to deal with sudden frequency drops following a loss of generator, will increase because of the limited inertia capability of wind plants. This paper quantifies the requirements for primary frequency response and analyses the benefits of frequency response provision from DSR. The results show dramatic changes in frequency response requirements driven by high penetration of wind. Case studies carried out by using an advanced stochastic generation scheduling model suggest that the provision of frequency response from DSR could greatly reduce the system operation cost, wind curtailment and carbon emissions in the future GB system characterised by high penetration of wind. Furthermore, the results demonstrate that the benefit of DSR shows significant diurnal and seasonal variation, whereas an even more rapid (instant delivery of frequency response from DSR could provide significant additional value. Our studies also indicate that the competing technologies to DSR, namely battery storage and more flexible generation could potentially reduce its value by up to 35%, still leaving significant room to deploy DSR as frequency response provider.

  10. Wind Generation Participation in Power System Frequency Response: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Gevorgian, Vahan; Zhang, Yingchen

    2017-01-01

    The electrical frequency of an interconnected power system must be maintained close its nominal level at all times. Excessive under- and overfrequency excursions can lead to load shedding, instability, machine damage, and even blackouts. There is a rising concern in the electric power industry in recent years about the declining amount of inertia and primary frequency response (PFR) in many interconnections. This decline may continue due to increasing penetrations of inverter-coupled generation and the planned retirements of conventional thermal plants. Inverter-coupled variable wind generation is capable of contributing to PFR and inertia with a response that is different from that of conventional generation. It is not yet entirely understood how such a response will affect the system at different wind power penetration levels. The modeling work presented in this paper evaluates the impact of wind generation's provision of these active power control strategies on a large, synchronous interconnection. All simulations were conducted on the U.S. Western Interconnection with different levels of instantaneous wind power penetrations (up to 80%). The ability of wind power plants to provide PFR - and a combination of synthetic inertial response and PFR - significantly improved the frequency response performance of the system.

  11. Modification of UV-induced mutation frequencies in Chinese hamster- cells by dose fractionation, cycloheximide and caffeine treatments

    International Nuclear Information System (INIS)

    Chang, C.-C.; Schultz, R.; Trosko, J.E.; D'Ambrosio, S.M.; Setlow, R.B.

    1978-01-01

    Chinese hamster (V79) cells were irradiated with a fractionated regime of ultraviolet light (UV 1 +UV 2 ). The fractionation of a UV dose always increased the colony-forming ability but reduced (or it did not change) the mutation frequencies. Treatment with cycloheximide between the two UV irradiations resulted in two types of effects, depending on the protocols used. Long exposures to cycloheximide (i.e., >6h) for the entire period between UV 1 and UV 2 or partial treatment of cycloheximide (i.e., 3h) long before UV 2 always resulted in reduced colony-forming ability and enhanced or unchanged mutation frequencies. Exposure to cycloheximide for the entire period in the short fractionated regime (i.e., 4h) between UV 1 and UV 2 or partial treatment of cycloheximide just prior to UV 2 tended to give the opposite effects. Caffeine treatment before UV 2 , with or without UV 1 , significantly increased the mutation frequencies. These results suggest that an error-free postreplication repair system exists in Chinese hamster cells which is inhibitable by particular cycloheximide or caffeine treatments. (Auth.)

  12. The Number of Overlapping AID Hotspots in Germline IGHV Genes Is Inversely Correlated with Mutation Frequency in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Yuan, Chaohui; Chu, Charles C; Yan, Xiao-Jie; Bagnara, Davide; Chiorazzi, Nicholas; MacCarthy, Thomas

    2017-01-01

    The targeting of mutations by Activation-Induced Deaminase (AID) is a key step in generating antibody diversity at the Immunoglobulin (Ig) loci but is also implicated in B-cell malignancies such as chronic lymphocytic leukemia (CLL). AID has previously been shown to preferentially deaminate WRC (W = A/T, R = A/G) hotspots. WGCW sites, which contain an overlapping WRC hotspot on both DNA strands, mutate at much higher frequency than single hotspots. Human Ig heavy chain (IGHV) genes differ in terms of WGCW numbers, ranging from 4 for IGHV3-48*03 to as many as 12 in IGHV1-69*01. An absence of V-region mutations in CLL patients ("IGHV unmutated", or U-CLL) is associated with a poorer prognosis compared to "IGHV mutated" (M-CLL) patients. The reasons for this difference are still unclear, but it has been noted that particular IGHV genes associate with U-CLL vs M-CLL. For example, patients with IGHV1-69 clones tend to be U-CLL with a poor prognosis, whereas patients with IGHV3-30 tend to be M-CLL and have a better prognosis. Another distinctive feature of CLL is that ~30% of (mostly poor prognosis) patients can be classified into "stereotyped" subsets, each defined by HCDR3 similarity, suggesting selection, possibly for a self-antigen. We analyzed >1000 IGHV genes from CLL patients and found a highly significant statistical relationship between the number of WGCW hotspots in the germline V-region and the observed mutation frequency in patients. However, paradoxically, this correlation was inverse, with V-regions with more WGCW hotspots being less likely to be mutated, i.e., more likely to be U-CLL. The number of WGCW hotspots in particular, are more strongly correlated with mutation frequency than either non-overlapping (WRC) hotspots or more general models of mutability derived from somatic hypermutation data. Furthermore, this correlation is not observed in sequences from the B cell repertoires of normal individuals and those with autoimmune diseases.

  13. Structural health monitoring in composite materials using frequency response methods

    Science.gov (United States)

    Kessler, Seth S.; Spearing, S. Mark; Atalla, Mauro J.; Cesnik, Carlos E. S.; Soutis, Constantinos

    2001-08-01

    Cost effective and reliable damage detection is critical for the utilization of composite materials in structural applications. Non-destructive evaluation techniques (e.g. ultrasound, radiography, infra-red imaging) are available for use during standard repair and maintenance cycles, however by comparison to the techniques used for metals these are relatively expensive and time consuming. This paper presents part of an experimental and analytical survey of candidate methods for the detection of damage in composite materials. The experimental results are presented for the application of modal analysis techniques applied to rectangular laminated graphite/epoxy specimens containing representative damage modes, including delamination, transverse ply cracks and through-holes. Changes in natural frequencies and modes were then found using a scanning laser vibrometer, and 2-D finite element models were created for comparison with the experimental results. The models accurately predicted the response of the specimems at low frequencies, but the local excitation and coalescence of higher frequency modes make mode-dependent damage detection difficult and most likely impractical for structural applications. The frequency response method was found to be reliable for detecting even small amounts of damage in a simple composite structure, however the potentially important information about damage type, size, location and orientation were lost using this method since several combinations of these variables can yield identical response signatures.

  14. Modeling the frequency response of microwave radiometers with QUCS

    International Nuclear Information System (INIS)

    Zonca, A; Williams, B; Rubin, I; Meinhold, P; Lubin, P; Roucaries, B; D'Arcangelo, O; Franceschet, C; Mennella, A; Bersanelli, M; Jahn, S

    2010-01-01

    Characterization of the frequency response of coherent radiometric receivers is a key element in estimating the flux of astrophysical emissions, since the measured signal depends on the convolution of the source spectral emission with the instrument band shape. Laboratory Radio Frequency (RF) measurements of the instrument bandpass often require complex test setups and are subject to a number of systematic effects driven by thermal issues and impedance matching, particularly if cryogenic operation is involved. In this paper we present an approach to modeling radiometers bandpasses by integrating simulations and RF measurements of individual components. This method is based on QUCS (Quasi Universal Circuit Simulator), an open-source circuit simulator, which gives the flexibility of choosing among the available devices, implementing new analytical software models or using measured S-parameters. Therefore an independent estimate of the instrument bandpass is achieved using standard individual component measurements and validated analytical simulations. In order to automate the process of preparing input data, running simulations and exporting results we developed the Python package python-qucs and released it under GNU Public License. We discuss, as working cases, bandpass response modeling of the COFE and Planck Low Frequency Instrument (LFI) radiometers and compare results obtained with QUCS and with a commercial circuit simulator software. The main purpose of bandpass modeling in COFE is to optimize component matching, while in LFI they represent the best estimation of frequency response, since end-to-end measurements were strongly affected by systematic effects.

  15. Rich Medium Composition Affects Escherichia coli Survival, Glycation, and Mutation Frequency during Long-Term Batch Culture.

    Science.gov (United States)

    Kram, Karin E; Finkel, Steven E

    2015-07-01

    Bacteria such as Escherichia coli are frequently grown to high density to produce biomolecules for study in the laboratory. To achieve this, cells can be incubated in extremely rich media that increase overall cell yield. In these various media, bacteria may have different metabolic profiles, leading to changes in the amounts of toxic metabolites produced. We have previously shown that stresses experienced during short-term growth can affect the survival of cells during the long-term stationary phase (LTSP). Here, we incubated cells in LB, 2× yeast extract-tryptone (YT), Terrific Broth, or Super Broth medium and monitored survival during the LTSP, as well as other reporters of genetic and physiological change. We observe differential cell yield and survival in all media studied. We propose that differences in long-term survival are the result of changes in the metabolism of components of the media that may lead to increased levels of protein and/or DNA damage. We also show that culture pH and levels of protein glycation, a covalent modification that causes protein damage, affect long-term survival. Further, we measured mutation frequency after overnight incubation and observed a correlation between high mutation frequencies at the end of the log phase and loss of viability after 4 days of LTSP incubation, indicating that mutation frequency is potentially predictive of long-term survival. Since glycation and mutation can be caused by oxidative stress, we measured expression of the oxyR oxidative stress regulator during log-phase growth and found that higher levels of oxyR expression during the log phase are consistent with high mutation frequency and lower cell density during the LTSP. Since these complex rich media are often used when producing large quantities of biomolecules in the laboratory, the observed increase in damage resulting in glycation or mutation may lead to production of a heterogeneous population of plasmids or proteins, which could affect the

  16. A second mutation associated with apparent [beta]-hexosaminidase A pseudodeficiency: Identification and frequency estimation

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Z.; Chabot, T.; Triggs-Raine, B.L. (Univ. of Manitoba, Winnepeg (Canada)); Natowicz, M.R.; Prence, E.M. (Shriver Center for Mental Retardation, Waltham, MA (United States) Harvard Medical School, Boston, MA (United States)); Kaback, M.M.; Lim-Steele, S.T.; Brown, D. (Children' s Hospital, San Diego, CA (United States) Univ. of California, San Diego, CA (United States))

    1993-12-01

    Deficient activity of [beta]-hexosaminidase A (Hex A), resulting from mutations in the HEXA gene, typically causes Tay-Sachs disease. However, healthy individuals lacking Hex A activity against synthetic substrates (i.e., individuals who are pseudodeficient) have been described. Recently, an apparently benign C[sub 739]-to-T (Arg247Trp) mutation was found among individuals with Hex A levels indistinguishable from those of carriers of Tay-Sachs disease. This allele, when in compound heterozygosity with a second [open quotes]disease-causing[close quotes] allele, results in Hex A pseudodeficiency. The authors examined the HEXA gene of a healthy 42-year-old who was Hex A deficient but did not have the C[sub 739]-to-T mutation. The HEXA exons were PCR amplified, and the products were analyzed for mutations by using restriction-enzyme digestion or single-strand gel electrophoresis. A G[sub 805]-to-A (Gly269Ser) mutation associated with adult-onset G[sub m2] gangliosidosis was found on one chromosome. A new mutation, C[sub 745]-to-T (Arg 249Trp), was identified on the second chromosome. This mutation was detected in an additional 4/63 (6%) non-Jewish and 0/218 Ashkenazi Jewish enzyme-defined carriers. Although the Arg249Trp change may result in a late-onset form of G[sub M2] gangliosidosis, any phenotype must be very mild. This new mutation and the benign C[sub 739]-to-T mutation together account for [approximately]38% of non-Jewish enzyme-defined carriers. Because carriers of the C[sub 739]-to-T and C[sub 745]-to-T mutations cannot be differentiated from carriers of disease-causing alleles by using the classical biochemical screening approaches, DNA-based analyses for these mutations should be offered for non-Jewish enzyme-defined heterozygotes, before definitive counseling is provided. 46 refs., 5 figs., 2 tabs.

  17. High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease.

    Science.gov (United States)

    Pottier, C; Hannequin, D; Coutant, S; Rovelet-Lecrux, A; Wallon, D; Rousseau, S; Legallic, S; Paquet, C; Bombois, S; Pariente, J; Thomas-Anterion, C; Michon, A; Croisile, B; Etcharry-Bouyx, F; Berr, C; Dartigues, J-F; Amouyel, P; Dauchel, H; Boutoleau-Bretonnière, C; Thauvin, C; Frebourg, T; Lambert, J-C; Campion, D

    2012-09-01

    Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations. These mutations were not retrieved in 1500 controls of same ethnic origin. In a replication sample, including 15 ADEOAD cases, 2 unknown non-synonymous mutations (1 missense, 1 nonsense) were retrieved, thus yielding to a total of 7/29 unknown mutations in the combined sample. Using in silico predictions, we conclude that these seven private mutations are likely to have a pathogenic effect. SORL1 encodes the Sortilin-related receptor LR11/SorLA, a protein involved in the control of amyloid beta peptide production. Our results suggest that besides the involvement of the APP and PSEN genes, further genetic heterogeneity, involving another gene of the same pathway is present in ADEOAD.

  18. Wild-type and mutated IDH1/2 enzymes and therapy responses.

    Science.gov (United States)

    Molenaar, Remco J; Maciejewski, Jaroslaw P; Wilmink, Johanna W; van Noorden, Cornelis J F

    2018-04-01

    Isocitrate dehydrogenase 1 and 2 (IDH1/2) are key enzymes in cellular metabolism, epigenetic regulation, redox states, and DNA repair. IDH1/2 mutations are causal in the development and/or progression of various types of cancer due to supraphysiological production of D-2-hydroxyglutarate. In various tumor types, IDH1/2-mutated cancers predict for improved responses to treatment with irradiation or chemotherapy. The present review discusses the molecular basis of the sensitivity of IDH1/2-mutated cancers with respect to the function of mutated IDH1/2 in cellular processes and their interactions with novel IDH1/2-mutant inhibitors. Finally, lessons learned from IDH1/2 mutations for future clinical applications in IDH1/2 wild-type cancers are discussed.

  19. Frequency of Somatic TP53 Mutations in Combination with Known Pathogenic Mutations in Colon Adenocarcinoma, Non–Small Cell Lung Carcinoma, and Gliomas as Identified by Next-Generation Sequencing

    Directory of Open Access Journals (Sweden)

    Zahra Shajani-Yi

    2018-03-01

    Full Text Available The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective. In this study, we identified the frequency of individual TP53 mutations in patients with colon adenocarcinoma (48%, non–small cell lung carcinoma (NSCLC (36%, and glioma/glioblastoma (28% at our institution using next-generation sequencing. We also identified the occurrence of somatic mutations in numerous actionable genes including BRAF, EGFR, KRAS, IDH1, and PIK3CA that occurred concurrently with these TP53 mutations. Of the 480 tumors examined that contained one or more mutations in the TP53 gene, 219 were colon adenocarcinomas, 215 were NSCLCs, and 46 were gliomas/glioblastomas. Among the patients positive for TP53 mutations diagnosed with colon adenocarcinoma, 50% also showed at least one mutation in pathogenic genes of which 14% were BRAF, 33% were KRAS, and 3% were NRAS. Forty-seven percent of NSCLC patients harboring TP53 mutations also had a mutation in at least one actionable pathogenic variant with the following frequencies: BRAF: 4%, EGFR: 10%, KRAS: 28%, and PIK3CA: 4%. Fifty-two percent of patients diagnosed with glioma/glioblastoma with a positive TP53 mutation had at least one concurrent mutation in a known pathogenic gene of which 9% were CDKN2A, 41% were IDH1, and 11% were PIK3CA.

  20. Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation

    Directory of Open Access Journals (Sweden)

    N. Magdalena

    2005-05-01

    Full Text Available Fanconi anemia (FA is an autosomal recessive genetic disease characterized by progressive bone marrow failure, susceptibility to cancer and multiple congenital anomalies. There is important clinical variability among patients and the knowledge of factors which might predict outcome would greatly help the decision making regarding the choices of treatment and the appropriate time to start it. Future studies of the possible correlation between specific mutations with specific clinical presentations will provide the answer to one of these factors. At our Center we standardized a rapid and precise screening test using a mismatch PCR assay for a specific mutation (3788-3790del in exon 38 of gene FANCA in Brazilian FA patients. We present the results obtained after screening 80 non-consanguineous FA patients referred from all regions of Brazil with a clinical diagnosis of FA supported by cellular hypersensitivity to diepoxybutane. We were able to detect the 3788-3790del allele in 24 of the 80 (30% FA patients studied. Thirteen of the 80 (16.25% were homozygotes and 11 of the 80 (13.75% were compound heterozygotes, thus confirming the high frequency of the FANCA 3788-3790del mutation in Brazilian FA patients. The identification of patients with specific mutations in the FA genes may lead to a better clinical description of this condition, also providing data for genotype-phenotype correlations, to a better understanding of the interaction of this specific mutation with other mutations in compound heterozygote patients, and ultimately to the right choices of treatment for each patient with improvement of the prognosis on future studies.

  1. Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation.

    Science.gov (United States)

    Magdalena, N; Pilonetto, D V; Bitencourt, M A; Pereira, N F; Ribeiro, R C; Jeng, M; Pasquini, R

    2005-05-01

    Fanconi anemia (FA) is an autosomal recessive genetic disease characterized by progressive bone marrow failure, susceptibility to cancer and multiple congenital anomalies. There is important clinical variability among patients and the knowledge of factors which might predict outcome would greatly help the decision making regarding the choices of treatment and the appropriate time to start it. Future studies of the possible correlation between specific mutations with specific clinical presentations will provide the answer to one of these factors. At our Center we standardized a rapid and precise screening test using a mismatch PCR assay for a specific mutation (3788-3790del in exon 38 of gene FANCA) in Brazilian FA patients. We present the results obtained after screening 80 non-consanguineous FA patients referred from all regions of Brazil with a clinical diagnosis of FA supported by cellular hypersensitivity to diepoxybutane. We were able to detect the 3788-3790del allele in 24 of the 80 (30%) FA patients studied. Thirteen of the 80 (16.25%) were homozygotes and 11 of the 80 (13.75%) were compound heterozygotes, thus confirming the high frequency of the FANCA 3788-3790del mutation in Brazilian FA patients. The identification of patients with specific mutations in the FA genes may lead to a better clinical description of this condition, also providing data for genotype-phenotype correlations, to a better understanding of the interaction of this specific mutation with other mutations in compound heterozygote patients, and ultimately to the right choices of treatment for each patient with improvement of the prognosis on future studies.

  2. Intraglomerular inhibition maintains mitral cell response contrast across input frequencies.

    Science.gov (United States)

    Shao, Zuoyi; Puche, Adam C; Shipley, Michael T

    2013-11-01

    Odor signals are transmitted to the olfactory bulb by olfactory nerve (ON) synapses onto mitral/tufted cells (MTCs) and external tufted cells (ETCs); ETCs provide additional feed-forward excitation to MTCs. Both are strongly regulated by intraglomerular inhibition that can last up to 1 s and, when blocked, dramatically increases ON-evoked MC spiking. Intraglomerular inhibition thus limits the magnitude and duration of MC spike responses to sensory input. In vivo, sensory input is repetitive, dictated by sniffing rates from 1 to 8 Hz, potentially summing intraglomerular inhibition. To investigate this, we recorded MTC responses to 1- to 8-Hz ON stimulation in slices. Inhibitory postsynaptic current area (charge) following each ON stimulation was unchanged from 1 to 5 Hz and modestly paired-pulse attenuated at 8 Hz, suggesting there is no summation and only limited decrement at the highest input frequencies. Next, we investigated frequency independence of intraglomerular inhibition on MC spiking. MCs respond to single ON shocks with an initial spike burst followed by reduced spiking decaying to baseline. Upon repetitive ON stimulation peak spiking is identical across input frequencies but the ratio of peak-to-minimum rate before the stimulus (max-min) diminishes from 30:1 at 1 Hz to 15:1 at 8 Hz. When intraglomerular inhibition is selectively blocked, peak spike rate is unchanged but trough spiking increases markedly decreasing max-min firing ratios from 30:1 at 1 Hz to 2:1 at 8 Hz. Together, these results suggest intraglomerular inhibition is relatively frequency independent and can "sharpen" MC responses to input across the range of frequencies. This suggests that glomerular circuits can maintain "contrast" in MC encoding during sniff-sampled inputs.

  3. Magnetic Frequency Response of HL-LHC Beam Screens

    Energy Technology Data Exchange (ETDEWEB)

    Morrone, M. [CERN; Martino, M. [CERN; De Maria, R. [CERN; Fitterer, M. [Fermilab; Garion, C. [CERN

    2017-10-12

    Magnetic fields used to control particle beams in accelerators are usually controlled by regulating the electrical current of the power converters. In order to minimize lifetime degradation and ultimately luminosity loss in circular colliders, current-noise is a highly critical figure of merit of power converters, in particular for magnets located in areas with high beta-function, like the High Luminosity Large Hadron Collider (HL-LHC) insertions. However, what is directly acting upon the beam is the magnetic field and not the current of the power converter, which undergoes several frequency-dependent transformations until the desired magnetic field, seen by the beam, is obtained. Beam screens are very rarely considered when assessing or specifying the noise figure of merit, but their magnetic frequency response is such that they realize relatively effective low pass filtering of the magnetic field produced by the system magnet-power converter. This work aims at filling this gap by quantifying the expected impact of different beam screen layouts for the most relevant HL-LHC insertion magnets. A welldefined post-processing technique is used to derive the frequency response of the different multipoles from multi-physics Finite Element Method (FEM) simulation results. In addition, a well approximated analytical formula for the low-frequency range of multi-layered beam screens is presented.

  4. Frequency-Independent Response of Self-Complementary Checkerboard Screens

    Science.gov (United States)

    Urade, Yoshiro; Nakata, Yosuke; Nakanishi, Toshihiro; Kitano, Masao

    2015-06-01

    This research resolves a long-standing problem on the electromagnetic response of self-complementary metallic screens with checkerboardlike geometry. Although Babinet's principle implies that they show a frequency-independent response, this unusual characteristic has not been observed yet due to the singularities of the metallic point contacts in the checkerboard geometry. We overcome this difficulty by replacing the point contacts with resistive sheets. The proposed structure is prepared and characterized by terahertz time-domain spectroscopy. It is experimentally confirmed that the resistive checkerboard structures exhibit a flat transmission spectrum over 0.1-1.1 THz. It is also demonstrated that self-complementarity can eliminate even the frequency-dependent transmission characteristics of resonant metamaterials.

  5. [Research progress of mutational spectrum and pathophysiology of WFS1 gene in Wolfram syndrome and nonsyndromic low frequency sensorineural hearing loss].

    Science.gov (United States)

    Shi, S M; Han, Y H; Wang, H B

    2016-09-07

    Compound homozygous or heterozygous mutations in WFS 1 can lead to autosomal recessive Wolfram syndrome (WS), and heterozygous mutations in WFS 1 can lead to autosomal dominant non-syndromic low frequency sensorineural hearing loss (LFSNHL). In addition, mutations in the WFS region has relationship with diabetes and psychiatric diseases. In this paper, we provide an overview of genetic research with different phenotypes, including WS and LFSNHL.

  6. Filter frequency response of time dependent signal using Laplace transform

    Energy Technology Data Exchange (ETDEWEB)

    Shestakov, Aleksei I. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2018-01-16

    We analyze the effect a filter has on a time dependent signal x(t). If X(s) is the Laplace transform of x and H (s) is the filter Transfer function, the response in frequency space is X (s) H (s). Consequently, in real space, the response is the convolution (x*h) (t), where hi is the Laplace inverse of H. Effects are analyzed and analytically for functions such as (t/tc)2 e-t/t$_c$, where tc = const. We consider lowpass, highpass and bandpass filters.

  7. Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.

    Science.gov (United States)

    Tatlisumak, Turgut; Putaala, Jukka; Innilä, Markus; Enzinger, Christian; Metso, Tiina M; Curtze, Sami; von Sarnowski, Bettina; Amaral-Silva, Alexandre; Jungehulsing, Gerhard Jan; Tanislav, Christian; Thijs, Vincent; Rolfs, Arndt; Norrving, Bo; Fazekas, Franz; Suomalainen, Anu; Kolodny, Edwin H

    2016-02-01

    Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

  8. Relationship between mutation frequency of GPA locus and cumulative dose among medical diagnostic X-ray workers

    International Nuclear Information System (INIS)

    Wang Jixian; Yu Wenru; Li Benxiao; Fan Tiqiang; Li Zhen; Gao Zhiwei; Chen Zhenjun; Zhao Yongcheng

    2000-01-01

    Objective: To explore the feasibility of using GPA locus mutation assay as a bio-dosimeter for occupational exposure to ionizing radiation. Methods: An improved technique of GPA locus mutation assay was used in th study. The frequencies of mutant RBC in peripheral blood of 55 medical X-ray workers and 50 controls employed in different calendar-year periods were detected. The relationship between mutation frequencies (MFs) and period of entry, working years and cumulative doses were analyzed. Results: The MFs were significantly elevated among X-ray workers employed before 1970. This finding is similar to the result of cancer epidemiological study among medical X-ray workers , in which the cancer risk was significantly increased only X-ray workers employed before 1970. The MFs of GPA increased with increasing cumulative dose. The dose-effect relationship of Nφ MF with cumulative dose was closer than that of NN MF. Conclusion: There are many problems to be solved for using GPA MF assay as a bio-dosimeter such as individual variation, specificity and calibration curve of dose-effect relationship

  9. Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern

    Science.gov (United States)

    Al-Shamsi, Humaid O.; Jones, Jeremy; Fahmawi, Yazan; Dahbour, Ibrahim; Tabash, Aziz; Abdel-Wahab, Reham; Abousamra, Ahmed O. S.; Shaw, Kenna R.; Xiao, Lianchun; Hassan, Manal M.; Kipp, Benjamin R.; Kopetz, Scott; Soliman, Amr S.; McWilliams, Robert R.; Wolff, Robert A.

    2016-01-01

    Background The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. Methods Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher’s exact test was used to determine the association between mutation status and clinical features. Results A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant. Conclusions This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation. PMID:28078112

  10. [Frequency of the most common mutations of the CFTR gene in peruvian patients with cystic fibrosis using the ARMS-PCR technique].

    Science.gov (United States)

    Aquino, Ruth; Protzel, Ana; Rivera, Juan; Abarca, Hugo; Dueñas, Milagros; Nestarez, Cecilia; Purizaga, Nestor; Diringer, Benoit

    2017-01-01

    To determine the frequency of the ten most common mutations of the CFTR gene reported in Latin Americausing amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) in patients with cystic fibrosis (CF) in two referral hospitals in Peru during the year 2014. The frequency of the ten most common mutations of the CFTR gene was assessed in patients of the Hospital Nacional Edgardo Rebagliati Martins and the Instituto Nacional de Salud del Niño, both located in Lima, Peru. Blood samples were collected from 36 patients with CF, and the ARMS-PCR technique was used to determine the presence of these mutations. The study group included 73.5% of patients with a known diagnosis of CF in the country when the study was carried out. ARMS-PCR allowed three of the mutations to be identified in a combined 30.6% of the alleles from patients with CF, and 64.9% of the mutated alleles were not identified. The mutations found were p.Phe508del (22,2%), p.Gly542* (6,9%), and p.Arg1162* (1,4%). There is significant variability in both the frequency and type of mutations present in our study population and in what has been reported in other Latin American countries. It is necessary to perform studies that use complete sequencing technology for the CFTR gene to identify other mutations present in our population.

  11. Extreme assay sensitivity in molecular diagnostics further unveils intratumour heterogeneity in metastatic colorectal cancer as well as artifactual low-frequency mutations in the KRAS gene.

    Science.gov (United States)

    Mariani, Sara; Bertero, Luca; Osella-Abate, Simona; Di Bello, Cristiana; Francia di Celle, Paola; Coppola, Vittoria; Sapino, Anna; Cassoni, Paola; Marchiò, Caterina

    2017-07-25

    Gene mutations in the RAS family rule out metastatic colorectal carcinomas (mCRCs) from anti-EGFR therapies. We report a retrospective analysis by Sequenom Massarray and fast COLD-PCR followed by Sanger sequencing on 240 mCRCs. By Sequenom, KRAS and NRAS exons 2-3-4 were mutated in 52.9% (127/240) of tumours, while BRAF codon 600 mutations reached 5% (12/240). Fast COLD-PCR found extra mutations at KRAS exon 2 in 15/166 (9%) of samples, previously diagnosed by Sequenom as wild-type or mutated at RAS (exons 3-4) or BRAF genes. After UDG digestion results were reproduced in 2/12 analysable subclonally mutated samples leading to a frequency of true subclonal KRAS mutations of 1.2% (2.1% of the previous Sequenom wild-type subgroup). In 10 out of 12 samples, the subclonal KRAS mutations disappeared (9 out of 12) or turned to a different sequence variant (1 out of 12). mCRC can harbour coexisting multiple gene mutations. High sensitivity assays allow the detection of a small subset of patients harbouring true subclonal KRAS mutations. However, DNA changes with mutant allele frequencies <3% detected in formalin-fixed paraffin-embedded samples may be artifactual in a non-negligible fraction of cases. UDG pre-treatment of DNA is mandatory to identify true DNA changes in archival samples and avoid misinterpretation due to artifacts.

  12. Analysis of mutation/rearrangement frequencies and methylation patterns at a given DNA locus using restriction fragment length polymorphism.

    Science.gov (United States)

    Boyko, Alex; Kovalchuk, Igor

    2010-01-01

    Restriction fragment length polymorphism (RFLP) is a difference in DNA sequences of organisms belonging to the same species. RFLPs are typically detected as DNA fragments of different lengths after digestion with various restriction endonucleases. The comparison of RFLPs allows investigators to analyze the frequency of occurrence of mutations, such as point mutations, deletions, insertions, and gross chromosomal rearrangements, in the progeny of stressed plants. The assay involves restriction enzyme digestion of DNA followed by hybridization of digested DNA using a radioactively or enzymatically labeled probe. Since DNA can be digested with methylation sensitive enzymes, the assay can also be used to analyze a methylation pattern of a particular locus. Here, we describe RFLP analysis using methylation-insensitive and methylation-sensitive enzymes.

  13. Mitochondrial mutations drive prostate cancer aggression

    DEFF Research Database (Denmark)

    Hopkins, Julia F.; Sabelnykova, Veronica Y.; Weischenfeldt, Joachim

    2017-01-01

    Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer...... in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer....

  14. Specific-locus experiments show that female mice exposed near the time of birth to low-LET ionizing radiation exhibit both a low mutational response and a dose-rate effect

    International Nuclear Information System (INIS)

    Selby, P.B.; Lee, S.S.; Kelly, E.M.; Bangham, J.W.; Raymer, G.D.; Hunsicker, P.R.

    1991-01-01

    Female mice were exposed to 300 R of 73-93 R/min X-radiation either as fetuses at 18.5d post conception (p.c.) or within 9h after birth. Combining the similar results from these 2 groups yielded a specific-locus mutation frequency of 9.4x10 -8 mutation/locus/R, which is statistically significantly higher than the historical-control mutation frequency, but much lower than the rate obtained by irradiating mature and maturing oocytes in adults. Other females, exposed at 18.5 days p.c. to 300 R of 0.79 R/min γ-radiation, yielded a mutation frequency that was statistically significantly lower than the frequency at high dose rates. The low-dose-rate group also had markedly higher fertility. It appears that the doe-rate effect for mutations induced near the time of birth may be more pronounced than that reported for mature and maturing oocytes of adults. A hypothesis sometimes advanced to explain low mutation frequencies recovered from cell populations that experience considerable radiation-induced cell killing is that there is selection against mutant cells. The reason for the relatively low mutational response following acute irradiation in the experiments is unknown; however, the finding of a dose-rate effect in these oocytes in the presence of only minor radiation-induced cell killing (as judged from fertility) makes it seem unlikely that selection was responsible for the low mutational response following acute exposure. Had selection been an important factor, the mutation frequency should have increased when oocyte killing was markedly reduced. (author). 32 refs.; 5 figs.; 5 tabs

  15. Evaluation the frequency of factor V Leiden mutation in pregnant women with preeclampsia syndrome in an Iranian population

    Directory of Open Access Journals (Sweden)

    Azadeh Azinfar

    2012-01-01

    Full Text Available Background: Role of genetic factors in etiology of preeclampsia is not confirmed yet.Objective: Gene defect frequency varies in different geographic areas as well as ethnic groups. In this study, the role of factor V Leiden mutation in the pathogenesis of preeclampsia syndrome among the pregnant population of northern shore of Persian Gulf in Iran, were considered.Materials and Methods: Between Jan. 2008 and Dec. 2009, in a nested case control study, pregnant women with preeclampsia (N=198 as cases and healthy (N=201 as controls were enrolled in the study. DNA were extracted from 10 CC peripheral blood and analyzed for presence of factor V Leiden mutation in these subjects. The maternal and neonatal outcomes of pregnancy according to the distribution of factor V Leiden were also compared among cases.Results: In total, 17(8.6% of cases and 2(1% of controls showed the factor V Leiden mutation. The incidence of factor V Leiden was typically higher in preeclamptic women than control group (OR: 9.34 %95 CI: 2.12-41.01. There was no difference in incidence rate of preterm delivery< 37 weeks (OR: 1.23 %95 CI: 0.38-4.02, very early preterm delivery<32 weeks (OR: 1.00 %95 CI: 0.12-8.46, intra uterine fetal growth restriction (IUGR (OR: 1.32 %95 CI: 0.15-11.30 ,and the rate of cesarean section (OR: 0.88 %95 CI: 0.29-2.62 among cases based on the prevalence of factor V Leiden mutation.Conclusion: The pregnant women with factor V Leiden mutation are prone for preeclampsia syndrome during pregnancy, but this risk factor was not correlated to pregnancy complications in the studied women

  16. Frequency of epidermal growth factor receptor mutations in Jordanian lung adenocarcinoma patients at diagnosis

    Directory of Open Access Journals (Sweden)

    Natheir Obeidat

    2016-01-01

    Conclusion: The present study revealed that the EGFR mutations rate in Jordanian patients with adenocarcinoma of the lung was higher than in African-American, and some white Caucasian patients, and was lower than in patients in East Asia, and other countries of South Asia.

  17. The Splicing Efficiency of Activating HRAS Mutations Can Determine Costello Syndrome Phenotype and Frequency in Cancer

    DEFF Research Database (Denmark)

    Hartung, Anne-Mette; Swensen, Jeff; Uriz, Inaki E

    2016-01-01

    by the efficiency of exon 2 inclusion resulting from the different HRAS mutations. Finally, we show that a splice switching oligonucleotide (SSO) that blocks access to the critical ESE causes exon 2 skipping and halts proliferation of cancer cells. This unravels a potential for development of new anti......-cancer therapies based on SSO-mediated HRAS exon 2 skipping....

  18. Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes.

    NARCIS (Netherlands)

    Bonifati, V.; Rohe, C.F.; Breedveld, G.J.; Fabrizio, E.; Mari, M. De; Tassorelli, C.; Tavella, A.; Marconi, R.; Nicholl, D.; Chien, H.F.; Fincati, E.; Abbruzzese, G.; Marini, P.; Gaetano, A. De; Horstink, M.W.I.M.; Maat-Kievit, J.A.; Sampaio, C.; Antonini, A.; Stocchi, F.; Montagna, P.; Toni, V.; Guidi, M.; Dalla Libera, A.; Tinazzi, M.; Pandis, F. De; Goldwurm, S.; Klein, A. de; Barbosa, E.; Lopiano, L.; Martignoni, E.; Lamberti, P.; Vanacore, N.; Meco, G.; Oostra, B.A.

    2005-01-01

    OBJECTIVE: To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (<50 years) parkinsonism. METHODS: The authors studied 134 patients (116 sporadic and 18 familial; 77% Italian) and 90 Italian controls. The whole PINK1

  19. The Splicing Efficiency of Activating HRAS Mutations Can Determine Costello Syndrome Phenotype and Frequency in Cancer.

    Directory of Open Access Journals (Sweden)

    Anne-Mette Hartung

    2016-05-01

    Full Text Available Costello syndrome (CS may be caused by activating mutations in codon 12/13 of the HRAS proto-oncogene. HRAS p.Gly12Val mutations have the highest transforming activity, are very frequent in cancers, but very rare in CS, where they are reported to cause a severe, early lethal, phenotype. We identified an unusual, new germline p.Gly12Val mutation, c.35_36GC>TG, in a 12-year-old boy with attenuated CS. Analysis of his HRAS cDNA showed high levels of exon 2 skipping. Using wild type and mutant HRAS minigenes, we confirmed that c.35_36GC>TG results in exon 2 skipping by simultaneously disrupting the function of a critical Exonic Splicing Enhancer (ESE and creation of an Exonic Splicing Silencer (ESS. We show that this vulnerability of HRAS exon 2 is caused by a weak 3' splice site, which makes exon 2 inclusion dependent on binding of splicing stimulatory proteins, like SRSF2, to the critical ESE. Because the majority of cancer- and CS- causing mutations are located here, they affect splicing differently. Therefore, our results also demonstrate that the phenotype in CS and somatic cancers is not only determined by the different transforming potentials of mutant HRAS proteins, but also by the efficiency of exon 2 inclusion resulting from the different HRAS mutations. Finally, we show that a splice switching oligonucleotide (SSO that blocks access to the critical ESE causes exon 2 skipping and halts proliferation of cancer cells. This unravels a potential for development of new anti-cancer therapies based on SSO-mediated HRAS exon 2 skipping.

  20. Magnetic Frequency Response of HL-LHC Beam Screens

    CERN Document Server

    Morrone, M; De Maria, R; Fitterer, M; Garion, C

    2017-01-01

    Magnetic fields used to control particle beams in accelerators are usually controlled by regulating the electrical current of the power converters. In order to minimize lifetime degradation and ultimately luminosity loss in circular colliders, current-noise is a highly critical figure of merit of power converters, in particular for magnets located in areas with high beta-function, like the High Luminosity Large Hadron Collider (HL-LHC) insertions. However, what is directly acting upon the beam is the magnetic field and not the current of the power converter, which undergoes several frequency-dependent transformations until the desired magnetic field, seen by the beam, is obtained. Beam screens are very rarely considered when assessing or specifying the noise figure of merit, but their magnetic frequency response is such that they realize relatively effective low pass filtering of the magnetic field produced by the system magnet-power converter. This work aims at filling this gap by quantifying the expected im...

  1. Mutagenic treatments towards increasing the frequency of day-neutral mutations and standardization of procedures for tissue culture, in potato

    International Nuclear Information System (INIS)

    Upadhya, M.D.; Chandra, R.; Abraham, M.J.

    1976-01-01

    Various chemical mutagens and gamma radiation have been used on single dormant eyes and true seeds with a view to finding effective mutagenic treatment for the induction of day-length neutral mutants in potato using an effective screening technique for the isolation of day-length neutral mutants. Sodium meta bisulphite (SMS) was found to be an efficient mutagen in inducing mutations for this trait in true seeds although the same concentrations, when used for treating the single tuber eyes proved lethal. Pre-soaking the seeds for 24 hrs prior to treatment with 0.0025M SMS gave highest frequency of the mutants followed by 48 hrs presoaking, indicating a sensitive stage during the cell cycle in true seeds. Other mutagen treatments gave different frequencies of mutations. The highest frequency of day-length neutral mutants was observed when seeds irradiated with 40 Kr of gamma radiation were treated with 0.05M hydrazinium dichloride solution. Screening procedures have also been standardised with the development of synethetic media for the isolation of biochemical mutants at the true seed level. Initial efforts have yielded mutants resistant to LD 100 doses of ethionine. Another aspect of the study was to develop a proper potato callus culture technique. A medium has been developed to produce and maintain callus from potato leaf strips. Efforts on the regeneration of shoot and roots from callus, have so far lead to differentiation of callus to form roots. The ultimate aim of these studies is to develop plantlets from single cell which would form the units of mutation induction and isolation. (author)

  2. Response of air stagnation frequency to anthropogenically enhanced radiative forcing

    International Nuclear Information System (INIS)

    Horton, Daniel E; Diffenbaugh, Noah S; Harshvardhan

    2012-01-01

    Stagnant atmospheric conditions can lead to hazardous air quality by allowing ozone and particulate matter to accumulate and persist in the near-surface environment. By changing atmospheric circulation and precipitation patterns, global warming could alter the meteorological factors that regulate air stagnation frequency. We analyze the response of the National Climatic Data Center (NCDC) air stagnation index (ASI) to anthropogenically enhanced radiative forcing using global climate model projections of late-21st century climate change (SRESA1B scenario). Our results indicate that the atmospheric conditions over the highly populated, highly industrialized regions of the eastern United States, Mediterranean Europe, and eastern China are particularly sensitive to global warming, with the occurrence of stagnant conditions projected to increase by 12–25% relative to late-20th century stagnation frequencies (3–18 + days yr −1 ). Changes in the position/strength of the polar jet, in the occurrence of light surface winds, and in the number of precipitation-free days all contribute to more frequent late-21st century air mass stagnation over these high-population regions. In addition, we find substantial inter-model spread in the simulated response of stagnation conditions over some regions using either native or bias corrected global climate model simulations, suggesting that changes in the atmospheric circulation and/or the distribution of precipitation represent important sources of uncertainty in the response of air quality to global warming. (letter)

  3. Aircraft Fault Detection Using Real-Time Frequency Response Estimation

    Science.gov (United States)

    Grauer, Jared A.

    2016-01-01

    A real-time method for estimating time-varying aircraft frequency responses from input and output measurements was demonstrated. The Bat-4 subscale airplane was used with NASA Langley Research Center's AirSTAR unmanned aerial flight test facility to conduct flight tests and collect data for dynamic modeling. Orthogonal phase-optimized multisine inputs, summed with pilot stick and pedal inputs, were used to excite the responses. The aircraft was tested in its normal configuration and with emulated failures, which included a stuck left ruddervator and an increased command path latency. No prior knowledge of a dynamic model was used or available for the estimation. The longitudinal short period dynamics were investigated in this work. Time-varying frequency responses and stability margins were tracked well using a 20 second sliding window of data, as compared to a post-flight analysis using output error parameter estimation and a low-order equivalent system model. This method could be used in a real-time fault detection system, or for other applications of dynamic modeling such as real-time verification of stability margins during envelope expansion tests.

  4. Loss of function mutations in EPHB4 are responsible for vein of Galen aneurysmal malformation.

    Science.gov (United States)

    Vivanti, Alexandre; Ozanne, Augustin; Grondin, Cynthia; Saliou, Guillaume; Quevarec, Loic; Maurey, Helène; Aubourg, Patrick; Benachi, Alexandra; Gut, Marta; Gut, Ivo; Martinovic, Jelena; Sénat, Marie Victoire; Tawk, Marcel; Melki, Judith

    2018-04-01

    See Meschia (doi:10.1093/brain/awy066) for a scientific commentary on this article.Vein of Galen aneurysmal malformation is a congenital anomaly of the cerebral vasculature representing 30% of all paediatric vascular malformations. We conducted whole exome sequencing in 19 unrelated patients presenting this malformation and subsequently screened candidate genes in a cohort of 32 additional patients using either targeted exome or Sanger sequencing. In a cohort of 51 patients, we found five affected individuals with heterozygous mutations in EPHB4 including de novo frameshift (p.His191Alafs*32) or inherited deleterious splice or missense mutations predicted to be pathogenic by in silico tools. Knockdown of ephb4 in zebrafish embryos leads to specific anomalies of dorsal cranial vessels including the dorsal longitudinal vein, which is the orthologue of the median prosencephalic vein and the embryonic precursor of the vein of Galen. This model allowed us to investigate EPHB4 loss-of-function mutations in this disease by the ability to rescue the brain vascular defect in knockdown zebrafish co-injected with wild-type, but not truncated EPHB4, mimicking the p.His191Alafs mutation. Our data showed that in both species, loss of function mutations of EPHB4 result in specific and similar brain vascular development anomalies. Recently, EPHB4 germline mutations have been reported in non-immune hydrops fetalis and in cutaneous capillary malformation-arteriovenous malformation. Here, we show that EPHB4 mutations are also responsible for vein of Galen aneurysmal malformation, indicating that heterozygous germline mutations of EPHB4 result in a large clinical spectrum. The identification of EPHB4 pathogenic mutations in patients presenting capillary malformation or vein of Galen aneurysmal malformation should lead to careful follow-up of pregnancy of carriers for early detection of anomaly of the cerebral vasculature in order to propose optimal neonatal care. Endovascular

  5. Study of porous bed diffusion using the frequency response method

    International Nuclear Information System (INIS)

    Billy, J.

    1967-11-01

    The flow of an inert mixture of two gases across a catalytic bed is accompanied by diffusion phenomena in the inter-particulate space and inside the particles themselves, and adsorption phenomena at the surface of the particles. These phenomena are analyzed in turn and three coefficients which characterize each of them are defined. With a view to carrying out an experimental study by the frequency response method, the differential system deduced from the preceding analysis is then resolved with the help of two simplifying hypotheses; two relationships are given which make it possible to calculate the two diffusion coefficients and the absorption coefficient. (author) [fr

  6. Detection of low frequency FGFR3 mutations in the urine of bladder cancer patients using next-generation deep sequencing

    Directory of Open Access Journals (Sweden)

    Millholl

    2012-06-01

    Full Text Available John M Millholland, Shuqiang Li, Cecilia A Fernandez, Anthony P ShuberPredictive Biosciences Inc, Lexington, MA, USAAbstract: Biological fluid-based noninvasive biomarker assays for monitoring and diagnosing disease are clinically powerful. A major technical hurdle for developing these assays is the requirement of high analytical sensitivity so that biomarkers present at very low levels can be consistently detected. In the case of biological fluid-based cancer diagnostic assays, sensitivities similar to those of tissue-based assays are difficult to achieve with DNA markers due to the high abundance of normal DNA background present in the sample. Here we describe a new urine-based assay that uses ultradeep sequencing technology to detect single mutant molecules of fibroblast growth factor receptor 3 (FGFR3 DNA that are indicative of bladder cancer. Detection of FGFR3 mutations in urine would provide clinicians with a noninvasive means of diagnosing early-stage bladder cancer. The single-molecule assay detects FGFR3 mutant DNA when present at as low as 0.02% of total urine DNA and results in 91% concordance with the frequency that FGFR3 mutations are detected in bladder cancer tumors, significantly improving diagnostic performance. To our knowledge, this is the first practical application of next-generation sequencing technology for noninvasive cancer diagnostics.Keywords: FGFR3, mutation, urine, single molecule, sequencing, bladder cancer

  7. Increased frequency of co-existing JAK2 exon-12 or MPL exon-10 mutations in patients with low JAK2(V617F) allelic burden.

    Science.gov (United States)

    Nussenzveig, Roberto H; Pham, Ha T; Perkins, Sherrie L; Prchal, Josef T; Agarwal, Archana M; Salama, Mohamed E

    2016-01-01

    The frequency of co-existing JAK2(V617F)/MPL and JAK2(V617F)/JAK2 exon-12 mutations has not been previously investigated in MPNs. Poor survival was reported in primary myelofibrosis with low JAK2(V617F) allelic burden. However, mutational status of JAK2 exon-12 or MPL were not reported in these patients. This study developed a cost-effective multiplex high resolution melt assay that screens for mutations in JAK2 gene exons-12 and -14 ((V617F)) and MPL gene exon-10. Co-existing mutations with JAK2(V617F) were detected in 2.9% (6/208; two JAK2 exon-12 and four MPL exon-10) patient specimens with known JAK2(V617F) (allelic-burden range: 0.1-96.8%). Co-existing mutations were detected in specimens with MPL exon-10 mutation should be pursued.

  8. Assessment of Optimal Flexibility in Ensemble of Frequency Responsive Loads

    Energy Technology Data Exchange (ETDEWEB)

    Kundu, Soumya; Hansen, Jacob; Lian, Jianming; Kalsi, Karanjit

    2018-04-19

    Potential of electrical loads in providing grid ancillary services is often limited due to the uncertainties associated with the load behavior. A knowledge of the expected uncertainties with a load control program would invariably yield to better informed control policies, opening up the possibility of extracting the maximal load control potential without affecting grid operations. In the context of frequency responsive load control, a probabilistic uncertainty analysis framework is presented to quantify the expected error between the target and actual load response, under uncertainties in the load dynamics. A closed-form expression of an optimal demand flexibility, minimizing the expected error in actual and committed flexibility, is provided. Analytical results are validated through Monte Carlo simulations of ensembles of electric water heaters.

  9. Environmentally responsive genome-wide accumulation of de novo Arabidopsis thaliana mutations and epimutations

    KAUST Repository

    Jiang, Caifu

    2014-10-14

    Evolution is fueled by phenotypic diversity, which is in turn due to underlying heritable genetic (and potentially epigenetic) variation. While environmental factors are well known to influence the accumulation of novel variation in microorganisms and human cancer cells, the extent to which the natural environment influences the accumulation of novel variation in plants is relatively unknown. Here we use whole-genome and whole-methylome sequencing to test if a specific environmental stress (high-salinity soil) changes the frequency and molecular profile of accumulated mutations and epimutations (changes in cytosine methylation status) in mutation accumulation (MA) lineages of Arabidopsis thaliana. We first show that stressed lineages accumulate ∼100% more mutations, and that these mutations exhibit a distinctive molecular mutational spectrum (specific increases in relative frequency of transversion and insertion/deletion [indel] mutations). We next show that stressed lineages accumulate ∼45% more differentially methylated cytosine positions (DMPs) at CG sites (CG-DMPs) than controls, and also show that while many (∼75%) of these CG-DMPs are inherited, some can be lost in subsequent generations. Finally, we show that stress-associated CG-DMPs arise more frequently in genic than in nongenic regions of the genome. We suggest that commonly encountered natural environmental stresses can accelerate the accumulation and change the profiles of novel inherited variants in plants. Our findings are significant because stress exposure is common among plants in the wild, and they suggest that environmental factors may significantly alter the rates and patterns of incidence of the inherited novel variants that fuel plant evolution.

  10. Environmentally responsive genome-wide accumulation of de novo Arabidopsis thaliana mutations and epimutations

    KAUST Repository

    Jiang, Caifu; Mithani, Aziz; Belfield, Eric J.; Mott, Richard; Hurst, Laurence D.; Harberd, Nicholas P.

    2014-01-01

    Evolution is fueled by phenotypic diversity, which is in turn due to underlying heritable genetic (and potentially epigenetic) variation. While environmental factors are well known to influence the accumulation of novel variation in microorganisms and human cancer cells, the extent to which the natural environment influences the accumulation of novel variation in plants is relatively unknown. Here we use whole-genome and whole-methylome sequencing to test if a specific environmental stress (high-salinity soil) changes the frequency and molecular profile of accumulated mutations and epimutations (changes in cytosine methylation status) in mutation accumulation (MA) lineages of Arabidopsis thaliana. We first show that stressed lineages accumulate ∼100% more mutations, and that these mutations exhibit a distinctive molecular mutational spectrum (specific increases in relative frequency of transversion and insertion/deletion [indel] mutations). We next show that stressed lineages accumulate ∼45% more differentially methylated cytosine positions (DMPs) at CG sites (CG-DMPs) than controls, and also show that while many (∼75%) of these CG-DMPs are inherited, some can be lost in subsequent generations. Finally, we show that stress-associated CG-DMPs arise more frequently in genic than in nongenic regions of the genome. We suggest that commonly encountered natural environmental stresses can accelerate the accumulation and change the profiles of novel inherited variants in plants. Our findings are significant because stress exposure is common among plants in the wild, and they suggest that environmental factors may significantly alter the rates and patterns of incidence of the inherited novel variants that fuel plant evolution.

  11. The frequency of Tay-Sachs disease causing mutations in the Brazilian Jewish population justifies a carrier screening program

    Directory of Open Access Journals (Sweden)

    Roberto Rozenberg

    Full Text Available CONTEXT: Tay-Sachs disease is an autosomal recessive disease characterized by progressive neurologic degeneration, fatal in early childhood. In the Ashkenazi Jewish population the disease incidence is about 1 in every 3,500 newborns and the carrier frequency is 1 in every 29 individuals. Carrier screening programs for Tay-Sachs disease have reduced disease incidence by 90% in high-risk populations in several countries. The Brazilian Jewish population is estimated at 90,000 individuals. Currently, there is no screening program for Tay-Sachs disease in this population. OBJECTIVE: To evaluate the importance of a Tay-Sachs disease carrier screening program in the Brazilian Jewish population by determining the frequency of heterozygotes and the acceptance of the program by the community. SETTING: Laboratory of Molecular Genetics - Institute of Biosciences - Universidade de São Paulo. PARTICIPANTS: 581 senior students from selected Jewish high schools. PROCEDURE: Molecular analysis of Tay-Sachs disease causing mutations by PCR amplification of genomic DNA, followed by restriction enzyme digestion. RESULTS: Among 581 students that attended educational classes, 404 (70% elected to be tested for Tay-Sachs disease mutations. Of these, approximately 65% were of Ashkenazi Jewish origin. Eight carriers were detected corresponding to a carrier frequency of 1 in every 33 individuals in the Ashkenazi Jewish fraction of the sample. CONCLUSION: The frequency of Tay-Sachs disease carriers among the Ashkenazi Jewish population of Brazil is similar to that of other countries where carrier screening programs have led to a significant decrease in disease incidence. Therefore, it is justifiable to implement a Tay-Sachs disease carrier screening program for the Brazilian Jewish population.

  12. The frequency of Tay-Sachs disease causing mutations in the Brazilian Jewish population justifies a carrier screening program.

    Science.gov (United States)

    Rozenberg, R; Pereira, L da V

    2001-07-05

    Tay-Sachs disease is an autosomal recessive disease characterized by progressive neurologic degeneration, fatal in early childhood. In the Ashkenazi Jewish population the disease incidence is about 1 in every 3,500 newborns and the carrier frequency is 1 in every 29 individuals. Carrier screening programs for Tay-Sachs disease have reduced disease incidence by 90% in high-risk populations in several countries. The Brazilian Jewish population is estimated at 90,000 individuals. Currently, there is no screening program for Tay-Sachs disease in this population. To evaluate the importance of a Tay-Sachs disease carrier screening program in the Brazilian Jewish population by determining the frequency of heterozygotes and the acceptance of the program by the community. Laboratory of Molecular Genetics--Institute of Biosciences--Universidade de São Paulo. 581 senior students from selected Jewish high schools. Molecular analysis of Tay-Sachs disease causing mutations by PCR amplification of genomic DNA, followed by restriction enzyme digestion. Among 581 students that attended educational classes, 404 (70%) elected to be tested for Tay-Sachs disease mutations. Of these, approximately 65% were of Ashkenazi Jewish origin. Eight carriers were detected corresponding to a carrier frequency of 1 in every 33 individuals in the Ashkenazi Jewish fraction of the sample. The frequency of Tay-Sachs disease carriers among the Ashkenazi Jewish population of Brazil is similar to that of other countries where carrier screening programs have led to a significant decrease in disease incidence. Therefore, it is justifiable to implement a Tay-Sachs disease carrier screening program for the Brazilian Jewish population.

  13. Spectrum and Frequency of Mutations Induced by Gamma Radiations in Three Varieties of Nigerian Sesame (Sesamum indicum L.

    Directory of Open Access Journals (Sweden)

    Muhammad Liman MUHAMMAD

    2018-03-01

    Full Text Available Insufficient genetic variability is one of the major problems of plant breeding programmes, especially in sesame. Gamma radiation has been reported to be very effective in creating genetic variability in plants. Three varieties of Nigerian sesame were assessed for spectrum and frequency of mutation induced by Gamma radiations in M1 and M2 generations. The varieties (NCRIBEN-04E, NCRIBEN-01M and NCRIBEN-03L were treated with four different doses of gamma rays (250, 350, 450 and 550 Gy. The treated and untreated seeds (control were sown in planting bags (under field condition to raise M1 plants. Four treatments: V1D5, V2D3, V3D2 and V3D4 (from M1 plants were selected and bulked to obtain M2 populations. The results of M1 revealed four mutant fruit traits: multicarpellate capsule, multiple capsule per leaf axil, indehiscent capsule and terminal capsules. The highest frequencies of the traits in M1 generation were 2.50×10-2, 9.17×10-2, 1.67×10-2and3.33×10-2 respectively. The highest branching (7 was from NCRIBEN-01M, while the least (2 was from NCRIBEN-04E. The M2 plants were grouped into eight M2 lines. The dose range (250-550 Gy was proved to be effective in inducing viable mutations in sesame.

  14. Studies on chlorophyll and viable mutations in green gram (Vigna radiata L. Wilczek) II: Response to mutagen

    Energy Technology Data Exchange (ETDEWEB)

    Krishnaswami, S; Rathinam, M [Tamil Nadu Agricultural Univ., Coimbatore (India). Dept. of Agricultural Botany

    1980-09-01

    The frequency and spectrum of chlorophyll and viable mutations in relation to type and dose of mutagen and cluster progenies were studied in four green gram cultivars viz., Kopergaon, Pusa Baisakhi, L. 24/2 and Sel. 122 subjected to two levels of EMS and gamma irradiation, severally and in conjunction. While chlorophyll mutations did not vary with the mutagen dose, viable mutations exhibited a direct relationship. Combinations of the mutagens were more effective in mutation induction. While no difference was manifested between the cluster families in respect of chlorophyll mutations, progenies of the second cluster recorded less viable mutations than either the first or the third. Viridis and xanthoviridis among chlorophyll mutations, and those affecting plant duration and stature among viable were more predominant.

  15. Different frequencies of drug resistance mutations among HIV-1 subtypes circulating in China: a comprehensive study.

    Directory of Open Access Journals (Sweden)

    Hongshuai Sui

    Full Text Available The rapid spreading of HIV drug resistance is threatening the overall success of free HAART in China. Much work has been done on drug-resistant mutations, however, most of which were based on subtype B. Due to different genetic background, subtypes difference would have an effect on the development of drug-resistant mutations, which has already been proved by more and more studies. In China, the main epidemic subtypes are CRF07_BC, CRF08_BC, Thai B and CRF01_AE. The depiction of drug resistance mutations in those subtypes will be helpful for the selection of regimens for Chinese. In this study, the distributions difference of amino acids at sites related to HIV drug resistance were compared among subtype B, CRF01_AE, CRF07_BC and CRF08_BC strains prevalent in China. The amino acid composition of sequences belonging to different subtypes, which were obtained from untreated and treated individuals separately, were also compared. The amino acids proportions of 19 sites in RT among subtype B, CRF01_AE and CRF08_BC have significant difference in drug resistance groups (chi-square test, p<0.05. Genetic barriers analysis revealed that sites 69, 138, 181, 215 and 238 were significantly different among subtypes (Kruskal Wallis test, p<0.05. All subtypes shared three highest prevalent drug resistance sites 103, 181 and 184 in common. Many drug resistant sites in protease show surprising high proportions in almost all subtypes in drug-naïve patients. This is the first comprehensive study in China on different development of drug resistance among different subtypes. The detailed data will lay a foundation for HIV treatment regimens design and improve HIV therapy in China.

  16. The Frequency of MEFV Gene Mutations and Genotypes in Sanliurfa Province, South-Eastern Region of Turkey, after the Syrian Civil War by Using Next Generation Sequencing and Report of a Novel Exon 4 Mutation (I423T

    Directory of Open Access Journals (Sweden)

    Evren Gumus

    2018-05-01

    Full Text Available Background: Familial Mediterranean Fever (FMF is a genetic disorder characterized by recurrent episodes of fever and abdominal pain. Mutations in the Mediterranean fever (MEFV gene are localized on the p arm of chromosome 16. Over 333 MEFV sequence variants have been identified so far in FMF patients, which occur mostly in the 2nd and 10th exons of the gene. Methods: In this study, 296 unrelated patients with clinical suspicion of FMF, which were admitted during January–December 2017, were retrospectively reviewed to identify the frequency of MEFV gene mutations by using next generation sequencing. Results: Eighteen different mutations, 45 different genotypes and a novel exon 4 (I423T mutation were identified in this study. This mutation is the fourth mutation identified in exon 4.The most frequent mutation was R202Q, followed by M694V, E148Q, M680I, R761H, V726A and R354W. Conclusions: One of the most important aims of this study is to investigate the MEFV mutation type and genotype of migrants coming to Sanliurfa after the civil war of Syria. This study also examines the effect of the condition on the region’s gene pool and the distribution of different types of mutations. Our results indicated that MEFV mutations are highly heterogeneous in our patient population, which is consistent with the findings of other studies in our region. Previously used methods, such as Restriction Fragment Length Polymorphism (RFLP, do not define uncommon or especially novel mutations. Therefore, Next Generation Sequencing (NGS analysis of the MEFV gene could be useful for finding novel mutations, except for those located on exon 2 and 10.

  17. The Frequency of MEFV Gene Mutations and Genotypes in Sanliurfa Province, South-Eastern Region of Turkey, after the Syrian Civil War by Using Next Generation Sequencing and Report of a Novel Exon 4 Mutation (I423T).

    Science.gov (United States)

    Gumus, Evren

    2018-05-07

    Familial Mediterranean Fever (FMF) is a genetic disorder characterized by recurrent episodes of fever and abdominal pain. Mutations in the Mediterranean fever (MEFV) gene are localized on the p arm of chromosome 16. Over 333 MEFV sequence variants have been identified so far in FMF patients, which occur mostly in the 2nd and 10th exons of the gene. In this study, 296 unrelated patients with clinical suspicion of FMF, which were admitted during January⁻December 2017, were retrospectively reviewed to identify the frequency of MEFV gene mutations by using next generation sequencing. Eighteen different mutations, 45 different genotypes and a novel exon 4 (I423T) mutation were identified in this study. This mutation is the fourth mutation identified in exon 4.The most frequent mutation was R202Q, followed by M694V, E148Q, M680I, R761H, V726A and R354W. One of the most important aims of this study is to investigate the MEFV mutation type and genotype of migrants coming to Sanliurfa after the civil war of Syria. This study also examines the effect of the condition on the region’s gene pool and the distribution of different types of mutations. Our results indicated that MEFV mutations are highly heterogeneous in our patient population, which is consistent with the findings of other studies in our region. Previously used methods, such as Restriction Fragment Length Polymorphism (RFLP), do not define uncommon or especially novel mutations. Therefore, Next Generation Sequencing (NGS) analysis of the MEFV gene could be useful for finding novel mutations, except for those located on exon 2 and 10.

  18. Mutation frequencies in male mice and the estimation of genetic hazards of radiation in men: (specific-locus mutations/dose-rate effect/doubling dose/risk estimation)

    International Nuclear Information System (INIS)

    Russell, W.L.; Kelly, E.M.

    1982-01-01

    Estimation of the genetic hazards of ionizing radiation in men is based largely on the frequency of transmitted specific-locus mutations induced in mouse spermatogonial stem cells at low radiation dose rates. The publication of new data on this subject has permitted a fresh review of all the information available. The data continue to show no discrepancy from the interpretation that, although mutation frequency decreases markedly as dose rate is decreased from 90 to 0.8 R/min (1 R = 2.6 X 10 -4 coulombs/kg) there seems to be no further change below 0.8 R/min over the range from that dose rate to 0.0007 R/min. Simple mathematical models are used to compute: (a) a maximum likelihood estimate of the induced mutation frequency at the low dose rates, and (b) a maximum likelihood estimate of the ratio of this to the mutation frequency at high dose rates in the range of 72 to 90 R/min. In the application of these results to the estimation of genetic hazards of radiation in man, the former value can be used to calculate a doubling dose - i.e., the dose of radiation that induces a mutation frequency equal to the spontaneous frequency. The doubling dose based on the low-dose-rate data compiled here is 110 R. The ratio of the mutation frequency at low dose rate to that at high dose rate is useful when it becomes necessary to extrapolate from experimental determinations, or from human data, at high dose rates to the expected risk at low dose rates. The ratio derived from the present analysis is 0.33

  19. Heart tissue of harlequin (hq)/Big Blue mice has elevated reactive oxygen species without significant impact on the frequency and nature of point mutations in nuclear DNA

    Energy Technology Data Exchange (ETDEWEB)

    Crabbe, Rory A. [Department of Biology, University of Western Ontario, London, Ontario, N6A 5B7 (Canada); Hill, Kathleen A., E-mail: khill22@uwo.ca [Department of Biology, University of Western Ontario, London, Ontario, N6A 5B7 (Canada)

    2010-09-10

    Age is a major risk factor for heart disease, and cardiac aging is characterized by elevated mitochondrial reactive oxygen species (ROS) with compromised mitochondrial and nuclear DNA integrity. To assess links between increased ROS levels and mutations, we examined in situ levels of ROS and cII mutation frequency, pattern and spectrum in the heart of harlequin (hq)/Big Blue mice. The hq mouse is a model of premature aging with mitochondrial dysfunction and increased risk of oxidative stress-induced heart disease with the means for in vivo mutation detection. The hq mutation produces a significant downregulation in the X-linked apoptosis-inducing factor gene (Aif) impairing both the antioxidant and oxidative phosphorylation functions of AIF. Brain and skin of hq disease mice have elevated frequencies of point mutations in nuclear DNA and histopathology characterized by cell loss. Reports of associated elevations in ROS in brain and skin have mixed results. Herein, heart in situ ROS levels were elevated in hq disease compared to AIF-proficient mice (p < 0.0001) yet, mutation frequency and pattern were similar in hq disease, hq carrier and AIF-proficient mice. Heart cII mutations were also assessed 15 days following an acute exposure to an exogenous ROS inducer (10 mg paraquat/kg). Acute paraquat exposure with a short mutant manifestation period was insufficient to elevate mutation frequency or alter mutation pattern in the post-mitotic heart tissue of AIF-proficient mice. Paraquat induction of ROS requires mitochondrial complex I and thus is likely compromised in hq mice. Results of this preliminary survey and the context of recent literature suggest that determining causal links between AIF deficiency and the premature aging phenotypes of specific tissues is better addressed with assay of mitochondrial ROS and large-scale changes in mitochondrial DNA in specific cell types.

  20. Heart tissue of harlequin (hq)/Big Blue mice has elevated reactive oxygen species without significant impact on the frequency and nature of point mutations in nuclear DNA

    International Nuclear Information System (INIS)

    Crabbe, Rory A.; Hill, Kathleen A.

    2010-01-01

    Age is a major risk factor for heart disease, and cardiac aging is characterized by elevated mitochondrial reactive oxygen species (ROS) with compromised mitochondrial and nuclear DNA integrity. To assess links between increased ROS levels and mutations, we examined in situ levels of ROS and cII mutation frequency, pattern and spectrum in the heart of harlequin (hq)/Big Blue mice. The hq mouse is a model of premature aging with mitochondrial dysfunction and increased risk of oxidative stress-induced heart disease with the means for in vivo mutation detection. The hq mutation produces a significant downregulation in the X-linked apoptosis-inducing factor gene (Aif) impairing both the antioxidant and oxidative phosphorylation functions of AIF. Brain and skin of hq disease mice have elevated frequencies of point mutations in nuclear DNA and histopathology characterized by cell loss. Reports of associated elevations in ROS in brain and skin have mixed results. Herein, heart in situ ROS levels were elevated in hq disease compared to AIF-proficient mice (p < 0.0001) yet, mutation frequency and pattern were similar in hq disease, hq carrier and AIF-proficient mice. Heart cII mutations were also assessed 15 days following an acute exposure to an exogenous ROS inducer (10 mg paraquat/kg). Acute paraquat exposure with a short mutant manifestation period was insufficient to elevate mutation frequency or alter mutation pattern in the post-mitotic heart tissue of AIF-proficient mice. Paraquat induction of ROS requires mitochondrial complex I and thus is likely compromised in hq mice. Results of this preliminary survey and the context of recent literature suggest that determining causal links between AIF deficiency and the premature aging phenotypes of specific tissues is better addressed with assay of mitochondrial ROS and large-scale changes in mitochondrial DNA in specific cell types.

  1. The Frequency of c.550delA Mutation of the CANP3 Gene in the Polish LGMD2A Population.

    Science.gov (United States)

    Dorobek, Małgorzata; Ryniewicz, Barbara; Kabzińska, Dagmara; Fidziańska, Anna; Styczyńska, Maria; Hausmanowa-Petrusewicz, Irena

    2015-11-01

    Limb girdle muscular dystrophy 2A (LGMD2A) is the most frequent LGMD variant in the European population, representing about 40% of LGMD. The c.550delA mutation in the CANP3 (calcium activated neutral protease 3) gene is the most commonly reported mutation in LGMD2A. Prevalence of this mutation in the Polish population has not been previously investigated. The aim of this study was to identify and estimate the frequency of the c.550delA mutation in Polish LGMD2A patients. Polymerase chain reaction-sequencing analysis, restriction fragment length polymorphism polymerase chain reaction method. We analyzed 76 families affected with LGMD and identified 62 probands with mutations in the CANP3 gene. C.550delA was the most common mutation identified, being found in 78% of the LGMD2A families. The remaining mutations observed multiple times were as follows: c.598-612del15ntd; c.2242C>T; c.418dupC; c.1356insT, listed in terms of decreasing frequency. Two novel variants in the CANP3 gene, that is, c.700G>A Gly234Arg and c.661G>A Gly221Ser were also characterized. Overall, mutations in the LGMD2A gene were estimated to be present in 81% of patients with the LGMD phenotype who were without sarcoglycans and dysferlin deficiency on immunocytochemical analysis. The frequency of the heterozygous c.550delA mutation in the healthy Polish population was estimated at 1/124. The c.550delA is the most frequent CANP3 mutation in the Polish population, thus sequencing of exon 4 of this gene could identify the majority of LGMD2A patients in Poland.

  2. Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study.

    Science.gov (United States)

    Porter, Danielle P; Daeumer, Martin; Thielen, Alexander; Chang, Silvia; Martin, Ross; Cohen, Cal; Miller, Michael D; White, Kirsten L

    2015-12-07

    At Week 96 of the Single-Tablet Regimen (STaR) study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF) developed resistance mutations compared to those treated with efavirenz (EFV)/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq) was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33), as well as baseline samples from control subjects with virologic response (n = 118). Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20%) were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.

  3. Emergent HIV-1 Drug Resistance Mutations Were Not Present at Low-Frequency at Baseline in Non-Nucleoside Reverse Transcriptase Inhibitor-Treated Subjects in the STaR Study

    Directory of Open Access Journals (Sweden)

    Danielle P. Porter

    2015-12-01

    Full Text Available At Week 96 of the Single-Tablet Regimen (STaR study, more treatment-naïve subjects that received rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF developed resistance mutations compared to those treated with efavirenz (EFV/FTC/TDF by population sequencing. Furthermore, more RPV/FTC/TDF-treated subjects with baseline HIV-1 RNA >100,000 copies/mL developed resistance compared to subjects with baseline HIV-1 RNA ≤100,000 copies/mL. Here, deep sequencing was utilized to assess the presence of pre-existing low-frequency variants in subjects with and without resistance development in the STaR study. Deep sequencing (Illumina MiSeq was performed on baseline and virologic failure samples for all subjects analyzed for resistance by population sequencing during the clinical study (n = 33, as well as baseline samples from control subjects with virologic response (n = 118. Primary NRTI or NNRTI drug resistance mutations present at low frequency (≥2% to 20% were detected in 6.6% of baseline samples by deep sequencing, all of which occurred in control subjects. Deep sequencing results were generally consistent with population sequencing but detected additional primary NNRTI and NRTI resistance mutations at virologic failure in seven samples. HIV-1 drug resistance mutations emerging while on RPV/FTC/TDF or EFV/FTC/TDF treatment were not present at low frequency at baseline in the STaR study.

  4. A frequency domain global parameter estimation method for multiple reference frequency response measurements

    Science.gov (United States)

    Shih, C. Y.; Tsuei, Y. G.; Allemang, R. J.; Brown, D. L.

    1988-10-01

    A method of using the matrix Auto-Regressive Moving Average (ARMA) model in the Laplace domain for multiple-reference global parameter identification is presented. This method is particularly applicable to the area of modal analysis where high modal density exists. The method is also applicable when multiple reference frequency response functions are used to characterise linear systems. In order to facilitate the mathematical solution, the Forsythe orthogonal polynomial is used to reduce the ill-conditioning of the formulated equations and to decouple the normal matrix into two reduced matrix blocks. A Complex Mode Indicator Function (CMIF) is introduced, which can be used to determine the proper order of the rational polynomials.

  5. Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda.

    Science.gov (United States)

    Stölzel, Ulrich; Köstler, Erich; Schuppan, Detlef; Richter, Matthias; Wollina, Uwe; Doss, Manfred O; Wittekind, Christian; Tannapfel, Andrea

    2003-03-01

    To examine the role of hemochromatosis (HFE) gene mutations, which are associated with porphyria cutanea tarda (PCT), in the therapeutic response to chloroquine. We retrospectively analyzed a database (Excel version 2001 [Microsoft Excel, Redmond, Wash]; date range of search, 1985-1999) of chloroquine-treated patients with PCT on whether HFE mutations (C282Y and H63D) might have influenced the clinical response, urinary porphyrin excretion, liver enzyme activities, and serum iron markers. Serum samples and corresponding complete sets of data before and after therapy were available in 62 of 207 patients with PCT who were treated exclusively with chloroquine. Academic teaching hospital. For treatment, low-dose chloroquine diphosphate, 125 to 250 mg twice weekly, was used during a median time of 16 months (range, 12-26 months). Of the 62 German patients with PCT, 37 (60%) carries HFE mutations. Chloroquine therapy was accompanied by clinical remission and reduced urinary porphyrin excretion (P<.001) in the 24 patients (39%) with HFE wild type as well as in 35 HFE heterozygous patients with PCT (56%). Decreases of serum iron markers following chloroquine therapy were limited to patients with PCT and HFE wild type. All patients homozygous for the C282Y mutation (3 [5%] of 62) had high serum iron, ferritin, and transferrin saturation and failed to respond to chloroquine treatment. The therapeutic response to chloroquine was not compromised by C282Y heterozygosity and compound heterozygosity of HFE mutations. Because HFE C282Y homozygotes (+/+) did not respond to chloroquine and a decrease in serum iron concentration was limited to patients with PCT and HFE wild type, phlebotomy should be first-line therapy in patients with PCT and HFE mutations.

  6. Radiation-induced mutation frequency in marked chromosome of Macaca mulatta

    International Nuclear Information System (INIS)

    Dzhemilev, Z.A.; Machavariani, M.G.

    1976-01-01

    The symmetric and asymmetric exchange frequencies of marked (nucleolus forming) chromosomes were studied in the lymphocytes and epithelial kidney cells irradiated by X-rays at G 0 , both in vivo and in vitro. Symmetric and asymmetric exchange frequencies were found to be equal. In both the types of Macaca mulatta cells, the exchange frequency in the long arm appeared to be higher than theoretically expected. The increased exchange in the long arm is thought to be due to a greater quantity of late replicating heterochromatin in it. The short arm of marked chromosome of epithelial kidney cells enters the exchange in accordance to its length in mitosis, but exchange number in the short arm chromosome in lymphocytes is lower than in epithelial cells. This difference is caused likely by different functioning of the nucleolus forming heterochromatin. (author)

  7. Frequency-dependence of the slow force response.

    Science.gov (United States)

    von Lewinski, Dirk; Zhu, Danan; Khafaga, Mounir; Kockskamper, Jens; Maier, Lars S; Hasenfuss, Gerd; Pieske, Burkert

    2008-05-01

    Stretch induces biphasic inotropic effects in mammalian myocardium. A delayed component (slow force response, SFR) has been demonstrated in various species, however, experimental conditions varied and the underlying mechanisms are controversial. The physiological relevance of the SFR is poorly understood. Experiments were performed in ventricular muscle strips from failing human hearts and non-failing rabbit hearts. Upon stretch, twitch force was assessed at basal conditions (1 Hz, 37 degrees C) and after changing stimulation frequency with and without blockade of the Na+/H+-exchanger-1 (NHE1) or reverse-mode Na+/Ca2+-exchange (NCX). Action potential duration (APD) was assessed using floating electrodes. Low stimulation rates (0.2 Hz) potentiated and higher stimulation rates (2 and 3 Hz) reduced the SFR. The extent of SFR inhibition by NHE1 or NCX inhibition was not affected by stimulation rate. APD decreased at 0.2 Hz but was not altered at higher stimulation rates. The data demonstrate frequency-dependence of the SFR with greater positive inotropic effects at lower stimulation rates. Subcellular mechanisms underlying the SFR are not fundamentally affected by stimulation rate. The SFR may have more pronounced physiological effects at lower heart rates.

  8. LOFT PSMG Speed Control System frequency response analysis

    International Nuclear Information System (INIS)

    Hansen, H.R.

    1977-01-01

    An analysis was done to gain insight into the shape of the open loop frequency response of the PSMG Speed Control System. The results of the analysis were used as a guide to groom the proportional band and reset time settings of the 2 mode controller in the speed control system. The analysis shows that when an actuator with a timing of 90 degrees per 60 seconds is installed in the system the proportional band and reset time should be 316% and 1 minute. Whereas when grooming the system a proportional band and reset time of 150% and 1.5 minutes were found to be appropriate. The closeness of the settings show that even though a linear model was used to describe the non-linear PSMG Speed Control System, it was accurate enough to be used as a guide to groom the proportional band and reset time settings

  9. Nano-resonator frequency response based on strain gradient theory

    International Nuclear Information System (INIS)

    Miandoab, Ehsan Maani; Yousefi-Koma, Aghil; Pishkenari, Hossein Nejat; Fathi, Mohammad

    2014-01-01

    This paper aims to explore the dynamic behaviour of a nano-resonator under ac and dc excitation using strain gradient theory. To achieve this goal, the partial differential equation of nano-beam vibration is first converted to an ordinary differential equation by the Galerkin projection method and the lumped model is derived. Lumped parameters of the nano-resonator, such as linear and nonlinear springs and damper coefficients, are compared with those of classical theory and it is demonstrated that beams with smaller thickness display greater deviation from classical parameters. Stable and unstable equilibrium points based on classic and non-classical theories are also compared. The results show that, regarding the applied dc voltage, the dynamic behaviours expected by classical and non-classical theories are significantly different, such that one theory predicts the un-deformed shape as the stable condition, while the other theory predicts that the beam will experience bi-stability. To obtain the frequency response of the nano-resonator, a general equation including cubic and quadratic nonlinearities in addition to parametric electrostatic excitation terms is derived, and the analytical solution is determined using a second-order multiple scales method. Based on frequency response analysis, the softening and hardening effects given by two theories are investigated and compared, and it is observed that neglecting the size effect can lead to two completely different predictions in the dynamic behaviour of the resonators. The findings of this article can be helpful in the design and characterization of the size-dependent dynamic behaviour of resonators on small scales. (paper)

  10. High-frequency response and the possibilities of frequency-tunable narrow-band terahertz amplification in resonant tunneling nanostructures

    International Nuclear Information System (INIS)

    Kapaev, V. V.; Kopaev, Yu. V.; Savinov, S. A.; Murzin, V. N.

    2013-01-01

    The characteristics of the high-frequency response of single- and double-well resonant tunneling structures in a dc electric field are investigated on the basis of the numerical solution of a time-dependent Schrödinger equation with open boundary conditions. The frequency dependence of the real part of high frequency conductivity (high-frequency response) in In 0.53 Ga 0.47 As/AlAs/InP structures is analyzed in detail for various values of the dc voltage V dc in the negative differential resistance (NDR) region. It is shown that double-well three-barrier structures are promising for the design of terahertz-band oscillators. The presence of two resonant states with close energies in such structures leads to a resonant (in frequency) response whose frequency is determined by the energy difference between these levels and can be controlled by varying the parameters of the structure. It is shown that, in principle, such structures admit narrow-band amplification, tuning of the amplification frequency, and a fine control of the amplification (oscillation) frequency in a wide range of terahertz frequencies by varying a dc electric voltage applied to the structure. Starting from a certain width of the central intermediate barrier in double-well structures, one can observe a collapse of resonances, where the structure behaves like a single-well system. This phenomenon imposes a lower limit on the oscillation frequency in three-barrier resonant tunneling structures.

  11. Efficient molecular screening of Lynch syndrome by specific 3' promoter methylation of the MLH1 or BRAF mutation in colorectal cancer with high-frequency microsatellite instability.

    Science.gov (United States)

    Nakagawa, Hitoshi; Nagasaka, Takeshi; Cullings, Harry M; Notohara, Kenji; Hoshijima, Naoko; Young, Joanne; Lynch, Henry T; Tanaka, Noriaki; Matsubara, Nagahide

    2009-06-01

    It is sometimes difficult to diagnose Lynch syndrome by the simple but strict clinical criteria, or even by the definitive genetic testing for causative germline mutation of mismatch repair genes. Thus, some practical and efficient screening strategy to select highly possible Lynch syndrome patients is exceedingly desirable. We performed a comprehensive study to evaluate the methylation status of whole MLH1 promoter region by direct bisulfite sequencing of the entire MLH1 promoter regions on Lynch and non-Lynch colorectal cancers (CRCs). Then, we established a convenient assay to detect methylation in key CpG islands responsible for the silencing of MLH1 expression. We studied the methylation status of MLH1 as well as the CpG island methylator phenotype (CIMP) and immunohistochemical analysis of mismatch repair proteins on 16 cases of Lynch CRC and 19 cases of sporadic CRCs with high-frequency microsatellite instability (MSI-H). Sensitivity to detect Lynch syndrome by MLH1 (CCAAT) methylation was 88% and the specificity was 84%. Positive likelihood ratio (PLR) was 5.5 and negative likelihood ratio (NLR) was 0.15. Sensitivity by mutational analysis of BRAF was 100%, specificity was 84%, PLR was 6.3 and NLR was zero. By CIMP analysis; sensitivity was 88%, specificity was 79%, PLR was 4.2, and NLR was 0.16. BRAF mutation or MLH1 methylation analysis combined with MSI testing could be a good alternative to screen Lynch syndrome patients in a cost effective manner. Although the assay for CIMP status also showed acceptable sensitivity and specificity, it may not be practical because of its rather complicated assay.

  12. Modification of UV-induced mutation frequency and cell survival of Escherichia coli B/r WP2 trpE65 by treatment before irradiation

    International Nuclear Information System (INIS)

    Doudney, C.O.; Rinaldi, C.N.

    1984-01-01

    The UV radiation survival curve of exponentially growing cultures of Escherichia coli B/r WP2 trpE65 was modified by pretreatment for short incubation periods (up to 20 min) with chloramphenicol such that an extended exponential section of intermediate slope appeared between the shoulder and the final exponential slope. Surges of mutation to tryptophan independence occurred with each increase in slope of the survival curve. These surges were separated by extended sections of little mutation. Nalidixic acid prevented both the changes in survival and mutation. Mutation curves obtained with overnight cultures had three extended sections of little mutation alternating with section of high mutation. Reincubation for 60 min in fresh medium reduced or eliminated the low-response sections. These reappeared after 80 to 90 min, when DNA had doubled in the culture and before the initial synchronous cell divisions had occurred. Nalidixic acid prevented this reappearance

  13. A hypermorphic epithelial β-catenin mutation facilitates intestinal tumorigenesis in mice in response to compounding WNT-pathway mutations

    Directory of Open Access Journals (Sweden)

    Michael Buchert

    2015-11-01

    Full Text Available Activation of the Wnt/β-catenin pathway occurs in the vast majority of colorectal cancers. However, the outcome of the disease varies markedly from individual to individual, even within the same tumor stage. This heterogeneity is governed to a great extent by the genetic make-up of individual tumors and the combination of oncogenic mutations. In order to express throughout the intestinal epithelium a degradation-resistant β-catenin (Ctnnb1, which lacks the first 131 amino acids, we inserted an epitope-tagged ΔN(1-131-β-catenin-encoding cDNA as a knock-in transgene into the endogenous gpA33 gene locus in mice. The resulting gpA33ΔN-Bcat mice showed an increase in the constitutive Wnt/β-catenin pathway activation that shifts the cell fate towards the Paneth cell lineage in pre-malignant intestinal epithelium. Furthermore, 19% of all heterozygous and 37% of all homozygous gpA33ΔN-Bcat mice spontaneously developed aberrant crypt foci and adenomatous polyps, at frequencies and latencies akin to those observed in sporadic colon cancer in humans. Consistent with this, the Wnt target genes, MMP7  and Tenascin-C, which are most highly expressed in benign human adenomas and early tumor stages, were upregulated in pre-malignant tissue of gpA33ΔN-Bcat mice, but those Wnt target genes associated with excessive proliferation (i.e. Cdnn1, myc were not. We also detected diminished expression of membrane-associated α-catenin and increased intestinal permeability in gpA33ΔN-Bcat mice in challenge conditions, providing a potential explanation for the observed mild chronic intestinal inflammation and increased susceptibility to azoxymethane and mutant Apc-dependent tumorigenesis. Collectively, our data indicate that epithelial expression of ΔN(1-131-β-catenin in the intestine creates an inflammatory microenvironment and co-operates with other mutations in the Wnt/β-catenin pathway to facilitate and promote tumorigenesis.

  14. The mutation frequency of Drosophila melanogaster populations living under conditions of increased background radiation due to the Chernobyl accident

    International Nuclear Information System (INIS)

    Zainullin, V.G.; Rakin, A.O.; Shevchenko, V.A.; Myasnyankina, E.N.; Generalova, M.V.

    1992-01-01

    One of the problems facing the program in the wake of the Chernobyl accident is the estimation of genetic damage to plants and animals. Special attention was directed to studying the influence of radioactive pollutants at the accident site by means of an appropriate test system, using standard genetic subjects. The present study describes such investigations. Levels of persistent genetic damage in natural populations of Drosophila melanogaster found in the vicinity of the Chernobyl accident site were examined from August 1986-September 1989. Evidence is presented which indicates a relationship between the levels of radioactive pollution resulting from the Chernobyl accident and increasing genetic damage to exposed populations. The possible reasons for the decrease of mutation frequency observed in 1988 and 1989 are also discussed. Furthermore, evidence is presented which suggests that radiosensitive Drosophila mutants may be particularly sensitive indicators of radioactive pollution. (author). 16 refs.; 6 figs

  15. Dose-response curve for translocation frequency with single pair of painted chromosome. A comparison with dicentric and micronuclei frequency

    Energy Technology Data Exchange (ETDEWEB)

    Venkatachalam, P.; Paul, S.F.D.; Mohankumar, M.N.; Prabhu, B.K.; Gajendiran, N.; Jeevanram, R.K

    2000-07-01

    A translocation dose-response curve using a single pair of painted chromosomes was constructed. The translocation frequencies observed at different doses were compared to those obtained for dicentrics (DC) and micronuclei (MN). The translocation and DC frequency followed the Poisson distribution and MN showed over-dispersion. The translocation and DC frequencies were nearly the same for each dose point. Micronuclei showed a comparatively lower frequency. The alpha/beta ratio for translocations (0.916) and DC (0.974) were comparable, whereas the value for MN (1.526) was much higher. The equal frequencies of translocations and DC observed for a given dose indicated that genomic translocation frequency estimated using a single pair of painted chromosomes provides a reliable and easy method to measure translocation frequency. (autho000.

  16. Dose-response curve for translocation frequency with single pair of painted chromosome. A comparison with dicentric and micronuclei frequency

    International Nuclear Information System (INIS)

    Venkatachalam, P.; Paul, S.F.D.; Mohankumar, M.N.; Prabhu, B.K.; Gajendiran, N.; Jeevanram, R.K.

    2000-01-01

    A translocation dose-response curve using a single pair of painted chromosomes was constructed. The translocation frequencies observed at different doses were compared to those obtained for dicentrics (DC) and micronuclei (MN). The translocation and DC frequency followed the Poisson distribution and MN showed over-dispersion. The translocation and DC frequencies were nearly the same for each dose point. Micronuclei showed a comparatively lower frequency. The alpha/beta ratio for translocations (0.916) and DC (0.974) were comparable, whereas the value for MN (1.526) was much higher. The equal frequencies of translocations and DC observed for a given dose indicated that genomic translocation frequency estimated using a single pair of painted chromosomes provides a reliable and easy method to measure translocation frequency. (author)

  17. Frequency of CHEK2 mutations in a population based, case–control study of breast cancer in young women

    International Nuclear Information System (INIS)

    Friedrichsen, Danielle M; Malone, Kathleen E; Doody, David R; Daling, Janet R; Ostrander, Elaine A

    2004-01-01

    The cell-cycle checkpoint kinase (CHEK)2 protein truncating mutation 1100delC has been associated with increased risk for breast or prostate cancer. Multiple studies have found an elevated frequency of the 1100delC variant in specific stratifications of breast cancer patients with a family history of the disease, including BRCA1/BRCA2 negative families and families with a history of bilateral disease or male breast cancer. However, the 1100delC mutation has only been investigated in a few population-based studies and none from North America. We report here on the frequency of three CHEK2 variants that alter protein function – 1100delC, R145W, and I175T – in 506 cases and 459 controls from a population based, case–control study of breast cancer conducted in young women from western Washington. There was a suggestive enrichment in the 1100delC variant in the cases (1.2%) as compared with the controls (0.4%), but this was based on small numbers of carriers and the differences were not statistically significant. The 1100delC variant was more frequent in cases with a first-degree family history of breast cancer (4.3%; P = 0.02) and slightly enriched in cases with a family history of ovarian cancer (4.4%; P = 0.09). The CHEK2 variants are rare in the western Washington population and, based on accumulated evidence across studies, are unlikely to be major breast cancer susceptibility genes. Thus, screening for the 1100delC variant may have limited usefulness in breast cancer prevention programs in the USA

  18. Pathogenic mutations in TULP1 responsible for retinitis pigmentosa identified in consanguineous familial cases

    Science.gov (United States)

    Ullah, Inayat; Kabir, Firoz; Iqbal, Muhammad; Gottsch, Clare Brooks S.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

    2016-01-01

    Purpose To identify pathogenic mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous familial cases. Methods Seven large familial cases with multiple individuals diagnosed with retinitis pigmentosa were included in the study. Affected individuals in these families underwent ophthalmic examinations to document the symptoms and confirm the initial diagnosis. Blood samples were collected from all participating members, and genomic DNA was extracted. An exclusion analysis with microsatellite markers spanning the TULP1 locus on chromosome 6p was performed, and two-point logarithm of odds (LOD) scores were calculated. All coding exons along with the exon–intron boundaries of TULP1 were sequenced bidirectionally. We constructed a single nucleotide polymorphism (SNP) haplotype for the four familial cases harboring the K489R allele and estimated the likelihood of a founder effect. Results The ophthalmic examinations of the affected individuals in these familial cases were suggestive of RP. Exclusion analyses confirmed linkage to chromosome 6p harboring TULP1 with positive two-point LOD scores. Subsequent Sanger sequencing identified the single base pair substitution in exon14, c.1466A>G (p.K489R), in four families. Additionally, we identified a two-base deletion in exon 4, c.286_287delGA (p.E96Gfs77*); a homozygous splice site variant in intron 14, c.1495+4A>C; and a novel missense variation in exon 15, c.1561C>T (p.P521S). All mutations segregated with the disease phenotype in the respective families and were absent in ethnically matched control chromosomes. Haplotype analysis suggested (p<10−6) that affected individuals inherited the causal mutation from a common ancestor. Conclusions Pathogenic mutations in TULP1 are responsible for the RP phenotype in seven familial cases with a common ancestral mutation responsible for the disease phenotype in four of the seven families. PMID:27440997

  19. The Frequency of Factor V Leiden, Prothrombin G20210A and Methylenetetrahydrofolate Reductase C677T Mutations in Migraine Patients

    Directory of Open Access Journals (Sweden)

    Ruhsen Öcal

    2010-12-01

    Full Text Available OBJECTIVE: Migraine is an independent risk factor for ischemic stroke, but its pathophysiology is still unclear. Genetic factors that predispose patients to thrombosis have been studied in patients with migraine to highlight the pathogenesis, but the results remain controversial. In this study, the frequencies of factor V Leiden (FVL, prothrombin (Pt G20210A and methylenetetrahydrofolate reductase (MTHFR C677T mutations were investigated. METHODS: One hundred and sixty patients aged of 15 to 55 years with no history of systemic disease and who had been diagnosed as migraine according to the International Headache Society (IHS diagnostic criteria at Baskent University Hospital Neurology Outpatient Clinics were investigated for FVL, Pt G20210A and MTHFR C677T mutations from their genomic DNA, and the results were compared with those of healthy controls. RESULTS: One hundred and fifty five (96.9% of 160 migraine patients were homozygote normal, 5 (3.1% were heterozygote and none of them were homozygote mutant for FVL. The control group had 9.8% heterozygote individuals but the difference between the percentages was not statistically significant (p> 0.05. There were no homozygote mutant individuals in the Turkish population study in normal subjects like our study. Thirty nine (24.4% of 160 migraine patients were heterozygote and 8 (5% were homozygote mutant for MTHFR C677T. The control group had 37 (34.9% heterozygote and 6 (5.6% homozygote mutant individuals. The difference between the percentages was not statistically significant (p= 0.15. Three (1.9% of 160 migraine patients were heterozygote and 5 (2.9% of the control group were heterozygote mutant for Pt G20210A mutation. The control group had 37 (34.9% heterozygote and 6 (5.6% homozygote mutant individuals. The difference between the percentages was not statistically significant (p= 0.420. CONCLUSION: Our study indicates that FVL, Pt G20210A and MTHFR C677T gene mutations, which are considered

  20. The Frequency of Factor V Leiden, Prothrombin G20210A and Methylenetetrahydrofolate Reductase C677T Mutations in Migraine Patients

    Directory of Open Access Journals (Sweden)

    Ruhsen Öcal

    2010-12-01

    Full Text Available OBJECTIVE: Migraine is an independent risk factor for ischemic stroke, but its pathophysiology is still unclear. Genetic factors that predispose patients to thrombosis have been studied in patients with migraine to highlight the pathogenesis, but the results remain controversial. In this study, the frequencies of factor V Leiden (FVL, prothrombin (Pt G20210A and methylenetetrahydrofolate reductase (MTHFR C677T mutations were investigated. METHODS: One hundred and sixty patients aged of 15 to 55 years with no history of systemic disease and who had been diagnosed as migraine according to the International Headache Society (IHS diagnostic criteria at Baskent University Hospital Neurology Outpatient Clinics were investigated for FVL, Pt G20210A and MTHFR C677T mutations from their genomic DNA, and the results were compared with those of healthy controls. RESULTS: One hundred and fifty five (96.9% of 160 migraine patients were homozygote normal, 5 (3.1% were heterozygote and none of them were homozygote mutant for FVL. The control group had 9.8% heterozygote individuals but the difference between the percentages was not statistically significant (p> 0.05. There were no homozygote mutant individuals in the Turkish population study in normal subjects like our study. Thirty nine (24.4% of 160 migraine patients were heterozygote and 8 (5% were homozygote mutant for MTHFR C677T. The control group had 37 (34.9% heterozygote and 6 (5.6% homozygote mutant individuals. The difference between the percentages was not statistically significant (p= 0.15. Three (1.9% of 160 migraine patients were heterozygote and 5 (2.9% of the control group were heterozygote mutant for Pt G20210A mutation. The control group had 37 (34.9% heterozygote and 6 (5.6% homozygote mutant individuals. The difference between the percentages was not statistically significant (p= 0.420. CONCLUSION: Our study indicates that FVL, Pt G20210A and MTHFR C677T gene mutations, which are considered

  1. Frequency and Clinical Implication of the R450H Mutation in the Thyrotropin Receptor Gene in the Japanese Population Detected by Smart Amplification Process 2

    Science.gov (United States)

    Yanagawa, Yoshimaro; Aoki, Tomoyuki; Morimura, Tadashi; Araki, Osamu; Kimura, Takao; Ogiwara, Takayuki; Kotajima, Nobuo; Yanagawa, Masumi; Murakami, Masami

    2014-01-01

    In Japanese pediatric patients with thyrotropin (TSH) resistance, the R450H mutation in TSH receptor gene (TSHR) is occasionally observed. We studied the frequency and clinical implication of the R450H mutation in TSHR in the general population of Japanese adults using smart amplification process 2 (SmartAmp2). We designed SmartAmp2 primer sets to detect this mutation using a drop of whole blood. We analyzed thyroid function, antithyroid antibodies, and this mutation in 429 Japanese participants who had not been found to have thyroid disease. Two cases without antithyroid antibodies were heterozygous for the R450H mutation in TSHR. Thus, the prevalence of this mutation was 0.47% in the general population and 0.63% among those without antithyroid antibodies. Their serum TSH concentrations were higher than the average TSH concentration not only in subjects without antithyroid antibodies but also in those with antithyroid antibodies. The R450H mutation in TSHR is relatively common in the Japanese population and potentially affects thyroid function. The present study demonstrates that the SmartAmp2 method is useful to detect the R450H mutation in TSHR, which is one of the common causes of TSH resistance in the Japanese population. PMID:24895636

  2. INVESTIGATION OF RANGES AND FREQUENCY OF MUTATIONS IN THE embB GENE IN MYCOBACTERIUMTUBERCULOSIS ASSOCIATED WITH RESISTANCE TO ETHAMBUTOL USING REAL-TIME POLYMERASE CHAINREACTION

    Directory of Open Access Journals (Sweden)

    Yu. S. Аlyapkinа

    2017-01-01

    Full Text Available Based on real-time allele-specific polymerase chain reaction, the ranges of potential mutations in codons of 306 and 405 of the embBgene in Mycobacterium tuberculosis associated with resistance to ethambutol were investigated. 5 different mutations were detected in codon 306 and 3 mutations were found in codon 406 of the embB gene. The detected mutations were confirmed by sequencing and mass spectrometry. By analyzing the frequency of detected mutations of , the set of reagents was developed for rapid testing of susceptibility tuberculous mycobacteria to ethambutol by multi-competitive allele-specific real-time PCR. Out of 107 tested specimens of clinical isolates, mutations of the embB gene of M. tuberculosis were detected in 49 (45.8% specimens, and no mutations were found in 58 (52.2% specimens. 39 (36.4% specimens had mutations in codon 306 of the embB gene, and 9 (8.4% specimens had a mutation in codon 406, and 1 (0.9% specimen had mutations in both codons 306 and 406. The high level of agreement in the results of molecular genetic and bacteriological tests (84% proved the significance of mutations in codons 306 and 406 of the embB gene in M. tuberculosis and the need for their identification in order to detect ethambutol resistant strains of M. tuberculosis. When using molecular genetic tests, the sensitivity level made 75.8%, while the specificity of standard culture-based methods makes 95.6%.

  3. Low frequency steady-state brain responses modulate large scale functional networks in a frequency-specific means.

    Science.gov (United States)

    Wang, Yi-Feng; Long, Zhiliang; Cui, Qian; Liu, Feng; Jing, Xiu-Juan; Chen, Heng; Guo, Xiao-Nan; Yan, Jin H; Chen, Hua-Fu

    2016-01-01

    Neural oscillations are essential for brain functions. Research has suggested that the frequency of neural oscillations is lower for more integrative and remote communications. In this vein, some resting-state studies have suggested that large scale networks function in the very low frequency range (frequency characteristics of brain networks because both resting-state studies and conventional frequency tagging approaches cannot simultaneously capture multiple large scale networks in controllable cognitive activities. In this preliminary study, we aimed to examine whether large scale networks can be modulated by task-induced low frequency steady-state brain responses (lfSSBRs) in a frequency-specific pattern. In a revised attention network test, the lfSSBRs were evoked in the triple network system and sensory-motor system, indicating that large scale networks can be modulated in a frequency tagging way. Furthermore, the inter- and intranetwork synchronizations as well as coherence were increased at the fundamental frequency and the first harmonic rather than at other frequency bands, indicating a frequency-specific modulation of information communication. However, there was no difference among attention conditions, indicating that lfSSBRs modulate the general attention state much stronger than distinguishing attention conditions. This study provides insights into the advantage and mechanism of lfSSBRs. More importantly, it paves a new way to investigate frequency-specific large scale brain activities. © 2015 Wiley Periodicals, Inc.

  4. Impaired replication stress response in cells from immunodeficiency patients carrying Cernunnos/XLF mutations.

    Directory of Open Access Journals (Sweden)

    Michal Schwartz

    Full Text Available Non-Homologous End Joining (NHEJ is one of the two major pathways of DNA Double Strand Breaks (DSBs repair. Mutations in human NHEJ genes can lead to immunodeficiency due to its role in V(DJ recombination in the immune system. In addition, most patients carrying mutations in NHEJ genes display developmental anomalies which are likely the result of a general defect in repair of endogenously induced DSBs such as those arising during normal DNA replication. Cernunnos/XLF is a recently identified NHEJ gene which is mutated in immunodeficiency with microcephaly patients. Here we aimed to investigate whether Cernunnos/XLF mutations disrupt the ability of patient cells to respond to replication stress conditions. Our results demonstrate that Cernunnos/XLF mutated cells and cells downregulated for Cernunnos/XLF have increased sensitivity to conditions which perturb DNA replication. In addition, under replication stress, these cells exhibit impaired DSB repair and increased accumulation of cells in G2/M. Moreover Cernunnos/XLF mutated and down regulated cells display greater chromosomal instability, particularly at fragile sites, under replication stress conditions. These results provide evidence for the role of Cernunnos/XLF in repair of DSBs and maintenance of genomic stability under replication stress conditions. This is the first study of a NHEJ syndrome showing association with impaired cellular response to replication stress conditions. These findings may be related to the clinical features in these patients which are not due to the V(DJ recombination defect. Additionally, in light of the emerging important role of replication stress in the early stages of cancer development, our findings may provide a mechanism for the role of NHEJ in preventing tumorigenesis.

  5. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes

    NARCIS (Netherlands)

    Ruijs, M.W.G.; Verhoef, S.; Rookus, M.A.; Pruntel, R.; van der Hout, A.H.; Hogervorst, F.B.L.; Kluijt, I.; Sijmons, R.H.; Aalfs, C.M.; Wagner, A.; Ausems, M.G.E.M.; Hoogerbrugge, N.; van Asperen, C.J.; Gómez García, E.B.; Meijers-Heijboer, H.; ten Kate, L.P.; Menko, F.H.; van 't Veer, L.J.

    2010-01-01

    Background Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome. Most families fulfilling the classical diagnostic criteria harbour TP53 germline mutations. However, TP53 germline mutations may also occur in less obvious phenotypes. As a result, different criteria

  6. Degeneracy, frequency response and filtering in IMRT optimization

    International Nuclear Information System (INIS)

    Llacer, Jorge; Agazaryan, Nzhde; Solberg, Timothy D; Promberger, Claus

    2004-01-01

    This paper attempts to provide an answer to some questions that remain either poorly understood, or not well documented in the literature, on basic issues related to intensity modulated radiation therapy (IMRT). The questions examined are: the relationship between degeneracy and frequency response of optimizations, effects of initial beamlet fluence assignment and stopping point, what does filtering of an optimized beamlet map actually do and how could image analysis help to obtain better optimizations? Two target functions are studied, a quadratic cost function and the log likelihood function of the dynamically penalized likelihood (DPL) algorithm. The algorithms used are the conjugate gradient, the stochastic adaptive simulated annealing and the DPL. One simple phantom is used to show the development of the analysis tools used and two clinical cases of medium and large dose matrix size (a meningioma and a prostate) are studied in detail. The conclusions reached are that the high number of iterations that is needed to avoid degeneracy is not warranted in clinical practice, as the quality of the optimizations, as judged by the DVHs and dose distributions obtained, does not improve significantly after a certain point. It is also shown that the optimum initial beamlet fluence assignment for analytical iterative algorithms is a uniform distribution, but such an assignment does not help a stochastic method of optimization. Stopping points for the studied algorithms are discussed and the deterioration of DVH characteristics with filtering is shown to be partially recoverable by the use of space-variant filtering techniques

  7. Degeneracy, frequency response and filtering in IMRT optimization

    Energy Technology Data Exchange (ETDEWEB)

    Llacer, Jorge [EC Engineering Consultants LLC, 130 Forest Hill Drive, Los Gatos, CA 95032 (United States); Agazaryan, Nzhde [Department of Radiation Oncology, University of California, Los Angeles, CA 90095 (United States); Solberg, Timothy D [Department of Radiation Oncology, University of California, Los Angeles, CA 90095 (United States); Promberger, Claus [BrainLAB AG, Ammerthalstrasse 8, 85551 Heimstetten (Germany)

    2004-07-07

    This paper attempts to provide an answer to some questions that remain either poorly understood, or not well documented in the literature, on basic issues related to intensity modulated radiation therapy (IMRT). The questions examined are: the relationship between degeneracy and frequency response of optimizations, effects of initial beamlet fluence assignment and stopping point, what does filtering of an optimized beamlet map actually do and how could image analysis help to obtain better optimizations? Two target functions are studied, a quadratic cost function and the log likelihood function of the dynamically penalized likelihood (DPL) algorithm. The algorithms used are the conjugate gradient, the stochastic adaptive simulated annealing and the DPL. One simple phantom is used to show the development of the analysis tools used and two clinical cases of medium and large dose matrix size (a meningioma and a prostate) are studied in detail. The conclusions reached are that the high number of iterations that is needed to avoid degeneracy is not warranted in clinical practice, as the quality of the optimizations, as judged by the DVHs and dose distributions obtained, does not improve significantly after a certain point. It is also shown that the optimum initial beamlet fluence assignment for analytical iterative algorithms is a uniform distribution, but such an assignment does not help a stochastic method of optimization. Stopping points for the studied algorithms are discussed and the deterioration of DVH characteristics with filtering is shown to be partially recoverable by the use of space-variant filtering techniques.

  8. Frequency of canine nt230(del4) MDR1 mutation in prone pure breeds, their crosses and mongrels in Israel - insights from a worldwide comparative perspective.

    Science.gov (United States)

    Dekel, Yaron; Machluf, Yossy; Stoler, Aviad; Aderet, Arava; Baumel, Daniel; Kellerman, Efrat; Plotsky, Yoram; Noked Partouche, Oshrat; Elhalal, Gal; Ben-Shlomo, Izhar; Bercovich, Dani

    2017-11-13

    Sensitivity to macrocyclic lactones, which are commonly used in veterinary clinics, was first found in Rough Collies, and was attributed in 2001 to a 4 bp deletion in the MDR1 gene. The list of affected breeds currently includes 13 breeds. Researchers from different countries and continents examined the allelic frequencies of the nt230(del4) MDR1 mutation, emphasizing the clinical importance of this test not only to mutation-prone dogs, but also to their crosses and mongrels, since treatment of a deletion carrier with these compounds may lead to its death. In this study, the allelic frequencies of nt230(del4) MDR1 mutation in affected breeds, their crosses, unrelated pure breeds and mongrels are reported for the state of Israel (n = 1416 dogs). The Israeli data were compared with reports from the US, Europe, UK, Australia and Japan. The allelic frequencies of nt230(del4) MDR1 mutation in Israel for Australian, Swiss and German Shepherds (31%, 17% and 2.4%, respectively) are similar to the corresponding frequencies worldwide, much higher for Border Collies (4.8%), twice lower for Rough Collies (28%, compared to 55% or more elsewhere), and ~1% for mongrels. The frequencies for crosses of Australian Shepherd and Border Collies in Israel are 4 and 1.6 times lower, respectively, compared to the frequencies for the respective pure breeds. This work, that for the first time presents the frequency of nt230(del4) MDR1 mutation in Israel, along with a worldwide survey, has implications for clinicians, owners and breeders of sheepdogs and their crosses and supports the need for extra care in treatment and in future breeding. Of note, the relative proportion of affected breeds, in the overall tested dogs, might be higher than their actual proportion in Israel due to directed samples collection by veterinarians for clinical purposes, as these are mainly limited to certain affected breeds or dogs that resemble them.

  9. TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.

    Science.gov (United States)

    Harley, Margaret E; Murina, Olga; Leitch, Andrea; Higgs, Martin R; Bicknell, Louise S; Yigit, Gökhan; Blackford, Andrew N; Zlatanou, Anastasia; Mackenzie, Karen J; Reddy, Kaalak; Halachev, Mihail; McGlasson, Sarah; Reijns, Martin A M; Fluteau, Adeline; Martin, Carol-Anne; Sabbioneda, Simone; Elcioglu, Nursel H; Altmüller, Janine; Thiele, Holger; Greenhalgh, Lynn; Chessa, Luciana; Maghnie, Mohamad; Salim, Mahmoud; Bober, Michael B; Nürnberg, Peter; Jackson, Stephen P; Hurles, Matthew E; Wollnik, Bernd; Stewart, Grant S; Jackson, Andrew P

    2016-01-01

    DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions.

  10. Input signal shaping based on harmonic frequency response function for suppressing nonlinear optical frequency in frequency-scanning interferometry

    Science.gov (United States)

    Zhu, Yu; Liu, Zhigang; Deng, Wen; Deng, Zhongwen

    2018-05-01

    Frequency-scanning interferometry (FSI) using an external cavity diode laser (ECDL) is essential for many applications of the absolute distance measurement. However, owing to the hysteresis and creep of the piezoelectric actuator inherent in the ECDL, the optical frequency scanning exhibits a nonlinearity that seriously affects the phase extraction accuracy of the interference signal and results in the reduction of the measurement accuracy. To suppress the optical frequency nonlinearity, a harmonic frequency synthesis method for shaping the desired input signal instead of the original triangular wave is presented. The effectiveness of the presented shaping method is demonstrated through the comparison of the experimental results. Compared with an incremental Renishaw interferometer, the standard deviation of the displacement measurement of the FSI system is less than 2.4 μm when driven by the shaped signal.

  11. Influence of radiation exposure rate on somatic mutation frequency and loss of reproductive integrity in tradescantia stamen hairs

    International Nuclear Information System (INIS)

    Ichikawa, S.; Nauman, C.H.; Sparrow, A.H.; Takahashi, C.S.

    1978-01-01

    Inflorescences of Tradescantia clone 02 (2n=12), hetero- or hemi-zygous for flower color, were exposed to a series of γ-ray exposures at two different exposure rates, 29.3 R/min and 0.026-0.52 R/min. Pink mutation-response curves, and survival curves based on reproductive integrity, were constructed for each of the exposure rates. Loss of reproductive integrity was also assessed at high (256 R/min) and low (0.52-4.17 R/min) γ-ray exposure rates in T. blossfeldiana (2n=72). All observations were made on stamen hairs. The higher exposure rate was 1.3-1.7 times more effective in inducing pink mutations in clone 02. A greater efficiency of the higher exposure rate was also found for both taxa at the loss of reproductive integrity endpoint. The D 0 values obtained at the higher exposure rates, 154 R for clone 02 and 720 R for T. blossfeldiana, were significantly lower than the corresponding values of 270 R and 1880 R obtained at the lower exposure rates. These D 0 's differ by factors of 1.75 and 2.61 for clone 02 and T. blossfeldiana, respectively. D 0 's for the two taxa were found to be inversely correlated with their interphase chromosome volumes. (Auth.)

  12. Frequency and phenotype of patients carrying TPM2 and TPM3 gene mutations in a cohort of 94 patients with congenital myopathy

    DEFF Research Database (Denmark)

    Citirak, Gülsenay; Witting, Nanna; Duno, Morten

    2014-01-01

    , two related female patients and two sporadic, male patients were found to carry mutations in the tropomyosin 2 (TPM2) and tropomyosin 3 (TPM3) genes, respectively. This indicates a low (4.3%) frequency of TPM2 and TPM3 mutations as a cause of congenital myopathy. Compared to previously described...... patients carrying the same mutations as found in our study (c.503G>A, and c.502C>T in TPM3, and c.415_417delGAG in TPM2), clinical presentation and muscle morphological findings differed in our patients. Differences included variation in distribution of muscle weakness, presence of scoliosis and ptosis...... had nemaline myopathy and fiber size disproportion, while three patients had congenital fiber type disproportion (CFTD) on muscle biopsies. TPM2-related CFTD has only been described in two cases, indicating that mutations in TPM2 are rare causes of CFTD....

  13. Estimation of the frequency of occult mutations for an autosomal recessive disease in the presence of genetic heterogeneity: application to genetic hearing loss disorders.

    Science.gov (United States)

    Kimberling, William J

    2005-11-01

    The routine testing for pathologic mutation(s) in a patient's DNA has become the foundation of modern molecular genetic diagnosis. It is especially valuable when the phenotype shows genetic heterogeneity, and its importance will grow as treatments become genotype specific. However, the technology of mutation detection is imperfect and mutations are often missed. This can be especially troublesome when dealing with a recessive disorder where the combination of genetic heterogeneity and missed mutation creates an imprecision in the genotypic assessment of individuals who do not appear to have the expected complement of two pathologic mutations. This article describes a statistical approach to the estimation of the likelihood of a genetic diagnosis under these conditions. In addition to providing a means of testing for missed mutations, it also provides a method of estimating and testing for the presence of genetic heterogeneity in the absence of linkage data. Gene frequencies as well as estimates of sensitivity and specificity can be obtained as well. The test is applied to GJB2 recessive nonsyndromic deafness, Usher syndrome types Ib and IIa, and Pendred-enlarged vestibular aqueduct syndrome. Copyright 2005 Wiley-Liss, Inc.

  14. Analysis of relation between the mutation frequencies and somatic recombination induced by neutrons and the age of D. Melanogaster larvae

    International Nuclear Information System (INIS)

    Guzman R, J.; Zambrano A, F.; Paredes G, L.; Delfin L, A.; Quiroz R, C.

    1998-01-01

    Neutrons are subatomic particles with neutral electric charge, equal zero, which are emitted during the fissile material fission in nuclear reactors. It is known a little about biological effects induced by neutrons. There is a world interest in the use of reactors and accelerators for patients radiotherapy using neutrons with the purpose to destroy malignant cells of deep tumours where traditional methods have not given satisfactory results. There for it is required to do wide studies of biological effects of neutrons as well as their dosimetry. It was used the Smart test (Somatic Mutation and Recombination Test) of D. Melanogaster for quantifying the mutation induction and somatic recombination induced by neutrons of the National Institute of Nuclear Research reactor, at power of 300 and 1000 k W, with equivalent doses calculated 95.14 and 190.2 Sv for 300 k W and of 25.64 and 51.29 Sv for 1000 k W, using larvae with 72 or 96 hours aged. It was observed a linear relation between equivalent dose and genetic effects frequency, these last were greater when the reactor power was 1000 k W than those 300 k W. It was observed too that the damage was greater in 96 hours larvae than those 72 hours. The stain size presented an inverse relation with respect to larvae age. It is concluded that the Smart system is sensitive to neutrons effect and it responds of a directly proportional form to radiation dose, as well as to dose rate. It is noted more the effect when are used larvas in pre pupa stage where the irradiation target (imagal cells) is greater. The Smart is sensitive to damage induced by neutrons , thus can be used to studying its direct biological effects or by the use of chemical modulators. (Author)

  15. Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations.

    Science.gov (United States)

    Mallo, Mar; Del Rey, Mónica; Ibáñez, Mariam; Calasanz, M José; Arenillas, Leonor; Larráyoz, M José; Pedro, Carmen; Jerez, Andrés; Maciejewski, Jaroslaw; Costa, Dolors; Nomdedeu, Meritxell; Diez-Campelo, María; Lumbreras, Eva; González-Martínez, Teresa; Marugán, Isabel; Such, Esperanza; Cervera, José; Cigudosa, Juan C; Alvarez, Sara; Florensa, Lourdes; Hernández, Jesús M; Solé, Francesc

    2013-07-01

    Lenalidomide is an effective drug in low-risk myelodysplastic syndromes (MDS) with isolated del(5q), although not all patients respond. Studies have suggested a role for TP53 mutations and karyotype complexity in disease progression and outcome. In order to assess the impact of complex karyotypes on treatment response and disease progression in 52 lenalidomide-treated patients with del(5q) MDS, conventional G-banding cytogenetics (CC), single nucleotide polymorphism array (SNP-A), and genomic sequencing methods were used. SNP-A analysis (with control sample, lymphocytes CD3+, in 30 cases) revealed 5q losses in all cases. Other recurrent abnormalities were infrequent and were not associated with lenalidomide responsiveness. Low karyotype complexity (by CC) and a high baseline platelet count (>280 × 10(9) /l) were associated with the achievement of haematological response (P = 0·020, P = 0·013 respectively). Unmutated TP53 status showed a tendency for haematological response (P = 0·061). Complete cytogenetic response was not observed in any of the mutated TP53 cases. By multivariate analysis, the most important predictor for lenalidomide treatment failure was a platelet count <280 × 10(9) /l (Odds Ratio = 6·17, P = 0·040). This study reveals the importance of a low baseline platelet count, karyotypic complexity and TP53 mutational status for response to lenalidomide treatment. It supports the molecular study of TP53 in MDS patients treated with lenalidomide. © 2013 John Wiley & Sons Ltd.

  16. Effect of low dose gamma radiation on stamen-hairs of different clones of Tradescantia presenting variability in the frequency of spontaneous mutations

    International Nuclear Information System (INIS)

    Takahashi, C.S.

    1976-01-01

    Changes in the frequency of spontaneous somatic mutations were studied for three different clones of Tradescantia heterozygotes for flower and stamen-hair color keeping them under controlled or natural conditions in order to verify the effect of different environmental conditions on the different genotypes. The effect of inflorescence age on the variation of spontaneous mutations was studied choosing young and old inflorescences of a same plant. Low dose irradiation experiments were carried out with those clones to elucidate the radiation effects on the clones presenting changes in the frequency of spontaneous mutations. The chronic-and acute irradiation effects of low dose irradiation of the stamen-hair of Tradescantia were also studied. Results are discussed. (M.A.) [pt

  17. Frequency of the hemochromatosis HFE mutations C282Y, H63D, and S65C in blood donors in the Faroe Islands

    DEFF Research Database (Denmark)

    Milman, Nils; á Steig, Torkil; Koefoed, Pernille

    2004-01-01

    on the HFE gene was assessed by genotyping using the polymerase chain reaction (PCR) technique and calculated from direct allele counting. We found no C282Y homozygous subjects; 28 (14.0%) subjects were C282Y heterozygous and four subjects were C282Y/H63D compound heterozygous (2.0%). The C282Y allele......The aim of the study was to assess the frequencies of the hereditary hemochromatosis HFE mutations C282Y, H63D, and S65C in the population in the Faroe Islands. The series comprised 200 randomly selected blood donors of Faroese heritage. The frequency of the C282Y, H63D, and S65C mutations.......6%. Screening of larger groups of the Faroese population for HFE mutations especially C282Y should be considered in order to establish the penetrance....

  18. Efficient 3D frequency response modeling with spectral accuracy by the rapid expansion method

    KAUST Repository

    Chu, Chunlei; Stoffa, Paul L.

    2012-01-01

    Frequency responses of seismic wave propagation can be obtained either by directly solving the frequency domain wave equations or by transforming the time domain wavefields using the Fourier transform. The former approach requires solving systems

  19. Somatic mutation frequency in the stamen hairs of Tradescantia KU 7 and KU 9 clones exposed to low-level gamma rays

    International Nuclear Information System (INIS)

    Ichikawa, S.; Nagashima, C.; Takahashi, C.S.

    1981-01-01

    Two triploid clones (KU 7 and KU 9) of Tradescantia heterozygous for flower color were exposed to 1 to 42.3R of gamma rays or the scattering radiation in the gamma field of the Institute of Radiation . Breeding. Occurrence of somatic pink mutations in the stamen hairs was investigated 10 to 16 (or 14) days after irradiation. The mutation frequency was found to increase linearly with increasing gamma-ray exposure in the both clones, and the frequencies of 0.437 and 0.468 pink mutant events per 10 3 hairs per R were determined for KU 7 and KU 9, respectively. When the data collected in the present study were analyzed together with those obtained in earlier experiments in the gamma field, linear relationships of the somatic mutation frequency with gamma-ray (2.1 to 201.6R) and scattering radiation (0.72 to 57.6R) exposures were confirmed. Scattering radiation was found to have a genetical efficiency more than two times higher than that of gamma rays. Variation of spontaneous mutation frequency observed in the present study and in earlier studies was inversely correlated to temperature variation

  20. Frequency of Tabagism and N34S and P55S Mutations of Serine Peptidase Inhibitor, Kazal Type 1 (SPINK1) and R254W Mutation of Chymotrypsin C (CTRC) in Patients With Chronic Pancreatitis and Controls.

    Science.gov (United States)

    da Costa, Marianges Zadrozny Gouvêa; Pires, Júlia Glória Lucatelli; Nasser, Paulo Dominguez; Ferreira, Camila da Silva; Teixeira, Ana Cristina de Sá; Paranaguá-Vezozzo, Denise Cerqueira; Guarita, Dulce Reis; Carrilho, Flair José; Ono, Suzane Kioko

    2016-10-01

    This study aimed to investigate the association between chronic pancreatitis and smoking or genetic mutations. The study sample comprised 148 patients with chronic pancreatitis, 110 chronic alcoholic subjects without pancreatic disease, and 297 volunteer blood donors. Of the patients with chronic pancreatitis, 74% had alcoholic etiology and 26% had idiopathic pancreatitis. The frequency of smoking was 91.4% in patients with alcoholic pancreatitis, higher than 73.3% in alcoholic subjects without pancreatitis (P pancreatitis and blood donors. The N34S mutation of serine peptidase inhibitor, Kazal type 1 (SPINK1) was found in 2.7% of patients with chronic alcoholic pancreatitis, in 5.3% of patients with idiopathic pancreatitis, and in 0.4% of blood donors (P = 0.02). The P55S mutation of SPINK1 was found in 2.7% of patients with alcoholic pancreatitis and in 0.7% of blood donors (P = 0.12). The R254W mutation of chymotrypsin C was found in 0.9% of patients with alcoholic pancreatitis, in 0.9% of chronic alcoholic subjects without pancreatitis, and in 0.4% of blood donors (P = 0.75). In all cases, the mutations were heterozygous. Smoking and the N34S mutation of SPINK1 were positively correlated with chronic pancreatitis.

  1. Mutation in LIM2 Is Responsible for Autosomal Recessive Congenital Cataracts.

    Directory of Open Access Journals (Sweden)

    Bushra Irum

    increased after birth to a level that was sustained through the postnatal time points.A novel missense mutation in LIM2 is responsible for autosomal recessive congenital cataracts.

  2. 78 FR 45479 - Frequency Response and Frequency Bias Setting Reliability Standard

    Science.gov (United States)

    2013-07-29

    ... and Balancing Authorities to avoid overloading the Pacific AC ties. See NERC Petition, Exh. F at 62..., plays a crucial role in how fast frequency declines following the sudden loss of generation.\\63\\ When...

  3. Measuring the photodetector frequency response for ultrasonic applications by a heterodyne system with difference- frequency servo control.

    Science.gov (United States)

    Koch, Christian

    2010-05-01

    A technique for the calibration of photodiodes in ultrasonic measurement systems using standard and cost-effective optical and electronic components is presented. A heterodyne system was realized using two commercially available distributed feedback lasers, and the required frequency stability and resolution were ensured by a difference-frequency servo control scheme. The frequency-sensitive element generating the error signal for the servo loop comprised a delay-line discriminator constructed from electronic elements. Measurements were carried out at up to 450 MHz, and the uncertainties of about 5% (k = 2) can be further reduced by improved radio frequency power measurement without losing the feature of using only simple elements. The technique initially dedicated to the determination of the frequency response of photodetectors applied in ultrasonic applications can be transferred to other application fields of optical measurements.

  4. Different effects of dose rate on radiation-induced mutation frequency in various germ-cell stages of the mouse, and their implications for the analysis of tumorigenesis

    International Nuclear Information System (INIS)

    Russell, W.L.

    1979-01-01

    The following factors affecting mutation induction by radiation in mice are discussed: dose rate, cell stage, and sex. It is suggested that for cancers of presumed mutational origin, the risk from chronic radiation exposure may be only one-third the risk from acute exposure. This is based only on responses of spermatogonia; other cell types behave quite differently. Specific and general applications are discussed

  5. Reduction of spontaneous somatic mutation frequency by a low-dose X irradiation of Drosophila larvae and possible involvement of DNA single-strand damage repair.

    Science.gov (United States)

    Koana, Takao; Takahashi, Takashi; Tsujimura, Hidenobu

    2012-03-01

    The third instar larvae of Drosophila were irradiated with X rays, and the somatic mutation frequency in their wings was measured after their eclosion. In the flies with normal DNA repair and apoptosis functions, 0.2 Gy irradiation at 0.05 Gy/min reduced the frequency of the so-called small spot (mutant cell clone with reduced reproductive activity) compared with that in the sham-irradiated flies. When apoptosis was suppressed using the baculovirus p35 gene, the small spot frequency increased four times in the sham-irradiated control group, but the reduction by the 0.2-Gy irradiation was still evident. In a non-homologous end joining-deficient mutant, the small spot frequency was also reduced by 0.2 Gy radiation. In a mutant deficient in single-strand break repair, no reduction in the small spot frequency by 0.2 Gy radiation was observed, and the small spot frequency increased with the radiation dose. Large spot (mutant cell clone with normal reproductive activity) frequency was not affected by suppression of apoptosis and increased monotonically with radiation dose in wild-type larvae and in mutants for single- or double-strand break repair. It is hypothesized that some of the small spots resulted from single-strand damage and, in wild-type larvae, 0.2 Gy radiation activated the normal single-strand break repair gene, which reduced the background somatic mutation frequency.

  6. Frequency Response Function Based Damage Identification for Aerospace Structures

    Science.gov (United States)

    Oliver, Joseph Acton

    Structural health monitoring technologies continue to be pursued for aerospace structures in the interests of increased safety and, when combined with health prognosis, efficiency in life-cycle management. The current dissertation develops and validates damage identification technology as a critical component for structural health monitoring of aerospace structures and, in particular, composite unmanned aerial vehicles. The primary innovation is a statistical least-squares damage identification algorithm based in concepts of parameter estimation and model update. The algorithm uses frequency response function based residual force vectors derived from distributed vibration measurements to update a structural finite element model through statistically weighted least-squares minimization producing location and quantification of the damage, estimation uncertainty, and an updated model. Advantages compared to other approaches include robust applicability to systems which are heavily damped, large, and noisy, with a relatively low number of distributed measurement points compared to the number of analytical degrees-of-freedom of an associated analytical structural model (e.g., modal finite element model). Motivation, research objectives, and a dissertation summary are discussed in Chapter 1 followed by a literature review in Chapter 2. Chapter 3 gives background theory and the damage identification algorithm derivation followed by a study of fundamental algorithm behavior on a two degree-of-freedom mass-spring system with generalized damping. Chapter 4 investigates the impact of noise then successfully proves the algorithm against competing methods using an analytical eight degree-of-freedom mass-spring system with non-proportional structural damping. Chapter 5 extends use of the algorithm to finite element models, including solutions for numerical issues, approaches for modeling damping approximately in reduced coordinates, and analytical validation using a composite

  7. Mutational rectification of plant type for introducing responsiveness to nitrogen in rice

    International Nuclear Information System (INIS)

    Chakrabarti, S.N.; Sen, S.

    1975-01-01

    Dhairal, a local indica cultigen, although is very popular in many parts of Eastern India to several desirable traits, possesses the draw-back of low response to the application of nitrogen fertilizer. Attempts were made to alter the plant type and introduce the trait of 'high-responsiveness to nitrogen fertilizer' into this variety through induction of mutation using once and recurrent X-ray radiation. In field trails with several mutant strains along with the control selections in successive seasons at various levels of nitrogen (0 to 180 kg N/ha), selection x nitrogen interaction and the differential responses of the mutant strains were noted to be highly significant with regard to grain yield. Increased genotypic variance for grain yield at high 'N' level indicated the change in 'spread' amongst mutant strains. Few strains showed considerably high response to nitrogen application as expressed from grain yield and performance with regard to several agronomic attributes. (author)

  8. CiOpt: a program for optimization of the frequency response of linear circuits

    OpenAIRE

    Miró Sans, Joan Maria; Palà Schönwälder, Pere

    1991-01-01

    An interactive personal-computer program for optimizing the frequency response of linear lumped circuits (CiOpt) is presented. CiOpt has proved to be an efficient tool in improving designs where the inclusion of more accurate device models distorts the desired frequency response, as well as in device modeling. The outputs of CiOpt are the element values which best match the obtained and the desired frequency response. The optimization algorithms used (the Fletcher-Powell and Newton's methods,...

  9. Day-Ahead Scheduling Considering Demand Response as a Frequency Control Resource

    Directory of Open Access Journals (Sweden)

    Yu-Qing Bao

    2017-01-01

    Full Text Available The development of advanced metering technologies makes demand response (DR able to provide fast response services, e.g., primary frequency control. It is recognized that DR can contribute to the primary frequency control like thermal generators. This paper proposes a day-ahead scheduling method that considers DR as a frequency control resource, so that the DR resources can be dispatched properly with other resources. In the proposed method, the objective of frequency control is realized by defining a frequency limit equation under a supposed contingency. The frequency response model is used to model the dynamics of system frequency. The nonlinear frequency limit equation is transformed to a linear arithmetic equation by piecewise linearization, so that the problem can be solved by mixed integer linear programming (MILP. Finally, the proposed method is verified on numerical examples.

  10. Repair capability and the cellular age response for killing and mutation induction after UV

    International Nuclear Information System (INIS)

    Wood, R.D.; Burki, H.J.; California Univ., Berkeley

    1982-01-01

    The cell-cycle response for killing and mutation induction by ultraviolet irradiation was measured in synchronous Chinese hamster ovary cells (CHO wild-type) and in a UV-hypersensitive mutant (43-3B) derived from this line. The CHO 43-3B line shows a greatly enhanced sensitivity to killing (D 0 of 0.3 as compared to 3.2 J/m 2 for the wild-type), is hypermutable, and deficient in DNA repair. For the wild-type, a characteristic age response is seen for killing by UV, with maximum sensitivity in early-S and resistance increasing through the S-phase. There is also a life-cycle specificity for induction of diphtheria-toxin resistance in late-G 1 and early-S. Relatively little variation is seen through the cell cycle for induced 6-thioguanine and ouabain resistance. In contrast, the 43-3B cell line shows a relatively 'flat' response to UV throughout the cell cycle, for both killing and mutation induction. Therefore it appears that the characteristic age responses seen in the wild-type CHO are associated with the function of an essentially error-free repair process. (orig./AJ)

  11. Effect of input compression and input frequency response on music perception in cochlear implant users.

    Science.gov (United States)

    Halliwell, Emily R; Jones, Linor L; Fraser, Matthew; Lockley, Morag; Hill-Feltham, Penelope; McKay, Colette M

    2015-06-01

    A study was conducted to determine whether modifications to input compression and input frequency response characteristics can improve music-listening satisfaction in cochlear implant users. Experiment 1 compared three pre-processed versions of music and speech stimuli in a laboratory setting: original, compressed, and flattened frequency response. Music excerpts comprised three music genres (classical, country, and jazz), and a running speech excerpt was compared. Experiment 2 implemented a flattened input frequency response in the speech processor program. In a take-home trial, participants compared unaltered and flattened frequency responses. Ten and twelve adult Nucleus Freedom cochlear implant users participated in Experiments 1 and 2, respectively. Experiment 1 revealed a significant preference for music stimuli with a flattened frequency response compared to both original and compressed stimuli, whereas there was a significant preference for the original (rising) frequency response for speech stimuli. Experiment 2 revealed no significant mean preference for the flattened frequency response, with 9 of 11 subjects preferring the rising frequency response. Input compression did not alter music enjoyment. Comparison of the two experiments indicated that individual frequency response preferences may depend on the genre or familiarity, and particularly whether the music contained lyrics.

  12. Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution.

    Science.gov (United States)

    Marez, D; Legrand, M; Sabbagh, N; Lo Guidice, J M; Spire, C; Lafitte, J J; Meyer, U A; Broly, F

    1997-06-01

    The polymorphic cytochrome P450 CYP2D6 is involved in the metabolism of various drugs of wide therapeutic use and is a presumed susceptibility factor for certain environmentally-induced diseases. Our aim was to define the mutations and alleles of the CYP2D6 gene and to evaluate their frequencies in the European population. Using polymerase chain reaction-single strand conformation polymorphism analysis, 672 unrelated subjects were screened for mutations in the 9 exons of the gene and their exon-intron boundaries. A total of 48 point mutations were identified, of which 29 were novel. Mutations 1749 G-->C, 2938 C-->T and 4268 G-->C represented 52.6%, 34.3% and 52.9% of the mutations in the total population, respectively. Of the eight detrimental mutations detected, the 1934 G-->A, the 1795 Tdel and the 2637 Adel accounted for 65.8%, 6.2% and 4.8% respectively, within the poor metabolizer subgroup. Fifty-three different alleles were characterized from the mutation pattern and by allele-specific sequencing. They are derived from three major alleles, namely the wild-type CYP2D6*1A, the functional CYP2D6*2 and the null CYP2D6*4A. Five allelic variants (CYP2D6*1A, *2, *2B, *4A and *5) account for about 87% of all alleles, while the remaining alleles occur with a frequency of 0.1%-2.7%. These data provide a solid basis for future epidemiological, clinical as well as interethnic studies of the CYP2D6 polymorphism and highlight that the described single strand conformation polymorphism method can be successfully used in designing such studies.

  13. Loss of function JAK1 mutations occur at high frequency in cancers with microsatellite instability and are suggestive of immune evasion.

    Science.gov (United States)

    Albacker, Lee A; Wu, Jeremy; Smith, Peter; Warmuth, Markus; Stephens, Philip J; Zhu, Ping; Yu, Lihua; Chmielecki, Juliann

    2017-01-01

    Immune evasion is a well-recognized hallmark of cancer and recent studies with immunotherapy agents have suggested that tumors with increased numbers of neoantigens elicit greater immune responses. We hypothesized that the immune system presents a common selective pressure on high mutation burden tumors and therefore immune evasion mutations would be enriched in high mutation burden tumors. The JAK family of kinases is required for the signaling of a host of immune modulators in tumor, stromal, and immune cells. Therefore, we analyzed alterations in this family for the hypothesized signature of an immune evasion mutation. Here, we searched a database of 61,704 unique solid tumors for alterations in the JAK family kinases (JAK1/2/3, TYK2). We used The Cancer Genome Atlas and Cancer Cell Line Encyclopedia data to confirm and extend our findings by analyzing gene expression patterns. Recurrent frameshift mutations in JAK1 were associated with high mutation burden and microsatellite instability. These mutations occurred in multiple tumor types including endometrial, colorectal, stomach, and prostate carcinomas. Analyzing gene expression signatures in endometrial and stomach adenocarcinomas revealed that tumors with a JAK1 frameshift exhibited reduced expression of interferon response signatures and multiple anti-tumor immune signatures. Importantly, endometrial cancer cell lines exhibited similar gene expression changes that were expected to be tumor cell intrinsic (e.g. interferon response) but not those expected to be tumor cell extrinsic (e.g. NK cells). From these data, we derive two primary conclusions: 1) JAK1 frameshifts are loss of function alterations that represent a potential pan-cancer adaptation to immune responses against tumors with microsatellite instability; 2) The mechanism by which JAK1 loss of function contributes to tumor immune evasion is likely associated with loss of the JAK1-mediated interferon response.

  14. Benefits of Demand-Side Response in Providing Frequency Response Service in the Future GB Power System

    Energy Technology Data Exchange (ETDEWEB)

    Teng, Fei, E-mail: fei.teng09@imperial.ac.uk; Aunedi, Marko; Pudjianto, Danny; Strbac, Goran [Department of Electrical and Electronic Engineering, Imperial College London, London (United Kingdom)

    2015-08-18

    The demand for ancillary service is expected to increase significantly in the future Great Britain (GB) electricity system due to high penetration of wind. In particular, the need for frequency response, required to deal with sudden frequency drops following a loss of generator, will increase because of the limited inertia capability of wind plants. This paper quantifies the requirements for primary frequency response and analyses the benefits of frequency response provision from demand-side response (DSR). The results show dramatic changes in frequency response requirements driven by high penetration of wind. Case studies carried out by using an advanced stochastic generation scheduling model suggest that the provision of frequency response from DSR could greatly reduce the system operation cost, wind curtailment, and carbon emissions in the future GB system characterized by high penetration of wind. Furthermore, the results demonstrate that the benefit of DSR shows significant diurnal and seasonal variation, whereas an even more rapid (instant) delivery of frequency response from DSR could provide significant additional value. Our studies also indicate that the competing technologies to DSR, namely battery storage, and more flexible generation could potentially reduce its value by up to 35%, still leaving significant room to deploy DSR as frequency response provider.

  15. Benefits of Demand-Side Response in Providing Frequency Response Service in the Future GB Power System

    International Nuclear Information System (INIS)

    Teng, Fei; Aunedi, Marko; Pudjianto, Danny; Strbac, Goran

    2015-01-01

    The demand for ancillary service is expected to increase significantly in the future Great Britain (GB) electricity system due to high penetration of wind. In particular, the need for frequency response, required to deal with sudden frequency drops following a loss of generator, will increase because of the limited inertia capability of wind plants. This paper quantifies the requirements for primary frequency response and analyses the benefits of frequency response provision from demand-side response (DSR). The results show dramatic changes in frequency response requirements driven by high penetration of wind. Case studies carried out by using an advanced stochastic generation scheduling model suggest that the provision of frequency response from DSR could greatly reduce the system operation cost, wind curtailment, and carbon emissions in the future GB system characterized by high penetration of wind. Furthermore, the results demonstrate that the benefit of DSR shows significant diurnal and seasonal variation, whereas an even more rapid (instant) delivery of frequency response from DSR could provide significant additional value. Our studies also indicate that the competing technologies to DSR, namely battery storage, and more flexible generation could potentially reduce its value by up to 35%, still leaving significant room to deploy DSR as frequency response provider.

  16. Outer hair cell piezoelectricity: frequency response enhancement and resonance behavior.

    Science.gov (United States)

    Weitzel, Erik K; Tasker, Ron; Brownell, William E

    2003-09-01

    Stretching or compressing an outer hair cell alters its membrane potential and, conversely, changing the electrical potential alters its length. This bi-directional energy conversion takes place in the cell's lateral wall and resembles the direct and converse piezoelectric effects both qualitatively and quantitatively. A piezoelectric model of the lateral wall has been developed that is based on the electrical and material parameters of the lateral wall. An equivalent circuit for the outer hair cell that includes piezoelectricity shows a greater admittance at high frequencies than one containing only membrane resistance and capacitance. The model also predicts resonance at ultrasonic frequencies that is inversely proportional to cell length. These features suggest all mammals use outer hair cell piezoelectricity to support the high-frequency receptor potentials that drive electromotility. It is also possible that members of some mammalian orders use outer hair cell piezoelectric resonance in detecting species-specific vocalizations.

  17. Dielectric response of KCN crystals at ultra-low frequencies

    OpenAIRE

    Ziemath, Ervino C.; Aegerter, Michel A.; Slaets, J.

    1987-01-01

    We describe an ultra low frequency equipment employing programmable digital technique. The system is used to measure the dielectric parameters et, en and tg d or pure KCN crystals as a function of temperature in the frequency range 10-2 Hz to 40 Hz. The relaxation time of the Cn dipoles presents a classical temperature activated reorientation behaviour characterized by an Arrhenius law t=to exp (U/kT) with t0=7,26 x 10-15 s and U = 0,147 eV.

  18. Patients with primary breast and primary female genital tract diffuse large B cell lymphoma have a high frequency of MYD88 and CD79B mutations.

    Science.gov (United States)

    Cao, Xin-Xin; Li, Jian; Cai, Hao; Zhang, Wei; Duan, Ming-Hui; Zhou, Dao-Bin

    2017-11-01

    This study is to retrospectively evaluate the prevalence of MYD88 and CD79B mutations and the clinicopathologic characteristics of patients with primary diffuse large B cell lymphoma (DLBCL) of the female genital tract and breast. The characteristics, treatments, and outcomes of 19 patients diagnosed with primary DLBCL of the female genital tract and breast, who had formalin-fixed and paraffin-embedded tissues obtained from diagnostic samples diagnosed between January 2004 and June 2016, were analyzed retrospectively. Nineteen female patients (7 with primary breast and 12 with primary female genital tract DLBCL) were included in this retrospective study. Eleven patients (57.9%) carried a MYD88 mutation, including 10 with MYD8 L265P and 1 with the MYD88 L265S mutation. Seven patients (36.8%) harbored a CD79B mutation, which included two cases with CD79B Y196H, two cases with CD79B Y196N, one case with CD79B Y196D, one case with CD79B Y196F, and one case with CD79B Y196X. Four cases had both MYD88 and CD79B mutations. The clinicopathologic parameters, progression-free survival (PFS), and overall survival (OS) of the MYD88 mutation-carrying group were not significantly different from those of the MYD88 wild-type group except for higher LDH levels. Six patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), while 13 patients received rituximab plus CHOP, and 13 patients received central nervous system prophylaxis. The median OS and PFS were 73 and 56 months, respectively. Patients with primary breast and primary female genital tract DLBCL have a high frequency of MYD88 and CD79B mutations. The presence of these mutations does not affect survival but may offer additional therapeutic options.

  19. POLE proofreading mutations elicit an anti-tumor immune response in endometrial cancer

    Science.gov (United States)

    van Gool, Inge C; Eggink, Florine A; Freeman-Mills, Luke; Stelloo, Ellen; Marchi, Emanuele; de Bruyn, Marco; Palles, Claire; Nout, Remi A; de Kroon, Cor D; Osse, Elisabeth M; Klenerman, Paul; Creutzberg, Carien L; Tomlinson, Ian PM; Smit, Vincent THBM; Nijman, Hans W

    2015-01-01

    Purpose Recent studies have shown that 7-12% of endometrial cancers (ECs) are ultramutated due to somatic mutation in the proofreading exonuclease domain of the DNA replicase POLE. Interestingly, these tumors have an excellent prognosis. In view of the emerging data linking mutation burden, immune response and clinical outcome in cancer, we investigated whether POLE-mutant ECs showed evidence of increased immunogenicity. Experimental design We examined immune infiltration and activation according to tumor POLE proofreading mutation in a molecularly defined EC cohort including 47 POLE-mutant tumors. We sought to confirm our results by analysis of RNAseq data from the TCGA EC series and used the same series to examine whether differences in immune infiltration could be explained by an enrichment of immunogenic neoepitopes in POLE-mutant ECs. Results Compared to other ECs, POLE-mutants displayed an enhanced cytotoxic T cell response, evidenced by increased numbers of CD8+ tumor infiltrating lymphocytes and CD8A expression, enrichment for a tumor-infiltrating T cell gene signature, and strong upregulation of the T cell cytotoxic differentiation and effector markers T-bet, Eomes, IFNG, PRF and granzyme B. This was accompanied by upregulation of T cell exhaustion markers, consistent with chronic antigen exposure. In-silico analysis confirmed that POLE-mutant cancers are predicted to display more antigenic neo-epitopes than other ECs, providing a potential explanation for our findings. Conclusions Ultramutated POLE proofreading-mutant ECs are characterized by a robust intratumoral T cell response, which correlates with, and may be caused by an enrichment of antigenic neo-peptides. Our study provides a plausible mechanism for the excellent prognosis of these cancers. PMID:25878334

  20. A Mutation in the Dmp1 Gene Alters Phosphate Responsiveness in Mice

    Science.gov (United States)

    Gerard-O'Riley, Rita L.; Acton, Dena; McQueen, Amie K.; Strobel, Isabel E.; Witcher, Phillip C.; Feng, Jian Q.; Econs, Michael J.

    2017-01-01

    Mutations in the dentin matrix protein 1 (DMP1) gene cause autosomal recessive hypophosphatemic rickets (ARHR). Hypophosphatemia in ARHR results from increased circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Similarly, elevated FGF23, caused by mutations in the PHEX gene, is responsible for the hypophosphatemia in X-linked hypophosphatemic rickets (XLH). Previously, we demonstrated that a Phex mutation in mice creates a lower set point for extracellular phosphate, where an increment in phosphorus further stimulates Fgf23 production to maintain low serum phosphorus levels. To test the presence of the similar set point defect in ARHR, we generated 4- and 12-week-old Dmp1/Galnt3 double knockout mice and controls, including Dmp1 knockout mice (a murine model of ARHR), Galnt3 knockout mice (a murine model of familial tumoral calcinosis), and phenotypically normal double heterozygous mice. Galnt3 knockout mice had increased proteolytic cleavage of Fgf23, leading to low circulating intact Fgf23 levels with consequent hyperphosphatemia. In contrast, Dmp1 knockout mice had little Fgf23 cleavage and increased femoral Fgf23 expression, resulting in hypophosphatemia and low femoral bone mineral density (BMD). However, introduction of the Galnt3 null allele to Dmp1 knockout mice resulted in a significant increase in serum phosphorus and normalization of BMD. This increased serum phosphorus was accompanied by markedly elevated Fgf23 expression and circulating Fgf23 levels, an attempt to reduce serum phosphorus in the face of improving phosphorus levels. These data indicate that a Dmp1 mutation creates a lower set point for extracellular phosphate and maintains it through the regulation of Fgf23 cleavage and expression. PMID:28005411

  1. Presenilin 1 mutation decreases both calcium and contractile responses in cerebral arteries.

    Science.gov (United States)

    Toussay, Xavier; Morel, Jean-Luc; Biendon, Nathalie; Rotureau, Lolita; Legeron, François-Pierre; Boutonnet, Marie-Charlotte; Cho, Yoon H; Macrez, Nathalie

    2017-10-01

    Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early-onset Alzheimer's disease or sporadic late-onset Alzheimer's disease, respectively. PS1 has been essentially studied in neurons and its mutation was shown to alter intracellular calcium (Ca 2+ ) signals. Here, we showed that PS1 is expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca 2+ signals and contractile responses of vascular SMC. Agonist-induced contraction of cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo. Spontaneous activity of Ca 2+ sparks through ryanodine-sensitive channels (RyR) was unchanged, whereas the RyR-mediated Ca 2+ -release activated by caffeine was shorter in PS1dE9 SMC when compared with control. Moreover, PS1dE9 mutation decreased the caffeine-activated capacitive Ca 2+ entry, and inhibitors of SERCA pumps reversed the effects of PS1dE9 on Ca 2+ signals. PS1dE9 mutation also leads to the increased expression of SERCA3, phospholamban, and RyR3. These results show that PS1 plays a crucial role in the cerebrovascular system and the vascular reactivity is decreased through altered Ca 2+ signals in PS1dE9 mutant mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Halliday, Gary M. [Dermatology Research Laboratories, Division of Medicine, Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital at the University of Sydney, Sydney, NSW (Australia)]. E-mail: garyh@med.usyd.edu.au

    2005-04-01

    Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans.

  3. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

    International Nuclear Information System (INIS)

    Halliday, Gary M.

    2005-01-01

    Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans

  4. Developmental changes in ERP responses to spatial frequencies

    NARCIS (Netherlands)

    van den Boomen, Carlijn; Jonkman, Lisa M; Jaspers-Vlamings, Petra H J M; Cousijn, Janna; Kemner, Chantal

    2015-01-01

    Social interaction starts with perception of other persons. One of the first steps in perception is processing of basic information such as spatial frequencies (SF), which represent details and global information. However, although behavioural perception of SF is well investigated, the developmental

  5. Harmonic Phase Responses of Radio Frequency Electronics: Wireline Test

    Science.gov (United States)

    2015-12-01

    low- or intermediate -frequency port is terminated in a matched load. The radios were powered and left in standby mode (i.e., turned on and tuned, but...M HIGGINS D LIAO A MARTONE D MCNAMARA G MAZZARO K RANNEY M RESSLER K SHERBONDY G SMITH A SULLIVAN

  6. Influence of magnetizing and filtering frequencies on Barkhausen noise response

    Czech Academy of Sciences Publication Activity Database

    Stupakov, Oleksandr; Melikhov, Y.

    2014-01-01

    Roč. 50, č. 4 (2014), s. 6100104 ISSN 0018-9464 R&D Projects: GA ČR GA13-18993S Institutional support: RVO:68378271 Keywords : Barkhausen effect * filtering * frequency measurement * magnetic field measurement Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.386, year: 2014

  7. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma

    NARCIS (Netherlands)

    Schindler, G.; Capper, D.; Meyer, J.; Janzarik, W.; Omran, H.; Herold-Mende, C.; Schmieder, K.; Wesseling, P.; Mawrin, C.; Hasselblatt, M.; Louis, D.N.; Korshunov, A.; Pfister, S.; Hartmann, C.; Paulus, W.; Reifenberger, G.; Deimling, A. Von

    2011-01-01

    Missense mutations of the V600E type constitute the vast majority of tumor-associated somatic alterations in the v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) gene. Initially described in melanoma, colon and papillary thyroid carcinoma, these alterations have also been observed in primary

  8. Biological and clinical evidence for somatic mutations in BRCA1 and BRCA2 as predictive markers for olaparib response in high-grade serous ovarian cancers in the maintenance setting.

    Science.gov (United States)

    Dougherty, Brian A; Lai, Zhongwu; Hodgson, Darren R; Orr, Maria C M; Hawryluk, Matthew; Sun, James; Yelensky, Roman; Spencer, Stuart K; Robertson, Jane D; Ho, Tony W; Fielding, Anitra; Ledermann, Jonathan A; Barrett, J Carl

    2017-07-04

    To gain a better understanding of the role of somatic mutations in olaparib response, next-generation sequencing (NGS) of BRCA1 and BRCA2 was performed as part of a planned retrospective analysis of tumors from a randomized, double-blind, Phase II trial (Study 19; D0810C00019; NCT00753545) in 265 patients with platinum-sensitive high-grade serous ovarian cancer. BRCA1/2 loss-of-function mutations were found in 55% (114/209) of tumors, were mutually exclusive, and demonstrated high concordance with Sanger-sequenced germline mutations in matched blood samples, confirming the accuracy (97%) of tumor BRCA1/2 NGS testing. Additionally, NGS identified somatic mutations absent from germline testing in 10% (20/209) of the patients. Somatic mutations had >80% biallelic inactivation frequency and were predominantly clonal, suggesting that BRCA1/2 loss occurs early in the development of these cancers. Clinical outcomes between placebo- and olaparib-treated patients with somatic BRCA1/2 mutations were similar to those with germline BRCA1/2 mutations, indicating that patients with somatic BRCA1/2 mutations benefit from treatment with olaparib.

  9. Effect of randomness on multi-frequency aeroelastic responses resolved by Unsteady Adaptive Stochastic Finite Elements

    International Nuclear Information System (INIS)

    Witteveen, Jeroen A.S.; Bijl, Hester

    2009-01-01

    The Unsteady Adaptive Stochastic Finite Elements (UASFE) method resolves the effect of randomness in numerical simulations of single-mode aeroelastic responses with a constant accuracy in time for a constant number of samples. In this paper, the UASFE framework is extended to multi-frequency responses and continuous structures by employing a wavelet decomposition pre-processing step to decompose the sampled multi-frequency signals into single-frequency components. The effect of the randomness on the multi-frequency response is then obtained by summing the results of the UASFE interpolation at constant phase for the different frequency components. Results for multi-frequency responses and continuous structures show a three orders of magnitude reduction of computational costs compared to crude Monte Carlo simulations in a harmonically forced oscillator, a flutter panel problem, and the three-dimensional transonic AGARD 445.6 wing aeroelastic benchmark subject to random fields and random parameters with various probability distributions.

  10. High-frequency ultrasound-responsive block copolymer micelle.

    Science.gov (United States)

    Wang, Jie; Pelletier, Maxime; Zhang, Hongji; Xia, Hesheng; Zhao, Yue

    2009-11-17

    Micelles of a diblock copolymer composed of poly(ethylene oxide) and poly(2-tetrahydropyranyl methacrylate) (PEO-b-PTHPMA) in aqueous solution could be disrupted by high-frequency ultrasound (1.1 MHz). It was found that, upon exposure to a high-intensity focused ultrasound (HIFU) beam at room temperature, the pH value of the micellar solution decreased over irradiation time. The infrared spectroscopic analysis of solid block copolymer samples collected from the ultrasound irradiated micellar solution revealed the formation of carboxylic acid dimers and hydroxyl groups. These characterization results suggest that the high-frequency HIFU beam could induce the hydrolysis reaction of THPMA at room temperature resulting in the cleavage of THP groups. The disruption of PEO-b-PTHPMA micelles by ultrasound was investigated by using dynamic light scattering, atomic force microscopy, and fluorescence spectroscopy. On the basis of the pH change, it was found that the disruption process was determined by a number of factors such as the ultrasound power, the micellar solution volume and the location of the focal spot of the ultrasound beam. This study shows the potential to develop ultrasound-sensitive block copolymer micelles by having labile chemical bonds in the polymer structure, and to use the high-frequency HIFU to trigger a chemical reaction for the disruption of micelles.

  11. Determination of the theoretical and experimental zero-power frequency response of Ghana Research Reactor-1

    International Nuclear Information System (INIS)

    Intsiful, J.D.K.; Akaho, E.H.K.; Tetteh, G.K.

    1997-12-01

    The frequency response measurements of a reactor at low power help in determining the kinetic parameters of a reactor and ultimately in investigating its stability with respect to small perturbations in reactivity. In this report, we present the results of the zero-power frequency response measurements of GHARR-1 by rod method and its analytical analogue. The comparison in calculated and measured values is reasonably good in the frequency range used (author)

  12. Loss of function mutations in RP1 are responsible for retinitis pigmentosa in consanguineous familial cases

    Science.gov (United States)

    Kabir, Firoz; Ullah, Inayat; Ali, Shahbaz; Gottsch, Alexander D.H.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

    2016-01-01

    Purpose This study was undertaken to identify causal mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous families. Methods Large consanguineous families were ascertained from the Punjab province of Pakistan. An ophthalmic examination consisting of a fundus evaluation and electroretinography (ERG) was completed, and small aliquots of blood were collected from all participating individuals. Genomic DNA was extracted from white blood cells, and a genome-wide linkage or a locus-specific exclusion analysis was completed with polymorphic short tandem repeats (STRs). Two-point logarithm of odds (LOD) scores were calculated, and all coding exons and exon–intron boundaries of RP1 were sequenced to identify the causal mutation. Results The ophthalmic examination showed that affected individuals in all families manifest cardinal symptoms of RP. Genome-wide scans localized the disease phenotype to chromosome 8q, a region harboring RP1, a gene previously implicated in the pathogenesis of RP. Sanger sequencing identified a homozygous single base deletion in exon 4: c.3697delT (p.S1233Pfs22*), a single base substitution in intron 3: c.787+1G>A (p.I263Nfs8*), a 2 bp duplication in exon 2: c.551_552dupTA (p.Q185Yfs4*) and an 11,117 bp deletion that removes all three coding exons of RP1. These variations segregated with the disease phenotype within the respective families and were not present in ethnically matched control samples. Conclusions These results strongly suggest that these mutations in RP1 are responsible for the retinal phenotype in affected individuals of all four consanguineous families. PMID:27307693

  13. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations

    Science.gov (United States)

    Deng, Kai; Pertea, Mihaela; Rongvaux, Anthony; Wang, Leyao; Durand, Christine M.; Ghiaur, Gabriel; Lai, Jun; McHugh, Holly L.; Hao, Haiping; Zhang, Hao; Margolick, Joseph B.; Gurer, Cagan; Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George D.; Deeks, Steven G.; Strowig, Till; Kumar, Priti; Siliciano, Janet D.; Salzberg, Steven L.; Flavell, Richard A.; Shan, Liang; Siliciano, Robert F.

    2015-01-01

    Despite antiretroviral therapy (ART), HIV-1 persists in a stable latent reservoir1, 2, primarily in resting memory CD4+ T cells3, 4. This reservoir presents a major barrier to the cure of HIV-1 infection. To purge the reservoir, pharmacological reactivation of latent HIV-1 has been proposed5 and tested both in vitro and in vivo6–8. A key remaining question is whether virus-specific immune mechanisms including cytolytic T lymphocytes (CTL) can clear infected cells in ART-treated patients after latency is reversed. Here we show that there is a striking all or none pattern for CTL escape mutations in HIV-1 Gag epitopes. Unless ART is started early, the vast majority (>98%) of latent viruses carry CTL escape mutations that render infected cells insensitive to CTLs directed at common epitopes. To solve this problem, we identified CTLs that could recognize epitopes from latent HIV-1 that were unmutated in every chronically infected patient tested. Upon stimulation, these CTLs eliminated target cells infected with autologous virus derived from the latent reservoir, both in vitro and in patient-derived humanized mice. The predominance of CTL-resistant viruses in the latent reservoir poses a major challenge to viral eradication. Our results demonstrate that chronically infected patients retain a broad spectrum viral-specific CTL response and that appropriate boosting of this response may be required for the elimination of the latent reservoir. PMID:25561180

  14. Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

    Science.gov (United States)

    Hitti, Jane; Halvas, Elias K; Zheng, Lu; Panousis, Constantinos G; Kabanda, Joseph; Taulo, Frank; Kumarasamy, Nagalingeswaran; Pape, Jean William; Lalloo, Umesh; Sprenger, Heather; Klingman, Karin L; Chan, Ellen S; McMahon, Deborah; Mellors, John W

    2014-11-01

    Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

  15. Carrier frequency of GJB2 gene mutations c.35delG, c.235delC and c.167delT among the populations of Eurasia.

    Science.gov (United States)

    Dzhemileva, Lilya U; Barashkov, Nikolay A; Posukh, Olga L; Khusainova, Rita I; Akhmetova, Vita L; Kutuev, Ildus A; Gilyazova, Irina R; Tadinova, Vera N; Fedorova, Sardana A; Khidiyatova, Irina M; Lobov, Simeon L; Khusnutdinova, Elza K

    2010-11-01

    Hearing impairment is one of the most common disorders of sensorineural function and the incidence of profound prelingual deafness is about 1 per 1000 at birth. GJB2 gene mutations make the largest contribution to hereditary hearing impairment. The spectrum and prevalence of some GJB2 mutations are known to be dependent on the ethnic origin of the population. This study presents data on the carrier frequencies of major GJB2 mutations, c.35delG, c.167delT and c.235delC, among 2308 healthy persons from 18 various populations of Eurasia: Russians, Bashkirs, Tatars, Chuvashes, Udmurts, Komi-Permyaks and Mordvins (Volga-Ural region of Russia); Belarusians and Ukrainians (East Europe); Abkhazians, Avars, Cherkessians and Ingushes (Caucasus); Kazakhs, Uighurs and Uzbeks (Central Asia); and Yakuts and Altaians (Siberia). The data on c.35delG and c.235delC mutation prevalence in the studied ethnic groups can be used to investigate the prospective founder effect in the origin and prevalence of these mutations in Eurasia and consequently in populations around the world.

  16. Comparative analysis of drug resistance mutations in the human immunodeficiency virus reverse transcriptase gene in patients who are non-responsive, responsive and naive to antiretroviral therapy.

    Science.gov (United States)

    Misbah, Mohammad; Roy, Gaurav; Shahid, Mudassar; Nag, Nalin; Kumar, Suresh; Husain, Mohammad

    2016-05-01

    Drug resistance mutations in the Pol gene of human immunodeficiency virus 1 (HIV-1) are one of the critical factors associated with antiretroviral therapy (ART) failure in HIV-1 patients. The issue of resistance to reverse transcriptase inhibitors (RTIs) in HIV infection has not been adequately addressed in the Indian subcontinent. We compared HIV-1 reverse transcriptase (RT) gene sequences to identify mutations present in HIV-1 patients who were ART non-responders, ART responders and drug naive. Genotypic drug resistance testing was performed by sequencing a 655-bp region of the RT gene from 102 HIV-1 patients, consisting of 30 ART-non-responding, 35 ART-responding and 37 drug-naive patients. The Stanford HIV Resistance Database (HIVDBv 6.2), IAS-USA mutation list, ANRS_09/2012 algorithm, and Rega v8.02 algorithm were used to interpret the pattern of drug resistance. The majority of the sequences (96 %) belonged to subtype C, and a few of them (3.9 %) to subtype A1. The frequency of drug resistance mutations observed in ART-non-responding, ART-responding and drug-naive patients was 40.1 %, 10.7 % and 20.58 %, respectively. It was observed that in non-responders, multiple mutations were present in the same patient, while in responders, a single mutation was found. Some of the drug-naive patients had more than one mutation. Thymidine analogue mutations (TAMs), however, were found in non-responders and naive patients but not in responders. Although drug resistance mutations were widely distributed among ART non-responders, the presence of resistance mutations in the viruses of drug-naive patients poses a big concern in the absence of a genotyping resistance test.

  17. Corrections for frequency domain transformations of Winfrith binary cross correlator responses

    International Nuclear Information System (INIS)

    Cummins, J.D.

    1968-04-01

    This report considers the corrections for frequency domain transformations of Winfrith binary cross correlator responses; (i) for the finite bandwidth of the equivalent input signal; (2) for the finite time required for the actuator to move between the two positions appropriate to the two levels of the periodic binary chain code input and (3) for the averaging of experimental determinations of the system frequency response and calculations of the standard deviations of the modulus and phase of the frequency responses determined from the cross correlator responses. (author)

  18. Frequency response in surface-potential driven electrohydrodynamics

    DEFF Research Database (Denmark)

    Ejsing, Louise Wellendorph; Smistrup, Kristian; Pedersen, Christian Møller

    2006-01-01

    Using a Fourier approach we offer a general solution to calculations of slip velocity within the circuit description of the electrohydrodynamics in a binary electrolyte confined by a plane surface with a modulated surface potential. We consider the case with a spatially constant intrinsic surface...... capacitance where the net flow rate is, in general, zero while harmonic rolls as well as time-averaged vortexlike components may exist depending on the spatial symmetry and extension of the surface potential. In general, the system displays a resonance behavior at a frequency corresponding to the inverse RC...

  19. Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma

    Science.gov (United States)

    Ilieva, Kristina M.; Correa, Isabel; Josephs, Debra H.; Karagiannis, Panagiotis; Egbuniwe, Isioma U.; Cafferkey, Michiala J.; Spicer, James F.; Harries, Mark; Nestle, Frank O.; Lacy, Katie E.; Karagiannis, Sophia N.

    2014-01-01

    Malignant melanoma is associated with poor clinical prognosis; however, novel molecular and immune therapies are now improving patient outcomes. Almost 50% of melanomas harbor targetable activating mutations of BRAF which promote RAS-RAF-MEK-ERK pathway activation and melanoma proliferation. Recent evidence also indicates that melanomas bearing mutant BRAF may also have altered immune responses, suggesting additional avenues for treatment of this patient group. The small molecule inhibitors selective for mutant BRAF induce significant but short-lived clinical responses in a proportion of patients, but also lead to immune stimulatory bystander events, which then subside with the emergence of resistance to inhibition. Simultaneous BRAF and MEK inhibition, and especially combination of BRAF inhibitors with new immunotherapies such as checkpoint blockade antibodies, may further enhance immune activation, or counteract immunosuppressive signals. Pre-clinical evaluation and ongoing clinical trials should provide novel insights into the role of immunity in the therapy of BRAF-mutant melanoma. PMID:25385327

  20. Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM.

    Science.gov (United States)

    Biswas, Nidhan K; Chandra, Vikas; Sarkar-Roy, Neeta; Das, Tapojyoti; Bhattacharya, Rabindra N; Tripathy, Laxmi N; Basu, Sunandan K; Kumar, Shantanu; Das, Subrata; Chatterjee, Ankita; Mukherjee, Ankur; Basu, Pryiadarshi; Maitra, Arindam; Chattopadhyay, Ansuman; Basu, Analabha; Dhara, Surajit

    2015-01-21

    Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy response in GBM is predetermined in its neoplastic clones via a specific set of mutations that alter relevant pathways. We describe exome-wide enrichment of variant allele frequencies (VAFs) in neurospheres displaying contrasting phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ-effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ-effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh) pathways in reversible TMZ-effect cells. Next, we validated the likely involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as well as on GBM patients, by extracting RNA-sequencing-based gene expression data from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ non-responder neurosphere in vitro by treating them with the FDA-approved pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate that the Hh-pathway impedes sustained TMZ-response in GBM and could be a potential therapeutic target to enhance TMZ-response in this malignancy.

  1. HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

    KAUST Repository

    Boulbes, Delphine R.

    2014-11-11

    Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.

  2. HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

    KAUST Repository

    Boulbes, Delphine R.; Arold, Stefan T.; Chauhan, Gaurav B.; Blachno, Korina V.; Deng, Nanfu; Chang, Wei-Chao; Jin, Quanri; Huang, Tzu-Hsuan; Hsu, Jung-Mao; Brady, Samuel W.; Bartholomeusz, Chandra; Ladbury, John E.; Stone, Steve; Yu, Dihua; Hung, Mien-Chie; Esteva, Francisco J.

    2014-01-01

    Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.

  3. Frequency of CCR5 Delta-32 Mutation in Human Immunodeficiency Virus (HIV-seropositive and HIV-exposed Seronegative Individuals and in General Population of Medellin, Colombia

    Directory of Open Access Journals (Sweden)

    Francisco J Díaz

    2000-04-01

    Full Text Available Repeated exposure to human immunodeficiency virus (HIV does not always result in seroconversion. Modifications in coreceptors for HIV entrance to target cells are one of the factors that block the infection. We studied the frequency of Delta-32 mutation in ccr5 gene in Medellin, Colombia. Two hundred and eighteen individuals distributed in three different groups were analyzed for Delta-32 mutation in ccr5 gene by polymerase chain reaction (PCR: 29 HIV seropositive (SP, 39 exposed seronegative (ESN and 150 individuals as a general population sample (GPS. The frequency of the Delta-32 mutant allele was 3.8% for ESN, 2.7% for GPS and 1.7% for SP. Only one homozygous mutant genotype (Delta-32/Delta-32 was found among the ESN (2.6%. The heterozygous genotype (ccr5/Delta-32 was found in eight GPS (5.3%, in one SP (3.4% and in one ESN (2.6%. The differences in the allelic and genotypic frequencies among the three groups were not statistically significant. A comparison between the expected and the observed genotypic frequencies showed that these frequencies were significantly different for the ESN group, which indirectly suggests a protective effect of the mutant genotype (Delta-32/Delta-32. Since this mutant genotype explained the resistance of infection in only one of our ESN persons, different mechanisms of protection must be playing a more important role in this population.

  4. Efficient 3D frequency response modeling with spectral accuracy by the rapid expansion method

    KAUST Repository

    Chu, Chunlei

    2012-07-01

    Frequency responses of seismic wave propagation can be obtained either by directly solving the frequency domain wave equations or by transforming the time domain wavefields using the Fourier transform. The former approach requires solving systems of linear equations, which becomes progressively difficult to tackle for larger scale models and for higher frequency components. On the contrary, the latter approach can be efficiently implemented using explicit time integration methods in conjunction with running summations as the computation progresses. Commonly used explicit time integration methods correspond to the truncated Taylor series approximations that can cause significant errors for large time steps. The rapid expansion method (REM) uses the Chebyshev expansion and offers an optimal solution to the second-order-in-time wave equations. When applying the Fourier transform to the time domain wavefield solution computed by the REM, we can derive a frequency response modeling formula that has the same form as the original time domain REM equation but with different summation coefficients. In particular, the summation coefficients for the frequency response modeling formula corresponds to the Fourier transform of those for the time domain modeling equation. As a result, we can directly compute frequency responses from the Chebyshev expansion polynomials rather than the time domain wavefield snapshots as do other time domain frequency response modeling methods. When combined with the pseudospectral method in space, this new frequency response modeling method can produce spectrally accurate results with high efficiency. © 2012 Society of Exploration Geophysicists.

  5. A double expansion method for the frequency response of finite-length beams with periodic parameters

    Science.gov (United States)

    Ying, Z. G.; Ni, Y. Q.

    2017-03-01

    A double expansion method for the frequency response of finite-length beams with periodic distribution parameters is proposed. The vibration response of the beam with spatial periodic parameters under harmonic excitations is studied. The frequency response of the periodic beam is the function of parametric period and then can be expressed by the series with the product of periodic and non-periodic functions. The procedure of the double expansion method includes the following two main steps: first, the frequency response function and periodic parameters are expanded by using identical periodic functions based on the extension of the Floquet-Bloch theorem, and the period-parametric differential equation for the frequency response is converted into a series of linear differential equations with constant coefficients; second, the solutions to the linear differential equations are expanded by using modal functions which satisfy the boundary conditions, and the linear differential equations are converted into algebraic equations according to the Galerkin method. The expansion coefficients are obtained by solving the algebraic equations and then the frequency response function is finally determined. The proposed double expansion method can uncouple the effects of the periodic expansion and modal expansion so that the expansion terms are determined respectively. The modal number considered in the second expansion can be reduced remarkably in comparison with the direct expansion method. The proposed double expansion method can be extended and applied to the other structures with periodic distribution parameters for dynamics analysis. Numerical results on the frequency response of the finite-length periodic beam with various parametric wave numbers and wave amplitude ratios are given to illustrate the effective application of the proposed method and the new frequency response characteristics, including the parameter-excited modal resonance, doubling-peak frequency response

  6. The frequencies and clinical implications of mutations in 33 kinase-related genes in locally advanced rectal cancer: a pilot study.

    LENUS (Irish Health Repository)

    Abdul-Jalil, Khairun I

    2014-08-01

    Locally advanced rectal cancer (LARC: T3\\/4 and\\/or node-positive) is treated with preoperative\\/neoadjuvant chemoradiotherapy (CRT), but responses are not uniform. The phosphatidylinositol 3-kinase (PI3K), MAP kinase (MAPK), and related pathways are implicated in rectal cancer tumorigenesis. Here, we investigated the association between genetic mutations in these pathways and LARC clinical outcomes.

  7. Mutations of the SRY-responsive enhancer of SOX9 are uncommon in XY gonadal dysgenesis.

    Science.gov (United States)

    Georg, I; Bagheri-Fam, S; Knower, K C; Wieacker, P; Scherer, Gerd; Harley, V R

    2010-01-01

    During mouse sex determination, SRY upregulates the core testis-specific enhancer of Sox9, TESCO. Mutations in human SRY are found in one third of cases with XY pure gonadal dysgenesis (XY GD; Swyer syndrome), while two thirds remain unexplained. Heterozygous SOX9 mutations can cause XY GD in association with the skeletal malformation syndrome campomelic dysplasia. We hypothesized that human TESCO mutations could cause isolated XY GD. Sixty-six XY GD cases with an intact SRY were analyzed for TESCO point mutations or deletions. No mutations were identified. We conclude that TESCO mutations are not a common cause of XY GD. Copyright © 2010 S. Karger AG, Basel.

  8. Temporal frequency of knockdown resistance mutations, F1534C and V1016G, in Aedes aegypti in Chiang Mai city, Thailand and the impact of the mutations on the efficiency of thermal fogging spray with pyrethroids.

    Science.gov (United States)

    Plernsub, Suriya; Saingamsook, Jassada; Yanola, Jintana; Lumjuan, Nongkran; Tippawangkosol, Pongsri; Walton, Catherine; Somboon, Pradya

    2016-10-01

    In Thailand, control of dengue outbreaks is currently attained by the use of space sprays, particularly thermal fogging using pyrethroids, with the aim of killing infected Aedes mosquito vectors in epidemic areas. However, the principal dengue vector, Aedes aegypti, is resistant to pyrethroids conferred mainly by mutations in the voltage-gated sodium channel gene, F1534C and V1016G, termed knockdown resistance (kdr). The objectives of this study were to determine the temporal frequencies of F1534C and V1016G in Ae. aegypti populations in relation to pyrethroid resistance in Chiang Mai city, and to evaluate the impact of the mutations on the efficacy of thermal fogging with the pyrethroid deltamethrin. Larvae and pupae were collected from several areas around Chiang Mai city during 2011-2015 and reared to adulthood for bioassays for deltamethrin susceptibility. These revealed no trend of increasing deltamethrin resistance during the study period (mortality 58.0-69.5%, average 62.8%). This corresponded to no overall change in the frequencies of the C1534 allele (0.55-0.66, average 0.62) and G1016 allele (0.34-0.45, average 0.38), determined using allele specific amplification. Only three genotypes of kdr mutations were detected: C1534 homozygous (VV/CC); G1016/C1534 double heterozygous (VG/FC); and G1016 homozygous (GG/FF) indicating that the F1534C and V1016G mutations occurred on separate haplotypic backgrounds and a lack of recombination between them to date. The F1 progeny females were used to evaluate the efficacy of thermal fogging spray with Damthrin-SP(®) (deltamethrin+S-bioallethrin+piperonyl butoxide) using a caged mosquito bioassay. The thermal fogging spray killed 100% and 61.3% of caged mosquito bioassay placed indoors and outdoors, respectively. The outdoor spray had greater killing effect on C1534 homozygous and had partially effect on double heterozygous mosquitoes, but did not kill any G1016 homozygous mutants living outdoors. As this selection

  9. Frequency of the LRRK2 G2019S mutation in late-onset sporadic patients with Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Hsin Fen Chien

    2014-05-01

    Full Text Available Mutations in the LRRK2 gene, predominantly G2019S, have been reported in individuals with autosomal dominant inheritance and sporadic Parkinson’s disease (PD. The G2019S mutation has an age-dependent penetrance and evidence shows common ancestry. The clinical manifestations are indistinguishable from idiopathic PD. Its prevalence varies according to the population studied ranging from less than 0.1% in Asians to 41% in North African Arabs. This study aimed to identify G2019S mutation in Brazilian idiopathic PD patients. Method: We sampled 100 PD patients and 100 age- and gender-matched controls. Genetical analysis was accomplished by polymerase chain reaction (PCR. Results: No G2019S mutations were found in both patients with sporadic PD and controls. Conclusions: Our results may be explained by the relatively small sample size.

  10. Frequency of the CHEK2 1100delC mutation among women with breast cancer: an international study.

    Science.gov (United States)

    Zhang, Shiyu; Phelan, Catherine M; Zhang, Phil; Rousseau, Francois; Ghadirian, Parviz; Robidoux, Andre; Foulkes, William; Hamel, Nancy; McCready, David; Trudeau, Maureen; Lynch, Henry; Horsman, Douglas; De Matsuda, Maria Lourdes Leon; Aziz, Zeba; Gomes, Magda; Costa, Mauricio Magalhaes; Liede, Alexander; Poll, Aletta; Sun, Ping; Narod, Steven A

    2008-04-01

    A founder allele in the CHEK2 gene (1100delC) has been associated with an elevated risk of breast cancer. This allele is responsible for the majority of CHEK2-associated breast cancers in women from northern European countries; however, within Europe, it seems to be rare in countries that are close to the Mediterranean. The frequency of the 1100delC allele has not been measured in non-White populations. We measured the frequency of the CHEK2 founder allele in 3,882 breast cancer patients and 8,609 controls from various countries. The allele was not seen among Asian patients (from Pakistan or the Philippines) and was present in 1 of 155 cases from Brazil. Among White women, the allele was present in 1.5% of 825 familial cases of breast cancer and in 0.7% of 1,106 patients with nonfamilial breast cancer. The allele was equally frequent in Jewish and non-Jewish patients. We estimate that the CHEK2 1100delC allele is associated with an odds ratio of 2.6 for breast cancer, which corresponds to a lifetime risk of approximately 24% in Ontario.

  11. Levels of H-ras codon 61 CAA to AAA mutation: response to 4-ABP-treatment and Pms2-deficiency.

    Science.gov (United States)

    Parsons, Barbara L; Delongchamp, Robert R; Beland, Frederick A; Heflich, Robert H

    2006-01-01

    DNA mismatch repair (MMR) deficiencies result in increased frequencies of spontaneous mutation and tumor formation. In the present study, we tested the hypothesis that a chemically-induced mutational response would be greater in a mouse with an MMR-deficiency than in the MMR-proficient mouse models commonly used to assay for chemical carcinogenicity. To accomplish this, the induction of H-ras codon 61 CAA-->AAA mutation was examined in Pms2 knockout mice (Pms2-/-, C57BL/6 background) and sibling wild-type mice (Pms2+/+). Groups of five or six neonatal male mice were treated with 0.3 micromol 4-aminobiphenyl (4-ABP) or the vehicle control, dimethylsulfoxide. Eight months after treatment, liver DNAs were isolated and analysed for levels of H-ras codon 61 CAA-->AAA mutation using allele-specific competitive blocker-PCR. In Pms2-proficient and Pms2-deficient mice, 4-ABP treatment caused an increase in mutant fraction (MF) from 1.65x10(-5) to 2.91x10(-5) and from 3.40x10(-5) to 4.70x10(-5), respectively. Pooling data from 4-ABP-treated and control mice, the approximately 2-fold increase in MF observed in Pms2-deficient as compared with Pms2-proficient mice was statistically significant (P=0.0207) and consistent with what has been reported previously in terms of induction of G:C-->T:A mutation in a Pms2-deficient background. Pooling data from both genotypes, the increase in H-ras MF in 4-ABP-treated mice, as compared with control mice, did not reach the 95% confidence level of statistical significance (P=0.0606). The 4-ABP treatment caused a 1.76-fold and 1.38-fold increase in average H-ras MF in Pms2-proficient and Pms2-deficient mice, respectively. Furthermore, the levels of induced mutation in Pms2-proficient and Pms2-deficient mice were nearly identical (1.26x10(-5) and 1.30x10(-5), respectively). We conclude that Pms2-deficiency does not result in an amplification of the H-ras codon 61 CAA-->AAA mutational response induced by 4-ABP.

  12. Maturity Onset Diabetes of the Young (MODY) in Tunisia: Low frequencies of GCK and HNF1A mutations.

    Science.gov (United States)

    Ben Khelifa, S; Martinez, R; Dandana, A; Khochtali, I; Ferchichi, S; Castaño, L

    2018-04-20

    Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes characterized by autosomal dominant inheritance, an early clinical onset and a primary defect in β-cell function. Mutations in the GCK and HNF1A genes are the most common cause of MODY among Caucasians. The etiology of MODY in Tunisia stills a challenge for researchers. The aim of this study was to screen for mutations in GCK, HNF1A, HNF4A and INS genes in North African Tunisians subjects, in whom the clinical profile was very suggestive of MODY. A total of 23 unrelated patients, with clinical presentation of MODY were tested for mutations in GCK, HNF1A, HNF4A and INS genes, using Denaturing High Performance Liquid Chromatography (DHPLC), Multiplex Ligation-depend Probe Amplification (MLPA) and sequencing analysis. We identified the previously reported mutation c-169C > T in one patient as well as a new mutation c-457C > T in two unrelated patients. No mutations were detected in the HNF1A and INS genes. Despite restrictive clinical criteria used for selecting patients in this study, the most common genes known for MODY do not explain the majority of cases in Tunisians. This suggests that there are others candidate or unidentified genes contributing to the etiology of MODY in Tunisians families. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Thiamine responsive megaloblastic anemia: a novel SLC19A2 compound heterozygous mutation in two siblings.

    Science.gov (United States)

    Mozzillo, Enza; Melis, Daniela; Falco, Mariateresa; Fattorusso, Valentina; Taurisano, Roberta; Flanagan, Sarah E; Ellard, Sian; Franzese, Adriana

    2013-08-01

    Thiamine responsive megaloblastic anemia (TRMA) is an autosomal recessive disease caused by loss of function mutations in the SLC19A2 gene. TRMA is characterized by anemia, deafness, and diabetes. In some cases, optic atrophy or more rarely retinitis pigmentosa is noted. We now report two sisters, the eldest of which presented to a different hospital during childhood with sensorineural deafness, which was treated with a hearing prosthesis, insulin requiring diabetes, retinitis pigmentosa, optic atrophy, and macrocytic anemia. These features initially suggested a clinical diagnosis of Wolfram syndrome (WS). Therapy with thiamine was initiated which resulted in the resolution of the anemia. The younger sister, who was affected with sensorineural deafness, was referred to our hospital for non-autoimmune diabetes. She was found to have macrocytosis and ocular abnormalities. Because a diagnosis of TRMA was suspected, therapy with insulin and thiamine was started. Sequencing analysis of the SLC19A2 gene identified a compound heterozygous mutation p.Y81X/p.L457X (c.242insA/c.1370delT) in both sisters. Non-autoimmune diabetes associated with deafness and macrocytosis, without anemia, suggests a diagnosis of TRMA. Patients clinically diagnosed with WS with anemia and/or macrocytosis should be reevaluated for TRMA. © 2012 John Wiley & Sons A/S.

  14. Ultra-wide frequency response measurement of an optical system with a DC photo-detector

    KAUST Repository

    Kuntz, Katanya B.; Wheatley, Trevor A.; Song, Hongbin; Webb, James G.; Mabrok, Mohamed; Huntington, Elanor H.; Yonezawa, Hidehiro

    2017-01-01

    Precise knowledge of an optical device's frequency response is crucial for it to be useful in most applications. Traditional methods for determining the frequency response of an optical system (e.g. optical cavity or waveguide modulator) usually rely on calibrated broadband photo-detectors or complicated RF mixdown operations. As the bandwidths of these devices continue to increase, there is a growing need for a characterization method that does not have bandwidth limitations, or require a previously calibrated device. We demonstrate a new calibration technique on an optical system (consisting of an optical cavity and a high-speed waveguide modulator) that is free from limitations imposed by detector bandwidth, and does not require a calibrated photo-detector or modulator. We use a low-frequency (DC) photo-detector to monitor the cavity's optical response as a function of modulation frequency, which is also used to determine the modulator's frequency response. Knowledge of the frequency-dependent modulation depth allows us to more precisely determine the cavity's characteristics (free spectral range and linewidth). The precision and repeatability of our technique is demonstrated by measuring the different resonant frequencies of orthogonal polarization cavity modes caused by the presence of a non-linear crystal. Once the modulator has been characterized using this simple method, the frequency response of any passive optical element can be determined to a fine resolution (e.g. kilohertz) over several gigahertz.

  15. Ultra-wide frequency response measurement of an optical system with a DC photo-detector

    KAUST Repository

    Kuntz, Katanya B.

    2017-01-09

    Precise knowledge of an optical device\\'s frequency response is crucial for it to be useful in most applications. Traditional methods for determining the frequency response of an optical system (e.g. optical cavity or waveguide modulator) usually rely on calibrated broadband photo-detectors or complicated RF mixdown operations. As the bandwidths of these devices continue to increase, there is a growing need for a characterization method that does not have bandwidth limitations, or require a previously calibrated device. We demonstrate a new calibration technique on an optical system (consisting of an optical cavity and a high-speed waveguide modulator) that is free from limitations imposed by detector bandwidth, and does not require a calibrated photo-detector or modulator. We use a low-frequency (DC) photo-detector to monitor the cavity\\'s optical response as a function of modulation frequency, which is also used to determine the modulator\\'s frequency response. Knowledge of the frequency-dependent modulation depth allows us to more precisely determine the cavity\\'s characteristics (free spectral range and linewidth). The precision and repeatability of our technique is demonstrated by measuring the different resonant frequencies of orthogonal polarization cavity modes caused by the presence of a non-linear crystal. Once the modulator has been characterized using this simple method, the frequency response of any passive optical element can be determined to a fine resolution (e.g. kilohertz) over several gigahertz.

  16. Distinguishing Buried Objects in Extremely Shallow Underground by Frequency Response Using Scanning Laser Doppler Vibrometer

    Science.gov (United States)

    Touma Abe,; Tsuneyoshi Sugimoto,

    2010-07-01

    A sound wave vibration using a scanning laser Doppler vibrometer are used as a method of exploring and imaging an extremely shallow underground. Flat speakers are used as a vibration source. We propose a method of distinguishing a buried object using a response range of a frequencies corresponding to a vibration velocities. Buried objects (plastic containers, a hollow steel can, an unglazed pot, and a stone) are distinguished using a response range of frequencies. Standardization and brightness imaging are used as methods of discrimination. As a result, it was found that the buried objects show different response ranges of frequencies. From the experimental results, we confirmed the effectiveness of our proposed method.

  17. The determination of frequency response function of the RSG Gas by laplace transform analysis

    International Nuclear Information System (INIS)

    Tukiran, S.; Surian, P.; Jujuratisbela, U.

    1997-01-01

    The response function of the RSG-GAS reactor system to the reactivity perturbations is necessary to be analyzed due to the interrelation with reliability and safety of reactor operation. the response depends on the power frequency response function H(s), while H(s) depends on the zero power frequency response function Z(s) and dynamic power coefficient of reactivity Kp(s) determination of the frequency response function of the RSG-GAS reactor was done by Fourier transform analysis method. Z(s) was obtained by fourier transform of P(t) and Cj(t) became P(S) and Cj(s) in point kinetic equations. Second order of simpson rule was used for completion of its numerical integration. then. LYMPR (Laplace transform for multipurpose reactor) code was made with fortran 77 computer language in vax 8550 system. the LTMPR code is able to determine the frequency response function and period-reactivity relation of RSG-GAS reactor by rod drop method. Profile of power as rod drop, zero power (without reactivity feedback) was used for determination frequency response of RSG-GAS reactor. The results of calculations are in a good agreement with experiment result, so the LTMPR code can be used for analysis response frequency of the RSG-GAS reactor

  18. Classification of frequency response areas in the inferior colliculus reveals continua not discrete classes.

    Science.gov (United States)

    Palmer, Alan R; Shackleton, Trevor M; Sumner, Christian J; Zobay, Oliver; Rees, Adrian

    2013-08-15

    A differential response to sound frequency is a fundamental property of auditory neurons. Frequency analysis in the cochlea gives rise to V-shaped tuning functions in auditory nerve fibres, but by the level of the inferior colliculus (IC), the midbrain nucleus of the auditory pathway, neuronal receptive fields display diverse shapes that reflect the interplay of excitation and inhibition. The origin and nature of these frequency receptive field types is still open to question. One proposed hypothesis is that the frequency response class of any given neuron in the IC is predominantly inherited from one of three major afferent pathways projecting to the IC, giving rise to three distinct receptive field classes. Here, we applied subjective classification, principal component analysis, cluster analysis, and other objective statistical measures, to a large population (2826) of frequency response areas from single neurons recorded in the IC of the anaesthetised guinea pig. Subjectively, we recognised seven frequency response classes (V-shaped, non-monotonic Vs, narrow, closed, tilt down, tilt up and double-peaked), that were represented at all frequencies. We could identify similar classes using our objective classification tools. Importantly, however, many neurons exhibited properties intermediate between these classes, and none of the objective methods used here showed evidence of discrete response classes. Thus receptive field shapes in the IC form continua rather than discrete classes, a finding consistent with the integration of afferent inputs in the generation of frequency response areas. The frequency disposition of inhibition in the response areas of some neurons suggests that across-frequency inputs originating at or below the level of the IC are involved in their generation.

  19. The effect of feeding frequency on insulin and ghrelin responses in human subjects

    DEFF Research Database (Denmark)

    Solomon, Thomas; Chambers, Edward S; Jeukendrup, Asker E

    2008-01-01

    Recent work shows that increased meal frequency reduces ghrelin responses in sheep. Human research suggests there is an interaction between insulin and ghrelin. The effect of meal frequency on this interaction is unknown. Therefore, we investigated the effect of feeding frequency on insulin...... and ghrelin responses in human subjects. Five healthy male volunteers were recruited from the general population: age 24 (SEM 2)years, body mass 75.7 (SEM 3.2) kg and BMI 23.8 (SEM 0.8) kg/m(2). Volunteers underwent three 8-h feeding regimens: fasting (FAST); low-frequency(two) meal ingestion (LOFREQ......(MEAL)); high-frequency (twelve) meal ingestion (HIFREQ(MEAL)). Meals were equi-energetic within trials,consisting of 64% carbohydrate, 23% fat and 13% protein. Total energy intake was equal between feeding trials. Total area under the curve for serum insulin and plasma ghrelin responses did not differ between...

  20. Five recurrent BRCA1/2 mutations are responsible for cancer predisposition in the majority of Slovenian breast cancer families

    Directory of Open Access Journals (Sweden)

    Novakovic Srdjan

    2008-09-01

    Full Text Available Abstract Background Both recurrent and population specific mutations have been found in different areas of the world and more specifically in ethnically defined or isolated populations. The population of Slovenia has over several centuries undergone limited mixing with surrounding populations. The current study was aimed at establishing the mutation spectrum of BRCA1/2 in the Slovenian breast/ovarian cancer families taking advantage of a complete cancer registration database. A second objective was to determine the cancer phenotype of these families. Methods The original population database was composed of cancer patients from the Institute of Oncology Ljubljana in Slovenia which also includes current follow-up status on these patients. The inclusion criteria for the BRCA1/2 screening were: (i probands with at least two first degree relatives with breast and ovarian cancer; (ii probands with only two first degree relatives of breast cancer where one must be diagnosed less than 50 years of age; and (iii individual patients with breast and ovarian cancer, bilateral breast cancer, breast cancer diagnosed before the age of 40 and male breast cancer without any other cancer in the family. Results Probands from 150 different families met the inclusion criteria for mutation analysis of which 145 consented to testing. A BRCA1/2 mutation was found in 56 (39%. Two novel large deletions covering consecutive exons of BRCA1 were found. Five highly recurrent specific mutations were identified (1806C>T, 300T>G, 300T>A, 5382insC in the BRCA1 gene and IVS16-2A>G in the BRCA2 gene. The IVS16-2A>G in the BRCA2 gene appears to be a unique founder mutation in the Slovenian population. A practical implication is that only 4 PCR fragments can be used in a first screen and reveal the cancer predisposing mutation in 67% of the BRCA1/2 positive families. We also observed an exceptionally high frequency of 4 different pathogenic missense mutations, all affecting one of

  1. Classification of frequency response areas in the inferior colliculus reveals continua not discrete classes

    OpenAIRE

    Palmer, Alan R; Shackleton, Trevor M; Sumner, Christian J; Zobay, Oliver; Rees, Adrian

    2013-01-01

    A differential response to sound frequency is a fundamental property of auditory neurons. Frequency analysis in the cochlea gives rise to V-shaped tuning functions in auditory nerve fibres, but by the level of the inferior colliculus (IC), the midbrain nucleus of the auditory pathway, neuronal receptive fields display diverse shapes that reflect the interplay of excitation and inhibition. The origin and nature of these frequency receptive field types is still open to question. One proposed hy...

  2. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Aguirre

    2007-06-01

    Full Text Available RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA. Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA.RPE65-mutant dogs were studied with fMRI. Prior to therapy, retinal and subcortical responses to light were markedly diminished, and there were minimal cortical responses within the primary visual areas of the lateral gyrus (activation amplitude mean +/- standard deviation [SD] = 0.07% +/- 0.06% and volume = 1.3 +/- 0.6 cm(3. Following therapy, retinal and subcortical response restoration was accompanied by increased amplitude (0.18% +/- 0.06% and volume (8.2 +/- 0.8 cm(3 of activation within the lateral gyrus (p < 0.005 for both. Cortical recovery occurred rapidly (within a month of treatment and was persistent (as long as 2.5 y after treatment. Recovery was present even when treatment was provided as late as 1-4 y of age. Human RPE65-LCA patients (ages 18-23 y were studied with structural magnetic resonance imaging. Optic nerve diameter (3.2 +/- 0.5 mm was within the normal range (3.2 +/- 0.3 mm, and occipital cortical white matter density as judged by voxel-based morphometry was slightly but significantly altered (1.3 SD below control average, p = 0.005. Functional magnetic resonance imaging in human RPE65-LCA patients revealed cortical responses with a markedly diminished activation volume (8.8 +/- 1.2 cm(3 compared to controls

  3. A new mutation in WFS1 gene (C.1522-1523delTA, Y508fsX421) may be responsible for early appearance of clinical features of Wolfram syndrome and suicidal behaviour.

    Science.gov (United States)

    Aluclu, Mehmet Ufuk; Bahceci, Mithat; Tuzcu, Alpaslan; Arikan, Senay; Gokalp, Deniz

    2006-12-01

    Wolfram syndrome (WS) is an autosomal recessive disorder characterized by the association of juvenile-onset diabetes mellitus and optic atrophy. It is also known by the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). We diagnosed Wolfram syndrome in 2 male siblings and determined a new mutation (c. 1522-1523delTA, Y508fsX421). Both affected siblings were homozygous, other family members were heterozygous. Dilated renal outflow tracts in the third decade, and neuropsychiatric disorders including bipolar disorder and neurosensorial deafness appear in the fourth decade in ordinary WS, whereas these features appeared in second decade in our patients. This mutation may be responsible for early appearance of dilated renal outflow tracts and multiple neurological abnormalities. Psychiatric disturbances such as suicide were reported at increased frequency in Wolfram patients and in heterozygous carriers. Suicidal behaviour occurred in our patients when they were yet 11 and 13 years old. Therefore, our findings may indicate that there may be a relationship between this WFS1 mutation and mood disorder such as suicidal behaviour. We determined a new mutation (c. 1522-1523delTA, Y508fsX421) in WS1 gene in 2 siblings with Wolfram syndrome. This mutation may be responsible for early appearance of clinical features of Wolfram syndrome, and there may be a relationship between this mutation and suicidal behaviour.

  4. Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses.

    Science.gov (United States)

    Lau, Colleen M; Nish, Simone A; Yogev, Nir; Waisman, Ari; Reiner, Steven L; Reizis, Boris

    2016-03-07

    A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L). Constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. Pre-leukemic mice with the Flt3(ITD) knock-in allele manifested an expansion of classical DCs (cDCs) and plasmacytoid DCs. The expansion originated in DC progenitors, was cell intrinsic, and was further enhanced in Flt3(ITD/ITD) mice. The mutation caused the down-regulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Both canonical Batf3-dependent CD8(+) cDCs and noncanonical CD8(+) cDCs were expanded and showed specific alterations in their expression profiles. Flt3(ITD) mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T (T reg) cells. Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity without T reg cells. Thus, the FLT3-ITD mutation directly affects DC development, indirectly modulating T cell homeostasis and supporting T reg cell expansion. We hypothesize that this effect of FLT3-ITD might subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner. © 2016 Lau et al.

  5. Real Time Optimal Control of Supercapacitor Operation for Frequency Response

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Yusheng; Panwar, Mayank; Mohanpurkar, Manish; Hovsapian, Rob

    2016-07-01

    Supercapacitors are gaining wider applications in power systems due to fast dynamic response. Utilizing supercapacitors by means of power electronics interfaces for power compensation is a proven effective technique. For applications such as requency restoration if the cost of supercapacitors maintenance as well as the energy loss on the power electronics interfaces are addressed. It is infeasible to use traditional optimization control methods to mitigate the impacts of frequent cycling. This paper proposes a Front End Controller (FEC) using Generalized Predictive Control featuring real time receding optimization. The optimization constraints are based on cost and thermal management to enhance to the utilization efficiency of supercapacitors. A rigorous mathematical derivation is conducted and test results acquired from Digital Real Time Simulator are provided to demonstrate effectiveness.

  6. Frequency of bullying at work, physiological response, and mental health.

    Science.gov (United States)

    Hansen, Åse Marie; Hogh, Annie; Persson, Roger

    2011-01-01

    The present study aimed to elucidate the relationship between bullying at work and cortisol secretion. Of particular interest was to examine whether frequently and occasionally bullied persons differed from nonbullied persons. The study included 1944 employees (1413 women and 531 men) from 55 workplaces in Denmark (16 private and 39 public workplaces). During a work day three saliva samples were collected at awakening, +30 min later, and at 20:00 hours, and analyzed for cortisol concentrations. Mental health was assessed using items on somatic, cognitive, stress, and depressive mood. Of the 1944 employees, 1.1% was frequently bullied and 7.2% occasionally bullied. Frequently bullied persons reported poorer mental health and had a 24.8% lower salivary cortisol concentration compared with the nonbullied reference group. Occasionally bullied persons had a poorer self-reported mental health, but their cortisol concentrations did not deviate from the group of nonbullied persons. The associations remained significant even after controlling for age, gender, exact time of sampling, mental health, and duration of bullying. Bullying occurred at 78% of the workplaces (43 workplaces); frequent bullying occurred at 21% of the workplaces (40%). Frequent bullying was associated with lower salivary cortisol concentrations. No such association was observed for occasional bullying. Whether the generally lower secretion of cortisol among the frequently bullied persons indicate an altered physiological status remains to be evaluated in future studies. Yet, the physiological response seems to underscore the possibility that bullying indeed may have measurable physiological consequences. Hence, the physiological response supports the mental symptoms found among the frequently bullied. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. IPNV with high and low virulence: host immune responses and viral mutations during infection

    Directory of Open Access Journals (Sweden)

    Skjesol Astrid

    2011-08-01

    Full Text Available Abstract Background Infectious pancreatic necrosis virus (IPNV is an aquatic member of the Birnaviridae family that causes widespread disease in salmonids. IPNV is represented by multiple strains with markedly different virulence. Comparison of isolates reveals hyper variable regions (HVR, which are presumably associated with pathogenicity. However little is known about the rates and modes of sequence divergence and molecular mechanisms that determine virulence. Also how the host response may influence IPNV virulence is poorly described. Methods In this study we compared two field isolates of IPNV (NFH-Ar and NFH-El. The sequence changes, replication and mortality were assessed following experimental challenge of Atlantic salmon. Gene expression analyses with qPCR and microarray were applied to examine the immune responses in head kidney. Results Significant differences in mortality were observed between the two isolates, and viral load in the pancreas at 13 days post infection (d p.i. was more than 4 orders of magnitude greater for NFH-Ar in comparison with NFH-El. Sequence comparison of five viral genes from the IPNV isolates revealed different mutation rates and Ka/Ks ratios. A strong tendency towards non-synonymous mutations was found in the HRV of VP2 and in VP3. All mutations in VP5 produced precocious stop codons. Prior to the challenge, NFH-Ar and NFH-El possessed high and low virulence motifs in VP2, respectively. Nucleotide substitutions were noticed already during passage of viruses in CHSE-214 cells and their accumulation continued in the challenged fish. The sequence changes were notably directed towards low virulence. Co-ordinated activation of anti-viral genes with diverse functions (IFN-a1 and c, sensors - Rig-I, MDA-5, TLR8 and 9, signal transducers - Srk2, MyD88, effectors - Mx, galectin 9, galectin binding protein, antigen presentation - b2-microglobulin was observed at 13 d p.i. (NFH-Ar and 29 d p.i. (both isolates

  8. Dramatic Response with Single-Agent Ibrutinib in Multiply Relapsed Marginal Zone Lymphoma with MYD88L265P Mutation

    Directory of Open Access Journals (Sweden)

    Ryan C. Lynch

    2017-09-01

    Full Text Available The B-cell receptor signaling pathway is important in the lymphomagenesis of many lymphomas, including marginal zone lymphoma (MZL. Herein we describe a case of extranodal MZL refractory to multiple lines of therapy. The presence of an IgM paraprotein prompted further evaluation, and the patient was found to have an MYD88L265P mutation. Treatment with ibrutinib led to a dramatic response with prompt resolution of symptoms and significant improvement in measurable sites of disease. The excellent response to ibrutinib in our patient with MYD88L265P-mutated refractory MZL supports a biological rationale for its use.

  9. Analysis of mutant frequencies and mutation spectra in hMTH1 knockdown TK6 cells exposed to UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fotouhi, Asal [Center for Radiation Protection Research, Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University (Sweden); Hagos, Winta Woldai [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Ilic, Marina; Wojcik, Andrzej; Harms-Ringdahl, Mats [Center for Radiation Protection Research, Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University (Sweden); Gruijl, Frank de [Department of Dermatology, Leiden University Medical Center, Leiden (Netherlands); Mullenders, Leon; Jansen, Jacob G. [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Haghdoost, Siamak, E-mail: Siamak.Haghdoost@su.se [Center for Radiation Protection Research, Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University (Sweden)

    2013-11-15

    Highlights: • hMTH1 protects cells from mutagenesis induced by UVA and UVB, but not UVC. • No protective role of hMTH1 in cell survival post UVB and UVC irradiation. • hMTH1 prevents induction of transition-type mutations at AT and GC post UVA irradiation. • 2-OH-dATP rather than 8-oxo-dGTP in the nucleotide pool likely contributes in UVA-induced mutations. - Abstract: Ultraviolet radiation is a highly mutagenic agent that damages the DNA by the formation of mutagenic photoproducts at dipyrimidine sites and by oxidative DNA damages via reactive oxygen species (ROS). ROS can also give rise to mutations via oxidation of dNTPs in the nucleotide pool, e.g. 8-oxo-dGTP and 2-OH-dATP and subsequent incorporation during DNA replication. Here we show that expression of human MutT homolog 1 (hMTH1) which sanitizes the nucleotide pool by dephosphorylating oxidized dNTPs, protects against mutagenesis induced by long wave UVA light and by UVB light but not by short wave UVC light. Mutational spectra analyses of UVA-induced mutations at the endogenous Thymidine kinase gene in human lymphoblastoid cells revealed that hMTH1 mainly protects cells from transitions at GC and AT base pairs.

  10. Frequency of Hereditary Hemochromatosis (HFE) Gene Mutations in Egyptian Beta Thalassemia Patients and its Relation to Iron Overload.

    Science.gov (United States)

    Enein, Azza Aboul; El Dessouky, Nermine A; Mohamed, Khalda S; Botros, Shahira K A; Abd El Gawad, Mona F; Hamdy, Mona; Dyaa, Nehal

    2016-06-15

    This study aimed to detect the most common HFE gene mutations (C282Y, H63D, and S56C) in Egyptian beta thalassemia major patients and its relation to their iron status. The study included 50 beta thalassemia major patients and 30 age and sex matched healthy persons as a control group. Serum ferritin, serum iron and TIBC level were measured. Detection of the three HFE gene mutations (C282Y, H63D and S65C) was done by PCR-RFLP analysis. Confirmation of positive cases for the mutations was done by sequencing. Neither homozygote nor carrier status for the C282Y or S65C alleles was found. The H63D heterozygous state was detected in 5/50 (10%) thalassemic patients and in 1/30 (3.3%) controls with no statistically significant difference between patients and control groups (p = 0.22). Significantly higher levels of the serum ferritin and serum iron in patients with this mutation (p = 001). Our results suggest that there is an association between H63D mutation and the severity of iron overload in thalassemic patients.

  11. Experimental Evolution of Mycobacterium tuberculosis in Human Macrophages Results in Low-Frequency Mutations Not Associated with Selective Advantage.

    Directory of Open Access Journals (Sweden)

    Valentina Guerrini

    Full Text Available Isolates of the human pathogen Mycobacterium tuberculosis recovered from clinical samples exhibit genetic heterogeneity. Such variation may result from the stressful environment encountered by the pathogen inside the macrophage, which is the host cell tubercle bacilli parasitize. To study the evolution of the M. tuberculosis genome during growth inside macrophages, we developed a model of intracellular culture in which bacteria were serially passaged in macrophage-like THP-1 cells for about 80 bacterial generations. Genome sequencing of single bacterial colonies isolated before and after the infection cycles revealed that M. tuberculosis developed mutations at a rate of about 5.7 × 10-9 / bp/ generation, consistent with mutation rates calculated during in vivo infection. Analysis of mutant growth in macrophages and in mice showed that the mutations identified after the cyclic infection conferred no advantage to the mutants relative to wild-type. Furthermore, activity testing of the recombinant protein harboring one of these mutations showed that the presence of the mutation did not affect the enzymatic activity. The serial infection protocol developed in this work to study M. tuberculosis genome microevolution can be applied to exposure to stressors to determine their effect on genome remodeling during intra-macrophage growth.

  12. Study on DFIG wind turbines control strategy for improving frequency response characteristics

    Science.gov (United States)

    Zhao, Dongmei; Wu, Di; Liu, Yanhua; Zhou, Zhiyu

    2012-01-01

    The active and reactive power decoupling control for the double-fed induction generator wind turbines(DFIG) does not play a positive role to the frequency response ability of power grid because it performs as the hidden inertia for the power grid. If we want to improve the transient frequency stability of the wind turbine when it is integrated with the system, we must ameliorate its frequency response characteristics. The inability of frequency control due to DFIG decoupling control could be overcome through releasing (or absorbing) a part of the kinetic energy stored in the rotor, so as to increase (or decrease) active power injected to the power system when the deviation of power system frequency appears. This paper discusses the mathematical model of the variable speed DFIG, including the aerodynamic model, pitch control system model, shaft model, generator model and inverter control model, and other key components, focusing on the mathematical model of the converters in rotor side and grid side. Based on the existing model of wind generator, the paper attaches the frequency control model on the platform of the simulation software DIgSILENT/PowerFactory. The simulation results show that the proposed control strategy can response quickly to transient frequency deviation and prove that wind farms can participate in the system frequency regulation to a certain extent. Finally, the result verifies the accuracy and plausibility of the inverter control model which attaches the frequency control module.

  13. An inhibitor of potentially lethal damage (PLD) repair reduces the frequency of γ-ray mutations in cultured Chinese hamster V79 cells

    International Nuclear Information System (INIS)

    Yokoiyama, A.; Kada, T.; Kuroda, Y.

    1992-01-01

    Cordycepin (3'-deoxyadenosine, 3 - dA) is an RNA antimetabolite and a radiosensitizer in cultured mammalian cells. In the present paper, the effects of 3'-dA on γ-ray-induced lethality and 6-thioguanine (6TG)-resistant mutations in cultured Chinese hamster V79 cells were examined. 3'-dA had the effect of sensitizing the lethality induced by γ-rays. The potentially lethal damage (PLD) repair produced by post-incubation cells in Hanks' solution after γ-irradiation was almost completely suppressed by 5x10 -5 M 3'-dA. When cells were irradiated with 10 Gy γ-rays and incubated with 3'-dA for 5 h, the frequency of 6TG-resistant mutations induced by γ-rays decreased to 1/6 of that of the irradiated cells incubated without 3'-dA. The decrease in the frequency of γ-ray-induced mutations was dependent on the length of incubation time with 3'-dA. It is suggested that the inhibition of PLD repair by 3'-dA may be that of error-prone repair. (author). 26 refs.; 5 figs

  14. Frequency response variation of two offshore wind park transformers with different tap changer positions

    DEFF Research Database (Denmark)

    Arana Aristi, Iván; Holbøll, Joachim; Sørensen, T

    2010-01-01

    This paper presents the results of several sweep frequency response analysis (SFRA) measurements performed on two identical offshore wind farm transformers. A comparison is made between the transformers based on different recommended measurements and procedures, different measurement systems...

  15. A noise level prediction method based on electro-mechanical frequency response function for capacitors.

    Science.gov (United States)

    Zhu, Lingyu; Ji, Shengchang; Shen, Qi; Liu, Yuan; Li, Jinyu; Liu, Hao

    2013-01-01

    The capacitors in high-voltage direct-current (HVDC) converter stations radiate a lot of audible noise which can reach higher than 100 dB. The existing noise level prediction methods are not satisfying enough. In this paper, a new noise level prediction method is proposed based on a frequency response function considering both electrical and mechanical characteristics of capacitors. The electro-mechanical frequency response function (EMFRF) is defined as the frequency domain quotient of the vibration response and the squared capacitor voltage, and it is obtained from impulse current experiment. Under given excitations, the vibration response of the capacitor tank is the product of EMFRF and the square of the given capacitor voltage in frequency domain, and the radiated audible noise is calculated by structure acoustic coupling formulas. The noise level under the same excitations is also measured in laboratory, and the results are compared with the prediction. The comparison proves that the noise prediction method is effective.

  16. Multiscale energy reallocation during low-frequency steady-state brain response.

    Science.gov (United States)

    Wang, Yifeng; Chen, Wang; Ye, Liangkai; Biswal, Bharat B; Yang, Xuezhi; Zou, Qijun; Yang, Pu; Yang, Qi; Wang, Xinqi; Cui, Qian; Duan, Xujun; Liao, Wei; Chen, Huafu

    2018-05-01

    Traditional task-evoked brain activations are based on detection and estimation of signal change from the mean signal. By contrast, the low-frequency steady-state brain response (lfSSBR) reflects frequency-tagging activity at the fundamental frequency of the task presentation and its harmonics. Compared to the activity at these resonant frequencies, brain responses at nonresonant frequencies are largely unknown. Additionally, because the lfSSBR is defined by power change, we hypothesize using Parseval's theorem that the power change reflects brain signal variability rather than the change of mean signal. Using a face recognition task, we observed power increase at the fundamental frequency (0.05 Hz) and two harmonics (0.1 and 0.15 Hz) and power decrease within the infra-slow frequency band ( .955) of their spatial distribution and brain-behavior relationship at all frequency bands. Additionally, the reallocation of finite energy was observed across various brain regions and frequency bands, forming a particular spatiotemporal pattern. Overall, results from this study strongly suggest that frequency-specific power and variability may measure the same underlying brain activity and that these results may shed light on different mechanisms between lfSSBR and brain activation, and spatiotemporal characteristics of energy reallocation induced by cognitive tasks. © 2018 Wiley Periodicals, Inc.

  17. Prevalence and evolution of low frequency HIV drug resistance mutations detected by ultra deep sequencing in patients experiencing first line antiretroviral therapy failure.

    Science.gov (United States)

    Vandenhende, Marie-Anne; Bellecave, Pantxika; Recordon-Pinson, Patricia; Reigadas, Sandrine; Bidet, Yannick; Bruyand, Mathias; Bonnet, Fabrice; Lazaro, Estibaliz; Neau, Didier; Fleury, Hervé; Dabis, François; Morlat, Philippe; Masquelier, Bernard

    2014-01-01

    Clinical relevance of low-frequency HIV-1 variants carrying drug resistance associated mutations (DRMs) is still unclear. We aimed to study the prevalence of low-frequency DRMs, detected by Ultra-Deep Sequencing (UDS) before antiretroviral therapy (ART) and at virological failure (VF), in HIV-1 infected patients experiencing VF on first-line ART. Twenty-nine ART-naive patients followed up in the ANRS-CO3 Aquitaine Cohort, having initiated ART between 2000 and 2009 and experiencing VF (2 plasma viral loads (VL) >500 copies/ml or one VL >1000 copies/ml) were included. Reverse transcriptase and protease DRMs were identified using Sanger sequencing (SS) and UDS at baseline (before ART initiation) and VF. Additional low-frequency variants with PI-, NNRTI- and NRTI-DRMs were found by UDS at baseline and VF, significantly increasing the number of detected DRMs by 1.35 fold (plow-frequency DRMs modified ARV susceptibility predictions to the prescribed treatment for 1 patient at baseline, in whom low-frequency DRM was found at high frequency at VF, and 6 patients at VF. DRMs found at VF were rarely detected as low-frequency DRMs prior to treatment. The rare low-frequency NNRTI- and NRTI-DRMs detected at baseline that correlated with the prescribed treatment were most often found at high-frequency at VF. Low frequency DRMs detected before ART initiation and at VF in patients experiencing VF on first-line ART can increase the overall burden of resistance to PI, NRTI and NNRTI.

  18. Effects of mistuning and matrix structure on the topology of frequency response curves

    Science.gov (United States)

    Afolabi, Dare

    1989-01-01

    The stability of a frequency response curve under mild perturbations of the system's matrix is investigated. Using recent developments in the theory of singularities of differentiable maps, it is shown that the stability of a response curve depends on the structure of the system's matrix. In particular, the frequency response curves of a cylic system are shown to be unstable. Consequently, slight parameter variations engendered by mistuning will induce a significant difference in the topology of the forced response curves, if the mistuning transformation crosses the bifurcation set.

  19. Sensitivity and Frequencies of Dystrophin Gene Mutations in Thai DMD/BMD Patients As Detected by Multiplex PCR

    Directory of Open Access Journals (Sweden)

    Thanyachai Sura

    2008-01-01

    Full Text Available Background: Duchenne muscular dystrophy (DMD, a lethal X-linked disease affecting 1 in 3500 male births, and its more benign variant, Becker muscular dystrophy (BMD, are caused by mutations in the dystrophin gene. Because of its large size, analysing the whole gene is impractical. Methods have been developed to detect the commonest mutations i.e. the deletions of the exons. Although these tests are highly specific, their sensitivity is inherently limited by the prevalence of deletions, which differs among different populations.

  20. High Frequency of AML1/RUNX1 Point Mutations in Radiation-Associated Myelodysplastic Syndrome Around Semipalatinsk Nuclear Test Site

    OpenAIRE

    Dinara, ZHARLYGANOVA; Hironori, HARADA; Yuka, HARADA; Sergey, SHINKAREV; Zhaxybay, ZHUMADILOV; Aigul, ZHUNUSOVA; Naylya J., TCHAIZHUNUSOVA; Kazbek N., APSALIKOV; Vadim, KEMAIKIN; Kassym, ZHUMADILOV; Noriyuki, KAWANO; Akiro, KIMURA; Masaharu, HOSHI; Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University; Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University

    2008-01-01

    It is known that bone marrow is a sensitive organ to ionizing radiation, and many patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in MDS/AML patients among atomic bomb survivors and radiation therapy-related MDS/AML patients. In this study, we investigated the AML1 mutations in radiation-exposed patients wi...

  1. The spectrum of mutation produced by low dose radiation

    International Nuclear Information System (INIS)

    Morley, Alexander A.; Turner, David R.

    2004-01-01

    Inherited mutations are the basis of evolution and acquired mutations in humans are important in ageing, cancer and possibly various forms of tissue degeneration. Mutations are responsible for many of the long-term effects of radiation. However, sensitive direct detection of mutations in humans has been difficult. The aims of the project were to develop methods for the sensitive enumeration of mutations in DNA, to measure mutation frequencies in a wide variety of tissue types and to quantify the mutational effect of direct oxidative damage produced by radiation, at both high and low doses. The project was successful in developing a sensitive method which could detect mutations directly in the genetic material, DNA at a sensitivity of 1 mutated molecule in 1000000000 unmutated molecules. However a number of methodological problems had to be overcome and lack of ongoing funding made it impossible to fulfill all of the aims of the project

  2. Matrilin-3 chondrodysplasia mutations cause attenuated chondrogenesis, premature hypertrophy and aberrant response to TGF-β in chondroprogenitor cells.

    Science.gov (United States)

    Jayasuriya, Chathuraka T; Zhou, Fiona H; Pei, Ming; Wang, Zhengke; Lemme, Nicholas J; Haines, Paul; Chen, Qian

    2014-08-21

    Studies have shown that mutations in the matrilin-3 gene (MATN3) are associated with multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). We tested whether MATN3 mutations affect the differentiation of chondroprogenitor and/or mesenchymal stem cells, which are precursors to chondrocytes. ATDC5 chondroprogenitors stably expressing wild-type (WT) MATN3 underwent spontaneous chondrogenesis. Expression of chondrogenic markers collagen II and aggrecan was inhibited in chondroprogenitors carrying the MED or SEMD MATN3 mutations. Hypertrophic marker collagen X remained attenuated in WT MATN3 chondroprogenitors, whereas its expression was elevated in chondroprogenitors expressing the MED or SEMD mutant MATN3 gene suggesting that these mutations inhibit chondrogenesis but promote hypertrophy. TGF-β treatment failed to rescue chondrogenesis markers but dramatically increased collagen X mRNA expression in mutant MATN3 expressing chondroprogenitors. Synovium derived mesenchymal stem cells harboring the SEMD mutation exhibited lower glycosaminoglycan content than those of WT MATN3 in response to TGF-β. Our results suggest that the properties of progenitor cells harboring MATN3 chondrodysplasia mutations were altered, as evidenced by attenuated chondrogenesis and premature hypertrophy. TGF-β treatment failed to completely rescue chondrogenesis but instead induced hypertrophy in mutant MATN3 chondroprogenitors. Our data suggest that chondroprogenitor cells should be considered as a potential target of chondrodysplasia therapy.

  3. Dissecting the Contributions of Cooperating Gene Mutations to Cancer Phenotypes and Drug Responses with Patient-Derived iPSCs

    Directory of Open Access Journals (Sweden)

    Chan-Jung Chang

    2018-05-01

    Full Text Available Summary: Connecting specific cancer genotypes with phenotypes and drug responses constitutes the central premise of precision oncology but is hindered by the genetic complexity and heterogeneity of primary cancer cells. Here, we use patient-derived induced pluripotent stem cells (iPSCs and CRISPR/Cas9 genome editing to dissect the individual contributions of two recurrent genetic lesions, the splicing factor SRSF2 P95L mutation and the chromosome 7q deletion, to the development of myeloid malignancy. Using a comprehensive panel of isogenic iPSCs—with none, one, or both genetic lesions—we characterize their relative phenotypic contributions and identify drug sensitivities specific to each one through a candidate drug approach and an unbiased large-scale small-molecule screen. To facilitate drug testing and discovery, we also derive SRSF2-mutant and isogenic normal expandable hematopoietic progenitor cells. We thus describe here an approach to dissect the individual effects of two cooperating mutations to clinically relevant features of malignant diseases. : Papapetrou and colleagues develop a comprehensive panel of isogenic iPSC lines with SRSF2 P95L mutation and chr7q deletion. They use these cells to identify cellular phenotypes contributed by each genetic lesion and therapeutic vulnerabilities specific to each one and develop expandable hematopoietic progenitor cell lines to facilitate drug discovery. Keywords: induced pluripotent stem cells, myelodysplastic syndrome, CRISPR/Cas9, gene editing, mutational cooperation, splicing factor mutations, spliceosomal mutations, SRSF2, chr7q deletion

  4. Matrilin-3 Chondrodysplasia Mutations Cause Attenuated Chondrogenesis, Premature Hypertrophy and Aberrant Response to TGF-β in Chondroprogenitor Cells

    Directory of Open Access Journals (Sweden)

    Chathuraka T. Jayasuriya

    2014-08-01

    Full Text Available Studies have shown that mutations in the matrilin-3 gene (MATN3 are associated with multiple epiphyseal dysplasia (MED and spondyloepimetaphyseal dysplasia (SEMD. We tested whether MATN3 mutations affect the differentiation of chondroprogenitor and/or mesenchymal stem cells, which are precursors to chondrocytes. ATDC5 chondroprogenitors stably expressing wild-type (WT MATN3 underwent spontaneous chondrogenesis. Expression of chondrogenic markers collagen II and aggrecan was inhibited in chondroprogenitors carrying the MED or SEMD MATN3 mutations. Hypertrophic marker collagen X remained attenuated in WT MATN3 chondroprogenitors, whereas its expression was elevated in chondroprogenitors expressing the MED or SEMD mutant MATN3 gene suggesting that these mutations inhibit chondrogenesis but promote hypertrophy. TGF-β treatment failed to rescue chondrogenesis markers but dramatically increased collagen X mRNA expression in mutant MATN3 expressing chondroprogenitors. Synovium derived mesenchymal stem cells harboring the SEMD mutation exhibited lower glycosaminoglycan content than those of WT MATN3 in response to TGF-β. Our results suggest that the properties of progenitor cells harboring MATN3 chondrodysplasia mutations were altered, as evidenced by attenuated chondrogenesis and premature hypertrophy. TGF-β treatment failed to completely rescue chondrogenesis but instead induced hypertrophy in mutant MATN3 chondroprogenitors. Our data suggest that chondroprogenitor cells should be considered as a potential target of chondrodysplasia therapy.

  5. Frequency-dependent effects of background noise on subcortical response timing.

    Science.gov (United States)

    Tierney, A; Parbery-Clark, A; Skoe, E; Kraus, N

    2011-12-01

    The addition of background noise to an auditory signal delays brainstem response timing. This effect has been extensively documented using manual peak selection. Peak picking, however, is impractical for large-scale studies of spectrotemporally complex stimuli, and leaves open the question of whether noise-induced delays are frequency-dependent or occur across the frequency spectrum. Here we use an automated, objective method to examine phase shifts between auditory brainstem responses to a speech sound (/da/) presented with and without background noise. We predicted that shifts in neural response timing would also be reflected in frequency-specific phase shifts. Our results indicate that the addition of background noise causes phase shifts across the subcortical response spectrum (70-1000 Hz). However, this noise-induced delay is not uniform such that some frequency bands show greater shifts than others: low-frequency phase shifts (300-500 Hz) are largest during the response to the consonant-vowel formant transition (/d/), while high-frequency shifts (720-1000 Hz) predominate during the response to the steady-state vowel (/a/). Most importantly, phase shifts occurring in specific frequency bands correlate strongly with shifts in the latencies of the predominant peaks in the auditory brainstem response, while phase shifts in other frequency bands do not. This finding confirms the validity of phase shift detection as an objective measure of timing differences and reveals that this method detects noise-induced shifts in timing that may not be captured by traditional peak latency measurements. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Frequency Response of the Sample Vibration Mode in Scanning Probe Acoustic Microscope

    International Nuclear Information System (INIS)

    Ya-Jun, Zhao; Qian, Cheng; Meng-Lu, Qian

    2010-01-01

    Based on the interaction mechanism between tip and sample in the contact mode of a scanning probe acoustic microscope (SPAM), an active mass of the sample is introduced in the mass-spring model. The tip motion and frequency response of the sample vibration mode in the SPAM are calculated by the Lagrange equation with dissipation function. For the silicon tip and glass assemblage in the SPAM the frequency response is simulated and it is in agreement with the experimental result. The living myoblast cells on the glass slide are imaged at resonance frequencies of the SPAM system, which are 20kHz, 30kHz and 120kHz. It is shown that good contrast of SPAM images could be obtained when the system is operated at the resonance frequencies of the system in high and low-frequency regions

  7. Frequency of V1016I and F1534C mutations in the voltage-gated sodium channel gene in Aedes aegypti in Venezuela.

    Science.gov (United States)

    Alvarez, Leslie C; Ponce, Gustavo; Saavedra-Rodriguez, Karla; Lopez, Beatriz; Flores, Adriana E

    2015-06-01

    The V1016I and F1534C mutations in the voltage-gated sodium channel gene have been associated with resistance to pyrethroids and DDT in Aedes aegypti mosquitoes. A study was carried out to determine the frequency of I1016 and C1534 by real-time PCR in five natural populations of Ae. aegypti in Venezuela during 2008, 2010 and 2012, as well as in a strain selected with 0.14 µg of deltamethrin for 15 generations. In natural populations, frequencies of I1016 varied between 0.01 and 0.37, and frequencies of C1534 between 0.35 and 1.0. In the Pampanito strain, the frequency of I1016 increased from 0.02 in F1 up to 0.5 in F15 and from 0.35 up to fixation for C1534 after selection with deltamethrin. The results showed that C1534 frequencies are higher than I1016 frequencies in natural populations of Ae. aegypti in Venezuela, and that deltamethrin selected the C1534 more rapidly than I1016. © 2014 Society of Chemical Industry.

  8. KIT polymorphisms and mutations determine responses of neoplastic mast cells to bafetinib (INNO-406).

    Science.gov (United States)

    Peter, Barbara; Hadzijusufovic, Emir; Blatt, Katharina; Gleixner, Karoline V; Pickl, Winfried F; Thaiwong, Tuddow; Yuzbasiyan-Gurkan, Vilma; Willmann, Michael; Valent, Peter

    2010-09-01

    Advanced systemic mastocytosis (SM) is characterized by uncontrolled growth of neoplastic mast cells (MC) and drug resistance. The tyrosine kinase receptor KIT is often mutated and activated and thus contributes to malignant growth of MC. Therefore, KIT-targeting drugs are currently tested for their ability to block growth of malignant MC. We determined the effects of the multikinase inhibitor INNO-406 (bafetinib) on primary neoplastic MC, the canine mastocytoma cell line C2, the human MC leukemia cell line HMC-1.1 bearing the KIT mutant V560G, and HMC-1.2 cells harboring KIT V560G and KIT D816V. INNO-406 was found to inhibit proliferation in HMC-1.1 cells (IC(50): 30-40 nM), but not in HMC-1.2 cells or primary neoplastic cells in patients with KIT D816V-positive SM. In canines, growth-inhibitory effects of INNO-406 were seen in C2 cells (IC(50): 50-100 nM) exhibiting a KIT exon 11 internal tandem-duplication and in primary neoplastic MC harboring wild-type exon 11, whereas no effects were seen in MC exhibiting a polymorphism at amino acid 581 in exon 11. INNO-406 was found to block KIT phosphorylation and expression in HMC-1.1 cells and C2 cells, but not in HMC-1.2 cells, whereas Lyn-phosphorylation was blocked by INNO-406 in all types of MC. In neoplastic MC, the major target of INNO-406 appears to be KIT. Drug responses may depend on the presence and type of KIT mutation. In human MC, the KIT D816V mutant introduces resistance, and in canine mastocytomas, an exon 11 polymorphism may be indicative of resistance against INNO-406.

  9. On the quantification of SSVEP frequency responses in human EEG in realistic BCI conditions.

    Directory of Open Access Journals (Sweden)

    Rafał Kuś

    Full Text Available This article concerns one of the most important problems of brain-computer interfaces (BCI based on Steady State Visual Evoked Potentials (SSVEP, that is the selection of the a-priori most suitable frequencies for stimulation. Previous works related to this problem were done either with measuring systems that have little in common with actual BCI systems (e.g., single flashing LED or were presented on a small number of subjects, or the tested frequency range did not cover a broad spectrum. Their results indicate a strong SSVEP response around 10 Hz, in the range 13-25 Hz, and at high frequencies in the band of 40-60 Hz. In the case of BCI interfaces, stimulation with frequencies from various ranges are used. The frequencies are often adapted for each user separately. The selection of these frequencies, however, was not yet justified in quantitative group-level study with proper statistical account for inter-subject variability. The aim of this study is to determine the SSVEP response curve, that is, the magnitude of the evoked signal as a function of frequency. The SSVEP response was induced in conditions as close as possible to the actual BCI system, using a wide range of frequencies (5-30 Hz, in step of 1 Hz. The data were obtained for 10 subjects. SSVEP curves for individual subjects and the population curve was determined. Statistical analysis were conducted both on the level of individual subjects and for the group. The main result of the study is the identification of the optimal range of frequencies, which is 12-18 Hz, for the registration of SSVEP phenomena. The applied criterion of optimality was: to find the largest contiguous range of frequencies yielding the strong and constant-level SSVEP response.

  10. Calibration-free absolute frequency response measurement of directly modulated lasers based on additional modulation.

    Science.gov (United States)

    Zhang, Shangjian; Zou, Xinhai; Wang, Heng; Zhang, Yali; Lu, Rongguo; Liu, Yong

    2015-10-15

    A calibration-free electrical method is proposed for measuring the absolute frequency response of directly modulated semiconductor lasers based on additional modulation. The method achieves the electrical domain measurement of the modulation index of directly modulated lasers without the need for correcting the responsivity fluctuation in the photodetection. Moreover, it doubles measuring frequency range by setting a specific frequency relationship between the direct and additional modulation. Both the absolute and relative frequency response of semiconductor lasers are experimentally measured from the electrical spectrum of the twice-modulated optical signal, and the measured results are compared to those obtained with conventional methods to check the consistency. The proposed method provides calibration-free and accurate measurement for high-speed semiconductor lasers with high-resolution electrical spectrum analysis.

  11. A mutation in the receptor Methoprene-tolerant alters juvenile hormone response in insects and crustaceans.

    Science.gov (United States)

    Miyakawa, Hitoshi; Toyota, Kenji; Hirakawa, Ikumi; Ogino, Yukiko; Miyagawa, Shinichi; Oda, Shigeto; Tatarazako, Norihisa; Miura, Toru; Colbourne, John K; Iguchi, Taisen

    2013-01-01

    Juvenile hormone is an essential regulator of major developmental and life history events in arthropods. Most of the insects use juvenile hormone III as the innate juvenile hormone ligand. By contrast, crustaceans use methyl farnesoate. Despite this difference that is tied to their deep evolutionary divergence, the process of this ligand transition is unknown. Here we show that a single amino-acid substitution in the receptor Methoprene-tolerant has an important role during evolution of the arthropod juvenile hormone pathway. Microcrustacea Daphnia pulex and D. magna share a juvenile hormone signal transduction pathway with insects, involving Methoprene-tolerant and steroid receptor coactivator proteins that form a heterodimer in response to various juvenoids. Juvenile hormone-binding pockets of the orthologous genes differ by only two amino acids, yet a single substitution within Daphnia Met enhances the receptor's responsiveness to juvenile hormone III. These results indicate that this mutation within an ancestral insect lineage contributed to the evolution of a juvenile hormone III receptor system.

  12. Characterization of Deficiencies in the Frequency Domain Forced Response Analysis Technique for Supersonic Turbine Bladed Disks

    Science.gov (United States)

    Brown, Andrew M.; Schmauch, Preston

    2011-01-01

    Turbine blades in rocket and jet engine turbomachinery experience enormous harmonic loading conditions. These loads result from the integer number of upstream and downstream stator vanes as well as the other turbine stages. Assessing the blade structural integrity is a complex task requiring an initial characterization of whether resonance is possible and then performing a forced response analysis if that condition is met. The standard technique for forced response analysis in rocket engines is to decompose a CFD-generated flow field into its harmonic components, and to then perform a frequency response analysis at the problematic natural frequencies. Recent CFD analysis and water-flow testing at NASA/MSFC, though, indicates that this technique may miss substantial harmonic and non-harmonic excitation sources that become present in complex flows. A substantial effort has been made to account for this denser spatial Fourier content in frequency response analysis (described in another paper by the author), but the question still remains whether the frequency response analysis itself is capable of capturing the excitation content sufficiently. Two studies comparing frequency response analysis with transient response analysis, therefore, of bladed-disks undergoing this complex flow environment have been performed. The first is of a bladed disk with each blade modeled by simple beam elements. Six loading cases were generated by varying a baseline harmonic excitation in different ways based upon cold-flow testing from Heritage Fuel Air Turbine Test. It was hypothesized that the randomness and other variation from the standard harmonic excitation would reduce the blade structural response, but the results showed little reduction. The second study was of a realistic model of a bladed-disk excited by the same CFD used in the J2X engine program. It was hypothesized that enforcing periodicity in the CFD (inherent in the frequency response technique) would overestimate the

  13. Frequency of the HFE C282Y and H63D mutations in Danish patients with clinical haemochromatosis initially diagnosed by phenotypic methods

    DEFF Research Database (Denmark)

    Milman, Nils; Koefoed, Pernille; Pedersen, Palle

    2003-01-01

    AIM: To assess the frequency of the C282Y and H63D mutations on the HFE gene in Danish patients with clinical hereditary haemochromatosis initially diagnosed by phenotypic methods. METHODS: In the period 1950-1985, an epidemiological survey in Denmark identified 179 patients with clinical...... diagnosis of clinical idiopathic haemochromatosis was made before blood samples were taken for HFE genotyping. The total series consisted of 58 patients (40 men and 18 women) with a median age of 60 yrs (range 18-74). HFE genotyping was performed by the polymerase chain reaction (PCR) technique. RESULTS...

  14. Generation of artificial time-histories, rich in all frequencies, from given response spectra

    International Nuclear Information System (INIS)

    Levy, S.; Wilkinson, J.P.D.

    1976-01-01

    In the design of nuclear power plants, it has been found desirable in certain instances to use the time-history method of dynamic analysis to determine the plant response to seismic input. In the implementation of this method, it is necessary to determine an adequate representation of the excitation as a function of time. Because many design criteria are specified in terms of design response spectra one is faced with the problem of generating a time-history whose own response spectrum approximates as far as possible to the originally specified design response spectrum. One objective of this paper is to present a method of synthesizing such time-histories from a given design response spectrum. The design response spectra may be descriptive of floor responses at a particular location in a plant, or they may be descriptive of seismic ground motions at a plant site. The method described in this paper allows the generation of time histories that are rich in all frequencies in the spectrum. This richness is achieved by choosing a large number of closely-spaced frequency points such that the half-power points of adjacent frequencies overlap. Examples are given concerning seismic design response spectra, and a number of points are discussed concerning the effect of frequency spacing on convergence. (Auth.)

  15. High frequency of Plasmodium falciparum chloroquine resistance marker (pfcrt T76 mutation) in Yemen: an urgent need to re-examine malaria drug policy.

    Science.gov (United States)

    Al-Mekhlafi, Abdulsalam M; Mahdy, Mohammed A K; Al-Mekhlafi, Hesham M; Azazy, Ahmed A; Fong, Mun Yik

    2011-05-27

    Malaria remains a significant health problem in Yemen with Plasmodium falciparum being the predominant species which is responsible for 90% of the malaria cases. Despite serious concerns regarding increasing drug resistance, chloroquine is still used for the prevention and treatment of malaria in Yemen. This study was carried out to determine the prevalence of choloroquine resistance (CQR) of P. falciparum isolated from Yemen based on the pfcrt T76 mutation. A cross-sectional study was carried out among 511 participants from four governorates in Yemen. Blood samples were screened using microscopic and species-specific nested PCR based on the 18S rRNA gene to detect and identify Plasmodium species. Blood samples positive for P. falciparum were used for detecting the pfcrt T76 mutation using nested-PCR. The prevalence of pfcrt T76 mutation was 81.5% (66 of 81 isolates). Coastal areas/foothills had higher prevalence of pfcrt T76 mutation compared to highland areas (90.5% vs 71.8%) (p = 0.031). The pfcrt T76 mutation had a significant association with parasitaemia (p = 0.045). Univariate analysis shows a significant association of pfcrt T76 mutation with people aged > 10 years (OR = 9, 95% CI = 2.3 - 36.2, p = 0.001), low household income (OR = 5, 95% CI = 1.3 - 19.5, p = 0.027), no insecticide spray (OR = 3.7, 95% CI = 1.16 - 11.86, p = 0.025) and not sleeping under insecticide treated nets (ITNs) (OR = 4.8, 95% CI = 1.38 - 16.78, p = 0.01). Logistic regression model confirmed age > 10 years and low household income as predictors of pfcrt T76 mutation in Yemen P. falciparum isolates. The high prevalence of pfcrt T76 mutation in Yemen could be a predictive marker for the prevalence of P. falciparum CQR. This finding shows the necessity for an in-vivo therapeutic efficacy test for CQ. P. falciparum CQR should be addressed in the national strategy to control malaria.

  16. Frequency-dependent transient response of an oscillating electrically actuated droplet

    International Nuclear Information System (INIS)

    Dash, S; Kumari, N; Garimella, S V

    2012-01-01

    The transient response of a millimeter-sized sessile droplet under electrical actuation is experimentally investigated. Under dc actuation, the droplet spreading rate increases as the applied voltage is increased due to the higher electrical forces induced. At sufficiently high dc voltages, competition between the electrical actuation force, droplet inertia, the retarding surface tension force and contact line friction leads to droplet oscillation. The timescale for the droplet to attain its maximum wetted diameter during step actuation is analyzed. Systematic experiments are conducted over a frequency range of 5–200 Hz and actuation voltages of 40–80 V rms to determine the dependence of droplet oscillation on these parameters. The response of the droplet to different actuation frequencies and voltages is determined in terms of its contact angle and contact radius variation. The frequency of the driving force (equal to twice the frequency of the applied electrical signal) determines the mode of oscillation of the droplet which, together with its resonance characteristics, governs whether the droplet contact angle and contact radius vary in phase or out of phase with each other. In addition to the primary frequency response at the electrical forcing frequency, the droplet oscillation exhibits sub-harmonic oscillation at half of the forcing frequency that is attributed to the parametric nature of the electrical force acting on the triple contact line of the droplet. (paper)

  17. Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response.

    Science.gov (United States)

    Rice, Gillian I; Bond, Jacquelyn; Asipu, Aruna; Brunette, Rebecca L; Manfield, Iain W; Carr, Ian M; Fuller, Jonathan C; Jackson, Richard M; Lamb, Teresa; Briggs, Tracy A; Ali, Manir; Gornall, Hannah; Couthard, Lydia R; Aeby, Alec; Attard-Montalto, Simon P; Bertini, Enrico; Bodemer, Christine; Brockmann, Knut; Brueton, Louise A; Corry, Peter C; Desguerre, Isabelle; Fazzi, Elisa; Cazorla, Angels Garcia; Gener, Blanca; Hamel, Ben C J; Heiberg, Arvid; Hunter, Matthew; van der Knaap, Marjo S; Kumar, Ram; Lagae, Lieven; Landrieu, Pierre G; Lourenco, Charles M; Marom, Daphna; McDermott, Michael F; van der Merwe, William; Orcesi, Simona; Prendiville, Julie S; Rasmussen, Magnhild; Shalev, Stavit A; Soler, Doriette M; Shinawi, Marwan; Spiegel, Ronen; Tan, Tiong Y; Vanderver, Adeline; Wakeling, Emma L; Wassmer, Evangeline; Whittaker, Elizabeth; Lebon, Pierre; Stetson, Daniel B; Bonthron, David T; Crow, Yanick J

    2009-07-01

    Aicardi-Goutières syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level. The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid. Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response.

  18. Selective attention modulates human auditory brainstem responses: relative contributions of frequency and spatial cues.

    Directory of Open Access Journals (Sweden)

    Alexandre Lehmann

    Full Text Available Selective attention is the mechanism that allows focusing one's attention on a particular stimulus while filtering out a range of other stimuli, for instance, on a single conversation in a noisy room. Attending to one sound source rather than another changes activity in the human auditory cortex, but it is unclear whether attention to different acoustic features, such as voice pitch and speaker location, modulates subcortical activity. Studies using a dichotic listening paradigm indicated that auditory brainstem processing may be modulated by the direction of attention. We investigated whether endogenous selective attention to one of two speech signals affects amplitude and phase locking in auditory brainstem responses when the signals were either discriminable by frequency content alone, or by frequency content and spatial location. Frequency-following responses to the speech sounds were significantly modulated in both conditions. The modulation was specific to the task-relevant frequency band. The effect was stronger when both frequency and spatial information were available. Patterns of response were variable between participants, and were correlated with psychophysical discriminability of the stimuli, suggesting that the modulation was biologically relevant. Our results demonstrate that auditory brainstem responses are susceptible to efferent modulation related to behavioral goals. Furthermore they suggest that mechanisms of selective attention actively shape activity at early subcortical processing stages according to task relevance and based on frequency and spatial cues.

  19. Frequency of c.35delG Mutation in GJB2 Gene (Connexin 26 in Syrian Patients with Nonsyndromic Hearing Impairment

    Directory of Open Access Journals (Sweden)

    Hazem Kaheel

    2017-01-01

    Full Text Available Background. Hearing impairments (HI are the most common birth defect worldwide. Very large numbers of genes have been identified but the most profound is GJB2. The clinical interest regarding this gene is very pronounced due to its high carrier frequency (0.5–5.4% across different ethnic groups. This study aimed to determine the prevalence of common GJB2 mutations in Syrian patients with profound sensorineural HI. Methods. We carried out PCR, restriction enzyme based screening, and sequencing of 132 Syrian patients diagnosed clinically with hereditary deafness for different GJB2 mutations. Results. The result revealed that, in GJB2 gene, c.35delG is the most prevalent among affected studied subjects (13.64%, followed by c.457G>A (2.4%. Conclusion. The benefit of this study on the one hand is its first report of prelingual deafness causative gene mutations identified by sequencing technology in the Syrian families. It is obvious from the results that the deployment in biomedical research is highly effective and has a great impact on the ability to uncover the cause of genetic variation in different genetic diseases.

  20. Dissociable neural response signatures for slow amplitude and frequency modulation in human auditory cortex.

    Science.gov (United States)

    Henry, Molly J; Obleser, Jonas

    2013-01-01

    Natural auditory stimuli are characterized by slow fluctuations in amplitude and frequency. However, the degree to which the neural responses to slow amplitude modulation (AM) and frequency modulation (FM) are capable of conveying independent time-varying information, particularly with respect to speech communication, is unclear. In the current electroencephalography (EEG) study, participants listened to amplitude- and frequency-modulated narrow-band noises with a 3-Hz modulation rate, and the resulting neural responses were compared. Spectral analyses revealed similar spectral amplitude peaks for AM and FM at the stimulation frequency (3 Hz), but amplitude at the second harmonic frequency (6 Hz) was much higher for FM than for AM. Moreover, the phase delay of neural responses with respect to the full-band stimulus envelope was shorter for FM than for AM. Finally, the critical analysis involved classification of single trials as being in response to either AM or FM based on either phase or amplitude information. Time-varying phase, but not amplitude, was sufficient to accurately classify AM and FM stimuli based on single-trial neural responses. Taken together, the current results support the dissociable nature of cortical signatures of slow AM and FM. These cortical signatures potentially provide an efficient means to dissect simultaneously communicated slow temporal and spectral information in acoustic communication signals.

  1. SLC45A2 mutation frequency in Oculocutaneous Albinism Italian patients doesn't differ from other European studies.

    Science.gov (United States)

    Mauri, Lucia; Barone, Luca; Al Oum, Muna; Del Longo, Alessandra; Piozzi, Elena; Manfredini, Emanuela; Stanzial, Franco; Benedicenti, Francesco; Penco, Silvana; Patrosso, Maria Cristina

    2014-01-01

    Oculocutaneous Albinism (OCA) is a heterogeneous group of inherited diseases involving hair, skin and eyes. To date, six forms are recognized on the effects of different melanogenesis genes. OCA4 is caused by mutations in SLC45A2 showing a heterogeneous phenotype ranging from white hair, blue irides and nystagmus to brown/black hair, brown irides and no nystagmus. The high clinic variety often leads to misdiagnosis. Our aim is to contribute to OCA4 diagnosis defining SLC45A2 genetic variants in Italian patients with OCA without any TYR, OCA2 and TYRP1 gene defects. After the clinical diagnosis of OCA, all patients received genetic counseling and genetic test. Automatic sequencing of TYR, OCA2, and TYRP1 genes was performed on DNA of 117 albino patients. Multiplex Ligation-dependent Probe Amplification (MLPA) was carried out on TYR and OCA2 genes to increase the mutation rate. SLC45A2 gene sequencing was then executed in the patients with a single mutation in one of the TYR, OCA2, TYRP1 genes and in the patients, which resulted negative at the screening of these genes. SLC45A2 gene analysis was performed in 41 patients and gene alterations were found in 5 patients. Four previously reported SLC45A2 mutations were found: p.G100S, p.W202C, p.A511E and c.986delC, and three novel variants were identified: p.M265L, p.H94D, and c.1156+1G>A. All the alterations have been detected in the group of patients without mutations in the other OCA genes. Three new variants were identified in OCA4 gene; the analysis allowed the classification of a patient previously misdiagnosed as OA1 because of skin and hair pigmentation presence. The molecular defects in SLC45A2 gene represent the 3.4% in this cohort of Italian patients, similar to other Caucasian populations; our data differ from those previously published by an Italian researcher group, obtained on a smaller cohort of patients. © 2013 Elsevier B.V. All rights reserved.

  2. The frequency of a disease-causing point mutation in the gene coding for medium-chain acyl-CoA dehydrogenase in sudden infant death syndrome

    DEFF Research Database (Denmark)

    Banner, Jytte; Gregersen, N; Kølvraa, S

    1993-01-01

    A number of rare inherited metabolic disorders are known to lead to death in infancy. Deficiency of medium-chain acyl CoA dehydrogenase has, on clinical grounds, been related particularly to sudden infant death syndrome. The contribution of this disorder to the etiology of sudden infant death...... syndrome is still a matter of controversy. The present study investigated 120 well-defined cases of sudden infant death syndrome in order to detect the frequency of the most common disease-causing point mutation in the gene coding for medium-chain acyl-CoA dehydrogenase (G985) compared with the frequency...... in the general population. A highly specific polymerase chain reaction assay was applied on dried blood spots. No over-representation of homo- or heterozygosity for G985 appears to exist in such a strictly defined population, for which reason it may be more relevant to look at a broader spectrum of clinical...

  3. Resistance to DDT and pyrethroids and increased kdr mutation frequency in An. gambiae after the implementation of permethrin-treated nets in Senegal.

    Directory of Open Access Journals (Sweden)

    Mamadou O Ndiath

    Full Text Available The aim of this study was to evaluate the susceptibility to insecticides of An. gambiae mosquitoes sampled in Dielmo (Senegal, in 2010, 2 years after the implementation of Long Lasting Insecticide-treated Nets (LLINs and to report the evolution of kdr mutation frequency from 2006 to 2010.WHO bioassay susceptibility tests to 6 insecticides were performed on adults F0, issuing from immature stages of An. gambiae s.l., sampled in August 2010. Species and molecular forms as well as the presence of L1014F and L1014S kdr mutations were assessed by PCR. Longitudinal study of kdr mutations was performed on adult mosquitoes sampled monthly by night landing catches from 2006 to 2010.No specimen studied presented the L1014S mutation. During the longitudinal study, L1014F allelic frequency rose from 2.4% in year before the implementation of LLINs to 4.6% 0-12 months after and 18.7% 13-30 months after. In 2010, An. gambiae were resistant to DDT, Lambda-cyhalothrin, Deltamethrin and Permethrin (mortality rates ranging from 46 to 63% but highly susceptible to Fenitrothion and Bendiocarb (100% mortality. There was significantly more RR genotype among An. gambiae surviving exposure to DDT or Pyrethroids. An. arabiensis represented 3.7% of the sampled mosquitoes (11/300 with no kdr resistance allele detected. An. gambiae molecular form M represented 29.7% of the mosquitoes with, among them, kdr genotypes SR (18% and SS (82%. An. gambiae molecular form S represented 66% of the population with, among them, kdr genotype SS (33.3%, SR (55.6% and RR (11.1%. Only 2 MS hybrid mosquitoes were sampled and presented SS kdr genotype.Biological evidence of resistance to DDT and pyrethroids was detected among An. gambiae mosquitoes in Dielmo (Senegal within 24 months of community use of LLINs. Molecular identification of L1014F mutation indicated that target site resistance increased after the implementation of LLINs.

  4. Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis

    Science.gov (United States)

    Mejlachowicz, Dan; Nolent, Flora; Maluenda, Jérome; Ranjatoelina-Randrianaivo, Hanitra; Giuliano, Fabienne; Gut, Ivo; Sternberg, Damien; Laquerrière, Annie; Melki, Judith

    2015-01-01

    Arthrogryposis multiplex congenita (AMC) is characterized by the presence of multiple joint contractures resulting from reduced or absent fetal movement. Here, we report two unrelated families affected by lethal AMC. By genetic mapping and whole-exome sequencing in a multiplex family, a heterozygous truncating MAGEL2 mutation leading to frameshift and a premature stop codon (c.1996delC, p.Gln666Serfs∗36) and inherited from the father was identified in the probands. In another family, a distinct heterozygous truncating mutation leading to frameshift (c.2118delT, p.Leu708Trpfs∗7) and occurring de novo on the paternal allele of MAGEL2 was identified in the affected individual. In both families, RNA analysis identified the mutated paternal MAGEL2 transcripts only in affected individuals. MAGEL2 is one of the paternally expressed genes within the Prader-Willi syndrome (PWS) locus. PWS is associated with, to varying extents, reduced fetal mobility, severe infantile hypotonia, childhood-onset obesity, hypogonadism, and intellectual disability. MAGEL2 mutations have been recently reported in affected individuals with features resembling PWS and called Schaaf-Yang syndrome. Here, we show that paternal MAGEL2 mutations are also responsible for lethal AMC, recapitulating the clinical spectrum of PWS and suggesting that MAGEL2 is a PWS-determining gene. PMID:26365340

  5. Spatial frequency information modulates response inhibition and decision-making processes.

    Directory of Open Access Journals (Sweden)

    Sara Jahfari

    Full Text Available We interact with the world through the assessment of available, but sometimes imperfect, sensory information. However, little is known about how variance in the quality of sensory information affects the regulation of controlled actions. In a series of three experiments, comprising a total of seven behavioral studies, we examined how different types of spatial frequency information affect underlying processes of response inhibition and selection. Participants underwent a stop-signal task, a two choice speed/accuracy balance experiment, and a variant of both these tasks where prior information was given about the nature of stimuli. In all experiments, stimuli were either intact, or contained only high-, or low- spatial frequencies. Overall, drift diffusion model analysis showed a decreased rate of information processing when spatial frequencies were removed, whereas the criterion for information accumulation was lowered. When spatial frequency information was intact, the cost of response inhibition increased (longer SSRT, while a correct response was produced faster (shorter reaction times and with more certainty (decreased errors. When we manipulated the motivation to respond with a deadline (i.e., be fast or accurate, removal of spatial frequency information slowed response times only when instructions emphasized accuracy. However, the slowing of response times did not improve error rates, when compared to fast instruction trials. These behavioral studies suggest that the removal of spatial frequency information differentially affects the speed of response initiation, inhibition, and the efficiency to balance fast or accurate responses. More generally, the present results indicate a task-independent influence of basic sensory information on strategic adjustments in action control.

  6. A novel and lethal de novo LQT-3 mutation in a newborn with distinct molecular pharmacology and therapeutic response.

    Directory of Open Access Journals (Sweden)

    John R Bankston

    2007-12-01

    Full Text Available SCN5A encodes the alpha-subunit (Na(v1.5 of the principle Na(+ channel in the human heart. Genetic lesions in SCN5A can cause congenital long QT syndrome (LQTS variant 3 (LQT-3 in adults by disrupting inactivation of the Na(v1.5 channel. Pharmacological targeting of mutation-altered Na(+ channels has proven promising in developing a gene-specific therapeutic strategy to manage specifically this LQTS variant. SCN5A mutations that cause similar channel dysfunction may also contribute to sudden infant death syndrome (SIDS and other arrhythmias in newborns, but the prevalence, impact, and therapeutic management of SCN5A mutations may be distinct in infants compared with adults.Here, in a multidisciplinary approach, we report a de novo SCN5A mutation (F1473C discovered in a newborn presenting with extreme QT prolongation and differential responses to the Na(+ channel blockers flecainide and mexiletine. Our goal was to determine the Na(+ channel phenotype caused by this severe mutation and to determine whether distinct effects of different Na(+ channel blockers on mutant channel activity provide a mechanistic understanding of the distinct therapeutic responsiveness of the mutation carrier. Sequence analysis of the proband revealed the novel missense SCN5A mutation (F1473C and a common variant in KCNH2 (K897T. Patch clamp analysis of HEK 293 cells transiently transfected with wild-type or mutant Na(+ channels revealed significant changes in channel biophysics, all contributing to the proband's phenotype as predicted by in silico modeling. Furthermore, subtle differences in drug action were detected in correcting mutant channel activity that, together with both the known genetic background and age of the patient, contribute to the distinct therapeutic responses observed clinically.The results of our study provide further evidence of the grave vulnerability of newborns to Na(+ channel defects and suggest that both genetic background and age are

  7. CDKL5 and ARX mutations are not responsible for early onset severe myoclonic epilepsy in infancy.

    Science.gov (United States)

    Nabbout, Rima; Depienne, Christel; Chipaux, Mathilde; Girard, Benoit; Souville, Isabelle; Trouillard, Oriane; Dulac, Olivier; Chelly, Jamel; Afenjar, Alexandra; Héron, Delphine; Leguern, Eric; Beldjord, Cherif; Bienvenu, Thierry; Bahi-Buisson, Nadia

    2009-11-01

    Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome (DS) is a distinctive epilepsy syndrome often associated with de novo mutations in the SCN1A gene. However, 25-30% patients with SMEI/DS are negative for SCN1A mutation screening, suggesting that other molecular mechanisms may account for these disorders. Given the overlapping and heterogeneous clinical features of CDKL5- and ARX-related epilepsies and SMEI/DS, we postulated that CDKL5 mutations in females and ARX mutations gene in males may be associated with early onset seizures forms of SMEI/DS. Twenty-eight patients with early onset SMEI/DS before 6 months negative for SCN1A mutational screening were selected and screened for mutations in the ARX gene in males (n=14) or the CDKL5 gene in females (n=14). No mutations in either gene were found except one intronic variation of uncertain pathogenicity in the CDKL5 gene. All patients started seizures at mean age of 3.48 months. Thirteen patients had familial history of epilepsy or febrile seizures. Patients evolved toward refractory epilepsy with generalized tonic clonic seizures (18/28) and myoclonia (23/28) and severe neurological impairment with autistic features (13/28), ataxia (14/28) and spasticity (5/28). No patient ever exhibited infantile spasms, dystonia, or Rett-like features. Our results illustrate that mutation screening of ARX and CDKL5 is not effective in patients selected on the basis of clinical signs associated to early onset SMEI/DS. In addition, they might reflect that other phenotypic features associated with CDKL5 mutations (Rett-like features, infantile spasm) or ARX mutations (dystonia, spasticity) are more distinctive. 2009 Elsevier B.V. All rights reserved.

  8. The human oculomotor response to simultaneous visual and physical movements at two different frequencies

    Science.gov (United States)

    Wall, C.; Assad, A.; Aharon, G.; Dimitri, P. S.; Harris, L. R.

    2001-01-01

    In order to investigate interactions in the visual and vestibular systems' oculomotor response to linear movement, we developed a two-frequency stimulation technique. Thirteen subjects lay on their backs and were oscillated sinusoidally along their z-axes at between 0.31 and 0.81 Hz. During the oscillation subjects viewed a large, high-contrast, visual pattern oscillating in the same direction as the physical motion but at a different, non-harmonically related frequency. The evoked eye movements were measured by video-oculography and spectrally analysed. We found significant signal level at the sum and difference frequencies as well as at other frequencies not present in either stimulus. The emergence of new frequencies indicates non-linear processing consistent with an agreement-detector system that have previously proposed.

  9. Frequency Response of Graphene Electrolyte-Gated Field-Effect Transistors

    Directory of Open Access Journals (Sweden)

    Charles Mackin

    2018-02-01

    Full Text Available This work develops the first frequency-dependent small-signal model for graphene electrolyte-gated field-effect transistors (EGFETs. Graphene EGFETs are microfabricated to measure intrinsic voltage gain, frequency response, and to develop a frequency-dependent small-signal model. The transfer function of the graphene EGFET small-signal model is found to contain a unique pole due to a resistive element, which stems from electrolyte gating. Intrinsic voltage gain, cutoff frequency, and transition frequency for the microfabricated graphene EGFETs are approximately 3.1 V/V, 1.9 kHz, and 6.9 kHz, respectively. This work marks a critical step in the development of high-speed chemical and biological sensors using graphene EGFETs.

  10. Antagonistic pleiotropy and mutation accumulation contribute to age-related decline in stress response.

    Science.gov (United States)

    Everman, Elizabeth R; Morgan, Theodore J

    2018-02-01

    As organisms age, the effectiveness of natural selection weakens, leading to age-related decline in fitness-related traits. The evolution of age-related changes associated with senescence is likely influenced by mutation accumulation (MA) and antagonistic pleiotropy (AP). MA predicts that age-related decline in fitness components is driven by age-specific sets of alleles, nonnegative genetic correlations within trait across age, and an increase in the coefficient of genetic variance. AP predicts that age-related decline in a trait is driven by alleles with positive effects on fitness in young individuals and negative effects in old individuals, and is expected to lead to negative genetic correlations within traits across age. We build on these predictions using an association mapping approach to investigate the change in additive effects of SNPs across age and among traits for multiple stress-response fitness-related traits, including cold stress with and without acclimation and starvation resistance. We found support for both MA and AP theories of aging in the age-related decline in stress tolerance. Our study demonstrates that the evolution of age-related decline in stress tolerance is driven by a combination of alleles that have age-specific additive effects, consistent with MA, as well as nonindependent and antagonistic genetic architectures characteristic of AP. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  11. Field Experience with Sweep Frequency Response Analysis for Power Transformer Diagnosis

    OpenAIRE

    Ambuj Kumar; Sunil Kumar Singh; Shrikant Singh

    2015-01-01

    Sweep frequency response analysis has been turning out a powerful tool for investigation of mechanical as well as electrical integration of transformers. In this paper various aspect of practical application of SFRA has been studied. Open circuit and short circuit measurement were done on different phases of high voltage and low voltage winding. A case study was presented for the transformer of rating 31.5 MVA for various frequency ranges. A clear picture was presented fo...

  12. Mode of recording and modulation frequency effects of auditory steady state response thresholds

    OpenAIRE

    Jalaei, Bahram; Shaabani, Moslem; Zakaria, Mohd Normani

    2017-01-01

    Abstract Introduction The performance of auditory steady state response (ASSR) in threshold testing when recorded ipsilaterally and contralaterally, as well as at low and high modulation frequencies (MFs), has not been systematically studied. Objective To verify the influences of mode of recording (ipsilateral vs. contralateral) and modulation frequency (40 Hz vs. 90 Hz) on ASSR thresholds. Methods Fifteen female and 14 male subjects (aged 18–30 years) with normal hearing bilaterally were ...

  13. Allele frequencies of hemojuvelin gene (HJV I222N and G320V missense mutations in white and African American subjects from the general Alabama population

    Directory of Open Access Journals (Sweden)

    Bohannon Sean B

    2004-12-01

    Full Text Available Abstract Background Homozygosity or compound heterozygosity for coding region mutations of the hemojuvelin gene (HJV in whites is a cause of early age-of-onset iron overload (juvenile hemochromatosis, and of hemochromatosis phenotypes in some young or middle-aged adults. HJV coding region mutations have also been identified recently in African American primary iron overload and control subjects. Primary iron overload unexplained by typical hemochromatosis-associated HFE genotypes is common in white and black adults in Alabama, and HJV I222N and G320V were detected in a white Alabama juvenile hemochromatosis index patient. Thus, we estimated the frequency of the HJV missense mutations I222N and G320V in adult whites and African Americans from Alabama general population convenience samples. Methods We evaluated the genomic DNA of 241 Alabama white and 124 African American adults who reported no history of hemochromatosis or iron overload to detect HJV missense mutations I222N and G320V using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP technique. Analysis for HJV I222N was performed in 240 whites and 124 African Americans. Analysis for HJV G320V was performed in 241 whites and 118 African Americans. Results One of 240 white control subjects was heterozygous for HJV I222N; she was also heterozygous for HFE C282Y, but had normal serum iron measures and bone marrow iron stores. HJV I222N was not detected in 124 African American subjects. HJV G320V was not detected in 241 white or 118 African American subjects. Conclusions HJV I222N and G320V are probably uncommon causes or modifiers of primary iron overload in adult whites and African Americans in Alabama. Double heterozygosity for HJV I222N and HFE C282Y may not promote increased iron absorption.

  14. The effect of sampling rate and anti-aliasing filters on high-frequency response spectra

    Science.gov (United States)

    Boore, David M.; Goulet, Christine

    2013-01-01

    The most commonly used intensity measure in ground-motion prediction equations is the pseudo-absolute response spectral acceleration (PSA), for response periods from 0.01 to 10 s (or frequencies from 0.1 to 100 Hz). PSAs are often derived from recorded ground motions, and these motions are usually filtered to remove high and low frequencies before the PSAs are computed. In this article we are only concerned with the removal of high frequencies. In modern digital recordings, this filtering corresponds at least to an anti-aliasing filter applied before conversion to digital values. Additional high-cut filtering is sometimes applied both to digital and to analog records to reduce high-frequency noise. Potential errors on the short-period (high-frequency) response spectral values are expected if the true ground motion has significant energy at frequencies above that of the anti-aliasing filter. This is especially important for areas where the instrumental sample rate and the associated anti-aliasing filter corner frequency (above which significant energy in the time series is removed) are low relative to the frequencies contained in the true ground motions. A ground-motion simulation study was conducted to investigate these effects and to develop guidance for defining the usable bandwidth for high-frequency PSA. The primary conclusion is that if the ratio of the maximum Fourier acceleration spectrum (FAS) to the FAS at a frequency fsaa corresponding to the start of the anti-aliasing filter is more than about 10, then PSA for frequencies above fsaa should be little affected by the recording process, because the ground-motion frequencies that control the response spectra will be less than fsaa . A second topic of this article concerns the resampling of the digital acceleration time series to a higher sample rate often used in the computation of short-period PSA. We confirm previous findings that sinc-function interpolation is preferred to the standard practice of using

  15. Effect of uvs1, uvs2 and xrs mutations on the radiosensitivity and the induced mitotic recombination frequency in diploid yeast cells

    International Nuclear Information System (INIS)

    Suslova, N.G.; Fedorova, I.V.; Zheleznyakova, N.Yu.

    1975-01-01

    The influence of the loci of radiosensitivity uvs1, uvs2, and xrs in the homozygous state at the diploid level on the sensitivity to UV and ionizing radiation and induced mitotic recombination was studied in the yeast Sacch. cerevisiae. Hypersensitivity to UV irradiation was detected in the diploids uvs2 uvs2 xrs xrs in comparision with the corresponding control. The diploid uvs1 uvs1 uvs2 uvs2 does not differ in UV sensitivity from the diploid uvs1 uvs1 UVS2 UVS2. These facts demonstrate that the uvs1 and uvs2 mutations, on the one hand, and the xrs mutations, on the other, normally control different pathways of elimination of UV-induced damages. It was shown that the diploid uvs2 uvs2 xrs3 xrs3 is far more sensitive to the lethal action of x rays than the control diploid UVS2 UVS2 xrs3 xrs3. Consequently, the mutations uvs2 and xrs3 block different modes of repair of damages induced by ionizing radiation. In all the double-mutant diploids, the frequency of mitotic recombination induced by UV rays increases sharply in comparison with that of the radioresistant diploids UVS UVS XRS XRS and the UV-sensitive diploids uvs2 uvs2 XRS XRS. Possible causes of the observed phenomenon are discussed. It was established that in a diploid homozygous for the loci uvs2 xrs5, the frequency of mitotic recombination induced by x rays increases extremely sharply. This fact confirms the hypothesis that the gene product of the locus uvs2 participates in the repair of DNA after the action of ionizing radiation. (author)

  16. Generation of artificial time-histories, rich in all frequencies from given response spectra

    International Nuclear Information System (INIS)

    Levy, S.; Wilkinson, J.P.D.

    1975-01-01

    In order to apply the time-history method of seismic analysis, it is often desirable to generate a suitable artificial time-history from a given response spectrum. The method described in this paper allows the generation of such a time-history that is also rich in all frequencies in the spectrum. This richness is achieved by choosing a large number of closely-spaced frequency points such that the adjacent frequencies have their half-power points overlap. The adjacent frequencies satisfy the condition that the frequency interval Δf near a given frequency f is such that (Δf)/f<2c/csub(c) where c is the damping of the system and csub(c) is the critical damping. In developing an artificial time-history, it is desirable to specify the envelope and duration of the record, very often in such a manner as to reproduce the envelope property of a specific earthquake record, and such an option is available in the method described. Examples are given of the development of typical articifial time-histories from earthquake design response spectra and from floor response spectra. (Auth.)

  17. Generation of artificial time-histories, rich in all frequencies, from given response spectra

    International Nuclear Information System (INIS)

    Levy, S.; Wilkinson, J.P.D.

    1975-01-01

    In order to apply the time-history method of seismic analysis, it is often desirable to generate a suitable artificial time-history from a given response spectrum. The method described allows the generation of such a time-history that is also rich in all frequencies in the spectrum. This richness is achieved by choosing a large number of closely-spaced frequency points such that the adjacent frequencies have their half-power points overlap. The adjacent frequencies satisfy the condition that the frequency interval Δf near a given frequency f is such that (Δf)/f<2c/csub(c) where c is the damping of the system and csub(c) is the critical damping. In developing an artificial time-history, it is desirable to specify the envelope and duration of the record, very often in such a manner as to reproduce the envelope property of a specific earthquake record, and such an option is available in the method described. Examples are given of the development of typical artificial time-histories from earthquake design response spectra and from floor response spectra

  18. The brain responses to different frequencies of binaural beat sounds on QEEG at cortical level.

    Science.gov (United States)

    Jirakittayakorn, Nantawachara; Wongsawat, Yodchanan

    2015-01-01

    Beat phenomenon is occurred when two slightly different frequency waves interfere each other. The beat can also occur in the brain by providing two slightly different frequency waves separately each ear. This is called binaural beat. The brain responses to binaural beat are in discussion process whether the brain side and the brain area. Therefore, this study aims to figure out the brain responses to binaural beat by providing different binaural beat frequencies on 250 carrier tone continuously for 30 minutes to participants and using quantitative electroencephalography (QEEG) to interpret the data. The result shows that different responses appear in different beat frequency. Left hemisphere dominance occur in 3 Hz beat within 15 minutes and 15 Hz beat within 5 minutes. Right hemisphere dominance occurs in 10 Hz beat within 25 minute. 6 Hz beat enhances all area of the brain within 10 minutes. 8 Hz and 25 Hz beats have no clearly responses while 40 Hz beat enhances the responses in frontal lobe. These brain responses can be used for brain modulation application to induce the brain activity in further studies.

  19. R102W mutation in the RS1 gene responsible for retinoschisis and recurrent glaucoma

    Directory of Open Access Journals (Sweden)

    Xiu-Feng Huang

    2014-02-01

    Full Text Available AIM: To identify the mutations in RS1 gene associated with typical phenotype of X-linked juvenile retinoschisis (XLRS and a rare condition of concomitant glaucoma.METHODS: Complete ophthalmic examinations were performed in the proband. The coding regions of the RS1 gene that encode retinoschisin were amplified by polymerase chain reaction and directly sequenced.RESULTS: The proband showed a typical phenotype of XLRS with large peripheral retinal schisis in both eyes, involving the macula and combined with foveal cystic change, reducing visual acuity. A typical phenotype of recurrent glaucoma with high intraocular pressure (IOP and reduced visual field was also demonstrated with the patient. Mutation analysis of RS1 gene revealed R102W (c.304C>T mutations in the affected male, and his mother was proved to be a carrier with the causative mutation and another synonymous polymorphism (c.576C>CT.CONCLUSION: We identified the genetic variations of a Chinese family with typical phenotype of XLRS and glaucoma. The severe XLRS phenotypes associated with R102W mutations reveal that the mutation determines a notable alteration in the function of the retinoschisin protein. Identification of the disease-causing mutation is beneficial for future clinical references.

  20. Antibiotic resistance in Pseudomonas aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system

    DEFF Research Database (Denmark)

    Mandsberg, Lotte F; Ciofu, Oana; Kirkby, N

    2009-01-01

    ,8-dihydro-8-oxodeoxyguanosine) than PAO1 after exposure to PMNs, and they developed resistance to antibiotics more frequently. The mechanisms of resistance were increased β-lactamase production and overexpression of the MexCD-OprJ efflux-pump. Mutations in either the mutT or the mutY gene were found...... in resistant HP clinical isolates from patients with CF, and complementation with wild-type genes reverted the phenotype. In conclusion, oxidative stress might be involved in the development of resistance to antibiotics. We therefore suggest the possible use of antioxidants for CF patients to prevent...

  1. TED, an Autonomous and Rare Maize Transposon of the Mutator Superfamily with a High Gametophytic Excision Frequency[W

    Science.gov (United States)

    Li, Yubin; Harris, Linda; Dooner, Hugo K.

    2013-01-01

    Mutator (Mu) elements, one of the most diverse superfamilies of DNA transposons, are found in all eukaryotic kingdoms, but are particularly numerous in plants. Most of the present knowledge on the transposition behavior of this superfamily comes from studies of the maize (Zea mays) Mu elements, whose transposition is mediated by the autonomous Mutator-Don Robertson (MuDR) element. Here, we describe the maize element TED (for Transposon Ellen Dempsey), an autonomous cousin that differs significantly from MuDR. Element excision and reinsertion appear to require both proteins encoded by MuDR, but only the single protein encoded by TED. Germinal excisions, rare with MuDR, are common with TED, but arise in one of the mitotic divisions of the gametophyte, rather than at meiosis. Instead, transposition-deficient elements arise at meiosis, suggesting that the double-strand breaks produced by element excision are repaired differently in mitosis and meiosis. Unlike MuDR, TED is a very low-copy transposon whose number and activity do not undergo dramatic changes upon inbreeding or outcrossing. Like MuDR, TED transposes mostly to unlinked sites and can form circular transposition products. Sequences closer to TED than to MuDR were detected only in the grasses, suggesting a rather recent evolutionary split from a common ancestor. PMID:24038653

  2. TED, an autonomous and rare maize transposon of the mutator superfamily with a high gametophytic excision frequency.

    Science.gov (United States)

    Li, Yubin; Harris, Linda; Dooner, Hugo K

    2013-09-01

    Mutator (Mu) elements, one of the most diverse superfamilies of DNA transposons, are found in all eukaryotic kingdoms, but are particularly numerous in plants. Most of the present knowledge on the transposition behavior of this superfamily comes from studies of the maize (Zea mays) Mu elements, whose transposition is mediated by the autonomous Mutator-Don Robertson (MuDR) element. Here, we describe the maize element TED (for Transposon Ellen Dempsey), an autonomous cousin that differs significantly from MuDR. Element excision and reinsertion appear to require both proteins encoded by MuDR, but only the single protein encoded by TED. Germinal excisions, rare with MuDR, are common with TED, but arise in one of the mitotic divisions of the gametophyte, rather than at meiosis. Instead, transposition-deficient elements arise at meiosis, suggesting that the double-strand breaks produced by element excision are repaired differently in mitosis and meiosis. Unlike MuDR, TED is a very low-copy transposon whose number and activity do not undergo dramatic changes upon inbreeding or outcrossing. Like MuDR, TED transposes mostly to unlinked sites and can form circular transposition products. Sequences closer to TED than to MuDR were detected only in the grasses, suggesting a rather recent evolutionary split from a common ancestor.

  3. Characterization of Deficiencies in the Frequency Domain Forced Response Analysis Technique for Turbine Bladed Disks

    Science.gov (United States)

    Brown, Andrew M.; Schmauch, Preston

    2012-01-01

    Turbine blades in rocket and jet engine turbomachinery experience enormous harmonic loading conditions. These loads result from the integer number of upstream and downstream stator vanes as well as the other turbine stages. The standard technique for forced response analysis to assess structural integrity is to decompose a CFD generated flow field into its harmonic components, and to then perform a frequency response analysis at the problematic natural frequencies. Recent CFD analysis and water-flow testing at NASA/MSFC, though, indicates that this technique may miss substantial harmonic and non-harmonic excitation sources that become present in complex flows. These complications suggest the question of whether frequency domain analysis is capable of capturing the excitation content sufficiently. Two studies comparing frequency response analysis with transient response analysis, therefore, have been performed. The first is of a bladed disk with each blade modeled by simple beam elements. It was hypothesized that the randomness and other variation from the standard harmonic excitation would reduce the blade structural response, but the results showed little reduction. The second study was of a realistic model of a bladed-disk excited by the same CFD used in the J2X engine program. The results showed that the transient analysis results were up to 10% higher for "clean" nodal diameter excitations and six times larger for "messy" excitations, where substantial Fourier content around the main harmonic exists.

  4. Hereditary Breast Cancer: Mutations Within BRCA1 and BRCA2 with Phenotypic Responses

    National Research Council Canada - National Science Library

    Lynch, Henry T

    2000-01-01

    To date we have seventy-three Hereditary Breast/Ovarian Cancer families with identified BRCA1 or BRCA2 genetic mutations, wherein 24 additional cases of slides and tissue blocks have been retrieved...

  5. Nonsyndromic retinitis pigmentosa is highly prevalent in the Jerusalem region with a high frequency of founder mutations.

    Science.gov (United States)

    Sharon, Dror; Banin, Eyal

    2015-01-01

    Nonsyndromic retinitis pigmentosa (RP) is the most common inherited retinal degeneration, and prevalence of the disease has been reported in populations of American and European origin with a relatively low consanguinity rate. Our aim was to determine the prevalence of nonsyndromic RP in the Jerusalem region, which has a population of about 1 million individuals with a high rate of consanguinity. The patients' clinical data included eye exam findings (visual acuity, anterior segment, and funduscopy) as well as electroretinographic (ERG) testing results under scotopic and photopic conditions. Mutation analysis on a subgroup of patients was performed mainly with candidate gene analysis and homozygosity mapping. We evaluated the medical records of patients with degenerative retinal diseases residing in the Jerusalem region who were examined over the past 20 years in a large tertiary medical center. A total of 453 individuals affected with nonsyndromic RP were diagnosed at our center, according to funduscopic findings and ERG testing. Based on the estimated population size of 945,000 individuals who reside in the vicinity of Jerusalem, the prevalence of nonsyndromic RP in this region is 1:2,086. The prevalence of RP was higher among Arab Muslims (1:1,798) compared to Jews (1:2,230), mainly due to consanguineous marriages that are more common in the Arab Muslim population. To identify the genetic causes of RP in our cohort, we recruited 383 patients from 183 different families for genetic analysis: 70 with autosomal recessive (AR) inheritance, 15 with autosomal dominant, 86 isolate cases, and 12 with an X-linked inheritance pattern. In 64 (35%) of the families, we identified the genetic cause of the disease, and we revised the inheritance pattern of 20 isolate cases to the AR pattern; 49% of the families in our cohort had AR inheritance. Interestingly, in 42 (66%) of the genetically identified families, the cause of disease was a founder mutation. Previous studies

  6. Ataxia telangiectasia mutated (ATM) interacts with p400 ATPase for an efficient DNA damage response.

    Science.gov (United States)

    Smith, Rebecca J; Savoian, Matthew S; Weber, Lauren E; Park, Jeong Hyeon

    2016-11-04

    Ataxia telangiectasia mutated (ATM) and TRRAP proteins belong to the phosphatidylinositol 3-kinase-related kinase family and are involved in DNA damage repair and chromatin remodeling. ATM is a checkpoint kinase that is recruited to sites of DNA double-strand breaks where it phosphorylates a diverse range of proteins that are part of the chromatin and DNA repair machinery. As an integral subunit of the TRRAP-TIP60 complexes, p400 ATPase is a chromatin remodeler that is also targeted to DNA double-strand break sites. While it is understood that DNA binding transcriptional activators recruit p400 ATPase into a regulatory region of the promoter, how p400 recognises and moves to DNA double-strand break sites is far less clear. Here we investigate a possibility whether ATM serves as a shuttle to deliver p400 to break sites. Our data indicate that p400 co-immunoprecipitates with ATM independently of DNA damage state and that the N-terminal domain of p400 is vital for this interaction. Heterologous expression studies using Sf9 cells revealed that the ATM-p400 complex can be reconstituted without other mammalian bridging proteins. Overexpression of ATM-interacting p400 regions in U2OS cells induced dominant negative effects including the inhibition of both DNA damage repair and cell proliferation. Consistent with the dominant negative effect, the stable expression of an N-terminal p400 fragment showed a decrease in the association of p400 with ATM, but did not alter the association of p400 with TRRAP. Taken together, our findings suggest that a protein-protein interaction between ATM and p400 ATPase occurs independently of DNA damage and contributes to efficient DNA damage response and repair.

  7. Impact of low-frequency hotspot mutation R282Q on the structure of p53 DNA-binding domain as revealed by crystallography at 1.54 Å resolution

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Chao [Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702 (United States); Tan, Yu-Hong [Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697 (United States); Shaw, Gary [Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702 (United States); Zhou, Zheng; Bai, Yawen [Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892 (United States); Luo, Ray [Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697 (United States); Ji, Xinhua, E-mail: jix@ncifcrf.gov [Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702 (United States)

    2008-05-01

    The impact of hotspot mutation R282Q on the structure of human p53 DNA-binding domain has been characterized by X-ray crystallography and molecular-dynamics simulations. Tumor suppressor p53 is a sequence-specific DNA-binding protein and its central DNA-binding domain (DBD) harbors six hotspots (Arg175, Gly245, Arg248, Arg249, Arg273 and Arg282) for human cancers. Here, the crystal structure of a low-frequency hotspot mutant, p53DBD(R282Q), is reported at 1.54 Å resolution together with the results of molecular-dynamics simulations on the basis of the structure. In addition to eliminating a salt bridge, the R282Q mutation has a significant impact on the properties of two DNA-binding loops (L1 and L3). The L1 loop is flexible in the wild type, but it is not flexible in the mutant. The L3 loop of the wild type is not flexible, whereas it assumes two conformations in the mutant. Molecular-dynamics simulations indicated that both conformations of the L3 loop are accessible under biological conditions. It is predicted that the elimination of the salt bridge and the inversion of the flexibility of L1 and L3 are directly or indirectly responsible for deactivating the tumor suppressor p53.

  8. Frequency response function (FRF) based updating of a laser spot welded structure

    Science.gov (United States)

    Zin, M. S. Mohd; Rani, M. N. Abdul; Yunus, M. A.; Sani, M. S. M.; Wan Iskandar Mirza, W. I. I.; Mat Isa, A. A.

    2018-04-01

    The objective of this paper is to present frequency response function (FRF) based updating as a method for matching the finite element (FE) model of a laser spot welded structure with a physical test structure. The FE model of the welded structure was developed using CQUAD4 and CWELD element connectors, and NASTRAN was used to calculate the natural frequencies, mode shapes and FRF. Minimization of the discrepancies between the finite element and experimental FRFs was carried out using the exceptional numerical capability of NASTRAN Sol 200. The experimental work was performed under free-free boundary conditions using LMS SCADAS. Avast improvement in the finite element FRF was achieved using the frequency response function (FRF) based updating with two different objective functions proposed.

  9. Engineering Inertial and Primary-Frequency Response for Distributed Energy Resources: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Dall-Anese, Emiliano [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Zhao, Changhong [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Guggilam, Swaroop [University of Minnesota; Dhople, Sairaj V [University of Minnesota; Chen, Yu C [University of British Columbia; Zhao, Changhong [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-12-19

    We propose a framework to engineer synthetic-inertia and droop-control parameters for distributed energy resources (DERs) so that the system frequency in a network composed of DERs and synchronous generators conforms to prescribed transient and steady-state performance specifications. Our approach is grounded in a second-order lumped-parameter model that captures the dynamics of synchronous generators and frequency-responsive DERs endowed with inertial and droop control. A key feature of this reduced-order model is that its parameters can be related to those of the originating higher-order dynamical model. This allows one to systematically design the DER inertial and droop-control coefficients leveraging classical frequency-domain response characteristics of second-order systems. Time-domain simulations validate the accuracy of the model-reduction method and demonstrate how DER controllers can be designed to meet steady-state-regulation and transient-performance specifications.

  10. DNA mutation motifs in the genes associated with inherited diseases.

    Directory of Open Access Journals (Sweden)

    Michal Růžička

    Full Text Available Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate. These sites are termed hotspots and exhibit a higher mutation frequency than expected by chance. In contrast, DNA sequences with lower mutation frequencies than expected by chance are termed coldspots. Mutation hotspots are usually derived from a mutation spectrum, which reflects particular population where an effect of a common ancestor plays a role. To detect coldspots/hotspots unaffected by population bias, we analysed the presence of germline mutations obtained from HGMD database in the 5-nucleotide segments repeatedly occurring in genes associated with common inherited disorders, in particular, the PAH, LDLR, CFTR, F8, and F9 genes. Statistically significant sequences (mutational motifs rarely associated with mutations (coldspots and frequently associated with mutations (hotspots exhibited characteristic sequence patterns, e.g. coldspots contained purine tract while hotspots showed alternating purine-pyrimidine bases, often with the presence of CpG dinucleotide. Using molecular dynamics simulations and free energy calculations, we analysed the global bending properties of two selected coldspots and two hotspots with a G/T mismatch. We observed that the coldspots were inherently more flexible than the hotspots. We assume that this property might be critical for effective mismatch repair as DNA with a mutation recognized by MutSα protein is noticeably bent.

  11. A Phex Mutation in a Murine Model of X-linked Hypophosphatemia Alters Phosphate Responsiveness of Bone Cells

    OpenAIRE

    Ichikawa, Shoji; Austin, Anthony M.; Gray, Amie K.; Econs, Michael J.

    2012-01-01

    Mutations in the PHEX gene cause X-linked hypophosphatemia (XLH). Hypophosphatemia in XLH results from increased circulating levels of a phosphaturic hormone, fibroblast growth factor 23 (FGF23), which inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D (calcitriol) synthesis. The current standard therapy for XLH – high dose phosphate and calcitriol – further increases FGF23 concentrations, suggesting that patients with XLH may have an altered response to extracellular phosphate...

  12. Role of Wind Power in Primary Frequency Response of an Interconnection: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y. C.; Gevorgian, V.; Ela, E.; Singhvi, V.; Pourbeik, P.

    2013-09-01

    The electrical frequency of an interconnection must be maintained very close to its nominal level at all times. Large frequency deviations can lead to unintended consequences such as load shedding, instability, and machine damage, among others. Turbine governors of conventional generating units provide primary frequency response (PFR) to ensure that frequency deviations are not significant duringlarge transient events. Increasing penetrations of variable renewable generation, such as wind and solar power, and planned retirements of conventional thermal plants - and thus a reduction in the amount of suppliers with PFR capabilities - causes concerns about a decline of PFR and system inertia in North America. The capability of inverter-coupled wind generation technologies to contribute toPFR and inertia, if appropriately equipped with the necessary control features, can help alleviate concerns. However, these responses differ from those supplied by conventional generation and inertia, and it is not entirely understood how variable renewable generation will affect the system response at different penetration levels. This paper evaluates the impact of wind generation providing PFRand synthetic inertial response on a large interconnection.

  13. Bias and frequency response of the permeability of CoZrNb/SiO2 multilayers

    International Nuclear Information System (INIS)

    Louis, E.; Jeong, I.S.; Walser, R.M.

    1990-01-01

    Compared to single-layer films, CoZrNb/SiO 2 multilayers with amorphous, soft magnetic films exhibit increased high-frequency response (to about 100 MHz) that is not understood. We studied single and multilayer films in this system and observed three distinct types of magnetic bias and frequency responses (phases I--III). The high-frequency responses of phase II and III films were reduced from that of phase I. Phase changes were produced in the single-layer amorphous CoZrNb films by varying the film thickness, and in double-layer (N=2) and multilayer (N>2) films by varying the magnetic layer thickness. The phase boundaries in the former were shifted by magnetostatic coupling of the perpendicular component of M. These studies indicated that phase I films had uniform planar magnetizations, while phase II and III films had perpendicular components. The results are summarized in the form of a phase diagram (film thickness versus inverse film separation), which suggests that the frequency response of multilayer thin films is enhanced when the individual magnetic layers are sufficiently thin to insure a planar magnetization (phase I)

  14. Improved low frequency room responses by considering finiteness of room boundary surfaces

    DEFF Research Database (Denmark)

    Jeong, Cheol-Ho

    2013-01-01

    surface impedance values that are assigned to all the boundary surfaces, the suggested reflection coefficient is found to improve low frequency responses compared to the infinite panel theory; larger improvements are found for a more disproportionate room, more absorptive surfaces, and surfaces having...

  15. Determining generator parameters of Camargos hydroelectric power plant through frequency response measurement

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Sebastiao E.M. de; Padua Guarini, Antonio de [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil); Souza, Joao A. de; Valgas, Helio M; Pinto, Roberto del Giudice R. [Companhia Energetica de Minas Gerais (CEMIG), Belo Horizonte, MG (Brazil)

    1994-12-31

    This work describes the results of the set frequency response tests performed in the generator number 2, 6.9 kV, 25 MVA, of Camargos hydroelectric power plant, CEMIG, and the parameters relatives to determined structures of model. This tests are unpublished in Brazil. (author) 7 refs., 16 figs., 7 tabs.

  16. Sizing of an Energy Storage System for Grid Inertial Response and Primary Frequency Reserve

    DEFF Research Database (Denmark)

    Knap, Vaclav; Chaudhary, Sanjay Kumar; Stroe, Daniel Loan

    2016-01-01

    Large-scale integration of renewable energy sources in power system leads to the replacement of conventional power plants (CPPs) and consequently challenges in power system reliability and security are introduced. This study is focused on improving the grid frequency response after a contingency ...

  17. Auditory Magnetoencephalographic Frequency-Tagged Responses Mirror the Ongoing Segmentation Processes Underlying Statistical Learning.

    Science.gov (United States)

    Farthouat, Juliane; Franco, Ana; Mary, Alison; Delpouve, Julie; Wens, Vincent; Op de Beeck, Marc; De Tiège, Xavier; Peigneux, Philippe

    2017-03-01

    Humans are highly sensitive to statistical regularities in their environment. This phenomenon, usually referred as statistical learning, is most often assessed using post-learning behavioural measures that are limited by a lack of sensibility and do not monitor the temporal dynamics of learning. In the present study, we used magnetoencephalographic frequency-tagged responses to investigate the neural sources and temporal development of the ongoing brain activity that supports the detection of regularities embedded in auditory streams. Participants passively listened to statistical streams in which tones were grouped as triplets, and to random streams in which tones were randomly presented. Results show that during exposure to statistical (vs. random) streams, tritone frequency-related responses reflecting the learning of regularities embedded in the stream increased in the left supplementary motor area and left posterior superior temporal sulcus (pSTS), whereas tone frequency-related responses decreased in the right angular gyrus and right pSTS. Tritone frequency-related responses rapidly developed to reach significance after 3 min of exposure. These results suggest that the incidental extraction of novel regularities is subtended by a gradual shift from rhythmic activity reflecting individual tone succession toward rhythmic activity synchronised with triplet presentation, and that these rhythmic processes are subtended by distinct neural sources.

  18. Frequency response for electromotility of isolated outer hair cells of the guinea pig

    NARCIS (Netherlands)

    Wit, HP; vanDijk, P; Segenhout, HM

    1996-01-01

    Frequency and impulse responses were determined for isolated guinea pig outer hair cells by electrically stimulating the cells between two wire electrodes with white noise. Cells were attached to the bottom of a small culture dish at one end while the other end was freely moving. Results have the

  19. Time and Frequency Domain Response of Grape Berries to Nondestructive Impact during the Harvesting Period

    Czech Academy of Sciences Publication Activity Database

    Trnka, Jan; Pavloušek, P.; Nedomová, Š.; Buchar, J.

    2016-01-01

    Roč. 47, č. 1 (2016), s. 24-33 ISSN 0022-4901 Institutional support: RVO:61388998 Keywords : berry´s response * dominant frequency * elastic modulus * grape berries Subject RIV: BO - Biophysics Impact factor: 1.290, year: 2016 http://onlinelibrary.wiley.com

  20. Bias Errors due to Leakage Effects When Estimating Frequency Response Functions

    Directory of Open Access Journals (Sweden)

    Andreas Josefsson

    2012-01-01

    Full Text Available Frequency response functions are often utilized to characterize a system's dynamic response. For a wide range of engineering applications, it is desirable to determine frequency response functions for a system under stochastic excitation. In practice, the measurement data is contaminated by noise and some form of averaging is needed in order to obtain a consistent estimator. With Welch's method, the discrete Fourier transform is used and the data is segmented into smaller blocks so that averaging can be performed when estimating the spectrum. However, this segmentation introduces leakage effects. As a result, the estimated frequency response function suffers from both systematic (bias and random errors due to leakage. In this paper the bias error in the H1 and H2-estimate is studied and a new method is proposed to derive an approximate expression for the relative bias error at the resonance frequency with different window functions. The method is based on using a sum of real exponentials to describe the window's deterministic autocorrelation function. Simple expressions are derived for a rectangular window and a Hanning window. The theoretical expressions are verified with numerical simulations and a very good agreement is found between the results from the proposed bias expressions and the empirical results.

  1. Visuomotor Entrainment and the Frequency-Dependent Response of Walking Balance to Perturbations.

    Science.gov (United States)

    Franz, Jason R; Francis, Carrie; Allen, Matt; Thelen, Darryl G

    2016-08-26

    Visuomotor entrainment, or the synchronization of motor responses to visual stimuli, is a naturally emergent phenomenon in human standing. Our purpose was to investigate the prevalence and resolution of visuomotor entrainment in walking and the frequency-dependent response of walking balance to perturbations. We used a virtual reality environment to manipulate optical flow in ten healthy young adults during treadmill walking. A motion capture system recorded trunk, sacrum, and heel marker trajectories during a series of 3-min conditions in which we perturbed a virtual hallway mediolaterally with systematic changes in the driving frequencies of perceived motion. We quantified visuomotor entrainment using spectral analyses and balance deficits using trunk sway, gait variability, and detrended fluctuation analyses (DFA). ML kinematics were highly sensitive to visual perturbations, and instinctively synchronized (i.e., entrained) to a broad range of driving frequencies of perceived ML motion. However, the influence of visual perturbations on metrics of walking balance was frequency-dependent and governed by their proximity to stride frequency. Specifically, we found that a driving frequency nearest to subjects' average stride frequency uniquely compromised trunk sway, gait variability, and step-to-step correlations. We conclude that visuomotor entrainment is a robust and naturally emerging phenomenon during human walking, involving coordinated and frequency-dependent adjustments in trunk sway and foot placement to maintain balance at the whole-body level. These findings provide mechanistic insight into how the visuomotor control of walking balance is disrupted by visual perturbations and important reference values for the emergence of balance deficits due to age, injury, or disease.

  2. Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss.

    NARCIS (Netherlands)

    Bespalova, I.N.; Camp, G. van; Bom, S.J.H.; Brown, D.J.; Cryns, K.; Wan, A.T. de; Erson, A.E.; Flothmann, K.; Kunst, H.P.M.; Kurnool, P.; Sivakumaran, T.A.; Cremers, C.W.R.J.; Leal, S.M.; Burmeister, M.; Lesperance, M.M.

    2001-01-01

    Non-syndromic low frequency sensorineural hearing loss (LFSNHL) affecting only 2000 Hz and below is an unusual type of hearing loss that worsens over time without progressing to profound deafness. This type of LFSNHL may be associated with mild tinnitus but is not associated with vertigo. We have

  3. Saccade frequency response to visual cues during gait in Parkinson's disease: the selective role of attention.

    Science.gov (United States)

    Stuart, Samuel; Lord, Sue; Galna, Brook; Rochester, Lynn

    2018-04-01

    Gait impairment is a core feature of Parkinson's disease (PD) with implications for falls risk. Visual cues improve gait in PD, but the underlying mechanisms are unclear. Evidence suggests that attention and vision play an important role; however, the relative contribution from each is unclear. Measurement of visual exploration (specifically saccade frequency) during gait allows for real-time measurement of attention and vision. Understanding how visual cues influence visual exploration may allow inferences of the underlying mechanisms to response which could help to develop effective therapeutics. This study aimed to examine saccade frequency during gait in response to a visual cue in PD and older adults and investigate the roles of attention and vision in visual cue response in PD. A mobile eye-tracker measured saccade frequency during gait in 55 people with PD and 32 age-matched controls. Participants walked in a straight line with and without a visual cue (50 cm transverse lines) presented under single task and dual-task (concurrent digit span recall). Saccade frequency was reduced when walking in PD compared to controls; however, visual cues ameliorated saccadic deficit. Visual cues significantly increased saccade frequency in both PD and controls under both single task and dual-task. Attention rather than visual function was central to saccade frequency and gait response to visual cues in PD. In conclusion, this study highlights the impact of visual cues on visual exploration when walking and the important role of attention in PD. Understanding these complex features will help inform intervention development. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  4. Minisequencing mitochondrial DNA pathogenic mutations

    Directory of Open Access Journals (Sweden)

    Carracedo Ángel

    2008-04-01

    Full Text Available Abstract Background There are a number of well-known mutations responsible of common mitochondrial DNA (mtDNA diseases. In order to overcome technical problems related to the analysis of complete mtDNA genomes, a variety of different techniques have been proposed that allow the screening of coding region pathogenic mutations. Methods We here propose a minisequencing assay for the analysis of mtDNA mutations. In a single reaction, we interrogate a total of 25 pathogenic mutations distributed all around the whole mtDNA genome in a sample of patients suspected for mtDNA disease. Results We have detected 11 causal homoplasmic mutations in patients suspected for Leber disease, which were further confirmed by standard automatic sequencing. Mutations m.11778G>A and m.14484T>C occur at higher frequency than expected by change in the Galician (northwest Spain patients carrying haplogroup J lineages (Fisher's Exact test, P-value Conclusion We here developed a minisequencing genotyping method for the screening of the most common pathogenic mtDNA mutations which is simple, fast, and low-cost. The technique is robust and reproducible and can easily be implemented in standard clinical laboratories.

  5. Role of KEAP1/NRF2 and TP53 mutations in lung squamous cell carcinoma development and radiotherapy response prediction

    Science.gov (United States)

    Jeong, Youngtae; Hoang, Ngoc T.; Lovejoy, Alexander; Stehr, Henning; Newman, Aaron M.; Gentles, Andrew J.; Kong, William; Truong, Diana; Martin, Shanique; Chaudhuri, Aadel; Heiser, Diane; Zhou, Li; Say, Carmen; Carter, Justin N.; Hiniker, Susan M.; Loo, Billy W.; West, Robert B.; Beachy, Philip; Alizadeh, Ash A.; Diehn, Maximilian

    2016-01-01

    Lung squamous cell carcinomas (LSCC) pathogenesis remains incompletely understood and biomarkers predicting treatment response remain lacking. Here we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histological and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in non-small lung cancer (NSCLC) patients and could be non-invasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs. PMID:27663899

  6. Specific-locus mutation frequencies in mouse stem-cell spermatogonia at very low radiation dose rates, and their use in the estimation of genetic hazards of radiation in man

    International Nuclear Information System (INIS)

    Russell, W.L.; Kelly, E.M.

    1982-01-01

    Experiments were undertaken to augment the information on the lowest radiation dose rates feasible for scoring transmitted induced mutations detected by the specific-locus method in the mouse. This is the type of information most suitable for estimating genetic hazards of radiation in man. The results also aid in resolving conflicting possibilities about the relationship between mutation frequency and radiation dose at low dose rates

  7. Extension of a nonlinear systems theory to general-frequency unsteady transonic aerodynamic responses

    Science.gov (United States)

    Silva, Walter A.

    1993-01-01

    A methodology for modeling nonlinear unsteady aerodynamic responses, for subsequent use in aeroservoelastic analysis and design, using the Volterra-Wiener theory of nonlinear systems is presented. The methodology is extended to predict nonlinear unsteady aerodynamic responses of arbitrary frequency. The Volterra-Wiener theory uses multidimensional convolution integrals to predict the response of nonlinear systems to arbitrary inputs. The CAP-TSD (Computational Aeroelasticity Program - Transonic Small Disturbance) code is used to generate linear and nonlinear unit impulse responses that correspond to each of the integrals for a rectangular wing with a NACA 0012 section with pitch and plunge degrees of freedom. The computed kernels then are used to predict linear and nonlinear unsteady aerodynamic responses via convolution and compared to responses obtained using the CAP-TSD code directly. The results indicate that the approach can be used to predict linear unsteady aerodynamic responses exactly for any input amplitude or frequency at a significant cost savings. Convolution of the nonlinear terms results in nonlinear unsteady aerodynamic responses that compare reasonably well with those computed using the CAP-TSD code directly but at significant computational cost savings.

  8. Induced micro-mutations in rice - the frequency and spectrum of gamma ray induced height variations in rice variety-Jaya

    International Nuclear Information System (INIS)

    Nair, N.K.; Ninan, C.A.

    1975-01-01

    Seeds of rice variety, Jaya, treated with moderate doses of (10, 20 and 30 kR) gamma rays were subjected to study the relative magnitude of induced variability and the type of mutations induced for height of plant in M 2 and M 3 generations. Progenies of 3352 M 1 spikes, totalling to 35691 M 2 plants and their subsequent progenies in M 3 were analysed. To get wider variability, very large populations in all the generations were studied. The mean value, genetic variance and phenotypic frequency distribution with and between generations were studied. The treated population showed no significant shift in mean values from that of control. The variance was greater in the irradiated material compared to control. The variability was found to shift in both plus and minus direction from that of control with a higher frequency in the minus direction in M 2 . A high frequency of dwarf mutants was observed in 20 kR treated population in the M 2 generation. The segregation ratio was higher in M 2 compared to M 3 generation. (author)

  9. Improved Detection of Vowel Envelope Frequency Following Responses Using Hotelling's T2 Analysis.

    Science.gov (United States)

    Vanheusden, Frederique J; Bell, Steven L; Chesnaye, Michael A; Simpson, David M

    2018-05-11

    Objective detection of brainstem responses to natural speech stimuli is an important tool for the evaluation of hearing aid fitting, especially in people who may not be able to respond reliably in behavioral tests. Of particular interest is the envelope frequency following response (eFFR), which refers to the EEG response at the stimulus' fundamental frequency (and its harmonics), and here in particular to the response to natural spoken vowel sounds. This article introduces the frequency-domain Hotelling's T (HT2) method for eFFR detection. This method was compared, in terms of sensitivity in detecting eFFRs at the fundamental frequency (HT2_F0), to two different single-channel frequency domain methods (F test on Fourier analyzer (FA) amplitude spectra [FA-F-Test] and magnitude-squared coherence [MSC]) in detecting envelope following responses to natural vowel stimuli in simulated data and EEG data from normal-hearing subjects. Sensitivity was assessed based on the number of detections and the time needed to detect a response for a false-positive rate of 5%. The study also explored whether a single-channel, multifrequency HT2 (HT2_3F) and a multichannel, multifrequency HT2 (HT2_MC) could further improve response detection. Four repeated words were presented sequentially at 70 dB SPL LAeq through ER-2 insert earphones. The stimuli consisted of a prolonged vowel in a /hVd/ structure (where V represents different vowel sounds). Each stimulus was presented over 440 sweeps (220 condensation and 220 rarefaction). EEG data were collected from 12 normal-hearing adult participants. After preprocessing and artifact removal, eFFR detection was compared between the algorithms. For the simulation study, simulated EEG signals were generated by adding random noise at multiple signal to noise ratios (SNRs; 0 to -60dB) to the auditory stimuli as well as to a single sinusoid at the fluctuating and flattened fundamental frequency (f0). For each SNR, 1000 sets of 440 simulated epochs

  10. Low-dose mutation-response relationships in Tradescantia; principles and comparison to mutagenesis following low-dose gaseous chemical mutagen exposure

    International Nuclear Information System (INIS)

    Nauman, C.H.; Sparrow, A.H.; Underbrink, A.G.; Schairer, L.A.

    1976-01-01

    Inflorescences of several clones of Tradescantia heterozygous for flower color have been treated with ionizing radiation and with the gaseous form of several known or suspected chemical mutagens. Pink somatic mutations were subsequently scored in the stamen hair cells of mature flowers and dose-/exposure-response curves constructed. Results indicate clearly that there is no evidence for a threshold for mutation response following x or neutron irradiation. Results so far obtained for gaseous chemical mutagens are less clear, but also suggest that there is no threshold for mutation response

  11. Incidence and Carrier Frequency of CFTR Gene Mutations in Pregnancies With Echogenic Bowel in Nova Scotia and Prince Edward Island.

    Science.gov (United States)

    Miller, Michelle E; Allen, Victoria M; Brock, Jo-Ann K

    2018-03-01

    Fetal echogenic bowel (echogenic bowel) is associated with cystic fibrosis (CF), with a reported incidence ranging from 1% to 13%. Prenatal testing for CF in the setting of echogenic bowel can be done by screening parental or fetal samples for pathogenic CFTR variants. If only one pathogenic variant is identified, sequencing of the CFTR gene can be undertaken, to identify a second pathogenic variant not covered in the standard screening panel. Full gene sequencing, however, also introduces the potential to identify variants of uncertain significance (VUSs) that can create counselling challenges and cause parental anxiety. To provide accurate counselling for families in the study population, the incidence of CF associated with echogenic bowel and the carrier frequency of CFTR variants were investigated. All pregnancies for which CF testing was undertaken for the indication of echogenic bowel (from Nova Scotia and Prince Edward Island) were identified (January 2007-July 2017). The CFTR screening and sequencing results were reviewed, and fetal outcomes related to CF were assessed. A total of 463 pregnancies with echogenic bowel were tested. Four were confirmed to be affected with CF, giving an incidence of 0.9% in this cohort. The carrier frequency of CF among all parents in the cohort was 5.0% (1 in 20); however, when excluding parents of affected fetuses, the carrier frequency for the population was estimated at 4.1% (1 in 25). CFTR gene sequencing identified an additional VUS in two samples. The incidence of CF in pregnancies with echogenic bowel in Nova Scotia and Prince Edward Island is 0.9%, with an estimated population carrier frequency of 4.1%. These results provide the basis for improved counselling to assess the risk of CF in the pregnancy, after parental carrier screening, using Bayesian probability. Counselling regarding VUSs should be undertaken before gene sequencing. Copyright © 2017 Society of Obstetricians and Gynaecologists of Canada. Published by

  12. A theoretical response of the electrostatic parallel plate to constant and low-frequency accelerations

    International Nuclear Information System (INIS)

    Lee, Ki Bang

    2009-01-01

    A theoretical response of an electrostatic gap-closing actuator based on parallel plates to constant and low-frequency accelerations has been derived as a function of the applied acceleration and voltage. The nonlinear equation of motion is obtained in a dimensionless form from the fact that the inertial and damping forces are neglected at a frequency much less than the resonant frequency of the parallel plate, and thereafter the nonlinear equation is solved for the stable inter-plate gap at the acceleration and voltage. From the derived solution, the pull-in acceleration is obtained as a function of the applied voltage, and the pull-in voltage is also expressed as a function of the acceleration. The closed-form solution is validated by comparison with a numerical solution. The theoretical solution is in excellent agreement with the numerical results when the actuator is exposed to a constant acceleration as well as a low-frequency acceleration. The theoretical solution and pull-in acceleration and voltage thus provide guidance to prescribe operational constraints for devices that use the parallel plate actuator and to predict the response of the electrostatic gap-closing parallel plates to constant and low-frequency acceleration

  13. Low Frequency Dispersion Mechanism of Dielectric Response for Oil-paper Insulation Diagnosis

    Institute of Scientific and Technical Information of China (English)

    ZHOU Lijun; LI Xianlang; WU Guangning

    2013-01-01

    Both the real part and imaginary part of complex permittivity approximately have a log-linear frequency dependency at low frequencies,especially at ultra-low frequencies under conditions of different moisture concentrations and temperatures,which is recognized as the low frequency dispersion (LFD).In order to explain this dispersion,a new mechanism of dielectric response of LFD of oil-paper insulation is proposed.A simplified one-dimensional mathematical model of concentration polarization carrier caused by slow migration is developed and solved,which indicates that ion mobility is closely related to the size of gap and the adsorption capacity of cellulose molecular chains to ions.A stochastic statistical model of the carrier mobility induced LFD is also developed.Moreover,actual tests under 50 ℃and 2% moisture content were put forward,as well as simulations with according current waveforms.The simulation results agreed well with the experimental data in that concentration polarization of carriers caused by slow migration is the probable cause of low frequency dispersion ofdielectric response for oil-paper insulation diagnosis.

  14. Enhancement of gamma-ray-induced mutation frequency in rice by post-treatment with chloral hydrate, methanol and their mixtures with ethanol

    International Nuclear Information System (INIS)

    Reddy, T.P.; Vaidyanath, K.

    1979-01-01

    An evaluation has been made of the mutagenic activity of ethanol, chlorate hydrate (CH) and methanol on rice seed. In independent treatments with ethanol, methanol, CH and four aqueous mixtures of these chemicals, chlorophyll-deficient mutants were not recovered in the M 2 generation. However, in sequential treatments with gamma rays + CH, gamma rays + methanol and gamma rays + aqueous mixtures of these chemicals, significant increases in the yields of chlorophyll mutations were observed as compared to that of a 30 kR gamma ray treatment. In contrast, post-irradiation treatment with ethanol failed to provoke any increase in the frequency of chlorophyll mutants in the M 2 generation. The results indicate that CH and methanol alone and mixed with ethanol can potentiate gamma ray-induced genetic lesions in rice seed. (author)

  15. Mutation, somatic mutation and diseases of man

    International Nuclear Information System (INIS)

    Burnet, F.M.

    1976-01-01

    The relevance of the intrinsic mutagenesis for the evolution process, genetic diseases and the process of aging is exemplified. The fundamental reaction is the function of the DNA and the DNA-enzymes like the DNA-polymerases in replication, repair, and transcription. These defects are responsible for the mutation frequency and the genetic drift in the evolution process. They cause genetic diseases like Xeroderma pigmentosum which is described here in detail. The accumulation of structural and functional mistakes leads to diseases of old age, for example to autoimmune diseases and immune suppression. There is a proportionality between the duration of life and the frequency of mistakes in the enzymatic repair system. No possibility of prophylaxis or therapy is seen. Methods for prognosis could be developed. (AJ) [de

  16. Influence of Clay Content, Mineralogy and Fabric On Radar Frequency Response of Aquifer Materials

    Science.gov (United States)

    West, L. J.; Handley, K.

    High frequency electromagnetic methods such as ground penetrating radar (GPR) and time domain reflectometry (TDR) are widely employed to measure water saturation in the vadose zone and water filled porosity in the saturated zone. However, previous work has shown that radar frequency dielectric properties are strongly influenced by clay as well as by water content. They have also shown that that the dielectric response of clay minerals is strongly frequency dependent, and that even a small proportion of clay such as that present in many sandstone aquifers can have a large effect at typi- cal GPR frequencies (around 100MHz). Hence accurate water content/porosity deter- mination requires clay type and content to be taken into account. Reported here are dielectric measurements on clay-sand mixtures, aimed at investigating the influence of clay mineralogy, particle shape, and the geometrical arrangement of the mixture constituents on GPR and TDR response. Dielectric permittivity (at 50-1000MHz) was measured for mixtures of Ottawa Sand and various clay minerals or clay size quartz rock flour, using a specially constructed dielectric cell. Both homogeneous and layered mixtures were tested. The influence of pore water salinity, clay type, and particle arrangement on the dielectric response is interpreted in terms of dielectric dispersion mechanisms. The appropriateness of var- ious dielectric mixing rules such as the Complex Refractive Index Method (CRIM) for determination of water content or porosity from field GPR and TDR data are dis- cussed.

  17. Broadband frequency and angular response of a sinusoidal bull’s eye antenna

    Science.gov (United States)

    Beaskoetxea, U.; Navarro-Cía, M.; Beruete, M.

    2016-07-01

    A thorough experimental study of the frequency and beaming angle response of a metallic leaky-wave bull’s eye antenna working at 77 GHz with a sinusoidally corrugated profile is presented. The beam scanning property of these antennas as frequency is varied is experimentally demonstrated and corroborated through theoretical and numerical results. From the experimental results the dispersion diagram of the n  =  -1 and n  =  -2 space harmonics is extracted, and the operation at different frequency regimes is identified and discussed. In order to show the contribution of each half of the antenna, numerical examples of the near-field behavior are also displayed. Overall, experimental results are in good qualitative and quantitative agreement with theoretical and numerical calculations. Finally, an analysis of the beamwidth as a function of frequency is performed, showing that it can achieve values below 1.5° in a fractional bandwidth of 4% around the operation frequency, which is an interesting frequency-stable broadside radiation.

  18. Broadband frequency and angular response of a sinusoidal bull’s eye antenna

    International Nuclear Information System (INIS)

    Beaskoetxea, U; Beruete, M; Navarro-Cía, M

    2016-01-01

    A thorough experimental study of the frequency and beaming angle response of a metallic leaky-wave bull’s eye antenna working at 77 GHz with a sinusoidally corrugated profile is presented. The beam scanning property of these antennas as frequency is varied is experimentally demonstrated and corroborated through theoretical and numerical results. From the experimental results the dispersion diagram of the n   =  −1 and n   =  −2 space harmonics is extracted, and the operation at different frequency regimes is identified and discussed. In order to show the contribution of each half of the antenna, numerical examples of the near-field behavior are also displayed. Overall, experimental results are in good qualitative and quantitative agreement with theoretical and numerical calculations. Finally, an analysis of the beamwidth as a function of frequency is performed, showing that it can achieve values below 1.5° in a fractional bandwidth of 4% around the operation frequency, which is an interesting frequency-stable broadside radiation. (paper)

  19. Dynamic pressure probe response tests for robust measurements in periodic flows close to probe resonating frequency

    Science.gov (United States)

    Ceyhun Şahin, Fatma; Schiffmann, Jürg

    2018-02-01

    A single-hole probe was designed to measure steady and periodic flows with high fluctuation amplitudes and with minimal flow intrusion. Because of its high aspect ratio, estimations showed that the probe resonates at a frequency two orders of magnitude lower than the fast response sensor cut-off frequencies. The high fluctuation amplitudes cause a non-linear behavior of the probe and available models are neither adequate for a quantitative estimation of the resonating frequencies nor for predicting the system damping. Instead, a non-linear data correction procedure based on individual transfer functions defined for each harmonic contribution is introduced for pneumatic probes that allows to extend their operating range beyond the resonating frequencies and linear dynamics. This data correction procedure was assessed on a miniature single-hole probe of 0.35 mm inner diameter which was designed to measure flow speed and direction. For the reliable use of such a probe in periodic flows, its frequency response was reproduced with a siren disk, which allows exciting the probe up to 10 kHz with peak-to-peak amplitudes ranging between 20%-170% of the absolute mean pressure. The effect of the probe interior design on the phase lag and amplitude distortion in periodic flow measurements was investigated on probes with similar inner diameters and different lengths or similar aspect ratios (L/D) and different total interior volumes. The results suggest that while the tube length consistently sets the resonance frequency, the internal total volume affects the non-linear dynamic response in terms of varying gain functions. A detailed analysis of the introduced calibration methodology shows that the goodness of the reconstructed data compared to the reference data is above 75% for fundamental frequencies up to twice the probe resonance frequency. The results clearly suggest that the introduced procedure is adequate to capture non-linear pneumatic probe dynamics and to

  20. Low-frequency response in antiferromagnetically coupled Fe/Cr multilayers

    International Nuclear Information System (INIS)

    Aliev, F.G.; Guerrero, R.; Martinez, J.L.; Moshchalkov, V.V.; Bruynseraede, Y.; Villar, R.

    2001-01-01

    We have studied the magnetic field dependences of the real (χ) and imaginary (χ') contributions to the low-frequency magnetic susceptibility in epitaxial antiferromagnetically coupled [Fe(Cr(1 0 0)] n (n=10-50) multilayers. For the magnetic field directed along (1 1 0), the magnetic susceptibility shows on orientation phase transition. For the magnetic field either along the easy or the hard axes we observe a strong enhancement of the χ'(H) (i.e. magnetic losses) at low magnetic fields (H<50 Oe), which we relate to AC field-induced domain wall movement. This response is strongly dependent on frequency and temperature

  1. Comparative studies of dose-response curves for recessive lethal mutations induced by ethylnitrosourea in spermatogonia and in spermatozoa of Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, I.; Ayaki, T.; Ohshima, K.

    1984-01-01

    Induction of recessive lethal mutation by N-ethyl-N-nitrosourea (ENU) was studied for the second chromosome of spermatogonia and spermatozoa in Drosophila melanogaster. ENU (0.03, 0.3, and 1.0 mM) was given to flies by dissolving it in feeding sucrose solution. When plotted against absorbed doses of ENU, the observed frequencies to recessive lethals showed a linear relationship for induction in spermatozoa but a sigmoidal relationship for induction in spermatogonia. These results suggest that in spermatogonia ENU-induced mutational damage is more repairable in a lower dose range of ENU. Mosaic lethal mutations were induced by ENU but not in spermatogonia.

  2. BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

    Science.gov (United States)

    Wunderle, Marius; Gass, Paul; Häberle, Lothar; Flesch, Vivien M; Rauh, Claudia; Bani, Mayada R; Hack, Carolin C; Schrauder, Michael G; Jud, Sebastian M; Emons, Julius; Erber, Ramona; Ekici, Arif B; Hoyer, Juliane; Vasileiou, Georgia; Kraus, Cornelia; Reis, Andre; Hartmann, Arndt; Lux, Michael P; Beckmann, Matthias W; Fasching, Peter A; Hein, Alexander

    2018-05-03

    BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

  3. A marked response to icotinib in a patient with large cell neuroendocrine carcinoma harboring an EGFR mutation: A case report.

    Science.gov (United States)

    Wang, Yuehong; Shen, Yi Hong; Ma, Shanni; Zhou, Jianying

    2015-09-01

    The present study reports the case of an 84-year-old male with primary pulmonary large cell neuroendocrine carcinoma (LCNEC) harboring an epidermal growth factor receptor (EGFR) gene mutation that exhibited a long-lasting response to the EGFR-tyrosine kinase inhibitor (EGFR-TKI) icotinib. The patient had an extensive smoking history, a poor performance status, and presented with an irregular mass in the middle lobe of the right lung on computed tomography (CT) and an enlarged left supraclavicular lymph node on physical examination. Right middle lobe bronchial brushing during fiberoptic bronchoscopy identified poorly-differentiated cancer cells. The left supraclavicular lymph node was biopsied and a diagnosis of metastatic LCNEC was determined. Furthermore, an EGFR exon 19 deletion was identified by DNA sequencing. Following diagnosis, icotinib was administered at a dose of 125 mg three times a day. Chest CT scans were performed after 1 month of treatment, which indicated that the tumor was in partial remission. This marked response to icotinib lasted for 8 months. Thus, the present case illustrates the possibility of identifying EGFR mutations in LCNEC and indicates that EGFR-tyrosine kinase inhibitors may be an alternative treatment strategy for patients with LCNEC harboring activating EGFR mutations.

  4. Auditory steady-state responses in cochlear implant users: Effect of modulation frequency and stimulation artifacts.

    Science.gov (United States)

    Gransier, Robin; Deprez, Hanne; Hofmann, Michael; Moonen, Marc; van Wieringen, Astrid; Wouters, Jan

    2016-05-01

    Previous studies have shown that objective measures based on stimulation with low-rate pulse trains fail to predict the threshold levels of cochlear implant (CI) users for high-rate pulse trains, as used in clinical devices. Electrically evoked auditory steady-state responses (EASSRs) can be elicited by modulated high-rate pulse trains, and can potentially be used to objectively determine threshold levels of CI users. The responsiveness of the auditory pathway of profoundly hearing-impaired CI users to modulation frequencies is, however, not known. In the present study we investigated the responsiveness of the auditory pathway of CI users to a monopolar 500 pulses per second (pps) pulse train modulated between 1 and 100 Hz. EASSRs to forty-three modulation frequencies, elicited at the subject's maximum comfort level, were recorded by means of electroencephalography. Stimulation artifacts were removed by a linear interpolation between a pre- and post-stimulus sample (i.e., blanking). The phase delay across modulation frequencies was used to differentiate between the neural response and a possible residual stimulation artifact after blanking. Stimulation artifacts were longer than the inter-pulse interval of the 500pps pulse train for recording electrodes ipsilateral to the CI. As a result the stimulation artifacts could not be removed by artifact removal on the bases of linear interpolation for recording electrodes ipsilateral to the CI. However, artifact-free responses could be obtained in all subjects from recording electrodes contralateral to the CI, when subject specific reference electrodes (Cz or Fpz) were used. EASSRs to modulation frequencies within the 30-50 Hz range resulted in significant responses in all subjects. Only a small number of significant responses could be obtained, during a measurement period of 5 min, that originate from the brain stem (i.e., modulation frequencies in the 80-100 Hz range). This reduced synchronized activity of brain stem

  5. A study of dose effect response and the interrelationship between cell survival, mutation and chromosomal aberration

    International Nuclear Information System (INIS)

    Chadwick, K.H.; Leenhouts, H.P.; Werry, P.A.Th.J.; Ramulu, K.S.

    1980-01-01

    Research was carried out on four topics: generation of cell reproductive death and mutation induction in cell cultures of Haplopappus gracilis by ionizing radiation; radiation induced repair in Saintpaulia epidermis cells; analysis of the combined effect of radiation with other mutagens; and the effect of very low doses of radiation on the Oenothera model system. (Auth.)

  6. Prediction of power system frequency response after generator outages using neural nets

    Energy Technology Data Exchange (ETDEWEB)

    Djukanovic, M B; Popovic, D P [Electrotechnicki Inst. ' Nikola Tesla' , Belgrade (Yugoslavia); Sobajic, D J; Pao, Y -H [Case Western Reserve Univ., Cleveland, OH (United States)

    1993-09-01

    A new methodology is presented for estimating the frequency behaviour of power systems necessary for an indication of under-frequency load shedding in steady-state security assessment. It is well known that large structural disturbances such as generator tripping or load outages can initiate cascading outages, system separation into islands, and even the complete breakup. The approach provides a fairly accurate method of estimating the system average frequency response without making simplifications or neglecting non-linearities and small time constants in the equations of generating units, voltage regulators and turbines. The efficiency of the new procedure is demonstrated using the New England power system model for a series of characteristic perturbations. The validity of the proposed approach is verified by comparison with the simulation of short-term dynamics including effects of control and automatic devices. (author)

  7. Psychophysical and physiological responses to gratings with luminance and chromatic components of different spatial frequencies.

    Science.gov (United States)

    Cooper, Bonnie; Sun, Hao; Lee, Barry B

    2012-02-01

    Gratings that contain luminance and chromatic components of different spatial frequencies were used to study the segregation of signals in luminance and chromatic pathways. Psychophysical detection and discrimination thresholds to these compound gratings, with luminance and chromatic components of the one either half or double the spatial frequency of the other, were measured in human observers. Spatial frequency tuning curves for detection of compound gratings followed the envelope of those for luminance and chromatic gratings. Different grating types were discriminable at detection threshold. Fourier analysis of physiological responses of macaque retinal ganglion cells to compound waveforms showed chromatic information to be restricted to the parvocellular pathway and luminance information to the magnocellular pathway. Taken together, the human psychophysical and macaque physiological data support the strict segregation of luminance and chromatic information in independent channels, with the magnocellular and parvocellular pathways, respectively, serving as likely the physiological substrates. © 2012 Optical Society of America

  8. Role of growth temperature on the frequency response characteristics of pentacene-based organic devices

    International Nuclear Information System (INIS)

    Shao, Yayun; Zhang, Yang; He, Wenqiang; Wu, Sujuan; Zeng, Min; Zhang, Zhang; Gao, Xingsen; Lu, Xubing; Liu, J-M; Liu, Chuan; Minari, Takeo

    2015-01-01

    The ac frequency response characteristics (FRC) of organic thin film transistors and metal-insulator semiconductor diodes were highly improved by controlling the morphology and electrical characteristics of semiconducting pentacene films. The devices with films grown at 50 °C show much higher cutoff frequency and better frequency stability of flat-band voltage, as compared to those with films grown at other temperatures below or above. The improvement mainly originates from the maximum field effect carrier mobility of 0.78 cm 2 V −1 s −1 and a small metal/organic contact resistance (R c ) obtained in the optimum thin film transistors. Our results indicate growth temperature precisely tunes the film microstructure and metal/semiconductor interface, which together determine the FRC of pentacene-based organic devices. (paper)

  9. Comparison of the frequency response characteristics of catheter-mounted piezoelectric and micromanometric phonotransducers.

    Science.gov (United States)

    Garcia, J C; Layton, S A; Rubal, B J

    1989-05-01

    This study compares the frequency response characteristics of catheter-mounted piezoelectric sound transducers with micromanometric transducers. The tip of a 8F catheter with two piezoelectric transducers and two micromanometers was inserted into a water-filled chamber that had a speaker fixed at one end. The speaker was driven by a power amplifier and sine wave generator. The outputs of the transducers were connected to a low-level amplifier. The piezoelectric transducer behaved as a tunable high-pass filter that could be modified by altering the input impedance of the low level amplifier; the frequency response characteristics were examined at five input impedances ranging from 0.96 to 11.8 megohms. The peak-to-peak outputs of the piezoelectric and pressure transducers were recorded at frequency ranges from DC to 1 kHz with a wide-band oscilloscope. The ratio of the outputs from the piezotransducer and micromanometer (Vph/Vpr) was plotted vs. frequency for each input impedance and analyzed to determine the piezotransducer's output resistance and equivalent capacitance; roll-off frequencies were then calculated. The equivalent capacitance of the piezo-element was determined to be 500-700 picofarads. Series capacitance acted with network resistance to produce a predictable frequency-dependent change in signal amplitude and phase angle. The inherent noise of the pressure transducer was found to be approximately 0.2 mm Hg, while the noise of the piezoelectric transducer was immeasurably low. The piezoelectric phonotransducers were superior to micromanometer transducers in their higher gain and lower noise, suggesting that these transducers may prove useful to physiologic and clinical studies for measuring intravascular sound.

  10. A fortran programme for determining frequency responses for linear systems with time delays

    International Nuclear Information System (INIS)

    Milsom, P.R.

    1966-11-01

    In this report a digital computer programme for evaluating frequency responses is described. In its standard form the programme is capable of determining the gain and phase of up to 35 variables over a range of up to 30 frequencies for a system described by up to 65 equations. The equations must be either first order differential or algebraic and either type may include time delayed terms. Up to 50 such terms are permissible throughout the equation set. Provision is made for up to 10 inputs and up to 50 differentiated input terms are permitted throughout the equation set. However, it is possible for the user to increase a maximum dimension, albeit at the expense of another array dimension. In punching the data from the equations the user has no sorting or arranging of coefficients to do, and the equations may be in any order. The specifying of other input information, such as frequency range, the inputs to be perturbed and the variables for which frequency responses are required, is also very straightforward. (author)

  11. High frequency switched-mode stimulation can evoke postsynaptic responses in cerebellar principal neurons

    Directory of Open Access Journals (Sweden)

    Marijn Van Dongen

    2015-03-01

    Full Text Available This paper investigates the efficacy of high frequency switched-mode neural stimulation. Instead of using a constant stimulation amplitude, the stimulus is switched on and off repeatedly with a high frequency (up to 100kHz duty cycled signal. By means of tissue modeling that includes the dynamic properties of both the tissue material as well as the axon membrane, it is first shown that switched-mode stimulation depolarizes the cell membrane in a similar way as classical constant amplitude stimulation.These findings are subsequently verified using in vitro experiments in which the response of a Purkinje cell is measured due to a stimulation signal in the molecular layer of the cerebellum of a mouse. For this purpose a stimulator circuit is developed that is able to produce a monophasic high frequency switched-mode stimulation signal. The results confirm the modeling by showing that switched-mode stimulation is able to induce similar responses in the Purkinje cell as classical stimulation using a constant current source. This conclusion opens up possibilities for novel stimulation designs that can improve the performance of the stimulator circuitry. Care has to be taken to avoid losses in the system due to the higher operating frequency.

  12. Frequency response analysis of cylindrical shells conveying fluid using finite element method

    International Nuclear Information System (INIS)

    Seo, Young Soo; Jeong, Weui Bong; Yoo, Wan Suk; Jeong, Ho Kyeong

    2005-01-01

    A finite element vibration analysis of thin-walled cylindrical shells conveying fluid with uniform velocity is presented. The dynamic behavior of thin-walled shell is based on the Sanders' theory and the fluid in cylindrical shell is considered as inviscid and incompressible so that it satisfies the Laplace's equation. A beam-like shell element is used to reduce the number of degree-of-freedom by restricting to the circumferential modes of cylindrical shell. An estimation of frequency response function of the pipe considering of the coupled effects of the internal fluid is presented. A dynamic coupling condition of the interface between the fluid and the structure is used. The effective thickness of fluid according to circumferential modes is also discussed. The influence of fluid velocity on the frequency response function is illustrated and discussed. The results by this method are compared with published results and those by commercial tools

  13. Electrical Grid Stability Enhancement using Smart Home Frequency-response Grid -Friendly Appliance System

    Directory of Open Access Journals (Sweden)

    Muawiya A. Kaigama

    2016-03-01

    Full Text Available Load shedding is a powerful scheme used for corrective and preventive measures; corrective to restore system’s stability and preventive to avoid catastrophic failure. However, the affected end users are deprived of power supply absolutely with no choice. This paper presents the design, development, feasibility and merits of Frequency-response Grid -Friendly Appliance System (FRGFAS in a smart home. FRGFAS is a decentralized Adaptive Load Shaving(ALS device that supports grid’s system stability by sensing grid’s frequency deterioration level and turns ON/OFF loads accordingly. The FRGFAS permits end users to carry out load shaving at their scale of preference in smart homes via flexible demand responses and automates outdoor lighting to optimum operational hours. FRGFAS obviate load shedding by shaving loads whenever the system is in distress and reset loads supply to the normal state when it stabilizes, this Consequently increases the end user comfort zone and averts a blackout.

  14. Frequency response control of semiconductor laser by using hybrid modulation scheme.

    Science.gov (United States)

    Mieda, Shigeru; Yokota, Nobuhide; Isshiki, Ryuto; Kobayashi, Wataru; Yasaka, Hiroshi

    2016-10-31

    A hybrid modulation scheme that simultaneously applies the direct current modulation and intra-cavity loss modulation to a semiconductor laser is proposed. Both numerical calculations using rate equations and experiments using a fabricated laser show that the hybrid modulation scheme can control the frequency response of the laser by changing a modulation ratio and time delay between the two modulations. The modulation ratio and time delay provide the degree of signal mixing of the two modulations and an optimum condition is found when a non-flat frequency response for the intra-cavity loss modulation is compensated by that for the direct current modulation. We experimentally confirm a 8.64-dB improvement of the modulation sensitivity at 20 GHz compared with the pure direct current modulation with a 0.7-dB relaxation oscillation peak.

  15. Frequency response testing at Experimental Breeder Reactor II using discrete-level periodic signals

    International Nuclear Information System (INIS)

    Rhodes, W.D.; Larson, H.A.

    1990-01-01

    The Experimental Breeder Reactor 2 (EBR-2) reactivity-to-power frequency-response function was measured with pseudo-random, discrete-level, periodic signals. The reactor power deviation was small with insignificant perturbation of normal operation and in-place irradiation experiments. Comparison of results with measured rod oscillator data and with theoretical predictions show good agreement. Moreover, measures of input signal quality (autocorrelation function and energy spectra) confirm the ability to enable this type of frequency response determination at EBR-2. Measurements were made with the pseudo-random binary sequence, quadratic residue binary sequence, pseudo-random ternary sequence, and the multifrequency binary sequence. 10 refs., 7 figs., 3 tabs

  16. Contact area affects frequency-dependent responses to vibration in the peripheral vascular and sensorineural systems.

    Science.gov (United States)

    Krajnak, Kristine; Miller, G R; Waugh, Stacey

    2018-01-01

    Repetitive exposure to hand-transmitted vibration is associated with development of peripheral vascular and sensorineural dysfunctions. These disorders and symptoms associated with it are referred to as hand-arm vibration syndrome (HAVS). Although the symptoms of the disorder have been well characterized, the etiology and contribution of various exposure factors to development of the dysfunctions are not well understood. Previous studies performed using a rat-tail model of vibration demonstrated that vascular and peripheral nervous system adverse effects of vibration are frequency-dependent, with vibration frequencies at or near the resonant frequency producing the most severe injury. However, in these investigations, the amplitude of the exposed tissue was greater than amplitude typically noted in human fingers. To determine how contact with vibrating source and amplitude of the biodynamic response of the tissue affects the risk of injury occurring, this study compared the influence of frequency using different levels of restraint to assess how maintaining contact of the tail with vibrating source affects the transmission of vibration. Data demonstrated that for the most part, increasing the contact of the tail with the platform by restraining it with additional straps resulted in an enhancement in transmission of vibration signal and elevation in factors associated with vascular and peripheral nerve injury. In addition, there were also frequency-dependent effects, with exposure at 250 Hz generating greater effects than vibration at 62.5 Hz. These observations are consistent with studies in humans demonstrating that greater contact and exposure to frequencies near the resonant frequency pose the highest risk for generating peripheral vascular and sensorineural dysfunction.

  17. Low frequency complex dielectric (conductivity) response of dilute clay suspensions: Modeling and experiments.

    Science.gov (United States)

    Hou, Chang-Yu; Feng, Ling; Seleznev, Nikita; Freed, Denise E

    2018-04-11

    In this work, we establish an effective medium model to describe the low-frequency complex dielectric (conductivity) dispersion of dilute clay suspensions. We use previously obtained low-frequency polarization coefficients for a charged oblate spheroidal particle immersed in an electrolyte as the building block for the Maxwell Garnett mixing formula to model the dilute clay suspension. The complex conductivity phase dispersion exhibits a near-resonance peak when the clay grains have a narrow size distribution. The peak frequency is associated with the size distribution as well as the shape of clay grains and is often referred to as the characteristic frequency. In contrast, if the size of the clay grains has a broad distribution, the phase peak is broadened and can disappear into the background of the canonical phase response of the brine. To benchmark our model, the low-frequency dispersion of the complex conductivity of dilute clay suspensions is measured using a four-point impedance measurement, which can be reliably calibrated in the frequency range between 0.1 Hz and 10 kHz. By using a minimal number of fitting parameters when reliable information is available as input for the model and carefully examining the issue of potential over-fitting, we found that our model can be used to fit the measured dispersion of the complex conductivity with reasonable parameters. The good match between the modeled and experimental complex conductivity dispersion allows us to argue that our simplified model captures the essential physics for describing the low-frequency dispersion of the complex conductivity of dilute clay suspensions. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Optimization of a space spectrograph main frame and frequency response analysis of the frame

    Science.gov (United States)

    Zhang, Xin-yu; Chen, Zhi-yuan; Yang, Shi-mo

    2009-07-01

    A space spectrograph main structure is optimized and examined in order to satisfy the space operational needs. The space spectrograph will be transported into its operational orbit by the launch vehicle and it will undergo dynamic environment in the spacecraft injection period. The unexpected shocks may cause declination of observation accuracy and even equipment damages. The main frame is one of the most important parts because its mechanical performance has great influence on the operational life of the spectrograph, accuracy of observation, etc. For the reason of cost reduction and stability confirming, lower weight and higher structure stiffness of the frame are simultaneously required. Structure optimization was conducted considering the initial design modal analysis results. The base modal frequency raised 10.34% while the whole weight lowered 8.63% compared to the initial design. The purpose of this study is to analyze the new design of main frame mechanical properties and verify whether it can satisfy strict optical demands under the dynamic impact during spacecraft injection. For realizing and forecasting the frequency response characteristics of the main structure in mechanical environment experiment, dynamic analysis of the structure should be performed simulating impulse loads from the bottom base. Therefore, frequency response analysis (FRA) of the frame was then performed using the FEA software MSC.PATRAN/NASTRAN. Results of shock response spectrum (SRS) responses from the base excitations were given. Stress and acceleration dynamic responses of essential positions in the spacecraft injection course were also calculated and spectrometer structure design was examined considering stiffness / strength demands. In this simulation, maximum stresses of Cesic material in two acceleration application cases are 45.1 and 74.1 MPa, respectively. They are all less than yield strengths. As is demonstrated from the simulation, strength reservation of the frame is

  19. Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals.

    Science.gov (United States)

    Pelot, N A; Behrend, C E; Grill, W M

    2017-08-01

    There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics' vBloc ® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed 're-excitation', arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our results indicate that compound neural or downstream muscle

  20. Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals

    Science.gov (United States)

    Pelot, N. A.; Behrend, C. E.; Grill, W. M.

    2017-08-01

    Objective. There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics’ vBloc® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. Approach. We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. Main results. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed ‘re-excitation’, arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Significance. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our

  1. Spectrally resolved, broadband frequency response characterization of photodetectors using continuous-wave supercontinuum sources

    Science.gov (United States)

    Choudhury, Vishal; Prakash, Roopa; Nagarjun, K. P.; Supradeepa, V. R.

    2018-02-01

    A simple and powerful method using continuous wave supercontinuum lasers is demonstrated to perform spectrally resolved, broadband frequency response characterization of photodetectors in the NIR Band. In contrast to existing techniques, this method allows for a simple system to achieve the goal, requiring just a standard continuous wave(CW) high-power fiber laser source and an RF spectrum analyzer. From our recent work, we summarize methods to easily convert any high-power fiber laser into a CW supercontinuum. These sources in the time domain exhibit interesting properties all the way down to the femtosecond time scale. This enables measurement of broadband frequency response of photodetectors while the wide optical spectrum of the supercontinuum can be spectrally filtered to obtain this information in a spectrally resolved fashion. The method involves looking at the RF spectrum of the output of a photodetector under test when incident with the supercontinuum. By using prior knowledge of the RF spectrum of the source, the frequency response can be calculated. We utilize two techniques for calibration of the source spectrum, one using a prior measurement and the other relying on a fitted model. Here, we characterize multiple photodetectors from 150MHz bandwidth to >20GHz bandwidth at multiple bands in the NIR region. We utilize a supercontinuum source spanning over 700nm bandwidth from 1300nm to 2000nm. For spectrally resolved measurement, we utilize multiple wavelength bands such as around 1400nm and 1600nm. Interesting behavior was observed in the frequency response of the photodetectors when comparing broadband spectral excitation versus narrower band excitation.

  2. Approximate bandpass and frequency response models of the difference of Gaussian filter

    Science.gov (United States)

    Birch, Philip; Mitra, Bhargav; Bangalore, Nagachetan M.; Rehman, Saad; Young, Rupert; Chatwin, Chris

    2010-12-01

    The Difference of Gaussian (DOG) filter is widely used in optics and image processing as, among other things, an edge detection and correlation filter. It has important biological applications and appears to be part of the mammalian vision system. In this paper we analyse the filter and provide details of the full width half maximum, bandwidth and frequency response in order to aid the full characterisation of its performance.

  3. Frequencies of CCR5-D32, CCR2-64I and SDF1-3’A mutations in Human Immunodeficiency Virus (HIV seropositive subjects and seronegative individuals from the state of Pará in Brazilian Amazonia

    Directory of Open Access Journals (Sweden)

    Fernanda Andreza de Pinho Lott Carvalhaes

    2005-12-01

    Full Text Available The distribution of genetic polymorphisms of chemokine receptors CCR5-delta32, CCR2-64I and chemokine (SDF1-3’A mutations were studied in 110 Human Immunodeficiency Virus type 1 (HIV-1 seropositive individuals (seropositive group and 139 seronegative individuals (seronegative group from the population of the northern Brazilian city of Belém which is the capital of the state of Pará in the Brazilian Amazon. The CCR5-delta32 mutation was found in the two groups at similar frequencies, i.e. 2.2% for the seronegative group and 2.7% for the seropositive group. The frequencies of the SDF1-3’A mutation were 21.0% for the seronegative group and 15.4% for the seropositive group, and the CCR2-64I allele was found at frequencies of 12.5% for the seronegative group and 5.4% for the seropositive group. Genotype distributions were consistent with Hardy-Weinberg expectations in both groups, suggesting that none of the three mutations has a detectable selective effect. Difference in the allelic and genotypic frequencies was statistically significant for the CCR2 locus, the frequency in the seronegative group being twice that found in the seropositive group. This finding may indicate a protective effect of the CCR2-64I mutation in relation to HIV transmission. However, considering that the CCR2-64I mutation has been more strongly associated with a decreased risk for progression for AIDS than to the resistance to the HIV infection, this could reflect an aspect of population structure or a Type I error.

  4. Calculation and applications of the frequency dependent neutron detector response functions

    International Nuclear Information System (INIS)

    Van Dam, H.; Van Hagen, T.H.J.J. der; Hoogenboom, J.E.; Keijzer, J.

    1994-01-01

    The theoretical basis is presented for the evaluation of the frequency dependent function that enables to calculate the response of a neutron detector to parametric fluctuations ('noise') or oscillations in reactor core. This function describes the 'field view' of a detector and can be calculated with a static transport code under certain conditions which are discussed. Two applications are presented: the response of an ex-core detector to void fraction fluctuations in a BWR and of both in and ex-core detectors to a rotating neutron absorber near or inside a research reactor core. (authors). 7 refs., 4 figs

  5. Determination of ferroelectric contributions to electromechanical response by frequency dependent piezoresponse force microscopy.

    Science.gov (United States)

    Seol, Daehee; Park, Seongjae; Varenyk, Olexandr V; Lee, Shinbuhm; Lee, Ho Nyung; Morozovska, Anna N; Kim, Yunseok

    2016-07-28

    Hysteresis loop analysis via piezoresponse force microscopy (PFM) is typically performed to probe the existence of ferroelectricity at the nanoscale. However, such an approach is rather complex in accurately determining the pure contribution of ferroelectricity to the PFM. Here, we suggest a facile method to discriminate the ferroelectric effect from the electromechanical (EM) response through the use of frequency dependent ac amplitude sweep with combination of hysteresis loops in PFM. Our combined study through experimental and theoretical approaches verifies that this method can be used as a new tool to differentiate the ferroelectric effect from the other factors that contribute to the EM response.

  6. Uncertainty quantification of dynamic responses in the frequency domain in the context of virtual testing

    Science.gov (United States)

    Brehm, Maik; Deraemaeker, Arnaud

    2015-04-01

    For the development of innovative materials, construction types or maintenance strategies, experimental investigations are inevitable to validate theoretical approaches in praxis. Numerical simulations, embedded in a general virtual testing approach, are alternatives to expensive experimental investigations. The statistical properties of the dynamic response in the frequency domain obtained from continuously measured data are often the basis for many developments, such as the optimization of damage indicators for structural health monitoring systems or the investigation of data-based frequency response function estimates. Two straightforward numerical simulation approaches exist to derive the statistics of a response due to random excitation and measurement errors. One approach is the sample-based technique, wherein for each excitation sample a time integration solution is needed. This can be computationally very demanding if a high accuracy of the statistical properties is of interest. The other approach consists in using the relationship between the excitation and the response directly in the frequency domain, wherein a weakly stationary process is assumed. This approach is inherently related to an infinite time response, which can hardly be derived from measured data. In this paper, a novel approach is proposed that overcomes the limitation of both aforementioned methods, by providing a fast analytical probabilistic framework for uncertainty quantification to determine accurately the statistics of short time dynamic responses. It is assumed that the structural system is known and can be described by deterministic parameters. The influences of signal processing techniques, such as linear combinations, windowing, and segmentation used in Welch's method, are considered as well. The performance of the new algorithm is investigated in comparison to both previous approaches on a three degrees of freedom system. The benchmark shows that the novel approach outperforms

  7. Mutations induced by ultraviolet light

    International Nuclear Information System (INIS)

    Pfeifer, Gerd P.; You, Young-Hyun; Besaratinia, Ahmad

    2005-01-01

    The different ultraviolet (UV) wavelength components, UVA (320-400 nm), UVB (280-320 nm), and UVC (200-280 nm), have distinct mutagenic properties. A hallmark of UVC and UVB mutagenesis is the high frequency of transition mutations at dipyrimidine sequences containing cytosine. In human skin cancers, about 35% of all mutations in the p53 gene are transitions at dipyrimidines within the sequence 5'-TCG and 5'-CCG, and these are localized at several mutational hotspots. Since 5'-CG sequences are methylated along the p53 coding sequence in human cells, these mutations may be derived from sunlight-induced pyrimidine dimers forming at sequences that contain 5-methylcytosine. Cyclobutane pyrimidine dimers (CPDs) form preferentially at dipyrimidines containing 5-methylcytosine when cells are irradiated with UVB or sunlight. In order to define the contribution of 5-methylcytosine to sunlight-induced mutations, the lacI and cII transgenes in mouse fibroblasts were used as mutational targets. After 254 nm UVC irradiation, only 6-9% of the base substitutions were at dipyrimidines containing 5-methylcytosine. However, 24-32% of the solar light-induced mutations were at dipyrimidines that contain 5-methylcytosine and most of these mutations were transitions. Thus, CPDs forming preferentially at dipyrimidines with 5-methylcytosine are responsible for a considerable fraction of the mutations induced by sunlight in mammalian cells. Using mouse cell lines harboring photoproduct-specific photolyases and mutational reporter genes, we showed that CPDs (rather than 6-4 photoproducts or other lesions) are responsible for the great majority of UVB-induced mutations. An important component of UVB mutagenesis is the deamination of cytosine and 5-methylcytosine within CPDs. The mutational specificity of long-wave UVA (340-400 nm) is distinct from that of the shorter wavelength UV and is characterized mainly by G to T transversions presumably arising through mechanisms involving oxidized DNA

  8. Evolution of a G protein-coupled receptor response by mutations in regulatory network interactions

    DEFF Research Database (Denmark)

    Di Roberto, Raphaël B; Chang, Belinda; Trusina, Ala

    2016-01-01

    All cellular functions depend on the concerted action of multiple proteins organized in complex networks. To understand how selection acts on protein networks, we used the yeast mating receptor Ste2, a pheromone-activated G protein-coupled receptor, as a model system. In Saccharomyces cerevisiae......, Ste2 is a hub in a network of interactions controlling both signal transduction and signal suppression. Through laboratory evolution, we obtained 21 mutant receptors sensitive to the pheromone of a related yeast species and investigated the molecular mechanisms behind this newfound sensitivity. While...... demonstrate that a new receptor-ligand pair can evolve through network-altering mutations independently of receptor-ligand binding, and suggest a potential role for such mutations in disease....

  9. Retinitis Pigmentosa Mutations in Bad Response to Refrigeration 2 (Brr2) Impair ATPase and Helicase Activity.

    Science.gov (United States)

    Ledoux, Sarah; Guthrie, Christine

    2016-06-03

    Brr2 is an RNA-dependent ATPase required to unwind the U4/U6 snRNA duplex during spliceosome assembly. Mutations within the ratchet helix of the Brr2 RNA binding channel result in a form of degenerative human blindness known as retinitis pigmentosa (RP). The biochemical consequences of these mutations on Brr2's RNA binding, helicase, and ATPase activity have not yet been characterized. Therefore, we identified the largest construct of Brr2 that is soluble in vitro, which truncates the first 247 amino acids of the N terminus (Δ247-Brr2), to characterize the effects of the RP mutations on Brr2 activity. The Δ247-Brr2 RP mutants exhibit a gradient of severity of weakened RNA binding, reduced helicase activity, and reduced ATPase activity compared with wild type Δ247-Brr2. The globular C-terminal Jab1/Mpn1-like domain of Prp8 increases the ability of Δ247-Brr2 to bind the U4/U6 snRNA duplex at high pH and increases Δ247-Brr2's RNA-dependent ATPase activity and the extent of RNA unwinding. However, this domain of Prp8 does not differentially affect the Δ247-Brr2 RP mutants compared with the wild type Δ247-Brr2. When stimulated by Prp8, wild type Δ247-Brr2 is able to unwind long stable duplexes in vitro, and even the RP mutants capable of binding RNA with tight affinity are incapable of fully unwinding short duplex RNAs. Our data suggest that the RP mutations within the ratchet helix impair Brr2 translocation through RNA helices. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Alkylating agent (MNU)-induced mutation in space environment

    Science.gov (United States)

    Ohnishi, T.; Takahashi, A.; Ohnishi, K.; Takahashi, S.; Masukawa, M.; Sekikawa, K.; Amano, T.; Nakano, T.; Nagaoka, S.

    2001-01-01

    In recent years, some contradictory data about the effects of microgravity on radiation-induced biological responses in space experiments have been reported. We prepared a damaged template DNA produced with an alkylating agent (N-methyl-N-nitroso urea; MNU) to measure incorrect base-incorporation during DNA replication in microgravity. We examined whether mutation frequency is affected by microgravity during DNA replication for a DNA template damaged by an alkylating agent. Using an in vitro enzymatic reaction system, DNA synthesis by Taq polymerase or polymerase III was done during a US space shuttle mission (Discovery, STS-91). After the flight, DNA replication and mutation frequencies were measured. We found that there was almost no effect of microgravity on DNA replication and mutation frequency. It is suggested that microgravity might not affect at the stage of substrate incorporation in induced-mutation frequency.

  11. Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations.

    Science.gov (United States)

    Osada, Takuya; Chen, Minyong; Yang, Xiao Yi; Spasojevic, Ivan; Vandeusen, Jeffrey B; Hsu, David; Clary, Bryan M; Clay, Timothy M; Chen, Wei; Morse, Michael A; Lyerly, H Kim

    2011-06-15

    Wnt/β-catenin pathway activation caused by adenomatous polyposis coli (APC) mutations occurs in approximately 80% of sporadic colorectal cancers (CRC). The antihelminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevelled-2 (Dvl2) expression, resulting in diminished downstream β-catenin signaling. In this study, we determined whether niclosamide could inhibit the Wnt/β-catenin pathway in human CRCs and whether its inhibition might elicit antitumor effects in the presence of APC mutations. We found that niclosamide inhibited Wnt/β-catenin pathway activation, downregulated Dvl2, decreased downstream β-catenin signaling, and exerted antiproliferative effects in human colon cancer cell lines and CRC cells isolated by surgical resection of metastatic disease, regardless of mutations in APC. In contrast, inhibition of NF-κB or mTOR did not exert similar antiproliferative effects in these CRC model systems. In mice implanted with human CRC xenografts, orally administered niclosamide was well tolerated, achieved plasma and tumor levels associated with biologic activity, and led to tumor control. Our findings support clinical explorations to reposition niclosamide for the treatment of CRC.

  12. Theta frequency background tunes transmission but not summation of spiking responses.

    Directory of Open Access Journals (Sweden)

    Dhanya Parameshwaran

    Full Text Available Hippocampal neurons are known to fire as a function of frequency and phase of spontaneous network rhythms, associated with the animal's behaviour. This dependence is believed to give rise to precise rate and temporal codes. However, it is not well understood how these periodic membrane potential fluctuations affect the integration of synaptic inputs. Here we used sinusoidal current injection to the soma of CA1 pyramidal neurons in the rat brain slice to simulate background oscillations in the physiologically relevant theta and gamma frequency range. We used a detailed compartmental model to show that somatic current injection gave comparable results to more physiological synaptically driven theta rhythms incorporating excitatory input in the dendrites, and inhibitory input near the soma. We systematically varied the phase of synaptic inputs with respect to this background, and recorded changes in response and summation properties of CA1 neurons using whole-cell patch recordings. The response of the cell was dependent on both the phase of synaptic inputs and frequency of the background input. The probability of the cell spiking for a given synaptic input was up to 40% greater during the depolarized phases between 30-135 degrees of theta frequency current injection. Summation gain on the other hand, was not affected either by the background frequency or the phasic afferent inputs. This flat summation gain, coupled with the enhanced spiking probability during depolarized phases of the theta cycle, resulted in enhanced transmission of summed inputs during the same phase window of 30-135 degrees. Overall, our study suggests that although oscillations provide windows of opportunity to selectively boost transmission and EPSP size, summation of synaptic inputs remains unaffected during membrane oscillations.

  13. Multi-frequency response of a cylinder subjected to vortex shedding and support motions

    Energy Technology Data Exchange (ETDEWEB)

    Vikestad, Kyrre

    1998-12-31

    This thesis deals with an experimental investigation of vortex induced vibrations of a circular cylinder. The purpose of the experiment was to identify the influence from a controlled disturbance of the cylinder motions on the response caused by vortex shedding. The cylinder investigated is 2 m long and the diameter is 10 cm. The cylinder is elastically mounted in an apparatus using springs, where the foundation of one of the springs can have a harmonic motion. The apparatus is placed on a carriage in a 25 m long towing tank. Towing velocities are varied between 0.140 m/s and 0.655 m/s corresponding to reduced velocity range from 2.8 to 13.2. The still water natural frequency is 0.497 Hz, and the natural frequency in air is 0.634 Hz. The cylinder is only able to oscillate in the cross-flow direction. The support motion frequency was varied between 0.26 Hz and 1.01 Hz, and the force motion amplitude was varied using 2, 4 and 6 cm support amplitudes. Three sets of experiments were carried out: (1) Still water oscillations due to harmonic support motion excitation, support amplitude and frequencies varied, (2) Towing tests with no support motion, the velocity is varied, (3) Combined excitation: Towing tests with support motion. All possible combinations of experiments (1) and (2) are carried out. The two first experiments provide reference values for the combined excitation experiments and for verification purposes. The results reveal the ability of the external disturbance to influence the vortex shedding process both regarding frequency and the resulting response amplitudes. Results for added mass, in-line drag and damping are also obtained. The work may be of use in deep water floating petroleum production. 81 refs., 73 figs., 6 tabs.

  14. High frequency of the recurrent c.1310_1313delAAGA BRCA2 mutation in the North-East of Morocco and implication for hereditary breast-ovarian cancer prevention and control.

    Science.gov (United States)

    Laarabi, Fatima-Zahra; Ratbi, Ilham; Elalaoui, Siham Chafai; Mezzouar, Loubna; Doubaj, Yassamine; Bouguenouch, Laila; Ouldim, Karim; Benjaafar, Noureddine; Sefiani, Abdelaziz

    2017-06-02

    To date, a limited number of BRCA1/2 germline mutations have been reported in hereditary breast and/or ovarian cancer in the Moroccan population. Less than 20 different mutations of these two genes have been identified in Moroccan patients, and recently we reported a further BRCA2 mutation (c.1310_1313delAAGA; p.Lys437IlefsX22) in three unrelated patients, all from the North-East of the country. We aimed in this study to evaluate the frequency and geographic distribution of this BRCA2 frameshift mutation, in order to access its use as the first-line BRCA genetic testing strategy for Moroccan patients. We enrolled in this study 122 patients from different regions of Morocco, with suggestive inherited predisposition to breast and ovarian cancers. All subjects gave written informed consent to BRCA1/2 genetic testing. According to available resources of our lab and enrolled families, 51 patients were analyzed by the conventional individual exon-by-exon Sanger sequencing, 23 patients were able to benefit from a BRCA next generation sequencing and a target screening for exon 10 of BRCA2 gene was performed in 48 patients. Overall, and among the 122 patients analyzed for at least the exon 10 of the BRCA2 gene, the c.1310_1313delAAGA frameshift mutation was found in 14 patients. Genealogic investigation revealed that all carriers of this mutation shared the same geographic origin and were descendants of the North-East of Morocco. In this study, we highlighted that c.1310_1313delAAGA mutation of BRCA2 gene is recurrent with high frequency in patients from the North-East region of Morocco. Therefore, we propose to use, in public health strategies, the detection of this mutation as the first-line screening tests in patients with breast and ovarian cancer originated from this region.

  15. Frequency Response Studies using Receptance Coupling Approach in High Speed Spindles

    Science.gov (United States)

    Shaik, Jakeer Hussain; Ramakotaiah, K.; Srinivas, J.

    2018-01-01

    In order to assess the stability of high speed machining, estimate the frequency response at the end of tool tip is of great importance. Evaluating dynamic response of several combinations of integrated spindle-tool holder-tool will consume a lot of time. This paper presents coupled field dynamic response at tool tip for the entire integrated spindle tool unit. The spindle unit is assumed to be relying over the front and rear bearings and investigated using the Timoshenko beam theory to arrive the receptances at different locations of the spindle-tool unit. The responses are further validated with conventional finite element model as well as with the experiments. This approach permits quick outputs without losing accuracy of solution and further these methods are utilized to analyze the various design variables on system dynamics. The results obtained through this analysis are needed to design the better spindle unit in an attempt to reduce the frequency amplitudes at the tool tip to improvise the milling stability during cutting process.

  16. Geometrical Feature Extraction from Ultrasonic Time Frequency Responses: An Application to Nondestructive Testing of Materials

    Directory of Open Access Journals (Sweden)

    Naranjo Valery

    2010-01-01

    Full Text Available Signal processing is an essential tool in nondestructive material characterization. Pulse-echo inspection with ultrasonic energy provides signals (A-scans that can be processed in order to obtain parameters which are related to physical properties of inspected materials. Conventional techniques are based on the use of a short-term frequency analysis of the A-scan, obtaining a time-frequency response (TFR, to isolate the evolution of the different frequency-dependent parameters. The application of geometrical estimators to TFRs provides an innovative way to complement conventional techniques based on the one-dimensional evolution of an A-scan extracted parameter (central or centroid frequency, bandwidth, etc.. This technique also provides an alternative method of obtaining similar meaning and less variance estimators. A comparative study of conventional versus new proposed techniques is presented in this paper. The comparative study shows that working with binarized TFRs and the use of shape descriptors provide estimates with lower bias and variance than conventional techniques. Real scattering materials, with different scatterer sizes, have been measured in order to demonstrate the usefulness of the proposed estimators to distinguish among scattering soft tissues. Superior results, using the proposed estimators in real measures, were obtained when classifying according to mean scatterer size.

  17. Effect of Scour on the Natural Frequency Responses of the Meteorological Mast in the Taiwan Strait

    Directory of Open Access Journals (Sweden)

    Wei-Chen Tseng

    2018-04-01

    Full Text Available The meteorological mast (met mast for the Taiwan Power Company’s offshore wind farm is located in Taiwan Strait near Changhua County. The p–y curve method recommended in the current offshore foundation design codes does not account for the local scour around the pile foundation; it overestimates the lateral pile deformation and underestimates the foundation stiffness. This paper presents a method to correct the initial modulus of subgrade reaction and modify the ultimate lateral resistance caused by the local scour. The natural frequency of the met mast structure is also determined by a numerical model and verified with the measured data in situ. A comprehensive parameter study is performed to analyze the effect of scour on the dynamic responses of the met mast. Two types of foundation model, a coupled-springs foundation model and a distributed-springs foundation model, are considered in the dynamic analysis of the met mast. The results demonstrate that using a distributed-springs foundation model provides a relatively accurate estimate of the natural frequencies of the met mast structure. Furthermore, the scour exerted significant effects on certain modes of the vibration responses. The natural frequencies of the met mast structure can be reduced by approximately 14% due to scour, particularly in the horizontal bending modes. This paper also provides a preliminary strategy for structural monitoring and analysis to detect scour damage on offshore wind turbines with monopile foundations.

  18. Board meeting frequency and corporate social responsibility (CSR reporting: Evidence from Malaysia

    Directory of Open Access Journals (Sweden)

    Nurulyasmin Binti Ju Ahmad

    2017-05-01

    Full Text Available This study aims at determining the effectiveness of board meeting frequency on Corporate Social Responsibility (CSR reporting by public listed companies on the Main Market of Bursa Malaysia. A CSR reporting index consisting of 51 items was developed based on six themes: General, Community, Environment, Human Resource, Marketplace and Other. A content analysis was used to determine the extent of CSR reporting. An Ordinary Least Square (OLS regression was employed in determining the association between board meeting frequency and CSR reporting. The finding of the study is that advising tendency (frequency of board meetings is not associated with CSR reporting. Overall this study strengthens the idea that advising tendency of the board is essential to companies in order to safeguard all stakeholders’ interests. Accordingly, regulators and policymakers should be more stringent in monitoring company’s conformance towards regulations. This study provides a new avenue of knowledge and contributes to the literature on the practices of the board of directors and corporate social responsibility reporting in the context of a semi-developed country

  19. Management Process of a Frequency Response Flight Test for Rotorcraft Flying Qualities Evaluation

    Directory of Open Access Journals (Sweden)

    João Otávio Falcão Arantes Filho

    2016-07-01

    Full Text Available This paper applies the frequency response methodology to characterize and analyze the flying qualities of longitudinal and lateral axes of a rotary-wing aircraft, AS355-F2. Using the results, it is possible to check the suitability of the aircraft in accordance with ADS-33E-PRF standard, whose flying qualities specifications criteria are based on parameters in the frequency domain. The key steps addressed in the study involve getting, by means of flight test data, the closed-loop dynamic responses including the design of the instrumentation and specification of the sensors to be used in the flight test campaign, the definition of the appropriate maneuvers characteristics for excitation of the aircraft, the planning and execution of the flight test to collect the data, and the proper data treatment, processing and analysis after the flight. After treatment of the collected data, single input-single output spectral analysis is performed. The results permit the analysis of the flying qualities characteristics, anticipation of the demands to which the pilot will be subjected during closed-loop evaluations and check of compliance with the aforementioned standard, within the range of consistent excitation frequencies for flight tests, setting the agility level of the test aircraft.

  20. Tunable optical response at the plasmon-polariton frequency in dielectric-graphene-metamaterial systems

    Science.gov (United States)

    Calvo-Velasco, D. M.; Porras-Montenegro, N.

    2018-04-01

    By using the scattering matrix formalism, it is studied the optical properties of one dimensional photonic crystals made of multiple layers of dielectric and uniaxial anisotropic single negative electric metamaterial with Drude type responses, with inclusions of graphene in between the dielectric-dielectric interfaces (DGMPC). The transmission spectra for transverse electric (TE) and magnetic (TM) polarization are presented as a function of the incidence angle, the graphene chemical potential, and the metamaterial plasma frequencies. It is found for the TM polarization the tunability of the DGMPC optical response with the graphene chemical potential, which can be observed by means of transmission or reflexion bands around the metamaterial plasmon-polariton frequency, with bandwidths depending on both the incidence angle and the metamaterial plasma frequency. Also, the transmission band is observed when losses in the metamaterial slabs are considered for finite systems. The conditions for the appearance of these bands are shown analytically. We consider this work contributes to open new possibilities to the design of photonic devices with DGMPCs.

  1. Non-local spatial frequency response of photopolymer materials containing chain transfer agents: I. Theoretical modelling

    International Nuclear Information System (INIS)

    Guo, Jinxin; Gleeson, Michael R; Liu, Shui; Sheridan, John T

    2011-01-01

    The non-local photopolymerization driven diffusion (NPDD) model predicts that a reduction in the non-local response length within a photopolymer material will improve its high spatial frequency response. The introduction of a chain transfer agent reduces the average molecular weight of polymer chains formed during free radical polymerization. Therefore a chain transfer agent (CTA) provides a practical method to reduce the non-local response length. An extended NPDD model is presented, which includes the chain transfer reaction and most major photochemical processes. The addition of a chain transfer agent into an acrylamide/polyvinyl alcohol photopolymer material is simulated and the predictions of the model are examined. The predictions of the model are experimentally examined in part II of this paper

  2. Time-frequency analysis of railway bridge response in forced vibration

    Science.gov (United States)

    Cantero, Daniel; Ülker-Kaustell, Mahir; Karoumi, Raid

    2016-08-01

    This paper suggests the use of the Continuous Wavelet Transform in combination with the Modified Littlewood-Paley basis to analyse bridge responses exited by traversing trains. The analysis provides an energy distribution map in the time-frequency domain that offers a better resolution compared to previous published studies. This is demonstrated with recorded responses of the Skidträsk Bridge, a 36 m long composite bridge located in Sweden. It is shown to be particularly useful to understand the evolution of the energy content during a vehicle crossing event. With this information it is possible to distinguish the effect of several of the governing factors involved in the dynamic response including vehicle's speed and axle configuration as well as non-linear behaviour of the structure.

  3. Multiple linear regression to estimate time-frequency electrophysiological responses in single trials.

    Science.gov (United States)

    Hu, L; Zhang, Z G; Mouraux, A; Iannetti, G D

    2015-05-01

    oscillations, obtaining single-trial estimate of response latency, frequency, and magnitude. This permits within-subject statistical comparisons, correlation with pre-stimulus features, and integration of simultaneously-recorded EEG and fMRI. Copyright © 2015. Published by Elsevier Inc.

  4. Mutation breeding newsletter. No. 33

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1989-01-01

    This issue of the newsletter reports a number of research news and research abstracts on application of radiation induced mutation techniques to increase mutagenesis and mutation frequency in plant breeding projects.

  5. Mutation breeding newsletter. No. 33

    International Nuclear Information System (INIS)

    1989-01-01

    This issue of the newsletter reports a number of research news and research abstracts on application of radiation induced mutation techniques to increase mutagenesis and mutation frequency in plant breeding projects

  6. Intracellular responses to frequency modulated tones in the dorsal cortex of the mouse inferior colliculus

    Directory of Open Access Journals (Sweden)

    Ruediger eGeis

    2013-01-01

    Full Text Available Frequency modulations occur in many natural sounds, including vocalizations. The neuronal response to frequency modulated (FM stimuli has been studied extensively in different brain areas, with an emphasis on the auditory cortex and the central nucleus of the inferior colliculus. Here, we measured the responses to FM sweeps in whole-cell recordings from neurons in the dorsal cortex of the mouse inferior colliculus. Both up- and downward logarithmic FM sweeps were presented at two different speeds to both the ipsi- and the contralateral ear. Based on the number of action potentials that were fired, between 10-24% of cells were selective for rate or direction of the FM sweeps. A somewhat lower percentage of cells, 6-21%, showed selectivity based on EPSP size. To study the mechanisms underlying the generation of FM selectivity, we compared FM responses with responses to simple tones in the same cells. We found that if pairs of neurons responded in a similar way to simple tones, they generally also responded in a similar way to FM sweeps. Further evidence that FM selectivity can be generated within the dorsal cortex was obtained by reconstructing FM sweeps from the response to simple tones using three different models. In about half of the direction selective neurons the selectivity was generated by spectrally asymmetric synaptic inhibition. In addition, evidence for direction selectivity based on the timing of excitatory responses was also obtained in some cells. No clear evidence for the local generation of rate selectivity was obtained. We conclude that FM direction selectivity can be generated within the dorsal cortex of the mouse inferior colliculus by multiple mechanisms.

  7. Case report of a KIT-mutated melanoma patient with an excellent response to apatinib and temozolomide combination therapy

    Directory of Open Access Journals (Sweden)

    Luo C

    2017-09-01

    Full Text Available Cong Luo,1 Jiayu Shen,2 Jieer Ying,1 Xianhua Fang,3 Xiaohong Wang,1 Zhixuan Fu,4 Peng Liu5 1Department of Abdominal Oncology, Zhejiang Cancer Hospital, 2The Second Clinical Medical College, Zhejiang Chinese Medical University, 3Department of Pathology, 4Department of Colorectal Surgery, 5Department of Radiotherapy, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China Abstract: Malignant melanoma is one kind of malignant disease which has high rates of mortality, metastasis, and poor prognosis. The therapeutic landscape is rapidly changing with the development of novel agents in recent decades, such as anti-PD-1 agents, anti-CTLA-4 agents, and BRAF inhibitors. However, since most of these novel agents are very expensive, not all patients can afford them. Apatinib is a novel oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2 and may also be effective on Ret, c-KIT, and c-src. Temozolomide (TMZ is a second-generation alkylating agent and a cytotoxic drug for melanoma treatment. In this work, we reported a case of metastatic melanoma with an excellent response to apatinib/TMZ combination therapy with progression-free survival for more than one year. This patient showed high expression of CD117, VEGFR-3, and KIT mutation in exon 11, suggesting that apatinib may induce clinical response via inhibiting VEGFR and c-KIT. Apatinib/TMZ combination therapy could be a new option for the treatment of advanced melanoma with KIT mutation. Keywords: advanced melanoma, KIT mutation, apatinib, temozolomide, combination therapy

  8. Modeling and characterization of an electromagnetic system for the estimation of Frequency Response Function of spindle

    Science.gov (United States)

    Tlalolini, David; Ritou, Mathieu; Rabréau, Clément; Le Loch, Sébastien; Furet, Benoit

    2018-05-01

    The paper presents an electromagnetic system that has been developed to measure the quasi-static and dynamic behavior of machine-tool spindle, at different spindle speeds. This system consists in four Pulse Width Modulation amplifiers and four electromagnets to produce magnetic forces of ± 190 N for the static mode and ± 80 N for the dynamic mode up to 5 kHz. In order to measure the Frequency Response Function (FRF) of spindle, the applied force is required, which is a key issue. A dynamic force model is proposed in order to obtain the load from the measured current in the amplifiers. The model depends on the exciting frequency and on the magnetic characteristics of the system. The predicted force at high speed is validated with a specific experiment and the performance limits of the experimental device are investigated. The FRF obtained with the electromagnetic system is compared to a classical tap test measurement.

  9. Western Wind and Solar Integration Study Phase 3 – Frequency Response and Transient Stability

    Energy Technology Data Exchange (ETDEWEB)

    Miller, N. W. [GE Energy Management, Schenectady, NY (United States); Shao, M. [GE Energy Management, Schenectady, NY (United States); Pajic, S. [GE Energy Management, Schenectady, NY (United States); D' Aquila, R. [GE Energy Management, Schenectady, NY (United States)

    2014-12-01

    Power system operators and utilities worldwide have concerns about the impact of high-penetration wind and solar generation on electric grid reliability (EirGrid 2011b, Hydro-Quebec 2006, ERCOT 2010). The stability of North American grids under these conditions is a particular concern and possible impediment to reaching future renewable energy goals. Phase 3 of the Western Wind and Solar Integration Study (WWSIS-3) considers a 33% wind and solar annual energy penetration level that results in substantial changes to the characteristics of the bulk power system, including different power flow patterns, different commitment and dispatch of existing synchronous generation, and different dynamic behavior of wind and solar generation. WWSIS-3 evaluates two specific aspects of fundamental frequency system stability: frequency response and transient stability.

  10. A time-frequency analysis method to obtain stable estimates of magnetotelluric response function based on Hilbert-Huang transform

    Science.gov (United States)

    Cai, Jianhua

    2017-05-01

    The time-frequency analysis method represents signal as a function of time and frequency, and it is considered a powerful tool for handling arbitrary non-stationary time series by using instantaneous frequency and instantaneous amplitude. It also provides a possible alternative to the analysis of the non-stationary magnetotelluric (MT) signal. Based on the Hilbert-Huang transform (HHT), a time-frequency analysis method is proposed to obtain stable estimates of the magnetotelluric response function. In contrast to conventional methods, the response function estimation is performed in the time-frequency domain using instantaneous spectra rather than in the frequency domain, which allows for imaging the response parameter content as a function of time and frequency. The theory of the method is presented and the mathematical model and calculation procedure, which are used to estimate response function based on HHT time-frequency spectrum, are discussed. To evaluate the results, response function estimates are compared with estimates from a standard MT data processing method based on the Fourier transform. All results show that apparent resistivities and phases, which are calculated from the HHT time-frequency method, are generally more stable and reliable than those determined from the simple Fourier analysis. The proposed method overcomes the drawbacks of the traditional Fourier methods, and the resulting parameter minimises the estimation bias caused by the non-stationary characteristics of the MT data.

  11. Analysis of dispersed frequency response for ionic glasses: influence of electrode and nearly constant loss effects

    International Nuclear Information System (INIS)

    Macdonald, J Ross

    2005-01-01

    Analysis by D L Sidebottom of the dispersive frequency response of the real-part of the conductivity, σ'(ω), for many alkali phosphate and metaphosphate glasses, using a fitting model involving a 'universal dynamic response' power law with an exponent n and a constant-loss term, led to anomalous n behaviour that he explained as arising from variable constriction of the local cation conduction space. In order to obtain adequate fits, he eliminated from the data all low-frequency decreases of σ'(ω) below the dc plateau, ones actually associated with electrode effects. Such a cut-off does not, however, eliminate electrode effects possibly present in the high-frequency part of the data range. The results of the present detailed analysis and fitting of both synthetic data and several of his experimental data sets show unequivocally that his anomalous n behaviour arose from neglecting electrode effects. Their inclusion, with or without data cut-off in the fitting model, leads to the expected high-frequency slope value of n = 2/3 associated with bulk conduction, as required by recently published topological effective-dimension considerations for dielectric relaxation in conductive systems. Further, the effects of the inclusion in a full fitting model of series and possibly parallel complex constant-phase-element contributions, representing electrode and nearly constant loss effects, respectively, have been investigated in detail. Such composite models usually lead to best fitting of either the full or cut-off complex data when they include the semi-universal, topologically based K1 bulk model, one indirectly derived from the assumption of stretched-exponential temporal behaviour

  12. Responses of the ear to low frequency sounds, infrasound and wind turbines.

    Science.gov (United States)

    Salt, Alec N; Hullar, Timothy E

    2010-09-01

    Infrasonic sounds are generated internally in the body (by respiration, heartbeat, coughing, etc) and by external sources, such as air conditioning systems, inside vehicles, some industrial processes and, now becoming increasingly prevalent, wind turbines. It is widely assumed that infrasound presented at an amplitude below what is audible has no influence on the ear. In this review, we consider possible ways that low frequency sounds, at levels that may or may not be heard, could influence the function of the ear. The inner ear has elaborate mechanisms to attenuate low frequency sound components before they are transmitted to the brain. The auditory portion of the ear, the cochlea, has two types of sensory cells, inner hair cells (IHC) and outer hair cells (OHC), of which the IHC are coupled to the afferent fibers that transmit "hearing" to the brain. The sensory stereocilia ("hairs") on the IHC are "fluid coupled" to mechanical stimuli, so their responses depend on stimulus velocity and their sensitivity decreases as sound frequency is lowered. In contrast, the OHC are directly coupled to mechanical stimuli, so their input remains greater than for IHC at low frequencies. At very low frequencies the OHC are stimulated by sounds at levels below those that are heard. Although the hair cells in other sensory structures such as the saccule may be tuned to infrasonic frequencies, auditory stimulus coupling to these structures is inefficient so that they are unlikely to be influenced by airborne infrasound. Structures that are involved in endolymph volume regulation are also known to be influenced by infrasound, but their sensitivity is also thought to be low. There are, however, abnormal states in which the ear becomes hypersensitive to infrasound. In most cases, the inner ear's responses to infrasound can be considered normal, but they could be associated with unfamiliar sensations or subtle changes in physiology. This raises the possibility that exposure to the

  13. The non-equilibrium response of a superconductor to pair-breaking radiation measured over a broad frequency band

    Energy Technology Data Exchange (ETDEWEB)

    Visser, P. J. de, E-mail: p.j.devisser@tudelft.nl [Kavli Institute of NanoScience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft (Netherlands); Yates, S. J. C. [SRON Netherlands Institute for Space Research, Landleven 12, 9747AD Groningen (Netherlands); Guruswamy, T.; Goldie, D. J.; Withington, S. [Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Neto, A.; Llombart, N. [Faculty of Electrical Engineering, Mathematics and Computer Science, Terahertz Sensing Group, Delft University of Technology, Mekelweg 4, 2628 CD Delft (Netherlands); Baryshev, A. M. [SRON Netherlands Institute for Space Research, Landleven 12, 9747AD Groningen (Netherlands); Kapteyn Astronomical Institute, University of Groningen, Landleven 12, 9747 AD Groningen (Netherlands); Klapwijk, T. M. [Kavli Institute of NanoScience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft (Netherlands); Physics Department, Moscow State Pedagogical University, Moscow 119991 (Russian Federation); Baselmans, J. J. A. [SRON Netherlands Institute for Space Research, Sorbonnelaan 2, 3584 CA Utrecht (Netherlands); Faculty of Electrical Engineering, Mathematics and Computer Science, Terahertz Sensing Group, Delft University of Technology, Mekelweg 4, 2628 CD Delft (Netherlands)

    2015-06-22

    We have measured the absorption of terahertz radiation in a BCS superconductor over a broad range of frequencies from 200 GHz to 1.1 THz, using a broadband antenna-lens system and a tantalum microwave resonator. From low frequencies, the response of the resonator rises rapidly to a maximum at the gap edge of the superconductor. From there on, the response drops to half the maximum response at twice the pair-breaking energy. At higher frequencies, the response rises again due to trapping of pair-breaking phonons in the superconductor. In practice, this is a measurement of the frequency dependence of the quasiparticle creation efficiency due to pair-breaking in a superconductor. The efficiency, calculated from the different non-equilibrium quasiparticle distribution functions at each frequency, is in agreement with the measurements.

  14. The non-equilibrium response of a superconductor to pair-breaking radiation measured over a broad frequency band

    International Nuclear Information System (INIS)

    Visser, P. J. de; Yates, S. J. C.; Guruswamy, T.; Goldie, D. J.; Withington, S.; Neto, A.; Llombart, N.; Baryshev, A. M.; Klapwijk, T. M.; Baselmans, J. J. A.

    2015-01-01

    We have measured the absorption of terahertz radiation in a BCS superconductor over a broad range of frequencies from 200 GHz to 1.1 THz, using a broadband antenna-lens system and a tantalum microwave resonator. From low frequencies, the response of the resonator rises rapidly to a maximum at the gap edge of the superconductor. From there on, the response drops to half the maximum response at twice the pair-breaking energy. At higher frequencies, the response rises again due to trapping of pair-breaking phonons in the superconductor. In practice, this is a measurement of the frequency dependence of the quasiparticle creation efficiency due to pair-breaking in a superconductor. The efficiency, calculated from the different non-equilibrium quasiparticle distribution functions at each frequency, is in agreement with the measurements

  15. Speech-evoked brainstem frequency-following responses during verbal transformations due to word repetition.

    Science.gov (United States)

    Galbraith, G C; Jhaveri, S P; Kuo, J

    1997-01-01

    Speech-evoked brainstem frequency-following responses (FFRs) were recorded to repeated presentations of the same stimulus word. Word repetition results in illusory verbal transformations (VTs) in which word perceptions can differ markedly from the actual stimulus. Previous behavioral studies support an explanation of VTs based on changes in arousal or attention. Horizontal and vertical dipole FFRs were recorded to assess responses with putative origins in the auditory nerve and central brainstem, respectively. FFRs were recorded from 18 subjects when they correctly heard the stimulus and when they reported VTs. Although horizontal and vertical dipole FFRs showed different frequency response patterns, dipoles did not differentiate between perceptual conditions. However, when subjects were divided into low- and high-VT groups (based on percentage of VT trials), a significant Condition x Group interaction resulted. This interaction showed the largest difference in FFR amplitudes during VT trials, with the low-VT group showing increased amplitudes, and the high-VT group showing decreased amplitudes, relative to trials in which the stimulus was correctly perceived. These results demonstrate measurable subject differences in the early processing of complex signals, due to possible effects of attention on the brainstem FFR. The present research shows that the FFR is useful in understanding human language as it is coded and processed in the brainstem auditory pathway.

  16. Patients harboring EGFR mutation after primary resistance to crizotinib and response to EGFR-tyrosine kinase inhibitor

    Directory of Open Access Journals (Sweden)

    Wang WX

    2016-01-01

    Full Text Available Wenxian Wang,1 Xiaowen Jiang,1 Zhengbo Song,1,2 Yiping Zhang1,2 1Department of Chemotherapy, Zhejiang Cancer Hospital, 2Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang, People’s Republic of China Abstract: Anaplastic lymphoma kinase (ALK rearrangement lung cancer responds to ALK tyrosine kinase inhibitors. It is known that many cases ultimately acquired resistance to crizotinib. However, a case of primary resistance is rare. We present a case of harboring exon 19 deletion in epidermal growth factor receptor in ALK rearranged lung adenocarcinoma, who experienced a partial tumor response to icotinib after failure with crizotinib therapy and chemotherapy. Considering the partial response, we conclude that it is important to find the cause of resistance to crizotinib. We detected gene mutations with plasma by the next-generation sequencing; the next-generation sequencing demonstrates an attractive system to identify mutations improving the outcome of patients with a deadly disease. Keywords: non-small cell lung cancer, anaplastic lymphoma kinase, crizotinib, epidermal growth factor receptor

  17. Recombinant Marburg viruses containing mutations in the IID region of VP35 prevent inhibition of Host immune responses.

    Science.gov (United States)

    Albariño, César G; Wiggleton Guerrero, Lisa; Spengler, Jessica R; Uebelhoer, Luke S; Chakrabarti, Ayan K; Nichol, Stuart T; Towner, Jonathan S

    2015-02-01

    Previous in vitro studies have demonstrated that Ebola and Marburg virus (EBOV and MARV) VP35 antagonize the host cell immune response. Moreover, specific mutations in the IFN inhibitory domain (IID) of EBOV and MARV VP35 that abrogate their interaction with virus-derived dsRNA, lack the ability to inhibit the host immune response. To investigate the role of MARV VP35 in the context of infectious virus, we used our reverse genetics system to generate two recombinant MARVs carrying specific mutations in the IID region of VP35. Our data show that wild-type and mutant viruses grow to similar titers in interferon deficient cells, but exhibit attenuated growth in interferon-competent cells. Furthermore, in contrast to wild-type virus, both MARV mutants were unable to inhibit expression of various antiviral genes. The MARV VP35 mutants exhibit similar phenotypes to those previously described for EBOV, suggesting the existence of a shared immune-modulatory strategy between filoviruses. Published by Elsevier Inc.

  18. Dose response and mutation induction by ion beam irradiation in buckwheat

    International Nuclear Information System (INIS)

    Morishita, T.; Yamaguchi, H.; Degi, K.; Shikazono, N.; Hase, Y.; Tanaka, A.; Abe, T.

    2003-01-01

    The biological effects of ion beams were investigated to pursue the development of a method for breeding by mutation in buckwheat. Common buckwheat (Botansoba, Bot) and tartary buckwheat (Rotundatiem, Rot) seeds were exposed to various ions in linear energy transfer (LET) at 9-630 keV/μm. The lethal dose 50 (LD 50 ) of ion beams were 10-300 Gy (Bot) and 30-500 Gy (Rot). It was indicated that a penetrating depth in excess of 1.7 mm is necessary to thoroughly saturate the target, and ions with a penetrating depth of less than 2.2 mm were affected by the presence of hulls. The maximum values of the relative biological effectiveness were 17.7 (Rot) and 22.5 (Bot) at 305 keV/μm. The effective cross sections increased with the LET, and the maximum values were 2.7 (Rot) and 3.0 μm 2 (Bot). The mutation induction effects of He and C ions were higher than those of gamma rays

  19. A UV-induced mutation in neurospora that affects translational regulation in response to arginine

    International Nuclear Information System (INIS)

    Freitag, M.; Dighde, N.; Sachs, M.S.

    1996-01-01

    The Neurospora crassa arg-2 gene encodes the small subunit of arginine-specific carbamoyl phosphate synthetase. The levels of arg-2 mRNA and mRNA translation are negatively regulated by arginine. An upstream open reading frame (uORF) in the transcript's 5' region has been implicated in arginine-specific control. An arg-2-hph fusion gene encoding hygromycin phosphotransferase conferred arginine-regulated resistance to hygromycin when introduced into N. crassa. We used an arg-2-hph strain to select for UV-induced mutants that grew in the presence of hygromycin and arginine, and we isolated 46 mutants that had either of two phenotypes. One phenotype indicated altered expression of both arg-2-hph and arg-2 genes; the other, altered expression of arg-2-hph but not arg-2. One of the latter mutations, which was genetically closely linked to arg-2-hph, was recovered from the 5' region of the arg-2-hph gene using PCR Sequence analyses and transformation experiments revealed a mutation at uORF codon 12 (Asp to Asn) that abrogated negative regulation. Examination of the distribution of ribosomes on arg-2-hph transcripts showed that loss of regulation had a translational component, indicating the uORF sequence was important for Arg-specific translational control. Comparisons with other uORFs suggest common elements in translational control mechanisms

  20. Effect of frequency and flexibility ratio on the seismic response of deep tunnels

    Directory of Open Access Journals (Sweden)

    Eimar Sandoval

    2017-06-01

    Full Text Available Two-dimensional dynamic numerical analyses have been conducted, using FLAC 7.0, to evaluate the seismic response of underground structures located far from the seismic source, placed in either linear-elastic or nonlinear elastoplastic ground. The interaction between the ground and deep circular tunnels with a tied interface is considered. For the simulations, it is assumed that the liner remains in its elastic regime, and plane strain conditions apply to any cross section perpendicular to the tunnel axis. An elastoplastic constitutive model is implemented in FLAC to simulate the nonlinear ground. The effect of input frequency and relative stiffness between the liner and the ground, on the seismic response of tunnels, is evaluated. The response is studied in terms of distortions normalized with respect to those of the free field, and load demand (axial forces and bending moments in the liner. In all cases, i.e. for linear-elastic and nonlinear ground models, the results show negligible effect of the input frequency on the distortions of the cross section, for input frequencies smaller than 5 Hz; that is for ratios between the wave length and the tunnel opening (λ/D larger than ten for linear-elastic and nine for nonlinear ground. Larger normalized distortions are obtained for the nonlinear than for the linear-elastic ground, for the same relative stiffness, with differences increasing as the tunnel becomes more flexible, or when the amplitude of the dynamic input shear stress increases. It has been found that normalized distortions for the nonlinear ground do not follow a unique relationship, as it happens for the linear-elastic ground, but increase as the amplitude of the dynamic input increases. The loading in the liner decreases as the structure becomes more flexible with respect to the ground, and is smaller for a tunnel placed in a stiffer nonlinear ground than in a softer nonlinear ground, for the same flexibility ratio.

  1. Experimental determination of frequency response function estimates for flexible joint industrial manipulators with serial kinematics

    Science.gov (United States)

    Saupe, Florian; Knoblach, Andreas

    2015-02-01

    Two different approaches for the determination of frequency response functions (FRFs) are used for the non-parametric closed loop identification of a flexible joint industrial manipulator with serial kinematics. The two applied experiment designs are based on low power multisine and high power chirp excitations. The main challenge is to eliminate disturbances of the FRF estimates caused by the numerous nonlinearities of the robot. For the experiment design based on chirp excitations, a simple iterative procedure is proposed which allows exploiting the good crest factor of chirp signals in a closed loop setup. An interesting synergy of the two approaches, beyond validation purposes, is pointed out.

  2. Response of Cultured Neuronal Network Activity After High-Intensity Power Frequency Magnetic Field Exposure

    Directory of Open Access Journals (Sweden)

    Atsushi Saito

    2018-03-01

    Full Text Available High-intensity and low frequency (1–100 kHz time-varying electromagnetic fields stimulate the human body through excitation of the nervous system. In power frequency range (50/60 Hz, a frequency-dependent threshold of the external electric field-induced neuronal modulation in cultured neuronal networks was used as one of the biological indicator in international guidelines; however, the threshold of the magnetic field-induced neuronal modulation has not been elucidated. In this study, we exposed rat brain-derived neuronal networks to a high-intensity power frequency magnetic field (hPF-MF, and evaluated the modulation of synchronized bursting activity using a multi-electrode array (MEA-based extracellular recording technique. As a result of short-term hPF-MF exposure (50–400 mT root-mean-square (rms, 50 Hz, sinusoidal wave, 6 s, the synchronized bursting activity was increased in the 400 mT-exposed group. On the other hand, no change was observed in the 50–200 mT-exposed groups. In order to clarify the mechanisms of the 400 mT hPF-MF exposure-induced neuronal response, we evaluated it after blocking inhibitory synapses using bicuculline methiodide (BMI; subsequently, increase in bursting activity was observed with BMI application, and the response of 400 mT hPF-MF exposure disappeared. Therefore, it was suggested that the response of hPF-MF exposure was involved in the inhibitory input. Next, we screened the inhibitory pacemaker-like neuronal activity which showed autonomous 4–10 Hz firing with CNQX and D-AP5 application, and it was confirmed that the activity was reduced after 400 mT hPF-MF exposure. Comparison of these experimental results with estimated values of the induced electric field (E-field in the culture medium revealed that the change in synchronized bursting activity occurred over 0.3 V/m, which was equivalent to the findings of a previous study that used the external electric fields. In addition, the results suggested that

  3. Spectral-Amplitude-Coded OCDMA Optimized for a Realistic FBG Frequency Response

    Science.gov (United States)

    Penon, Julien; El-Sahn, Ziad A.; Rusch, Leslie A.; Larochelle, Sophie

    2007-05-01

    We develop a methodology for numerical optimization of fiber Bragg grating frequency response to maximize the achievable capacity of a spectral-amplitude-coded optical code-division multiple-access (SAC-OCDMA) system. The optimal encoders are realized, and we experimentally demonstrate an incoherent SAC-OCDMA system with seven simultaneous users. We report a bit error rate (BER) of 2.7 x 10-8 at 622 Mb/s for a fully loaded network (seven users) using a 9.6-nm optical band. We achieve error-free transmission (BER < 1 x 10-9) for up to five simultaneous users.

  4. Wavelet-Based Frequency Response Function: Comparative Study of Input Excitation

    Directory of Open Access Journals (Sweden)

    K. Dziedziech

    2014-01-01

    Ful